1. Long-term Efficacy and Safety of Catheter Ablation for AF: What is the Evidence? AHA QCOR Washington DC D. George Wyse MD PhD May 20, 2010

2. Disclosures* * All < $10,000 DSMB, SC or Grant Reviewer (Research) Advisory Board Speaker Boerhinger Ingelheim (PHRI); RE-LY; RE-LYABLE Medtronic (Mayo) – TRENDS; PACIFIC Sanofi Aventis/Bristol Myers Squibb (PHRI) - ACTIVE-A; ACTIVE –W; ACTIVE-I Bristol Myers Squibb/Pfizer (DCRI) – ARISTOTLE Sanofi Aventis – BOREALIS, DETECT-AF Biotronik (Axio) - IMPACT Boston Scientific/Guident (PHRI) - SIMPLE NHLBI (DCRI; U Penn) – TACT; COAG European Commission – FP-7 Grant Applications Sanofi Aventis (PHRI) – POSEIDON Merck Bayer Sanofi Aventis BMS PHRI – Population Health Research Institute – McMaster University DCRI – Duke Clinical Research Institute; Mayo – Mayo Clinic Axio – Axio Research Corporation U. Penn – University of Pennsylvania

3. Outline Key Patient Characteristics of RCT of LA/PV RFA and AAD Quantitative “Gradient” between Groups of SR vs. AF in AAD vs. RFA RCT Goals for Therapy of AF Reduce Mortality Prevent Stroke/SE Preserve/Improve Ventricular Function and Prevent CHF Relief of Symptoms RFA of AV Junction and Pacemaker

4. Age and Duration of Follow-up in RTC of LA/PV Catheter Ablation for RFA StudyNMean/median AgeMean FU Haissaguerre (2000)90510.7 Natale (2000)15590.8 Oral (2003)40510.5 RAAFT Pilot (2005)70531.0 APAF (2006)198561.0 CACAF (2006)137621.0 A4 (2008)112511.0 CABANA Pilot (2009)60641.0 AAD RCT: AFFIRM, AF-CHF & ATHENA N = ~ 10,000 Mean Age = 70y Mean FU = 4.5y Table unpublished, courtesy of Win Shen – Mayo University

5. Quantitative “Gradient” SR vs. AF; AAD vs. RFA New Engl J Med 2002;347:1825 New Engl J Med 2008;358:2667 New Engl J Med 2008;359:1778 AF-CHF AFFIRM PABA-CHF – not “prevalence” Gradient = 40% Gradient = 70% Gradient = 40%

6. Goals of Therapy for AF

7. Reduce Mortality

8. Death After RFA for AF Short-term Circulation 2005;111:1100 Percent Based on 45, 115 procedures in 35, 569 patients between 1995-2006 = 0.98 per 1,000 JACC 2009;53:1798

9. Death After RFA for AF Long-term J Am Coll Cardiol 2003;42:185 65 ± 9 years PAF = 69% No CV Dis = 34% LVEF = 54 ± 12% Death in RCT vs. AAD RR = -0.003 (95% CI -0.01- 0.02; p = 0.74) Am Heart J 2009;158:15 + Annual Mortality in AFFIRM ~ 3.5%

10. Prevent Stroke/SE

11. Stroke/TIA from RFA for AF Short-term “Yin-Yang” of Anticoagulation Circulation 2005;111:1100 Percent

12. Stroke/SE after RFA Short-term Circulation 2006;114:759 Stroke in RCT vs. AAD RR = 0.004 (95% CI -0.01-0.02; p = 0.54) Am Heart J 2009;158:15

13. Impact of Absence of AF on Stroke * Neurology 1993;43:32 & Arch Intern Med 2005:165:1185

14. Perception of AF after RFA Circulation 2005;112:307 Episodes of AF% Episodes with No Symptoms

15. AF Patterns Before/After AF Ablation with 24/7 Monitoring J Cardiovasc Electrophysiol 2007;18:818 “Permanent Cure” after 3 mo blanking = 3/14

16. Preserve/Improve Ventricular Function & Prevent CHF

17. RFA and LV Function A meta analysis of RCT A = RR for reduced LVEF vs. normal LVEF B = Absolute % LVEF after vs. before RFA

18. Relief of Symptoms

19. Symptoms Ablation vs. AAD J Am Med Assoc 2010;303:333 Symptomatic AF Failed at least 1 AAD No amiodarone in 6 months LA diameter <5cm Mean age = 56y Mean follow-up = 13 months

20. Symptoms of AF CCS- SAF Class N = 484 Circ Arrhythmia EP 2009:2;218 Symptom Class Percent

21. CABANA Trial Design Qualifying AF RF Ablation PV isolation ± Center Preferred Enhancements Drug Therapy Rate or Rhythm Control R

22. Ablate [and Pace]

23. Effects of AV Junction Ablation & Pace A Meta Analysis Circulation 2000;101:1138

24. PACIFIC Trial Pilot R R