1. Cardioversion of Atrial Fibrillation Clinical Issues Christopher Granger, MD Director, Cardiac Care Unit Duke University Medical Center December 2007

2. Cardioversion of Atrial Fibrillation Clinical Issues   When and why cardiovert?   Why not wait for spontaneous cardioversion?   When and why acutely cardiovert?   How to acutely cardiovert   Electrical   Pharmacologic   Both

6. AFFIRM Baseline Characteristics  Age = 69.7 ± 9.0 yrs  39% female  > 2 days of AF in 69%  CHF class > II in 9%  Symptomatic AF in 88%  Age = 69.7 ± 9.0 yrs  39% female  > 2 days of AF in 69%  CHF class > II in 9%  Symptomatic AF in 88%

9. Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) Trial (n=522) Van Gelder, I. et al. N Engl J Med 2002;347:1834-1840 CV death, HF, thromboembolic complications, bleeding, pacemaker, and SAEs.

10. Trials of Rate vs Rhythm Control ACC/AHA/ESC Guidelines 2006

12. Implications of Trials: Guideline Statement Theoretically, rhythm control should have advantages over rate control, yet a trend toward lower mortality was observed in the rate- control arm of the AFFIRM study and did not differ in the other trials from the outcome with the rhythm control strategy. This might suggest that attempts to restore sinus rhythm with presently available antiarrhythmic drugs are obsolete. The RACE and AFFIRM trials did not address AF in younger, symptomatic patients with little underlying heart disease, in whom restoration of sinus rhythm by cardioversion antiarrhythmic drugs or non- pharmacological interventions still must be considered a useful therapeutic approach. One may conclude from these studies that rate control is a reasonable strategy in elderly patients with minimal symptoms related to AF. An effective method for maintaining sinus rhythm with fewer side effects would address a presently unmet need. ACC/AHA/ESC Guidelines 2006

14. www.cardiosource.com Results No difference in primary endpoint of CV death between groups (Figure) Cardioversion 39% vs 8% Also no difference in total mortality (31.8% vs. 32.9%, p = 0.73), stroke (2.6% vs. 3.6%, p = 0.32), worsening heart failure (27.6% vs. 30.8%, p = 0.17), or composite (42.7% vs. 45.8%, p = 0.20) Higher hospitalization rates (46% vs 39% p=.006) and cost with rhythm control Bradyarrhythmias ↑ in rhythm control group Conclusions Among patients with heart failure and atrial fibrillation, use of rhythm control was not associated with differences in CV mortality compared with rate control Results were similar to AFFIRM trial, which also showed no impact on mortality with rhythm control vs. rate control for management of atrial fibrillation AF-CHF % Trial Design: AF-CHF was a randomized trial of rhythm control (n = 682) vs. rate control (n = 694) in patients with heart failure and atrial fibrillation. Rhythm control included use of electrical cardioversion combined with antiarrhythmic drugs, including amiodarone as first-line therapy. Primary endpoint was CV death, with mean follow-up of 3 years. Rhythm Control Rate Control CV Death (HR 1.06, p = 0.59) Bradyarrhythmia (p = 0.007) Presented at AHA Roy 2007

15. When and Why Acutely Cardiovert?

16. AF Begets AF AF causes changes in atrial electrophysiology that promote AF maintenance AF causes changes in atrial electrophysiology that promote AF maintenance Wijffels Circulation 1995; 92: 1954-68

17. Lip GY Lancet 2007;370:604-18

19. Paroxysmal AF <48 hours (n=100) Amiodarone IV (3 gm) vs IV placebo Cotter EHJ 1999; 20:1833-42 Paroxysmal AF <1 week (n=100) Amiodarone IV (1.2 gm) vs placebo Galve JACC 1996;27:1079-82 30/50 (60%) placebo patients converted 32/50 (64%) placebo patients converted High Rates of Spontaneous Cardioversion for Recent-onset AF

20. Likelihood of Spontaneous Conversion of Atrial Fibrillation to Sinus Rhythm Danias J Am Coll Cardiol. 1998;31:588-92 356 pts with AF < 72 h Symptoms of < 24 h was only independent predictor of spontaneous conversion (OR: 1.8, p < 0.0001) 356 pts with AF < 72 h Symptoms of < 24 h was only independent predictor of spontaneous conversion (OR: 1.8, p < 0.0001) < 24 h 24 - 72 h Total < 24 h 24 - 72 h Total 292 64 356 292 64 356 73% 45% 68% 73% 45% 68% AF duration n n Conversion

21. How often does spontaneous conversion occur over 8 weeks?

23. Klein A et al. N Engl J Med 2001;344:1411-1420

24. Clinical Outcomes at 8 Weeks among Patients with Atrial Fibrillation of More Than 2 Days Duration

25. Spontaneous Conversion of Patients with AF Scheduled for Electrical Cardioversion An ACUTE Trial Ancillary Study Tejan-Sie J Am Coll Cardiol 2007;42:1638-1643 Conversion According to Duration of Pre-existing AF Daily Conversion According to Strategy

26. Spontaneous Conversion of Patients with AF Scheduled for Electrical Cardioversion An ACUTE Trial Ancillary Study Tejan-Sie J Am Coll Cardiol 2007;42:1638-1643 Multivariable Model Predicting Spontaneous Conversion

27. Conversion of Recent-Onset AF to Sinus Rhythm: Effects of Different Drug Protocols Mean conversion time: Flecainide: 2.6 hrs Propafenone: 3.0 hrs Mean conversion time: Flecainide: 2.6 hrs Propafenone: 3.0 hrs Conversion rates to sinus rhythm (%) * p < 0.05 vs placebo ** p < 0.01 vs placebo * p < 0.05 vs placebo ** p < 0.01 vs placebo Boriani Pacing Clin Electrophysiol. 1998;21(11 Pt 2):2470-4 * ** 417 hospitalized pts with AF onset ≤ 7 days

28. Cardioversion of atrial flutter and fibrillation after ibutilide infusion (67 y/o, 15 days duration, half with prior episode) Stambler Circulation. 1996;94:1613-1621

30. Predictors of Cardioversion with Ibutilide 201 patients treated Zaqqa AJC 2000

31. Saliba J Am Coll Cardiol 1999;34:2031-34  Biphasic shock  Refractory to standard cardioversion (failed 2 attempts)  >3 month in 55%  SR in 46 (84%) of the 55 pts

32. Oral NEJM 1999;340:1849-54 100 consecutive patients l 50 assigned conventional DC l 50 pretreated with 1 mg ibutilide 100 consecutive patients l 50 assigned conventional DC l 50 pretreated with 1 mg ibutilide Cardioversion success (%)

33. How often does spontaneous conversion occur after months of AF?

34. n AF 7 to 360 days duration (110 average) n CHF, recent MI, bradycardia excluded n AF 7 to 360 days duration (110 average) n CHF, recent MI, bradycardia excluded Lancet. 2000;356:1789-94

35. Rhythm or rate control in atrial fibrillation: Pharmacological Intervention in Atrial Fibrillation (PIAF) Trial Lancet. 2000;356:1789-94 Amiodarone group:  23% converted during amio load  76% had electrical cardioversion Primary outcome: no difference

36. n 665 patients, 68 y/o n Persistent AF, 76% < 1yr n On warfarin n 665 patients, 68 y/o n Persistent AF, 76% < 1yr n On warfarin Spontaneous Conversion 28 Days N Engl J Med 2005;352:1861-72

37. Electrical n More effective (90%) n Quick n One procedure with TEE n Cardioversion itself safe Electrical n More effective (90%) n Quick n One procedure with TEE n Cardioversion itself safe Pharmacological n Works well for recent onset, for atrial flutter n Avoid sedation n Less expensive n Early maintenance enhanced by some drugs Advantages and Disadvantages

38. What do the Guidelines Say? Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). Circulation. 2006;114:e257-e354.

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44. Cardioversion of Atrial Fibrillation Clinical Issues   Cardioversion is common practice, albeit not well supported in trials that have been done   Most new onset, and many paroxysmal atrial fibrillation episodes, are treated with cardioversion if they do not spontaneously convert in 24 to 48 hours   While electrical cardioversion generally preferred, acute pharmacologic cardioversion has a role, that is not well defined