Europace Advance Access published May 17, 2013 CLINICAL RESEARCH Europace doi:10.1093/europace/eut106 Arrhythmic complications after electrical cardioversion of acute atrial fibrillation: The FinCV study Toni Grönberg 1, Ilpo Nuotio 2, Marko Nikkinen 3, Antti Ylitalo 4, Tuija Vasankari 1, Juha E.K. Hartikainen3, and K.E. Juhani Airaksinen 1* Received 25 January 2013; accepted after revision 3 April 2013 Aims To determine the incidence and risk factors of arrhythmic complications after electrical cardioversion of acute atrial fibrillation (AF). ..................................................................................................................................................................................... Methods Our retrospective multicentre study collected data from 7660 cardioversions of acute (,48 h) AF in 3143 consecutive and results patients. Immediate arrhythmic complications were evaluated after 6906 (90.2%) electrical cardioversions performed in 2868 patients. We also assessed the predictors of arrhythmic complications and whether post-cardioversion bradycardia or asystole led to later a permanent pacemaker implantation. Altogether, 63 (0.9%) electrical cardioversions resulted in bradyarrhythmia in 54 patients. Asystole (.5 s) occurred immediately after 51 cardioversions leading to a short resuscitation in seven cases and two patients needed extrinsic pacing after the cardioversion. In nine cases, asystole was followed by bradycardia. Bradycardic ventricular rate (,40 b.p.m.) alone was seen after 12 procedures. No ventricular arrhythmias needing intervention were detected. Old age [odds ratio (OR) 1.1; 95% confidence interval (CI) 1.05–1.10, P , 0.0001], female sex (OR 2.5; 95% CI 1.4 –4.8, P ¼ 0.004), and unsuccessful cardioversion (OR 2.2; 95% CI 1.1 –4.6, P ¼ 0.03) were the independent predictors of bradycardic complications. Slow ventricular rate, use of digoxin, beta blocker, or antiarrhythmic medication did not increase the risk of bradycardic complications. Pacemaker was implanted in 24 (44.4%) patients after a median delay of 66 days. ..................................................................................................................................................................................... Conclusion Bradycardic complications are rare and usually benign after cardioversion of acute AF. They seem to reflect sinus node dysfunction and often result in later implantation of a permanent pacemaker. ----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords Atrial fibrillation † Cardioversion † Arrhythmic complication † Bradycardia Introduction Atrial fibrillation (AF) is the most common tachyarrhythmia and is a major burden to modern health care system associated with significant morbidity and mortality.1 Since 1960s, direct current cardioversion has been successfully used to terminate highly symptomatic AF2 and according to the current guidelines, recent onset AF (,48 h) may be cardioverted to sinus rhythm under appropriate anticoagulation.3 Small retrospective cohort studies have shown that electrical cardioversion is a safe and efficient procedure.4 – 6 There is an increased risk for thromboembolic complications if no adequate anticoagulation is used. Arrhythmias, most often bradycardia and sinus arrest are also known complications after cardioversion of AF. The pre-operative identification of highrisk patients may be useful, but there are no large-scale studies on the incidence and risk factors of acute arrhythmic complications after electrical cardioversion of acute AF. The purpose of this analysis was to evaluate the incidence, risk factors, and clinical consequences of arrhythmic complications in a large patient population undergoing electrical cardioversion of acute AF. * Corresponding author: Tel: +358 2 3131005; fax: +358 2 3132030, Email: juhani.airaksinen@tyks.fi Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2013. For permissions please email: journals.permissions@oup.com. Downloaded from http://europace.oxfordjournals.org/ at Turku University Library on May 20, 2013 1 Heart Center, Turku University Hospital, Kiinamyllynkatu 4-8, FIN-20520 Turku, Finland; 2Division of Medicine, Department of Acute Internal Medicine, Turku University Hospital, Kiinamyllynkatu 4-8, FIN-20520 Turku, Finland; 3Heart Center, Kuopio University Hospital, P.O. Box 1777, FIN-70211 Kuopio, Finland; and 4Heart Center, Satakunta Central Hospital, Sairaalantie 3, FIN-28500 Pori, Finland Page 2 of 4 What’s new? † No previous study has focused on arrhythmic complications after electrical cardioversion of acute atrial fibrillation. † Our multicentre study with a large number of patients shows that immediate arrhythmic complications are rare and essentially bradyarrhythmias. † Older women are a high-risk group for these complications. † Post-cardioversion bradyarrhythmias seem to reflect sinus node dysfunction and .40% of patients were later treated with a permanent pacemaker. The FinCV study (ClinicalTrials.gov Identifier: NCT01380574) is a part of a wider protocol in progress to assess acute complications of cardiac procedures in Western Finland.7 – 9 In this study, data were collected at the emergency clinics of two university hospitals from 2003 through 2010 and at one central hospital during the year 2010. Emergency department patients (age ≥18 years) with a primary diagnosis of AF were identified, and patient records and databases were used to assess the type and duration of AF, relevant clinical data, and cardioversion details. Patients living outside the catchment area of the hospital were excluded to get complete follow-up data. None of the patients was excluded by the severity of symptoms caused by the AF. A total of 7660 consecutive cardioversions were identified in 3143 patients with acute (duration of symptoms ,48 h) AF. For this analysis, we focused on 2868 patients who underwent 6906 electrical cardioversions and chemical cardioversions were excluded from the present analysis. Diagnosis of AF was confirmed by 12-lead ECG according to the standard criteria. Synchronized direct-current cardioversions were performed according to the contemporary guidelines under general anaesthesia with propofol, midazolam, or ethomidate, propofol being the most commonly used anaesthetic.10 Six hours of fasting was required before the cardioversion in patients with no haemodynamic problems. Electrocardiogram, blood pressure, and oxygen saturation were monitored continuously. Either paddles or pads were used and positions with pads were antero-posterior or antero-lateral. Initial energy (70–200 J) was chosen according to clinical characteristics of the patient and increased to 200 –360 J for subsequent shocks. Transition to biphasic devices occurred in 2004. Cardioversion was considered successful if sinus rhythm was restored and the patient was discharged from the cardioversion unit in sinus rhythm. The primary study outcome measures were bradycardia defined as heart rate ,40 b.p.m. and asystole .5 s immediately after the cardioversion. We also recorded ventricular tachycardia and ventricular fibrillation in the emergency room and deaths were recorded during the hospital stay. The case notes of all patients with bradycardic complications were checked for implantation of a pacemaker after the cardioversion episode. Statistical analyses Statistical analyses were performed using SPSS for Windows 17.0 software (SPSS Inc.) and SAS software version 9.3 (SAS Institute Inc.). Data are presented as mean values + SD or frequency percentages. The x2 and Fisher’s exact tests were used to compare differences between proportions. Student’s t-test was used for analysis of continuous data. Differences were considered significant if the null hypothesis could be rejected at the 0.05 probability level. Since primary study outcome was binary and repeated cardioversions of same individuals were included in analyses, the generalized linear model (GENMOD) procedure with repeated measures option was used in the univariate and multivariate analyses. Results A total of 3143 patients underwent 7660 cardioversions (electrical or medical) for acute AF in emergency clinics of three hospitals. Electrical cardioversion was used to convert 6906 (90.2%) attacks of AF in 2868 patients. The mean age of the patients averaged 62.4 + 12.3 years and cardioversion was performed on males 4470 times (64.7%). The success rate for electrical cardioversion was 94.2%. The incidence of bradyarrhythmic complications was 63 (0.9%) in 54 patients after 6906 electrical cardioversions. There were 51 (0.7%) cases of asystole (.5 s) followed by bradycardia in 9 patients. In seven cases, the asystole resulted in short resuscitation and two patients were treated with extrinsic pacing. Significant bradycardia alone (,40 b.p.m.) was registered in 12 patients immediately after cardioversion. There were no cases of ventricular fibrillation or Table 1 Clinical characteristics of patients with and without bradycardic complications after cardioversion No complications (N 5 6843) Asystole or bradycardia (N 5 63) P value ................................................................................ Age (years) 62.3 + 12.3 72.2 + 7.1 0.000 Female sex 2395 (35.0) 41 (65.1) 0.000 Hypertension Diabetes 3351 (49.0) 677 (9.9) 32 (50.8) 6 (9.5) 0.77 0.92 Known vascular disease Heart failure 2058 (30.1) 26 (41.3) 0.054 384 (5.6) 5 (7.9) 0.40 No previous history of atrial fibrillation Beta-blockers 1484 (21.7) 9 (14.3) 0.16 5223 (76.3) 47 (74.6) 0.75 Digoxin 476 (7.0) 6 (9.5) 0.45 Amiodarone Dronedarone 273 (4.0) 30 (0.4) 2 (3.2) 0 (0) 1.00 1.00 Flecainide 970 (14.2) 4 (6.3) 0.076 Propafenone Quinidine or disopyramide Ventricular rate (of AF) Unsuccessful cardioversion 109 (1.6) 75 (1.1) 1 (1.6) 0 (0) 1.00 1.00 109 + 26 111 + 22 0.46 390 (5.7) 8 (12.7) 0.03 Values are mean + SD or number (%). Downloaded from http://europace.oxfordjournals.org/ at Turku University Library on May 20, 2013 Methods T. Grönberg et al. Page 3 of 4 Arrhythmic complications after electrical cardioversion of acute AF ventricular tachycardia needing intervention. Only one death (due to aortic dissection) occurred within 24 h after cardioversion. Baseline characteristics of patients according to the incidence of bradycardic complications are summarized in Table 1. Bradycardic complications were rare (0.2%) in younger (,65 years) male patients, but the incidence increased significantly to 3.1% in older female patients (Figure 1). Bradycardic complications were more common after unsuccessful cardioversion (2.0 vs. 0.8%, P ¼ 0.03), but the pericardioversion use of propafenone, flecainide, amiodarone, or dronedarone did not increase the risk of bradyarrhythmias. In multivariate analysis, old age [odds ratio (OR) 1.1; 95% confidence interval (CI) 1.05 –1.10, P , 0.0001], female sex (OR 2.5; 95% CI 1.4 –4.8, P ¼ 0.004), and unsuccessful cardioversion (OR 2.2; 95% CI 1.1 –4.6, P ¼ 0.03) were confirmed to be significant independent predictors of bradycardic complications. Slow Male 3.0% Female 2.0% 1.0% <64 65-74 >75 Figure 1 The incidence of bradyarrhythmic complications according to sex and age. Discussion Our study shows that electrical cardioversion of acute AF is safe and immediate arrhythmic complications are rare and essentially bradyarrhythmias. Bradycardic complications occurred in 0.9% of the electrical cardioversions and were mostly transient and seldom needed any specific treatment. Advanced age was the major predictor of bradycardic complications. Secondly, female gender also increased the risk of bradycardic complications, but contrary to expectations, slow ventricular rate during AF or drugs such as beta blockers and digoxin were not associated with increased risk for asystole or bradycardia. An interesting new finding in our study was that .40% of the patients with bradycardic complications after cardioversion were later treated with a permanent pacemaker implantation. Sinus node dysfunction is associated with increased risk of AF.11 Cardioversion results in temporary asystole and can be considered as a surrogate for assessment of sinus node recovery time during electrophysiological study. Thus, asystole after cardioversion seems to reveal subtle SND. One common denominator for SND and AF is atrial fibrosis.12 It has been suggested that SND and AF may be manifestations of ‘fibrotic atrial cardiomyopathy’.13 Recently published study demonstrated the importance of regional remodelling near the Table 2 Previously published studies on bradyarrhythmic complications after electrical cardioversion of AF Author No. of cases Age Success (%) Male (%) Type of AF (acute/persistent) 74 94% acute 89 124 Median 60 Mean 57 74 98% acute 97 Definitions of bradycardia or asystole Bradycardia or asystole (%) New bradycardia requiring medication or pacing New arrhythmia requiring medication or pacing Bradycardia ,50/min 0 .............................................................................................................................................................................. Scheuermeyer et al.18 Scheuermeyer et al.19 Burton et al. 5 216 388 Mean 61 55 99% acute 86 Michael et al.20 80 Mean 62 56 21% acute 89 Bradycardia ,60/min, atrio-ventricular blocks 0 712 Mean 65 65 Persistent 88 NA 1.0 543 2522 Mean 67 Mean 63 72 69 Persistent Persistent 88 NA NA Asystole .10 s or bradycardia within 4 weeks requiring specific treatment 1.5 1.0 Siaplaouras et al.23 111 Mean 65 NA Persistent 100 Sinus arrest with escape rhythm 0.9 Botkin et al.4 532 Mean 65 69 Persistent 90 NA 0.8 Pisters et al.6 Morani et al.21 Gallagher et al.22 0 0.3 Downloaded from http://europace.oxfordjournals.org/ at Turku University Library on May 20, 2013 4.0% ventricular rate of AF, digoxin, or beta-blockers did not increase the risk of bradycardic complications. A permanent pacemaker was implanted in 24 (44.4%) patients with bradycardic complications. The main indication for pacemaker implantation was sinus node dysfunction (SND) revealed in the cardioversion. The median time between the index cardioversion and pacemaker implantation was 66 days (mean 299 days). In eight patients, pacemaker was implanted within a week after the index cardioversion. The only significant predictor for implantation of pacemaker after bradyarrhythmia was unsuccessful cardioversion (OR 6.2; 95% CI 1.1 –33.6, P ¼ 0.045). Page 4 of 4 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. Acknowledgements Acknowledgements to clinical investigators for the collection of the data by centre: Turku University Hospital, Turku: I Nuotio, T Grönberg, T Vasankari, A Karmi, KEJ Airaksinen. Satakunta Central Hospital, Pori: M Ampio, K Ruuhijärvi, A Ylitalo. Kuopio University Hospital, Kuopio: M Nikkinen, P Autere, E Parikka, T Rautiainen, S Rissanen, M-L Sutinen, M Tuhkalainen, JEK Hartikainen. 18. Conflict of interest: none declared. 20. Funding 21. 17. 19. This work was supported by unrestricted grants from the Finnish Foundation for Cardiovascular Research, Helsinki, Finland. 22. References 23. 1. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA 2001;285:2370 –5. Lown B, Perlroth MG, Kaidbey S, Abe T, Harken DE. ‘Cardioversion’ of atrial fibrillation. A report on the treatment of 65 episodes in 50 patients. N Engl J Med 1963; 269:325 – 31. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH et al. 2012 focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Europace 2012;14:1385 –413. Botkin SB, Dhanekula LS, Olshansky B. Outpatient cardioversion of atrial arrhythmias: efficacy, safety, and costs. Am Heart J 2003;145:233 –8. Burton JH, Vinson DR, Drummond K, Strout TD, Thode HC, McInturff JJ. Electrical cardioversion of emergency department patients with atrial fibrillation. Ann Emerg Med 2004;44:20–30. Pisters R, Nieuwlaat R, Prins MH, Le Heuzey JY, Maggioni AP, Camm AJ et al. Clinical correlates of immediate success and outcome at 1-year follow-up of real-world cardioversion of atrial fibrillation: the Euro Heart Survey. Europace 2012;14:666 –74. Korkeila P, Mustonen P, Koistinen J, Nyman K, Ylitalo A, Karjalainen P et al. Clinical and laboratory risk factors of thrombotic complications after pacemaker implantation: a prospective study. Europace 2010;12:817–24. Airaksinen KE, Biancari F, Karjalainen P, Mikkola R, Kuttila K, Porela P et al. Safety of coronary artery bypass surgery during therapeutic oral anticoagulation. Thromb Res 2011;128:435 –9. Annala AP, Karjalainen PP, Biancari F, Niemelä M, Ylitalo A, Vikman S et al. Long-term safety of drug-eluting stents in patients on warfarin treatment. Ann Med 2012;44: 271 –8. Fuster V, Rydén LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al. ACC/ AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: full text: 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) developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Europace 2006;8:651 –745. Ferrer MI. The sick sinus syndrome in atrial disease. JAMA 1968;206:645 –6. Burstein B, Nattel S. Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation. J Am Coll Cardiol 2008;51:802 – 9. Kottkamp H. Fibrotic atrial cardiomyopathy: a specific disease/syndrome supplying substrates for atrial fibrillation, atrial tachycardia, sinus node disease, AV node disease, and thromboembolic complications. J Cardiovasc Electrophysiol 2012;23: 797 –9. Chang HY, Lin YJ, Lo LW, Chang SL, Hu YF, Li CH et al. Sinus node dysfunction in atrial fibrillation patients: the evidence of regional atrial substrate remodelling. Europace 2013;15:205 –11. Levy T, Walker S, Rochelle J, Paul V. Evaluation of biatrial pacing, right atrial pacing, and no pacing in patients with drug refractory atrial fibrillation. Am J Cardiol 1999;84: 426 –9. Carlson MD, Ip J, Messenger J, Beau S, Kalbfleisch S, Gervais P et al. A new pacemaker algorithm for the treatment of atrial fibrillation: results of the Atrial Dynamic Overdrive Pacing Trial (ADOPT). J Am Coll Cardiol 2003;42:627–33. Hohnloser SH, Healey JS, Gold MR, Israel CW, Yang S, van Gelder I et al. Atrial overdrive pacing to prevent atrial fibrillation: insights from ASSERT. Heart Rhythm 2012;9: 1667 –73. Scheuermeyer FX, Grafstein E, Stenstrom R, Innes G, Heslop C, Macphee J et al.. Thirty-day and 1-year outcomes of emergency department patients with atrial fibrillation and no acute underlying medical cause. Ann Emerg Med 2012;60:755 –65. Xavier Scheuermeyer F, Grafstein E, Stenstrom R, Innes G, Poureslami I, Sighary M. Thirty-day outcomes of emergency department patients undergoing electrical cardioversion for atrial fibrillation or flutter. Acad Emerg Med 2010;17:408 –15. Michael JA, Stiell IG, Agarwal S, Mandavia DP. Cardioversion of paroxysmal atrial fibrillation in the emergency department. Ann Emerg Med 1999;33:379 –87. Morani G, Cicoira M, Pozzani L, Angheben C, Zanotto G, Vassanelli C. Outpatient electrical cardioversion of atrial fibrillation: 8 years’ experience. Analysis of shockrelated arrhythmias. Pacing Clin Electrophysiol 2009;32:1152 – 8. Gallagher MM, Yap YG, Padula M, Ward DE, Rowland E, Camm AJ. Arrhythmic complications of electrical cardioversion: relationship to shock energy. Int J Cardiol 2008; 123:307 – 12. Siaplaouras S, Buob A, Heisel A, Böhm M, Jung J. Outpatient electrical cardioversion of atrial fibrillation: efficacy, safety and patients’ quality of life. Int J Cardiol 2005;105: 26 –30. Downloaded from http://europace.oxfordjournals.org/ at Turku University Library on May 20, 2013 sinus node in AF patients.14 Pacemaker treatment has been reported to reduce the incidence of AF.15,16 On the other hand, the largest, prospective, multicentre trial failed to show any benefit from atrial overdrive pacing on the incidence of new-onset AF.17 In our study, unsuccessful cardioversion was found to be the only predictor which triggered implantation of pacemaker after bradycardic complication. We cannot provide explanation for this finding, although it seems reasonable to assume that the long pauses caused by the shocks together with inability to gain sinus rhythm had led to the decision. To the best of our knowledge, no previous study has focused on arrhythmic complications after electrical cardioversion of acute AF. Previously published studies4 – 6,18 – 23 have been retrospective and most of them have dealt with elective cardioversion of persistent AF (Table 2). Patient populations have been heterogeneous and the criteria for bradycardia have been variable or not available. Our results differ from those of previous small acute AF studies which have reported nearly non-existent risk of complications (0– 0.3%). Because of the low number of patients, none of the previous studies could demonstrate any risk factors for bradycardic complications. In line with the present findings, clinically meaningful ventricular arrhythmias were absent. The incidence of bradyarrhythmias after cardioversion of persistent AF has ranged from 0.8 to 1.5% suggesting that the longer duration of AF may increase bradycardic episodes after cardioversion. One limitation of our study is the retrospective analysis of case notes and databases that may underestimate the number of minor events which were not deemed clinically significant. On the other hand, retrospective study avoids any selection bias and may give a more realistic insight to real life. Our findings cannot be applied to elective or pharmacological cardioversions of AF. In conclusion, our large retrospective study shows that electrical cardioversion of acute AF is a safe procedure. Bradycardic complications are rare, but should be taken into consideration especially when treating older female patients. They seem to uncover subtle SND and often lead to a permanent pacemaker implantation. T. Grönberg et al.