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Current Management of Atrial Fibrillation: An Evidence-Based Approach John D. Hummel, MD Ohio State University Medical Center Ross Heart Hospital Columbus, Ohio Learning Objectives • Understand the guidelines for anticoagulation and where there is latitude for physician decision making. • Be able to discriminate between patients requiring restoration of sinus rhythm vs. rate control alone. • Be able to determine when patients should be evaluated for curative ablation. Projected Number of Adults With AF in the US: 1995 to 2050. Adults with AF, MM 6 5 4.78 5.16 5.42 5.61 4.34 4 3.80 3 2 2.08 2.26 2.44 2.66 2.94 3.33 1 Year Go A, et al. JAMA. 2001;285:2370-2375. 20 60 20 50 20 45 20 40 20 35 20 30 20 25 20 20 20 15 20 10 20 05 20 00 19 95 0 Atrial Fibrillation: Costs to the Health Care System ALOT!! 35% of arrhythmia hospitalizations Average hospital stay = 5 days Mean cost of hospitalization = $18,800 Does not include: Costs of outpatient cardioversions Costs of drugs/side effects/monitoring Costs of AF-induced strokes Estimated US cost burden 15.7 billion Classification of Atrial Fibrillation ACC/AHA/ESC Guidelines First Detected Paroxysmal (Self-terminating) Persistent (Not self-terminating) Permanent DIAGNOSTIC WORKUP • • • • • • • • • • Minimum Evaluation History and physical – Sx with AF, CV dz Electrocardiogram – WPW, LVH, MI Echocardiogram – LVH, LAE, EF, Valve Dz Labs – TSH, Renal fxn, LFTs Additional Testing ETT – CAD, Exercise induced SVT / AF Holter / Event Monitor – Confirm AF and Sxs TEE – LA clot EPS – SVT triggered AF AHA / ACC / ECS Guidelines 2006 Incidence of AF Based on Presence or Absence of OSA 20 – 15 – OSA Cumulative 10 – Frequency of AF (%) 5– No OSA 0– 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Years Number at Risk OSA No OSA 844 709 569 478 397 333 273 214 173 134 110 94 70 46 29 8 2,209 1,902 1,616 1,317 1,037 848 641 502 393 296 217 195 130 94 69 28 Cumulative frequency curves for incident atrial fibrillation (AF) for subjects < 65 years of age with and without obstructive sleep apnea (OSA) during an average 4.7 years of follow-up. p = 0.002 Gami, et al. JACC 2007;49:565-71 AF: TREATMENT OPTIONS Rate control Pharmacologic • Ca2+ blockers • -blockers • Digitalis • Amiodarone Nonpharmacologic • Ablate and pace Prevent remodeling Maintenance of SR Pharmacologic Class IA Class IC Class III -blocker ACE-I ARB Adapted from Prystowsky, Am J Cardiol. 2000;85:3D-11D. Stroke prevention Nonpharmacologic Pharmacologic • Warfarin • Thrombin inhibitor • Heparin • Aspirin Catheter ablation Surgery (MAZE) Nonpharmacologic Pacing • Removal / isolation LA appendage Risk Factors for Thromboembolism in AF High-Risk Factors=2 Previous CVA / TIA / Embolism Mitral Stenosis Prosthetic heart valve Moderate-Risk Factors=1 Age > 75 yrs HTN CHF DM EF < 35% Weaker-Risk Factors~½ Female CAD Thyrotoxicosis Age 65 – 74 yrs AHA / ACC / ECS Guidelines 2006 Recommended Therapy High-risk factor or > 2 moderate-risk factors Coumadin INR 2-3 (mechanical valve INR > 2.5) 1 moderate-risk factor ASA or Coumadin No risk factors ASA 81-325mg daily AF THERAPY ANTITHROMBOTIC RX AND RHYTHM CONTROL OR ? RATE CONTROL AFFIRM Trial: Rate vs Rhythm Control Management Strategy Trial • Design – 5-year, randomized, parallel-group study comparing rate control vs. AARx attempt at NSR – Primary endpoint: overall mortality • Patient population – – – – – – – 4060 patients with AF and risk factors for stroke Minimal symptoms Mean Age = 69 yo Hx of hypertension: 70.8% CAD: 38.2% Enlarged LA: 64.7% Depressed EF: 26.0% The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833. AFFIRM: All-Cause Mortality 30 Rate Rhythm 25 Mortality, % 20 p=0.078 unadjusted 15 p=0.068 adjusted 10 5 0 0 1 2 3 Rhythm N: 2033 1932 Time (years) 1807 1316 Rate N: 2027 1925 1825 The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833. 1328 4 5 780 255 774 236 AFFIRM: Adverse Events Rate Rhythm Ischemic stroke 77 (5.5%)* 80 (7.1%)* INR < 2.0 27 (35%) 17 (21%) Not taking warfarin 25 (32%) 44 (55%) * p=0.79 The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833. Atrial fibrillation Rate control – Drug Therapy: Digoxin – controls resting rate, OK in CHF patients . Beta, Ca+2 blockers – controls resting and exercise rates. Best therapy – combination of beta blocker and digoxin. Even in the best of circumstances pacing support is sometimes required Goal: Chronic afib – mean 24hr HR < 80-90 bpm AF Rate vs. Rhythm Control Trials: Implications • AFFIRM has demonstrated that rate control is an acceptable primary therapy in a selected high-risk subgroup of AF patients • Continuous anticoagulation seems warranted in all patients with risk factors for stroke – Asymptomatic recurrences • Is there a role for rhythm control? Time to first recurrence of AF. Time 0 is the day of randomization 100 – Rate Control 80 – Rhythm Control Percent With AF Recurrence 60 – 40 – Log rank statistic = 58.62 p < 0.0001 20 – 0– 0 1 2 3 4 5 6 Time (years) N, Events (%) Rate control: 563, 3 (0) 167, 383 (69) 98, 440 (80) 42, 472 (87) 10, 481 (92) 2, 484 (95) Rhythm control: 729, 2 (0) 344, 356 (50) 250, 422 (60) 143, 470 (69) 73, 494 (75) 18, 503 (79) Raitt, et al. Am H J 2006 Impact of AF on Risk of Death: Framingham Heart Study Kaplan-Meier mortality curves for age and sex matched subjects (independent of cardiac conditions and risk factors) Benjamin, E. J. et al. Circulation 1998;98:946-95 Improvement in Left Ventricular (LV) Function and Dimensions after Ablation in Patients with Congestive Heart Failure Hsu, L. et al. N Engl J Med 2004;351:2373-2383 Rhythm Control for AF: Commonly Used Oral Antiarrhythmic Drugs Class IA Class IC Class III Quinidine Propafenone Sotalol Procainamide Propafenone SR Amiodarone Disopyramide Flecainide Dofetilide Procainamide, disopyramide, and amiodarone are not FDA-approved for treatment of AF. Miller and Zipes. In: Braunwald, et al (eds). Heart Disease. 6th ed. 2001. ORGAN TOXICITY • Examples: – Lupus, agranulocytosis, thrombocytopenia, optic neuritis, pulmonary fibrosis, hepatitis, etc. • Negligible: – Dofetilide, flecainide, propafenone, sotalol • Acceptable: – Azimilide, disopyramide • High: – Amiodarone, procainamide, quinidine Drug-Induced Proarrhythmia - Torsades Factors Which Influence Ventricular Proarrhythmia Risk • • • • • • • Hypokalemia, hypomagnesemia Long QT at baseline CHF / Decreased EF / Ventricular hypertrophy Bradycardia Female gender Reduced drug metabolism or clearance Amiodarone has lowest risk Alternatives to Drug therapy “Non-Pharmacologic Therapy” Coumadin – LAA closure (Watchman) Rate Control – AVN RFA + PCMK AARx – Adjunctive AFL RFA AARX – Curative Afib RFA WATCHMAN® LAA Filter System Complete AVN ablation Pacemaker Placement AVN RF ablation Objective Benefits of AV nodal Ablation 70 55 50 mean 54 + 7 60 mean 34 + 5 LVESD (mm) LVEF (%) 45 50 mean 43 + 8 40 p < 0.001 30 40 mean 40 + 5 35 30 p < 0.003 25 20 20 Before After A Left ventricular ejection fraction (%) Rodriguez LM. Am J Cardiol. 1993;72:1137-1141. Before After B Left ventricular end systolic diameter (mm) Complete AVN Ablation Advantages: 100% efficacy 85% symptomatic improvement Improved EF (LV remodeling) Eliminates need for rate control drugs Disadvantages: Pacemaker dependant Good Candidates: Tachy / Brady Syndrome PCMK in Place – CHF with BiV device Medication refractory / intolerant Elderly 60 F with PAF treated with Rythmol Presented with recurrent tachycardia Atrial Flutter Circuit Atrial Flutter Circuit Atrial Flutter Ablation Atrial Flutter RFA Atrial Flutter Ablation Approximately 15% of AF patients treated with an AA will develop AFL Advantages: 95% efficacy ≈ 80% arrhythmia control if AARx continued As primary Rx: RFA more effective than AARx Disadvantages: Invasive Good Candidates: Typical AFL (IVC / TV isthmus) Primary AFL or AARx related AFL Pathophysiology of AF • Initiation – Pulmonary vein atrial ectopy • Maintenance – Atrial myocardium • Termination Normal Sinus Rhythm Right & Left Atria Electrograms During AF Surface, Right & Left Atria Surface Right Atrium Disorganized Organized Left Atrium Complex Atrial Anatomy Around Pulmonary Veins Beginnings of “Non Pharmacologic ” Therapies for AFib • Minneapolis Feb 1999 • Haisseguerre – Bordeaux, France • Designed a circular catheter to map the pulmonary veins • “Pulmonary Vein Isolation” • Atrial muscle bundles span the transition zone from the pulmonary veins into the atria – trigger for AFib • Ablation – use energy in the radiowave frequency to dessicate tissue at culprit sites Fib Focal Origin of Atrial Fibrillation Hassaiguerre M, NEJM, 1998 • 94% of AF triggers from Pulmonary Veins • “90 – 95% of all AF is initiated by PV ectopy” RA LA SVC 17 31 FO Pulmonary Veins 6 IVC CS 11 74 yo medically refractory AF, Echo – Normal AA Rx - Verapamil, Rythmol, Betapace, Norpace I II III V1 RSPV dist RSPV prox LIPV RA * Lasso Catheter Circular Mapping & Ablation Catheter in Right Superior Pulmonary Vein Atrial Fibrillation Ablation Atrial Shell and Cardiac MRI 45 yo F with medically refractory Highly Symptomatic PAF 45 yo F with Medically Refractory PAF CT Scan / Carto Images – PA View 45 yo with PAF Conversion of AF to NSR, LSPV with AF Abl Lasso LSPV CS Who Should Have Ablation • Symptomatic Patients • Failed Class I or III Drug therapy • Pts. not tolerating chronic medical therapy Procedure • • • • Arrive on day of procedure “Table-time” - 4 hours Usually discharged the next day Limited activity for 3-5 days then no restrictions Success Rates • • • • >1000 procedures Cure rate is about 80-85% at 1 year 1.45 procedures per pt Success rate is highly dependent on other variables: – – – – – High blood pressure Sleep apnea Number of years with AFib Size of the atria Other heart disease Complications • Complications ≈ 1.5% – – – – – Tamponade – 0.6% Pulmonary vein stenosis – 0.6% TIA / CVA – 0.5% Esophageal-LA fistula - 0 Groin Bleeding / Hematoma • No deaths • No inadvertent damage to the esophagus (Last 200 pts complications < 1%) New Technology Coming to Increase Efficacy and Decrease Risk of Complications Stereotactic – Magnetic Catheter Navigation Energy Sources High Intensity Focused Ultrasound (HIFU) Cryoablation Lasar Left Atrial Appendage Closure Stereotactic Navigation Automatic Catheter Access to Pulmonary Veins Automatic Catheter Access to Right Inferior Pulmonary Vein Point and Click: Mapping Near Site of Early Activation Atrial Fibrillation Ablation Evolution of the Moving Target Esophageal Fistulas Left Atrial Flutters Tamponade TIA/CVA Early Rumors (20 hr cases) Mid 90’s Left Sided Focal IVUS / Transeptal Right Sided Linear WACA + Linear Lasso Hybrid Approaches 3D Mapping CT integration 2006 Fractionated Egms PV Isolation PV Stenosis Phrenic Nerve Injury The Trouble With a Moving Target Back to the Right Side Need for Stereotaxis, Cryoablation, HIFU? A-Fib vs. EP Labs AF TREATMENT GOALS • AF is rarely life-threatening and is typically recurrent • Treatment goals in symptomatic pts – frequency of recurrences – duration of recurrences – severity of recurrences • Minimize risk of tachycardia induced cardiomyopathy • Safety is primary concern Atrial Fibrillation: Ablation vs Drug Rx. Ablation 80% success PV stenosis AE fistula TIA/CVA Drug Rx. 50% success Proarrhythmia End Organ Toxicity No Free Lunch Torsades AE fistula PV stenosis