Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Presenter Disclosure Information John F. Beshai, MD RethinQ Trial Results Disclosures Information: The following relationships exist related to this presentation: Consultant - St. Jude Medical, Atricure Research Grant - St. Jude Medical R Grimm : Speaker - St. Jude, Medtronic, GE Research Grant - GE S Nagueh: Speaker - Medtronic Consultant - St. Jude J Baker : no disclosures S Beau: no disclosures S Greenberg: Consultant - Medtronic, St. Jude, Boston Scientific L Pires: Consultant - St. Jude P Tchou: no disclosures The Resynchronization Therapy in Normal QRS (RethinQ) Study John F. Beshai, MD, Richard A. Grimm, DO, Sherif F. Nagueh, MD, James H. Baker II, MD, Scott L. Beau, MD, Steven M. Greenberg, MD, Luis A. Pires, MD, Patrick J. Tchou, MD for the RethinQ study investigators Study Sponsored by St. Jude Medical Background • Currently, indications for cardiac resynchronization therapy (CRT) include QRS duration > 120ms, LVEF < 35% and NYHA Class III-IV. • 20-30% of patients do not respond to CRT despite application of established selection criteria. • Patients with normal conduction or a slightly prolonged QRS duration also exhibit mechanical abnormalities due to intraventricular dyssynchrony. • Myocardial Tissue Doppler Imaging (TDI) allows both the velocity and timing of regional longitudinal motion to be measured. • LV dyssynchrony may also be useful in predicting the benefit of CRT before implantation of the pulse generator. Hypothesis • We hypothesized that patients with NYHA class III, left ventricular ejection fraction less than or equal to 35%, narrow QRS duration < 130 ms, and evidence of mechanical dyssynchrony on echocardiography may benefit from cardiac resynchronization therapy. Study Design Overall Objective Determine CRT safety and efficacy in patients who are candidates for an ICD with NYHA Class III, narrow QRS duration (<130 ms) and evidence of mechanical dyssynchrony as measured by echocardiography/Tissue Doppler Imaging Primary Endpoint Improvement in Peak VO2 during CPET of at least 1.0ml/kg/min at 6 months. Secondary Endpoints Improvement in quality of life score at 6-months Improvement in NYHA classification at 6-months Inclusion and Exclusion Criteria Inclusion Criteria Exclusion Criteria • NYHA class III HF • NYHA class I, II, or IV • LVEF ≤ 35% • Permanent Atrial Fibrillation • Evidence of mechanical dyssynchrony • Recent MI, unstable angina or cardiac revascularization • QRS duration < 130ms • Prior cardiac resynchronization therapy Echo Criteria for LV Dyssynchrony Mechanical dyssynchrony considered present if either • M-Mode - Septal posterior wall mechanical delay (SPWMD) ≥ 130 ms OR • Tissue Doppler Imaging (TDI) of the basal ventricular segments in apical 4/2/3 chamber views - Septal to lateral delay ≥ 65ms OR - Antero-septal to posterior delay ≥ 65ms Study Design 172 patients randomized in 34 centers Randomized to CONTROL or CRT Stratified by QRS < 120 ms or ≥ 120 ms And Ischemic or Non-ischemic CM CONTROL Followed for 6-months CRT Followed for 6-months Results Baseline Characteristics Control (n = 85) CRT (n = 87) Age (yr), Mean ± SD 58 ± 14 60 ± 12 Male sex, n(%) 49 (58%) 62 (71%) NYHA III, n(%) 84 (99%) 87 (100%) QRS Duration (ms), Mean ± SD 106 ± 13 107 ± 12 Ischemic Cardiomyopathy, n(%) 43 (51%) 47 (54%) 26 ± 6 25 ± 5 77 (91%) 79 (93%) 74 (87%) 10 (12%) 77 (89%) 84 (97%) 73 (84%) 7 (8%) Left ventricular ejection fraction (%) Medications, n(%) ACE inhibitor or substitute§ Beta-Blocker Diuretic § Antiarrhythmic Includes ARBs and other ACE substitutes, including Hydralazine Baseline Mechanical Dyssynchrony Mechanical Dyssynchrony Control CRT Parameters ms ms SPWMD - M-Mode n = 12 n=9 Mean ± SD 165 ± 27 151 ± 22 Septal to lateral - TDI n = 69 n = 67 Mean ± SD 99 ± 29 96 ± 28 Antero-septal to posterior n = 55 n = 59 - TDI 106 ± 29 94 ± 23 Mean ± SD Baseline Echocardiographic Data LV end systolic diameter (mm) Mean +/- 1 SD p = 0.06 40 40 60 60 p = 0.29 80 80 LV end diastolic diameter (mm) Mean +/- 1 SD n = 87 20 n = 85 Control CRT 0 0 20 Control n = 85 CRT n = 87 Baseline Echocardiographic Data (Cont) LV end systolic volume (mL) Mean +/- 1 SD 300 300 LV end diastolic volume (mL) Mean +/- 1 SD Control n = 87 50 50 0 Control 0 n = 85 CRT 100 200 100 p = 0.43 200 p = 0.61 n = 85 CRT n = 87 Baseline Evaluations Peak VO2(ml/kg/min) Exercise Duration (min) 15 Mean +/- 1 SD p = 0.85 p = 0.85 5 5 10 15 10 20 25 Mean +/- 1 SD Control n = 85 n = 87 0 0 n = 85 Control CRT CRT n = 87 Baseline Evaluations (Cont) Six-minute Hall Walk Distance (m) Mean +/- 1 SD 400 p = 0.43 p = 0.95 40 200 60 300 80 100 Quality of Life Score Mean +/- 1 SD 20 Control n = 85 n = 87 0 0 n = 85 CRT 100 Control CRT n = 87 Patient Flow Analysis • 172 patients randomized (87 CRT and 85 control) • 11 patients in CRT group and 5 patients in control group not included in endpoint analysis –< 6 months of follow up (7 patients) –Unable to complete CPET at 6 month visit for reason other than worsening HF (3 patients) –Death not due to worsening HF (3 patients) –Withdrawal prior to 6 month visit (3 patients) • 156 patients (76 CRT and 80 control) were available for efficacy analysis Results - Primary Endpoint Peak VO2 (ml/kg/min) Median & 95% CI p = 0.63 41% 46% 0 8 p = 0.75 20 10 40 60 12 80 14 100 % Improved in Peak VO2 Baseline 6-months Control (n = 80) CRT (n = 76) Control n = 80 CRT n = 76 Results - Secondary Endpoints Quality of Life NYHA Class 70 100 Median & 95% CI p = 0.006 64% 54% 50 60 60 80 p = 0.91 40 41% 20 40 29% 0 30 8%5% Baseline 6-months Control (n = 80) CRT (n = 76) Improved No Change Worsened Control (n = 80) CRT (n = 76) LV Volumes and Dimensions Change in LVEDD/ LVESD Median & 95% CI p = 0.71 p = 0.81 LVEDV LVESV p = 0.49 p = 0.34 LVEDD LVESD -40 -4 -2 -20 0 0 2 10 4 Change in LVEDV/ LVESV Median & 95% CI Control CRT Peak VO2 by sub-group Peak VO2 (% improved from baseline) (% improved from baseline) 100 100 Peak VO2 p = 0.82 p = 0.45 p = 0.25 40 40 60 60 80 80 p = 0.02 n = 55 CRT n = 41 n = 59 CRT n = 40 Control n = 36 n = 39 0 n = 25 Control 0 20 Control n = 17 Control 20 CRT CRT QRS ≥ 120 ms QRS < 120 ms Ischemic Non-ischemic Summary • This prospective, multi-center, randomized trial was designed to evaluate the effectiveness of CRT therapy in a HF population with narrow QRS duration and evidence of mechanical dyssynchrony. • There was no statistical significant difference in the change in Peak VO2 between the treatment and control group during cardiopulmonary exercise testing. • No improvement in other objective parameters including 6-minute walk test, LV reverse remodeling, and secondary endpoint - quality of life score . Summary • NYHA class improved to a greater extent in the treatment group than in the control group. • Although numbers were small in the sub-group analysis, there was no statistically significant difference in the primary endpoint between ischemic and non-ischemic patients. • Patients with QRS duration 120 - 130 ms demonstrated an improvement in peak VO2. Conclusion • CRT did not improve Peak VO2 during exercise in patients with NYHA Class III heart failure, QRS duration <130ms, EF ≤ 35% and mechanical dyssynchrony as specified in this trial. • While there was a statistically significant improvement of NYHA class, a secondary endpoint, there was no improvement in qualityof-life, 6-minute walking test, or echocardiographic measures of reverse LV remodeling • A subgroup of patients with QRS duration between 120 ms and 130 ms demonstrated an improvement from CRT, however patients with QRS duration < 120 ms did not demonstrate improvement • The subgroup of patients stratified on the basis of cardiomyopathy etiology did not demonstrate an improvement in peak VO2.