1. Muhammad S Ajmal MBBS Aravind Herle MD FACC

2. Atrial fibrillation (AF) A supraventricular tachyarrhythmia characterized by uncoordinated atrial activation with consequent deterioration of atrial mechanical function. The estimated prevalence of AF is 0.4% to 1% in the general population, increasing with age to 8% in patients older then 80. 2.2 million people in USA and 4.5 million people in Europe has AF. Fuster, V. et al. Circulation 2006;114:e257-e354

3. Clinical manifestations Available data suggests that quality of life is considerably impaired in patients with AF compared to age-matched controls. Asymptomatic phase. Subjective symptoms: Fatigue, palpitations, chest pain, dyspnea, lightheadedness or syncope. Exacerbation of heart failure. Embolic complications including Stroke. Fuster, V. et al. Circulation 2006;114:e257-e354

4. Management Strategic objectives: 1. Prevention of thromboembolism. 2. Rate control. 3. Correction of rhythm disturbance.

5. Prevention of thromboembolism. Studies have shown increase risk of stroke in patients with AF. The simplest risk assessment scheme is the CHADS 2 score. Studies showed clear relationship between CHAD2 score and risk of stroke. European Heart Journal (2010) 31, 2369-2429

6. Rate or Rhythm control Randomized clinical trials have shown rate control to be at least non- inferior to rhythm control therapies. Choice must be individualized, depending on the symptoms, patient preferences, comorbid conditions, and the ongoing response to treatment. Rate control is a reasonable initial therapy for patients with persistent AF. European Heart Journal (2010) 31, 2369-2429

7. Rhythm Control Rhythm control is preferable in following conditions: 1. Symptomatic AF not responding to rate control. 2. Congestive heart failure. 3. Patient preference to achieve sinus rhythm, specially in younger population who are intolerant to AF. 4. Unable to tolerate rate control agents.

8. Rhythm control Pharmacological cardioversion. Electrical cardioversion.

9. Pharmacological cardioversion Recent meta-analysis of 45 clinical trials, comprising of 12559 patients showed that class 1A,1C and 3 drugs increase the likelihood of maintaining sinus rhythm but increase adverse events. Mortality was low in most studies(0-4.4%) but Class 1A drugs were associated with increased mortality. Cochrane Database Syst Rev 2007;4:CD005049

10. 2011 Writing Group Members, et al. Circulation 2011;123:104-123

11. Electrical cardioversion Delivery of an electrical shock synchronized with the intrinsic activity of the heart by sensing the R wave of the EKG to ensure that electrical stimulation does not occur during the vulnerable phase of the cardiac cycle. Performed under light anesthesia with prophylactic anti- coagulation. Success rate in literature varies between 70-99% depending upon the definition of success. Fuster, V. et al. Circulation 2006;114:e257-e354

12. Review of Literature Factors that predispose to AF recurrence: 1. Duration of AF before electrical cardioversion. 2. Number of previous recurrences. 3. Increased left atrial size. 4. Coronary heart disease or pulmonary or mitral valve disease. European Heart Journal (2010) 31, 2369-2429

13. ACC/AHA/ESC Guidelines Regarding Pharmacological Enhancement of Electrical Cardioversion. Pretreatment with Amiodarone, Flecainide, Ibutilide, Propafenone and Sotalol can be useful to enhance the success of direct-current cardioversion and prevent recurrent atrial fibrillation. Class 2A (Level of evidence B). Efficacy of Beta blockers, Verapamil, Diltiazem, Disopyramide, Procainamide or Dofetilide to enhance the success of direct current cardioversion is uncertain. Class 2B (Level of evidence C). Fuster, V. et al. Circulation 2006;114:e257-e354 European Heart Journal (2010) 31, 2369-2429

14. Review of Literature The role of Antiarrhythmic drugs to enhance the acute success rate of electrical cardioversion remains unclear. No large randomized clinical trials. Few small trials showed conflicting evidence that pretreatment with class 1c and class 3 agents enhance the acute success of electrical cardioversion of AF. Comparative efficacy of various drugs used for pretreatment is unknown. European Heart Journal (2010) 31, 2369-2429

15. Study Objectives: 1. Acute success rate of electrical cardioversion of AF at Mercy Hospital? 2. Efficacy of pretreatment with rhythm control drugs to improve the acute success rate of electrical cardioversion of AF. 3. Compare efficacy of various rhythm control drugs used for pretreatment. 4. Identify other predictors of successful electrical cardioversion of AF.

16. Study Design. Retrospective chart review. IRB Approval; Consent waived. HIPAA compliance. Inclusion criteria: All patients who underwent electrical cardioversion for AF during 2007-10 were included in the study. Exclusions: Patients in atrial flutter or any other atrial arrhythmia’s were excluded from the study.

17. Study Design Patients were divided into two groups. One group received pretreatment with rhythm control drugs before electrical cardioversion and other group did not. Rhythm control drugs included class 1c or class 3 Antiarrhythmic drugs. Pretreament was defined as initiation of rhythm control drugs any time before the procedure.

18. Study Design Total cases of electrical cardioversion at Mercy Hospital during 2007-10 Patients in atrial flutter at time of cardioversion. Excluded from atrial fibrillation group. Patients with atrial fibrillation that underwent electrical cardioversion. Patients who did not receive pretreatment. Patients who received pretreatment. Un-successful cardioversion Successful cardioversion Un-successful cardioversion

19. Study Design Following additional data was collected about each patient: Age. Sex. Clinical setting. Duration of AF. Persistent or paroxysmal AF. Hx of Hyperthyroidism. Hx of COPD.

20. Study Design Size of left atrium. Left ventricular ejection fraction. Hx of Hypertension. Anti-coagulation status. TEE before procedure. Number of shocks. Energy settings of the shock.

21. Baseline Characteristics. Both groups were closely matched. Only statistically significant difference was Duration of AF longer then 6 months in pretreatment group compared with the other group (83% and 68% respectively). P=0.0155

22. Successful electrical cardioversion Acute conversion to sinus rhythm confirmed by post- cardioversion EKG. Maintenance of rhythm for at least 2 hours or until the patient left the cath lab. IRAF and sub acute recurrences within first 2 hours were included as failure of cardioversion.

23. Hypothetical illustration of cardioversion failure. Fuster, V. et al. Circulation 2006;114:e257-e354

24. Results: Total cases of electrical cardioversion. 304 Patients in atrial flutter 49 Excluded from atrial fibrillation group. Patients in atrial fibrillation. 255 Patients who did not receive pretreatment 154 Patients who received pretreatment 101 Un-successful cardioversion 12 Successful cardioversion 89 Successful cardioversion 125 Un-successful Cardioversion 29

25. Results. Overall success rate of electrical cardioversion of AF at Mercy Hospital: 84%. Success rate in patients who received pretreatment: 88% Success rate in patients with no pretreatment: 81% This difference was not statistically significant. (p=0.1647).

26. Results: Acute Success rate of electrical cardioversion of Atrial flutter was 96%.

27. Success rates of individual Antiarrhythmic drugs Anti-Arrhythmic drugs Patients receiving pretreatment Un-Successful cardioversions Success rate Dronedarone 16 571% Amiodarone 25 196% Propafenone 19 0100% Sotalol 30 487% Dofetilide 2 0100% Flecainide 5 0100% Ibutilide 4 250%

28. Efficacy of Dronedarone in pharmacological enhancement of electrical cardioversion Dronedarone, a newer class 3 Antiarrhythmic drug had lower success rate when used for pretreatment compared with Amiodarone and Propafenone. This difference was statistically significant. ( P=0.0261 and P=0.0135 respectively). Dronedarone sub-group also had a lower success rate compared with Sotalol, Flecainide and Dofetilide, but the difference was not statistically significant.

29. Table 2-3).Baseline characteristics of Patients in Dronedarone and Amiodarone/Propafenone sub-groups did not show any statistically significant differences in terms of duration of atrial fibrillation, size of left atrium and LVEF.

30. Efficacy of Dronedarone DAFNE trial showed that in patients with persistent AF, Dronedarone converted only 5.8% to sinus rhythm (3.1 % converted with placebo) and did not improve the acute success rate of electrical cardioversion. DIONYSOS trial showed that Dronedarone was inferior to Amiodarone in preventing recurrence of AF including unsuccessful electrical cardioversion but was better tolerated. Eur Heart J (2003) 24 (16): 1481-1487. J Am Coll Cardiol, 2009; 54:1089-1095

31. Factor Successful cardioversion Un-successful cardioversion Statistical significance Mean Age64.65 SD 12.0462.21 SD 11.38p=0.5338 Sex Male=67% Female 33% Males=70% Female=30% p=0.8552 Duration of atrial fibrillation >6months69%.68%. p=1.00 Size of left atrium>4.5 cm61%.85%. p=0.0126 LVEF<50%34%.36%.p=0.8528 Hx of COPD6%.12%. p=0.1781 Hx of HTN93%.94%.p=0.7143 Clinical Setting In-patient=34% Out-patient=66% In-patient=31% Out-patient=69% p=0.7157 Hyperthyroidism<1% p=1.00 Average# of shocks1.4/Patient2.51/patient Energy Settings194J/Shock211J/Shock Other predictors of Successful electrical cardioversion

32. Conclusions Pretreatment with class 1c or 3 Antiarrhythmic drugs failed to show statistically significant evidence of enhancing the acute success rate of electrical cardioversion of AF. But, a confounding bias exist. Pretreatment with Dronedarone was inferior to Amiodarone and Propafenone in improving the acute success rate of electrical cardioversion of AF. Size of left atrium is inversely related to the likelihood of successful electrical cardioversion and this association is statistically significant.

33. Limitations of the study Retrospective study. Small sample size for each sub-groups. Limited follow up after electrical cardioversion to determine the probability of maintenance of sinus rhythm.

34. Acknowledgement Dr. Aravind Herle. Dr. Khalid J Qazi. CHS IRB Team. HIM staff.

35. Questions

36. Thank You