Risk of new-onset atrial fibrillation and stroke after radiofrequency ablation of isolated, typical atrial flutter Jessica Voight, MD,*† Mehmet Akkaya, MD,*† Porur Somasundaram, MD,‡ Rehan Karim, MD,§ Salimah Valliani, MBSS,¶ Younghoon Kwon, MD,*† Selcuk Adabag, MD, MS* From the *Division of Cardiology, Veterans Administration Medical Center, Minneapolis, Minnesota, † Department of Medicine, University of Minnesota, Minneapolis, Minnesota, ‡St. Lukes Medical Center, Duluth, Minnesota, §Hennepin County Medical Center, Minneapolis, Minnesota, and ¶Aga Khan University Medical College, Karachi, Pakistan. BACKGROUND Radiofrequency ablation (RFA) is considered a curative procedure for typical atrial flutter (AFL); however, patients remain at risk for developing new atrial fibrillation (AF). OBJECTIVE The purpose of this study was to determine the incidence and predictors of new-onset AF and stroke after RFA of isolated AFL in a multicenter cohort. METHODS The study included 315 consecutive patients who underwent successful RFA of isolated, typical AFL from 2006 to 2013 at 4 community and teaching hospitals. Patients with any history of AF prior to RFA were excluded. RESULTS During 2.5 ⫾ 1.8 years of follow-up after RFA, 80 patients (25%) developed new AF. In multivariate analysis, after adjusting for baseline medical therapy, obstructive sleep apnea and left atrial enlargement were independently associated with the development of new AF. Presence of a cardiac implantable electronic device (CIED) was associated with a 3.6-fold (95% confidence interval 1.9–6.6, P o.0001) increase in the likelihood of AF detection. New AF was detected in 48% of patients with CIED
Introduction Radiofrequency ablation (RFA) is considered a first-line therapy to achieve rhythm control in patients with typical atrial flutter (AFL).1 With success rates exceeding 90%, the procedure is often considered to be “curative” and has been performed in some patients with isolated AFL to avoid longterm anticoagulation.2 However, after RFA of AFL, patients are still at risk for developing atrial fibrillation (AF) because of risk factors common to both arrhythmias. In previous studies, this risk was reported to be between 16% and 68%.2–10 However, the majority of those patients already had a history of paroxysmal AF prior to ablation. Furthermore, although Address reprint requests and correspondence: Dr. Jessica Voight, University of Minnesota Health, Department of Medicine, 420 Delaware St, SE, MMC 284, Minneapolis, MN 55455. E-mail address: voigh022@ umn.edu.
and 35% of those who underwent Holter ECG vs 19% of those with clinical follow-up only (P o.0001). Anticoagulation was stopped in 58% patients an average of 3.3 ⫾ 4.8 months after RFA. Stroke occurred in 3 patients (1%) during the follow-up period. CONCLUSION New AF occurs in Z25% of patients after RFA of isolated typical AFL, but stroke is relatively rare. Obstructive sleep apnea and left atrial enlargement are risk factors for AF. The presence of a CIED significantly enhances the likelihood of detecting new AF, demonstrating the importance of arrhythmia surveillance after RFA of AFL. KEYWORDS Atrial fibrillation; Atrial flutter; Cardiac implantable electronic device; Obstructive sleep apnea; Radiofrequency ablation ABBREVIATIONS AF ¼ atrial fibrillation; AFL ¼ atrial flutter; CIED ¼ cardiac implantable electronic device; COPD ¼ chronic obstructive pulmonary disease; ECG ¼ electrocardiogram; RFA ¼ radiofrequency ablation (Heart Rhythm 2014;11:1884–1889) I 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
some cardiac risk factors for developing AF after RFA of AFL have been identified, chronic obstructive pulmonary disease (COPD), obesity, and obstructive sleep apnea, which are highly prevalent in the United States, were not examined in this context.11–13 Finally, absence of long-term follow-up after RFA of AFL has reduced the ability to quantify the risk of stroke in these patients. Thus, the objective of this multicenter investigation was to determine the incidence and risk factors for developing new-onset AF after successful RFA of isolated (ie, no prior history of AF) typical AFL and to examine the long-term stroke risk in patients with a high prevalence of obesity, sleep apnea, and COPD. We tested the hypotheses that (1) obesity, sleep apnea, and COPD would be independently associated with development of new AF after RFA of AFL; and (2) there would be an elevated risk of stroke in patients in whom anticoagulation was stopped after RFA of AFL.
1547-5271/$-see front matter B 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.hrthm.2014.06.038
Voight et al
Atrial Fibrillation and Stroke After Flutter Ablation
Methods Patient selection Between January 2006 and June 2013, all patients who underwent successful RFA of typical AFL were reviewed. Patients were excluded from the analysis if they had any history of AF in their medical record or had any 12-lead electrocardiogram (ECG) or cardiac implantable electronic device (CIED) interrogation demonstrating AF. Thus, 315 consecutive patients who underwent successful RFA of isolated typical AFL at the Veterans Affairs Medical Center, Minneapolis, Minnesota (n = 165); St. Luke’s Hospital, Duluth, Minnesota (n = 52); University of Minnesota Medical Center, Minneapolis, Minnesota (n = 51); and the Hennepin County Medical Center, Minneapolis, Minnesota (n = 47) were included in the present retrospective analysis. The study protocol was approved by the Institutional Review Boards of all participating sites. The requirement for individual consent was waived.
Definitions Typical AFL was identified on 12-lead ECG based on the characteristic sawtooth pattern of inverted regular flutter waves with a cycle length of approximately 200 ms, most readily visible in the inferior leads with corresponding positive flutter waves in lead V1.14 AF was characterized by the replacement of regular p waves with uncoordinated fibrillatory waves with an irregular ventricular rate.14 A minimum of 30 seconds of documented AF was necessary to confirm this diagnosis.
Predictor variables Demographic, clinical, laboratory, ECG and echocardiographic data, pharmacy records, and ablation procedure details were obtained retrospectively from electronic medical records. For this purpose, all outpatient clinic notes from cardiology, primary care, and emergency medicine services as well as any inpatient hospitalizations were reviewed. Echocardiographic parameters were obtained from the most recent echocardiogram prior to RFA. Clinical diagnoses, including COPD and obstructive sleep apnea, were ascertained based on a history of these conditions in the electronic medical records. All CIEDs in study patients were implanted prior to undergoing RFA of AFL.
Catheter ablation Study patients underwent a limited electrophysiologic study prior to RFA. Activation sequence in the flutter circuit was determined by a decapolar catheter inserted into the coronary sinus. Depending on the attending electrophysiologist’s preference, either a duo-decapolar Halo catheter (Biosense Webster, Diamond Bar, CA) positioned around the tricuspid valve annulus or electroanatomic mapping with the CARTO system (Biosense Webster) was used to define the AFL circuit. Cavo-tricuspid isthmus dependence of the tachycardia was confirmed by entrainment maneuvers. Induction of tachycardia was attempted in patients with paroxysmal AFL
1885 who presented to the electrophysiology laboratory in sinus rhythm. Temperature-directed RFA (60 W, 60ºC) was performed across the cavo-tricuspid isthmus with an 8-mm-tip ablation catheter, connecting the tricuspid valve annulus to the inferior vena cava. Ablation was deemed successful if evidence of bidirectional block at the ablation line was confirmed by differential pacing, activation sequence on the Halo catheter while pacing from either side of the ablation line, or by electroanatomic mapping.
Outcome variables The primary outcome variable was the development of new AF at any point in time after successful RFA of isolated typical AFL. For this purpose, all ECGs, including Holter and event monitors, and CIED interrogations were carefully reviewed. Holter and event recorder monitoring during follow-up were performed at the attending electrophysiologist’s discretion. Decision to stop or continue anticoagulation after RFA was also made by the treating electrophysiologist. Stroke after RFA was ascertained from the electronic medical records.
Statistical analysis Continuous variables are given as mean ⫾ SD. Categorical variables are given as percentages. Baseline characteristics of the patients who did vs those who did not develop AF were compared using the t test for continuous variables and the χ2 test for categorical variables. Logistic regression analysis was used to identify baseline characteristics associated with the development of AF. Variables associated with AF in univariable analysis with P o.1 were entered into a multivariable model. Using backward stepwise elimination, the final multivariable model was constructed after removing variables with P 4.05. Kaplan–Meier survival curves were constructed to depict time to development of AF in patients with vs those without CIEDs. Survival curves were compared with log-rank test. P o.05 was considered significant. All analyses were performed using SPSS statistical software (version 19, IBM Corp, Armonk, NY).
Results Baseline characteristics The average age of the 315 study patients was 65 ⫾ 12 years; 92% of the patients were men. At the time of RFA, 55% of the study patients were obese (body mass index Z30 kg/m2), 29% had a diagnosis of obstructive sleep apnea, and 25% had a history of COPD. On echocardiography, 34% had left ventricular ejection fraction o50%. Mean CHADS2 score was 1.9 ⫾ 1.2 (62% had CHADS2 score Z2). Baseline characteristics in relation to the development of AF are given in Table 1. Length of follow-up was 2.5 ⫾ 1.8 years.
Development of AF New-onset AF was detected in 80 patients (25%), 2.1 ⫾ 1.7 years after RFA of AFL (101 AF/1000 patient-year followup). In univariate analysis, patients who developed AF
1886 Table 1
Heart Rhythm, Vol 11, No 11, November 2014 Baseline characteristics of the study patients at the time of radiofrequency ablation of atrial flutter
Variable
Develop new AF (n ¼ 80)
No AF (n ¼ 235)
P value
Age (years) Male Body mass index (kg/m2) Hypertension Diabetes mellitus Obstructive sleep apnea Chronic obstructive pulmonary disease Estimated glomerular filtration rate Z60 mL/min/1.73 m2 Coronary heart disease Prior myocardial infarction Congestive heart failure CHADS2 score Angiotensin-converting enzyme inhibitor/aldosterone receptor blocker Beta blocker Statin Antiarrhythmic medications Left ventricular ejection fraction (%) Left atrial diameter (mm) Left ventricular internal dimension—diastole (mm) Valvular disease (%)
66 ⫾ 10 94% 32 ⫾ 7 84% 39% 40% 28% 68% 40% 18% 39% 2.0 ⫾ 1.1 60% 73% 74% 15% 50 ⫾ 12 47 ⫾ 7 52 ⫾ 9 30%
64 ⫾ 12 92% 32 ⫾ 7 80% 37% 26% 25% 75% 34% 13% 26% 1.9 ⫾ 1.2 55% 63% 52% 6% 50 ⫾ 13 44 ⫾ 8 52 ⫾ 8 25%
.316 .520 .511 .262 .835 .014 .617 .227 .302 .291 .036 .335 .466 .107 .001 .007 .667 .014 .676 .402
AF ¼ atrial fibrillation.
during follow-up were more likely to have obstructive sleep apnea, heart failure, left atrial enlargement, antiarrhythmic therapy, and statin therapy (Table 2). In multivariate analysis, after adjustment for baseline medical therapy, the presence of obstructive sleep apnea and left atrial enlargement was independently associated with the development of new AF after RFA of AFL (Table 3).
Utility of surveillance monitoring A total of 54 patients had CIEDs, and 29 patients had ambulatory ECG screening with Holter or event monitor during follow-up. New-onset AF was detected in 48% of patients with CIED, 35% of those with Holter/event monitors, and 19% of those with clinical follow-up only (P o.0001). Detection of AF was 3.6 times (odds ratio 3.56, 95% confidence interval 1.93–6.57, P o.0001) more likely in patients with a CIED than in those without one. Time to AF was shorter in patients with CIEDs or long-term ECG monitoring vs clinical follow-up (Figure 1).
Stroke risk Baseline mean CHADS2 score was 1.9 ⫾ 1.2. Anticoagulation eventually was discontinued in 184 patients (58%), 3.3 ⫾ 4.8 months after RFA. Mean CHADS2 score of the patients in whom anticoagulation was discontinued (2.0 ⫾ 1.2) did not differ significantly from that of the patients who Table 2 Univariate predictors of new-onset atrial fibrillation after successful ablation of isolated, typical atrial flutter Clinical variable
Odds ratio (confidence interval) P value
Obstructive sleep apnea Left atrial diameter (mm) Statin therapy Heart failure Antiarrhythmic therapy
1.94 (1.14–3.32) 1.05 (1.01–1.08) 2.65 (1.51–4.63) 1.77 (1.03–3.02) 3.01 (1.31–6.91)
.02 .02 .001 .04 .01
were asked to continue anticoagulation (1.8 ⫾ 1.2) (P ¼ .25). Stroke occurred in 3 patients (1%) during follow-up, including 1 patient in the immediate post-RFA period (Table 4). Mean time to stroke occurrence was 6 months. Anticoagulation had been stopped in 1 of these 3 patients before the stroke occurred. The remaining 2 patients who experienced stroke had therapeutic levels of anticoagulation at the time of stroke. At the time of stroke, all 3 patients were in normal sinus rhythm on ECG. However, AF eventually was detected in all 3 of these patients (mean time to AF ¼ 12 months).
Discussion In this multicenter study of patients who underwent successful RFA of isolated typical AFL, at least 25% developed new AF during follow-up. History of obstructive sleep apnea and left atrial dilation were independently associated with developing AF. Notably, method of surveillance was the most important factor in the detection of AF; patients with a CIED had a 43 times higher likelihood of being diagnosed with AF. Indeed, AF was detected in 48% of patients with a CIED and 35% of those with Holter ECG or event monitor, demonstrating the importance of arrhythmia surveillance post-RFA. Finally, despite the relatively high risk of AF, the incidence of post-RFA stroke was 1%. There is an accumulating body of evidence linking sleep disordered breathing with the risk for cardiovascular disease. Table 3 Multivariate predictors of new-onset atrial fibrillation after successful ablation of isolated, typical atrial flutter* Clinical variable
Odds ratio (confidence interval) P value
Obstructive sleep apnea 1.81 (1.004 – 3.26) Left atrial diameter (mm) 1.04 (1.001 – 1.08)
.048 .04
* Adjusted for baseline medical therapy and surveillance methodology.
Voight et al
Atrial Fibrillation and Stroke After Flutter Ablation
Figure 1 Kaplan–Meier curve illustrating probability of survival free of atrial fibrillation during postablation follow-up with respect to the method of surveillance. Numbers under the curve are the number of patients at risk. CIED ¼ cardiac implantable electronic device.
Obstructive sleep apnea is a known risk factor for AF in the general population and can make management of AF more complicated.15–17 A limited number of epidemiologic studies, including the Sleep Heart Health Study, have demonstrated that nocturnal AF episodes occur more frequently in those with sleep disordered breathing.18 However, the observation that obstructive sleep apnea was an independent predictor of developing new AF after RFA of AFL is a novel finding. Treatment of obstructive sleep apnea with continuous positive airway pressure has been shown to reduce the likelihood of recurrent episodes of AF.19 Thus, the results of this investigation suggest that vigorous screening and treatment of obstructive sleep apnea in patients undergoing RFA for AFL might reduce future episodes of AF. In this study, new-onset AF was detected in almost 50% of patients with a CIED, which was significantly higher than those who were followed clinically. These patients might represent those with asymptomatic or “silent” AF, which has been reported to account for at least one third of AF patients.20–22 Several investigators previously reported that the incidence of silent AF depends on the intensity of rhythm monitoring, the duration of follow-up, and the AF burden in the cohort studied.21,22 Ziegler et al22 concluded that intermittent and symptom-based surveillance with Holter Table 4 Patient 1 2 3
1887 monitoring is inaccurate and unreliable compared to continuous monitoring for identifying patients with AF. Thus, our finding of a higher incidence of post-RFA development of AF in patients with a CIED, which provides continuous surveillance, is not surprising. However, one must also consider the possibility that patients with sinus node dysfunction or other conduction system abnormality or structural heart disease who require CIED implantation have a higher incidence of AF than the general population.21,23 Although ambulatory Holter/event ECG monitors provide longer surveillance than sporadic 12-lead ECG and clinical follow-up, these methods only capture the heart rhythm for a relatively short period of time, and they are likely to miss episodes of silent paroxysmal AF. Mittal et al24 performed long-term EGC monitoring with an implantable loop recorder in patients who underwent RFA of isolated typical AFL. Of the 20 patients who were implanted post-RFA, 55% were found to have new AF within 62 ⫾ 38 days after ablation. This figure is remarkably similar to the incidence of AF in patients with a CIED in our cohort. Although implanting a loop recorder may not be feasible for all patients who undergo RFA of AFL because of the added invasiveness and cost, this technique potentially could be applied to those patients with a higher risk of developing new AF. There is no consensus on the length of anticoagulation beyond 3 weeks after RFA of AFL, and the current practice guidelines do not provide adequate guidance for clinicians on this subject. In this multicenter investigation, anticoagulation was stopped in 58% of patients 3.3 ⫾ 4.8 months after RFA. However, the development of new AF often was delayed (average 2 years after RFA). Furthermore, reliance on only clinical or ECG detection of AF may misguide a physician’s assessment of stroke risk, resulting in inappropriate withdrawal of anticoagulation.21 The ASSERT trial showed that subclinical atrial tachyarrhythmias 4 6 minutes in duration on CIED monitoring were associated with a 2.5 times increased risk for ischemic stroke in patients without a clinical diagnosis of AF.25 Welles et al26 reported that an elevated CHADS2 was an independent predictor of ischemic stroke/transient ischemic attack in patients without documented AF and that they may benefit from lifelong anticoagulation for primary stroke prevention. Although our incidence of stroke in the follow-up period was low (only 3 patients [1%]), this may be due to inadequate length of follow-up or continuation of anticoagulation. Thus, clinicians might elect to continue anticoagulation indefinitely in patients with a higher CHADS2 score or those at higher risk for new AF based on comorbidities.
Clinical characteristics of patients who experienced post-RFA stroke CHADS2 score 3 2 4
Time to stroke (months) *
0 7 11
AF ¼ atrial fibrillation; RFA ¼ radiofrequency ablation. * Stroke occurred on post-RFA day 2.
Anticoagulation stopped prior to stroke
Develop AF
Time to AF (months)
No No Yes
Yes Yes Yes
8 6 22
1888 In this study, statin therapy was associated with an increased risk of new-onset AF after RFA of AFL in univariable analysis (Table 2). This is contrary to several reports indicating that statin therapy is associated with a reduction in the incidence of AF.27–29 However, a comparison of the patients in this study who received statin therapy to those who did not revealed that patients receiving statin therapy had many more comorbidities (data not shown). Thus, selection bias was the most likely cause of the increased incidence of post-RFA development of new AF in patients who received statin therapy. It is likely that a similar bias was also at play for postablation continuation of antiarrhythmic therapy, which was also associated with an increased risk of AF (Table 2). Indeed, physicians might have elected to continue antiarrhythmic therapy after ablation in patients who they suspected of being at higher risk for AF.
Heart Rhythm, Vol 11, No 11, November 2014
2.
3.
4.
5.
6.
7.
8.
Study strengths and limitations The strengths of this investigation include the multicenter patient population and the larger sample size in comparison to previous reports on this topic. Furthermore, the selection of patients with no prior history of AF before RFA was important in assessing the risk of new AF. However, there were several limitations. First, a large percentage of the study cohort was male. This may reduce the generalizability of our results to women. Second, although patients’ electronic medical records were thoroughly reviewed for any history of AF prior to RFA of AFL, there may have been some cases of silent AF that were undiagnosed. Similarly, it is possible that asymptomatic episodes of AF might have been missed in patients who were followed after RFA by clinical means only. Third, follow-up duration might not have been long enough to detect a substantial number of strokes. Finally, because of the retrospective, multicenter design, practice patterns varied between centers and practitioners. Indeed, it is important that multicenter studies be standardized and have adequate follow-up. A prospective multicenter cohort study might abolish these limitations.
Conclusion
9.
10.
11.
12.
13.
14.
15.
16.
New-onset AF occurred in at least 25% of patients who underwent successful RFA of isolated typical AFL. History of obstructive sleep apnea and left atrial dilation were independently associated with the development and detection of new AF. The presence of a CIED increased the likelihood of AF detection by more than 3 times. Only 1% of patients experienced stroke during follow-up. Higher detection of AF in patients with CIED emphasizes the importance of arrhythmia surveillance post-RFA.
18.
References
21.
1. Blomstrom-Lundqvist C, Scheinman MM, Aliot EM, et al. ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias— executive summary. 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 Develop Guidelines for the Management of Patients with Supraventricular Arrhythmias)
17.
19. 20.
22. 23.
developed in collaboration with NASPE-Heart Rhythm Society. J Am Coll Cardiol 2003;42:1493–1531. Spector P, Reynolds MR, Calkins H, Sondhi M, Xu Y, Martin A, Williams CJ, Sledge I. Meta-analysis of ablation of atrial flutter and supraventricular tachycardia. Am J Cardiol 2009;104:671–677. Tomson TT, Kapa S, Bala R, Riley MP, Lin D, Epstein AE, Deo R, Dixit S. Risk of stroke and atrial fibrillation after radiofrequency catheter ablation of typical atrial flutter. Heart Rhythm 2012;9:1779–1784. Chinitz JS, Gerstenfeld EP, Marchlinski FE, Callans DJ. Atrial fibrillation is common after ablation of isolated atrial flutter during long-term follow-up. Heart Rhythm 2007;4:1029–1033. Moubarak G, Pavin D, Laviolle B, Solnon A, Kervio G, Daubert JC, Mabo P. Incidence of atrial fibrillation during very long-term follow-up after radiofrequency ablation of typical atrial flutter. Arch Cardiovasc Dis 2009;102:525–532. Ellis K, Wazni O, Marrouche N, et al. Incidence of atrial fibrillation postcavotricuspid isthmus ablation in patients with typical atrial flutter: left-atrial size as an independent predictor of atrial fibrillation recurrence. J Cardiovasc Electrophysiol 2007;18:799–802. Laurent V, Fauchier L, Pierre B, Grimard C, Babuty D. Incidence and predictive factors of atrial fibrillation after ablation of typical atrial flutter. J Interv Card Electrophysiol 2009;24:119–125. Bertaglia E, Zoppo F, Bonso A, Proclemer A, Verlato R, Corò L, Mantovan R, D’Este D, Zerbo F, Pascotto P. Long term follow up of radiofrequency catheter ablation of atrial flutter: clinical course and predictors of atrial fibrillation occurrence. Heart 2004;90:59–63. Bertaglia E, Bonso A, Zoppo F, Proclemer A, Verlato R, Corò L, Mantovan R, Themistoclakis S, Raviele A, Pascotto P. Different clinical courses and predictors of atrial fibrillation occurrence after transisthmic ablation in patients with preablation lone atrial flutter, coexistent atrial fibrillation, and drug induced atrial flutter. Pacing Clin Electrophysiol 2004;27:1507–1512. Bandini A, Golia P, Caroli E, Biancoli S, Galvani M. Atrial fibrillation after typical atrial flutter ablation: a long-term follow-up. J Cardiovasc Med (Hagerstown) 2011;12:110–115. Wang TJ, Parise H, Levy D, D’Agostino RB Sr, Wolf PA, Vasan RS, Benjamin EJ. Obesity and the risk of new-onset atrial fibrillation. JAMA 2004;292: 2471–2477. Wanahita N, Messerli FH, Bangalore S, Gami AS, Somers VK, Steinberg JS. Atrial fibrillation and obesity–results of a meta-analysis. Am Heart J 2008;155: 310–315. Buch P, Friberg J, Scharling H, Lange P, Prescott E. Reduced lung function and risk of atrial fibrillation in the Copenhagen City Heart Study. Eur Respir J 2003;21:1012–1016. Fuster V, Ryden LE, Cannom DS, et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in partnership with the European Society of Cardiology and in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. J Am Coll Cardiol 2011;57:e101–e198. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000;342: 1378–1384. Gottlieb DJ, Yenokyan G, Newman AB, O’Connor GT, Punjabi NM, Quan SF, Redline S, Resnick HE, Tong EK, Diener-West M, Shahar E. Prospective study of obstructive sleep apnea and incident coronary heart disease and heart failure: the Sleep Heart Health Study. Circulation 2010;122:352–360. Redline S, Yenokyan G, Gottlieb DJ, et al. Obstructive sleep apnea-hypopnea and incident stroke: the Sleep Heart Health Study. Am J Respir Crit Care Med 2010;182:269–277. Mehra R, Benjamin EJ, Shahar E, Gottlieb DJ, Nawabit R, Kirchner HL, Sahadevan J, Redline S. Association of nocturnal arrhythmias with sleepdisordered breathing: the Sleep Heart Health Study. Am J Respir Crit Care Med 2006;173:910–916. Goyal SK, Sharma A. Atrial fibrillation in obstructive sleep apnea. World J Cardiol 2013;5:157–163. Savelieva I, Camm AJ. Clinical relevance of silent atrial fibrillation: prevalence, prognosis, quality of life, and management. J Interv Card Electrophysiol 2000;4: 369–382. Rho RW, Page RL. Asymptomatic atrial fibrillation. Prog Cardiovasc Dis 2005;48:79–87. Ziegler PD, Koehler JL, Mehra R. Comparison of continuous versus intermittent monitoring of atrial arrhythmias. Heart Rhythm 2006;3:1445–1452. Elkayam LU, Koehler JL, Sheldon TJ, Glotzer TV, Rosenthal LS, Lamas GA. The influence of atrial and ventricular pacing on the incidence of atrial fibrillation: a meta-analysis. Pacing Clin Electrophysiol 2011;34:1593–1599.
Voight et al
Atrial Fibrillation and Stroke After Flutter Ablation
24. Mittal S, Pokushalov E, Romanov A, Ferrara M, Arshad A, Musat D, Preminger M, Sichrovsky T, Steinberg JS. Long-term ECG monitoring using an implantable loop recorder for the detection of atrial fibrillation after cavotricuspid isthmus ablation in patients with atrial flutter. Heart Rhythm 2013;10:1598–1604. 25. Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med 2012;366:120–129. 26. Welles CC, Whooley MA, Na B, Ganz P, Schiller NB, Turakhia MP. The CHADS2 score predicts ischemic stroke in the absence of atrial fibrillation among subjects with coronary heart disease: data from the Heart and Soul Study. Am Heart J 2011;162:555–561.
1889 27. Mithani S, Akbar MS, Johnson DJ, Kuskowski M, Apple KK, Bonawitz-Conlin J, Ward HB, Kelly RF, McFalls EO, Bloomfield HE, Li JM, Adabag S. Dose dependent effect of statins on postoperative atrial fibrillation after cardiac surgery among patients treated with beta blockers. J Cardiothorac Surg 2009;4: 61. (10.1186/1749-8090-4-61). 28. Wang Z, Zhang Y, Gao M, Wang J, Wang Q, Wang X, Su L, Hou Y. Statin therapy for the prevention of atrial fibrillation: a meta-analysis of randomized controlled trials. Pharmacotherapy 2011;31:1051–1062. 29. Adabag AS, Nelson DB, Bloomfield HE. Effects of statin therapy on preventing atrial fibrillation in coronary disease and heart failure. Am Heart J 2007;154:1140–1145.
CLINICAL PERSPECTIVES This multicenter study of patients who underwent radiofrequency ablation (RFA) of isolated, typical atrial flutter (AFL) illustrates that at least 25% of patients without documented atrial fibrillation (AF) before ablation develop new AF during an average 2.5 years of follow-up after ablation. Occurrence of new AF was particularly high (50%) in patients with a cardiac implantable electronic device (CIED), demonstrating the importance of continuous arrhythmia surveillance in these patients. Obstructive sleep apnea and left atrial size were associated with a higher risk of developing new-onset AF after RFA of isolated typical AFL. Although AF was common after RFA of AFL, the incidence of stroke was relatively low. This information is clinically helpful in selecting patients for RFA of AFL and in identifying those, such as patients with sleep apnea and enlarged left atrium, who would benefit from close arrhythmia surveillance after RFA. In addition, these results may indirectly suggest continuation of systemic anticoagulation after RFA of AFL in select patients who are likely to develop AF and have a higher risk of thromboembolism.
Introduction Radiofrequency ablation (RFA) is considered a first-line therapy to achieve rhythm control in patients with typical atrial flutter (AFL).1 With success rates exceeding 90%, the procedure is often considered to be “curative” and has been performed in some patients with isolated AFL to avoid longterm anticoagulation.2 However, after RFA of AFL, patients are still at risk for developing atrial fibrillation (AF) because of risk factors common to both arrhythmias. In previous studies, this risk was reported to be between 16% and 68%.2–10 However, the majority of those patients already had a history of paroxysmal AF prior to ablation. Furthermore, although Address reprint requests and correspondence: Dr. Jessica Voight, University of Minnesota Health, Department of Medicine, 420 Delaware St, SE, MMC 284, Minneapolis, MN 55455. E-mail address: voigh022@ umn.edu.
and 35% of those who underwent Holter ECG vs 19% of those with clinical follow-up only (P o.0001). Anticoagulation was stopped in 58% patients an average of 3.3 ⫾ 4.8 months after RFA. Stroke occurred in 3 patients (1%) during the follow-up period. CONCLUSION New AF occurs in Z25% of patients after RFA of isolated typical AFL, but stroke is relatively rare. Obstructive sleep apnea and left atrial enlargement are risk factors for AF. The presence of a CIED significantly enhances the likelihood of detecting new AF, demonstrating the importance of arrhythmia surveillance after RFA of AFL. KEYWORDS Atrial fibrillation; Atrial flutter; Cardiac implantable electronic device; Obstructive sleep apnea; Radiofrequency ablation ABBREVIATIONS AF ¼ atrial fibrillation; AFL ¼ atrial flutter; CIED ¼ cardiac implantable electronic device; COPD ¼ chronic obstructive pulmonary disease; ECG ¼ electrocardiogram; RFA ¼ radiofrequency ablation (Heart Rhythm 2014;11:1884–1889) I 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
some cardiac risk factors for developing AF after RFA of AFL have been identified, chronic obstructive pulmonary disease (COPD), obesity, and obstructive sleep apnea, which are highly prevalent in the United States, were not examined in this context.11–13 Finally, absence of long-term follow-up after RFA of AFL has reduced the ability to quantify the risk of stroke in these patients. Thus, the objective of this multicenter investigation was to determine the incidence and risk factors for developing new-onset AF after successful RFA of isolated (ie, no prior history of AF) typical AFL and to examine the long-term stroke risk in patients with a high prevalence of obesity, sleep apnea, and COPD. We tested the hypotheses that (1) obesity, sleep apnea, and COPD would be independently associated with development of new AF after RFA of AFL; and (2) there would be an elevated risk of stroke in patients in whom anticoagulation was stopped after RFA of AFL.
1547-5271/$-see front matter B 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.hrthm.2014.06.038
Voight et al
Atrial Fibrillation and Stroke After Flutter Ablation
Methods Patient selection Between January 2006 and June 2013, all patients who underwent successful RFA of typical AFL were reviewed. Patients were excluded from the analysis if they had any history of AF in their medical record or had any 12-lead electrocardiogram (ECG) or cardiac implantable electronic device (CIED) interrogation demonstrating AF. Thus, 315 consecutive patients who underwent successful RFA of isolated typical AFL at the Veterans Affairs Medical Center, Minneapolis, Minnesota (n = 165); St. Luke’s Hospital, Duluth, Minnesota (n = 52); University of Minnesota Medical Center, Minneapolis, Minnesota (n = 51); and the Hennepin County Medical Center, Minneapolis, Minnesota (n = 47) were included in the present retrospective analysis. The study protocol was approved by the Institutional Review Boards of all participating sites. The requirement for individual consent was waived.
Definitions Typical AFL was identified on 12-lead ECG based on the characteristic sawtooth pattern of inverted regular flutter waves with a cycle length of approximately 200 ms, most readily visible in the inferior leads with corresponding positive flutter waves in lead V1.14 AF was characterized by the replacement of regular p waves with uncoordinated fibrillatory waves with an irregular ventricular rate.14 A minimum of 30 seconds of documented AF was necessary to confirm this diagnosis.
Predictor variables Demographic, clinical, laboratory, ECG and echocardiographic data, pharmacy records, and ablation procedure details were obtained retrospectively from electronic medical records. For this purpose, all outpatient clinic notes from cardiology, primary care, and emergency medicine services as well as any inpatient hospitalizations were reviewed. Echocardiographic parameters were obtained from the most recent echocardiogram prior to RFA. Clinical diagnoses, including COPD and obstructive sleep apnea, were ascertained based on a history of these conditions in the electronic medical records. All CIEDs in study patients were implanted prior to undergoing RFA of AFL.
Catheter ablation Study patients underwent a limited electrophysiologic study prior to RFA. Activation sequence in the flutter circuit was determined by a decapolar catheter inserted into the coronary sinus. Depending on the attending electrophysiologist’s preference, either a duo-decapolar Halo catheter (Biosense Webster, Diamond Bar, CA) positioned around the tricuspid valve annulus or electroanatomic mapping with the CARTO system (Biosense Webster) was used to define the AFL circuit. Cavo-tricuspid isthmus dependence of the tachycardia was confirmed by entrainment maneuvers. Induction of tachycardia was attempted in patients with paroxysmal AFL
1885 who presented to the electrophysiology laboratory in sinus rhythm. Temperature-directed RFA (60 W, 60ºC) was performed across the cavo-tricuspid isthmus with an 8-mm-tip ablation catheter, connecting the tricuspid valve annulus to the inferior vena cava. Ablation was deemed successful if evidence of bidirectional block at the ablation line was confirmed by differential pacing, activation sequence on the Halo catheter while pacing from either side of the ablation line, or by electroanatomic mapping.
Outcome variables The primary outcome variable was the development of new AF at any point in time after successful RFA of isolated typical AFL. For this purpose, all ECGs, including Holter and event monitors, and CIED interrogations were carefully reviewed. Holter and event recorder monitoring during follow-up were performed at the attending electrophysiologist’s discretion. Decision to stop or continue anticoagulation after RFA was also made by the treating electrophysiologist. Stroke after RFA was ascertained from the electronic medical records.
Statistical analysis Continuous variables are given as mean ⫾ SD. Categorical variables are given as percentages. Baseline characteristics of the patients who did vs those who did not develop AF were compared using the t test for continuous variables and the χ2 test for categorical variables. Logistic regression analysis was used to identify baseline characteristics associated with the development of AF. Variables associated with AF in univariable analysis with P o.1 were entered into a multivariable model. Using backward stepwise elimination, the final multivariable model was constructed after removing variables with P 4.05. Kaplan–Meier survival curves were constructed to depict time to development of AF in patients with vs those without CIEDs. Survival curves were compared with log-rank test. P o.05 was considered significant. All analyses were performed using SPSS statistical software (version 19, IBM Corp, Armonk, NY).
Results Baseline characteristics The average age of the 315 study patients was 65 ⫾ 12 years; 92% of the patients were men. At the time of RFA, 55% of the study patients were obese (body mass index Z30 kg/m2), 29% had a diagnosis of obstructive sleep apnea, and 25% had a history of COPD. On echocardiography, 34% had left ventricular ejection fraction o50%. Mean CHADS2 score was 1.9 ⫾ 1.2 (62% had CHADS2 score Z2). Baseline characteristics in relation to the development of AF are given in Table 1. Length of follow-up was 2.5 ⫾ 1.8 years.
Development of AF New-onset AF was detected in 80 patients (25%), 2.1 ⫾ 1.7 years after RFA of AFL (101 AF/1000 patient-year followup). In univariate analysis, patients who developed AF
1886 Table 1
Heart Rhythm, Vol 11, No 11, November 2014 Baseline characteristics of the study patients at the time of radiofrequency ablation of atrial flutter
Variable
Develop new AF (n ¼ 80)
No AF (n ¼ 235)
P value
Age (years) Male Body mass index (kg/m2) Hypertension Diabetes mellitus Obstructive sleep apnea Chronic obstructive pulmonary disease Estimated glomerular filtration rate Z60 mL/min/1.73 m2 Coronary heart disease Prior myocardial infarction Congestive heart failure CHADS2 score Angiotensin-converting enzyme inhibitor/aldosterone receptor blocker Beta blocker Statin Antiarrhythmic medications Left ventricular ejection fraction (%) Left atrial diameter (mm) Left ventricular internal dimension—diastole (mm) Valvular disease (%)
66 ⫾ 10 94% 32 ⫾ 7 84% 39% 40% 28% 68% 40% 18% 39% 2.0 ⫾ 1.1 60% 73% 74% 15% 50 ⫾ 12 47 ⫾ 7 52 ⫾ 9 30%
64 ⫾ 12 92% 32 ⫾ 7 80% 37% 26% 25% 75% 34% 13% 26% 1.9 ⫾ 1.2 55% 63% 52% 6% 50 ⫾ 13 44 ⫾ 8 52 ⫾ 8 25%
.316 .520 .511 .262 .835 .014 .617 .227 .302 .291 .036 .335 .466 .107 .001 .007 .667 .014 .676 .402
AF ¼ atrial fibrillation.
during follow-up were more likely to have obstructive sleep apnea, heart failure, left atrial enlargement, antiarrhythmic therapy, and statin therapy (Table 2). In multivariate analysis, after adjustment for baseline medical therapy, the presence of obstructive sleep apnea and left atrial enlargement was independently associated with the development of new AF after RFA of AFL (Table 3).
Utility of surveillance monitoring A total of 54 patients had CIEDs, and 29 patients had ambulatory ECG screening with Holter or event monitor during follow-up. New-onset AF was detected in 48% of patients with CIED, 35% of those with Holter/event monitors, and 19% of those with clinical follow-up only (P o.0001). Detection of AF was 3.6 times (odds ratio 3.56, 95% confidence interval 1.93–6.57, P o.0001) more likely in patients with a CIED than in those without one. Time to AF was shorter in patients with CIEDs or long-term ECG monitoring vs clinical follow-up (Figure 1).
Stroke risk Baseline mean CHADS2 score was 1.9 ⫾ 1.2. Anticoagulation eventually was discontinued in 184 patients (58%), 3.3 ⫾ 4.8 months after RFA. Mean CHADS2 score of the patients in whom anticoagulation was discontinued (2.0 ⫾ 1.2) did not differ significantly from that of the patients who Table 2 Univariate predictors of new-onset atrial fibrillation after successful ablation of isolated, typical atrial flutter Clinical variable
Odds ratio (confidence interval) P value
Obstructive sleep apnea Left atrial diameter (mm) Statin therapy Heart failure Antiarrhythmic therapy
1.94 (1.14–3.32) 1.05 (1.01–1.08) 2.65 (1.51–4.63) 1.77 (1.03–3.02) 3.01 (1.31–6.91)
.02 .02 .001 .04 .01
were asked to continue anticoagulation (1.8 ⫾ 1.2) (P ¼ .25). Stroke occurred in 3 patients (1%) during follow-up, including 1 patient in the immediate post-RFA period (Table 4). Mean time to stroke occurrence was 6 months. Anticoagulation had been stopped in 1 of these 3 patients before the stroke occurred. The remaining 2 patients who experienced stroke had therapeutic levels of anticoagulation at the time of stroke. At the time of stroke, all 3 patients were in normal sinus rhythm on ECG. However, AF eventually was detected in all 3 of these patients (mean time to AF ¼ 12 months).
Discussion In this multicenter study of patients who underwent successful RFA of isolated typical AFL, at least 25% developed new AF during follow-up. History of obstructive sleep apnea and left atrial dilation were independently associated with developing AF. Notably, method of surveillance was the most important factor in the detection of AF; patients with a CIED had a 43 times higher likelihood of being diagnosed with AF. Indeed, AF was detected in 48% of patients with a CIED and 35% of those with Holter ECG or event monitor, demonstrating the importance of arrhythmia surveillance post-RFA. Finally, despite the relatively high risk of AF, the incidence of post-RFA stroke was 1%. There is an accumulating body of evidence linking sleep disordered breathing with the risk for cardiovascular disease. Table 3 Multivariate predictors of new-onset atrial fibrillation after successful ablation of isolated, typical atrial flutter* Clinical variable
Odds ratio (confidence interval) P value
Obstructive sleep apnea 1.81 (1.004 – 3.26) Left atrial diameter (mm) 1.04 (1.001 – 1.08)
.048 .04
* Adjusted for baseline medical therapy and surveillance methodology.
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Atrial Fibrillation and Stroke After Flutter Ablation
Figure 1 Kaplan–Meier curve illustrating probability of survival free of atrial fibrillation during postablation follow-up with respect to the method of surveillance. Numbers under the curve are the number of patients at risk. CIED ¼ cardiac implantable electronic device.
Obstructive sleep apnea is a known risk factor for AF in the general population and can make management of AF more complicated.15–17 A limited number of epidemiologic studies, including the Sleep Heart Health Study, have demonstrated that nocturnal AF episodes occur more frequently in those with sleep disordered breathing.18 However, the observation that obstructive sleep apnea was an independent predictor of developing new AF after RFA of AFL is a novel finding. Treatment of obstructive sleep apnea with continuous positive airway pressure has been shown to reduce the likelihood of recurrent episodes of AF.19 Thus, the results of this investigation suggest that vigorous screening and treatment of obstructive sleep apnea in patients undergoing RFA for AFL might reduce future episodes of AF. In this study, new-onset AF was detected in almost 50% of patients with a CIED, which was significantly higher than those who were followed clinically. These patients might represent those with asymptomatic or “silent” AF, which has been reported to account for at least one third of AF patients.20–22 Several investigators previously reported that the incidence of silent AF depends on the intensity of rhythm monitoring, the duration of follow-up, and the AF burden in the cohort studied.21,22 Ziegler et al22 concluded that intermittent and symptom-based surveillance with Holter Table 4 Patient 1 2 3
1887 monitoring is inaccurate and unreliable compared to continuous monitoring for identifying patients with AF. Thus, our finding of a higher incidence of post-RFA development of AF in patients with a CIED, which provides continuous surveillance, is not surprising. However, one must also consider the possibility that patients with sinus node dysfunction or other conduction system abnormality or structural heart disease who require CIED implantation have a higher incidence of AF than the general population.21,23 Although ambulatory Holter/event ECG monitors provide longer surveillance than sporadic 12-lead ECG and clinical follow-up, these methods only capture the heart rhythm for a relatively short period of time, and they are likely to miss episodes of silent paroxysmal AF. Mittal et al24 performed long-term EGC monitoring with an implantable loop recorder in patients who underwent RFA of isolated typical AFL. Of the 20 patients who were implanted post-RFA, 55% were found to have new AF within 62 ⫾ 38 days after ablation. This figure is remarkably similar to the incidence of AF in patients with a CIED in our cohort. Although implanting a loop recorder may not be feasible for all patients who undergo RFA of AFL because of the added invasiveness and cost, this technique potentially could be applied to those patients with a higher risk of developing new AF. There is no consensus on the length of anticoagulation beyond 3 weeks after RFA of AFL, and the current practice guidelines do not provide adequate guidance for clinicians on this subject. In this multicenter investigation, anticoagulation was stopped in 58% of patients 3.3 ⫾ 4.8 months after RFA. However, the development of new AF often was delayed (average 2 years after RFA). Furthermore, reliance on only clinical or ECG detection of AF may misguide a physician’s assessment of stroke risk, resulting in inappropriate withdrawal of anticoagulation.21 The ASSERT trial showed that subclinical atrial tachyarrhythmias 4 6 minutes in duration on CIED monitoring were associated with a 2.5 times increased risk for ischemic stroke in patients without a clinical diagnosis of AF.25 Welles et al26 reported that an elevated CHADS2 was an independent predictor of ischemic stroke/transient ischemic attack in patients without documented AF and that they may benefit from lifelong anticoagulation for primary stroke prevention. Although our incidence of stroke in the follow-up period was low (only 3 patients [1%]), this may be due to inadequate length of follow-up or continuation of anticoagulation. Thus, clinicians might elect to continue anticoagulation indefinitely in patients with a higher CHADS2 score or those at higher risk for new AF based on comorbidities.
Clinical characteristics of patients who experienced post-RFA stroke CHADS2 score 3 2 4
Time to stroke (months) *
0 7 11
AF ¼ atrial fibrillation; RFA ¼ radiofrequency ablation. * Stroke occurred on post-RFA day 2.
Anticoagulation stopped prior to stroke
Develop AF
Time to AF (months)
No No Yes
Yes Yes Yes
8 6 22
1888 In this study, statin therapy was associated with an increased risk of new-onset AF after RFA of AFL in univariable analysis (Table 2). This is contrary to several reports indicating that statin therapy is associated with a reduction in the incidence of AF.27–29 However, a comparison of the patients in this study who received statin therapy to those who did not revealed that patients receiving statin therapy had many more comorbidities (data not shown). Thus, selection bias was the most likely cause of the increased incidence of post-RFA development of new AF in patients who received statin therapy. It is likely that a similar bias was also at play for postablation continuation of antiarrhythmic therapy, which was also associated with an increased risk of AF (Table 2). Indeed, physicians might have elected to continue antiarrhythmic therapy after ablation in patients who they suspected of being at higher risk for AF.
Heart Rhythm, Vol 11, No 11, November 2014
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8.
Study strengths and limitations The strengths of this investigation include the multicenter patient population and the larger sample size in comparison to previous reports on this topic. Furthermore, the selection of patients with no prior history of AF before RFA was important in assessing the risk of new AF. However, there were several limitations. First, a large percentage of the study cohort was male. This may reduce the generalizability of our results to women. Second, although patients’ electronic medical records were thoroughly reviewed for any history of AF prior to RFA of AFL, there may have been some cases of silent AF that were undiagnosed. Similarly, it is possible that asymptomatic episodes of AF might have been missed in patients who were followed after RFA by clinical means only. Third, follow-up duration might not have been long enough to detect a substantial number of strokes. Finally, because of the retrospective, multicenter design, practice patterns varied between centers and practitioners. Indeed, it is important that multicenter studies be standardized and have adequate follow-up. A prospective multicenter cohort study might abolish these limitations.
Conclusion
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New-onset AF occurred in at least 25% of patients who underwent successful RFA of isolated typical AFL. History of obstructive sleep apnea and left atrial dilation were independently associated with the development and detection of new AF. The presence of a CIED increased the likelihood of AF detection by more than 3 times. Only 1% of patients experienced stroke during follow-up. Higher detection of AF in patients with CIED emphasizes the importance of arrhythmia surveillance post-RFA.
18.
References
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1. Blomstrom-Lundqvist C, Scheinman MM, Aliot EM, et al. ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias— executive summary. 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 Develop Guidelines for the Management of Patients with Supraventricular Arrhythmias)
17.
19. 20.
22. 23.
developed in collaboration with NASPE-Heart Rhythm Society. J Am Coll Cardiol 2003;42:1493–1531. Spector P, Reynolds MR, Calkins H, Sondhi M, Xu Y, Martin A, Williams CJ, Sledge I. Meta-analysis of ablation of atrial flutter and supraventricular tachycardia. Am J Cardiol 2009;104:671–677. Tomson TT, Kapa S, Bala R, Riley MP, Lin D, Epstein AE, Deo R, Dixit S. Risk of stroke and atrial fibrillation after radiofrequency catheter ablation of typical atrial flutter. Heart Rhythm 2012;9:1779–1784. Chinitz JS, Gerstenfeld EP, Marchlinski FE, Callans DJ. Atrial fibrillation is common after ablation of isolated atrial flutter during long-term follow-up. Heart Rhythm 2007;4:1029–1033. Moubarak G, Pavin D, Laviolle B, Solnon A, Kervio G, Daubert JC, Mabo P. Incidence of atrial fibrillation during very long-term follow-up after radiofrequency ablation of typical atrial flutter. Arch Cardiovasc Dis 2009;102:525–532. Ellis K, Wazni O, Marrouche N, et al. Incidence of atrial fibrillation postcavotricuspid isthmus ablation in patients with typical atrial flutter: left-atrial size as an independent predictor of atrial fibrillation recurrence. J Cardiovasc Electrophysiol 2007;18:799–802. Laurent V, Fauchier L, Pierre B, Grimard C, Babuty D. Incidence and predictive factors of atrial fibrillation after ablation of typical atrial flutter. J Interv Card Electrophysiol 2009;24:119–125. Bertaglia E, Zoppo F, Bonso A, Proclemer A, Verlato R, Corò L, Mantovan R, D’Este D, Zerbo F, Pascotto P. Long term follow up of radiofrequency catheter ablation of atrial flutter: clinical course and predictors of atrial fibrillation occurrence. Heart 2004;90:59–63. Bertaglia E, Bonso A, Zoppo F, Proclemer A, Verlato R, Corò L, Mantovan R, Themistoclakis S, Raviele A, Pascotto P. Different clinical courses and predictors of atrial fibrillation occurrence after transisthmic ablation in patients with preablation lone atrial flutter, coexistent atrial fibrillation, and drug induced atrial flutter. Pacing Clin Electrophysiol 2004;27:1507–1512. Bandini A, Golia P, Caroli E, Biancoli S, Galvani M. Atrial fibrillation after typical atrial flutter ablation: a long-term follow-up. J Cardiovasc Med (Hagerstown) 2011;12:110–115. Wang TJ, Parise H, Levy D, D’Agostino RB Sr, Wolf PA, Vasan RS, Benjamin EJ. Obesity and the risk of new-onset atrial fibrillation. JAMA 2004;292: 2471–2477. Wanahita N, Messerli FH, Bangalore S, Gami AS, Somers VK, Steinberg JS. Atrial fibrillation and obesity–results of a meta-analysis. Am Heart J 2008;155: 310–315. Buch P, Friberg J, Scharling H, Lange P, Prescott E. Reduced lung function and risk of atrial fibrillation in the Copenhagen City Heart Study. Eur Respir J 2003;21:1012–1016. Fuster V, Ryden LE, Cannom DS, et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in partnership with the European Society of Cardiology and in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. J Am Coll Cardiol 2011;57:e101–e198. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000;342: 1378–1384. Gottlieb DJ, Yenokyan G, Newman AB, O’Connor GT, Punjabi NM, Quan SF, Redline S, Resnick HE, Tong EK, Diener-West M, Shahar E. Prospective study of obstructive sleep apnea and incident coronary heart disease and heart failure: the Sleep Heart Health Study. Circulation 2010;122:352–360. Redline S, Yenokyan G, Gottlieb DJ, et al. Obstructive sleep apnea-hypopnea and incident stroke: the Sleep Heart Health Study. Am J Respir Crit Care Med 2010;182:269–277. Mehra R, Benjamin EJ, Shahar E, Gottlieb DJ, Nawabit R, Kirchner HL, Sahadevan J, Redline S. Association of nocturnal arrhythmias with sleepdisordered breathing: the Sleep Heart Health Study. Am J Respir Crit Care Med 2006;173:910–916. Goyal SK, Sharma A. Atrial fibrillation in obstructive sleep apnea. World J Cardiol 2013;5:157–163. Savelieva I, Camm AJ. Clinical relevance of silent atrial fibrillation: prevalence, prognosis, quality of life, and management. J Interv Card Electrophysiol 2000;4: 369–382. Rho RW, Page RL. Asymptomatic atrial fibrillation. Prog Cardiovasc Dis 2005;48:79–87. Ziegler PD, Koehler JL, Mehra R. Comparison of continuous versus intermittent monitoring of atrial arrhythmias. Heart Rhythm 2006;3:1445–1452. Elkayam LU, Koehler JL, Sheldon TJ, Glotzer TV, Rosenthal LS, Lamas GA. The influence of atrial and ventricular pacing on the incidence of atrial fibrillation: a meta-analysis. Pacing Clin Electrophysiol 2011;34:1593–1599.
Voight et al
Atrial Fibrillation and Stroke After Flutter Ablation
24. Mittal S, Pokushalov E, Romanov A, Ferrara M, Arshad A, Musat D, Preminger M, Sichrovsky T, Steinberg JS. Long-term ECG monitoring using an implantable loop recorder for the detection of atrial fibrillation after cavotricuspid isthmus ablation in patients with atrial flutter. Heart Rhythm 2013;10:1598–1604. 25. Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med 2012;366:120–129. 26. Welles CC, Whooley MA, Na B, Ganz P, Schiller NB, Turakhia MP. The CHADS2 score predicts ischemic stroke in the absence of atrial fibrillation among subjects with coronary heart disease: data from the Heart and Soul Study. Am Heart J 2011;162:555–561.
1889 27. Mithani S, Akbar MS, Johnson DJ, Kuskowski M, Apple KK, Bonawitz-Conlin J, Ward HB, Kelly RF, McFalls EO, Bloomfield HE, Li JM, Adabag S. Dose dependent effect of statins on postoperative atrial fibrillation after cardiac surgery among patients treated with beta blockers. J Cardiothorac Surg 2009;4: 61. (10.1186/1749-8090-4-61). 28. Wang Z, Zhang Y, Gao M, Wang J, Wang Q, Wang X, Su L, Hou Y. Statin therapy for the prevention of atrial fibrillation: a meta-analysis of randomized controlled trials. Pharmacotherapy 2011;31:1051–1062. 29. Adabag AS, Nelson DB, Bloomfield HE. Effects of statin therapy on preventing atrial fibrillation in coronary disease and heart failure. Am Heart J 2007;154:1140–1145.
CLINICAL PERSPECTIVES This multicenter study of patients who underwent radiofrequency ablation (RFA) of isolated, typical atrial flutter (AFL) illustrates that at least 25% of patients without documented atrial fibrillation (AF) before ablation develop new AF during an average 2.5 years of follow-up after ablation. Occurrence of new AF was particularly high (50%) in patients with a cardiac implantable electronic device (CIED), demonstrating the importance of continuous arrhythmia surveillance in these patients. Obstructive sleep apnea and left atrial size were associated with a higher risk of developing new-onset AF after RFA of isolated typical AFL. Although AF was common after RFA of AFL, the incidence of stroke was relatively low. This information is clinically helpful in selecting patients for RFA of AFL and in identifying those, such as patients with sleep apnea and enlarged left atrium, who would benefit from close arrhythmia surveillance after RFA. In addition, these results may indirectly suggest continuation of systemic anticoagulation after RFA of AFL in select patients who are likely to develop AF and have a higher risk of thromboembolism.
