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ASERNIP S Australian Safety and Efficacy Register of New Interventional Procedures-Surgical Systematic review of intraoperative ablation for the treatment of atrial fibrillation ASERNIP-S REPORT NO. 38 July 2004 Australian Safety & Efficacy Register of New Interventional Procedures – Surgical The Royal Australasian College of Surgeons A Systematic Review of Intraoperative Ablation for the Treatment of Atrial Fibrillation ISBN: 0 909844 64 X Published Date: July, 2004 ___________________________________________________________________________ This report should be cited in the following manner: Hazel SJ, et al. Systematic review of Intraoperative Ablation for the Treatment of Atrial Fibrillation. ASERNIP-S Report No.38. Adelaide, South Australia: ASERNIP-S, July, 2004 Copies of these reports can be obtained from: The Australian Safety and Efficacy Register of New Interventional Procedures - Surgical The Royal Australasian College of Surgeons PO Box 553, Stepney, South Australia 5069 AUSTRALIA Fax: 61-8-83622077 E-mail: [email protected] http://www.surgeons.org/open/asernip-s.htm The Safety and Efficacy Classification for the Systematic Review of Intraoperative Ablation for the Treatment of Atrial Fibrillation was ratified by: The ASERNIP-S Management Committee on July 8, 2004 The Council of the Royal Australasian College of Surgeons on July 30, 2004 Table Of Contents Executive Summary ..................................................................................................................................... i The ASERNIP-S Classification System.................................................................................................. iv Safety and Efficacy Classification............................................................................................................. v Review Group Membership ..................................................................................................................... vi 1.0 OBJECTIVE .................................................................................................................................... 1 2.0 INTRODUCTION ......................................................................................................................... 1 2.1 Pathogenesis of Atrial Fibrillation .............................................................................................. 1 2.2 Conventional Therapies ............................................................................................................... 2 2.2.1 Medical Management of Atrial Fibrillation (AF)......................................................... 2 2.2.2 Electrical Cardioversion and Pacing of Atrial Fibrillation (AF)................................ 3 2.2.3 Catheter ablation of Atrial Fibrillation (AF) ................................................................ 4 2.2.4 Surgical Treatment of Atrial Fibrillation (AF) ............................................................. 4 2.2.5 Maze-III Challenges......................................................................................................... 6 2.3 Intraoperative Ablation Techniques........................................................................................... 6 2.4 Summary......................................................................................................................................... 7 3.0 METHODS ...................................................................................................................................... 7 3.1 Literature Search Protocol ........................................................................................................... 7 3.1.1 Inclusion Criteria.............................................................................................................. 7 3.2 Literature Search Strategies.......................................................................................................... 9 3.3 Literature Database ..................................................................................................................... 11 3.4 Assessment Methods .................................................................................................................. 13 3.4.1 Outcome Measures ........................................................................................................ 13 4.0 DESCRIPTION AND METHODOGICAL ANALYSIS OF STUDIES.......................... 13 4.1 Designation of Levels of Evidence and Critical Appraisal ...................................................... 13 4.1.1 Cryotherapy Ablation .................................................................................................... 14 4.1.2 Radiofrequency Ablation .............................................................................................. 18 4.1.3 Microwave Ablation ...................................................................................................... 24 4.1.4 Laser Ablation ................................................................................................................ 25 4.1.5 Radiofrequency versus Microwave Ablation ............................................................. 25 4.1.6 Maze-III........................................................................................................................... 26 5.0 RESULTS........................................................................................................................................ 27 5.1 SAFETY.......................................................................................................................................... 27 5.1.1 Mortality .......................................................................................................................... 27 5.1.2 Bleeding, blood loss, blood transfusion requirement ............................................... 39 5.1.3 Stroke/ transient ischaemic attack/ other thromboembolism................................ 45 5.1.4 Complications related to cardiac surgery.................................................................... 50 5.1.5 Oesophageal injury ........................................................................................................ 61 5.1.6 Other major perioperative complications................................................................... 62 5.2 EFFICACY..................................................................................................................................... 65 5.2.1 Sinus rhythm (SR) .......................................................................................................... 65 5.2.2 Atrial fibrillation (AF).................................................................................................... 77 5.2.3 Junctional rhythm........................................................................................................... 87 5.2.4 Atrial flutter (AFl) .......................................................................................................... 91 5.2.5 Heart function ................................................................................................................ 96 5.2.6 Pacemakers.................................................................................................................... 111 5.2.7 Catheter ablation .......................................................................................................... 120 5.2.8 Electrical cardioversion ............................................................................................... 124 5.2.9 Continued antiarrhythmic treatment......................................................................... 127 5.2.10 Continued anticoagulant requirement....................................................................... 133 5.2.11 Surgical times and lengths of hospital stay............................................................... 136 5.2.12 Ablation times............................................................................................................... 147 5.2.13 Hospital and ICU stay ................................................................................................. 149 5.2.14 Reoperation and readmission..................................................................................... 153 5.2.15 Exercise testing............................................................................................................. 157 6.0 DISCUSSION ..............................................................................................................................158 6.1 Study Limitations .........................................................................................................................158 6.2 Safety and efficacy of intraoperative ablation ..........................................................................158 6.2.1 Efficacy.......................................................................................................................... 158 6.2.2 Safety.............................................................................................................................. 161 6.3 Factors influencing efficacy........................................................................................................163 6.3.1 Energy source ............................................................................................................... 163 6.3.2 Lesion set....................................................................................................................... 165 6.3.3 Type of AF.................................................................................................................... 166 6.3.4 Measurement of SR/AF.............................................................................................. 166 6.3.5 Atrial contraction ......................................................................................................... 166 6.3.6 Antiarrhythmic medication......................................................................................... 167 6.4 Safety..............................................................................................................................................167 6.4.1 Anticoagulant therapy and risk of stroke.................................................................. 167 6.4.2 Oesophageal perforation............................................................................................. 168 6.4.3 Circumflex artery injury............................................................................................... 168 6.4.4 Length of CPB.............................................................................................................. 169 6.5 Possible indications and contraindications for intraoperative ablation ...............................169 6.6 Uptake of intraoperative ablation for AF.................................................................................170 6.7 Considerations for further research ..........................................................................................170 7.0 CONCLUSIONS.........................................................................................................................171 8.0 ACKNOWLEDGEMENTS .....................................................................................................171 9.0 REFERENCES............................................................................................................................172 List of Tables 1 Databases searched ........................................................................................................................... 9 2 Summary of the exclusion process for the methodological review papers ............................ 12 3 Summary of the final exclusion process for the systematic review papers............................. 12 4 Included studies according to level of evidence and energy source......................................... 14 5 Cryotherapy Ablation- Comparative non-randomised studies ................................................. 17 6 Cryotherapy Ablation Case Series ................................................................................................. 18 7 Radiofrequency Ablation- RCT and Non-randomised Comparative Studies ........................ 22 8 RFA Case Series Included Studies................................................................................................. 23 9 MWA RCT and Non-randomised Comparative Included Studies .......................................... 25 10 MWA Case Series Included Studies .............................................................................................. 25 11 Maze-III included studies ............................................................................................................... 26 12 Mortality- Biatrial CA +CS versus CS .......................................................................................... 27 13 Mortality- Left atrial CA +CS versus CS...................................................................................... 28 14 Mortality- Biatrial CA versus Maze-III......................................................................................... 28 15 Mortality- Kosakai maze versus CA.............................................................................................. 29 16 Mortality- Kosakai maze RAA+ versus RAA- ............................................................................ 29 17 Mortality- Biatrial versus left atrial CA ......................................................................................... 29 18 Mortality- Biatrial versus right atrial CA....................................................................................... 29 19 Mortality- Biatrial CA Case Series ................................................................................................. 30 20 Mortality- Left atrial CA Case Series............................................................................................. 31 21 Mortality- Biatrial RFA+MVS versus MVS RCT ....................................................................... 31 22 Mortality- Biatrial RFA+CS versus CS ......................................................................................... 32 23 Mortality- Left atrial RFA versus CS ............................................................................................ 33 24 Mortality- RFA versus Maze-III .................................................................................................... 33 25 Mortality- Biatrial versus left atrial RFA....................................................................................... 34 26 Mortality- Biatrial RFA Case Series............................................................................................... 35 27 Mortality- Left atrial RFA Case Series .......................................................................................... 36 28 Mortality- Left atrial MWA versus CS RCT ................................................................................ 37 29 Mortality- Left atrial MWA versus CS .......................................................................................... 37 30 Mortality- Biatrial MWA Case Series ............................................................................................ 37 31 Mortality- Left atrial MWA Case Series........................................................................................ 38 32 Bleeding- Biatrial CA+CS versus CS ........................................................................................... 40 33 Bleeding- Left atrial CA+CS versus CS ....................................................................................... 40 34 Bleeding- CA versus Maze-III ....................................................................................................... 40 35 Bleeding- Biatrial versus right atrial CA ....................................................................................... 41 36 Bleeding and blood transfusion- Biatrial versus left atrial CA.................................................. 41 37 Blood loss- Kosakai maze versus biatrial CA .............................................................................. 41 38 Bleeding- Biatrial CA Case Series .................................................................................................. 42 39 Bleeding and blood transfusion- Left atrial CA Case Series ..................................................... 42 40 Bleeding- Left atrial RFA versus CS ............................................................................................. 42 41 Bleeding- Biatrial versus left atrial CA .......................................................................................... 43 42 Bleeding- Biatrial RFA Case Series................................................................................................ 43 43 Blood loss- Biatrial RFA Case Series ............................................................................................ 43 44 Bleeding- Left atrial RFA Case Series........................................................................................... 44 45 Blood loss and transfusion- Left atrial RFA Case Series ........................................................... 44 46 Bleeding- MWA versus CS ............................................................................................................. 44 47 Bleeding- Left atrial MWA Case Series......................................................................................... 45 48 Bleeding and blood loss- MWA versus RFA............................................................................... 45 49 Stroke- Biatrial CA+CS versus CS ................................................................................................ 46 50 Stroke and other thromboembolism- Biatrial CA versus Maze-III ......................................... 46 51 Stroke- Kosakai maze versus CA .................................................................................................. 46 52 Stroke and transient ischaemic attack- Biatrial CA Case Series................................................ 47 53 Stroke and transient ischaemic attack- Left atrial CS Case Series ............................................ 47 54 Stroke and other thromboembolism- Left atrial RFA versus CS............................................. 47 55 Stroke and transient ischaemic attack- Left atrial RFA versus CS ........................................... 48 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 Transient ischaemic attack- Biatrial versus left atrial RFA ........................................................ 48 Stroke, other thromboembolisms and TIAs- Biatrial RFA Case Series .................................. 49 Stroke, other thromboembolism and TIAs- Left atrial RFA Case Series ............................... 49 Stroke- Biatrial MWA Case Series ................................................................................................. 50 Stroke- Left atrial MWA Case Series ............................................................................................ 50 Stroke- MWA versus RFA.............................................................................................................. 50 Mediastinitis- KM versus CA ......................................................................................................... 51 Wound infection- Biatrial CA Case Series ................................................................................... 51 Wound infection/sternal instability or mediastinitis- Biatrial RFA versus CS....................... 52 Mediastinitis- Biatrial RFA versus CS........................................................................................... 52 Mediastinitis- Biatrial versus left atrial RFA ................................................................................ 52 Wound infection- Biatrial RFA Case Series................................................................................. 52 Wound infection- Left atrial RFA Case Series ............................................................................ 53 Pulmonary insufficiency- Kosakai maze versus CA ................................................................... 53 Pulmonary insufficiency- Biatrial CA Case Series....................................................................... 53 Pulmonary insufficiency- Biatrial RFA versus CS ...................................................................... 54 Pulmonary insufficiency- Left atrial RFA versus CS.................................................................. 54 Pulmonary insufficiency- Biatrial RFA Case Series .................................................................... 54 Pulmonary insufficiency- Left atrial RFA Case Series ............................................................... 55 Low cardiac output- CA versus Maze-III ................................................................................... 55 Low cardiac output- Biatrial CA Case Series ............................................................................... 56 Low cardiac output- Biatrial CA.................................................................................................... 56 Low cardiac output- Left atrial RFA versus CS .......................................................................... 56 Low cardiac output- Biatrial RFA Case Series ............................................................................ 57 Low cardiac output- Left atrial RFA Case Series........................................................................ 57 Low cardiac output- Left atrial MWA Case Series ..................................................................... 57 Low cardiac output- MWA versus RFA....................................................................................... 57 Renal failure- CA versus Maze-III................................................................................................. 58 Renal failure- Kosakai maze versus CA........................................................................................ 58 Renal failure- Biatrial CA Case Series ........................................................................................... 58 Renal failure- Biatrial CA Case Series ........................................................................................... 59 IABP- Left atrial CA+CS versus CS ............................................................................................. 59 IABP- CA versus Maze-III............................................................................................................. 59 IABP- Left atrial CA Case Series................................................................................................... 60 IABP- Biatrial RFA Case Series..................................................................................................... 60 IABP- MWA versus RFA ............................................................................................................... 60 Miscellaneous complications- Left atrial CA versus CS............................................................. 62 Miscellaneous complications- Kosakai maze versus CS ............................................................ 62 Miscellaneous complications- Biatrial CA Case Series............................................................... 62 Miscellaneous complications- Left atrial CA Case Series .......................................................... 63 Miscellaneous complications- Biatrial versus left atrial RFA .................................................... 63 Miscellaneous complications- Biatrial RFA Case Series ............................................................ 63 Miscellaneous complications- Left atrial RFA Case Series........................................................ 64 Miscellaneous complications- Left atrial MWA Case Series ..................................................... 64 Miscellaneous complications- MWA versus RFA ...................................................................... 64 Sinus rhythm- Biatrial CA+CS versus CS ................................................................................... 65 Sinus rhythm- Left atrial CA+CS versus CS .............................................................................. 66 Sinus rhythm- CA versus Maze-III .............................................................................................. 66 Sinus rhythm- KM versus CA........................................................................................................ 66 Sinus rhythm- KM-RAA versus KM+RAA ................................................................................ 67 Sinus rhythm- Biatrial versus left atrial CA.................................................................................. 67 Sinus rhythm- KM versus Maze-III ............................................................................................. 67 Sinus rhythm- Biatrial CA Case Series.......................................................................................... 68 Sinus rhythm- Left atrial CA Case Series ..................................................................................... 69 Sinus rhythm- Biatrial RFA+MVS versus MVS RCT................................................................ 69 Sinus rhythm- Biatrial RFA versus CS.......................................................................................... 70 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 Sinus rhythm- Left atrial RFA versus CS ..................................................................................... 70 Sinus rhythm- RFA versus Maze-III............................................................................................. 71 Sinus rhythm- Biatrial versus left atrial RFA ............................................................................... 71 Sinus rhythm- Biatrial RFA Case Series ....................................................................................... 72 Sinus rhythm- Left atrial RFA Case Series................................................................................... 73 Sinus rhythm- Left atrial MWA versus CS RCT......................................................................... 74 Sinus rhythm- Left atrial MWA versus CS................................................................................... 74 Sinus rhythm- MWA Comparison of two lesion sets ................................................................ 74 Sinus rhythm- Biatrial MWA Case Series..................................................................................... 74 Sinus rhythm- Left atrial MWA Case Series ................................................................................ 75 Sinus rhythm- MWA versus RFA.................................................................................................. 75 Atrial fibrillation- Biatrial CA+CS versus CS .............................................................................. 77 Atrial fibrillation- Left atrial CA+CS versus CS.......................................................................... 78 Atrial fibrillation- CA versus Maze-III ......................................................................................... 78 Atrial fibrillation- Kosakai maze versus CA ................................................................................ 79 Atrial fibrillation- Biatrial versus left atrial CA............................................................................ 79 Atrial fibrillation- Biatrial CA Case Series .................................................................................... 80 Atrial fibrillation- Left atrial CA Case Series ............................................................................... 80 Atrial fibrillation- Biatrial RFA+MVS versus MVS RCT.......................................................... 81 Atrial fibrillation- Biatrial RFA versus CS ................................................................................... 81 Atrial fibrillation- Left atrial RFA versus CS ............................................................................... 82 Atrial fibrillation- Biatrial versus left atrial RFA ........................................................................ 82 Atrial fibrillation- Biatrial RFA Case Series ................................................................................. 83 Atrial fibrillation- Left atrial RFA Case Series............................................................................. 84 Atrial fibrillation- Left atrial MWA versus CS RCT .................................................................. 84 Atrial fibrillation- Left atrial MWA versus CS............................................................................. 85 Atrial fibrillation- Biatrial MWA Case Series .............................................................................. 85 Atrial fibrillation- Left atrial MWA Case Series .......................................................................... 85 Atrial fibrillation- MWA versus RFA............................................................................................ 86 Junctional rhythm- Biatrial CA+CS versus CS............................................................................ 88 Junctional rhythm- Left atrial CA+CS versus CS....................................................................... 88 Junctional rhythm- CA versus Maze-III....................................................................................... 88 Junctional rhythm- Biatrial versus left atrial CA ....................................................................... 89 Junctional rhythm- Biatrial CA Case Series ................................................................................. 89 Junctional rhythm- Left atrial RFA versus CS............................................................................. 89 Junctional rhythm- Biatrial RFA Case Series............................................................................... 90 Junctional rhythm- Left atrial RFA Case Series ......................................................................... 90 Junctional rhythm- MWA versus RFA ......................................................................................... 91 Atrial flutter- Biatrial CA+CS versus CS...................................................................................... 91 Atrial flutter- CA versus Maze-III................................................................................................. 92 Atrial flutter- Biatrial CA Case Series .......................................................................................... 92 Atrial flutter- Left atrial CA Case Series....................................................................................... 92 Atrial flutter- Left atrial RFA versus CS....................................................................................... 93 Atrial flutter- Biatrial versus left atrial RFA................................................................................. 93 Atrial flutter- Biatrial RFA Case Series ......................................................................................... 94 Atrial flutter- Left atrial RFA Case Series .................................................................................... 94 Atrial flutter- Left atrial MWA Case Series .................................................................................. 95 Atrial flutter- MWA versus RFA ................................................................................................... 95 Atrial contraction- CA versus Maze-III ....................................................................................... 97 Atrial contraction- Biatrial CA Case Series .................................................................................. 97 Atrial contraction- Left atrial CA Case Series.............................................................................. 98 Atrial contraction- Biatrial RFA+MVS versus MVS RCT ........................................................ 98 Atrial contraction- Biatrial RFA versus CS .................................................................................. 99 Atrial contraction- Left atrial RFA versus CS ............................................................................. 99 Atrial contraction- Biatrial RFA versus Maze-III ....................................................................... 99 Atrial contraction- Biatrial versus left atrial RFA ..................................................................... 100 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 Atrial contraction- Biatrial RFA Case Series.............................................................................. 100 Atrial contraction- Left atrial RFA Case Series ......................................................................... 101 Atrial contraction- Left atrial MWA versus CS ........................................................................ 101 Atrial contraction- MWA1 versus MWA2 ................................................................................. 102 Atrial contraction- Left atrial MWA Case Series ..................................................................... 102 A/E ratio- CA versus Maze-III ................................................................................................... 106 A/E ratio- Right atrial CA Case Series....................................................................................... 106 A/E ratio- Left atrial CA Case Series ......................................................................................... 106 A/E ratio- Biatrial RFA Case Series ........................................................................................... 107 A/E ratio- Left atrial RFA Case Series....................................................................................... 107 Atrial filling fraction- Biatrial CA Case Series ........................................................................... 107 Atrial filling fraction- Biatrial RFA versus CS ........................................................................... 108 Atrial filling fraction- Biatrial RFA Case Series......................................................................... 108 Atrial filling fraction- Left atrial MWA Case Series.................................................................. 108 Peak A-wave velocity- CA versus Maze-III............................................................................... 109 Peak A-wave velocity- Biatrial CA Case Series.......................................................................... 109 Peak A-wave velocity- Biatrial CA Case Series.......................................................................... 110 Peak A-wave velocity- Biatrial RFA Case Series ....................................................................... 110 Peak A-wave velocity- Left atrial RFA Case Series .................................................................. 110 Pacemakers- Biatrial CA+CS versus CS..................................................................................... 111 Pacemakers- Left atrial CA+CS versus CS ................................................................................ 112 Pacemakers- CA versus Maze-III................................................................................................ 112 Pacemakers- Kosakai maze versus CA ....................................................................................... 112 Pacemakers- Biatrial versus left atrial CA .................................................................................. 113 Pacemaker- Biatrial CA Case Series ............................................................................................ 113 Pacemaker- Left atrial CA Case Series........................................................................................ 114 Pacemaker- Biatrial RFA versus CS RCT .................................................................................. 114 Pacemaker- Biatrial RFA versus CS ............................................................................................ 114 Pacemaker- RFA versus Maze-III ............................................................................................... 115 Pacemaker- Biatrial versus left atrial RFA.................................................................................. 115 Pacemaker- Biatrial RFA Case Series.......................................................................................... 116 Pacemaker- Left atrial RFA Case Series ..................................................................................... 116 Pacemaker- Left atrial MWA versus CS ..................................................................................... 117 Pacemaker- Biatrial MWA Case Series ....................................................................................... 117 Pacemaker- Left atrial MWA Case Series................................................................................... 117 Pacemaker- MWA versus RFA.................................................................................................... 118 Catheter ablation- Left atrial CA+CS versus CS....................................................................... 120 Catheter ablation- Left atrial CA Case series ............................................................................. 121 Catheter ablation- Biatrial RFA Case Series............................................................................... 122 Catheter ablation- Left atrial RFA Case Series.......................................................................... 123 Catheter ablation- Left atrial MWA Case Series ....................................................................... 123 Electrical cardioversion- Biatrial CA+CS versus CS .............................................................. 124 Electrical cardioversion- Left atrial CA+CS versus CS .......................................................... 124 Electrical cardioversion- Biatrial CA Case Series...................................................................... 124 Electrical cardioversion- Left atrial CA Case Series ................................................................. 125 Electrical cardioversion- Left atrial RFA versus CS ................................................................. 125 Electrical cardioversion- Biatrial versus left atrial RFA ........................................................... 125 Electrical cardioversion- Biatrial RFA Case Series ................................................................... 126 Electrical cardioversion- Left atrial RFA Case Series............................................................... 126 Electrical cardioversion- Left atrial MWA versus CS RCT..................................................... 127 Electrical cardioversion- Left atrial MWA Case Series ............................................................ 127 Antiarrhythmic drugs- Biatrial CA+CS versus CS .................................................................. 128 Antiarrhythmic drugs- Left atrial CA+CS versus CS .............................................................. 128 Antiarrhythmic drugs- CA versus Maze-III .............................................................................. 129 Antiarrhythmic drugs- Biatrial versus left atrial CA ................................................................ 129 Antiarrhythmic drugs- Biatrial CA Case Series ......................................................................... 129 224 225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 263 264 265 266 267 268 279 270 271 272 273 274 275 276 277 278 279 280 Antiarrhythmic drugs- Left atrial CA Case Series..................................................................... 130 Antiarrhythmic drugs- Left atrial RFA versus CS..................................................................... 130 Antiarrhythmic drugs- Biatrial RFA versus Maze-III .............................................................. 130 Antiarrhythmic drugs- RFA versus cardioversion .................................................................... 131 Antiarrhythmic drugs- Biatrial RFA Case Series....................................................................... 131 Antiarrhythmic drugs- Left atrial RFA Case Series .................................................................. 132 Antiarrhythmic drugs- Left atrial MWA versus CS RCT ........................................................ 132 Antiarrhythmic drugs- Left atrial MWA versus CS .................................................................. 133 Antiarrhythmic drugs- Left atrial MWA Case Series................................................................ 133 Anticoagulant- Biatrial CA+CS versus CS ................................................................................ 134 Anticoagulant- Biatrial CA versus Maze-III ............................................................................. 134 Anticoagulant- Left atrial CA Case Series .................................................................................. 134 Anticoagulant- Left atrial RFA versus CS.................................................................................. 135 Anticoagulant- RFA versus Maze-III ......................................................................................... 135 Anticoagulant- Biatrial RFA Case Series .................................................................................... 135 CPB and cross clamping- Biatrial CA+CS versus CS .............................................................. 136 CPB and cross clamping- Left atrial CA+CS versus CS.......................................................... 136 CPB and cross clamping times- CA versus Maze-III............................................................... 137 CPB and cross clamping times- Kosakai maze versus CA...................................................... 137 CPB and cross clamping times- Kosakai-RAA versus Kosakai+RAA ................................. 137 CPB and cross clamping times- Biatrial versus left atrial CA ................................................. 138 CPB and cross clamping times- Biatrial CA Case Series ......................................................... 138 CPB and cross clamping times- Left atrial CA Case Series..................................................... 138 CPB and cross clamping times- Biatrial RFA+MVS versus MVS RCT ............................... 139 CPB and cross clamping times- Biatrial RFA versus CS ......................................................... 139 CPB and cross clamping times- Left atrial RFA+CS versus CS ............................................ 140 CPB and cross clamping times- RFA versus Maze-III ............................................................ 140 CPB and cross clamping times- Biatrial versus left atrial RFA............................................... 140 CPB and cross clamping times- Biatrial RFA Case Series....................................................... 141 CPB and cross clamping times- Left atrial RFA Case Series .................................................. 141 CPB and cross clamping times- Left atrial MWA+CS versus CS RCT ................................ 141 CPB and cross clamping times- Biatrial MWA Case Series .................................................... 142 CPB and cross clamping times- Left atrial MWA Case Series................................................ 142 CPB and cross clamping times- MWA versus RFA ................................................................. 142 Ablation times- Left atrial CA Case Series................................................................................. 147 Ablation times- Biatrial versus left atrial RFA........................................................................... 147 Ablation times- Biatrial RFA Case Series................................................................................... 148 Ablation times- Left atrial RFA Case Series .............................................................................. 148 Ablation times- Left atrial MWA Case Series............................................................................ 149 Ablation times- MWA versus RFA ............................................................................................. 149 Hospital stay- Biatrial CA+CS versus CS................................................................................... 150 Hospital stay- Left atrial CA+CS versus CS .............................................................................. 150 ICU stay- Biatrial CA Case Series................................................................................................ 150 Hospital stay- Left atrial CA Case Series.................................................................................... 150 Hospital and ICU stay- Biatrial RFA versus CS........................................................................ 151 Hospital stay- Left atrial RFA versus CS.................................................................................... 151 ICU stay- RFA versus Maze-III................................................................................................... 151 Hospital stay- Biatrial RFA Case Series...................................................................................... 152 Hospital and ICU stay- Left atrial RFA Case Series................................................................. 152 Hospital stay- MWA versus CS RCT.......................................................................................... 152 Hospital and ICU stay- MWA versus RFA................................................................................ 152 Re-operation- Biatrial CA+CS versus CS ................................................................................. 153 Re-operation- Left atrial CA+CS versus CS ............................................................................. 153 Re-operation- CA versus Maze-III ............................................................................................ 153 Re-operation- Biatrial versus right atrial CA.............................................................................. 153 Re-operation- Biatrial CA Case Series ........................................................................................ 154 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 Re-operation- Left atrial CA Case Series.................................................................................... 154 Reoperation- RFA+MVS versus MVS ....................................................................................... 154 Reoperation- Biatrial RFA versus CS ........................................................................................ 155 Re-operation- Left atrial RFA versus CS ................................................................................... 155 Re-operation- Biatrial versus left atrial RFA.............................................................................. 155 Reoperation- Biatrial RFA Case Series ....................................................................................... 156 Reoperation- Left atrial RFA Case Series ................................................................................. 156 Re-operation- Left atrial MWA.................................................................................................... 157 Re-operation- MWA versus RFA................................................................................................ 157 Major efficacy outcomes – Non-randomised comparative CA studies................................. 159 Major efficacy outcomes from RFA studies .............................................................................. 160 Major efficacy outcomes from MWA studies............................................................................ 161 Major safety outcomes – Non-randomised comparative CA studies.................................... 162 Major safety outcomes from RFA studies ................................................................................. 163 Major safety outcomes from MWA studies............................................................................... 163 List of 1 2 3 4 5 6 7 8 9 Figures Diagrammatic representation of Maze-III.........................................................................5 Median proportion of mortality....................................................................................... 39 Median proportion of patients in SR ............................................................................................ 76 Median proportion of patients in AF............................................................................................ 87 Median proportion of patients with right atrial contraction ................................................... 103 Median proportion of patients with left atrial contraction...................................................... 105 Median proportion of patients requiring a pacemaker............................................................. 119 Cardiopulmonary bypass times .................................................................................................... 144 Cross clamping times..................................................................................................................... 146 List of Appendices A Hierarchy of Evidence................................................................................................................... 180 B Exclusions ....................................................................................................................................... 181 C Study Profile and Data Extraction Tables C.1 Cryotherapy ablation....................................................................................................... 190 C.2 Radiofrequency ablation................................................................................................. 229 C.3 Microwave ablation ......................................................................................................... 276 C.4 Laser ablation ................................................................................................................... 285 C.5 Microwave versus radiofrequency ablation ................................................................. 286 D Safety and Efficacy Tables D.1 Safety- Cryotherapy ablation ......................................................................................... 288 D.2 Safety- Radiofrequency ablation.................................................................................... 298 D.3 Safety- Microwave ablation............................................................................................ 309 D.4 Safety- Laser ablation...................................................................................................... 313 D.5 Safety- Microwave versus radiofrequency ablation.................................................... 314 D.6 Efficacy- Cryotherapy ablation...................................................................................... 315 D.7 Efficacy- Radiofrequency ablation................................................................................ 339 D.8 Efficacy- Microwave ablation........................................................................................ 365 D.9 Efficacy- Laser ablation.................................................................................................. 371 D.10 Efficacy-Microwave versus radiofrequency ablation ................................................. 372 D.11 Efficacy- Exercise testing............................................................................................... 374 D.12 Safety- Case reports......................................................................................................... 375 E E.1 Methods of measurement of atrial contraction .......................................................... 378 E.2 Use of antiarrhythmic medication ................................................................................ 380 E.3 Conditions for discontinuation of anticoagulant therapy ......................................... 382 E.4 Analysis of risk factors for recurrence of AF ............................................................. 384 Executive Summary Objective The aim of this review was to assess the safety and efficacy of intraoperative surgical ablation techniques for the treatment of atrial fibrillation (AF) compared to other surgical procedures, including cardiac surgery (CS) alone, or the Maze-III procedure, the current gold standard surgical treatment for AF. Methods Search strategy — Studies were identified by searching MEDLINE®, EMBASE, The Cochrane Library, Science Citation Index, PubMed, Clinical Trials Database (US), NHS Centre for Research and Dissemination, NHS Health Technology Assessment (UK), National Research Register (UK), National Institute of Health (US) and Meta Register of Controlled Trials, from inception to January 13, 2004. In addition, online abstracts for relevant conferences were searched, and additional articles identified through the reference sections of the retrieved studies. Studies using the Maze-III procedure were identified for benchmark data, including randomised controlled trials (RCTs) and nonrandomised comparative studies where the comparator was not intraoperative ablation, and case series. Study selection — RCT, non-randomised comparative studies and case series were included in which intraoperative ablation, using any of the available energy sources (cryotherapy, radiofrequency, microwave, laser) and any standardised lesion pattern (left and/or right atrial), were performed. Patients were over 18 years of age with AF (paroxysmal, persistent or permanent); operations were via median sternotomy, with cardiopulmonary bypass (CPB). Case reports of major complications were also used. Patient safety outcomes included: blood loss, stroke, other thromboembolisms; wound infection, pulmonary insufficiency, low cardiac output, renal failure, oesophageal injury, circumflex artery injury and mortality. Efficacy outcomes included: heart rhythm, atrial function, pacemaker requirement, electrical cardioversion, operation, CPB and cross clamping time, hospital stay, reoperation, reintervention for catheter ablation, and continued antiarrhythmic and anticoagulant requirements. Data collection and analysis — Data from the included studies were extracted by the ASERNIP-S Researcher using standardised data extraction tables developed a priori and checked by a second researcher. Relative risks (RR) for dichotomous outcome measures with 95% confidence intervals (CI) were calculated for some outcomes in individual i RCTs where it helped the interpretation of results. For non-randomised studies, median values were calculated for sets of comparable interventions. Results A total of 69 studies using intraoperative ablation were identified, plus 15 studies with Maze-III surgery as a benchmark. There were 30 studies using cryotherapy ablation (CA): 14 non-randomised comparative studies (four CA versus CS, five CA versus Maze-III, four studies with internal comparisons and one questionnaire study) and 16 case series. A total of 29 studies used radiofrequency ablation (RFA): one RCT comparing biatrial RFA versus CS, nine non-randomised comparative studies (five RFA versus CS, one RFA versus cardioversion, one RFA versus Maze-III and two biatrial versus left atrial RFA) and 19 case series. One RCT compared left atrial microwave ablation (MWA) versus CS, two non-randomised comparative studies compared left atrial MWA versus CS, and five case series used MWA. Finally, one case series used laser ablation and one nonrandomised comparative study compared RFA versus MWA. No studies comparing intraoperative ablation with medical management were located. Evidence was mostly limited by the many variations of energy sources and ablation patterns used in the included studies. The primary efficacy outcome was conversion to normal sinus rhythm (SR), which was greater with CA, RFA and MWA versus CS alone. In the RCTs, the relative risk (RR) of patients being in SR at 12 months follow-up after RFA compared with MV surgery alone was 3.82 (95% CI: 1.35 to 10.81, p=0.01) in Khargi et al. (2001), while at three months follow-up in Schuetz et al. (2003) the RR was 3.24 (95% CI: 1.09 to 9.65, p=0.03). Conversion to SR was at least 68% for all the different energy sources and lesion sets. There were no consistent differences in efficacy between CA versus Maze-III, and insufficient evidence for this comparison using other energy sources. In the one study comparing different energy sources, there were no significant differences in efficacy between RFA versus MWA. Addition of ablation significantly increased CPB and cross clamping times versus CS alone. Left atrial versus biatrial CA or RFA generally appeared to decrease CPB and cross clamping times without influencing efficacy. Atrial function results were difficult to interpret due to the varying criteria used to assess effective atrial contraction. There were no consistent differences in mortality when ablation was compared to CS or Maze-III surgery, and there did not appear to be any greater risk of bleeding with CA or RFA versus CS. Not enough evidence was presented to make any conclusions about stroke incidence. Small numbers of oesophageal perforation and circumflex artery stenosis, both of which may be lethal, were reported, mostly in case reports. All of the oesophageal perforations were associated with unipolar non-irrigated RFA. ii Conclusion and recommendations On the basis of the evidence presented in this systematic review, The ASERNIP-S Review Group agreed on the following classifications and recommendations concerning the safety and efficacy of intraoperative ablation for the treatment of AF: Classification Evidence rating- The available evidence was assessed as being poor. Safety- There was insufficient evidence to determine if intraoperative ablation was more or less safe than cardiac surgery alone, or the Maze-III procedure. Associated risks relating to longer bypass times, plus the possibility of oesophageal perforation and circumflex artery injuries, are potential concerns. There were no studies comparing intraoperative ablation with medical management of AF, therefore safety could not be evaluated. Efficacy- Intraoperative ablation is at least as efficacious as cardiac surgery alone, or the Maze-III procedure. There were no studies comparing intraoperative ablation with medical management of AF, therefore efficacy could not be evaluated. ASERNIP-S Recommendations A randomised controlled trial of intraoperative ablation should be performed, designed and powered sufficiently to measure long term survival and stroke rate. The comparator would be cardiac surgery alone. Surgeons performing intraoperative ablation for the treatment of AF should also participate in a national audit. Important note The information contained in this report is a distillation of the best available evidence located at the time the searches were completed as stated in the protocol. Please consult with your medical practitioner if you have further questions relating to the information provided, as the clinical context may vary from patient to patient. iii The ASERNIP-S Classification System Evidence Rating The evidence for ASERNIP-S systematic reviews is classified as Good, Average or Poor, based on the quality and availability of this evidence. High quality evidence is defined here as having a low risk of bias and no other significant flaws. While high quality randomised controlled trials are regarded as the best kind of evidence for comparing interventions, it may not be practical or ethical to undertake them for some surgical procedures, or the relevant randomised controlled trials may not yet have been carried out. This means that it may not be possible for the evidence on some procedures to be classified as good. Good Most of the evidence is from a high quality systematic review of all relevant randomised trials or from at least one high quality randomised controlled trial of sufficient power. The component studies should show consistent results, the differences between the interventions being compared should be large enough to be important, and the results should be precise with minimal uncertainty. Average Most of the evidence is from high quality quasi-randomised controlled trials, or from nonrandomised comparative studies without significant flaws, such as large losses to followup and obvious baseline differences between the comparison groups. There is a greater risk of bias, confounding and chance relationships compared to high-quality randomised controlled trials, but there is still a moderate probability that the relationships are causal. An inconclusive systematic review based on small randomised controlled trials that lack the power to detect a difference between interventions and randomised controlled trials of moderate or uncertain quality may attract a rating of average. Poor Most of the evidence is from case series, or studies of the above designs with significant flaws or a high risk of bias. A poor rating may also be given if there is insufficient evidence. iv Safety and Efficacy Classification SAFETY * • At least as safe compared to comparator procedure(s) This grading is based on the systematic review showing that the new intervention is at least as safe as the comparator. • Safety cannot be determined This grading is given if the evidence is insufficient to determine the safety of the new intervention. • Less safe compared to comparator* procedure(s) This grading is based on the systematic review showing that the new intervention is not as safe as the comparator. EFFICACY * • At least as efficacious compared to comparator procedure(s) This grading is based on the systematic review showing that the new intervention is at least as efficacious as the comparator. • Efficacy cannot be determined This grading is given if the evidence is insufficient to determine the efficacy of the new intervention. • Less efficacious compared to comparator* procedure(s) This grading is based on the systematic review showing that the new intervention is not as efficacious as the comparator. RESEARCH RECOMMENDATIONS It may be recommended that an audit or a controlled (ideally randomised) clinical trial be undertaken in order to strengthen the evidence base. CLINICAL RECOMMENDATIONS Additional recommendations for use of the new intervention in clinical practice may be provided to ensure appropriate use of the procedure by sufficiently qualified/experienced centres and on specific patient types (where appropriate). * A comparator may be the current ”gold standard” procedure, an alternative procedure, a nonsurgical procedure or no treatment (natural history). v Review Group Membership Protocol Surgeon Mr James Edwards Department of Cardiothoracic Surgery Royal Adelaide Hospital North Terrace Adelaide SA 5000 Advisory Surgeon Mr Hugh Paterson Department of Cardiothoracic Surgery Westmead Hospital PO Box 533 Wentworthville NSW 2145 Surgeon from Another Specialty Mr Russell Stitz Unit 24/2nd Floor Wesley Medical Centre 40 Chasely Street Auchenflower Qld 4066 Invited Member Professor John Horowitz Department of Cardiology The Queen Elizabeth Hospital 28 Woodville Rd Woodville South SA 5011 ASERNIP-S Surgical Director Professor Guy Maddern ASERNIP-S Royal Australasian College of Surgeons PO Box 553 Stepney SA 5069 ASERNIP-S Researchers Dr Susan Hazel Ms Rebecca Morgan Dr Marie Andrew vi 1.0 OBJECTIVE The primary objective was to assess the safety and efficacy of intraoperative ablation techniques for the treatment of atrial fibrillation. Intraoperative ablation was compared to other surgical therapeutic techniques or medical management, on the basis of a systematic assessment of the literature. Energy sources included radiofrequency, microwave, cryotherapy, laser and ultrasound. Comparative surgical techniques included the Maze III procedure, isolated cardiac surgery, and medical management. 2.0 INTRODUCTION 2.1 Pathogenesis of atrial fibrillation Atrial fibrillation (AF) is the most common form of cardiac arrhythmia, affecting the atria (upper chambers) of the heart. Electrical impulses are usually transmitted uniformly to all parts of the atria, but in AF the excitation and recovery of the atria are chaotic. As a result the atria ‘fibrillate’ instead of undergoing effective contraction. Atrial fibrillation is associated with three serious sequelae: 1) an irregular heartbeat, causing patient discomfort and anxiety, 2) loss of synchronous contraction decreases efficient heart pump action, resulting in varying levels of congestive heart failure, and 3) sluggish blood flow in the left atrium, which increases the likelihood of thromboembolism. Standardised nomenclature exists for classifying AF. If a patient has two or more episodes of AF it is considered recurrent, and may be subclassified as paroxysmal, persistent, or permanent (Levy et al. 2003). Paroxysmal AF can last for up to seven days (more typically less than 48 hours), and reverts spontaneously to SR. Persistent AF continues for more than seven days, does not terminate spontaneously, but can be converted to SR by pharmacologic or electrical cardioversion. Permanent AF occurs when the AF does not spontaneously revert to SR, and interventions to try to convert to SR are ineffective, or not attempted. For every decade of age, the incidence of AF doubles, from an incidence of 0.5% at 50 to 59 years of age to almost 9% at 80 to 89 years (Kannel et al. 1998). Based on almost four decades of Framingham Study data, the prevalence of AF is also increasing. In this study, data have been prospectively collected since 1948 from 5209 residents of Framingham, Massachusetts, USA (Benjamin et al. 1998). There were 3.2% of men aged 65 to 84 years with AF in 1968-70, which had increased to 9.1% by 1987 to 1989 (Kannel et al. 1998). Men have a greater risk of developing AF than women, even after adjustment for age and other predisposing conditions. Hypertension and diabetes are significant independent predictors of AF, while risk of AF is greater in patients with heart failure, valvular heart disease, and myocardial infarction. Atrial fibrillation is an independent predictor of mortality (Maisel and Stevenson, 2003; Wyse et al. 2001), and is associated with a 1.5-fold to 2-fold increase in total and cardiovascular mortality (Benjamin et al. 1998; Kannel et al. 1998). Patients with AF are also at a higher risk of having a stroke. It has been estimated that as many as 15% of all strokes in the US may be related to AF (Rockson and Albers 2004). Additionally, when AF is present following cardiac surgery, it is a major determinant of postoperative stroke (Lahtinen et al. 2004). 1 Although there is frequently a co-existence of AF and heart failure, valvular heart disease, and myocardial infarction, surgical treatment of these conditions does not always cure the AF. For example, in 100 consecutive AF patients having mitral valve surgery, only 26% spontaneously reverted to SR (Kalil et al. 1999). Furthermore, AF is not an innocent bystander in patients having cardiac surgery for other reasons, as the presence of preoperative AF in patients who underwent CABG was found to be both a marker for the high-risk patients, and also in itself significantly reduced long-term survival (Quader et al. 2004). The pathophysiology of AF has been extensively studied, but the complex nature of the arrhythmia means many factors remain unknown. Normally contraction of the heart is controlled by electrical signals, originating from the sinus node (natural heart pacemaker) in the upper right atrium. The electrical signal follows natural electrical pathways through the atria, causing them to contract, and passes to the ventricles through the atrioventricular node. However, in AF the electrical circuits in the atria become uncoordinated and chaotic. Permanent AF does not require a stimulus to continue, as the atria are always fibrillating. By contrast when AF is in the early stages or is intermittent (paroxysmal), there may be discrete areas of arrhythmia origin. With improvements in the methods used to measure the electrical activity of the heart, these areas can now be mapped. Haissaguerre et al. (1998) demonstrated that AF often originates from a site within the orifice of one or more of the pulmonary veins. Despite this at least 10% of patients with intermittent AF have a triggering mechanism that does not involve the pulmonary veins (Haisaguerre et al. 1998; Schmitt et al. 2004), and even if the pulmonary veins are ablated, other arrhythmic foci can be unmasked. One of the problems with chronic AF is that the changes in atrial electrophysiology produced by AF, in turn make the atria more vulnerable to AF (Wijffels et al. 1995). During permanent AF, the electrical circuits sustain themselves, with changes in the atria including electrical and anatomical remodelling, such as atrial enlargement (size and thickness) and stretching (Allessie 1999). 2.2 Conventional therapies The following procedures are used in the treatment of AF: 2.2.1 Medical management of atrial fibrillation (AF) Rate or rhythm control The medical management of AF focuses on control of either heart rate, or heart rhythm. Recently a randomised, multicentre comparison of rate versus rhythm control study was completed, called the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial. In a total of over 4000 patients, management with rhythm control offered no survival advantage over rate control, and may have a higher risk of adverse drug effects (Wyse et al. 2002). It will be interesting to evaluate the longer-term effect of these findings on the medical management of patients with AF. The antiarrhythmic drugs that are used in patients with AF have been classified into the following groups: Class I: block the sodium channel e.g. lidocaine, quinidine, procainamide. Class II: act indirectly on electrophysiological parameters by blocking beta-adrenergic receptors e.g. propanolol, metoprolol Class III: act by poorly understood mechanisms. These drugs prolong repolarisation, or increase the refractory period (time the heart cannot respond to another electrical signal) in the heart, with little effect on the rate of depolarisation. e.g. amiodarone, sotalol. They are the 2 most frequently used antiarrhythmic drugs for the treatment of AF in patients with heart failure (Wolbrette 2003). Class IV: relatively selective AV nodal calcium-channel blockers, e.g. verapamil. Miscellaneous group: e.g. digoxin, adenosine. Antiarrhythmics drugs are associated with significant side effects, for example amiodarone is associated with corneal microdeposits, gastrointestinal changes, and skin photosensitivity and discolouration (Martino et al. 2001). In addition, class III antiarrhythmic agents can have potentially life threatening pro-arrhythmic effects (Wolbrette 2003). Anticoagulant therapy Since AF significantly increases the risk of stroke and other thromboembolisms, patients with AF are routinely treated with long-term anticoagulation. The most commonly used anticoagulants are warfarin and aspirin, with newer agents including low-molecular weight heparin and thrombin inhibitors. A recent Cochrane Review of 14 studies concluded that warfarin, and aspirin to a lesser extent, help reduce the risk of stroke in patients with AF, although warfarin in particular carries an associated risk of haemorrhage (Segal et al. 2003). Specific blood coagulation levels (known as an international normalised ratio or INR) are necessary to significantly reduce both the incidence, and severity and risk of death from stroke (Hylek et al. 2003). However, anticoagulation is contraindicated in people who are at high risk for bleeding including patients : over 75 years of age; with over consumption of alcohol; with hypertension; and having a risk of bleeding for other reasons eg. liver failure (Fitzmaurice, Biann and Lip 2002). In patients with concomitant heart disease, medical management either 1) does not address the underlying heart disease, or 2) is contraindicated in the presence of structural heart disease, such as mitral stenosis, poor ventricular function, or a dilated left atrium. In addition, some patients are intolerant of the medication and/or the remaining physical symptoms associated with AF. 2.2.2 Electrical cardioversion and pacing of atrial fibrillation (AF) External electrical cardioversion under general anaesthesia is safe and effective as a treatment for AF, with success rates of 65% to 90% (Peters et al. 2002). Unfortunately longer term success rates are lower, with only 47% of patients with serial electrical cardioversion remaining in SR after a median follow-up of seven years (Crijns et al. 1996). Internal cardioversion under sedation, (percutaneous electrode catheters deliver synchronized lowenergy shocks between the right atrium and coronary sinus, or left pulmonary artery) can restore SR in up to 90% of patients when external cardioversion has failed (Schmitt et al. 1996). This type of internal cardioversion has also been developed for use as an implantable atrial defibrillator. Major limitations include frequent recurrences of arrhythmia, and patient intolerance to repeated painful cardioversion shocks (Geller et al. 2003). Atrial pacing can be effective for secondary prevention of AF in some patients, but there are no clear predictors of which patients will benefit the most from this therapy (Packer et al. 2003). Current studies have been limited by variations in the population studies, differences in pacing protocols, and a lack of uniform end points (Saliba 2003) and the use of pacing as a primary therapy for the prevention of recurrent AF have not been validated. 3 2.2.3 Catheter ablation of atrial fibrillation (AF) Percutaneous catheters can be used to deliver energy to focal areas of the heart. The energy sources most commonly used have been radiofrequency or cryotherapy. Mapping techniques are essential during the procedure, to diagnose the precise area of the heart initiating the arrhythmia. As many as 90% of patients with AF with one focus can be cured, while only 50% of patients with three or more foci will convert to normal SR (Peters et al. 2002). Complications of catheter ablation can include: systemic embolism, pulmonary vein stenosis, pericardial effusion, cardiac tamponade, and phrenic nerve paralysis (Fuster et al. 2001). Development of both the catheter-based energy sources, and mapping of the electrical activity of the heart, may expand the use of these techniques in the future. While catheter ablation is a curative approach, a last resort for patients with refractory AF is catheter ablation of the atrioventricular node (AV), a palliative approach. Ablation of the AV node means the patient will require a permanent pacemaker (Peters et al. 2002). Long-term survival does not appear to be significantly affected by the ablation of the AV node (Ozcan et al. 2001). Although it is associated with improved quality of life, particularly in the most symptomatic patients (Lee et al. 1998), this technique has obvious disadvantages. The patient has to rely on a pacemaker for life; and the atria continue to fibrillate, meaning the risk of stroke remains. 2.2.4 Surgical treatment of atrial fibrillation (AF) Cardiac Surgery In the majority of patients who have AF associated with an underlying heart disease, surgical correction of the heart disease will not result in conversion to normal SR. Therefore, surgical techniques designed to treat AF have been developed as an adjunct to the primary cardiac surgical procedure, although they may also be used in isolation. Maze Procedure The original surgical technique devised by James Cox was known as the Maze-I procedure (Cox 1991). The Maze-I procedure involved a maze-like pattern of surgical incisions in the right and left atria, acting as electrically insulating scars to prevent transmission of the arrhythmia. It was modified to become the Maze-II procedure due to late effects on the sinoatrial node affecting control of heart rate (i.e. chronotropic problems), and intra-atrial conduction delays resulting in reduced left atrial contraction. Changes to the incisions in the Maze-II meant exposure for the left atrial incisions was extremely difficult, and the Maze-II did not appear to correct all the problems associated with the Maze-I (Cox et al. 1995a). Therefore the Maze-III was developed, with two minor modifications of the Maze-II: a left atrial incision was moved posteriorly, and the atrial septotomy was also moved posteriorly. This resulted in significant technical and functional improvements, and the Maze-III became the gold standard for the surgical treatment of AF. 4 The incisions which make up the Maze-III procedure are outlined in Figure 1. There are incisions to both the right and left atria, and excision of the right and left atrial appendages. In addition, cryotherapy is used to ablate tissue at the: 1) tricuspid end of the T incision in the right atrial free wall, 2) level of the tricuspid annulus, 3) coronary sinus, and 4) end of the mitral valve incision. Figure 1: Diagrammatic representation of Maze-III. The mitral and tricuspid valves are lightly shaded; the incisions hatched; and circles represent the cryoablation sites. RAA: right atrial appendage; LAA: left atrial appendage In a total of 198 patients operated on using the Maze-III procedure, the Kaplan-Meier estimate of freedom from AF was 92% at 14 years follow-up in patients who had a lone procedure (n=112), and 97% at 10 years follow-up in patients who had a concomitant cardiac procedure (n=86) (Prasad et al. 2003). The risk of stroke was also significantly reduced: in 306 patients who had the maze procedure (all variants) between 1987 and 1999, only two perioperative strokes (0.7%) occurred, and in 265 patients followed up to 11.5 years after surgery, only one late minor stroke occurred (Cox et al. 1999). Since 19% of these patients had a thromboembolic event prior to the maze surgery, this result is even more impressive. 5 2.2.5 Maze-III challenges The Maze-III procedure has provided excellent clinical results, but in spite of this it has not been widely performed around the world. The major problems with the Maze-III procedure that have prevented greater uptake have been: 1) the high level of technical difficulty, 2) the increased bypass and cross-clamping times, and 3) the significant risk of bleeding from the numerous incisions in the atria. In an effort to make the surgery easier and to reduce operation times and the risk of bleeding, alternative energy sources have been developed to replace the surgical incisions of the MazeIII. 2.3 Intraoperative ablation techniques It has been recently suggested surgery for AF has reached a ‘tipping point’ (Martin et al. 2003) with the development of new technologies, and increased understanding of the pathophysiology of AF. The energy sources that have been developed for intraoperative ablation are as follows: Cryotherapy Ablation (CA) Cryotherapy ablation (CA) utilizes a probe to deliver a very cold substance to the tissue, causing rapid cooling to -60 oC. The lesions do not damage tissue collagen, hence preserving the myocardial architecture. This minimises thrombus formation, and the risk of perioperative bleeding and perforation of the atrial wall is lower than with a cut-and-sew technique. It is also easy for the surgeon to monitor lesion formation, as the spreading “iceball” is visible. A current limitation of cryoablation is the rigidity of the probes, reducing flexibility and ease of operation. A newer cryoprobe (SurgiFrost, CryoCath Technologies Inc, Quebec, Canada) uses inert argon gas as a refrigerant, and reaches temperatures as low as -144oC (Doll et al. 2004). The probe temperature is controlled by the flow and pressure of argon gas, and is adjustable by the surgeon. Radiofrequency Ablation (RFA) Radiofrequency energy destroys myocardial tissue by heating at the electrode-tissue interface, and creating a superficial ‘burn’. Radiofrequency energy can be used with either unipolar or bipolar probes. The RF catheters can also vary in whether they are saline-irrigated or dry probes. In saline-irrigated RFA the surface temperature is cooled and direct heating is directed below the surface, resulting in greater lesion depth and increased likelihood of a transmural lesion. The power (Watts), saline irrigation speed (mL per minute) electrode diameter, and application time are the main factors determining the total amount of delivered RF energy. With dry RFA there is a greater risk of surface charring, and a restricted depth of tissue penetration. Microwave Ablation (MWA) Microwave energy causes the vibration and rotation of the dipoles of water molecules, generating heat by friction. Microwave probes create a single linear line of tissue coagulation, and do not cause boiling, charring, smoking, or perforation (Williams et al. 2002). The energy can be transmitted through blood, desiccated tissue, and scars. Factors influencing the penetration depth of the microwave energy include: 1) dielectric properties of the tissue 2) frequency of the microwave energy, and 3) antenna design. Energy delivery times are typically less than one minute, and microwave energy may result in deeper lesions with more even penetration compared to radiofrequency energy. Microwave energy is considered safe to 6 use on the beating heart, as blood in vessels under the probe is moving too fast to be injured. However, experimental studies have shown that high width-depth ratios and incomplete transmural lesions can be a problem with microwave ablation (Viola et al. 2002). Microwave probes have also been relatively difficult to manipulate, although new more malleable probes are now being marketed (eg. Flex 4™, AFx Inc, Fremont, California). Laser Ablation Laser energy consists of high-energy optical waves delivered through an optical coupling fibre and a radiating fibre tip. Neodymium-yytrium-aluminium garnet (Nd:YAG) is the laser energy most commonly used. The biological effects of laser energy are caused by a combination of direct heating and mechanical damage, resulting from cellular explosions caused by shock waves (Viola et al. 2002). An advantage of laser energy is it allows the creation of sharp and narrow ablation lines, as the laser light penetrates the tissue directly and only heats tissue within the limits of the beam. Currently there is limited clinical experience with the use of laser ablation. 2.4 Summary Atrial fibrillation is the most common form of heart arrhythmia, and its incidence and cost to the community are increasing. A wide variety of medical and minimally invasive methods are currently used to treat patients with AF. Despite this, a number of patients remain refractory or intolerant to these treatments. Although AF commonly coexists with other heart diseases, surgical correction of the underlying disease also fails to prevent the arrhythmia in the majority of patients. The Maze-III procedure is a safe and effective surgical treatment for AF, but its uptake has been limited, mainly related to the high level of technical difficulty; increased operation times; and risk of blood loss. A number of alternative techniques, using ablative energy to replace surgical incisions, are increasingly being used. Even though these intraoperative ablation methods appear promising, the risks of procedural complications, and their long-term effectiveness in treating AF, remain unknown. The safety and efficacy of intraoperative ablation therapies in comparison to other surgical techniques, or the medical management of AF, needs to be assessed. 3.0 METHODS 3.1 Literature search protocol 3.1.1 Inclusion criteria Papers were selected for inclusion in this systematic review on the basis of the following criteria: Participants Human individuals aged over 18 years with atrial fibrillation. 7 New Intervention Included studies must concern the new intervention, defined as intraoperative ablation using cryotherapy, radiofrequency, microwave or laser energy, for the treatment of AF. They may use any of the commercially available probes, and any acceptable standardized lesion pattern. Operations should be performed by median sternotomy with cardiopulmonary bypass, but may be as a concomitant or lone procedure. Any procedures using video or robotic assistance were excluded. Lesion patterns were analysed separately according to whether they were in both atria (biatrial) versus only the left or right atrium. Comparative Intervention Included studies must concern the comparative interventions, defined as the surgical treatment (including isolated surgery or the Maze-III procedure), or medical management of AF. Outcomes The papers included contained information on at least one of the following outcomes of the new or comparative intervention. 1. Perioperative and postoperative mortality of patients 2. Perioperative and postoperative morbidity of patients which may include, but not be limited to: - Cardiac rhythm (AF, sinus rhythm, junctional rhythm, atrial flutter) - Atrial transport function - Requirement for anti-arrhythmic medication - Requirement for anticoagulant medication - Stroke or other thromboembolism - Bleeding - Wound infection - Oesophageal injury - Pulmonary insufficiency - Requirement for pacemaker 3. Perioperative and postoperative factors for patients which may include, but not be limited to: - Operation time - Length of ICU stay - Reoperation - Readmission 4. Convalescence of patients which may include, but not be limited to: - Postoperative care requirements - Length of hospital stay - Time until resumption of usual activities - Quality of life measures 5. Costs and resource use 8 Types of studies Randomised controlled trials, historical and/or non-randomised comparative studies, case series and case reports were included for review. Other study types were included if they were considered relevant and if valid reasons were given in the protocol. Where appropriate, additional relevant published material in the form of letters, conference material, commentaries, editorials and abstracts were included as background information. Language Restriction Searches were conducted without language restriction. Foreign language papers were subsequently excluded only if the findings supported those reported in well-designed studies published in the English language. 3.2 Literature search strategies Databases searched The databases searched are shown in Table 1. Table 1: Databases searched Database MEDLINE® MEDLINE® in process and other non-indexed citations EMBASE The Cochrane Library Science Citation Index PubMed Clinical Trials Database (US) NHS Centre for Research and Dissemination NHS Health Technology Assessment (UK) National Research Register (UK) Platform Ovid Ovid Edition Week 1 1984 to 13/1/04 1966 to 13/1/04 Ovid Web of Science NLM Gateway http://www.clinicaltrials.gov/ Week 1 1974 to 13/1/04 Week 1 1966 to Issue 1, 2004 30/9/03 30/9/03 Searched 13/1/04 http://www.york.ac.uk/inst/crd/ Searched 13/1/04 http://www.ncchta.org/ Searched 13/1/04 National Institute of Health (US) Meta Register of Controlled Trials http://www.nih.gov/ Searched 13/1/04 http://www.controlled-trials.com/ Searched 13/1/04 http://www.doh.gov.uk/research/n 2004, Issue 1 rr.htm 9 Search Terms The following search terms were used: Terms used for MEDLINE 1. radiofrequency or radio-frequency or radio frequency 2. microwave 3. cryo$ 4. laser ablat$ 5. ultrasound ablat$ or ultra-sound ablat$ or ultra sound ablat$ 6. RFA 7. ablat$ 8. atrial fibrillation (MeSH) or arrhythmia (MeSH) 9. tachycardia (MeSH) 10. 1 or 2 or 3 or 4 or 5 or 6 or 7 11. 8 or 10 12. 11 NOT 9 Terms used for MEDLINE® in process and other non-indexed citations 1. radiofrequency or radio-frequency or radio frequency 2. microwave 3. cryo$ 4. laser ablat$ 5. ultrasound ablat$ or ultra-sound ablat$ or ultra sound ablat$ 6. RFA 7. Ablat$ 8. Atrial fibrillation or AF or arrhythmia or arrhythmia 9. 1 or 2 or 3 or 4 or 5 or 6 or 7 10. 8 AND 9 Terms used for EMBASE 1. radiofrequency or radio-frequency or radio frequency 2. microwave 3. cryo$ 4. laser ablat$ 5. ultrasound ablat$ or ultra-sound ablat$ or ultra sound ablat$ 6. RFA 7. Ablat$ 8. Heart atrium fibrillation (EMTREE) 9. 1 or 2 or 3 or 4 or 5 or 6 or 7 10. 7 AND 8 Since few direct comparative studies were anticipated, we also searched for studies of MazeIII surgery (see Methods for further details). 10 Terms used for Maze-III surgery Terms used for MEDLINE 1. 2. 3. 4. 5. atrial fibrillation (MeSH) or arrhythmia (MeSH) tachycardia (MeSH) maze 1 or 2 3 AND 4 Terms used for MEDLINE® in process and other non-indexed citations 1. Atrial fibrillation or AF or arrhythmia or arrhythmia 2. maze 3. 1 AND 2 Terms used for EMBASE 1. Heart atrium fibrillation (EMTREE) 2. maze 3. 1 AND 2 Note: * is a truncation character that retrieves all possible suffix variations of the root word e.g. surg* retrieves surgery, surgical, surgeon, etc. In Cochrane the truncation character is *; in Current Contents, Embase and Medline (Ovid) it is $. # is a wildcard symbol that substitutes for one required character in Current Contents, Embase and Medline (Ovid). In addition, online abstracts for the Annual Meetings for the American Association for Thoracic Surgery (2002-3), American Heart Association (2003), The European Association for Cardio-thoracic Surgery (1999-2003), and NASPE (Heart Rhythm Society, 2001-3) were searched. The bibliographies of all publications retrieved were manually searched for relevant references that may have been missed during the database searches (pearling). 3.3 Literature database The number of articles retrieved for each search category is listed in Table 1. The ASERNIPS Researcher excluded articles that, on the basis of their abstract, clearly did not meet the inclusion criteria. 11 Table 2: Summary of the exclusion process for the methodological review papers retrieved from the literature databases Search Category Total Number Total Number Retrieved Available After Exclusions Intraoperative Ablation 4123 204 Maze III Procedure (+ Maze) 596 69 The foreign language papers retrieved were not translated unless, based on their abstract, they offered significantly different or more extensive results to those reported in the English language papers. Exclusions by ASERNIP-S Researcher Two hundred and four publications were found describing intraoperative ablation for the treatment of atrial fibrillation. Two reviewers independently applied the selection criteria to these studies, and excluded publications that did not meet the inclusion criteria. Relevant information contained in excluded papers was used to inform and expand the review discussion. These studies and the reason for their exclusion are detailed in Appendix B. Some of the reasons for exclusion included: • more than one type of surgical procedure was used, and the results not reported separately • the surgery was performed using minimally invasive techniques • outcomes were not relevant Inclusions by ASERNIP-S Researcher Following the final exclusion process there were 69 publications describing intraoperative ablation for the treatment of atrial fibrillation, and 15 publications describing the Maze-III procedure. A summary of the number of papers excluded is given in Table 3 below. Table 3: Summary of the final exclusion process for the systematic review papers, based on the full text article RCTs Non-RCTs Procedure Initial Initial Number Total Excluded Number Reviewed Intraoperative Ablation 2 204 135 69 Maze-III 69 54 15 Abbreviations: RCT – randomised controlled trial; Non-RCT – studies that were not randomised controlled trials, including case series 12 3.4 Assessment methods The levels of evidence were assessed according to the Hierarchy of Evidence, given in Appendix A. A meta-analysis was not performed because the studies were generally of poor evidence quality plus varied widely in outcome measures and study design. Relative risks (RR) for dichotomous outcome measures with 95% confidence intervals (CI) were calculated for some outcomes in individual RCTs where it helped the interpretation of results. For nonrandomised studies, median values were calculated for sets of comparable interventions. As few comparative studies with a Maze-III arm were anticipated, the included Maze-III studies were used to provide a benchmark, indirect comparison. The Maze-III studies had to follow the surgical procedure described by Cox (Cox et al. 1995a and b); where the Maze-I and –II were also performed and the results not given separately, the studies were excluded. 3.4.1 Outcome measures For this review, the question of safety was addressed in terms of whether intraoperative ablation was more or less likely to cause injury or harm to the patient, in comparison to cardiac surgery alone, the Cox Maze III procedure, or cardioversion. The safety outcomes were assessed in terms of perioperative outcomes, including: blood loss, stroke, transitory cerebral ischaemic attack, other thromboembolism, bleeding, wound infection, mediastinitis, pulmonary insufficiency, low cardiac output syndrome, renal failure, requirement for intra-aortic balloon pumping, oesophageal injury, and mortality. Any other reported outcome reflecting patient safety was also tabulated. In terms of efficacy, the question was whether intraoperative ablation produced equivalent clinical outcomes, in comparison to cardiac surgery, the Maze-III procedure, or cardioversion. The primary outcome was a return to normal heart rhythm. Cardiac outcomes (cardiac rhythm, atrial function, requirement for pacemaker, use of electrical cardioversion) were assessed both perioperatively and during longer term follow-up. In addition, perioperative surgical efficacy outcomes included: time on cardiopulmonary bypass, cross clamping time, ablation time, lengths of ICU and hospital stays, reoperation, and continued requirement for anticoagulant and antiarrhythmic medications. Other efficacy outcomes reported in the studies were also tabulated where relevant. 4. DESCRIPTION AND METHODOGICAL ANALYSIS OF STUDIES 4.1 Designation of levels of evidence and critical appraisal The evidence presented in the selected studies was classified according to the National Health and Medical Research Council (NHMRC) Hierarchy of Evidence (see Appendix A). Study quality was assessed using a number of parameters including: quality of study methodology reporting; methods of randomisation and allocation concealment (RCTs); blinding of patients or outcomes assessors; attempts made to minimise bias; sample sizes and the ability to measure ‘true effect’; losses to follow-up; applicability of results outside of the study sample; and statistical methods used to describe and evaluate the study data. 13 The included studies are shown in Tables 5 and 6 for CA, Tables 7 and 8 for RFA, and Tables 9 and 10 for the MWA. Some authors and/or centres have published a number of reports using intraoperative ablation to treat AF. These reports are likely to have a common pool of patients. Therefore, the most recent complete publication was used in the review. Where a report of an earlier subset of patients reported an outcome not stated in the later paper, this information was also used. Studies were also classified as to whether surgery was: • lone or concomitant, and • included the left and/or right atrium The final number of studies included with each energy source and according to the level of evidence is shown in Table 4 below: Table 4: Included studies according to level of evidence and energy source Energy source RCT Non-RCT Case Series Total Cryotherapy 0 14 16 30 Radiofrequency 1 9 19 29 Microwave 1 2 5 8 Laser 1 1 Radiofrequency 1 1 versus Microwave Total Included Studies 69 Study descriptions Study profiles for each included study are given in Appendix C. The studies were divided into groups depending on the energy source used for intraoperative ablation. Comparative studies within each energy source grouping were sub-grouped, according to the comparisons made. 4.1.1 Cryotherapy ablation Thirty studies were identified in which intraoperative CA was used to treat AF (see Table 5). Fourteen were comparative non-randomised studies, and sixteen were case series. There were three studies comparing biatrial CA versus cardiac surgery (Handa et al. 1999; Sueda et al. 1997; Yuda et al. 2004), one study comparing left atrial CA versus CS (Gaita et al. 2000), and five studies comparing biatrial CA versus Maze-III surgery (Ishii et al. 2001; Kim et al. 2001; Kosakai et al. 1995; Lee et al. 2001; Nishiyama et al. 2003). Another four studies made internal comparisons: one study with a Kosakai maze versus CA (Nakajima et al. 2002), one study with a Kosakai maze with removal versus retention of the right atrial appendage (Yoshihara et al. 2000), one study with biatrial versus left atrial CA (Takami et al. 1999), and one study with biatrial versus right atrial CA (Schaff et al. 2000). In addition, a questionnaire compared the Kosakai maze and Maze-III procedures (Kosakai 2000). 14 Non-randomised Comparative Studies Biatrial CA+CS versus CS Three comparative studies included patients after biatrial CA+CS versus CS alone. Two of these studies used concurrent controls, while in one study historical controls were used. Handa et al. (1999) included concurrent controls, with a retrospective review of data from clinical reports. Patients were consecutive, but the decision to add the CA maze was made depending on the surgeon, and related to the surgeon’s experience and the anticipated difficulty with the concurrent valve surgery. Later in the study with greater experience, the surgeon rarely decided against the CA maze on the basis of the concomitant surgery. Therefore, a selection bias was present whereby patients earlier in the study were likely to be those with more simple concurrent procedures. Indeed, there were no patients with previous cardiac operations in the CA+CS group, versus 14% (8/58) patients with previous surgery in the CS group (p=0.02), and less of the CA+CS versus CS patients had CABG (18% versus 36%, p=0.05). In Yuda et al. (2004), the CA patients were selected from a larger group (26/66, 39%), who had postoperative exercise testing more than three months after surgery. This group may not have been representative of the larger group. By definition they must also have survived surgery, so this study could not be used to assess perioperative mortality. Finally, only six patients were included in the control group, with small group size limiting the applicability of the results outside this group. Sueda et al. (1997) was a non-randomised study using historical controls, with the basis of patient selection not stated. All patients had mitral valve surgery, with additional aortic valve or tricuspid procedures included in some patients. Left atrial CA+CS versus CS Gaita et al. (2000) reported a retrospective study with concurrent controls. The control group consisted of consecutive patients with AF who refused the CA. Patients were well matched for age, duration of AF, and heart valve disease, indicating selection bias may have been less likely to affect the results. CA versus Maze-III One study with concurrent controls compared CA versus Maze-III. Nishiyama et al. (2003) is in abstract form, and study details were limited. Patients were consecutive, but it was not stated how they were selected. The only outcome reported was heart rhythm. Four studies with historical controls compared CA versus Maze-III. Kosakai et al. (1995) compared patients with two cryotherapy lesion sets (CA1 and Kosakai maze) versus Maze-III surgery. The two CA groups were consecutive and concurrent, however, the Maze-III patients were historical with a median operating date approximately one year earlier. Although the groups were matched for preoperative characteristics, such as age and left atrial diameter, there were a higher proportion of patients having redo operations in the Kosakai maze (30%, 21/70) versus the Maze-III (6%, 1/17) groups (p<0.05). In addition, a number of outcomes (eg. mortality, stroke) were expressed in the total patient group, and values for each separate group not stated. Therefore these data could not be used. Ishii et al. (2001) compared patients who had CA (Radial Incision Approach) versus the Maze-III. There was a large difference in follow-up length between the two groups, with a range of 34 to 52 months (mean 41.2 months) after Maze-III versus follow-up of more than one year in only 15/32 patients after CA. Therefore the two patient groups were being compared at different stages of follow-up, which could have influenced results. 15 Kim et al. (2001) also had the problem of a difference in follow-up between the two groups: a mean of 29 months after CA versus 47 months following Maze-III. However, all patients were followed for at least two years. There were differences between the CA and Maze-III patients in duration of pre-surgical AF: a mean of 91 months (SD 83 months) for CA patients versus 37 months (SD 41 months) for Maze-III patients (p=0.016). Other pre-operative characteristics were similar between the two groups. Lee et al. (2001) reported patients after CA versus Maze-III, using an historical Maze-III patient group. There were important differences in pre-operative characteristics between the groups: the gender mix was 19/34 (male/female) in the CA versus 18/12 in the Maze-III group (p=0.03). In addition, the left atrial dimension was significantly larger in the CA (mean 63 mm) versus the Maze-III (mean 58 mm) patients, and more of the CA versus Maze-III patients had a giant left atrium (diameter > 60mm). As a result, selection bias may have influenced outcomes. Internal Comparisons Kosakai maze versus CA One retrospective (Level III-3) study compared patients after a Kosakai maze versus CA (Nakajima et al. 2002). The Kosakai patients were all operated on before the CA patients, and 110 hospital survivors from each group selected for the study. There were 55% (110/199) of Kosakai patients selected versus 45% (110/244) of the CA patients. Selection criteria were not stated. Patients were paired according to age, duration of pre-surgical AF (> 10 years), preoperative left atrial dimension (>70 mm), history of previous cardiac surgery, and concomitant aortic valve surgery. Since only hospital survivors were used, the hospital mortality could not be compared between these groups. There were fewer Kosakai versus CA patients with a history of stroke (11% versus 22%, p=0.02), and coronary artery disease (2% versus 9%, p=0.03). Therefore selection bias could have influenced the outcomes. Performance bias may also have occurred as crystalloid cardioplegia was used early in the period when the Kosakai maze surgery was being performed, but tepid blood cardioplegia was used exclusively in the CA patients. Kosakai maze with removal or retention of the right atrial appendage (RAA) In Yoshihara et al. (2000) patients with removal of the RAA were operated on at least three years before the patients with retention of the RAA. However, consecutive patients were used in both groups. No significant differences in pre-operative characteristics between the two groups were reported. Biatrial versus left atrial CA One retrospective study with historical controls compared patients after biatrial versus left atrial CA. In Takami et al. (1999) it was not stated whether the patients were consecutive or not, or the basis of the patient selection. Patients with biatrial CA were operated on over one year before the left atrial CA patients. However, reported preoperative characteristics were not significantly different between the two groups. Biatrial versus right atrial CA One study compared biatrial versus right atrial CA, with overlap in the time of operation between the two groups. Schaff et al. (2000) did not report the basis of patient selection, follow-up period, or the number of patients lost to follow-up. Important pre-operative characteristics, such as duration of pre-surgical AF and pre-surgical left atrial size, were also 16 not stated. In addition safety outcomes were poorly reported, with only mortality and bleeding requiring re-operation reported. Table 5: Cryotherapy Ablation- Comparative non-randomised studies Study Level Intervention Lone Left atrium Right atrium Y Y Not stated Y 21/36 Not stated Y Y/N Not stated Y N Frigitronics 32 18 Y I Y I Y Y I Y I Y Y Y I Y I Y Y I Y I Y Y Frigitronics 32 13 23 18 14 70 17 53 30 9 11 Y Y Y Y CCS-200, Cooper Surgical 110 110 N N Y Y Y Y Not stated 20 22 N N Y Y Y N Not stated 30 20 50/173 N Y N Y Y Not stated 173 42 Non-randomised comparative studies- Biatrial CA versus CS Handa et al. III-2 CA + MVS N 1999 MVS Sueda et al. III-3 CA + MVS N 1997 MV Yuda et al. III-3 CA + MVS N 2004 MV Non-randomised comparative studies- Left atrial CA versus CS Gaita et al. III-2 CA + CS N 2000 CS Non-randomised comparative studies- CA versus Cox Maze III Ishii et al. 2001 III-3 CA + CS 3/32 Maze-III + CS Kim et al. 2001 III-3 CA N Maze-III N Kosakai et al. IIICA Initial Modification N 1995 2/3 Kosakai maze N Maze-III N Lee et al. 2001 III-3 CA + MVS+/- CS N Maze-III + MVS +/- CS N Nishiyama et al. III-2 CA + ASD N 2003 (abstract) Maze-III + ASD N Internal Comparisons Kosakai maze versus CA Nakajima et al. III-3 Kosakai maze N 2002 Cryoablation N Kosakai maze with removal or retention of RAA Yoshihara et al. III-3 CA Kosakai maze -RAA 2000 CA Kosakai maze +RAA Biatrial versus Left atrial CA Takami et al. III-3 Cryoablation Biatrial 1999 Cryoablation LA CA versus Right maze Schaff et al. IIICA Modified Maze 2000 2/3 CA Right Maze Questionnaire- Kosakai maze versus Maze-III Kosakai 2000 III-3 Kosakai maze Maze-III Device Not stated Not stated Frigitronics Cryoprobe 3cm length n 39 58 36 15 26 6 34/111 Y Y Not stated 1119 9 I I 835 13/835 CA: cryoablation; CS: cardiac surgery; MVS: mitral valve surgery; ASD: atrial septal defect; RAA: right atrial appendage; Y: yes; N: no; I: surgical incision Questionnaire- Kosakai maze versus Maze-III In Kosakai (2000) a questionnaire was sent to 517 Japanese hospitals performing cardiac surgery. Answers were returned from 288 (56%) of hospitals, reporting 2547 surgical treatments for either AF or atrial flutter. Results were included for a total of 1954 patients after the Kosakai maze (n=1119) or Maze-III (n=835) procedures, in the other patients the exact surgical procedure was uncertain. Patients were further divided into those having AF alone (lone), or AF associated with mitral valve disease, congenital heart disease, or no causeand-effect relationship between the reason for surgery and the AF. There is likely to have 17 been selection bias depending on the hospitals replying to the questionnaire. In addition, the operation procedures (cardioplegic solution, body temperature, medication) were not stated, and could have differed significantly between the hospitals. In the publication itself, discrepancies occurred between the numbers reported in the text and tables. Case Series The included cryotherapy case series are shown in Table 6. As case series are the lowest level of evidence available for assessing interventions, a full methodological critique of their study profiles will not be included. There were eight case series in which biatrial CA was applied, with two studies published in abstract form. In only two studies consecutive patients were used (Fukada et al. 1998; Izumoto et al. 2000). There were eight case series of left atrial CA patients, also with two in abstract form. Only one study reported the use of consecutive patients (Hoffmeister et al. 2003). Table 6: Cryotherapy Ablation Case Series Study Level Intervention Lone Left atrium Right atrium Device n Biatrial: Case Series Ad et al. 2003a IV CA + CS N Y Y Not stated 51 (abstract) Ad et al.2003b IV CA + CS 5/50 Y Y Not stated 50 (abstract) Arai et al.1999 IV KM + CS Y Y Not stated 30 Fukada et al.1998 IV CA + CS N Y Y Not stated 29 Izumoto et al.2000 IV CA + CS N Y Y Not stated 104 Morishita et al. 2000 IV CA +/- CS 2/12 Y Y 1.5 cm cryoprobe 12 Shimizu et al.1997 IV CA Y Y Y Not stated 6 Yuda et al.2001 IV CA + CS N Y Y Not stated 94 Left atrial: Case Series Hoffmeister et al. IV CA + CS N Y N Not stated 19 2003 (abstract) Imai et al.2001 IV CA + MVS ± CS N Y N T-shaped cryoprobe 32 Kondo et al.2003 IV CA + CS 2/31 Y N/I 31 Manasse et al.2003 IV CA + CS 1/95 Y N Frigitronics 95 Naito et al.2001 IV CA + MVS N Y N Not stated 30 (abstract) Sueda et al.2001 IV CA + MVS N Y N Not stated 12 Usui et al. 2002 IV CA + CS N Y N Not stated 41 Yamauchi et al.2002 IV CA + CS N Y N Not stated 40 CA: cryoablation; CS: cardiac surgery; KM: Kosakai maze; MVS: mitral valve surgery; N: no: Y: yes; I: surgical incision 4.1.2 Radiofrequency ablation Twenty-nine studies were identified in which intraoperative RFA was used to treat AF (see Table 7 and 8). There were one RCT, nine non-randomised comparative studies, and nineteen case series. The RCT and three non-randomised studies compared biatrial RFA versus CS alone (Khargi et al. 2002; Chen et al. 2001; Patwardhan et al. 1997; Riying et al. 1998); two studies compared left atrial RFA versus CS (Guang et al. 2002; Mantovan et al. 2003); one 18 study compared RFA versus cardioversion (Thomas et al. 2003); and one study compared RFA versus Maze-III surgery (Chiappini et al. 2004). In addition, internal comparisons were made between biatrial versus left atrial RFA (Güden et al. 2002; Deneke et al. 2002a). Randomised Controlled Trial Biatrial RFA versus CS Khargi et al. (2001) and Deneke et al. (2002b) reported on the same randomised controlled trial comparing biatrial RFA versus CS alone. The inclusion criteria were: patients with permanent AF for more than one year prior to surgery, or two failed medical or electrical cardioversions six months before surgery. In addition, all patients had MV disease requiring surgical intervention. This is important as structural heart disease is likely to affect the outcome of surgery to treat AF. No exclusion criteria were stated. Patients were randomised to have MV surgery with or without RFA, however, it was not stated whether any method of allocation concealment was used, and there was no information about blinding of patients or outcome assessors. No power calculations to determine sample sizes necessary to detect statistically significant differences were reported. Loss of patients to follow-up was stated, with two of the CS patients unable to attend the outpatient clinic at one year follow-up. Major faults were: • Small group sizes (n=15 per group). • A difference of five years in mean age between the two groups (64.7 in RFA versus 69.7 in CS patients) which was almost statistically significant (p=0.053), and a difference in sex ratio, with 40% of males in the RFA group versus 20% of males in the CS group, the p value was not stated. With small group sizes this may have been due to chance, or an indication randomisation did not work properly. • The energy level, duration of RFA, and irrigation speed were changed during the study. • Early electrical cardioversion was used in the first twenty patients, but abandoned in the last ten patients as the procedure did not appear to results in any long-term cardiac rhythm stability. • Postoperative antiarrhythmic medication was changed from sotalol to metoprolol partway through the trial, as the result of a sudden cardiac death in an RFA patient which may have been related to the proarrhythmic effects of sotalol. In addition, two of the RFA patients remained in AF after surgery, which it was speculated may have been due to non-transmural lesions. Since postoperative mapping was not performed, this was not confirmed. There were some discrepancies in the two published reports, for example in Khargi et al. two patients in the CS group had MV plasty, while in Deneke et al. (2002) it was stated that all patients had MV prostheses. Non-randomised Comparative Studies Biatrial RFA versus CS The included studies consisted of one study with concurrent RFA and CS patients (Chen et al. 2001), one study with overlapping periods between the RFA versus CS patient groups (Patwardhan et al. 2003), and one study with historical controls (Riying et al. 1998). Chen et al. (2001) used two different RFA lesion sets (RFA1 and RFA2) versus CS alone. The only inclusion criterion was presence of chronic AF, and the basis of patient selection was not stated. Selection bias may have been a problem, as there were more male patients, more patients with combined mitral stenosis and regurgitation, fewer patients receiving 19 digitalis, and fewer patients with tricuspid valve disease in RFA1. In RFA2 there were fewer patients receiving β-blocker and calcium channel blockers. Patwardhan et al. (2003) included CS patients as a control group, operated on during the early period of the RFA group. However, follow-up in the CS patients was restricted to six months, while follow-up was 12 to 53 months in the RFA patients. The mean age of the patients was less than in the other included studies: a mean of 32.5 years in the RF and 33.0 years in the CS group. Patients in the RFA group were all operated on by the same surgeon, whereas in the CS group other surgeons were used, with the potential for performance bias. Although the p values were not given, there appeared to be a difference in sex ratio between the two groups: 51% (43/84) of patients were male in the RFA versus 38% (24/64) of males in the CS group. The basis of patient selection was not stated. Heart rhythm outcomes were not given for the CS group in the early postoperative period. Riying et al. (1998) was a poorly reported study. The study start date was stated, but not the end, and it was unknown whether patients were overlapping, concurrent or with historical controls. Details of the patients in the control group were not given, it was simply stated ‘their age, sex, clinical characteristics were similar to those of the treatment group’. Heart rhythm results were given only for the first month in hospital. In the control group it was stated that five patients had transient SR and AF recurred when they left hospital, but it can only be surmised that the remaining patients were in AF. It was reported there were no severe complications in the RFA group, but the definition of a severe complication was not given, and mortality was not stated. Biatrial RFA versus Cardioversion One study comparing RFA and cardioversion patients was included. Patients were likely to have received biatrial RFA surgery for a period before the other patients were cardioverted, although it was only stated that cardioversion occurred more than six months previously. The major aim of the study was to compare left atrial volume and function after biatrial RFA versus cardioversion, and patients were selected as those who had stable SR after the procedures. Therefore this study could not be used to compare the two procedures in their efficacy in converting patients to SR. An original group of 42 consecutive patients underwent biatrial RFA, but only 50% (21/42) of these were selected. Selection bias may have influenced results, as there were a lower proportion of males in the RFA group (p=0.03) and a longer duration of pre-surgical AF (mean values: RFA 51 months versus cardioversion 7 months, p=0.0001). Left atrial RFA versus CS Two studies with concurrent controls were included with comparison between patients having left atrial RFA and CS alone. Guang et al. (2002) used a retrospective study with concurrent controls to compare the effects of left atrial RFA versus CS. The inclusion criteria were: chronic AF for more than one year and relatively good cardiac function. Exclusion criteria were: NYHA functional class IV, or age more than 60 years. During the surgery cardioversion was used to test the sinus node function, and if this was inadequate, the RFA was not performed. The CS group was selected to be of similar age, AF duration, cardiomegaly, left atrial size, and pre-operative NYHA functional class, and no statistically significant differences in pre-operative patient characteristics were present. Operations in both groups were performed by the same surgeon, reducing performance bias. Mantovan et al. (2003) consisted of patients who had left atrial RFA versus patients having cardiac surgery during the same period who refused RFA. No significant differences in baseline characteristics were reported between the two groups. Surgery for RFA was 20 performed in four different Italian centres, however, CS was performed in only two centres. There was variation in postoperative antiarrhythmic medication use, as treatment was recommended in every case, but left to the referring physician to implement. Biatrial RFA versus Maze-III Chiappini et al. (2004) studied patients who underwent Maze-III surgery before biatrial RFA was used as a surgical treatment for AF. There was a significant difference between follow-up periods in the two groups: a range of 20 to 91 months in the Maze-III versus 7 to 22 months in the RFA group (p<0.05). All operations were performed by the same surgeon, reducing the confounding factor of different surgeons. Biatrial versus left atrial RFA Güden et al. (2002) used concurrent patients with prospective data collection. There was a selection bias, as patients had right atrial RFA when the right atrium had to be opened for tricuspid valve inspection, atrial septal defects, or if they previously had an atrial flutter. Therefore, there were twelve (52%) of tricuspid valve operations performed in the biatrial group versus none in the left atrial group, and three atrial septal procedures in the biatrial versus none in the left atrial group. Although p values were not stated there also appeared to be more males in the biatrial versus left atrial groups; 26% (10/29) versus 48% (11/12), respectively. Results were expressed as a percentage instead of numbers of patients, making it difficult to be certain how many patients were included in each outcome. Deneke et al. (2003) studied patients who had undergone biatrial RFA a range of one to 50 months previously versus left atrial RFA at four to 20 months previously. Hence a significant difference in follow-up period between the two groups was present (p=0.05). All of the patients who had open heart surgery plus RFA were included in the study. There was a selection bias as all patients who had paroxysmal AF were treated with a left atrial RFA procedure. Thus the biatrial group would have contained patients with persistent AF, and the left atrial the paroxysmal AF patients. All procedures were performed in the same hospital, however, it was not stated whether they were performed by the same surgeon. There were fewer patients with MV disease in the left atrial group. Although the lesion patterns were not changed, the lesion device was changed twice during the study period, and as the groups were not concurrent this would mean patients were not operated on with the same ablation devices. It should also be noted the patients included in the RCT (Khargi et al. 2001; Deneke et al. 2002b) are likely to be part of the biatrial RFA group in this study. 21 Table 7: Radiofrequency Ablation- RCT and Non-randomised Comparative Studies Study Level Intervention Lone Left Right Device atrium atrium RF ABLATION- Biatrial Lesion Set: RCT - RFA versus Cardiac Surgery Khargi et al. 2001 II RFA + MVS N Y Y SICTRA (Sprinklr, Deneke et al. MVS Medtronic, MN) 2002b RF ABLATION- Biatrial Lesion Set: RCT and Non-randomised studies versus Cardiac Surgery Chen et al. 2001 III-2 RFA1 N Y Y Quadripolar steerable RFA2 N Y Y electrode catheter CS (Mansfield, USA) Patwardhan et al. III-2/3 RFA + CS N Y Y Bipolar forceps 2003 CS Riying et al. 1998 III-3 RFA + CS N Y Y RF probe MV surgery RF ABLATION- Biatrial Lesion Set: Non-randomised study versus Cardioversion Thomas et al. III-2 RFA 6/21 Y Y Cobra or Unipolar RF 2003 Cardioversion device RF ABLATION- Left Lesion Set: RCT and Non-randomised studies versus Cardiac Surgery Guang et al. 2002 III-2 RFA + MVS N Y N EPT 2000 MVS Mantovan et al. III-2 RFA + CS N Y N ThermaLine® 2003 CS RF ABLATION: Non-randomised comparative studies versus Cox Maze III Chiappini et al. III-3 RFA + CS N Y Y Cobra Flex 2004 M-III + CS N I I RF ABLATION: Non-randomised comparative studies- Internal Comparisons Güden et al. 2002 III-2 RFA Biatrial N Y Y Medtronic RFA Left atrial N Y N Cardioblate pen Deneke et al. III-2 RFA Biatrial N Y Y SICTRA (Sprinklr, 2002a RFA Left atrial N Y N Medtronic, MN MVS: mitral valve surgery; RFA1: first RFA lesion set; RFA2: second RFA lesion set; M-III: Maze-III procedure. n 15 15 13 48 58 18 26 25 25 21 33 96 87 103 27 40 30 39 23 49 21 Case Series As case series are the lowest quality of evidence available for assessing interventions, a full methodological critique of their study profiles will not be included. In seven case series biatrial RFA was performed. Three studies had consecutive patients (Damiano et al. 2003; Hornero et al. 2002; Prasanna et al. 2001), while one was a registry study in which it was stated all patients were included, regardless of the risk and urgency of the procedure (Raman et al. (2003). The nature of patient selection was not stated in the remaining two studies (Sos et al. 2002; Thomas et al. 2003). Twelve case series were included using left atrial RFA. In only two studies was it stated that consecutive patients were reported (Kottkamp et al. 1999; Ruchat et al. 2002). In the remaining ten studies it was not stated whether or not the patients were consecutive. 22 Table 8: RFA Case Series Included Studies Study Level Intervention RF ABLATION: Case series- Biatrial lesion sets Damiano et al. IV RFA 2003 (abstract) Hornero et al. IV RFA + CS 2002 Prasanna et al. IV RFA + CS 2001 Raman et al. 2003 IV RFA + CS Sie et al. 2001 IV RFA + CS Lone Left atrium Right atrium NS Y Y Not stated 26 N Y Y ThermaLine® 55 N Y Y Cautery pen 25 N N Y Y Y Y 132 122 Y Y Y Y Cobra® HAT 200S Sulzer-Osypka GmbH ThermaLine® RF handheld devices Y N 132 Y N ThermaLine® + Cobra® Cobra® Y Y N N Cobra® Atricure 29 50 Y N Modified HAT 200S Sulzer-Osypka GmbH Cobra® 12 Sulzer-Osypka GmbH ThermaLine® ThermaLine® ThermaLine® Cobra® 65 Sos et al. 2002 IV RFA + CS N Thomas et al. IV RFA + CS 17/47 2003 RF ABLATION: Case series- Left atrial lesion sets Benussi et al. IV RFA + CS N 2002 Biederman et al. IV RFA + CS N 2002 Geidel et al. 2003 IV RFA + CS N Gillinov et al. IV RFA + CS N 2003 (abstract) Kottkamp et al. IV RFA + CS N 1999 Kress et al. 2002 Le Tourneau et al. 2003 (abstract) Mohr et al. 2002 IV IV RFA + CS RFA + MVS N N Y Y 2/23 2/70 IV RFA + CS N Y N Müller et al. 2002 IV RFA + CS N Y N Ruchat et al. 2002 IV RFA + CS N Y 8/40 Starck et al. 2003 IV RFA + CS N Y N Williams et al. IV RFA + CS N Y Y/N 2001 NS: not stated; CS: cardiac surgery; Y: yes; N: no; MVS: mitral valve surgery 23 Device n 10 47 10 23 70 95 40 100 48 4.1.3 Microwave ablation Eight studies were identified in which intraoperative MWA was used to treat AF (see Tables 9 and 10). There was one RCT comparing left atrial MWA versus CS alone (Schuetz et al. 2003), and one non-randomised study with the same comparison (Spitzer and Knaut 2002). A third non-randomised study compared two MWA lesion sets (Knaut et al. 2003). One case series reported biatrial MWA and four case series reported left atrial MWA. RCT Left atrial MWA versus CS Schuetz et al. (2003) is a prospective randomised open labelled clinical trial. Patients were selected from a group who presented at the clinic for surgical treatment of valve disease, and/or who required coronary artery bypass grafting for coronary artery disease. The stratification was done according to the presence of permanent AF regardless of the concomitant cardiac disease, however, the method of stratification was not stated. Allocation concealment was also not reported. It was not stated whether the patients were consecutive, nor if any exclusion criteria were used. Significant selection bias may therefore have occurred. Patients who received cardiac surgery alone had a significantly longer duration of pre-surgical AF compared to the MWA patients (mean 9.2 versus 3.8 years, p=0.05), although the proportion of patients with permanent AF for more than three months was not different between the two groups. No sensitivity analysis was performed. Important safety outcomes such as stroke, bleeding and wound infection were also not reported. The sample sizes were quite small, and it was stated ‘preliminary data’ were reported. Non-randomised Comparative Studies Left atrial MWA versus CS Spitzer and Knaut (2002) included patients who underwent cardiac surgery alone, or in combination with biatrial MWA. Consecutive patients were included, with all patients operated on by the same surgeon. The inclusion criteria were: patients with permanent AF undergoing elective cardiac surgery, who also had an indication for surgical treatment of the AF (clinical, haematological, or prognostic). No exclusion criteria were given. Clinical characteristics of the selected patients appeared similar, although the p values were not given. MWA1 versus MWA2 Knaut et al. (2003) is a study comparing two different MWA lesion sets. Since it is published in abstract form, details of the study design are limited. It is stated that the patients were consecutive, however, whether the surgery was performed concurrently, or a historical group was used, was not stated. Since six month follow-up was stated for the second lesion set, and one year follow-up for the first lesion set, it is likely that patients were not operated on concurrently. The most serious flaw is that the details of the lesion sets were not stated. It is likely that one lesion set was the same as previously published by Spitzer and Knaut (2002), however, the other is unknown. Results were expressed as percentage values, making it impossible to determine the number of patients at the end of follow-up. 24 Table 9: MWA RCT and Non-randomised Comparative Included Studies Study Level Intervention Lone Left atrium MW ABLATION: RCT and Non-randomised studies Schuetz et al. II MWA + CS N 2003 CS Spitzer and Knaut III-2 MWA + NS 2002 CS MW ABLATION: Internal Comparison Knaut et al. 2003 III-? MWA1 N (abstract) MWA2 N Right atrium Y N Y N Y NS N NS Device AFx™ Flex 2 Not stated n 24 19 136 51 137 75 NS: not stated; N: no; Y: yes Case Series As case series are the lowest level of evidence available for assessing interventions, a full methodological critique of their study profiles will not be included. One case series was included in which biatrial MWA was used. The method of patient selection was not stated in this study (Chiappini et al. 2003). There were four included case series where left atrial MWA was used. In two studies consecutive patients were included (Knaut et al. 2002; Zembala et al. 2003). In the other two studies the basis of patient selection was not stated. Table 10: MWA Case Series Included Studies Study Level Intervention Lone Left atrium MW ABLATION- Biatrial: Case Series Chiappini et al. IV MWA + CS N 2003 MW ABLATION- Left atrial: Case Series Gillinov et al. IV MWA + MVS N 2002 Knaut et al. IV MWA + MVS N 2002 Venturini et al. IV MWA + MVS N 2003 Zembala et al. IV MWA + MVS N 2003 CS: cardiac surgery; N: no; Y: yes; MVS: mitral valve surgery Right atrium Device n Y Y AFx Flex 4™ 10 Y N AFx 10 Y N Y N AFx Lynx or Flex™ AFx Flex™ Y N AFx Flex 2™ 105 41 42 4.1.4 Laser ablation One case series was included using laser energy for intraoperative ablation of AF. Vigilance et al. (2003) was an abstract with only six patients. There were limited data and a follow-up of only three months. 4.1.5 Radiofrequency versus microwave ablation One Level III-2/3 study in which RFA versus MWA were compared was included. Wisser et al. (2004) included patients treated with RFA versus MWA, using the same lesion set. The RFA surgery was performed before the MWA, so patients were not concurrent although the study period for each group was not stated. Consecutive patients were used, and all patients 25 had chronic permanent AF. No significant differences in preoperative patient characteristics were reported. 4.1.6 Maze-III Since the Maze-III procedure is acknowledged as the gold standard surgical treatment for AF and Maze-III data from the included intraoperative ablation studies was limited, studies were also included using the Maze-III procedure. These are shown in Table 11 below. Data were used only as a benchmark, and the studies were considered as case series, hence a full methodological critique is not included. Table 11: Maze-III included studies Study Level Albåge et al. 2000 Albirini et al. 1997 IV IV Chen et al. 2002 D’Alessandro et al. 2003 (abstract) Isobe et al. 2001 Jessurun et al. 2000 Jessurun et al. 2003 IV IV Intervention Lone Maze-III ± CS Maze-III + MVR±CABG Maze-III + MVS Maze-III + CS 17/26 N 26 8 N N 56 21 IV IV IV n Maze-III + CS N 40 Maze-III Y 41 Maze-III Y 32 Maze-III + CS N 32 Kim et al. 1999 IV Maze-III + MVS N 75 Lönnerholm et al. 2000 IV Maze-III ± CS 41/48 48 Millar et al. 2000 IV Maze-III ± CS 19/76 76 Pasic et al. 1999 IV Maze-III + MVS N 30 Prasad et al.2003 IV Maze-III ± CS 112/198 198 Raanani et al. 2001 IV Maze-III + CS N 47 Sandoval et al. 1996 IV Maze-III ± CS 3/21 21 Sundt III et al. 1997 IV Maze-III + CS 86/143 143 CS: cardiac surgery; MVS: mitral valve surgery; MVR: mitral valve replacement; CABG: coronary artery bypass grafting; N: no; Y: yes 26 5.0 RESULTS 5.1 Safety 5.1.1 Mortality Ablative surgery to treat AF is usually performed as a concurrent procedure with other cardiac surgery. Cardiac surgery in itself is associated with a small, but significant mortality rate. The major question is whether intraoperative ablation increases the risk of mortality versus the comparative procedures. Cryotherapy Ablation Non-randomised Comparative Studies Biatrial CA+CS versus CS Three studies reported mortality rates after biatrial CA+CS versus CS alone (see Table 12). The median proportion of deaths was 0% in both groups. Mortality rates ranged from 0% to 8% after CA+CS, and 0% to 7% after CS alone. No deaths occurred in Sueda et al. (1997) or Yuda et al. (2004), with follow-up at least two months in all patients. Handa et al. (1999) reported no perioperative mortality, but in later follow-up 8% (3/39) of biatrial CA+CS versus 7% (4/58) of CS patients died. In the biatrial CA+CS group, one patient died of congestive heart failure, one patient had ventricular tachycardia, and one patient died of unknown causes. In the CS group one patient died of pulmonary embolism, one patient of intracerebral haemorrhage, one patient of cerebral infarction, and one patient with myocardial infarction. Follow-up was to a mean of 21 months. Table 12: Mortality- Biatrial CA +CS versus CS Level Handa et al. 1999 III-2 Sueda et al. 1997 III-3 Yuda et al. 2004 III-2 Median Range [ ]: SD; ( ): range; BA: biatrial Mortality (%) BA CA CS 0% 0% 8% 7% 0% 0% 0% 0% 0% 0% (0%-8%) (0%-7%) n/N BA CA 0/39 3/39 0/36 0/26 n/N CS 0/58 4/58 0/15 0/6 Follow-up 30 days Mean 21 months (≥ 6 months) Mean 18 months (2-51 months 14.6[6.6] months (> 2 months) Handa et al. (1999) also reported the cumulative survival in each group. Following biatrial CA+CS the cumulative survival was 91.8 [4.6] (n=26) at one year; 91.8 [4.6] (n=15) at two years and 91.8 [4.6] (n=3) at three years. When CS alone was performed the cumulative survival was 96.0 [2.8] (n=36) at one year; 96.0 [2.8] (n=22) at two years; and 85.9 [7.2] (n=11) at three years. There was no significant difference in cumulative survival between the two groups (p>0.05). 27 Left atrial CA+CS versus CS One study reported mortality rates after left atrial CA+CS versus CS alone (see Table 13). In Gaita et al. (2000) total mortality was 9% (3/32) after left atria CA+CS versus 11% (2/18) after CS alone. In the left atrial CA+CS group, one patient died three weeks postoperatively due to septicaemia; and in later follow-up one patient with chronic AF died of heart failure (four months), and one patient in SR died of intracerebral haemorrhage (seven months). In patients who had CS alone, two patients died of heart failure, one on the first day and one at three months postoperatively. There was no significant difference in early mortality rates between the two groups. Table 13: Mortality- Left atrial CA +CS versus CS Level Mortality (%) LA CA CS Gaita et al. 2000 III-2 3% 6%pns 6% 6% 9% 11% pns: statistically non-significant; LA: left atrial n/N LA CA 1/32 2/32 3/32 n/N CS 1/18 1/18 2/18 Follow-up 30 days 12 months Total Biatrial CA versus Maze-III Three studies reported mortality rates in patients after MA versus Maze-III (see Table 14). The median proportion of deaths following both biatrial CA and Maze-III surgery was 0%, with a range of 0% to 6% for biatrial CA and 0% to 8% for Maze-III surgery. Follow-up was to 30 days in two studies (Kim et al. 2001; Lee et al. 2001) and at least 34 months in Ishii et al. 2001. In Ishii et al. (2001) there were two (6%) early fatalities in the biatrial CA group: one patient had an ischaemic-reperfusion injury of the lower extremity, and one patient died of a perioperative myocardial infarction. Following the Maze-III, one patient (8%) died at ten months postoperatively due to inappropriate antibiotic therapy after dental treatment. Table 14: Mortality- Biatrial CA versus Maze-III Level Ishii et al. 2001 III-3 Mortality (%) BA CA Maze-III 6% NS NS 8% Kim et al. 2001 III-3 0% 0% Lee et al. 2001 III-3 0% 0% Median 0% 0% Range (0%-6%) (0%-8%) [ ]: SD; ( ): range; NS: not stated; BA: biatrial n/N BA CA 2/32 NS n/N Maze-III NS 1/13 0/23 0/53 0/18 0/30 Follow-up 30 days 41.2[5.6] months (34-52 months) 30 days 30 days Kosakai maze versus CA One study reported mortality rate after Kosakai maze versus CA (see Table 15). In Nakajima et al. (2002) 2% (2/110) of the Kosakai maze versus 1% (1/110) of the CA patients died. Following the Kosakai maze, one patient died due to anticoagulant related bleeding, and one due to a stroke. In the CA group one patient died from a stroke. Mean follow-up was approximately 64 months in the Kosakai maze and 19 months in the CA group. The actuarial survival was also reported, and at three years was 91.7% after the Kosakai maze versus 98.0% after CA (p=0.32). 28 Table 15: Mortality- Kosakai maze versus CA Level Nakijima et al. 2002 [ ]: SD Mortality (%) Kosakai CA III-3 2% 1% n/N Kosakai n/N CA 2/110 1/110 Follow-up Kosakai CA 64.1[27.4] 18.8[10.8] months months Kosakai maze with retention (RAA+) versus removal (RAA-) of the RAA One study reported mortality rates after the Kosakai maze, with and without removal of the RAA (see Table 16). In Yoshihara et al. (2000) there were no deaths in either group at up to 30 days follow-up. Table 16: Mortality- Kosakai maze RAA+ versus RAALevel Yoshihara et al. 2000 III-3 RAA: right atrial appendage Mortality (%) Kosakai -RAA Kosakai+RAA 0% 0% n/N n/N Follow-up 0/20 0/22 30 days Biatrial versus left atrial CA One study reported mortality rates after biatrial versus left atrial CA (see Table 17). There were no deaths in patients of either group in Takami et al. (1999), at follow-up of at least eight months. Table 17: Mortality- Biatrial versus left atrial CA Level Takami et al. 1999 III-3 Mortality (%) BA CA LA CA 0% n/N BA CA LA CA 0% 0/30 0/20 Follow-up (15-51 months) (8-23 months) NS: not stated; ( ): range; BA: biatrial; LA: left atrial Biatrial versus right atrial CA One study reported mortality rates after biatrial versus right atrial CA (see Table 18). Schaff et al. (2000) reported 1% (2/173) of patients died in the biatrial CA versus 2% (1/42) after right atrial CA, to 30 days follow-up. In the biatrial group, one patient died from septicaemia and pneumonia, and the other patient died following congenital heart defect repair. Following right atrial CA one patient died, also following congenital heart defect repair. There were no later deaths in the right atrial group, but this was not stated for the biatrial CA patients. The p values were not stated. Table 18: Mortality- Biatrial versus right atrial CA Level Mortality (%) BA CA RA CA Schaff et al. 2000 1% 2% III-2/3 NS 0% BA: biatrial; RA: right atrial; NS: not stated n/N BA CA 2/173 NS 29 Follow-up RA CA 1/42 0/42 30 days Not stated Case Series Biatrial CA Case Series Eight case series reported mortality rate after biatrial CA (see Table 19). The median proportion of deaths following biatrial CA was 4%, with a range of 0% to 12%. Follow-up was to 30 days in two of the studies, and at least four months in the other six studies. No deaths occurred in two studies (Fukada et al. 1998; Shimizu et al. 1997). The causes of death (and time after follow-up) in the studies in which they were stated were: • one patient with pulmonary infection, sepsis and multiple organ dysfunction (four months) (Arai et al. 1999); • perioperatively, three patients with multiple organ failure and one patient with cerebral infarction and acute renal failure (Izumoto et al. 2000); • at up to 60 months follow-up, three patients with heart failure, three patients with cancer, one patient with chronic pleuritis due to tuberculosis and one patient with unknown causes (Izumoto et al. 2001); and • one patient had cerebral haemorrhage and multiple organ failure (32 months) and one patient had sudden death (29 months) after having successful electrical cardioversion for recurrence of AF at 28 months (Yuda et al. 2001). Table 19: Mortality- Biatrial CA Case Series Level Biatrial Ad et al. 2003a Ad et al. 2003b IV Mortality (%) 4% 4% IV 2% 6% Arai et al. 1999 0% IV 3% Fukada et al. 1998 0% IV 0% Izumoto et al. 2000 4% IV 8% 12% Morishita et al. 2000 IV 8% Shimizu et al. 1997 IV 0% Yuda et al. 2001 0% IV 2% Median 4% Range (0%-12%) [ ]: SD; { }: Type of variance not stated; ( ): range n/N Follow-up 2/50 2/51 1/51 3/51 0/30 1/30 0/29 0/29 4/104 8/104 12/104 1/12 0/6 0/94 2/94 Operative Operative 19{5} months Total 30 days 4 months 30 days Not stated 30 days 60 months Total 30 days (4-32 months) 30 days 2.2[0.9] years Left atrial CA Case Series Seven case series reported mortality rates after left atrial CA (see Table 20). The median proportion of deaths was 0%, with a range of 0% to 11%. Follow-up was to 30 days in three studies, and at least one month in the remaining studies. No deaths occurred in four of the studies (Imai et al. 2001; Naito et al. 2001; Sueda et al. 2001; Yamauchi et al. 2002). However, the patients in Imai et al. (2001) were a selected group who had survived for more than one year. The two patient deaths in Hoffmeister et al. (2003) were of non-cardiac causes. One operative death in Manasse et al. (2003) was directly related to the CA procedure, as there was a tear of the posterior left atrial wall caused by retracting the cryoprobe before thawing was completed. The other perioperative death in this study was due to septicaemia, at one month 30 postoperatively. Deaths in later follow-up were due to: pneumonia in one patient (49 days); stroke in three patients; heart failure in one patient (three months); cancer in one patient; and unknown causes in one patient (14 months). Table 20: Mortality- Left atrial CA Case Series Level Mortality (%) n/N Follow-up IV IV IV 11% 0% 7% 2% 7% 9% 0% 0% 0% 0% (0%-11%) 2/19 0/32 2/31 2/95 7/95 9/95 0/30 0/12 0/40 28.8 months (1-48 months) (13-66 months) 30 days 30 days 36.4 months Total 30 days (5-14 months) 30 days Left atrial Hoffmeister et al. 2003 Imai et al. 2001 Kondo et al. 2003 Manasse et al. 2003 IV Naito et al. 2001 Sueda et al. 2001 Yamauchi et al. 2002 Median Range ( ): range IV IV IV Radiofrequency Ablation Randomised Controlled Trial Biatrial RFA+MVS versus MVS One RCT reported mortality rates in patients after biatrial RFA versus CS (see Table 21). In Khargi et al. (2001) there were no deaths in either group at up to 30 days. At later followup four patients (4/15) died after biatrial RFA versus one patient (1/15) after CS alone. In the biatrial RFA+MVS group one patient died from fatal coumadin-related renal bleeding; one patient died of mediastinitis on the 45th day postoperatively (the patient was obese, diabetic and the prolonged operative time was a risk factor); one patient had sudden cardiac death at six weeks postoperatively (possibly due to pro-arrhythmic effects of sotalol); and one patient had lethal respiratory failure seven months postoperatively, related to pre-existing chronic obstructive pulmonary disease. Following CS alone, one patient died of lethal respiratory failure at 10 months postoperatively, also related to pre-existing chronic obstructive pulmonary disease. No significant difference in mortality was seen between the two groups (p>0.05). Table 21: Mortality- Biatrial RFA+MVS versus MVS RCT Level Mortality (%) n/N Follow-up BA RFA CS BA RFA CS BA RFA CS Khargi et al. 2001 0% 0% 0/15 0/15 30 days II 27% 7%pns 4/15 1/15 22[7] months 21[6] months [ ]: SD; pns: statistically non-significant; BA: biatrial: MVS: mitral valve surgery 31 Non-randomised Comparative Studies Biatrial RFA versus CS Three studies reported mortality rates after biatrial RFA+CS versus CS alone (See Table 22). There was a median incidence of mortality of 5% (range 0% to 17%) after biatrial RFA+CS versus 7% (range 0% to 17%) after CS alone. Follow-up was only to hospital discharge after CS alone in Riying et al. (1998), with a minimum of three months follow-up in the remaining groups. The p values were not given. The causes of death were not stated in Chen et al. (2001). In Patwardhan et al. (2003) most patients died from low cardiac output: seven patients after biatrial RFA versus eight patients after CS alone. In addition, one patient died due to mediastinitis in each group, plus one patient died from disseminated intravascular coagulation and one from cerebral embolism in the CS group. Table 22: Mortality- Biatrial RFA+CS versus CS Level Chen et al. 2001 Patwardhan et al. 2003 III-2 III-3 Mortality (%) BA RFA CS RFA1: 15% 7% RFA2: 2% RFA1: 0% 0% RFA2: 0% RFA1: 15% 7% RFA2: 2% 5% 7% 10% 17% 7% 0% 17% 17% n/N BA RFA 2/13 1/48 0/13 0/48 2/13 1/48 3/61 8/84 6/84 14/84 Follow-up CS 4/58 BA RFA 30 days CS 30 days 0/58 (37-47 months) (3-32 months) Total (35-109 months) TOTAL TOTAL 4/58 4/58 11/64 0/64 11/64 30 days 23.6[12.5] months Total Total 6 months Total Hospital discharge Riying et 0/25 0/25 (3-24 months) III-3 0% 0% al. 1998 Median 5% 7% Range (0%-17%) (0%-17%) RFA1: first RFA lesion set; RFA2: second RFA lesion set; NS: not stated; ( ): range; [ ]: SD; BA: biatrial Left atrial RFA versus CS Two studies reported mortality rates after left atrial RFA versus CS (see Table 23). Mortality rates after left atrial RFA were 0% to 4% versus 0% to 7% after CS. Follow-up in both studies was at least one year. In Guang et al. (2002) no deaths occurred in either group. However, in Mantovan et al. (2003) total mortality rates were 4% (4/103) in the left atrial RFA versus 7% (2/27) in the CS group (p>0.05). The early death in the left atrial RFA group was due to oesophageal perforation and resultant complications (Mantovan et al. 2003). The later deaths in this group were related to: left atrial thrombus and sudden death in one patient who was in SR without atrial contraction; stroke in one patient with AF at one month postoperatively; and severe left ventricular cardiomyopathy with functional mitral insufficiency and dysthyroidism in one patient in SR without atrial contraction, who died suddenly eight months postoperatively. In the CS group one patient died of an abdominal infarction (one month); and one patient had sudden death of unknown cause (five months). 32 Table 23: Mortality- Left atrial RFA versus CS Level Mortality (%) n/N LA RFA CS LA RFA Guang et al. 2002 III-2 0% 0% 0/96 Mantovan et al. 1% 0% 1/103 III-2 2003 3% 7% 3/103 4% 7%pns 4/103 Range (0%-4%) (0%-7%) LA: left atrial; [ ]: SD; ( ): range; pns: statistically non-significant Follow-up CS 0/87 0/27 2/27 2/27 3 years 30 days 12.5[5] months Total RFA versus Maze-III One study reported mortality rates after RFA versus Maze-III surgery (see Table 24). There were 8% (3/40) of deaths in the biatrial RFA versus 7% (2/30) in the Maze-III group by the 30 day follow-up. The p value was not stated. One patient in each group died during early follow-up due to left ventricular disruption, believed to be the result of severe calcification of the mitral valve annulus and subvalvular apparatus. In addition, in the RFA group one patient died of sepsis; and one patient died of severe hepatic cirrhosis (20 years duration). Following Maze-III surgery one additional patient died of multiorgan failure. The cumulative rate of survival for complete follow-up (at least 7 months) was also calculated, and was 92.8% in the RFA versus 90.4% after Maze-III (p=0.91). Table 24: Mortality- RFA versus Maze-III Level Chiappini et al. 2004 BA: biatrial III-3 Mortality (%) RFA Maze-III 8% 7% n/N RFA 3/40 Follow-up Maze-III 2/30 30 days Biatrial versus left atrial RFA Two studies reported mortality rates after biatrial versus left atrial RFA (see Table 25). In Güden et al. the mortality rate was 3% (1/39) for the biatrial versus 4% (1/23) in the left atrial group. The patient in the biatrial group had a sudden cardiac death, and the left atrial RFA patient died of unexplained causes. Follow-up was a mean of 104 days. Deneke et al. (2002a) reported a total mortality rate of 12% (6/49) in the biatrial versus 10% (2/21) in the left atrial patients. The later deaths in the biatrial RFA group were related to: renal bleeding in one patient (40 days); mediastinitis in one patient (45 days); sudden cardiac death in one patient (four months); progressive respiratory insufficiency in two patients (seven months and 16 months); and unknown causes in one patient (non-cardiac or cerebral ischaemia, 33 months). Earlier deaths in the left atrial group were from mediastinitis at 21 days postoperatively, and severe postoperative pyoderma with sepsis at 28 days. It should be noted that follow-up was longer in the biatrial versus left atrial group. The p values were not stated in either study. Deneke et al. (2002a) also reported cumulative survival rates, which were 77.9% in the biatrial versus 90.5% of patients in the left atrial group (p=0.88). 33 Table 25: Mortality- Biatrial versus left atrial RFA Level Güden et al. 2002 Deneke et al. 2002a III-2 III- 2/3 Mortality (%) BA RFA LA RFA n/N BA RFA LA RFA Follow-up BA RFA LA RFA 3% 4% 1/39 1/23 Mean 104 days (45-245 days) 0% 12% 10% 0% 0/49 6/49 2/21 0/21 To 30 days 18[14] months 11[10] months (1-50 months) (4-20 months) Total 12% 10% 6/49 [ ]: SD; ( ): range; NS: not stated; BA: biatrial; LA: left atrial 2/21 Case Series Biatrial RFA Case Series Seven case series reported mortality rates in patients after biatrial RFA (see Table 26). The median proportion of deaths was 5%, with a range of 0% to 12%. Follow-up was 30 days in Damiano et al. (2003), and a mean of at least 6 months in five of the other studies. There were no patient deaths in three studies (Damiano et al. 2003; Prasanna et al. 2001; Sos et al. 2002). The causes of death (and time after follow-up) in the studies in which they were stated were: • In Hornero et al. (2002) one patient had sudden death (22 days) and had a history of chronic renal failure. Two later deaths were due to sudden death of unknown causes in a patient who had concomitant atrioventricular canal defect; and cerebral haemorrhage in one patient, probably related to anticoagulant medication. • Raman et al. (2003) reported nine patient deaths to 30 days: one patient with remote aortic dissection after replacement of the ascending aorta; one patient with a fragile calcified aortic root that leaked after valve replacement (also had severe liver dysfunction caused by coagulopathy and tamponade); one decompensated patient on a balloon pump with uncontrolled AF and large ventricular infarcts, and severe aortic regurgitation, who arrested soon after anaesthetic induction and was salvaged, but had no recovery of ventricular function by the fifth day; one bleeding duodenal ulcer (day 8); one cardiogenic shock caused by a large infarct, complicating a delayed low output syndrome (day six); perioperative gut ischaemia in one patient; low systemic vascular resistance syndrome resistant to norephinephrine and vasopressin in one patient; and low cardiac output in two elderly patients. There was a single death at later follow-up, in a patient with infective endocarditis complicated by liver failure (eight months). • Sie et al. (2001) reported five early deaths: one patient died intraoperatively due to rupture of the mitral annulus; one patient died of coma vigil due to late tamponade; two patients died of low cardiac output syndrome; and one patient died of multiple organ failure. At later follow-up, ten patients died: five due to cardiac causes; four were non-cardiac related, and the cause was not specified in one patient. • In Thomas et al. (2003) two patients died within 48 hours of surgery with cardiac failure. Another two patients died during later follow-up, one patient from presumed ventricular tachycardia and one from prostatic carcinoma. When reported at both early and later follow-up, no consistent differences in early versus later deaths were apparent. Cumulative survival was also calculated by Sie et al. (2001), and was 90% at three years follow-up. 34 Table 26: Mortality- Biatrial RFA Case Series Biatrial Damiano et al. 2003 Hornero et al. 2002 Level Mortality (%) n/N Follow-up IV 0% 2% 4% 5% 0% 7% 1% 8% 4% 8% 12% 0% 4% 4% 9% 5% (0%-12%) 0/26 1/55 2/55 3/55 0/25 9/132 1/132 10/132 5/122 10/122 15/122 0/10 2/47 2/47 4/47 30 days 30 days Mean 7 months (1-16 months) Total (3.2-3.8 years) 30 days Mean 6.4 months (3-24 months) Total 30 days Mean 39 months Total (1.5-5 months) 30 days (0.6-4.2 years) Total IV Prasanna et al. 2001 Raman et al. 2003 IV IV Sie et al. 2001 IV Sos et al. 2002 Thomas et al. 2003 IV IV Median Range ( ): range Left atrial RFA Nine case series reported mortality rates after left atrial RFA (see Table 27). The median proportion of deaths was 5%, with a range of 0% to 13%. Follow-up was to 30 days in five studies, and a mean of at least 138 days in the remaining four studies. No patient deaths occurred in only one study (Geidel et al. 2003). The causes of death (and time after follow-up) in the studies in which they were stated were: • In Benussi et al. there were three early deaths: one patient with a previous stroke died on day 12 due to bilateral pneumonia causing prolonged ventilatory support and septicaemia; and two patients died after hospital discharge due to cardiac arrest in one patient, possibly related to myocardial infarction, and a stroke related to inadequate anticoagulation in the other patient. There were also three late deaths: sudden death in one patient; stroke in a patient with refractory AF; and mediastinal lymphoma in one patient. • Kottkamp reported the death of one patient, who developed haemodynamic deterioration and ventricular fibrillation 24 hrs postoperatively, underwent reoperation, but died of low cardiac output syndrome. • Kress et al. (2002) also reported an early death in a patient with ventricular arrhythmia, who had a recent myocardial infarction and low LVEF. • Le Tourneau et al. (2003) had an early procedure related death, in a patient with an RF induced circumflex artery stenosis. The two later deaths in this study were due to multiorgan failure in one patient, and pulmonary infection in one patient. • Early deaths in Müller et al. (2002) were due to a stroke (day 16), and late pericardial tamponade (day 26). • Ruchat et al. (2002) reported three early deaths: one death in the operating theatre due to cardiogenic shock; one sudden cardiac death due to perioperative embolic myocardial infarction (day four); and one patient with a left retro-orbital tumour and severe vasoplegia after AVR with multiple organ failure (day three). Later deaths resulted from septic shock in one patient (five months), and one death after colectomy for cancer. • Starck et al. (2003) reported five early deaths: four patients with impaired left ventricular function preoperatively died due to low cardiac output syndrome followed 35 by multiorgan failure; and one patient with sudden onset massive haemorrhage from the suture line of the left atriotomy (day 6). This patient had been treated with corticosteroids for a long time prior to surgery, and the autopsy showed abnormally fragile atrial tissue. • In Williams et al. (2001) there were three early and three later deaths. Early deaths were due to right heart failure/acute hypertensive crisis in one patient (day three); and multisystem organ failure in two patients (days 8 and 30). Later deaths were related to acute lung injury/multisystem organ failure in one patient (day 38), multisystem organ failure in one patient (39 days) and perforation of the right colon in one patient (38 days). All deaths occurred while patients were still in hospital. In the studies reporting mortality at early and later follow-up, there were no consistent differences in deaths in early versus later times. Benussi et al. (2002) also presented the cumulative survival in patients after left atrial RFA: at three years there was 94% survival (95% CI: 88% to 99%). Table 27: Mortality- Left atrial RFA Case Series Level Mortality (%) n/N Follow-up IV 2% 2% 5% 0% 3/132 3/132 6/132 0/29 30 days 16.9[14.2] months Total 30 days IV 8% 1/12 30 days IV 4% 1/23 30 days IV 3% 2/70 Mean 549 days IV 4% 8% 5% 13% 5% 6% 6% 13% 5% (0%-13%) 4/95 3/40 2/40 5/40 5/100 3/48 3/48 6/48 30 days 30 days 12.5[7.9] months Total 30 days 30 days 138[96] days Total Left atrial Benussi et al. 2002 IV Geidel et al. 2003 Kottkamp et al. 1999 Kress et al. 2002 Le Tourneau et al. 2003 Müller et al. 2002 Ruchat et al. 2002 IV Starck et al. 2003 Williams et al. 2001 IV IV Median Range [ ]: SD; ( ): range Microwave Ablation Randomised Controlled Trial Left atrial MWA versus CS One RCT reported mortality rates after MWA versus CS (see Table 28). In Schuetz et al. (2003) the mortality rate to 30 days was 4% (1/24) in the left atrial MWA versus 5% (1/19) in the CS group. After left atrial MWA, the patient died of cerebral air embolism of unknown origin, while one patient died of refractory heart failure following CS alone. There was no statistical difference in mortality to 30 days between the two groups (RevMan RR 0.78, 95% CI: 0.05 to 13.39). In follow-up to one year there were no further deaths in either group. 36 Table 28: Mortality- Left atrial MWA versus CS RCT Level Mortality (%) LA MWA CS Schuetz et al. 4% 5%pns II 2003 0% 0% 4% 5%pns LA: left atrial; pns: statistically non-significant n/N LA MWA 1/24 0/24 1/24 Follow-up CS 1/19 0/19 1/19 30 days 12 months Total Non-randomised Comparative Studies Left atrial MWA versus CS One comparative study reported mortality rates after MWA versus CS (see Table 29). In Spitzer and Knaut (2002) the mortality rate to 30 days was 2% (2/136) in the left atrial MWA versus 8% (4/51) in the CS group. Two patients died in the left atrial MWA group due to low cardiac output (day one) and sudden cardiac death (day 20). When CS alone was performed, four patients died: one with bilateral lung emboli; one with intractable left heart failure; one with toxic gastrointestinal gangrene; and one with left sided heart failure plus ischaemic enterocolitis. The p value was not given. Table 29: Mortality- Left atrial MWA versus CS Level Spitzer and Knaut 2002 LA: left atrial III-2/3 Mortality (%) LA MWA CS 2% 8% n/N LA MWA 2/136 Follow-up CS 4/51 30 days MWA1 versus MWA2 Knaut et al. (2003) reported cumulative survival after the two MWA ablation patterns. Cumulative survival at six months was 98.5% following MWA1 versus 97.3% after MWA2. The p value was not given. Case Series Biatrial MWA One case series reported the mortality rate after biatrial MWA (see Table 30). In Chiappini et al. (2003) one patient (1/10) died by the 30 day follow-up, due to rupture of the left ventricle after MV plus aortic valve replacement. The patient had a severely calcified mitral annulus. There were no further deaths to a mean of 12.4 months follow-up. Table 30: Mortality- Biatrial MWA Case Series Level Mortality (%) n/N Follow-up IV 10% 0% 10% 1/10 0/10 1/10 30 days Mean 12.4 months Total Biatrial Chiappini et al. 2003 Left atrial MWA Three case series reported mortality rates after left atrial MWA (see Table 31). The mortality rates ranged from 0% to 2%. Follow-up was 30 days in one study and a range of one to 21 months in the other two studies. No deaths occurred in Venturini et al. (2003). A single patient died in each of the other two studies: 1% (1/105) in Knaut et al. (2002), and 2% (1/42) in Zembala et al. (2003). The patient in Knaut et al. (2002) died from right sided heart failure on day 20 postoperatively; 37 and the patient in Zembala et al. (2003) died eight months postoperatively with a fatal cerebral thromboembolic event. Table 31: Mortality- Left atrial MWA Case Series Left atrial Knaut et al. 2002 Venturini et al. 2003 Zembala et al. 2003 Level Mortality (%) n/N Follow-up IV IV 1% 0% 0% 2% 2% 1% (0%-2%) 105/105 41/41 30 days (5-21 months) 30 days (1-14 months) Total IV Median Range ( ): range 42/42 MWA versus RFA One study reported mortality after MWA versus RFA (Wisser et al. 2004). In the RFA groups there was one early mortality (1/23, 4%) related to liver failure, and one death in later followup (1/23, 4%) due to unexplained causes. Thus total mortality in the MWA group was 9% (2/23). It was not stated whether any deaths occurred following RFA surgery. Maze-III Fifteen Maze-III studies reported mortality rates following surgery. The median proportion of deaths was 3%, with a range of 0% to 10%. Summary of mortality Comparative Studies Intraoperative ablation did not appear to result in any increase in mortality compared with cardiac surgery alone. In the RCTs, there was no significant increase in mortality after biatrial RFA plus MV surgery versus MV surgery alone (p>0.05), although more patients died in the biatrial RFA versus CS group (27% versus 7%) (Khargi et al. 2001). In Schuetz et al. (2003) there was no significant difference in mortality between left atrial MWA plus CS versus CS groups. The non-randomised comparative studies were consistent with these findings. Compared to CS alone, there was no apparent difference in mortality following: biatrial or left atrial CA; biatrial or left atrial RFA; or left atrial MWA. There also appeared to be no difference in the incidence of mortality between either CA or RFA versus the Maze-III procedure. Within the internal comparison groups, there were no differences in mortality when CA or RFA was applied using a biatrial or left atrial lesion set. The study groups in which a median could be calculated (groups with three or more studies) are illustrated below, with a box plot to demonstrate the variance within studies of each group (Figure 2). In the CA groups there was a range of 0% to 4% in median proportion of mortality, with no apparent difference between the biatrial versus left atrial groups. When RFA was used the median mortality ranged from 4% to 9%, also with no obvious difference between the lesion sets. Little data was available to evaluate MWA and laser ablation. Out of three case series, a median of 1% of patients died after left atrial MWA. 38 In the four Maze-III arms of the comparative studies, a median proportion of 4% of patients died. When cardiac surgery was performed alone, a median of 7% of patients died across twelve studies. (4%; n=4) Maze-III (7%; n=12) Cardiac surgery LA MWA case series (1%; n=3) LA RFA case series (5%; n=9) BA RFA case series (5%; n=7) LA RFA (4%; n=4) BA RFA (9%; n=8) LA CA case series (0%; n=7) BA CA case series (4%; n=8) BA CA (0%; n=12) 0 10 20 30 40 50 Mortality (%) Figure 2: Median proportion of mortality The box represents the 10th and 90th percentiles, the line the median value, and the error bars the 5th and 95th percentiles. Outliers of more than 1.5 box lengths outside the median are shown as • (Median; no of studies) BA: biatrial; LA: left atrial; CA: cryotherapy ablation; RFA: radiofrequency ablation; MWA: microwave ablation 5.1.2 Bleeding, blood loss, blood transfusion requirement One of the disadvantages of the Maze-III procedure is the potential for significant blood loss, due to the multiple incisions to the atria. The risk of serious bleeding is exacerbated by a requirement for peri-operative anticoagulant medication to minimise the likelihood of thromboembolic complications. Techniques in which surgical incisions are replaced by other ablative techniques, such as cryotherapy or radiofrequency ablation, may have a reduced risk of significant blood loss. In the included studies bleeding was often only reported when it required re-operation, and where this was the case it is stated in the text. 39 Cryotherapy Ablation Non-randomised Comparative Studies Biatrial CA+CS versus CS One comparative study reported the incidence of bleeding after biatrial CA+CS versus CS (see Table 32). In Handa et al. (1999) there were bleeding complications in both groups, with 3% (1/39) of the CA+CS versus 2% (1/58) of the CS patients having postoperative bleeding. The p value was not given. It was stated the bleeding was not warfarin related in either patient. Table 32: Bleeding- Biatrial CA+CS versus CS Level Handa et al. 1999 BA: biatrial III-2 Bleeding (%) BA CA CS 3% 2% n/N BA CA 1/39 CS 1/58 Left atrial CA+CS versus CS One comparative study reported the incidence of bleeding after left atrial CA+CS versus CS (see Table 33). In Gaita et al. (2000) the incidence of bleeding was 3% (1/32) after CA+CS versus 0% following CS alone. The p value was not given. Table 33: Bleeding- Left atrial CA+CS versus CS Level Gaita et al. 2000 LA: left atrial III-2 Bleeding (%) LA CA CS 3% 0% n/N LA CA 1/32 CS 0/18 Biatrial CA versus Maze-III Two studies reported the incidence of bleeding after biatrial CA versus Maze-III (see Table 34). No bleeding occurred after CA in either study. Following Maze-III surgery, 15% (2/13) of patients had bleeding in Ishii et al. (2001), whereas no patients had postoperative bleeding after Maze-III in Kim et al. (2001). The p value was not given in either study. Table 34: Bleeding- CA versus Maze-III Level Ishii et al. 2001 Kim et al. 2001 BA: biatrial III-3 III-3 Bleeding (%) BA CA Maze-III 0% 15% 0% 0% n/N BA CA 0/32 0/23 Maze-III 2/13 0/18 Biatrial versus right atrial CA One study reported the incidence of bleeding after biatrial versus right atrial CA (see Table 35). In Schaff et al. (2000) 6% (11/173) of patients had bleeding requiring re-exploration after biatrial CA group, versus none when cryotherapy was limited to the right atrium. The p value was not given. 40 Table 35: Bleeding- Biatrial versus right atrial CA Level Schaff et al. 2000 III-2/3 Bleeding (%) BA CA RA CA 6% 0% n/N BA CA n/N RA CA 11/173 0/42 BA: biatrial; RA: right atrial Biatrial versus left atrial CA One study reported blood loss and blood transfusion requirement after biatrial versus left atrial CA (see Table 36). In Takami et al. (1999) there was no significant difference in blood loss following biatrial versus left atrial CA. Although 38% (8/21) of biatrial versus 13% (2/15) patients required a blood transfusion after surgery, this was also not statistically significant. Table 36: Bleeding and blood transfusion- Biatrial versus left atrial CA Level Takami et al. 1999 III-3 Bleeding (mL) BA CA LA CA 708[576] N 687[302]pns BA CA RA CA 30 20 Blood transfusion (%) n/N BA CA LA CA BA CA RA CA Takami et al. 1999 III-3 38% 13%pns 8/21a 2/15a a: data restricted to patients who underwent MV surgery with or without tricuspid annuloplasty as a concomitant procedure; pns: statistically non-significant; BA: biatrial; LA: left atrial Kosakai maze versus CA One comparative study reported blood loss after Kosakai maze versus biatrial CA (see Table 37). In Nakajima et al. (2002) there was no significant difference in blood loss during surgery using the Kosakai maze or CA. However, blood loss from chest tube drainage was significantly greater after the Kosakai maze (mean 745 mL) versus CA (mean 590 mL, p<0.05). Table 37: Blood loss- Kosakai maze versus biatrial CA Level Bleeding (mL) N Kosakai maze BA CA Kosakai maze In operation In operation 960[880] 940[730]pns Nakajima et al. III-3 110 a Chest tube 2002 Chest tube 590[353]* 745[618] *: p<0.05; a: chest tube drainage in first 12 hours in ICU; BA: biatrial BA CA 110 Case Series Biatrial CA Case Series Two case series reported the incidence of bleeding after biatrial CA (see Table 38). In both Izumoto et al. (2000) and Yuda et al. (2001) a single patient (1%) suffered cerebral bleeding following biatrial CA. 41 Table 38: Bleeding- Biatrial CA Case Series Level Bleeding (%) n/N IV IV 1% 1% 1/104 1/94 Biatrial Izumoto et al. 2000 Yuda et al. 2001 Left atrial CA Case Series Two case series reported the incidence of bleeding following left atrial CA (see Table 39). In Imai et al. (2001) there were no cases of bleeding requiring re-operation, while in Manasse et al. (2003) 2% (2/95) patients were reopened on the first postoperative day due to bleeding. It was stated this bleeding was not related to the ablation procedure. One case series reported the requirement for blood transfusion after left atrial CA (see Table 39). In Kondo et al. (2003) 58% (18/31) of patients required a blood transfusion during surgery, while 65% (20/31) of patients had a blood transfusion postoperatively. Table 39: Bleeding and blood transfusion- Left atrial CA Case Series Level Bleeding (%) n/N Left atrial Imai et al. 2001 Manasse et al. 2003 IV IV 0/32 2/95 Kondo et al. 2003 IV 0% 2% Transfusion (%) During surgery 58% Postoperative 65% 18/31 20/31 Radiofrequency Ablation Non-randomised Comparative Studies Left atrial RFA versus CS One study reported the incidence of bleeding and blood loss after left atrial RFA versus CS alone (see Table 40). In Guang et al. (2002) there were 4% (4/96) of the left atrial RFA versus 3% (3/87) of the CS patients with bleeding reported as a complication. The p value was not reported. However, there was no significant difference in the quantity of blood loss for the left atrial RFA (mean 494 mL) versus CS (mean 476 mL) procedures (p>0.05). Table 40: Bleeding- Left atrial RFA versus CS Level Bleeding (%) LA RFA CS Guang et al. 2002 III-2 4% 3% Bleeding (mL) Guang et al. 2002 III-2 494[100] 476[116]pns LA: left atrial; pns: statistically non-significant; [ ]: SD n/N LA RFA 4/96 N 96 CS 3/87 87 Biatrial versus left atrial RFA One study reported the incidence of bleeding after biatrial versus left atrial CA (see Table 41). In Güden et al. (2002) there were 5% (2/39) of the biatrial versus 4% (1/23) of the left atrial CA patients with bleeding reported. In all patients the bleeding was associated with the left atrial appendage amputation site. The p value was not given. 42 One study reported transfusion requirement after biatrial versus left atrial CA (see Table 41). In Deneke et al. (2002a) 4% (2/49) patients needed a blood transfusion after biatrial RFA versus 5% (1/21) after left atrial RFA. The p value was not stated. Table 41: Bleeding- Biatrial versus left atrial CA Level Güden et al. 2002 III-2 Bleeding (%) BA RFA LA RFA 5% BA RFA 4% n/N LA RFA 2/39 1/23 2/49 1/21 Transfusion (%) Deneke et al. 2002a III-3 4% 5% BA: biatrial; LA: left atrial Case Series Biatrial RFA Five studies reported the incidence of bleeding after biatrial RFA (see Table 42). The median proportion of patients with bleeding was 2%, with a range of 0% to 7%. In Patwardhan et al. (2003) 2% (2/84) of patients had intracranial bleeding following warfarin. Hornero et al. (2002) stated that 6% (3/55) patients had bleeding requiring reoperation, while no patients required re-operation for bleeding in Sos et al. (2002). A single patient in Raman et al. (2003) suffered a fatal bleeding duodenal ulcer. Table 42: Bleeding- Biatrial RFA Case Series Level Bleeding (%) n/N Biatrial Hornero et al. 2002 IV 6% 3/55 Khargi et al. 2001a IV 7% 1/15 Patwardhan et al. 2003 a IV 2% 2/84 Raman et al. 2003 IV 1% 1/132 Sos et al. 2002 IV 0% 0/10 Median 2% Range (0%-7%) a: comparative study, but bleeding incidence only reported in biatrial RFA group; ( ): range Two studies reported blood loss after biatrial RFA (see Table 43). In Chen et al. (2001) the average maximum daily pericardial tube drainage in the first postoperative day was 365 mL, while in Sos et al. (2002) the mean postoperative blood loss was 741 mL. Table 43: Blood loss- Biatrial RFA Case Series Level Blood loss (mL) N Biatrial Chen et al. 2001a IV 365[116] 12 Sos et al. 2002 IV 741[475] 10 a: comparative study, blood loss not stated in CS group, data from RFII/III patients in Chen et al. 1998; maximum pericardial tube drainage in first 24 hours; [ ]: SD 43 Left atrial RFA Five studies reported the incidence of bleeding after left atrial RFA (see Table 44). The median proportion of patients with bleeding was 3%, with a range of 0% to 8%. In Starck et al. (2003) there were 3% (3/100) cases of bleeding: in two cases bleeding from the suture line of the resected left atrial appendage was managed successfully, while in the third there was a fatal massive haemorrhage from the suture line of the left atriotomy. Kottkamp et al. (1999) reported a single patient (1/12, 8%) with bleeding after CABG, resulting in cardiac tamponade. This patient had uneventful re-operation and recovery. Table 44: Bleeding- Left atrial RFA Case Series Level Bleeding (%) n/N IV IV IV IV IV 2% 8% 0% 3% 3% 3% (0%-8%) 3/132 1/12 0/95 1/40 3/100 Left atrial Benussi et al. 2002 Kottkamp et al. 1999 Müller et al. 2002 Ruchat et al. 2002 Starck et al. 2003 Median Range ( ): range Two case series reported blood loss following left atrial CA (See Table 45). Mean blood losses were 358 mL in Benussi et al. (2002) and 845 mL in Ruchat et al. (2002). Blood transfusion requirements were also reported by Benussi et al. (2000), in an earlier subset of the Benussi et al. (2002) study. In this study 15% (6/40) of patients required a blood transfusion following left atrial RFA. Table 45: Blood loss and transfusion- Left atrial RFA Case Series Level Left atrial Benussi et al. 2002 Ruchat et al. 2002 Blood loss (mL) N IV IV 358[204] 132 845[248] 40 Transfusion (%) n/N Benussi et al. 2002 IV 15% 6/40a a: patients from earlier study, Benussi et al. 2000; [ ]: SD Microwave Ablation Non-randomised Comparative Studies Left atrial MWA versus CS One study reported the incidence of bleeding after left atrial MWA versus CS alone (see Table 46). In Spitzer and Knaut (2002) there were no complications due to bleeding in either the MWA or CS groups. Table 46: Bleeding- MWA versus CS Level Spitzer and Knaut 2002 LA: left atrial III-2/3 Bleeding (%) LA MWA CS 0% 0% 44 n/N LA MWA 0/136 CS 0/51 Case Series Left atrial MWA One study reported the incidence of bleeding after left atrial MWA (see Table 47). In Venturini et al. (2003) there were no cases of bleeding requiring re-operation. Table 47: Bleeding- Left atrial MWA Case Series Level Bleeding (%) n/N IV 0% 0/41 Left atrial Venturini et al. 2003 MWA versus RFA One study reported bleeding complications and blood loss following MWA versus RFA (see Table 48). There were 9% (2/23) patients with bleeding complications after MWA versus 0% (1/19) after RFA. Average blood loss following MWA was 498 mL versus 526 mL after RFA. The p values were not given. Table 48: Bleeding and blood loss- MWA versus RFA Level Wisser et al. 2004 III-2/3 Wisser et al. 2004 [ ]: SD III-2/3 Bleeding (%) MWA RFA 9% 0% Blood loss (mL) 498[292] 526[145] n/N MWA 2/23 RFA 0/19 N 23 19 Maze-III Eight of the included Maze-III studies reported bleeding complications after surgery. A median proportion of 4% of patients suffered bleeding following surgery, with a range of 4% to 19%. Only two of the Maze-III studies reported blood loss after surgery. In Kim et al. (1999) blood loss was a mean of 822 mL in patients with redo surgery (n=14) and 985 mL in non-redo patients (n=61); and in Sandoval et al. (1996) there was intraoperative blood loss of greater than 600 mL in 33% (7/21) of patients. 5.1.3 Stroke/ transient ischaemic attack/ other thromboembolism One of the main risks associated with uncontrolled AF is of stroke and other thromboembolisms. Successful AF surgery should lead to a reduction in the risk of stroke and other thromboembolisms. As well as strokes and other thromboembolisms, transient ischaemic attacks were also included in this category. A transient ischaemic attack is the result of a brief interruption of blood flow to the brain, and is sometimes called a mini-stroke. Symptoms typically last eight to 14 minutes, although they may persist for 24 hours. Permanent damage is unlikely. A transient ischaemic attack requires prompt medical attention, otherwise the risk of stroke can be high. 45 Cryotherapy Ablation Non-randomised Comparative Studies Biatrial CA versus CS One study reported stroke incidence after biatrial CA versus CS (see Table 49). In Handa et al. (1999) there were no strokes after CA+CS versus 7% (4/58) reported after MV surgery alone. Follow-up was at least six months. The p value was not given. Table 49: Stroke- Biatrial CA+CS versus CS Level Handa et al. 1999 Stroke (%) BA CA CS III-2 0% 7% n/N BA CA n/N CS 39/39 58/58 Follow-up Mean 12 months ≥ 6 months BA: biatrial Biatrial CA versus Maze-III One study reported the incidence of stroke after CA versus Maze-III surgery (see Table 50). In Ishii et al. (2001) there were no strokes or other thromboembolisms in either group. Table 50: Stroke and other thromboembolism- Biatrial CA versus Maze-III Level Ishii et al. 2001 III-3 Stroke (%) BA CA Maze-III 0% 0% n/N BA CA Maze-III 0/32 0/13 Follow-up BA CA Maze-III 41.2[5.6] months > 12 months (34-52 months) [ ]: SD; ( ): range; BA: biatrial Kosakai maze versus CA One study reported the incidence of stroke after Kosakai maze versus CA (see Table 51). In Nakajima et al. (2002) there were 2% (2/110) of patients with a stroke after Kosakai maze versus 1% (1/110) after CA. The p value was not given. Freedom from stroke was also calculated using the Kaplan-Meier method. In the Kosakai maze patients, 99% were free from stroke at one year (n=110), two years (n=92) and three years (n=51) postoperatively. Values were the same in the CA group: 99% freedom from stroke at one (n=77) and two years (n=6). Table 51: Stroke- Kosakai maze versus CA Level Stroke (%) KM CA Nakajima et al. III-3 2% 2002 [ ]: SD; KM: Kosakai maze 1% n/N KM CA 2/110 1/110 Follow-up KM CA 64.1[27.4] 18.8[10.8] months months Case Series Biatrial CA Two case series reported the incidence of stroke or transient ischaemic attacks after biatrial CA (see Table 52). Izumoto et al. (2000) reported 5% (5/104) of patients had cerebrovascular accidents during the 60 month follow-up. Yuda et al. did not report strokes, but 2% (2/94) of patients had a transient ischaemic attack at 12 and 24 months postoperatively. Both patients were in regular heart rhythm. 46 Table 52: Stroke and transient ischaemic attack- Biatrial CA Case Series Level Stroke (%) n/N Follow-up IV 5% 5/104 IV 2% TIA 2/94 60 months Early: 3.1[3.3] months Late: 2.2[0.9] years Biatrial Izumoto et al. 2000 Yuda et al. 2001 TIA: transient ischaemic attack; [ ]: SD Left atrial CA Three case series reported stroke or transient ischaemic attacks in patients after left atrial CA (see Table 53). In Gaita et al. (2000) one patient died of a stroke at seven months postoperatively. The patient was not taking anticoagulants as a bioprosthesis had been used. Patients also had lethal strokes in Manasse et al. (2003): 3% (3/95) of patients had a lethal stroke by a mean of 36.4 months follow-up. In addition, 1% (1/95) of patients had a transient ischaemic attack in the perioperative period, which had resolved by hospital discharge. However, Kondo et al. (2003) reported no strokes in patients after left atrial CA, with a follow-up of at least 12 months. Table 53: Stroke and transient ischaemic attack- Left atrial CS Case Series Level Left atrial Gaita et al. 2000a Kondo et al. 2003 Manasse et al. 2003 Stroke (%) n/N Follow-up IV IV 3% 1/32 18 months 0% 0/31 (12-60 months) 3% 3/95 36.4 months IV 1% TIA 1/95 30 days a: comparative study but stroke incidence not reported in CS group; ( ): range; TIA: transient ischaemic attack Radiofrequency Ablation Non-randomised Comparative Study Biatrial RFA versus CS Two studies reported the incidence of stroke or other thromboembolisms after biatrial RFA versus CS (see Table 54). In Chen et al. (2001) there was one patient (1/13, 8%) who had a perioperative stroke after the first RFA lesion set, but no patients had a stroke after either the second RFA lesion set, or CS alone. Patwardhan et al. (2003) reported 1% (1/84) of patients with a perioperative thromboembolism after biatrial RFA. The patient had a fatal valvular thrombosis. Following CS alone, 2% (1/64) of patients had a stroke in-hospital, while 5% (3/64) were hospitalised for a stroke during the six month follow-up. Table 54: Stroke and other thromboembolism- Left atrial RFA versus CS Level Stroke (%) n/N Follow-up BA RFA CS BA RFA CS Chen et al. 2001 RFA1: 8% 1/13 0% 0/58 30 days III-2 RFA2: 0% 0/48 Patwardhan et 1% OT 2% 1/64 30 days III-3 1/84 al. 2003 5% 3/64 6 months RFA1: first RFA lesion set; RFA2: second RFA lesion set; OT: other thromboembolism; BA: biatrial 47 Left atrial RFA versus CS Two studies reported stroke and transient ischaemic attack incidence after left atrial RFA versus CS alone (see Table 55). No strokes occurred after either left atrial RFA versus CS at up to 30 days postoperatively in Guang et al. (2002). However, in Mantovan et al. (2003) after left atrial RFA 1% (1/103) of patients had a fatal stroke; 1% (1/103) had a transient ischaemic attack; and 3% (3/103) suffered from left atrial thrombi. In the group with CS alone, one patient (1/27, 4%) had a fatal abdominal infarction. Table 55: Stroke and transient ischaemic attack- Left atrial RFA versus CS Level Stroke (%) n/N Follow-up LA RFA CS LA RFA CS Guang et al. 2002 III-2 0% 0% 0/96 0/87 30 days Mantovan et al. III-3 1% S NS 1/103 NS 30 days 2003 1% TIA NS 1/103 NS 3% OT 4% OT 3/103 1/27 TIA: transient ischaemic attack; OT: other thromboembolism; NS: not stated; LA: left atrial Biatrial versus left atrial RFA One study reported the incidence of transient ischaemic attacks after biatrial versus left atrial RFA (see Table 56). In the patients with biatrial RFA, there were 4% (2/49) of transient ischaemic attacks in the after biatrial RFA, versus 10% (2/21) of patients after left atrial RFA (Deneke et al. 2002a. The p value was not given. Table 56: Transient ischaemic attack- Biatrial versus left atrial RFA Level Stroke (%) n/N BA RFA LA RFA BA RFA LA RFA Deneke et al. 2002a III-3 4% TIA 10% TIA 2/49 2/21 BA: biatrial; LA: left atrial; TIA: transient ischaemic attack Follow-up First days Case Series Biatrial RFA Six case series reported the incidence of stroke, other thromboembolism, or transient ischaemic attacks after biatrial RFA (see Table 57). The incidence of stroke after biatrial RFA ranged from 0% (Prasanna et al. 2001) to 2% (1/55, Hornero et al. 2002). Follow up was from 30 days (Hornero et al. 2002; Sie et al. 2001) to more than three years (Prasanna et al. 2001). Transient ischaemic attacks occurred in 2% (1/55, Hornero et al. 2002) to 10% (1/10, Sos et al. 2002) of patients after biatrial RFA. In Hornero et al. (2002) and Sos et al. (2002) the transient ischaemic attacks occurred within three days of surgery, while in Thomas et al. (2003) 4% (2/47) of patients had transient ischaemic attacks in late follow-up. Prasanna et al. (2001) and Raman et al. (2003) reported no thromboembolisms occurred after biatrial RFA. Follow-up was at least three months. 48 Table 57: Stroke, other thromboembolisms and transient ischaemic attacks- Biatrial RFA Case Series Level Biatrial Hornero et al. 2002 Stroke (%) n/N 2% S 1/55 2% TIA 1/55 Prasanna et al. 2001 0% S 0/25 IV 0% OT 0/25 Raman et al. 2003 IV 0% OT 0/132 Sie et al. 2001 IV 1% S 1/122 Sos et al. 2002 IV 10% TIA 1/10 Thomas et al. 2003 IV 4% TIA 2/47 S: stroke; TIA: transient ischaemic attack; OT: other thromboembolism IV Follow-up 30 days (3.2-3.8 years) 3 months 30 days Day 3 (0.6-4.2 years) Left atrial RFA Seven case series reported the incidence of stroke, other thromboembolism or transient ischaemic attacks in patients following left atrial RFA (see Table 58). Six studies reported the incidence of stroke, with a median proportion of 2%, and range 0% to 9%. Follow-up was to 30 days in five studies, and a mean of 16.9 months in the other study (Benussi et al. 2002). There were no strokes in two of the studies (Kress et al. 2002; Starck et al. 2003). In Benussi et al. (2002) a stroke occurred in 2% (2/132) patients in early and 1% (1/132) of patients at later follow-up. No thromboembolisms occurred up to 30 days follow-up in either Starck et al. (2003) or Williams et al. (2001). One study reported 3% (1/40) of patients had a transient ischaemic attack (Ruchat et al. 2002). This occurred on the third postoperative day, when it was stated the anticoagulation therapy was not optimal. Table 58: Stroke, other thromboembolism and transient ischaemic attack- Left atrial RFA Case Series Level Stroke (%) n/N Follow-up Left atrial Benussi et al. 2002 2% S 2/132 30 days 1% S 1/132 16.9[14.2] months 2% S 3/132 Total Kress et al. 2002 IV 0% S 0/23 30 days Le Tourneau et al. 2003 IV 9% S 6/70 30 days Müller et al. 2002 IV 2% S 2/95 30 days Ruchat et al. 2002 IV 3% TIA 1/40 Day 3 Starck et al. 2003 0% S 0/100 IV 30 days 0% OT 0/100 Williams et al. 2001 IV 0% OT 0/48 30 days Median (stroke) 2% Range (stroke) (0%-9%) S: stroke; TIA: transient ischaemic attack; OT: other thromboembolism; [ ]: SD; ( ): range IV Benussi et al. (2002) also stated the actuarial freedom from stroke. At three years, 98% of patients were free of stroke (95% CI: 88% to 99%). 49 Microwave Ablation Case Series Biatrial MWA One case series reported incidence of stroke after biatrial MWA (see Table 59). No strokes occurred in Chiappini et al. (2003) at up to a 30 day follow-up. Table 59: Stroke- Biatrial MWA Case Series Level Stroke (%) n/N Follow-up IV 0% 0/10 30 days Biatrial Chiappini et al. 2003 Left atrial MWA Two case series reported the incidence of stroke after left atrial MWA (see Table 60). There were no strokes to 12 months follow-up in Spitzer and Knaut (2002), and 2% (1/42) of strokes at one month or more postoperatively in Zembala et al. (2003). Table 60: Stroke- Left atrial MWA Case Series Level Stroke (%) n/N Left atrial Spitzer and Knaut 2002a IV 0% 0/136 Zembala et al. 2003 IV 2% 1/42 a: comparative study but stroke not reported in CS; ( ): range Follow-up 12 months (1-14 months) MWA versus RFA The incidence of stroke was reported in one study after MWA versus RFA (see Table 61). In Wisser et al. (2004) there were no strokes in either group, with mean follow-up of 24.2 months in the MWA versus 12.1 months in the RFA groups. Table 61: Stroke- MWA versus RFA Level Wisser et al. 2004 †: p<0.01 III-2/3 Stroke (%) MWA RFA 0% 0% n/N MWA RFA 0/23 0/19 Follow-up MWA RFA 24.2[1.3] months 12.1[1.2] months† Maze-III Nine of the included Maze-III studies reported the incidence of stroke. A median proportion of 0% of patients had a stroke following surgery, with a range of 0% to 5%. Other thromboembolisms were also reported in three studies, with a median proportion of 1%, and a range of 0% to 2%. Transient ischaemic attacks occurred in a median of 1% of patients across three studies (range 0% to 1%). 5.1.4 Complications related to cardiac surgery A number of complications are related to any form of cardiac surgery, rather than intraoperative ablation per se. These include: wound infection, sternal instability, mediastinitis, pulmonary insufficiency, renal failure and intra-aortic balloon pumping. Although these complications can occur with any form of cardiac surgery, they need to be considered in case intraoperative ablation increases their incidence, which may be related to greater manipulation, or longer operative times. 50 Pulmonary insufficiency is a possible exception in this group of complications as, if ablation around the pulmonary vessels results in stenosis of the pulmonary veins, it may lead to pulmonary insufficiency. When pulmonary insufficiency is reported as an acute complication following surgery this is less likely, but there is the possibility later cases are related to the ablation procedure. Wound infection/sternal instability/mediastinitis Cryotherapy Ablation Non-randomised Comparative Studies Kosakai maze versus CA One study reported the incidence of mediastinitis after Kosakai maze versus CA (see Table 62). In Nakajima et al. (2002) there were 1% (1/110) of patients with mediastinis after CA, with no cases of mediastinitis after Kosakai maze. The p value was not given. Table 62: Mediastinitis- KM versus CA Level Nakajima et al. 2002 Mediastinitis (%) Kosakai maze CA 0% 1% III-3 n/N Kosakai maze 0/110 CA 1/110 Case Series Biatrial CA One case series reported the incidence of wound infection after biatrial CA (see Table 63). In Izumoto et al. (2000) 3% (3/87) of patients had wound infections following biatrial CA. Table 63: Wound infection- Biatrial CA Case Series Biatrial Izumoto et al. 2000 Level Wound infection (%) n/N IV 3% 3/87 Radiofrequency Ablation Randomised Controlled Trial Biatrial RFA versus CS One RCT reported the incidence of wound infection/sternal instability or mediastinitis after biatrial RFA versus CS (see Table 64). In Khargi et al. (2001) there were 20% (4/15) of patients who had wound infection/sternal instability after biatrial RFA versus 7% (2/15) of patients after CS alone (RR 2.36 95% CI: 0.36 to 15.45, p=0.37). In addition one patient (7%) had mediastinitis following biatrial RFA, whereas no cases of mediastinitis occurred after CS alone (RR 3.21 95%CI: 0.12 to 85.20, p=0.49). 51 Table 64: Wound infection/sternal instability or mediastinitis- Biatrial RFA versus CS Level (%) n/N BA RFA CS BA RFA CS 20% WI/SI 7% WI/SIpns 4/15 1/15 7% M 0% Mpns 1/15 0/15 WI/SI: wound infection/sternal instability; M: mediastinitis; BA: biatrial; pns: statistically non-significant Khargi et al. 2001 II Non-randomised Comparative Studies Biatrial RFA versus CS One study reported the incidence of mediastinitis after biatrial RFA versus CS (see Table 65). In Patwardhan et al. (2003) there were 1% (1/84) of patients with mediastinitis after biatrial RFA versus 2% (1/64) after CS alone. The p value was not given. Table 65: Mediastinitis- Biatrial RFA versus CS Level Patwardhan et al. 2003 BA: biatrial III-3 Mediastinitis (%) BA RFA CS 1% 2% n/N BA RFA 1/84 CS 1/64 Biatrial versus left atrial RFA One study reported the incidence of mediastinitis after biatrial versus left atrial RFA (see Table 66). In Deneke et al. (2002a) there were 2% (1/49) of patients with mediastinitis after biatrial versus 5% (1/21) of patients after left atrial RFA. The mediastinitis was fatal in both cases. Table 66: Mediastinitis- Biatrial versus left atrial RFA Level Deneke et al. 2002a III-3 BA: biatrial; LA: left atrial Mediastinitis (%) BA RFA LA RFA 2% 5% n/N BA RFA 1/49 LA RFA 1/21 Case Series Biatrial RFA Case Series One case series reported the incidence of wound infection after biatrial RFA (see Table 67). Sie et al. (2001) stated 1% (1/122) of patients had a sternal wound infection after biatrial RFA. Table 67: Wound infection- Biatrial RFA Case Series Biatrial Sie et al. 2001 Level Wound infection (%) n/N IV 1% 1/122 Left atrial RFA Case Series One case series reported the incidence of wound infection after left atrial RFA (see Table 68). In Benussi et al. (2002) one patient (1/132, 1%) had a deep sternal wound infection after left atrial RFA. 52 Table 68: Wound infection- Left atrial RFA Case Series Left atrial Benussi et al. 2002 Level Wound infection (%) n/N IV 1% 1/132 Maze-III Two of the Maze-III included studies reported wound infection after surgery, with 4% in Albåge et al. (2000) and 3% in Millar et al. (2000). Mediastinitis was reported in only one study, with 1% of patients (2/198) having the condition. Pulmonary insufficiency Pulmonary insufficiency is a complication of any cardiac surgery. However, it is of particular concern following ablative surgery to treat AF, as most of the lesion patterns are close to the pulmonary veins, and pulmonary vein stenosis is a potential complication. In addition, pulmonary vein stenosis is not an uncommon complication following catheter ablation of AF (Saad et al. 2003). Cryotherapy Ablation Non-randomised Comparative Studies Kosakai maze versus CA One study reported the incidence of pulmonary insufficiency after Kosakai maze versus CA (see Table 69). In Nakajima et al. (2002) there were 1% (1/110) of patients with pulmonary insufficiency after the Kosakai maze versus none after CA. The patient required a tracheotomy. Table 69: Pulmonary insufficiency- Kosakai maze versus CA Level Nakajima et al. 2002 III-3 Pulmonary insufficiency (%) Kosakai maze CA 1% 0% n/N Kosakai maze 1/110 n/N CA 0/110 Follow-up Perioperative Case Series Biatrial CA Case Series Two case series reported the incidence of pulmonary insufficiency after biatrial CA (see Table 70). Similar rates of pulmonary insufficiency were present in both studies: 6% (5/87) in Izumoto et al. (1998) and 8% (1/12) in Morishita et al. 2000. Izumoto et al. (1998) classified pulmonary insufficiency as requirement for intubation more then 48 hours, or need for re-intubation due to respiratory failure. Table 70: Pulmonary insufficiency- Biatrial CA Case Series Level Pulmonary insufficiency (%) Biatrial Izumoto et al. 1998a IV 6% Morishita et al. 2000 IV 8% a: an earlier subset of the Izumoto et al. (2000) patients 53 n/N Follow-up 5/87 1/12 30 days Not stated Radiofrequency Ablation Randomised Controlled Trial Biatrial RFA versus CS One RCT reported the incidence of pulmonary insufficiency after biatrial RFA versus CS (see Table 71). In Khargi et al. (2001) there was one patient in each group with fatal pulmonary insufficiency during longer term follow-up. Table 71: Pulmonary insufficiency- Biatrial RFA versus CS Level Khargi et al. 2001 BA: biatrial II Pulmonary insufficiency (%) BA RFA CS 7% 7% n/N BA RFA 1/15 Follow-up CS 1/15 21-22 months Left atrial RFA versus CS One study reported the incidence of pulmonary insufficiency after left atrial RFA versus CS (see Table 72). In Guang et al. (2002) there were 2% (2/96) of left atrial RFA and 2% (2/87) of CS patients with pneumothorax after surgery. Table 72: Pulmonary insufficiency- Left atrial RFA versus CS Level Pulmonary insufficiency (%) LA RFA CS Guang et al. 2002 III-2 2% 2%pns LA: left atrial; pns: statistically non-significant n/N LA RFA CS 2/96 2/87 Follow-up 30 days Case Series Biatrial RFA Two case series reported the incidence of pulmonary insufficiency after biatrial RFA (see Table 73). In Deneke et al. (2002a) 4% (2/49) of patients suffered from fatal pulmonary insufficiency, at seven and sixteen months postoperatively. Sos et al. (2002) reported that one patient (1/10, 10%) required prolonged intubation after surgery for severe pulmonary hypertension, later complicated by pneumonia. Table 73: Pulmonary insufficiency- Biatrial RFA Case Series Level Pulmonary insufficiency (%) n/N Biatrial Deneke et al. 2002aa IV 4% 2/49 Sos et al. 2002 IV 10% 1/10 a: comparative study but pulmonary insufficiency not reported in CS group Follow-up 16 months 30 days Left atrial RFA Three case series reported the incidence of pulmonary insufficiency after left atrial RFA (see Table 74). The median incidence of pulmonary insufficiency was 2% (range 1% to 10%) in the three studies, with follow-up to 30 days. In Benussi et al. (2002) one patient (1/132, 1%) had pulmonary insufficiency following prolonged ventilatory support and bilateral pneumonia, and died on day 12. Pulmonary insufficiency was present in 2% (2/103) of patients in Mantovan et al. (2003), with pneumothorax in one patient and pleural effusion in another. Müller et al. (2002) reported that 54 10% (9/95) of patients required ventilatory support for more than 24 hours, with two having left-sided pleural effusion due to fluid retention. Table 74: Pulmonary insufficiency- Left atrial RFA Case Series Level Pulmonary insufficiency (%) n/N Left atrial Benussi et al. 2002 IV 1% 1/132 Mantovan et al. 2003a IV 2% 2/103 Müller et al. 2002 IV 10% 9/95 Median 2% Range (1%-10%) a: comparative study but pulmonary insufficiency not reported in CS group Follow-up 30 days 30 days 30 days Microwave Ablation Case Series Left atrial MWA None of the studies reported the incidence of pulmonary insufficiency after left atrial MWA. However, Knaut et al. (2002) reported that no cases of stenosis of the pulmonary veins were observed in ten patients after left atrial MWA. There were also no cases of either pulmonary vein stenosis or pulmonary hypertension in 42 patients who had left atrial MWA in Zembala et al. (2003). Maze-III Three of the included Maze-III studies reported pulmonary insufficiency after surgery. A median proportion of 7% of patients had pulmonary insufficiency following Maze-III, with a range of 1% to 8%. Low Cardiac Output Cryotherapy Ablation Non-randomised Comparative Studies CA versus Maze-III One study reported the incidence of low cardiac output after CA versus Maze-III (see Table 75). In Kim et al. (2001) 4% (1/23) of patients had low cardiac output after CA versus 6% (1/18) after Maze-III. The p value was not given. Table 75: Low cardiac output- CA versus Maze-III Level Kim et al. 2001 III-3 Low cardiac output (%) CA Maze-III 4% 6% 55 n/N CA 1/23 Maze-III 1/18 Case Series Biatrial CA One case series reported the incidence of low cardiac output after biatrial CA (see Table 76). Izumoto et al. (1998) reported that 2% (2/87) of patients had low cardiac output after biatrial CA. Table 76: Low cardiac output- Biatrial CA Case Series Level Low cardiac output (%) n/N IV 2% 2/87 Biatrial Izumoto et al. 1998 Left atrial CA Two case series reported the incidence of low cardiac output after left atrial CA (see Table 77). The incidence of low cardiac output was 3% (1/31) in Kondo et al. (2003) and 8% (8/95) in Manasse et al. (2003). Table 77: Low cardiac output- Biatrial CA Level Low cardiac output (%) n/N IV IV 3% 8% 1/31 8/95 Left atrial Kondo et al. 2003 Manasse et al. 2003 Radiofrequency Ablation Non-randomised Comparative Studies Left atrial RFA versus CS One study reported the incidence of low cardiac output after left atrial RFA versus CS (see Table 78). In Patwardhan et al. (2003) 8% (7/84) of the left atrial RFA versus 13% (8/64) of the CS patients suffered low cardiac output. The low cardiac output was fatal in all cases. The p value was not given. Table 78: Low cardiac output- Left atrial RFA versus CS Level Patwardhan et al. 2003 LA: left atrial III-3 Low cardiac output (%) LA RFA CS 8% 13% n/N LA RFA 7/84 CS 8/64 Case Series Biatrial RFA Two case series reported the incidence of low cardiac output after biatrial RFA (see Table 79). There were 2% of patients in both studies with low cardiac output (Raman et al. 2003; Sie et al. 2001). In each report low cardiac output was given as the cause of death. 56 Table 79: Low cardiac output- Biatrial RFA Case Series Biatrial Raman et al. 2003 Sie et al. 2001 Level Low cardiac output (%) n/N IV IV 2% 2% 3/132 2/122 Left atrial RFA One case series reported the incidence of low cardiac output after left atrial RFA (see Table 80). In Kottkamp et al. (1999) low cardiac output was the cause of death in one patient (1/12, 8%). Table 80: Low cardiac output- Left atrial RFA Case Series Left atrial Kottkamp et al. 1999 Level Low cardiac output (%) n/N IV 8% 1/12 Microwave Ablation Case Series Left atrial RFA One case series reported the incidence of low cardiac output after left atrial MWA (see Table 81). Spitzer and Knaut reported that low cardiac output was the cause of death in 1% (1/136) of patients. Table 81: Low cardiac output- Left atrial MWA Case Series Left atrial Spitzer and Knaut 2002 Level Low cardiac output (%) n/N IV 1% 1/136 MWA versus RFA One study reported the incidence of low cardiac output after MWA versus RFA (see Table 82). In Wisser et al. (2004) there was one patient in each group with low cardiac output after surgery; 4% (1/23) in the MWA versus 5% (1/19) in the RFA group. The p value was not given. Table 82: Low cardiac output- MWA versus RFA Level Wisser et al. 2004 III-2/3 Low cardiac output (%) MWA RFA 4% 5% n/N MWA 1/23 RFA 1/19 Maze-III Three of the included Maze-III studies reported low cardiac output after surgery. A median proportion of 5% of patients had low cardiac output following Maze-III surgery, with a range of 2% to 15%. 57 Renal failure Acute renal failure is a known complication following cardiopulmonary bypass and cardiac surgery. Cryotherapy Ablation Non-randomised Comparative Studies CA versus Maze-III One study reported the incidence of renal failure after CA versus Maze-III surgery (see Table 83). In Kim et al. (2001) there were 4% (1/23) of CA versus 6% (1/18) of Maze-III patients who had acute renal failure after surgery. The p value was not stated. Table 83: Renal failure- CA versus Maze-III Level Kim et al. 2001 III-3 Renal failure (%) CA Maze-III 4% 6% CA 1/23 n/N Maze-III 1/18 Kosakai maze versus CA One study reported the incidence of renal failure after the Kosakai maze versus CA (see Table 84). In Nakajima et al. (2002) there were 3% (3/110) of patients with acute renal failure after the Kosakai maze versus none after CA. The p value was not stated. Table 84: Renal failure- Kosakai maze versus CA Level Nakajima et al. 2002 III-3 Renal failure (%) Kosakai maze CA 3% 0% n/N Kosakai maze 3/110 n/N CA 0/110 Case Series Biatrial CA One case series reported the incidence of renal failure after biatrial CA (see Table 85). Izumoto et al. (1998) stated that 1% (1/87) of patients had acute renal failure after biatrial CA, with the single case being fatal. Table 85: Renal failure- Biatrial CA Case Series Level Renal failure (%) Biatrial Izumoto et al. 1998a IV 1% a: earlier subset of Izumoto et al. (2000) patients n/N 1/87 Left atrial CA Two case series reported the incidence of renal failure after left atrial CA (see Table 86). In Manasse et al. (2003) one patient (1/95, 1%) required dialysis after surgery, while in Kondo et al. (2003) one patient (1/31, 3%) had fatal acute renal failure after left atrial RFA. 58 Table 86: Renal failure- Biatrial CA Case Series Left atrial Kondo et al. 2003 Manasse et al. 2003 Level Renal failure(%) n/N IV IV 3% 1% 1/31 1/95 Maze-III Three of the included Maze-III studies reported renal failure after surgery. A median proportion of 2% of patients had renal failure following Maze-III surgery, with a range of 1% to 3%. Intra-aortic balloon pump (IABP) An intra-aortic balloon pump (IABP) is a device which increases oxygen supply to the heart, and is usually used for a short time while waiting for the heart to regain function after cardiac surgery. A large tube is inserted through a catheter into the femoral artery, then threaded into the aorta. The tube is attached to a balloon pump machine, and air is pumped in, resulting in inflation or deflation of the balloon at specific times during the heart beat. This helps to push blood forward into the body, and backwards into the heart’s blood vessels. Cryotherapy Ablation Non-randomised Comparative Studies Left atrial CA+CS versus CS One study reported the proportion of patients requiring IABP after left atrial CA+CS versus CS (see Table 87) In Gaita et al. (2000) 3% (1/32) of patients required IABP after left atrial CA+CS versus none after CS alone. The p value was not given. Table 87: IABP- Left atrial CA+CS versus CS Level IABP (%) LA CA CS Gaita et al. 2000 IV 3% 0% LA: left atrial; IABP: intra-aortic balloon pumping n/N LA CA 1/32 CS 0/18 CA versus Maze-III One study reported the use of IABP after CA versus Maze-III (see Table 88). Kosakai et al. (1995) stated 14% (2/14) of patients required IABP after the first ablation set, and 3% (2/70) after the Kosakai maze. In comparison, no patients had IABP after Maze-III surgery. No difference was seen between IABP use in the CA versus Maze-III groups (p>0.05). Table 88: IABP- CA versus Maze-III Level IABP (%) n/N n/N CA Maze-III CA Maze-III Kosakai et al. 1995 III-2/3 CA1: 14% 14/14 0%pns 17/17 KM: 3% 70/70 CA1: first CA lesion set; KM: Kosakai maze; pns: statistically non-significant, KM versus Maze-III; IABP: intra-aortic balloon pumping 59 Case Series Left atrial CA Two case series reported the use of IABP after left atrial CA (see Table 89). Manasse et al. (2003) used IABP in one patient (1/95, 1%), while no patients in Imai et al. (2001) used this technique. Table 89: IABP- Left atrial CA Case Series Level IABP (%) Left atrial Imai et al. 2001 IV 0% Manasse et al. 2003 IV 1% IABP: intra-aortic balloon pumping n/N 0/32 1/95 Radiofrequency Ablation Case Series Biatrial RFA Two case series reported the use of IABP after biatrial RFA (see Table 90). The proportion of patients who underwent IABP was 1% (1/132) in Raman et al. (2003) and 6% (7/122) in Sie et al. (2001). Table 90: IABP- Biatrial RFA Case Series Level IABP (%) Biatrial Raman et al. 2003 IV 1% Sie et al. 2001 IV 6% IABP: intra-aortic balloon pumping n/N 1/132 7/122 MWA versus RFA One study reported the use of IABP after MWA versus RFA (see Table 91). In Wisser et al. (2004) there was one patient requiring IABP after MWA (1/23, 4%) versus no patients following RFA (1/19). Table 91: IABP- MWA versus RFA Level Wisser et al. 2004 III-2/3 IABP: intra-aortic balloon pumping IABP (%) MWA RFA 4% 0% n/N MWA 1/23 n/N RFA 0/19 Maze-III Two of the included Maze-III case series reported the use of intra-aortic pumps after surgery. There were 1% (1/76) of patients requiring intra-aortic pump treatment in Millar et al. (2000) and 4% (9/198) in Prasad et al. (2003). 60 5.1.5 Oesophageal injury The oesophagus lies immediately beneath the left atrium, and can be vulnerable to damage during procedures involving the pulmonary veins. If damage to the oesophagus is severe enough, perforation can result. Oesophageal perforation is associated with a high risk of morbidity and mortality (Brinster et al. 2004); even with optimal treatment mortality is approximately 20%. Oesophageal perforation may also rarely follow transoesophageal echocardiography (Massey et al. 2000). Radiofrequency Ablation Case Series Left atrial RFA In Mantovan et al. (2003) one patient had a fatal oesophageal perforation following left atrial RFA. The patient complained of progressive fainting and dysphagia several days after surgery, and gastroscopy revealed an oesophageal perforation. During autopsy there were no left atrial perforations, but the inferior third of the oesophagus showed inflammatory necrosis with fistulation into the right inferior lobar bronchus. Mohr et al. (2002) and Starck et al. (2003) reported no oesophageal injury occurred in patients in their studies after left atrial RFA. However, Starck et al. (2003) in an addendum to their publication, wrote that ‘In the first 100 cases reported we did not experience any serious radiofrequency ablation related complications; however in our 249th case, we unfortunately saw an (o)esophageal perforation with lethal outcome…’. Fatal oesophageal perforation was also described 22 days postoperatively after left atrial RFA in a case report (Sonmez et al. 2003; see Appendix D.12). Microwave Non-randomised Comparative Studies Left atrial MWA versus CS Spitzer and Knaut (2002) reported no oesophageal injury occurred in either the left atrial MWA or CS groups. Maze-III No cases of oesophageal perforation were reported in the fifteen included Maze-III studies. 61 5.1.6 Other major perioperative complications Other major perioperative complications were included as miscellaneous reported disorders that did not fit into the previous categories. These included septicaemia, left ventricular rupture, and coronary artery stenosis. Cryotherapy Ablation Left atrial CA versus CS In Gaita et al. (2000) one patient (1/32, 3%) had fatal septicaemia and died three weeks following left atrial RFA versus no cases of septicaemia after CS alone (see Table 92). Table 92: Miscellaneous complications- Left atrial CA versus CS Level Gaita et al. 2000 LA: left atrial III-2 Complication septicaemia LA CA+CS (%) n/N 3% 1/32 CS (%) 0% n/N 0/18 Kosakai maze versus CS In Nakajima et al. (2002) there were 5% (5/110) patients who required high dose catecholamines for support after the Kosakai maze versus no patients requiring high dose catecholamines after CA (see Table 93). Table 93: Miscellaneous complications- Kosakai maze versus CS Level Nakajima et al. 2002 Complication III-3 Requirement for high dose catecholamine Kosakai maze (%) n/N (%) n/N 5% 0% 0/110 5/110 CA Case Series Biatrial CA Other serious complications were reported in two case series after biatrial CA (see Table 94). In Fukada et al. (1998) it was stated there were no further serious complications in 29 patients after biatrial CA. However, in Izumoto et al. (2000) one patient (1/104, 1%) had a circumflex artery stenosis, which was considered to be related to the site of CA. The patient required redo surgery, including CABG. In addition, two patients (2/104, 2%) had left ventricular rupture following surgery, fatal in both cases. Table 94: Miscellaneous complications- Biatrial CA Case Series Biatrial Fukada et al. 1998 Izumoto et al. 2000 Level Complication (%) n/N IV Serious complications Circumflex artery stenosis Left ventricular rupture 0% 1% 2% 0/29 1/104 2/104 IV 62 Left atrial CA Two case series reported other complications after left atrial CA. In Sueda et al. (2001) it was reported no patients had any further serious complications (see Table 95). However, in Manasse et al. (2003) there was one serious complication: an operative death was directly related to the CA procedure, with a tear of the posterior left atrial wall as a result of retracting the cryoprobe before thawing was completed. Table 95: Miscellaneous complications- Left atrial CA Case Series Level Complication (%) n/N IV IV Tear of left atrial wall Serious complications 1% 0% 1/95 0/12 Left atrial Manasse et al. 2003 Sueda et al. 2001 Radiofrequency Ablation Non-randomised Comparative Study Biatrial versus left atrial RFA One comparative study reported the incidence of pericardial effusion after biatrial versus left atrial RFA (see Table 96). In Deneke et al. (2002a) there were 4% (2/49) patients with pericardial effusion after biatrial RFA versus 5% (1/21) after left atrial RFA. The p value was not given. Table 96: Miscellaneous complications- Biatrial versus left atrial RFA Level Deneke et al. 2002a III-3 BA: biatrial; LA: left atrial Complication BA RFA (%) n/N 4% 2/49 Pericardial effusion LA RFA (%) n/N 5% 1/21 Case Series Biatrial RFA One case series reported other complications after biatrial RFA (see Table 97). In Sie et al. (2001) two other serious complications were reported. In two patients rupture of the right ventricle occurred, not fatal in either case. One patient had a fatal mitral annulus rupture intraoperatively. There was also one case of non-fatal endocarditis. Table 97: Miscellaneous complications- Biatrial RFA Case Series Level Complication (%) n/N IV Right ventricular perforation Rupture of mitral annulus Endocarditis 2% 1% 1% 2/122 1/122 1/122 Biatrial Sie et al. 2001 Left atrial RFA Three case series reported other serious complications after left atrial RFA (see Table 98). In Le Tourneau et al. (2003) one patient had RFA induced stenosis of the circumflex artery. This study was in abstract form, and further details of the patient were not given. In two studies no other serious complications occurred (Benussi et al. 2002; Geidel et al. 2003). 63 Table 98: Miscellaneous complications- Left atrial RFA Case Series Left atrial Benussi et al. 2002 Geidel et al. 2003 Le Tourneau et al. 2003 Level Complication (%) n/N IV IV IV Procedure related complications Severe complications Circumflex artery stenosis 0% 0% 1% 0/132 0/29 1/70 Microwave Ablation Case Series Left atrial MWA Two case series reported other complications following left atrial MWA (see Table 99). In Spitzer and Knaut (2002) one patient (1/136) had ventricular fibrillation which required resuscitation. However, in Zembala et al. (2003) there were no major in-hospital complications. Table 99: Miscellaneous complications- Left atrial MWA Case Series Level Complication Left atrial Spitzer and Knaut Ventricular fibrillation necessitating IV 2002a resuscitation Zembala et al.2003 IV Major in-hospital complications a: comparative study, but results not stated in CS group (%) n/N 1% 1/136 0% 0/42 MWA versus RFA One study reported a serious complication after MWA versus RFA (see Table 100). In Wisser et al. (2004) on the first postoperative day, there were 4% (1/23) of MWA versus 5% (1/19) of RFA patients with severe systemic inflammatory response syndrome. Table 100: Miscellaneous complications- MWA versus RFA Level Wisser et al. 2004 III-2/3 Complication Severe systemic inflammatory response syndrome MWA (%) n/N (%) n/N 4% 5% 1/19 1/23 RFA Maze-III Other major complications were reported in six of the included Maze-III studies. Three studies reported pericardial or pleural effusion in 3% to 35% of patients (Albåge et al. 2000; Lonnerholm et al. 2000; Pasic et al. 1999); one study reported aggravation of hemiplegia in 1% of patients (Kim et al. 1999); two studies reported postoperative myocardial infarction (Raanani et al. 2001; Sundt III et al. 1997); and one study reported pancreatitis (Sundt III et al. 1997). 64 5.2 Efficacy Heart rhythm The primary outcome for an operation to treat atrial fibrillation (AF) is the return of normal heart rhythm. Normal heart rhythm, or sinus rhythm (SR), is characterised by a coordinated contraction of the atria and ventricles. Other possible outcomes include the continuation or recurrence of AF, atrial flutter, junctional rhythm, other atrial tachycardias, and pacemaker rhythm. Follow-up periods differed greatly between the studies, and results must be considered in terms of this variation. In the early postoperative period, up until the time the atria heal from the surgery, the local refractory periods of the heart may be shortened. This means postoperative arrhythmias are more common than at later follow-up (Cox 2004). 5.2.1 Sinus rhythm (SR) Cryotherapy Ablation Non-randomised comparative studies Biatrial CA + CS versus CS Three studies reported the incidence of SR after biatrial CA+CS versus CA alone (see Table 101). The median proportion of patients with SR successfully restored after biatrial CA was 78% (range 69% to 82%) compared to 20% (range 0% to 53%) in the group with CS alone. Follow-up periods were at least six months. The p values were not reported. One study reported more biatrial CA patients in SR in early versus later follow-up (Sueda et al. 1997), while in another study more patients were in SR at later follow-up (Handa et al. 1999). Table 101: Sinus rhythm- Biatrial CA+CS versus CS Level Handa et al. 1999 III-2 Sueda et al. 1997 III-3 Yuda et al. 2004 III-3 Median Range [ ]: SD; BA: biatrial SR (%) BA CA CS 72% 43% 82% 53% 86% 27% 78% 20% 69% 0% 78% 20% (69%-82%) (0%-53%) n/N BA CA 28/39 32/39 31/36 28/36 18/26 n/N CS 25/58 31/58 4/15 3/15 0/6 Follow-up Hospital discharge Mean 21 months (≥ 6 months) Hospital discharge 6 months 14.6[6.6] months (> 2 months) Left atrial CA + CS versus CS One study reported the incidence of SR after left atrial CA+CS versus CS alone (see Table 102). A statistically significant difference in patients in SR was reported by Gaita et al. (2000), with SR in 90% (18/20) of CA+CS versus 25% (4/16) of CS patients, at 12 months follow-up (p<0.0001). 65 Table 102: Sinus rhythm- Left atrial CA+CS versus CS Level Gaita et al. 2000 III-2 SR (%) CA+CS 74% 90% CS 26% 25%§ n/N n/N Follow-up 23/31 18/20 4/17 4/16 1 month 12 months §: p<0.0001 CA versus Maze-III Five studies reported the incidence of SR after CA versus Maze-III (see Table 103). The median proportion of patients with SR successfully restored after CA in the four studies was 75% (range 36% to 91%) compared to 83% (range 67% to 92%) in the Maze-III group, with follow-up periods from the third postoperative day (Lee et al. 2001) to at least one year in the other four studies. In three studies the proportions of patients in SR were similar between the CA and Maze-III groups (Ishii et al. 2001; Kim et al. 2001; Kosakai et al. 1995), with the p value (p>0.05) given only for Kim et al. 2001. In Lee et al. (2001), significantly more patients were in SR on the third postoperative day in the CA (83%) versus Maze-III (57%) group (p<0.05). In Nishiyama et al. (2003) a lower proportion of patients were in SR at a mean of 26.8 months following CS (4/11) versus Maze-III (6/9), with the p value not stated. Table 103: Sinus rhythm- CA versus Maze-III Level Ishii et al. 2001 Kim et al. 2001 Kosakai et al. 1995 III-3 III-3 III-2/3 SR (%) n/N CA Maze-III CA 91% 91% CA1: 86% Kosakai: 81% Total: 85% 83% 92% 89%pns 29/32 21/23 60/70 11/14 71/84 44/53 82% n/N MazeIII 12/13 16/18 14/17 Follow-up > 12 months 29[4] months 41.2[5.6] months 47[14] months (1.0-3.1 years) Lee et al. 2001 III-3 57%* 17/30 3rd day postoperative Nishiyama et al. III-2/3 4/11 6/9 26.8{22.8} months 36% 67% 2003 (abstract) Median 75% 83% Range (36%-91%) (67%-92%) [ ]: SD; ( ): range; { }: variance not stated; pns: statistically non-significant; *: p<0.05 CA1: First CA modification; Kosakai: Kosakai maze Kosakai maze (KM) versus CA One study reported the incidence of SR after KM versus CA (see Table 104). Nakajima et al. (2002) stated that, at the end of follow-up, 76% (84/110) of patients were in SR following KM, and 84% were in SR following CA (92/110), with no significant difference between the groups (p>0.05). The mean follow-up periods were 64.1 and 18.8 months, respectively. At the time of hospital discharge 86% (95/110) of patients were in SR in both groups. Table 104: Sinus rhythm- KM versus CA Level Nakijima et al. 2002 III-3 SR (%) KM CA 86% 86% 76% 84%pns n/N KM 95/110 84/110 n/N CA 95/110 92/110 [ ]: SD; pns: statistically non-significant; KM: Kosakai maze 66 Follow-up KM CA Hospital discharge 64.1[27.4] 18.8[10.8] months months Kosakai maze with removal (K-RAA) versus retention (K+RAA) of the right atrial appendage (RAA). One study compared CA combined with either removal or retention of the RAA (see Table 105). At a month postoperatively similar rates of conversion to SR were present in the two groups; with 82% (18/22) of K-RAA versus 80% (16/20) of K+RAA patients in SR (p>0.05). Table 105: Sinus rhythm- KM-RAA versus KM+RAA Level SR (%) Kosakai -RAA Kosakai+RAA Yoshihara et al. 2000 III-3 82% 80%pns pns: statistically non-significant; RAA: right atrial appendage n/N -RAA 18/22 n/N +RAA 16/20 Follow-up 1 month Biatrial versus left atrial CA A single comparative study compared biatrial versus left atrial CA (see Table 106). In Takami et al. (1999) similar proportions of patients converted to SR in the two groups; 83% (25/30) of patients with a biatrial lesion set, and 80% (16/20) of patients with a left atrial lesion set. Mean follow-up periods were 34.1 and 17.8 months, respectively. At hospital discharge, only 60% (18/30) of patients in the biatrial and 70% (14/20) in the left atrial group were in SR. Table 106: Sinus rhythm- Biatrial versus left atrial CA Level Takami et al. 1999 III-3 SR (%) BA CA LA CA 60% 70% 83% 80% n/N BA CA 18/30 25/30 n/N LA CA 14/20 16/20 Follow-up BA CA LA CA Hospital discharge 34.1[11.3] months 17.8[3.8] months (15-51 months) (8-23 months) [ ]: SD; ( ): range; BA: biatrial; LA: left atrial Kosakai maze (KM) versus Maze-III (Questionnaire) Kosakai (2000) presented results from a questionnaire, which compared a large number of patients who underwent the Kosakai maze or Maze-III (see Table 107). The follow-up periods were not stated. Heart rhythm converted to SR after the KM versus Maze-III in 85% versus 62% of patients following lone AF surgery, 74% versus 76% of patients following MV + AF surgery, 87% versus 91% of patients after congenital heart + AF surgery, and 80% versus 74% of patients following other + AF surgery, respectively. Table 107: Sinus rhythm- KM versus Maze-III Level SR (%) n/N n/N Follow-up KM Maze-III KM Maze-III III-3 Lone: 85% Lone: 62% 29/34 8/13 MVS: 74% MVS: 76% 707/956 559/735 Unknown CG: 87% CG: 91% 65/75 51/56 Other: 80% Other: 74% 43/54 23/31 KM: Kosakai maze; Lone: no concomitant surgery; MVS: mitral valve surgery; CG: congenital heart surgery; Other: other concomitant procedures Questionnaire Kosakai 2000 67 Case Series Biatrial CA Five case series studies reported the incidence of SR following biatrial CA (see Table 108). The median proportion of patients who converted to SR following biatrial CA was 72%, with a range of 59% to 100%. Apart from Fukada et al. (1998), where the follow-up period was not reported, the average length of follow-up was at least 3.1 months. The only study to compare early (mean 3.1 months) to later (mean 2.2 years) conversion to SR was Yuda et al. (2001), with 80% (75/94) of patients in SR at the earlier and 70% (66/94) in SR at the later time period. Table 108: Sinus rhythm- Biatrial CA Case Series Biatrial Arai et al. 1999 Fukada et al. 1998 Izumoto et al. 2000 Shimizu et al. 1997 Yuda et al. 2001 Median Range [ ]: SD; ( ): range Level SR (%) n/N Follow-up IV IV IV IV 72% 59% 73% 100% Early 80% Late 70% 72% (59%-100%) 22/30 17/29 53/72 6/6 75/94 66/94 12.3 months (1-25 months) Not stated 44.6[1.1] months 4-32 months Early: 3.1[3.3] months Late: 2.2[0.9] years Izumoto et al. (2000) also reported the probability of SR maintenance following biatrial CA, using the method of Kaplan-Meier. The SR maintenance rate was defined as the patients continuously maintaining SR, with no AF for more than one month. At one year the SR maintenance rate was 88.8% (SD 3.7%), and at five years 64.8% (SD 7.5%). A subgroup of these patients were reported in an earlier publication, with results compared in patients undergoing MV replacement (n=31), or MV plasty (n=56; Izumoto et al. 1998). Comparison of SR maintenance rates in these two groups revealed similar results, although at one year the rate was slightly higher in the MV replacement group. In the replacement group SR maintenance was 95.7% (SD 4.3%) at one year and 65.0% (SD 11.1%) at five years, and in the MV repair group it was 88.6% (SD 5.4%) and 67.6% (SD 9.1%) at one and five years, respectively. Left atrial CA Eight case series studies reported SR conversion rates in patients following CA of the left atrium (see Table 109). The median proportion of patients converting to SR was 77%, with a range of 72% to 83%. Follow-up periods varied from soon after the surgery (Yamauchi et al. 2002) to 66 months postoperatively (Imai et al. 2001). Yamauchi et al. (2002) included patients who had either focal or linear ablation lines, with the pattern determined by electrophysiological studies of the site or origin of the arrhythmia. Slightly fewer patients were in SR following linear (76%, 22/29) versus focal (82%, 9/11) CA. 68 Table 109: Sinus rhythm- Left atrial CA Case Series Left atrial Hoffmeister et al. 2003 Imai et al. 2001 Kondo et al. 2003 Manasse et al. 2003 Naito et al. 2001 Sueda et al. 2001 Usui et al. 2002 Yamauchi et al. 2002 Level SR (%) n/N Follow-up IV 74% 14/19 1-48 months IV IV IV IV IV IV 75% 24/32 36.9[14.1] months (13-66 months) 72% 21/29 37.7[15.0] months (12-60 months) 81% 70/86 36.4 months 80% 24/30 16.5{6.7} months 83% 10/12 5-14 months 74% 30/41 Not stated 78% total 24/31 total IV After surgery 82% focal 9/11 focal 76% linear 22/29 linear Median 77% Range (72%-83%) [ ]: SD; { }: Type of variance not stated; ( ): range; Focal: focal CA; Linear: linear CA Radiofrequency Ablation (RFA) Randomised Controlled Trial Biatrial RFA versus CS Khargi et al. (2001) compared SR conversion in patients following biatrial RFA plus MV surgery, versus MV surgery alone (see Table 110). The RFA resulted in more patients in SR versus MV surgery alone. There was a significant difference between the RFA versus MVS groups from three months follow-up, but no significant difference on the first postoperative day when only 8/15 RFA patients were in SR. At 12 months the RR of patients in SR with RFA compared with MV surgery alone was 3.82 (95% CI: 1.35 to 10.81, p=0.01). The number of patients in SR was also expressed as a cumulative frequency, using the Kaplan-Meier method. At six and 12 months follow-up, the frequency of patients in SR in the RFA group was 0.733 and 0.800, respectively. These numbers were lower (p<0.001) at each time point in the MVS group: 0.267 at both six and 12 month follow-up. Table 110: Sinus rhythm- Biatrial RFA+MVS versus MVS RCT Level SR (%) n/N BA RFA MVS BA RFA Khargi et al. 2001 II 53% 27% 8/15 69% 27%* 9/13 83% 27%* 10/12 82% 33%* 9/11 82% 21%* 9/11 *: p<0.05 (RevMan); MVS: mitral valve surgery; BA: biatrial Follow-up MVS 4/15 4/15 4/15 5/15 3/14 Day 1 3 months 6 months 9 months 12 months Non-randomised Comparative Studies Biatrial RFA versus CS Three non-randomised comparative studies compared SR conversion after RFA plus CS versus CS alone (see Table 111). The proportions of patients in SR ranged from 73% to 88% following RFA, versus 0% to 11% after CS alone. Follow-up times were from within 22 days postoperatively, to 109 months. 69 There were significantly more patients in SR in the biatrial RFA versus CS groups in Patwardhan et al. (2003), but the p values were not stated in the other two studies. Riying et al. 1998 presented results only up to hospital discharge. In Chen et al. (2001), two slightly different lesion patterns were used, with the first showing less success than the second; 73% versus 87% of patients in SR, respectively. Table 111: Sinus rhythm- Biatrial RFA versus CS Level Chen et al. 2001 III-2 SR (%) BA RFA RFA1: 73% RFA2: 87% Total: 84% 86% 79% CS 11% n/N BA RFA 8/11 41/47 49/58 72/84 66/84 CS 6/54 Follow-up BA RFA CS RFA1: 43 months (37-47 months) (35-109 months) RFA2: 16 months (3-32 months) 3 weeks 6 months 23.6[12.5] months Within 22 days Hospital postoperatively discharge NS Patwardhan NS III-3 6%‡ et al. 2003 4/64 Riying et III-3 88% 0% 22/25 0/25 al. 1998 Range (73%-88%) (0%-11%) [ ]: SD; ( ): range; RFA1: first RFA ablation set; RFA2: second RFA ablation set; NS: not stated; BA: biatrial; ‡: p<0.001 Left atrial RFA versus CS Two comparative non-randomised studies included patients undergoing left atrial RFA versus CS (see Table 112). Proportions of patients in SR ranged from 77% to 81% following left atrial RFA, versus 11% to 25% after CS alone. Follow-up times were from a mean of 12.5 months, to three years. Guang et al. (2002) reported significantly more patients in SR in the RFA group compared to CS alone, at both early (79% versus 33%, p<0.01; hospital discharge) and later (77% versus 25%; p<0.01; 3 years) follow-up. Mantovan et al. (2003) did not report p values, but there were more patients in SR following RFA (81%) versus CS (11%), at a mean of 12.5 months follow-up. In Mantovan et al. (2003) the proportion of left atrial RFA patients in SR was lower at hospital discharge (63%, 65/103) versus the end of follow-up (81%, 83/103). In contrast, in the CS group, there were fewer patients in SR at the end of follow-up (11%, 3/27 versus 26%, 7/27 at hospital discharge). Table 112: Sinus rhythm- Left atrial RFA versus CS Level SR (%) LA RFA CS 79% 33%† Guang et al. III-2 77% 25%† 2002 Mantovan et 79% 26% III-2 al. 2003 63% 18% 81% 11% [ ]: SD; †: p<0.01; LA: left atrial n/N LA RFA 76/96 74/96 81/103 65/103 83/102 Follow-up CS 29/87 22/87 7/27 5/27 3/27 Hospital discharge 3 years After surgery Hospital discharge 12.5[5] months RFA versus Maze-III One comparative non-randomised study compared RFA versus the Maze-III procedure (see Table 113). In these patients 85% (34/40) of the RFA versus 73% (22/30) of the Maze-III patients were in SR (Chiappini et al. 2004). The follow-up was restricted to hospital discharge. 70 A cumulative frequency of SR was also calculated, using the Kaplan-Meier method. At a mean of 16.5 months follow-up the cumulative frequency of SR was 88.5% in the RFA group, and at a mean of 73.2 months 68.9% of the Maze-III group were in SR (p>0.05). Table 113: Sinus rhythm- RFA versus Maze-III Level Chiappini et al. 2004 BA: biatrial III-3 SR (%) BA RFA Maze III 85% 73% n/N BA RFA Maze-III 34/40 22/30 Follow-up Hospital discharge Biatrial versus left atrial RFA Two comparative non-randomised studies reported SR after biatrial versus left atrial RFA (see Table 114). Conversion to SR by the end of follow-up was 69% (Deneke et al. 2002a) and 95% (Güden et al. 2002) in the biatrial, and 76% and 81%, respectively, in the left atrial RFA groups. Followup varied from a mean of 104 days to 18 months. Güden et al. reported no significant difference (p>0.05) between proportions of SR in the biatrial and left atrial groups, from perioperative to a mean of 104 days follow-up. At the end of follow-up 95% (37/39) of the biatrial, and 81% (19/23) of the left atrial RFA patients were in SR. In Deneke et al. (2002a) similar percentages of patients were in SR in both groups at the end of follow-up, 69% (34/49) versus 76% (16/21) in the biatrial and left atrial patients, respectively. The p value was not stated in this study. No consistent changes in the proportions of patients in SR occurred between the early and later follow-up in the two studies. Table 114: Sinus rhythm- Biatrial versus left atrial RFA Level SR (%) n/N Follow-up BA RFA LA RFA BA RFA LA RFA BA RFA LA RFA Güden et 87% 91%pns 34/39 21/23 Perioperative III-2 al. 2002 95% 91%pns 37/39 21/23 Hospital discharge 95% 81%pns 37/39 19/23 104 days (45-245 days) Deneke et 55% 63% 27/49 13/21 1 month III- 2/3 69% 76% 34/49 16/21 al. 2002a 18[14] months 11[10] months Range 69%-95% 76%-81% [ ]: SD; ( ): range; pns: statistically non-significant; BA: biatrial; LA: left atrial Deneke et al. also calculated the cumulative frequency of SR (Kaplan-Meier). The frequency of SR was: 65% in the biatrial versus 82% in the left atrial group at three months; 68% in the biatrial versus 82% in the left atrial group at six months; and 75% in the biatrial group at a mean of 18 months, versus 82% in the left atrial group at a mean of 11 months follow-up. No p values were stated. Case Series Biatrial RFA Seven case series reported SR conversion in patients following biatrial RFA (see Table 115). The median proportion of patients in SR following surgery was 89%, with a range of 72% to 100%. Follow-up ranged from 1.5 months (Sos et al. 2002) to 4.2 years (Thomas et al. 2003), and was not stated in Damiano et al. (2003). Raman et al. (2003) determined SR conversion as the patients came off cardiopulmonary bypass, when 100% (132/132) of patients were in SR. This percentage declined to 83% (72/87) by three months postoperatively. Prasanna et al. (2001) also reported a high 71 proportion of patients in SR on the operating table (96%, 24/25), although this number remained the same at a mean of 3.5 years follow-up. Hornero et al. (2002) reported a similar number of patients in SR at hospital discharge (44/54) and a mean of seven months follow-up (46/52). The probability of maintenance of SR using the Kaplan-Meier method was calculated by Thomas et al. (2003). In this study at three years follow-up, 79% of patients were predicted to be in SR, while at four years 68% were likely to remain in SR. Table 115: Sinus rhythm- Biatrial RFA Case Series Level Biatrial Damiano et al. 2003 Hornero et al. 2002 SR (%) n/N Follow-up IV 92% 24/26 Not stated 81% 44/54 Hospital discharge IV 89% 46/52 7 months (1-16 months) Prasanna et al. 2001 96% 24/25 Operating table IV 96% 24/25 3.5 years (3.2-3.8 years) Raman et al. 2003 100% 132/132 Off CPB 83% 72/87 3 months IV 90% 45/50 6 months 100% 15/15 12 months Sie et al. 2001 IV 72% 77/107 39 months Sos et al. 2002 IV 80% 8/10 3 months (1.5-5 months) Thomas et al. 2003 IV 69% 29/42 Median 2.9 years (0.6-4.2 years) Williams et al. 2001 88% RFA1 7/8 IV 100% RFA2 3/3 138[96] days Total: 91% 10/11 Median 89% Range (72%-100%) [ ]: SD; ( ): range; CPB: cardiopulmonary bypass; RFA1: first RFA ablation lesion set; RFA2: second RFA ablation lesion set Left atrial RFA Twelve case series reported the incidence of SR following RFA restricted to the left atrium (see Table 116). The median proportion of patients with SR following surgery was 79%, with a range of 55% to 100%. Follow-up periods were from less than three months (Kress et al. 2002) to 20 months (Kottkamp et al. 1999). In the studies where the perioperative to later follow-up proportions of SR were reported, the general pattern was a high success rate immediately postoperative, which was lower in the perioperative period, and then higher from approximately three months. For example, in Ruchat et al. (2002) there were 98% (39/40) patients in SR immediately after surgery; 60% (22/37) at hospital discharge; and 68% (25/37) at a mean of 12.5 months follow-up. In Kress et al. (2002) the figures were given separately for patients who had not reached three month follow-up (63%, 5/8), and those at greater than three months follow-up (100%, 14/14). 72 Table 116: Sinus rhythm- Left atrial RFA Case Series Left atrial Benussi et al. 2002 Biederman et al. 2002 Geidel et al. 2003 Level SR (%) n/N Follow-up IV 81% 87/108 16.9[14.2] months (≥ 6 months) IV 60% 6/10 3-6 months 86% 88% 92% 100% 64% 60% 18/21 14/16 12/13 5/5 32/50 30/50 IV 55% 6/11 IV 74% 73% 63% 100% 17/23 16/22 5/8 14/14 3 months 6 months 9 months 12 months After surgery Hospital discharge 11[6] months (range 3-20 months) Immediately post-ablation Hospital discharge < 3 months > 3 months IV 92% 63/68 2 years 67% 62% 13% 84% 98% 60% 68% 80% 79% 79% (55%-100%) 20/30 13/21 12/95 80/95 39/40 22/37 25/37 72/90 27/34 6 months 12 months First week 6 and 12 months Immediately after surgery Hospital discharge 12.5[7.9] months Mean 7.3 months 138[96] days IV Gillinov et al. 2003 Kottkamp et al. 1999 Kress et al. 2002 Le Tourneau et al. 2003 Mohr et al. 2002 Müller et al. 2002 IV IV IV Ruchat et al. 2002 IV Starck et al. 2003 Williams et al. 2001 Median Range [ ]: SD; ( ): range IV IV Microwave Ablation (MWA) Randomised Controlled Trial (RCT) Left atrial MWA versus CS A single RCT reported SR conversion in patients following left atrial MWA versus CS alone (see Table 117). There were significantly more patients in SR after MWA versus CS alone from immediately postoperatively to three months follow-up. At three months there were 57% (12/21) of MWA versus 18% (3/17) CS patients in SR (RR 3.24, 95% CI: 1.09 to 9.65, p=0.03). With the reduction in patient numbers at later follow-up, there was no statistical difference between the groups, although more patients were in SR in the MWA versus CS group. The highest proportion of patients in SR in the MWA group was immediately postoperatively, when 92% were in SR (22/24). 73 Table 117: Sinus rhythm- Left atrial MWA versus CS RCT Level SR (%) LA MWA CS Schuetz et al. II 92% 32%† 2003 61% 16%* 57% 18%* 67% 30% 80% 33% †: p<0.01; *: p<0.05 (RevMan); LA: left atrial n/N LA MWA 22/24 14/23 12/21 12/18 12/15 Follow-up CS 6/19 3/19 3/17 3/10 3/9 Immediately postoperative Hospital discharge 3 months 6 months 12 months Non-randomised Comparative Study Left atrial MWA versus CS Spitzer and Knaut (2002) studied patients following either MWA or CS alone (see Table 118). Significantly more patients were in SR following MWA versus CS alone, with 62% (69/111) of the MWA versus 10% (5/45) of the CS patients in SR, at 12 months follow-up (p<0.0001). Table 118: Sinus rhythm- Left atrial MWA versus CS Level Spitzer and Knaut III-2/3 2002 §: p<0.0001; LA: left atrial SR (%) LA MWA CS 64% 8%§ 62% 10%§ n/N LA MWA 71/111 69/111 Follow-up CS 4/45 5/45 6 months 12 months Comparison of two MWA lesion sets One study reported SR conversion after two different MWA lesion sets (see Table 119). Results were given separately for MV surgery (MVS), coronary artery surgery (CA) and aortic valve replacement (AVR). The proportion of patients in SR was higher after the second lesion set with each concomitant procedure, but no p values were given. Since the numbers of patients in each subgroup were not given, the results could only be expressed as a percentage. Table 119: Sinus rhythm- MWA Comparison of two lesion sets Level SR (%) n/N Follow-up MWA1 MWA2 MWA1 MWA2 Knaut et al. 2003 62% MVS 88% MVS ?/137 ?/75 III-2/3 6 months (abstract) 68% CAS 78% CAS (Total) (Total) 78% AVR 85% AVR MVS: mitral valve surgery; CAS: coronary artery surgery; AVR: aortic valve replacement; ?: unknown Case Series Biatrial MWA Only one case series, with small patient numbers, stated the conversion to SR after biatrial MWA (see Table 120). At a mean follow-up of 12.4 months, there were 7/9 patients in SR (Chiappini et al. 2003). Table 120: Sinus rhythm- Biatrial MWA Case Series Biatrial Chiappini et al. 2003 Level SR (%) n/N Follow-up IV 78% 7/9 Mean 12.4 months 74 Left atrial MWA Four case series reported the proportions of patients in SR following MWS to the left atrium (see Table 121). The median percentage of SR was 68%, with a range of 60% to 83%. Follow-up was to hospital discharge in one study (Gillinov et al. 2002), to 12 months in a second (Knaut et al. 2002), and unknown in the remaining two studies (Venturini et al. 2003 and Zembala et al. 2003). In Knaut et al. (2002) successful restoration of SR occurred in 61% (42/69) and 58% (37/64) of patients at 6 and 12 months, respectively. Venturini et al. (2003) reported the highest successful conversion to SR of 83%, although the period of follow-up was not stated. Table 121: Sinus rhythm- Left atrial MWA Case Series Left atrial Gillinov et al. 2002 Knaut et al. 2002 Venturini et al. 2003 Zembala et al. 2003 Median Range Level SR (%) n/N Follow-up IV 60% 61% 58% 83% 76% 68% (60%-83%) 6/10 42/69 37/64 34/41 32/42 Hospital discharge 6 months 12 months Not stated Not stated IV IV IV Laser Ablation A single case series reported results following laser ablation for the treatment of AF. Vigilance et al. (2003) followed six patients for three months postoperatively. In these patients 6/6 (100%) were in SR at the end of the study. RFA versus MWA One study reported the proportion of patients in SR following MWA versus RFA (see Table 122). In Wisser et al. (2004) there were 60% (12/20) of MWA versus 57% (8/14) RFA patients in SR at the latest follow-up. This was 24 months in the MWA and 12 months in the RFA group. There was no consistent difference in the proportion of patients in SR from three months to the end of follow-up. The p values were not given. Table 122: Sinus rhythm- MWA versus RFA Level Wisser et al. 2004 III-2/3 SR (%) MWA 59% 55% 59% 60% n/N RFA 47% 61% 57% NS MWA 13/22 12/22 13/22 12/20 Follow-up RFA 9/19 11/18 8/14 NS 3 months 6 months 12 months 24 months NS: not stated Maze-III The proportion of patients in SR was stated in fourteen of the Maze-III studies. The median proportion of patients in SR after surgery was 92%, with a range of 75% to 100%. Follow-up was at least three months in all but one study, where the length was not stated. 75 Summary of SR results Comparative Studies Intraoperative ablation resulted in better patient conversion to SR than cardiac surgery alone. In the RCTs, significantly more patients were in SR after biatrial RFA plus MV surgery versus MV surgery alone (Khargi et al. 2001); and left atrial MWA plus CS restored more patients to SR than CS alone (Schuetz et al. 2003). The non-randomised comparative studies were consistent with these findings. Compared to CS alone, more patients converted to SR following: biatrial or left atrial CA, biatrial or left atrial RFA; and left atrial MWA. In addition, there did not appear to be a significant difference in SR conversion when either CA or RFA was compared to Maze-III surgery. With the comparative internal comparison studies, there was no apparent difference in conversion to SR when CA or RFA was used in a biatrial or left atrial lesion set. The study groups in which a median could be calculated (groups with three or more studies) are illustrated below, with a box plot to demonstrate the variance within studies of each group (Figure 3). The SR incidence at the latest follow-up period for each study was used. The cardiac surgery and Maze-III groups were taken from the relevant arms of the comparative studies. Maze-III (78%; n=6) (16%; n=12) Cardiac surgery LA MWA case series (68%; n=4) (80%; n=12) LA RFA case series BA RFA case series (90%; n=8) LA RFA (79%; n=4) BA RFA (83%; n=8) LA CA case series (77%; n=8) BA CA case series (72%; n=5) (82%; n=13) BA CA 0 20 40 60 80 100 Patients in SR (%) Figure 3: Median proportion of patients in SR The box represents the 10th and 90th percentiles, the line the median value, and the error bars the 5th and 95th percentiles. Outliers of more than 1.5 box lengths outside the median are shown as • (Median; no of studies) BA: biatrial; LA: left atrial; CA: cryotherapy ablation; RFA: radiofrequency ablation; MWA: microwave ablation 76 A median of more than 70% of patients were in SR in both CA and RFA studies, versus only 16% after CS alone (indirect comparisons). There were six included studies with a Maze-III comparative arm, and in these studies a median proportion of 78% of patients were in SR after Maze-III surgery. Little data was available to evaluate MWA and laser ablation. Out of four case series, a median of 68% of patients were in SR after left atrial MWA. There were no consistent differences in conversion to SR in CA performed with a biatrial or left atrial lesion set. However, more patients appeared to be in SR after biatrial versus left atrial RFA: 83% and 90% after biatrial RFA versus 79% and 80% after left atrial RFA in the comparative and case series groups, respectively. 5.2.2 Atrial fibrillation (AF) Intraoperative ablation for AF is designed to prevent recurrence of the heart arrhythmia. When AF does recur following surgery, the procedure can be considered a failure. Consideration of follow-up period is important, since incidence of arrhythmias (including AF) may be higher in the early postoperative period. Although the heart rhythm at later follow-up is likely to be more stable, arrhythmias can recur even months after surgery. In the included studies, the numbers of patients free from AF were sometimes stated, rather than the number in SR. The number of patients free from AF may not always equal to the number in SR, as patients could have other non-AF heart arrhythmias. Therefore, the numbers were not extrapolated unless the heart rhythm was specified. Cryotherapy Ablation Non-randomised comparative studies Biatrial CA+CS versus CS Three comparative studies reported the incidence of AF in patients following biatrial CA+CS versus CS alone (see Table 123). The median proportion of patients with AF following CA was 19% (range 10% to 31%) versus 80% (range 36% to 100%) after CS alone. All follow-up periods were greater than two months. The p values were not given. In two studies reporting the incidence of AF at both early and later follow-up, in the CA+CS group the percentage of patients with AF increased slightly over time. In patients who had CS alone, no consistent changes in frequency of AF occurred between early and later follow-up. Table 123: Atrial fibrillation- Biatrial CA+CS versus CS Level AF (%) BA CA+CS 5% 10% 11% 19% Handa et III-2 al. 1999 Sueda et III-3 al. 1997 Yuda et III-2 31% al. 2004 Median 19% Range (10%-31%) ( ): range; BA: biatrial CS 41% 36% 73% 80% n/N BA CA+CS 2/39 4/39 4/36 7/36 n/N CS 24/58 21/58 11/15 12/15 Hospital discharge Mean 21 months (≥ 6 months) Hospital discharge 6 months 100% 8/26 6/6 > 2 months 80% (36%-100%) 77 Follow-up Handa et al. (1999) reported freedom from AF at hospital discharge in 95% of the CA and 50% of the CS patients. Using the method of Kaplan-Meier, freedom from AF in the CA versus CS groups was: 94.7% [3.6%] (n=35) versus 46.6% [6.5%] (n=27) at 3 months; 81.5% [6.9%] (n=21) versus 41.2% [6.5%] (n=18) at one year; and 74.0% [8.0%] (n=12) versus 26.3% [6.5%] (n=8) at two years (Handa et al. 1999). Sueda et al. (1997) stated that 86% (31/36) and 78% (28/36) of CA patients, and only 27% (4/15) and 20% (3/15) of the CS patients were free of AF, at one and six months postoperatively, respectively. The p values were not given. Left atrial CA+CS versus CS One comparative study reported the incidence of AF in patients after left atrial CA+CS versus CS alone (see Table 124). Statistical significance was stated in the early postoperative period in Gaita et al. (2000), with more patients in AF in the CS (78%) versus the CA+CS (16%) group (p<0.001). The incidence of AF decreased from hospital discharge to 12 months follow-up in both groups. Table 124: Atrial fibrillation- Left atrial CA+CS versus CS Level AF (%) LA CA Gaita et al. III-2 16% 2000 26% 26% 10% 10% ‡: p<0.001; LA: left atrial CS 78%‡ 88% 76% 75% 75% n/N LA CA 5/32 8/31 8/31 3/30 2/20 n/N CS 14/18 15/17 13/17 12/16 12/16 Follow-up Early postoperative Hospital discharge 1 month 6 months 12 months CA versus Maze-III Four studies reported AF incidence after CA versus the Maze-III procedure (see Table 125). The median proportion of patients remaining in AF at the latest follow-up in the CA group was 9% (range 0% to 16%), compared to 7% (0% to 18%) following Maze-III surgery. Only one study (Kim et al. 2001) reported patients in AF at perioperative and later follow-up periods, with a reduction in AF incidence in both groups over time (57% to 9% at mean 29 months in CA; 67% to 6% at mean 47 months in Maze-III). Using the first CA modification, Kosakai et al. (1995) stated no patients remained in AF at between 1.0 and 3.1 years (n=14) but 16% (11/70) of the Kosakai maze and 18% (3/17) of the Maze-III patients were still in AF. Following 6 months follow-up Lee et al. reported that no patients remained in AF in either the CA or M-III groups. Table 125: Atrial fibrillation- CA versus Maze-III Level Ishii et al. 2001 Kim et al. 2001 Kosakai et al. 1995 III-3 III-3 III-2/3 AF (%) BA CA Maze-III n/N BA CA n/N Maze-III Follow-up BA CA Maze-III 10% 8% 1/10 1/13 Postoperative 57% 9% 0% 1st 16% Kosakai Total: 13% 67% 6% 13/23 2/23 0/14 11/70 11/84 12/18 1/18 Perioperative 29[4] months 47[14] months 3/17 (1.0-3.1 years) NS NS 6 months 18% Lee et al. III-3 0% 0% 2001 Median 9% 7% Range (0%-16%) (0%-18%) [ ]: SD; ( ): range; NS: Not stated; BA: biatrial 78 Kosakai maze versus CA One study compared AF incidence after cryotherapy using a Kosakai Maze versus CA (see Table 126). Most patients remained in AF during the perioperative period in Nakijima et al. (2002), with 60% (66/110) and 54% (59/110) of patients in AF in the KM and CA groups, respectively. This proportion decreased in both groups by hospital discharge (14% versus 15%, respectively), and at longer follow-up, 24% (26/110) of the KM patients (mean 64.1 months) and 16% (18/110) of the CA patients (mean 18.8 months) were in AF. Freedom from AF was also calculated using the Kaplan-Meier method, with values in the KM versus CA of: 92.6% (n=88) versus 97.7% (n=62) at one year; 90.4% (n=73) versus 97.7% (n=4) at three years; and 86.7% (n=39) in the KM group at five years. Table 126: Atrial fibrillation- Kosakai maze versus CA Level Nakijima et al. 2002 III-3 AF (%) Kosakai CA 60% 54% 14% 15% 24% 16% n/N Kosakai 66/110 15/110 26/110 n/N CA 59/110 17/110 18/110 Follow-up Kosakai CA Perioperative Hospital discharge 64.1[27.4] months 18.8[10.8] months [ ]: SD Biatrial versus left atrial CA One study compared the patients remaining in AF after biatrial versus left atrial CA (see Table 127). Proportions of patients in AF were similar in both groups at hospital discharge and later follow-up (Takami et al. 1999). There were 10% (3/30) of patients in AF in the biatrial versus 15% (3/20) of patients in AF in the left atrial group at the end of follow-up, a mean of 34.1 months in the biatrial and 17.8 months in the left atrial group. Table 127: Atrial fibrillation- Biatrial versus left atrial CA Level AF (%) BA CA LA CA Takami et III-3 17% 20% al. 1999 10% 15% [ ]: SD; BA: biatrial; LA: left atrial n/N BA CA 5/30 3/30 n/N LA CA 4/20 3/20 Follow-up Hospital discharge 34.1[11.3] months 17.8[3.8] months Case Series Biatrial CA Five case series reported AF incidence after biatrial CA (see Table 128). The median proportion of patients in AF following biatrial CA was 25%, with a range of 2% to 35%. Follow-up times were a mean of at least 3.1 months, and not stated in Fukada et al. (1998). Izumoto et al. (2000) reported little difference in the percentage of patients in AF from the immediate postoperative period to a mean of over 44 months follow-up. Conversely, Yuda et al. (2001) found the number of patients in AF increased over time. 79 Table 128: Atrial fibrillation- Biatrial CA Case Series Level Biatrial Ad et al. 2003a Ad et al. 2003b Arai et al. 1999 Fukada et al. 1998 Izumoto et al. 2000 AF (%) n/N Follow-up IV IV IV IV 6% 48 2% 51 28% 30 35% 29 21% 100 IV 22% 72 Yuda et al. 2001 20% 94 IV 30% 94 Median 25% Range (6%-35%) [ ]: SD; { }: Type of variance not stated; ( ): range 8.3{3.1} months Mean 19 months Mean 12.3 months Not stated Immediately postoperative 44.6[1.1] months 3.1[3.3] months 2.2[0.9] years Left atrial CA Four case series studies reported the incidence of AF following left atrial CA (see Table 129). The median proportion of patients remaining in AF was 21%, with a range of 16% to 25%. Follow-up periods were short in three of the studies, only up to three days postoperatively, but 60 months in Kondo et al. (2003). Kondo et al. (2003) reported a reduction in the proportion of patients in AF over time. Table 129: Atrial fibrillation- Left atrial CA Case Series Left atrial Imai et al. 2001 Kondo et al. 2003 Sueda et al. 2001 Yamauchi et al. 2002 Median Range ( ): range Level AF (%) n/N Follow-up IV 16% 58% 21% 25% 21% 21% (16%-25%) 5/32 18/31 6/29 3/12 6/29 After surgery 2-15 days postoperative 12-60 months First 3 days postoperative After surgery IV IV IV Although Manasse et al. (2003) did not report the numbers of patients with AF at the end of the follow-up period, the freedom from AF at six and 12 months was given. Three slightly different RF ablation patterns were used and results given separately for each. At six months follow-up, freedom from AF was 90.4%, 90.5% and 97.4%, using RFA1 (n=22), RFA2 (n=32) and RFA3 (n=41), respectively. Twelve month freedom from AF was 72.7%, 90.5% and 92.0%, for the RFA1, RFA2 and RFA3 groups, respectively. Thus freedom from AF was reasonably stable in the RFA-2 and -3 groups, but decreased following RFA1. Radiofrequency Ablation (RFA) Randomised controlled trial Biatrial RFA+MVS versus MVS A single RCT reported the proportions of patients in AF after either RFA or CS alone (see Table 130). There were fewer patients in AF following RFA versus CS. At one year follow-up there were 18% (2/11) RFA patients in AF versus 79% (11/14) CS patients (RR 0.23 95% CI: 0.06 to 0.83, p=0.03) 80 In the RFA group the proportion of patients in AF decreased from the first postoperative day to six month follow-up, whereas in the CS patients the proportion of patients in AF over time was relatively stable. Table 130: Atrial fibrillation- Biatrial RFA+MVS versus MVS RCT Level AF (%) n/N BA RFA MVS BA RFA Khargi et al. 47% 73% 7/15 2001 31% 73%* 4/13 II 17% 73%* 2/12 18% 67%* 2/11 18% 79%* 2/11 *: p<0.05 (Rev Man); BA: biatrial; MVS: mitral valve surgery Follow-up MVS 11/15 11/15 11/15 10/15 11/14 Day 1 3 months 6 months 9 months 12 months Non-randomised Comparative Studies Biatrial RFA versus CS Three comparative studies reported the numbers of patients with AF following biatrial RFA, versus CS alone (see Table 131). The range of proportions of AF was 7% to 20% in the RFA, and 89% to 100% in the CS group. Follow-up periods were from hospital discharge (Riying et al. 1998) to 109 months (Chen et al. 2001). In Chen et al. (2001) two variations of RFA were used. At each time point there was a lower proportion of patients in AF after the RFA2 versus the RFA1 procedure. Table 131: Atrial fibrillation- Biatrial RFA versus CS Level Chen et al. 2001 III-2 AF (%) BA RFA 15% RFA1 10% RFA2 18% RFA1 7% RFA2 Total: 9% 13% 20% CS 89% n/N BA RFA CS 2/13 5/48 48/54 2/11 3/47 5/58 9/70 14/70 50/53 Follow-up First 2 weeks (37-47 months) (3-32 months) (35-109 months) 3 weeks Patwardhan IIINS 23.6[12.5] months 6 months et al. 2003 2/3 94% Hospital Riying et 3/25 25/25 First 22 days III-3 12% 100% discharge al. 1998 Range (7%-20%) (89%-100%) ( ): range; [ ]: SD; BA: biatrial; RFA1: first RFA ablation set; RFA2: second RFA ablation set; NS: not stated Patwardhan et al. (2003) also reported freedom from AF in the RFA group. At one year follow-up 84% of patients were free from AF (95% CI: 74%-91%). By three years 79% of patients remained free from AF (95% CI 62% to 89%), with the same percentage at five years, but a larger confidence interval (79%; 95% CI 51% to 93%). Left atrial RFA versus CS One comparative study reported AF after left atrial RFA versus CS alone (see Table 132). Guang et al. (2002) reported that, following RFA, more patients were in AF at the three year follow-up (23%, 20/87), than at hospital discharge (12%, 10/87). However, during the same time period, the proportion of patients in AF also increased in the CS group, from 56% (49/87) to 75% (65/87). Freedom from AF at three years follow-up was 77% in the RFA versus 25% in the CS group (p<0.01). 81 Table 132: Atrial fibrillation- Left atrial RFA versus CS Level Guang et III-2 al. 2002 LA: left atrial AF (%) LA RFA CS 12% 56% 23% 75% n/N LA RFA CS 12/96 49/87 22/96 65/87 Follow-up Hospital discharge 3 years Biatrial versus left atrial RFA One comparative study reported the incidence of AF after biatrial versus left atrial RFA (see Table 133). Güden et al. (2002) used a Holter monitor to determine the number of patients in AF. There were significantly more patients who had episodes of AF during follow-up in the left atrial (43%, 17/23) versus the biatrial RFA group (5%, 2/39; p<0.001). None of the patients in either group remained in AF intra-operatively, but the highest incidence of AF was one month postoperatively: 8% (3/39) in the biatrial versus 29% (7/23) in the left atrial RFA group. At the end of follow-up (45-245 days) there were 5% (2/39) of the biatrial and 19% (4/23) of the left atrial patients remaining in AF. The p values were not stated. Table 133: Atrial fibrillation- Biatrial versus left atrial RFA Level AF (%) BA RFA LA RFA Güden et al. 0% 0% 2002 5% 14% III-2 8% 29% 5% 19% 5% 43%‡ BA: biatrial; LA: left atrial; ‡: p<0.001 BA RFA 0/39 2/39 3/39 2/39 2/39 n/N LA RFA 0/23 3/23 7/23 4/23 17/23 Follow-up Intra-operative Hospital discharge 1 month 45-245 days During follow-up Case Series Biatrial RFA Nine case series reported the proportion of patients in AF after biatrial RFA (see Table 134). The median percentage of patients in AF at the end of follow-up was 13%, with a range of 4% to 31%. Follow-up was at least a mean of three months in all studies, excepting Damiano et al. (2003) in which the period of follow-up was not stated. Hornero et al. (2002) reported results from immediately following cardiopulmonary bypass, when only 11% (6/55) of patients remained in AF. This number increased to 44% (24/55) during hospital stay, but dropped to 8% (4/52) at a mean follow-up of seven months. Raman et al. (2003) also reported a decline of patients in AF from 16% (14/87) at three months to 10% (5/50) at six months postoperatively. In Sos et al. (2002) freedom from AF was 100% (10/10) when patients left the operating theatre. Sie et al. (2001) also expressed the freedom from AF using the Kaplan-Meier method. Proportions of patients free of AF were: 98% [1.5%] at one year; 86% [3.7%] at two years; and 78% [5.1%] at three years. 82 Table 134: Atrial fibrillation- Biatrial RFA Case Series Level Biatrial Damiano et al. 2003 Hornero et al. 2002 AF (%) n/N Follow-up IV 8% 2/26 Not stated 11% 6/55 After CPB 44% 24/55 In-hospital IV 17% 9/54 Hospital discharge 8% 4/52 7 months (1-16 months) Prasanna et al. 2001 IV 4% 1/25 3.5 years (3.2-3.8 years) Raman et al. 2003 16% 14/87 3 months IV 10% 5/50 6 months Sie et al. 2001 IV 17% 18/107 39 months Sos et al. 2002 30% 3/10 In-hospital IV 20% 2/10 3 months (1.5-5 months) Thomas et al. 2003 IV 24% 10/42 Median 2.9 years (0.6-4.2 years) Williams et al. 2001 IV 13% 1/8 138[96] days Deneke et al. 2002aa IV 31% 15/49 18[14] months (1-50 months) Median 13% Range (4%-31%) [ ]: SD; ( ): range; a: comparative study, but AF only reported in the biatrial RFA group. Left atrial RFA Ten case series reported the proportion of patients remaining in AF following left atrial RFA (see Table 135). The median percentage of patients remaining in AF after left atrial RFA was 23%, with a range of 11% to 38%. Follow-up was from hospital discharge (Ruchat et al. 2002) to a mean of 18.3 months (Le Tourneau et al. 2003). When the number of patients in AF was reported in the early postoperative period, a low proportion of patients were in AF in two studies. In Gillinov et al. (2003) 10% (5/50) of patients were in AF following surgery, while 4% (1/23) were in AF immediately post-ablation in Kress et al. (2002). Conversely, in Geidel et al. (2003), in the early postoperative period, 62% (18/29) of patients had AF. In two studies the numbers of patients in AF were not stated, but the proportion of patients free from AF was given. In Benussi et al. (2002) the proportion of patients without recurrence of AF was 79% (95% CI: 72% to 86%) at one year, and 77% (95% CI: 69% to 85%) at three years. In Müller et al. (2002) freedom from AF was 100% intra-operatively, but only 30% at one week postoperative. However, this number increased to 84% of patients free from AF at both six and 12 months postoperatively. 83 Table 135: Atrial fibrillation- Left atrial RFA Case Series Level AF (%) n/N Follow-up IV 40% 20% 62% 33% 10% 66% 32% 55% 18% 4% 18% 38% 0% 4/10 2/10 18/29 7/21 5/50 33/50 16/50 6/11 2/11 1/23 4/22 3/8 0/14 Up to 4 weeks 3-6 months Early postoperative 6 weeks After surgery In-hospital Hospital discharge Perioperative 11[6] months (range 3-20 months) Immediately post ablation Hospital discharge < 3 months > 3 months 31% 21/68 18.3 months Left atrial Biederman et al. 2002 Geidel et al. 2003 IV Gillinov et al. 2003 IV Kottkamp et al. 1999 Kress et al. 2002 IV IV Le Tourneau et al. 2003 Ruchat et al. 2002 Starck et al. 2003 IV IV IV 25% 9/37 Hospital discharge 28% 25/90 Hospital discharge 20% 18/90 7.3 months Williams et al. 2001 IV 21% 7/34 138[96] days Mantovan et al. 2003a IV 11% 7/61 1 year Median 23% Range (11%-38%) [ ]: SD; ( ): range; a: comparative study, but AF not reported in the CS group. Microwave Ablation Randomised Controlled Trial Left atrial MWA versus CS A single RCT evaluated the incidence of AF after MWA versus CS alone (see Table 136). Schuetz et al. (2003) reported the results only up to hospital discharge, when 39% (9/23) of the MWA and 84% (16/19) of the CS patients were still in AF. Results were also given as freedom from AF. The highest proportion of patients free from AF in both groups was in the early postoperative period, with 92% (22/24) of the MWA versus 47% (9/19) of the CS patients free from AF (p<0.05). At 12 months follow-up 80% (12/15) of the MWA versus 33% (3/9) of patients were free from AF (p<0.05). Table 136: Atrial fibrillation- Left atrial MWA versus CS RCT Level Schuetz et al. 2003 II AF (%) LA MWA CS 8% 68% 39% 84% Freedom from AF (%) 92% 47%* 61% 16%* 57% 18%* 67% 30%* 80% 33%* n/N LA MWA CS 2/24 13/19 9/23 16/19 LA MWA CS 22/24 9/19 14/23 3/19 12/21 3/17 12/18 3/10 12/15 3/9 *: p<0.05; LA: left atrial 84 Follow-up Immediately postoperative Hospital discharge Postoperative Hospital discharge 3 months 6 months 12 months Non-randomised Comparative Study Left atrial MWA versus CS One comparative study reported the percentage of patients in AF following MWA versus CS alone (see Table 137). In Spitzer and Knaut (2002) at both six and 12 month follow-up, 25% of MWA patients were in AF. Although p values were not given, a higher proportion of patients were in AF following CS alone, with 92% at six months and 90% at 12 months. Table 137: Atrial fibrillation- Left atrial MWA versus CS Level Spitzer and Knaut 2002 LA: left atrial III-2 AF (%) LA MWA CS 25% 92% 25% 90% n/N LA MWA CS 28/111 41/45 28/111 40/45 Follow-up 6 months 12 months Case Series Biatrial MWA One case series using biatrial MWA reported the incidence of AF after surgery (see Table 138). In Chiappini et al. (2003) at the end of follow-up (mean 12.4 months), 22% (2/9) of the patients remained in AF. Table 138: Atrial fibrillation- Biatrial MWA Case Series Biatrial Chiappini et al. 2003 Level AF (%) n/N Follow-up IV 22% 2/9 12.4 months Left atrial MWA Four case series reported AF incidence following MWA to the left atrium (see Table 139). The median proportion of patients remaining in AF in these studies was 36%, with a range of 30% to 39%. Follow-up was from hospital discharge to 12 months, but not stated in Zembala et al. (2003). Gillinov et al. (2002) and Venturini et al. (2003) presented results only up to hospital discharge, when 30% (3/10) and 39% (16/41) of patients remained in AF, respectively. In Zembala et al. (2003) the number of patients with AF increased from hospital discharge (24%, 10/42), to the end of follow-up (33%, 14/42), although the period of follow-up was not stated. Table 139: Atrial fibrillation- Left atrial MWA Case Series Level Left atrial Gillinov et al. 2002 Knaut et al. 2002 Venturini et al. 2003 Zembala et al. 2003 Median Range IV IV IV IV AF (%) n/N Follow-up 80% 30% 35% 38% 39% 24% 33% 36% (30%-39%) 8/10 3/10 24/69 24/64 16/41 10/42 14/42 Perioperative Hospital discharge 6 months 12 months Hospital discharge Hospital discharge Not stated 85 MWA versus RFA One study reported the incidence of AF following MWA versus RFA (see Table 140). In Wisser et al. (2004) there were 20% (4/20) of MWA versus 21% (3/14) of RFA patients in AF at the end of follow-up. This was 24 months in the MWA and 12 months in the RFA group. When the patients were admitted to the ICU there were no patients in AF in either group. The p values were not given. Freedom from AF at 12 months follow-up was also reported: 81% of MWA versus 80% of RFA patients did not have AF (p>0.05). Table 140: Atrial fibrillation- MWA versus RFA Level Wisser et al. 2004 III-2/3 AF (%) MWA RFA 0% 0% 23% 21% 18% 22% 18% 21% 20% NS n/N MWA 0/23 5/22 4/22 4/22 4/20 Follow-up RFA 0/19 4/19 4/18 3/14 NS Admission to ICU 3 months 6 months 12 months 24 months NS: not stated Maze-III Atrial fibrillation was reported in eleven of the included Maze-III case series. The median proportion of patients in AF postoperatively was 5%, with a range of 3% to 26%. Follow-up was to hospital discharge in one study, at least three months in six studies, and not reported in two studies. Summary of AF results Comparative Studies Intraoperative ablation resulted in fewer patients in AF at the end of follow-up versus cardiac surgery alone. In the RCTs, significantly more patients were free from AF after biatrial RFA plus MV surgery versus MV surgery alone (Khargi et al. 2001); and after left atrial MWA plus CS versus CS alone (Schuetz et al. 2003). The non-randomised comparative studies were consistent with these results. In comparison to CS alone, fewer patients were in AF following: biatrial or left atrial CA; biatrial or left atrial RFA; and left atrial MWA. There did not appear to be a significant difference in incidence of AF when CA was compared to Maze-III surgery. With the internal comparison studies, there was no apparent difference in the numbers of patients remaining in AF when biatrial versus left atrial CA was used. However, there may have been fewer patients remaining in AF when RFA was applied in a biatrial versus left atrial pattern. The study groups in which a median could be calculated (groups with three or more studies) are illustrated below, with box plots to demonstrate both the median and variance in the studies within each group (Figure 4). All intraoperative ablation groups had a lower proportion of patients in AF compared to CS alone, with 84% (n=11) of patients remaining in AF after CS alone. In the CA and RFA treatment groups, a median proportion of 25% or less of patients remained in AF. The median proportion of patients in AF in the Maze-III study arms was 7% (n=4). 86 There was no apparent difference between biatrial versus left atrial lesion sets with cryotherapy. In the biatrial CA comparative studies, 12% of patients remained in AF (n=11), while in the case series 25% of biatrial CA (n=5) and 21% of left atrial CA (n=4) patients were in AF. However, with RFA fewer patients appeared to be in AF after biatrial versus left atrial lesion sets: 15% versus 21% in the comparative studies and 13% versus 21% for the case series in the biatrial versus left atrial RFA groups, respectively. Only four case series reported AF after left atrial MWA, with 36% of patients remaining in AF after surgery. (7%; n=4) Maze-III CS (84%; n=11) LA MWA case series (36%; n=4) LA RFA case series (21%; n=10) BA RFA case series (13%; n=9) BA RFA (15%; n=6) LA CA case series (21%; n=4) (25%; n=6) BA CA case series BA CA (12%; n=10) 0 20 40 60 80 100 Patients in AF (%) Figure 4: Median proportion of patients in AF The box represents the 10th and 90th percentiles, the line the median value, and the error bars the 5th and 95th percentiles. Outliers are represented by * when more than 1.5 box lengths from the median. (Median; no of studies) BA: biatrial; LA: left atrial; CA: cryotherapy ablation; RFA: radiofrequency ablation 5.2.3 Junctional rhythm The sinus node is the natural pacemaker of the heart, and consists of a cluster of cells in the upper wall of the right atrium. A junctional rhythm (also known as nodal rhythm) occurs when the heart is controlled by the atrioventricular (AV) node, instead of the sinus node. The AV node is a cluster of cells in the centre of the heart between the atria and ventricles, which normally acts as a gate to slow the electrical signal before it passes down to the ventricles. In junctional rhythm, the impulse arises in the AV node, ascends to the atria, and descends to the ventricles. Following cardiac surgery, postoperative junctional rhythms represent an escape mechanism, caused by temporary or permanent damage to the sinus node, and may be either too slow (bradycardia) or too fast (tachycardia). The length of follow-up is relevant for the included studies, as junctional rhythms are more common in the early postoperative period, with their incidence decreasing at longer term follow-up. 87 Cryotherapy Ablation (CA) Non-randomised Comparative Studies Biatrial CA+CS versus CS One study reported the incidence of junctional rhythm after biatrial CA+CS versus CS alone (see Table 141). The percentage of patients in junctional rhythm was 3% (1/39) in the CA group versus 0% in the CS group at a mean of 21 months follow-up. More patients were in junctional rhythm at hospital discharge, with 23% (9/39) in the CA+CS group versus 2% (1/58) after CS alone. The p value was not given at either time point. Table 141: Junctional rhythm- Biatrial CA+CS versus CS Level Handa et al. 1999 BA: biatrial III-2 Junctional rhythm (%) BA CA+CS CS 23% 2% 3% 0% n/N BA CA+CS 9/39 1/39 n/N CS 1/58 0/58 Follow-up Hospital discharge Mean 21 months (≥ 6 months) Left atrial CA versus CS One study reported the incidence of junctional rhythm after left atrial CA+CS versus CS (see Table 142). In Gaita et al. (2000) in the early postoperative period there were 6% (2/32) patients in junctional rhythm after left atrial CA+CS versus none after CS alone. The p value was not stated. Table 142: Junctional rhythm- Left atrial CA+CS versus CS Level Gaita et al. 2000 LA: left atrial III-2 Junctional rhythm (%) LA CA+CS CS 6% 0% n/N LA CA+CS 2/32 n/N CS 0/18 Follow-up Early postoperative Biatrial CA versus Maze-III One comparative study reported the number of patients in junctional rhythm after CA versus Maze-III surgery (see Table 143). Kosakai et al. (1995) used two modifications of CA surgery, the first modification (CA1) and the Kosakai maze. Junctional rhythm was present in 14% (2/14) of patients following CA1, and 3% (2/70) of Kosakai maze patients. Follow-up was at least one year. No patients were in junctional rhythm following the Maze-III operation. Table 143: Junctional rhythm- CA versus Maze-III Level Junctional rhythm (%) n/N n/N BA CA Maze-III BA CA Maze-III Kosakai et al. 1995 III-2/3 CA1: 14% 2/14 KM: 3% 0% 2/70 0/17 Total: 5% 4/84 KM: Kosakai maze; CA1: first CA ablation line set; ( ): range; BA: biatrial 88 Follow-up (1.0-3.1 years) Biatrial versus left atrial CA A single comparative study reported junctional rhythm in patients following biatrial versus left atrial CA (see Table 144). Junctional rhythm occurred in both groups at hospital discharge: 23% (7/30) of the biatrial versus 10% (2/20) of the left atrial patients (Takami et al. 1999). However, no patients in either group were still in junctional rhythm at the end of follow-up, a minimum of eight months postoperatively. Table 144: Junctional rhythm- Biatrial versus left atrial CA Level Takami et al. 1999 III-3 Junctional rhythm (%) BA CA LA CA 23% 10% 0% 0% n/N n/N BA CA 7/30 0/30 LA CA 2/20 0/20 Follow-up Hospital discharge 34.1[11.3] months 17.8[3.8] months (15-51 months) (8-23 months) [ ]: SD; ( ): range; BA: biatrial; LA: left atrial Case Series Biatrial CA A single case series reported patients in junctional rhythm following biatrial CA (see Table 145). Fukada et al. (1998) stated 7% (2/29) of patients were in junctional rhythm after biatrial CA. The period of follow-up was not given. Table 145: Junctional rhythm- Biatrial CA Case Series Biatrial Fukada et al. 1998 Level Junctional rhythm (%) n/N Follow-up IV 7% 2/29 Not stated Radiofrequency Ablation Non-randomised Comparative Studies Left atrial RFA versus CS A single study reported the incidence of junctional rhythm after left atrial RFA versus CS alone (see Table 146). In Guang et al. (2002) at the time of hospital discharge, similar percentages of patients were in junctional rhythm following left atrial RFA (9%, 9/96) versus CS alone (8%, 7/87). Results were not reported at later follow-up. Table 146: Junctional rhythm- Left atrial RFA versus CS Level Guang et al. 2002 LA: left atrial III-2 Junctional rhythm (%) LA RFA CS 9% 8% n/N LA RFA CS 9/96 7/87 89 Follow-up Hospital discharge Case Series Biatrial RFA Three case series stated the incidence of junctional rhythm in patients following biatrial RFA (see Table 147). There was a median proportion of 2% of patients in junctional rhythm after biatrial RFA (range 1% to 31%). Follow-up was from in-hospital to at least three months. A higher proportion of patients were in junctional rhythm in the early postoperative period. In Hornero et al. (2002) 31% (17/55) of patients were in junctional rhythm in-hospital; the incidence was not given for later follow-up. Chen et al. (2001) also reported a high incidence of junctional rhythm within two weeks postoperatively, with 31% (4/13) of patients with the first RFA lesion set and 15% (7/48) of patients with the second lesion set. At later follow-up only 2% (1/42) of patients with the second lesion set remained in junctional rhythm. Table 147: Junctional rhythm- Biatrial RFA Case Series Level Junctional rhythm (%) n/N Follow-up 4/13 7/48 0/13 1/42 1/55 2 weeks IV RFA1: 31% RFA2: 15% RFA1: 0% RFA2: 2% 2% Biatrial Chen et al. 2001a (3-32 months) Total Hornero et al. IV 31% 17/55 In-hospital (> 48 hours) 2002 23.6[12.5] months Patwardhan et al. IV 1% 1/70 (12-53 months) 1997a Median 2% Range (1%-31%) ( ): range; a: comparative study, with the incidence of junctional rhythm only reported in the biatrial RFA group; RFA1: first RFA lesion set; RFA2: second RFA lesion set Left atrial RFA One case series reported patients in junctional rhythm following left atrial RFA (see Table 148). In Gillinov et al. (2003) there were 26% (13/26) patients in junctional rhythm after surgery, but only 2% (1/50) by hospital discharge. Table 148: Junctional rhythm- Left atrial RFA Case Series Left atrial Gillinov et al. 2003 Level Junctional rhythm (%) n/N Follow-up IV 26% 2% 13/50 1/50 After surgery Hospital discharge MWA versus RFA One study reported the proportion of patients in junctional rhythm after MWA versus RFA (see Table 149). In Wisser et al. (2004) there were 5% (1/22) of MWA versus 11% (2/19) of RFA patients in junctional rhythm at three months follow-up. However, by the end of follow-up no patients in either group remained in junctional rhythm Follow-up was 24 months in the MWA, and 12 months in the RFA group. The p values were not given. 90 Table 149: Junctional rhythm- MWA versus RFA Level Junctional rhythm (%) MWA RFA 5% 11% 5% 0% 0% 0% 0% NS Wisser et al. 2004 III-2/3 n/N MWA 1/22 1/22 0/22 0/20 Follow-up RFA 2/19 0/18 0/14 NS 3 months 6 months 12 months 24 months NS: not stated Maze-III Eleven of the included Maze-III studies reported junctional rhythm after surgery. A median proportion of 5% of patients were in junctional rhythm after Maze-III surgery, with a range of 3% to 26%. 5.2.4 Atrial flutter (AFl) Atrial flutter (AFl) is a heart arrhythmia sharing clinical features with AF, but the underlying mechanism is more easily treated using percutaneous catheter-based techniques. Both atrial flutter and AF can co-exist in the same patient, and atrial flutter can degenerate into AF if left untreated. Typical AFl involves a single re-entrant circuit in the right atrium around the tricuspid valve annulus, in a counter-clockwise direction. Atypical AFl has the opposite activation sequence, clockwise around the tricuspid valve annulus. Atypical AFl most often results from previous surgical atriotomy scars, and does not require the tricuspid annular isthmus for a re-entrant circuit. Catheter ablation is possible, but anatomical obstacles may be more difficult to define compared to typical atrial flutter. In most studies, it was stated if patients were in AFl, but the type of AFl (typical or atypical) was often not given. Where the type of AFl was specified, it is stated in the results. Cryotherapy Ablation Non-randomised Comparative Studies Biatrial CA+CS versus CS One study reported the incidence of AFl after biatrial CA+CS versus CS alone (see Table 150). In Handa et al. (1999), 5% (2/39) of the CA+CS versus 2% (1/58) of CS patients were in AFl, at a mean of 21 months follow-up. The p value was not given. Table 150: Atrial flutter- Biatrial CA+CS versus CS Level Handa et al. 1999 III-2 Atrial flutter (%) BA CA+CS CS 0% 5% 5% 2% n/N BA CA+CS 0/39 2/39 BA: biatrial 91 n/N CS 3/58 1/58 Follow-up Hospital discharge Mean 21 months (≥ 6 months) CA versus Maze-III One study reported the incidence of AFl after CA versus the Maze-III procedure (see Table 151). Lee et al. (2001) reported at six months follow-up no patients were in AFl after either procedure. Table 151: Atrial flutter- CA versus Maze-III Level Lee et al. 2001 Atrial flutter (%) CA Maze-III 0% 0% III-3 n/N CA 0/53 n/N Maze-III 0/30 Follow-up 6 months Case Series Biatrial CA One case series reported the incidence of AFl after biatrial CA (see Table 152). In Sueda et al. (1997) there were 3% (1/36) of patients in AFl at hospital discharge, and 6% (2/36) at six months follow-up. Table 152: Atrial flutter- Biatrial CA Case Series Level Biatrial Sueda et al. 1997a Atrial flutter (%) n/N Follow-up Hospital discharge 3% 1/36 2/36 6 months 6% a: comparative study but atrial flutter only reported in biatrial CA group IV Left atrial CA Two case series reported patients with AFl after left atrial CA (see Table 153). No patients had AFl at 5 to 14 months in Sueda et al. (2001), whereas 10% (4/41) of patients had AFl in Usui et al. (2002). All four patients had typical AFl, diagnosed using electrophysiological study, but the length of follow-up was not stated. Table 153: Atrial flutter- Left atrial CA Case Series Left atrial Sueda et al. 2001 Usui et al. 2002 ( ): range Level Atrial flutter (%) n/N Follow-up IV IV 0% 10% 0/12 4/41 (5-14 months) Not stated Radiofrequency Ablation Non-randomised Comparative Study Left atrial RFA versus CS One study reported the incidence of AFl following left atrial RFA versus CS alone (see Table 154) In Guang et al. (2002), no RFA patients were in AFl, at up to three years follow-up. However, 2% (2/87) of patients were in AFl at hospital discharge following CS alone, and one patient in this group remained in AFl at three year follow-up. 92 Table 154: Atrial flutter- Left atrial RFA versus CS Level Guang et al. 2002 LA: left atrial III-2 Atrial flutter (%) LA RFA CS 0% 2% 0% 1% n/N LA RFA CS 0/96 2/87 0/96 1/87 Follow-up Hospital discharge 3 years Biatrial versus left atrial RFA One study reported the incidence of AFl following biatrial versus left atrial RFA (see Table 155). Güden et al. stated 19% (4/23) of patients were in AFl after left atrial RFA versus 0% (0/39) following biatrial RFA, a significant difference (p<0.05). Follow-up was a mean of 104 days. The diagnosis of atrial flutter was made using Holter monitoring. Table 155: Atrial flutter- Biatrial versus left atrial RFA Level Atrial flutter (%) BA RFA LA RFA Güden et al. III-2 0% 19%* 2002 ( ): range; *: p<0.05; BA: biatrial; LA: left atrial n/N Follow-up BA RFA LA RFA 0/39 4/23 Mean 104 days (45-245 days) Case Series Biatrial RFA Five case series reported the incidence of AFl after biatrial RFA (see Table 156). The median proportion of patients in AFl following biatrial RFA was 2%, with a range of 1% to 10%. Follow-up was from hospital discharge to a mean of 15 months. The highest incidence of AFl was 10%, but this study had only ten patients, with limited follow-up to hospital discharge (Sos et al. 2002). In this study, the patient had atypical AFl of left atrial origin at hospital discharge, confirmed by electrophysiological study. Where results were given from early to later follow-up, the incidence of AFl tended to be higher in the early postoperative period. For example, in Hornero et al. (2002) 11% (6/55) of patients were in AFl in-hospital, and only a single patient (1/52) at a mean of 7 months. Thomas et al. (2000) reported 96% (24/25) of patients were in AFl postoperatively. This was from an earlier subset of the later study. In the later study, one patient (1/42) was in AFl at a mean of 15 months (Thomas et al. 2003). 93 Table 156: Atrial flutter- Biatrial RFA Case Series Level Atrial flutter (%) n/N Follow-up Biatrial Chen et al. 2001a RFA1: NS 13 2 weeks RFA2: 2% 1/48 2 weeks IV RFA1: 9% 1/11 (37-47 months) RFA2: 2% 1/42 (3-32 months) 4% 2/53 Total Hornero et al. 2002 11% 6/55 In-hospital IV 2% 1/54 Hospital discharge 2% 1/52 Mean 7 months (1-16 months) Raman et al. 2003 1% 1/87 3 months IV 0% 0/50 6 months 0% 0/15 12 months Sos et al. 2002 10% 1/10 In-hospital IV 10% 1/10 Hospital discharge Thomas et al. 2000 96% 24/25 Postoperative IV Thomas et al. 2003 2% 1/42 15[18] months Median 2% Range (1%-10%) [ ]: SD; ( ): range; RFA1: first RFA ablation set; RFA2: second RFA ablation set; a: comparative study, but AFl not reported in the CS group; NS: not stated Left atrial RFA Seven case series studies reported the incidence of AFl after left atrial RFA (see Table 157). The median proportion of patients in AFl was 8%, with a range of 0% to 27%. Follow-up varied from hospital discharge to one year. Benussi et al. (2002) stated 8% of patients (10/132) were in typical AFl, diagnosed by electrophysiological study. Conversely Mohr et al. (2002) and Kottkamp et al. (1999) stated patients were in atypical AFl. The two studies with the highest incidence of AFl (Biederman et al. (2002); Kottkamp et al. 1999) were the studies which had the smallest patient numbers. No consistent changes in the incidence of AFl between early and later follow-up periods were apparent in Mohr et al. (2002). Table 157: Atrial flutter- Left atrial RFA Case Series Left atrial Benussi et al. 2002 Biederman et al. 2002 Gillinov et al. 2003 Kottkamp et al. 1999 Mohr et al. 2002 Level Atrial flutter (%) n/N Follow-up IV 8% 11/132 9[6.3] months IV 20% 2/10 4 weeks IV 4% 2/50 Hospital discharge IV 27% 3/11 11[6] months (3-20 months) 5% 3% 5% 0% 15% 8% (0%-27%) 3/65 1/30 1/21 0/95 6/37 Hospital discharge 6 months 12 months After hospital discharge Hospital discharge IV Müller et al. 2002 Ruchat et al. 2002 Median Range [ ]: SD; ( ): range IV IV 94 Microwave Ablation Case Series Left atrial MWA Three case series reported the incidence of AFl in patients after left atrial MWA (see Table 158). The median proportion of patients in AFl was 13%, with a range of 5% to 13%. Results were given for both atypical and typical AFl in Spitzer and Knaut (2002), with more patients in atypical versus typical AFl in this study (11% (12/111) atypical versus 2% (2/111) typical at 12 months). Table 158: Atrial flutter- Left atrial MWA Case Series Level Left atrial Knaut et al. 2002 Atrial flutter (%) n/N IV 4% 69 5% 64 Schuetz et al. 2003a IV 13% 24 Spitzer and Knaut 2% typical 2/111 2002a 2% typical 2/111 9% atypical 10/111 IV 11% atypical 12/111 11% Total 12/111 13% Total 14/111 Median 13% Range (5%-13%) a: comparative study, but AFl not reported in CS group Follow-up 6 months 12 months Not stated 6 months 12 months 6 months 12 months Total 6 months Total 12 months MWA versus RFA One study reported the incidence of atrial flutter following MWA versus RFA (see Table 159). In Wisser et al. (2004) there were no patients with atrial flutter at three months after MWA, and one patient (1/22, 5%) at six months follow-up. When RFA was used, there were 5% (1/19) of patients with atrial flutter at three months, and no patients with atrial flutter at six months follow-up. The type of atrial flutter was not specified, and p values were not given. Table 159: Atrial flutter- MWA versus RFA Level Wisser et al. 2004 III-2/3 Atrial flutter (%) MWA RFA 0% 5% 5% 0% n/N MWA 0/23 1/22 Follow-up RFA 1/19 0/18 3 months 6 months Maze-III Three of the included Maze-III studies reported AFl after surgery. There was a median proportion of 1% of patients with AFl after the Maze-III procedure, with a range of 1% to 19%. 95 5.2.5 Heart function Atrial Contraction Surgical incisions to the atria may result in a loss of contractile function of the heart muscle, and/or cause damage to the sinus node. An important question following intraoperative ablation is whether the atria can contract normally. Loss of atrial contraction can lead to 1) a compromise in overall heart function, contributing to heart failure, and 2) stasis of blood in the atria, increasing the risk of thromboembolism. The technique used most frequently to determine atrial contraction is Doppler echocardiography. Measurements used for Doppler echocardiography are based on the ‘Awaves’ and ‘E-waves’. The A-wave is defined as the peak filling velocity at atrial contraction, and the E-wave as the peak early diastolic filling velocity. These Doppler waves are measured for both tricuspid (right) and mitral (left) inflow. In some studies the presence of atrial contraction was given for the patients who were in SR, and it was not possible to extrapolate the number to the total group. When this was the case it is stated in the text. Also, some studies stated the number of patients with right and left atrial contraction, but not the number with biatrial contraction. The biatrial contraction was not extrapolated from these figures. Effective atrial contraction is also used to determine whether a patient should continue to use anticoagulant therapy. When patients have both normal SR and effective atrial contraction, anticoagulation therapy may be stopped. Cryotherapy Ablation Non-randomised Comparative Studies CA versus Maze-III Three studies reported atrial contraction after CA versus Maze-III (see Table 160). Transmitral atrial contraction was reported in all three studies, with a median proportion of 91% (70% to 98%) of CA versus 78% (61% to 92%) of Maze-III patients having left atrial contraction. Follow-up was immediately after surgery in Ishii et al. (2001), and at least six months in the other two studies. In Kim et al. (2001) there was no significant difference in the proportion of patients with left atrial contraction between the CA (70%, 16/23) versus Maze-III (11/18) groups (p>0.01). This was also the case in Lee et al. (2001) in the early postoperative period, however, at six months follow-up more patients had left atrial contraction in the CA (98%, 52/53) versus Maze-III (78%, 23/30) groups (p<0.01). In this study the proportion of patients with left atrial contraction increased in both groups from early postoperative to six month follow-up. Two studies reported right atrial contraction, with 91% of patients after CA versus 89% to 92% of patients after Maze-III having a transtricuspid A-wave. There was no statistically significant difference between the groups in Kim et al. (2001), and the p value was not given in Ishii et al. (2001). 96 Table 160: Atrial contraction- CA versus Maze-III Level Ishii et al. 2001 Kim et al. 2001 Lee et al. 2001 III-3 Right atrial CA Maze-III 91% 92% (12/13) (27/30) 91% 89%pns (21/23) (16/18) CA Left atrial Maze-III 91% (27/30) 92% (12/13) 70% 61%pns (16/23) (11/18) III-3 68% 55%pns (36/53) (17/30) NS NS 98% 78%† (52/53) (23/30) Median 91% 78% Range 91% (89%-92%) (70%-98%) (61%-92%) [ ]: SD; ( ): range; NS: not stated; pns: statistically non-significant; †: p<0.01 III-3 Follow-up Immediately after surgery 29[4] 47[14] months months Postoperative 6 months Case Series Biatrial CA Four case series reported atrial contraction after biatrial CA (see Table 161). Left atrial contraction was stated in three studies. A median proportion of 55% of patients had transmitral contraction, with a range of 38% to 80%. Follow-up was from one month (Sueda et al. 1997) to at least six months in the other two studies. Yuda et al. (1998) presented results from a subgroup of patients divided into those with and without a giant left atrium (GLA). When patients had GLA only 21% (4/19) had left atrial contraction, compared with 66% (21/32) when GLA was not present. Two studies presented right atrial contraction in patients after biatrial CA. In Ad et al. (2003a) all patients (10/10) had right atrial contraction one week after surgery, while in Sueda et al. (1997) 81% (29/36) of patients had right atrial contraction. Table 161: Atrial contraction- Biatrial CA Case Series Biatrial Ad et al. 2003 Sueda et al. 1997a Level Right atrial IV IV 100% (10/10) 81% (29/36) Left atrial Follow-up 80% (8/10) 1 week 6 months 61% 1 month (22/36) Yuda et al. 2001 IV 50% (47/94) 3.1[3.3] months 38% (36/94) 2.2[0.9] years GLA: 21% (4/19)b 12 months nonGLA: 66% (21/32) 12 months Total: 49% (25/51) 12 months Yuda et al. 2004 a IV 38% (10/26) 16.8[13.4] months Median 55%c Range (81%-100%) (38%-80%) [ ]: SD; ( ): range; a: comparative study but atrial contraction not reported in CS group; GLA: giant left atrium; b; Yuda et al. 1998; c: not including the subgroup of Yuda et al. (1998). Left atrial CA Five case series reported atrial contraction in patients after left atrial RFA (see Table 162). Left atrial contraction was reported in three studies, and was present in a median of 58% of patients (range 38% to 62%). Right atrial contraction was reported in the same three studies, and was present in a median proportion of 75% of patients (range 72% to 100%). Follow-up was from hospital discharge (Kondo et al. 2003) to at least five months in the other two studies. 97 Biatrial contraction was reported by two studies. Manasse et al. (2003) stated more than 80% (36/45) of patients had contraction of both atria at least three months following surgery. It should be noted that this was a subgroup of patients who were in SR, and the percentage would have been lower in the entire group. In Gaita et al. (2000) 83% (24/29) of patients had contraction of both atria at nine months follow-up. Table 162: Atrial contraction- Left atrial CA Case Series Level Left atrial Gaita et al. 2000a IV Imai et al. 2001 IV Right atrial 100% (14/14)a Left atrial 38% (12/32) Biatrial Follow-up 83% (24/29) 9 months 36.9[14.1] months (13-66 months) Hospital discharge Kondo et al. 2003 IV 72% (21/29) 62% (18/29) Manasse et al. IV >80% (3-9 months) 2003 (>36/45a) Sueda et al. 2001 IV 75% (9/12) 58% (7/12) (5-14 months) Median 75% 58% Range (72%-100%) (38%-62%) [ ]: SD; ( ): range; a: subgroup of patients with SR, but not possible to extrapolate number to entire group; a: comparative study but atrial contraction only reported in left atrial CA group Radiofrequency Ablation (RFA) Randomised Comparative Studies Biatrial RFA versus CS One RCT reported atrial contraction after biatrial RFA versus CA (see Table 163). Left atrial contraction was reported from day 12 to one year of follow-up. No significant differences in left atrial contraction between the RFA versus CS groups were present (RR at 12 months 3.6 95% CI 0.62 to 21.03, p=0.15).Left atrial contraction increased from day 12 (33%, 3/15) to six months (58%, 7/15) of follow-up after RFA. However, contraction of the left atrium was stable from day 12 after CS alone. Right atrial contraction was reported only at six and 12 months of follow-up. Significantly more patients had right atrial contraction at one year after RFA (82%, 9/11) versus CS alone (25%, 3/12; RR 13.5 95% CI 1.80 to 101.13, p=0.01). The same proportion of patients had contraction of both atria as those with left atrial contraction. Table 163: Atrial contraction- Biatrial RFA+MVS versus MVS RCT Level Right atrial BA RFA MVS NS NS Left atrial Biatrial Follow-up BA RFA MVS BA RFA MVS Khargi et II 33% 27%pns Day 12 NS NS al. 2001 (5/15) (4/15) 83% 27%† 58% 27%pns 6 months 58% 27%pns (10/12) (4/15) (4/15) (7/12) (4/15) (7/12) 82% 25%* 25%pns 55% 25%pns 12 months 55% (9/11) (3/12) (3/12) (6/11) (3/12) (6/11) NS: not stated; pns: statistically non-significant (RevMan); BA: biatrial; MVS: mitral valve surgery 98 Non-randomised Comparative Studies Biatrial RFA versus CS One study reported atrial contraction after biatrial RFA versus CS (see Table 164). In Chen et al. (2001) significantly more patients had left and right atrial contraction following RFA versus CS alone. Follow-up was from a mean of 16 months in the RFA2 patients to 61 months after CS. There were 11 % (6/54) patients with both left and right atrial contraction after CS alone. When biatrial RFA was performed using two different lesion sets, there were 55% and 74% of patients with left atrial contraction, and 73% and 81% of patients with right atrial contraction. Table 164: Atrial contraction- Biatrial RFA versus CS Level Right atrial Left atrial RFA CS RFA CS Chen et III-2 RFA1: 73% RFA1: 55% al. 2001 (6/11) (8/11) 11%† 11%† (6/54) (6/54) RFA2: 81% RFA2: 74% (38/47) (35/47) RFA1: first RFA lesion set; RFA2: second RFA lesion set; †: p<0.01 Follow-up Mean 43 months Mean 16 months Mean 61 months Left atrial RFA versus CS One study reported biatrial contraction after left atrial RFA versus CS (see Table 165). In Mantovan et al. (2003) there were 65% (66/102) of patients with biatrial contraction after left atrial RFA versus only 11% (3/27) after CS alone. Follow-up was on average greater than one year. The p value was not given. Table 165: Atrial contraction- Left atrial RFA versus CS Level Mantovan et al. 2003 [ ]: SD; LA: left atrial III-2 Biatrial LA RFA CS 65% (66/102) 11% (3/27) Follow-up 12.5[5] months RFA versus Maze-III One study reported biatrial contraction after biatrial RFA versus Maze-III (see Table 166). In Chiappini et al. (2004) a similar proportion of patients had biatrial contraction after RFA (77%) versus Maze-III surgery (70%; p>0.05). The patient numbers could not be calculated as only the percentages were given in the study. Table 166: Atrial contraction- Biatrial RFA versus Maze-III Level Chiappini et al. 2004 III-3 pns: statistically non-significant RFA 77% Biatrial Maze-III 70%pns Follow-up 6 months Biatrial versus left atrial RFA Two studies reported atrial contraction after biatrial versus left atrial RFA (see Table 167). Left atrial contraction was reported by Güden et al. (2002): 74% of biatrial RFA versus 52% of left atrial RFA patients having contraction of the left atrium at one and six months after surgery. The p value was not given. Right atrial contraction was reported in both studies, with a range of 89% to 92% having transtricuspid contraction in the biatrial RFA versus 71% to 100% in the left atrial RFA 99 groups. No consistent difference in right atrial contraction was present between the two groups. Biatrial contraction was also reported in Deneke et al. (2002a). Both atria had effective contraction in a lower proportion of patients, 79% (19/24) of biatrial versus 92% (12/13) of left atrial patients. Follow-up was at least an average of 11 months. Table 167: Atrial contraction- Biatrial versus left atrial RFA Level Right atrial BA RFA LA RFA Left atrial BA LA RFA RFA 74% 52% 74% 52% Biatrial BA LA RFA RFA Follow-up BA LA RFA RFA 1 month 6 months Güden et III-2 89% 71% 89% al. 2002a 71% Deneke III-2/3 79% 92% 18[14] 11[10] 92% 100% et al. (19/24) (12/13) months months (22/24) (13/13) b 2002a Range (89%-92%) (71%-100%) a: results given as percentages, not possible to extrapolate patient numbers; LA: left atrial; BA: biatrial; b: a subgroup of patients in SR, not possible to extrapolate results to entire group; [ ]: SD Case Series Biatrial RFA Five case series reported atrial contraction after biatrial RFA (see Table 168). Follow-up was at least an average of three months. The median proportion of patients with left atrial contraction was 64%, with a range of 10% to 96%. The proportion of patients with contraction of the left atrium increased from the perioperative period to later follow-up in both studies where early and later measurements were reported (Hornero et al. 2002; Prasanna et al. 2001). A median of 79% of patients had right atrial contraction after biatrial RFA, with a range of 40% to 96%. The proportion of patients with right atrial contraction remained unchanged from the operating table to three months follow-up in Prasanna et al. (2001), but increased from 50% (27/54) at hospital discharge to 85% (44/52) at a mean of seven months follow-up in Hornero et al. (2002). Table 168: Atrial contraction- Biatrial RFA Case Series Level Biatrial Hornero et IV al. 2002 Patwardhan IV et al. 2003 Prasanna et IV al. 2001 Sie et al. IV 2001 Sos et al. IV 2002 Median Range [ ]: SD; ( ): range Right atrial Left atrial Biatrial Follow-up 50% (27/54) 85% (44/52) 37% (20/54) 73% (38/52) 37% (20/54) 73% (38/52) Hospital discharge Mean 7 months (1-16 months) 79% (55/70) 63% (44/70) 23.6[12.5] months (12-53 months) 96% (24/25) 96% (24/25) 80% (20/25) 96% (24/25) Operating table 3 months 69% (74/107) 64% (68/107) Mean 39 months 40% (4/10) 10% (1/10) Mean 3 months (1.5-5 months) 79% (40%-96%) 64% (10%-96%) 100 Left atrial RFA Six case series reported atrial contraction after left atrial RFA (see Table 169). Five studies reported left atrial contraction following left atrial RFA. The median proportion of patients with contraction of the left atrium was 68%, with a range of 26% to 84%. Followup was at least six months. Ruchat et al. (2002) reported patients had no left atrial contraction at hospital discharge, but 26% (8/29) had recovered left atrial function at over one year of follow-up. One study reported right atrial contraction. In Ruchat et al. (2002) no patients had right atrial contraction at hospital discharge. Biatrial contraction was reported in two studies. There were 81% (87/108) of patients with biatrial contraction at six months in Benussi et al. (2002), and 92% at two years follow-up in Le Tourneau et al. (2003). Table 169: Atrial contraction- Left atrial RFA Case Series Level Right atrial Left atrial Biatrial Left atrial Benussi et IV 81% (87/108) al. 2002 Kress et al. IV 56% (5/9) 2002a Le IV Tourneau 92%a et al. 2003 Müller et IV 84%a al. 2002 Ruchat et IV 0% 0% al. 2002 26% (8/29 SR) Starck et IV 80% (72/90) al. 2003 Median 68% Range (0%-88%) (26%-84%) (81%-92%) a: not possible to deduce the number of patients; [ ]: SD; ( ): range Follow-up 6 months 32.5[28.4] weeks (1-100 weeks) 2 years 6 months Hospital discharge 14[5] months 7.3 months Microwave Ablation Non-randomised Comparative Study Left atrial MWA versus CS Atrial contraction was reported in one study after left atrial MWA versus CS (see Table 170). In Spitzer and Knaut (2002) significantly more patients had biatrial contraction after MWA (62%, 69/111)) versus CS alone (10%, 5/45; p<0.0001). In both groups all patients in SR had biatrial contraction. Table 170: Atrial contraction- Left atrial MWA versus CS Level Spitzer and Knaut 2002 III-2 Biatrial LA MWA CS 62% 10%§ (69/111) (5/45) §: p<0.0001; LA: left atrial 101 Follow-up 12 months MWA1 versus MWA2 One study reported atrial contraction following two different MWA lesion sets (see Table 171). In Knaut et al. (2003) at six months follow-up, results were given according to the type of concurrent surgery performed. The proportion of patients with biatrial contraction at six months follow-up was higher after MWA2 versus MWA1, with concurrent MV surgery, coronary artery surgery, or aortic valve replacement. Table 171: Atrial contraction- MWA1 versus MWA2 Level Biatrial Follow-up MWA1 MWA2 Knaut et al. III-2/3 MVS: 62% MVS: 88% 6 months 2003 CABG: 70% CABG: 78% AVR: 80% AVR: 85% MWA1: first MWA lesion set; MWA2: second MWA lesion set; MVS: MV surgery; CABG: coronary artery bypass grafting; AVR: aortic valve replacement Case Series Left atrial MWA One case series reported atrial contraction after left atrial MWA (see Table 172). In Knaut et al. (2002) 49% (18/37) of patients had right atrial contraction one year after left atrial MWA. Contraction of both atria was present in only 43% (16/37) of patients at the same time point. Table 172: Atrial contraction- Left atrial MWA Case Series Left atrial Knaut et al. 2002 Level Right atrial Biatrial Follow-up IV 49% (18/37) 43% (16/37) 12 months Maze-III There were six Maze-III studies reporting right atrial contraction, and nine studies reporting left atrial contraction. Right atrial contraction occurred in a median of 95% of patients, with a range of 76% to 100%. There were a lower proportion of patients with left atrial contraction, with a median of 73%, and a range of 50% to 92%. 102 Summary results atrial contraction Right atrial contraction Comparative Studies Intraoperative ablation resulted in a greater number of patients with right atrial contraction than cardiac surgery alone. In the RCT comparing biatrial RFA plus MV surgery versus MV surgery alone, significantly more patients had right atrial contraction after RFA plus MV surgery versus MV surgery (Khargi et al. 2001). The non-randomised comparative studies were consistent with these findings. Compared to CS alone, more patients had right atrial contraction following: biatrial or left atrial RFA; and left atrial MWA. There did not appear to be a significant difference in right atrial contraction when either CA or RFA was compared to Maze-III surgery. In one internal comparison study, there was no apparent difference in right atrial contraction following biatrial versus left atrial RFA. The study groups in which a median proportion of right atrial contraction could be calculated (groups with three or more studies) are illustrated below, with box plots to demonstrate both median and variance in the studies within each group (Figure 5). In the intraoperative ablation groups, a median of 75% to 86% of patients had right atrial contraction. A median of 89% of patients had right atrial contraction after Maze-III surgery in the three studies with a Maze-III comparative study arm. Maze-III (89%; n=3) BA RFA CS (79%; n=5) BA RFA (86%; n=4) LA CA case series (75%; n=3) 0 20 40 60 80 100 Right atrial contraction (%) Figure 5: Median proportion of patients with right atrial contraction The box represents the 10th and 90th percentiles, and the line the median value. Insufficient numbers of studies were included to include error bars of the 5th and 95th percentiles. (Median; no of studies) BA: biatrial; LA: left atrial; CA: cryotherapy ablation; RFA: radiofrequency ablation 103 Left atrial contraction Comparative Studies Intraoperative ablation resulted in a greater number of patients with left atrial contraction than cardiac surgery alone only in some of the studies. In the RCT comparing biatrial RFA plus MV surgery versus MV surgery alone, there was no significant difference between the two groups in the proportion of patients with left atrial contraction (55% versus 25%), possibly because the study was underpowered for this result (Khargi et al. 2001). In the non-randomised comparative studies, compared to CS alone, more patients appeared to have left atrial contraction following biatrial or left atrial RFA. When compared to the MazeIII procedure, in two of three CA comparative studies there was no apparent difference in left atrial contraction between the groups (Ishii et al. 2001; Kim et al. 2001), but in the third study significantly more patients had left atrial contraction after CA versus Maze-III surgery (Lee et al. 2001). There was no significant difference in incidence of left atrial contraction between RFA and Maze-III surgery. In one internal comparison study, there was no significant difference in left atrial contraction following biatrial versus left atrial RFA. The study groups in which a median proportion of left atrial contraction could be calculated (groups with three or more studies) are illustrated below, with box plots to demonstrate both median and variance in the studies within each group (Figure 6). In the intraoperative ablation groups, the median proportions of left atrial contraction were less than for right atrial contraction. There was a median of 91% of patients with left atrial contraction, in three biatrial CA comparative studies. In the biatrial CA case series, a median of only 50% of patients had left atrial contraction versus 58% in the left atrial CA case series. The RFA groups had a median of 64% to 70% of patients with left atrial contraction, with the highest value (72%) in the BA RFA comparative group. The four study arms for the Maze-III procedure had a median proportion of 74% of patients with left atrial contraction, also less than for right atrial contraction (89%). 104 Maze-III (78%; n=3) (11%; n=3) Cardiac Surgery LA RFA case series (68%; n=4) BA RFA case series (64%; n=5) (70%; n=3) BA RFA (58%; n=3) LA CA case series BA CA case series (50%; n=4) BA CA (91%; n=3) 0 20 40 60 80 100 Mortality (%) Figure 6: Median proportion of patients with left atrial contraction The box represents the 10th and 90th percentiles, and the line the median value. Insufficient numbers of studies were included to include error bars of the 5th and 95th percentiles. (Median; no of studies) BA: biatrial; LA: left atrial; CA: cryotherapy ablation; RFA: radiofrequency ablation A/E Ratio As mentioned previously, the A-wave is defined as the peak filling velocity at atrial contraction, and the E-wave as the peak early diastolic filling velocity. The ratio of A/E is used as an index of atrial contraction, with a higher ratio indicative of better atrial function. A A/E ratio was only calculated in patients with SR, therefore the A/E ratios are from the subgroup of patients with SR after surgery. Cryotherapy Ablation Non-randomised Comparative Studies CA versus Maze-III One study reported A/E ratios after CA versus Maze-III (see Table 173). Ishii et al. (2001) reported A/E ratios in patients at one to 12 months after CA, and compared them to a group of Maze-III patients at a mean follow-up of 41 months. The left A/E ratio in the CA versus Maze-III patients at one month was not significantly different (0.37 versus 0.25, p>0.05), but at three or more months the left A/E ratio was significantly higher in the CA versus Maze-III patients (0.52 versus 0.25, p<0.05). The right A/E ratios were generally higher than values for the left, but were not significantly different between the CA versus Maze-III patients. 105 Table 173: A/E ratio- CA versus Maze-III Study Right A/E ratio Left atrial A/E ratio CA Maze-III CA Maze-III Ishii et 0.64[0.27]pns 0.37[0.20]pns al. 2001 0.87[0.24]pns 0.66[0.17] 0.52[0.18]* 0.25[0.07] 0.71[0.22]pns 0.44[0.11]* 0.58[0.09]pns 0.52[0.15]* [ ]: SD; ( ): range; pns: statistically non-significant; *: p<0.05 CA 15 n Maze-III 8 Follow-up 1 month 3 months 6 months 12 months Mean 41 months (34-52 months) Case Series Biatrial CA One case series reported A/E ratio after biatrial CA (see Table 174). Fukada et al. (1998) reported results in patients with and without rheumatic heart disease, at a mean of at least three months after biatrial CA. The left atrial A/E ratio was significantly higher in the non-rheumatic patients versus those with rheumatic heart disease (0.42 versus 0.25, p<0.05). However, there was no difference in right atrial A/E ratio between the rheumatic (0.62) versus non-rheumatic (0.67) patients. Table 174: A/E ratio- Right atrial CA Case Series Study Right A/E ratio Left atrial A/E ratio n Follow-up Biatrial Fukada et al. R: 0.62[0.18] R: 0.25[0.06] 10 R: 3.2[2.5] months 1998 Non-R: 0.67[0.08] Non-R: 0.42[0.15]* 7 Non-R: 4.5[4.4] months [ ]: SD; R: rheumatic; Non-R: non-rheumatic; *: p<0.05; pns: statistically non-significant Left atrial CA One case series reported A/E ratios after left atrial CA (see Table 175). Imai et al. (2001) reported the numbers of patients with an A/E ratio of less than 0.3, since they used an A/E ratio of greater than 0.3 as the cut-off point for effective atrial contraction. The left A/E ratio was less than 0.3 in approximately one third (35%, 7/20) of patients. More patients had effective right atrial contraction, as the A/E ratio was less than 0.3 in only 7% (1/14) of the patients. Follow-up was a mean of over three years. Table 175: A/E ratio- Left atrial CA Case Series Left atrial Imai et al. 2001 [ ]: SD Right A/E Left A/E Follow-up <0.3 in 1/14 (7%) <0.3 in 7/20 (35%) 36.9[14.1] months Radiofrequency Ablation Case Series Biatrial RFA Case Series Two case series reported A/E ratios after biatrial RFA (see Table 176). Left atrial A/E ratios were a mean of 0.30 and 0.56 in the two studies, with follow-up of at least 122 days (Hornero et al. 2002; Thomas et al. 2000). The right atrial A/E ratio was stated in only one study, with an average A/E ratio of 0.81 (Thomas et al. 2000). 106 Table 176: A/E ratio- Biatrial RFA Case Series Study Right A/E ratio Left atrial A/E ratio Biatrial Hornero et al. 2002 NS 0.30[0.61] Thomas et al. 2000 0.81[0.09] 0.56[0.10] a: 39% (9/23) of total patients; [ ]: SD; ( ): range; NS: not stated n Follow-up 38 9a 7 months (1-16 months) 122[80] days Left atrial RFA Case Series Two case series reported A/E ratios in patients after left atrial RFA (see Table 177). In Benussi et al. (2002) the left atrial A/E ratio was a mean of 0.48, and the right atrial A/E ratio a mean of 0.71. Ruchat et al. (2002) used a cut-off A/E ratio of greater than 0.5 to demonstrate effective atrial contraction. In 74% (15/20) patients the left A/E ratio was less than 0.5, meaning they did not have effective left atrial contraction. Follow-up was greater than one year in both studies. Table 177: A/E ratio- Left atrial RFA Case Series Study Right A/E ratio Left atrial A/E ratio Left atrial Benussi et al. 0.48[1.3] 0.71[2.0] 2002 Ruchat et al. <0.5 in 74% (15/20) 2002 [ ]: SD; a: Number deduced by extrapolation n Follow-up 87 16.9[14.2] months 20a 14[5] months Atrial Filling Fraction The atrial filling fraction (AFF) is derived as the ratio of the time-velocity integral of the Awave versus total diastolic filling, expressed as a percentage value. A patient’s AFF is an index of atrial systolic pump function (Ramachandran et al. 2003), and an estimate of the contribution of atrial contraction to ventricular filling. Higher AFF values indicate better atrial pump function. Values for AFF are only given for the subgroup of patients in SR. Cryotherapy Ablation Case Series Biatrial CA Case Series One case series reported AFF in patients after biatrial CA (see Table 178). In Yuda et al. (2001) the left AFF was a mean of 17% at both early (3.1 months) and late (2.2 years) follow-up. It was stated that the mean value for the left AFF was less than the normal range. Table 178: Atrial filling fraction- Biatrial CA Case Series Study Biatrial Yuda et al. 2001 Left AFF (%) 17[6] 17[5] [ ]: SD; AFF; atrial filling fraction n Follow-up 35 35 3.1[3.3] months 2.2[0.9] months 107 Radiofrequency Ablation Non-randomised Comparative Studies Biatrial RFA versus CS One study reported AFF after RFA versus CS (see Table 179). In Chen et al. (2001) there were no significant differences in AFF between the RFA versus CS group. The left AFF was 21% to 25% after RFA versus 33% after CS alone (p>0.05). Higher values were present for right AFF: 38% to 39% after RFA versus 40% following CS (p>0.05). Follow-up was a mean of 16 months after the second RFA lesion set, and an average of over three years in the other groups. Table 179: Atrial filling fraction- Biatrial RFA versus CS Study Chen et al. 2001 Right AFF (%) BA RFA CS Left AFF (%) BA RFA CS n BA RFA Follow-up CS RFA1: 43 months 61 33[8]pns 6 40[6]pns RFA2: 16 months months [ ]: SD; pns: statistically non-significant; RFA1: first RFA lesion set; RFA2: second RFA lesion set; AFF: atrial filling fraction; BA: biatrial RFA1: 21[8] RFA2: 25[12] RFA1: 38[6] RFA2: 39[10] RFA1: 8 RFA2: 41 Case Series Biatrial RFA Case Series One case series reported left A/E ratio in patients after biatrial RFA (see Table 180). The left AFF was a mean of 27% at a median of 2.9 years after biatrial RFA. Table 180: Atrial filling fraction- Biatrial RFA Case Series Study Left AFF (%) n Follow-up Thomas et al. 2003 27[14] 29 [ ]: SD; ( ): range; AFF: atrial filling fraction Median 2.9 years (0.6-4.2 years) Microwave Ablation Case Series Left atrial MWA Case Series One study reported left AFF after left atrial MWA (see Table 181). In Venturini et al. (2003) a left AFF of more than 30% was defined as normal left atrial function; less than 20% classified as severe impairment; and 20% to 29% representing mild to moderate impairment. There were 15% (5/34) of patients with a left atrial AFF of less than 20%; 26% (9/34) of patients with left atrial AFF of 20% to 29%; and 59% (20/34) with a ‘normal’ left atrial AFF of greater than 30%. Follow-up was at least five months. Table 181: Atrial filling fraction- Left atrial MWA Case Series Left AFF (%) Left atrial Venturini et al. 2003 <20%: 15% 20-29%: 26% > 30%: 59% ( ): range; AFF; atrial filling fraction n Follow-up 34 14.2 months (5-21 months) 108 A-wave Peak Velocity The A-wave peak velocity is defined as the peak filling velocity, at either left or right atrial contraction. Cryotherapy Ablation Non-Randomised Comparative Studies CA versus Maze-III One study reported peak left atrial A-wave velocities after CA versus Maze-III (see Table 182). In Lee et al. (2001) there was a significant difference between left atrial peak A-wave velocities after CA (45 m/s) versus Maze-III (26 m/s) at thirty days follow-up (p<0.05). However, at six months there was no significant difference between the CA versus Maze-III patients (62 m/s versus 49 m/s, p>0.05). Table 182: Peak A-wave velocity- CA versus Maze-III Study Left atrial peak velocity (m/s) CA Maze-III Lee et al. 2001 45 26* 62 49pns *: p<0.05; pns: statistically non-significant CA n Maze-III 53 30 Follow-up 30 days 6 months Case Series Biatrial CA One case series reported peak left atrial A-wave velocities after biatrial CA (see Table 183). In Yuda et al. (2001) the peak left atrial A-wave velocities were a mean of 44 cm/s in early (3.1 months) follow-up and 43 cm/s in later (2.2 years) follow-up. Table 183: Peak A-wave velocity- Biatrial CA Case Series LA Peak velocity (cm/s) n Follow-up 44[18] 43[13] 35 35 3.1[3.3] months 2.2[0.9] years Biatrial Yuda et al. 2001 ( ): range; [ ]: SD; LA: left atrial Radiofrequency Ablation Non-randomised Comparative Studies RFA versus Cardioversion One study reported peak left atrial A-wave velocity after RFA versus cardioversion (see Table 184). In Thomas et al. (2003) the peak A-wave velocity was not significantly different in patients after RFA (mean 600 cm/s) versus cardioversion (mean 700 cm/s, p>0.05). Follow-up was over one year on average. 109 Table 184: Peak A-wave velocity- Biatrial CA Case Series LA Peak A-wave velocity (cm/s) RFA Cardioversion n Cardioversion Follow-up RFA 21 33 15[18] months Thomas et al. 600[300] 700[200]pns 2003 [ ]: SD; LA: left atrial; pns: statistically non-significant Case Series Biatrial RFA Three case series reported peak left atrial A-wave velocity in patients after biatrial CS (see Table 185). The median left atrial peak A-wave velocities was 50 cm/s, with a range of 34 cm/s to 72 cm/s. Follow-up was three months in Raman et al. (2003), and over two years in the other two studies. Raman et al. (2003) reported peak A-wave velocity was a mean of 32 cm/s in patients with endocardial RFA versus a mean of 39 cm/s in patients after epicardial RFA. Table 185: Peak A-wave velocity- Biatrial RFA Case Series Biatrial Prasanna et al. 2001 Raman et al. 2003 LA Peak velocity (cm/s) n Follow-up 72[17] (42-104) 24 Mean 3.5 years (3.2-3.8 years) 32[2] endocardial 39[12] epicardial Mean: 34 54 18 Total: 72 3 months 29 Median 2.86 years Thomas et al. 50[30] 2003 Median 50 Range (34-72) ( ): range; [ ]: SD; NS: not stated; LA: left atrial Left atrial RFA Case Series Two case series reported peak A-wave velocity after left atrial RFA (see Table 186). Left atrial peak A-wave velocity was a mean of 76 cm/s in Benussi et al. (2002) and 92 cm/s in Kress et al. (2002). Follow-up was at least three months in both studies. Right atrial peak A-wave velocity was reported in Benussi et al. (2002): a mean of 51 cm/s. Table 186: Peak A-wave velocity- Left atrial RFA Case Series RA Peak velocity (cm/s) LA Peak velocity (cm/s) Left atrial Benussi et al. 51[18] 76[33] 2002 Kress et al. NS 92[33] (40-120) 2002 [ ]: SD; ( ): range; NS: not stated; RA: right atrial; LA: left atrial 110 n Follow-up 87 16.9[14.2] months 5 (3-15 months) 5.2.6 Pacemakers Heart pacemakers are battery operated devices that emit an electrical current to stimulate the heart when the heart rate is too slow. Slow heart rate, or bradycardia, can result in symptoms such as fainting, fatigue, weakness and chest pains. The sinus node is the natural heart pacemaker. The sinus node may not be functioning properly before surgery, but this is “masked” by the AF. Since electrophysiological studies are not obtained on all patients prior to surgery, the status of the sinus node is not always known. Therefore it is difficult to predict which patients will require a pacemaker. A pacemaker may only be necessary temporarily following surgery, or it may need to be permanently implanted. Damage to the sinus node arteries was a major complication of the Maze-I procedure, resulting in a high proportion of patients needing pacemakers after surgery. There are wide variations in the anatomy of the sinus node arteries between patients, and different intraoperative ablation lesion sets may result in sinus node damage, leading to pacemaker requirement. Cryotherapy Ablation Non-randomised Comparative Studies Biatrial CA+CS versus CS Two studies reported the incidence of patients requiring pacemakers after CA+CS versus CS alone (see Table 187). There were 3% and 12% of patients requiring a pacemaker after biatrial CA+CS versus 9% and 17% after CS alone. Follow-up was at least six months. In Sueda et al. (1997) 12% (3/26) of patients required a pacemaker after biatrial CA+CS, by six months of follow-up. Two patients had sinus bradycardia, and slow atrial flutter and bradycardia was present in another patient. A single patient required a pacemaker after cardiac surgery alone (1/6). Table 187: Pacemakers- Biatrial CA+CS versus CS Level Handa et al. 1999 III-2 Sueda et al. 1997 Range BA: biatrial III-3 Pacemaker (%) BA CA CS n/N BA CA n/N CS 3% 9% 1/39 5/58 12% (3%-12%) 17% (9%-17%) 3/26 1/6 Follow-up Mean 21 months (≥ 6 months) 6 months Left atrial CA versus CS One study reported pacemaker requirement in patients after left atrial CA versus CS alone (see Table 188). In Gaita et al. (2000) a high proportion of patients needed temporary pacemakers in the operative period: 38% (12/32) of patients after left atrial CA+CS versus 33% (6/18) of patients after CS alone (p>0.05). However, a permanent pacemaker was required by only one patient (1/32) in the left atrial CA+CS group versus no patients following CS alone. 111 Table 188: Pacemakers- Left atrial CA+CS versus CS Level Pacemaker (%) LA CA CS Gaita et al. III-2 38% temporary 33% temporarypns 2000 3% permanent 0% permanent pns: statistically non-significant; LA: left atrial n/N LA CA 12/32 1/32 n/N CS 6/18 0/18 Follow-up Operative Early postoperative Biatrial CA versus Maze-III In three studies the incidence of pacemakers was reported after biatrial CA versus Maze-III surgery (see Table 189). A median of 0% of patients required a pacemaker after CA (range 0% to 6%) versus 6% (range 0% to 15%) after the Maze-III procedure. Follow-up varied from early postoperative, to a mean of 47 months. The p values were not stated in any of the studies. In two of the three studies, a pacemaker was not required after CA (Kim et al. 2001; Lee et al. 2001), although in the second study follow-up was only until the third postoperative day. After the Maze-III procedure a pacemaker was not required in only one of the three studies. Table 189: Pacemakers- CA versus Maze-III Level Pacemaker (%) CA Maze-III 6% 15% 0% 6% 0% 0% 0% 6% (0%-6%) (0%-15%) Ishii et al. 2001 III-3 Kim et al. 2001 III-3 Lee et al. 2001 III-3 Median Range [ ]: SD; ( ): range n CA 2/32 0/23 0/53 n Maze-III 2/13 1/18 0/30 Follow-up CA Maze-III > 12 months 41.2[5.6] months 29[4] months 47[14] months 3rd day postoperative Kosakai maze versus CA One comparative study reported pacemaker requirements after the Kosakai maze versus CA (see Table 190). In Nakijima et al. (2002) there were 6% (7/110) of Kosakai maze versus 3% (3/110) of CA patients with an implanted pacemaker. Follow-up was lengthy in both groups: a mean of 64.1 months after KM and 18.8 months after CA. Table 190: Pacemakers- Kosakai maze versus CA Level Nakijima et al. 2002 III-3 Pacemaker (%) KM CA 6% 3% n/N KM n/N CA Follow-up KM CA 7/110 3/110 64.1[27.4] months 18.8[10.8] months [ ]: SD; KM: Kosakai maze Biatrial versus left atrial CA Two comparative studies reported pacemaker incidence after biatrial versus left atrial CA (see Table 191). There were 4% and 7% of patients who needed pacemakers after biatrial CA versus 0% and 5% after left atrial CA. The p values were not stated. Follow-up was a mean of 34.1 in the biatrial and 17.8 in the left atrial groups in Takami et al. (1999). The follow-up period was not stated in Schaff et al. (2000). 112 Table 191: Pacemakers- Biatrial versus left atrial CA Level Pacemaker (%) BA CA LA CA 4% 0% n/N BA CA 7/179 Schaff et al. 2000 III-2/3 Takami et al. III-3 7% 5% 2/30 1999 [ ]: SD; [ ] SD; ( ): range; BA: biatrial; LA: left atrial n/N LA CA 0/42 1/20 Follow-up Not stated 34.1[11.3] months 17.8[3.8] months (15-51 months) (8-23 months) Case Series Biatrial CA Six case series reported the incidence of pacemakers in patients after biatrial CA (see Table 192). The median proportion of patients requiring a pacemaker after biatrial CA was 7%, with a range of 3% to 21%. Follow-up periods were at least one year in five of the studies, but not stated by Fukada et al. (1998). In the patients who required pacemakers in Izumoto et al. (2000) and Yuda et al. (2001), the pacemaker was necessary because of sick sinus syndrome in all of these patients. Fukada et al. (1998) reported that out of the six patients (21%) with a pacemaker postoperatively, one patient already had a pacemaker prior to the surgery. Table 192: Pacemaker- Biatrial CA Case Series Level Biatrial Ad et al. 2003b Arai et al. 1999 Fukada et al. 1998 Izumoto et al. 2000 Kosakai et al. 1995a Pacemaker (%) n/N Follow-up IV IV IV IV 6% 3/50 19{5} months 13% 4/30 12.3 months (1-25 months) 21% 6/29 Not stated 6% 6/104 44.6[1.1] months CA1: 14% 2/14 IV (1.0-3.1 years) KM: 3% 2/70 Total 5% 4/84 Yuda et al. 2001 IV 7% 94 2.2[0.9] years Median 7% Range (3%-21%) [ ]: SD; { }: Type of variance not stated; ( ) range; a: Comparative study, but pacemaker requirement not given for the CS group; CA1: first CA lesion set: KM: Kosakai maze Left atrial CA Six case series reported the incidence of pacemakers in patients after left atrial CA (see Table 193). The median proportion of patients requiring a pacemaker was 8% after left atrial CA, with a range of 2% to 16%. Follow-up periods were only perioperative in one study, and at least five months in four studies. The follow-up was not stated in Usui et al. (2002). There was a slight decrease in pacemaker requirement from early to later follow-up in Manasse et al. (2003): 4% (4/95) in-hospital and 2% (2/95) at a mean of 36.4 months. In Yamauchi et al. (2002), either focal or linear CA was used, depending on the results of intraoperative electrophysiological mapping of the arrhythmia. After surgery, pacemakers were necessary in 18% (2/11) of patients after focal CA, and 3% (1/29) after linear CA. 113 Table 193: Pacemaker- Left atrial CA Case Series Left atrial Imai et al. 2001 Kondo et al. 2003 Manasse et al. 2003 Level Pacemaker (%) n/N Follow-up IV IV 16% 16% 4% 2% 8% 2% Focal: 18% Linear: 3% Total: 7% 8% (2%-16%) 4/24 5/31 4/95 2/95 1/12 1/41 2/11 1/29 3/40 36.9[14.1] months (13-66 months) 37.7[15.0] months (12-60 months) In-hospital 36.4 months 5-14 months Not stated IV Sueda et al. 2001 Usui et al. 2002 Yamauchi et al. 2002 IV IV IV Median Range [ ]: SD; ( ) : range After surgery Radiofrequency Ablation Randomised Controlled Trial Biatrial RFA versus CS One RCT reported pacemaker requirements after biatrial RFA versus CS alone (see Table 194). Khargi et al. (2001) found in both groups that only one patient had a pacemaker at the end of follow-up, a mean of 22 months in the RFA and 21 months in the CS group. This difference was not statistically significant (RR=1.27; 95% CI: 0.09 to 18.14, p=0.86; RevMan). Table 194: Pacemaker- Biatrial RFA versus CS RCT Level Pacemaker (%) n/N BA RFA CS BA RFA CS Khargi et al. 2001 II 9% 7%pns 1/11 1/14 [ ]: SD; pns: statistically non-significant (RevMan); BA: biatrial Follow-up 22[7] months 21[6] months Non-randomised Comparative Studies Biatrial RFA versus CS One study reported the incidence of pacemakers in patients after biatrial RFA versus CS alone (see Table 195). In Patwardhan et al. (2003) no patients had a pacemaker in either the biatrial RFA or CS groups, with follow-up of at least six months. Table 195: Pacemaker- Biatrial RFA versus CS Level Patwardhan et al. 2003 [ ]: SD; BA: biatrial III-2/3 Pacemaker (%) BA RFA CS 0% 0% n/N BA RFA CS 0/84 0/64 114 Follow-up 23.6[12.5] months 6 months RFA versus Maze-III One study reported the incidence of pacemakers in patients after RFA versus Maze-III (see Table 196). Requirement for pacemakers were similar between the groups, with 8% (3/40) of the RFA versus 7% (2/30) of the Maze-III patients requiring a pacemaker. The p value was not stated. Follow-up was seven months or greater in all patients. Table 196: Pacemaker- RFA versus Maze-III Level Chiappini et al. III-3 2004 [ ]: SD; ( ): range Pacemaker (%) RFA Maze-III 8% 7% RFA n/N Maze-III 3/40 2/30 Follow-up RFA Maze-III 16.5[2.5] months 73.2[4.2] months (7-22 months) (20-91 months) Biatrial versus left atrial RFA Two studies reported the incidence of pacemakers in patients after biatrial versus left atrial RFA (see Table 197). Pacemakers were required in 2% and 13% of the biatrial RFA versus 0% and 10% of the left atrial RFA patients. Follow-up was only to the perioperative period in Güden et al. (2002) and at least one month in Deneke et al. (2002a). In Güden et al. (2002) 13% (5/39) of the biatrial versus 10% (2/23) of the left atrial RFA patients required a pacemaker during the perioperative period. At longer follow-up, no pacemakers were required in the left atrial RFA patients of Deneke et al. (2002a), and only one pacemaker (1/49) in the biatrial RFA patients. Table 197: Pacemaker- Biatrial versus left atrial RFA Level Güden et al. 2002 Deneke et al. 2002a Pacemaker (%) BA RFA LA RFA n/N BA RFA LA RFA III-2 13% 10% 5/39 2/23 III- 2/3 2% 0% 1/49 0/21 (2%-13%) (0%-10%) Range Follow-up Perioperative 18[14] months (1-50 months) 11[10] months (4-20 months) [ ]: SD; ( ): range; BA: biatrial; LA: left atrial Case Series Biatrial RFA Six case series reported the incidence of pacemakers after biatrial RFA (see Table 198). The median proportion of patients requiring a pacemaker after biatrial RFA was 5%, with a range of 0% to 20%. Follow-up was at least 1.5 months in all patients. In two of the studies a higher proportion of patients required pacemakers in early versus later follow-up: in Sos et al. (2002) 6/10 patients required a pacemaker in the first few days, and only one patient still had a pacemaker at later follow-up; and in Thomas et al. (2003) 32% (8/25) of patients had a temporary pacemaker with 20% (5/25) still having a pacemaker at a median of 2.9 years follow-up. 115 Table 198: Pacemaker- Biatrial RFA Case Series Level Pacemaker (%) n/N Follow-up IV RFA1: NS RFA2: 4% 13 2/48 16 months (3-32 months) IV 0% 0/25 3.5 years (3.2-3.8 years) IV 3% 4/132 12 months Biatrial Chen et al. 2001a Prasanna et al. 2001 Raman et al. 2003 Sie et al. 2001 Sos et al. 2002 IV 5% 6/122 39 months 60% temporary 6/10 1-5 days IV 10% permanent 1/10 Mean 3 months (1.5-5 months) Thomas et al. 32% temporary 8/25 72 hours IV 2003 20% permanent 5/25 Median 2.9 years (0.6-4.2 years) Median 5% Range (0%-20%) ( ): range; a: comparative study, but pacemaker requirement not stated in CS group; RFA1: first RFA lesion set; RFA2: second RFA lesion set; NS: not stated Left atrial RFA Twelve case series reported pacemaker incidence after left atrial RFA (see Table 199). The median proportion of patients requiring a pacemaker after left atrial RFA was 3%, with a range of 0% to 27%. Follow-up was seven months or more in most studies, with a minimum mean follow-up of 138 days. In five studies no patients required a pacemaker at the end of follow-up (Benussi et al. 2002; Geidel et al. 2003; Guang et al. 2002; Starck et al. 2003; Williams et al. 2001). The studies with the higher pacemaker incidence had the smallest patient numbers; 20% (2/10) in Biederman et al. 2002, and 27% (3/11) in Kottkamp et al. 1999). Table 199: Pacemaker- Left atrial RFA Case Series Left atrial Benussi et al. 2002 Biederman et al. 2002 Geidel et al. 2003 Guang et al. 2002a Kottkamp et al. 1999 Kress et al. 2002 Level Pacemaker (%) n/N Follow-up IV 0% 0/132 16.9[14.2] months IV 20% 2/10 (3-6 months) IV 0% 3% 0% 0/29 3/96 0/96 12 months Hospital discharge 3 years 27% 3/11 11[6] months (3-20 months) IV IV IV 4% 1/23 32.5[28.4] weeks (1-100 weeks) Le Tourneau et al. IV 3% 2/69 Mean 549 days 2003 a Mantovan et al. 2003 IV 1% 1/102 12.5[5] months Müller et al. 2002 IV 6% 6/95 8 months (1-24 months) Ruchat et al. 2002 IV 3% 1/40 12.5[7.9] months Starck et al. 2003 IV 0% 0/100 Mean 7.3 months Williams et al. 2001 IV 0% 0/48 138[96] days Median 2% Range (0%-27%) [ ]: SD; ( ): range; a: comparative studies but pacemaker requirement not stated in CS group 116 Microwave Ablation Non-randomised Comparative Study Left atrial MWA versus CS One study reported pacemaker incidence after left atrial MWA versus CS alone (see Table 200). In Spitzer and Knaut (2002) there were similar pacemaker requirements in both groups: 18% (20/111) of patients after left atrial MWA versus 16% (7/45) of patients after CS alone. Follow-up was to one year, and the p value was not given. Table 200: Pacemaker- Left atrial MWA versus CS Level Spitzer and Knaut 2002 LA: left atrial III-2 Pacemaker (%) LA MWA CS 18% 16% n/N LA MWA 20/111 Follow-up CS 7/45 1 year Case Series Biatrial MWA One case series reported pacemaker incidence after biatrial MWA (see Table 201). No pacemakers were required in ten patients after biatrial MWA, at an average of over 12 months follow-up (Chiappini et al. 2003). Table 201: Pacemaker- Biatrial MWA Case Series Biatrial Chiappini et al. 2003 Level Pacemaker (%) n/N Follow-up IV 0% 0/10 Mean 12.4 months Left atrial MWA Four case series reported pacemaker incidence after left atrial MWA (see Table 202). A median of 10% of patients required a pacemaker after left atrial MWA, with a range of 0% to 18%. Knaut et al. (2002) reported 18% (19/105) of patients with a pacemaker, however, the follow-up was less than 20 days. The follow-up was not stated in two studies. Table 202: Pacemaker- Left atrial MWA Case Series Level Pacemaker (%) n/N Follow-up Left atrial Knaut et al. 2002 IV 18% 19/105 <20 days Schuetz et al. 2003a IV 13% 2/15 1 year Venturini et al. 2003 IV 0% 0/41 Not stated Zembala et al. 2003 IV 7% 3/42 Not stated Median 10% Range (0%-18%) a: comparative study but pacemaker incidence not reported in CS group 117 MWA versus RFA One study reported pacemaker incidence after MWA versus RFA (see Table 203). In Wisser et al. (2004) there were 20% (4/20) of MWA versus 12% (3/14) of RFA patients with a pacemaker at the end of follow-up (24 months in MWA and 12 months in RFA group). The p values were not given. Table 203: Pacemaker- MWA versus RFA Level Wisser et al. 2004 III-2/3 Pacemaker (%) MWA RFA 14% 16% 18% 17% 23% 21% 20% NS n/N MWA 3/22 4/22 5/22 4/20 Follow-up RFA 3/19 3/18 3/14 NS 3 months 6 months 12 months 24 months NS: not stated Maze-III Pacemaker requirement was reported in eleven of the included Maze-III studies. There were a median proportion of patients requiring a pacemaker of 8%, with a range of 3% to 57%. The highest proportion of 57% represented temporary pacemakers in the early postoperative period (Sandoval et al. 1996). Summary pacemaker results Comparative Studies Intraoperative ablation did not appear to result in higher pacemaker requirement than cardiac surgery alone. In the RCT, there was no significant difference in the proportion of patients with pacemakers after biatrial RFA plus MV surgery versus MV surgery alone (Khargi et al. 2001). The non-randomised comparative studies were consistent with this finding. Compared to CS alone, there was no difference in pacemaker requirement in patients after: biatrial or left atrial CA; biatrial RFA; and left atrial MWA. There was also no apparent difference in the proportion of patients needing pacemakers after Maze-III surgery versus RFA or CA. In the comparative internal comparison studies, there did not appear to be a difference in the number of patients with pacemakers in the biatrial versus left atrial lesion sets, when RFA or CA was used. 118 The study groups in which a median proportion of pacemaker requirements could be calculated (groups with three or more studies) are illustrated below, with box plots to demonstrate both median and variance in the studies within each group (Figure 7). The median proportions of patients with a pacemaker were similar across all of the studies. Thus a median of 8% of patients had a pacemaker in the six studies with cardiac surgery alone, versus a range of median values of 2% to 10% in the intraoperative ablation groups. The pacemaker requirement in the Maze-III studies was not higher than the other groups: a median of 7% in the four comparative Maze-III studies. (n=4; 7%) Maze-III Cardiac surgery (n=6; 8%) LA MWA case series (n=4; 10%) LA RFA case series (n=12; 2%) BA RFA case series (n=6; 5%) BA RFA (n=5; 5%) LA CA case series (n=6; 8%) BA CA case series (n=6; 7%) LA CA (n=9; 4%) BA CA 0 20 40 60 80 100 Pacemaker (%) Figure 7: Median proportion of patients requiring a pacemaker The box represents the 10th and 90th percentiles, and the line the median value. The error bars indicate the 5th and 95th percentiles. Outliers (•) are more than 1.5 box lengths from the median value. (Median; no of studies) 119 5.2.7 Catheter ablation Catheter ablation is the primary treatment for most supraventricular arrhythmias, including focal atrial tachycardia, atrial flutter, and Wolff-Parkinson-White syndrome (Calkins et al. 1999). The technique involves the percutaneous introduction of electrode catheters into the heart, under guidance (usually fluoroscopic), to record electrical signals from the areas initiating the arrhythmia. When the mechanism of the arrhythmia is identified, one of the electrode catheters is navigated to the critical site, and ablative energy (eg. radiofrequency, cryotherapy) is delivered to disrupt the origin of the abnormal electrical signals. Catheter ablation may be necessary following intraoperative ablation of AF to treat intractable arrhythmias occurring postoperatively. For example, atypical atrial flutter may arise from surgical scars, and gaps in ablation lines can also lead to heart arrhythmias. Cryotherapy Ablation Non-randomised Comparative Study Left atrial CA+CS versus CS One comparative study reported the use of catheter ablation after left atrial CA+CS versus CS (see Table 204). In Gaita et al. (2000) 7% (2/31) of patients had catheter ablation after CA+CS versus none after CS alone. The two patients had episodes of paroxysmal atrial tachycardia, and both had an electrophysiological study. In one patient the origin of the arrhythmia was identified, and focal ablation was successful. In the other patient the site was not found, with RF catheter ablation between the right inferior pulmonary vein and the mitral annulus unsuccessful. Table 204: Catheter ablation- Left atrial CA+CS versus CS Study/Level Gaita et al. 2000 No (%) CA+CS: 2/31 (7%) Level III-2 CS: 0/16 Arrhythmia Paroxysmal atrial tachycardia Site of arrhythmia/ catheter ablation 1) Radial activation modified by intervening scar tissue- focal ablation successful (n=1). 2) Ablation between the right inferior pulmonary vein and the mitral annulus (n=1). Success Y N Not applicable Case Series Left atrial CA Three case series reported catheter ablation after left atrial CA (see Table 205). The median proportion of patients who had catheter ablation was 6%, with a range of 3% to 10%. In Imai et al. (2001) two patients (6%) underwent catheter ablation for persistent atrial flutter. In the first patient ablation of the tricuspid valve-coronary sinus isthmus was successful, while in the second patient modification of the atrioventricular node with subsequent pacemaker implantation was used. Two patients (3%) also underwent catheter ablation in Manasse et al. (2003). RF catheter ablation was performed to treat left atrial flutter, resulting from a gap in the surgical ablation line, and was successful in both patients. Four patients (10%) in Usui et al. (2002) had catheter ablation to treat atrial flutter or atrial tachycardia. Catheter ablation was successful in 120 the first three patients, but in the fourth the incisional atrial flutter was cured, but a counterclockwise common atrial flutter through the right atrial isthmus remained. Table 205: Catheter ablation- Left atrial CA Case series Study/Level Imai et al. 2001 Level IV Manasse et al. 2003 Level IV Usui et al. 2002 Level IV No (%) 2/32 (6%) Arrhythmia AFl 2/95 (3%) Left AFl Success Y Y Y 4/41 (10%) 1) Counterclockwise common AFl and left atrial tachycardia (n=1). 2) Counterclockwise common AFl (n=1). 3) Paroxysmal AFl with counterclockwise and clockwise AFL and an incisional AFl (n=1). 4) AFl (n=1) Median Range Site of arrhythmia/ catheter ablation Tricuspid valve-coronary sinus isthmus ablation (n=1). Modification of the atrioventricular node. Gap in the left atrial surgical ablation line. 1) Right atrial isthmus. Y 2) Right atrial isthmus Y 3) Incisional AFl around the right atriotomy. Linear ablation at the right atrial isthmus, and linear ablation between the right atriotomy and the inferior vena cava. 4) Incisional AFl around the right atriotomy. Linear ablation between the right atriotomy and the inferior vena cava. Y N 6% (3%-10%) AFl: atrial flutter Radiofrequency Ablation Case Series Biatrial RFA Three case series reported the use of catheter ablation after biatrial RFA (see Table 206). The median proportion of patients having catheter ablation was 3%, with a range of 2% to 52%. In Sie et al. (2001) four patients (3%) had His bundle ablation (the start of the His-Purkinje system which conducts electrical signals in the ventricles) for symptomatic atrial flutter, and required pacemakers subsequently. Thomas et al. (2003) reported 52% (22/42) of patients required RF catheter ablation following biatrial RFA, primarily for inducible atrial flutter. Details of the site of catheter ablation and success of the procedure were not reported. However, in an earlier report with a subgroup of the patients (Thomas et al. 2000), further details of the catheter ablations in ten of the patients were given. In four patients His bundle ablation was performed, while in six patients electrophysiological studies showed clear deficiencies in the lines of intraoperative RF ablation. In five of these patients the deficiency corresponded to the position of the original endocardial linear lesion in the posterior left atrium. One patient in Deneke et al. (2002a) also had a gap in the intraoperative ablation line, necessitating catheter ablation. 121 Table 206: Catheter ablation- Biatrial RFA Case Series Study/Level Sie et al. 2001 Level IV Thomas et al. 2003 Level IV No (%) 4/122 (3%) Arrhythmia AFl Site of arrhythmia/ catheter ablation His bundle ablation Success Y 22/42 (52%) Mainly inducible AFl NS NS 10/25 (40%)1 Not stated 1) His bundle ablation (n=4) Discontinuities in intraoperative RFA lines. 2) Catheter ablation in the tricuspid annulusinferior vena cava isthmus lesion, close to the tricuspid valve annulus (n=1) 3) at the point where the posterior left atrial lesions meet the atrioventricular junction, with ablation inside the coronary sinus (n=5). A gap between the intercaval intraoperative ablation line and the upper caval vein. Ablation in the right atrium to close the gap. Y Deneke et al. 1/49 (2%) Atypical AFl 2002aa Level IV Median 3% Range (2%-52%) 1: Thomas et al. 2000; a: comparative study, but catheter ablation not reported in left atrial RFA group; AFl: atrial flutter Y Y Y Left atrial RFA Four case series reported the use of catheter ablation after left atrial RFA (see Table 207). The median proportion of patients requiring catheter ablation was 7% with a range 2% to 9%. In Benussi et al. (2002) 12/132 (9%) patients required catheter ablation. Typical AFl was treated in ten patients by catheter ablation of the cavo-tricuspid isthmus. In the other two patients, transeptal left atrial mapping was performed for AFl and highly symptomatic persistent AF. The arrhythmias were due to an incomplete left encircling ablation. Catheter ablation was successful in all patients. In Kottkamp et al. (1999) one patient had catheter ablation to treat AFl around the right atrial scar, while in Mantovan et al. (2003) two patients (2%) had catheter ablation. One patient had a focal incessant atrial tachycardia arising from the coronary sinus, and in the other patient common atrial flutter was present. These procedures were all successful. A single patient with atrial tachycardia was also treated by catheter ablation in Kress et al. (2002), but the site of ablation and success of the procedure were not reported. 122 Table 207: Catheter ablation- Left atrial RFA Case Series Study/Level Benussi et al. 2002 Level IV No (%) 12/132 (9%) Kottkamp et al. 1999 Level IV 1/11 (9%) Arrhythmia 1)Typical AFl (n=10) 2) 2:1 paroxysmal atrial tachcardia (n=1) 3) AF (n=1) Persistent AFl Site of arrhythmia/ catheter ablation 1) Cavo-tricuspid isthmus (n=10) 2) and 3) Incomplete left encircling ablation (n=2) Incision reentry around the scar at the right atrial free wall. The lower end of the incision connected to the inferior caval vein was ablated successfully. Not stated Success Y Y Y Kress et al. 1/22 (5%) Paroxysmal atrial NS 2002 tachycardia Level IV Mantovan et 2/103 1) Focal incessant atrial Coronary sinus Y al. 2003a (2%) tachycardia Level IV 2) Common AFl Not stated Y Median 7% Range (2%-9%) a: comparative study, but catheter ablation not reported in CS group; NS: not stated; AFl: atrial flutter Microwave Ablation Case Series Left atrial MWA Two case series reported the use of catheter ablation in patients following left atrial MWA (see Table 208). The proportions of patients undergoing catheter ablation were 2% and 8%. In Schuetz et al. (2003) it was stated that catheter ablation was successfully performed in 8% (2/24) of patients. However, the type of arrhythmia and site of catheter ablation were not stated. One patient in Zembala et al. (2003) had percutaneous RF catheter ablation for atypical atrial flutter. The electrophysiological study showed left atrial arrhythmias, treated successfully at three months postoperatively. Table 208: Catheter ablation- Left atrial MWA Case Series Study/Level No (%) Arrhythmia Site of arrhythmia/ catheter ablation NS Success Schuetz et 2/24 (8%) NS Y al. 2003a Level IV Zembala et 1/42 (2%) Atypical AFl Left atrial arrhythmias Y al. 2003 Level IV Range (2%-8%) NS: not stated; a: RCT but catheter ablation not reported in CS group; AFl: atrial flutter Maze-III In one of the included Maze-III studies catheter ablation was performed. Albåge et al. (2000) reported one patient (1/26, 4%) with early postoperative recurrence of AF, which was not converted to SR by either electrical or pharmacological cardioversion. This patient underwent His bundle ablation and permanent pacemaker implantation. 123 5.2.8 Electrical cardioversion Synchronised external electrical cardioversion is used in patients under general anaesthesia, to try to convert them from AF to SR. The shock energy and waveform, electrode size and position, and transthoracic impedance can affect the likelihood of the cardioversion being successful (Peters et al. 2002). In patients following intraoperative ablation for AF, electrical cardioversion is used when the arrhythmia persists, to try to convert them from AF to SR. Cryotherapy Ablation Biatrial CA+CS versus CS One comparative study reported the use of electrical cardioversion after CA+CS versus CS alone (see Table 209). In Sueda et al. (1997) 28% (10/36) of patients had electrical cardioversion after biatrial CA+CS versus 20% (3/15) after CS alone. Cardioversion was performed up to 30 days postoperatively. The p values were not given. Half of the patients in the biatrial CA+CS group who had electrical cardioversion converted successfully to SR, while it was not successful in any of the CS patients. Table 209: Electrical cardioversion- Biatrial CA+CS versus CS Level Sueda et al. 1997 BA: biatrial III-3 Cardioversion (%) BA CA CS 28% 20% n/N BA CA 10/36 n/N CS 3/15 Success BA CA CS 50% 0% Follow-up 30 days Left atrial CA+CS versus CS One comparative study reported the use of electrical cardioversion after left atrial CA+CS versus CS alone (see Table 210). In Gaita et al. (2000) there were 37% (12/32) of patients having electrical cardioversion after left atrial CA versus 94% (17/18; p<0.01) after CS alone. Cardioversion was performed up to one month postoperatively. The success rate was not stated. Table 210: Electrical cardioversion- Left atrial CA+CS versus CS Level Cardioversion (%) LA CA CS Gaita et al. 2000 III-2 37% 94%† †: p<0.01; NS: not stated; LA: left atrial n/N LA CA 12/32 n/N CS 17/18 Success LA CA CS NS NS Follow-up 1 month Case Series Biatrial CA One case series reported the use of electrical cardioversion after biatrial CA (see Table 211). A single patient (1%) had successful electrical cardioversion after biatrial CA, with a followup of 28 months (Yuda et al. 2001). Table 211: Electrical cardioversion- Biatrial CA Case Series Biatrial Yuda et al. 2001 Level Cardioversion (%) n/N Success Follow-up IV 1% 1/94 100% 28 months 124 Left atrial CA Two case series reported the use of electrical cardioversion after left atrial CA (see Table 212). The proportion of patients having electrical cardioversion after left atrial CA was 16% (5/32) in Imai et al. (2001) and 25% (3/12) in Sueda et al. (2001). Cardioversion was not successful in any of the patients in Sueda et al. (2001), but 60% (3/5) of patients successfully converted to SR in Imai et al. (2001). Follow-up was to 30 days. Table 212: Electrical cardioversion- Left atrial CA Case Series Level Cardioversion (%) n/N Success Follow-up Left atrial Imai et al. 2001 IV 16% 5/32 60% 30 days Sueda et al. 2001 IV 25% 3/12 0% Hospital discharge Range (11%-44%) ( ): range; a: cardioversion was electrical and/or pharmacological; NS: not stated Radiofrequency Ablation Non-randomised Comparative Studies Left atrial RFA versus CS One study reported the use of electrical cardioversion following left atrial RFA versus CS (see Table 213). In Mantovan et al. (2003) at more than three months follow-up, electrical cardioversion had been performed in 21% (22/103) of left atrial RFA versus 11% (3/27) of the CS patients (p>0.05). In the left atrial RFA group, 3% (3/103) of the patients underwent cardioversion whilst they were in-hospital. The success of the cardioversions was not stated. Table 213: Electrical cardioversion- Left atrial RFA versus CS Level Follow-up Cardioversion (%) n/N Success LA RFA CS LA RFA CS LA RFA CS Mantovan 3/103 NS NA 3% NS III-2 22/103 3/27 NS NS et al. 2003 21% 11%pns pns: statistically non-significant; NS: not stated; NA: not applicable; LA: left atrial In-hospital >3 months Biatrial versus left atrial RFA One study reported the use of electrical cardioversion after biatrial versus left atrial RFA (see Table 214). In Deneke et al. (2002a) 24% (12/49) of patients had electrical cardioversion within 30 days postoperatively after biatrial RFA versus no patients after left atrial RFA. The p value was not stated. Out of the twelve patients who had cardioversion after biatrial RFA, only one patient (8%) remained in SR. As a result, the authors stated they now wait six months before attempting electrical cardioversion, in patients fail to spontaneously convert to SR. Table 214: Electrical cardioversion- Biatrial versus left atrial RFA Level Cardioversion (%) BA RFA LA RFA n/N BA RFA LA RFA Deneke et III- 2/3 24% 0% 12/49 0/21 al. 2002a NS: not stated; NA: not applicable; BA: biatrial; LA: left atrial 125 Success BA LA RFA RFA 8% NA Follow-up BA LA RFA RFA NS NA Case Series Biatrial RFA Three case series reported the use of electrical cardioversion after biatrial RFA (see Table 215). There was a median proportion of 8% of patients who had electrical cardioversion after biatrial RFA, with a range of 0% to 20%. Out of only ten patients in Sos et al. (2002), two patients had cardioversion, which was unsuccessful in both patients. However, in Raman et al. (2003) cardioversion was successful in 90% (10/11) of patients. Table 215: Electrical cardioversion- Biatrial RFA Case Series Level Biatrial Chen et al. 2001a Cardioversion (%) n/N Success Follow-up RFA1: 0 0/11 NA 30 days RFA2: 0 0/47 Raman et al. 2003 4% 5/132 2 weeks IV 4% 5/132 3 months 8% 10132 90% Total Sos et al. 2002 IV 20% 2/10 0% (1.5-5 months) Median 8% Range (0%-20%) a: comparative study but cardioversion not stated in CS group; RFA1: first RFA lesion set; RFA2: second RFA lesion set; ( ): range; NA: not applicable IV Left atrial RFA Four case series reported the use of electrical cardioversion following left atrial RFA (see Table 216). The median proportion of patients who underwent electrical cardioversion after left atrial RFA was 28%, with a range of 9% to 62%. Follow-up was to 30 days in two studies, and early postoperative in the other two studies. Electrical cardioversion was successful in none (0/2) of the patients in Kottkamp et al. (1999); and over half (11/18) of the patients in Geidel et al. (2003). The success was not stated in the other studies. Table 216: Electrical cardioversion- Left atrial RFA Case Series Level Cardioversion(%) Left atrial Geidel et al. 2003 IV 62% Gillinov et al. 2003 IV 38% Kottkamp et al. IV 18% 1999 Kress et al. 2002 IV 9% Median 28% Range (9%-62%) [ ]: SD; ( ): range; NS: not stated n/N Success Follow-up 18/29 19/50 61% NS 30 days 30 days 2/11 0% Early postoperative 2/22 NS Before hospital discharge 126 Microwave Ablation (MWA) Randomised Controlled Trial (RCT) Left atrial MWA versus CS One RCT reported the number of patients who had electrical cardioversion after left atrial MWA versus CS alone (see Table 217). Schuetz et al. (2003) reported that 8% (2/24) of patients had successful electrical cardioversion up to 30 days postoperatively after left atrial MWA versus none of the patients had cardioversion after CS alone. Table 217: Electrical cardioversion- Left atrial MWA versus CS RCT Level Schuetz et al. 2003 Cardioversion (%) LA MWA CS II 8% n/N LA MWA CS 2/24 0/19 0% Success LA MWA CS 100% NA Follow-up 30 days NA: not applicable; LA: left atrial Case Series Left atrial MWA Two case series reported the use of electrical cardioversion after left atrial MWA (see Table 218). In Venturini et al. (2003) 39% (16/41) of patients had electrical cardioversion at one month postoperatively. Spitzer and Knaut did not report the number of patients who had electrical cardioversion, but stated that, on average, patients had 1.4 cardioversions. The success of the procedure was not stated in either study. Table 218: Electrical cardioversion- Left atrial MWA Case Series Level Cardioversion (%) n/N Success Follow-up Left atrial Spitzer and Knaut IV Mean 1.4 136 NS Postoperative 2002a Venturini et al. 2003 IV 39% 16/41 NS 1 month NS: not stated; a: comparative study, but electrical cardioversion not stated in CS group 5.2.9 Continued antiarrhythmic treatment Antiarrhythmic drugs are used to try to convert patients to a normal heart rhythm. In a number of the included studies, antiarrhythmic drugs were used routinely in all patients after the surgery. Patients were then weaned off these drugs when they remained in SR. The patients who stayed on antiarrhythmic medication may be considered as a failure of the ablative surgery. However, some of these patients were resistant to antiarrhythmics prior to surgery, and response to these drugs is an improvement in the management of their AF. Some of the included studies reported only the patients in SR who were taking antiarrhythmic medication, and this is noted in the tables. In these studies there may also have been patients with arrhythmias who were taking these drugs, but it was not possible to extrapolate the result to the total group. 127 Cryotherapy Ablation Non-randomised Comparative Studies Biatrial CA+CS versus CS Two studies reported antiarrhythmic drug treatment after CA+CS versus CS (see Table 219). The proportions of patients taking antiarrhythmic medication ranged from 54% to 55% in the biatrial CA+CS group, and 17% to 78% in the CS group. Follow-up was at least six months. In Handa et al. (1999) more patients were taking antiarrhythmic medication in the CS versus the CA+CS group (p<0.05), while in Yuda et al. (2004) there were 54% (14/26) taking medication in the CA+CS versus only 17% (1/6) in the CS group. The p value was not given in this study. Handa et al. (1999) also stated the average number of drugs taken by patients at follow-up, with a mean of 0.71 (SD 0.76) in the biatrial CA+CS patients versus a mean of 1.16 (SD 0.79) in patients after CS alone (p=0.01). Table 219: Antiarrhythmic drugs- Biatrial CA+CS versus CS Level Handa et al. 1999 III-2 Antiarrhythmic (%) BA CA CS 55% Yuda et al. 2004 III-2 54% Range (54%-55%) ( ): range; *: p<0.05; BA: biatrial n/N BA CA n/N CS 78%* 32/58 30/39 17% (17%-78%) 14/26 1/6 Follow-up Mean 21 months (≥ 6 months) > 6 months Left atrial CA+CS versus CS One study reported antiarrhythmic drug treatment after left atrial CA+CS versus CS (see Table 220). Gaita et al. (2000) reported antiarrhythmic medication use only in the patients in SR, at three to twelve months of follow-up. At three months 19% (5/27) of the CA+CS patients in SR were taking antiarrhythmic medication, while at 12 months this had dropped to 11% (2/18). In the CS group at each time point, two SR patients were taking antiarrhythmics (2/4). Table 220: Antiarrhythmic drugs- Left atrial CA+CS versus CS Level Gaita et al. 2000 III-2 Antiarrhythmic (%) LA CA CS 19% (SR) 50% (SR) 19% (SR) 50% (SR) 19% (SR) 50% (SR) 11% (SR) 50% (SR) n/N LA CA 5/27 5/27 5/26 2/18 n/N CS 2/4 2/4 2/4 2/4 Follow-up 3 months 6 months 9 months 12 months ( ): range; *: p<0.05 CA versus Maze-III One study reported antiarrhythmic drug use after CA versus Maze-III surgery (see Table 221). In Kim et al. (2001) 9% (2/23) of patients in the CA and 6% (1/18) of patients in the Maze-III groups were taking antiarrhythmic medication (p>0.05). Follow-up was an average of 29 months after CA and 47 months after the Maze-III. 128 Table 221: Antiarrhythmic drugs- CA versus Maze-III Level Antiarrhythmic (%) CA Maze-III Kim et al. 2001 III-3 9% 6%pns [ ]: SD; pns: statistically non-significant n/N CA 2/23 n/N Maze-III 1/18 Follow-up CA Maze-III 29[4] months 47[14] months Biatrial versus left atrial CA One study reported antiarrhythmic medication use after biatrial versus left atrial CA (see Table 222). Takami et al. (1999) reported the number of patients in SR who took antiarrhythmic medication at the end of follow-up: a mean of 34.1 months in the biatrial and 17.8 months in left atrial groups. At this time 60% (15/25) of biatrial versus 63% (10/16) of left atrial patients in SR were taking antiarrhythmic drugs. Table 222: Antiarrhythmic drugs- Biatrial versus left atrial CA Level Antiarrhythmic (%) BA CA LA CA Takami et al. III-3 60% 63% 1999 (SR) (SR) [ ]: SD; BA: biatrial; LA: left atrial n/N BA CA n/N LA CA 15/25 10/16 Follow-up BA CA LA CA 34.1[11.3] 17.8[3.8] months months Case Series Biatrial CA Three case series reported the use of antiarrhythmic medication after biatrial CA (see Table 223). There was a median of 17% of patients who were still taking antiarrhythmic medication after biatrial CA, with a range of 17% to 28%. Follow-up was from early postoperative (Sueda et al. 1997) to more than three months in the other two studies. In Sueda et al. (1997) it was stated that antiarrhythmics were used in 28% (10/36) patients in the early postoperative period, and five of these patients were in SR. Table 223: Antiarrhythmic drugs- Biatrial CA Case Series Level Antiarrhythmic (%) n/N Follow-up Biatrial Ad et al. 2003a IV 17% 9/51 > 3 months Shimizu et al. 1997 IV 17% 1/6 (4-32 months) Sueda et al. 1997 IV 28% 10/36 Early postoperative Median 17% Range (17%-28%) ( ): range; a: comparative study but antiarrhythmic medication was not reported in CS patients. Left atrial CA Four case series reported antiarrhythmic medication use after left atrial CA (see Table 224). The median proportion of patients taking antiarrhythmic medication was 26%, with a range of 11% to 54%. In three of the studies only the patients in SR taking antiarrhythmic medication were stated (Hoffmeister et al. 2003; Imai et al. 2001; Manasse et al. 2003). Follow-up ranged from early postoperative to a mean of almost 37 months. In Imai et al. (2001) at more than one year postoperatively, over half the patients in SR were taking Class –I or -IV agents (13/24), and 29% (7/24) were taking digitalis. Sueda et al. (2001) used digitalis and disopyramide (Class I) early postoperatively in 25% (3/12) of patients to treat recurrent AF, with this treatment unsuccessful. 129 Table 224: Antiarrhythmic drugs- Left atrial CA Case Series Left atrial Hoffmeister et al. 2003 Imai et al. 2001 Level Antiarrhythmic (%) n/N Follow-up IV 11% (SR) 2/14 (1-48 months) 29% digitalis (SR) 7/24 36.9[14.1] months 54% Class I/IV (SR) 13/24 (13-66 months) Manasse et al. 2003 IV 27% (SR) 19/70 Mean 36.4 months Sueda et al. 2001 IV 25% 3/12 Early postoperative Medianb 26% Range (11%-54%) ( ): range; [ ]: SD; b: For calculation of the median, in Imai et al. (2001) 54% was used, as it was not possible to determine how many patients were taking both digitalis and a Class I/IV drug. IV Radiofrequency Ablation Non-randomised Comparative Studies Left atrial RFA versus CS One study reported the use of antiarrhythmic medication after left atrial RFA versus CS (see Table 225). Mantovan et al. (2003) reported significantly more patients were using antiarrhythmic drugs after left atrial RFA (64%, 65/102) versus CS alone (26%, 7/27; p<0.01). Follow-up was at least four months. The majority of the patients were taking amiodarone: 53% of the left atrial RFA versus 22% of the CS patients (p<0.01). Table 225: Antiarrhythmic drugs- Left atrial RFA versus CS Level Antiarrhythmic (%) LA RFA CS Mantovan et al. 2003 III-2 64% 26%† [ ]: SD; ( ): range; †: p<0.01; LA: left atrial n/N LA RFA CS 65/102 7/27 Follow-up 12.5[5] months (4-24 months) Biatrial RFA versus Maze-III One study reported the use of antiarrhythmic drugs after biatrial RFA versus Maze-III surgery (see Table 226). Chiappini et al. (2004) reported 23% (9/40) of biatrial RFA versus 33% (10/30) of Maze-III patients were taking antiarrhythmic medication at the end of follow-up. This was a mean of 16.5 months in the RFA versus 73.2 months in the Maze-III group. Patients were taking either sotalol or amiodarone. The p value was not given. Table 226: Antiarrhythmic drugs- Biatrial RFA versus Maze-III Level Chiappini et al. 2004 [ ]: SD; IV Antiarrhythmic (%) BA RFA Maze-III 23% 33% n/N BA RFA Maze-III 9/40 130 10/30 Follow-up BA RFA Maze-III 16.5[2.5] months 73.2[4.2] months CA versus cardioversion One study reported the use of antiarrhythmic drugs after RFA versus cardioversion (see Table 227). In Thomas et al. (2003) there were 10% (2/21) of RFA patients versus 64% (21/33) of cardioversion patients who were taking antiarrhythmic medication at a mean of 15 months follow-up. The drugs used were sotalol and amiodarone. The p value was not given. Table 227: Antiarrhythmic drugs- RFA versus cardioversion Level Thomas et al. 2003 III-2 [ ]: SD; Cv: electrical cardioversion Antiarrhythmic (%) RFA Cv 10% 64% n/N RFA 2/21 Follow-up Cv 21/33 15[18] months Case Series Biatrial RFA Four case series reported the use of antiarrhythmic medication after biatrial RFA (see Table 228). The proportion of patients using antiarrhythmic medication ranged from 0% to 49%. A median was not calculated, as Prasanna et al. (2001) reported no patients were taking amiodarone after biatrial RFA, but they may have been taking other antiarrhythmic drugs. Follow-up was a minimum of three months. The use of antiarrhythmic drugs was not stated in Sie et al. (2001), but it was reported in an earlier subset of patients that 30% (17/57) of biatrial RFA patients not in AF or AFl were using antiarrhythmic drugs after surgery (Sie et al. 2001b). Thomas et al. (2003) reported separately the patients in SR and in AF using antiarrhythmic medication. There were 14% (4/29) of patients in SR and 46% (6/13) of patients in AF taking antiarrhythmic drugs at greater than six months follow-up. . Table 228: Antiarrhythmic drugs- Biatrial RFA Case Series Biatrial Prasanna et al. 2001 Raman et al. 2003 Sie et al. 2001b Thomas et al. 2003 Level Antiarrhythmic (%) n/N Follow-up IV 0% (amiodarone) 0/25 3 months IV 0% 0/15 ~24 months IV 30% (non AF/AFl) 59/121 Mean 40 months (12-80 months) 14% SR 46% AF 24% Total (0%-49%) 4/29 6/13 10/42 Median 2.86 years (0.6-4.2 years) IV Range ~: approximately; ( ): range Left atrial RFA Four case series reported the use of antiarrhythmic drugs after left atrial RFA (see Table 229). The median proportion of patients taking antiarrhythmics after left atrial RFA was 47%, with a range of 19% to 66%. Follow-up was at least an average of 138 days. Benussi et al. (2002) reported results in patients who were in SR, with 38% (33/87) of patients using antiarrhythmic medication. Williams et al. (2001) reported results separately for patients in SR or AF or AFl. There were 53% (18/34) of patients in SR taking antiarrhythmics versus 63% (5/8) of patients with AF or AFl. The drug used was amiodarone. 131 Table 229: Antiarrhythmic drugs- Left atrial RFA Case Series Left atrial Benussi et al. 2002 Le Tourneau et al. 2003 Starck et al. 2003 Williams et al. 2001 Level Antiarrhythmic (%) n/N Follow-up IV 38% (SR) 33/87 16.9[14.2] months IV 66% 46/70 549 days IV 19% 17/90 53% (SR) 18/34 IV 63% (AF/AFl) 5/8 55% Total 23/42 Median 47% Range (19%-66%) [ ]: SD; ( ): range; AF/AFl: atrial fibrillation or atrial flutter 7.3 months 138[96] days Microwave Ablation Randomised Controlled Trial Left atrial MWA versus CS One RCT reported the use of antiarrhythmic medication after left atrial MWA versus CS (see Table 230). Schuetz et al. (2003) reported that 73% (11/15) of left atrial MWA versus 56% (5/9) of CS patients were still taking antiarrhythmic medication at one year follow-up. There was no significant difference between the groups (RR 2.2 95% CI 0.38 to 12.57, p=0.38). A full three month course of antiarrhythmic medication was taken by 85% (17/20) of the left atrial MWA versus 100% (9/9) of the CS patients. Medication had to be discontinued in five of the CS patients, due to new onset bradycardia (n=3), drug-related side effects (n=1), or non compliance (n=1). Table 230: Antiarrhythmic drugs- Left atrial MWA versus CS RCT Level Antiarrhythmic (%) LA MWA CS Schuetz et al. 2003 II 73% 56%pns pns: statistically non-significant (RevMan); LA: left atrial n/N LA MWA 11/15 Follow-up CS 5/9 12 months Non-randomised Comparative Studies Left atrial MWA versus CS One study reported the use of antiarrhythmic drugs following left atrial MWA versus CS (see Table 231). Spitzer and Knaut (2002) reported the results separately in patients who had MV surgery or CABG (MVS/CABG). Follow-up was to one year. A lower proportion of MVS/CABG patients used β-blockers after left atrial MWA versus CS: 20%/19% of left atrial MWA versus 66%/56% of CS. Conversely more MVS/CABG patients used sotalol following left atrial MWA versus CS: 52%/64% of left atrial MWA versus 7%/33% of CS. A low proportion of patients used amiodarone after left atrial MWA (7%/6%), whereas none of the CS patients used amiodarone. 132 Table 231: Antiarrhythmic drugs- Left atrial MWA versus CS Level Antiarrhythmic (%) n Followup LA MWA CS LA MWA CS MVS/CABG MVS/CABG β-blocker: 20%/19% β-blocker: 66%/56% III-2 111 Total 45 Total 1 year Class I: 4%/0% Class I: 3%/0% Sotalol: 52%/64% Sotalol: 7%/33% Amiodarone: 7%/6% Amiodarone: 0%/0% NS: not stated; MVS: mitral valve surgery; CABG: coronary artery bypass grafting; LA: left atrial Spitzer and Knaut 2002 Case Series Left atrial MWA One case series reported the use of antiarrhythmic medication after left atrial MWA (see Table 232). Venturini et al. (2003) stated that most patients who were free of AF were taking amiodarone (74%, 25/34) at a minimum of five months postoperative. Smaller numbers of patients were using sotalol (9%, 3/34) and digoxin (18%, 6/34). Table 232: Antiarrhythmic drugs- Left atrial MWA Case Series Left atrial Venturini et al. 2003 Level Antiarrhythmic (%) n/N Follow-up IV 74% amiodarone (AF-) 9% sotalol (AF-) 18% digoxin (AF-) 25/34 3/34 6/34 14.2 months (5-21 months) AF-: patients free of AF Maze-III Continued antiarrhythmic medication was reported in eight of the included Maze-III studies. The median proportion of patients remaining on antiarrhythmic medication after surgery was 20%, with a range of 8% to 79%. 5.2.10 Continued anticoagulant requirement Since patients with AF are at increased risk of stroke, it is recommended that they routinely use anticoagulant medication. However, anticoagulant therapy is also associated with the risk of side effects. Therefore a major goal of surgery to treat AF is to successfully convert patients to SR, and allow them to cease taking anticoagulant medication. Unfortunately in patients who have non-biological valves implanted as a concomitant procedure, anticoagulation therapy is required, even if the patient maintains normal SR. Some of the included studies reported only the patients in SR who were taking anticoagulant medication, and this is stated in the text and tables. 133 Cryotherapy Ablation Non-randomised Comparative Studies Biatrial CA+CS versus CS One study reported the use of anticoagulant therapy after CA+CS versus CS (see Table 233). In Handa et al. (1999) 37% (14/39) of CA+CS patients versus 50% (29/58) of CS patients were using anticoagulants at more than six months postoperatively. This difference was not statistically significant (p>0.05). Table 233: Anticoagulant- Biatrial CA+CS versus CS Level Handa et al. 1999 III-2 Anticoagulant (%) BA CA CS 37% n/N BA CA n/N CS 14/39 29/58 50%pns Follow-up Mean 21 months ≥ 6 months pns: statistically non-significant; BA: biatrial Biatrial CA versus Maze-III One study reported the use of anticoagulant therapy after biatrial CA versus Maze-III (see Table 234). In Ishii et al. (2001) 63% (20/32) of CA patients were still taking anticoagulants at greater than 12 months postoperatively versus 77% (10/13) of the Maze-III patients at a mean of 41.2 months. The p value was not given. Table 234: Anticoagulant- Biatrial CA versus Maze-III Level Ishii et al. 2001 III-3 [ ]: SD; BA: biatrial Anticoagulant (%) BA CA Maze-III 63% 77% n/N BA CA 20/32 n/N Maze-III 10/13 Follow-up > 12 months 41.2[5.6] months Case Series Left atrial CA Two case series reported the use of anticoagulant therapy in patients after left atrial CA (see Table 235). Imai et al. (2001) stated all patients (19/19) who underwent either MV replacement or CABG in addition to left atrial CA, were using anticoagulants more than one year after surgery. However, none of the five patients who had valve repair were still using anticoagulants at this time. In Manasse et al. (2003) only patients in SR were reported, with 21% (15/70) taking anticoagulants at a mean of 36.4 months follow-up. Table 235: Anticoagulant- Left atrial CA Case Series Left atrial Imai et al. 2001 Level Anticoagulant (%) n/N Follow-up IV 100% MVR/CABG 0% Valve repair 19/19 0/5 36.9[14.1] months (13-66 months) Manasse et al. IV 21% (SR) 15/70 36.4 months 2003 ( ): range; MVR: MV replacement; CABG: coronary artery bypass grafting 134 Radiofrequency Ablation Non-randomised Comparative Studies Left atrial RFA versus CS One study reported the use of anticoagulant therapy in patients after left atrial RFA versus CS (see Table 236). In Mantovan et al. (2003) there were 60% (62/103) of patients taking anticoagulants versus 93% (25/27) after CS alone (p<0.01). Follow-up was at least four months in all patients. Table 236: Anticoagulant- Left atrial RFA versus CS Level Anticoagulant (%) LA RFA CS n/N LA RFA Mantovan et III-2 60% 93%† al. 2003 †: p<0.01; LA: left atrial; [ ]: SD; ( ): range 62/103 Follow-up CS 25/27 12.5[5] months (4-24 months) RFA versus Maze-III One study reported the use of anticoagulant therapy in patients after biatrial RFA versus Maze-III (see Table 237). Chiappini et al. (2004) stated 73% (29/40) of patients were still using warfarin at a mean of 16.5 months follow-up versus 40% (12/30) after CS alone (p>0.05). Table 237: Anticoagulant- RFA versus Maze-III Level Anticoagulant (%) RFA Maze-III Chiappini et III-3 73% 40%pns al. 2004 pns: statistically non-significant; [ ]: SD n/N Maze-III RFA 29/40 12/30 Follow-up RFA Maze-III 16.5[2.5] 73.2[4.2] months months Case Series Biatrial RFA Three case series reported the use of anticoagulants after biatrial RFA (see Table 238). Chen et al. (2001) stated that 69% (40/58) of patients in SR were still using anticoagulants at least three months postoperatively. Although patients without prosthetic valves should not require anticoagulants, 41% (25/61) of MV repair and 68% (15/22) of patients with biological valves were still taking anticoagulants at least one year postoperatively. In Raman et al. (2003), at three months 30% (4/12) of patients were using an anticoagulant, while at one year 25% (3/12) were still using anticoagulant therapy. Table 238: Anticoagulant-Biatrial RFA Case Series Biatrial Chen et al. 2001a Raman et al. 2003 Level Anticoagulant (%) n/N Follow-up IV 69% (SR) 40/58 (3-47 months) 30% 4/12 3 months 20% 2/12 6 months 25% 3/12 12 months 41% MV repair 25/61 Mean 40 months Sie et al. IV 68% biological valve 15/22 (12-80 months) 2003 a: comparative study but anticoagulant use not reported in CS group IV 135 Maze-III Continued anticoagulant therapy was reported in five of the included Maze-III studies. A median proportion of 21% of patients were still taking anticoagulant therapy after the MazeIII procedure, with a range of 8% to 48%. 5.2.11 Surgical times and lengths of hospital stay CPB and cross clamping Cryotherapy Ablation Non-randomised Comparative Studies Biatrial CA+CS versus CS Three comparative studies reported CPB and cross clamping times after biatrial CA+CS versus CS (see Table 239). The CPB times were 122 and 196 minutes in the biatrial CA+CS group versus 58 and 156 minutes with CS alone. Times for CPB were significantly longer in the biatrial CA+CS versus CS patients in Handa et al. (1999), but there was no significant difference in CPB times between biatrial CA+CS versus CS in Sueda et al. (1997). Cross clamping times ranged were 69 and 126 minutes in the biatrial CA+CS group versus 36 and 97 minutes in the CS group. Patients were cross clamped for a significantly greater time after biatrial CA+CS versus CS both studies. Table 239: CPB and cross clamping- Biatrial CA+CS versus CS CPB (min) BA CA CS Cross clamping (min) BA CA n CS BA CA CS Handa et 122[40] 58[27]§ 69[18] 36[14]§ 39 al.1999 Sueda et al. 196[53] 156[26]pns 126[35] 97[27]* 36 1997 Range (122-196) (58-156) (69-126) (36-97) [ ]: SD; ( ): range; *: p<0.05; †: p<0.01; §: p<0.0001; pns: statistically non-significant; BA: biatrial 58 15 Left atrial CA+CS versus CS One comparative study reported CPB and cross clamping times after left atrial CA+CS versus CS (see Table 240). The CPB times were significantly longer in the left atrial CA+CS versus CS group (mean 84 versus 63 minutes, p<0.01). Similarly, the cross clamp times were also significantly longer in the left atrial CA+CS versus CS patients (mean 68 versus 48 minutes, p<0.01). Table 240: CPB and cross clamping- Left atrial CA+CS versus CS Gaita et al.2000 [ ]: SD; †: p<0.01 CPB (min) LA CA 84[18] CS 63[21]† Cross clamping (min) LA CA CS 68[17] 48[20]† 136 n LA CA 32 CS 18 CA versus Maze-III Two studies reported on CPB times and three studies reported cross clamping times after CA versus Maze-III (see Table 241). The CPB times were 169 to 185 minutes after CA versus 195 to 240 minutes after Maze-III. In both Kim et al. (2001) and Lee et al. (2001) CPB times were significantly longer after Maze-III versus CA surgery. Patients were cross clamped for a median of 132 minutes (range 104 to 174 minutes) after CA versus 146 minutes (135 to 165 minutes) after Maze-III. These times were significantly longer after Maze-III versus CA in Kim et al. (2001, p<0.01); not significantly different between the groups in Ishii et al. (2001); and the p value was not stated in Lee et al. (2001). Table 241: CPB and cross clamping times- CA versus Maze-III CPB (min) CA Cross clamping (min) Maze-III CA Maze-III Ishii et al.2001 174[37] 165[48]pns Kim et al.2001 185[42] 240[33]‡ 104[18] 135[29]† Lee et al.2001 169[30] 195[56]* 132[23] 146[41] Median 132 146 Range (169-185) (195-240) (104-174) (135-165) [ ]: SD; ( ): range; *: p<0.05; ‡: p<0.001; pns: statistically non-significant n CA 10 23 53 Maze-III 13 18 30 Kosakai maze versus CA One study reported the CPB times after Kosakai maze versus CA (see Table 242). In Nakijima et al. (2002) patients were on CPB for longer during Kosakai maze (mean 214 minutes) versus CA (mean 186 minutes, p<0.01). The cross clamping times were not stated. Table 242: CPB and cross clamping times- Kosakai maze versus CA CPB (min) Kosakai Nakijima et al.2002 214[47] NS: not stated; [ ]: SD; †: p<0.01 CA 186[56]† Cross clamping (min) Kosakai NS n CA NS Kosakai 110 CA 110 Kosakai maze with removal (-RAA) versus retention (+RAA) of the RAA One study reported CPB and cross clamping times after Kosakai maze with removal or retention of the RAA (see Table 243). No significant differences in either CPB times (mean 205 minutes versus 196 minutes) or cross clamping times (mean 140 minutes versus 129 minutes) were present after Kosakai maze with retention versus removal of the RAA (Yoshihara et al. 2000). Table 243: CPB and cross clamping times- Kosakai-RAA versus Kosakai+RAA CPB (min) Kosakai -RAA Cross clamping (min) Kosakai+RAA Kosakai -RAA Yoshihara et 202[50] 196[29]pns 140[41] al. 2000 pns: statistically non-significant: RAA: right atrial appendage n Kosakai+RAA Kosakai -RAA Kosakai +RAA 129[23]pns 20 22 Biatrial versus left atrial CA One study reported CPB and cross clamping times in patients after biatrial versus left atrial CA (see Table 244). Cardiopulmonary bypass and cross clamping times were shorter in patients after left atrial versus biatrial CA (Takami et al. 1999). The CPB times were a mean of 248 minutes after 137 biatrial versus 200 minutes after left atrial (p<0.05); and cross clamping times were a mean of 152 minutes after biatrial versus 135 minutes after left atrial CA (p<0.01). Table 244: CPB and cross clamping times- Biatrial versus left atrial CA CPB (min) Cross clamping (min) BA CA LA CA BA CA LA CA Takami et al. 1999 248[59] 200[26]* 152[28] 135[16]† [ ]: SD; *: p<0.05; †: p<0.01; BA: biatrial; LA: left atrial n BA CA 21 LA CA 15 Case Series Biatrial CA Three case series reported on CPB and cross clamping times after biatrial CA (see Table 245). Cardiopulmonary bypass times were a mean of 177 minutes and 209 minutes (Izumoto et al. 2000; Fukada et al. 1998). In Arai et al. (1999) it was stated that patients were on CPB for 66 minutes extra compared to patients who did not have biatrial CA. Cross clamping times were a mean of 122 minutes and 150 minutes (Izumoto et al. 2000; Fukada et al. 1998). Patients were cross clamped for almost 57 minutes extra compared to patients who did not have biatrial CA in Arai et al. (1999). Table 245: CPB and cross clamping times- Biatrial CA Case Series CPB (min) Biatrial Arai et al. 1999 Fukada et al. 1998 Izumoto et al. 2000 [ ]: SD Cross clamping (min) n +66 +57 30 209[34] 150[32] 29 177[70] 122[31] 87 Left atrial CA Three case series reported CPB and cross clamping times in patients after left atrial CA (see Table 246). The median CPB time was 146 minutes, with a range of 85 to 191 minutes. Cross clamp times were a median of 109 minutes, and the range was 69 to 124 minutes. Table 246: CPB and cross clamping times- Left atrial CA Case Series CPB (min) Left atrial Imai et al. Kondo et al. Manasse et al. Median Range [ ]: SD; ( ): range 191[33] 146[39] 85 146 (85-191) Cross clamping (min) n 124[27] 109[36] 69 109 (69-124) 32 31 95 138 Radiofrequency Ablation Randomised Controlled Trial Biatrial RFA+MVS versus MVS One RCT reported the CPB and cross clamp times after biatrial RFA versus CS (see Table 247). Khargi et al. stated that both CPB and cross clamping times were significantly increased with biatrial RFA versus CS alone. The CPB times averaged 188 minutes during biatrial RFA versus 127 minutes during CS alone (p<0.05). Similar differences occurred in cross clamping times: an average of 103 minutes during biatrial RFA versus 84 minutes for CS alone (p<0.05). Table 247: CPB and cross clamping times- Biatrial RFA+MVS versus MVS RCT CPB (min) Cross clamping time (min) BA RFA MVS BA RFA MVS Khargi et al. 188 127* 103 84* *: p<0.05; MVS: mitral valve surgery; BA: biatrial n BA RFA 15 MVS 15 Non-randomised Controlled Studies Biatrial RFA versus CS Two studies reported CPB and cross clamping times after biatrial RFA versus CS (see Table 248). Cardiopulmonary bypass times were a mean of 96 and 273 minutes in the biatrial RFA patients versus 89 and 156 minutes during CS alone (Chen et al. 2001; Patwardhan et al. 2003). The CPB time was significantly longer during biatrial RFA versus CS in Chen et al. (2001, p<0.01), but there was no significant difference between groups in Patwardhan et al. (2003). Cross clamping times were a mean of 53 and 200 minutes during biatrial RFA versus 55 and 106 minutes after CS alone. Patients were cross clamped significantly longer during biatrial RFA versus CS in Chen et al. (2001), with times similar between the groups in Patwardhan et al. (2003). Table 248: CPB and cross clamping times- Biatrial RFA versus CS CPB (min) BA RFA RFA1: 263[60] RFA2: 273[54] CS Cross clamping time (min) BA RFA CS RFA1: 192 [53] 106[44]‡ RFA2: 200[46] n BA RFA RFA1: 13 RFA2: 48 CS Chen et al. 156[50]‡ 58 2001 Patwardhan 96[24] 89[36]pns 53[15] 55[22]pns 84 64 et al. 2003 [ ]: SD: pns: statistically non-significant; †: p<0.01; RFA1: first RFA ablation set; RFA2: second RFA ablation set; BA: biatrial Left atrial RFA versus CS Two studies reported CPB times and one study reported cross clamping times during left atrial RFA versus CS (see Table 249). The CPB times were a mean of 138 and 148 minutes during left atrial RFA versus 91 to 117 minutes during CS alone. Patients were on CPB significantly longer during left atrial RFA versus CS in Guang et al. (2002, p<0.01) and Mantovan et al. (2003, p<0.05). 139 In Guang et al. (2002) patients were cross clamped for significantly more time during left atrial RFA (mean 57 minutes) versus CS (mean 33 minutes, p<0.01). Cross clamp times were not stated in Mantovan et al. (2003). Table 249: CPB and cross clamping times- Left atrial RFA+CS versus CS CPB (min) LA RFA Cross clamping time (min) LA RFA CS CS Guang et al. 138[11] 91[8]† 57[6] 2002 Mantovan et al. 148[50] 117[30]* NS 2003 †: p<0.01; *: p<0.05; [ ]: SD; NS: not stated; LA: left atrial n LA RFA CS 33[4]† 96 87 NS 103 27 RFA versus Maze-III One study reported CPB and cross clamping times during RFA versus Maze-III surgery (see Table 250). In Chiappini et al. (2004) the patients were on CPB for a shorter time during RFA (mean 126 minutes) versus Maze-III (mean 156 minutes, p<0.01). However, there was no significant different in cross clamping times between the groups (mean 105 versus 113 minutes in RFA versus Maze-III, p>0.05). Table 250: CPB and cross clamping times- RFA versus Maze-III CPB (min) RFA Maze-III Chiappini et al.2004 126[33] 156[40]† †: p<0.01; [ ]: SD; pns: statistically non-significant Cross clamping time (min) RFA Maze-III 105[32] 113[26]pns n RFA 40 Maze-III 30 Biatrial versus left atrial RFA One study reported CPB and cross clamping times during biatrial versus left atrial RFA (see Table 251). In Deneke et al. (2002a) CPB times were significantly longer during biatrial RFA (mean 179 minutes) versus left atrial RFA (mean 146 minutes, p<0.05). However, the cross clamping times were similar between the two groups: a mean of 101 minutes during biatrial RFA versus 98 minutes during left atrial RFA. Table 251: CPB and cross clamping times- Biatrial versus left atrial RFA CPB (min) BA RFA Cross clamping time (min) BA RFA LA RFA LA RFA Deneke et al. 179[35] 146[34]* 101[20] 98[24]pns 2002a [ ]: SD; *: p<0.05; BA: biatrial; LA: left atrial; pns: statistically non-significant n BA RFA LA RFA 49 21 Case Series Biatrial RFA Three case series reported CPB and cross clamping times during biatrial RFA (see Table 252). The CPB times were a median of 158 minutes (range 109 to 227 minutes) in the three studies. Patients were cross clamped for a median of 117 minutes (range 70 to 119 minutes). 140 Table 252: CPB and cross clamping times- Biatrial RFA Case Series CPB (min) Biatrial Sie et al. Sos et al. Thomas et al. Median Range [ ]: SD; ( ): range Cross clamping (min) 227[65] 109[47] 158[37] 158 (109-227) n 119[46] 70[47] 117[29] 117 (70-119) 122 10 25 Left atrial RFA Nine case series reported CPB and cross clamping times in patients during left atrial RFA (see Table 253). Median CPB time was 114 minutes, with a range of 93 to 142 minutes. Cross clamping times were a median of 85 minutes, with a range of 64 to 120 minutes. Table 253: CPB and cross clamping times- Left atrial RFA Case Series CPB (min) Left atrial Benussi et al. Biederman et al. Geidel et al. Kottkamp et al. Le Tourneau et al. Mohr et al. Müller et al. Ruchat et al. Starck et al. Median Range [ ]: SD: ( ): range Cross clamping (min) n 111[25] 73[18] 132 93 70 10 142[21] 104[24] 105[19] 73[17] 29 12 120[29] 70 69[28] 64[17] 109[5] 96[31] 73 (64-120) 234 48 40 100 114[38] 110[32] 138[32] 136[36] 113 (93-142) Microwave Ablation Randomised Controlled Trial Left atrial MWA versus CS One RCT reported CPB and cross clamping times during MWA versus CS (see Table 254). In Schuetz et al. (2003) patients were on CPB for an average of 121 minutes during MWA versus 104 minutes during CS alone (p>0.05). Cross clamping times were significantly longer in the left atrial MWA (100 minutes) versus the CS (74 minutes) patients (p<0.05). Table 254: CPB and cross clamping times- Left atrial MWA+CS versus CS RCT CPB (min) LA MWA CS Cross clamping time (min) LA MWA CS Schuetz et al. 121[27] 104[45]pns 100[25] 2003 [ ]: SD; pns: statistically non-significant; *: p<0.05; LA: left atrial 141 74[44]* n LA MWA CS 24 19 Case Series Biatrial MWA One case series reported CPB and cross clamping times in patients during biatrial MWA (see Table 255). In Chiappini et al. (2003) patients having biatrial MWA were on CPB for an average of 123 minutes, and cross clamped for a mean of 99 minutes. Table 255: CPB and cross clamping times- Biatrial MWA Case Series CPB (min) Biatrial Chiappini et al. (2003) Cross clamping (min) n 99 10 123 Left atrial MWA One case series reported CPB and cross clamping times in patients during left atrial MWA (see Table 256). In Knaut et al. (2002) the average CPB time was 116 minutes and the average cross clamping time 84 minutes in patients during left atrial MWA. Table 256: CPB and cross clamping times- Left atrial MWA Case Series CPB (min) Left atrial Knaut et al. 2002 [ ]: SD Cross clamping (min) n 84[10] 105 116[15] MWA versus RFA One study reported CPB and cross clamping times during MWA versus RFA (see Table 257). In Wisser et al. (2004) the average CPB times were 165 minutes during MWA versus 164 minutes in the RFA patients. The average cross clamping times were 88 minutes in the MWA versus 91 minutes in the RFA patients. There did not appear to be a difference in times between the groups, although the p values were not given. Table 257: CPB and cross clamping times- MWA versus RFA Wisser et al. 2004 [ ]: SD CPB (min) MWA 165[34] RFA 164[48] Cross clamping time (min) MWA RFA 88[15] 91[25] n MWA 23 RFA 19 Maze-III Cardiopulmonary bypass and cross clamping times were reported in ten of the included MazeIII studies. The median time patients were on CPB was 169 minutes (range of 120 to 251 minutes). Patients were cross clamped for a median period of 93 minutes (range 69 to 151 minutes). 142 Summary Cardiopulmonary bypass Comparative Studies The comparison of CPB times between intraoperative ablation versus cardiac surgery alone provided variable results, with some studies reporting significantly greater CPB times with intraoperative ablation and others finding no significant difference. In the RCTs, CPB times were significantly longer for biatrial RFA plus MV surgery versus MV surgery alone (Khargi et al. 2001); but not significantly different in patients having left atrial MWA plus CS versus CS alone (Schuetz et al. 2003). The non-randomised comparative studies also provided variable results. Patients were on CPB significantly longer during left atrial CA and RFA versus CS alone. However, studies reported conflicting results within other groups: CPB times were significantly longer for biatrial CA in Handa et al. 1999, but not Sueda et al. 1997; and for biatrial RFA they were significantly longer in Chen et al. (2001) but not Patwardhan et al. (2003). Maze-III surgery did require longer CPB times than both CA and RFA. Within the internal comparison studies, CPB times were significantly longer for biatrial versus left atrial lesion patterns for both CA and RFA. 143 The study groups in which a median CPB time could be calculated (groups with three or more studies) are illustrated below, with a box plot to demonstrate the variance within studies of each group (Figure 8). The median CPB times in the CA studies were 196 and 146 minutes. Times between studies were variable, and it was not possible to compare the biatrial versus left atrial groups. When RFA was used the median CPB times in the biatrial groups were 164 and 158 minutes versus 146 and 113 minutes in the left atrial RFA groups. This suggests the left atrial RFA may have reduced CPB times versus the biatrial RFA procedure. There were insufficient MWA studies to plot. The median CPB time when cardiac surgery alone was performed was less than for all of the intraoperative ablation groups. In nine of the comparative CS studies median CPB time was 104 minutes. Three Maze-III study arms were included, with a median CPB time of 195 minutes. Maze-III (195; n=3) (104; n=9) Cardiac surgery (113; n=8) LA RFA case series BA RFA case series (158; n=3) LA RFA (146; n=3) BA RFA (164; n=6) LA CA case series (146; n=3) BA CA (196; n=19) 0 50 100 150 200 250 Cardiopulmonary bypass time (min) Figure 8: Cardiopulmonary bypass times The box represents the 10th and 90th percentiles, the line the median value, and the error bars the 5th and 95th percentiles. Outliers of more than 1.5 box lengths outside the median are shown as • (Median; no of studies) BA: biatrial; LA: left atrial; CA: cryotherapy ablation; RFA: radiofrequency ablation; MWA: microwave ablation 144 Cross clamping Comparative Studies In the majority of studies cross clamping times were significantly longer with intraoperative ablation versus cardiac surgery alone. In the RCTs, cross clamping times were significantly longer for biatrial RFA plus MV surgery versus MV surgery alone (Khargi et al. 2001); and also for left atrial MWA plus CS versus CS alone (Schuetz et al. 2003). In the non-randomised comparative studies, patients were cross clamped for significantly longer than CS alone during: biatrial and left atrial CA; and left atrial RFA. In one biatrial RFA study, cross clamping time was significantly longer than CS alone (Chen et al. 2001), but in the other study there was no significant difference in cross clamping times between the two groups (Patwardhan et al. 2003). Similarly, there was a significant difference in cross clamping times between Maze-III and CA in one study (Kim et al. 2001), but not in the other studies (Ishii et al. 2001; Lee et al. 2001). However, cross clamping times for Maze-III surgery were not significantly different versus RFA. When internal comparisons were made, cross clamping times were significantly longer for biatrial versus left atrial CA; but not for biatrial versus left atrial RFA. 145 The study groups in which a median cross clamp time could be calculated (n ≥ 3) are illustrated below, with a box plot to demonstrate the variance within studies of each group (Figure 9). The median cross clamping times with the biatrial comparative studies was 131 minutes, and in the left atrial CA case series it was 109 minutes. Therefore there may have been a slight reduction in cross clamping time in the left atrial versus biatrial CA procedures. The median cross clamping times in the biatrial studies were 102 and 117 minutes. In comparison in the left atrial RFA case series the median cross clamping time was 73 minutes. Again, it appeared that the left atrial RFA may have reduced cross clamping times compared to the biatrial procedure. There were insufficient studies to plot the MWA studies. In the cardiac surgery alone comparative study arms the median cross clamping time was only 65 minutes. However, patients in the Maze-III studies had a longer cross clamp time, a median of 141 minutes. Maze-III (141; n=4) (65; n=8) Cardiac surgery LA RFA case series (73; n=9) (117; n=3) BA RFA case series (102; n=6) BA RFA (109; n=3) LA CA case series BA CA (131; n=8) 0 50 100 150 200 Cross clamp time (min) Figure 9: Cross clamping times The box represents the 10th and 90th percentiles, the line the median value, and the error bars the 5th and 95th percentiles. Outliers of more than 1.5 box lengths outside the median are shown as • (Median; no of studies) BA: biatrial; LA: left atrial; CA: cryotherapy ablation; RFA: radiofrequency ablation; MWA: microwave ablation 146 5.2.12 Ablation times Cryotherapy Ablation Case Series Left atrial CA Two case series reported the ablation times in patients having left atrial CA (see Table 258). In Kondo et al. (2003) the ablation time was a mean of 31 minutes, while in Manasse et al. (2003) the left atrial CA took between 15 and 20 minutes. Table 258: Ablation times- Left atrial CA Case Series Ablation time(min) Left atrial Kondo et al. 2003 Manasse et al. 2003 [ ]: SD ( ): range n 31[5] (15-20) 31 95 Radiofrequency Ablation Non-randomised Comparative Studies Biatrial versus left atrial RFA One study reported ablation times during biatrial versus left atrial RFA (see Table 259). In Güden et al. (2002) the total ablation time was between 15 to 21 minutes during biatrial RFA versus 9 to 12 minutes during left atrial RFA. Table 259: Ablation times- Biatrial versus left atrial RFA Ablation time (min) BA RFA Güden et al. 2002 (9-12) Left ablation (6-9) Right ablation (15-21) Total ( ): range; BA: biatrial; LA: left atrial n LA RFA BA RFA LA RFA (9-12) Left ablation 39 23 Case Series Biatrial RFA Seven case series reported the ablation times for biatrial RFA (see Table 260). The median ablation time was 30 minutes, with a range of 3 to 59 minutes. In Hornero et al. (2002) the left ablation took longer than the right ablation (mean 22 versus 13 minutes), while in Patwardhan et al. (2003) the left ablation was shorter than the right ablation (mean 9 versus 15 minutes). Damiano et al. (2003) is in abstract form, and the ablation times seem short. It was stated that there were an average of three RF applications to the left and right atria, and the ablation times may have been for each separate ablation. 147 Table 260: Ablation times- Biatrial RFA Case Series Biatrial Chen et al. 2001a Damiano et al. 2003 Hornero et al. 2002 Patwardhan et al. 1997 Ablation time(min) n RFA1: 55[12] RFA2: 59[15] 0.44{0.17} Left ablationb 0.46 {0.22} Right ablation 22[7] Left ablation 13[5] Right ablation Total 35 9[3] Left atrial 15[5] Right atrial 24 Total 13 48 26 55 84 Prasanna et al. 3 25 2001 Riying et al. 1998 (10-15) 25 Sie et al. 2001 14[3] 122 Median (min)c 30 Range (min) (3-59) ( ): range; [ ]: SD; { }: type of variance not stated; a: comparative studies; b: times were for isolation of the pulmonary veins only; C: Median was calculated using Chen et al. 2001, Hornero et al. 2002, Patwardhan et al. 1997, Prasanna et al. 2001, and Sie et al. 2001. Left atrial RFA Nine case series reported ablation times for left atrial RFA (see Table 261). The median left atrial RFA ablation time was 19 minutes, with a range of 9 to 40 minutes. Benussi et al. (2002) used epicardial RFA in most patients, but where this was contraindicated (eg. epicardial thickening and adhesions) the RFA was performed endocardially. The average times for endocardial (18 minutes) RFA were longer than epicardial RFA (7 minutes). Table 261: Ablation times- Left atrial RFA Case Series Ablation time(min) Left atrial Benussi et al. 2002 Geidel et al. 2003 n 9[5] Total 7[3] epicardial 18[4] endocardial 17[5] 10.0[2.0] minus adjustment of equipment 132 107 25 29 Gillinov et al. 16[6] 50 2003 Kottkamp et al. 19[4] (16-28) 12 1999 Kress et al. 2002 40[20] 23 Le Tourneau et al. 18[4] 70 2003 Ruchat et al. 2002 19[5] 40 Starck et al. 2003 19[7] 100 Williams et al. Rarely > 20 48 2001 Median (n=9)a 19 Range (9-40) a: Williams et al. (2001) was not used to calculate the median; [ ]: SD; ( ): range 148 Microwave Ablation Case Series Left atrial MWA Three studies reported ablation times for left atrial MWA (see Table 263). In Schuetz et al. (2003) MWA took an average of 11 minutes, while in Gillinov et al. (2002) left atrial MWA required 10 to 15 minutes, and in Spitzer and Knaut (2002) the ablation time was up to 15 minutes. Table 263: Ablation times- Left atrial MWA Case Series Ablation time(min) n Left atrial Gillinov et al. 2002 (10-15) 10 Schuetz et al. 2003a 11[2] 24 Spitzer and Knaut 2002 Up to 15 136 ( ): range; a: comparative study but ablation times only relevant to MWA group MWA versus RFA One study reported ablation times during MWA versus RFA (see Table 264). In Wisser et al. (2004) ablation times were significantly longer in the MWA (mean 23 minutes) versus the RFA (mean 17 minutes) patients (p<0.05). Table 264: Ablation times- MWA versus RFA Wisser et al. 2004 *: p<0.05 Ablation time (min) MWA RFA 23[2] 17[1]* n MWA 23 RFA 19 5.2.13 Hospital and ICU stay Cryotherapy Ablation Non-randomised Comparative Studies Biatrial CA+CS versus CS One study reported hospital stay for CA+CS versus CS alone (see Table 265). In Handa et al. (1999) patients were in hospital significantly longer after CA+CS (mean 13 days) versus CS (mean 9 days, p<0.01). Table 265: Hospital stay- Biatrial CA+CS versus CS Hospital Stay (days) BA CA Handa et al.1999 13[6] †: p<0.01; [ ]: SD; ( ): range; BA: biatrial n CS 9[3]† BA CA 39 149 CS 58 Left atrial CA+CS versus CS One study reported hospital stay for left atrial CA+CS versus CS alone (see Table 266). In Gaita et al. (1999) Patients were in hospital for a mean of seven days after left atrial CA+CS versus six days after CS alone. The p value was not given. Table 266: Hospital stay- Left atrial CA+CS versus CS Hospital Stay (days) LA CA Gaita et al.1999 7[4] (5-22) [ ]: SD; ( ): range; LA: left atrial n CS 6[2] LA CA 32 CS 18 Case Series Biatrial CA One case series reported ICU stay following biatrial CA (see Table 267). In Izumoto et al. (1998) patients stayed in the ICU an average of five hours following biatrial CA. Table 267: ICU stay- Biatrial CA Case Series ICU stay (hrs) Biatrial Izumoto et al. 1998 [ ]: SD 5[8] n 87 Left atrial Two case series reported hospital stay after left atrial CA (see Table 268). Patients were in hospital an average of seven (Manasse et al. 2003) to 38 days (Kondo et al. 2003) following left atrial CA. Table 268: Hospital stay- Left atrial CA Case Series Hospital Stay (days) Left atrial Kondo et al. 2003 Manasse et al. 2003 [ ]: SD; ( ): range 38[18] (21-74) 7 (5-49) n 31 95 Radiofrequency Ablation Non-randomised Comparative Studies Biatrial RFA versus CS One study reported hospital and ICU stay in patients after biatrial RFA versus CS (see Table 269). In Chen et al. (2001) the average lengths of hospital stay were 21 and 19 days in the two RFA groups versus 17 days after CS (p>0.05). The lengths of ICU stay were seven hours after RFA versus six hours following CS alone (p>0.05). 150 Table 269: Hospital and ICU stay- Biatrial RFA versus CS Hospital Stay (days) ICU stay (hrs) n BA RFA CS BA RFA CS BA RFA CS RFA1: 7[10] 13 Chen et al. RFA1: 21[13] pns pns 6[7] 58 17[15] RFA2: 7[14] 48 2001 RFA2: 19[19] [ ]: SD; ( ): range; RFA1: first RFA lesion set; RFA2: second RFA lesion set; pns: statistically non-significant; BA: biatrial Left atrial RFA versus CS One study reported hospital stay after left atrial RFA versus CS (see Table 270). Patients were in hospital for an average of eleven days after left atrial RFA versus ten days after CS alone (Mantovan et al. 2003). The p value was not stated. Table 270: Hospital stay- Left atrial RFA versus CS Mantovan et al. 2003 [ ]: SD; LA: left atrial Hospital Stay (days) LA RFA CS 11[4] 10[3] n LA RFA 103 CS 27 RFA versus Maze-III One study reported ICU stay in patients after RFA versus Maze-III (see Table 271). Patients stayed in the ICU for an average of two hours after RFA versus five hours after Maze-III surgery (Chiappini et al. 2004). This difference was not statistically significant. Table 271: ICU stay- RFA versus Maze-III ICU stay (hrs) BA RFA Maze-III Chiappini et al. 2004 2 5pns pns: statistically non-significant; BA: biatrial n BA RFA 40 Maze-III 30 Case Series Biatrial RFA Two case series reported hospital stay in patients after biatrial RFA (see Table 272). Patients stayed in hospital for between 11 days (Sos et al. 2002) and 12 days (Hornero et al. 2002) after biatrial RFA. Table 272: Hospital stay- Biatrial RFA Case Series Hospital Stay (days) Biatrial Hornero et al. 2002 Sos et al. 2002 [ ]: SD; ( ): range 12 (6-65) 11[6] (7-26) n 55 10 Left atrial RFA Two case series reported the hospital and ICU stay in patients after left atrial RFA (see Table 273). Patients spent between seven to 12 days in hospital and two to three hours in the ICU following left atrial RFA (Benussi et al. 2002; Ruchat et al. 2002). 151 Table 273: Hospital and ICU stay- Left atrial RFA Case Series Hospital Stay (days) Left atrial Benussi et al. 2002 Ruchat et al. 2002 Range [ ]: SD; ( ): range 7[4] 12[5] (7-12) ICU stay (hrs) n 2[2] 3[2] (2-3) 132 40 Microwave Ablation Randomised Controlled Trial Left atrial MWA versus CS One RCT reported hospital stay in patients after MWA versus CS (see Table 274). In Schuetz et al. (2003) patients spent an average of 22 days in hospital after left atrial MWA versus 20 days after CS alone (p>0.05). Table 274: Hospital stay- MWA versus CS RCT Hospital Stay (days) n LA MWA CS LA MWA Schuetz et al. 2003 22[13] (9-52) 20[11] (12-57)pns 24 [ ]: SD; ( ): range; pns: statistically non-significant; LA: left atrial CS 19 MWA versus RFA One study reported hospital and ICU stays following MWA versus RFA (see Table 275). In Wisser et al. (2004) the average hospital stays were 12.8 days after MWA versus 12.0 days following RFA. The ICU stays were an average of 1.7 days after MWA versus 1.6 days after RFA. The p values were not given. Table 275: Hospital and ICU stay- MWA versus RFA Hospital Stay (days) MWA RFA Wisser et al. 2004 [ ]: SD 12.8[3.4] 12.0[5.1] ICU stay (days) MWA RFA 1.7[2.5] 1.6[1.2] n MWA n=23 hospital n=22 ICU RFA n=19 hospital n=18 ICU 5.2.14 Reoperation and readmission Patients may require re-operation soon after surgery to correct bleeding, or for other reasons, such as failure of a prosthetic valve. When the reasons for reoperation were specified, they were divided into reoperation for bleeding, or for other reasons. Non-randomised Comparative Studies Biatrial CA+CS versus CS Two studies reported re-operation after CA+CS versus CS (see Table 276). In Handa et al. (1999) 5% (2/39) of CA+CS patients versus 2% (1/58) of CS patients had reoperation, at greater than 30 days postoperative. The p value was not given. 152 Table 276: Re-operation- Biatrial CA+CS versus CS Level Handa et al. 1999 BA: biatrial III-2 Reoperation (%) BA CA CS 5% other 2% other n/N BA CA 2/39 n/N CS 1/58 Time > 30 days Left atrial CA+CS versus CS One study reported re-operation after left atrial CA+CS versus CS (see Table 277). In Gaita et al. (2000) 3% (1/32) of patients had re-operation for bleeding, and another 3% (1/32) were re-operated on for other reasons. None of the CS patients underwent re-operation. Re-operation was performed within 30 days of surgery in all cases. Table 277: Re-operation- Left atrial CA+CS versus CS Level Gaita et al. 2000 III-2 Reoperation (%) LA CA CS 3% bleeding 0% bleeding 3% other 0% other 6% total 0% total n/N LA CA 1/32 1/32 2/32 n/N CS 0/18 0/18 0/18 Time 30 days 30 days Total CA versus Maze-III One study reported re-operation after CA versus Maze-III (see Table 278). In Ishii et al. (2001) none of the CA patients, but 15% (2/13) of the Maze-III patients underwent re-operation up to 30 days postoperatively. The p value was not given. Table 278: Re-operation- CA versus Maze-III Level Ishii et al. 2001 III-3 Reoperation (%) CA Maze-III 0% 15% n/N CA 0/32 n/N Maze-III 2/13 Time 30 days Biatrial versus right atrial CA One study reported re-operation after biatrial versus left atrial CA (see Table 279). In Schaff et al. (2000) there were 6% (10/173) of patients requiring re-operation following biatrial CA versus none after left atrial CA. The p value was not given. Table 279: Re-operation- Biatrial versus right atrial CA Level Schaff et al. 2000 III-2/3 RA: right atrial; BA: biatrial Reoperation (%) BA CA RA CA 6% 0% n/N BA CA 10/173 n/N RA CA 0/42 Time 30 days Case Series Biatrial CA Two case series reported rates of re-operation after biatrial CA (see Table 280). In Izumoto et al. (2000) there were 8% (7/87) patients requiring re-exploration for bleeding after biatrial CA, and 2% (2/104) patients requiring re-operation for other reasons. No patients required re-operation in Yuda et al. (2001), to a mean follow-up of more than two years. 153 Table 280: Re-operation- Biatrial CA Case Series Level Biatrial Izumoto et al. IV 2000 Yuda et al. 2001 IV [ ]: SD; a: Izumoto et al. 1998 Reoperation (%) n/N Follow-up 8% bleedinga 2% other 0% other 7/87 2/104 0/94 1 month 2.2[0.9] years Left atrial CA Two case series reported rates of re-operation after left atrial CA (see Table 281). Manasse et al. (2003) stated 2% (2/95) of patients requiring re-operation due to bleeding, while another 3% (3/95) were operated on again for failure of MV plasty or replacement. In Imai et al. (2001) no patients required re-operation during follow-up, at a mean of almost 37 months follow-up. Table 281: Re-operation- Left atrial CA Case Series Left atrial Imai et al. 2001 Manasse et al. 2003 Level Reoperation (%) n/N Follow-up IV 0% bleeding 0/32 36.9[14.1] months IV 2% bleeding 3% other 5% total 2/95 3/95 5/95 7 days [ ]: SD Radiofrequency Ablation Randomised Controlled Trial Biatrial RFA+MVS versus CMVS One RCT reported rate of re-operation in patients after biatrial RFA versus CS (see Table 282). There were 7% (1/15) of patients after both biatrial RFA and CS alone who required reoperation for sternal instability in the early postoperative period (Khargi et al. 2001). Table 282: Reoperation- RFA+MVS versus MVS Level Reoperation (%) BA RFA MVS Khargi et al. 2001 II 7% other 7% other BA: biatrial; MVS: mitral valve surgery 154 n/N BA RFA 1/15 n/N MVS 1/15 Follow-up 30 days Non-randomised Comparative Studies Biatrial RFA versus CS One study reported re-operation rates after biatrial RFA versus CS (see Table 283). Patwardhan et al. (1997) stated a similar number of patients required re-operation in both groups: 7% (6/84) after biatrial RFA versus 6% (4/64) following CS alone. Follow-up was a mean of 23.6 months after biatrial RFA versus six months for CS. Table 283: Reoperation- Biatrial RFA versus CS Level Patwardhan et al. 1997 [ ]: SD; BA: biatrial III-3 Reoperation (%) BA RFA CS 7% other 6% other n/N BA RFA 6/84 n/N CS 4/64 Follow-up 23.6[12.5] months 6 months Left atrial RFA versus CS One study reported the rate of re-operation after left atrial RFA versus CS (see Table 284). In Guang et al. (2002) 2% (2/96) of patients required re-operation for bleeding after left atrial RFA versus 1% (1/87) after CS alone. The p value was not given. Table 284: Re-operation- Left atrial RFA versus CS Level Guang et al. 2002 LA: left atrial III-2 Reoperation (%) LA RFA CS 2% bleeding 1% bleeding n/N LA RFA 2/96 n/N CS 1/87 Follow-up 30 days Biatrial versus left atrial RFA One study reported the rate of re-operation after biatrial versus left atrial RFA (see Table 285). In Güden et al. (2002) 5% (2/39) of biatrial RFA patients versus 4% (1/23) of left atrial RFA patients required re-operation for bleeding. In all cases bleeding was associated with the left atrial appendage resection site. Table 285: Re-operation- Biatrial versus left atrial RFA Level Güden et al. 2002 III-2 BA: biatrial; LA: left atrial Reoperation (%) BA RFA LA RFA 5% bleeding 4% bleeding n/N BA RFA 2/39 n/N LA RFA 1/23 Follow-up 30 days Case Series Biatrial RFA Four case series reported re-operation after biatrial RFA (see Table 286). The median proportion of patients requiring re-operation was 6%, with a range of 0% to 9%. In Hornero et al. (2002) 6% (3/55) of patients required re-exploration for bleeding; 9% of patients (11/122) required reoperation for other reasons in Sie et al. (2001); and no patients were re-operated for bleeding in Sos et al. (2002). In Raman et al. (2003) 5% (6/132) of patients were readmitted for recurrent AF, sinus bradycardia, or both, in the first three months follow-up. 155 Table 286: Reoperation- Biatrial RFA Case Series Biatrial Hornero et al. 2002 Raman et al. 2003 Sie et al. 2001 Sos et al. 2002 Median Range Level Reoperation (%) n/N Follow-up IV IV IV IV 6% bleeding 5% readmission 9% other 0% bleeding 6% (0%-9%) 3/55 7/132 11/122 0/10 30 days 3 months 30 days 3 months Left atrial RFA Six case series reported the rate of re-operation after left atrial RFA (see Table 287). A median proportion of 3% of patients required re-operation, with a range of 0% to 17%. Most of the cases of re-operation were due to bleeding. The number of patients requiring reoperation for bleeding was from 0% in Müller et al. (2002) to 8% (1/12) in Kottkamp et al. (1999). There were also patients requiring re-operation for other reasons: 1% (1/103) in Mantovan et al. (2003) to 8% (1/12) in Mantovan et al. (2003). Table 287: Reoperation- Left atrial RFA Case Series Level Reoperation (%) n/N Follow-up Left atrial Benussi et al. 2002 2% bleeding 3/132 1% other 1/132 3% total 4/132 Kottkamp et al. 1999 8% bleeding 1/12 IV 8% other 1/12 17% total 2/12 Mantovan et al. 2003a IV 1% other 1/103 Müller et al. 2002 IV 0% bleeding 0/95 Ruchat et al. 2002 IV 3% bleeding 1/40 Starck et al. 2003 IV 2% bleeding 2/100 Median 3% Range (0%-17%) a: comparative study but re-operation not reported in CS group IV 30 days 30 days 30 days 30 days 30 days 30 days Microwave Ablation Case Series Left atrial MWA Three case series reported rates of re-operation in patients after left atrial MWA (see Table 288). The median proportion of patients requiring re-operation was 0%, with a range of 0% to 1%. In all three studies no patients required re-exploration for bleeding (Knaut et al. 2002; Spitzer and Knaut 2002; Venturini et al. 2003). However, in Spitzer and Knaut (2002) one patient (1/132, 1%) had re-operation for other reasons. 156 Table 288: Re-operation- Left atrial MWA Level Left atrial Knaut et al. 2002 Spitzer and Knaut 2002a Reoperation (%) n/N IV 0% other 0/105 0% bleeding 0/136 IV 1% other 1/136 1% total 1/136 Venturini et al. 2003 IV 0% bleeding 0/41 Median 0% Range (0%-1%) a: comparative study but re-operation not reported in CS group Follow-up 30 days 30 days 30 days MWA versus RFA One study reported the incidence of reoperation for bleeding after MWA versus RFA (see Table 289). In Wisser et al. (2004) there were two patients (2/23, 9%) who required reoperation for bleeding after MWA. In comparison no patients required reoperation for bleeding after RFA. The p value was not given. Table 289: Re-operation- MWA versus RFA Level Wisser et al. 2004 III-2/3 Reoperation (%) MWA RFA 9% bleeding 0% bleeding n/N MWA 2/23 n/N RFA 0/19 Follow-up 30 days 5.2.15 Exercise testing Only two of the studies included in this review performed exercise testing. The results are summarised in Appendix D.11. Cryotherapy ablation Biatrial CA versus CS Yuda et al. (2004) performed exercise testing in patients prior to surgery and following biatrial CA (n=26) versus CS alone (n=6). The biatrial CA patients were divided into those having SR (n=18) or AF (n=8) after surgery. Mean periods of follow-up to exercise testing were 14.6 months in the biatrial CA-SR group; 19.1 months in the biatrial CA-AF group; and 17.4 months in the CS group. There were no significant differences apparent between the biatrial CA versus CS groups. When the preoperative values were compared with those after surgery, in the biatrial CA-SR patients there were significant increases in: maximum work load; peak heart rate; systolic blood pressure at rest; systolic blood pressure at peak; and peak VO2. There were no apparent differences in values before and after surgery in the biatrial CA-AF group, and only the peak VO2 increased significantly in the CS patients. 157 Radiofrequency ablation Randomised Controlled Trial Biatrial RFA+MVS versus MVS Exercise testing was performed in the RCT comparing biatrial RFA plus MV surgery (n=11) versus MV surgery alone (n=11; Deneke et al. 2002b). There was a significantly greater maximum work load of a mean of 73 watts in the biatrial RFA versus 43 watts in the MVS groups (p<0.01). However, there were no significant differences in peak heart rate, mean heart rate increase, peak VO2 or anaerobic threshold between the two groups. 6.0 DISCUSSION 6.1 Study limitations The conclusions of this systematic review of intraoperative ablation for treatment of AF were limited by the published studies that were available. There were only two RCTs of average quality, and the remaining data was obtained from lower level evidence, non-randomised comparative studies and case series. More importantly the studies themselves differed greatly, both in the type of energy source used and the specific lesion pattern, reducing the number of studies for each comparison. Follow-up periods ranged from the early postoperative period to several years after surgery. Arrhythmias are more common soon after surgery, and in studies with short follow-up, fewer patients may have been in SR compared with later follow-up. Conversely, longer follow-up times are needed to demonstrate patients do remain in SR for a long period after intraoperative ablation. 6.2 Safety and efficacy of intraoperative ablation Due to the complexity of the findings of this review, the main results from the comparative studies have been summarised here. Please refer to the Results section and tables for more detail, and for references to the individual studies. 6.2.1 Efficacy Cryotherapy Ablation (CA) Biatrial CA versus CS There appeared to be more patients in SR and fewer patients in AF following biatrial CA versus CS alone, in three non-randomised comparative studies (Table 290). There were no apparent differences in incidence of atrial flutter, or of pacemaker requirement, between the two groups. Cross clamping times were significantly longer for the biatrial CA versus CS patients, with CPB times also significantly longer in one study, but not different in the other study. 158 Left atrial CA versus CS In a single comparative non-randomised study, more patients were in SR and fewer in AF following left atrial CA versus CS alone. No difference was seen in pacemaker incidence between the two groups. Both CPB and cross clamping times were significantly longer in the left atrial CA versus CS groups. CA versus Maze-III When CA was compared to Maze-III surgery, there was no apparent difference in conversion to SR in three studies. However, in the fourth study significantly more patients had converted to SR following CA versus Maze-III. There appeared to be no difference in the proportion of patients in AF, atrial flutter, or with pacemakers between the two groups. Right atrial contraction was similar between the two groups in two studies. Left atrial contraction was also similar following CA or Maze-III surgery in two studies, but significantly more patients had left atrial contraction after CA versus Maze-III in a third study. The CPB times were significantly longer for Maze-III versus CA, with cross clamping times also longer for MazeIII in one study, but in the other two studies there were no apparent differences in cross clamping times between the two groups. Biatrial versus left atrial CA When CA was applied in a biatrial or left atrial lesion set, the proportion of patients in SR, AF, and requiring a pacemaker were similar between the two groups. However, CPB and cross clamping times were significantly longer for the biatrial than the left atrial CA surgery. Table 290: Major efficacy outcomes – Non-randomised comparative CA studies Biatrial CA versus CS Left atrial CA versus CS SR ↑ 3 studies1 ↑ 1 study AF Atrial flutter Pacemaker Right atrial contraction Left atrial contraction Right A/E ratio Left A/E ratio CPB ↓ 3 studies1 ↔ 1 study2 ↔ 2 studies2 ↓ 1 study Cross clamp ↔ 1 study CA versus Maze-III ↔ 3 studies4 ↑ 1 study ↔ 4 studies2 ↔ 1 study ↔ 3 studies2 Biatrial versus Left atrial CA ↔ 1 study2 ↔ 1 study2 ↔ 1 study ↔ 2 studies ↔ 2 studies ↑ 1 study ↔ 1 study ↑ 1 study ↑ 1 study ↔ 1 study ↑ 1 study ↓ 2 studies ↑ 1 study ↓ 1 study ↑ 1 study ↔ 2 studies3 ↑: more patients in first versus second group; ↓: fewer patients in first versus second group; ↔: equal number of patients in first and second groups; 1: p values not given, but consistent differences between groups; 2: p value not given; 3: p value not given in 1 study; 4: p value given in only one study ↑ 2 studies ↑ 1 study 159 Radiofrequency Ablation Biatrial RFA versus CS In the RCT, there were significantly more patients in SR, and fewer patients in AF, following biatrial RFA versus CS alone (Khargi et al. 2001; Table 291). Adding biatrial RFA to the surgery did not alter the proportion of patients requiring pacemakers after surgery. It did, however, result in more patients with right atrial contraction, although there were no significant differences in left or biatrial contraction between the two groups. Both CPB and cross clamping times were significantly longer, for biatrial RFA plus CS versus CS alone. The results for the non-randomised comparative studies were consistent with the RCT. The only differences were a significant increase in left atrial contraction after biatrial RFA versus CS in one study; and one of the two studies did not show a significant increase in CPB or cross clamping times when biatrial RFA was added to the procedure. Left atrial RFA versus CS In two studies the left atrial RFA versus CS comparisons were similar to the results with biatrial RFA. In addition, one of the studies reported no difference in incidence of atrial flutter between the two groups; biatrial contraction was significantly increased by left atrial RFA; and both CPB and cross clamping times were consistently increased. Biatrial versus left atrial RFA When biatrial versus left atrial RFA were compared, no difference was seen in the proportion of patients in SR after surgery. In contrast, one study showed an increased number of patients in AF and atrial flutter after left atrial versus biatrial RFA. No consistent differences in atrial contraction were present between the two groups. The CPB times were significantly longer for biatrial versus left atrial RFA in one study, but cross clamping times were not significantly different. Table 291: Major efficacy outcomes from RFA studies SR AF BA RFA versus CS ↑ 1 RCT ↑ 3 studies1 ↓ 1 RCT ↓ 3 studies3 LA RFA versus CS RFA versus MazeIII BA versus LA RFA ↑ 2 studies1 ↔ 2 studies2 ↓ 1 study3 ↓ 1 study Atrial flutter Pacemaker ↔ 1 study ↓ 1 study ↔ 1 RCT 3 ↔ 1 study ↔ 1 study3 Right atrial ↑ 1 RCT ↔ 2 studies3 contraction ↑ 1 study Left atrial ↔ 1 RCT ↔/↑ 1 study3 contraction ↑ 1 study Biatrial contraction ↑ 1 study3 ↔ 1 study ↔/↑ 1 study3 ↔ 1 RCT CPB ↑ 1 RCT ↑ 2 studies ↑ 1 study ↑ 1 study ↑ 1 study ↔ 1 study Cross clamp ↑ 1 RCT ↑ 1 study ↑ 1 study ↔ 1 study ↔ 1 study ↔ 1 study ↑: more patients in first versus second group; ↓: fewer patients in first versus second group; ↔: equal number of patients in first and second groups; 1: p values given in only one study, but consistent differences between groups; 2: p value given in only one study; 3: p values not given 160 Microwave Ablation Left atrial MWA versus CS In the RCT, left atrial MWA resulted in significantly more patients in SR, and fewer in AF, with no difference seen in pacemaker requirement versus CS alone (Table 292). The CPB times were not significantly different between left atrial MWA versus CS, but cross clamping times were significantly increased by the left atrial MWA. Results of one non-randomised comparative study, of left atrial MWA versus CS, were consistent with the RCT. In addition, pacemaker requirements were not apparently different between the groups; but biatrial contraction was present in more patients after left atrial MWA than CS alone. Table 292: Major efficacy outcomes from MWA studies SR AF LA MWA versus CS ↑ 1 RCT ↑1 study ↓ 1 RCT ↓ 1 study3 Atrial flutter Pacemaker ↔ 1 study3 Biatrial ↑ 1 study contraction CPB ↔ 1 RCT Cross clamp ↑ 1 RCT ↑: more patients in first versus second group; ↓: fewer patients in first versus second group; ↔: equal number of patients in first and second groups; 1: p values given in only one study, but large and consistent difference between groups 2: p value given in only one study; 3: p value not given. 6.2.2 Safety Cryotherapy Ablation Biatrial CA versus CS There were no apparent differences in mortality rate in three studies, or bleeding complications in one study, following biatrial CA versus CS alone (Table 293). There may have been a slight decrease in the incidence of stroke and other thromboembolisms in the biatrial CA group, but the p value was not given. Left atrial CA versus CS In one included study, there were no differences in either incidence of mortality, or of bleeding complications, in the left atrial CA versus CS patients. CA versus Maze-III There were no apparent differences in mortality between CA and Maze-III patients in three studies. Single studies reported similar levels of bleeding, stroke and other thromboembolism, and low cardiac output between the two groups. There may have been a reduction in incidence of bleeding requiring re-exploration after CA versus Maze-III in one study, (0%, 0/23 versus 15%, 2/13) but the p value was not given (Ishii et al. 2001). 161 Biatrial versus left atrial CA In one included study there were no apparent differences in mortality or bleeding complications after biatrial versus left atrial CA. Table 293: Major safety outcomes – Non-randomised comparative CA studies Biatrial CA versus CS ↔ 3 studies1 Left atrial CA versus CS ↔ 1 study CA Biatrial versus versus Maze-III left atrial CA Mortality ↔ 3 studies1 ↔ 1 study Bleeding ↔/↓ 1 study1 1 1 ↔ 1 study ↔ 1 study ↔ 1 study ↔ 1 study1 Strokea ↔/↓ 1 study1 ↔ 1 study1 Low cardiac output ↔ 1 study1 ↓: fewer patients in first versus second group; ↔: equal number of patients in first and second groups; 1: p values not given; a: stroke and other thromboembolisms Radiofrequency ablation The main safety outcomes for the radiofrequency comparative studies are summarised below (Table 294). The numbers of studies reporting each outcome are shown, and where there appeared to be a difference but the p value was not stated, this is shown in the footnotes. Biatrial RFA versus CS In the RCT there were no significant differences in mortality, wound infections, or pulmonary insufficiency after biatrial RFA versus CS alone (Khargi et al. 2001). The results of the nonrandomised comparative studies were consistent with the RCT. Left atrial RFA versus CS In two studies there were similar rates of both mortality and stroke following left atrial RFA versus CS. The incidence of bleeding complications, pulmonary insufficiency, and low cardiac output after surgery also did not appear to differ between the left atrial RFA and CS groups, with results reported in one study. RFA versus Maze-III One included study reported no apparent difference in the incidence of mortality following RFA versus Maze-III surgery. Biatrial versus left atrial RFA There were similar mortality rates in patients who had biatrial versus left atrial RFA in two studies, and proportions of bleeding and wound infection between the two groups were also similar in one study. 162 Table 294: Major safety outcomes from RFA studies Biatrial RFA versus CS Mortality Bleeding Strokea Wound infectionb Pulmonary insufficiency Low cardiac output ↔ 1 RCT ↔ 3 studies1 Left atrial RFA versus CS RFA versus MazeIII ↔ 2 studies2 ↔ 1 study1 ↔ 1 study ↔ 2 studies1 ↔ 1 RCT ↔ 1 study1 ↔ 1 RCT Biatrial versus left atrial RFA ↔ 2 studies1 ↔ 1 study1 ↔ 1 study1 ↔ 1 study ↔ 1 study1 ↔: equal number of patients in first and second groups; 1: p values not given; a: stroke and other thromboembolisms; b: wound infection or mediastinitis Microwave Ablation The main safety outcomes for the microwave comparative studies are summarised below (Table 295). The numbers of studies reporting each outcome are shown, and where there appeared to be a difference but the p value was not stated, this is shown in the footnotes. In the included RCT, there were no significant differences in mortality between patients who had left atrial MWA or CS alone (Schuetz et al. 2003). The results from a non-randomised comparative study confirmed this result, with bleeding complications also apparently similar between the two groups. Table 295: Major safety outcomes from MWA studies LA MWA versus CS Mortality ↔ 1 RCT ↔ 1 study1 Bleeding ↔ 1 study1 ↔: equal number of patients in first and second groups; 1: p value not given 6.3 Factors influencing efficacy 6.3.1 Energy source With the many combinations of both different energy sources and ablation patterns used in the included studies of this review, it is difficult to compare the energy sources. Only one included non-randomised comparative study was found, which directly compared RFA and MWA. No apparent differences in major safety and efficacy outcomes between RFA versus MWA were seen in this study (Wisser et al. 2004). Further comparative studies using different energy sources will be necessary, to determine whether there are significant differences in outcome according to the type of energy source used. However, separate comparisons of CA, RFA and MWA indicated the various ablation techniques were more effective than CS alone, and similar to Maze-III. When a surgical incision is made, there is no question about whether it is transmural, or not. This is not the case with energy ablation, as it is not usually possible to see intraoperatively 163 whether the lesion has passed through the full thickness of cardiac tissue. The ablation can be performed for a set time and energy level, but in patients with thicker or more fibrosed atrial tissue, this may not form a transmural lesion. It is also more difficult to obtain transmural lesions in patients with mitral valve disease than in normal atrial tissue in vitro (Santiago et al. 2003). While a transmural lesion has been considered essential to provide conduction block, in two recent conference presentations it was reported non-transmural unipolar RF (Argenziano et al. 2004) or microwave (van Brakel et al. 2004) ablation could still result in electrophysiological block. Ideally, surgeons should be able to measure whether or not there is conduction block intraoperatively, but further technological advances are needed to enable this to occur. As well as non-transmural lesions, there may also be gaps between lesion lines. These gaps can lead to postoperative arrhythmias, as described in the included studies in which electrophysiological studies and catheter ablation were performed after surgery (pp.120-123). For example, left sided atrial flutter resulted from a gap in the left atrial CA ablation line in Manasse et al. (2003); and arrhythmias also resulted from gaps in RFA lines in Thomas et al. (2003) and Benussi et al. (2002). Generally cryoablation requires a longer ablation time than either radiofrequency or microwave ablation. In an invited commentary Cox stated extensive experimental and clinical experience confirms permanent cardiac tissue ablation needs at least two minutes of cryoprobe application (Fukada et al. 1998). Some of the included CA studies used less than two minutes of ablation (Lee et al. 2001; Fukada et al. 1998; Morishita et al. 2000; Takami et al. 1999; Usui et al. 2002), while in other studies the period of cryoablation were not stated. As well as the ablation time itself, the probe has to thaw sufficiently for the probe to be removed: the death of a patient in Manasse et al. (2003) resulted from withdrawal of the cryoprobe too quickly, with tearing of the atrial wall. In comparison, RFA and MWA times were typically less than one minute. Radiofrequency probes are either unipolar or bipolar, and irrigated or non-irrigated. Unipolar catheters produce broad lesions, and a surgeon may not be able to reliably measure the transmurality of the lesion (Hamner et al. 2003). To prevent partial thickness lesion, operators have used multiple applications and long ablation times for individual lesions, but this can increase collateral damage. The bipolar devices overcome these limitations by delivering energy focused between two opposing electrodes, embedded in the jaws of a clamp (Hamner et al. 2003). The focused energy delivery shortens the ablation times, minimises lesion width, and reduces the potential for adjacent tissue injury. Furthermore, when the probe is irrigated, this may cool the tissue surface, and result in a lesion of greater depth (Petersen et al. 1999). These devices can also be linked to computer software, to monitor tissue impedance, an index of the transmurality of the lesion. Another problem which was reported with the use of RFA was that if the energy is set too high and rapid boiling of intracellular fluid occurs, ‘tissue pops’ result. In Wisser et al. (2004) it was stated this occurred rarely, but when it did the atrium usually required sutures. Güden et al. (2002) also stated that tissue injury caused by RFA was easily repaired with sutures. 164 6.3.2 Lesion set The Maze-III has been the gold standard surgical method of treating AF, and surgeons have taken the complex pattern of Maze-III incisions and created numerous variations on the theme, some having little in common with the original. In an editorial, James Cox pointed out the many combinations of lesion sets which have been used, including: ‘left-sided mazes’, ‘right-sided mazes’, pulmonary encirclement only, and connection of pulmonary vein orifices in various combinations with or without a lesion down to the mitral valve annulus (Cox 2001). Kress has summarised optimal lesion patterns, and concluded by saying “there is no lesion pattern that is ‘best’ for all patients, but the least complicated lesion pattern that is safe and easy to deliver and shown to be effective for a given population can be considered the best for those patients” (Kress 2002). Kress also suggested ablation of the right atrium is necessary only in patients with known right atrial flutter, giant right atrium, or having a planned right atriotomy. The included studies of this review were sub-divided according to whether the lesion sets included both atria versus only the left or right atrium. Overall there were no apparent differences in safety and efficacy outcomes when comparing biatrial versus left atrial ablation, apart from one comparative non-randomised study reporting a significant increase in the incidence of episodes of AF, and of atrial flutter, with left atrial versus biatrial RFA (Güden et al. 2002). Further studies will be necessary to definitively decide whether ablation to both atria is necessary, and, if so, in which patient group. Cox has stated it is essential to block all electrical conduction along the inferior portion of the left atrium, between the inferior pulmonary veins and the posterior mitral annulus (Cox 1995a). While lesion sets involving one or both atria are obviously different, it is also possible that in some patients more subtle differences in lesion pattern could significantly affect outcomes. For example, in Manasse et al. (2003) three slightly different CA lesion patterns of the left atrial wall were used. The lesion set involving focal ablation of each pulmonary vein was significantly less effective than the two other sets, both of which included connecting lesions between the pulmonary veins, and to the mitral annulus. In most of the studies the lesions were placed endocardially, but in some studies epicardial lines were used. For example, in Gillinov et al. (2002) MWA was performed epicardially to the left atrium, while a combination of endocardial and epicardial RFA lesions were used in Chen et al. (2001). It has been proposed epicardial ablation is safer than endocardial ablation, since energy is directed into the atrium, rather than going outwards into adjacent structures, such as the oesophagus (Kress 2002). In addition, cardiopulmonary bypass is not necessary for epicardial lesions, allowing less invasive procedures to be performed. It is not possible for nitrous oxide cryotherapy to be placed epicardially to the blood filled atrium (Kress 2002), which may limit the evolution of techniques involving this type of probe. The lesion sets used also varied depending on whether the atrial appendages were resected, ablated, or ignored. More than 90% of cardiac thromboemboli may originate from the LAA, and a randomised clinical trial is currently underway to test occlusion of the left atrial appendage during routine coronary artery bypass graft surgery for long-term stroke prevention (Crystal et al. 2003). Surgery which leaves the LAA intact may be associated with a higher risk of thromboembolism, although further studies will be necessary to test this hypothesis. 165 The left atrial appendage is a fragile tissue, and one included study discussed the risk of bleeding complications following its amputation (Güden et al. 2002). It was stated the surgeons now suture the amputation site after RFA has been performed, so there is no chance of the RFA weakening the suture line. 6.3.3 Type of AF Atrial fibrillation can be classified as paroxysmal, persistent, or permanent, depending on the duration and response to treatment of the episodes (Levy et al. 2003). A significant confounding factor in the included studies was that patient groups were mixed, with paroxysmal, persistent and permanent AF included. Adding to this problem, standardised nomenclature for the classification of AF was not always used, for example, if paroxysmal AF was present for a long period of time, patients were said to have chronic AF. This is an important factor since the outcomes for paroxysmal AF may be better than for persistent or permanent AF. In Handa et al. (1999) survival analysis of freedom from recurrent AF at two years was 100% in the paroxysmal AF versus 74% in the chronic AF patients. In addition, a survey of cost of care for patients with AF in France found patients with persistent or permanent AF were hospitalised more frequently and more likely to die compared to those with paroxysmal AF (Le Heuzey et al. 2004). 6.3.4 Measurement of SR/AF The presence of SR, and absence of AF, comprised the major efficacy outcomes. Cardiac rhythm was usually determined by 12-lead ECG or 24 hour Holter monitor, at irregular intervals during the follow-up. If arrhythmia occurred between follow-up appointments, the patient would have to be aware of the problem and visit the doctor, otherwise it would go unreported. In addition, a study of 110 patients with a history of AF was conducted in Germany, with a device implanted having dedicated functions for AF detection and electrogram storage (Israel et al. 2004). The surprising result was that a significant proportion (38%) of patients who had relapses of AF for more than 48 hours were totally asymptomatic. If cardiac rhythm is monitored sporadically during follow-up, the true incidence of AF is likely to be underestimated. However, for comparative studies, this would apply equally to the patients in both groups. 6.3.5 Atrial contraction A secondary outcome for the success of intraoperative ablation is the presence of effective atrial contraction. This outcome is also important for the clinical management of these patients, as a number of studies did not stop anticoagulant medication until effective atrial contraction had been demonstrated. The included studies used a variety of measures to determine effective atrial contraction. These methods are summarised in Appendix E.1. While transthoracic Doppler echocardiography was the most common method used to determine atrial contraction, there were a wide variety of cut-off points used to conclude that contraction was effective (see Appendix x). These included: presence of an A-wave; peak velocity ≥ 10 cm/s or > 25 cm/s; A/E ratio of > 0.3 or ≥ 0.5; transtricuspid A wave ≥ 15 cm/s and transmitral A wave of ≥ 25 cm/s; transmitral flow > 40 cm/s; or an atrial filling fraction of > 30%. There are no current guidelines to state what does constitute effective atrial contraction. The range of cut-off points used for atrial contraction to be considered effective mean it is possible in some studies patients were considered to have effective atrial contraction, when in fact they did not. In fact, when results were reported for different 166 measures of atrial contraction in this review, the results did not always agree. For example, in Ishii et al. (2001) there was no significant difference in left atrial contraction between CA versus Maze-III using presence of the transmitral A wave, but the left atrial A/E ratio was significantly greater in patients after CA versus Maze-III surgery. In the 2003 ACC/AHA/ASE Guideline update for the clinical application of echocardiography, the use of echocardiography for the postoperative evaluation of atrial function in patients following the Maze procedure was given a Class IIb category, meaning the usefulness/efficacy is not well established, by evidence or opinion (Cheitlin et al. 2003). More studies are necessary to provide guidelines for the echocardiographic measurement of atrial contraction. Cox et al. (1996) has suggested atrial contraction should be evaluated by a battery of tests including: direct visualisation, transoesophageal or transthoracic echocardiography; atrioventricular pacing versus ventricular pacing at the same paced rates; and magnetic resonance imaging. He suggests each of these tests may give a false negative answer (miss effective contraction), but not a false positive result (conclude contraction was effective when it was not). 6.3.5 Antiarrhythmic medication A number of studies routinely used antiarrhythmic medication after surgery, whether or not the patient was in SR or AF. The studies that reported whether or not antiarrhythmic medication was routinely used after surgery are listed in Appendix E.2. The most commonly used drug was amiodarone, with digoxin, disopyramide, sotalol, procainamide, and metoprolol also used. Some studies routinely used antiarrhythmic medication in all patients to six months postoperatively (Sueda et al. 1997; Khargi et al. 2001; Chiappini et al. 2004; Deneke et al. 2002a; Benussi et al. 2002; Ruchat et al. 2002; Chiappini et al. 2003). The routine use of antiarrhythmic medication may have been a confounding factor in assessing the number of patients who were in SR, as very few studies reported the number of patients in SR who were also taking medication. Ideally, intraoperative ablation should enable patients to remain in SR without the requirement for any other therapy. However, if patients were refractory to these drugs prior to surgery, the fact that antiarrhythmic medication is effective after intraoperative ablation may be an advantage. 6.4 Safety 6.4.1 Anticoagulant therapy and risk of stroke Patients with AF are at a high risk of stroke. Anticoagulant medication was routinely used postoperatively to prevent stroke and other thromboembolism in patients while they were still likely to suffer cardiac arrhythmias. However, there were varying indications used by the studies to stop anticoagulant treatment in patients. The studies which reported routine anticoagulant use and/or the prerequisites used for halting anticoagulant therapy, are listed in Appendix E.3. Three months seemed to be the most common period for routine anticoagulant use. The most common prerequisite for stopping anticoagulants was for patients to have SR, evidence of atrial contraction, and no mechanical valves (Gaita et al. 2000; Chen et al. 2001; 167 Mantovan et al. 2003; Hornero et al. 2002; Sos et al. 2002; Benussi et al. 2002; Müller et al. 2002; Ruchat et al. 2002; Starck et al. 2003; Chiappini et al. 2003). However, some studies only stated the time that anticoagulants were routinely used after surgery and not the precondition for them to be stopped; and others ceased anticoagulation as long as patients were in stable SR (Mohr et al. 2002; Spitzer and Knaut et al. 2002; Knaut et al. 2002). Larger studies would be needed to provide evidence for how long after intraoperative ablation a patient should be routinely anticoagulated, and whether they need to have both SR and atrial contraction for medication to be stopped. While AF is recognised as increasing the risk of stroke, a recent study has suggested that patients in atrial flutter may have the same risk of stroke as those with AF (Lelorier et al. 2004), so these patients may need aggressive anticoagulant therapy as well. The effect of intraoperative ablation on the risk of stroke cannot be evaluated from the evidence in this review. In one study there may have been a reduction in the incidence of stroke after biatrial CA versus CA (Handa et al. 1999), but the p value was not given. It has been reported the risk of stroke after the Maze procedure is reduced, as in a group of 306 patients, with a significant number having a stroke (n=40) or transient ischaemic attack (n=18) before surgery, there have been only two perioperative strokes (Cox, Ad and Palazzo 1999). In 265 patients followed up to 11.5 years after surgery, there has been only one late minor stroke. Patients in this cohort underwent the Maze-I, -II and –III procedures, and a proportion of them were operated on using minimally invasive surgery. Results from intraoperative ablation will need to be available for larger groups of patients, and for follow-up periods of years rather than months, to be able to assess the effects on stroke incidence. 6.4.2 Oesophageal perforation Oesophageal perforation is a serious potential complication of intraoperative ablation. The oesophagus lies immediately beneath sites of left atrial ablation, thus is vulnerable to collateral damage. It has been proposed that oesophageal injury occurs as the result of a combination of a number of factors including: type and handling of ablation device, ablation time, lesion pattern, and surgical access (Khargi et al. 2004). All of the cases of oesophageal perforation which were reported followed unipolar RFA, without irrigation. Three fatal oesophageal perforations were found in published reports (Mantovan et al. 2003; Starck et al. 2003; Sonmez et al. 2003; see Appendix D.12), although it is possible that other cases have occurred which have not been published. If unipolar RFA is used, particularly in non-irrigated probes, surgeons must be conscious of the risk of oesophageal damage. 6.4.3 Circumflex artery injury Injury to the circumflex artery caused by intraoperative ablation was reported in two of the included studies. This injury is related to the connecting lesion from the mitral annulus to the pulmonary veins (Kress 2002). In Izumoto et al. (2000) one patient had a circumflex artery stenosis at the site of CA, and required redo surgery with CABG. Le Tourneau et al. (2003) reported a patient with circumflex artery stenosis after left atrial RFA, but no further details were given. There has also been a case report, describing significant narrowing of the right and circumflex coronary arteries in cryoablated areas following Maze-III surgery (Berreklouw et al. 1999; see Appendix D.12). 168 Patients having intraoperative ablation to treat AF usually have concurrent heart disease, including coronary artery disease. These patients would have a high background risk of a coronary blockage, and therefore it is possible that damage to the circumflex arteries could be missed postoperatively. Surgeons should be aware of the coronary arteries during the ablation. The risk of collateral circumflex artery injury may be reduced by giving cardioplegia during heat application to the area, and avoiding the lesion altogether if the circumflex artery appears to be too superficial to the endocardium (Kress 2002). 6.4.4 Length of CPB In this review intraoperative ablation resulted in significantly longer CPB times compared to CS alone. Although there were no significant results indicating that increased CPB time was a problem in the patients in these studies, increased CPB times have been associated with higher complication rates. Sadeghi et al. (2002) found increased bypass times were a significant predictor of operative mortality in patients having primary coronary artery bypass surgery; and using sensitive kidney-specific proteins, Boldt et al. (2003) demonstrated CPB times of more than 90 minutes were associated with more pronounced kidney damage than times less than 70 minutes. Deep sternal wound infections in CABG patients are also related to longer CPB times (Wang and Chang 2000). The safety outcomes were designed to include complications related to longer bypass times (eg. wound infections, renal failure), but many of the reports did not state if these complications did or did not occur. Future studies with more uniform reporting of these outcomes will be needed to address whether the longer CPB times are associated with any cost to the patient. 6.5 Possible indications and contraindications for intraoperative ablation There were 19 studies in which significant risk factors for recurrence of AF were reported (see Appendix E.4). Methods varied from uni- and multi-variate analysis to t-test or X2 test. The conclusions made depended on the study profile, for example a study could not find a significant influence of rheumatic heart disease on recurrence of AF if none of the patients had rheumatic heart disease. The factors found to significantly increase the risk of recurrent AF following the surgery in the order of the frequency of reports were: duration of preoperative AF (n=10), left atrial dimensions (n=9), rheumatic heart disease (n=3), age (n=3), cardiothoracic ratio (n=2), fwave (n=2), right atrial dimensions (n=2), presence of AF at hospital discharge (n=2), previous mitral valve surgery (n=1), tricuspid regurgitation (n=1), preoperative left ventricular ejection fraction (n=1), sex (male/female, n=1), coronary artery disease (n=1), ablation pattern (n=1), replacement or repair valve surgery (n=1) and chronic versus paroxysmal AF (n=1). Therefore, the most important patient characteristics influencing the success of intraoperative ablation appeared to be the duration the patients had AF prior to surgery, and the size of the left atrium. 169 6.6 Uptake of intraoperative ablation for AF The Maze-III procedure has given excellent long-term results in patients with AF. At the Cleveland Clinic there has been an increase in the number of patients having the Maze-III, from about 20 patients each year during the 1990s, to more than 300 patients during 2002 (McCarthy and Gillinov 2003). This represented over 9% of all patients undergoing cardiac surgery at the Cleveland Clinic during 2002. With the advent of new intraoperative ablation devices, the numbers of patients having surgical treatment of AF is likely to escalate, as the procedure is less technically demanding of the surgeon, and also less invasive. 6.7 Considerations for further research While there is evidence that intraoperative ablation is more effective than cardiac surgery alone in converting patients to normal SR, further studies will be necessary to conclude which lesion sets and energy sources provide the highest levels of safety and efficacy. The patient group will need to be carefully considered when designing these trials, as the efficacy could be influenced by factors including left atrial size, duration of preoperative AF, and co-existing heart disease. Kress has speculated that comparing the efficacy of lesion patterns will require too many patients in each treatment in order to achieve statistical power, as differences are not likely to be very large (Kress 2002). However, if standard lesion sets are used in a sufficient number of studies, the use of meta-analysis may still allow statistically significant conclusions to be made. Outcomes measures which were not well assessed in the included studies include: risk of stroke and other thromboembolisms; quality of life; exercise tolerance; and cost effectiveness of the procedure. Future studies are warranted to specifically address these secondary outcomes. In addition, there were no comparisons found between intraoperative ablation and medical management of AF. There are many unanswered questions in relation to AF, and a better understanding of the mechanisms involved in the initiation and maintenance of this arrhythmia will aid the development of the surgical treatment of AF. Other technological advances will also be important in this progress, for example improvements in intraoperative mapping techniques would allow the site or sites of origin of the AF to be identified, allowing changes to standard lesion patterns in patients who do not conform to the usual foci of origin. These could also be used to confirm conduction block after lesion sets are placed. Finally, there are already a number of published reports using minimally invasive techniques of surgical ablation in the treatment of AF (Ad et al. 2002; Doll et al. 2003; Maessen et al. 2002; Melo et al. 2000; Walther et al. 2000). These techniques involve a less invasive approach compared to median sternotomy, and may be performed off cardiopulmonary bypass. Therefore, a major operation could be avoided in patients who did not require another procedure. Minimally invasive ablation will need to be thoroughly assessed for safety and efficacy, but it is likely it will dramatically increase the number of patients who will benefit from the surgical cure of AF in the future. 170 7.0 CONCLUSIONS The primary objective of this review was to assess the safety and efficacy of intraoperative ablation for the treatment of AF. The conclusions were limited by the many variations of energy sources and ablation patterns used. More studies were available using CA and RFA, less for MWA, and only one abstract reported the use of laser ablation. The primary efficacy outcome was conversion to SR: which showed an increase with CA, RFA and MWA versus CS alone. No consistent differences in efficacy were present between CA versus Maze-III, with insufficient evidence for this comparison using the other energy sources. Addition of intraoperative ablation increased CPB and cross clamping times versus CS alone. Other efficacy outcomes, including pacemaker requirements and atrial flutter, were not consistently altered by intraoperative ablation. Left atrial versus biatrial CA or RFA appeared to decrease cardiopulmonary bypass and cross clamping times, without influencing efficacy. However, one study did demonstrate a significant increase in atrial flutter with left atrial versus biatrial RFA ablation. The secondary outcome of atrial function was difficult to interpret due to the different criteria used for effective atrial contraction. This is an important area for future investigation, as the decision to stop anticoagulant therapy was often based on the presence of contraction of the atrium. There were no consistent differences in mortality when intraoperative ablation was compared to CS and Maze-III. A major complication of the Maze-III, postoperative bleeding, appeared similar between CA and RFA versus CS. Other safety outcomes which may have been influenced by longer CPB and cross clamping times, such as wound infection and low cardiac output, were also not consistently altered. The length of follow-up was generally insufficient to make any conclusions about whether intraoperative ablation altered the risk of stroke. The main complications reported were postoperative oesophageal perforation and circumflex artery stenosis, both of which may be lethal. It would appear patients are at particular risk of oesophageal perforation after unipolar non-irrigated RFA, but further studies are needed with thorough monitoring of patients for these events. Atrial fibrillation is the most common cardiac arrhythmia. 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Heart Surgery Forum 2003;6(5):403-408. 179 APPENDICES APPENDIX A – HIERARCHY OF EVIDENCE Table 1: Designation of levels of evidence Level of Evidence Study Design I Evidence obtained from a systematic review of all relevant randomised controlled trials. II Evidence obtained from at least one properly designed randomised controlled trial. III-1 Evidence obtained from well-designed pseudo-randomised controlled trials (alternate allocation or some other method). III-2 Evidence obtained from comparative studies (including systematic reviews of such studies) with concurrent controls and allocation not randomised, cohort studies, case-control studies, or interrupted timeseries with a control group. III-3 Evidence obtained from comparative studies with historical control, two or more single arm studies, or interrupted time series without a parallel control group. IV Evidence obtained from case-series, either post-test or pre-test/posttest. APPENDIX B - EXCLUSIONS The following papers were excluded from the methodological assessment as outlined in section 3.3 of the review. Intraoperative Ablation Exclusions: Abe T, Kukawi K, Mawatari T, Sakata J, Komatsu K, Urita R, and Komatsu S. Maze operation for chronic atrial fibrillation with valvular heart diseases. [Japanese]. Kyobu Geka - Japanese Journal of Thoracic Surgery. 1996;49(9):709-713. Reason for exclusion: No English translation available (Japanese). Ad N, Suyderhoud JP, Kim YD, Makary MA, DeGroot KW, Lue HC, Pirovic EA, Duvall WZ, and Cox JL. Benefits of prophylactic continuous infusion of furosemide after the maze procedure for atrial fibrillation. Journal of Thoracic & Cardiovascular Surgery. 2002;123(2):232-236. Reason for exclusion: 30/75 operated on using minimally invasive approach. Adragaõ P, Queirose M, Aguiar C, Teles R, Cavaco D, Neves J, Abecasis M, Ribeiras R, Bonhorst D, and Seabra-Gomes R. Evaluation of bilateral pulmonary vein isolation for the treatment of atrial fibrillation: Value of postoperative electrophysiological study. [Portuguese, English]. Revista Portuguesa de Cardiologia. 2002;21(11):1281-1293. Reason for exclusion: 2/20 not by median sternotomy. Akpinar B, Guden M, Sagbas E, Sanisoglu I, Ozbek U, Caynak B, and Bayindir O. Combined radiofrequency modified maze and mitral valve procedure through a port access approach: early and mid-term results. European Journal of Cardio-Thoracic Surgery. 2003;24(2):223-230. Reason for exclusion: Port access approach. Bando K, Kobayashi J, Hirata M, Satoh T, Niwaya K, Tagusari O, Nakatani S, Yagihara T, Kitamura S, and Akins C. Early and late stroke after mitral valve replacement with a mechanical prosthesis: Risk factor analysis of a 24-year experience. Journal of Thoracic & Cardiovascular Surgery. 2003;126(2):358-364. Reason for exclusion: Mixed surgical procedures. Bando K, Kobayashi J, Kosakai Y, Hirata M, Sasako Y, Nakatani S, Yagihara T, and Kitamura S. Impact of Cox maze procedure on outcome in patients with atrial fibrillation and mitral valve disease. Journal of Thoracic & Cardiovascular Surgery. 2002;124(3):575-583. Reason for exclusion: Mixed surgical procedures. Betts TR, Roberts PR, Allen SA, Salmon AP, Keeton BR, Haw MP, and Morgan JM. Electrophysiological mapping and ablation of intra-atrial reentry tachycardia after fontan surgery with the use of a noncontact mapping system. Circulation. 2000;102(4):419-425. Reason for exclusion: Patients not in atrial fibrillation. Cai Z, Sun G, and Du R. Treatment of atrial fibrillation using maze procedure by radiofrequency ablation. [Chinese]. Chung-Hua Wai Ko Tsa Chih [Chinese Journal of Surgery]. 1997;35(12):719-721. Reason for exclusion: No English translation available (Chinese). Chiappini B, Martin-Suarez S, LoForte A, Di Bartolomeo R, and Marinelli G. Surgery for atrial fibrillation using radiofrequency catheter ablation. Journal of Thoracic & Cardiovascular Surgery. 2003;126(6):1788-1791. Reason for exclusion: Same patients reported in a comparative study. Damiano RJ Jr, Gaynor SL, Bailey M, Prasad S, Cox JL, Boineau JP, and Schuessler RP. The long-term outcome of patients with coronary disease and atrial fibrillation undergoing the Cox maze procedure. Journal of Thoracic & Cardiovascular Surgery. 2003;126(6):2016-2021. Reason for exclusion: Mixed surgical procedures. Deal BJ, Mavroudis C, Backer CL, Buck SH, and Johnsrude C. Comparison of anatomic isthmus block with the modified right atrial maze procedure for late atrial tachycardia in Fontan patients. Circulation. 2002;106(5):575579. 181 Reason for exclusion: Patients with atrial tachycardia, not atrial fibrillation. Doll N, Kiaii BB, Fabricius AM, Bucerius J, Kornherr P, Krakor R, Gummert JF, Walther T, and Mohr FW. Intraoperative left atrial ablation (for atrial fibrillation) using a new argon cryocatheter: early clinical experience. Annals of Thoracic Surgery. 2003;76(5):1711-1715. Reason for exclusion: Median sternotomy only in 8/28 patients. Fukushima K, Emori T, Shimizu W, Kurita T, Aihara N, Kosakai Y, Isobe K, Shimomura K, Kawashima Y, and Ohe T. Delayed improvement of autonomic nervous abnormality after the Maze procedure: Time and frequency domain analysis of heart rate variability using 24 hour Holter monitoring. Heart (British Cardiac Society). 1997;78(5):499-504. Reason for exclusion: Outcomes not relevant. Harada A, Konishi T, Fukata M, Higuchi K, Sugimoto T, Sasaki K, McKinnie JJ, and Ferguson TB, Jr. Intraoperative map guided operation for atrial fibrillation due to mitral valve disease. Annals of Thoracic Surgery. 2000;69(2):446-451. Reason for exclusion: Mixed surgical procedures, data not separated. Hattori R, Kosakai Y, Yamamoto F, Sasako Y, Kobayashi J, and Kitamura S. Maze procedure for a lone atrial fibrillation. [Japanese]. Kyobu Geka - Japanese Journal of Thoracic Surgery. 1999;52(10):803-808. Reason for exclusion: Mixed surgical procedures. Hirata M. Effect of maze procedure in patients with atrial fibrillation undergoing valve replacement. Journal of Heart Valve Disease. 2002;11(5):719-725. Reason for exclusion: Mixed surgical procedures, data not separated. Isobe F and Kawashima Y. The outcome and indications of the Cox maze III procedure for chronic atrial fibrillation with mitral valve disease. Journal of Thoracic & Cardiovascular Surgery.1998;116(2):220-227. Reason for exclusion: Mixed surgical procedures, data not separated. Itoh T, Okamoto H, Nimi T, Morita S, Sawazaki M, Ogawa Y, Asakura T, Yasuura K, Abe T, Murase M, and Cox JL. Left atrial function after Cox's maze operation concomitant with mitral valve operation. Annals of Thoracic Surgery.1995;60(2):354-360. Reason for exclusion: Mixed surgical procedures, surgical technique not clear. Izumoto H, Kawazoe K, Kitahara H, Nasu M, Sasaki T, Kamata J, Tsuji I, and Yagi Y. Can the maze procedure be combined safely with mitral valve repair? Journal of Heart Valve Disease.1997;6(2):166-170. Reason for exclusion: Comparative study. Comparator patient group underwent mitral valve surgery alone but did not have atrial fibrillation. Kamata J, Nakai K, Chiba N, Hosokawa S, Sato Y, Nasu M, Sasaki T, Kitahara H, Izumoto H, Yagi Y, Itoh C, Hiramori K, and Kawazoe K. Electrocardiographic nature of restored sinus rhythm after Cox maze procedure in patients with chronic atrial fibrillation who also had other cardiac surgery. Heart (British Cardiac Society). 1997; 77(1):50-55. Reason for exclusion: Surgical technique not clear. Kawaguchi AT, Kosakai Y, Sasako Y, Eishi K, Nakano K, and Kawashima Y. Risks and benefits of combined maze procedure for atrial fibrillation associated with organic heart disease. Journal of the American College of Cardiology.1996;28(4):985-990. Reason for exclusion: Comparative study, mixed surgical procedures. Kawaguchi AT, Kosakai Y, Isobe F, Sasako Y, Eishi K, Nakano K, Takahashi N, and Kawashima Y. Factors affecting rhythm after the maze procedure for atrial fibrillation. Circulation. 1996;94(9 II):II139-II142. Reason for exclusion: Mixed surgical procedures. Kawahira Y, Uemura H, Yagihara T, Yoshikawa Y, and Kitamura S. Renewal of the Fontan circulation with concomitant surgical intervention for atrial arrhythmia. Annals of Thoracic Surgery. 2001;71(3):919-921. Reason for exclusion: n=4, patients had either atrial fibrillation or atrial flutter. 182 Kobayashi J, Kosakai Y, Isobe F, Sasako Y, Nakano K, Eishi K, and Kawashima Y. Rationale of the Cox maze procedure for atrial fibrillation during redo mitral valve operations. Journal of Thoracic & Cardiovascular Surgery. 1996;112(5):1216-1221. Reason for exclusion: Comparative study, mixed surgical procedures. Kobayashi J, Kosakai Y, Nakano K, Sasako Y, Eishi K, and Yamamoto F. Improved success rate of the maze procedure in mitral valve disease by new criteria for patients' selection. European Journal of Cardio-Thoracic Surgery. 1998;13(3):247-252. Reason for exclusion: Mixed surgical procedures. Kobayashi J, Sasako Y, Bando K, Minatoya K, Niwaya K, and Kitamura S. Ten-year experience of chordal replacement with expanded polytetrafluoroethylene in mitral valve repair. Circulation. 2000;102(19 III):III30III34. Reason for exclusion: Maze surgery part of a series, results only for whole group. Kobayashi J, Sasako Y, Bando K, Niwaya K, Tagusari O, Nakajima H, Ishida M, and Kitamura S. Eight-year experience of combined valve repair for mitral regurgitation and maze procedure. Journal of Heart Valve Disease. 2002;11(2):165-171. Reason for exclusion: Mixed surgical procedures (73/85 patients had Kosakai maze, and 12/85 patients had Maze III). Kobayashi J, Yamamoto F, Nakano K, Sasako Y, Kitamura S, and Kosakai Y. Maze procedure for atrial fibrillation associated with atrial septal defect. Circulation. 1998;98(19 II):II399-II402. Reason for exclusion: Mixed surgical procedures. Kosakai Y, Isobe F, Kawaguchi A, Sasako Y, Eishi K, Nakano S, Kito Y, and Kawashima Y. Therapeutic experience with 90 cases undergoing maze operation. [Japanese]. Rinsho Kyobu Geka. 1994;14(5):440-441. Reason for exclusion: No English translation available (Japanese). Paper may be descriptive only. Lee JW, Park NH, Choo SJ, Jo MS, Song H, Song MG, and Aklog L. Surgical outcome of the maze procedure for atrial fibrillation in mitral valve disease: Rheumatic versus degenerative. Annals of Thoracic Surgery. 2003;75(1):57-61. Reason for exclusion: Mixed surgical procedures (Maze-III and modified Maze). Lehto M, Parikka H, Simpanen J, Virolainen J, Werkkala K, and Toivonen L. [Treatment of atrial fibrillation with the means of linear ablation during cardiac surgery]. [Finnish]. Duodecim. 2003;119(9):872-877. Reason for exclusion: No English translation available (Finnish). Li L, Wang E, and Wang Z. Evaluation of the cardiac performance after maze procedure in chronic atrial fibrillation. [Chinese]. Chinese Journal of Cardiology 1996;24(6):416-420. Reason for exclusion: No English translation available (Chinese). Li L, Wang Z, and Zhang B. Electrophysiological evaluation of maze procedure in chronic atrial fibrillation. [Chinese]. Chinese Journal of Cardiology 1996;24(1):24-27. Reason for exclusion: No English translation available (Chinese). Lozano IG, Basterrechea JU, Montes JM, Page JCG, Fernandez MS, Bautista A, Gibanel MAC, Gonzalez MG, and Andrade MdA. Tecnica de MAZE para el tratamiento de la fibrilacion auricular: experiencia inicial. Revista Espanola de Cadiologia. 1998;51(11):901-907. Reason for exclusion: No English translation available (Spanish). Maessen JG, Nijs JF. MA Smeets JL, Vainer J, and Mochtar B. Beating-heart surgical treatment of atrial fibrillation with microwave ablation. Annals of Thoracic Surgery. 2002;74(4):S1307-S1311. Reason for exclusion: 6/24 surgery off pump. Mavroudis C, Backer CL, Deal BJ, and Johnsrude CL. Fontan conversion to cavopulmonary connection and arrhythmia circuit cryoablation. Journal of Thoracic & Cardiovascular Surgery. 1998;115(3):547-556. Reason for exclusion: Patients with atrial tachycardia, not specified as atrial fibrillation. 183 Mavroudis C, Backer CL, Deal BJ, Johnsrude C, Strasburger J, Bradley SM, and Fontan F. Total cavopulmonary conversion and maze procedure for patients with failure of the Fontan operation. Journal of Thoracic & Cardiovascular Surgery. 2001;122(5):863-871. Reason for exclusion: Some patients < 18 yrs. Melo J, Adragao P, Neves J, Ferreira MM, Pinto MM, Rebocho MJ, Parreira L, and Ramos T. Surgery for atrial fibrillation using radiofrequency catheter ablation: Assessment of results at one year. European Journal of Cardio-Thoracic Surgery. 1999;15(6):851-855. Reason for exclusion: Not all median sternotomy. Melo J, Adragao PR, Neves J, Ferreira M, Rebocho M, Teles R, and Morgado F. Electrosurgical treatment of atrial fibrillation with a new intraoperative radiofrequency ablation catheter. Thoracic & Cardiovascular Surgeon. 1999;47(3):S370-S372. Reason for exclusion: Not all median sternotomy. Melo J, Adragao P, Neves J, Ferreira M, Timoteo A, Santiago T, Ribeiras R, and Canada M. Endocardial and epicardial radiofrequency ablation in the treatment of atrial fibrillation with a new intra-operative device. European Journal of Cardio-Thoracic Surgery. 2000;18(2):182-186. Reason for exclusion: Not all median sternotomy. Mukaida M, Yagi Y, Shiina S, Sasaki T, Abe K, Komoda K, Kawazoe K, Kamada J, Chiba M, and Musha T. Clinical evaluation of 35 cases of chronic atrial fibrillation undergoing maze operation. [Japanese]. Rinsho Kyobu Geka. 1994;14(5):438-439. Reason for exclusion: No English translation available (Japanese). Muraki S, Tsukamoto M, Kobayashi T, Fukada J, Morishita K, and Abe T. Preserved atrial response to dobutamine stress after the modified maze procedure for chronic atrial fibrillation: Echocardiographic assessment of atrial function. Journal of Cardiac Surgery. 2002;17(2):148-154. Reason for exclusion: Outcome not relevant. Nakamura M, Niinuma H, Chiba M, Ueshima K, Arakawa N, Yagi Y, Kawazoe K, and Hiramori K. Effect of the maze procedure for atrial fibrillation on atrial and brain natriuretic peptide. American Journal of Cardiology. 1997;79(7):966-970. Reason for exclusion: Very minor modification of Maze-III. Nakano K, Eishi K, Kobayashi J, Sasako Y, and Kosakai Y. Surgical treatment for prolapse of the anterior mitral leaflet. Journal of Heart Valve Disease. 1997;6(5):470-474. Reason for exclusion: Subgroup with 19/39 having Maze, but only presence of sinus rhythm reported. Nakano K, Eishi K, Sasako Y, Kobayashi J, and Kosakai Y. Extensive indication of mitral valvuloplasty for nonrheumatic mitral regurgitation and postoperative QOL. [Japanese]. Nippon Kyobu Geka Gakkai Zasshi - Journal of the Japanese Association for Thoracic Surgery. 1997;45(8):1090-1095. Reason for exclusion: Patients with Maze surgery part of a larger group. Ngodngamthaweesuk M, Subhannachart W, Supakul V, Boonkasem S, Attanawanich S, and Masnaragorn P. Modified Cox maze procedure for atrial fibrillation with mitral valve disease. Journal of the Medical Association of Thailand. 2002;85(11):1182-1188. Reason for exclusion: Modifications to Maze-III are incisions, not ablations. Nitta T, Imura H, Bessho R, Hosaka H, Yamauchi S, and Tanaka S. Wavelength and conduction inhomogeneity in each atrium in patients with isolated mitral valve disease and atrial fibrillation. Journal of Cardiovascular Electrophysiology. 1999;10(4):521-528. Reason for exclusion: Outcomes not relevant. Setty S. P, Finucane K, Skinner JR, and Kerr AR. Extracardiac conduit with a limited maze procedure for the failing Fontan with atrial tachycardias. Annals of Thoracic Surgery. 2002;74(6):1992-1997. Reason for exclusion: n=3 patients >18 years old. Complex surgery and mixed patients. 184 Sueda T, Nagata H, Shikata H, Orihashi K, Morita S, Sueshiro M, Okada K, and Matsuura Y. Simple left atrial procedure for chronic atrial fibrillation associated with mitral valve disease. Annals of Thoracic Surgery. 1996;62(6):1796-1800. Reason for exclusion: Likely to be the same group as in Sueda et al. 1997 comparative study (included). Sueda T, Shikata H, Orihashi K, Morita S, Mitsui N, Okada K, Sueshiro M, Takeda K, Nagata H, and Matsuura Y. Efficacy of left atrial only procedure for the treatment of chronic atrial fibrillation associated with mitral valve disease. [Japanese]. Nippon Kyobu Geka Gakkai Zasshi - Journal of the Japanese Association for Thoracic Surgery. 1996;44(6):785-789. Reason for exclusion: Japanese paper. Likely to be the same group as in Sueda et al. 1997 comparative study (included). Szalay ZA, Skwara W, Pitschner HF, Faude I, Klovekorn WP, and Bauer EP. Midterm results after the MiniMaze procedure. European Journal of Cardio-Thoracic Surgery. 1999;16(3):306-311. Reason for exclusion: No ablation used. Tamai J, Kosakai Y, Yoshioka T, Ohnishi E, Takaki H, Okano Y, and Kawashima Y. Delayed improvement in exercise capacity with restoration of sinoatrial node response in patients after combined treatment with surgical repair for organic heart disease and the Maze procedure for atrial fibrillation. Circulation 1995;91(9):2392-2399. Reason for exclusion: Mixed surgical procedures. Tanaka H, Narisawa T, Mori T, Masuda M, Suzuki T, and Takaba T. Pulmonary vein isolation for chronic atrial fibrillation associated with mitral valve disease: the midterm results. Annals of Thoracic & Cardiovascular Surgery. 2002;8(2):88-91. Reason for exclusion: Four cases with surgical incisions and nine cases with cryoablation not reported separately. Tang H, Huang H, Liu S, Xiao X, Tian Z, Shi Y, Duan W, and Xu K. Evaluation of modified maze procedure by Doppler tissue imager. [Chinese]. Hua-Hsi i Ko Ta Hsueh Hsueh Pao [Journal of West China University of Medical Sciences]. 2000;31(1):107-109. Reason for exclusion: No English translation available (Chinese). Tuinenburg AE, Van Gelder IC, Tieleman RG, Grandjean JG, Huet RC, van der Maaten JM, Pieper EG, De Kam PJ, Ebels T, and Crijns HJ. Mini-maze suffices as adjunct to mitral valve surgery in patients with preoperative atrial fibrillation. Journal of Cardiovascular Electrophysiology. 2000;11(9):960-967. Reason for exclusion: Surgery like a limited Cox-Maze, cryoablation in the same places as Cox Maze. Walther T, Falk V, Walther C, Krauss B, Hindricks G, Kottkamp H, Kostelka M, Diegeler A, Autschbach R, and Mohr FW. Combined stentless mitral valve implantation and radiofrequency ablation. Annals of Thoracic Surgery. 2000;70(3):1080-1082. Reason for exclusion: Mixed surgical approach (median sternotomy or minimally invasive). Wang Z, Zhang B, and Zhu J. Maze procedure for chronic atrial fibrillation associated with mitral valve disease. [Chinese]. Chung-Hua Wai Ko Tsa Chih [Chinese Journal of Surgery]. 1997;35(11):670-674. Reason for exclusion: Surgical technique unclear. No English translation available (Chinese). Watanabe M, Murakami M, Furukawa H, Nakahara H, Tanaka H, and Sunamori M. Decreased plasma brain natriuretic peptide levels after a successful maze procedure. Journal of Heart Valve Disease. 2003;12(3):287291. Reason for exclusion: Mixed surgical procedures (modified Maze-III or left atrial Maze procedure). Weinstein S, Cua C, Chan D, and Davis JT. Outcome of symptomatic patients undergoing extracardiac Fontan conversion and cryoablation. Journal of Thoracic & Cardiovascular Surgery. 2003;126(2):529-536. Reason for exclusion: Two patients only. Wellens F, Casselman F, Geelen P, Brugada P, Van Praet F, De Geest R, Degrieck I, and Vanermen H. Combined atrial fibrillation and mitral valve surgery using radiofrequency technology. Seminars in Thoracic & Cardiovascular Surgery 2002;14(3):219-225. Reason for exclusion: Not all median sternotomy. 185 Williams MR, Argenziano M, and Oz MC. Microwave ablation for surgical treatment of atrial fibrillation. Seminars in Thoracic & Cardiovascular Surgery. 2002;14(3):232-237. Reason for exclusion: Limited outcome data. Yoshihara F, Nishikimi T, Kosakai Y, Isobe F, Matsuoka H, Takishita S, Kawashima Y, Saito Y, Matsuo H, and Kangawa K. Atrial natriuretic peptide secretion and body fluid balance after bilateral atrial appendectomy by the maze procedure. Journal of Thoracic & Cardiovascular Surgery. 1998;116(2):213-219. Reason for exclusion: Outcomes not relevant. Yoshihara F, Nishikimi T, Sasako Y, Hino J, Kobayashi J, Minatoya K, Bando K, Kosakai Y, Horio T, Suga S, Kawano Y, Matsuoka H, Yutani C, Matsuo H, Kitamura S, Ohe T, and Kangawa K. Plasma atrial natriuretic peptide concentration inversely correlates with left atrial collagen volume fraction in patients with atrial fibrillation: plasma ANP as a possible biochemical marker to predict the outcome of the maze procedure. Journal of the American College of Cardiology. 2002;39(2):288-294. Reason for exclusion: Outcomes not relevant. Maze-III Excluded Studies: Ad N and Cox JL. Combined mitral valve surgery and the Maze III procedure. Seminars in Thoracic & Cardiovascular Surgery. 2002;14(3):206-209. Reason for exclusion: Mixed surgical procedures (Maze III, cryosurgical Maze III and minimally invasive approach). Cox JL, Ad N, and Palazzo T. Impact of the maze procedure on the stroke rate in patients with atrial fibrillation. Journal of Thoracic & Cardiovascular Surgery. 1999;118(5):833-840. Reason for exclusion: Mixed surgical procedures (Maze I, II and III) and minimally invasive approach. Cox JL, Ad N, Palazzo T, Fitzpatrick S, Suyderhoud JP, DeGroot KW, Pirovic EA, Lou HC, Duvall WZ, and Kim YD. Current status of the Maze procedure for the treatment of atrial fibrillation. Seminars in Thoracic & Cardiovascular Surgery. 2000;12(1):15-19. Reason for exclusion: Mixed surgical procedures (Maze I, II and III with Maze III using different techniques). Cox JL, Ad N, Palazzo T, Fitzpatrick S, Suyderhoud JP, DeGroot KW, Pirovic EA, Lou HC, Duvall WZ, and Kim YD. The Maze-III procedure combined with valve surgery. Seminars in Thoracic & Cardiovascular Surgery. 2000;12(1):53-55. Reason for exclusion: All Maze III, but would have used different techniques. Cox JL, Boineau JP, Schuessler RB, Kater KM, and Lappas DG. Five-year experience with the maze procedure for atrial fibrillation. Annals of Thoracic Surgery. 1993;56(4):814-823. Reason for exclusion: Mixed surgical procedures (Maze I, II and III). Cunha B, Kalil RA, Albrecht AS, Lima GG, and Kruse JC. Evaluation of the heart rate and arrhythmias following the maze procedure for chronic atrial fibrillation. Arquivos Brasileiros de Cardiologia. 1999;72(5):607-614. Reason for exclusion: No cryoablation used. Deal BJ, Mavroudis C, and Backer CL. Beyond Fontan conversion: Surgical therapy of arrhythmias including patients with associated complex congenital heart disease. Annals of Thoracic Surgery. 2003;76(2):542-553. Reason for exclusion: n=2, case reports (Maze III). Doty DB, Dilip KA, and Millar RC. Mitral valve replacement with homograft and maze III procedure. Annals of Thoracic Surgery. 2000;69(3):739-742. Reason for exclusion: n=3, case reports (Maze III). Feinberg MS, Waggoner AD, Kater KM, Cox JL, Lindsay BD, and Perez JE. Restoration of atrial function after the maze procedure for patients with atrial fibrillation: Assessment by Doppler echocardiography. Circulation. 1994;90(5 II):II285-II292. 186 Reason for exclusion: Surgery likely to be Maze I. Feinberg MS, Waggoner AD, Kater KM, Cox JL, and Perez JE. Echocardiographic automatic boundary detection to measure left atrial function after the maze procedure. Journal of the American Society of Echocardiography. 1995;8(2):139-148. Reason for exclusion: Surgery likely to be Maze I. Gregori Jr F, Cordeiro CO, Couto WJ, da Silva SS, de Aquino WK, Nechar Jr A, McCarthy PM, and Scalia GM. Cox maze operation without cryoablation for the treatment of chronic atrial fibrillation. Annals of Thoracic Surgery. 1995;60(2):361-364. Reason for exclusion: No cryoablation used. Jatene MB, Marcial MB, Tarasoutchi F, Cardoso RA, Pomerantzeff P, and Jatene, AD. Influence of the maze procedure on the treatment of rheumatic atrial fibrillation - Evaluation of rhythm control and clinical outcome in a comparative study. European Journal of Cardio-Thoracic Surgery. 2000;17(2):117-124. Reason for exclusion: Mixed surgical procedures (Maze I and Maze III). Kalil RA, Albrecht A, Lima GG, Vasconcellos D, Cunha B, Hatem D, Moreno P, Abrahao R, Sant'Anna JR, Prates PR, and Nesralla IA. Results of the surgical treatment of chronic atrial fibrillation. Arquivos Brasileiros de Cardiologia. 1999;73(2):144-148. Reason for exclusion: No cryoablation used. Kalil RA, Nesralla PL, Lim, GG, Leiria TL, Abrahao R, Moreno P, Prates PR, Sant'Anna JR, and Nesralla IA. Assessment of thromboembolism after the Cox-Maze procedure for chronic atrial fibrillation secondary to mitral valve lesion. Arquivos Brasileiros de Cardiologia. 2002;78(4):378-381. Reason for exclusion: No cryoablation used. McCarthy PM, Castle LW, Maloney JD, Trohman RG, Simmons TW, White RD, Klein AL, Cosgrove III, DM, and Dembitsky WP. Initial experience with the maze procedure for atrial fibrillation. Journal of Thoracic & Cardiovascular Surgery. 1993;105(6):1077-1087. Reason for exclusion: Maze-I used. McCarthy PM, Gillinov AM, Castle L, Chung M, and Cosgrove D, III. The Cox-Maze procedure: the Cleveland Clinic experience. Seminars in Thoracic & Cardiovascular Surgery. 2000;12(1):25-29. Reason for exclusion: Mixed surgical procedures (Maze-I, II and III). Melo JQ, Neves JP, Abecasis LM, Adragao P, Ribeiras R, and Seabra-Gomes R. Operative risks of the maze procedure associated with mitral valve surgery. Cardiovascular Surgery. 1997;5(1):112-116. Reason for exclusion: Mixed surgical procedures (Maze-I and Maze-III). Only 4 patients received Maze-III. Melo JQ, Neves J, Adragao P, Ribeiras R, Ferreira MM, Bruges L, Canada M, and Ramos T. When and how to report results of surgery on atrial fibrillation. European Journal of Cardio-Thoracic Surgery. 1997;12(5):739744. Reason for exclusion: Mixed surgical procedures (Maze-I, III and IIIA, pulmonary vein isolation). Only 4 patients received Maze III. Sandoval N, Velasco, V. M, Orjuela, H, Caicedo, V, Santos, H, Rosas, F, Correa, JR, Melgarejo, I, and Morillo, C. A. Concomitant mitral valve or atrial septal defect surgery and the modified Cox-maze procedure. American Journal of Cardiology. 1996;77 (8):591-596. Reason for exclusion: Surgical technique unclear. May be earlier Maze procedure. Vigano, M, Graffigna A, Ressia L, Minzioni G, Pagani F, Aiello M, and Gazzoli F. Surgery for atrial fibrillation. European Journal of Cardio-Thoracic Surgery. 1996;10(7):490-497. Reason for exclusion: Surgical technique unclear. Likely to be Maze-I. Vogt PR, La Rocca H-P, Candinas R, Gasser J, Zund G, Schonbeck M, Genoni M, Turina MI, Guiraudon G, Penn O, Melo J, and Murphy D. Temporary loss of cardiac autonomic innervation after the maze procedure. European Journal of Cardio-Thoracic Surgery 1997;12(1):75-81. Reason for exclusion: Maze-I in all patients. 187 Yashima N, Nasu M, Kawazoe K, and Hiramori K. Serial evaluation of atrial function by Doppler echocardiography after the maze procedure for chronic atrial fibrillation.[see comment]. European Heart Journal. 1997;18(3):496-502. Reason for exclusion: Surgical technique unclear. May be Maze-I/II. 188 APPENDIX C – METHODOLOGICAL ASSESSMENT AND DATA EXTRACTION TABLES Glossary for Appendices Measurement Abbreviations g J kHz mL mm o C W gram joule kilo Hertz millilitre millimetre degrees Celsius watt Cardiac Abbreviations AF — atrial fibrillation ASD — atrial septal defect AVP — aortic valve plasty AVR — aortic valve replacement BA — biatrial bpm — beats per minute CAD — coronary artery disease CABG — coronary artery bypass graft CAD — coronary artery disease CPB — cardiopulmonary bypass ECG — electrocardiogram LA — left atrial LAA — left atrial appendage LVEF — left ventricular ejection fraction MV — mitral valve MVP — mitral valve plasty MVR — mitral valve replacement MVS — mitral valve surgery RA — right atrial RAA — right atrial appendage TV — tricuspid valve TVP — tricuspid valve plasty General Abbreviations INR — international normalised ratio MWA — microwave ablation NR — not reported NYHA class — New York Heart Association functional status pns — statistically non-significant RFA — radiofrequency ablation * — p<0.05 [ ] — SD { } — type of variance not known § — p<0.0001 † — p<0.01 ‡ — p<0.001 CA — cryotherapy ablation 189 Appendix C.1.1: Intraoperative ablation- Cryotherapy Comparative Biatrial CA versus CS Authors Intervention Study design Study population Handa et al. 1999 Patients underwent either mitral valve surgery alone (MVS) or MV surgery plus cryoablation modified maze (BACA) Surgical access: Not stated CPB Cannulation: Not stated Note: 71% of MV patients maintained on normothermic CPB, versus 40% of patients in CM group (p<0.0001). Cardioplegia: Not stated Body temperature: 40% maintained on normothermic CPB Lesion device: CRYOABLATION/ Not stated Energy level: Not stated Energy rate: Not applicable Surgery: Similar to Cox-Maze III with two modifications: Right lesions: The incision along the medial aspect of the right atrium from the tricuspid valve annulus to the cut edge of the RAA is replaced by a line of cryolesions. This minimises the risk of interruption of coronary blood supply to the sinoatrial node. Atrial incisions: To facilitate closure of the left atrial incisions, the LAA is inverted and amputated after making a standard left atriotomy and incising the interatrial septum. The left atrial incision encircling the pulmonary veins joins the orifice of the LAA, and this orifice is closed horizontally rather than perpendicularly to the encircling incision (from Schaff et al. 2000). Type of concurrent surgery: MV surgery in all patients, >50% had posterior leaflet repair with plication/partial resection and suture repair. Anterior leaflet repairs in 25-30% of patients. Posterior ring annuloplasty in almost all patients (MVS: 95% and BACA: 97%). Repair of atrial septal defects or patent foramen ovale (n=14). TV repair: n=6 Pericardectomy: n=1 AVR with tissue valve: n=1 No difference in above associated procedures between groups. CABG: MVS: 21 (36%) BACA: 7 (18%) p=0.05 Medication: Treatment with antiarrhythmic agents routinely resumed for 6-8 wks postoperatively; and warfarin routinely 3-6 months after MV repair. Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Not stated Level of Evidence: III-2 Retrospective review of data from operative notes, anaesthesia records, clinical case histories, laboratory investigations (including ECGs, echocardiograms and cardiac catheterisation reports). Basis of Patient Selection: Consecutive patients. Decision to add BACA made by surgeon on the basis of surgeon’s experience and anticipated difficulty with MV repair. With experience rarely decided against BACA on basis of concomitant surgery, more likely to be due to local factors at surgery. Eligibility Rate: Patients selected from those having mitral valve surgery; 39/97 (40%) given concomitant BACA. Follow-up: At least 6 months postoperative in all patients. Mean follow-up 21 months. Lost to Follow-up: 7 late deaths, but their data used in follow-up 1 yr: MVS: 36/58 BACA: 26/39 2 yrs: MVS: 22/58 BACA: 15/39 3 yrs: MVS:11/58 BACA: 3/39 Study Period: 1/93-12/96 Operator Details: Not stated; two hospital services were included. Sample Size: MVS: n=58 BACA: n=39 J Thorac Cardiovasc Surg 1999;118:628635 Schaff et al. Sem Thorac Cardiovasc Surg 2000;12:30-37 Location Divisions of Thoracic and Cardiovascular Surgery and Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minn. USA 190 Patient Diagnosis: All patients had chronic AF or multiple episodes of paroxysmal AF. Chronic AF: MVS: 36/58 (62%) BACA: 31/39 (79%) pns Mean Age (yrs): MVS: 69[19] BACA: 65[13] pns Gender Mix (male/female): MVS: 39/19 BACA: 23/16 pns Patient Co-morbidities: History of rheumatic fever: MVS: 4/58(7%) BACA: 6/39 (15%) pns History of stroke: MVS: 4/58(7%) BACA: 4/39 (10%) pns Duration of pre-surgical AF (months): MVS: 28[53] (n=58) BACA: 45[63] (n=39) p=0.03 (paroxysmal AF considered as 0 months) MVS: 42[62] (n=36) BACA: 58[66] (n=31) pns (without the paroxysmal AF) Pre-surgical atrial size: Not stated Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Causes of mitral regurgitation: Ruptured chordae: MVS: 31/58 (53%) BACA: 10/39 (26%) Prolapse: MVS: 11/58 (19%) BACA: 10/39 (26%) Ischaemic: MVS: 5/58 (9%) BACA: 5/39 (13%) Rheumatic: MVS: 4/58 (7%) BACA: 4/39 (10%) Endocarditis: MVS: 4/58 (7%) BACA: 4/39 (10%) Other: MVS: 3/58 (5%) BACA: 6/39 (15%) Underlying heart disease: Coronary artery disease: MVS: 26/58 (45%) BACA: 8/39 (21%) p=0.01 Previous myocardial infarct: MVS: 5/58 (9%) BACA: 3/39 (8%) pns Other: NYHA class III/IV: MVS: 51/58 88%) BACA: 30/39 (77%) pns History of cardioversion: MVS: 6/58 (10%) BACA: 4/39 (10%) pns Previous heart surgery: MVS: 8/58(14%) BACA: 0 p=0.02 Inclusion/Exclusion criteria Inclusion Criteria: Patients with MV disease and AF. Exclusion Criteria: Not stated Appendix C.1.1: Authors Sueda et al. 1997 Ann Thorac Surg 1997;63:1070-5 Location First Department of Surgery, Hiroshima University, School of Medicine, Hiroshima, Japan Intraoperative ablation- Cryotherapy Comparative Biatrial CA versus CS continued Intervention Mitral valve surgery plus cryo-Maze (BACA) and mitral valve surgery alone (MVS). Lesion device: CRYOABLATION/ Not stated Energy level: -60 oC for 2 minutes. Energy rate: Not applicable Surgery: Left ablations: Cryoablation of posterior wall of left atrium, directed to the incision edges between the upper and lower left pulmonary veins, and to two areas of the posterior left atrial wall 1) from the left upper atrial incision edge into the posterior MV annulus, and 2) from the left lower atrial incision edge into the centre of the posterior MV annulus. Right ablations: In patients having tricuspid annuloplasty, cryoablation to the atrial septal wall between the inferior vena cava and the tricuspid annulus isthmus to prevent postoperative atrial flutter. Performed in 21/36 patients. Atrial appendages: LAA excised. Atrial incisions: Left atrial procedure performed through a left vertical atriotomy extended to the left margin of the left pulmonary veins. Right vertical atriotomy used for tricuspid annuloplasty, where performed. Sequence of surgery: CBP initiated then left atriotomy. LAA excised, then cryoablation of left atrium. Cryoablation of right atrium when performed was prior to tricuspid valve surgery. Both groups Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Type of concurrent surgery: MV repair or replacement (P or R) BACA: 11 MVS: 5 MVP or R + tricuspid annuloplasty BACA: 15 MVS: 4 MVPor R + aortic valve replacement BACA: 4 MVS: 4 MVP + aortic valve replacement + tricuspid annuloplasty BACA: 6 MVS: 2 Medication: All patients took anticoagulant (warfarin and aspirin), low dose of digitalis (0.125 to 0.25mg/day) and disopyramide (200-300 mg/day). Disopyramide ended at 6 months postoperatively. Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Performed every 3 months postoperatively. Echocardiography: Transthoracic and transoesophageal echocardiography performed. Study design Level of Evidence: III-3 Non randomised comparative study with historical controls. Intention-to-Treat Analysis: Not stated Basis of Patient Selection: Not stated Follow-up: Mean 18 months (range 2-51 months). Eligibility Rate: Not stated Lost to Follow-up: Not stated Study Period: MVS: <2/93 BACA: introduced >3/93, surgery performed over 51 months. Operator Details: Not stated Study population Sample Size: BACA: 36 MVS: 15 Inclusion/Exclusion criteria Inclusion Criteria: MV disease and chronic AF. Patient Diagnosis: MV disease and chronic AF. Exclusion Criteria: Not stated Mean Age: BACA: 61.0[10.3] MVS: 54.7[10.6] Gender Mix (male/female): BACA: 14/22 MVS: 5/10 Patient Co-morbidities: Complicated heart disease Coronary heart disease BACA: 1 MVS: 0 Congenital heart disease BACA: 1 MVS: 0 Duration of pre-surgical AF (yrs): BACA: 7.8[5.7] MVS: 8.2[4.6] Pre-surgical atrial size: Left atrial diameter (mm) BACA: 53.8[9.9] MVS: 54.6 [5.9] pns Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Solitary mitral BACA: 11/36 (31%) MVS: 4/15 (27%) Mitral+aortic BACA: 4/36 (11%) MVS: 4/15 (27%) Mitral+aortic+tricuspid BACA: 6/36 (17%) MVS: 2/15 (13%) Underlying heart disease: Rheumatic: Degenerative BACA: 21:15 MVS: 11:4 Other: P wave (Fine: Coarse) BACA: 14:22 MVS: 3:12 191 Appendix C.1.1: Intraoperative ablation- Cryotherapy Comparative Biatrial CA versus CS continued Authors Intervention Yuda et al. 2004 Patients with AF and MV disease given MV surgery plus cryoablation maze (BACA) or MV surgery alone (MVS). Lesion device: CRYOABLATION/ Energy level: Not stated Energy rate: Not applicable Surgery: Left lesions: Cryoablation from the circumferential atriotomy toward the LAA, and of the interatrial septum from both the left and right atria to reinforce transmural penetration of ablation. Right lesions: Cryoablation of the end of the right atriotomies, tricuspid annulus, and junction with the inferior vena cava. Atrial appendages: RAA and LAA amputated Atrial incisions: From the incision made for RAA amputation the right atriotomy extended in curvilinear fashion to the junction with the inferior vena cava. From the midpoint of this atriotomy an additional incision started toward the tricuspid annulus. Superior vena cava transected distal to the junction with the right atrium. Left atrium entered in front of right pulmonary veins as in regular MV operation. Left atriotomy extended to encircle the orifices of the pulmonary veins. At the circumferential atriotomy, the left ventricle was disconnected from the pulmonary veins and suspended with left atrial cuff to facilitate atriotomy and cryoablation. Order of surgery: Not stated Description of surgery from Kosakai et al. 1994 Heart 2004;90:64-69 Location Division of Cardiology, National Cardiovascular Centre, Suita, Osaka, Japan Both groups Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Type of concurrent surgery: BACA: MV surgery: 26 Aortic valve surgery: 9 Tricuspid annuloplasty: 9 Left atrial plication: 1 Medication: Prior to surgery: Diuretics: BACA: 20 MVS: 4 Digitalis: BACA: 25 MVS: 6 Calcium antagonists: BACA: 5 MVS: 1 Angiotensin converting enzyme inhibitors: BACA: 7 MVS: 2 Antiarrhythmic drugs: BACA: 6 MVS: 0 Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: A standard 12 lead ECG was recorded from all patients 1 month after discharge. Echocardiography: Performed before (1.7[2.5] months) and after (16.8[13.4] months) surgery. Arbitrarily considered an A wave peak velocity ≥ 10 cm/s to be evidence of effective atrial contraction. Study design Level of Evidence: III-2 Retrospective study with concurrent controls Intention-to-Treat Analysis: Not stated Basis of Patient Selection: Follow-up (months): BACA-SR: 14.6[6.6] BACA-AF: 19.1[9.3] MVS: 17.4[15.5] All > 6 months Eligibility Rate: 26/66 (39.4%) of patients with BACA and cardiac surgery eligible for study. Lost to Follow-up: Not stated Study population Inclusion/Exclusion criteria Sample Size: BACA: 26 MVS: 6 Inclusion Criteria: Chronic AF > 6 months and requirement for MV surgery. Patient Diagnosis: chronic AF > 6 months Mean Age: BACA-SR (n=18): 59[8] (range 37-69) BACA-AF (n=8): 54[9] (range 46-72) MVS: 59[21] (range 44-73) Gender Mix: BACA-SR (n=18): 10/8 BACA-AF (n=8): 5/3 MVS: 3/3 Patient Co-morbidities: Not stated Duration of pre-surgical AF (yr): BACA: 7.6[7.2] (range 0.5-30) MVS: 18.2[7.4] (range 10-31) Pre-surgical atrial size: Left atrial diameter (mm): BACA-SR (n=18): 56.1[8.4] BACA-AF (n=8): 60.3[14.0] MVS: 71.8[12.9] C vs BACA-SR p=0.026 Pre-surgical LVEF (%): Not stated Study Period: 7/92-5/96 Operator Details: Not stated Indication for concurrent surgery: Mitral stenosis: BACA: 7 MVS: 2 Mitral regurgitation: BACA: 8 MVS: 1 Mitral stenosis + regurgitation: BACA: 9 MVS: 1 Aortic regurgitation: BACA: 6 MVS: 1 Aortic regurgitation + stenosis: BACA: 2 MVS: 0 Aortic stenosis: BACA: 1 Prosthetic MV failure: BACA: 2 MVS: 2 Tricuspid regurgitation: BACA-SR: 17/18 BACA-AF: 6/8 MVS: 6/6 pns Underlying heart disease: Not stated Other: NYHA class: BACA: I: 3 II: 20 III: 3 MVS: I: 1 II: 4 III: 1 Left ventricular end diastolic diameter (mm): BACA-SR: 51.4[9.8] BACA-AF: 59.3[10.4] MVS: 55.4[9.1] pns Fractional shortening (%): BACA-SR: 33.4[8.5] BACA-AF: 33.2[7.0] MVS: 31.1[8.5] 192 Exclusion Criteria: 37/66 patients had no cardiopulmonary testing after surgery and were excluded. 3/66 patients had cardiopulmonary testing < 6 months after surgery and were excluded. Authors Yuda et al. 2004 continued Intervention Study design Other: 1 BACA patient underwent programmed rehabilitation after surgery. Study population pns Right ventricular peak pressure gradients (RVPG; mm Hg): BACA-SR: 29.8[12] BACA-AF: 28.5[8.0] (n=16) MVS: 39.3[13.6] (n=6) pns RVPG > 25 mm Hg BACA-SR: 5/6 BACA-AF: 8/16 MVS: 2/6 p=0.09 Exercise testing (2.6[2.6] months before surgery): Maximum work load (w): BACA-SR: 101[30] BACA-AF: 96[27] MVS: 94[26] pns Heart rate at rest (beats/min): BACA-SR: 88[15] BACA-AF: 89[15]] MVS: 78[15] pns Heart rate at peak (beats/min): BACA-SR: 182[24] BACA-AF: 175[21] MVS: 168[25] pns Systolic blood pressure at rest (mm Hg): BACA-SR: 132[21] BACA-AF: 120[13] MVS: 127[11] pns Systolic blood pressure at peak (mm Hg): BACA-SR: 172[25] BACA-AF: 171[21] MVS: 176[24] pns 193 Inclusion/Exclusion criteria Appendix C.1.2: Intraoperative ablation- Cryotherapy Comparative Left atrial CA versus CS Authors Intervention Study design Study population Gaita et al. 2000 Patients with chronic AF undergoing heart valve surgery due to mitral or aortic valve disease, or both plus cryoablation (LACA) and heart valve surgery without cryoablation (CS) Lesion device: CRYOABLATION/ Dual-probe cardiac cryosurgical system (Frigitronics, Cooper Surgical, Shelton, Connecticut). Pressure in two cylinders (N2O) always maintained above 720 psi. Two probes used simultaneously, close to each other. Energy level: Temperature fell abruptly to -60 oC at probe tip when gas delivered and maintained 2 minutes. Energy rate: Not applicable Surgery: Left ablations: Cryoablation connecting the four pulmonary veins, and both right and left lower pulmonary veins to posterior mitral annulus. Right ablations: None Atrial appendages: The LAA was externally ligated. Atrial incisions: Left atrium opened through left paraseptal incision. Sequence of surgery: Left atrium opened after cold cardioplegic arrest. Mitral or aortic valves operated on first then ablation performed. Mitral or aortic prosthesis inserted, if required, at the end of the surgery. Level of Evidence: III-2 Non randomised retrospective comparative study with concurrent controls. Sample Size: LACA: 32 J Am Coll Card 2000;36:159-166 Location Division of Cardiology, Hospital of Asti, Asti and Unit of Cardiac Surgery, Istituto Clinico Humanitas, Rozzano (Milano) Italy Both groups Surgical access: Not stated CPB Cannulation: Double venous cannulation Cardioplegia: Cold cardioplegic arrest Body temperature: Moderate hypothermia Type of concurrent surgery: no(%) MVR: LACA: 20(63) CS: 8(45) pns AVR: LACA: 3(9) CS: 4(22) pns MVR+AVR: LACA: 1(3) CS: 4(22)pns MVP: LACA: 8(25) CS: 2(11) pns Bioprostheses LACA: 6(19) CS: 2(11) pns CABG: LACA: 5(16) CS: 1(6)pns IABP: LACA: 1(3) CS: 0 pns Medication: Amiodarone infusion (150mg loading dose 10-15 min; 1 mg/min 6 hrs; 0.5 mg/min until oral administration) started after weaning from bypass, regardless of heart rate or rhythm. Oral amiodarone (600mg/day for 10 days; 400 mg/day for 10 days; 200 mg/day) given to all patients, except one given propafenone (300 mg bid) due to previous dysthyroidism. Inotropes used in all patients in immediate postoperative period in both groups. High doses used due to low cardiac output syndrome: LACA: 3 patients (9%) with low cardiac output syndrome (1 SR patient; 1 AF patient; 1 junctional rhythm patient). CS: 2 patients, both with AF. At the end of CPB adrenaline (0.025 gamma/kg/min) given to all patients. Pacemaker: Not stated Cardioversion: Intraoperative direct current cardioversion routinely performed in all patients with AF. During hospital stay electrical cardioversion used in all patients with AF. Intention-to-Treat Analysis: Not stated Basis of Patient Selection: 18 consecutive patients with chronic AF matched for age, AF duration and heart valve disease treated with valve surgery, but who refused cryoablation, were used as the control group. Follow-up: Clinical examination, ECG and Holter monitoring at 1, 3, 6, 9, 12 and 18 months All patients with minimum 9 months follow-up. Eligibility Rate: Not stated Lost to Follow-up: At 12 months 9/29 LACA and 1/17 CS lost to follow-up. Study Period: Not stated Operator Details: All operations performed by the same surgeon. 194 Inclusion/Exclusion criteria Inclusion Criteria: Patients with chronic AF CS: 18 Patient Diagnosis: Chronic AF Mean Age: LACA: 62 [10] CS: 68 [8] Exclusion Criteria: Not stated pns Gender Mix (male/female): LACA: 14/18 CS: 3/15 pns Patient Co-morbidities: Previous embolic episodes LACA: 3 (9%) CS: 2 (11%) pns Duration of pre-surgical AF: LACA: 6.1 [5.2] CS: 6.9 [4.3] Pre-surgical atrial size: Left atrial diameter (mm) LACA: 52.5 [6.5] CS: 52.9 [6.2] pns pns Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Mitral stenosis LACA: 9 (28%) CS: 4 (22%) pns Mitral regurgitation LACA: 7 (23%) CS: 2 (11%) pns Mitral stenosis+regurg. LACA: 11 (34%) CS: 4(22%) pns Aortic stenosis LACA: 1 (3%) CS: 2 (11%) pns Aortic stenosis+regurg. LACA: 1(3%) CS: 2(11%) pns Mitral plus aortic LACA: 3 (9%) CS: 4 (22%) pns Other: Reoperation LACA: 5 (16%) CS: 3 (17%) pns Authors Gaita et al. 2000 continued Intervention Study design Electrocardiogram: Postoperatively monitored by continuous ECG. Transthoracic echocardiography: Performed at discharge and 3 and 6 months postoperatively. Other: An atrial biopsy was performed after cryoablation in 8 patients at the beginning of study to confirm the lesion was transmural. 195 Study population Inclusion/Exclusion criteria Appendix C.1.3: Authors Ishii et al. 2001 Ann Thorac Surg 2001;71:572-576 Nitta et al. Ann Thorac Surg 1999;68:805-811 (1999a) Nitta et al. Ann Thorac Surg 1999;67:27-35 (1999b) (surgical technique) Location Department of Cardiothoracic Surgery, Nippon Medical School, Tokyo, Japan Intraoperative ablation- Cryotherapy Comparative CA versus Maze-III Intervention Patients underwent a Radial Incision Approach using cryotherapy (CA) including cryoablation, or the traditional Maze-III (M-III). CA: Lesion device: CRYOABLATION/ 5- and 15-mm cryoprobes (Frigitronics, Inc, Coopersurgical, Shelton, CT, USA) (Nitta et al. 1999a) Energy level: 2 min at -60 oC (Nitta et al. 1999b.) Energy rate: Not applicable Lesion set: Left lesions: The posterior left atrium around each pulmonary vein orifice was ablated circumferentially. The narrow isthmus of atrial tissue between upper and lower right pulmonary veins orifices was ablated. Number of cryoablations in left atrium ≥ 9 (Nitta et al.1999a). Right lesions: Cryoablation at the tricuspid end of the T incision and at the tricuspid end of the anteromedial incision down from the RAA at the level of the tricuspid annulus. Atrial appendages: RAA not excised, but incised at the lateral right atrium. In addition, major bridging trabeculae in the RAA divided to eliminate reentry using these structures. Atrial incisions: Right atrium: The RAA incision is extended down to the tricuspid valve annulus anteriomedially and from the appendage tip in the opposite direction, toward the lower RA inferiorly (as in MazeIII). The other two right atrial incisions the same as the Maze. A T incision placed from the level of the top of the inferior vena cava cannula across the lower RA free wall, extended to the top of the right AV groove. After retraction of the RA free wall the T incision is extended to the tricuspid annulus. Left atrium: An incision beginning at the anterior limbus of the fossa ovalis, extending inferioposteriorly toward the lower posterior interatrial septum and to the right posteroinferior wall of the LA, passing near the right and left lower pulmonary vein orifices, and continuing down to the MV annulus at the commissure between the middle and posteriomedial scallops. The other incision begins at the superior LA between the right and left upper pulmonary veins, connecting with the LAA excision line and extending anteromedially downward to the MV annulus at the anterolateral commissure. The septal incision placed from the posterior lower septum extending up to the anterior limbus. Order of surgery: Not stated Study design Level of Evidence: III-3 Intention-to-Treat Analysis: Not stated Basis of Patient Selection: Not stated Study population Sample Size: CA: 32 M-III: 13 Patient Diagnosis: AF Mean Age: CA: 63.4[9.1] (range 45-77) M-III: 56.9[5.2] Gender Mix: CA:15/17 M-III: 9/4 Patient Co-morbidities: Not stated Follow-up (months): CA: > 12 M-III: 41.2[5.6] (range 34-52) Eligibility Rate: Not stated Duration of pre-surgical AF (yrs): CA: Range 1-20 (All > 1 yr; diagnosis not accurate, relied on patient memory). M-III: Not stated Lost to Follow-up: CA: 21/32 > 3 months postoperative 15/32 at > 1 yr postoperative (2 deaths) M-III: 12/13 at > 3 months postoperative 8/13 at ≥ 34 months Pre-surgical atrial size: Left atrial dimension (mm): Study Period: CA: 11/97-7/99 M-III: 11/93-6/95 Underlying heart disease: Not stated Operator Details: Not stated Both groups Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Type of concurrent surgery: CA: Valvuloplasty/Prosthetic valve replacement: 28 1-2 mechanical valves: 11 Atrial septal defect: 1 196 CA: 51[10] M-III: 53[7] Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Valvular heart disease: CA: 28/32 M-III: 11/13 Left atrial thrombosis: CA: 3 ASD: CA: 1 Other: Cardiothoracic Ratio (%): CA: 56.4[4.9] M-III: 58.1[5.6] NYHA class: I: CA: 4 M-III: 0 II: CA: 22 M-III: 6 III: CA: 6 M-III: 7 Inclusion/Exclusion criteria Inclusion Criteria: Patients with chronic AF for at least 1 year. Exclusion Criteria: Not stated Authors Ishii et al. 2001 continued Intervention M-III: 3 patients did not receive mechanical valve replacement Medication: Patients receiving mechanical valves were placed on warfarin postoperatively. 9/10 patients in the CA group received coumadin (Nitta et al.1999a). Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: CA: Transthoracic echocardiography performed in all patients who survived the surgery (30/32) and in 15 patients > 1 yr postoperatively. M-III: Transthoracic echocardiography at 41.2[5.6] months (34-52 months) after surgery in 8/13 patients. Study design 197 Study population Inclusion/Exclusion criteria Appendix C.1.3: Authors Kim et al. 2001 Ann Thorac Surg 2001;71:816-822 Location Departments of Thoracic and Cardiovascular Surgery, and Internal Medicine, College of Medicine, Seoul National University, Seoul, Korea Intraoperative ablation- Cryotherapy Comparative CA versus Maze-III continued Intervention Patients treated with the Maze-III (M-III) or a modified Cox-Maze III with cryoablation (CA). Lesion device: CRYOABLATION/Not stated Energy level: Not stated Energy rate: Not applicable Lesion set: M-III: Maze-III CA: Left lesions: Cryoablation on the bridge between the LAA and margin of the pulmonary vein encircling incision. Right lesions: Not stated Atrial appendages: LAA obliterated externally or internally instead of excising it. The RAA was not excised. Atrial incisions: Compared to the Cox-Maze III, the T-incision of the right atrium from the lower portion of the posterior longitudinal right atriotomy toward the tricuspid annulus was omitted, and the lateral incision of the RA onto the RAA was extended more inferiorly toward the inferior vena cava. Order of surgery: Left atrial procedures performed first, followed by interatrial septotomy prior to RA procedures. Mobilised posterior LA after initial left atriotomy under cardioplegic arrest. Reduced CPB times by performing the RA procedures during rewarming of the patients. Both groups: Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Usually used antegrade cold blood cardioplegia for induction and maintenance of cardiac arrest, and warm blood cardioplegia just before releasing the aortic cross clamp. Body temperature: moderate hypothermia (25-28 oC) Type of concurrent surgery: MVR: M-III: 13 (text 10) CA: 8 (text 7) Redo-MVR: M-III: 2 CA: 10 MVP: M-III: 3 CA: 5 TVP: M-III: 3 CA: 1 Medication: Not stated Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Standard 12-lead ECG daily during postoperative hospital stay, and 1, 3, 6, 12, 18, and 24th month postoperatively. Echocardiography: Transthoracic echocardiography performed before discharge, and in the 1, 6, 12 and 24th postoperative month. Presence of right and left atrial mechanical function determined by presence on Doppler echocardiography of the A- and E-waves. When presence of an A wave in the ventricular inflow was ambiguous, the systemic venous flow or pulmonary venous flow pattern was evaluated for presence of atrial reversal. Study design Level of Evidence: III-3 Groups not concurrent. Intention-to-Treat Analysis: Not stated Basis of Patient Selection: Chronic AF and MV disease. Follow-up: All patients followed > 2yrs M-III: 47[14] months CA: 29[4] months Eligibility Rate: Not stated Lost to Follow-up: Not stated Study Period: M-III: 4/94-10/96 CA: 11/96-12/97 Operator Details: Not stated 198 Study population Sample Size: M-III: 18 CA: 23 Patient Diagnosis: chronic AF Mean Age (yr): M-III: 40[10] CA: 46[12] pns Gender Mix (male/female): M-III: 5/13 CA: 7/16 pns Patient Co-morbidities: Not stated Duration of pre-surgical AF (months): M-III: 37[41] CA: 91[83] p=0.016 Pre-surgical atrial size: Left atrial diameter (mm): M-III: 58[9] CA: 63[13] pns Pre-surgical LVEF (%): M-III: 53[8] CA: 57[7] pns Indication for concurrent surgery: Not stated Underlying heart disease: Not stated Other: Cardiac index (L/min/m2): M-III: 2.4[0.6] CA: 2.2[0.5] pns Inclusion/Exclusion criteria Inclusion Criteria: Chronic AF and MV disease Exclusion Criteria: Patients with nonrheumatic MV disease and patients who also required aortic valve operation or CABG in addition to MV surgery were excluded. Appendix C.1.3: Authors Kosakai et al. 1995 Circulation 1995;92:359-364 (556) Location National Cardiovascular Center, Osaka, Japan Intraoperative ablation- Cryotherapy Comparative CA versus Maze-III continued Intervention Patients underwent the Maze-III (M-III; n=17), the initial modification (CA1; n=14) or the Kosakai Maze (KM; n=70). Lesion device: CRYOABLATION/ Not stated Energy level: Not stated Energy rate: Not applicable Surgery: Initial modification: Pattern similar to Cox Maze -II Left lesions: An ablation from the left side of the encircling incision of the pulmonary veins to the base of the excised LAA, and an ablation to complete the incision to the mitral annulus. Right lesions: The T incision extended to the tricuspid annulus using ablation. An anterior right ablation performed beginning at the anteriomedial base of the excised RAA to the level of the tricuspid valve. Atrial appendages: LAA and RAA excised. Atrial incisions: In the LA an encircling incision around the pulmonary veins, an incision from the right side of the encircling incision to the superior vena cava, and an incision line towards the mitral annulus. In the RA a line of incision between the superior and inferior vena cava, and a T incision from half way along this line across the RA free wall to the top of the right AV groove. Order of surgery: Not stated Kosakai Maze: Left lesions: Ablation from the circumferential atriotomy toward the LAA, and the interatrial septum from both the left and right atria to reinforce transmural penetration of cryothermia. Right lesions: Ablation of the end of the right atriotomies, tricuspid annulus, and junction with the inferior vena cava. Atrial appendages: RAA and LAA amputated Atrial incisions: From the incision made for RAA amputation the right atriotomy extended in curvilinear fashion to the junction with the inferior vena cava. From the midpoint of this atriotomy an additional incision started toward the tricuspid annulus. Superior vena cava is transacted distal to the junction with the RA. Left atrium entered in front of right pulmonary veins as in regular MV operation. Left atriotomy extended to encircle the orifices of the pulmonary veins. At the circumferential atriotomy, the left ventricle was disconnected from the pulmonary veins and suspended with LA cuff to facilitate atriotomy and ablation. Order of surgery: Not stated Description of KM surgery from Kosakai et al. 1994 Both groups: Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Antegrade infusion of St Thomas’ solution (10 mL/kg) every 30 min with topical cooling. Body temperature: Not stated Study design Level of Evidence: III-2/3 M-III and KM concurrent and CA1 historical. Intention-to-Treat Analysis: Not stated Basis of Patient Selection: KM and CA1 patients were consecutive. Follow-up (yrs): 1.92[0.54] (range 1-3.1) Eligibility Rate: Lost to Follow-up: Study Period: Median operative date: M-III: 6/93 KM: 7/93 CA1: 7/92 Operator Details: Not stated Study population Sample Size: M-III: n=17 KM: n=70 CA1: n=14 Total: n=101 Patient Diagnosis: Chronic sustained AF: 93 Paroxysmal AF or atrial flutter: 8 Mean Age (yrs): M-III: 55.7[10.0] KM: 58.0[8.7] CA1: 58.6[8.9] pns Total 57.7[9.0] Gender Mix (male/female): 43/58 Patient Co-morbidities: Not stated Duration of pre-surgical AF (yrs): M-III: 7.5[5.1] KM: 9.4[7.8] CA1: 7.3[3.8] pns Total: < 3 months 1/101 (1%), 3-12 months 6/101 (6%), 1-5 yrs 32/101 (32%), 5-10 yrs 18/101 (18%) 10-20 yrs 34/101 (34%), 20 or greater yrs 10/101 (10%) Pre-surgical left atrial size (mm): M-III: 58.1[18.4] KM: 56.6[12.2] CA1: 58.2[11.4] pns Giant left atrium, %: M-III: 5/17 (29.4) KM: 11/70 (15.7%) CA1:1/14 (7.1%) pns Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Mitral related, % M-III:16/17 (94.1) KM:59/70 (84.3) CA1:11/14 (78.6) pns Underlying heart disease: Rheumatic, %: M-III: 13/17 (73.6) KM: 45/70 (64.3) CA1: 9/14 (64.3) pns Other: NYHA: M-III: 2.27[0.42] KM: 2.28[0.67] CA1: 2.14[0.35] F wave (mV) (range 0-0.45): M-III: 0.18[0.09] KM: 0.15[0.09] CA1: 0.16[0.08] pns Redo operation, %: M-III: 1/17 (5.9) KM: 21/70 (30.0) CA1: 2/14 (14.3) p<0.05 M-III vs KM Cardiothoracic Ratio (%) (range 40-99): 199 Inclusion/Exclusion criteria Inclusion Criteria: Initially (CA1) selected patients undergoing a simple operation to include the maze procedure. For the KM and M-III patients the application of the combined approach was extended. Exclusion Criteria: Patients judged not to tolerate the combined surgery did not have the Kosakai Maze (KM). Authors Kosakai et al. 1995 continued Intervention Type of concurrent surgery: Total: 86/101 had MV surgery. 65/101 had mechanical valves, 1/101 had a bioprosthesis, and 35/101 reparative surgery. MV repair (%): M-III: 5/17 (29.4) KM: 22/70 (31.4) CA1: 8/14 (57.1) pns Medication: Antiarrhythmics used to treat postoperative atrial arrhythmias, usually class I-A. Patients who had arrhythmias were maintained on antiarrhythmics to suppress triggering effects and to stabilise atrial rhythm before discontinuation of warfarin. Anticoagulation was discontinued only in patients with atrial rhythm and documented contraction 3-6 months after surgery. Antiarrhythmics were tapered after anticoagulation was discontinued or after cardiac rhythm was considered stable. Pacemaker: Temporary wires used to pace the patient, to monitor the rhythm, or to overdrive the atrium. Cardioversion: Postoperative atrial arrhythmias treated with DC cardioversion if they were haemodynamically deleterious or not responding to overdrive pacing or antiarrhythmics. Electrocardiogram: Not stated Echocardiography: Not stated Study design 200 Study population M-III: 61.8[7.5] KM: 63.9[10.1] CA1: 62.2[6.3] pns P wave: M-III: 7/17 (41.2) KM:48/70 (68.6) CA1: 2/14 (14.3) KM vs M-III p<0.05 Inclusion/Exclusion criteria Appendix C.1.3: Intraoperative ablation- Cryotherapy Comparative CA versus Maze-III continued Authors Intervention Study design Study population Inclusion/Exclusion criteria Lee et al. 2001 Patients underwent Maze-III (M-III) or a modified Cryo-Maze (CA) procedure. Lesion device: CRYOABLATION/ 15 degree angled 30mm long freeze tip with 9-mm diameter (Frigitronics Cardiac Cryosurgical System 200). Energy level: Not stated Energy rate: -60 oC for 2 minutes in the left atrium and for 1 minute in the right atrium. The duration of freezing sometimes varied at the surgeon’s discretion, depending on myocardial thickness. Surgery: M-III: Maze-III CA: Left ablations: To complete pulmonary isolation, the cryoprobe was passed through a 1 cm linear incision over the left upper pulmonary vein. Through this opening the left pulmonary veins were isolated with ablation by joining the cryolesions with the previously created pulmonary isolation incisions from the right side. Coronary sinus also cryoablated. Right ablations: The RA free wall between the RA incision and the tricuspid annulus was cryoablated. The counter-incision to the RAA incision, which reaches the tricuspid annulus, the incision connecting the two vena cavae, and the atrial septal incision were all ablated. Atrial appendages: Rough trabeculated tip of LAA resected. Atrial incisions: 5 cm incision in the RAA. A longitudinal left atriotomy made through the interatrial groove. Cephalad end of this incision directed in sharp postero-inferior direction towards right inferior pulmonary vein. Incision continued variably towards the left inferior pulmonary vein. Some of thin LA roof resected in enlarged LA. Caudal end of inter-atrial groove incision extended leftward, short of reaching left inferior pulmonary vein. If large part of LA resected, the upper and lower parts of pulmonary isolation converged near mid-point between the left and right inferior pulmonary veins. If resection minimal, upper and lower pulmonary isolation incisions not joined and ran parallel. A vertical incision in the posterior LA wall extending from the inferior pulmonary isolation incision to the left atrioventricular groove was made. Prior to repair of the LA wall, some of the LA between the lower margin of the pulmonary isolation and the MV annulus was resected, depending on degree of LA redundancy. Right atrial incision near the inferior vena cava. Sequence of surgery: Procedure started with incision in RAA, through which direct retrograde coronary sinus cardioplegic cannulation performed. Left atriotomy made on commencing CPB. After LA incisions, ablation and resection, the MV procedure was performed. After RA ablations were made the heart, while still cross clamped, was perfused retrogradely with warm blood. Just prior to releasing crossclamp, the patient was placed in steep reverse Trendelenberg position. Retrospective historically controlled study Sample Size: M-III: n=30 CA: n=53 Inclusion Criteria: AF Lee et al. Ann Thorac Surg 2001;72:1479-83 Location Department of Thoracic and Cardiovascular Surgery, and Division of Cardiology, Asan Medical Center, university of Ulsan, Seoul, Korea Level of Evidence: III-3 Intention-to-Treat Analysis: Not stated Basis of Patient Selection: Not stated Patient Diagnosis: AF Mean Age (yrs): M-III: 45 [8 ] CA: 48 [13 ]pns Eligibility Rate: Not stated Gender Mix (male/female): M-III: 18/12 CA: 19/34 p=0.03 Follow-up: 6 months Patient Co-morbidities: Not stated Lost to Follow-up: Not stated Duration of pre-surgical AF (yrs): M-III: 3.1 [ 3] CA: 4.8 [ 4] NS Study Period: 7/97 to 12/99 M-III: < 1/99 CA: > 1/99 Operator Details: Not stated Pre-surgical atrial size: Left atrial dimension (mm) M-III: 58 [9 ] CA: 63 [9 ] p=0.02 Pre-surgical LVEF (%): M-III: 57 [10 ] CA: 55 [10 ] (note doesn’t say L ventricle) pns Indication for concurrent surgery: Not stated Underlying heart disease (rheumatic): M-III: 20/30 (67%) CA: 36/51 (68%) pns Other: F-wave type (fine %) M-III: 41 CA: 47 pns Giant left atrium defined as maximum anterioposterior LA diameter >60mm by transthoracic echocardiography on 2D mode. CA>M-III patients with giant LA. 201 Exclusion Criteria: Not stated Authors Lee et al. 2001 continued Intervention Study design Both Groups: Surgical access: Median sternotomy. CPB Cannulation: Ascending aorta and superior and inferior vena cava separately cannulated. Cardioplegia: Warm antegrade induction followed by tepid intermittent antegrade and retrograde cardioplegia with a terminal “hot shot” infusion before declamping. This usually induced spontaneous cardiac contractions. Body temperature: Normothermia Type of concurrent surgery no(%): Mitral valve valvuloplasty M-III: 26/30 (87) CA: 35/53 (66) Other M-III: 13/30 (43) CA: 26/53 (49) Aortic valve replacement (AVR) M-III: 3 CA: 4 AVR + others M-III: 1 CA: 3 Tricuspid valvuloplasty (TVP) M-III: 6 CA: 15 TVP + others M-III: 2 CA: 2 Miscellaneous M-III: 1 CA: 2 Mitral valve repair (%): M-III: 87 CA: 66 pns Medication: If anticoagulants or codarone were administered preadmission they were continued for at least 6 months. Continued administration of minimal diuretics for 6 months. Pacemaker: No requirement for pacing. Cardioversion: Not stated Electrocardiogram: Preoperative, early postoperative and 6 months follow-up. Transthoracic echocardiography: Preoperative, early postoperative and 6 months follow-up. 202 Study population Inclusion/Exclusion criteria Appendix C.1.3: Intraoperative ablation- Cryotherapy Comparative CA versus Maze-III continued Authors Intervention Nishiyama et al. Patients underwent either a traditional Cox maze III procedure (M-III) or a cryoablation maze procedure (CA). Lesion device: CRYOABLATION/ cryoprobe 3 cm in length Energy level: -80 oC Energy rate: Not applicable Lesion set: M-III: Maze-III procedure CA: Left lesions: Encircling of the four pulmonary veins through the ASD. Right lesions: Not stated Atrial appendages: Not stated Atrial incisions: No left atrial incision. Order of surgery: Not stated AHA 2003 (abstract) Location Iwate Medical University, Morioka, Japan; University of Oklahoma, Oklahoma City, OK, USA Both groups: Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Type of concurrent surgery: ASD closure Medication: Not stated Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Not stated Study design Level of Evidence: III-2 Study population Inclusion/Exclusion criteria Sample Size: M-III: 9 CA: 11 Inclusion Criteria: Patients with chronic AF undergoing surgical ASD closure. Patient Diagnosis: Chronic AF Basis of Patient Selection: Consecutive patients Mean Age (y): M-III: 63[5] CA: 56[13] pns Eligibility Rate: Not stated Gender Mix (male/female): M-III: 5/4 CA: 6/5 pns Follow-up (months): 26.8[22.8] Patient Co-morbidities: Not stated Duration of pre-surgical AF: Not stated Lost to Follow-up: Not stated Pre-surgical atrial size: Left atrial dimension (cm): M-III: 4.3[0.8] CA: 4.5[0.8] pns Study Period: Not stated Pre-surgical LVEF (%): Not stated Operator Details: Not stated Indication for concurrent surgery: ASD Underlying heart disease: Not stated Other: Pulmonary arterial pressure (mmHg): M-III: 24.5[8.6] CA: 20.7[7.2] pns 203 Exclusion Criteria: Not stated Appendix C.1.41: Intraoperative ablation- Cryotherapy Comparative Internal Comparison Kosakai maze versus CA Authors Intervention Nakajima et al. 2002 Patients were divided into those who underwent a Cryo-Maze (CA) and those who underwent a Kosakai-maze (KM) Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Crystalloid cardioplegia used early in the period for KM but not for CA surgery. Now use tepid blood cardioplegia. Body temperature: Not stated Lesion device: CRYOABLATION/ 20 o angled 4 cm linear probe (CCS-200, Cooper Surgical, Shelton, CT) Energy level: -80 oC for 2 minutes. Energy rate: Not applicable. Surgery: Kosakai Maze: Left lesions: Cryoablation from the circumferential atriotomy toward the LAA, and the interatrial septum from both the left and right atria to reinforce transmural penetration of cryothermia. Right lesions: Cryoablation of the end of the right atriotomies, tricuspid annulus, and junction with the inferior vena cava. Atrial appendages: RAA and LAA amputated. Atrial incisions: From the incision made for RAA amputation the right atriotomy is extended in curvilinear fashion to the junction with the inferior vena cava. From the midpoint of this atriotomy an additional incision started toward the tricuspid annulus. Superior vena cava is transacted distal to the junction with the RA. Left atrium entered in front of right pulmonary veins as in regular MV operation. Left atriotomy extended to encircle the orifices of the pulmonary veins. At the circumferential atriotomy, the left ventricle was disconnected from the pulmonary veins and suspended with LA cuff to facilitate atriotomy and ablation. Order of surgery: Not stated Description of surgery from Kosakai et al. 1994 Cryo-Maze: Designed to avoid injury to the sinus node or sinus node artery. Left ablations: Cryoablation used to complete the left sided encircling line around the pulmonary veins. The site of cryoablation on the interatrial septum differed from the KM: performed between the fossa ovalis and RA incision. The cryoablation to the LAA and MV the same as in the KM. Right ablations: Cryoablation of the sinus node, tricuspid annulus, and to complete the lower end of the RA incision towards the inferior vena cava. Atrial appendages: LAA partly preserved and RAA fully preserved. LAA ligated from the epicardial side. Atrial incisions: For simple MV operations only the right-sided left atrium was incised. Right atriotomy as for the Kosakai Maze. Sequence of surgery: Not stated Circulation 2002;106 (suppl1):I-46-I-50 Location Department of Cardiovascular Surgery, National Cardiovascular Center, Osaka, Japan Study design Level of Evidence: III-3 Study population Inclusion/Exclusion criteria Sample Size: CA: n=110 KM: n=110 Inclusion Criteria: Patients were paired according to age, preoperative duration of AF > 10 yrs, preoperative left atrial dimension > 70 mm, history of previous cardiac surgery, and concomitant aortic valve operation. Only hospital survivors were paired. Patient Diagnosis: AF Basis of Patient Selection: Total of 414 patients operated on in period: From 9/98- 199 patients had CA. 244 patients had KM before the introduction of the CA 110 pairs of hospital survivors in CA and KM groups were assigned to study. Eligibility Rate: 220/414 (53.1%) Follow-up (months): CA: 18.8[10.8] KM: 64.1[27.4] p<0.0001 Lost to Follow-up: CA: 77/110 at 1 yr, 40/110 at 2 yrs, 6/110 at 3 yrs KM: 105/110 at 1 yr, 92/110 at 3 yrs, 51/110 at 5 yrs, 26/110 at 7 yrs, 8/110 at 9 yrs Mean Age (yrs): CA: 60.4[9.0] KM: 58.1[10.0] p=0.10 Gender Mix (male/female): CA: 65/45 KM: 54/56 p=0.13 Patient Co-morbidities: History of stroke: CA: 24 (22%) KM: 12 (11%) p=0.02 History of thromboembolism: CA: 2 (2%) KM: 2 (2%) p=1.0 Thrombus in left atrium: CA: 5 (5%) KM: 7 (6%) p=0.55 Duration of pre-surgical AF (yrs): CA: 5.7[5.4] KM: 5.7[5.6] p=0.64 > 10 yrs: CA: 22 (20%) KM: 22(20%) Exclusion Criteria: Patients who died during hospitalisation. p=1.0 Pre-surgical atrial size: Mean left atrial diameter (mm): CA: 56.6[9.9] KM: 55.8[10.6] p=0.66 > 70 mm: CA: 8 (7%) KM: 8 (7%) p=1.0 Pre-surgical LVEF (%): Not stated Study Period: 5/92-6/01 Indication for concurrent surgery: Coronary artery disease: CA: 9 (8%) KM: 2 (2%) p=0.03 Operator Details: Not stated Underlying heart disease: Not stated Other: NYHA class: I/II: CA: 101 (90%) KM: 88 (82%) p=0.01 III/IV: CA: 9 (10%) KM: 22 (20%) Previous cardiac surgery: CA: 11 (10%) KM: 11 (10%) p=1.0 f-wave in V1 lead (mV): CA: 0.18[0.12] KM: 0.17[0.13] p=0.63 Cardiothoracic ratio (%): CA: 59.5[6.7] KM: 60.5[7.0] p=0.11 Left ventricular diastolic diameter (mm): CA: 54.2[10.3] KM: 52.7[10.1] p=0.14 204 Authors Nakajima et al. 2002 continued Intervention Study design Type of concurrent surgery: All patients had MV surgery. Mechanical valve replacement: CA: 61 (55%) KM: 61 (55%) p=1.0 Repair or biological valve replacement: CA: 49 (45%) KM: 49 (45%) p=1.0 Aortic valve procedure: CA: 34 (31%) KM: 34 (31%) Tricuspid annuloplasty: CA: 20 (18%) KM: 33 (30%) p=0.04 CABG: CA: 9 (8%) KM: 3 (3%) p=0.07 Medication: Perioperative AF or atrial flutter treated with group Ia and Ic antiarrhythmic drugs. Verapamil or β-blocker added for treatment of high ventricular rate. Group III antiarrhythmic drugs, sotalol or amiodarone, never been used. Antiarrhythmic drugs gradually withdrawn 3 months postoperative. Warfarin routinely administered to all patients for 3 months. If SR maintained, anticoagulation terminated in patients with MVP or biological valve implantation. Then small dose of aspirin given if contraction of left atrium absent or LA > 55mm. Pacemaker: Not stated Cardioversion: Performed if necessary. Electrocardiogram: Constantly monitored until cardiac rhythm became stable. At follow-up 3 monthly. Echocardiography: Echocardiography with pulsed Doppler study every 3 months on follow-up. Study population Left ventricular systolic diameter (mm): CA: 37.0[8.7] KM: 37.0[8.7] p=0.66 Fractional shortening (%): CA: 32.1[0.8] KM: 31.2[0.9] p=0.63 205 Inclusion/Exclusion criteria Appendix C.1.5: Intraoperative ablation- Cryotherapy Comparative Internal Comparison Kosakai maze + RAA versus - RAA Authors Intervention Yoshihara et al. 2000 Patients underwent either a Kosakai Maze, including RAA excision (KMR-) or a Kosakai Maze with retention of the RAA (KMR+) Lesion device: CRYOABLATION/ Device not stated. Energy level: Not stated Energy rate: Not applicable Lesion set: Kosakai Maze. The only difference in the KMR+ group was that instead of the RA appendectomy, right atriotomy and cryoablation were extended to the tip of the RAA. Left lesions: Cryoablation from the circumferential atriotomy toward the LAA, and the interatrial septum from both the left and right atria to reinforce transmural penetration of cryothermia. Right lesions: Cryoablation of the end of the right atriotomies, tricuspid annulus, and junction with the inferior vena cava. Atrial appendages: RAA and LAA amputated. Atrial incisions: From the incision made for RAA amputation the right atriotomy is extended in curvilinear fashion to the junction with the inferior vena cava. From the midpoint of this atriotomy an additional incision started toward the tricuspid annulus. Superior vena cava is transacted distal to the junction with the RA. Left atrium entered in front of right pulmonary veins as in regular MV operation. Left atriotomy extended to encircle the orifices of the pulmonary veins. At the circumferential atriotomy, the left ventricle was disconnected from the pulmonary veins and suspended with LA cuff to facilitate atriotomy and ablation. Order of surgery: Not stated Description of surgery from Kosakai et al. 1994 Both groups Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Type of concurrent surgery: Open mitral commissurotomy: KMR-: 1 KMR+: 2 p=0.68 MVR: KMR-: 14 KMR+: 11 p=0.68 MVP: KMR-: 5 KMR+: 6 p=0.68 Ventricular septal defect closure: KMR-: 2 KMR+: 0 p=0.33 ASD closure: KMR-: 0 KMR+: 1 Plus AVR: KMR-: 7 KMR+: 5 Medication: Furosemide and dopamine were administered after surgery. Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Performed before and about 3 wks after surgery. J Thorac Cardiovasc Surg 2000;119:790794 Location National Cardiovascular Center Research Institute, the Division of Cardiovascular Surgery and Hypertension, and the Department of Cardiovascular Medicine, Okayama University Medical School, Okayama, Japan Study design Level of Evidence: III-3 Study population Inclusion/Exclusion criteria Sample Size: KMR-: n= 22 KMR+: n=20 Inclusion Criteria: Patients with AF as a result of organic heart disease. Patient Diagnosis: AF Intention-to-Treat Analysis: Not stated Basis of Patient Selection: Consecutive patients in both groups. Mean Age: KMR-: 57.2[9.4] KMR+: 53.1[7.4] p=0.12 Gender Mix (male/female): KMR-: 16/6 KMR+: 10/10 p=0.13 Patient Co-morbidities: Not stated Follow-up: Not stated Duration of pre-surgical AF (months): Not stated Eligibility Rate: Not stated Lost to Follow-up: None Study Period: KMR-:11/94-6/95 KMR+: 5/98-1/99 Operator Details: Not stated Pre-surgical atrial size: Left atrial dimension (mm): KMR-: 57.8[12.9] KMR+: 55.8[9.0] p=0.59 Pre-surgical LVEF (%): KMR-: 47.8[13.8] KMR+: 51.5[8.7] p=0.39 Indication for concurrent surgery: Mitral stenosis: KMR-: 9 KMR+: 10 Mitral regurgitation: KMR-: 7 KMR+: 5 Mitral stenosis + regurgitation: KMR-: 4 KMR+: 4 p=0.84 Ventricular septal defect: KMR-: 0 KMR+: 1 Atrial septal defect: KMR-: 2 KMR+: 0 p=0.33 Aortic valve diseases: KMR-: 7 KMR+: 5 Underlying heart disease: Not stated Other: Body surface area (m2): KMR-: 1.64[0.16] KMR+: 1.57[0.20] p=0.21 Cardiac Index (L/min/m2): KMR-: 2.6[0.5] KMR+: 2.6[0.8] p=0.86 Left ventricular dimension in end-diastole (mm): KMR-: 53.0[13.2] KMR+: 52.8[7.0] p=0.96 Left ventricular fractional shortening (%): KMR-:32.7[7.5] KMR+: 32.4[8.4] p=0.90 206 Exclusion Criteria: Not stated Appendix C.1.6: Intraoperative ablation- Cryotherapy Comparative Internal Comparison Biatrial CA versus Left atrial CA Authors Intervention Takami et al. 1999 Patients received either biatrial CA with cardiac surgery (BACA), or a simplified left atrial cryoablation with cardiac surgery (LACA). Patients also subdivided into those who underwent MV operations with or without tricuspid annuloplasty, (BACA/M (n=21) and LACA/M (n=15)) Lesion device: CRYOABLATION/ Not stated Energy level: -60o C for 1.5 minutes. Energy rate: Not applicable Lesion set: BACA: Left lesions: Ablation from LA incision to the posterior MV annulus and interatrial septum. Right lesions: Ablation delivered toward the RA free wall and the tricuspid ring at the site of the base of the posterior leaflet. Superior and inferior vena cavae ablated longitudinally on the anterior aspect. Atrial appendages: LAA and RAA excised. Atrial incisions: Right-sided left atriotomy extended circularly extending to the base of the excised LAA. Right atrial incision parallel to the interatrial sulcus extended toward the TV. Order of surgery: Surgery performed after clamping the aorta. LACA: Left lesions: Cryoablation toward the incision ridge between the upper and lower left pulmonary veins from the base of the excised LAA to the left upper atrial incision edge, from the left lower atrial incision edge to the posterior MV annulus, and the interatrial septum. Right lesions: Additional cryoablation directed toward the RA isthmus between the tricuspid annulus and inferior vena cava to prevent postoperative atrial flutter. Atrial appendages: LAA excised. Atrial incisions: Right atrium incised obliquely to insert a cannula into the coronary sinus for cardioplegia. Right-sided left atriotomy extended to left margin of the left pulmonary veins. Order of surgery: Aorta cross clamped prior to ablation. Both groups Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Retrograde cardioplegia in LACA. Body temperature: Not stated Type of concurrent surgery: MVR: BACA: 10 LACA: 9 MVR+TV annuloplasty: BACA: 8 LACA: 5 MVR+CABG: BACA: 1 LACA: 0 MVP: BACA: 3 LACA: 1 AVR: BACA: 3 LACA: 0 AVR+MVR: BACA: 3 LACA: 2 AVR+MVR+ tricuspid annuloplasty: BACA: 2 LACA: 2 TVR: BACA: 0 LACA: 1 Medication: Not stated Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: 12 lead ACG at hospital discharge and > 6 months postoperative Echocardiography: Not stated J Card Surg 1999;14:103-108 Location Nagoya University School of Medicine, Department of Thoracic Surgery, Nagoya, Japan Study design 207 Level of Evidence: III-3 Retrospective study Intention-to-Treat Analysis: Not stated Basis of Patient Selection: Not stated Study population Sample Size: BACA: 30 LACA: 20 Patient Diagnosis: AF Mean Age (yrs): BACA: 54.7[8.8] LACA: 58.3[8.7] Gender Mix (male/female): BACA: 11/19 LACA: 9/11 Patient Co-morbidities: Not stated Follow-up (months): BACA: 34.1[11.3] (range 15-51) LACA: 17.8[3.8] (range 8-23) Left atrial diameter (mm): BACA: 52.0[9.5] LACA: 52.3[6.4] pns Eligibility Rate: Not stated Pre-surgical LVEF (%): BACA: 60.1[16.0] LACA: 58.7[12.2] pns Lost to Follow-up: Not stated Indication for concurrent surgery: MV disease: BACA: 27 LACA: 19 AV disease: BACA: 8 LACA: 4 Tricuspid valve disease: BACA: 10 LACA: 8 Study Period: Not stated Operator Details: Not stated Inclusion/ Exclusion criteria Inclusion Criteria: AF Duration of pre-surgical AF (months): Underlying heart disease: Not stated Other: Cardiac index (l/min/m2): BACA: 2.42[0.46] LACA: 2.59[0.52] pns Cardiothoracic ratio (%): BACA: 61.9[6.9] LACA: 59.2[5.8] pns Heart rate (beats/min): BACA: 82.4[11.7] LACA: 85.1[15.3] pns F wave voltage in V1 lead (mV): BACA: 0.25[0.17] LACA: 0.19[0.12] pns QRS (ms): BACA: 97.1[11.5] LACA: 101.0[11.5] pns QTc (ms): BACA: 429.7[33.7] LACA: 432.2[32.1] pns Exclusion Criteria: Not stated Appendix C.1.7: Authors Schaff et al. 2000 Sem Thorac Cardiovasc Surg 2000;12:30-37 Location Division of Cardiovascular Surgery, Mayo Clinic and Mayo Foundation, Rochester, MN, USA Intraoperative ablation- Cryotherapy Comparative Internal Comparison Biatrial CA versus Right atrial CA Intervention Patients underwent a modified maze with cryoablation (CA), or a modified right maze with cryoablation (RACA). Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Lesion device: CRYOABLATION/ Not stated Energy level: Not stated Energy rate: Not applicable Surgery: Modified maze: Similar to Maze-III. The two modifications are: Right lesions: The incision along the medial aspect of the RA from the tricuspid valve annulus to the cut edge of the RAA is replaced by a line of cryolesions to minimise the risk of interruption of coronary blood supply to the sinoatrial node. Atrial incisions: To facilitate closure of the LA incisions, the LAA is inverted and amputated after making a standard left atriotomy and incising the interatrial septum. The LA incision that encircles the pulmonary veins joins the orifice of the LAA, and this orifice is closed horizontally rather than perpendicularly to the encircling incision. Modified right maze: Right lesions: As for the Modified Maze Left lesions: None Type of concurrent surgery: Valve repair/replacement: CA: 99 RACA: 40 (tricuspid) Congenital: CA: 9 RACA: 2 CABG: CA: 15 RACA: 0 None: CA: 50 RACA: 0 Medication: Patients given diuretics, most commonly furosemide, until weight is below that measured preoperatively. Systemic anticoagulation with Coumadin (sodium warfarin; Dupont Merck Pharmaceutical Company, Wilmington, DE, USA) during the first 6 weeks postoperatively. Pacemaker: 8/221 patients had pacemakers placed preoperatively. Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Not stated Study design Level of Evidence: III-2/3 Study population Sample Size: CA: 173 RACA: 42 Patient Diagnosis: AF Basis of Patient Selection: Not stated Mean Age (y): CA: 60 RACA: 40 Eligibility Rate: Not stated Gender Mix (male/female): CA: 116/57 RACA: 22/20 Follow-up (months): Not stated Patient Co-morbidities: Not stated Lost to Follow-up: Not stated Duration of pre-surgical AF: Not stated Pre-surgical atrial size: Not stated Study Period: 3/93-3/99 The study period for each group was not stated. Indication for concurrent surgery: Not stated Operator Details: Not stated Underlying heart disease: Not stated 208 Pre-surgical LVEF (%): Not stated Inclusion/Exclusion criteria Inclusion Criteria: AF Exclusion Criteria: Not stated Appendix C.1.1: Authors Kosakai 2000 Sem Thorac Cardiovasc Surg 2000;12:44-52 Location Cardiovascular Surgery, Takarazuka Municipal Hospital, Kohama, Takarazuka, Hyogo, Japan Intraoperative ablation- Cryotherapy Comparative Internal Comparison Kosakai maze versus CA Questionnaire Intervention Patients operated on using Maze-III (M-III) or Kosakai Maze (KM) procedures. Patients divided into those with AF alone (L), AF associated with MV disease (MV), AF associated with congenital heart disease (C), and those with no cause-and-effect relationship between the basic ailment and AF (O). Note: Maze-II, and left- and right-sided Maze procedures were excluded from the results. Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Lesion device: Not stated Energy level: Not stated Energy rate: Not stated Surgery: Kosakai-Maze procedure (n=1119). Left lesions: Cryoablation from the circumferential atriotomy toward the LAA, and the interatrial septum from both the left and right atria to reinforce transmural penetration of cryothermia. Right lesions: Cryoablation of the end of the right atriotomies, tricuspid annulus, and junction with the inferior vena cava. Atrial appendages: RAA and LAA amputated. Atrial incisions: From the incision made for RAA amputation the right atriotomy extended in curvilinear fashion to the junction with the inferior vena cava. From the midpoint of this atriotomy an additional incision started toward the tricuspid annulus. Superior vena cava transacted distal to the junction with the RA. Left atrium entered in front of right pulmonary veins as in regular MV operation. Left atriotomy extended to encircle the orifices of the pulmonary veins. At the circumferential atriotomy, the left ventricle was disconnected from the pulmonary veins and suspended with the LA cuff to facilitate atriotomy and cryoablation. Order of surgery: Not stated Description of surgery from Kosakai et al. 1994 Type of concurrent surgery: Not stated Medication: Not stated Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Not stated Study design Level of Evidence: III-3 Questionnaire Basis of Patient Selection: A questionnaire sent to 517 Japanese hospitals that perform cardiac surgery. Answers returned from 288 hospitals stating 2547 treatments for AF or atrial flutter performed. Eligibility Rate: Not stated Study population Sample Size: M-III: n=835 KM: n=1119 L: M-III: n=13 KM: n=34 Inclusion/Exclusion criteria Inclusion Criteria: Patients with AF. Patient Diagnosis: AF Exclusion Criteria: Not stated Mean Age (y): Not stated Gender Mix (male/female): Not stated Patient Co-morbidities: Not stated Duration of pre-surgical AF: Not stated Pre-surgical atrial size: Mean left atrial diameter (mm): Not stated Follow-up: Not stated Pre-surgical LVEF (%): Not stated Lost to Follow-up: Not stated Indication for concurrent surgery: Not stated Study Period: Not stated Underlying heart disease: Not stated Operator Details: Not stated 209 Appendix C.1.9: Intraoperative ablation- Cryotherapy Case Series Biatrial CA Authors Intervention Ad et al. 2003 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Lesion device: CRYOABLATION/ Not stated Energy level: Not stated Energy rate: Not applicable Surgery: Cox-Maze III with cryoablation replacing incisions. Specific surgical details not given. Left lesions: Right lesions: Atrial appendages: Atrial incisions: Order of surgery: Type of concurrent surgery: Combined valve surgery: 51 with 82 procedures Medication: Not stated Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Not stated The Society for Heart Valve Disease 2nd Biennial Meeting 2003 (abstract) Location Hadassah University Hospital, Jerusalem, Israel Study design Level of Evidence: IV Study population Inclusion/Exclusion criteria Sample Size: n=106 Inclusion Criteria: AF Patient Diagnosis: AF Basis of Patient Selection: Not stated Mean Age (y): Not stated Eligibility Rate: Not stated Gender Mix (male/female): Not stated Follow-up (months): 19[5] Patient Co-morbidities: Not stated Lost to Follow-up: Not stated Duration of pre-surgical AF (yrs): Not stated Study Period: 1/00-03 Pre-surgical atrial size: Not stated Pre-surgical LVEF (%): Not stated Operator Details: Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Rheumatic heart disease: 23/51 210 Exclusion Criteria: Not stated Appendix C.1.9: Intraoperative ablation- Cryotherapy Case Series Biatrial CA continued Authors Intervention Ad et al. 2003 Surgical access: Not stated AHA (abstract) CPB Cannulation: Not stated Location Hadassah University Hospital, Jerusalem, Israel Study design Level of Evidence: IV Study population Inclusion/Exclusion criteria Sample Size: n=50 Inclusion Criteria: AF Patient Diagnosis: AF Cardioplegia: Not stated Basis of Patient Selection: Not stated Mean Age (yrs): 63{9} Body temperature: Not stated Eligibility Rate: Not stated Gender Mix (male/female): 20/30 Lesion device: CRYOABLATION/ Not stated Follow-up (months): 8.3[3.1] Patient Co-morbidities: Not stated Energy level: Not stated Energy rate: Not applicable Surgery: A complete bi-atrial maze using cryothermal energy only. Specific details of the surgical procedure were not given. Duration of pre-surgical AF(yrs): 5.7 (range 0.25-25) Lost to Follow-up: Not stated Pre-surgical atrial size: Left atrial size (cm): 6.43{0.31} (range 4.9-9.1) Study Period: 1/02-5/03 Pre-surgical LVEF (%): Not stated Operator Details: Not stated Type of concurrent surgery: Lone: 5/50 (10%) Combined with 67 surgical procedures: 45/50 (90%) Indication for concurrent surgery: Valve disease: 86% Underlying heart disease: Rheumatic heart disease: 60% Medication: Not stated Other: Previous surgery: 18% Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Not stated 211 Exclusion Criteria: Not stated Appendix C.1.9: Intraoperative ablation- Cryotherapy Case Series Biatrial CA continued Authors Intervention Arai et al. 1999 Surgical access: Not known CPB Cannulation: Not known Cardioplegia: Not known Body temperature: Not known Lesion device: CRYOABLATION/ Energy level: Not known Energy rate: Not known Surgery: Kosakai maze Left lesions: Cryoablation from the circumferential atriotomy toward the LAA, and the interatrial septum from both the left and right atria to reinforce transmural penetration of cryothermia. Right lesions: Cryoablation of the end of the right atriotomies, tricuspid annulus, and junction with the inferior vena cava. Atrial appendages: RAA and LAA amputated. Atrial incisions: From the incision made for RAA amputation the right atriotomy extended in curvilinear fashion to the junction with the inferior vena cava. From the midpoint of this atriotomy an additional incision started toward the tricuspid annulus. Superior vena cava transacted distal to the junction with the RA. Left atrium entered in front of right pulmonary veins as in regular MV operation. Left atriotomy extended to encircle the orifices of the pulmonary veins. At the circumferential atriotomy, the left ventricle was disconnected from the pulmonary veins and suspended with the LA cuff to facilitate atriotomy and cryoablation. Order of surgery: Not stated Description of surgery from Kosakai et al. 1994 Type of concurrent surgery: MVP+TAP: 3 MVP+TAP+AVR: 1 MAP+TAP: 7 MAP+TAP+AVR: 1 MAP+TAP+CABG: 1 MVR+TAP:8 MVR+TAP+AVR: 2 MVR+TAP+CABG: 2 MVR+AVR: 1 MVP+AVR: 1 AVR: 1 Atrial septal defect repair + TAP: 2 Medication: Not known Pacemaker: Not known Cardioversion: Not known Electrocardiogram: Not known Echocardiography: Not known Jpn J Thorac Surg 1999;52:379-383 (Japanese paper, data taken from English abstract and tables) Location Department of Cardiovascular Surgery, Kumamoto Central Hospital, Kumamoto, Japan Study design Level of Evidence: IV Study population Inclusion/Exclusion criteria Sample Size: n=30 Inclusion Criteria: AF Patient Diagnosis: AF Basis of Patient Selection: Not known Eligibility Rate: Not known Follow-up (months): 12.3 (range 1-25) Lost to Follow-up: Not known Study Period: 10/95-10/97 Operator Details: Not known Mean Age (y): 60.9 (range 37-75) Gender Mix (male/female): Not known Patient Co-morbidities: Not known Duration of pre-surgical AF: Not known Pre-surgical atrial size: Mean left atrial diameter (mm): Patients with restored SR: 51.2[7.8] Patients remaining in AF: 63.8[19.5] p<0.05 Pre-surgical LVEF (%): Patients with restored SR: 70.5[11.7] Patients remaining in AF: 67.6[13.7] Indication for concurrent surgery: Not known Underlying heart disease: Not known Other: Cardiothoracic Ratio: Patients with restored SR: 59.2[5.4] Patients remaining in AF: 67.7[8.1] p<0.05 NYHA class: Patients with restored SR: 2.65[0.75] Patients remaining in AF: 2.78[0.67] pns 212 Exclusion Criteria: Not known Appendix C.1.9: Intraoperative ablation- Cryotherapy Case Series Biatrial CA continued Authors Intervention Study design Study population Fukada et al. 1998 Patients divided into those with postoperative atrial rhythm (AR; n=17) and those without atrial rhythm (NAR; n=12) Surgical access: Not stated CPB Cannulation: Bicaval venous drainage, direct cannulation of superior vena cava and cannulation of inferior vena cava through lower RA. Cardioplegia: Not stated Body temperature: Not stated Lesion device: CRYOABLATION/ Device not stated. Energy level: -60 oC for 1 minute. Energy rate: Not applicable Surgery: Left ablations: Cryoablation directed toward the incisional ridge between the upper and lower left pulmonary veins, from the base of the excised LAA to left upper atrial incisional edge, and from the edge of the left lower atrial incision into the posterior MV annulus. Right ablations: The lateral RA incision towards the inferior vena cava, and the tricuspid annulus were cryoablated. A posterior longitudinal line from the superior vena cava to the inferior vena cava was ablated. Atrial appendages: RAA and LAA amputated. Atrial incisions: Lateral incision, parallel to right AV groove, made from the base of the excised RAA toward the inferior vena cava. From the midpoint of this atriotomy, a T incision was begun toward the tricuspid annulus. A left vertical atriotomy was extended to the left margin of the left pulmonary veins. Sequence of surgery: On CPB the RAA was amputated. Cryoablation was performed after onset of cardiac arrest. The tricuspid annulus was ablated later. Left atrial incision made, the LAA excised, and left ablations performed. Concomitant surgical procedures then performed. Type of concurrent surgery: Aortic, mitral and tricuspid operations: 4 Mitral and tricuspid operations: 13 MV alone: 8 Medication: Digoxin and procainamide administered in all patients for 2 wks. Then converted to oral route and continued until 3 months postoperatively. Patients with combined valve replacement continued to have warfarin, and the other patients with MVP or commissurotomy were treated with aspiring for 3 months postoperatively. Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Transthoracic at a mean of 3.8[3.5] months (range 1-11 months) postoperatively. Other: Cardiac catheterisation for haemodynamic assessment before and 1 month postoperatively. Level of Evidence: IV Sample Size: n=29 Basis of Patient Selection: Consecutive patients Patient Diagnosis: AF Ann Thorac Surg 1998;65:1566-70 Location Department of Thoracic and Cardiovascular Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan Eligibility Rate: Not stated Mean Age (yrs): 59.8[10.5] (range 34-74) Gender Mix (male/female): 14/15 Follow-up: Follow-up to echocardiography in patients with SR (17/29): Rheumatic (n=10): 3.2[2.5] months Non-rheumatic (n=7): 4.5[4.4] months Patient Co-morbidities: Not stated Duration of pre-surgical AF: Not stated Pre-surgical atrial size: Mean left atrial diameter (mm): Not stated Lost to Follow-up: Not stated Pre-surgical LVEF (%): Not stated Study Period: 1/95-3/97 Indication for concurrent surgery: Not stated Operator Details: Not stated Underlying heart disease: Rheumatic: 22 Nonrheumatic mitral regurgitation: 7 Annular dilatation: 2/7 Leaflet prolapse: 4/7 Chordal rupture: 1/7 213 Inclusion/Exclusion criteria Inclusion Criteria: AF Exclusion Criteria: Not stated Appendix C.1.9: Intraoperative ablation- Cryotherapy Case Series Biatrial CA continued Authors Intervention Izumoto et al. 2000 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Moderate hypothermia Lesion device: CRYOABLATION/ Not stated Energy level: Not stated Energy rate: Not applicable Surgery: Atriotomies basically the same as Maze-III with cryoablation replacing some of the atriotomies (Note: Not the same as the Kosakai Maze). Left ablations: An ablation line completed the left atriotomy to encircle the pulmonary veins. Another line from the left atriotomy connected the right vertical ablation line, plus a line towards the mitral annulus. Also an ablation line from circumferential ablation near the left superior pulmonary vein to the base of the LAA. Right ablations: An ablation line to replace the posterior longitudinal right atriotomy, and a line in the anterior limbus. Atrial appendages: LAA and RAA excised. Atrial incisions: The standard left atriotomy was extended inferiorly and superiorly around the left superior and inferior pulmonary veins. Sequence of surgery: After CPB and cardioplegic arrest, the left atriotomy was performed. The LAA was excised, and the left ablations performed. The left atriotomy was closed halfway and the MV procedure performed if needed. After complete closure of the left atriotomy, caval snares were tightened and the RAA excised. Right atriotomy made, and right cryoablations completed. (Kamata et al. 1997) Type of concurrent surgery: MVR: 30 MV repair: 48 AVR: 8 AV repair: 1 CABG: 2 Other cardiac operations: 11 Subgroup: MVR: SR: 5 AF: 3 MVP: SR: 7 AF: 7 Open mitral commissurotomy: SR: 2 AF: 3 Direct closure: SR: 1 AF: 1 Patch closure: SR: 1 AF: 0 Medication: Anticoagulation therapy started when recurrence of AF documented. Inotropes administered to every patient postoperatively. Pharmacological suppression used when haemodynamically significant supraventricular tachyarrhythmia occurred. The use and choice of antiarrhythmics was by preference of the referring cardiologists, if any. Patients with AF and/or mechanical cardiac valve(s) were anticoagulated permanently. Patients with repaired valve or implanted biological valves were anticoagulated temporarily for 3 months. Pacemaker: Not stated Cardioversion: Used if other methods unsuccessful. Electrocardiogram: Not stated Echocardiography: Not stated Eur J Cardiothoracic Surg 2000;17:25-29 JJTCVS 2001;49:5861 Ann Thorac Surg 1998;66:800-804 J Cardiovasc Surg 1998b J Thorac Cardiovasc Surg 1997 Location Department of Cardiovascular Surgery, Iwate Medical University Memorial Heart Center, Iwate Medical University, Morioka, Iwate, Japan Study design Study population Inclusion/Exclusion criteria Level of Evidence: IV Retrospective data collection. Sample Size: n=104 Subgroup 1: Patients with restored SR (SR; n=15) or who remained in AF (AF; n=15) (Izumoto et al. 1998). Inclusion Criteria: Chronic AF and cardiac surgery Patient Diagnosis: Chronic AF (> 3 month duration) Exclusion Criteria: Not stated Basis of Patient Selection: Consecutive patients Eligibility Rate: Not stated Follow-up (months): 44.6[1.1] Lost to Follow-up: Follow-up complete in 99/100 (99%) of long term survivors 98/104 at 12 months 97/104 at 24 months 92/104 at 36 months 58/104 at 48 months 14/104 at 60 months Study Period: 3/93-8/95 Clinical data collected between 6-7/98. Operator Details: Not stated Mean Age (yrs): 59.7 (range 21-77) (n=100) Subgroup 1: SR: 61.3[9.1] AF: 63.7[6.3] pns Gender Mix (male/female): 45/55 (n=100) Subgroup 1: SR: 5/10 AF: 6/9 pns Patient Co-morbidities: History of hypertension: MVP: 12/56 (21.4%) MVR: 1/31 (3.2%) 4/87 (4.6%) diabetic 3/87 (3.4%) hyperlipidaemia (n=87; Izumoto et al. 1998) Duration of pre-surgical AF (months): Total: 119.1[83.2] (range 5-360) MVP: 116.8[82.0] MVR: 123.1[86.4] (n=87; Izumoto et al. 1998) Pre-surgical atrial size: Subgroup 1: Left atrial dimension (mm): SR: 58.8[11.3] AF: 73.3[14.3] p<0.01 (n=86; Izumoto et al. 1998b). Pre-surgical LVEF (%): Subgroup 1: SR: 59.1[13.3] AF: 60.5[12.1] pns (n=86; Izumoto et al. 1998b). Indication for concurrent surgery: MV disease: 78 Aortic valve disease: 9 Congenital heart diease: 8 Other cardiac diseases: 5 Subgroup 1: Mitral regurgitation: SR: 10 AF: 6 Mitral stenosis: SR: 3 AF: 4 Mitral stenosis + regurgitation: SR: 1 AF: 3 Atrial septal defect: SR: 1 AF: 2 Underlying heart disease: Rheumatic heart disease: 49/87 214 Authors Intervention Study design Izumoto et al. 2000 continued Study population MVP: 22/56 (39.3%) MVR: 9/31 (29.0%) Congestive heart failure: 59/87 (67.8%) (n=87; Izumoto et al. 1998) Other: Previous cardiac surgery: 8/100 (8%) NYHA class: 2.5[0.7] Subgroup 1: HR at rest (beats/min): SR: 80.9[16.0] AF: 75.2[18.3] pns Maximal HR (beats/min): SR: 170.0[31.9] AF: 149.1[21.3] p<0.05 VT (mL/min/kg): SR: 12.6[1.7] AF: 12.5[2.4] pns Peak VO2 (ml/min/kg): SR: 19.1[4.5] AF: 17.0[3.1] pns Cardiac index (L/min/m2): SR: 2.4[0.4] AF: 2.7[0.5] pns Right atrial pressure (mmHg): SR: 3.3[2.2] AF: 7.6[3.0] p<0.01 Pulmonary capillary wedge pressure (mmHg): SR: 10.9[4.3] AF: 16.8[4.4] p<0.01 215 Inclusion/Exclusion criteria Appendix C.1.9: Intraoperative ablation- Cryotherapy Case Series Biatrial CA continued Authors Intervention Study design Study population Inclusion/Exclusion criteria Morishita et al. 2000 Surgical access: Not stated CPB Cannulation: Ascending aortic and bicaval cannulations. Venous return to the inferior vena cava was inserted via the RAA. Cardioplegia: Not stated Body temperature: Not stated Lesion device: CRYOABLATION/ 1.5 cm cryoprobe Energy level: -60 oC for 90 seconds Energy rate: Not applicable Surgery: Left ablations: Pulmonary veins isolated with cryoablation, and the space between the LAA and annulus of the MV and between the pulmonary vein isolation and annulus of the MV also cryoablated. Right ablations: The space between the T incision and the tricuspid valve annulus, and the space between the RAA and the anteromedial tricuspid valve and annulus were cryoablated. The space between the fossa ovalis and the longitudinal incision was ablated. Atrial appendages: LAA and RAA ligated. Atrial incisions: Standard left atriotomy. Lateral longitudinal incision of RA free wall, parallel to crista terminalis. A T incision made from a point one-third the distance below the longitudinal incision, and the incision extended to the tricuspid valve annulus. Atrial septum divided at the fossa ovalis alone. Sequence of surgery: Left atriotomy made under cross clamp. Left ablations performed, then left atriotomy sutured. Right atrial incision made, and the inferior vena cava venous return cannula moved from the RAA to the longitudinal incision. The right atrial incision was extended, and the right ablations performed. The T incision sutured, and the venous return cannula again placed in RAA insertion site. The space between the fossa ovalis and the right longitudinal incision was ablated, and the LAA ligated just before weaning from CPB, and the RAA ligated when removing the drainage tube. Type of concurrent surgery: None: 2 MVR: 6 MVR + tricuspid annuloplasty: 1 Tricuspid annuloplasty: 1 Double valve replacement: 2 Medication: Not stated Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Not stated Level of Evidence: IV Sample Size: n=12 Inclusion Criteria: Permanent atrial fibrillation. Basis of Patient Selection: Patient Diagnosis: AF Eligibility Rate: Not stated Mean Age (yrs): 60.6[10.6] (range 47-77) Follow-up: Not stated Gender Mix (male/female): 8/4 Lost to Follow-up: 1/12 patients died. Follow-up incomplete in 1/12. Patient Co-morbidities: Thromboembolism: 1 (8.3%) Chronic heart failure: 8 (66.7%) J Cardiovasc Surg 2000;41:575-577 Location Department of Cardiovascular Surgery, Gunma Heart Institute, Gunma, Japan Study Period: 7/95-12/96 Operator Details: Not stated Duration of pre-surgical AF: 9.0[9.5] (range 0.5-30) Pre-surgical atrial size: Mean left atrial diameter (cm): 5.2[1.0] Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Mitral stenosis: 4 Tricuspid regurgitation: 2 Mitral regurgitation: 5 Aortic stenosis: 1 Dilated cardiomyopathy: 1 Post-AVR: 1 Underlying heart disease: Not stated Other: Cardiothoracic ratio (%): 58.6[9.4] NYHA class: II: 3 III: 5 IV: 4 216 Exclusion Criteria: Not stated Appendix C.1.9: Intraoperative ablation- Cryotherapy Case Series Biatrial CA continued Authors Intervention Shimizu et al. 1997 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Lesion device: CRYOABLATION/ Device not stated Energy level: Not stated Energy rate: Not applicable Surgery: Left lesions: Cryoablation from the circumferential atriotomy toward the LAA; the interatrial septum from both the left and right atria to reinforce transmural penetration of cryothermia; and to the mitral annulus. Right lesions: Cryoablation of the end of the right atriotomies, tricuspid annulus, and junction with the inferior vena cava. Atrial appendages: RAA and LAA amputated Atrial incisions: From the incision made for RAA amputation the right atriotomy extended in curvilinear fashion to the junction with the inferior vena cava. From the midpoint of this atriotomy an additional incision started toward the tricuspid annulus. Superior vena cava is transacted distal to the junction with the right atrium. Left atrium entered in front of right pulmonary veins as in regular MV operation. Left atriotomy extended to encircle the orifices of the pulmonary veins. At the circumferential atriotomy, the left ventricle was disconnected from the pulmonary veins and suspended with left atrial cuff to facilitate atriotomy and cryoablation. Order of surgery: Not stated From Kosakai et al. Type of concurrent surgery: None Medication: Following surgery patients discharged without antiarrhythmic therapy. Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: standard ECG used to monitor rhythm and Holter monitor at 1, 3, 6 and 12 months and every 6 months thereafter. Echocardiography: Not stated Other: Electrophysiological studies performed before and 35[8] days (range 2243 d) postoperative. Performed without sedation during post-absorptive state after all antiarrhythmic medications discontinued for at least 5 drug half-lives. Jpn Circ J 1997;61:988-996 Location Division of Cardiology, Department of Internal Medicine, and Department of Cardiovascular Surgery, National Cardiovascular Center, Suita, Osaka, Japan Study design Level of Evidence: IV Study population Inclusion/Exclusion criteria Sample Size: n=6 Inclusion Criteria: Lone and paroxysmal AF. Patient Diagnosis: Lone and paroxysmal AF Basis of Patient Selection: Not stated Mean Age (y): 47[7] (range 37-54) Eligibility Rate: Not stated Gender Mix (male/female): 6/0 Follow-up (months): 21[11] (range 4-32) Patient Co-morbidities: Not stated Duration of pre-surgical AF (yrs): 8[7] (range 4-23) Lost to Follow-up: Not stated Pre-surgical atrial size: Mean left atrial diameter (mm): ‘within normal range’. Study Period: Not stated Pre-surgical LVEF (%): Not stated Operator Details: Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Not stated Other: Cardiothoracic ratio ‘within normal range’. Episodes of AF without medication during Holter recording (no/day): 11[8] (range 2-38) Mean duration of single episode of AF (hr): 3.6[5.2] 6/6 patients had rapid ventricular conduction during episodes of AF with mean heart rate 152[21] beats/min No of antiarrhythmic drugs: 8.7[1.4] (range 7-11) Note: drugs (eg. digoxin and β-adrenergic antagonists) ineffective in preventing episodes of AF or lessening associated symptoms. Electrophysiological data before surgery: Sinus Cycle Length (ms): 902[103] (range 750-1040) Sinus node recovery time (ms) : 1218[215] (range 920-1510) Corrected sinus node recovery time (ms): 316[154] (range 100-580) % sinus node recover time (%): 135[16] (range 112-162) Atrial-His conduction time (ms): 73[16] (range 45-90) His-Purkinji conduction time (ms): 45[4] (range 40-50) Maximum pacing rate at 1:1 AV (beats/min): 170[11] (range 150-180) AV nodal effective refractory period (ms): 237[29] (range 200-290) 217 Exclusion Criteria: Not stated Authors Intervention Study design Study population Atrial effective refractory period (ms) in: High right atrial lateral wall: 218[19] (range 190-240) Middle right atrial septum: 232[19] (range 200-250) Lateral coronary sinus: 225[24] (range 180-250) Fragmented atrial activity (ms): 37[24] (range 10-80) Conduction delay zone (ms): 37[16] (range 20-60) Mean activation time to: High right atrial anterolateral site (ms): 23[6] Low right atrial lateral site (ms): 39[10] High right atrial anteroseptal site (ms): 36[9] AF induced in all 6 patients (5 sustained, 1 non sustained) before surgery. Pacing protocols to induce AF included 2 extra stimuli at the high right atrial lateral wall during isoproterenol infusion (2 patients), 2 extra stimuli at the high right atrial lateral wall (2 patients) and a single extra stimulus at the lateral coronary sinus (1 patient). In the other patient the AF was spontaneously induced. Shimizu et al. 1997 continued 218 Inclusion/Exclusion criteria Appendix C.1.9: Yuda et al. 2001 J Am Coll Cardiol 2001;37:1622-1627 Yuda et al. 1998 J Am Coll Cardiol 1998;31:1097-1102 (subgroup for outcomes) Location Divisions of Cardiology and Cardiovascular Surgery, National Cardiovascular Center, Osaka, Japan Intraoperative ablation- Cryotherapy Case Series Biatrial CA continued Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Lesion device: CRYOABLATION/ Not stated Energy level: Not stated Energy rate: Not applicable Surgery: Left lesions: Cryoablation from the circumferential atriotomy toward the LAA, and the interatrial septum from both the left and right atria to reinforce transmural penetration of cryothermia. Right lesions: Cryoablation of the end of the right atriotomies, tricuspid annulus, and junction with the inferior vena cava. Atrial appendages: RAA and LAA amputated Atrial incisions: From the incision made for RAA amputation the right atriotomy extended in curvilinear fashion to the junction with the inferior vena cava. From the midpoint of this atriotomy an additional incision started toward the tricuspid annulus. Superior vena cava is transacted distal to the junction with the right atrium. Left atrium entered in front of right pulmonary veins as in regular MV operation. Left atriotomy extended to encircle the orifices of the pulmonary veins. At the circumferential atriotomy, the left ventricle was disconnected from the pulmonary veins and suspended with left atrial cuff to facilitate atriotomy and cryoablation. Order of surgery: Left atrium entered after institution of cardiac arrest, atriotomies and mitral valve surgery carried out before cryoablations. Tricuspid annuloplasty completed before aortic crossclamp released. Heart reperfused and right atrium closed. (Description of surgery from Kosakai et al. 1994) Type of concurrent surgery: MVR: 57 MVP: 32 Open mitral commissurotomy: 5 AVR: 26 AVP: 4 TAP: 34 CABG: 1 Left atrial plication: 8 Medication: Not stated Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: standard 12-lead ECG recorded from all patients every 2-3 days during hospital period and at regular monthly visits to hospital after discharge. Echocardiography: Transthoracic echocardiography performed before surgery (1.6[3.6] months), and early (< 6 months 3.1[3.3] months and late (> 1 y 2.2[0.9] y) after surgery. On Doppler echocardiography arbitrarily considered a peak A wave velocity ≥10cm/s was evidence of effective atrial contraction. Sample Size: n=94 Level of Evidence: IV Retrospective study Basis of Patient Selection: Consecutive except for 10 patients (see exclusion criteria). Patient Diagnosis: AF and mitral valve disease Mean Age (y): 58[9] (range 32-75) Gender Mix (male/female): 35/59 Patient Co-morbidities: Not stated Eligibility Rate: 94/104 consecutive patients used in study Follow-up: 2.2[0.9] y Early period: 3.1[3.3] months Late period: 2.2[0.9] yrs Duration of pre-surgical AF (yrs): 8.7[6.7] (range 0.5-30) Pre-surgical atrial size: Mean left atrial diameter (mm): 59[13] Pre-surgical LVEF (%): Not stated Lost to Follow-up: Not stated Study Period: 6/92-10/94 Operator Details: Not stated Indication for concurrent surgery: Mitral stenosis: 27 Mitral regurgitation: 37 Mitral stenosis + regurgitation: 18 Prosthetic mitral valve failure: 12 Underlying heart disease: Not stated Other: Left ventricular end-diastolic diameter (mm): 54[9] Left ventricular fractional shortening (%): 35[9] 219 Inclusion Criteria: MV disease and AF Exclusion Criteria: 10 patients excluded from analysis (3 patients who died during the hospital period and 7 patients who did not regularly visit the hospital after discharge). Appendix C.1.10: Intraoperative ablation- Cryotherapy Case Series Left atrial CA Authors Intervention Hoffmeister et al. 2003 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Lesion device: CRYOABLATION/ Not stated Energy level: Not stated Energy rate: Not applicable Surgery: Left lesions: Isolation of the pulmonary vein ostia, and extension of lesion lines to the mitral annulus. Right lesions: None Atrial appendages: LAA excised. Atrial incisions: Not stated Order of surgery: Not stated Type of concurrent surgery: Valvular surgery: 9/19 CABG: 4/19 Valvular surgery + CABG: 6/19 Medication: Not stated Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Not stated NASPE 2003 (Abstract #102610) Location Saint Elizabeths Medical Center, Boston, MA, USA Study design Level of Evidence: IV Study population Inclusion/Exclusion criteria Sample Size: n=19 Inclusion Criteria: Paroxysmal or chronic AF. Patient Diagnosis: Paroxysmal or chronic AF Basis of Patient Selection: Consecutive patients Mean Age (y): 65.2 Eligibility Rate: Not stated Gender Mix (male/female): 9/10 Follow-up (months): 28.8 (range 1-48) Patient Co-morbidities: Not stated Duration of pre-surgical AF: Not stated Lost to Follow-up: Not stated Pre-surgical atrial size: Left atrial dimension (mm): 4.5 Study Period: Not stated Pre-surgical LVEF (%): 37.9 Operator Details: Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Not stated 220 Exclusion Criteria: Not stated Appendix C.1.10: Intraoperative ablation- Cryotherapy Case Series Left atrial CA continued Authors Intervention Imai et al. 2001 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Cold blood cardioplegia Body temperature: Mild hypothermia Lesion device: CRYOABLATION/ T-shaped cryoprobe 20 mm in length and 8 mm in width. Energy level: -60 oC for 2 mins Energy rate: Not applicable Surgery: Left ablations: Cryoablation applied to posterior wall of LA between the upper and lower incision ridges. After encircling the orifices of four pulmonary veins, another two ablation lines added from encircling line of pulmonary veins toward the posterior MV annulus and toward the centre of the posterior MV annulus. Right ablations: None Atrial appendages: LAA excised. Atrial incisions: Left-sided vertical atriotomy extending to the left margin of the left pulmonary veins Sequence of surgery: Ablation first performed, then the concurrent surgery. Type of concurrent surgery: MVR: 8 TAP: 9 AVR: 6 CABG: 1 Closure of patent foramen ovale-closure: 1 TAP+AVR: 5 TAP+CABG: 1 TAP+closure of patent foramen ovale-closure: 1 TAP+ligation of patent ductus arteriosus: 1 TAP+AVR+CABG: 1 (Note: numbers= total procedures, not number of patients) 2 valves: 17 3 valves: 6 Medication: Antiarrhythmic agents of class I or IV and digitalis given in all patients postoperatively and discontinued at 3-6 months follow-up. Patients with AF continued medications. Pacemaker: 2 patients already had pacemakers due to symptomatic bradycardia. Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Not stated Ann Thorac Surg 2001;71:577-581 Note: may be limited overlap with Sueda et al. 2001 Location First Department of Surgery, Hiroshima University School of Medicine, Minamiku, Hiroshima, Japan Study design Level of Evidence: IV Retrospective data review Study population Inclusion/Exclusion criteria Sample Size: n=32 Inclusion Criteria: Chronic AF refractory to medical treatments. Patient Diagnosis: Chronic AF Basis of Patient Selection: 32 of unknown number with follow-up > 1 yr Mean Age (yrs): 64.2[7.9] (range 47-82) Eligibility Rate: Not stated Patient Co-morbidities: Not stated Follow-up (months): 36.9[14.1] (range 13-66) Total of 98.5 patient-years. Duration of pre-surgical AF (yrs): 9.3[7.2] (range 0.42-25) Lost to Follow-up: 26/32 at 1 yr, 20/32 at 2 yrs, 10/32 at 3 yrs, 6/32 at 4 yrs, 2/32 at 5 yrs, 0/32 at 6 yrs Study Period: 2/93Operator Details: All patients operated on by same surgical team. Gender Mix (male/female): 17/15 Pre-surgical atrial size: Mean left atrial diameter (mm): SR: 53.1[9.4] AF: 56.3[8.4] p=0.24 Pre-surgical LVEF (%): SR: 58.6[11.1] AF: 50.0[18.3] pns Indication for concurrent surgery: Mitral valve disease: Stenosis: 10 Regurgitation: 18 Stenosis + regurgitation: 4 Underlying heart disease: Rheumatic: 14 Degenerative: 18 Other: Amplitude of f-wave at lead V1 (mV): SR: 0.18[0.09] AF: 0.14[0.09] pns Cardiothoracic ratio (%): SR: 57.3[8.2] AF: 62.2[4.7] p=0.0775 221 Exclusion Criteria: Not stated Appendix C.1.10: Intraoperative ablation- Cryotherapy Case Series Left atrial CA Authors Intervention Kondo et al. 2003 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Warm blood cardioplegia Body temperature: Normothermia Lesion device: CRYOABLATION (n=30) and RADIOFREQUENCY (n=1)/ Not stated Energy level: Cryoablation at -60 oC for 2 minutes and RF energy at 1500 W and 70 oC for 2 minutes. Energy rate: Not applicable Surgery: Left ablations: Ablation between the upper and lower edge of the atriotomy encircling the orifices of the pulmonary veins. Isolation involved LAA and encircling ablated line, LAA, and posterolateral part of mitral annulus, lower atriotomy line, and middle part of mitral annulus. Right superior pulmonary vein was isolated individually. Right ablations: None Atrial appendages: Isolated using ablation. Performed ablation without excision or oversewing in cases in which there was no thrombus in LAA. Atrial incisions: Right-sided left atriotomy made and extended to left margin of left pulmonary veins. No atriotomy in atrial septum or RA if not necessary to perform surgery on tricuspid valve or annulus. Sequence of surgery: Ablation performed first then concomitant surgery. Type of concurrent surgery: MVR: 20 Mitral annuloplasty: 3 Open mitral commissurotomy: 6 AVR: 4 TVP: 7 CABG: 3 Medication: No patient was given special prophylactic medication postoperatively for prevention of AF. Patients with AF during hospitalisation given class I or IV antiarrhythmic agents. Medication gradually decreased if SR became stable. Warfarin used in every case of MVR or persistent AF. Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Used to evaluate postoperative rhythm. Echocardiography: transthoracic echocardiography preoperatively. Ann Thorac Surg 2003;75:1490-1494 Location Department of Cardiovascular Surgery, Aomori Rousai Hospital, Aomori, Japan Study design Level of Evidence: IV Study population Inclusion/Exclusion criteria Sample Size: n=31 Inclusion Criteria: Chronic AF refractory to medical treatment. Patient Diagnosis: chronic AF Basis of Patient Selection: Not known Mean Age (y): 59.8 (range 45-76) Eligibility Rate: Not stated Gender Mix (male/female): 13/8 Follow-up (months): 37.7[15.0] (range 12-60) Patient Co-morbidities: Repeated thromboembolism and thrombotic obstruction of the abdominal aorta: 2 (patients with lone AF) History of cerebral infarction: 8 Lost to Follow-up: 2/31 (6.5%) deaths Duration of pre-surgical AF (months): 77.3 (range 3-300) Study Period: 6/97-5/01 Operator Details: All patients had surgery by same surgeon and surgical team. Pre-surgical atrial size: Mean left atrial diameter (mm): left atrial dilatation in all patients Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Mitral regurgitation: 13 Mitral stenosis: 12 Mitral stenosis + regurgitation: 4 Aortic regurgitation: 5 Tricuspid regurgitation: 8 Angina pectoris: 3 Underlying heart disease: Not stated Other: Cardiomegaly in all patients. Previous open heart surgery: 7 (open mitral commissurotomy in 6 and correction of atrial septal defect in 1). 222 Exclusion Criteria: Not stated Appendix C.1.10: Intraoperative ablation- Cryotherapy Case Series Left atrial CA Authors Intervention Manasse et al. 2003 Surgical access: Not stated CPB Cannulation: Double venous cannulation, routine CPB. Cardioplegia: Cold cardioplegic arrest. Body temperature: Moderate hypothermia. Lesion device: CRYOABLATION/ Dual probe cryosurgical system (Frigitronics, Cooper Surgical, Shelton, CN, USA) maintaining the nitrous oxide pressure in the cylinders above 720 pounds/ square inch. Energy level: Applications of 2 min (or 3 min between the inferior left pulmonary vein and posterior mitral leaflet) at -60oC using two probes simultaneously to avoid any gap and reduce the overall application time. Energy rate: Not applicable Surgery: Left ablations: Three different lesion sets were used: 4PV (n=22) Four focal ablations of the pulmonary vein orifices. 7F (n=32) A continuous ablation line joined the right inferior pulmonary vein, right superior pulmonary vein, left superior pulmonary vein and left inferior pulmonary vein, and this was then connected to the MV. CT (n=41) There were three slightly different lesions patterns, all having in common the exclusion of the four pulmonary veins (hence the name ‘closed techniques). The first consisted of an ablation box around all four pulmonary veins, with separate lines between both inferior pulmonary veins and the MV. The second pattern was similar, with the only difference that the line between the right and left inferior pulmonary veins was not included. In the third variation the ablation box around the four pulmonary veins was used, but there was only one line to the MV, from the left inferior pulmonary vein. All ablation patterns: Right ablations: None Atrial appendages: The LAA was externally ligated when present. Atrial incisions: Paraseptal left atrial incision. Sequence of surgery: The left atrium was opened after cardioplegic arrest, and the ablations started. The concomitant procedure was carried out after the ablation. Type of concurrent surgery: MV surgery: 83 MVP: 22 MVP + CABP: 2 MVR: 36 MVR+CABP: 4 MVR+AVR: 5 MVR+TVP: 7 MVP+AVR: 2 MVP+TVP: 2 MVR+AVR:TVP: 2 MVR+ atrial septal defect: 1 Tricuspid valve surgery: 2 TVP: 1 TVP+ suture mitral prosthesis: 1 Aortic valve surgery: 8 AVR: 6 AVR + CABG: 2 Eur J Cardio-thorac Surg 2003;24:731740 Location Department of Cardiac Surgery, Istituto Clinico Humanitas, Milano, and Department of Cardiology, Ospedale di Asti, Asti, Italy Study design Level of Evidence: IV Prospective cohort study Basis of Patient Selection: Consecutive patients All patients but 2 referred for valvular disease (1 with lone AF and 1 with coronary disease). Eligibility Rate: Not stated Follow-up(months): Median 36 months (range 6-54) Lost to Follow-up: Follow-up in 86/95 Only 45/51 patients in SR had echocardiography at 3-9 months postoperatively. Study population Inclusion/Exclusion criteria Sample Size: n=95 4PV: n=22 7F: n=32 CT: n=41 Inclusion Criteria: All patients with permanent AF or persistent AF enrolled. Permanent AF= continuous AF not susceptible to cardioversion lasting more than 6 months preoperatively. Persistent AF = AF lasting more than 6 months preoperatively but transiently cardiovertible, or lasting less than 6 months in presence of severely disabling symptomatology in spite of medical therapy and/or electrical cardioversion attempts. Patient Diagnosis: Permanent AF (n=95) Persistent AF in 32/95 (33.7%) 4PV: 31.82 7F: 37.5 CT: 31.71 pns between groups Mean Age (yrs): Total: 61[10] 4PV: 61[9] 7F: 60[11] CT: 62[9] pns between groups Gender Mix (male/female): 4PV: 8/14 7F: 15/17 CT: 17/24 Total: 40/55 Patient Co-morbidities: Systemic embolization (n=12; %): 4PV: 13.6 7F: 9.4 CT: 14.6 Total: 12.6 Duration of pre-surgical AF (months): Permanent AF: 4PV: 56[41] 7F: 47[43] CT: 83[58] Total: 65[52] AF lasted more than 60 months in 43.5% of patients p=0.04 between groups Study Period: 4/98-5/02 Operator Details: All operations performed at same institution by different surgeons. Pre-surgical atrial size: Mean left atrial diameter (mm): 4PV: 53.47[10.73] 7F: 69.08[35.7] CT: 95.67[34.19] Total: 65.17[51.99] p<0.01 between groups Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Not stated Underlying heart disease: MV involvement (n=84; %): 4PV: 81.81 7F: 90.62 CT: 90.24 Total: 88.42 pns between groups Severe tricuspidalisation (n=13; %): 4PV: 13.64 7F: 28.12 CT: 2.44 Total: 13.68 p=0.02 between groups Lone aortic valve disease: 6.3% Lone tricuspid valve disease: 1.1% Complex valvular disease: 17.9% Other: NYHA (n=95; %): 223 Exclusion Criteria: Patients with very depressed low ejection fraction (<25%) were excluded so as not to prolong the ischaemic clamping time strictly necessary for main surgical procedure. Limited surgical exposure, as for right mini-thoracotomies, was not a contraindication. Authors Manasse et al. 2003 continued Intervention Study design Study population I-II: 4PV: 54.5 7F: 37.5 CT: 17.1 Total: 32.7 III-IV: 4PV: 45.5 7F: 62.5 CT: 82.9 Total: 67.3 Previous electrical cardioversion (n=27; %): 4PV: 22.7 7F: 37.5 CT: 24.4 Total: 28.4 Redo surgery: 23/95 (24.2%) Heart port access: 5/95 (5.3%) CABG: 1 No concomitant surgery: 1 Medication: All patients given amiodarone by iv infusion (600 mg/250 at 20 mL/hr) when weaned from CPB regardless of heart rhythm and rate. On 2nd postoperative day oral amiodarone started (200 mg twice/day) unless propafenone was preferred because of dysthyroidism. A pharmacological (or electrical) cardioversion always attempted before discharge if AF or atrial flutter were present. Withdrawal of antiarrhythmic therapy 3-6 months postoperatively suggested to referring doctor in absence of AF or atrial flutter. Oral anticoagulation withdrawn in absence of mechanical prosthesis at 3 months. Anticoagulation therapy in patients preoperatively (n=49; %): 4PV: 59.1 7F: 46.9 CT: 51.2 Total: 51.6 Pacemaker: Intra-operative direct cardioversion performed in all patients with AF after weaning from bypass. Cardioversion: Electrical (or pharmacological) cardioversion always attempted before discharge if AF or atrial flutter present. Electrocardiogram: Routine at 1, 6 and 12 months and once a year. Echocardiography: Routine at 1, 6 and 12 months and once a year. 224 Inclusion/Exclusion criteria Appendix C.1.10: Intraoperative ablation- Cryotherapy Case Series Left atrial CA Authors Intervention Naito et al. 2001 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Lesion device: CRYOABLATION/ Not stated Energy level: -80 oC for 3 minutes. Energy rate: Not applicable Surgery: Left lesions: Ablation of the four pulmonary vein orifices. Right lesions: None Atrial appendages: Not stated Atrial incisions: No additional incisions to those needed for MV surgery. Order of surgery: Not stated Type of concurrent surgery: MV surgery. Medication: Not stated Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Holter monitoring performed at 3 months followup. Echocardiography: 3 months after surgery transoesophageal echocardiography performed. Circulation 2001;104(17):159 (abstract) Location Yokohama Rosai Hospital, Yokohama, Japan Study design Level of Evidence: IV Basis of Patient Selection: Not stated Study population Inclusion/Exclusion criteria Sample Size: n=30 Inclusion Criteria: Patients with chronic AF and requiring MV surgery, with left atrial dimension under 65mm. Patient Diagnosis: Chronic AF Type 1-2 AF in left atrium. Mean Age (yrs): 64[11] Eligibility Rate: Not stated Gender Mix (male/female): 14/16 Follow-up (months): 16.5[6.7] Lost to Follow-up: Not stated Patient Co-morbidities: Not stated Duration of pre-surgical AF: Not stated Pre-surgical atrial size: < 65 mm Study Period: Not stated Pre-surgical LVEF (%): Not stated Operator Details: Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Not stated 225 Exclusion Criteria: Not stated Appendix C.1.10: Intraoperative ablation- Cryotherapy Case Series Left atrial CA Authors Intervention Study design Study population Inclusion/Exclusion criteria Sueda et al. 2001 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Cold blood cardioplegia Body temperature: 33 oC Lesion device: CRYOABLATION/ Device not stated Energy level: -60 oC for 3 min Energy rate: Not applicable Surgery: Left ablations: Complementary cryoablation applied to the remnant of the circular incision between the left upper pulmonary vein and the left lower pulmonary vein. i.e. all pulmonary vein orifices isolated. Right ablations: None Atrial appendages: When there was a mural thrombus in the LAA, the thrombus was excised and the orifice of the LAA closed with a running suture. Atrial incisions: Right-sided vertical incision in LA extended to the left margin of both left pulmonary vein orifices. Sequence of surgery: Concomitant surgery performed after ablation. Type of concurrent surgery: MVR: 1 MVR+TVP: 6 MVR+AVR: 3 MVR+AVR+TVP: 1 MVR+ plication of LAA: 1 Medication: Antiarrhythmic drugs (digoxin 0.25 mg/d and disopyramide 300 mg/d) given to all patients until time of discharge. Pacemaker: 1 patient had preoperative VVI pacemaker Cardioversion: Used in early postoperative period for recurrent AF. Electrocardiogram: Not stated Echocardiography: Preoperative echocardiogram Other: Before institution of CPB, intraoperative atrial mapping performed. Level of Evidence: IV Sample Size: n=12 Inclusion Criteria: AF Basis of Patient Selection: Not stated Patient Diagnosis: AF Ann Thorac Surg 2001;71:1189-1193 Location First Department of Surgery, Hiroshima University School of Medicine, Hiroshima, Japan Eligibility Rate: Not stated Mean Age (y): 60.4[14.6] (range 24-82) Gender Mix (male/female): 4/8 Follow-up: 8 months (range 5-14 months) Study Period: Past 14 months Patient Co-morbidities: Hyperthyroidism: 2 Diabetes mellitus: 2 Dialysis: 1 Thrombus: 1 Cerebral embolism: 1 Premature ventricular contraction: 1 Atrial tachycardia: 1 Sick sinus syndrome: 1 Operator Details: Not stated Duration of pre-surgical AF (y): 8.0[6.8] (range 1-20) Lost to Follow-up: Not stated Pre-surgical atrial size: Mean left atrial diameter (mm): 52.6[7.3] (range 45-65) Pre-surgical LVEF (%): 61.8[13.5] (range 31-77) Indication for concurrent surgery: Mitral regurgitation + tricuspid regurgitation: 7 Mitral stenosis + regurgitation + tricuspid regurgitation: 1 Mitral stenosis + aortic valve regurgitation: 1 Mitral stenosis + regurgitation + aortic stenosis + regurgitation: 1 Mitral stenosis + regurgitation + aortic regurgitation: 1 Mitral + aortic + tricuspid valve regurgitation: 1 Underlying heart disease: Not stated 226 Exclusion Criteria: Not stated Appendix C.1.10: Intraoperative ablation- Cryotherapy Case Series Left atrial CA Authors Intervention Usui et al. 2002 Surgical access: Not stated CPB Cannulation: Bicaval venous drainage and arterial return to the ascending aorta. Cardioplegia: Antegrade or retrograde cold blood cardioplegia. Body temperature: Lesion device: CRYOABLATION/ Device not stated. Energy level: -60 oC for 90 s for the left lesions, and -60 oC for 60 seconds several times for the right ablations (when added). Energy rate: Not applicable Surgery: Left lesions: Cryoablation delivered at the left margin of both left pulmonary vein orifices towards the left atriotomy ridge to isolate all four pulmonary vein orifices. Also directed adjacent to the centre of the posterior MV annulus and the base of the excised LAA. Right lesions: Sometimes when a right atriotomy was performed (n=2+ unknown) cryoablation delivered between the tricuspid valvular annulus and the inferior vena cava orifice. Atrial appendages: LAA resected and sutured at its base. Atrial incisions: An extended right-sided left atriotomy. Order of surgery: After aortic cross clamping and arrest of the heart with cardioplegia, the LAA resected and sutured at its base and the atriotomy made. Type of concurrent surgery: Not stated Medication: Not stated Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Not stated Ann Thorac Surg 2002;73:1457-1459 Location Department of Cardio-Thoracic Surgery, Nagoya University Graduate School of Medicine, and First Department of Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan Study design Level of Evidence: IV Study population Inclusion/Exclusion criteria Sample Size: n=41 Inclusion Criteria: AF Patient Diagnosis: AF Basis of Patient Selection: Not stated Mean Age (yrs): Not stated Eligibility Rate: Not stated Gender Mix (male/female): Not stated Follow-up (months): Not stated Patient Co-morbidities: Not stated Duration of pre-surgical AF(yrs): Not stated Lost to Follow-up: Not stated Pre-surgical atrial size: Not stated Study Period: 97- Pre-surgical LVEF (%): Not stated Operator Details: Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Not stated 227 Exclusion Criteria: Not stated Appendix C.1.10: Intraoperative ablation- Cryotherapy Case Series Left atrial CA Authors Intervention Yamauchi et al . 2001 Surgical access: Median sternotomy CPB Cannulation: Ascending aorta and both vena cavae. Cardioplegia: Bidirectional cardioplegia including terminal warm blood cardioplegia. Body temperature: Normothermia Lesion device: CRYOABLATION/ Device not stated. Energy level: Not stated Energy rate: Not applicable Surgery: Left ablations: In the case of MVR before the attachment of the mitral mechanical valve, ablation lesions placed at a point near one third of the posteromedial commissure of the mitral annulus. A LA posterior longitudinal linear ablation then performed by making a cryolesion extending from the posterior mitral annulus to the incisional line of the roof of the transverse sinus of the pericardium including both right inferior and superior pulmonary veins. Another posterior longitudinal linear cryolesion, including both left inferior and superior pulmonary veins, made starting from 1cm from the mitral annulus to the incisional line of the roof of the transverse sinus of the pericardium (n=29/40). If the precise location of the focus or reentry circuit was found using mapping, ablation was placed at that point (n=11/40). The focus was: LAA: 6 Left superior pulmonary vein: 3 Reentry: 2 (1/2 was a line from the left inferior and superior pulmonary veins). Right ablations: None Atrial appendages: LAA not resected Atrial incisions: Combined superior-transseptal approach to the LA. Sequence of surgery: Atrial mapping performed prior to CPB and surgery. Type of concurrent surgery: MVR: 17 MVP: 5 MVR+TVP: 11 MVR+AVR: 2 AVR: 1 AVR+open mitral commissurotomy: 1 MVP+intracardiac repair: 1 Intracardiac repair: 2 Medication: Heparinisation performed prior to CPB. Pacemaker: Not stated Cardioversion: Not used perioperatively. Electrocardiogram: Not stated Echocardiography: Not stated Ann Thorac Surg 2002;74:450-457 Location Department of Thoracic and Cardiovascular Surgery, Chiba Hokusoh Hospital, Nippon Medical School, Tokyo, Japan Study design Level of Evidence: IV Study population Inclusion/Exclusion criteria Sample Size: n=40 Inclusion Criteria: AF Patient Diagnosis: AF Basis of Patient Selection: Not stated Mean Age (y): 60.0[8.1] (range 44-76) Eligibility Rate: Not stated Gender Mix (male/female): 18/22 Follow-up: Not stated Patient Co-morbidities: Not stated Lost to Follow-up: Not stated Duration of pre-surgical AF (y): 8.1[5.6] (range 0.4-20) Note: n=36, duration unknown in 4 patients. Study Period: Not stated Pre-surgical atrial size: Mean left atrial diameter (mm): Not stated Operator Details: Not stated Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Mitral regurgitation: 14 Mitral + tricuspid regurgitation: 2 Mitral + tricuspid regurgitation + endocardial cushion defect: 1 Mitral regurgitation + atrial septal defect: 1 Mitral stenosis: 4 Mitral + aortic stenosis: 1 Mitral stenosis + aortic regurgitation: 1 Mitral stenosis + tricuspid regurgitation: 5 Mitral stenosis + left atrial thrombus: 4 Mitral stenosis + tricuspid regurgitation + left atrial thrombus: 3 Mitral stenosis + tricuspid regurgitation + posterior percutaneous transluminal mitral commissurotomy: 1 Mitral + aortic stenosis + posterior closed mitral commissurotomy: 1 Atrial septal defect: 1 Aortic stenosis: 1 Underlying heart disease: Rheumatic: 26 Degenerative: 9 Congenital: 3 Chorda rupture: 1 Infective endocarditis: 1 228 Exclusion Criteria: Not stated Appendix C.2.1: Intraoperative ablation- Radiofrequency Comparative Biatrial RFA versus CS Authors Intervention Study design Study population Khargi et al. 2001 Deneke et al. 2002a Mitral valve plus RF Maze (RF) Mitral valve alone (MVS) Prospective RCT Sample Size: RF: 15 MVS: 15 Ann Thorac Surg 2001;72:S1090-5 Eur H Journal 2002;23:558-566 RF: Lesion device: RADIOFREQUENCY/ SICTRA catheter (Sprinklr; Medtronic, Minneapolis, MN) with a 7F (2.33mm) diameter, a 4mm tip length and 13 irrigation holes. The catheter was connected by an infusion pump with a 0.9% NaCl infusion bag. Catheter connected to a radiofrequency generator (CardioRythm-ATAKR, Medtronic). Energy level: First 4 patients 20W for 60-100 seconds, and 32W for 1025 seconds for the last 8 patients. Also used 25W for 45-75 seconds, and 32W for a time not stated, the number of patients at these levels was not stated. Energy rate: 220ml/h at 20W; 250 ml/h at 32 W; 320 ml/h at 32 W Surgery: Left ablations: Endocardial rim of the ostium of pulmonary veins ablated. RF line between left and right pulmonary veins. Lesion from left pulmonary vein to midportion of posterior mitral annulus. Lesion from left lateral rim of orifice of left inferior pulmonary vein to rim of LAA orifice. Right ablations: RF lesions posterocranial end of S3 into the superior caval vein (R1) and from the posterocaudal end of S3 into the inferior caval vein (R2). R3 made from the anterior edge of S3 close to the AV groove traversing the endocardium to middle of the posterior part of the tricuspid annulus. R4 from medial cut edge from the RAA to the anteroseptal commissural area of tricuspid valve. R5 from posterocranial edge of S3 traversing to posterior area of foramen ovale to posterior rim of coronary sinus orifice then curving to inferior caval vein, ablating the ‘isthmus’. Atrial appendages: RAA excised (S1). LAA resected or ablated (if adhesions prevented resection). Atrial incisions: Perpendicular incision 3-4 cm long from the middle of the incision of RAA excision traversing the lateral free wall of the RA (S2). Curved incision from the AV groove, about 2-3 cm cranially and anterior from the inferior caval vein and continuing posterocranially behind the sulcus terminalis (S3). Left atrium opened in the interatrial groove. Sequence of surgery: The RA incisions and ablations were performed, the aorta cross clamped and cardioplegia administered. Left atrial incisions and ablations then performed. Cross clamp removed and incisions of RA closed. Note: Main difference versus Maze-III was each pulmonary vein orifice was isolated separately but over its complete orifice circumference, whereas Maze III isolates all four pulmonary veins orifices as an entire one-piece-tissue island. Did not ablate within the pulmonary vein orifices to avoid pulmonary vein stenosis. Ablation lines in RA and LA Level of Evidence: II Location Departments of Cardiothoracic Surgery, Cardiology and Pathology, Berufsgenossenscha ftliche, Kliniken Bergmannsheil University Hospital, Bochum, Germany. Method of allocation concealment: Not stated Eligibility Rate: 30/49 patients with MVR alone. 19 patients had SR Intention-to-Treat Analysis: Not stated Basis of Patient Selection: Not stated Follow-up (months): RF: 22[7] median 21 MVS: 21[6] median 20 Lost to Follow-up: RF: 100% survivors MVS: 12/14 (86%) of survivors 2 patients unable to attend outpatient cardiology clinic at 12 months, 1 unable to travel, 1 had severe psychosis. Both patients had ECG. Study Period: 2/98 to 10/99 Operator Details: Not stated Patient Diagnosis: Chronic AF > 1yr and MV disease Mean Age: RF: 64.7 (range 49-75; median 63) MVS: 69.7 yrs (range 64-77; median 63), p=0.053 Gender Mix (male/female): RF: 6/9 MVS: 3/12 Patient Co-morbidities: RF: 1 patient obese and diabetic, 1 patient chronic obstructive pulmonary disease MVS: 1 patient chronic obstructive pulmonary disease Duration of pre-surgical AF (yrs): RF: 3.6 (range 1-10; median 2) MVS: 3.7 (range 1-30; median 2) pns Pre-surgical atrial size (mm): RF: 59.8 [5.3] MVS: 57.8 [6.4] pns Pre-surgical LVEF (%): RF: 64 [11 ] MVS: 61 [9 ] pns Indication for concurrent surgery: MVS insufficiency: RF: 8 MVS: 10 MVS stenosis: RF: 2 MVS: 3 Combination: RF: 5 MVS: 2 Underlying heart disease: Underlying heart disease degenerative in 14, MV prolapse in 1, rheumatic heart disease in 5, unknown in 10. 229 Inclusion/Exclusion criteria Inclusion Criteria: Permanent AF > 1 year or at least two nonsuccessful medical or electrical cardioversions 6 months before surgery. MV disease. Exclusion Criteria: Not stated Authors Intervention Khargi et al. 2002 continued were performed in addition to cut and suture lines to open both atria. Study design Both Groups: Surgical access: Median sternotomy CPB Cannulation: Aorta, superior caval vein and inferior caval vein Cardioplegia: Cold antegrade blood administered after RA procedure complete. Body temperature: Not stated Type of concurrent surgery: Mitral valve: RF: 14 mechanical valve 1 biological valve MVS: 2 mitral valve plasty, 13 mechanical valve (Note: in Deneke et al. 2002 stated all patients received prosthetic valves). Medication: Sotalol 40 mg bid started on first post op day. Dose increased to 80mg bid on third postoperative day and to 160mg bid if no bradyarrhythmia. Replaced at 6 months by metoprolol at least 95mg.day. All patients Coumadin INR 2.2-2.5 started on first postoperative day. Pacemaker: Atrium atrium inhibition mode (AAI) if possible or DDD mode. Cardioversion: If AF persisted during first 24 postoperative hours. Not done in last 10 patients as did not contribute to long-term rhythm stability. Electrocardiogram: 24hr (Holter) ECG obtained at 6 and 12 months. ECG at third, sixth and ninth postoperative visit. Transthoracic echocardiography: Transmitral and transtricuspid Doppler, 12th postoperative day and 6 and 12 months. Other: Spiro-ergometry (bicycle ergometry and ramp protocol with workload raise of 10 Watts/min) performed at 6 month follow-up. 230 Study population Inclusion/Exclusion criteria Appendix C.2.1: Intraoperative ablation- Radiofrequency Comparative Biatrial RFA versus CS continued Authors Intervention Chen et al. 2001 Patients were treated with RF Maze II/III (RFII/III) RF Maze IV (RFIV) or valvular operations alone (CS) Lesion device: RADIOFREQUENCY/ Quadripolar steerable electrode catheter (Mansfield, Watertown, MA, USA) with a 4-mm distal electrode and 2-mm electrode spacing between the distal two electrodes. RF generator (EPT-1000; EP Technologies, Sunnyvale, CA, USA) delivered a continuous, quasi-sinusoidal, unmodulated RF output at 500 kHz from the distal electrode to a cutaneous dispersive pad attached to the posterior chest. CRYOABLATION/ 15-mm head cryoprobe; Frigitronics, Shelton, CT, USA. Energy level: 30-50 Watts/ 30 sec for radiofrequency and -60 oC for 3 min for cryoablation. Energy rate: Not applicable Surgery: RFII/III: (from Chen et al. 1998) Fundamentally the same as Maze-II or -III with RFA or cryoablation by direct visualisation to replace incisions. RFII or -III performed on the basis of the course of sinus nodal arteries. Left ablations: RF ablation to complete an encircling line around the pulmonary veins, with a connecting ablation from the left upper corner of the pulmonary vein isolation to the base of the LAA ligation. A posteroinferior vertical left ablation, from the lower rim of the pulmonary vein isolation to the mid-posterior MV annulus. Cryoablation applied to produce endocardial lesions at the MV annulus over the coronary sinus, and the anterioseptal and posterosuperior part of the interatrial septum. Right ablations: RF first applied to epicardial surface of the RA before CPB, starting from junction of superior vena cava and RA toward inferior vena cava, 1 cm away from the sinus node but parallel to sulcus terminalis. A second line begun obliquely from this line toward the AV groove. A third line made between the first line and LA incision (III) or between the superior vena cava and LA incision (II). Endocardial RFA to lateral part of isthmus between tricuspid annulus and inferior vena cava, except for first 3 patients. Cryoablation of the posterolateral part of the tricuspid annulus. Atrial appendages: RAA excised. LAA ligated after RF ablation around its base. Atrial incisions: Right atrium entered by incision on lateral part from the base of the resected RAA. Standard left atriotomy in the interatrial groove. Sequence of surgery: Right epicardial ablations performed, RAA excised, and CPB commenced. Remaining RA ablations performed endocardially in RA under partial CPB and in LA after cardioplegia and LA incision. RFIV: Left ablations: RF ablation of the right and left pulmonary veins separately, with a connecting ablation line between the two sets of pulmonary veins. The other ablation lines were the same as for RFIII. Right ablations: As for RFII/III Atrial appendages: As for RFII/III Atrial incisions: As for RFII/III Sequence of surgery: Not stated Both groups: J Cardiovasc Electrophysiol 2001;12:867-874 Ann Thorac Surg 1998;65:1666-72 Location Division of Cardiology, Department of Medicine, and the Division of Cardiovascular Surgery, Chang Gung Memorial Hospital, Kaohsiung and the Department of Biological Sciences, National Sun Yat-Sen University, Taiwan, Republic of China Study design Level of Evidence: III-3 Non randomised retrospective comparative study Intention-to-Treat Analysis: Not stated Study population Sample Size: RFII/III: 13 RFIV: 48 CS: 58 Patient Diagnosis: Mitral valve disease and chronic AF (> 4 wks) Basis of Patient Selection: Not stated Mean Age: RFII/III: 49.4[13.2] range 32-76 RFIV: 52.9[10.8] range 26-71 CS: 54.7[12.3] range 21-76 pns Follow-up: at least 24 months RFII/III 43 (range 37-47) RFIV: 16 (range 3-32) Gender Mix male/female: RFII/III: 10/3 RFIV: 22/26 RFII/III vs RFIV p<0.05 Eligibility Rate: Not stated Patient Co-morbidities: History of embolism (%) RFII/III: 0 RFIV: 16.7 CS: 12.1 Hypertension (%) RFII/III: 0 RFIV: 6.3 CS: 0 Hyperthyroidism (%) RFII/III: 0 RFIV: 6.3 CS: 0 Diabetes mellitus (%) RFII/III: 0 RFIV: 2.1 CS: 0 Lost to Follow-up: RFII/III: 11/11 survivors at 24 months RFIV: 9/47 survivors CS: 54/54 survivors at 24 months Note: longitudinal study so varying lengths of follow-up. Study Period: 12/95-9/99 Operator Details: Not stated CS: 27/31 Duration of pre-surgical AF (months): RFII/III 33.2[30.2] RFIV: 47.3[48.8] CS: 33.7[33.3] pns Pre-surgical atrial size: Left atrium (mm) RFII/III: 55.1[6.1] RFIV: 54.7[8.2] CS: 58.2[12.4] Pre-surgical LVEF (%): Ejection fraction RFII/III: 56.2[15.1] RFIV: 61.6[11.4] CS: 62.5[14.3] Indication for concurrent surgery: Not stated Underlying heart disease (%): MV stenosis RFII/III: 0 RFIV: 27.1 CS: 20.7 MV regurgitation RFII/III: 23.1 RFIV: 39.6 CS: 43.1 MV stenosis + regurgitation RFII/III: 76.9 RFIV: 33.3 CS: 36.2 231 Inclusion/Exclusion criteria Inclusion Criteria: Chronic AF Exclusion Criteria: Not stated Authors Intervention Chen et al. 2001 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Type of concurrent surgery, No(%): MV replacement RFII/III: 9(69) RFIV: 29(60) CS: 45(78) RFII/III plus RFIV: mechanical n=33, tissue n=5 CS: mechanical valve n=40 tissue n=5 MV repair RFII/III: 4(31) RFIV: 19(40) CS: 13(22) Aortic valve replacement RFII/III: 5(39) RFIV: 5(10) CS: 14(24) RFII/III+ RFIV: mechanical n=8 tissue n=2 CS: mechanical n=11 tissue n=3 Aortic valve repair RFII/III: 0 RFIV: 2(4) CS: 0 Tricuspid valve replacement RFII/III: 0 RFIV: 1(2) CS: 0 Tricuspid annuloplasty RFII/III: 3(23) RFIV: 32(67) CS: 34(59) RFII/III versus RFIV p=0.03 CABG RFII/III: 1(8) RFIV: 4(8) CS: 3(5) Medication: No patients taking Class I or III antiarrhythmic agents at time of study. Patients taking digitalis (%) RFII/III: 76.9 RFIV: 93.8 CS: 100.0 RFII/III vs CS p=0.005 β blockade (%) RFII/III: 7.7 RFIV: 4.2 CS: 19.0 RFIV vs CS p=0.02 Calcium channel blocker (%) RFII/III: 15.4 RFIV: 4.2 CS: 29.3 RFIV vs CS p=0.001 ACE inhibitor (%) RFII/III: 46.2 RFIV: 45.8 CS: 32.8 pns Postoperative intravenous heparin was administered to patients in all groups, and activated partial thromboplastin time kept between 1.5-2 times control. Warfarin was used in all patients and discontinued only when patients had SR and documented atrial contraction by echocardiography. Antiarrhythmic drugs NOT routinely used. Pacemaker: Both atrial and ventricular temporary pacing wires were used to pace the patient if there was any postoperative sinus node dysfunction or bradycardia. Cardioversion: NOT used. Electrocardiogram: Cardiac rhythm was monitored continuously after surgery until a stable rhythm returned. After discharge monthly ECGs. Echocardiography: Transthoracic echocardiographic examinations performed before, 3, 6, 12, 18 and 24 months postoperative in all RFII/III and RFIV patients but only after 3 months in the CS group. Study design Study population RFII/III vs RFIV and CS p<0.01 Aortic valve disease RFII/III: 46.0 RFIV: 23.0 CS: 29.0 pns Tricuspid valve disease RFII/III: 31.0 RFIV: 67.0 CS: 64.0 RFII/III vs RFIV p=0.03 Rheumatic heart disease RFII/III: 76.9 RFIV: 68.8 CS: 70.7 pns Coronary artery disease RFII/III: 7.7 RFIV: 10.4 CS: 5.2 pns Other: Left ventricular end-diastolic diameter (mm) RFII/III: 60.7[10.5] RFIV: 54.0[8.7] CS: 57.7[11.1] Left ventricular end-systolic diameter (mm) RFII/III: 42.2[11.1] RFIV: 35.3[8.1] CS: 37.7[10.1] 232 Inclusion/Exclusion criteria Appendix C.2.1: Radiofrequency Comparative Biatrial RFA versus CS continued Authors Intervention Patwardhan et al. 2003 Valve surgery plus RFM (RF) versus Valve surgery alone (CS) RF: Lesion device: RADIOFREQUENCY/ Bayonet shaped standard bipolar forceps with active tip length of 7-mm drawing power from a microbipolar port of Valleylab Force 4 electrosurgical unit (Valleylab, Boulder, CO, USA). CRYOABLATION/ 3-mm retinal handheld cryoprobe working on compressed nitrous oxide gas. Energy level: Radiofrequency: 45W for atrial wall < 3mm and 55W for 3mm or greater (visual judgement) Cryoablation: -60 0C Energy rate: Not applicable Surgery: (from Patwardhan et al. 1997) Left ablations: Radiofrequency- Encircling pulmonary vein linear coagulation performed through LA incision. Superior part of encircling pulmonary vein coagulation carried out keeping one blade of the forceps in the transverse sinus and the other inside the LA, while the inferior part was coagulated by keeping one blade behind and one inside the atrium. From this line, coagulation was carried out up to 5mm short of the MV annulus. The left sided pulmonary veins encircled from inside, raising a fold with the forceps in first 3 patients and in the others the LAA was partly excised to perform procedure with one blade inside and one outside the atrium. The junction of the left sided pulmonary veins and LA ablated through the opening in the LAA. Ablation line from the base of the LAA to the encircling pulmonary vein line. Cryoablation- Cryoablation of the atrial muscle up to the mitral annulus. Cryoprobe placed externally on the empty coronary sinus in the AV groove. Right ablations: Radiofrequency- Ablation line from the superior vena cava to the inferior vena cava on the posterolateral wall. A transverse ablation joined this line to the sutured LA incision. A line from the superior vena cava to the inferior vena cava ablation line, across the fossa ovalis to the atrial wall, anterior to the coronary sinus and stopping 5-mm short of the Tendon of Todaro. Another line made from the superior vena cava to the inferior vena cava line, across the lateral wall of RA to short of the tricuspid annulus. Cryoablation- None Atrial appendages: In last 16 patients the LAA partly excised to perform RF ablation. The base of the LAA was coagulated from outside in first 3 cases, and in last 16 patients through the opening following appendage excision. RAA excised. Atrial incisions: Left atriotomy from right superior pulmonary vein to behind inferior vena cava. In the RA a lateral incision made from the amputated RAA, halfway to the interatrial groove. Sequence of surgery: Left sided procedure performed and cardiotomies closed. Warm hyperkalaemic sanguinous reperfusion over Ind J Thorac Cardiovasc Surg 2003;19:136-140 Location Departments of Cardiovascular & Thoracic Surgery, and Department of Cardiology, KEM Hospital , Mumbai, and Department of Cardiovascular & Thoracic Surgery, LTMG Hospital, Mumbai, India Patwardhan et al. Study design Study population Inclusion/Exclusion criteria Level of Evidence: III-3 Sample Size: RF: 84 CS: 64 Inclusion Criteria: AF lasting more than 3 months as evident from previous ECGs. Intention-to-Treat Analysis: Not stated Basis of Patient Selection: Not stated Follow-up (months) : RF: 23.6[12.5] months (range 12 -53 months). CS: 6 months Eligibility Rate: Not stated Lost to Follow-up: Study Period: RF: 8/96-2/99 and 3/997/00 CS: 8/96-2/99 Operator Details: The patients in the RF group were operated on by a single surgeon; the patients in the V group were operated by other surgeons. In the RF group 69 patients were operated on at the LTMG Hospital, and 15 patients were operated at the KEM hospital in the later period. 233 Patient Diagnosis: AF Mean Age (yrs): RF: 32.5[11.0] CS: 33.0[12.9] Gender Mix (male/female): RF: 43/41 CS: 24/40 Patient Co-morbidities: Pulmonary arterial hypertension: Mild: RF: 5 CS: 5 Moderate: RF: 20 CS: 12 Severe: RF: 59 CS: 47 Duration of pre-surgical AF: Not stated Pre-surgical atrial size: RF (cm): 5.63[1.12] CS: 5.3[0.97] Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Not stated Other: NYHA class: II: RF: 24 CS: 16 III: RF: 50 CS: 39 IV: RF: 10 CS: 9 Exclusion Criteria: Not stated Authors Intervention 2003 continued 3 min, followed by release of aortic cross clamp with core rewarming. Caval tapes were snugged and RAA amputated to perform RA ablation during the reperfusion period, with patient being rewarmed. Right atriotomy closed and caval tapes unsnugged. Both groups Surgical access: Not stated CPB Cannulation: Bicaval Cardioplegia: Cold sanguinous cardioplegic arrest. Body temperature: Moderately hypothermic. Type of concurrent surgery: MVR: RF: 46 CS: 37 Open mitral commissurotomy: RF: 8 CS: 3 MVR+AVR: RF: 9 CS: 11 Open mitral commissurotomy + AVR: RF: 11 CS: 1 MVR+AV repair: RF: 1 Redo MVR: RF: 5 MVR+CABG: CS: 1 Medication: No prolonged preoperative antiarrhythmic or anticoagulant drugs. In all patients ventricular rate control and antifailure medication was allowed to continue until the day before surgery. Inotropes were administered postoperatively, if indicated. Haemodynamically significant supraventricular tachyarrhythmias were treated with pharmacological (or electrical) cardioversion. All patients received antifailure medication postoperatively, including digoxin, frusemide, potassium supplement and spironolactone. Patients with mechanical valves received anticoagulants. Oral amiodarone was given for 3 weeks at 100-200 mg twice daily, depending on body weight. Target INR for anticoagulation was 2-3. Pacemaker: Two atrial and two ventricular epicardial temporary pacing wires placed at end of surgery. Cardioversion: None pre-operatively. Postoperatively used to treat haemodynamically significant supraventricular tachyarrhythmias. Electrocardiogram: All patients had 12-lead ECG and atrial monopolar and bipolar ECG recordings regularly during the postoperative period. In the RF patients a 12-lead ECG was recorded monthly during the first six months and bimonthly later. In the V group a six month follow-up with 12-lead ECG was performed. Echocardiography: Obtained within 3 months of surgery. All survivors in SR underwent echocardiography with pulsed wave Doppler study, to see presence of an A-wave across the mitral and tricuspid valves. Study design 234 Study population Inclusion/Exclusion criteria Appendix C.2.1: Intraoperative ablation- Radiofrequency Comparative Biatrial RFA versus CS continued Authors Intervention Study design Study population Inclusion/Exclusion criteria Riying et al. 1998 RF Maze plus heart surgery (RF): Mitral valve surgery (MVS) Lesion device: RADIOFREQUENCY/ RF generator same as one previously used for RF catheter ablation. Probe was specific, with a curve in the front and 20-mm length and 2-mm diameter. Energy level: 30 to 50 Watts, impedance 80 to 100 ohms (from porcine heart experiment). Duration of ablation 20-90 sec. The probe positioned manually on atrial endocardial surface, if impedance rose abruptly after 20 seconds the generator was shut off immediately, followed by appearance of 20 mm long and 5 mm wide white transmural lesion, indicating successful ablation. If generator not shut off in time, temperature at probe-tissue interface > 1000C and eschar formed around probe. Eschar removed and procedure repeated. Energy rate: Not applicable Surgery: Lesion pattern as in Maze-III. No further details given. Non randomised comparative study. Sample Size: RF: 25 MVS: 25 Inclusion Criteria: AF Level of Evidence: III-3 Patient Diagnosis: RF: mitral valve disease/atrial septal defect with AF. MVS: rheumatic heart disease with AF. Exclusion Criteria: Not stated Chinese Medical Journal 1998;111:927-928 Location Department of Cardiology, Tangdu Hospital, 4th Military Medical University, Xi’an, China Both groups Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Type of concurrent surgery: RF: mitral valve replacement 24 patients, atrioseptopexy 1 patient Medication: Not stated Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Transthoracic echocardiography: Not stated Intention-to-Treat Analysis: Not stated Basis of Patient Selection: Not stated Mean Age: RF: 44.1 yrs (range 30-57) Gender Mix: (male/female): 14/11 Follow-up: Not stated Eligibility Rate: Not stated Lost to Follow-up: Not stated Study Period: 2/95Operator Details: Not stated Patient Co-morbidities: Not stated Duration of pre-surgical AF: 11 patients 1-6 yrs, remainder not definitive 1-5 yrs Pre-surgical atrial size: RF: Patients with slight (n=5), moderate (n=16) and severe (n=4) atrial enlargement. Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: RF: rheumatic heart disease with MV stenosis and regurgitation in 23 patients; congenital atrial septal defect 1 patient; severe MV prolapse 1 patient. Underlying heart disease: During hospitalisation RF: heart function II (n=6); heart function III (n=13); heart function IV (n=6). 235 Appendix C.2.2: Intraoperative ablation- Radiofrequency Comparative Left atrial RFA versus CS Authors Intervention Study design Study population Guang et al. 2002 Mitral valve plus RFA (RF) versus MV surgery alone (MVS) Lesion device: RADIOFREQUENCY/ EPT2000 radiofrequency machine and ablation probe. Probe modified from a RFA catheter wire of 2 mm diameter into the shape of ‘L’ with length 20 cm and width 2.5 cm. Energy level: 30 Watts/s temperature 90-100oC Energy rate: Not applicable Surgery: Differences with Maze-III: In Maze-III the LA dome incision is moved posteriorly, which causes the atrial septotomy to move posteriorly as well. In present method did not perform LA incisions, so reduced possibility of injuring sinus blood supply from left coronary artery. Left ablations: Encircling isolation of the orifices of pulmonary veins performed by endocardial RF. Connecting line between the ablation line of the LAA and the encircling of the pulmonary veins. Ablation line from the right side of the encircling ablation of the pulmonary veins to the incision between the inferior and superior vena cavae. Cryoablation around the coronary sinus. Right ablations: None Atrial appendages: RAA excised. Base of LAA ablated from inside with RF, and the appendage ligated. Atrial incisions: Right atrial incisions made the same as in the Maze-III procedure. Atrial septal incision posterior to orifice of the superior vena cava to expose the LA. A vertical posterior left atriotomy placed from the inferior rim of the encircling ablation of the orifices of pulmonary veins down to the level of the posterior MV annulus, and the fibres dissected away from the coronary sinus. Sequence of surgery: Right atrial incisions made on beating hearts without aortic cross clamping. Atrial septal incision made after cross clamping. After LA isolation, MVR was performed. The LA incision and atrial septal incisions were closed. After closure of the left heart, the crossclamp was released and tricuspid valvoplasty performed in patients with more than moderate tricuspid insufficiency, then the RA closed. Both groups: Surgical access: Median sternotomy CPB Cannulation: Not stated Cardioplegia: Cold blood cardioplegia repeated every 30 minutes. Body temperature: Moderate hypothermia (25-280C). Type of concurrent surgery: St Jude mechanical mitral valves Tricuspid valvoplasty : RF: 36 (38%) MVS: 39 (45%) Carpentier-Edwards ring annuloplasty: RFA: 3 Modified Devega annuloplasty: RF: 33 MVS: 2 Devega annuloplasty: MVS: 37 Medication: Routinely resumed treatment with antiarrhythmic drugs for 2-3 months after the operation in patients with arrhythmia. Warfarin after MVR. Pacemaker: Not stated Cardioversion: Performed intraoperatively to decide if RFA would be performed or not. Electrocardiogram: Not stated Transthoracic echocardiography: Not stated Non randomised retrospective historical comparative study with concurrent controls Sample Size: RF: 96 MVS: 87 Patient Diagnosis: Chronic AF >1yr Mean Age (yrs): RF: 40.6 [9.3] (range 18-60) MVS: 41.6 [9.9] pns Gender Mix: (male/female): RF: 37(38.5%)/59(61.5%) MVS: 39(44.8%)/48(55.2%) pns Patient Co-morbidities: History of Stroke no(%) RF: 9(9.4) MVS: 7 (8) pns Duration of pre-surgical AF (months): RF: 117.0 [59.4] in table and 121[61] in text MVS: 128.6 [70.5] pns Pre-surgical atrial size: Left atrial diameter (mm) RF: 62.7 [7.6] in table and 63.8 [5.0] in text MVS: 64.5 [5.1] p=0.072 Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Tricuspid lesion (no(%)) RF: 36 (37.5) MVS: 39(44.8) pns Mitral stenosis RF: 35 (36.4) MVS: 40(46) Mitral regurgitation RF: 9 (9.4) MVS: 10 (11.5) Mitral stenosis + regurgitation RF: 54 (54.2) MVS: 46 (42.5) pns 39 RF patients had more than moderate tricuspid insufficiency Underlying heart disease: Rheumatic MV disease in RF group. Eur J Cardio-Thor Surg 2002;21:249254 Location Division of Cardiovascular Surgery, Cardiovascular Disease Institute of Xijing Hospital, The 4th Military Medical University, Xi’an, People’s Republic of China 236 Level of Evidence: III-2 Intention-to-Treat Analysis: Not stated Basis of Patient Selection: Not stated Follow-up: 3 years Eligibility Rate: Not stated Lost to Follow-up: None Study Period: 3/94-12/96 Operator Details: Surgery in both groups performed by the same surgeon. Other: All patients in NYHA Class II or II preop NYHA Class III (no(%)) RF: 55(57.3) MVS: 59 (67.8) pns Cardiothoracic ratio (%) RF: 59.9 [5.7] MVS: 60.9 [5.8] pns Inclusion/Exclusion criteria Inclusion Criteria: Chronic AF> 1yr and relatively good cardiac function Control: Not stated Exclusion Criteria: During the surgery, before the decision to do the modified maze, cardioversion was performed to test the sinus function of the patients. If the patient did not resume SR or if the SR was too slow the patient did not receive the RF Maze. No patient in NYHA Class IV No patient older than 60 yrs Appendix C.2.2: Intraoperative ablation- Radiofrequency Comparative Left atrial RFA versus CS continued Authors Intervention Mantovan et al. 2003 Patients treated with cardiac surgery and RF ablation (RF) or cardiac surgery without RF ablation (CS) Lesion device: RADIOFREQUENCY/ probe with a malleable shaft and 7 electrodes (Thermaline®, EP Technologies [EPT], Sunnyvale, CA, USA). EPT 1000 generator used as the energy source. Energy level: 60 oC to 70 oC for 60 s. In the event of a rise in impedance the pulse was repeated. Generator set at 50 W. Energy rate: Not applicable Lesion set: Left lesions: Circumferential isolation of right and left pulmonary veins, a line connecting the previous lines, and a lesion connecting the line encircling the left veins to the mitral annulus. Right lesions: None Atrial appendages: LAA excluded. Atrial incisions: The LA was opened, when necessary, through a left paraseptal incision in front of the right pulmonary veins. Order of surgery: Cold cardioplegic arrest started before LA opened. LAA exclusion and mitral and additional surgical procedures performed after RF ablation. Both groups: Surgical access: Not stated CPB Cannulation: Double venous cannulation. Cardioplegia: Cold cardioplegic arrest. Body temperature: Moderate hypothermia Type of concurrent surgery: Mitral surgery: RF: 89 (86%) CS: 25 (92%) pns Aortic surgery: RF: 32 (31%) CS: 9 (33.3%) pns Tricuspid surgery: RF: 19 (18%) CS: 3 (11.1%) pns CABG: RF: 5 (5%) CS: 3 (11.1%) pns Atrial septal defect: RF: 5 (5%) CS: 1 (3.7%) pns Other: RF: 2 (1.9%) CS: 0 pns Associated pathologies: RF: 47 (46%) CS: 11 (41%) pns Mitral bioprosthesis or valvuloplasty: RF: 52 (58%) CS: 12 (48%) pns Medication: All patients were treated with oral anticoagulation before surgery, which was discontinued 4 days before surgery and subcutaneous low-molecular weight heparin or IV heparin started. Oral anticoagulation restarted on first postoperative day. Oral anticoagulation discontinued after 3-6 months in patients with stable SR, biatrial contraction, and no mechanical prosthesis. 12 hr before surgery amiodarone infusion (1200 mg/24 hr) started and maintained for 24 hr. Antiarrhythmic treatment recommended in every case, treatment established by referring physician. Pacemaker: Not stated Cardioversion: Intraoperative direct current cardioversion routinely J Cardiovasc Electrophysiol 2003;14:1289-1295 Location Cardiovascular Department, Ospedale Regionale “Santa Maria dei Battuti” di Treviso, Treviso, Cardiovascular Department, Ospedale Civile “Umberto I” di Mestre, Mestre, Cardiovascular Department, Università di Padova, Padova and Cardiovascular Department, Ospedale Civile di Mirano, Mirano, Italy Study design Level of Evidence: III-2 Intention-to-Treat Analysis: Not stated Basis of Patient Selection: RF: consecutive patients. C: patients who underwent surgery during the same period who refused RF ablation. Follow-up (months): 12.5[5] (range 4-24) Eligibility Rate: Not stated Lost to Follow-up: RF: 102/103 patients to ‘latest follow-up’ and 61/103 at 1 year. Study Period: 12/99-12/01 Operator Details: Operations performed in 4 different Italian centres. Treviso: RF: 51 (50%) CS: 15 (55%) Mestre: RF: 25 (24%) CS: 0 Padua: RF: 17 (16%) CS: 12 (45%) Mirano: RF: 10 (10%) CS: 0 Study population Sample Size: RF: n=103 CS: n=27 Patient Diagnosis: AF in all patients Chronic AF: RF: 82 (80%) CS: 22 (81%) pns Mean Age: RF: 62[11] CS: 64[7] pns Gender Mix: RF: 39/64 CS: 6/21 pns Patient Co-morbidities: Not stated Duration of pre-surgical AF (months): RF: 42[46] CS: 40[24] pns Pre-surgical atrial size: Mean left atrial diameter (mm): RF: 56[8] CS: 57[13] pns End-diastolic diameter (mm): RF: 54[9] CS: 55[10] pns End-systolic diameter (mm): RF: 34[8] CS: 35[9] pns Pre-surgical LVEF (%): RF: 61[11]] CS: 61[13] pns Indication for concurrent surgery: Primary disease: MV disease: RF: 89 (86%) CS: 25 (92%) pns Mitral stenosis + regurgitation: RF: 46 CS: 12 Mitral regurgitation: RF: 36 CS: 8 Mitral stenosis: RF: 7 CS: 5 Aortic valve disease: RF: 10 (10%) CS: 2 (7.4%) pns Aortic stenosis + regurgitation: RF: 5 CS: 0 Aortic regurgitation: RF: 3 CS: 0 Aortic stenosis: RF: 2 CS: 2 (2 patients had associated ascending aorta dilatation requiring surgical correction) Atrial septal defect: RF: 3 (3.4%) CS: 0 pns Ventricular septal defect: RF: 1 (1.1%) CS: 0 pns Associated pathologies: RF: 47 (46%) CS: 14 (52%) pns Underlying heart disease: History of rheumatic fever: RF: 46 (45%) CS: 14 (52%) pns History of rheumatic fever according to sex in RF group: M: 9/39 (23%) F: 37/65 (57%) p=0.001 Other: Antiarrhythmic treatment: RF: 26 (25%) CS: 6 (22%) pns 237 Inclusion/Exclusion criteria Inclusion Criteria: AF Exclusion Criteria: Not stated Authors Mantovan et al. 2003 continued Intervention Study design performed in all patients with AF. Postoperative cardioversion established by referring physician. Electrocardiogram: Continuous ECG during hospital stay, and followup at 3, 6, 12 and 24 months postoperative. Echocardiography: Transthoracic echocardiography performed in all patients, transoesophageal echocardiography not routinely performed. Doppler echocardiography and Holter monitoring performed between 3 and 6 months and after 12 and 24 months. Atrial contraction considered to be present when transtricuspid and transmitral flow on pulsed Doppler showed an A-wave with at least 50% of the E-wave. Study population Amiodarone: RF: 19 (18%) CS: 4 (15%) pns 238 Inclusion/Exclusion criteria Appendix C.2.3: Intraoperative ablation- Radiofrequency Comparative Left atrial RFA versus Cardioversion Authors Intervention Thomas et al. 2004 Patients underwent a RF Maze procedure (RF) or cardioversion (Cv). Lesion device: RADIOFREQUENCY/ Two hand-held devices. 1) In 5 cases the Cobra probe was used (Boston Scientific, Natick, MA, USA). 2) Device with four 6-mm x 2-mm electrodes with a 3mm interelectrode distance mounted in sequence on a 33mm long flexible tip. Simultaneous, in-phase unipolar ablation performed between all four electrodes and the large surface electrode. Energy level: 1) Temperature set at 80 oC-90 oC for 60-120 seconds. 2) 80 oC-90 oC over single period of 60 seconds Energy rate: Not applicable Surgery: Left ablations: In the LA lesions encircled the left and right pulmonary veins separately, with lines connecting the inferior and superior veins on each side, and the left and right veins to the MV. A line also joined the MV to the LAA roof incision and LAA excision site. Right ablations: The lesions in the RA encircled the tricuspid valve, and joined the inferior and superior vena cava and coronary sinus. A line also joined the tricuspid valve and excised RAA, and the tricuspid valve and the lateral RA running anteriorly to the crista terminalis. Atrial appendages: LAA and RAA excised. Atrial incisions: Left atrial roof incision, and excisions of the LAA and RAA. Sequence of surgery: Atrial appendages excised to gain access to the endocardial surface of the heart. Both groups Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Type of concurrent surgery: RF: Tricuspid valve repair: 1 MV repair/MVR/annuloplasty: 7 AVR: 1 CABG: 2 CABG+MV repair/ MVR+AVR or ASD: 4 Medication: Not stated Pacemaker: Not stated Cardioversion: RF: Not stated Cv: 33/33 Electrocardiogram: Not stated Echocardiography: Doppler M-mode and 2-dimensional echocardiography at > 6 months after either intervention, at an average of 15[18] months. Am J Cardiol 2004;93:165-170 Note: Overlap with RF group and Thomas et al. case series patients. Location Westmead Hospital, University of Sydney, NSA, Australia AND UCSF, California, USA Study design Level of Evidence: III-2 Study population Inclusion/Exclusion criteria Sample Size: RF: n=21 Cv: n=33 Inclusion Criteria: Patients with highly symptomatic AF unresponsive to pharmacologic therapy or were undergoing heart surgery for correction of another cardiac condition with concurrent problematic AF. Patients who underwent RF ablation and were in SR in long-term follow-up. Patient Diagnosis: AF Intention-to-Treat Analysis: Not stated Basis of Patient Selection: RF: Original group of 42 consecutive RF ablation patients; 29/42 patients selected who were in SR at long-term follow-up; 8/29 had paroxysmal AF preoperatively and were excluded; 21/29 included in study. Cv: Consecutive patients cardioverted to stable SR > 6 months previously. Mean Age: RF: 62[11] Cv: 65[10] pns Gender Mix: RF: 11/10 Cv: 24/9 p=0.03 Patient Co-morbidities: Coronary disease: RF: 4/21 Cv: 11/33 pns Hypertension: RF: 9/21 Cv: 14/33 pns Diabetes mellitus: RF: 2/21 Cv: 2/33 pns Stroke: RF: 0 Cv: 3/33 Duration of pre-surgical AF (months): RF: 51[9] Cv: 7[2] p=0.0001 Pre-surgical atrial size: Not stated Pre-surgical LVEF (%): Not stated Follow-up (months): 15[18] Eligibility Rate: Not stated Indication for concurrent surgery: MV disease: RF: 13/21 Cv: 12/33 pns Lost to Follow-up: None Underlying heart disease: Not stated Study Period: 7/95-12/01 Other: Body surface area: RF: 1.9[0.2] Cv: 1.9[0.23] pns Operator Details: Not stated 239 Exclusion Criteria: Persistent AF. Appendix C.2.4: Intraoperative ablation- Radiofrequency Comparative RFA versus Maze-III Authors Intervention Chiappini et al.2004 Patients underwent either the Maze-III procedure (M-III) or radiofrequency ablation according to the Cox-Maze III pattern (RF). RF: Lesion device: RADIOFREQUENCY/ Hand-held probe (Cobra Flex; Boston Scientific, San Jose, CA, USA). Energy level: Temperature guided energy applications performed with a pre-selected catheter tip temperature of 70 oC for 2 minutes in the LA and 90 seconds in the RA. Energy rate: Not applicable Surgery: M-III: Cox-Maze III RF: Left lesions: The LA incision was completed with ablation to isolate the right pulmonary veins. The left pulmonary veins were isolated separately, with a connecting ablation line between the right and left encircling lines. Ablation lines were also performed from the ablation line isolating the left pulmonary veins to the base of the LAA amputation site and from the base of the LAA amputation site to the posterior MV annulus. Right lesions: An ablation line was drawn on the right-sided aspect of the interatrial septum starting from the middle of the posterior longitudinal right atriotomy, across the interatrial septum up to the caudal aspect of the os of the coronary sinus and to the tricuspid valve, and extended to the inferior vena cava cannulation site. Atrial appendages: LAA excised and the amputation site resutured with 4-O Prolene (Ethicon, Somerville, NJ, USA). Atrial incisions: Access to the inside of the LA through a standard atriotomy in the interatrial groove, as for a MV procedure. Conventional right atriotomy was a posterior longitudinal incision. Sequence of surgery: The aorta was cross clamped and the heart arrested before the ablation began. Excision of the LAA then ablation of the LA. MV procedure followed LA ablation. After rewarming and release of the cross clamp the RF ablation of the right side was completed. Both groups Surgical access: Not stated CPB Cannulation: CPB with bicaval and aortic cannulation. Cardioplegia: Antegrade crystalloid cardioplegia. Body temperature: Moderate hypothermia (32 oC). Type of concurrent surgery: MVR: M-III: 4 RF: 13 MVR+TVP: M-III: 13 RF: 11 MVR+AVR: M-III: 4 RF: 8 MVR+AVR+TVP: M-III: 8 RF: 5 TVP+atrial septal defect repair + ventricular septal defect closure: M-III: 1 RF: 0 TVP+ atrial septal defect repair:: M-III: 0 RF: 1 AVR: M-III: 0 RF: 1 AVR+CABG: M-III: 0 RF: 1 Ann Thorac Surg 2004;77:87-92 Location Department of Cardiovascular Surgery, Policlinico S. Orsola-Malpighi, University of Bologna, Bologna, Italy Study design Level of Evidence: III-3 Study population Inclusion/Exclusion criteria Sample Size: M-III: 30 RF: 40 Inclusion Criteria: Chronic AF Patient Diagnosis: Chronic AF Intention-to-Treat Analysis: Not stated Basis of Patient Selection: Not stated Follow-up (months): 15.5 (range 7-74) M-III: 73.2[4.2] (range 20-91) RF: 16.5[2.5] (range 7-22) p<0.05 Eligibility Rate: Not stated Lost to Follow-up: Lost due to death: M-III: 2/30 RF: 3/40 Study Period: M-III: 4/95-3/01 RF: 4/01-6/92 Operator Details: All operations performed by the same surgeon. 240 Mean Age (y): M-III: 60.9[13.9] RF: 62.0[11.6] pns Gender Mix (M/F): M-III: 6/24 RF: 8/32 pns Patient Co-morbidities: Not stated Duration of pre-surgical AF (months): M-III: 53.5 RF: 61.9 pns Pre-surgical atrial size: Left atrial dimension (mm): M-III: 56.4[8.1] RF: 56.1[7.6] pns Pre-surgical LVEF (%): M-III: 58.0[11.4] RF: 56.8[13.3] pns Indication for concurrent surgery: Not stated Underlying heart disease: Not stated Other: NYHA class: M-III: 2.7[0.7] RF: 2.8[0.5] pns Exclusion Criteria: Not stated Authors Chiappini et al. 2004 continued Intervention Study design Redo operations: M-III: 6/30 (20%) RF: 6/40 (15%) pns Medication: Routine antiarrhythmic prophylactic treatment, with amiodarone the drug of choice. Amiodarone begun after induction of anaesthesia with a 300 mg IV bolus, followed by 1200 mg/24 hour IV until the end of the first postoperative day. Beginning on the second postoperative day oral administration of 200 mg/24 hr was begun. After discharge, maintenance of 200 mg/24 hour was continued. Treatment was discontinued 6 months after operation. Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: 12-lead ECG during each follow-up visit. At least one Holter monitoring of rhythm was performed in each group 6 months after hospital discharge. Echocardiography: 6 months postoperatively transthoracic echocardiography performed, including transmitral and transtricuspid Doppler echocardiography. Detection of E and A waves was used in evaluating atrial contraction. 241 Study population Inclusion/Exclusion criteria Appendix C.2.5: Intraoperative ablation- Radiofrequency Comparative Biatrial versus Left atrial RFA Authors Intervention Güden et al. 2002 Biatrial RFA (BARF) or left atrial RFA (LARF) Surgical access: Median sternotomy CPB Cannulation: Bicaval Cardioplegia: Antegrade and retrograde tepid (32oC) blood cardioplegia Body temperature: Not stated Lesion device: RADIOFREQUENCY/ Medtronic Cardioblate surgical ablation pen, a hand-held, unipolar, irrigated RF ablation device. Saline irrigation through 9 tip openings conducts RF current away from tip, creating a virtual electrode. The tip of the pen slowly oscillated over the endocardial tissue during procedure. Energy level: Power generator produces power output of 20-30 W. Used 25 W Energy rate: 5 mL/min irrigation rate. Surgery: Left-sided: Left ablations: An ablation line was placed from the LAA to the left superior pulmonary vein. Isolation of the right pulmonary veins completed by circular ablation line (part of right isolation was incision). Left pulmonary veins encircled and a connecting line made between both islands of pulmonary veins, as near to the LA roof as possible to avoid injury to the oesophagus. An ablation line from the left pulmonary veins to posterior mitral annulus performed with caution so as not to injure the circumflex coronary artery. Circumflex artery located with surgeon’s left index finger or administration of retrograde cardioplegia. In some cases, after placement of surgical instrument in coronary sinus from right side, had to push up against the LA wall to locate where the coronary sinus ended on left side, an ablation line from middle of MV ablation line down toward the base of the atria was performed to prevent the reentry pathways moving between the atria through the coronary sinus. Right ablations: None Atrial appendages: The LAA amputated and sutured afterwards, or a circumferential RF lesion created around its base and the orifice oversewn from the inside of the atrium. Atrial incisions: Left atrial incision through the interatrial groove. Sequence of surgery: Left atrial incision made after cardioplegic arrest. A large sling used to go around the inferior vena cava for CBP, using this sling the heart was lifted and turned toward the surgeon to facilitate better exposure of the LAA. LAA excised or isolated, then left ablation lines placed. LAA amputation site sutured after left ablations. Concomitant procedures performed after completing left-sided ablation. Right-sided (for biatrial): Right ablations: The endocardial surface was ablated between the superior and inferior caval cannulation sites. RFA lines were made from the excised RAA to the anterior tricuspid leaflet, and from the caudal Ann Thorac Surg 2002;74:S1301-1306 Location Departments of Cardiovascular Surgery and Anesthesia, Kadir Has University, Florence Nightingale Hospital, Istanbul, Turkey Study design Study population Inclusion/Exclusion criteria Sample Size: n=62 BARF: n=39 LARF: n=23 Patient Diagnosis: Not stated Inclusion Criteria: Patients with at least 6 months of persistent AF. Basis of Patient Selection: Not stated Mean Age (yrs): Total 52[14] BARF: 50[12.9] LARF: 53[14] Exclusion Criteria: Not stated Eligibility Rate: Not stated Gender Mix (male/female): BARF: 10/29 LARF: 11/12 Follow-up (days): mean 104 (range 45-245) Patient Co-morbidities: Not stated Level of Evidence: III-2 Prospective data collection Duration of pre-surgical AF: Not stated Lost to Follow-up: 24/62 had atrial transport test at 6 months postoperatively. Study Period: 2/01-12/01 Pre-surgical atrial size: Mean left atrial diameter (mm): Pre-surgical LVEF (%): BARF: 50[10] LARF: 52[10] Indication for concurrent surgery: Not stated Operator Details: Not stated Note: Dr Akpinar disclosed a financial relationship with Medtronic, Inc. 242 Underlying heart disease: Rheumatic MV disease: BARF: 51% LARF: 43% Other: Six patients had previous closed mitral commissurotomy Authors Güden et al. 2002 continued Intervention Study design end of the posterior longitudinal incision at the AV groove to the posterior portion of the annulus of the tricuspid valve. Ablation line then made on the right side of the interatrial septum, starting from the middle of the right atriotomy across the fossa ovalis up to the caudal aspect of the coronary sinus, followed by an ablation line from this point to inferior vena cava and up to the posterior annulus of the tricuspid valve. Atrial appendages: RAA excised. Atrial incisions: A 4 cm incision was made anteriorly from the amputated RAA toward the inferior vena cavae. A second posterior longitudinal and lateral incision made at the dorsolateral aspect of the RA and extended to the AV groove reaching the interatrial septum. Sequence of surgery: Right ablations performed during rewarming on partial bypass after closure of the cross clamp. Modifications: In 6 patients with previous closed mitral commissurotomy and 3 patients with thin fragile tissue, the LAA was not amputated. A circumferential RFA around the base of the LAA within the LA was performed, followed by oversewing the orifice. Type of concurrent surgery: MVR: BARF: 7 LARF: 4 MVP: BARF: 3 LARF: 5 MVR+tricuspid valve plasty: BARF: 4 LARF: 0 MVP+ tricuspid valve plasty: BARF: 5 LARF: 0 MVP+ atrial septal defect: BARF: 3 LARF: 0 MVR+AVR: BARF: 3 LARF: 2 MVP+AVR: BARF: 4 LARF: 4 CABG: BARF: 2 LARF: 2 CABG+MVP: BARF: 3 LARF: 3 AVR+MVR+ tricuspid valve plasty: BARF: 3 LARF: 0 AVR+CABG: BARF: 2 LARF: 3 Reoperation: BARF: 4 LARF: 2 Medication: Anticoagulation the same as for routine open heart surgery. Patients receiving mechanical valves continued to be treated with coumadin. Patients who remained in SR, the INR kept around 2 for aortic valves and 2.5-3 for MV surgery. Patients given 200mg/d of amiodarone on a routine basis for 3 months postoperatively. Pacemaker: Temporary pacing wires routinely used for pacing or overdriving the atrium when necessary. Cardioversion: Do not favour early cardioversion for patients in postoperative AF and reserve this for patients in AF 3 months postoperatively. Electrocardiogram: All patients had 24 hour Holter during hospitalisation. Echocardiography: The transoesophageal echocardiographic probe removed during left sided ablation to prevent damage to oesophagus. Transthoracic echocardiography at 1 and 6 months postoperatively. 243 Study population Inclusion/Exclusion criteria Appendix C.2.5: Intraoperative ablation- Radiofrequency Comparative Biatrial versus Left atrial RFA continued Authors Intervention Deneke et al. 2002b Khargi et al. 2003 Patients underwent either a biatrial RFA procedure (BARF) or a left atrial RFA procedure (LARF). Lesion device: RADIOFREQUENCY/ SICTRA catheter (Sprinklr; Medtronic, Minneapolis, MN) with a 7F (2.33mm) diameter, a 4mm tip length and 13 irrigation holes. The catheter was connected by an infusion pump with a 0.9% NaCl infusion bag. Catheter connected to a radiofrequency generator (CardioRythm-ATAKR, Medtronic) RF ablation (SICTRA). Energy level: 20-32 Watt Energy rate: 200-320 ml NaCl 0.9%/ hour. Lesion set: Biatrial procedure (from Khargi et al. 2001) Left ablations: Endocardial rim of the ostium of pulmonary veins RF ablated. RF line between left and right pulmonary veins. Lesion from left pulmonary vein to the midportion of posterior mitral annulus. RF lesion from left lateral rim of orifice of left inferior pulmonary vein to rim of LAA orifice. (n=55 had left ablations only) Right ablations: RF lesions from the posterocranial end of S3 into the superior caval vein (R1) and from the posterocaudal end of S3 into the inferior caval vein (R2). R3 made from the anterior edge of S3 close to the AV groove traversing the endocardium to middle of the posterior part of the tricuspid annulus. R4 from medial cut edge from the RAA to the anteroseptal commissural area of tricuspid valve. R5 from posterocranial edge of S3 traversing to posterior area of foramen ovale to posterior rim of coronary sinus orifice then curving to inferior caval vein, ablating the ‘isthmus’. (n=49 had right ablations performed) Atrial appendages: RAA excised (S1). LAA resected or ablated (if adhesions prevented resection). Atrial incisions: Perpendicular incision 3-4 cm long from the middle of the incision of RAA excision traversing the lateral free wall of the RA (S2). Curved incision from the AV groove, about 2-3 cm cranially and anterior from the inferior caval vein and continuing posterocranially behind the sulcus terminalis (S3). Left atrium opened in the interatrial groove. Sequence of surgery: The RA incisions and ablations were performed, the aorta cross clamped and cardioplegia administered. Left atrial incisions and ablations then performed. Cross clamp removed and incisions of RA closed. Left atrial procedure: As above, but the right lesions were omitted. J Am Coll Cardiol 2002;39:1644-1650 Interactive Cardiovascular and Thoracic Surgery 2003;2:241-245 Location Department of Cardiothoracic Surgery, and Department of Cardiology, Berufsgenossenscha ftliche Kliniken BergmannsheilUniversity Hospital, Bochum, Germany Study design Level of Evidence: III-2/3 Study population Inclusion/Exclusion criteria Sample Size: BARF: n=49 LARF: n=21 Inclusion Criteria: Patients with at least 1 year of chronic or permanent AF or unsuccessful direct-current shock cardioversion 6 months before inclusion. All patients had an indication for openheart surgery, independent of AF. Khargi et al. 2003 On admission to hospital each patient had an extended ECG recording of the V2 and II leads. If an episode of sawtoothed atrial wave pattern or an episode of regularity was observed on this recording, biatrial lesions were performed. All patients with paroxysmal AF had a left atrial lesion pattern. Patient Diagnosis: AF Basis of Patient Selection: All patients undergoing a combination of open-heart surgery and the modified Maze procedure were included. Eligibility Rate: Not stated Follow-up (months): BARF: 18[14] (range 1-50) LARF: 11[10] (range 4-20) p=0.046 Lost to Follow-up: BARF: 3 mo: 39/49 6 mo: 36/49 12 mo: 29/49 24 mo: 21/49 36 mo: 7/49 48 mo: 2/49 6 deaths during follow-up LARF: 3 mo: 19/21 6 mo: 17/21 12 mo: 7/21 2 deaths during follow-up Study Period: 3/97-2/01 All data collected between 3/97-2/01. Operator Details: All surgical procedures performed in the Clinic of Cardiothoracic Surgery, “Bergmannsheil” University Hospital. Both groups Surgical access: Median sternotomy CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated 244 Mean Age (yrs): BARF: 65[9] LARF: 69[9] p=0.118 Gender Mix (male/female): Not stated Patient Co-morbidities: Not stated Duration of pre-surgical AF (yrs): BARF:9[8] (range 1-15) LARF: 13[17] (range 1-25) p=0.538 Pre-surgical atrial size: LA dimension (mm): BARF: 51[10] LARF: 47[8] p=0.224 Pre-surgical LVEF (%): BARF: 59[10] LARF: 56[10] p=0.453 Indication for concurrent surgery: Not stated Underlying heart disease: Not stated Exclusion Criteria: Not stated Authors Intervention Deneke et al. 2002 continued Type of concurrent surgery: MVR: BARF: 25 LARF: 3 MVP: BARF: 2 LARF: 0 MVR+AVR: BARF: 1 LARF: 1 AVR: BARF: 6 LARF: 4 Aorta-coronary bypass surgery (+MVR): BARF: 15(2) LARF: 13(4) Medication: Sotalol (80 mg twice daily) for at least 6 months, up to April 1999, then metoprolol succinate (47.5-95 mg/day) in an equipotent dose. Standard anticoagulation therapy as following valve replacement. Pacemaker: Not stated Cardioversion: Performed in patients with recurrent AF. Electrocardiogram: All patients on admission to hospital had a standard ECG and 24 hour Holter recording performed at follow-up visits after 3, 6 and 12 months. Holter monitoring performed 6 months postoperatively. Echocardiography: Transthoracic echocardiography performed on admission to hospital and after 6 months postoperative. Detection of E and A waves was considered to be atrial contraction. Study design 245 Study population Inclusion/Exclusion criteria Appendix C.2.6: Intraoperative ablation- Radiofrequency Case Series Biatrial RFA Authors Intervention Damiano et al.2003 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Lesion device: RADIOFREQUENCY/ Bipolar device Energy level: Not stated Energy rate: Not applicable Surgery: RF ablation used to isolate the pulmonary veins, and the other incisions of the Maze-III performed either with RF or incisions. Left lesions: Isolation of the pulmonary veins. Right lesions: Not stated Atrial appendages: Not stated Atrial incisions: Not stated Order of surgery: Not stated Type of concurrent surgery: Not stated Medication: Not stated Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Not stated Other: Electrical isolation of the pulmonary veins was documented with intraoperative pacing in all patients. Atrial function and pulmonary vein patency were assessed by postoperative MRI or 3D computed tomography at 1 month postoperatively. JACC 2003; 498A (abstract) Location Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, MO, USA. Study design Level of Evidence: IV Study population Inclusion/Exclusion criteria Sample Size: n=26 Inclusion Criteria: Chronic or paroxysmal AF. Patient Diagnosis: Chronic AF: 9 Paroxysmal AF: 17 Basis of Patient Selection: Consecutive patients Mean Age (y): 60.1[12.2] Eligibility Rate: Not stated Gender Mix (male/female): 17/9 Follow-up (months): Not stated Patient Co-morbidities: Not stated Duration of pre-surgical AF (yrs): 7.6[6.9] Lost to Follow-up: Not stated Pre-surgical atrial size: Not stated Study Period: 02- Pre-surgical LVEF (%): Not stated Operator Details: Surgery performed at three medical centres. Indication for concurrent surgery: Not stated 246 Underlying heart disease: Not stated Exclusion Criteria: Not stated Appendix C.2.6: Intraoperative ablation- Radiofrequency Case Series Biatrial RFA continued Authors Intervention Hornero et al. 2002 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Cool blood retrograde cardioplegia Body temperature: Not stated Lesion device: RADIOFREQUENCY/ Radiofrequency probe was a surgical malleable probe (ThermaLine®, EP Technologies) with 7x10 mm long coil-type electrodes and 3 mm interelectrode spacing, with 2 indifferent electrodes placed on the patient’s back. Energy level: 100 W for 120 seconds with maximum set temperature of 85 oC. Ablations were assessed macroscopically and when the line was discontinuous it was repeated. Energy rate: Not applicable Surgery: Left ablations: Endocardial lesions. Left and right pulmonary vein ostiums independently isolated by means of two circumferential endocardial lesions, connected with a line along the atrium posterior wall. Two additional endocardial ablation lines connected the circumference of the left pulmonary veins first with the mitral annulus, and second with the LAA. Right ablations: Epicardial lesions. Three RA ablation lines made. First along the crista terminalis from the superior to the inferior vena cava and prolonged through isthmus vena cava-tricuspid annulus, and the second line at the lower part of the RA from the interatrial groove to the tricuspid annulus. The last line prolonged parallel to the tricuspid annulus and extended along the RAA. With tricuspid valve disease the ablation line in the RA was replaced by an incision. Pulmonary veins encircled. Atrial appendages: Not excised. LAA internally sutured when a thrombus present. Atrial incisions: In all patients the LA approached through a standard left atriotomy just posterior to the interatrial groove. RA incision replaced the ablation line in patients requiring tricuspid valve surgery. Order of surgery: Right atrial ablations before CPB started. To prevent possible RFA complications the echocardiographic probe was removed from the oesophagus during the ablation time, RFA was applied before the metallic prosthetic material was implanted, during epicardial ablations the epicardium and nearby structures were protected by surgical gauze, during the endocardial ablation a rubber leaflet was placed on the posterior side of the heart to avoid transmural retrocardiac burns, all endocardial lesions with post-ablation charring were cleaned with surgical gauze, continuous cool blood retrograde perfusion in the ablation points near the circumflex artery, and lesions <1 cm from the pulmonary vein ostia were avoided. Difficult regions to ablate were atrial regions with difficult approach, such as ostia of left pulmonary veins, and epicardial fatty areas and epicardial areas of fibrosis in reoperations. Interactive Cardiovasc Thorac Surg 2002;1:72-77 Location Cardiac Surgery Department of the University General Hospital, Valencia, Spain Study design Level of Evidence: IV Study population Inclusion/Exclusion criteria Sample Size: n=55 Inclusion Criteria: Permanent AF (> 3months). Patient Diagnosis: Permanent AF (> 3months) Basis of Patient Selection: Consecutive patients. Mean Age (yrs): 58[9] Eligibility Rate: Not stated Gender Mix (male/female): 21/34 Follow-up: 7 months (range 1-16) Patient Co-morbidities: Diabetes mellitus: 7/55 (12.7%) Arterial hypertension: 7 (12.7%) Respiratory pathology: 5 (9%) Previous embolism: 11 (20%) Chronic renal failure: 1 (1.8%) Lost to Follow-up: Not stated Study Period: 6/00-12/01 Operator Details: Not stated Duration of pre-surgical AF (yrs): 5.6[4.2] (range 3 months-16 yrs) < 3 yrs: 18/55 3-6 yrs: 10/55 > 6 yrs: 27/55 Pre-surgical atrial size: Mean left atrial diameter (mm): Patients with AF/atrial flutter postoperatively: 59[7] Patients with no recurrence: 48[7] Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Mitral/tricuspid valves: 36 Aortic-mitral valves: 14 Coronary artery disease: 2 Congenital disease: 1 Underlying heart disease: Not stated Other: No of antiarrhythmic drugs used: 2.0[0.7] Reoperations: 7 (12.7%) 247 Exclusion Criteria: Not stated Authors Hornero et al. 2002 continued Intervention Study design Type of concurrent surgery: MVR: 23 MVP: 6 MVR+TVP: 3 MVP + TVP: 3 MVP+CABG: 1 MVP+TVP+CABG: 1 MVR+AVR: 9 MVR+AVR+TVP: 3 MVR+ACR+CABG: 2 AVR: 2 CABG: 2 Medication: Amiodarone initiated intraoperatively (200 mg/day) and stopped on 3rd month postoperatively in patients with SR. All patients treated with spirolactone 50-100 mg daily during hospital stay. Anticoagulation suspended at 3rd month in patients without cardiac mechanical prosthesis and with effective echocardiographic atrial contraction. Pacemaker: DDD stimulation during first 48 hrs postoperative. Cardioversion: After discharge new AF/atrial flutter were treated with external cardioversion. No cardioversions done after first 3 months postoperatively. Electrocardiogram: At hospital discharge, and 3rd, 6th and 12th month postoperatively. Echocardiography: At hospital discharge, and 3rd, 6th and 12th month postoperatively. 248 Study population Inclusion/Exclusion criteria Appendix C.2.6: Intraoperative ablation- Radiofrequency Case Series Biatrial RFA continued Authors Intervention Prasanna et al. 2001 Surgical access: Not stated CPB Cannulation: Conventional with bicaval venous cannulation and ascending aortic cannulation. Cardioplegia: Antegrade cold blood cardioplegia. Body temperature: Normothermic Lesion device: RADIOFREQUENCY/ Ordinary cautery pencil connected to a diathermy machine (Valley Lab Force 40 S™ Valleylab, Inc CO or Excalibur Plus PC™, Conmed Corp, NY, USA), Valley Lab Force device had 500 kHz damped sinusoidal bursts with repetition frequency of 31.25 kHz and rated load of 300 ohms. The Conmed Excalibur device had 540 kHz damped sinusoidal bursts with repetition frequency of 20 kHz and rated load of 500 ohms. Energy level: 40 W with a theoretical energy delivery of 40 Joules/second. Lesions placed by slow progression of the pencil so the tissue blanched when the cautery arc was moved. Energy rate: Not applicable Surgery: Left ablations: Lesions placed circumferentially at 1 cm from pulmonary vein orifices. Lesion touching each of previous lesions and mitral annulus at 5 o’clock connects all 4 lesions. A lesion placed from outer lesion to ligated LAA. In giant LA (> 7 cm) optional cruciate lesion placed within circum-pulmonary vein lesion. Right ablations: From the posterior wall of the superior vena cava to the RA junction a lesion was drawn across the fossa ovalis to the inferior vena cava cannula, veering towards the mouth of the coronary sinus and burning the inferior mouth of the coronary sinus, including as much ostium as possible. Then, from the inferior vena cava ablating the atrial isthmus and proceeding to the tricuspid valve orifice at 5 o’clock. Then from the middle of the first lesion laterally towards the atrial wall, ablating the atrial crista and proceeding further laterally to meet the atriotomy. The 4th lesion is from the superior end of the atriotomy to the RAA stopping at the cannulation orifice, and then restarting at the diametrically opposite point and continuing the lesion towards the dome of the LA. Care taken to search for the sinus node artery and interrupt the cautery lesion 3-mm either side of the artery. Area of sinus node avoided during placement of all lesions. Atrial appendages: LAA ligated externally. Atrial incisions: Right atrium opened. Vertical left atriotomy. Sequence of surgery: Right lesions drawn on the beating perfused heart. The retrograde cannula was placed back into the coronary sinus and any tricuspid procedure performed. Atriotomy closed and heart arrested. Left atriotomy and MV procedure performed. Left lines placed while controlled warm retrograde normokalaemic reperfusion being done. Left atriotomy closed. Note: In discussion lesion set more like Maze-II than Maze-III. Lesion Heart Surgery Forum 2001;4:340345 Location Sri Jayadeva Institute of Cardiology, Bangalore, India Study design Study population Inclusion/Exclusion criteria Sample Size: n=25 Inclusion Criteria: Patients with chronic AF (> 6 months) and left atrial size > 5.5 cm with associated MV disease. Level of Evidence: IV Patient Diagnosis: AF Basis of Patient Selection: In a previous study, on total CPB a cardioversion was performed in patients with no left atrial clot, and all patients who did not cardiovert to SR were included in the present study. Consecutive cases. Mean Age (yrs): Not stated Gender Mix (male/female): Not stated Patient Co-morbidities: LAA clot: 4 (16%) LAA + body clot: 4 (16%) Duration of pre-surgical AF: Not stated Eligibility Rate: Not stated Follow-up (yrs): 3.5 (range 3.2-3.8) Pre-surgical atrial size: Mean left atrial diameter (cm): 7.0 [0.75] (range 5.5-8.2) Pre-surgical LVEF (%): Not stated Lost to Follow-up: Not stated Study Period: 6 month period Operator Details: Not stated Indication for concurrent surgery: Mitral stenosis: 4 (16%) Mitral stenosis + tricuspid regurgitation (TR): 4 (16%) Mitral regurgitation (MR): 3 (12%) Mitral stenosis + MR + TR: 9 (36%) Mitral stenosis + MR + aortic stenosis+TR: 3 (12%) Mitral stenosis + aortic regurgitation (AR) + TR: 1 (4%) MR + aortic regurgitation + TR: 1 (4%) Underlying heart disease: Not stated 249 Exclusion Criteria: Patients with a left atrial clot were excluded. Authors Intervention Prasanna et al. 2001 continued was placed near the sinus node artery as it was found this usually caused a sudden conversion to SR. Type of concurrent surgery: open mitral valvotomy (OMV): 4 OMV + tricuspid annuloplasty: 4 MVP: 3 Mitral + tricuspid valve repair: 8 MVR + tricuspid valve repair: 1 Mitral + aortic + tricuspid valve repair: 1 MVR + AVR + tricuspid valve repair: 4 Medication: Patients in SR put on infusion of amiodarone (10 mg/kg/24hrs) then oral amiodarone 200 mg/day for 3 months, which was then stopped. Patients with nodal rhythm given intravenous aminophylline (18 mg/kg/24 hrs) with initial 200mg bolus on CPB. All patients who were not on coumadin for valve replacement were placed on 150 mg enteric-coated aspirin life-long. Pacemaker: Atrial and ventricular wires placed in all patients with temporary atrioventricular pacing when required. Cardioversion: Not stated Electrocardiogram: All patients had 24 hour Holter before discharge. (postoperative day 10). Labelled as converters if no AF episodes lasting more than 30 seconds in 24 hour period. Echocardiography: Transoesophageal routinely in all patients during surgery, and transthoracic postoperatively at 3, 6 and 12 months. Atrial transport function present if ‘A’ wave velocity >40 cm/s. Other: First 10 patients had sinus node recovery time (SNRT) studies. Normal limit for SNRT taken as 1,400 ms and corrected SNRT value considered normal if less than 525 ms. Study design 250 Study population Inclusion/Exclusion criteria Appendix C.2.6: Intraoperative ablation- Radiofrequency Case Series Biatrial RFA continued Authors Intervention Raman et al.2003 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Lesion device: RADIOFREQUENCY/ flexible, 7-electrode, temperature-controlled Cobra probe (EP Technologies; Boston Scientific Corp, San Jose, CA, USA). Energy level: 80 oC to 85 oC for 2 minutes. Energy rate: Not applicable Surgery: Left ablations: Endocardial lesions in patients with MV surgery, and epicardial lesions in aortic valve and CABG surgery. Endocardial (n=92): linear lesion along the roof of the LA, encircling lesion around right-sided pulmonary veins, encircling lesion around leftsided pulmonary veins with connecting lesion to the MV annulus, and connecting lesion to mitral annulus from lower right pulmonary vein orifice. Epicardial (n=40): linear lesion along the roof of the LA, encircling lesions around the left-sided pulmonary veins, encircling lesions around right-sided pulmonary veins with a connecting lesion toward the atrioventricular groove. Right ablations: Epicardial lesions common to all patients. Linear epicardial lesion from behind the sinoatrial node, approximately along the direction of the crista terminalis, curving up to the AV groove, with a connecting lesion from the inferior vena caval orifice to the right AV groove low on the body of the RA to create a block in the cavotricuspid isthmus area. Atrial appendages: Endocardial: LAA closed from within by suturing closed. Epicardial: ligation of the base of the LAA using purse string suture. Atrial incisions: Not stated Sequence of surgery: All epicardial lesions created during CPB. In early series, the posterior LA lesions created on an arrested heart to facilitate access. Later in series, the trend to perform these lesions on a decompressed heart during BPB, either with aid of left ventricular vent or bicaval cannulation. Other: Safety precautions prescribed for the surgery: 1. Adequate placement of adhesive grounding pads. 2. Withdrawal of transoesophageal echocardiographic probe from the mid-oesophagus and turning off the echocardiographic machine to minimise risk of oesophageal injury. Lesion set in posterior LA also avoided the most dependent portion of the LA, which was likely to be in contact with the oesophagus. 3. If the probe shut off, the system was shut down and restarted to avoid overheating the tissue. 4. Probe always placed under direct vision or by means of palpation, J Thorac Cardiovasc Surg 2003;126:13571365 Location Department of Cardiac Surgery, Austin and Repatriation Medical Centre, Heidelberg and the Baker Institute of Medical Research, Prahran, Victoria, Australia Study design Level of Evidence: IV Registry study Basis of Patient Selection: Primary indication the concomitant surgery in all cases, plus AF. All patients included, irrespective of the risk and urgency of the procedure. Study population Inclusion/Exclusion criteria Sample Size: n=132 Inclusion Criteria: Patients with established AF undergoing conventional cardiac surgical procedures. In the first half of the study all patients had AF documented on a preoperative 24 hour Holter monitor before being offered RF ablation. Initially only performed with MV surgery. Note: patient enrolment based on surgeon’s discretion. Patient Diagnosis: Chronic AF: 99 Paroxysmal AF: 28 Atrial flutter + AF: 5 Mean Age (y): 66[12] (range 21-86) Gender Mix (male/female): 91/41 (69%/31%) Patient Co-morbidities: Eligibility Rate: Not stated Follow-up (months): 6.4 (range 3-24) Lost to Follow-up: 9 deaths 12 patients had surgery within 3 months of publication and were not available for out-of-hospital follow-up. Complete clinical review in 110 patients. 87/134 at 3 months 50/134 at 6 months 15/134 at > 12 months Study Period: 3/00-3/02 Operator Details: Operations performed at 20 hospitals across Australia and New Zealand. When each new surgeon and centre was trained in the surgery, care was taken to ensure uniformity of the lesion sets and parameters used to create them. The purchase price of each probe also included a fee to help with the set-up and running costs of the registry. 251 Duration of pre-surgical AF (months): 36 (range 1-120) Pre-surgical atrial size: Mean left atrial diameter (n=87, patients with 3 months follow-up; mm): Endocardial RF ablation: 54[3] Epicardial RF ablation: 45[4] Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Not stated Exclusion Criteria: Not stated Authors Intervention Study design Raman et al. 2003 continued with care taken to ensure tissue contact to avoid collateral damage in surrounding structures and to ensure accurate lesion creation. 5. Lesions created close to the circumflex artery within the LA with infusion of cardioplegia. Lesions close to the right coronary artery on the right AV groove created with the heart beating. Primarily to avoid injury to the relevant coronary arteries. In addition, if right coronary artery large and mobile, this was dissected gently and pushed anteriorly out of the way of the probe. 6. Surgeons asked to watch the change in atrial tissue colour with the application of the RF energy. Type of concurrent surgery: Endocardial RF ablation on left atrium: MV: 62 MV+CABG: 10 AVR+MV: 7 CABG+ atrial septal defect closure: 1 Redo Ebstein repair: 1 Other; 11 Epicardial RF ablation on left atrium: CABG: 19 AVR: 9 AVR+CABG: 5 Other: 7 32 patients had a mechanical MV and 8 patients had a biologic prosthetic valve. Medication: Postoperative patients not started on any specific regimen of anticoagulation. As multicentre experience began, patients were encouraged to take low dose amiodarone (200mg/d) for 6 months unless specifically contraindicated, there was variable compliance to this by treating surgeons and patients. Often antiarrhythmics only used if patients in recurrent AF. Patients not anticoagulated unless required eg. mechanical valve implant. Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: ECG and Holter monitoring performed between 3 and 6 months postoperative to document SR. Echocardiography: Not stated A protocol of clinical, echocardiographic and ECG follow-up was suggested to each of the participating surgeons. Funds for animal research and travel grants were provided to Drs Raman and Power by EP Technologies. 252 Study population Inclusion/Exclusion criteria Appendix C.2.6: Intraoperative ablation- Radiofrequency Case Series Biatrial RFA continued Authors Intervention Study design Study population Sie et al. 2001 Surgical access: Median sternotomy CPB Cannulation: Standard aortic and bicaval cannulation Cardioplegia: Cold cardioplegic solution Body temperature: Moderate hypothermia (28 oC) Lesion device: RADIOFREQUENCY/ HAT 200S (Sulzer-Osypka GmbH, Grenzach-Wyhlen, Germany) delivered in a unipolar mode between the 4 mm tip electrode of a specially designed probe and a 10 X 16 cm external backplate electrode that was underneath the back of the patient. The ablation probe had a thermistor embedded centrally in the distal part of the tip electrode for continuous monitoring of catheter tip temperature. Ablation done in a bloodless operating field. Energy level: 500 Hz continuous sinusoidal unmodulated waveform with preselected catheter tip temperature of 60oC. Energy rate: Saline solution irrigation at 4 ml/minute. Surgery: All atrial incisions of Cox-Maze replaced by RF endocardial ablation lines, except for incisions to enter the left and right atrial cavity. Left ablations: Linear RF ablation lines included isolation of right pulmonary veins by a unilateral ablation line and left pulmonary veins were encircled and a connecting line drawn between both island of pulmonary veins. Also from ablation line isolating the left pulmonary vein to the base of the LAA amputation site and to the posterior MV anulus. Right ablations: RF energy used to extend the electrical block caused by the first surgical incision cranially as far as possible toward the superior caval cannulation site and caudally toward the inferior caval cannulation site. Additional RF ablation lines drawn from the medial aspect of the base of the excised RAA into the anulus of the tricuspid valve and from the caudal end of the first surgical incision at the AV groove to the posterior part of the anulus of the tricuspid valve. Finally, a line was drawn on the right-sided aspect of the interatrial septum starting from the middle of the posterior or longitudinal right atriotomy across the interatrial septum up to the caudal aspect of the coronary sinus extended to the inferior vena cava cannulation site. Atrial appendages: RAA and LAA excised. Atrial incisions: Right atrium opened through a posterior longitudinal incision starting caudally of the superior caval cannulation site at the dorsolateral aspect of the RA. This incision extended along the border of the interatrial septum, slightly curved and ending at the AV groove opposite the inferior caval cannulation site. Anterior incision approximately 4 cm long made from the middle of the anterolateral aspect of the base of the amputated RAA to the inferior caval vein orifice. Standard left atriotomy in the interatrial groove, as for an MV procedure. Sequence of surgery: Right ablations performed on the beating heart before cross clamping. Concomitant procedures (eg. aortic valve replacement and CABG) were performed immediately after aortic cross clamping and before completing the left-sided ablations. After left atriotomy, the LAA was excised, and then the left ablations performed. Level of Evidence: IV Sample Size: n=122 Basis of Patient Selection: Consecutive patients Patient Diagnosis: chronic AF J Thorac Cardiovasc Surg 2001;122:249256 Location Departments of Cardiothoracic Surgery and Cardiology and Cardioanesthesioloy, Isala Klinieken, Hospital De Weezenlanden, Zwolle and the Academic Hospital Maastricht, Maastricht, The Netherlands. Eligibility Rate: Not stated Mean Age (yrs): 69[10] (range 33-83) Gender Mix (male/female): 48/74 Follow-up: 39 months Lost to Follow-up: 15/122 (12.3%) patients died and were lost to follow-up 117/122 at 3 months 111/122 at 12 months 107/122 at 21 months 107/122 at 30 months 107/122 at 39 months Study Period: 11/95-7/99 Operator Details: All patients operated on by same surgeon (HTS) Patient Co-morbidities: Not stated Duration of pre-surgical AF (yrs): 5.6[6.7] (1-49) Pre-surgical atrial size (parasternal long-axis view; mm): Left atrial: 50[9] (31-80) Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Haemodynamically significant MV disease: 110 (90%) Aortic valve disease: 32 (26%) Tricuspid valve incompetence secondary to MV disease: 60 (49%) Atrial septal defect: 6 (4 associated with MV disease, 1 isolated, and 1 in combination with coronary artery disease). Underlying heart disease: Coronary artery disease: 41 (34%) Other: NYHA functional class II: 17 (14%) III: 103 (84%) IV: 2 (2%) Parasternal long axis: 50[9] mm Left ventricular end-diastolic dimension: 54[8] mm Previous cardiac surgery: 8 (6%) (MV surgery in 7 patients and aortic valve replacement in 1 patient) 253 Inclusion/Exclusion criteria Inclusion Criteria: Indication for cardiac surgery. AF > 1 yr Exclusion Criteria: Patients who needed urgent cardiac surgery. Authors Intervention Sie et al. 2001 continued After the left ablation line from the base of the LAA amputation site to the posterior MV annulus was performed, the MV procedure was carried out. The remaining left ablation lines were then performed. The septal part performed at later stage of operation just before closing the LA to prevent tearing the septum. After rewarming the LA closed and cross clamp released. The heart de-aired extensively before defibrillation and closing of the RA. Concomitant procedures performed immediately after aortic crossclamping and before completing the left-sided maze and MV surgery. Type of concurrent surgery: MV repair: 48/122 (39%) MV replacement: 60/122 (49%) MV replacement : + aortic valve replacement: 26 + CABG: 33 + tricuspid valve repair: 54 + closure of atrial septal defect: 3 + correction of cortriatriatum: 1 + carotid artery deobstruction: 1 + left ventricle reconstruction: 1 + ascending aorta replacement: 1 + aortic root replacement: 1 In 14 patients without MV surgery: Aortic valve replacement: 2 Aortic valve replacement + tricuspid valve repair: 4 CABG + tricuspid valve repair: 6 Aortic valve replacement + CABG: 4 Closure of atrial septal defect: 1 Closure of atrial septal defect + CABG: 4 Tricuspid valve repair: 1 CABG: 1 Medication: Ventricular rate control (calcium blockers and/or digoxin) continued to the day before surgery. Oral warfarin discontinued 2 days before surgery. β-adrenergic blockers were continued. Postoperative atrial arrhythmias were treated with sotalol (80-120 mg) or amiodarone (200 mg). Antiarrhythmic drugs were tapered gradually after cardiac rhythm was considered stable. Pacemaker: Temporary epicardial wires were attached to the right ventricle and RA during surgery and used to pace the patients, to monitor the rhythm or to overdrive the atrium. Occasionally atrial pacing or AV pacing was needed to wean the patient from bypass. Cardioversion: Occasionally atrial pacing or AV pacing needed to wean the patient from bypass. Postoperative combined with antiarrhythmic medication if needed. Electrocardiogram: Not stated Echocardiography: Obtained within 3 months prior to surgery. Postoperative echocardiography performed at 3 and 6 months. Study design 254 Study population Inclusion/Exclusion criteria Appendix C.2.6: Intraoperative ablation- Radiofrequency Case Series Biatrial RFA continued Authors Intervention Sos et al. 2002 Surgical access: Median sternotomy. CPB Cannulation: Not stated Cardioplegia: B/Braun® haematic cardioplegic solution (4oC; K=25mEq/l; pH=7.6; haematocrit = 20%) at 4oC by the retrograde pathway. The hypothermia of heart maintained by topical lavage with cold saline solution (4oC). Body temperature: Moderate systemic hypothermia of 30oC. Lesion device: RADIOFREQUENCY/ Malleable Thermaline® (Model 15.907, Boston Scientific Corporation, EP Technologies) surgical probe, with two null electrodes on the patients’s back. The surgical probe consisted of 7 10-mm long coil type electrodes, separated 3 mm, allows long lesions up to 9 cm when the ablation done simultaneously through all electrodes. Each electrode has two temperature sensors. The probe connected to an RF generator (EPT 1000XP) through a connection box (EPT Meca APM 830T), allows the electrodes to be used in each lesion to be selected based on anatomic variants of patient. Lesion assessed visually. Energy level: 100W for 120 seconds, with 85 oC limit for atria of normal thickness and 75 oC for thin-walled atria (<2mm). Thickness of atria evaluated grossly by the surgeon. Energy rate: Not applicable Surgery: Left ablations: Endocardial ablation lines with the ostium of left and right pulmonary veins isolated independently by means of two circumferential lesions linked by another line along the posterior wall of the atrium. The other two ablation lines connected the circumference of the left pulmonary veins with the mitral annulus and LAA. Right ablations: Epicardially two independent ablation lines created, first along crista terminalis from the superior cava to inferior cava, and second perpendicular to first line, from left lower pulmonary vein to the tricuspid annulus, along the RAA. Atrial appendages: RAA not resected. LAA closed by internal suture. Atrial incisions: The LA approached through the interatrial sulcus. Sequence of surgery: Procedure began in RA without CPB. Lesions through the RA made in conditions of myocardial normothermia. Next, the patient cannulated for CPB and heart stopped. All ablation lines in LA in myocardial hypothermia, less than 25oC. The ablation lines next to the circumflex coronary artery made simultaneously with retrograde perfusion via the coronary sinus of cold blood, at 4 oC. Concurrent surgical procedure then performed. Type of concurrent surgery: MVR: 6 MV repair (2 plasty and 1 commissurotomy). Aortic valve substitution: 1 Closure of atrial septal defect with mitral and tricuspid plasty: 1 Giant left atrium reduction: 1 Medication: At time of intervention all patients consumed some type of Rev Esp Cardiol 2002;55:235-244 Location Servicios de Cirugía Cardíaca y Cardiología, Hospital General Universitario de Valencia. Study design Level of Evidence: IV Study population Inclusion/Exclusion criteria Sample Size: n=10 Inclusion Criteria: Chronic AF > 6 months. Patient Diagnosis: AF Basis of Patient Selection: Not stated Mean Age (yrs): 60[1] (range 51-69) Eligibility Rate: Gender Mix (male/female): 4/6 Follow-up: 3 months (range 1-5.5 months) Patient Co-morbidities: 1 woman had medical history of hypothyroidism secondary to amiodarone. Lost to Follow-up: 5/10 patients follow-up > 3 months Duration of pre-surgical AF: 7.8[4.8] (range 7 months-14yrs) Documented by ECG (1 patient chronic AF < 3 yrs and 9 patients AF > 3 yrs) Study Period: 6/00-11/00 Operator Details: Not stated Pre-surgical atrial size: Mean left atrial diameter (mm): 57.3[8.3] (range 47-77) Volume of left atrium (ml): 147[111] (range 79-452) Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Mitral cardiac valve disease: 6 (rheumatic in 5, degenerative in 1) Mitroaortic cardiac valve disease: 2 Aortic cardiac valve disease of degenerative origin: 1 Incomplete atrioventricular canal: 1 Other: In 2 patients redo MV surgery ECG voltage of f wave in precordial lead V1: 0.074[0.08] mV (range 0.01-0.2 mV) Number of antiarrhythmic agents tried/patient: 1.9[0.3] (range 1-3) Most patients had taken at least 2 drugs, mostly digitalis and amiodarone. 255 Exclusion Criteria: Patients with associated coronary disease. Authors Intervention Sos et al. 2002 continued antiarrhythmic, with antiarrhythmic treatment not discontinued before intervention. Before initiating ablation for AF, sodium heparin administered (3mg/kg). During surgery the patient began treatment with amiodarone (300 mg/d iv bolus) which continued in immediate postoperative period (1200 mg iv for first 48 hrs). Amiodarone maintained for first 60 postoperative days and later discontinued in patients remaining in SR. Other antiarrhythmic drugs like digoxin, calcium antagonists, and beta-blockers were added as needed for patient’s condition. All patients received diuretic treatment with spironolactone, 50-100 mg/day during hospital stay. Anticoagulation discontinued in third month in patients without mechanical cardiac prosthesis and with effective atrial contraction in echocardiographic controls. Pacemaker: Three temporary atrial epicardial electrodes (in the LA roof, sinus node zone, and anterior part of the free RA wall) and two ventricular electrodes were left in place in all patients for stimulation, recording cardiac rhythms and/or atrial overstimulation. Cardioversion: Postoperative arrhythmias treated by cardioversion if they had haemodynamic effects. Electrocardiogram: At discharge and 3 months postoperative. Holter study made only when patient complained of new episodes of palpitations. Echocardiography: At discharge and 3 months postoperative Other: Unipolar epicardial triograms used to diagnosed and typify postoperative arrhythmias, grouping AF in 3 varieties; type A= regular atriograms separated by isoelectric segments, with little fragmentation; type B= irregular atriograms with disturbances in isoelectric line and/or marked fragmentation; type C= alternation of types A and B. Paroxysmal AF present when arrhythmias occurred in episodes less than 24 hours, with intervals of regular atrial rhythm, and chronic AF when episode > 24 hr. Study design 256 Study population Inclusion/Exclusion criteria Appendix C.2.6: Intraoperative ablation- Radiofrequency Case Series Biatrial RFA continued Authors Intervention Thomas et al.2003 Surgical access: Median sternotomy CPB Cannulation: Bicaval cannulation Cardioplegia: Cardioplegic solution Body temperature: Not stated Lesion device: RADIOFREQUENCY/ Two hand-held devices. 1) A straight or J-tipped electrode at the end of a 20-cm handle. The electrode was flat with 12 mm length and 2.5-mm width. Radiofrequency current delivered between the probe electrode and a large diathermy electrode positioned on the patient’s skin. 2) Device with 4 6mmx2mm electrode with a 3mm inter-electrode distance mounted in sequence on a 33mm long flexible tip. Simultaneous, in-phase unipolar ablation performed between all four electrodes and the large surface electrode. Energy level: 1) Temperature set at 80 oC-90 oC with time to achieve set temperature of approximately 30 seconds, and total application 60 seconds. 2) 80 oC-90 oC over single period of 60seconds. Energy rate: Not applicable Surgery: Left ablations: In the LA lesions encircled the left and right pulmonary veins separately, with lines connecting the inferior and superior veins on each side, and the left and right veins to the MV. A line also joined the MV to the LAA roof incision and LAA excision site. Right ablations: Lesions in RA encircled the tricuspid valve, and joined the inferior and superior vena cava and coronary sinus. A line also joined the tricuspid valve and excised RAA, and the tricuspid valve and lateral RA running anteriorly to the crista terminalis. Atrial appendages: LAA and RAA excised. Atrial incisions: LA roof incision, and excisions of the LAA and RAA. Sequence of surgery: Atrial appendages excised to gain access to the endocardial surface of the heart. Note: In the first patients postoperative atrial flutter was a problem, so the pattern of lesions was altered in the posterior LA. Type of concurrent surgery (n=25/42): Tricuspid valve repair, Star + aortic arch repair: 2 MV replacement/annuloplasty/ repair: 13 Aortic valve surgery: 1 CABG: 4 CABG + MV repair/MV + aortic valve replacement, atrial septal defect: 5 Medication: Not stated Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: ≥ 6 months postoperative Echocardiography: Transthoracic echocardiography ≥ 6 months postoperative. Other: In initial cohort routine electrophysiological studies performed at 6 months. Eur Heart J 2003;24:1942-51 J Am Coll Cardiol 2000;35:442-450 Location Department of Cardiology, Westmead Hospital, Sydney, Australia Study design Level of Evidence: IV Basis of Patient Selection: Not stated Study population Sample Size: n=47 Patient Diagnosis: Chronic AF: 37/52 (71%) Paroxysmal AF 15/52 (29%) Eligibility Rate: Not stated Mean Age (yrs): Patients restored to SR: 62.5[10.7] Patients with persistent AF: 60.2[11] Follow-up: Median 2.86 yrs (range 0.6-4.2) Gender Mix (male/female): Not stated Patient Co-morbidities: Not stated Lost to Follow-up: 42/47 reviewed by ECG and echocardiogram at ≥ 6 months 4 deaths, 1 lost to followup Duration of pre-surgical AF (months): 54[41] (range 4 months-12 yrs) Pre-surgical atrial size: Mean left atrial diameter (n=47, mm): 48.5[7.7] Study Period: 7/95-12/01 Pre-surgical LVEF (%): Not stated Operator Details: Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Not stated 257 Inclusion/Exclusion criteria Inclusion Criteria: Chronic or paroxysmal AF. Exclusion Criteria: Patients with complex congenital heart disease were excluded. Appendix C.2.7: Intraoperative ablation- Radiofrequency Case Series Left atrial RFA Authors Intervention Benussi et al.2002 Patients were ablated with a cooled tip multiple electrode (C-T), first generation temperature-controlled catheter (T-C1) or second generation temperature-controlled catheter (T-C2). Surgical access: Median sternotomy CPB Cannulation: Distal portion of ascending aorta and bicaval cannulation (Colangelo et al. 2003). Cardioplegia: Antegrade and retrograde cold blood cardioplegia. Body temperature: Normothermic 36 ± 0.5 oC (Colangelo et al. 2003) Lesion device: RADIOFREQUENCY/ three different linear RF catheters used. 1. 2/98-9/98 a cooled-tip (C-T) multiple electrode (4-6 ablating tips) custommade RF catheter. Only 1 tip at time could be activated. (1 min/tip, 1 cm/min). Pericardial cavity filled with 37 oC normal saline as designed to work in liquid medium in 23/132 (17.4%) of patients. 2. 10/98- started using temperature-controlled catheters. First generation malleable with 7 electrodes on distal end (T-C1; ThermaLine, Boston Scientific, Natick, MA). RF current delivered up to 2 mins. All 7 electrodes activated simultaneously, 12 cm long lesion/ 2 mins in 71 patients (53.8%) 3. 12/00- second generation temperature-controlled catheter (T-C2) Cobra, Boston Scientific). Similar to former version, but ablation time could exceed 2 mins in 38 patients (28.8%) Energy level: 1. 45W for epicardial and endocardial lesions 2. Temperature preset to 75-85 oC for epicardial ablations and 65-75 oC for endocardial ablations. 3. Settings 3 mins at 80-85 oC for epicardial ablations and 2-2.5 mins at 70-75 oC for endocardial ablations. Energy rate: Not applicable Surgery: Left ablations: Posterior hemiencircling ablation around orifices of right pulmonary veins performed epicardially. Marshall fold divided with diathermy and encircling lesion performed around orifices of left pulmonary veins. Left encircling line connected with base of LAA through another epicardial ablation. Two linear ablations performed endocardially. First connected the two encirclings on the posterosuperior atrial wall. This lesion kept cranial, opposite transverse sinus, to prevent damage to oesophagus. Last ablation connected LAA to posterior aspect of mitral annulus. Line reached the mitral posterior annulus far from the antero-lateral commissure. In patients with contraindications to epicardial ablation, the whole ablation was performed endocardially after cross-clamping with the same lesion set. This occurred in 25/132 (18.9%): 17 patients because of epicardial thickening and adhesions reflecting past flogistic event; 5 patients with evidence of a thrombus in the LAA due to a risk of thromboembolism; and 3 patients with permanent pacemakers. Right ablations: None Ann Thorac Surg 2002;74:1050-7 Colangelo et al. Perfusion 2003;18:19-24 Location Division of Cardiac Surgery and Division of Cardiology, Epidemiology Unit, Division of Anesthesis and Division of Arrhythmology, S Raffaele University Hospital, Milan, Italy Study design Basis of Patient Selection: Not stated Patient Diagnosis: Paroxysmal AF: 11 (8.3%) Chronic AF: 121 (91.7%) Eligibility Rate: Not stated Mean Age (yrs): 58.5[10.5] Follow-up: 16.9[14.2] median 13 Gender Mix (male/female): 64/68 Inclusion/Exclusion criteria Inclusion Criteria: Patients with AF undergoing elective open heart surgery. Chronic AF lasting at least 6 months and paroxysmal AF with documented weekly episodes despite antiarrhythmic medications. Patient Co-morbidities: 1 patient had a previous stroke. Exclusion Criteria: Not stated Level of Evidence: IV Lost to Follow-up: 108/132 (81.8%) of patients followed-up to 6 months postoperatively. Study Period: 2/98- Study population Sample Size: n=132 Duration of pre-surgical AF (months): Chronic AF (n=121) 41.8[66.7] (range 6-480, median 12). Pre-surgical atrial size: Left atrial diameter (mm): 57.2[11.7] Operator Details: Not stated Pre-surgical LVEF (%): 59[5.9] Indication for concurrent surgery: Not stated Underlying heart disease: Mitral rheumatic: 71 (53.8%) Mitral degenerative: 58 (43.9%) (97.7% with MV disease) Aortic valve disease: 7 (5.3%) Tricuspid regurgitation: 31 (23.5%) Coronary artery disease: 1 (0.8%) Hypertrophic obstructive cardiomyopathy: 1 (0.8%) Atrial septal defect: 1 (0.8%) Aneurysm of ascending aorta: 1 (0.8%) Other: NYHA I: 7 (5.3%) NYHA II: 72 (54.5%) NYHA III: 53 (40.2%) Previous heart surgery: 15 (11.4%) 258 Authors Benussi et al. 2002 continued Intervention Study design Atrial appendages: LAA excluded. From 2/98-6/98 the LAA was preserved in some patients before deciding on routine obliteration (13/132, 9.8%). Atrial incisions: Isolation of right pulmonary veins completed by standard left atriotomy. Sequence of surgery: After institution of CPB the operating table tilted 15 degrees to right to expose left pulmonary veins. Posterior ablation around right pulmonary veins performed off pump. Left atriotomy after cross clamping. To protect circumflex artery from heat trauma, low flow retrograde cardioplegia administered while ablating. Type of concurrent surgery: Mitral repair: 58 (44%) Mitral commissurotomy: 14 (10.6%) MV replacement: 56 (42.4%) Biological: 11 (8.3%) Mechanical: 45 (34.1%) Repair of mitral prosthetic leak: 1 (0.8%) Tricuspid annuloplasty: 31 (23.5%) AVR: 7 (5.3%) Myectomy-myotomy: 1 (0.8%) Replacement of ascending aorta: 1 (0.8%) Atrial septal defect repair: 1 (0.8%) CABG: 1 (0.8%) Two or more procedures: 37 (28%) Medication: No antiarrhythmic prophylaxis administered before surgery. Oral anticoagulation stopped and continuous drip of heparin administered until 6 hours before surgery. Heparin continuous drip started after resolution of postoperative bleeding and continued until therapeutic values of prothrombin time reached with oral anticoagulants. Antiarrhythmic prophylaxis carried out on routinely. Amiodarone (intravenous bolus 300 mg, followed by continuous infusion of 1,200 mg/24 hr until postoperative day 1 and oral administration of 200 mg /8 hrs until discharge followed by maintenance of 200 mg/day) given to 119/132 (90.2%) of patients. In patients with contraindication to amiodarone, 8 (6.1%) given propaphenon and 1 (0.8%) sotalol. 4 (3%) had no antiarrhythmic medication. Medications continued at least 6 months then tapered off with stable SR. 6 months postoperative oral anticoagulants discontinued in patients with stable SR and documented atrial contraction after MV repair or replacement with biological prosthesis. Pacemaker: Permanent pacemaker in 3 (2.3%) of patients preoperatively. Cardioversion: Patients not controlled by optimal medical management had at least one attempt at external DC shock cardioversion. Electrocardiogram: Baseline and 1, 3, 6 and 12 months postoperative then yearly (12-lead and Holter). Echocardiography: Baseline. All patients had transoesophageal echocardiography the day before surgery or in the operating room after anaesthesia induction to exclude LA thrombus. Performed at 1, 3, 6, and 12 months postoperatively. 259 Study population Inclusion/Exclusion criteria Appendix C.2.7: Intraoperative ablation- Radiofrequency Case Series Left atrial RFA continued Authors Intervention Biederman et al. 2002 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Lesion device: Not stated Energy level: Not stated Energy rate: Not stated Surgery: Left ablations: Separate encircling lesions of the right and left pulmonary veins. Connecting line to the mitral annulus. Right ablations: None Atrial appendages: Not stated Atrial incisions: Not stated Sequence of surgery: Not stated Type of concurrent surgery: MVR with mechanical prosthesis: 10/10 Medication: Not stated Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Not stated Folia Cardiol 2002;9:247-252 Location Klinika Kardiochirurgii Instytutu Kardiologii, Klinika Wad Nabytych Serca Instytutu Kardiologii and Samodzielna pracownia Elektrofizjologii Klinicznej Instytutu Kariologii, Warsaw, Poland. Study design Level of Evidence: IV Study population Inclusion/Exclusion criteria Sample Size: n=10 Inclusion Criteria: AF for minimum of 3 months presurgically. Patient Diagnosis: Continuous AF Basis of Patient Selection: Patients with pulmonary vein isolation included at random. (unclear what this means) Mean Age (yrs): Not stated Gender Mix (male/female): Eligibility Rate: Not stated Patient Co-morbidities: Not stated Follow-up: Not stated Duration of pre-surgical AF: range 6 months- 14 years Lost to Follow-up: Not stated Pre-surgical atrial size: Mean left atrial diameter (mm): Not stated Study Period: Not stated Pre-surgical LVEF (%): Not stated Operator Details: Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Not stated 260 Exclusion Criteria: Not stated Appendix C.2.7: Intraoperative ablation- Radiofrequency Case Series Left atrial RFA continued Authors Intervention Geidel et al. 2003 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Bretschneider-cardioplegia: 29/32 Body temperature: Not stated Lesion device: RADIOFREQUENCY/ Thermaline® device (n=25) or from 01/02 the Cobra® device (n=4) (Boston Scientific Corporation, San Jose, USA). Both almost identical, flexible electrosurgical probe with 7 electrode terminals for separate or combined use, a generator of RF energy, an ablation controller and connecting cables including two indifferent patch electrodes. Energy level: 100 W for 120 s in a monopolar fashion with local temperature set at 70oC. Energy rate: Not applicable Surgery: Left ablations: First lesion line isolated the right pulmonary veins from the inferior to the superior right pulmonary vein using the left atriotomy. Isolation of left pulmonary veins with semicircular ablation line close to the inferior, and another around the superior left pulmonary vein. Connected by a transverse lesion across the posterior wall of the LA. Right ablations: None Atrial appendages: Not excised/ isolated. Atrial incisions: Left atriotomy. Sequence of surgery: Not stated Type of concurrent surgery: Primary procedures: MV: bioprosthesis: 12 mechanical valve: 4 MVP: 6 Aortic: bioprosthesis: 6 Mitral+aortic: bioprosthesis: 1 Associated surgical procedures: Tricuspid valve repair: 7 CABG: 2 Prior heart surgery: 1 Myxoma: 1 Medication: Amiodarone started before the end of CPB (300 mg bolus infusion) followed by 900mg/day infusion for 3 days. Oral amiodarone 5x200 mg/day up to 7-10 g dependent on body weight begun, followed by 1x200 mg/day for 3 months. Antiarrhythmic drugs continued in patients with postoperative bradycardia. Persisting bradycardia for >10 days led to termination of amiodarone. Used at saturation dose for recurrent AF electrically cardioverted. Heparin given after cessation of postoperative bleeding. Patients with MVP or bioprosthetic valves had coumarin for 3 months, patients with mechanical valves lifelong anticoagulation. Aprotinin: 29/32 Pacemaker: patients with postoperative bradycardia externally paced. Permanent pacemakers when bradycardia persisted for 2 weeks. Cardioversion: Early recurrences of AF were DC cardioverted after Interactive Cardiovasc Thorac Surg 2003;2:160-165 Location Department of Cardiac Surgery and Department of Cardiology, AK St. Georg, Hamburg, Germany. Study design Level of Evidence: IV Study population Inclusion/Exclusion criteria Sample Size: n=29 Inclusion Criteria: Permanent AF at least 6 months. Patient Diagnosis: Permanent AF at least 6 months Basis of Patient Selection: Not stated Eligibility Rate: 29 patients included in study and 9 patients excluded i.e. 29/38 or 76.3% of patients included in study. Follow-up: 6.7[4.2] months Lost to Follow-up: 21/29 to 3 months 16/29 to 6 months 13/29 to 9 months 5/29 to 12 months Mean Age (yrs): 73.1[7.3] Gender Mix (male/female): 11/18 Patient Co-morbidities: Not stated Duration of pre-surgical AF (months): 54.1[50.8] Pre-surgical atrial size: Mean left atrial diameter (mm): 55.9[7.3] (small <56 mm in 18 patients and large ≥ 56mm in 11 patients) Pre-surgical LVEF (%): 59.1[11.1] Indication for concurrent surgery: Not stated Study Period: 02/01-02/02 Operator Details: Not stated Underlying heart disease: Mitral: rheumatic: 12 degenerative: 10 Mitral+aortic: rheumatic: 1 Aortic: rheumatic: 5 degenerative: 1 Other: Preoperative amiodarone: 5/29 NYHA class II: 3/29 III: 24/29 IV: 2/29 261 Exclusion Criteria: Paroxysmal AF or permanent AF for < 6 months Emergency operation Acute bacterial endocarditis Cachexia (BMI ≤ 24) Severe intracavitary thrombosis Extreme left atrial size (>72 mm) Authors Intervention Geidel et al. 2003 saturation with amiodarone. Electrocardiogram: On admission and before discharge. At 6 wks, 3, 6, 9 and 12 months postoperatively. Echocardiography: Transoesophageal on admission and before discharge. Other: Precautions to avoid thermic oesophageal injury: 1) cachectic patients excluded 2) a dry compress passed behind the LA before delivery of RF 3) the transoesophageal echocardiogram probe removed during ablation 4) a flexible ablation probe used and adapted to the tissue without pressure 5) local temperature set at only 70 oC and 6) RF ablation performed precisely only under direct view during conventional open heart valve surgery. Study design 262 Study population Inclusion/Exclusion criteria Appendix C.2.7: Intraoperative ablation- Radiofrequency Case Series Left atrial RFA continued Authors Intervention Gillinov et al. 2003 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Lesion device: RADIOFREQUENCY/ Atricure bipolar clamp. Energy level: 75 V and 750 mA. Energy delivery continued until tissue conductance between electrode in the jaws of the clamp decreases and reaches steady state for 2 seconds (Gillinov and McCarthy 2003). Energy rate: Not applicable Surgery: Left ablations: Standard left lesion set. Bilateral pulmonary vein isolation and connection lesions between the right and left pulmonary veins and between the LAA and left pulmonary veins. Atricure not used to create a connecting lesion to the mitral annulus for fear of damaging the circumflex coronary artery (Gillinov and McCarthy). Right ablations: None Atrial appendages: LAA excised or excluded in all patients. Atrial incisions: Not stated Sequence of surgery: Not stated Type of concurrent surgery: MV repair/replacement: 88% tricuspid valve repair: 32% CABG: 32% aortic valve replacement: 28% Medication: Patients with perioperative AF all were treated with antiarrhythmic medications. Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Not stated Heart Surgery Forum 6 Supp 1:S20, 2003 (abstract) Gillinov and McCarthy 2002 Location The Center for Atrial Fibrillation, The Cleveland Clinic Foundation, Cleveland, Ohio, USA Study design Level of Evidence: IV Basis of Patient Selection: Not stated Study population Inclusion/Exclusion criteria Sample Size: n=50 Inclusion Criteria: Permanent, persistent or paroxysmal AF. Patient Diagnosis: Permanent AF; 22 Persistent AF: 12 Paroxysmal AF: 16 Eligibility Rate: Not stated Mean Age (yrs): 69[10] (48% were 70 or older). Follow-up: Hospital discharge Lost to Follow-up: Not stated Gender Mix (male/female): Not stated Patient Co-morbidities: Not stated Duration of pre-surgical AF (months): 44 (range 1-240) Study Period: 8/02-12/02 Pre-surgical atrial size: Not stated Operator Details: Not stated Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Not stated 263 Exclusion Criteria: Not stated Appendix C.2.7: Intraoperative ablation- Radiofrequency Case Series Left atrial RFA continued Authors Intervention Study design Study population Inclusion/Exclusion criteria Kottkamp et al. 1999 Surgical access: Median sternotomy CPB Cannulation: Superior and inferior caval veins Cardioplegia: Retrograde clod blood cardioplegia Body temperature: Hypothermic (32oC) Lesion device: RADIOFREQUENCY/ Continuous sinusoidal unmodulated waveform of 500 Hz (modified HAT 200S, Sulzer-Osypka GmbH, Grenzach-Wyhlen, Germany). Energy delivered in unipolar mode between the 4-mm (first 2 patients) or 10-mm tip electrode of specially designed ablation probe (Sulzer-Osypka GmbH) and a 10x16 cm external backplate electrode placed underneath the patient’s back. Thermistor embedded in probe to monitor tip temperature. Energy level: 60-65 oC (10-mm electrode) or 70-75 oC (4-mm electrode) with ablation probe withdrawn after 20-30 seconds. Energy rate: Not applicable Surgery: Left ablations: Contiguous lesion line extending from posterior aspect of mitral annulus to left lower pulmonary vein. Second line connected left lower and upper pulmonary vein orifices. A third line coupled the left and right upper pulmonary veins. Finally, right upper and lower pulmonary vein orifices connected with contiguous lesion line. Care taken to advance tip of probe a few mm inside proximal parts of pulmonary veins for ablation of muscle strand that extended into walls of pulmonary veins. Right ablations: None Atrial appendages: LAA not excised. Atrial incisions: Right atrial-transseptal approach. RA opened with longitudinal incision at RA free wall. Interatrial septum dissected through the fossa ovalis for access to LA. No additional LA free wall incisions made. Sequence of surgery: MVR or MVP performed before RFA. Type of concurrent surgery: MVR: 8 MVP: 3 AVR: 1 Additional CABG: 3 (+ MVR:2 +MVP: 1) Medication: Postoperative AF within first 10 d postoperative treated with sotalol 240-320 mg, if stable SR achieved sotalol withdrawn after 3 months. Oral anticoagulant prescribed at least 6 months. Pacemaker: In case of sinus bradycardia, atrial pacing (AAI or DDD) performed with temporary wires placed at time of operation until complete sinus node recovery or implantation of permanent pacemaker. Cardioversion: Combined with sotalol for postoperative AF if necessary. Electrocardiogram: Presurgical 48 hour Holter monitoring. Postoperatively monitored with continuous ECG for first 7 days followed by 24 hour ECG. 12-lead and 24 hr ECGs performed at 3, 6, 12 and 18 months postoperatively, and referring physicians instructed to document on ECG any recurrences of arrhythmia. Echocardiography: Presurgical Level of Evidence: IV Sample Size: n=12 Basis of Patient Selection: All patients had an indication for valve surgery irrespective of AF. Consecutive patients who fulfilled inclusion criteria. Patient Diagnosis: Chronic persistent AF: 10 Chronic paroxysmal AF: 2 Eligibility Rate: Not stated Gender Mix (male/female): Not stated Follow-up (months): 11[6] (range 3-20) Patient Co-morbidities: Not stated Inclusion Criteria: Long lasting AF for more than 2 years (chronic, persistent or paroxysmal). With chronic paroxysmal AF the episodes were long-lasting and interrupted rarely by short periods of SR. Symptoms of palpitations and tachycardia related to irregular or tachyarrhythmic ventricular response during AF, previous thromboembolic events, and/or haemodynamic aspects of atrial contractile function. Effective anticoagulation for at least 2 months before surgery. J Cardiovasc Electrophysiol 1999;10:772-780 Location Departments of Cardiology and Angiology and Thoracic, Heart and Vessel Surgery, Hospital of the Westfälische WilhelmsUniversity, Münster, and Departments of Cardiology and Heart Surgery, University of Leipzig, Heart Center, Leipzig, Germany. Lost to Follow-up: Not stated Study Period: Not stated Operator Details: Not stated Mean Age (yrs): 67[9] (range 44-75) Duration of pre-surgical AF (yrs): Chronic persistent AF: 4.3[3.9] range 2-13 Chronic paroxysmal AF: 3 and 4 Pre-surgical atrial size: Mean left atrial diameter (mm): 56[7] (range 45-69) Enlarged in all patients. Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Combined MV disease: 7 MV regurgitation: 3 Mitral stenosis: 1 Combined aortic valve disease: 1 Additional coronary artery disease: 3 Underlying heart disease: Not stated Other: NYHA class: II/III: 12/12 264 Exclusion Criteria: Age > 75yrs, previous cardiac surgery, myocardial infarction within the last 3 months, other severe concomitant noncardiac diseases affecting perioperative risk. Appendix C.2.7: Intraoperative ablation- Radiofrequency Case Series Left atrial RFA continued Authors Intervention Kress et al. 2002 Two cohorts. Cohort 1 (n=13; C1) were operated on in Milwaukee. The second cohort (n=10; C2) was operated on in several centres in India. Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Cold blood cardioplegia. Body temperature: Not stated Lesion device: RADIOFREQUENCY/ Cobra electrosurgical unit (ESU; Boston Scientific/EP Technologies, San Jose, CA, USA) attached to two standard grounding pads applied to the back. 7-coil surgical probe with 2/3 electrodes per lesion to ensure good contact. If lesion didn’t appear uniform after probe removal and gap suspected on visual inspection, a repeat application done with a single electrode. Energy level: 80 oC for 60 seconds, and in patients with unusually thin atrial walls, 70 oC. Energy rate: Not applicable Surgery: Left ablations: Pulmonary veins isolated in pairs, the left and right separately. Atriotomy substitutes for anterior portion of right pulmonary vein lesion. Lesions placed on the LA, 1 cm from the pulmonary vein orifice. First connecting lesion is between the two pulmonary vein encircling lesions, at the level of the lower pulmonary veins where the atrial wall relatively thin. Second connecting lesion between the left pulmonary vein encircling lesion and the LAA isolating lesion. In some patients the left superior pulmonary vein and LAA sufficiently close so that the encircling lesions share a border and the second connecting lesion may not be necessary. Right ablations: Two patients had an additional lesion connecting the tricuspid valve annulus to inferior vena cava for preoperative atrial flutter. Atrial appendages: The line of LAA isolation lies within the LAA base to allow oversewing. The base of LAA everted to deliver lesion. If it is not possible, single-coil applications usually required to ablate within it. Repeat applications may be necessary in areas with trabeculation. In reoperations the LAA freed of pericardial adhesions before ablation due to proximity of the left phrenic nerve. LAA oversewn with a double suture line of 3-O prolene. Atrial incisions: Standard atriotomy incision in Waterston’s groove. Sequence of surgery: LAA oversewn after all ablations performed. Once heart arrested RFA performed before valve repair or replacement to avoid possible contact with suture or prosthesis. In reoperations an existing prosthesis removed before RFA. Important to pull back transoesophageal echocardiogram probe before lesions delivered. Type of concurrent surgery: C1: MVP: 6 MVR: 7 Other: in 12 patients including closure of patent foramen ovale (1), TVP (4), CABG (6), AVR (2) and right carotid endarterectomy (1) Sem Thorac Cardiovasc Surg 2002;14:210-218 Location Departments of Cardiothoracic Surgery and Electrophysiology, Aurora Sinai and St Luke’s Medical Centers, Milwaukee, WI, USA. Kress et al. 2002 Study design Level of Evidence: IV Basis of Patient Selection: Not stated Eligibility Rate: Not stated Study population Inclusion/Exclusion criteria Sample Size: n=23 Inclusion Criteria: 1) Chronic AF (persistent or permanent). 2) Paroxysmal AF that was either refractory to medical therapy or associated with cardiac compromise. Patient Diagnosis: Chronic AF: C1: 9/13 C2: 9/10 Paroxysmal AF: C1: 4/13 C2: 1/10 (Note: In text 19 patients have chronic AF and 4 patients paroxysmal AF) Follow-up (wks): C1: 39.9 (range 6-100 wks) C2: 23.5 (range 1-80) Total: 32.5[28.4] > 3months in 14 patients Mean Age (yrs): C1: 70.7[8.4] (range 55-88) C2: 42.6[8.6] (n=9/10) (range 28-60) Lost to Follow-up: 14/23 patients had follow-up of more than 3 months. Patient Co-morbidities: History of embolus: C1: 1 peripheral and 1 cerebral C2: 1 peripheral Study Period: May 6, 1999-May 25, 2001 Operator Details: All patients operated on by DCK. Gender Mix (male/female): Not stated Duration of pre-surgical AF: 74% of patients in chronic AF had AF for over 1 year. Pre-surgical atrial size: Mean left atrial diameter (cm): 5.4[0.7] C1: 5.4[0.8] C2: 5.6[0.6] Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Rheumatic disease: C1: 2/13 C2: 10/10 Other: 2 patients had redo sternotomy. 265 Exclusion Criteria: Left atrial size, age, or presence of rheumatic valvular disease not considered exclusion criteria. Authors Intervention continued C2: MVR: 7 MVR+TVP: 2 MVR+AVR: 1 Medication: Amiodarone (200mg/d) started once patients taking by mouth and continued for 3 months. Amiodarone continued up to 6 months if patient had not converted to SR at 3 months. Perioperative β-blocker administered routinely unless contraindicated. All patients anticoagulated for 6 weeks. Pacemaker: Two RA temporary pacing wires placed in all patients to perform 1) temporary pacing at 10 bpm above the intrinsic SR to suppress AF, 2) atrial electrograms to recognise the presence of Pwaves, fibrillatory waves, or flutter waves when ECG ambiguous, and 3)overdrive pacing of postoperative atrial flutter. Postoperative AF/flutter cardioverted within 48 hours to improve maintenance of SR. If AF/flutter recurred, patient received another attempt at cardioversion 2 weeks after discharge. Cardioversion: Not stated Electrocardiogram: ECG, rhythm strip, or pacemaker analyser telemetry used to confirm all follow-up rhythms. Echocardiography: Performed in 9/13 C1 patients during follow-up. Study design 266 Study population Inclusion/Exclusion criteria Appendix C.2.7: Intraoperative ablation- Radiofrequency Case Series Left atrial RFA continued Authors Intervention Le Tourneau et al. 2003 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Lesion device: RADIOFREQUENCY/ Eight tip RF probe Energy level: Not stated Energy rate: Not applicable Surgery: Left atrial only 68/70 Biatrial: 2/70 Left lesions: Not stated Right lesions: Not stated Atrial appendages: Not stated Atrial incisions: Not stated Order of surgery: Not stated Type of concurrent surgery: MV repair: 14 MVR: 56 (mechanical prosthesis: 32 bioprosthesis: 24) Medication: Not stated Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: ECG at 3, 6, 12 and 24 months postoperatively, 24 hour recording at 6 months postoperatively. Echocardiography: At 3, 6, 12 and 24 months postoperatively LVEF, left and right atrial size and function were measured. AHA 2003 (Abstract) The Society for Heart Valve Disease (SHVD) 2nd Biennial Meeting 2003 (Abstract) Location Hôpital Cardiologique, Lille, France. Study design Level of Evidence: IV Basis of Patient Selection: Not stated Study population Inclusion/Exclusion criteria Sample Size: n=70 Inclusion Criteria: Persistent or paroxysmal AF. Patient Diagnosis: Persistent AF: 51/70 Paroxysmal AF: 19/70 Mean Age (y): 64[10] Eligibility Rate: Not stated Gender Mix (male/female): 24/46 Follow-up (d): 549 Patient Co-morbidities: Not stated Lost to Follow-up: Not stated Duration of pre-surgical AF: Not stated Study Period: Not stated Pre-surgical atrial size: Not stated Operator Details: Not stated Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Mitral regurgitation: 46/70 Mitral stenosis: 24/70 Underlying heart disease: Not stated 267 Exclusion Criteria: Not stated Appendix C.2.7: Intraoperative ablation- Radiofrequency Case Series Left atrial RFA continued Authors Intervention Study design Study population Inclusion/Exclusion criteria Mohr et al. 2002 Group C: RFA combined with other cardiac surgery with conventional approach (n=65). Note: Two other groups presented (Group A: RFA as primary indication for surgery and minimally invasive approach, n=74; LARF: RFA and MV surgery with minimally invasive or conventional approach, n=95) but these two groups were not included due to the minimally invasive surgery. Total patient no= 234. Surgical access: Median sternotomy CPB Cannulation: Standard aortic and right atrial cannulation. Cardioplegia: Antegrade crystalloid or cold blood cardioplegia. Body temperature: Not stated Lesion device: RADIOFREQUENCY/ 10-mm T-shaped ablation probe (Osypka GmbH, Grenzach-Wyhlen, Germany) with alternating current delivered by a generator (350 kHz, modified HAT 200S; Osypka). Energy level: Maximum energy levels of 50 W in a unipolar mode between the tip electrode and a 10x16-cm external backplate electrode to achieve temperature of 60 oC at its tip. Energy rate: Not applicable Surgery: Left ablations: A contiguous lesion line extending from the inferior aspect of the mitral annulus to the left lower pulmonary vein was performed. Through a second line the left lower and upper pulmonary vein orifices were connected. Through a third line the left and right upper pulmonary veins were connected. Finally, the right upper and left lower pulmonary vein orifices were connected. An additional line at the LA roof was extended to the surgical incision. Right ablations: None Atrial appendages: The LAA not excised or ligated. Atrial incisions: The LA was incised parallel to the interatrial groove anterior to the right pulmonary veins. The RA was not opened except in cases of concomitant tricuspid repair. Where the LA was enlarged, Carpentier’s technique was used to downsize it, and in these cases the LAA was closed. Sequence of surgery: The ablation procedures always performed before concurrent surgery. Type of concurrent surgery: Concomitant procedure not MV surgery. Medication: When AF within 10 days postoperatively, patients given amiodarone, flecainide, or sotalol (with electric cardioversion). Patients in stable SR (presence of P wave) without additional antiarrhythmic therapy received anticoagulation for 3 months, patients with additional antiarrhythmic medication for 6 months. Pacemaker: 16/234 patients (6.8%) already had pacemakers prior to surgery due to symptomatic bradycardia (6, 2.6%) or total AV block (10, 4.3%). Cardioversion: In postoperative AF that occurred within 10 days Level of Evidence: IV Sample Size: n=65 Basis of Patient Selection: Not stated Patient Diagnosis: Chronic or paroxysmal AF. Inclusion Criteria: Primary indication chronic persistent AF or symptomatic chronic paroxysmal AF refractory to medical treatment. J Thorac Cardiovasc Surg 2002;123:919-927 J Thorac Cardiovasc Surg 2003;125:836842 Circulation 2002;106:2468 Location Divisions of Cardiac Surgery and Cardiology, Herzzentrum, University of Leipzig, Leipzig, Germany Eligibility Rate: Not stated Mean Age (yrs): 69.10[6.2] Gender Mix (male/female): 43/22 Follow-up: 12 months Lost to Follow-up: 30/65 at 6 months 21/65 at 12 months Study Period: 8/98-3/01 Patient Co-morbidities: Not stated Duration of pre-surgical AF (yrs): 8.2[5.2] Pre-surgical atrial size: Left atrial diameter (mm): 59.6[11.8] x 49.7[10.3] Pre-surgical LVEF (%): Operator Details: Not stated 50.73[13.7] Indication for concurrent surgery (n=234): Mitral stenosis: 52 (22.2%) MV regurgitation: 94 (40.2%) Severe tricuspid regurgitation: 18 (7.7%) Atrial septal defect: 4 (1.7%) Coronary artery disease: 34 (14.5%) Aortic valve stenosis: 31 (13.2%) Aortic valve insufficiency: 1 (0.4%) Underlying heart disease (n=234): Dilated cardiomyopathy: 8 (3.4%) 268 Exclusion Criteria: Not stated Note: in some operations RFA was performed prophylactically i.e. The patients did not have AF at the time of operation and did not have severe symptoms. They were coming for an atrial septal defect closure or an autograft replacement and were in SR. The same was true for CABG. Authors Intervention Mohr et al. 2002 continued electric cardioversion performed either alone or with medication. Electrocardiogram: All patients monitored daily with 12-lead ECG for first 5 days postoperatively. Two 24 hour ECG recordings performed for every patient. On discharge and at 6 months postoperatively ECG taken with Holter monitoring. Echocardiography: Transoesophageal echocardiography probe in place before and 3-6 days postoperatively to study LA contractility. Since first complication no longer have probe in oesophagus during ablation and switched to transthoracic echocardiography during early postoperative period. Other: An isolating scrub now placed into the sinus obliquus pericardii behind the LA wall to prevent the passage of electric and thermal energy through the oesophagus. Study design 269 Study population Inclusion/Exclusion criteria Appendix C.2.7: Intraoperative ablation- Radiofrequency Case Series Left atrial RFA continued Authors Intervention Study design Study population Inclusion/Exclusion criteria Müller et al. 2002 Herz 27:357-364 Surgical access: Median sternotomy CPB Cannulation: Separate caval cannulation. Cardioplegia: Current cardioplegic technique. Body temperature: Mild systemic hypothermia (32 oC, Pasic et al. 2001). Lesion device: RADIOFREQUENCY/ Flexible surgical RF probe and coagulation system (Coagulation ThermaLine System, Boston Scientific, San Jose, CA, USA). System consists of ablation controller, electrosurgical probe, connecting cables and a generator of RF energy. The probe has 7 electrodes on the distal part that coagulate the tissue when in contact with electrodes. During current delivery the monopolar radiofrequency current flows through tissue toward the indifferent electrodes. Temperature measured by thermocouples in probe. Used on dry field. Energy level: 70 oC for 2 minutes. Energy rate: Not applicable Surgery: Left ablations: Four standard LA maze lines, 2 lines isolating the ostia of the pulmonary veins and the other 2 connecting lines. All made endocardially. First line connects both ends of surgical atriotomy, completing isolation of right pulmonary veins. Second line isolates left pulmonary veins, this is an encircling line around the orifice of the pulmonary veins. If veins enlarged the encircling line completed by 2 applications of probe. Both lines encircling pulmonary veins approximately 10 mm from venous orifices to prevent late stenosis. Third line connects encircling line of left pulmonary veins and middle part of posterior MV annulus line should be placed inferiorally to prevent heat damage to circumflex artery. The last line connects the left-sided and right-sided encircling lines of pulmonary veins and runs along the roof of the atrium to prevent damage to the oesophagus or vagal nerves. Right ablations: None Atrial appendages: LAA left intact, LA thrombi in 2 patients but LAA appendage free of thrombi so LAA not oversewn. Atrial incisions: Standard approach to LA from right side through interatrial sulcus. Sequence of surgery: RF maze performed prior to concomitant procedure. Type of concurrent surgery: Isolated valve procedure/ CABG: 51 Combined procedure: 44 Medication: If patient remained in SR postoperatively not given antiarrhythmic medication. Early postoperative patients with junctional rhythm treated with continuous IV orciprenaline sulfate (Alupent; Boston Scientific, San Jose, CA, USA). Patients with AF during hospitalisation treated with digoxin in combination with verapamil or Level of Evidence: IV Sample Size: n=95 Inclusion Criteria: AF Basis of Patient Selection: Not stated Patient Diagnosis: AF AND Pasic et al. Ann Thorac Surg 2001;72:1481-1491 Location Deutsches Herzzentrum Berlin Eligibility Rate: Not stated Mean Age (y): 65 (range 30-85) Gender Mix (male/female): Not stated (Pasic et al. 20/28) Follow-up (months): 8 (range 1-24) Lost to Follow-up: Not stated Study Period: 9/99-9/01 Operator Details: Miralem Pasic and Roland Hetzer Patient Co-morbidities: Not stated Duration of pre-surgical AF (y): 6 (range 0.5-33) Pre-surgical atrial size: Mean left atrial diameter (mm): Pre-surgical LVEF (%): 57 (27-88) Indication for concurrent surgery: Not stated Underlying heart disease: Not stated 270 Exclusion Criteria: LVEF < 25%; extensive and diffuse coronary artery disease; acute valve endocarditis; calcification of the LA; extensive calcification of the MV annulus requiring annular decalcification; patients unwilling to undergo the procedure. Authors Intervention Müller et al. 2002 continued sotalol, or with sotalol or amiodarone alone. After discharge the same regimen of antiarrhythmics recommended for patients with episodes of postoperative supraventricular tachyarrhythmias, with medication tapered if rhythm became stable. Postoperative anticoagulation of heparin and then peroral phenprocoumon (Marcumar; Boston Scientific, San Jose, CA). If patients did not need long-term anticoagulation for other reasons, recommended anticoagulation with phenprocoumon for at least 6 months, then this could be discontinued or replaced with aspirin in patients with stable SR by 24 hour Holter monitoring and normal or nearly normal LA contraction by echocardiogram. Pacemaker: 6/95 patients had a pacemaker implanted prior to surgery Cardioversion: If medication unsuccessful, direct current shock recommended. Before cardioversion transoesophageal echocardiography necessary to exclude atrial thrombi. Temporary wires used for temporary pacing if necessary or to overdrive the atrium. Electrocardiogram: Postoperative rhythm evaluated with 12-lead ECG but 24 hour Holter monitoring not performed on all patients. Rhythm constantly monitored postoperatively until stable rhythm returned. Echocardiography: The echocardiographic probe removed from oesophagus during procedure to exclude possible interference with RFA and oesophageal injury. Study design 271 Study population Inclusion/Exclusion criteria Appendix C.2.7: Intraoperative ablation- Radiofrequency Case Series Left atrial RFA continued Authors Intervention Ruchat et al. 2002 Surgical access: Median sternotomy CPB Cannulation: Superior and inferior vena cava. Cardioplegia: Antegrade intermittent cold blood perfused every 20 minutes. Body temperature: Hypothermic (32 oC). Lesion device: RADIOFREQUENCY/ Electrosurgical probe Thermaline (Boston Scientific Corporation, San Jose, CA, USA) Energy level: 70 oC, maximal energy output 150 W and duration 120 seconds. Energy rate: Not applicable Surgery: Left ablations: Ablation around the pulmonary vein orifices and to the mitral annulus, and mitral orifice. Epicardial and endocardial applications of probe used from LAA resection edges to left atriotomy edges, finally joining the fibrous heart skeleton. Right ablations: In 8 patients a complementary RFA performed through the inferior vena cavo-tricuspid annulus (Cosios’s) isthmus. Atrial appendages: LAA systematically removed, except in 1 patient where the LAA was only sutured from inside due to severely adherent pericardium. Atrial incisions: LA opened parallel to interatrial groove in semicircular fashion around right pulmonary veins. The incision was extended superiorly behind the superior vena cava and inferiorly to the posterior wall of the LA. Sequence of surgery: Cardioplegic arrest before LA opened. Cardiosurgical procedures performed before RF ablation. Type of concurrent surgery: MVP: 12 MVR: 19 Double valve procedure: 6 AVR: 2 CABG: 1 Associated cardiac procedure: 3/40 CABG: 3 Medication: Antiarrhythmic agents (mainly amiodarone) prescribed in the event of recurrent AF or atrial flutter, routinely used during first 6 months. All patients anticoagulated in immediate postoperative period with IV heparin and oral anticoagulation with acenocoumarol before discharge and not stopped until real atrial transport demonstrated. Pacemaker: All patients received temporary atrial and ventricular epicardial pacemaker probes. DDD stimulation mode used in case of postoperative slow native beat. Cardioversion: External electric shock used to restore SR in refractory AF patients between 6 weeks and 3 months postoperative. Electrocardiogram: Preoperative standard ECG and Holter. Continuous during postoperative days. Echocardiography: Preop and follow-up at 1, 3, 6 and 12 months, with the same cardiologist performing procedure. Other: Preoperative complete right and left heart catheterisation Thoracic & Cardiovasc Surg 2002;50:155-159 Location Department of Cardiovascular Surgery and Department of Cardiology, University Hospital, Lausanne, Switzerland Study design Level of Evidence: IV Study population Inclusion/Exclusion criteria Sample Size: n=40 Patient Co-morbidities: Not stated Inclusion Criteria: Indication for cardiac surgery with chronic AF. Symptomatic drug refractory chronic AF according to the definition of the Working Group of Arrhythmias of the European Society of Cardiology. Duration of pre-surgical AF: median 24 months (range 4 months-18 yrs) Exclusion Criteria: Not stated Patient Diagnosis: Chronic AF Basis of Patient Selection: Consecutive Eligibility Rate: 40 out of 1,258 (3.2%) patients scheduled for elective heart surgery under CPB Follow-up: 12.5[7.9] months in 37/40 Lost to Follow-up: 3/39 due to death 6 months 29/40 12 months 21/40 24 months 11/40 36 months 4/40 Study Period: 5/98-3/01 Operator Details: Not stated Mean Age (yrs): 66.2[8.4] (range 48-78) Gender Mix (male/female): 26/14 Pre-surgical atrial size: Mean left atrial diameter (mm): 59[10] Pre-surgical LVEF (%): 58[7] (range 45-70) Indication for concurrent surgery: Mitral regurgitation: 23 Mitral stenosis: 4 Mitral mixed lesions: 10 Aortic regurgitation: 4 Aortic mixed lesion: 5 Coronary artery disease: 3 Underlying heart disease: Not stated Other: NYHA class: 2.8 (median III, range II-IV) Euro score 5.2[2.0] 272 Appendix C.2.7: Intraoperative ablation- Radiofrequency Case Series Left atrial RFA continued Authors Intervention Starck et al. 2003 Surgical access: Median sternotomy CPB Cannulation: Not stated Cardioplegia: Crystalloid or anterograde/retrograde blood cardioplegia In standard cases commonly used crystalloid cardioplegia, and in complex cases or patients with impaired left ventricular function blood cardioplegia. Now favour more generous anterograde and retrograde blood cardioplegia for maximal cardiac protection. Body temperature: Lesion device: RADIOFREQUENCY/ Thermaline® probe (Boston Scientific Corporation, San Jose, CA, USA). Distal part of instrument flexible and consists of 7 electrodes. At the tip of probe one active electrode measuring 8 mm, with 2 mm isolation to 6 further electrodes, each 12.5 mm in length. Seven electrodes can be activated in any combination. EPT-1000 XP Cardiac Ablation Controller used as RF generator, with a switch box (MECA Automatic Personality Module). Energy delivered as unipolar between the ablation electrode and 2 indifferent electrodes attached bilaterally to lower posterior chest of patient. During effective ablation, documented impedance values 40-80 Ohms. Inadequate contact defined as values greater than set impedance limits (300 Ohms) or temperature; the generator immediately discontinued ablation. Ablation usually performed in four ablation cycles. Energy level: Maximal 150 W, temperature controlled with integrated thermosensors. Set at 90-100 W and 70 oC for 120 seconds. Ablation lines confirmed visually. Energy rate: Not applicable Surgery: Left ablations: Isolation of the right pulmonary veins completed by a single semicircular ablation line to the left of the right pulmonary veins. Circular ablation then performed in the area of the posterior atrial wall around the orifices of the left pulmonary veins, maintaining a distance of 5-mm from the vessels to avoid stricture. Ablation line from the inferior left pulmonary vein the to MV annulus. In 69/100 patients able to perform complete procedure, in 31 patients could only complete bilateral pulmonary vein isolation, or complete ablation procedure without resection of LAA due to difficult anatomy, especially small LA or redo cases. Right ablations: None Atrial appendages: LAA resected and closed with a running doublerow suture. Atrial incisions: Semicircular left atriotomy performed parallel to the interatrial groove around the right pulmonary veins, extended superiorly behind the superior vena cava and inferiorly to the posterior LA wall. Thorac & Cardiovasc Surgeon 2003;51:147-153 Hemmer et al. 2000 Herzschr Eleckrophys 2000 and Cardiovasc J South Africa 2001 Location Sana Herzchirurgische Klinik, Stuttgart, Germnay Study design Level of Evidence: IV Study population Inclusion/Exclusion criteria Sample Size: n=100 Inclusion Criteria: Chronic or paroxysmal AF Patient Diagnosis: Chronic or paroxysmal AF Basis of Patient Selection: Not stated Mean Age (yrs): 65.7[10.4] Eligibility Rate: Not stated Gender Mix (male/female): 53/47 Follow-up (months): 7.3 (range 3-23) Patient Co-morbidities: Not stated Lost to Follow-up: 90/95 survivors had at least 3 months follow-up. Study Period: 11/99-1/01 Operator Details: Not stated Duration of pre-surgical AF: Mean duration 24.1 months Chronic AF > 1 yr: 38 Recent onset persistent AF (< 1yr) or paroxysmal: 62 Pre-surgical atrial size: Mean left atrial diameter (mm): 51.0[7.5] Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Primary cardiac pathology: MV disease: 43 Aortic valve disease: 28 Coronary artery disease: 27 Atrial septal defect: 2 Other: 9 patients had previous cardiac surgery (AVR: 6 MVP: 2 CABG: 1). 96/100 had undergone several unsuccessful attempts of pharmacological or electrical cardioversion. 273 Exclusion Criteria: Not stated Authors Starck et al. 2003 Intervention Study design Sequence of surgery: After induction of cardioplegic cardiac arrest, left atriotomy and left ablations performed. The ablations usually performed before cardiac surgery. In MV procedures, valve inspection and any resection of the valve/segments completed first. Valve repair/replacement always followed the ablation to avoid thermal damage to sutures. Type of concurrent surgery: MVP: 15 MVP+CABG: 6 MVP+CABG+ atrial septal closure+tricuspid valve repair: 1 Bioprosthetic MVR: 13 Mechanical MVR: 8 Bioprosthetic AVR: 11 Stentless bioprosthetic AVR: 3 Homograft AVR: 4 Ross operation AVR: 1 Mechanical bioprosthetic AVR: 4 Aortic valve decalcification: 1 David operation+replacement of ascending aorta: 2 Yacoub operation+replacement of ascending aorta: 2 CABG: 27 Atrial septal defect closure: 2 Medication: Antiarrhythmics only used in case of recurrence of AF or atrial flutter. All patients heparinised immediately postoperative and changed to oral systemic anticoagulation (phenprocoumon) prior to discharge. With regular supraventricular rhythm, recovery of atrial contraction and no other reason for anticoagulation, oral anticoagulation discontinued. If failure of ablation success, more aggressive antiarrhythmic treatment recommended. With AF recurrences during postoperative course, started with sotalol, then amiodarone. Pacemaker: Sequential temporary epicardial pacemaker probes place in all patients. AAI stimulation used in cases of slow spontaneous rate with normal AV conduction. Cardioversion: If more aggressive antiarrhythmic treatment not successful, electrical cardioversion recommended. Electrocardiogram: Used to monitor cardiac rhythm during postoperative stay of patient and 3 months postoperatively. Echocardiography: 3 months postoperatively. Restoration of atrial function defined by presence of A-wave. 274 Study population Inclusion/Exclusion criteria Appendix C.2.7: Intraoperative ablation- Radiofrequency Case Series Left atrial RFA continued Authors Intervention Study design Study population Inclusion/Exclusion criteria Williams et al. 2001 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Cold retrograde cardioplegia during lesion to mitral annulus. Body temperature: Not stated Lesion device: RADIOFREQUENCY/ Cobra (Boston Scientific-EP Technologies, San Jose, CA, USA) and RF generator (Cobra ESU, Boston Scientific-EP Technologies, San Jose, CA, USA). Surgical probe flexible with 7 available electrodes in close enough proximity for continuous linear lesions. Each electrode can be selectively turned on/off depending on length and location of desired lesion. Each electrode independently regulated by generator and containing 2 thermocouples 180 degrees apart. Each electrode turned on/off multiple times/s to maintain the temperature within a narrow band of set temperature. Energy level: 70-80 oC for 1 minute with maximal power output 150 W. Energy rate: Not applicable Surgery: The decision to perform right-sided lesions was based on the planned procedures and the surgeon’s preference. n=8 had right sided lesions, 3/8 had lesion set of Maze III and in the others the modification included a flutter lesion to the tricuspid annulus. In some cases a Maze-III was performed with RFA instead of incisions. Left ablations: Lesions made at discretion of surgeon, but all included isolation of pulmonary veins either with one circumferential island (like Maze III) or with separate right- and left-sided pulmonary vein lesions. Routinely performed lesion to MV annulus. Connecting line from pulmonary vein isolation to LAA isolation line. Right ablations: Also now doing routine right-sided lesion to tricuspid valve if the patient has a history of atrial flutter or the planned procedure includes a tricuspid valve repair. Performed in 8/48 patients. Atrial appendages: All patients had amputation or circumferential RFA of the LAA with oversewing of the orifice. Atrial incisions: Left atriotomy. Sequence of surgery: Not stated Type of concurrent surgery: MVR: 24 MVR/CABG: 8 Double valve: 5 Double valve/CABG: 2 Atrial septal defect: 1 AVR: 1 Reoperative Fontan: 1 Medication: No class I or III antiarrhythmic medications used. If AF recurred, patients treated with low dose amiodarone as tolerated. Amiodarone generally discontinued after 4 weeks unless primary cardiologist desired continued use. Anticoagulation at discretion of cardiologist, but recommended for 3 months if not otherwise required (eg. mechanical prosthesis). Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Not stated Level of Evidence: IV Prospective data collection Sample Size: n=48 Inclusion Criteria: One centre required persistent AF for at least 1 month before surgery, while the other two centres required at least 6 months of AF prior to surgery. Ann Thorac Surg 2001;71:1939-44 Location Division of Cardiothoracic Surgery, College of Physicians and Surgeons, Columbia University, New York, New York and Penrose Hospital, Colorado Springs, Colorado and Division of Cardiothoracic Surgery, University of Michigan, Ann Arbor, Michigan, USA Patient Diagnosis: AF Basis of Patient Selection: Not stated Mean Age (yrs): 65.0[12.5] Eligibility Rate: Not stated Gender Mix (male/female): Not stated Follow-up: 138[96] days Patient Co-morbidities: Not stated Lost to Follow-up: 6/48 lost due to death and excluded from further analysis. Duration of pre-surgical AF (yrs): 4.8[6.4] Pre-surgical atrial size: Mean left atrial diameter (cm): 6.0[1.5] Study Period: 7/99-9/00 Pre-surgical LVEF (%): Not stated Operator Details: Operations at three centres by eight different surgeons. Indication for concurrent surgery: Not stated 275 Underlying heart disease: Not stated Exclusion Criteria: Not stated Appendix C.3.1: Intraoperative ablation- Microwave Comparative Studies Left atrial MWA versus CS Authors Intervention Study design Study population Schuetz et al. 2003 MWA + heart surgery (MW) versus Cardiac surgery alone (CS) MW: Lesion device: MICROWAVE/ microwave probe (FLEX 2; AFx Inc, Fremont, CA) connected by a coaxial cable to a microwave generator. Ablation element a 25-mm long antenna at the distal end of probe. Energy level: Continuous energy flow of 2.45 GHz at 40 W for 25 seconds. Temperature kept below 40 oC; cooled after 5-6 ablations. Energy rate: Not applicable Lesion set Left lesions: Ablation lines started at mural mitral annulus, with continuous lines between the pulmonary veins encircling each vein separately, and lines connecting the pulmonary veins with the mitral annulus and LAA. The LAA also surrounded by a continuous ablation line. Number of ablation lines ranged from 17-38. Right lesions: None Atrial appendages: Oversewing of orifice of LAA. Atrial incisions: Left atriotomy performed. Order of surgery: Ablation performed immediately prior to the concomitant procedure, after arresting heart and placing on CPB. Both Groups: Surgical access: Median sternotomy CPB Cannulation: Not stated Cardioplegia Not stated Body temperature: Not stated Type of concurrent surgery: CABG: MW: 3 CS: 5 pns MVR (single/combined): MW: 16 CS: 7 p=0.03 Other: MW: 4 CS: 7 pns Medication: Medication maintained until day of surgery, except anticoagulation which was either discontinued 4 days prior surgery or if necessary switched to heparin (i.v. or s.c.). If SR restored and no contraindications given patients treated with amiodarone or sotalol. Antiarrhythmic therapy also used if clinically significant tachyarrhythmia occurred. All patients on phenprocoumon for minimum 3 months. Pacemaker: Not stated Cardioversion: All patients had a final attempt for electrical cardioversion (2x20 J) immediately before cannulation. Not successful in any patients. Electrocardiogram: Continuously monitored until discharge from ICU. ECG and 24-hour Holter monitoring prior to discharge. Follow-up ECG at 3, 6 and 12 months postoperative and 24-hour Holter at 12 month postoperatively. Echocardiography: Prior to operation LA dimensions measured by transthoracic or transoesphageal echocardiogram. RCT Prospective open labelled study. Random stratification with randomisation done according to diagnosis of AF regardless of concomitant cardiac disease. Sample Size: MW: n=24 Eur J Cardio-thorac Surg 2003;24:475480 Location Departments of Cardiac Surgery and Anesthesiology, Heart Center Augustinum, LudwigMaximillians University, Munich, Germany CS: n=19 Patient Diagnosis: MW and CS: Permanent AF* Mean Age: MW: 64.57[10.03] (range 45-81) CS: 70.21[7.9] range (54-82) pns Level of Evidence: II Gender Mix: MW: 12/12 Method of allocation concealment: Not stated Intention-to-Treat Analysis: Not stated Basis of Patient Selection: Not stated Follow-up: 12 months Lost to Follow-up: 1 patient died in each group. At discharge: MW: 23 CS: 19 3 months: MW: 21 CS: 17 6 months: MW: 18 CS: 10 12 months: MW: 15 CS: 9 CS: 14/5 pns Exclusion Criteria: Not stated Patient Co-morbidities: Not stated Duration of pre-surgical AF (yrs): MW: 3.8[2.84] (range 0.08-8.25) CS: 9.21[9.24] (range 0.08-24) p=0.05 Permanent AF > 3 months: MW: 88.8% CS: 87.5% pns Pre-surgical atrial size: Left atrial diameter (mm): MW: 54.9[11] (range 43-105) CS: 53.9[18.1] (range 35-95) pns Study Period: 2/01-9/02 Pre-surgical LVEF (%): MW: 62.8[13.2] (range 20-79) CS: 54.37[17.08] (range 28-88) pns Operator Details: Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Not stated 276 Inclusion/Exclusion criteria Inclusion Criteria: Permanent AF and surgical treatment of valve disease and/or CABG. *permanent AF= patients in which SR cannot be sustained after cardioversion or when the patient and physician have decided to let AF continue without further attempts to restore SR Appendix C.3.1: Intraoperative ablation- Microwave Comparative Studies Left atrial MWA versus CS continued Authors Intervention Spitzer and Knaut 2002 Cardiac surgery with microwave ablation (MW) versus patients with cardiac surgery alone (CS). Lesion device: MICROWAVE/ Lynx Microwave surgical ablation device at 2.45 GHz (AFx Inc. Fremont Blvd, Fremont, CA, USA). Probe contained a temperature monitor which measured the temperature continuously, and cut off at 90 oC. The temperature and duration of ablation was optimised in an animal model, to give a 3-5 mm lesion thickness which was transmural. Energy level: 40 Watts for 25 seconds. Energy rate: Not applicable Lesion set: Left lesions: The ablation probe was placed in the LA under direct vision, and continuous lines made from the annulus of the MV to where the inferior left pulmonary vein joins the atrium. The ablation line continued further over the superior left, then to the superior right and finishing at the inferior right pulmonary vein. The ablation lines went into the orifice of the pulmonary veins, and did not encircle them. Right lesions: In 4/136 cases with additional treatment for ASD or tricuspid disease, isthmus ablation performed with an ablation line from the septal part of the tricuspid valve continuing around the coronary sinus, and up to the superior part of the inferior vena cava. Atrial appendages: Not resected. Atrial incisions: Lateral incision of the LA. When ASD or tricuspid surgery was performed a right atriotomy was also performed. Order of surgery: CPB commenced at the beginning of the surgery. Both groups: Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Type of concurrent surgery: MV procedure: MW: 86 CS: 17 CABG: MW: 58 CS: 26 Tricuspid procedure: MW: 13 CS: 1 Aortic valve procedure: MW: 16 CS: 6 Atrial septal defect: MW: 15 CS: 1 Isolated procedure: MW: 88 CS: 33 Combined procedure: MW: 48 CS: 18 (Note: In the text it states that more than half of patients in both groups had a combined procedure.) Medication: When admitted to hospital all antiarrhythmic medication was stopped, and other cardiovascular medication continued. All patients treated postoperatively with anticoagulant (Phenprocoumon) at INR 2.0-3.0, patients who received a mechanical valve had an INR of 3.0-4.0. All patients in stable SR at 3 months postoperatively and no Herzschr Elektrophys 2002;13:225-232 Location Herzzentrum Dresden GmbH, Technische Universität Dresden, Dresden, Germany Study design Level of Evidence: III-2 Study population Inclusion/Exclusion criteria Sample Size: MW: n=136 CS: n=51 Inclusion Criteria: Patients with permanent AF undergoing elective cardiac surgery, and also with an indication for surgical treatment of the AF, including clinical, haematological or prognostic criteria. Patient Diagnosis: Permanent AF Intention-to-Treat Analysis: Not stated Basis of Patient Selection: Consecutive patients Follow-up: 1 year Mean Age (yr): MW: 68.4[7.8] (range 36.8-83.5) CS: 69.3[7.4] (range 37-86.9) Gender Mix (male/female): MW: 70/66 CS: 29/22 Patient Co-morbidities: Not stated Eligibility Rate: Not stated Lost to Follow-up: MW: 111/136 at 1 year CS: 45/51 at 1 year Patients were lost to followup due to additional deaths, transfer to another city, or transfer to another GP. Study Period: 12/98-12/01 Operator Details: Patients in both groups were all operated on by the same surgeon. 277 Duration of pre-surgical AF (yr): MW: 6.6[9.3] (range 0.1-57.2) CS: 5.7[6.2] (range 0.1-38.5) Pre-surgical atrial size: Left atrial diameter (mm): MW: 52.7[9.7] (range 30-102) CS: 50.3[8.5] (range 24-90) Pre-surgical LVEF (%): MW: 56.1[11.9] (range 32-80) CS: 54.9[9.7] (range 15-78) Indication for concurrent surgery: Not stated Underlying heart disease: Not stated Exclusion Criteria: Not stated Authors Intervention Spitzer and Knaut 2002 continued mechanical valve stopped anticoagulant treatment. Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Follow-up Holter ECG at 1, 3, 6 and 12 months postoperatively. Criteria for a successful operation stable SR in the 24 hour Holter ECG. Echocardiography: Transthoracic echocardiography performed at 1, 3, 6 and 12 months postoperatively. Study design 278 Study population Inclusion/Exclusion criteria Appendix C.3.2: Intraoperative ablation- Microwave Comparative Internal Comparison MWA1 versus MWA2 Authors Intervention Knaut et al. 2003 Patients underwent cardiac surgery plus MW ablation with the original ablation line concept (MW1) or MW ablation with a new ablation line concept (MW2). Lesion device: MICROWAVE/ Device not stated. Energy level: Not stated Energy rate: Not applicable Lesion set: Original ablation line concept as for Spitzer and Knaut 2002. Second ablation line set included circular ablation around the pulmonary veins of both sides, but details not specified. Both groups Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Type of concurrent surgery: Not stated Medication: Not stated Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Not stated EACTS 2003 and Sixth Annual Meeting of the International Society for Minimally Invasive Surgery 2003 (Abstract) Location Department of Cardiac Surgery, Heart Center Dresden University Hospital, Dresden, Germany. Study design Level of Evidence: III-? Study population Inclusion/Exclusion criteria Sample Size: MW1: 137 MW2: 75 (Total n=212) Inclusion Criteria: AF Patient Diagnosis: AF Intention-to-Treat Analysis: Not stated Basis of Patient Selection: Consecutive patients (EACTS 2003) Follow-up: 6 months Mean Age (yrs): MW1:67[4] MW2: 68[4] Gender Mix: 120/114 (n=234 EACTS 2003) Patient Co-morbidities: Not stated Eligibility Rate: Not stated Duration of pre-surgical AF (yrs): MW1: Paroxysmal AF 6.4[4.5] MW2: Paroxysmal AF 7.2[8] Lost to Follow-up: Not stated Pre-surgical atrial size: Left atrial diameter (mm): MW1: 52[7] MW2: 52[4] Study Period: Not stated Pre-surgical LVEF (%): MW1: range 32-80 MW2: range 20-83 Operator Details: Not stated Indication for concurrent surgery: MV disease: MW1: 82/137 MW2: 48/75 Coronary artery disease: MW1: 60/137 MW2: 30/75 AVD: MW1: 18/137 MW2: 31/75 Underlying heart disease: Not stated 279 Exclusion Criteria: Not stated Appendix C.3.3: Intraoperative ablation- Microwave Biatrial MWA Case Series Authors Intervention Chiappini et al. 2003 Surgical access: Not stated CPB Cannulation: Bicaval and aortic cannulation. Cardioplegia: Antegrade crystalloid cardioplegia used. Body temperature: Moderate hypothermia (32 oC). Lesion device: Flex 4 microwave ablation (Afx, Inc, Fremont, CA, USA) with 4-cm ablating element. Energy level: Continuous wave of 2.45 GHz and 35-45 W. Energy set at 65 W and application time 45 seconds. Energy rate: Not applicable. Surgery: Left ablations: The microwave probe was placed on the LA endocardium 5-10 mm medially from the right pulmonary vein orifices. Two applications needed to complete isolation of right pulmonary veins. Circumferential lesion around left pulmonary veins, at least 5 mm from their orifices. Connecting lesions from LAA to ablation line around left pulmonary veins and from here to antero-medial commissure of MV. A final lesion connected the two pulmonary vein encircling lesions. Right ablations: In the RA a single lesion was created along the crista terminalis from the superior vena cava to the inferior vena cava. A connecting lesion performed on to the atrioventricular groove low down opposite the orifice of the coronary sinus to create a block in the cavotricuspid isthmus area. Atrial appendages: LAA excised. Atrial incisions: Standard left atriotomy. Sequence of surgery: Left atriotomy, followed by ablations and then excision of LAA. Type of concurrent surgery: MVR and tricuspid valvuloplasty: 4 Aortic and MVR: 3 MVR: 1 Tricuspid valve replacement: 1 Atrial septal closure and tricuspid valvuloplasty: 1 Medication: All patients kept on low-dose amiodarone (200mg/day) for 6 months postoperatively. All patients had anticoagulation therapy with warfarin, with reconstructive surgery or biologic prosthesis this was stopped after 6 months in patients with SR and LA contraction, documented by echocardiography. Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Every day after operation rhythm controlled by a rest ECG. Echocardiography: Prior to discharge patients had transthoracic echocardiography. Interactive Cardiovasc and Thorac Surg 2003;2:327-330 Location Department of Cardiovascular Surgery, Policlinico S. Orsola-Malpighi, University of Bologna, Bologna, Italy Study design Level of Evidence: IV Study population Inclusion/Exclusion criteria Sample Size: n=10 Inclusion Criteria: Chronic AF Patient Diagnosis: Chronic AF Basis of Patient Selection: Not stated Mean Age (yrs): 61.7[9.2] (range 47-71) Eligibility Rate: Not stated Gender Mix (male/female): 4/6 Follow-up: Mean 12.4 months Patient Co-morbidities: Not stated Duration of pre-surgical AF (months): 82.8 (range 24-360) Lost to Follow-up: 1/10 patients died. Pre-surgical atrial size: Mean left atrial diameter (mm): 56.3[6.9] (range 54-66) Study Period: 10/01-3/02 Pre-surgical LVEF (%): Not stated Operator Details: Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Not stated 280 Exclusion Criteria: Not stated Appendix C.3.4: Intraoperative ablation- Microwave Left atrial MWA Case Series Authors Intervention Gillinov et al. 2002 Surgical access: Median sternotomy CPB Cannulation: Ascending aorta, superior vena cava and inferior vena cava. Cardioplegia: Cold blood cardioplegia delivered antegrade and retrograde. Body temperature: Lesion device: MICROWAVE/ Flexible microwave ablation tool (AFx In, Fremont, CA). Energy level: 65W, application time 45 seconds. Energy rate: Not applicable Surgery: Left ablations: Each set of pulmonary veins isolated separately. Microwave catheter placed on LA epicardium posterior and medial to the right pulmonary veins. The catheter positioned 5-10 mm from pulmonary vein orifices and oriented so energy transmitted form epicardium to endocardium. Surgeon observed developing lesion from endocardial surface, which turns yellow at completion of lesion. Connecting lesion from cut edge of LAA to ablation line around left pulmonary veins. Final lesion connects the two pulmonary vein encircling lesions. Probe placed on epicardium of posterior LA, and lesion created from right inferior pulmonary vein to left inferior pulmonary vein. At no time was energy directed to oesophagus or adjacent structures. Right ablations: None Atrial appendages: LAA excised. Atrial incisions: Lateral left atriotomy. Sequence of surgery: Ablation performed before MV surgery. Type of concurrent surgery: MV repair: 8 MV replacement: 2 Additional procedures tricuspid valve repair/replacement (n=4), CABG (n=3) and aortic valve replacement (n=2). Medication: Not stated Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Not stated Ann Thorac Surg 2002;74:1259-1261 Location Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, Cleveland, Oho, USA. Study design Level of Evidence: IV Basis of Patient Selection: Not stated Study population Inclusion/Exclusion criteria Sample Size: n=10 Inclusion Criteria: Chronic or paroxysmal AF. Patient Diagnosis: Chronic AF: 6 Paroxysmal AF: 4 Mean Age (yrs): Not stated Eligibility Rate: Not stated Gender Mix (male/female): Not stated Follow-up: Not stated Patient Co-morbidities: Not stated Lost to Follow-up: Not stated Duration of pre-surgical AF: Not stated Study Period: Not stated Pre-surgical atrial size: Not stated Operator Details: Not stated Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Not stated 281 Exclusion Criteria: Not stated Appendix C.3.4: Intraoperative ablation- Microwave Left atrial MWA Case Series continued Authors Intervention Knaut et al. 2002 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Lesion device: MICROWAVE/ Afx Lynx or Flex Microwave Surgical Ablation device. Lesions approximately 2cm in length for the Afx Lynx and 4cm in length for the Flex, connected visually. 2.45 GHz application frequency. Energy level: Flex: 65W for 45 seconds Energy rate: Not applicable Surgery: Left ablations: Microwave probe introduced into LA and started at posterior MV annulus, with ~3 applications so that the first complete lesions line ended ~ 1-1.5 cm deep in the lower left pulmonary vein. The next lesion line started at same depth and contralateral to first lesion line toward the upper left pulmonary vein. After 1-2 further lesions, the line ended at about the same level of the upper left pulmonary vein. The next lesion line started from upper left pulmonary vein and reached the upper right pulmonary vein after about 5 lesions. Procedure completed with 2-3 more applications extending from upper right to lower right pulmonary vein. Applications adapted to anatomic variations of pulmonary veins. Right ablations: Not stated Atrial appendages: Not stated Atrial incisions: Left atriotomy. Sequence of surgery: Left atriotomy followed by cardioplegic arrest. After the ablations the MV surgery and concomitant procedures were performed. Type of concurrent surgery: MV surgery in 105/105 MV repair: 44 MV replacement: 61 (10 biological and 51 mechanical) Additional surgery: Closure of atrial septal defect: 6 CABG: 17 Tricuspid valve reconstruction: 15 Aortic valve replacement: 8 Aortic ascendens replacement: 1 Medication: All patients received anticoagulation therapy. In reconstructive surgery anticoagulants stopped after 3 months in patients with SR. All patients received low-dose sotalol (induction 2x40 mg.day and in further clinical stay 3x80mg/day in patients <75kg and 2x160 mg in patients > 75kg). Sotalol discontinued after 3 months with stable SR. No other antiarrhythmic drugs with conversion potential were used. Pacemaker: Not stated Cardioversion: Performed when AF recurred, starting on postoperative day 8 and repeated twice during clinical follow-up when unsuccessful. Electrocardiogram: Every day after operation rhythm controlled by rest ECG. Holter performed during first 10 postoperative days and before discharge. Echocardiography: Performed before hospital discharge. Other: Atrial flutter treated by overstimulation. Sem Thorac Cardiovasc Surg 2002;14:226-231 Location Heart Center, Dresden University Hospital, Department of Thoracic and Cardiovascular Surgery, Dresden, Germany Study design Level of Evidence: IV Study population Sample Size: n=105 Inclusion/Exclusion criteria Inclusion Criteria: Chronic AF Patient Diagnosis: Chronic AF Basis of Patient Selection: Consecutive patients Mean Age (yrs): 68.6 (range 45-83) Eligibility Rate: Not stated Gender Mix (male/female): Not stated Follow-up: Up to 24 months Patient Co-morbidities: Not stated Lost to Follow-up: 69/105 at 6 months 64/105 at 12 months Duration of pre-surgical AF (yrs): 8.6[6.8] (range 0.6-58) Pre-surgical atrial size: Mean left atrial diameter (mm): 56[9.1] Study Period: 12/99Operator Details: Not stated Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Not stated 282 Exclusion Criteria: Secondary operative risk factors such as age or other comorbidities were not exclusion criteria. Appendix C.3.4: Intraoperative ablation- Microwave Left atrial MWA Case Series continued Authors Intervention Study design Study population Inclusion/Exclusion criteria Venturini et al. 2003 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Lesion device: MICROWAVE/ Flex catheter (AFx, Fremont, CA, USA). Energy level: 65 W for 60 seconds. Energy rate: Not applicable Surgery: Left lesions: Endocardial bilateral encircling isolation of ostia of pulmonary veins starting from right side and moving to left. Ablation of right pulmonary veins 1 or 2 applications and left pulmonary veins 3 to 4 applications. Right lesions: None Atrial appendages: Not stated Atrial incisions: Not stated Order of surgery: Not stated Type of concurrent surgery: MVP: 10/41 MVR: 12/41 MVR+AVR: 19/41 Tricuspid valve repair: 21/41 Medication: Most patients on oral digoxin before operation. Amiodarone infusion (900 mg/ 24 hrs) started in ICU for most patients. Patients with postoperative early atrial arrhythmias treated with IV amiodarone (300 mg/ 30 mins plus 900 mg/ 24 hrs) sometimes with low-dose (25 mg) atenolol. At discharge most patients on oral amiodarone. Pacemaker: Not stated Cardioversion: Direct current if necessary planned 1 month postoperatively. Electrocardiogram: 2 and 12 months postoperatively. Echocardiography: 2 and 12 months postoperatively. Level of Evidence: IV Sample Size: n=41 Inclusion Criteria: Permanent or paroxysmal AF. Basis of Patient Selection: Not stated Patient Diagnosis: Permanent AF: 30/41 (73.2%) Paroxysmal AF: 11/41 (26.8%) Heart Surgery Forum 2003;6:409411 Location Cardiovascular Department “Umberto I” Hospital, VeniceMestre, Italy. Eligibility Rate: Not stated Mean Age (yrs): 61 (range 45-76) Follow-up (months): 14.2 (range 5-21) Lost to Follow-up: Not stated Study Period: 6/01-12/02 Operator Details: Not stated Gender Mix (male/female): 10/31 Patient Co-morbidities: Not stated Duration of pre-surgical AF (months): median 24 (range 2-234) Pre-surgical atrial size: Mean left atrial diameter (mm): Not stated Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: MV regurgitation: 10/41 (24.4%) MV stenosis: 12/41 (29.3%) MV and aortic valve disease: 19/41 (46.3%) Tricuspid regurgitation: 21/41 (51.2%) Underlying heart disease: Not stated Other: NYHA class II: 31/41 (75.6%) 283 Exclusion Criteria: Not stated Appendix C.3.4: Intraoperative ablation- Microwave Left atrial MWA Case Series Authors Intervention Zembala et al. 2003 Zembala et al. 2002 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Lesion device: MICROWAVE/ Flex 2 ablation probe (AFx, Fremont, CA, USA) with microwaves at 2.45 GHz. (Zembala et al. 2002 Afx-Lynx device). Energy level: 40 W over 25 seconds. Energy rate: Not applicable Surgery: Left ablations: Ablation lines beginning from mitral annulus, directed up to ostium of left inferior vein, and then to left superior, right superior, and right inferior pulmonary vein ostia. Pulmonary vein lesions extended 10 mm into interior of each pulmonary vein (same lesion set as Knaut 1999). Right ablations: None Atrial appendages: LAA was oversewn. Atrial incisions: Not stated Sequence of surgery: Ablation conducted on arrested heart on CPB immediately prior concomitant surgery. Type of concurrent surgery: MV procedure: 42 + tricuspid repair/replacement: 12 MVR: 36 (85.7%) MVR+TVR: 1 (2.4%) MVR+TVP: 10 (23.8%) MVP: 6 (14.3%) MVP+TVP: 1 (2.4%) Medication: Patients received 80-120 mg sotalol/d, unless contraindicated, until 90 days postoperatively if stable SR demonstrated. 1 patient with sotalol intolerance received amiodarone (200 mg/day). Patients with postoperative AF recurrence or patients who did not convert to SR had increasing doses of sotalol up to 240 mg/day. Pacemaker: Not stated Cardioversion: Electrical cardioversion in patients when pharmacological conversion failed, after the patient was stabilised and demonstrated remission of pleural and/or pericardial effusion, normal blood pressure, and electrolyte and haematocrit levels. If first unsuccessful a second cardioversion performed 5 days later. Electrocardiogram: During hospital stay daily until discharge, 24 hour Holter monitor just prior to discharge, then Holter at specified postoperative time points. Echocardiography: Not stated Heart Surgery Forum 2003;6:403408 Kardiol Polska 2002;57: 223 Location Department of Cardiac Surgery and Transplantation and Department of Cardiology, Silesian Medical School, Silesian Center of Heart Diseases, Szpitalna, Poland. Study design Level of Evidence: IV Retrospective data collection Basis of Patient Selection: Consecutive patients Eligibility Rate: Not stated Follow-up (months): 7.3[3.7] (range 1-14) Study population Inclusion/Exclusion criteria Sample Size: n=42 Inclusion Criteria: Zembala et al. 2002 1. Indications for surgical replacement or reconstruction of the MV. 2. Permanent AF lasting > 12 months, documented in at least two ECG recordings. 3. Patients having elective surgery. Patient Diagnosis: Chronic AF (diagnosed 2 or more times by ECG). Mean Age (y): SR: 55.5[8.5] (median 58.0 range 39-68) AF: 57.4[7.8] (median 58.5 range 47-73) Gender Mix (male/female): 16/26 Patient Co-morbidities: Not stated Lost to Follow-up: Not stated Study Period: Not stated Operator Details: Not stated Duration of pre-surgical AF (y): SR: 3.6[2.3] (median 3.0 range 0.50-8.0) AF: 7.4[3.5] (median 7.0 range 2.0-13.0) ≥ 6 months: 42/42 Pre-surgical atrial size: Mean left atrial diameter (mm): SR: 54.9[7.5] (median 55.0 range 43.0-80.0) AF: 65.4[9.9] (median 64.0 range 53.0-83.0) Pre-surgical LVEF (%): Not stated Indication for concurrent surgery: Mitral regurgitation: 11/42 (26.2%) Complex lesion: 26/42 (61.9%) Mitral stenosis: 5/42 (11.9%) Underlying heart disease: Rheumatic: 41/42 Infective endocarditis: 1/42 284 Exclusion Criteria: Not stated Appendix C.4.1: Intraoperative ablation- Laser Case Series Authors Intervention Vigilance et al. 2003 Surgical access: Not stated CPB Cannulation: Not stated Cardioplegia: Not stated Body temperature: Not stated Lesion device: LASER/ Optimaze Surgical Ablation System using a 5cm probe. Energy level: 5 Watts/cm for 36 seconds. Energy rate: Not stated Surgery: Left lesions: Lesions around the base of the pulmonary veins and LAA. Two connecting lesions created from the pulmonary veins to the base of the LAA, and the other to the MV annulus. Right lesions: Not stated Atrial appendages: Not stated Atrial incisions: Not stated Order of surgery: Not stated Type of concurrent surgery: Not stated Medication: Not stated Pacemaker: Not stated Cardioversion: Not stated Electrocardiogram: Not stated Echocardiography: Not stated Heart Surgery Forum 6(2) 2003 6th Annual NewEra Cardiac Care: Innovation & Technology 2003 Location Division of Cardiothoracic Surgery, Columbia University, College of Physicians and Surgeons, New York, NY, USA Study design Level of Evidence: IV Study population Inclusion/Exclusion criteria Sample Size: n=6 Inclusion Criteria: AF Patient Diagnosis: AF Basis of Patient Selection: Not stated Mean Age (y): Not stated Eligibility Rate: Not stated Gender Mix (male/female): Not stated Follow-up (months): Not stated Patient Co-morbidities: Not stated Duration of pre-surgical AF: Not stated Lost to Follow-up: Not stated Pre-surgical atrial size: Not stated Study Period: Not stated Pre-surgical LVEF (%): Not stated Operator Details: Not stated Indication for concurrent surgery: Not stated Underlying heart disease: Not stated 285 Exclusion Criteria: Not stated Appendix C.5.1: Intraoperative ablation- MWA versus RFA Authors Intervention Wisser et al. 2004 Patients were treated with microwave ablation (MWA) or radiofrequency ablation (RFA). Lesion device: MWA: Afx® microwave generator and probe. It was stated the Flex 4 probe came to the market during the study, but this was not used in any of the patients (personal communication with Dr Wisser). RFA: Medtronic® unipolar surgical ablation pen, saline irrigated. Patient grounded by an indifferent electrode applied to the skin. Energy level: MWA: continuous wave of 2.45 GHz with variable power output. Energy set at 40 W for 25 seconds. Lesions overlapped. RFA: Power set at 30 W, frequency 484.2 kHz. The tip slowly oscillated about 10 times over the same area to create continuous lesions. Energy rate: RFA: saline irrigation 5 ml/minute. Lesion set: The same set in both groups, as in the Maze-III, but the atrial incisions were replaced by endocardial, linear ablation lines, except for incisions to enter the right and left atrium and for resection of the atrial appendages. Left lesions: Left lesions made as for Maze-III, except the left and right pulmonary veins were encircled separately, leading to two isolated islands of tissue, connected at the back of the atrium to form the figure of ‘H’. Right lesions: Lesion line drawn through the RAA amputation site to the annulus of the tricuspid valve. A line drawn from the corner of the lateral wall incision cranially into the superior vena cava and caudally into the inferior vena cava. Line from the incision to the posterior segment of the annulus of the tricuspid valve. Completed by a line from the edge of the incision, crossing the fossa ovalis and the isthmus into the coronary sinus and down into the inferior vena cava. Atrial appendages: Both excised. Atrial incisions: Incisions in the RA for the RAA excision, and on the lateral wall. Order of surgery: After CPB onset, venous inflow occluded. Rightsided lesions were performed on the beating heart. RAA amputated and right lesion lines drawn. Patient then cooled, the aorta cross clamped and heart arrested. Left atrium entered and lesions made, then concomitant valve surgery performed and LA closed. Cross clamp released and RA closed, with tricuspid valve surgery (when used) done on beating heart. Both groups Surgical access: Median sternotomy CPB Cannulation: Cannulation of both vena cava, standard fashion. Cardioplegia: Not stated Body temperature: Normothermia for right side of procedure and 32 oC for left side. Type of concurrent surgery: A tricuspid valve plasty was performed in all patients presenting with tricuspid valve regurgitation of grade 2 or Eur J Cardio-thorac Surg 25:1011-17 (2004) Location Departments of Cardiothoracic Surgery and Cardiology, University of Vienna, Vienna, Austria Study design Level of Evidence: III-2/3 Study population Inclusion/Exclusion criteria Sample Size: MWA: n=23 RFA: n=19 Inclusion Criteria: Chronic permanent AF for longer than 6 months despite complete antiarrhythmic therapy. Patient Diagnosis: Chronic permanent AF. Intention-to-Treat Analysis: Not stated Basis of Patient Selection: Consecutive patients, basis of selection into MWA or RFA not stated. Follow-up: MWA: 24.2[1.3] RFA: 12.1[1.2] p<0.01 Due to institutional circumstances started on MWA first, and RFA later. Mean Age (yrs): MWA: 65.6[11.9] RFA: 64.1[11.1] pns Total: 64.3[11.4] (range 38-82) Gender Mix (male/female): MWA: 10/13 RFA: 11/8 pns Patient Co-morbidities: Not stated Duration of pre-surgical AF (months): MWA: 61.9[28.9] (maximum 32 years) RFA: 53.5[49.0] (maximum 12 years) pns Total: 61.1[87] (range 6 months- 32 years) Pre-surgical atrial size (mm): MWA: 69.7[10.8] RFA: 74.0[14.3] pns Eligibility Rate: Not stated Lost to Follow-up: Follow-up complete except in one patient referred from a foreign country who did not attend follow-up. MWA: 22/23 12 months 20/23 24 months RFA: 19/19 3 months 18/19 6 months 14/19 12 months Pre-surgical LVEF (%): MWA: 55.7[8.2] RFA: 56.4[15.5] pns Indication for concurrent surgery: MV insufficiency: MWA: 8 RFA: 11 MV stenosis: MWA: 6 RFA: 1 Mixed MV lesion: MWA: 4 RFA: 4 Aortic valve stenosis: MWA: 4 RFA: 3 Aortic valve insufficiency: MWA: 1 RFA: 0 Coronary artery disease: MWA: 0 RFA: 1 Aneurysm ascending aorta: MWA: 1 RFA: 0 pns for all categories Study Period: 2/01-12/02 Operator Details: Not stated Underlying heart disease: Not stated Other: Euro Score: MWA: 5.2[2.4] (2-9) RFA: 6.0[1.8] (3-9) NYHA class: MWA: 3.3[0.7] RFA: 3.4[0.6] 286 Exclusion Criteria: Paroxysmal AF Authors Intervention Wisser et al. 2004 continued greater. MVP: MWA: 2 RFA: 4 MVP+TVP: MWA: 2 RFA: 2 MVP+AVR: MWA: 0 RFA: 1 MVP+CABG: MWA: 0 RFA: 1 MVR: MWA: 6 RFA: 4 MVR+TVP: MWA: 5 RFA: 1 MVR+AVR: MWA: 3 RFA: 1 MVR+AVR+TVP: MWA: 0 RFA: 1 MVR+ASD: MWA: 0 RFA: 1 AVR: MWA: 4 RFA: 2 AVR+TVP: MWA: 0 RFA: 1 AVR+replacement ascending aorta: MWA: 1 RFA: 0 Study design Medication: No antiarrhythmic medication given immediately after surgery. If AF occurred, amiodarone given, loaded with 3 X 200 mg daily. All patients received coumadine, targeting INR of 2.2-2.5. Pacemaker: Patients electrically paced in DDD or AAI mode immediately after surgery when necessary. Cardioversion: If AF persisted despite therapeutic amiodarone levels, DC shock up to twice 360 J was used. If AF observed during later follow-up, electrical cardioversion used at most twice. Electrocardiogram: Evaluated at 3, 6 and 12 moths follow-up and then yearly. Both 12-lead ECG and 24 hour Holter monitor. Echocardiography: Evaluated at 3, 6 and 12 months follow-up for left and right atrial diameter. Atrial contraction assessed by identification of a biphasic wave at the level of the tricuspid and MV using colour-coded Doppler echocardiography. 287 Study population Inclusion/Exclusion criteria APPENDIX D – SAFETY AND EFFICACY TABLES Appendix D.1.1: Safety Outcomes- Intraoperative ablation- Cryotherapy Comparative Biatrial CA versus CS Perioperative Outcomes Handa et al. 1999 Level III-3 CA + MVS CA + MVS n=39 n=58 Sueda et al. 1997 Level III-3 CA+MVS MVS n=36 n=15 Yuda et al. 2004 Level III-2 CA+MVS MVS n=26 n=6 Blood loss (mL) Transfusion required Stroke Transitory cerebral ischaemic accident 1/58 (1.7%) pulmonary embolism 1/582 (1.7%) Other thromboembolism Bleeding Wound infection/sternal instability Mediastinitis 1/391 (2.6%) 2/97 intubation > 72 hrs 2/97 pneumonitis 1/97 pneumothorax Pulmonary insufficiency Low cardiac Output Renal failure Intra-aortic balloon pump 2/97 (2.1%) Major complications (unspecified) Mortality to 30 d Postoperative Outcomes 0 0 0 0 FU = 18 months (range 2-51 months) FU = Mean 21 months (≥ 6 months) Oesophageal injury Stroke Freedom from stroke and anticoagulant related bleeding Anticoagulant related bleeding Mortality Cumulative Survival 0 100.0[0.0] n=26 1 yr3 95[5] 2 yrs4 100.0[0.0] n=15 2 yrs5 3/396 (7.7%) 91.8[4.6] n=26 1 yr 91.8[4.6] n=15 2 yrs 91.8[4.6] n=3 3 yrs 4/58 (6.9%) 94.0[3.4] n=35 86[6] 2 yrs 90.1[5.0] n=21 2 yrs* 3 4/587 (6.9%) 96.0[2.8] n=36 1 yr 96.0[2.8] n=22 2 yrs 85.9[7.2] n=11 3 yrs 0 1 0 : Patient did not receive anticoagulation with warfarin. : Not warfarin related. : Survival analyses of freedom from stroke and anticoagulant related bleeding. 4 : Survival analyses of freedom from stroke and anticoagulant related bleeding. 5 : Freedom from stroke and bleeding. 6 : 1 patient died of congestive heart failure, 1 patient had ventricular tachycardia, and 1 patient died of unknown causes. 7 : 1 patient died of pulmonary embolism, 1 patient died of intracerebral haemorrhage, 1 patient died of cerebral infarction, and 1 patient died of myocardial infarction. 8 : Derived by extrapolation 9 : Derived by extrapolation; [] = standard deviation; *: p<0.05 2 3 288 08 09 Appendix D.1.2: Safety Outcomes- Intraoperative ablation- Cryotherapy Comparative Left atrial CA versus CS Gaita et al. 2000 Level III-2 Perioperative Outcomes Blood loss (mL) Transfusion required Stroke Transitory cerebral ischaemic accident Other thromboembolism Bleeding Wound infection/sternal instability Mediastinitis Pulmonary insufficiency Low cardiac Output Renal failure Intra-aortic balloon pump Major complications (unspecified) Mortality to 30 d CA + CS n=32 CS n=18 1/32 (3.1%) 0 1/32 (3.1%) 0 pns 1/3210 (3.1%) 0 11 12 1/18 (5.6%)pns 1/32 (3.1%) FU= 18 months Postoperative Outcomes Oesophageal injury Stroke 1/3213 (3.1%) Freedom from stroke and anticoagulant related bleeding Anticoagulant related bleeding Mortality 2/3214 (6.3%) 1/1815 (5.6%) Cumulative Survival 10 : Septicaemia (fatal) : 1 patient died of septicaemia 3 weeks postoperatively. 12 : 1 patient died of heart failure one day postoperatively. 13 : Patient died of a stroke at 7 months postoperatively, they were not taking anticoagulants as a bioprosthesis was used. 14 : 1 patient with chronic AF died of heart failure 4 months postoperatively; and 1 patient in SR died of intracerebral haemorrhage at 7 months postoperatively. This patient was not taking anticoagulants as they received a prosthetic valve. 15 : 1 patient died of heart failure at 3 months postoperatively. 11 289 Appendix D.1.3: Safety Outcomes- Intraoperative ablation- Cryotherapy Comparative CA versus Maze-III Perioperative Outcomes Ishii et al. 2001 Level III-3 CA + CS Maze-III + CS n=32 n=13 Kim et al. 2001 Level III-3 CA n=23 Maze-III n=18 016 017 1/23 (4.3%) 1/23 (4.3%) (acute) 1/18 (5.6%) 1/18 (5.6%) (acute) 0 0 FU = 29[4] months FU = 47[14] months Blood loss (mL) Transfusion required Stroke 0 0 Transitory cerebral ischaemic accident Other thromboembolism 0 0 Bleeding 0 2/13 (15.4%) Wound infection/sternal instability Mediastinitis Pulmonary insufficiency Low cardiac Output Renal failure Intra-aortic balloon pump Oesophageal injury Major Complications (non specified) Mortality to 30 d Postoperative Outcomes 2/3218 (6.3%) FU > 12 months FU= 41.2[5.6] months (range 34-52) 0 0 Oesophageal injury Stroke Freedom from Stroke Anticoagulant related bleeding Mortality 1/1319 (7.7%) Cumulative Survival 16 : No postoperative bleeding. : No postoperative bleeding. 18 : In 1 patient ischaemic-reperfusion injury of the lower extremity, and in 1 patient perioperative myocardial infarction. 19 : Patient died following inappropriate antibiotic therapy after dental treatment, at 10 months postoperative. 17 290 Appendix D.1.3 continued: Safety Outcomes- Intraoperative ablation- Cryotherapy Comparative CA versus Maze-III Perioperative Outcomes CA 1st mod. n=14 Kosakai et al. 1995 Level III-2/3 Kosakai Maze n=70 Maze-III n=17 Lee et al. 2001 Level III-3 CA + CS Maze-III + CS n=53 n=30 Nishiyama et al. 2003 Level III-2/3 (abstract) CA + CS Maze-III + CS n=9 n=11 Blood loss (mL) Transfusion required Stroke 1/101 (1%) cerebral bleeding 1 month postoperative Transitory cerebral ischaemic accident ?20 ? 21 0 0 1/101 (1%) Other thromboembolism Bleeding 7/101 (7%) Wound infection/sternal instability Mediastinitis Pulmonary insufficiency Low cardiac Output Renal failure Intra-aortic balloon pump 0 2/70 (2.9%) 2/14 (14.3%) Oesophageal injury Major Complications (non specified) Mortality to 30 d 2/101 (2%) in-hospital Postoperative Outcomes Oesophageal injury Stroke Freedom from Stroke Anticoagulant related bleeding Mortality Cumulative Survival 20 : In total series 2 patients experienced a stroke, but it was not stated in which groups they were. In 1 patient stroke was pre-existent before the surgery, in the other no thrombus in the left atrial auricle was found on echocardiogram. 21 : In total series 2 patients experienced a stroke, but it was not stated in which groups they were. In 1 patient stroke was pre-existent before the surgery, in the other no thrombus in the left atrial auricle was found on echocardiogram. 291 Appendix D.1.4: Safety Outcomes- Intraoperative ablation- Internal Comparisons Perioperative Outcomes Blood loss (mL) Nakajima et al. 2002 Level III-3 Kosakai Maze n=110 960[880] (in operation) 22 745[618] Schaff et al. Level III-2/3 Biatrial CA Left atrial CA n=173 n=42 CA n=110 940[730] (in operation)pns 23 590[353] * Takami et al. 1999 Level III-3 Biatrial CA Left atrial CA n=30 n=20 708[576] 687[302]pns (n=15) (n=21) 2/15 (13.3%) pns 8/21 (39.1%) 24 (n=15) 25 (n=21) Transfusion required Stroke Transitory cerebral ischaemic accident Other thromboembolism Bleeding Wound infection/sternal instability 0 1/110 (0.9%) Mediastinitis 0 1/110 (0.9%) 1/110 (0.9%) (tracheotomy) 0pns 3/110 (2.7%) (acute) 0pns 4.5%26 0% Pulmonary insufficiency 11/173 (6.4%) requiring re-exploration 0 2/173 (1.2%)27 1/42 (2.4%)28 Low cardiac Output Renal failure Intra-aortic balloon pump Oesophageal injury Major Complications (non specified) Mortality to 30 d Postoperative Outcomes Oesophageal injury Stroke Freedom from Stroke Anticoagulant related bleeding Mortality Actuarial Survival 64.1[27.4] months 18.8[10.8] months 2/110 (1.8%) (1 lethal) 99.0% (n=110; 1 yr) 99.0 (n=92; 2 yrs) 99.0% (n=51; 3 yrs) 2/110 (1.8%) (1 lethal) 2/110 (1.8%) (1 stroke, 1 bleeding) 100% (n=109) 98.0% (3 yrs) (n=92) 98.0% (n=51) 1/110 (0.9%) (4 mo postop; lethal) 0 0 15-51 months 8-23 months 0 0 99.0% (n=77; 1 yr) 99.0% (n=6; 2 yrs) 1/110 (0.9%) 1/110 (0.9%) (stroke) 0 100% (n=77) 91.7% (3 yrs) (n=6) 22 : Blood loss from chest tube drainage in the first 12 hrs in ICU. : Blood loss from chest tube drainage in the first 12 hrs in ICU. 24 : n=21 patients with MV surgery +/- tricuspid annuloplasty 25 : n=15 patients with MV surgery +/- tricuspid annuloplasty 26 : Patients requiring high dose catecholamine (dopamine >8 µg/kg/min) 27 : 1 patient died of septicaemia and pneumonia, the other patient died following congenital heart defect repair. 28 : Patient had congenital heart defect repair. 23 292 Appendix D.1.4 continued: Safety Outcomes- Intraoperative ablation- Internal Comparisons Perioperative Outcomes Yoshihara et al. 2000 Level III-3 Kosakai MazeKosakai RAA Maze+RAA n=20 n=22 Kosakai 2000 Level III-2/3 Kosakai Maze n=1119 Maze-III n=835 Blood loss (mL) Transfusion required Stroke Transitory cerebral ischaemic accident Other thromboembolism Bleeding Wound infection/sternal instability Mediastinitis Pulmonary insufficiency Low cardiac Output Renal failure Intra-aortic balloon pump Oesophageal injury Major Complications (non specified) Mortality to 30 d 0 0 FU= Not stated Postoperative Outcomes Oesophageal injury Stroke Freedom from Stroke Anticoagulant related bleeding Mortality Cumulative Survival 293 Appendix D.1.5: Safety Outcomes- Cryotherapy Case Series Biatrial CA Perioperative Outcomes Blood loss (mL) Transfusion required Stroke Transitory cerebral ischaemic accident Other thromboembolism Bleeding Ad et al. 2003 Level IV (abstract) Ad et al. 2003 Level IV (abstract) Arai et al. 1999 Level IV Fukada et al. 1998 Level IV n=50 n=51 n=30 n=29 2/50 (4.0%) operative 2/51 (3.9%) operative FU= 8.3{3.1} months FU= 19{5} months Wound infection/sternal instability Mediastinitis Pulmonary insufficiency Low Cardiac Output Renal failure Intra-aortic balloon pump Major complications (unspecified) Mortality to 30 d Postoperative Outcomes Oesophageal injury Stroke Freedom from stroke Anticoagulant related bleeding Mortality 0 1 (late follow-up) 0 0 FU = 3.2[2.5] months29 or = 4.5[4]4] months30 1/30 (3.3%)31 Cumulative survival 29 : Rheumatic patients (n=10) : Non-rheumatic patients (n=7) 31 : Patient died at 4 months postoperatively due to pulmonary infection, sepsis and multiple organ dysfunction. This patient had low output syndrome for 3 days postoperatively. 30 294 Appendix D.1.5 continued: Safety Outcomes- Cryotherapy Case Series Biatrial CA Perioperative Outcomes Izumoto et al. 2000 n=104 or n=87 (Izumoto 1998) Morishita et al. 2000 Shimizu et al. 1997 Yuda et al. 2001 n=12 n=6 n=94 Blood loss (mL) Stroke 2/9432 (2.1%) Transitory cerebral ischaemic accident Other thromboembolism Bleeding Wound infection/sternal instability 1/104 (1.0%) (cerebral) 1/87 (1.1%) (GI bleed) 3/87 (3.4%) (all MVR) 133 (1.1%) Mediastinitis Pulmonary insufficiency Low cardiac Output Renal failure 5/87 (5.7%) 1/12 (8.3%) (respiratory failure) 2/87 (2.3%) 1/87 (1.1%) (fatal) Intra-aortic balloon pump Major complications (unspecified) Mortality to 30 d Postoperative Outcomes Oesophageal injury Stroke 3/10434 (2.9%) and 21/8735(24.1%) 4/10436 (3.8%) 1/12 (8.3%) 0 0 FU = 60 months 5/104 (4.8%) 3/87 (MVP: 1 MVR: 2) Freedom from stroke Mortality Cumulative Survival 8/99 (8.1%)37 5/87 (5.7%)38 1 yr: 95.1%[2.3%]40 5 yrs: 87.8%[3.4%] MVP: 1 yr: 98.1[1.9]41 5 yrs: 94.2[3.2] MVR: 1 yr: 85.7[5.9] 5 yrs: 82.9[6.4] 2/9439 (2.1%) 32 : At 12 and 24 months postoperatively, both had regular heart rhythm. : Cerebral haemorrhage. 34 : One patient developed a circumflex coronary artery stenotic lesion, considered related to the cryoablation, and needed redo surgery and CABG, 2 patients had left ventricular rupture. 35 Patients who suffered morbidity following surgery (Izumoto 1998). 36 : Stated as patients who died within 3 months of surgery. In Izumoto 2001 MV patients only (n=87) there were 4 operative deaths, 3 from multiple organ failure and 1 from cerebral infarction and acute renal failure. 2/4 deaths related to postoperative left ventricular rupture. 37 : Stated as patients who died after hospital discharge. 3 patients died of cardiac failure, 1 patient died of gastric cancer, 1 patient died of colon cancer, 1 patient died of ovarian cancer, 1 patient died of chronic pleuritis as a result of exacerbation tuberculosis, 1 patient died of unknown causes, 38 : n=87 MV patients (Izumoto 2001) 3 patients with MVP died, 2 had cardiac failure and 1 exacerbated pleuritis and 2 MVR patients died, 1 with cardiac failure and 1 with ovarian cancer. 39 : 1 patient died due to cerebral haemorrhage and multiple organ failure 32 months postoperatively, 1 patient died suddenly at 29 months postoperatively, had SR but reverted to AF at 28 months with successful electrical cardioversion. 40 : Kaplan-Meier method in 103 patients who survived > 1 month. 41 : Surgical survival in patients with MVR or MVP at 1 and 5 yrs (Izumoto 2001) 33 295 Appendix D.1.6: Safety Outcomes- Cryotherapy Case Series Left atrial CA Perioperative Outcomes Hoffmeister et al. 2003 (abstract) Imai et al. 2001 Kondo et al. 2003 Manasse et al. 2003 n=19 n=32 n=31 n=95 Blood loss (mL) 18/31(58.1%) (during surgery) 20/31 (64.5%) (postoperative) 0 Transfusion required Stroke 1/95 (1.1%) (resolved before discharge) Transitory cerebral ischaemic accident Other thromboembolism 0 (requiring re-exploration) Bleeding 2/95 (2.1%)42 Wound infection/sternal instability Mediastinitis Pulmonary insufficiency 1/31 (3.2%) (fatal) 1/31 (3.2%) (acute, fatal) Low cardiac Output Renal failure Intra-aortic balloon pump 0 8/95 (8.4%) 1/95 (1.1%) (requiring dialysis) 1/95 (1.1%) Major complications (unspecified) Mortality to 30 d Postoperative Outcomes Mean 28.8 months (1-48 months) 043 2/3144 (6.5%) FU= 13-66 months FU= 12-60 months Oesophageal injury Stroke Freedom from Stroke Anticoagulant related bleeding Mortality 0 2/19 (10.5%) (non-cardiac) 0 2/95 (2.1%)45 3/95 (3.2%)46 7/9547 (7.4%) Cumulative Survival 42 : Patients reopened on the first postoperative day due to bleeding not related to the ablation procedure. Patients were a selected group that had survived for > 1 yr. 44 : 1 patient with acute renal failure and 1 patient with low output syndrome. 45 : Intraoperative death due to a tear of the posterior left atrial wall as a result of retracting the cryoprobe before thawing was completed. One patient died 1 month postoperatively of septicaemia, the patient was in SR. 46 : 1/22 patients with first ablation line, had a lethal stroke 8 months postoperative, had a bioprosthetic AVR and was on oral anticoagulation because of persistent AF; 2/41 patients with third ablation line, one patient with a lethal stroke at 7 months postoperative, had CABG and was on oral anticoagulation because of persistent AF< the other patient had a bioprosthetic AVR and a lethal stroke at 45 months postoperative. 47 : 1 patient in AF died 49 days postoperatively due to pneumonia, 3 patients died of stroke; 1 patient died 3 months postoperatively of heart failure; 1 patient died at 14 months, they had needed intra-aortic balloon support and dialysis in immediate postoperative period for septicaemia;1 patient died at 39 months of cerebral cancer. 43 296 Appendix D.1.6 continued: Safety Outcomes- Cryotherapy Case Series Left atrial CA Perioperative Outcomes Naito et al. 2001 (abstract) Sueda et al. 2001 Usui et al. 2002 Yamauchi et al. 2002 n=30 n=12 n=41 n=40 Blood loss (mL) ` Transfusion required Stroke Transitory cerebral ischaemic accident Other thromboembolism Bleeding Wound infection/sternal instability Mediastinitis Pulmonary insufficiency Low cardiac Output Renal failure Intra-aortic balloon pump Major complications (unspecified) Mortality to 30 d Postoperative Outcomes Oesophageal injury Stroke Freedom from Stroke Anticoagulant related bleeding Mortality 0 0 0 FU = 16.5{6.7} months FU= 5-14 months 0 Cumulative Survival 297 0 Appendix D.2.1: Safety Outcomes- Intraoperative ablation- Radiofrequency Comparative Biatrial RFA versus CS Perioperative Outcomes Khargi et al. 2001 Level II RFA+ MVS MVS n=15 n=15 RFA I/II n=13 365[116] 48 (250-550) n=12 Blood loss (mL) Stroke 1/13 (7.7%) Chen et al. 2001 Level III-2 RFA IV n=48 CS n=58 0 0 Patwardhan et al. 2003 Level III-3 RFA CS n=84 n=64 Riying et al. 1998 III-3 RFA MVS n=25 n=25 1/64 (1.6%) in-hospital Transitory cerebral ischaemic accident 1/8449 (1.2%) Other thromboembolism Bleeding 2/8450 (2.4%) 1/15 (6.7%) 51 52 Wound infection/sternal instability 4/15 (20%) Mediastinitis 1/15 (6.7%) 0 Pulmonary insufficiency 1/15 (6.7%) 1/15 (6.7%) Low cardiac Output Renal failure Intra-aortic balloon pump Major complications (unspecified) Mortality to 30 d Postoperative Outcomes 0 2/15 (6.7%) 0 Mean FU = 21-22 months 1/84 (1.2%) 1/64 (1.6%) 7/84 (8.3) fatal 8/64 (12.5%) fatal 2/13 (15.4%) 1/48 (2.1%) 4/58 (6.9%) 8/8453 (9.5%) 11/6454 (17.2%) 0 43 months (37-47 months) 16 months (3-32 months) (35-109 months) 23.6[12.5] months (12-53 months) 6 months (3-24 months) Oesophageal injury Stroke Anticoagulant related bleeding Mortality 055 3/6456 (4.7%) 1/15 (6.7%) fatal 4/15 (26.7%)57 1/15 (6.7%)58pns 0 0 48 0 2/84 (2.4%) fatal 6/8459 (7.1%) 0 0 : Chen et al. 1998. Maximum daily pericardial tube drainage in first 24 hours : Acute valvular thrombosis, fatal 50 : Intracranial bleeding following Warfarin 51 : 3 patients had a wound infection, fatal in 1/3, and 1 patient sternal instability requiring reoperation. 52 : 1 patient had a wound infection and 1 patient sternal instability requiring reoperation. 53 : 1 patient died of mediastinitis, 7 patients died of low cardiac output. 54 : 8 patients died of low cardiac output, 1 patient died of mediastinitis, 1 patient died of disseminated intravascular coagulation, 1 patient died of cerebral embolism. 55 : To hospital discharge. 56 : Patients hospitalised for stroke during follow-up. 57 : 1 patient died from fatal coumadin-related renal bleeding; 1 patient died of mediastinitis on the 45th day postoperative, the patient was obese, diabetic and the prolonged operative time was a risk factor; 1 patient died at 6 weeks postoperative of sudden cardiac death, possibly due to the pro-arrhythmic effects of sotalol; and 1 patient had lethal respiratory failure at 7 months postoperative, related to pre-existing chronic obstructive pulmonary disease. 58 : Patient died of lethal respiratory failure, 10 months postoperative, related to pre-existing chronic obstructive pulmonary disease. 59 : Two patients due to intracranial bleeding following Warfarin therapy, 1 patient due to acute valvular thrombosis, 1 patient due to fungal endocarditis, 1 patient due to intractable failure, and 1 patient with sudden death of unknown cause. 49 298 [] = standard deviation; pns: statistically non-significant; ( ): range Appendix D.2.2: Safety Outcomes- Intraoperative ablation- Radiofrequency Comparative RFA versus Cardioversion Perioperative Outcomes RFA n=12 Thomas et al. 2003 III-2/3 Cardioversion n=33 Blood loss (mL) Transfusion required Stroke Transitory cerebral ischaemic accident Other thromboembolism Bleeding Wound infection/sternal instability Mediastinitis Pulmonary insufficiency Low cardiac Output Renal failure Intra-aortic balloon pump Oesophageal injury Major complications (unspecified) Mortality to 30 d 15[18] months Postoperative Outcomes Oesophageal injury Stroke Freedom from Stroke Anticoagulant related bleeding Mortality 0 0 Cumulative Survival 299 Appendix D.2.3: Safety Outcomes- Intraoperative ablation- Radiofrequency Comparative Left atrial RFA versus CS Perioperative Outcomes Guang et al. 2002 III-2 RFA + MVS n=96 Mantovan et al. 2003 III-3 Blood loss (mL) 494.1[100.4] 476.1[115.9] pns 0 0 MVS n=87 RFA + CS n=103 CS n=27 Transfusion required Stroke Transitory cerebral ischaemic accident 1/103 (1.0%) 3/10360 (2.9%) Other thromboembolism Bleeding 1/103 (fatal) (1.0%) 4/94 (4.2%) (3 GIT bleeding) 3/87 (3.4%) (1 GIT bleeding) 2/96 (2.1%) (pneumothorax) 2/87 (2.3%) (pneumothorax) 1/27 (3.7%) (fatal abdominal infarction) 3/2761 (11.1%) Wound infection/sternal instability Mediastinitis Pulmonary insufficiency 262 (1.9%) Low cardiac Output Renal failure Intra-aortic balloon pump Oesophageal injury 1/103 (1.0%) (fatal) Major Complications (non specified) Mortality to 30 d 0 0 1/103 (1.0%) (oesophageal injury) 0 FU = 12.5[5] months Postoperative Outcomes Oesophageal injury 1/103 (1.0%) fatal Stroke Freedom from Stroke Anticoagulant related bleeding Mortality 0 0 3/10363 (2.9%) 2/2764 (7.4%) Cumulative Survival pns: probability non-significant (p> 0.05) 60 : Three patients had left atrial thrombi, soon after surgery all had IV heparin followed by oral anticoagulants. One was on the posterior wall of the left atrium, and two were on the roof. They were all detected by transthoracic echocardiography. Two were in SR after surgery, in one the thrombus affected the mitral valve and required reoperation. 61 : One patient with peritoneal blood effusion, one patient with cardiac tamponade, and one patient with pericardial blood effusion. 62 : One patient had pneumothorax, and one patient pleural effusion. 63 : 1 patient died suddenly at 3 months, they had a left atrial thrombus, and were in SR without atrial contraction; 1 patient in AD died of a stroke 1 month postoperatively; 1 patient in SR without atrial contraction died suddenly 8 months postoperatively, she had severe left ventricular cardiomyopathy with function mitral insufficiency and dysthyroidism. 64 : 1 patient died 1 month postoperatively of an abdominal infarction; 1 patient died suddenly 5 months postoperatively of unknown causes. 300 Appendix D.2.4: Safety Outcomes- Intraoperative ablation- Radiofrequency Comparative RFA versus Maze-III Chiappini et al. 2004 III-3 RFA + CS Maze-III + CS n=40 n=30 Perioperative Outcomes Blood loss (mL) Transfusion required Stroke Transitory cerebral ischaemic accident Other thromboembolism Bleeding Wound infection/sternal instability Mediastinitis Pulmonary insufficiency Low cardiac Output Renal failure Intra-aortic balloon pump Oesophageal injury Major Complications (Non specified) 3/40 (7.5%)65 Mortality to 30 d 2/30 (6.7%)66 Postoperative Outcomes Oesophageal injury Stroke Freedom from Stroke Anticoagulant related bleeding Mortality Cumulative Survival pns 92.8% (Kaplan-Meier) 90.4% 65 : 1 patient died of sepsis, 1 patient died of severe hepatic cirrhosis of 20 yrs duration, and 1 patient died of left ventricular disruption, believed due to severe and very deep calcification of the annulus of the MV and the subvalve apparatus. 66 : 1 patient died of multiorgan failure and 1 patient died of a left ventricular disruption after MVR, believed due to severe and very deep calcification of the annulus of the MV and the subvalve apparatus. 301 Appendix D.2.5: Safety Outcomes- Intraoperative ablation- Radiofrequency Comparative Biatrial versus left atrial RFA Güden et al. 2002 III-2 Biatrial RFA Left atrial RFA n=39 n=23 Deneke et al. 2002a Level IIIBiatrial RFA n=49 Left atrial RFA n=21 2/49 (4.1%) (1 renal bleeding and 1 GIT bleeding) 1/21 (4.8%) 2/49 (4.1%) (first days postoperative) 2/21 (9.5%) (first days postoperative) Mediastinitis 1/49 (fatal) (2.0%) 1/21 (fatal) (4.8%) Pulmonary insufficiency 2/49 (fatal) (4.1%) Perioperative Outcomes Blood loss (mL) Transfusion required Stroke Transitory cerebral ischaemic accident Other thromboembolism Bleeding 2/3967 (5.1%) 1/2368 (4.3%) Wound infection/sternal instability Low cardiac Output Renal failure Intra-aortic balloon pump Oesophageal injury 2/62 (3.2%) 2/49 (4.1%) (pericardial effusion) 0 1/21 (4.8%) (pericardial effusion) 2/2169 (9.5%) FU= Mean 104 days (range 45-245) RFB: 18[14] months (range 1-50) RFL: 11[10] months (range 4-20) Major Complications (Non specified) Mortality to 30 d Postoperative Outcomes Oesophageal injury Stroke Anticoagulant related bleeding Mortality 1/39 (2.5%) (sudden cardiac death) 1 (4.3%) (unexplained causes) Cumulative Survival 6/4970 (12.2%) 77.9% 67 90.5% : Bleeding associated with the LAA amputation site in both cases. : Sudden massive bleeding at 6 hrs postoperative due to partial disruption of the LAA suture line. : 1 patient died of mediastinitis 21 days postoperative and 1 patient died of postoperative severe pyoderma with sepsis after 28 days. 70 : 1 patient died due to renal bleeding at 40 days postoperative, 1 patient died due to mediastinitis at 45 days postoperative, 1 patient had sudden cardiac death after 4 months postoperative, 1 patient died of progressive respiratory insufficiency at 7 months postoperative, 1 patient died due to respiratory insufficiency at 16 months postoperative, and 1 patient died of unknown causes (noncardiac or cerebral ischaemia) at 33 months postoperative). 68 69 302 Appendix D.2.6: Safety Outcomes- Intraoperative ablation- Radiofrequency Case Series Biatrial RFA Perioperative Outcomes Damiano et al. 2003 Level IV (abstract) Hornero et al. 2002 Level IV Prasanna et al. 2001 Level IV Raman et al. 2003 n=26 n=55 n=25 n=132 Blood loss (mL) Transfusion required 1/55 (1.8%) (fatal) 1/55 (1.8%) (3rd day postoperative) Stroke Transitory cerebral ischaemic accident Other thromboembolism 0 0 3/55 (5.5%) (requiring re-operation) Bleeding 0 1(0.8%) (fatal, bleeding duodenal ulcer) Wound infection/sternal instability Mediastinitis Pulmonary insufficiency 3/132 (2.3%) (recorded as cause of fatalities) Low Cardiac Output Renal failure 1/132 (0.8%) (patient died) Intra-aortic balloon pump Major complications (unspecified) Mortality to 30 d 0 1/55 71 (1.8%) Postoperative Outcomes Oesophageal injury Stroke 0 9/132 (6.8%)72 3.2-3.8 years Mean 6.4 months (3-24 months) 0 Freedom from stroke Anticoagulant related bleeding Mortality 2/5573 (3.6%) 71 0 1/132 74 (0.8%) : Patient with history of chronic renal failure with sudden death 22 days postop. : remote aortic dissection in a patient with replacement of ascending aorta in 1, severe liver dysfunction caused by coagulopathy and tamponade with a very fragile and calcified aortic root that leaked after valve replacement in 1, decompensated patient on a balloon pump with uncontrolled AF with large ventricular infarcts, severe aortic regurgitation and uncontrolled tachycardia, arrested soon after anaesthetic induction and was salvaged, no recovery of ventricular function on day 5 in 1 patient, bleeding duodenal ulcer on day 8 in 1 patient, cardiogenic shock as a result of a large infarct complicating a delayed low output syndrome on day 6 postoperatively in 1 patient, perioperative gut ischaemia in 1 patient, low systemic vascular resistance syndrome resistant to norephinephrine and vasopressin in 1 patient, and related to low output in 2 elderly patients 73 : 1 patient with atrioventricular canal defect had sudden death of unknown causes; and cerebral haemorrhage, probably due to acenocoumarol treatment. 74 : Patient with infective endocarditis complicated by liver failure at 8 months postoperatively. 72 303 Appendix D.2.6 continued: Safety Outcomes- Intraoperative ablation- Radiofrequency Case Series Biatrial RFA Perioperative Outcomes Blood loss (mL) Transfusion required Stroke Sie et al. 2001 Sos et al. 2002 Thomas et al. 2003 n=122 n=10 741[475] (postoperative) n=47 1/122 (0.8%) Transitory cerebral ischaemic accident 1/10 (postop day 3) Other thromboembolism Bleeding Wound infection/sternal instability 0 (requiring re-operation) 1/122 (0.8%) (sternal wound infection) Mediastinitis Pulmonary insufficiency Low cardiac Output 1/1075 2/122 (1.6%) (reported as causes of fatalities) Renal failure Intra-aortic balloon pump Major complications (unspecified) Mortality to 30 d Postoperative Outcomes 7/122 (5.7%) 3/12276 (2.5%) 5/7277 (6.9%) 5/122 (4.1%)78 7/200 (3.5%)79 39 months 080 2/47 (4.3%) (<48 hrs from pump failure) 1.5-5 months 0.6-4.2 years Oesophageal injury 2/47 81 (4.3%) 0 (patients in SR) Transient Ischaemic Attack Freedom from stroke Anticoagulant related bleeding Mortality Cumulative Survival 10/12282 (8.2%) 17/20083 (8.5%) 3 years: 90%[3.1%] 084 75 2/4785 (4.3%) : 1 patient required prolonged intubation (> 48 hrs) for secondary, severe pulmonary hypertension later complicated by nosocomial pneumonia : Right ventricular perforation in 2 patients and endocarditis in 1 patient 77 : 5/72 patients with pericardial effusion (Sie 2001) 78 : 1 patient died intraoperatively due to rupture of the mitral annulus; 1 patient died of coma vigil due to late tamponade; 2 patients died of low cardiac output syndrome; 1 patient died of multiple organ failure 79 : Sie et al. 2003 n=200 80 : Typographical error in text, “There was (no) hospital or late mortality…” 81 : At late follow-up 2 patients who still had AF had transient neurological deficits 82 : 5 cardiac; 1 non specified; 4 non-cardiac related 83 : Sie et al. 2003 abstract, n=200 84 : Typographical error in text, “There was (no) hospital or late mortality…” 85 : 1 patient from presumed ventricular tachycardia and 1 from prostatic carcinoma 76 304 Appendix D.2.7: Safety Outcomes- Intraoperative ablation- Radiofrequency Case Series Left atrial RFA Perioperative Outcomes Blood loss (mL) Transfusion required Stroke Benussi et al. 2002 Biederman et al. 2002 Geidel et al. 2003 n=132 n=10 n=29 Gillinov et al. 2003 (abstract) n=50 358[204] 6/4086 (15.0%) 2/132 (1 fatal) (1.5%) Transitory cerebral ischaemic accident Other thromboembolism Bleeding Wound infection/sternal instability 3/132 (2.3%) (requiring re-operation) 1/132 (0.8%) (deep sternal wound infection) Mediastinitis Pulmonary insufficiency 1/132 (0.8%) (reported as cause of fatality) Low cardiac Output Renal failure Intra-aortic balloon pump Major complications (unspecified) Mortality to 30 d Postoperative Outcomes Oesophageal injury Stroke Freedom from Stroke Anticoagulant related bleeding Mortality Cumulative Survival 0 (severe) 0 0 (procedure related) 3/13287 (2.3%) 16.9[14.2] months 1/132 (fatal) (0.8%) 3 yr actuarial: 98% 95% CI: 96%-100 % 3/13288 (2.3%) 3 yr: 94% 95% CI: 88%-99% 86 : Benussi 2000 : Patient with a previous stroke died on postop day 12 due to bilateral pneumonia causing prolonged ventilatory support and septicaemia; 2 patients died after discharge due to cardiac arrest, possibly related to myocardial infarction, and a stroke related to inadequate anticoagulation 88 : 1 patient with sudden death; 1 patient with refractory AF with a stroke; 1 patient with mediastinal lymphoma 87 305 Appendix D.2.7 continued: Safety Outcomes- Intraoperative ablation- Radiofrequency Case Series Left atrial RFA Perioperative Outcomes Kottkamp et al. 1999 Kress et al. 2002 n=12 n=23 Le Tourneau et al. 2003 Level IV n=70 Mohr et al. 2002 n=65 Blood loss (mL) Transfusion required Stroke 0 6/70 (8.6%) (embolic event) Transitory cerebral ischaemic accident Other thromboembolism Bleeding 1/1289 (8.3%) Wound infection/sternal instability Mediastinitis Pulmonary insufficiency Low cardiac Output 1/12 (8.3%) (fatal) Renal failure Intra-aortic balloon pump 1/7090 (1.4%) Major complications (unspecified) 91 92 Mortality to 30 d 1/12 (8.3%) 1/23 (4.3%) Postoperative Outcomes 3-20 months 1-100 weeks Oesophageal injury Stroke Freedom from stroke Anticoagulant related bleeding Mortality Cumulative Survival FU= 549 days 2/7093 (2.9%) 89 : Distal anastomosis of venous bypass graft to circumflex coronary artery causing cardiac tamponade. Uneventful re-operation and recovery. : Patient had an RF induced circumflex artery stenosis. 91 : Patient developed haemodynamic deterioration and ventricular fibrillation 24 hrs postop, re-operation but patient died of low cardiac output syndrome. 92 : Ventricular arrhythmia in patient with recent myocardial infarction and low LVEF 93 : 1 patient had multiorgan failure and 1 patient pulmonary infection (SHVD 2003). The time of the deaths relative to the surgery was not stated. 90 306 12 months 0 Appendix D.2.7 continued: Safety Outcomes- Intraoperative ablation- Radiofrequency Case Series Left atrial RFA Müller et al. 2002 Perioperative Outcomes n=95 Ruchat et al. 2002 Schläpfer et al. 2002 n=40 n=37 845[248] Blood loss (mL) Transfusion required Stroke 1/48 (2.1%) (Pasic et al. 2001) 1/4094 (2.5%) Transitory cerebral ischaemic accident 2/3795 (5.4%) Other thromboembolism Bleeding 0 (requiring re-operation) 1/40 (2.5%) (requiring re-operation) Wound infection/sternal instability Mediastinitis Pulmonary insufficiency 9/9596 (9.5%) Low cardiac Output Renal failure Intra-aortic balloon pump 3/3797 (8.1%) Major complications (unspecified) 98 99 Mortality to 30 d 2/48 (4.2%) 3/40 (7.5%) Postoperative Outcomes 1-24 months 12.5[7.9] months in n=37 Oesophageal injury Stroke Freedom from stroke Anticoagulant related bleeding Mortality 2/40101 (5.0%) 2/37100 (5.4%) 2/37102 (5.4%) Cumulative Survival 94 : On 3rd day postop, normal MRI, anticoagulation therapy not optimal : In 2 patients on the 6th and 9th days postoperative, no lesions on cerebral images, anticoagulation was still not optimal at this time. 96 : Patients needing postoperative ventilatory support > 24 hrs. 2/48 had left-sided pleural effusion due to fluid retention (Pasic et al. 2001) 97 : Cardiac tamponade in 2 patients, and in 1 patient on the 4th postoperative day a patient who had a previous cardiac tamponade had a sudden death, successfully resuscitated and had an implantation of a defibrillator. 98 : Deaths on postop days 16 and 26 due to a stroke, and late pericardial tamponade. 99 : 1 death in operating theatre due to cardiogenic shock, 1 sudden cardiac death due to perioperative embolic myocardial infarct on 4th postop day, 1 patient with left retro-orbital tumour and severe vasoplegia after AVR died on 3rd day postop of multiple organ failure. 100 : 1 patient in the operating room after cardiogenic shock, 1 patient on 3rd day postoperative due to myocardial rupture after an acute infarct. 101 : 1 death due to septic shock at 5th month postop, 1 death after colectomy for sigmoid cancer 102 : Deaths at 3rd and 6th month postoperative due to non-cardiac causes. 95 307 Appendix D.2.7 continued: Safety Outcomes- Intraoperative ablation- Radiofrequency Case Series Left atrial RFA Perioperative Outcomes Starck et al. 2003 Williams et al. 2001 n=100 n=48 Blood loss (mL) Transfusion required Stroke 0 Transitory cerebral ischaemic accident Other thromboembolism Bleeding 0 3/100103 (3.0%) (1 fatal) 0 5/100 (5%)104 3/48105 (6.3%) FU= 3-23 months FU= 138[96] days Wound infection/sternal instability Mediastinitis Pulmonary insufficiency Low cardiac Output Renal failure Intra-aortic balloon pump Major complications (unspecified) Mortality to 30 d Postoperative Outcomes Oesophageal injury Stroke Freedom from stroke Anticoagulant related bleeding Mortality 0106 3/48107 (6.3%) Cumulative survival 103 : Bleeding from the suture line of the resected LAA managed successfully in 2 patients and fatal massive haemorrhage from suture line of left atriotomy, reported as a cause of fatality. : 4 patients with impaired left ventricular function preoperatively died due to low cardiac output syndrome followed by multiorgan failure, 1 patient died on 6th postoperative day due to sudden onset massive haemorrhage from the suture line of the left atriotomy. Patient had been treated with corticosteroids for a long period prior to surgery, autopsy showed abnormally fragile atrial tissue. 105 : 1 patient 3 days postoperative with right heart failure/acute hypertensive crisis; 1 patient 30 days postoperative due to multisystem organ failure; 1 patient died 8 days postoperative with pneumonia/multisystem organ failure 106 : Noted in an Addendum “In the first 100 cases reported we did not experience any serious radiofrequency ablation related complications; however in our 249th case, we unfortunately saw an esophageal performation with lethal outcome….” 107 : 1 patient died 38 days postoperative due to acute lung injury/multisystem organ failure; 1 patient died 39 days postoperative due to multisystem organ failure; 1 patient died 38 days postoperative with a perforated right colon and multisystem organ failure. All deaths while patients still in hospital. 104 308 Appendix 3.1: Safety Outcomes- Intraoperative ablation- Microwave Comparative Studies Left atrial MWA versus CS Perioperative Outcomes Schuetz et al. 2003 Level II MWA + CS CS n=24 n=19 Spitzer and Knaut 2002 III-2 MWA + CS CS n=136 n=51 Blood loss (mL) Transfusion required Stroke 0 0 0 0 Transitory cerebral ischaemic accident Other thromboembolism Bleeding Wound infection/sternal instability Mediastinitis Pulmonary insufficiency 1/136 (fatal)108 Low cardiac Output Renal failure Intra-aortic balloon pump 1109 Major complications (unspecified) Mortality to 30 d Postoperative Outcomes 1/24110 (4.2%) 1/19111 (5.3%) 2/136112 (1.5%) FU = 12 months n=15/24 4/51113 (7.8%) FU = 12 months n=9/19 0 Oesophageal injury 0 Stroke Freedom from Stroke Anticoagulant related bleeding Mortality 0 0 Cumulative Survival [] = standard deviation 108 : Taken from cause of fatality. : One patient had to be resuscitated perioperatively due to ventricular fibrillation, and had damage to the brain. 110 : Patient died of cerebral air embolism of unknown origin. 111 : Patient with refractory heart failure. 112 : 1 patient died on first day postoperatively of low output syndrome, 1 patient died on day 20 with sudden cardiac death. 113 : In 1 patient bilateral embolus of lungs; 3 patients died after CABG (2/3 with AVR or thrombarterectomy with a carotid patch), 1/3 after intractable left heart failure, 1/3 with toxic gangrene of the GIT, and 1/3 with left sided heart failure + ischaemic enterocolitis. 109 309 Appendix 3.2: Safety Outcomes- Intraoperative ablation- Microwave Comparative Internal Comparison MWA1 versus MWA2 Perioperative Outcomes Knaut et al. 2003 (abstract) Level III-? MWA1 MWA2 n=137 n=75 Blood loss (mL) Transfusion required Stroke Transitory cerebral ischaemic accident Other thromboembolism Bleeding Wound infection/sternal instability Mediastinitis Pulmonary insufficiency Low cardiac Output Renal failure Intra-aortic balloon pump Oesophageal injury Major complications (unspecified) Mortality to 30 d 7/234 (3.0%) (perioperative, EACTS 2003) 6 months Postoperative Outcomes Oesophageal injury Stroke Freedom from Stroke Anticoagulant related bleeding Mortality Cumulative Survival 98.5% 97.3% 310 Appendix 3.3: Safety Outcomes- Intraoperative ablation- Microwave Biatrial MWA Case Series Perioperative Outcomes Chiappini et al. 2003 Level IV MWA + CS n=10 Blood loss (mL) Transfusion required Stroke Transitory cerebral ischaemic accident Other thromboembolism 0 Bleeding Wound infection/sternal instability Mediastinitis Pulmonary insufficiency Low Cardiac Output Renal failure Intra-aortic balloon pump Major complications (unspecified) Mortality to 30 d Postoperative Outcomes 1/10114 Mean 12.4 months Oesophageal injury Stroke Freedom from stroke Anticoagulant related bleeding Mortality 0 Cumulative survival 114 : Patient had a rupture of the left ventricle following mitro-aortic valve replacement, and had a severely calcified mitral annulus. 311 Appendix D.3.4: Safety Outcomes- Intraoperative ablation- Microwave Left atrial MWA Case Series Perioperative Outcomes Gillinov et al. 2002 Level IV MWA + MVS n=10 Knaut et al. 2002 Level IV MWA + MVS n=105 Venturini et al. 2003 Level IV MWA + MVS n=41 Zembala et al. 2003 Level IV MWA + MVS n=42 Blood loss (mL) Transfusion required Stroke Transitory cerebral ischaemic accident Other thromboembolism O (requiring re-exploration) Bleeding Wound infection/sternal instability Mediastinitis 0115 Pulmonary insufficiency 0116 Low cardiac Output Renal failure Intra-aortic balloon pump 0117 Major complications (unspecified) Mortality to 30 d Postoperative Outcomes FU= Not stated 1/105118 (1.0%) 0 0 FU= Up to 24 months 64/105 at 12 months FU = 5-21 months FU = 1-14 months Oesophageal injury 1/42 (2.4%) (fatal) Stroke Freedom from stroke Anticoagulant related bleeding 0 Mortality Cumulative Survival 115 : No stenosis of the pulmonary veins : Observed no cases of either pulmonary hypertension or pulmonary vein stenosis in up to 14 months postoperatively. 117 : No in-hospital complications. 118 : Patient died from right sided heart failure on day 20 postoperatively. 119 : Patient died 8 months postoperatively, discharged in AF and had a fatal cerebral thromboembolic event. 116 312 1/42119 (2.4%) Appendix D.4: Safety Outcomes- Intraoperative ablation- Laser Case Series Perioperative Outcomes Vigilance et al. 2003 Level IV n=6 Blood loss (mL) Transfusion required Stroke Transitory cerebral ischaemic accident Other thromboembolism Bleeding Wound infection/sternal instability Mediastinitis Pulmonary insufficiency Low cardiac Output Renal failure Intra-aortic balloon pump Oesophageal injury Major complications (unspecified) Mortality to 30 d Postoperative Outcomes Oesophageal injury Stroke Freedom from Stroke Anticoagulant related bleeding Mortality Cumulative Survival 313 Appendix D.5: Safety Outcomes- Intraoperative ablation- MWA versus RFA Perioperative Outcomes Blood loss (mL) Wisser et al. 2003 Level III-2/3 (abstract) MWA RFA n=23 n=19 498[292] 526[145] 0 0 2/23 (8.7%) 0 1/23 (4.3%) 1/19 (5.3%) 1/23 (4.3%) 0 1/23120 (4.3%) 1/19121 (5.3%) Transfusion required Stroke Transitory cerebral ischaemic accident Other thromboembolism Bleeding Wound infection/sternal instability Mediastinitis Pulmonary insufficiency Low cardiac Output Renal failure Intra-aortic balloon pump Oesophageal injury Major complications (unspecified) Mortality to 30 d Postoperative Outcomes 1/23 (4.3%) liver failure 24.2[1.3] months 12.1[1.2] months† Oesophageal injury Stroke Freedom from Stroke Anticoagulant related bleeding Mortality 1/23 (4.3%) unexplained causes Cumulative Survival 120 121 : severe systemic inflammatory response syndrome on first postoperative day : severe systemic inflammatory response syndrome on first postoperative day 314 Appendix D.6.1: Efficacy Perioperative and Postoperative- Cryotherapy Comparative Biatrial CA versus CS Handa et al. 1999 Level III-2 CA + MVS MVS n=39 n=58 Perioperative Outcomes Sueda et al. 1997 Level III-3 CA + MVS MVS n=36 n=15 Yuda et al. 2004 Level III-3 CA + MVS MVS n=26 n=6 Total operation time (hr) Time on cardiopulmonary bypass (min) Cross clamping time (min) 122[40] 58[27] § 69[18] 36[14] § 12.6[6.4] 9.3[3.4] † 2/39 (5.1%) (late)122 1/58 (1.7%) (late) 196[53] (range 120-320) 126[35] (range 76-218) 156[26]pns (range 95-260) 97[27] * (range 48-198) Ablation time (min) Length of ICU stay (days) Length of hospital stay (days) Reoperation Bleeding Other Readmission Postoperative Outcomes FU = Mean 21 months (≥ 6 months) Reintervention- Catheter ablation Continued anticoagulant requirement 37% 50% pns Continued antiarrhythmic requirement 55% 78% 122 10/36 (27.8%) (early postop) (successful in 5) : In the 3 patient with late reoperation, 2 had recurrent MV regurgitation and 1 had haemolysis. 315 14/26 (53.8%) 1/6 (16.7%) Appendix D.6.1 continued: Efficacy Perioperative Cardiac- Cryotherapy Comparative Biatrial CA versus CS Handa et al. 1999 Level III-2 CA + MVS n=39 Perioperative Cardiac Outcomes Sueda et al. 1997 Level III-3 CA + MVS MVS n=36 n=15 MVS n=58 Yuda et al. 2004 Level III-3 CA + MVS MVS n=26 n=6 Cardiac rhythm SR 28 (72%) hospital discharge 25 (43%) hospital discharge AF 2 (5%) hospital discharge 24 (41%) hospital discharge Junctional rhythm 9 (23%) hospital discharge 1 (2%) hospital discharge 0 hospital discharge 3 (5%) hospital discharge type not specified Typical atrial flutter 36/36 (immed. postop)123 26/36 (hospital stay) 31/36 (86.1%; hospital discharge) 10/36124 (27.8%; hospital stay) 4/36 (11.1%; hospital discharge) 5/15 (immed. postop) 4/15 (26.6%; hospital discharge) 10/15 (immed. postop) 11/15 (73.3%; hospital discharge) 1/36 (2.8%; hospital discharge) (type not stated) Atypical atrial flutter Other Disappearance rate of AF (%) 95% hospital discharge 5 (9%) pacemaker with AF 50% hospital discharge 86% (31/36; 1 mo) 27% (4/15; 1 mo) 3/15125 (20%) 5/58 (8.6%) 10/36 (27.8%) (total number unclear) 3/26 (11.5%) Cardiac function Right atrial contraction Left atrial contraction Cardioversion Pacemaker required 1/39 (2.6%) 123 : SR or nodal rhythm. : Recurrence of paroxysmal AF within 7 days. 125 : Cardioversion was performed, stated in 3 patients, but may have been more. 124 316 1/6 (16.7%) 17/26 (65%) 1 month Appendix D.6.1 continued: Efficacy Postoperative Cardiac- Cryotherapy Comparative Biatrial CA versus CS Handa et al. 1999 Level III-2 FU = Mean 21 months (≥ 6 months) Postoperative Cardiac Outcomes Heart Rhythm Sueda et al. 1997 Level III-3 Yuda et al. 2004 Level III-3 SR 32 (82%) 8/8 paroxysmal AF chronic AF ≤ 3 mo: 3/4 4-12 mo: 4/5 12 mo: 15/20 unknown: 2/2 31 (53%) 20/22 paroxysmal AF chronic AF ≤ 3 mo: 4/7 4-12 mo: 1/7 12 mo: 4/20 unknown: 2/2 28/36126 (77.8%) 6 months 3/15 (20%) 6 mo 18/26 (69%) > 2 mo AF 4 (10%) 21 (36%) 7/36127 (19.4%) 6 months 12/15 (80%) 6 mo 8/26 (31%) > 2 mo Junctional rhythm 1 (3%) 0 2 (5%) type not specified 1 (2%) type not specified Typical atrial flutter Atypical atrial flutter Other Cumulative Frequency of SR (Kaplan-Meier) Disappearance rate of AF 2/36128 (5.6%) 6 mo 5 (9%) pacemaker with AF 94.7[3.6] n=35 3 months129 81.5[6.9] n=21 1 yr 74[8] n=12 2 yrs 46.6[6.5] n=273 months 130 41.2[6.5] n=18 1 yr 26.3[6.5] n=8 2 yrs 78% (28/36; 6 mo) Heart function Right atrial contraction (transtricuspid A-wave) 29/31 (94%) Left atrial contraction (transmitral A-wave) 22/31 (71%) Biatrial contraction (trans-tricuspid+-mitral A-wave) Cardioversion- electrical Pacemaker 1/39 (2.6%) 5/58 (8.6%) 126 : Patients maintained SR or nodal rhythm despite episodes of atrial tachycardia or supraventricular premature beating. : 1 patient had paroxysmal AF plus atrial flutter. : 1 patient had atrial flutter plus paroxysmal AF. 129 : Kaplan-Meier 130 : Kaplan-Meier 131 : Stated as effective atrial contraction. 127 128 317 20% (3/15; 6 mo) * 10/18 (56%)131 6/6 Appendix D.6.2: Efficacy Perioperative and Postoperative- Cryotherapy Comparative Left atrial CA versus CS Gaita et al. 2000 Level III-2 CA + CS n=32 CS n=18 Time on cardiopulmonary bypass (min) 84[18] 63[21] † Cross clamping time (min) 68[17] 48[20] † 7[4] (range 5-22) 6[2]pns 1/32 (3.1%) 0pns 1 (3.1%) (valvular leak, within 1 wk) 0pns 20/32 at 12 months 16/18 at 12 months Perioperative Outcomes Total operation time (hr) Ablation time (min) Length of ICU stay (days) Length of hospital stay (days) Reoperation Bleeding Other Readmission Postoperative Outcomes Reintervention- Catheter ablation 132 2/31 (6.5%) 0/16 (0%) Continued anticoagulant requirement Continued antiarrhythmic requirement 5/31 (16.1%) 3 mo 5/30 (16.7%) 6 mo 5/29 (17.2%) 9 mo 2/20 (10.0%) 12 mo 2/16 (12.5%) 3 mo 2/16 (12.5%) 6 mo 2/16 (12.5%) 9 mo 2/16 (12.5%) 12 mo 132 : Two patients had episodes of paroxysmal atrial tachycardia. Both patients had an electrophysiologic study with a nonfluoroscopic mapping system (CARTO). In 1 patient there was a pattern of radial activation modified by intervening scar tissue, focal RF was successful. In 1 patient the atrial mapping did not determine the tachycardia mechanism, and RF energy between the right inferior pulmonary vein and the mitral annulus was unsuccessful. The patient had successful electrical cardioversion, sotalol therapy was begun, and was in SR. 318 Appendix D.6.2 continued: Efficacy Perioperative Cardiac- Cryotherapy Comparative Left atrial CA versus CS Gaita et al. 2000 Level III-2 Perioperative Cardiac Outcomes CA + CS n=32 CS n=18 25/32 (78%) early postop 23/31 (74%) hospital discharge 23/31 (74%) 1 month 5/32 (16%) early postop 8/31 (26%) hospital discharge 8/31 (26%) 1 month 2/32 (6%) early postop 4/18 (22%) early postop‡ 2/17 (12%) hospital discharge 4/17 (26%) 1 month 14/18 (78%) early postop‡ 15/17 (88%) hospital discharge 13/17 (74%) 1 month 0/18 early postop pns 12/32 (37%) 12 (38%) temporary(operative) 1/32 (3%) permanent133 (early postoperative) 17/18 (94%)† 6 (33%) temporary (operative) pns 0 permanent pns (early postoperative) Cardiac rhythm SR AF Junctional rhythm Typical atrial flutter Atypical atrial flutter Other Disappearance rate of AF (%) Cardiac function Right atrial contraction Left atrial contraction Cardioversion Pacemaker required 133 : Patient with AF requiring a permanent pacemaker because of symptomatic bradycardia. 319 Appendix D.6.2 continued: Efficacy Postoperative Cardiac- Cryotherapy Comparative Left atrial CA versus CS Gaita et al. 2000 Level III-2 Postoperative Cardiac Outcomes Heart Rhythm SR AF 20/32 at 12 months 16/18 at 12 months 3 months 27/31 (87%) (1/27 RFCA, 5/27 AAr) 6 months 27/30 (90%) (1/27 RFCA, 5/27 AAr) 9 months 26/29 (90%) (1/26 RFCA, 5/26 AAr) 12 months 18/20 (90%) (1/18 RFCA, 2/18 AAr) 3 months 4/31 (13%) 6 months 3/30 (10%) 9 months 3/29 (10%) 12 months 2/20 (10%) 3 months 4/16 (25%) § (2/4 AR) 6 months 4/16 (25%) § (2/4 AR) 9 months 4/16 (25%) § (2/4 AR) 12 months 4/16 (25%) § (2/4 AR) 3 months 12/16 (75%) 6 months 12/16 (75%) 9 months 12/16 (75%) 12 months 12/16 (75%) Junctional rhythm Typical atrial flutter Atypical atrial flutter Other Disappearance rate of AF Heart function Right atrial contraction (transtricuspid A-wave) Left atrial contraction (transmitral A-wave) Biatrial contraction (trans-tricuspid+-mitral A-wave) Cardioversion- electrical Pacemaker 24/26 (92%) 320 Appendix D.6.3: Efficacy Perioperative and Postoperative- Cryotherapy Comparative CA versus Maze-III Ishii et al. 2001 Level III-3 Perioperative Outcomes CA n=32 Maze-III n=13 174.2[36.8] (n=10; Nitta et al. 1999) 165.0[48.1] (n=13; Nitta et al. 1999) pns 0/32 2/13 (15.4%) FU > 12 months FU= 41.2[5.6] months (range 34-52) 20/32 (62.5%)134 10/13 (76.9%) Kim et al. 2001 Level III-3 CA Maze-III n=23 n=18 Total operation time (hr) Time on cardiopulmonary bypass (min) Cross clamping time (min) 185[42] 240[33] ‡ 104[18] 135[29] † 2/23 (8.7%) CA n=23 1/18 (5.6%)pns Maze-III n=18 Ablation time (min) Length of hospital stay (days) Reoperation Bleeding Other Readmission Postoperative Outcomes Reintervention- Catheter ablation Continued anticoagulant requirement Continued antiarrhythmic requirement Perioperative Cardiac Outcomes CA n=32 Maze-III n=13 1/10 (10%) postoperative (Nitta et al. 1999) 1/13 (7.7%) postoperative (Nitta et al. 1999) 13/23 (57%) perioperative 12/18 (67%) perioperative 2/32135 (6.3%) 2/13 (15.4%) (Nitta et al. 1999) 0 1/18 (5.6%) (tachycardia/brady cardia syndrome) Cardiac rhythm SR AF Junctional rhythm Typical atrial flutter Disappearance rate of AF (%) Cardiac function Right atrial contraction Left atrial contraction Cardioversion Pacemaker required 134 135 : In the patients who stopped using anticoagulants 3 patients had valvuloplasty, 3 patients had bioprosthetic valves, and 4 patients had no concurrent surgery. : Both patients had sick sinus syndrome on postoperative electrophysiological study. 321 Appendix D.6.3 continued: Efficacy Perioperative and Postoperative- Cryotherapy Comparative CA versus Maze-III Ishii et al. 2001 Level III-3 FU > 12 months FU= 41.2[5.6] months (range 34-52) Postoperative Cardiac Outcomes Kim et al. 2001 Level III-3 FU=29[4] months FU=47[14] months Heart Rhythm SR 90.6% 92.3% AF Junctional rhythm Typical atrial flutter Atypical atrial flutter 21/23 (91%)136 16/18 (89%)137pns 2/23 (8.7%) 1/18 (5.6%) 1/18 (5.6%) (pacemaker) Other Cumulative Frequency of SR (Kaplan-Meier) Probability of SR maintenance (%) Disappearance rate of AF (%) Heart function Right atrial contraction (transtricuspid A-wave) 21/21 (100%) 138 Left atrial contraction (transmitral A-wave) 90.6% 139 92.3% 16/21 (76%) 16/16 (100%)pns 140 12/16 (75%) pns Biatrial contraction (trans-tricuspid+-mitral A-wave) Right A/E ratio Left A/E ratio 0.64[0.27] 1 month pns 0.87[0.24] 3 months pns 0.71[0.22] 6 months pns 0.58[0.09] 12 months pns 0.37[0.20] 1 monthspns 0.52[0.18] 3 months* 0.44[0.11] 6 months* 0.52[0.15] 12 months* 0.66[0.17] 34-52 months (mean 41 months), n=8 0.25[0.07] 34-52 months (mean 41 months), n=8 Cardioversion Pacemaker 1/18 (5.6%) 136 : 2 patients taking antiarrhythmic medication : 1 patient taking antiarrhythmic medication 138 : Stated that left atrial function was present in all patients. 139 : Stated that left atrial function was present in all patients. 140 : Given as 11/16 in the table. 137 322 Appendix D.6.3 continued: Efficacy Perioperative and Postoperative- Cryotherapy Comparative CA versus Maze-III CA1 n=14 Perioperative Outcomes Kosakai et al. 1995 Level III-2/3 Kosakai Maze n=70 Maze-III n=17 Lee et al. Level III-3 CA Maze-III n=53 n=30 Nishiyama et al. Level III-2/3 (abstract) CA Maze-III n=9 n=11 Total operation time (hr) Time on cardiopulmonary bypass (min) 208[45] Cross clamping time (min) 127[18] 211[40] 248[34] 134[29] 163[34]† vs Kosakai maze 169[30] 195[56] * 132[23] 146[41] Ablation time (min) Length of ICU stay (days) Length of hospital stay (days) Reoperation Bleeding 8/101 (7.9%) for haemostasis or late cardiac tamponade Other Readmission Postoperative Outcomes FU= 1.0-3.1 years FU= 26.8{22.8} months Reintervention- Catheter ablation Continued anticoagulant requirement Warfarin continued in 6/36 (17%) without mechanical valves Continued antiarrhythmic requirement 29/101 (29%)141 141 : Antiarrhythmics used to suppress premature atrial contraction and paroxysmal atrial flutter, disopyramide (n=19), quinidine (n=6) or other medications (n=6). 323 Appendix D.6.3 continued: Efficacy Perioperative and Postoperative Cardiac- Cryotherapy Comparative CA versus Maze-III CA1 n=14 Kosakai et al. 1995 Level III-2/3 Kosakai Maze n=70 Lee et al. Level III-3 CA n=53 Maze-III n=30 57% operating room 83% 3d postop 50% operating room 57% 3d postop* Left atrial contraction 68% 55%pns A-wave velocity (m/s) 45 0 permanent pacing 26* 0 permanent pacing Perioperative Cardiac Outcomes Maze-III n=17 Nishiyama et al. Level III-2/3 (abstract) CA Maze-III n=9 n=11 Cardiac rhythm SR AF Cardiac function Right atrial contraction Pacemaker required 2/14 (14%) 2/70 (3%) Postoperative Cardiac Outcomes Cardiac rhythm FU= 1.0-3.1 years 6 months postoperative SR 12/14 (85.7%) 57/70 (81.4%) 14.17 (82.4%) AF 0 11/70 (15.7%) 3/17 (17.6%) 2/14 (14.3%) 2/70 (2.9%) 0 Junctional rhythm Typical atrial flutter Cardiac function Right atrial contraction (transtricuspid A-wave) 77/88 (88%) Left atrial contraction (transmitral A-wave) 64/88 (73%) 4/11 (36.4%) 0 0 1142 0 0 98%143 78%† 62 49pns Biatrial contraction (trans-tricuspid+-mitral A-wave) A wave peak velocity (cm/s) Cardioversion Pacemaker 142 143 : Patient in regular junctional rhythm without tachycardia or bradycardia. : Stated as patients with A-wave appearance, not stated whether it was right or left atrial. 324 FU= 26.8{22.8} months 6/9 (66.7%) Appendix D.6.4: Efficacy Perioperative and Postoperative- Cryotherapy Internal Comparisons Nakajima et al. 2002 Level III-3 Kosakai Maze CA n=110 n=110 Perioperative Outcomes Schaff et al. 2000 Level III-2/3 Biatrial CA Left atrial CA n=173 n=42 Total operation time (hr) Time on cardiopulmonary bypass (min) 214[47] 186[56] † Cross clamping time (min) 144[37] 134[43]144 * Ablation time (min) Length of ICU stay (days) Length of hospital stay (days) Reoperation Bleeding 11/173 (6.4%) Other Readmission FU= Not stated Postoperative Outcomes Reintervention- Catheter ablation Continued anticoagulant requirement Continued antiarrhythmic requirement 144 : CM took only 20-25 minutes additional cross clamp time versus MV surgery alone. 325 0 Appendix D.6.4 continued: Efficacy Perioperative and Postoperative Cardiac- Cryotherapy Internal Comparisons Nakajima et al. 2002 Level III-3 Kosakai Maze CA n=110 n=110 Perioperative Cardiac Outcomes Schaff et al. 2000 Level III-2/3 Biatrial CA Right atrial CA n=173 n=42 Cardiac rhythm SR AF 95/110 (86.4%) at discharge 66/110 (60%) perioperative 15/110 (14%) at discharge145 94/110 (85.5%) at dischargepns 59/110 (54%) perioperativepns 16/110 (15%) at dischargepns Transient AF: 38% of patients Junctional rhythm Typical atrial flutter Other 3/18146 (16.7%) Cardiac function Right atrial contraction Left atrial contraction Cardioversion- electrical Pacemaker required Postoperative Cardiac Outcomes 7/179 (3.9%)147 FU=64.1[27.4] months FU=18.8[10.8] months Heart Rhythm SR 84 (76%) AF 26 (24%) 92 (84%)pns ( 2 with pacemaker) 18 (16%) (1 with pacemaker) Junctional rhythm Typical atrial flutter Disappearance rate of AF (%) 92.6% (n=88) 1 yr148 90.4% (n=73) 3 yrs 86.7% (n=39) 5 yrs 97.7% (n=62) 1 yr 97.7% (n=4) 3 yrs 7/110 (6.4%) 3/110 (2.7%) Cardioversion- electrical Pacemaker 145 : Stated as either AF/ atrial flutter : Early postoperative atrial arrhythmias seen in first patients in the series, managed with medication. 147 : 7 pacemakers were used in a larger series including 6 extra patients. 148 : Analysed using Kaplan-Meier method 146 326 0 Appendix D.6.4 continued: Efficacy Perioperative and Postoperative- Cryotherapy Internal Comparisons Takami et al. 1999 Level III-3 Biatrial CA Left atrial CA n=30 n=20 Perioperative Outcomes Yoshihara et al. 2000 Level III-3 (abstract) KM-RAA KM+RAA n=20 n=22 Total operation time (hr) 440[80.2] (n=21)149 369[61.1] (n=15)150 † Time on cardiopulmonary bypass (min) 248.2[59.0] (n=21) 200.1[25.7] (n=15) * 201.5[49.9] 196.2[28.5]pns Cross clamping time (min) 152.2[28.2] (n=21) 134.9[15.8] (n=15) † 139.6[41.3] 128.9[23.0]pns 34.1[11.3] months (range 15-51 months) 17.8[3.8] months (range 8-23 months) 15/25 (60%) patients in SR 10/16 (62.5%) patients in SR Ablation time (min) Length of ICU stay (days) Length of hospital stay (days) Reoperation Bleeding Other Readmission Postoperative Outcomes Reintervention- Catheter ablation Continued anticoagulant requirement Continued antiarrhythmic requirement 149 150 : Patients who had MV surgery ± tricuspid annuloplasty : Patients who had MV surgery ± tricuspid annuloplasty 327 Kosakai 2000 Level III-2/3 Kosakai Maze Maze-III n=1119 n=835 Appendix D.6.4 continued: Efficacy Perioperative and Postoperative Cardiac- Cryotherapy Internal Comparisons Takami et al. 1999 Level III-3 Biatrial CA Left atrial CA n=30 n=20 Perioperative Cardiac Outcomes Yoshihara et al. 2000 Level III-3 (abstract) Kosakai Maze-RAA Kosakai Maze+RAA n=22 n=20 Kosakai 2000 Level III-2/3 Kosakai Maze n=1119 Maze-III n=835 Hospital discharge Cardiac rhythm SR 18/30 (60%) 13/20 (70%) AF 5/30 (17%) 4/20 (20%) Junctional rhythm 7/30 (23%) 2/20 (10%) 18/22 (82%) 1 month 16/20 (80%) pns 1 month Typical atrial flutter Disappearance rate of AF (%) Pacemaker required Postoperative Cardiac Outcomes 83% 80% 2/30 (6.7%) 1/20 (5%) FU=34.1[11.3] months (range 15-51) FU=17.8[3.8] months (range 8-23) FU = not stated Heart Rhythm SR 25/30 (83.3%) 16/20 (80%) AF 3/30 (10%) 3/20 (15%) 0 0 2 (pacemaker) 1 (pacemaker) Junctional rhythm 151 Lone: 29/34 (85.3%) MVS: 707/956 (74.0%) CG: 65/75 (86.7%) Other: 43/54 (79.6%) Typical atrial flutter Other Atrial function Right atrial contraction (transtricuspid A-wave) Left atrial contraction (transmitral A-wave) Cardioversion- electrical Pacemaker 151 : Note that in the publication the numbers are different between the text and the figures. The numbers in the text have been used for all results. 328 Lone: 8/13 (61.5%) MVS: 558/735 (75.9%) CG: 51/56 (91.1%) Other: 23/31 (74.2%) Appendix D.6.5: Efficacy Perioperative and Postoperative- Cryotherapy Biatrial Case Series Perioperative Outcomes Total operation time (hr) Ad et al. 2003 Level IV (abstract) Ad et al. 2003 Level IV (abstract) Arai et al. 1999 Level IV Fukada et al. 1998 Level IV n=51 n=50 n=30 n=29 + 65.9 mins (vs cases without a maze) +56.9 mins (vs cases without a maze) 209[34] (range 139-270) 149.5[32.2]152 (range 88-201) Time on cardiopulmonary bypass (min) Cross clamping time (min) Ablation time (min) Length of ICU stay (days) Length of hospital stay (days) Reoperation Bleeding Other Readmission Postoperative Outcomes FU= 8.3{3.1} months FU= 12.3 months Range 1-25 FU= 19{5} months Reintervention- Catheter ablation Continued anticoagulant requirement Continued antiarrhythmic requirement 152 17% > 3months (6 patients) : Time for MV operations with/without other valve operations from 1/90-12/91 in the same institution was 124.3[43.3] mins. 329 Appendix D.6.5 continued: Efficacy Perioperative and Postoperative Cardiac- Cryotherapy Biatrial Case Series Ad et al. 2003 Level IV (abstract) Ad et al. 2003 Level IV (abstract) Arai et al. 1999 Level IV Fukada et al. 1998 Level IV n=51 n=50 n=30 n=29 3/51 (6%)154 4/30 (13.3%)155 6/29 (20.7%)156 FU= 19{5} months FU= 12.3 months (1-25) Perioperative Cardiac Outcomes Cardiac rhythm SR 48/48 hospital discharge AF Other 17/51 (33.3%)153 Right atrial contraction 10/10 within 1 wk postoperative Cardiac function Left atrial contraction Pacemaker required Postoperative Cardiac Outcomes FU= 8.3{3.1} months Cardiac rhythm SR AF 158 3/48 (6.3%) Junctional rhythm Typical atrial flutter Disappearance rate of AF (%) Cardiac function Right atrial contraction (transtricuspid A-wave) Left atrial contraction (transmitral A-wave) 21/30 (72.4%) 17/29 (58.6%)157 8/30 (27.6%) 10/29 (34.5%)159 2/29 (6.9%) 98% 8/10 6 months (80%) Rheumatic: 0.25[0.06] (n=10) Non-rheumatic: 0.67[0.08] (n=7) Rheumatic: 0.25[0.06]* (n=10)160 Non-rheumatic: 0.42[0.15] (n=7) 161 6/29 (20.7%) Right A/E ratio Left A/E ratio Pacemaker 153 : Perioperative AF/ atrial flutter. : New pacemakers. : In 2 patients with bradycardia +AF, in 1 patient with bradycardia + junctional rhythm, and in 1 patient with complete AV block. 156 : 1 patient had a pacemaker before the surgery; 5 patients required a pacemaker due to bradycardia with AF or junctional rhythm. Patients did not recover SR. 157 : In patients with SR 10/17 had rheumatic heart disease and 7/17 had non-rheumatic heart disease. 158 : Persistent AF recurred in 3 patients, well controlled by antiarrhythmic drugs. 159 : All patients had rheumatic heart disease. 160 : There were 7/10 patients with rheumatic disease who had undetectable left atrial contraction. 161 : 1 patient had excellent left atrial contraction with an A/E of 0.69. 154 155 330 Appendix D.6.5 continued: Efficacy Perioperative and Postoperative- Cryotherapy Biatrial Case Series Perioperative Outcomes Total operation time (hr) Time on cardiopulmonary bypass (min) Izumoto et al. 2000 Level IV Morishita et al. 2000 Level IV Shimizu et al. 1997 Level IV Yuda et al. 2001 Level IV n=104 n=12 n=6 n=94 MV: 177.2[70.1] (n=87)162 MVP: 170.8[38.7] MVR: 188.8[105.5] MV: 121.7[30.8] (n=87)163 MVP: 122.7[30.8] MVR: 119.8[31.2] Cross clamping time (min) 149 Ablation time (min) MV: 5.3[7.9] (n=87)164 MVP: 3.4[1.9] MVR: 8.7[12.4] Length of ICU stay (days) Length of hospital stay (days) Reoperation Bleeding 7/87165 (8.0%) Other 2/104166 (1.9%) 0167 1/94 (1.1%) (congestive heart failure) Readmission Postoperative Outcomes Reintervention- Catheter ablation Continued anticoagulant requirement Continued antiarrhythmic requirement 1/6 (small dose cibenzoline) 162 : Izumoto 1998 : Izumoto 1998 164 : Izumoto 1998 165 : Izumoto 1998 Re-exploration for bleeding or tamponade. 166 : In 1 patient deterioration of mitral regurgitation required redo MVR, and in 1 patient a new stenotic lesion in the circumflex coronary artery and recurrence of mitral regurgitation required CABG and redo MV surgery 1 month postoperative. Note that in Izumoto et al. (1998) there were 3/87 patients with redo operations. 167 : No patients required repeat valve repair or replacement. 163 331 Appendix D.6.5 continued: Efficacy Perioperative Cardiac- Cryotherapy Biatrial Case Series Perioperative Cardiac Outcomes Cardiac rhythm SR AF Izumoto et al. 2000 Level IV Morishita et al. 2000 Level IV Shimizu et al. 1997 Level IV Yuda et al. 2001 Level IV n=104 n=12 n=6 n=94 Immediately postop 73/100 (73%) Izumoto 1998 (n=87) MVP: 35/56 (63%) MVR: 23/31 (74%) 21/100 (21%) 17/87 (Izumoto 1998) 11/12 6/6 Junctional rhythm Typical atrial flutter Atypical atrial flutter Other 6/100 (6%) (sick sinus syndrome) 7/87 (Izumoto 1998) Disappearance rate of AF (%) Cardiac function Right atrial contraction Left atrial contraction Cardioversion Pacemaker required 6/104 (5.8%) (sick sinus syndrome) 5/87 (sick sinus syndrome; Izumoto 1998 7/94 (7.4%) (sick sinus syndrome) 332 Appendix D.6.5 continued: Efficacy Postoperative Cardiac- Cryotherapy Biatrial Case Series Izumoto et al. 2000 Level IV Postoperative Cardiac Outcomes Morishita et al. 2000 Level IV Shimizu et al. 1997 Level IV 44.6[1.1] months 4-32 months SR 52/72 (73%) 6/6168 AF 16/72 (22%) Yuda et al. 2001 Level IV Early: 3.1[3.3] months Late: 2.2[0.9] yrs Yuda 1998 12 months Heart Rhythm Junctional rhythm Typical atrial flutter Other Probability of SR maintenance (%) 75/94 (80%)169 Early 66/94 (70%) Late 19/94 (20%) Early 28/94 (30%) Late 4/72 (6%)170 1 yr: 88.8%[3.7%]171 5 yrs: 64.8%[7.5%]% MVP: 1 yr: 88.6[5.4] (n=87)172 5 yrs: 67.6[9.1] MVR: 1 yr: 95.7[4.3] 5 yrs: 65.0[11.1] Disappearance rate of AF (%) Heart function Right atrial contraction (transtricuspid A-wave) 47/94 (50%) Early173 36/94 (38%) Latepns GLA: 4/19 (21%)174 nonGLA: 21/32 (66%) Left atrial contraction (transmitral A-wave) Biatrial contraction(trans-tricuspid+-mitral A-wave) 44[18] Early (n=35)175 43[13] Latepns GLA: 55[33] nonGLA: 44[14] A wave peak velocity (cm/s) Transtricuspid atrial filling fraction (%) 17[6] Early GLA: 17[5] Transmitral atrial filling fraction (%) 17[5] Late176pns nonGLA: 17[4] 1177 Cardioversion Pacemaker 168 : In 1 patient paroxysmal atrial tachycardia occurred 3 months postoperative, this was controlled with an antiarrhythmic (cibenzoline), in this patient 8 different drugs including cibenzoline were ineffective before surgery. 169 : Defined as patients with a regular rhythm. 170 : Sick sinus syndrome. 171 : Defined as the rate continuously maintaining SR as the baseline rhythm with an absence of AF of more than 1 month duration. Patient regarded as maintaining SR regardless of antiarrhythmic medication or electrical cardioversion. 172 Izumoto 2001 173 : Defined as a transmitral wave ≥ 10 cm/s. 174 : Yuda 1998 Patients divided into those with a giant left atrium (GLA; n=19) and those without a GLA (n=32). 175 : n=35 patients with atrial contraction in both the early and late stages. 176 : Lower than the normal range. 177 : Patient had successful cardioversion at 28 months postoperative. 333 Appendix D.6.6: Efficacy Perioperative and Postoperative- Cryotherapy Left atrial Case Series Perioperative Outcomes Total operation time (hr) Hoffmeister et al. 2003 Level IV (abstract) Imai et al. 2001 Level IV n=19 Time on cardiopulmonary bypass (min) Cross clamping time (min) Kondo et al. 2003 Level IV Manasse et al. 2003 Level IV n=32 n=31 n=95 191[33] (range 120-268) 124[27] (range 74-172) 279[86] (range 188-450) 146[39] (range 94-257) 109[36] (range 60-220) 30.6[5.4] (range 20-37) 85.3 (range 46-145) 69.0 (range 41-126) 37.5[18.4] (range 21-74)178 6.9 (range 5-49) Ablation time (min) 15-20 Length of ICU stay (days) Length of hospital stay (days) Reoperation Bleeding 2/95 (2.1%)179 0 Other 3/95 (3.2%)180 Readmission Postoperative Outcomes FU= 1-48 months Reintervention- Catheter ablation FU= 13-66 months 36.9[14.1] months 181 2/32 FU= 12-60 months 37.7[15.0] months 2/95 (2.9%)182 (6.3%) Re-intervention- Other Continued anticoagulant requirement Continued antiarrhythmic requirement 2/14(14.3%) in SR FU= 36.4 months 5/95 (5.3%)183 15/70 (21.4%) patients in SR184 19/19 (MVR±CABG) 0/5 (valve repair) Digitalis: 7/24 (29%) in SR Class I/IV: 13/24 (54%) in SR 19/70 (27.1%) patients in SR 178 : n=29, excludes fatalities. : Bleeding in-hospital and not related to the ablation procedure. 180 : In 2 patients on the 1st and 6th postoperative days for MVP failure, and in 1 patient on the 6th postoperative day for peri-valvular leak in a redo MVR. 181 : Tricuspid valve-coronary sinus isthmus ablation (n=1) and modification of the atrioventricular node (n=1). 182 : Patients submitted to a non-flurooscopic navigation system (CARTO), with RF ablation performed due to left atrial flutter with a gap in the surgical ablation line, successful in both patients. 183 : Reoperation at 2-3 month follow-up, due to MVP failure in 3 patients and peri-valvular leak in MVR in 2 patients. 184 : Oral anticoagulant used in these patients although they did not have a mechanical prosthesis, in 2 patients that was related to pre-operative systemic embolisation episodes. 179 334 Appendix D.6.6 continued: Efficacy Perioperative Cardiac- Cryotherapy Left atrial Case Series Perioperative Cardiac Outcomes Hoffmeister et al. 2003 Level IV (abstract) Imai et al. 2001 Level IV Kondo et al. Level IV Manasse et al. 2003 Level IV n=19 n=32 n=31 n=95 26/29 (90%)185 67/95 (70.5%) at discharge Cardiac rhythm SR AF 19/19 (immediate postop) 5/32 (15.6%) (after surgery) 18/31186 (58.1%) Junctional rhythm Typical atrial flutter Atypical atrial flutter Other Disappearance rate of AF (%) At discharge Cardiac function Right atrial contraction 21/21 (100%) Left atrial contraction Cardioversion- electrical 18/21 (85.7%) 5/32 (15.6%) (patients in SR) 18/31187 (58.1%) Cardioversion- electrical or pharmacological Pacemaker required 5/32189 (15.6%) (patients in SR) 5/31190 (16.1%) 185 42/95 (44.2%) inhospital188 4/95 (4.2%)191 In-hospital : Patients in SR or free from AF. The number in SR is likely to be n=21, the number of patients in SR who had atrial function measured. : AF recurring at 2-15 d postoperative. SR was restored in 15/18 with pharmacological or electrical cardioversion. 187 : Either electrical or pharmacological cardioversion was used in the early postoperative period in patients with recurrent AF. 188 : Note that cardioversion was used to indicate both electrical and pharmacological cardioversion. 189 : Patients required pacemakers because of sinus bradycardia (<50 beats/min) with/without sinus arrest. In 3/5 patients bradycardia was not symptomatic. Includes 1 patient with sinus node modification. 190 : Pacemaker required due to sinus bradycardia (n=3) or sinus node dysfunction (n=2). 191 : 1/22 patients with the first ablation pattern; 1/32 patients with the second ablation pattern, and 2/41 patients with the third ablation pattern. 186 335 Appendix D.6.6 continued: Efficacy Postoperative Cardiac- Cryotherapy Left atrial Case Series Hoffmeister et al. 2003 Level IV (abstract) Postoperative Cardiac Outcomes FU= 1-48 months Imai et al. 2001 Level IV FU= 13-66 months 36.9[14.1] months Kondo et al. Level IV FU= 12-60 months 37.7[15.0] months 24/32 (75%)192 21/29 (72.4%) Manasse et al. 2003 FU= 36.4 months Cardiac rhythm SR 14/19 (74%) 12/15 (valve surgery) 2/4 (CABG) 70/86 (81.4%) 6/29 (20.7%)193 AF Junctional rhythm Typical atrial flutter Atypical atrial flutter 23/29194 Other Cumulative Frequency of SR (Kaplan-Meier) Probability of SR maintenance (%) Proportion of patients without recurrence of AF (%) 3 yrs: 74.5% 95%CI: 59.2-89.8 6 months 1st ablation line: 90.4% nd 2 ablation line: 90.5% 3rd ablation line 97.4% 12 months 1st ablation line: 72.7% 2nd ablation line: 90.5% 3rd ablation line 92.0% Disappearance rate of AF (%) Cardiac function Right atrial contraction (transtricuspid A-wave) 14/14 (100%)195 Left atrial contraction (transmitral A-wave) 12/20196 (60%) >80% (n=45; 3-9 mo)197 Biatrial contraction (trans-tricuspid+-mitral A-wave) A wave peak velocity (cm/s) Right A/E ratio <0.3 in 1/14 Left A/E ratio <0.3 in 7/12 9/86 (10.5%) patients in SR successful 2/95 (2.1%)198 Cardioversion- electrical or pharmacological Pacemaker 192 : Reported as free of AF. In 5/24 atrial flutter or atrial tachycardia occurred and cardioversion was required, in 2 patients this was unsuccessful and catheter ablation was performed. : In 2 patients AF recurred at 2 months and 28 months postoperative. 194 : Patients free of AF. 195 : Doppler echocardiography performed within 6 months of the end of follow-up. 196 : Detectable at transmitral flow in 3/5 patients with pacemakers. 197 : Biatrial activity defined as presence of valid transmitral and/or tricuspid waves (>0.3m/s) on transthoracic echocardiography. 198 : 1/32 patients with the second ablation line, and 1/41 patients with the third ablation line. 193 336 Appendix D.6.6 continued: Efficacy Perioperative and Postoperative- Cryotherapy Left atrial Case Series Perioperative Outcomes Naito et al. 2001 Level IV (abstract) Sueda et al. 2001 Level IV Usui et al. 2002 Level IV n=30 n=12 n=41 Yamauchi et al. 2002 Level IV n=40 n=11 focal ablation n=29 linear ablation Total operation time (hr) Time on cardiopulmonary bypass (min) 168[35] (range 115-237] 108[30] (range 77-163) Cross clamping time (min) Ablation time (min) Length of ICU stay (days) Length of hospital stay (days) Reoperation Bleeding Other Readmission Postoperative Outcomes Reintervention- Catheter ablation FU = 16.5{6.7} months FU= 5-14 months 4/41199 (9.8%) Continued anticoagulant requirement Continued antiarrhythmic requirement 3/12200 (25%) 199 : In 1st patient with two kinds of atrial flutter, a counterclockwise common atrial flutter through the right atrial isthmus and a left atrial tachycardia. RF ablation (11 times, total 12,407J) used on right atrial isthmus 11 months postoperative was successful; 2nd patient who had intraoperative right atrial ablation, with counterclockwise common atrial flutter through the right atrial isthmus, RF ablation of right atrial isthmus (8 times, total 11,788J) successful; 3rd patient with paroxysmal atrial flutter, with counterclockwise and clockwise common atrial flutter, and an incisional atrial flutter around the right atriotomy. Complete linear ablation created at the right atrial isthmus (30 times, total 32,050J), and another linear ablation between the right atriotomy and the inferior vena cava (15 times, total 32,050J), successful; 4th patient who had intraoperative right ablation, an incisional atrial flutter around the right atriotomy. Linera ablation created between the right atriotomy and the inferior vena cava (22 times, total 30,152J). The incisional atrial flutter was cured, but a counterclockwise common atrial flutter through the right atrial isthmus remained. 200 : Patients given digitalis and disopyramide early postoperatively for recurrence of AF, treatment not successful. 337 Appendix D.6.6 continued: Efficacy Perioperative and Postoperative Cardiac- Cryotherapy Left atrial Case Series Perioperative Cardiac Outcomes Naito et al. 2001 Level IV (abstract) Sueda et al. 2001 Level IV Usui et al. 2002 Level IV n=30 n=12 n=41 30/30 (immediately postoperative) AF n=40 After surgery Focal: 9/11 Linear: 22/29 Linear: 6/29 Cardiac rhythm SR Yamauchi et al. 2002 Level IV 12/12 (immediately postoperative) 9/12 (at discharge)201 3/12202 0203 Typical atrial flutter Focal: 2/11 (pacemaker) Linear: 1/29 (pacemaker) Other Cardiac function Right atrial contraction Left atrial contraction 3/12 (25%)204 1/12 (8.3%) (sinus bradycardia) Cardioversion Pacemaker required Postoperative Cardiac Outcomes FU = 16.5{6.7} months FU = 5-14 months 24/30207 (80%) 10/12208 (83.3%) Focal: 2/11205 (18.2%) Linear: 1/29 (3.4%) 206 Cardiac rhythm SR AF Junctional rhythm Typical atrial flutter Cardiac function Right atrial contraction (transtricuspid A-wave) Left atrial contraction (transmitral A-wave) Cardioversion Pacemaker 74% 4/41209 9/10 (90%) 7/10 (70%) 1/41210 (2.4%) 201 : Paroxysmal AF or tachycardia occurred in 5/12 patients but disappeared following antiarrhythmic drugs. : recurrence within 3 days postoperatively. 203 : No evidence of atrial flutter originating in the right atrium. 204 : Cardioversion was unsuccessful. 205 : Patients needed pacemakers at 1 month postoperatively due to sick sinus syndrome, bot had very low amplitude of atrial electrograms. 206 : Sick sinus syndrome. 207 : With administration of class Ia drugs. 208 : 1 patient with AF at discharge spontaneously converted to SR at 3 months postoperative. 209 : All four patients had RF catheter ablation. 210 : DDD pacemaker at 2-4 months postoperative for sick sinus syndrome with brady- and tachycardia. 202 338 Appendix D.7.1: Efficacy Perioperative and Postoperative- Radiofrequency Biatrial RFA versus CS Khargi et al. 2001 Level II RFA+ MVS MVS n=15 n=15 270 190* (range 232-323) (range 128-314) 188 127* (range 165-230) (range 60-197) 103 84* (range 86-134) (range 38-112) Perioperative Outcomes Total operation time (hr) Time on cardiopulmonary bypass (min) Cross clamping time (min) Ablation time (min) Length of ICU stay (days) Length of hospital stay (days) RFA II/II n=13 Chen et al. 2001 Level III-2 RFA IV n=48 262.5[59.9] 272.7[54.2] 211 156.4[50.4] ‡ 191.8[52.8] 200.2[46.3] 212 105.6[44.3] ‡ 54.8[12.2] Total 32.0[6.0] Left213 7.2[10.4]pns 59.0[14.7] Total 35.6[10.5] Left 6.9[13.5]pns 5.7[6.6] 20.7[13.3]pns 18.8[19.2]pns 17.3[14.7] FU= 43 months (37-47) FU= 16 months (3-32) CS n=58 Reoperation Bleeding Other 1/15 (6.7%) (sternal instability) 1/15 (6.7%) (sternal instability) FU= 22[7] months Median 21 FU= 21[6] months Median 20 Readmission Postoperative Outcomes Reintervention- Catheter ablation Continued anticoagulant requirement 69% (40/58) patients with SR and no mechanical valves Continued antiarrhythmic requirement 211 : versus RFII/III and RFIV : versus RFII/III and RFIV 213 : The left atrial ablation time represents the additional ischaemic time for the RF procedure. 212 339 94% (51/54) Appendix D.7.1 continued: Efficacy Perioperative Cardiac- Radiofrequency Biatrial RFA versus CS Khargi et al. 2001 Level II RFA+ MVS MVS n=15 n=15 Perioperative Cardiac Outcomes RFA II/II n=13 Chen et al. 2001 Level III-2 RFA IV n=48 CS n=58 Cardiac rhythm SR AF Junctional rhythm 8/15 (53.3%) postop day 1 7/15 (46.7%) postop day 1 4/15 (26.7%) postop day 1 11/15 (73.3%) postop day 1 0/15 (0%) postop day 1216 0/15 (0%) postop day 1 7/13 (54%) within 2 wks 2/13 (15%) within 2 wks214 4/13 (31%; transient) within 2 wks 34/48 (71%) within 2 wks 5/48 (10%) within 2 wks215 7/48 (15%) within 2 wks217 1/48 (2%) within 2 wks218 Typical atrial flutter Atypical atrial flutter Other Disappearance rate of AF (%) Cardiac function Right atrial contraction Left atrial contraction 5/8 (62.5%) postop day 12 patients in SR 4/4 (100%) postop day 12 patients in SR 1/15 (6.7%) (DDD) (sinus bradycardia) 1/15 (6.7%) (VVI) bradycardia Cardioversion Pacemaker required 0 0 2/48 (4%)219 214 : Paroxysmal in 1 patient and persistent AF in 1 patient. : Paroxysmal AF in 2 patients and persistent AF in 3 patients. 216 : Number derived from extrapolation. 217 : Transient junctional rhythm in 5 patients, junctional rhythm and paroxysmal atrial tachycardia in 1 patient and persistent junctional rhythm in 1 patient. 218 : Persistent atrial flutter, type not specified. 219 : Two patients developed sick sinus syndrome and require permanent pacemakers. Electrophysiologic studies showed an absence of atrial electric potential and high stimulation threshold of both atria, suggesting irreversible myocardial damage present before the surgery. 215 340 Appendix D.7.1 continued: Efficacy Postoperative Cardiac- Radiofrequency Biatrial RFA versus CS Khargi et al. 2001 Level II FU= 22[7] months FU= 21[6] months Median 21 Median 20 Postoperative Cardiac Outcomes FU= 43 months (range 37-47) Chen et al. 2001 Level III-2 FU= 16 months (range 3-32) 8/11 (73%) within 3 mo 8/11 (73%) 37-47 mo§ 38/47 (81%) within 3 mo 41/47 (87%) 3-32 mo222§ 6/54 (11%) within 3 mo 6/54 (11%) 35-109 mo 2/11 (18%) 37-47 mo223 3/42 (7%) 3-32 mo pns 48/54 (89%) 35-109 mo‡ FU = 35-109 months Cardiac rhythm SR 9/13 (69%) 3 mo 10/12 (83%) 6 mo 9/11 (82%) 9 mo 9/11220 (82%) 12 mo AF 4/13 (31%) 3 mo 2/12 (17%) 6 mo 2/11 (18%) 9 mo 2/11 (18%) 12 mo 4/15 (27%) 3 mo 4/15 (27%) 6 mo 5/15 (33%) 9 mo 3/14 221(21%) 12 mo 11/15 (73%) 3 mo 11/15 (73%) 6 mo 10/15 (67%) 9 mo 11/14 (79%) 12 mo Junctional rhythm 1/42 (2%) 3-32 mo 1/11 (9%; persistent, type not specified) 37-47 mo Typical atrial flutter 1/42 (2%) 3-32 mo224 1/42 (2%) 3-32 mo225 Other Cumulative Frequency of SR (Kaplan-Meier) 0.7333 6 months 0.800 12 months 0.267 6 months * 0.267 12 months * 10/10 6 months 9/9 12 months 7/10 (70%) 6 months 6/9 (67%) 12 months 10/10 6 months 9/9 12 months 4/4 6 months 3/3 12 months 4/4 6 months 3/3 12 months 4/4 6 months 3/3 12 months Probability of SR maintenance (%) Disappearance rate of AF Cardiac function Right atrial contraction (transtricuspid A-wave) Left atrial contraction (transmitral A-wave) Biatrial contraction (trans-tricuspid+-mitral A-wave) 226 229 8/11 (73%; mean 43 mo)227 6/11 (55%; mean 43 mo)230 228 38/47 (81%; mean 16 mo) 231 35/47 (74%; mean 16 mo) 6/54 (11%; mean 61 mo) † vs both 6/54 (11%; mean 61 mo) † vs both A wave peak velocity (cm/s) Transtricuspid atrial filling fraction (%) 38.0[6.2] 39.1[9.8] 39.5[6.3] 3 mo pns Transmitral atrial filling fraction (%) 20.5[8.0] 25.0[11.6] 33.0[8.3] 3 mo pns 220 : In 2 patients the Holter monitor showed short runs of atrial tachycardia in <10% of the time interval. : In 1 patient the Holter monitor showed short runs of atrial tachycardia in <10% of the time interval. : Number of patients in SR determined by extrapolation. 223 : 1 paroxysmal AF and 1 persistent AF. 224 Persistent atrial flutter, type not specified. 225 Paroxysmal atrial tachycardia and sick sinus syndrome 226 : versus CS group 227 : Transtricuspid A waves of ≥15 cm/s considered indicative of effective restoration of atrial transport function. 228 : versus CS group 229 : versus CS group 230 : Transmitral A waves of ≥25 cm/s were considered indicative of effective restoration of atrial transport function. 231 : versus CS group 221 222 341 Appendix D.7.1 continued: Efficacy Perioperative and Postoperative- Radiofrequency Biatrial RFA versus CS Riying et al. 1998 III-3 Biatrial RFA MVS n=25 n=25 Patwardhan et al. 1997 Perioperative Outcomes Biatrial RFA n=84 CS n=64 96.1[24] 88.7[36.3]pns 52.8[15.3] 9.36[3.29]Left atrial232 14.86[5.37] Right atrial233 54.9[21.7] pns 6/84 (7.1%) cause not stated 4/64 (6.3%) cause not stated 23.6[12.5] months (12-53 months) 6 months Total operation time (hr) Time on cardiopulmonary bypass (min) Cross clamping time (min) Ablation time (min) 10-15 Length of ICU stay (days) Length of hospital stay (days) Reoperation Bleeding Other Readmission Postoperative Outcomes Reintervention- Catheter ablation Continued anticoagulant requirement Continued antiarrhythmic requirement 232 233 : The left atrial procedure used extra mins of cardioplegic arrest time. : The right atrial procedure used extra mins of reperfusion time. 342 Appendix D.7.1 continued: Efficacy Perioperative and Postoperative Cardiac- Radiofrequency Biatrial RFA versus CS Riying et al. 1998 III-3 Patwardhan et al. 1997 Biatrial RFA n=84 Perioperative Cardiac Outcomes CS n=64 Biatrial RFA n=25 MVS n=25 5/25 (20%) transient, in-hospital 25/25 (100%) hospital discharge Cardiac rhythm SR 60/70 (85.7%) 22/25 (88%) 234 AF 9/70 (12.9%) 3/25 (12%) within 22 days Junctional rhythm Typical atrial flutter 1/70 (1.4%) Pacemaker required 0 23.6[12.5] months (12-53 months) 6 months SR 55/70 (78.6%) 3/53 (5.7%) AF 14/70 (20.0%) 50/53 (94.3%) Postoperative Cardiac Outcomes Cardiac rhythm Junctional rhythm Typical atrial flutter Other Freedom from AF (%) Cardiac function Right atrial contraction (transtricuspid A-wave) Left atrial contraction (transmitral A-wave) Biatrial contraction (trans-tricuspid+-mitral A-wave) Cardioversion Pacemaker 234 1/70 (1.4%) 0 sick sinus syndrome 1 year: 84.2% (95%CI: 74.4-90.7%) 3 years: 78.7% (95%CI: 61.8-89.4%) 4 years: 78.7% (95%CI: 51.2-92.9%) 0 sick sinus syndrome 55/55 (100%) 44/55 (80%) 0 0 : Within 22 days; most patients had atrial flutter before recovering SR. 343 Appendix D.7.2: Efficacy Perioperative and Postoperative and Cardiac- Radiofrequency RFA versus Cardioversion Thomas et al. 2003 Level IIIRFA n=21 Perioperative Outcomes Cardioversion n=33 Length of ICU stay (days) Length of hospital stay (days) Reoperation FU= 15[18] months Postoperative Outcomes Reintervention- Catheter ablation Continued anticoagulant requirement Continued antiarrhythmic requirement Perioperative Cardiac Outcomes 2/21 (9.5%) (sotalol = 1; amiodarone = 1) RFA +/- CS n=21 21/33 (63.6%) (sotalol = 6; amiodarone = 15) Cv n=33 21/21 (pre-selected with SR) 33/33 (pre-selected with SR) 600[300] 700[200] Cardiac rhythm SR AF Postoperative Cardiac Outcomes Heart Rhythm SR AF Cardiac function A wave peak velocity (cm/s) Cardioversion Pacemaker 344 Appendix D.7.3: Efficacy Perioperative and Postoperative- Radiofrequency Left atrial RFA versus CS Guang et al. 2002 Level III-2 Perioperative Outcomes RFA n=96 MVS n=87 137.6[10.8] 90.9[7.7] † 56.9[6.2] 32.7[3.5] † Mantovan et al. 2003 Level III-2 RFA CS n=103 n=27 Total operation time (hr) Time on cardiopulmonary bypass (min) Cross clamping time (min) 4.9[0.9] 4.4[1.7] 148[50] 117[30] * 11.3[3.5] 10.3[2.7] Ablation time (min) Length of ICU stay (days) Length of hospital stay (days) Reoperation Bleeding 2/96 (2%) 1/87 (1%) Other 1/103235 (1.0%) Readmission Postoperative Outcomes FU= 12.5[5] months (4-24) Reintervention- Catheter ablation 2236 Continued anticoagulant requirement 60% 64% amiodarone 53% Continued antiarrhythmic requirement 235 93%† 26%† amiodarone 22%† : Patient had a left atrial thrombus soon after surgery which caused mitral valve malfunction requiring reoperation. : In 1 patient transcatheter ablation was performed for an automatic focal incessant atrial tachycardia arising from the coronary sinus, and in 1 patient RF ablation of common atrial flutter was performed. Both were successful. 236 345 Appendix D.7.3 continued: Efficacy Perioperative and Postoperative Cardiac- Radiofrequency Left atrial RFA versus CS Guang et al. 2002 Level III-2 Perioperative Cardiac Outcomes Mantovan et al. 2003 Level III-2 RFA n=96 MVS n=87 RFA n=103 CS n=27 76/96 (79%) hospital discharge 11/96 (12%) hospital discharge 9/96 (9%) hospital discharge 29/87 (33%) hospital †discharge 49/87 (56%)238 hospital discharge† 7/87 (8%) hospital discharge 2 (2%) hospital discharge type not specified §81/103 (79%) after surgery 65/103 (63%) hospital discharge237 7/27 (26%) after surgery 5/27 (18%) hospital discharge Cardiac rhythm SR AF Junctional rhythm Typical atrial flutter 0 hospital discharge Cardioversion 3/103 in-hospital (2.9%) 1/103 (1.0%) (complete AV block) FU= 12.5[5] months (4-24) 3/96 (3.1%) hospital discharge FU = 3 years Pacemaker required Postoperative Cardiac Outcomes Cardiac rhythm SR 74/96 (77%) 3 yrs 22/87 (25%) 3 yrs† AF 22/96 (23%) 3 yrs 65/87 (75%) 3 yrs† 83/102 (81%) during follow-up 63/81 (78%) permanent AF 20/21 (95%) paroxysmal/persistent AF 54/61 (9%) at 1 yr 19/102 (19%) during follow-up 7/61 (11%) at 1 yr 3/27 (11%)† Junctional rhythm Typical atrial flutter Disappearance rate of AF (%) Cardiac function Right atrial contraction (transtricuspid A-wave) Left atrial contraction (transmitral A-wave) Biatrial contraction (trans-tricuspid+-mitral Awave) Cardioversion Pacemaker 0 3 yrs 77% at 3 yrs 1/87 (1%) 3 yrs type not specified 25% at 3 yrs† 0 at 3 yrs 237 : Note: 49/82 (60%) permanent AF; 16/21 (76%) paroxysmal/persistent AF : Patients had a pacemaker with AF. 239 : Atrial tachycardia or atrial flutter. 3/11 in permanent atrial tachycardia or atrial flutter. 238 346 11/102 (11%) during follow-up239 1/27 (4%) during follow-up 66/83 (80%) 3/3 (100%)pns 21 (21%) 3 mo 3 (11%) 3 mo Appendix D.7.4: Efficacy Perioperative and Postoperative and Cardiac- Radiofrequency RFA versus Maze-III Chiappini et al. 2004 Level III-3 RFA Maze-III n=40 n=30 Perioperative Outcomes Total operation time (hr) Time on cardiopulmonary bypass (min) 126.3[33.4] 155.5[40.4] † Cross clamping time (min) 104.8[31.5] 113.0[26.1] pns Length of ICU stay (days) 2.4 4.8 pns Postoperative Outcomes 16.5[2.5] months (7-22) 73.2[4.2] months (20-91) 29/40 (73%) (warfarin) 9/40 (23%) (sotalol/amiodarone) RFA n=40 12/30 (40%)pns (warfarin) 10/30 (33%) (sotalol/amiodarone) Maze-III n=30 85% hospital discharge (cumulative rate of SR) 73.3% hospital discharge pns (cumulative rate of SR) 3/40 (7.5%) 16.5[2.5] months (7-22 months) 2/30 (6.7%) 73.2[4.2] months (20-91 months) 88.5%240 68.9% pns 76.5% 70.4% Reintervention- Catheter ablation Continued anticoagulant requirement Continued antiarrhythmic requirement Perioperative Cardiac Outcomes Cardiac rhythm SR AF Pacemaker required Postoperative Cardiac Outcomes Cardiac rhythm SR AF Cumulative Frequency of SR (Kaplan-Meier) Atrial function Right atrial contraction (transtricuspid A-wave) Left atrial contraction (transmitral A-wave) Biatrial contraction (trans-tricuspid+-mitral Awave) Cardioversion Pacemaker 240 : The figures the same for the 12-lead ECG cumulative rates of SR using Kaplan-Meier, and for the late restoration of SU using Holter monitoring. 347 Appendix D.7.5: Efficacy Perioperative and Postoperative- Biatrial versus Left atrial RFA Güden et al. 2002 Level III-2 Biatrial RFA Left atrial RFA n=39 n=23 Perioperative Outcomes Deneke et al. 2002a Level III-2/3 Biatrial RFA Left atrial RFA n=49 n=21 Total operation time (hr) Time on cardiopulmonary bypass (min) 179[35] 146[34] * Cross clamping time (min) 101[20] 98[24] pns Postoperative Outcomes 18[14] months (1-50) 11[10] months (4-20) Reintervention- Catheter ablation 1/49243 (2.0%) Ablation time (min) 9-12 Left ablation 6-9 Right ablation 9-12 Left ablation 2/39241 (5.1%) 1/23242 (4.3%) Length of ICU stay (days) Length of hospital stay (days) Reoperation Bleeding Other Readmission Continued anticoagulant requirement Continued antiarrhythmic requirement BA= biatrial; LA= left atrial 241 : Both patients required reoperation for bleeding associated with the LAA amputation site. : Reoperation required due to sudden massive bleeding at 6 hrs postoperative due to partial disruption of the LAA suture line. Patient recovered uneventfully. 243 : Patient with atypical atrial flutter, catheter ablation in the right atrium closing a gap between the intercaval intraoperative ablation line and the upper caval vein, was successful. 242 348 Appendix D.7.5 continued: Efficacy Perioperative Cardiac- Radiofrequency Biatrial versus Left atrial RFA Güden et al. 2002 Level III-2 Biatrial RFA Left atrial RFA n=39 n=23 Perioperative Cardiac Outcomes Deneke et al. 2002a Level IIIBiatrial RFA Left atrial RFA n=49 n=21 Cardiac rhythm 86.9% perioperative 94.8% hospital discharge 244 92% 1 mo 5.2% hospital discharge 7.9% 1 month 90.5% perioperativepns 85.7% hospital dischargepns 71% 1 mo pns 14.3% hospital discharge 28.6% 1 month 100% intraoperative 100% intraoperative Right atrial contraction 89.4% 1 mo245 71.4% mo pns Left atrial contraction 73.6% mo 52.4% mo pns SR AF 55% (cumulative SR rate at 1 month) 63% (cumulative SR rate at 1 month) 12/49246 (24.5%) time not stated 0 1/49 (2.0%) 0 Junctional rhythm Typical atrial flutter Atypical atrial flutter Other Disappearance rate of AF (%) Cardiac function Cardioversion Pacemaker required 13.1% perioperative 5.2% hospital discharge 7.9% 1 mo 9.5% perioperative 14.3% hospital discharge 28.6% 1 mo 244 : p=0.051 : Total number of patients with atrial function measured = 59 (both groups). 246 : Only 1 of the 12 patients cardioverted was converted to prolonged SR. 245 349 Appendix D.7.5 continued: Efficacy Postoperative Cardiac- Radiofrequency Biatrial versus Left atrial RFA Güden et al. 2002 Level III-2 Mean 104 days (45-245) Postoperative Cardiac Outcomes Deneke et al. 2002a Level III18[14] months (1-50) 11[10] months (4-20) Heart Rhythm SR AF 94.8% 5.2% 45-245 days 5.2%249 81.0%pns 19% 45-245 days 42.8%‡ 0250 19%* 34247/49 (69%) 16248/21 (76%) 15/49 (31%) Junctional rhythm Typical atrial flutter 2/49 (1-3 months)251 Atypical atrial flutter Other 252 34.2% 71.4%* Cumulative Frequency of SR (Kaplan-Meier) 65% (26/39) 3 months 68% (24/36) 6 months 75% (34/49) complete follow-up 82% (16/19) 3 months 82% (14/17) 6 months 82% (17/21) complete follow-up 22/24 (92%) 13/13 (100%) 19/24 (79%) 12/13 (92%) 1 0 Probability of SR maintenance (%) Disappearance rate of AF (%) Heart function Right atrial contraction (transtricuspid A-wave) Left atrial contraction (transmitral A-wave) 89.4% 6 mo253 71.4% 6 mo pns 73.6% 6 mo 52.4% 6 mo pns Biatrial contraction (trans-tricuspid+-mitral A-wave) A wave peak velocity (cm/s) Cardioversion Pacemaker 2/62 (3.2%; 3 mo postoperative) 5.2% 45-245 d 19.0% 45-245 d 1/39 (2.6%) complete AV block 247 : In 5/34 there were short runs of atrial tachycardia (<15% Holter interval). : In 2/16 patients were there short runs of atrial tachycardia, <15% of Holter recording. 249 : Episodes of AF using Holter monitoring. 250 : Episodes of atrial flutter using Holter monitoring 251 : In 1 patient increasing the sotalol dose from 80 to 160 mg twice daily, and in 1 patient catheter ablation was successful. 252 : Episodes of atrial arrhythmias using Holter monitoring. 253 : Patients with atrial transport measured at 6 months, n=24 (both groups). 248 350 Appendix D.7.6: Efficacy Perioperative and Postoperative- Radiofrequency Biatrial RFA Case Series Perioperative Outcomes Total operation time (hr) Damiano et al. 2003 Level IV (abstract) Hornero et al. 2002 Level IV Prasanna et al. 2001 Level IV Raman et al. 2003 Level IV n=26 n=55 n=25 n=132 Left: 0.44{0.17} Right 0.46{0.22} 13[5] right atrial 22[7] left atrial 3 Time on cardiopulmonary bypass (min) Cross clamping time (min) Ablation time (min) Length of ICU stay (days) Length of hospital stay (days) 11.5 (range 6-65) Reoperation Bleeding 3/55 (5.5%) Other Readmission 6/132254 (4.5%) Postoperative Outcomes Reintervention- Catheter ablation Continued anticoagulant requirement Continued antiarrhythmic requirement 254 255 0 (amiodarone after 3 months) : Readmissions for recurrent AF, sinus bradycardia or both in first 3 months postoperative. : 20% for mechanical valves. 351 32/132 (24.2%) warfarin 30% 3 mo255 20% 6 mo 3/12 12 mo 0/15 at ~ 24 mo Appendix D.7.6 continued: Efficacy Perioperative Cardiac- Radiofrequency Biatrial RFA Case Series Perioperative Cardiac Outcomes Damiano et al. 2003 Level IV (abstract) Hornero et al. 2002 Level IV Prasanna et al. 2001 Level IV Raman et al. 2003 Level IV n=26 n=55 n=25 n=132 44/54 (81.4%) hospital discharge 6/55 (10.9%) after CPB 24/55 (43.6%) in-hospital257 9/54 (16.6%) hospital discharge258 17/55 (30.9%) in-hospital (>48 hr) 259 6/55 (10.9%) in-hospital 1/54 (1.9%) hospital discharge 24/25 (96%) on operating table 132/132256 off CPB Cardiac rhythm SR AF Junctional rhythm Typical atrial flutter Atypical atrial flutter Other 41/55 (74.5%)260 in-hospital 13/55 (23.6%)261 in-hospital 1/55 (1.8%)262 in-hospital Disappearance rate of AF (%) Cardiac function Right atrial contraction 27/44 (15.9%) discharge Left atrial contraction Biatrial contraction Other 24/25 (96%) on operating table 20/25 (80%) operating table 23/25 day 10 20/44 (45.4%) discharge 17/44 (38.6%) (atonia auricular) Cardioversion Pacemaker required 0 256 5/132 (3.8%) within 2 wks 4/132 (3%)263 : All patients weaned off CPB in regular sinus or paced rhythm. : Paroxysmal AF: n=5; Persistent AF: n=19 : Persistent AF 259 : Type of atrial flutter not specified. 260 : Supraventricular arrhythmias. 261 : Transient first-degree atrioventricular block 262 : Transient third-degree atrioventricular block, patient had partial atrioventricular canal defect. 263 : 1 patient had redo repair of an Ebstein anomaly with significant fibrous reaction around the triangle of Kock; 1 patient had idiopathic viral cardiomyopathy 3 months postoperative and had sinus bradycardia after illness; 1 patient had a trans-septal approach for MV repair and pacemaker on day 4 for persistent AV block; 1 patietn with coronary artery disease had a pacemaker 6 months postoperative for sick sinus syndrome. 257 258 352 Appendix D.7.6 continued: Efficacy Postoperative Cardiac- Radiofrequency Biatrial RFA Case Series Damiano et al. 2003 Level IV (abstract) Hornero et al. 2002 Level IV Prasanna et al. 2001 Level IV FU= unknown Mean 7 months (1-16 months) n=25 SR 24/26 (92%) 46/52 (88.5%)264 24/25 (96%) AF 2/26 (8%) 4/52 (7.7%) 1/25 (4%)265 Postoperative Cardiac Outcomes Raman et al. 2003 Level IV n=132 endocardial RF (n=92) epicardial RF (n=40) Heart rhythm 72/87 (82.8%) 3 mo 45/50 (90.0%) 6 mo 15/15 (100%) 12 mo 14/87 (16.1%) 3 mo266 5/50 (10.0%) 6 mo267 Junctional rhythm Typical atrial flutter 1/87 (1.1%) 3 mo 0% 6 mo 0% 12 mo 1/52 (1.9%) (type not specified) Atypical atrial flutter 1/52 (1.9%)268 Other Cumulative Frequency of SR (Kaplan-Meier) Heart function Right atrial contraction (transtricuspid A-wave) 44/52 (84.6%) 38/52 (73.1%)269 Left atrial contraction (transmitral A-wave) 24/25 (96%) Biatrial contraction(trans-tricuspid+-mitral A-wave) Other 3/52 (5.7%) (atonia auricular) 71.8[17.4] (range 42-104) (mean left atrial A-wave velocity) Peak A wave velocity (cm/s) 1880[660] endocardial RF 470[300] epicardial RF* (peak transmitral early diastolic filling velocity 320[20] endocardial RF 390[120] epicardial RF (peak transmitral atrial filling velocity) Right A/E ratio Left A/E ratio 3.31[1.63] (side not specified) Cardioversion Pacemaker 0 264 : Includes 1 patient with sinus dysfunction without an indication for a pacemaker on Holter study. : Patient had a controlled rate and did not require additional rate controlling drugs. 266 : Patients with chronic or paroxysmal AF or pacemaker rhythm. 267 : Patients with chronic or paroxysmal AF or pacemaker rhythm. 268 : Paroxysmal atrial tachycardia 269 : In an additional 9 patients the left atrial kick was low (A-wave < 25cm/s). 265 353 5/132 (3.8%) within 3 mo 4/132 Appendix D.7.6 continued: Efficacy Perioperative and Postoperative- Radiofrequency Biatrial RFA Case Series Perioperative Outcomes Total operation time (hr) Time on cardiopulmonary bypass (min) Sie et al. 2001 Level IV Sos et al. 2002 Level IV Thomas et al. 2003 Level IV n=122 n=10 n=47 109[47] (range 65-170) 70[47] (range 38-114) 158[37] (n=25; Thomas et a. 2000) 117[29] (n=25; Thomas et a. 2000) 227[65] Cross clamping time (min) 119[46] Ablation time (min) 14[3] Length of ICU stay (days) Length of hospital stay (days) 10.9[5.9] (range 7-26) Reoperation Bleeding Other 0 11/122 (9%) cause not specified Readmission Postoperative Outcomes Reintervention- Catheter ablation Continued anticoagulant requirement Continued antiarrhythmic requirement 22/42271 (52.4%) 10/25272 (40.0%) 4/122 (3.3%)270 25/61 (41%) MV repair 15/22 (68%) biological valve (n=158; Sie et al. 2003)273 60/121 (49%) MV surgery (Sie et al. 2003) 4/29 patients in SR274 (13.8%) 270 : His bundle ablation for symptomatic atrial flutter. : Patients had additional RF ablation primarily for inducible atrial flutter. 272 : In this group 4 patients had His bundle ablation, and 6 patients had RF ablation following electrophysiologic studies which shoed clear deficiencies in lines of RF ablation. In 1 case the discontinuity was in the tricuspid annulus-inferior vena cava isthmus lesion close to the tricuspid valve annulus, and in 5 patients the deficiencies were sited at the point where the posterior left atrial lesions met the atrioventricular junction. The site of ablation in these 5 patients was always inside the coronary sinus, corresponding to the position of the original endocardial linear lesion in the posterior left atrium. 273 Sie et al. 2003 (abstract) 274 : Antiarrhythmic medication including sotalol, amiodarone and flecainide. 271 354 Appendix D.7.6 continued: Efficacy Perioperative Cardiac- Radiofrequency Biatrial RFA Case Series Perioperative Cardiac Outcomes Sie et al. 2001 Level IV Sos et al. 2002 Level IV Thomas et al. 2003 Level IV n=122 n=10 n=47 Cardiac rhythm 4/10 operating room 9/10 discharge 3/10 paroxysmal AF275 in-hospital SR AF Junctional rhythm 96% postop (n=25; Thomas et al. 2000) Typical atrial flutter 1/10 in-hospital 1/10 discharge276 6/10277 first 6 hrs 3/10 in-hospital278 2/10 in-hospital279 100% leaving operating room Atypical atrial flutter Other Disappearance rate of AF (%) 8/25 (38%) first 72 hrs280 17/25281 in-hospital Cardiac function Right atrial contraction Left atrial contraction Biatrial contraction Cardioversion Pacemaker required 2/10 6/122 (4.9%)282 6/10 (1-5 days)283 (temporary) 1/10 bradycardia (permanent) 8/25 (32%; temporary pacing in first 72 hrs284) 5/25 permanent285 (20%) 275 : The atriograms showed a regular pattern with cycle lengths ?210 ms that could be classified as atrial flutter or tachycardia, but the surface ECG showed variability between beats of ?30 ms, so they were considered new cases of AF. 276 : Electrophysiological study confirmed atypical atrial flutter of left atrial origin. 277 : Nodal escape rhythm in first 6 hrs postoperative that required temporary stimulation with DDD pacemaker. 278 : Patients with first and/or second degree atrioventricular block. 279 : Sinus node dysfunction. 280 : Patients with periods of sinus arrest or bradycardia requiring temporary pacing. (n=25; Thomas et al. 2000) 281 : Patients with atrial tachyarrhythmias prior to hospital discharge (n=25; Thomas et al. 2000). 282 : In 2 patients the pacemaker was placed before surgery in combination with His bundle ablation, 1 of these patients had symptomatic sinus node dysfunction; 4 patients had His bundle ablation and pacemaker because of symptomatic atrial flutter. In these 4 patients electroanatomic mapping showed a discontinuity in the tricuspid annulus-inferior vena cava isthmus lesion close to the tricuspid valve annulus. 283 : Nodal escape rhythm. 284 : Thomas et al. 2000 285 : 1 patient needed long-term pacing for sinus node dysfunction, and 4 patients had His bundle ablation and permanent pacemakers. 355 Appendix D.7.6 continued: Efficacy Postoperative Cardiac- Radiofrequency Biatrial RFA Case Series Sie et al. 2001 Level IV Postoperative Cardiac Outcomes FU = 39 months (n=107) Sos et al. 2002 Level IV FU = Mean 3 months (1.5-5 months) Thomas et al. 2003 Level IV FU = Median 2.86 yrs (0.6-4.2) 29/42 (69%; back-up pacemakers in 2) 13/42 (24%; pacemakers in 2)289 Cardiac rhythm SR 77/107 (72%) 8/10286 AF 18/107 (16.8%)287 2/10288 Junctional rhythm Typical atrial flutter 1/42 (2.4%) Atypical atrial flutter Other 6/107 (5.6%) atrial rhythm 6/107 (5.6%) pacemaker 79% (9%) 3 yrs 68% (13%) 4 yrs (Kaplan-Meier) Probability of SR maintenance (%) 98[1.5] 1 yr 86[3.7] 2 yrs 78[5.1] 3 yrs Disappearance rate of AF (%) Atrial function Right atrial contraction (transtricuspid A-wave) Left atrial contraction (transmitral A-wave) 74/89290 (83.1%) 4/10 69/89 (77.5%) 1/10 Biatrial contraction(trans-tricuspid+-mitral A-wave) Peak A wave velocity (cm/s) 4.5[1.4] (n=29) Transtricuspid atrial filling fraction (%) Transmitral atrial filling fraction (%) 25[2] Thomas et al. 2000 0.56[0.10] (n=9)291 Thomas et al. 2000 0.81[0.09] (n=9)292 Thomas et al. 2000 Right A/E ratio Left A/E ratio Cardioversion Pacemaker 286 : Including 2 patients with sinus node dysfunction, but did not have a pacemaker indication on Holter study. : Stated as persistent AF or atrial flutter. 288 : Patients had AF despite pharmacological treatment and electrical cardioversion. 289 : Persistent AF in 10 patients, paroxysmal AF in 1 patient. 290 : Doppler echocardiography performed on 89-107 (83%) of survivors, with SR, atrial rhythm, or AV sequential pacemakers. 291 : Performed 122[80] days postoperative. 292 : Performed 122[80] days postoperative. 287 356 Appendix D.7.7: Efficacy Perioperative and Postoperative- Radiofrequency Left atrial RFA Case Series Perioperative Outcomes Total operation time (hr) Time on cardiopulmonary bypass (min) Benussi et al. 2002 Level IV Biederman et al. 2002 Level IV n=132 n=10 Geidel et al. 2003 Level IV Gillinov et al. 2003 Level IV (abstract) n=29 n=50 188[21] Mean: 111[25] Epicardial: 111[25] Endocardial: 108[22] 1st catheter: 127[23] 2nd catheter: 108[24] 3rd catheter: 104[19] 293‡ Mean: 73[18] Epicardial: 71[17] Endocardial: 82[19] 294† 1st catheter: 79[20] 2nd catheter: 71[17] 3rd catheter: 72[16] Mean: 9.2[5.3] Epicardial: 6.6[3.4] §295Endocardial: 17.7[4.4] 1st catheter: 14.2[5.7] 2nd catheter: 7.4[4.6] 3rd catheter: 7.7[5.1] 296 ‡ 1.8[2.4] 6.6[3.9] Cross clamping time (min) Ablation time (min) Length of ICU stay (days) Length of hospital stay (days) Reoperation Bleeding Other 92.9 (range 85-98) 142[21] 69.9 (range 59-81) 105[19] 10.0[2.0] 16.6[5.4] Total297 16[6] 3/132 (2.2%) 1/132298 (0.8%) Readmission Postoperative Outcomes Reintervention- Catheter ablation Continued anticoagulant requirement 12/132299 (9.1%) Continued antiarrhythmic requirement 5/87 amiodarone 22/87 low-dose sotalol 2/87 class II 4/87 class I (patients in SR) Total: 33/87 (37.9%) 293 : versus 1st catheter : versus epicardial 295 : versus epicardial 296 : versus 1st catheter 297 : Includes adjustment of equipment and precise adaption of the probe to the tissue. 298 : 1 patient had a sternectomy and rectus muscle flap reconstruction for deep sternal wound infection. 299 : In 10 patients with typical atrial flutter RF ablation of the cavo-tricuspid isthmus was successful in all patients. In 2 patients transeptal left atrial mapping was performed, 1 had highly symptomatic 2:1 paroxysmal atrial tachycardia refractory to medical treatment, studied 29 months postoperative and other patient so disturbed by arrythmias they contemplated suicide. Studies showed incomplete left encircling ablation, catheter ablation successful in both. 294 357 Appendix D.7.7 continued: Efficacy Perioperative and Postoperative Cardiac- Radiofrequency Left atrial RFA Case Series Perioperative Cardiac Outcomes Benussi et al. 2002 Level IV n=132 Biederman et al. 2002 Level IV n=10 127/132 (96.2%) after surgery 7/10 during surgery 2/10 up to 4 wks Geidel et al. 2003 Level IV n=29 Gillinov et al. 2003 Level IV (abstract) n=50 Cardiac rhythm SR 4/10 up to 4 wks (paroxysmal in 3) AF 18/29 (62.1%) early postop Junctional rhythm 2/10 up to 4 wks300 Typical atrial flutter Other Cardioversion Pacemaker required 302 65/132 (49.2%) in-hospital 0 FU= 16.9[14.2] months Median 13 months Postoperative Cardiac Outcomes 2/10 303 305 2/10 18/29304 (62.1%) 0 FU= 3 -6 months Cardiac rhythm SR AF Typical atrial flutter 87/108 (80.6%) ≥ 6 mo 2/10 18/21 (85.7%) 3 mo 14/16 (87.5%) 6 mo 12/13 (92.3%) 9 mo 5/5 (100%) 12 mo 33.3% 6 wks 2/10 (ventricular pacing) 79% (95%CI 72-86) 1 yr 77%(95%CI 69-85) 3 yrs Patients without recurrence of AF (%) Atrial function Biatrial contraction (trans-tricuspid+-mitral A-wave) A wave peak velocity (cm/s) Right A/E ratio Left A/E ratio Pacemaker 6/10 10/132 (7.6%)306 Other 64% after surgery 60% at discharge 10% after surgery 33/50 (66%) in-hospital 32% at discharge 26% after surgery 2% at discharge 4% at discharge301 87/87307 51[18] Mean A-wave 76[33] Mean A-wave 0.71[2.0]308 0.48[1.3] 309 0 300 : Paroxysmal atrial flutter, type not specified. : Type not specified. : Arrythmias such as AF, atrial flutter and atrial tachycardias. 303 : Nodal rhythm; up to 4 weeks. 304 : Cardioversion was successful in 11 of the 18 patients. 305 : Pacemaker required due to nodal rhythm with slow ventricular response. 306 : Atrial flutter occurred 9[6.3] months postoperative. 307 : Stated that in all patients in SR at 3 or more months after surgery effective atrial contraction of both the left and right atrium was present. 308 : Stated as E/A ratio, values reciprocated. 309 : Stated as E/A ratio, values reciprocated. 301 302 358 19/50 (38%) Appendix D.7.7 continued: Efficacy Perioperative and Postoperative- Radiofrequency Left atrial RFA Case Series Perioperative Outcomes Total operation time (hr) Time on cardiopulmonary bypass (min) Kottkamp et al. 1999 Kress et al. 2002 Le Tourneau et al. 2003 n=12 n=23 n=70 104[24] (range 67-153) 73[17] (range 45-108) 19[4] (range 16-28) Cross clamping time (min) Ablation time (min) 120[29] 39.5[20] Mohr et al. 2002 n=65 167.1[53.3] (n=234) 114.1[38.1] (n=234) 69.0[28.4] (n=234) 18[4] Length of ICU stay (days) Length of hospital stay (days) Reoperation Bleeding 1/12310 (8.3%) Other 1/12311 (8.3%) Readmission Postoperative Outcomes Reintervention- Catheter ablation 1/11312 1/22313 (4.5%) Continued anticoagulant requirement Continued antiarrhythmic requirement 66% 310 : Patient with bleeding from the distal anastomosis of the venous bypass graft to the circumflex coronary artery, causing cardiac tamponade. : Patient with haemodynamic deterioration who subsequently died. 312 : Patient with atrial flutter which became persistent, had electrophysiologic study and incisional reentry around the scar at the right atrial free wall was diagnosed. The lower end of the incision connected to the inferior caval vein was ablated successfully with four RF pulses. 313 : Transcatheter ablation of paroxysmal atrial tachycardia at > 1 yr postoperatively. 311 359 Appendix D.7.7 continued: Efficacy Perioperative and Postoperative Cardiac- Radiofrequency Left atrial RFA Case Series Perioperative Cardiac Outcomes Kottkamp et al. 1999 Kress et al. 2002 Le Tourneau et al. 2003 Mohr et al. 2002 n=12 n=23 n=70 n=65 Cardiac rhythm SR 12/12 after surgery AF 6/11 (54.5%) perioperative 17/23 (74%) immed. post ablation 16/22 (73%) at discharge 1/23 (4%) immed. post ablation 4/22 (18%) at discharge314 47/65 (72.3%) at discharge 3/65 (4.6%) at discharge315 Atypical atrial flutter 316 Other 2/11318 (18.2%) 3/11319 (27.3%) FU = 11[6] months (3-20) Cardioversion Pacemaker required Postoperative Cardiac Outcomes 5/23 (22%) immed. post ablation 2/22 9%) at discharge317 2/22 before discharge 1/23 FU= 32.5[28.4] wks (1-100) 2/69 (SHVD 2003) FU= 549 days Cardiac rhythm SR 6/11 (54.5%) 320 AF 2/11 (18%) Atypical atrial flutter 5/8 (62.5%; FU < 3 mo) 14/14 (FU > 3 mo; pacemaker in 1) 3/8 (37.5%; FU < 3 mo) 0/14 (FU > 3 mo) 92% 2 yrs 21/68321 1/30 (3.3%) 6 mo 1/21 (4.8%) 12 mo 1/30 (3.3%) 6 mo323 1/21 (4.8%) 12 mo324 3/11322 (27%) Other 62.5% 2 yrs (SHVD 2003) Proportion of patients without recurrence of AF (%) Disappearance rate of AF (%) Cardiac function Right atrial contraction (transtricuspid A-wave) Left atrial contraction (transmitral A-wave) Biatrial contraction (trans-tricuspid+-mitral A-wave) A wave peak velocity (cm/s) 20/30 (66.7%) 6 mo 13/21 (61.9%) 12 mo 81.8% (9/11) 5/9 (55.6%)325 92% 2 yrs 920[330] (400-1200) 314 : Number taken from extrapolation of patients in SR and paced rhythm. Likely to be patients in AF/atrial flutter. : Note discrepancy between text and table, text states 4/65 discharged with atypical flutter. 316 : Paced with atrial capture. 317 : Paced with atrial capture. 318 : Early cardioversion for recurrence of AF, in which sotalol was unsuccessful. 319 : Pacemakers required at 8-14 days postoperative for sinus bradycardia. 320 : Some patients had a pacemaker. 321 : Patients who experienced at least one recurrence furing follow-up. 322 : Paroxysmal atypical atrial flutter with frequence episodes of self-terminating atrial flutter with normal ventricular response present in 2 patients. In 1 patietn atrial flutter became persistent and led to tachycardia due to 2:1 conduction, catheter ablation performed. 323 : SR with intermittent AF or atypical flutter. 324 : SR with intermittent AF or atypical flutter. 325 : Side not specified 315 360 Appendix D.7.7 continued: Efficacy Perioperative and Postoperative- Radiofrequency Left atrial RFA Case Series Perioperative Outcomes Total operation time (hr) Müller et al. 2002 Ruchat et al. 2002 n=95 n=40 245[61] Time on cardiopulmonary bypass (min) 110[32] (n=48; Pasic et al. 2001) 64[17] (n=48; Pasic et al. 2001) Cross clamping time (min) Ablation time (min) Length of ICU stay (days) 138[32] 109[5] 19[5] 2.7[2.2] Length of hospital stay (days) 12[5] Reoperation Bleeding 0 1/40 (2.5%) Other Readmission Postoperative Outcomes Reintervention- Catheter ablation Continued anticoagulant requirement Continued antiarrhythmic requirement 361 Appendix D.7.7 continued: Efficacy Perioperative and Postoperative Cardiac- Radiofrequency Left atrial RFA Case Series Perioperative Cardiac Outcomes Müller et al. 2002 Ruchat et al. 2002 n=95 n=40 95/95 leaving op room (SR or atrial pacing) 12/95 (12.6%) stable SR in 1st wk 39/40 (97.5%) immediately after surgery326 22/37 (60%) hospital discharge 9-10/37 (~25%) hospital discharge Cardiac rhythm SR AF Typical atrial flutter 0 after discharge 5-6/37 (~15%) hospital discharge Atypical atrial flutter 100% intraoperative 30% 1 wk Disappearance rate of AF (%) Atrial function Right atrial contraction 0 (transoesophageal echocardiography) Left atrial contraction 0 (transoesophageal echocardiography) Biatrial contraction Pacemaker required Postoperative Cardiac Outcomes 6/95327 1/40 8 months (1-24 months) 12.5[7.9] months 84% 6 months 84% 12 months 68% (n=37) 85% in last 20 patients328 Cardiac rhythm SR AF Disappearance rate of AF (%) 84% 6 months 84% 12 months Atrial function Right atrial contraction (transtricuspid A-wave) Left atrial contraction (transmitral A-wave) Biatrial contraction (trans-tricuspid+-mitral A-wave) 26% at 14[5] months 100% patients in SR (transoesophageal echocardiography) Right A/E ratio <0.5 in 74% SR patients at 14[5] months329 Left A/E ratio Cardioversion Pacemaker 326 : 1 patient with histologically proven atrial myocarditis did not revert to SR. : Pacemaker required due to bradycardia and persistent sinus node dysfunction. 328 : In text it was stated that a learning curve effect was noted, with a higher success rate of 85% SR restoration rate in the last 20 patients. 329 : A/E ratio of less than 0.5 demonstrates absence of efficient atrial transport. 327 362 Appendix D.7.7 continued: Efficacy Perioperative and Postoperative- Radiofrequency Left atrial RFA Case Series Starck et al. 2003 Williams et al. 2001 n=100 n=48 Perioperative Outcomes Total operation time (hr) 229.7[56.5] Time on cardiopulmonary bypass (min) 135.8[35.7] Cross clamping time (min) 95.9[30.5] Ablation time (min) Length of ICU stay (days) 18.8[6.9] rarely > 20 min Length of hospital stay (days) Reoperation Bleeding 2/100 (2%) Other Readmission Postoperative Outcomes Reintervention- Catheter ablation Continued anticoagulant requirement Continued antiarrhythmic requirement 17/90 (18.9%) (FU= 7.3 months) 18/34 patients in SR 5/8 patients in AF/atrial flutter (both amiodarone) Total: 23/42 (54.8%) 363 Appendix D.7.7 continued: Efficacy Perioperative and Postoperative Cardiac- Radiofrequency Left atrial RFA Case Series Perioperative Cardiac Outcomes Starck et al. 2003 Williams et al. 2001 n=100 n=48 Cardiac rhythm SR 68/95(71.6%) hospital discharge330 AF 25/90 (27.8%) n=90331 Other 27/95 (28.4%) irregular atrial rhythm 0 (leaving op theatre) 28/42 (67%) perioperative332 Disappearance rate of AF (%) Cardioversion Pacemaker required Postoperative Cardiac Outcomes 0 0 FU=Mean 7.3 months FU=138[96] days Cardiac rhythm SR 72/90 (80%) AF 18/90 (20%) Disappearance rate of AF (%) 34/42 (81%) 7/8 right-side lesion (3/3 Maze III-like lesion) 27/34 (79%) left-sided lesion 1/8 bi-atrial lesion 7/34 (21%) left-sided lesion (both AF/atrial flutter) 80% Heart function Right atrial contraction (transtricuspid A-wave) Left atrial contraction (transmitral A-wave) 72/90 (80%)333 Biatrial contraction (trans-tricuspid+-mitral A-wave) Cardioversion Pacemaker 330 : Stated as spontaneous regular supraventricular rhythm. : Patients followed up > 3 months. 332 : At least 1 episode of perioperative AF/atrial flutter. 333 : Stated that patients had SR and atrial contraction, whether it was left- or right- atrial contraction not specified. Criteria for presence of atrial contraction was the presence of an A-wave. 331 364 Appendix D.8.1: Efficacy Perioperative and Postoperative- Microwave Left atrial MWA versus CS Perioperative Outcomes Total operation time (hr) Time on cardiopulmonary bypass (min) Cross clamping time (min) Ablation time (min) Schuetz et al. 2003 Level II MWA CS n=24 n=19 244.7[63.1] 229.0[62.4] (145-340) (125-360) 120.6[27.3] 103.8[45.1]pns (47-195) (78-176) 99.6[24.8] * 74.0[44.3]* (31-146) (26-155) 11.3[2.3]334 Spitzer and Knaut 2002 Level III-? MWA CS n=136 n=51 15335 13{5} (EACTS 2003) Length of ICU stay (days) Length of hospital stay (days) 21.5[13.3] (9-52) 20.0[11.2] pns (12-57) Reoperation Bleeding 0 Other 1336 Readmission Postoperative Outcomes Reintervention- Catheter ablation FU= 12 months 337 2/24 FU = 1 yr (n=111) FU = 1 yr (n=45) (8.3%) Continued anticoagulant requirement Continued antiarrhythmic requirement At 1 yr in MV/CABG groups (%/%) 11/15 (73%; 12m) 17/20 completed 3 month course 5/9 (56%; 12m) 9/9 completed 3 month course Class I drug: 4/0 Sotalol: 52/64 Amiodarone: 7/6 β blocker: 20/19 334 : Number of ablation applications was 27.1[6]. : Prolonged surgical time by up to 15 min. 336 : Patient re-operated on two times because of endocarditis. 337 : Successful RF catheter ablation at 5 and 15 months postoperative. 335 365 Knaut et al. 2003 (abstract) Level III-? MWA1 MWA2 n=137 n=75 Class I drug: 3/0 Sotalol: 7/33 Amiodarone: 0/0 β blocker: 66/56 Appendix D.8.1 continued: Efficacy Perioperative Cardiac- Microwave Left atrial MWA versus CS Schuetz et al. 2003 Level II Perioperative Cardiac Outcomes Cardiac rhythm SR AF MWA CS n=24 n=19 Immediately postoperative (IP) and at hospital discharge (HD) 6/19 (32%%; IP) 22/24 (91.7%; IP) 3/19 (16%; HD) 14/23 (60.9%; HD) 13/19 (68%; IP) 2/24 (8.3%; IP) 16/19 (84%; HD) 9/23 (39.1%; HD) Spitzer and Knaut 2002 Level III-? MWA CS n=136 n=51 Junctional rhythm Typical atrial flutter Atypical atrial flutter 3338 Other Freedom from AF 22/24 (91.7%) postop 14/23 (60.8%) discharge 9/19 (47.4%) postop* 3/19 (15.8%) discharge* Cardiac function Right atrial contraction Left atrial contraction Cardioversion Pacemaker required 2/24 (8.3%) 3/24339 (12.5%) 0 Mean 1.4 18%340 338 16%341 : In the conference discussion at the end of the publication it was stated that 3 patients suffered from atypical atrial flutter. Patients with new onset bradycardia requiring a pacemaker because of sinus arrest (n=1) or atrioventricular dissociation (n=2). 340 : Two chamber pacemaker due to continuous bradycardia. 341 : Two chamber pacemaker due to continuous bradycardia. 339 366 Knaut et al. 2003 (abstract) Level III-? MWA1 MWA2 n=137 n=75 Appendix D.8.1 continued: Efficacy Postoperative Cardiac- Microwave Left atrial MWA versus CS Schuetz et al. 2003 Level II 12 months Postoperative Cardiac Outcomes Spitzer and Knaut 2002 Level III-? 1 yr Knaut et al. 2003 (abstract) Level III-? 6 months Cardiac rhythm SR 12/21 (57%; 3m)342 12/18 (67%; 6m) 12/15 (80%; 12m) 3/17 (18%; 3m) * 3/10 (30%; 6m) * 3/9 (33%; 12m) * AF 64% (6m) 62% (12m) MVS/CABG 54%/60% 25% (6m) 25% (12m) MVS/CABG 36%/24% 8% (6m) § 10% (12m) § MVS/CABG 9%/7%§ 92% (6m) 90% (12m) MVS/CABG 91%/93% 2% (6m) 2% (12m) MVS/CABG 0%/2% 9% (6m) 11% (12m) MVS/CABG 10%/14% 0% (6m) 0% (12m) MVS/CABG 0%/0% 0% (6m) 0% (12m) MVS/CABG O%/0% 62% (12m)343 10% (12m)344 MV surgery: 62% CAD: 68% AVR: 78% MV surgery: 88% CAD: 78% AVR: 85% MV surgery: 62% CAD: 70% AVR: 80% MV surgery: 88% CAD: 78% AVR: 85% Junctional rhythm Typical atrial flutter Atypical atrial flutter Other Probability of SR maintenance (%) Freedom from AF 12/21 (57.2%) 3 months 12/18 (66.7%) 6 months 12/15 (80.0%) 12 months 3/17 (17.6%) 3 months* 3/10 (30.0%) 6 months* 3/9 (33.3%) 12 months* Cardiac function Right atrial contraction (transtricuspid A-wave) Left atrial contraction (transmitral A-wave) Biatrial contraction (trans-tricuspid+-mitral A-wave) Cardioversion Pacemaker 342 : Data not given as patients in SR, but as patients free from AF. : Number extrapolated as text stated that all patients in SR had biatrial transport function on echocardiography. 344 : Number extrapolated as text stated that all patients in SR had biatrial transport function on echocardiography. 343 367 Appendix D.8.2: Efficacy Perioperative and Postoperative and Cardiac- Microwave Biatrial MWA Case Series Chiappini et al. 2003 Level IV n=10 Perioperative Outcomes Time on cardiopulmonary bypass (min) 123.3 (range 63-209) Cross clamping time (min) 98.9 (range 40-173)345 Ablation time (min) Length of ICU stay (days) Length of hospital stay (days) Reoperation Postoperative Outcomes Reintervention- Catheter ablation Continued anticoagulant requirement Continued antiarrhythmic requirement Perioperative Cardiac Outcomes Cardiac rhythm n=10 SR AF Other Pacemaker required Postoperative Cardiac Outcomes Cardiac rhythm SR AF When weaned off CPB 8/10 2/10 (regular paced rhythm) 0 FU = Mean 12.4 months At last follow-up 7/9 (77.8%) 2/9 (22.2%) Atrial function Right atrial contraction (transtricuspid A-wave) Left atrial contraction (transmitral A-wave) Cardioversion 345 : The increase in cross clamp time averaged only 10 min. 368 Appendix D.8.3: Efficacy Perioperative and Postoperative- Microwave Left atrial MWA Case Series Gillinov et al. 2002 Level IV n=10 Perioperative Outcomes Total operation time (hr) Knaut et al. 2002 Level IV Venturini et al. 2003 Level IV Zembala et al. 2003 Level IV n=105 n=41 n=42 178.5[22.0] (range 105-310) 116.2[14.5] (range 80-136) 84.3[10.4] (range 57-95) Time on cardiopulmonary bypass (min) Cross clamping time (min) Ablation time (min) 10-15 min Length of ICU stay (days) Length of hospital stay (days) Reoperation Bleeding Other 0 0346 Readmission Postoperative Outcomes Reintervention- Catheter ablation 1/42347 (2.4%) Continued anticoagulant requirement Amiodarone: 25/34348 (73.5%) Sotalol: 3/34 ((8.8%) Digoxin: 6/34 (17.6%) Continued antiarrhythmic requirement 346 : None due to prosthesis complications. : Patient had atypical atrial flutter 3 months postoperative, electrophysiological study showed left atrial arrhythmias, cured by percutaneous ablation with RF energy. 348 : In n=34 patients free of AF at follow-up. 347 369 Appendix D.8.3 continued: Efficacy Perioperative and Postoperative Cardiac- Microwave Left atrial MWA Case Series Perioperative Cardiac Outcomes Gillinov et al. 2002 Level IV Knaut et al. 2002 Level IV n=10 n=105 Cardiac rhythm SR AF 6/10 (at discharge) 8/10 (perioperative) 3/10 (at discharge) Venturini et al. 2003 Level IV Zembala et al. 2003 Level IV n=41 n=42 At discharge 25/41349 (61.0%) At discharge 32/42 (76%) 16/41 (39.0%) 10/42 (24%)350 Typical atrial flutter Other 1/10351 Cardioversion 16/41 (39.0%) (1 mo postop) 352 Pacemaker required 19/104 (18%) Postoperative Cardiac Outcomes 0 3/42 (7.1%) At final follow-up At last follow-up 34/41 (82.9%) 32/42353 (76.2%) FU= 12 months (n=64) Cardiac rhythm SR AF 42/69 (60.9%; 6m) 37/64 (57.8%; 12m) 24/69 (34.8%; 6m) 24/64 (37.5%; 12m) 14/42 (33.3%) Junctional rhythm Typical atrial flutter Atypical atrial flutter Cardiac function Right atrial contraction (transtricuspid A-wave) 3/69 (4%; 6m) 3/64 (5%; 12m) (type not specified) 1/42354 (2.4%) 18/37 (48.6%) 1 year Left atrial contraction (transmitral A-wave) Biatrial contraction(trans-tricuspid+-mitral A-wave) 16/37 (43.2%) 1 year Transtricuspid atrial filling fraction (%) <20%: 5/34355 20-29%: 9/34 >30%: 20/34 Transmitral atrial filling fraction (%) Cardioversion Pacemaker 349 : After discharge 4 patients spontaneously converted from AF to SR, and 4 patients spontaneously converted from SR to AF. : AF recurred in 26/42 patients at 6.7[6.9] (range 0-33) days postop. In 16/26 SR was regained through increased sotalol (n=4), cardioversion (n=10) or spontaneously (n=2). 351 : Sinus bradycardia (paced). 352 : Includes 16 patients with preoperative diagnosis of bradyarrhythmia. 353 : All 28 patients discharged in SR remained in SR, while 4/14 patients discharged in AF had converted to SR at last follow-up. 354 : Patient had atypical flutter 3 months postoperative, cured by catheter ablation. 355 : Atrial filling fraction <20% = severe impairment; 20-29% = mild-moderate impairment; >30% = normal. 350 370 Appendix D.9: Efficacy Perioperative and Postoperative and Cardiac- Laser Case Series Vigilance et al. 2003 Level IV n=6 Perioperative Outcomes Time on cardiopulmonary bypass (min) Cross clamping time (min) Reoperation Postoperative Outcomes Reintervention- Catheter ablation Continued anticoagulant requirement Continued antiarrhythmic requirement Perioperative Cardiac Outcomes n=6 Cardiac rhythm SR AF Postoperative Cardiac Outcome Cardiac rhythm SR 6/6 3 months AF Cardiac function Right atrial contraction (transtricuspid A-wave) Left atrial contraction (transmitral A-wave) Cardioversion Pacemaker 371 Appendix D.10: Efficacy Perioperative and Postoperative- Comparative MWA versus RFA Wisser et al. 2003 Level III-2/3 (abstract) MW A n=23 RFA n=19 Time on cardiopulmonary bypass (min) 165[34] 164[48] Cross clamping time (min) 88[15] 91[25] 23[2] 1.7[2.5] n=22 49 days n=1 12.8[3.4] 17[1]* 1.6[1.2] n=18 46 days n=1 12.0[5.1] 2/23 (8.7%) 0 24.2[1.3] months 12.1[1.2] months† Perioperative Outcomes Total operation time (hr) Ablation time (min) Length of ICU stay (days) Length of hospital stay (days) Reoperation Bleeding Other Readmission Postoperative Outcomes Reintervention- Catheter ablation Continued anticoagulant requirement Continued antiarrhythmic requirement 372 Appendix D.10 continued: Efficacy Perioperative and Postoperative Cardiac- Comparative MWA versus RFA Wisser et al. 2004 Level III-2/3 Perioperative Cardiac Outcomes MW n=23 RF n=19 0% admission to ICU 0% admission to ICU FU= 24.2[1.3] months FU=12.1[1.2] months Cardiac rhythm SR AF Junctional rhythm Typical atrial flutter Postoperative Cardiac Outcomes Cardiac rhythm SR AF Junctional rhythm Typical atrial flutter 13/22 (59.1%) 3 months 12/22 (54.5%) 6 months 13/22 (59.1%) 12 months 12/20 (60%) 24 months 5/22 (22.7%) 3 months 4/22 (18.1%) 6 months 4/22 (18.1%) 12 months 4/20 (20%) 1/22 (4.5%) 3 months 1/22 (4.5%) 6 months 0/22 12 months 0/20 24 months 0 3 months 1/22 (4.5%) 6 months 9/19 (47.4%) 3 months 11/18 (61.1%) 6 months 8/14 (57.1%) 12 months 4/19 (21.1%) 3 months 4/18 (22.2%) 6 months 3/14 (21.4%) 12 months 2/19 (10.5%) 3 months 0/18 6 months 0/14 12 months 1/19 (5.3%) 3 months356 0 6 months Other Freedom from AF 81% 12 months 80%pns 12 months 3/22 (13.6%) 3 months 4/22 (18.1%) 6 months 5/22 (22.7%) 12 months 4/20 (20%) 24 months 5/23 (21.7%)357 total 3/19 (15.8%) 3 months 3/18 (16.7%) 6 months 3/14 (21.4%) 12 months 4/19 (21.1%)358 total Cardiac function Right atrial contraction (transtricuspid A-wave) Left atrial contraction (transmitral A-wave) Cardioversion Pacemaker 356 : type not specified : AV block at 1, 3 and 6 months postoperatively and sick sinus syndrome at 3 and 5 months postoperatively. 358 : AV block in 2 patients at 1 month postoperatively, 1 patient had a pacemaker preoperatively due to bradycardia, and 1 patient had sick sinus syndrome at 9 months postoperatively. 357 373 Appendix D.11.1: Efficacy Outcomes- Exercise testing Biatrial CA versus CS Yuda et al. 2004 Exercise Testing CA-SR (n=18) CA-AF (n=8) Pre-surgery Maximum work load (watts) CA-SR: 101[30] CA-AF: 96[27] CS (n=6) CA-SR: 14.6[6.6] months CA-AF: 19.1[9.3] months CA-SR: 117[39]† (vs pre-) CA-AF: 112[31] Pre-surgery 17.4[15.5] months 94[26] 95[41] 78[15] 73[14] 168[25] 135[47] 127[11] 128[18] 176[24] 169[33] Heart rate At rest (beats/min) Peak (beats/min) Systolic blood pressure at rest (mm Hg) Systolic blood pressure at peak (mm Hg) A-SR: 88[15] CA-AF: 89[15] A-SR: 182[24] CA-AF: 175[21] A-SR: 132[21] CA-AF: 120[13] A-SR: 172[25] CA-AF: 171[21] Increase in peak VO2 pre- to post-surgery (%) MVR (n=12): 17.5[4.1] MVP (n=12): 18.6[4.9] Peak VO2 (ml/kg/min) CA-SR: 83[16] CA-AF: 85[17] CA-SR: 138[17]† (vs pre-) CA-AF: 159[23] CA-SR: 142[32]* (vs pre-) CA-AF: 136[18] CA-SR: 200[34]† (vs pre-) CA-AF: 197[25] CA-SR: 33.1[46.1] CA-AF: 15.6[25.2] MVR (n=12): 21.3[4.7] * (vs pre-) MVP (n=12): 20.2[5.7] pns (vs pre-) Appendix D.11.2: Efficacy Outcomes- Exercise testing Biatrial RFA versus CS RCT Khargi et al. 2001, Deneke et al. 2002 Exercise testing Maximum work load (watts) RFA + CS (n=11) CS (n=11) 6 months 6 months 73[29] median 76 43[16] median 38 † 96[16] 99[17] pns 21[11] 31[20] pns 9.3[3.4 8.5[3.2] pns 7.2[1.8] 6.4[2.3] pns Heart rate At rest (beats/min) Peak (beats/min) Mean heart rate increase (beats/min) Systolic blood pressure at rest (mm Hg) Systolic blood pressure at peak (mm Hg) Increase in peak VO2 pre- to post-surgery (%) Peak VO2 (ml/kg/min) Anaerobic threshold (VO2) 374 22.1[17.8]pns 15.3 18.6* (vs pre-) Appendix D.12: Case Reports Study Fayad et al. 2003 COMPLICATION: Circumflex artery stenosis one year after RFA. Study Berreklouw et al. 1999 COMPLICATION: Coronary artery narrowings one day after a Maze-III procedure Surgery Indication: Permanent atrial fibrillation resistant to medical therapy (antiarrhythmic drugs and cardioversion). Body temperature: Moderate hypothermia (28 oC). CPB cannulation: Not stated Cardioplegia: Haemodilution with repeated anterograde cold blood cardioplegia every 30 minutes. Ablation device: RADIOFREQUENCY/ Thermaline probe (Boston Scientific, San Jose, CA, USA) Energy level: 75 oC at 150 W for 120 seconds, six applications used. Surgery: Left lesions: Separate encircling lesions of the left and right pulmonary veins, with a line joining them at the mid-point. A line from approximately above the left inferior pulmonary vein to the mitral annulus. Right lesions: None Atrial appendages: Not stated Atrial incisions: Left atrial incision. No right atrial incisions. Order of surgery: Not stated Concomitant surgery: MVR for mitral stenosis using a mechanical prosthesis (Bicarbon27). Other: Preoperative coronary angiography Complications Patient: 63-year-old woman in SR after RFA. Presentation: One year postoperatively, presented to hospital with acute pulmonary oedema and severe angina. Diagnosis: ECG had normal SR with ST depression in the lateral leads, and troponin measurements within normal range. Echocardiograms showed satisfactory function of the MV with marked lateral and apical hypokinesia. Diagnostic angiography demonstrated stenosis of a long segment of the proximal part of the circumflex artery, including the first marginal branch, with thrombosis of the distal circumflex artery. No other stenotic or atherosclerotic lesions elsewhere in the coronary arteries. The circumflex stenosis was adjacent to the MV on the line of the RFA applications. Treatment: Percutaneous transluminal coronary angioplasty. Outcome: Complete recovery Surgery Indication: Progressive right heart failure with severe MV stenosis and AF with a rapid ventricular response of 160 to 220 beats per minute. Body temperature: Normothermic CPB cannulation: Not stated Cardioplegia: Antegrade and retrograde intermittent warm blood cardioplegia administered during the left-sided procedures. Ablation device: CRYOABLATION/ Frigitronics; CooperVision Compnay, Shelton, CR, USA) Energy level: -60 oC for 2 minutes Surgery: Cox Maze III Order of surgery: Not stated Concomitant surgery: MVR Other: Coronary angiography preoperatively showed a normal right and left coronary artery. Prior to going off bypass, a transoesophageal echocardiogram showed a good contracting left and right ventricle with normal dimensions. Patient weaned from bypass with low-dose inotropics with a cardiac index of 1.9 L/min/m2. Atrial and ventricular pacing using temporary wires was necessary as the patient showed no spontaneous heart rhythm. Complications Patient: 36-year-old female with a height of 155 cm and a weight of 51 kg (body surface area 1.40 m2). Presentation: On the first postoperative day, shortly after extubation, the patient had no cardiac output and needed to be resuscitated. An intraortic balloon pump was inserted. Diagnosis: Transoesophageal echocardiogram demonstrated akinesia inferiorly and posteriorly, leading to poor left ventricular function. The ECG showed pacemaker rhythm. On coronary angiogram, generalised smaller diameters of the coronary arteries with significant narrowing in the distal circumflex and right coronary arteries seen. Treatment: The circumflex coronary artery was dilated first, with a 3.0-mm angioplasty balloon. When this narrowing was dilated other narrowings developed proximally and distally from the initial point of dilatation. As the new narrowing did not disappear after intracoronary nitroglycerin, they were also dilated. Six dilations were performed in the circumflex coronary artery. With the same angioplasty balloon, the right coronary artery was dilated. New narrowing also developed in this vessel proximally and distally from the first dilatation, and these were dilated as well. In total, three dilatations of the right coronary artery were performed. At the end of the procedure both coronary arteries were patent again. Outcome: Patient remained in hospital for 45 days, but recovered completely. At discharge the echocardiogram showed a substantially recovered left ventricular function with hypokinesis in the infero-basal segments. A repeat coronary angiogram at 25 days after the procedures no longer showed narrowings. At 1 year follow-up the patient had SR. 375 Changes to surgery: Now perform one RFA application between the left pulmonary veins and the mitral annulus, more distally over the atrioventricular groove, thus avoiding the proximal part of the circumflex artery. Cold cardioplegia is also used just before the RFA application to minimise the thermic effect. The second RFA application changed to the anterior wall of the LA to avoid any oesophageal injury, and power output reduced to 100 W. Do not routinely perform angiography after RFA, but it is necessary in any patient presenting with angina after the procedure. Appendix D.12: Case Reports continued Study Manasse et al. 2003 COMPLICATION: Coronary artery stenosis 90 days postoperative following microwave ablation. Study Sueda et al. 1996 COMPLICATION: Myocardial infarction following a cryoablation maze. Surgery Indication: Six year history of chronic AF with multiple unsuccessful external electrical cardioversions. Patient had dyspnoea on effort and nocturnal paroxysmal dyspnoea (NYHA class III). Severe rheumatic MV stenosis. Body temperature: Not stated CPB cannulation: Not stated Cardioplegia: Not stated Ablation device: MICROWAVE/ Flex 4 probe (AFx Inc, Fremont, CA, USA) Energy level: 65 W for 90 seconds. Surgery: Left lesions: Epicardial ablation with a single encircling of the four pulmonary veins, the superior and inferior tract being the transverse and oblique sinus, respectively, the medial tract being parallel to the interatrial septum, and the lateral tract being lateral to the LAA. Right lesions: None Atrial appendages: Not stated Atrial incisions: Left atrial incision. Order of surgery: Ablating procedure carried out while the patient was on CPB. Concomitant surgery: MVR Other: Preoperative coronary angiogram showed normal coronary arteries. Cross clamping time was 65 minutes, and the CPB time was 94 minutes. Patient discharged on postoperative day 5 with SR and good general conditions. Complications Patient: 62-year-old man Presentation: On postoperative day 90 the patient had a recurrence of angina (NYHA class III) Diagnosis: Anterior myocardial infarction. The angiogram showed a critical left main trunk lesion also involving the proximal part of the left anterior descending and circumflex arteries. Treatment: AVR because of an underestimated aortic regurgitation. Myocardial revascularisation using a double bypass graft, with the left internal mammary artery grafted to the left anterior descending coronary artery and the left radial artery grafted to the obtuse marginal coronary artery (Y-grafted to the left mammary artery in situ). Outcome: Successful. Surgery Indication: Chronic AF during past 6 years. Several episodes of peripheral arterial emboli, as well as cerebral infarction. Transoesophageal echocardiogram showed a large thrombus in the LAA and an enlarged left atrium but no valvular disease. Body temperature: Not stated CPB cannulation: Not stated Cardioplegia: Not stated Ablation device: CRYOABLATION/ Device not stated. Energy level: -60 oC for 2 minutes Surgery: Maze procedure with cryoablation replacing incisions. Left lesions: Cryoablation to the posterior mitral annulus instead of direct incision. Right lesions: Cryoablation to the right atrioventricular groove. Atrial appendages: Not stated Atrial incisions: Not stated Order of surgery: Not stated Concomitant surgery: None Other: Preoperative angiograms showed no stenoses in the right or left coronary arteries. Peripheral arterial angiograms showed embolic obstruction of the left posterior tibial and right anterior tibial arteries. Spontaneous SR regained, and postoperative course uneventful except for one episode of paroxysmal atrial tachycardia. Transoesophageal echocardiography did not show any signs of left ventricular asynergy or left atrial thrombus. Discharge 24 days postoperative. Placed on low-dose warfarin sodium (2 mg/day) and dysopiramide (200 mg/day). Complications Patient: 68-year-old man Presentation: Episode of abrupt dyspnoea and tachycardia at 3 months postoperatively. Diagnosis: ECGs showed ST segment depression in leads II, III aVF and V4 to V6. Echocardiograms showed akinesis of the posterior left ventricular wall, with severe mitral regurgitation caused by prolapse of the anterior mitral leaflet. Coronary cineangiograms revealed an obstruction of the right coronary artery, and severe stenosis of the left circumflex coronary artery. These sites matched exactly the sites where cryoablation had been performed. Treatment: One month after onset of myocardial infarction, CABG performed by grafting to the left circumflex artery, and MVR also performed with preservation of the anterior and posterior leaflets. Outcome: Successful, discharged 35 days after the second operation. 376 Suggested modifications to surgery: In the transverse sinus the probe should be directed toward the patient’s back slightly to the feet, and when closing the lateral tract between the two left pulmonary veins it should be beyond the LAA (between the LAA and the pericardial sac). If the probe is placed at less than 90oC to the origin of the left main trunk or between the LAA and the heart, the left main trunk or the circumflex coronary artery can be seriously damaged. Note: This was the first case of myocardial infarction after cryoablation to the atrioventricular annulus in a clinical experience of 35 maze procedures. Appendix D.12: Case Reports continued Study Sonmez et al. 2003 COMPLICATION: Oesophageal perforation following RFA. Surgery Indication: Rheumatic aortic and MV disease plus AF for 6 years. Transoesophageal echocardiogram revealed severe aortic stenosis and regurgitation, MV and tricuspid valve regurgitation due to annulus dilatation, biatrial enlargement and mild left ventricular dysfunction. Body temperature: Not stated CPB cannulation: Bicaval cardiopulmonary bypass Cardioplegia: Cold cardioplegia. Ablation device: RADIOFREQUENCY/ Cobra RF System (Boston Scientific, Boston, Natick, MA, USA) Energy level: 80 oC for 120 seconds. Surgery: Left lesions: A C-shaped line as a continuation of the left atriotomy incision, encircling the right pulmonary veins. The two left pulmonary veins encircled in a second line, and both circles then connected by a transverse line. Another line created to connect the left pulmonary vein circle to the midportion of the posterior mitral annulus. Right lesions: None Atrial appendages: LAA orifice oversewn before closure of the left atrium. Atrial incisions: Left atriotomy. Order of surgery: During surgery transoesophageal echocardiography was not performed. The oesophagus was occupied solely by a nasogastric tube. The line connecting the left pulmonary vein and mitral annulus was performed using cold cardioplegia to protect the posterior sulcus. The ablation procedure performed before the valve operations, with an aorto-right coronary artery bypass performed last, using a saphenous vein graft. Concomitant surgery: MVR and AVR plus a De Vega repair of the tricuspid valve to reduce annular dilatation. Postoperative Recovery: Paroxysmal AF-atrial flutter occurred, treated with amiodarone. Discharge on postoperative day 7 while AF was alternating with SR. Other: Left atrial diameter 78 mm, and angiogram showed ostial stenosis of the right coronary artery of about 80%. 377 Complications Patient: 58-year-old woman Presentation: At 22 days postoperative, the patient was readmitted with fever (39 oC), shivering, and numbness in the right arm. The numbness spontaneously stopped after hospitalisation. Diagnosis: Transthoracic echocardiography showed normal functioning of the prosthetic valves, and the presence of a thrombus was suspected in the left atrial wall. Tranoesophageal echocardiography confirmed a thrombus near the LAA remnant as well. The patients neurological condition suddenly deteriorated so that they were unconscious, and were immediately transferred to the operating room. Treatment: CPB was instituted and the thrombus on the appendage remnant and around the pulmonary vein orifices was cleared. The MV prosthesis was inspected, then the left atrium closed and the patient weaned from bypass without problems. Sudden massive bleeding from the nasogastric tube developed before the chest was closed. Urgent oesophagoscopy revealed a bleeding laceration of 15 mm diameter on the anterior wall of the oesophagus, 33 cm from the incisors. The patient put on crush CPB again. Gas bubbles were detected in the left atrium, probably from the oesophagoscopy. Air was passing through this laceration into the left atrium, between the two circles created by the ablation lines around the right and left pulmonary veins. The laceration was repaired with a pericardial patch reinforced with sutures. The oesophageal bleeding stopped, and the nasogastric tube was kept in place. Outcome: Twenty-four hours later a CT scan showed wise ischaemic lesions on both hemispheres, the patient never recovered her neurological state, and died of multiorgan failure 20 days after the second intervention. Note: This case is the only procedure-related complication in 32 cases. Suggest that patients with a thin atrial wall resulting from atrial enlargement (> 60 mm diameter), as well as female patients, should be treated more cautiously. Now take the precautions of: 1) passing a gauze pad through the oblique sinus of the pericardium, 2) use continuous irrigating devices rather than the “dry” ones, 3) refrain from overlapping ablation lines (this requires considerable expertise), and 4) connecting the two circles with the transverse line at a higher level to avoid direct heat transmission to the oesophagus. Appendix E.1: Methods of measurement of atrial contraction. Level Method of Measurement CRYOTHERAPY ABLATION Non-randomised Comparative Studies Biatrial CA versus CS Sueda et al.1997 III-3 Transthoracic and transoesophageal echocardiography Yuda et al.2004 III-2 Doppler echocardiography Left atrial CA versus CS Gaita et al.2000 III-2 CA versus Maze-III Ishii et al.2001 III-3 Kim et al.2001 III-3 Kosakai et al. 1995 III-2/3 Lee et al. 2001 Case Series Biatrial Ad et al. 2003b (AHA) Fukada et al. 1998 III-3 IV IV Definition of Atrial Contraction Presence of an atrial kick. A-wave peak velocity ≥ 10 cm/s arbitrarily considered evidence of effective atrial contraction. Doppler echocardiography Not stated Transthoracic Doppler echocardiography Transthoracic Doppler echocardiography Atrial filling fraction and peak A/E ratio. No cut-off point stated. Presence of the A and E wave on the tricuspid and mitral inflow, respectively. When presence of A wave in the ventricular inflow was ambiguous, the systemic venous flow or pulmonary venous flow pattern evaluated for the presence of atrial reversal. Presence of an atrial A-wave. Transthoracic Doppler echocardiography Doppler echocardiography Presence of an atrial A-wave Yuda et al. 2001 Left atrial Imai et al. 2001 IV Doppler echocardiography Transthoracic Doppler echocardiography Doppler echocardiography IV Doppler echocardiography Kondo et al. 2003 Manasse et al. 2003 Sueda et al. 2001 IV IV IV Doppler echocardiography Transthoracic echocardiography Transthoracic echocardiography RADIOFREQUENCY ABLATION RCT Biatrial RFA versus CS II Transthoracic Doppler Khargi et al. 2001 echocardiography Deneke et al. 2002 Level II Non-randomised Comparative Studies Biatrial RFA versus CS III-2 Transthoracic Doppler Chen et al. Level III-2 echocardiography Patwardhan et al. 2003 III-2/3 Left atrial RFA versus CS Mantovan et al. III-2 Not stated Grades of atrial contractility determined by measurement of peak velocity of A-wave to E-wave. Transmitral wave ≥ 10 cm/s. Detectable A-wave on transmitral and transtricuspid flow. An A/E ratio of > 0.3 was stated as good recovery of Awave. Presence of an A-wave. Valid transmitral and/or tricuspid waves of > 0.3 m/s. ‘…apparent transvalvular flow during the atrial systolic phase..’ Presence of an A-wave. Pulsed-wave Doppler interrogation of the left and right ventricular inflows performed at the valve leaflet tips as they opened, or at the centre of the valve prosthesis on the apical four-chamber view. Peak velocities measured and averaged over five consecutive cardiac cycles. Transtricuspid A waves of ≥ 15 cm/s. Transmitral A waves of ≥ 25 cm/s. Presence of an A-wave. Doppler echocardiography Doppler echocardiography Atrial contraction considered to be present when transtricuspid and transmitral flow showed A-wave width at least 50% of the E-wave. Transthoracic Doppler echocardiography ‘Detection of E and A waves was used in evaluating the atrial contraction.’ RFA versus Maze-III Chiappini et al. III-3 378 Biatrial versus left atrial RFA III-2 Güden et al. III-2 Transthoracic Doppler echocardiography Doppler echocardiography Deneke et al. Case Series Biatrial RFA Hornero et al. 2002 Prasanna et al. IV IV Doppler echocardiography Transthoracic Doppler echocardiography Sie et al. IV Sos et al. Left atrial RFA Benussi et al. IV Transthoracic and transoesophageal Doppler echocardiography Doppler echocardiography IV Doppler echocardiography Kress et al. Le Tourneau et al. 2003 (abstract) Müller et al. IV IV Doppler echocardiography Doppler echocardiography IV Ruchat et al. IV Transoesophageal Doppler echocardiography Transthoracic Doppler echocardiography Not stated Detection of E- and A-waves. Transvalvular A-waves of >25 cm/s Transmitral flow velocities measured with a sample volume positioned at the level of the mitral tips in apical four chamber view. Effective left atrial transport considered a transmitral A-wave > 40 cm/s. Presence of an A-wave Presence of an A-wave A sample volume was positioned at the level of the tip of the atrio-ventricular valve in the apical four-chamber view. Peak velocities of the A- and E-waves were determined as the average of three consecutive beats. A peak A-wave velocity of 10 cm/s was arbitrarily considered as the cut-off for an effective atrial contraction. Not stated Not stated Presence of an A-wave Follow-up performed by the same cardiologist. Transport function, defined as the ratio of the peak velocity of the A and E waves (A/E ratio), with a normal range between 0.51.2, depending on the age of the patient. <0.5 was absence of efficient atrial transport. Presence of an A-wave. Starck et al. IV Doppler echocardiography MICROWAVE ABLATION Non-randomised Comparative Studies III-2 Transthoracic Doppler Spitzer and Knaut 2002 echocardiography III-? Doppler echocardiography Knaut et al. 2003 (abstract) Case Series Left atrial MWA Knaut et al. 2002 IV Transthoracic Doppler echocardiography Venturini et al. 2003 IV Not stated Not stated Presence of an A-wave (Knaut et al. 1999) Haemodynamic response of atrial contraction assessed by identifying a biphasic wave at the level of the tricuspid and mitral valves using colour-coded Doppler echocardiography. Left atrial function defined by the Atrial filling fraction (AFF) = Percentage of the diastolic ventricular filling given by the atrial contraction: [(Vti a)/(Vti a + Vti e)] where: Vti a = late velocity time integral Vti e ; early velocity time integral Severe impairment: AFF < 20% Mild to moderate impairment: AFF 20%-29% Normal: AFF > 30% Doppler echocardiography 379 Appendix E.2: Use of antiarrhythmic medication following surgery Study Level n n CRYOTHERAPY ABLATION Non-randomised comparative studies Biatrial CA versus CS Handa et al. III-2 58 39 1999 Sueda et al. III-3 36 15 1997 Left atrial CA versus CS Gaita et al. III-2 32 18 2000 CA versus Maze-III Kosakai et al. III-2/3 14 17 1995 70 Kosakai maze versus CA Nakajima et al. 2002 Case series Biatrial Fukada et al. IV 29 1998 Shimizu et al. IV 6 1997 Left atrial Imai et al. IV 32 2001 Kondo et al. 2003 Manasse et al. IV 95 2003 Sueda et al. IV 12 2001 RADIOFREQUENCY ABLATION Non-randomised comparative studies Biatrial RFA versus CS Khargi et al. II 15 15 2001 Chen et al. III-3 13 58 2001 48 Patwardhan et III-3 84 64 al. 2003 Left atrial RFA versus CS Guang et al. III-2 96 87 2002 Mantovan et III-2 103 27 al. 2003 RFA versus Maze-III Chiappini et III-3 40 30 al. 2004 Biatrial versus left atrial RFA Deneke et al. III-2/3 49 21 2003 Güden et al. III-2 39 23 2002 Case series Biatrial Hornero et al. IV 55 2002 Prassanna et IV 25 al. 2001 Raman et al. IV 132 2003 Sie et al. 2001 IV 122 Sos et al. 2002 IV 10 Drugs Period drugs routinely given Type not specified. 6-8 weeks Low dose digoxin and disopyramide (Class I). 6 months (disopyramide) Amiodarone in all patients but one, given propafenone. Withdrawn after 3 months in absence of AF recurrence Only used to treat postoperative arrhythmias. Not routinely given. Only used to treat perioperative AF or atrial flutter. Not routinely given. Digoxin and procainamide 3 months None Hospital discharge Class I or IV and digitalis. 3-6 months Only used to treat perioperative AF, when class I or IV given. Amiodarone or propafenone if dysthyroidism present. Digoxin and disopyramide. Not routinely given. Amiodarone or metoprolol 3-6 months Hospital discharge 6 months Antiarrhythmic drugs not used. Amiodarone 3 weeks Antiarrhythmic drugs used in patients with arrhythmias postoperatively. Amiodarone 24 hrs Amiodarone as drug of choice. 6 months Sotalol to 4/99 and metoprolol after 4/99. ≥ 6 months Amiodarone 3 months Amiodarone 3 months Amiodarone 3 months Patients encouraged to take low dose amiodarone unless contra-indicated. Variable compliance by patients and treating surgeons. Used to treat postoperative atrial arrhythmias. Amiodarone and other drugs (digoxin, calcium antagonists, β-blockers) added when required. 380 60 days Left atrial Benussi et al. 2002 Geidel et al. 2003 Hemmer et al. 2000 Kottkamp et al. 1999 Kress et al. 2002 Mohr et al. 2002 Müller et al. 2002 IV 132 IV 29 IV 42 IV 12 Only used for postoperative AF or atrial flutter. Sotalol used to treat postoperative AF IV 23 Amiodarone IV 65 IV 95 Used to treat postoperative AF. (amiodarone, sotalol, flecainide) Only used for AF recurrence (digoxin plus verapamil or sotalol, or sotalol or amiodarone alone). Used to treat recurrent AF or atrial flutter. Ruchat et al. IV 40 2002 Starck et al. IV 100 2003 Williams et IV 48 al. 2001 MICROWAVE ABLATION Case series Biatrial Chiappini et IV 10 al. 2003 Left atrial Knaut et al. IV 105 2002 Venturini et IV 41 al. 2003 Zembala et al. IV 42 2003 Amiodarone: 119/132 Propaphenon: 8/132 Sotalol: 1/132 None: 4/132 Amiodarone 6 months 3 months 3 months 6 months (‘routinely used’) Only for recurrent AF or atrial flutter. If AF recurred, low dose amiodarone. Amiodarone 6 months Sotalol 3 months Early atrial arrhythmias treated with amiodarone. Sotalol 90 days 381 Appendix E.3: Conditions to discontinue anticoagulant therapy Study Level n CRYOTHERAPY ABLATION Non-randomised comparative studies Schaff et al. III-2/3 173 2000 42 Gaita et al. III-2 32 2000 18 Handa et al. III-2 58 1999 39 Ishii et al. III-3 32 2001 13 Kosakai et al. III-2/3 14/70 1995 14 Nakajima et III-3 al. 2003 Case Series Biatrial Fukada et al. IV 29 1998 Izumoto et al. IV 104 2000 Left atrial Kondo et al. IV 31 2003 Manasse et al. IV 95 2003 RADIOFREQUENCY ABLATION RCT Khargi et al. II 2001 Non-randomised comparative study Chen et al. III-3 2001 Guang et al. III-2 2002 Güden et al. 2002 Mantovan et III-2 al. 2003 Patwardhan et III-3 al. 2003 Case series Biatrial Hornero et al. IV 55 2002 Prasanna et al. IV 25 2001 Sos et al. IV 10 2002 Left atrial Benussi et al. 2002 Geidel et al. 2003 Kottkamp et al. 1999 Kress et al. 2002 Mohr et al. 2002 Müller et al. 2002 Ruchat et al. 2002 Starck et al. 2003 Drugs Warfarin used routinely during first 6 weeks Routinely used 3 months. Discontinued in patients with valve repair in SR with atrial contraction confirmed by echocardiogarphy Warfarin routinely used 3-6 months after MV repair Warfarin routinely used for 3 months Discontinued in patients with atrial rhythm and documented atrial contraction 3-6 months postoperatively If consistent SR maintained, anticoagulation stopped at 3 months in patients with MV plasty or biological valves. If contraction of the left atrium was absent or left atrial dimension > 55 mm, aspirin was given. Warfarin used in all patients with valve replacement, and in patients with valve repair aspirin was used for 3 months postoperative All patients for 3 months. Discontinued in patients with repaired valves, or biological prostheses. Warfarin used in every case with MVR or persistent AF Withdrawn at 3 months in the absence of mechanical prosthesis All patients received warfarin Warfarin used in all patients. Discontinued only when patients had SR and documented atrial contraction by echocardiography Warfarin routinely used in patients with MVR Warfarin continued in patients with mechanical valves Warfarin discontinued at 3-6 months in patients with stable SR, biatrial contraction, and no mechanical prosthesis Used in patients with mechanical valves Discontinued at 3 months in patients without mechanical prosthesis, and with effective echocardiographic evidence of atrial contraction All patients not on warfarin for mechanical valves were placed on enteric-coated aspirin life-long Discontinued in patients in third month without mechanical prosthesis and with effective atrial contraction in echocardiographic controls IV 132 IV 12 Discontinued in patients with stable SR and documented atrial contraction after valve repair, or replacement with biological prosthesis Given for 3 months in patients with valve repair or biological valves, and life-long with mechanical valves. Used at least 6 months IV 23 All patients anticoagulated at least 6 weeks IV 65 IV 95 IV 40 Patients in stable SR without antiarrhythmic medication for 3 months, patients with antiarrhythmic medication for 6 months Warfarin recommended for 6 months, then discontinued or replaced with aspirin in patients with stable SR by 24 hr Holter monitoring and normal or nearly normal left atrial contraction by echocardiogram. Discontinued in patients with ‘real’ atrial transport demonstrated. IV 100 Discontinued in patients with regular supraventricular rhythm, recovery of atrial contraction, and no other reason for anticoagulation eg. mechanical valve 382 Williams et IV 48 al. 2001 MICROWAVE ABLATION RCT Schuetz et al. II 24 2003 19 Non-randomised comparative studies Spitzer and III-2 136 Knaut et al. 51 2002 Case Series Biatrial Chiappini et IV 10 al. 2003 Left atrial Knaut et al. 2002 IV 105 Recommended for 3 months if not otherwise required eg. mechanical valve All patients on phenprocoumon for a minimum of 3 months Discontinued at 3 months in all patients with stable SR and no mechanical valve. Warfarin stopped after 6 months in patients with reconstructive surgery or biologic prosthesis in SR, and with left atrial contraction documented by echocardiography. Stoped after 3 months in patients with reconstructive surgery and in SR. 383 Appendix E.4: Analysis of risk factors for recurrence of AF Study Level CRYOTHERAPY Non-randomised comparative Handa et al. 1999 III-2 Method Significant Univariate analysis No CA Hazard Ratio 4.27 95% CI: 2.07-8.85 (p<0.00001) Preoperative left atrial dimension Hazard Ratio 1.05 95% CI: 1.01-1.10 (p=0.01) Chronic AF Hazard Ratio 2.01 95% CI: 1.03-4.03 (p=0.05) No CA Hazard Ratio 4.4 95% CI: 1.9-10.5 (p=0.0007) Chronic AF Hazard Ratio 3.3 95% CI: 1.1-9.8 (p=0.03) Pre-operative severe tricuspid regurgitation p<0.05 CS n=58 CA n=39 Multivariate analysis Cox proportional hazards model Sueda et al. AF- n=31 AF+ n=5 Kosakai et al. 1995 AF- n=87 AF+ n=14 III-3 Students t-test or X2 III-2/3 Students t-test or X2 Non-significant (AF+ versus AF-) Preoperative Giant left atrium 6(43%) versus 11(13%) p<0.02 Duration of AF (years) 14.0[6.4] versus 8.0[6.8] p<0.001 Left atrial dimension (mm) 66.6[18.4] versus 55.6[11.7] p<0.001 Cardiothoracic Ratio (%) 69.8[12.0] versus 62.3[8.3] p<0.001 Postoperative Left atrial dimension (mm) 50.3[7.0] versus 43.1[7.2] p<0.001 Cardiothoracic ratio, 1 month (%) 61.9[5.4] versus 57.7[5.4] p<0.05 Cardiothoracic ratio, 3 months (%) 63.4[12.0] versus 55.9[7.2] p<0.05 384 Preoperative left atrial dimension Hazard Ratio 1.0 95% CI: 1.0-1.1 Age, AF duration, left atrial size (pre- and postoperative), cross clamping time, CPB time. NYHA class, ages, Mitral related disease, rheumatic heart disease, F wave, redo operation, operative date, arrest time, CPB time, repair, intra-aortic balloon pumping, blood loss. Appendix E.4 continued Study Case Series Biatrial Fukada et al. 1998 Level Method Significant Non-significant IV Student’s t test Age, sex, left atrial diameter, sinus node artery variation Yuda et al. 1998 IV X2 analysis Atrial rhythm (AR, n=17) Non atrial rhythm (NAR, n=12) Duration of AF (yrs) AR: 4.8[4.9] NAR: 14.9[11.2] p=0.004 f-wave (mV) AR: 0.24[0.08] NAR: 0.16[0.10] p=0.028 Rheumatic heart disease AR: 10/7 NAR: 12/0 p=0.023 Giant left atrium (GLA, n=19) Non-GLA (n=32) SR GLA: 58% Non-GLA: 84% p<0.05 Left atrial Imai et al. 2001 IV Fischer’s exact test Duration of AF (yrs) SR (n=24): 7.7[7.2] AF (n=8): 13.6[5.6] p=0.025 Kondo et al. 2003 IV X2 or Mann-Whitney U test Manasse et al. 2003 IV Univariate logistic regression model. SR (n=21) AF (n=6) Preoperative Duration of AF (months) SR: 48.6[54.2] AF: 119.3[98.2] p=0.04 f-wave at V1 (mV) SR: 0.24[0.08] AF: 0.12[0.08] p=0.03 Cardiothoracic ratio SR: 56.7[4.9] AF: 66.7[6.1] p=0.03 Sinus rhythm at discharge Age OR 0.92 (95% CI: 0.87-0.97) p<0.01 Preoperative factors Sex, age at surgery, f-wave, cardiothoracic ratio, left ventricular ejection fraction, left atrial dimension Intraoperative factors Duration of CPB, duration of cross clamping, tricuspid valve surgery, surgery to 3 valves Preoperative Age, sex, previous operation, left atrial diameter, tricuspid regurgitation. Operative Operation time, CPB time, cross clamping time, tricuspid annuloplasty. Postoperative Hospital stay Sex, left atrial diameter, AF duration, persistent AF, organic MV disease, tricuspid valve plasty, mitral stenosis, ablation pattern. Sex, left atrial diameter, AF duration, persistent AF, organic MV disease, tricuspid valve plasty, mitral stenosis, SR under treatment Multivariate logistic regression model Sinus rhythm at 6 months Age OR 1.08 (95% CI: 1.02-1.14) p=0.01 Ablation pattern (4 pulmonary veins) OR 3.92 (95% CI: 1.16-13.22) p=0.03 AF at discharge OR 8.27 (95% CI: 2.57-26.58) p<0.01 Ablation pattern (4 pulmonary veins) OR 6.78 (95% CI: 1.52-30.19) p=0.01 AF at discharge OR 7.39 (95% CI: 1.93-28.32) p<0.01 385 Age, sex, left atrial diameter, AF duration, persistent AF, organic MV disease, tricuspid valve plasty, mitral stenosis, SR under treatment Naito et al. 2001 IV NS Usui et al. 2002 IV Univariate unconditional logistic regerssion Method Study Level RADIOFREQUENCY Non-randomised Comparative Studies Chen et al. 2001 III-2 Maze Group Students t-test or Fishers exact test. Significance of multiple variables using stepwise discriminant analysis. Control group Students t-test Mantovan et al. 2003 III-2 Univariate linear regression analysis Predictive factors for maintenance of SR after ablation were age (< 75 years), left atrial diameter (< 60 mm) and duration of AF (< 8 years). Predictors of postoperative atrial flutter Age OR 0.879 p=0.0 Significant Maze Group Postoperative right atrial area (cm2) SR+: 18.1[4.4] SR-: 28.5[8.2] p=0.008 Postoperative left atrial diameter (mm) SR+ (n=49): 45.0[7.0] SR- (n=8): 51.0[8.0] p=0.03 Postoperative right atrial area Cutoff value 22.5 cm2 p=0.0001 Sensitivitya- 85.7% Specificityb- 66.7% Postoperative left atrial diameter Cutoff value 48.3 mm p=0.013 Sensitivity- 77.6% Specificity- 55.6% Control group Preoperative left atrial diameter (mm) SR+: 45.5[8.8] SR-: 59.6[12.3] p=0.009 On hospital discharge (SR n=65 AF n=38) Sex (female): SR: 54% AF: 76% p=0.03 Rheumatic heart disease: SR: 34% AF: 63% p=0.004 AF duration (months) SR: 33[34] AF: 53[56] p=0.035 Left atrial diameter (mm): SR: 55[9] AF: 59[8] p=0.04 On Follow-up (SR n=83 AF n=19) Rheumatic heart disease: SR: 38% AF: 68% p=0.022 AF duration (months): SR: 31[30] AF: 78[68] p=0.0008 At 1 year (SR n=54 AF n=7) Rheumatic heart disease SR: 37% AF: 63% p=0.041 386 Non-significant Maze Group Preoperative: Left atrial diameter, left atrial area, right atrial area. Postoperative: Left atrial area On discharge Age, mitral valve disease, paroxysmal AF, antiarrhythmic drugs, left ventricular ejection fraction On follow-up Sex, age, MV disease, AF duration, antiarrhythmic drugs, left atrial diameter, left ventricular ejection fraction At 1 year Sex, age, MV disease, AF duration, antiarrhythmic drugs, left atrial diameter, left ventricular ejection fraction Appendix E.4 continued Study Case Series Biatrial Hornero et al. 2002 Level Method Significant Non-significant IV Fisher exact test or MannWhitney test. Age, f-wave, reoperation, mitral/tricuspid valve disease, aortic-mitral valve disease, coronary artery disease, congenital heart disease, left atrial area, right atrial diameter, right atrial volume. Thomas et al. 2003 IV Paired t-test Comparison of patients with (AF-AFl, n=6) or without (C, n=46) AF and atrial flutter recurrence AF duration (years) C: 4.6[4.0] AF-AFl: 8.7[3.7] p=0.01 Left atrial diameter (mm) C: 48[7] AF-AFl: 61[6] p=0.01 Volume left atrium (cc) C: 87[30] AF-AFl: 134[43] p=0.01 Area right atrium (cm2) C: 18[3] AF-AFl: 22[5] p=0.03 Left atrial diameter at follow-up SR: 44.8[4.7] AF: 52.3[7.8] p=0.0001 Left atrial Benussi et al. 2002 IV Univariate analysis using Cox proportional-hazards regression model. Age (1 year increase) 1.09 (95% CI: 0.01-1.15) p<0.001 In-hospital postoperative arrhythmias Yes: 67% (95% CI: 55-79%) No: 90% (95% CI: 82-98%) Log rank test = 0.001 Duration of preoperative AF Multivariate proportionalhazards regression models. Duration of preoperative AF Le Tourneau et al. 2003 IV NS Müller et al. 2002 IV Univariate analysis Multivariate analysis Ruchat et al. 2002 IV Paired t- test Age (1 year increase) 1.07 (95% CI: 1.02-1.12) p=0.004 Early postoperative arrhythmias (yes/no) 2.48 (95% CI: 1.20-5.12) p=0.015 Predictive factors for AF recurrence (n=70) Rheumatic valve lesions p=0.005 Preoperative left ventricular ejection fraction: p=0.01 Previous MV surgery: p=0.047 Replacement of repair valve surgery: p=0.05 Predictors of postoperative AF (n=95) Presence of coronary artery disease p=0.033 Coronary artery disease OR 7.5 (95% CI: 2.24-25.13) p=0.027 Duration of chronic AF (SR n=25 AF n=12) SR: 19[25] AF: 68[63] p=0.01 387 Age, sex, height, weight, body surface area, MV disease, MV regurgitation, mitral stenosis, previous MV surgery, tricuspid valve disease, tricuspid incompetence, AV disease, aortic regurgitation, aortic stenosis, previous myocardial infarction, previous CABP, ascending aortic aneurysm, atrial septal defect and persistent foramen ovale, pulmonary hypertension, MV repair, RV repair, AV repair, MVR, AVR, CABG, ascending aorta replacement, closure of atrial septal defect or persistent foramen ovale, redo operation, duration of AF, LVEF, left ventricular end-diastolic diameter, right ventricular ejection fraction, right ventricular en-diastolic diameter, left atrial diameter, left ventricular end-diastolic pressure Left atrial diameter MICROWAVE ABLATION Case Series Zembala et al. 2003 IV Univariate analysis Risk of AF at hospital discharge (n=42) SR n=32 AF n=10 AF duration (years) SR: 3.6[2.3] AF: 7.4[3.5] Unadjusted OR: 1.64 (95% CI: 1.15-2.35) p=0.01 Left atrial diameter (mm) SR: 54.9[7.5] AF: 64.4[9.9] Unadjusted OR 1.14 (95% CI: 1.03-1.26) p=0.01 388 Sex, age, order of surgery, concomitant procedure.
