Journals | Policy | Permission

Cardiology Research

Original Article

Volume 3, Number 4, August 2012, pages 158-163

Adjunctive Pharmacotherapy for Elective Direct Current Cardioversion in Patients With Atrial Fibrillation

Atrial fibrillation (AF) is common with a prevalence between 0.4% and 1% in the general population [1]. Direct current cardioversion (DCCV) can restore sinus rhythm in patients with AF, and if sinus rhythm is maintained, there is an associated improvement in quality of life [2]. DCCV has an initial failure rate of around 25%, and 25% of patients will revert back to AF within 2 weeks of a successful procedure [3]. After 1 year, 70% may have reverted back to AF [4]. Maintenance of sinus rhythm may be improved by selection of appropriate patients [4-7], the use of antiarrhythmic drugs, or repeat DCCV [8]. Despite this, the long term success of the procedure remains poor.

There have been numerous studies of adjunctive pharmacological therapies to improve the initial success of DCCV. A number of antiarrhythmic drug have been shown to be of benefit [9-13]. What remains unclear is whether these drugs also promote maintenance of sinus rhythm in the early post-procedural period, or longer term [10, 14, 15]. More recently there has been evidence to suggest that inhibition of the renin-angiotensin-aldosterone system (RAAS) might not only improve the initial success rate of the procedure, but also subsequent maintenance of sinus rhythm [16, 17]. However, the evidence is conflicting and the studies often involved the use of concomitant antiarrhythmics [18-20].

The aim of this study was to determine which adjunctive pharmacological therapy, including antiarrhythmic drugs and RAAS inhibiting drugs, most successfully promotes DCCV and maintenance of sinus rhythm in unselected patients with AF.

This study was a single centre retrospective observational cohort study. All patients with atrial fibrillation who attended our hospital for an elective DC cardioversion between January 2010 and February 2012 were included, unless hospital records were unobtainable. Patients were identified and hospital records scrutinised for relevant data. Data recorded for each patient included age, sex, previous AF, previous DCCVs, medications, echocardiographic measurements, initial success of procedure, time to follow up and maintenance of sinus rhythm at follow up. Initial success of the procedure was defined as achieving sinus rhythm from DCCV and maintaining sinus rhythm until discharge on the same day.

The data were analysed in two multivariate logistical regression models. In the first analysis, restoration of sinus rhythm by DCCV was the dependent variable. The independent variables were those factors known, or believed, to influence the success of DCCV and/or maintenance of sinus rhythm thereafter. These included pharmacological therapies and also patient characteristics such as age, left atrial diameter and previous AF. Those patients who had been successfully cardioverted to sinus rhythm, and had subsequently had follow up, were included in the second logistical regression analysis. In the second model, the dependent variable was maintenance of sinus rhythm at follow up. Again, the independent variables were those factors known or believed to influence the success of DCCV and/or the maintenance of sinus rhythm thereafter. Statistical significance for both analyses was inferred at the 0.05 level.

One hundred and forty one patients were eligible for inclusion. Hospital documentation was not available for 11 patients, and these were excluded from the analyses. Of the 130 patients that had a DCCV, sinus rhythm was successfully restored in 105 (81%). Seventy one patients (68%) had documented follow up after successful DCCV, and off these, 22 (31%) had maintained sinus rhythm. The mean length of follow up was 190 days. The baseline characteristics of all patients, and those that had follow up after successful DCCV, are summarised in Table 1. The cohort was predominantly male (75%) with a mean age of 66.7 years (SD ± 10.44 years). All patients were established on their drug regime for at least 3 weeks prior to DCCV and antiarrhythmic and RAAS inhibiting drugs were continued unchanged in the post procedural period.

Click to view

Table 1. Baseline Characteristics

All 130 patients were included in the first analysis. In this analysis initial success of DCCV was the dependent variable. The results of the first logistical regression model are shown in Table 2. There were no significant associations between initial success of DCCV and the independent variables.

Click to view

Table 2. Multivariate Logistical Regression Analysis With Successful DCCV as the Dependent Variable

The seventy one patients that had follow up after successful DCCV and were included in the second regression model. In this analysis maintenance of sinus rhythm at follow up was the dependent variable. The results of the second logistical regression model are shown in Table 3. Only flecainide had a statistically significant association with maintenance of sinus rhythm at follow up (OR 2.14, SE ± 0.93, P = 0.02). Of the 14 patients taking flecainide, 11 had follow up and 5 had maintained sinus rhythm.

Click to view

Table 3. Multivariate Logistical Regression Analysis With Maintenance of Sinus Rhythm at Follow up Following Successful DCCV as the Dependent Variable

The main finding of this study was that flecainide therapy established prior to, and continued after, elective DCCV in unselected patients with AF, is associated with approximately a doubling of the odds of remaining in sinus rhythm at follow up. This is the first time an association has been shown between flecainide therapy and maintenance of sinus rhythm after DCCV in the longer term. A prior study with much a much shorter follow up period (4 weeks) failed to show an association between flecainide and maintenance of sinus rhythm [15].

Other antiarrhythmic drugs and RAAS inhibiting drugs had no association with successful DCCV or subsequent maintenance of sinus rhythm in this study. Amiodarone has previously been shown to increase the odds of a successful procedure compared to rate controlling medications in a number of trials, and there is some evidence to suggest that amiodarone also promotes maintenance of sinus rhythm over the subsequent 8 weeks [10]. The results presented here do not support the previous findings. This may be for a number of reasons. Firstly, this study involved an unselected cohort of patients. The benefit of amiodarone observed in small controlled trials may not directly translate into a benefit for unselected patients. Secondly, amiodarone is associated with potentially serious side effects, and non-compliance or discontinuation of amiodarone after DCCV is likely to have been more common in this cohort than in a controlled trial.

RAAS inhibition may reduce recurrence of AF after DCCV through a number of mechanisms, including attenuating changes in cardiac structure and function [21], preventing left atrial dilation, preventing atrial fibrosis, and preventing slowing of conduction velocities [22]. Which are independent of haemodynamic effects [23]. Despite these potential mechanisms there was no association between RAAS inhibiting drugs and maintenance of sinus rhythm in the current study. This finding is supported by a previous retrospective study [16]. Previous studies showing an association between maintenance of sinus rhythm and RAAS inhibition have also included antiarrythmic drugs [20]. Studies without concomitant antiarrythmics have failed to demonstrate the association [17, 24]. There are a number of possible explanations for the apparent discrepancy. The study presented here investigated RAAS inhibitors as an entire drug class. It is possible that some RAAS inhibiting drugs may have specific or exaggerated actions compared to other drugs of the same class, or have specific synergisms with antiarrhythmic drugs, but this remains to be tested.

The study presented here has a number of limitations. The observational nature of the current study means there may be a number of unknown and therefore uncontrolled confounding factors. However, the variables known to be associated with successful DCCV were included in the regression analysis, mitigating them as confounders. The observational nature of the study and the unselected cohort of patients enable a true reflection of the atrial fibrillation population, making the observations widely applicable. Follow up was incomplete, as would be expected with a retrospective analysis, and it is not clear whether those without follow up were more likely to have maintained sinus rhythm or not. Compliance with pharmacological therapy was not measured, and although antiarrhythmic and RAAS inhibiting medications were continued after DCCV, data concerning compliance. This may have implications for the results, as drugs such as amiodarone have potentially serious long term side effects, and are probably more likely to be discontinued that other well tolerated medications. However, this is a reflection of real clinical practise and does not affect the validity of the observations from the study presented here.

The current study has clear implications for clinical practise and future research. Further studies may be able address the limitations of the study presented here, and confirm the results in a larger cohort of patients. This would further define the role of pharmacological therapies in the maintenance of sinus rhythm after DCCV aiding clinical decision making. Currently, this is the only study showing an association between flecainide therapy and long term maintenance of sinus rhythm after elective DCCV for AF. There may be significant benefit in the longer term when compared to other antiarrhythmics and this should be taken into account by physicians when choosing adjunctive antiarrhythmics for DCCV.

Acknowledgments

None.

Financial Disclosures

None.

Grant Support

None.

1. Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologic features of chronic atrial fibrillation: the Framingham study. N Engl J Med. 1982;306(17):1018-1022.
   pubmed doi
2. Berry C, Stewart S, Payne EM, McArthur JD, McMurray JJ. Electrical cardioversion for atrial fibrillation: outcomes in "real-life" clinical practice. Int J Cardiol. 2001;81(1):29-35.
   pubmed doi
3. Van Gelder IC, Tuinenburg AE, Schoonderwoerd BS, Tieleman RG, Crijns HJ. Pharmacologic versus direct-current electrical cardioversion of atrial flutter and fibrillation. Am J Cardiol. 1999;84(9A):147R-151R.
   pubmed doi
4. Elesber AA, Rosales AG, Herges RM, Shen WK, Moon BS, Malouf JF, Ammash NM, et al. Relapse and mortality following cardioversion of new-onset vs. recurrent atrial fibrillation and atrial flutter in the elderly. Eur Heart J. 2006;27(7):854-860.
   pubmed doi
5. Van Gelder IC, Crijns HJ, Van Gilst WH, Verwer R, Lie KI. Prediction of uneventful cardioversion and maintenance of sinus rhythm from direct-current electrical cardioversion of chronic atrial fibrillation and flutter. Am J Cardiol. 1991;68(1):41-46.
   pubmed doi
6. Lown B. Electrical reversion of cardiac arrhythmias. Br Heart J. 1967;29(4):469-489.
   pubmed doi
7. Lundstrom T, Ryden L. Chronic atrial fibrillation. Long-term results of direct current conversion. Acta Med Scand. 1988;223(1):53-59.
   pubmed doi
8. Waris E, Kreus KE, Salokannel J. Factors influencing persistence of sinus rhythm after DC shock treatment of atrial fibrillation. Acta Med Scand. 1971;189(3):161-166.
   pubmed
9. Nergardh AK, Rosenqvist M, Nordlander R, Frick M. Maintenance of sinus rhythm with metoprolol CR initiated before cardioversion and repeated cardioversion of atrial fibrillation: a randomized double-blind placebo-controlled study. Eur Heart J. 2007;28(11):1351-1357.
   pubmed doi
10. Capucci A, Villani GQ, Aschieri D, Rosi A, Piepoli MF. Oral amiodarone increases the efficacy of direct-current cardioversion in restoration of sinus rhythm in patients with chronic atrial fibrillation. Eur Heart J. 2000;21(1):66-73.
    pubmed doi
11. Channer KS, Birchall A, Steeds RP, Walters SJ, Yeo WW, West JN, Muthusamy R, et al. A randomized placebo-controlled trial of pre-treatment and short- or long-term maintenance therapy with amiodarone supporting DC cardioversion for persistent atrial fibrillation. Eur Heart J. 2004;25(2):144-150.
    pubmed doi
12. Bianconi L, Mennuni M, Lukic V, Castro A, Chieffi M, Santini M. Effects of oral propafenone administration before electrical cardioversion of chronic atrial fibrillation: a placebo-controlled study. J Am Coll Cardiol. 1996;28(3):700-706.
    pubmed doi
13. Jacobs LO, Andrews TC, Pederson DN, Donovan DJ. Effect of intravenous procainamide on direct-current cardioversion of atrial fibrillation. Am J Cardiol. 1998;82(2):241-242.
    pubmed doi
14. Li H, Riedel R, Oldemeyer JB, Rovang K, Hee T. Comparison of recurrence rates after direct-current cardioversion for new-onset atrial fibrillation in patients receiving versus those not receiving rhythm-control drug therapy. Am J Cardiol. 2004;93(1):45-48.
    pubmed doi
15. Climent VE, Marin F, Mainar L, Gomez-Aldaravi R, Martinez JG, Chorro FJ, Roman P, et al. Effects of pretreatment with intravenous flecainide on efficacy of external cardioversion of persistent atrial fibrillation. Pacing Clin Electrophysiol. 2004;27(3):368-372.
    pubmed doi
16. Van Noord T, Crijns HJ, van den Berg MP, Van Veldhuisen DJ, Van Gelder IC. Pretreatment with ACE inhibitors improves acute outcome of electrical cardioversion in patients with persistent atrial fibrillation. BMC Cardiovasc Disord. 2005;5(1):3.
    pubmed doi
17. Zaman AG, Kearney MT, Schecter C, Worthley SG, Nolan J. Angiotensin-converting enzyme inhibitors as adjunctive therapy in patients with persistent atrial fibrillation. Am Heart J. 2004;147(5):823-827.
    pubmed doi
18. Grecu M, Olteanu RO, Olteanu SS, Georgescu CA. Does treatment with ACE inhibitors prevent the long term recurrences of lone atrial fibrillation after cardioversion?. Rom J Intern Med. 2007;45(1):29-33.
    pubmed
19. Madrid AH, Bueno MG, Rebollo JM, Marin I, Pena G, Bernal E, Rodriguez A, et al. Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study. Circulation. 2002;106(3):331-336.
    pubmed doi
20. Ueng KC, Tsai TP, Yu WC, Tsai CF, Lin MC, Chan KC, Chen CY, et al. Use of enalapril to facilitate sinus rhythm maintenance after external cardioversion of long-standing persistent atrial fibrillation. Results of a prospective and controlled study. Eur Heart J. 2003;24(23):2090-2098.
    pubmed doi
21. Shi Y, Li D, Tardif JC, Nattel S. Enalapril effects on atrial remodeling and atrial fibrillation in experimental congestive heart failure. Cardiovasc Res. 2002;54(2):456-461.
    pubmed doi
22. Nakashima H, Kumagai K, Urata H, Gondo N, Ideishi M, Arakawa K. Angiotensin II antagonist prevents electrical remodeling in atrial fibrillation. Circulation. 2000;101(22):2612-2617.
    pubmed doi
23. Li D, Shinagawa K, Pang L, Leung TK, Cardin S, Wang Z, Nattel S. Effects of angiotensin-converting enzyme inhibition on the development of the atrial fibrillation substrate in dogs with ventricular tachypacing-induced congestive heart failure. Circulation. 2001;104(21):2608-2614.
    pubmed doi
24. Disertori M, Latini R, Barlera S, Franzosi MG, Staszewsky L, Maggioni AP, Lucci D, et al. Valsartan for prevention of recurrent atrial fibrillation. N Engl J Med. 2009;360(16):1606-1617.
    pubmed doi

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Cardiology Research is published by Elmer Press Inc.