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Original article
The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation Mihoko Kawabata (MD, PhD)a,*, Masahiko Goya (MD, PhD)a, Takamitsu Takagi (MD)b, Shu Yamashita (MD)c, Shinsuke Iwai (MD)d, Masahito Suzuki (MD)e, Tomomasa Takamiya (MD)f, Tomofumi Nakamura (MD)f, Tatsuya Hayashi (MD)g, Atsuhiko Yagishita (MD)c, Takeshi Sasaki (MD, PhD)a, Yoshihide Takahashi (MD, PhD)g, Yuhichi Ono (MD)h, Hitoshi Hachiya (MD, PhD)b, Yasuteru Yamauchi (MD, PhD)c, Kenichiro Otomo (MD, PhD)h, Junichi Nitta (MD, PhD)e, Kaoru Okishige (MD, PhD)d, Mitsuhiro Nishizaki (MD, PhD, FJCC)f, Yoshito Iesaka (MD, PhD)b, Mitsuaki Isobe (MD, PhD, FJCC)i, Kenzo Hirao (MD, PhD)a a
Heart Rhythm Center, Tokyo Medical and Dental University, Tokyo, Japan Cardiovascular Center, Tsuchiura Kyodo Hospital, Ibaraki, Japan c Department of Cardiology, Musashino Red Cross Hospital, Tokyo, Japan d Division of Cardiology, Yokohama-City Minato Red Cross Hospital, Yokohama, Japan e Department of Cardiology, Saitama Red Cross Hospital, Saitama, Japan f Department of Cardiology, Yokohama Minami Kyosai Hospital, Yokohama, Japan g Department of Cardiology, National Disaster Medical Center, Tokyo, Japan h Department of Cardiology, Ome Municipal General Hospital, Tokyo, Japan i Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 20 October 2015 Received in revised form 28 December 2015 Accepted 10 January 2016 Available online xxx
Background: Atrial fibrillation (AF) often coexists with Wolff-Parkinson-White (WPW) syndrome. We compared the efficacy of Kent bundle ablation alone and additional AF ablation on accompanying AF, and examined which patients would still have a risk of AF after successful Kent bundle ablation. Methods: This retrospective multicenter study included 96 patients (56 15 years, 72 male) with WPW syndrome and AF undergoing Kent bundle ablation. Some patients underwent simultaneous pulmonary vein isolation (PVI) for AF. The incidence of post-procedural AF was examined. Results: Sixty-four patients underwent only Kent bundle ablation (Kent-only group) and 32 also underwent PVI (+PVI group). There was no significant difference in the basic patient characteristics between the groups. Additional PVI did not improve the freedom from residual AF compared to Kent bundle ablation alone (p = 0.53). In the Kent-only group, AF episodes remained in 25.0% during the follow-up (709 days). A univariate analysis showed that age 60 years, left atrial dimension 38 mm, B-type natriuretic peptide (BNP) 40 pg/ml, and concomitant hypertension were predictive factors for residual AF. However, in the multivariate analysis, only BNP 40 pg/ml remained as an independent predictive factor (HR = 17.1 and CI: 2.3–128.2; p = 0.006). Conclusions: Among patients with WPW syndrome and AF, Kent bundle ablation alone may have a sufficient clinical impact of preventing recurrence of AF in select patients. Screening the BNP level would help decide the strategy to manage those patients. ß 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Keywords: Wolff-Parkinson-White syndrome Atrial fibrillation Catheter ablation B-type natriuretic peptide
* Corresponding author at: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Tel.: +81 358035231; fax: +81 358030131. E-mail address: [email protected] (M. Kawabata). http://dx.doi.org/10.1016/j.jjcc.2016.01.007 0914-5087/ß 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Kawabata M, et al. The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation. J Cardiol (2016), http://dx.doi.org/ 10.1016/j.jjcc.2016.01.007
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Introduction Atrial fibrillation (AF) often occurs in patients with WolffParkinson-White (WPW) syndrome and its incidence is considerably higher than that in the general population, with citations ranging 9–38% [1–4]. Of special concern is that in patients with WPW syndrome, AF can degenerate into ventricular fibrillation, resulting in sudden death [5]. Some older studies reported that successful Kent bundle ablation also suppressed AF in WPW syndrome patients with AF [1,6], but recent studies indicate that this is not necessarily true [3,4,7–9]. Recently, catheter ablation has been widely accepted as a treatment option for symptomatic paroxysmal AF [10] and in clinical practice, ablation of Kent bundle and AF are frequently performed during the same session [11]. However, few reports have assessed the efficacy of additional AF ablation in preventing residual AF in such patients, or its necessity [12]. It is important to distinguish those in whom Kent bundle ablation is sufficient to control AF episodes from those who need further ablation of AF. Therefore, the purpose of this study was twofold: (1) to compare the efficacy of performing Kent bundle ablation only and additional AF ablation on the post-procedural AF incidence in these patients, and (2) to identify which subset of patients would still have a high risk of AF after the successful elimination of Kent bundle. Methods Study population and data collection This study was a retrospective multicenter study. The cohort of patients referred to 8 centers (Tokyo Medical and Dental University, Ome Municipal General Hospital, National Disaster Medical Center, Saitama Red Cross Hospital, Tsuchiura Kyodo Hospital, Musashino Red Cross Hospital, Yokohama-City Minato Red Cross Hospital, and Yokohama Minami Kyosai Hospital) for radiofrequency ablation of WPW syndrome from January 2008 through May 2013 was analyzed. Before the ablation, symptomatic AF was documented with 12-lead electrocardiograms (ECGs), and/or 24-h Holter recordings in all patients. Some patients underwent simultaneous first pulmonary vein isolation (PVI) for AF. Whether additional PVI was to be performed was decided by each physician. Patients who had undergone PVI beforehand were excluded from this study. Data collection included the clinical characteristics, demographic data, and electrophysiological data based on an analysis of the medical records. The left ventricular ejection fraction (LVEF) and left atrial dimension (LAD) were assessed by echocardiography. The B-type natriuretic peptide (BNP) level was measured prior to the electrophysiological (EP) study and ablation. EP study and ablation Invasive EP study and Kent bundle ablation were performed in all patients. Stimulation was performed to determine the shortest cycle length of 1:1 conduction via Kent bundle, and the effective refractory periods (ERP) of Kent bundle and right atrium. Incremental constant pacing was performed until 2:1 conduction block over Kent bundle was achieved. The ERP was defined as the longest interval between the last basic pacing cycle stimulus and a single extrastimulus that produced no excitation. In the EP study prior to Kent bundle ablation, the stimulation protocol was basic, i.e. without infusion of isoproterenol (ISP) and was not specifically intended to induce AF. AF inducibility was defined as occurring when AF with a duration of at least 1 min was induced.
The procedural endpoint of Kent bundle ablation was defined as the elimination of the Kent bundle conduction even after ISP infusion. The endpoint of AF ablation was PVI, which was defined as bidirectional conduction block between the left atrium and PVs. After completing the PVI, adenosine triphosphate was injected during ISP infusion to unmask any dormant conduction, which was eliminated by additional radiofrequency applications [13]. Clinical follow-up Patients were prescribed no antiarrhythmic medications after their procedure. The schedule of the outpatient follow-up was determined by each physician depending on the clinical status of the patient. Data on post-ablation AF were obtained from the patients’ medical charts. In those who had ceased being followed at the hospital where they had received the ablation, a questionnaire or telephone interview was performed to update the long-term outcome database in 2013–2014. In the survey, the patients were asked whether they had any symptoms suggesting tachyarrhythmia, which were palpitations (with or without a regularity of the heart beat), syncope, or dizziness. If they had such symptoms, they were encouraged to visit the centers to check up on the existence of arrhythmias. They were also asked whether they had had any arrhythmic events confirmed by their physicians, or whether they had current medications suggesting AF recurrence. Post-ablation AF was assumed when confirmed by 12-lead ECGs, 24-h Holter recordings, or records of the events by the patient’s portable ECG. For this analysis, we excluded any patients who were lost to follow-up. Ethical considerations All enrolled patients gave their written informed consent. This study was carried out in accordance with the Principles of the Declaration of Helsinki. The institutional clinical research ethics committees of all participating institutions approved the study protocol. Statistical analysis All data are expressed as the mean SD or numbers and percentages of patients. Data were censored if the patient had AF episodes after the elimination of Kent bundle. Differences in continuous variables were analyzed with an unpaired Student’s t-test. The Chi-square test or Fisher’s exact test was used to test for independence in contingency tables. The survival curve illustrating the freedom from post-procedural AF was assessed by the Kaplan– Meier method. To compare the survival curves between the groups, a log-rank test and Cox proportional hazards regression were used. A logistic regression analysis was used to compare the risk of postprocedural AF. The results were presented as hazard ratios (HRs) with 95% confidence intervals (CIs). A value of p < 0.05 was considered statistically significant. SPSS version 11.0.1 software (SPSS Inc., Chicago, IL, USA) was used for all statistical analyses. Results Clinical characteristics of the cohort A total of 104 WPW syndrome patients with clinically documented AF underwent Kent bundle ablation. Eight patients were lost during the follow-up and were excluded from the analysis, resulting in a population of 96 patients. The population ranged in age between 21 and 85 years, averaging 56 15 years, and 72 (75.0%) were male. Ninety-four (97.9%) patients had paroxysmal AF. There were 20 (20.8%) patients who had undergone
Please cite this article in press as: Kawabata M, et al. The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation. J Cardiol (2016), http://dx.doi.org/ 10.1016/j.jjcc.2016.01.007
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electrical cardioversion for hemodynamically unstable pseudoventricular tachycardia. At baseline, structural heart disease and comorbid hypertension (HT) were diagnosed in 6.3% and 33.3% of the patients, respectively. Their mean LAD was 35 7 mm, and the BNP level was 79.0 134 pg/ml. The patients were divided into two groups: the ‘Kent-only group’ consisting of the 64 patients who underwent Kent bundle ablation without PVI and the ‘+PVI group’ consisting of 32 patients who underwent Kent bundle ablation and PVI during the same session. Both groups were similar in terms of the demographic parameters and electrophysiological findings (Table 1). The suppression of AF after the elimination of Kent bundle – comparison between subgroups with or without additional PVI Kent bundle ablation was successful in all patients, with no recurrence of the Kent bundle conduction. During the follow-up (median 709 days), AF was detected in 22 of 96 patients (22.9%), including 16 of 64 in the Kent-only group (25.0%) and 6 of 32 in the +PVI group (18.8%). Kaplan–Meier analysis demonstrated that the freedom from post-procedural AF after 3 months was 87.5%, after 1 year 85.5%, and after 5 years 64.6% in the Kent-only group, while in the +PVI group it was 90.6% after 3 months, 87.1% after 1 year, and 77.8% after 5 years. The additional PVI did not improve the freedom from residual AF compared to Kent bundle ablation alone (p = 0.53, Fig. 1). Both patients with non-paroxysmal AF belonged to the +PVI group. The Kaplan–Meier analyses were similar even after excluding those with non-paroxysmal AF (p = 0.41). The predictive factors for AF recurrence after Kent bundle ablation alone – analysis of the Kent-only group A univariate analysis showed that older age (p = 0.008), larger LAD (p = 0.045), higher BNP level (p = 0.028), and concomitant HT (p = 0.044) were significantly related to residual AF (Table 2). The ROC curves showed that, exceeding age of 60 years, LAD of 38 mm, or BNP level of 40 pg/ml abruptly increased the risk of residual AF. In the EP findings, the shortest pacing cycle length for both the antegrade and retrograde 1 to 1 conduction via Kent bundle was
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significantly longer in those with residual AF (p = 0.029 and 0.017). Whether retrograde conduction via Kent bundle was present or AF was inducible during the session, did not influence the presence of residual AF after the Kent elimination. When the four univariate predictive demographic factors, age 60 years, LAD 38 mm, BNP 40 pg/ml, and concomitant HT, were evaluated using a multivariate analysis, BNP 40 pg/ml was the only independent predictor of residual AF (HR = 17.1 and CI: 2.3–128.2; p = 0.006, Table 3). In the Kent-only group we excluded 17 patients whose BNP level had not been measured before the ablation, leaving us with only 29 without and 18 with BNP 40 pg/ml. The Kaplan–Meier curves for the freedom from AF after the ablation in the 3 groups, namely, the Kent-only group with and without BNP 40 pg/ml and the +PVI group, showed that the Kent-only group with BNP 40 pg/ ml had a significantly worse outcome than the other two groups (p = 0.005, vs. the +PVI group and p = 0.0005, vs. the Kent-only group without BNP 40 pg/ml; Fig. 2). Among patients with BNP 40 pg/ml, there were 18 in the Kentonly group and 12 in the +PVI group. The Kaplan–Meier curves for the freedom from AF after the ablation in both categories revealed that the additional PVI significantly improved the outcome (p = 0.01; Fig. 3). Discussion In this retrospective multicenter study, we showed that in patients with WPW syndrome and AF, adding PVI to Kent bundle ablation suppressed AF no better than Kent bundle ablation alone (p = 0.53). In the Kent-only group, AF episodes were still observed in 25.0% of patients after Kent bundle ablation during a follow-up with a median of 709 days. The univariate analysis showed that age 60 years old, LAD 38 mm, BNP 40 pg/ml, and concomitant HT were predictive factors for post-procedural AF. However, in the multivariate analysis, only BNP 40 pg/ml remained as an independent predictive factor. The prevalence of WPW syndrome is estimated to be approximately 0.9–3% in the general population [14]. Paroxysmal AF often coexists with WPW syndrome, with a reported incidence
Table 1 Clinical characteristics of the cohort.
Gender (male/female) Age, years CAD, % Hypertension, % Valvular disease, % CHADS2 score LAD, mm LVEF, % BNP, pg/ml Paroxysmal atrial fibrillation, % Basic electrophysiological characteristics Presence of antegrade conduction via Kent bundle, % Presence of retrograde conduction via Kent bundle, % Left/right-sided Kent bundle Antegrade ERP of Kent bundle, ms Shortest pacing cycle length with 1:1 antegrade conduction of Kent bundle, ms Retrograde ERP of Kent bundle, ms Shortest pacing cycle length with 1:1 retrograde conduction of Kent bundle, ms AVRT CL, ms RA ERP, ms Shortest R–R interval during AF, ms Incidence of inducible AVRT, % Patients with multiple Kent bundle, %
Kent-only group (n = 64)
+PVI group (n = 32)
p-Value
45/19 54 15 5 30 3 0.58 0.89 35.4 7.3 (n = 51) 62.3 8.8 (n = 51) 71.0 118 (n = 47) 0
27/5 58 13 0 41 3 0.78 0.83 35.3 6.0 (n = 26) 63.4 11.9 (n = 26) 94.7 164 (n = 24) 6
0.10 0.22 0.29 0.20 0.74 0.28 0.95 0.64 0.49 0.11
69 84 47/17 269 41 292 50 294 75 307 80 337 57 236 44 283 83 56 3
66 72 24/8 332 102 (n = 16) 463 263 (n = 14) 295 51 (n = 15) 311 45 (n = 14) 339 45 272 72 (n = 24) 307 112 61 0
0.47 0.15 0.36 0.20 0.14 0.98 0.87 0.86 0.13 0.29 0.41 0.44
(n = 31) (n = 30) (n = 45) (n = 43) (n = 45)
AF, atrial fibrillation; AVRT, atrioventricular reentrant tachycardia; BNP, B-type natriuretic peptide; CAD, coronary artery disease; CL, cycle length; ERP, effective refractory period; LAD, left atrial dimension; LVEF, left ventricular ejection fraction; n = number of patients; PVI, pulmonary vein isolation; RA, right atrial.
Please cite this article in press as: Kawabata M, et al. The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation. J Cardiol (2016), http://dx.doi.org/ 10.1016/j.jjcc.2016.01.007
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Fig. 1. The incidence of atrial fibrillation (AF) after Kent bundle ablation in Wolff-Parkinson-White patients with AF, grouped by whether or not they underwent additional pulmonary vein isolation (PVI) simultaneously (the +PVI group and the Kent-only group). The additional PVI did not improve the freedom from residual AF compared to Kent bundle ablation alone (p = 0.53).
Table 2 Univariate analysis for residual AF after Kent bundle ablation alone.
Gender (male/female) Age, years CAD, % Hypertension, % Valvular disease, % CHADS2 score LAD, mm (n = 51) LVEF, % (n = 51) BNP, pg/ml (n = 47) Basic electrophysiological characteristics Presence of antegrade conduction via Kent bundle, % Presence of retrograde conduction via Kent bundle, % Left/right-sided Kent bundle Antegrade ERP of Kent bundle, ms (n = 31) Shortest pacing cycle length with 1:1 antegrade conduction of Kent bundle, ms (n = 30) Retrograde ERP of Kent bundle, ms (n = 45) Shortest pacing cycle length with 1:1 retrograde conduction of Kent bundle, ms (n = 43) AVRT CL, ms RA ERP, ms (n = 45) Shortest R-R interval during AF, ms Incidence of inducible AVRT, % Incidence of inducible AF, % Patients with multiple Kent bundle, %
Residual AF (n = 16)
No. AF (n = 48)
p-Value
11/5 63 14 13 50 6 0.88 1.0 38.5 8.7 (n = 15) 59.7 10.0 (n = 15) 146 143 (n = 13)
34/14 52 15 2 23 2 0.48 0.83 34.0 6.3 (n = 36) 63.4 8.1 (n = 36) 42.5 94.2 (n = 34)
0.55 0.008 0.15 0.044 0.44 0.12 0.045 0.17 0.028
50 88 13/3 245 25 (n = 4) 336 62 (n = 4)
75 88 34/14 273 42 (n = 27) 283 43 (n = 26)
0.06 1.00 0.32 0.22 0.029
331 108 (n = 10) 358 109 (n = 8)
284 61 (n = 35) 289 59 (n = 35)
0.08 0.017
334 40 226 31 (n = 12) 303 81 63 56 0
338 63 239 47 (n = 33) 276 83 54 33 4
0.88 0.36 0.29 0.40 0.09 0.55
AF, atrial fibrillation; AVRT, atrioventricular reentrant tachycardia; BNP, B-type natriuretic peptide; CAD, coronary artery disease; CL, cycle length; ERP, effective refractory period; LAD, left atrial dimension; LVEF, left ventricular ejection fraction; n = number of patients; RA, right atrial.
Table 3 Multivariate analysis for the predictors of residual AF after Kent bundle ablation alone. Risk factors Age 60 years LAD 38 mm BNP 40 pg/ml Hypertension
Odds ratio
95% confidence interval
p-Value
3.46 2.73 17.1 2.90
0.46–25.9 0.35–21.3 2.28–128.2 0.38–22.2
0.23 0.34 0.006 0.31
AF, atrial fibrillation; BNP, B-type natriuretic peptide; LAD, left atrial dimension.
of 9–38% [1–4]. AF with rapid conduction over Kent bundle can deteriorate into ventricular fibrillation, causing sudden death [5]. In WPW patients, the risk of sudden death is estimated to be 0.15% per patient-year [15], and it can be the initial presentation. Several potential mechanisms responsible for the occurrence of AF in WPW syndrome patients have been reported [16,17]. The majority is thought to be non-PV related, and is attributed to spontaneous degeneration of atrioventricular reciprocating tachycardia (AVRT) into AF, the electrical properties of Kent bundle, the effects of Kent bundle on the atrial architecture, and intrinsic atrial
Please cite this article in press as: Kawabata M, et al. The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation. J Cardiol (2016), http://dx.doi.org/ 10.1016/j.jjcc.2016.01.007
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Fig. 2. The post-procedural atrial fibrillation (AF)-free Kaplan–Meier curves of the 3 groups, including the pulmonary vein isolation (+PVI) group and the Kent-only group with or without B-type natriuretic peptide (BNP) 40 pg/ml. The Kent-only group with BNP 40 pg/ml had a significantly worse outcome than the other two groups (p = 0.005, vs. the +PVI group and p = 0.0005, vs. the Kent-only group without BNP 40 pg/ml).
Fig. 3. The post-procedural atrial fibrillation (AF)-free Kaplan–Meier curves of the patients with B-type natriuretic peptide (BNP) 40 pg/ml, grouped by whether or not they underwent additional pulmonary vein isolation (PVI) simultaneously (the +PVI group and the Kent-only group). The additional PVI significantly improved the freedom from residual AF compared to Kent bundle ablation alone (p = 0.01).
vulnerability; however, Derejko et al. suggested a potential role of the PVs also in patients with WPW syndrome and AF [8]. When such patients are scheduled to undergo Kent bundle ablation, the question arises as to how to address the accompanying AF. The reported effects of successful catheter ablation of Kent bundle on the incidence of AF are diverse. Previous studies reported that the rate of AF remission was 9–42% with Kent bundle ablation alone [3,4,7–9]. A recent study showed that the addition of PVI after successful ablation of paroxysmal supraventricular tachycardia (of
which 29 were patients with Kent bundle) reduced the AF recurrence rate, but the difference did not reach a statistical significance (p = 0.20) [12]. Our results in 96 patients with Kent bundle were similar to theirs, strengthening the notion that PVI may not be necessary in all patients with WPW syndrome and AF. Nevertheless, it would be useful if the subset of patients in whom AF ablation would be beneficial could be identified among patients undergoing Kent bundle ablation. So far, the literature suggests that the age is a factor affecting AF incidence in post Kent
Please cite this article in press as: Kawabata M, et al. The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation. J Cardiol (2016), http://dx.doi.org/ 10.1016/j.jjcc.2016.01.007
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bundle ablation patients. In particular, a significantly higher risk has been reported among patients aged 50 years or more [3,4,7]. Our patients who still had AF after elimination of Kent bundle were older, had larger LAD, higher BNP level, and higher concomitant HT incidence. These overlap with the AF risk factors identified in the Framingham study for the general population [18]. With respect to comorbidities, Borregaard et al. reported that the WPW group had a higher prevalence of heart failure, HT, valvular heart disease, ischemic heart disease, and congenital heart disease compared to the general population, all of which are associated with AF [4]. Among the risk factors we identified by the univariate analysis, we found that BNP 40 pg/ml was the only independent predictive factor. The BNP level is widely used to facilitate the diagnosis and guide the heart failure therapy [19]. A higher level of BNP is related to AF [20,21] and it could predict an AF risk in the general population [22]. It also has been reported to be a risk factor for the recurrence of AF after PVI [23]. To the best of our knowledge, this is the first report finding a relationship between the BNP level and remaining AF after elimination of Kent bundle in WPW patients. On the other hand, in line with the evidence from previous studies, there are some conditions other than heart failure associated with elevated BNP levels, including LV hypertrophy, tachycardia, right ventricular overload, myocardial ischemia, hypoxemia, renal dysfunction, advanced age, liver cirrhosis, sepsis, history of HT, and infection [20,24]. In some of our patients, the BNP level might have been elevated because of rapid ventricular response during AVRT, or concomitant HT, and not directly associated with AF itself. However, we think BNP 40 pg/ml might be a simple and useful index for differentiating patients who could benefit from additional PVI during Kent bundle ablation for AF prevention. Limitations of the study The main limitation was the retrospective nature of our study. The post-ablation follow-up, and details of the ablation procedure, such as the patients’ sedation state, and which company’s catheters, programmable stimulator, electrophysiology work station, three-dimensional mapping system, radiofrequency energy supply or settings were used, etc. were determined according to the discretion of each participating center. Therefore, they were diverse and not uniform in detail among the patients. The indication for PVI in the same session of Kent bundle ablation also depended on each center, and was determined by the AF burden or patients’ symptoms. However, the baseline characteristics of the ‘Kent-only group’ and ‘+PVI group’ were similar. Moreover, the fundamentals of our procedures were common and widely accepted in real clinical practice. We missed some preprocedural data because of the retrograde fashion of this study. To assess the impact of the BNP level on the freedom from AF after the ablation, we excluded 17 patients in the Kent-only group whose BNP levels were missing, which may have biased the results. Second, the follow-up did not allow the complete detection of asymptomatic AF episodes, which may have led to an underestimation of the true incidence of AF. It has been reported that episodes of subclinical AF are almost eight times as common as episodes of clinical AF [25]. In general, patients who received AF ablation receive careful follow-up because of relatively high recurrence rate, but those who received Kent bundle ablation did less carefully because of high success rate. If it would be less intensive in the Kent-only group, the recurrence rate must be underestimated. The diverse follow-up across the centers might influence the detection of post-ablation AF. Third, it might be difficult for patients to differentiate AVRT from AF precisely when they experience palpitations. Therefore, the AF burden before Kent bundle ablation, which is thought to be
influential in the prognosis of AF, or the style of AF occurrence, whether AVRT degenerated into AF, or atrial premature contractions triggered AF, could not be evaluated accurately. This time we could not find the EP characteristics which might have be related to the persistence of AF after Kent bundle ablation. Fourth, although we found that BNP 40 pg/ml was a predictive factor for residual AF, the BNP level might fluctuate. It might be related to the frequency of the tachyarrhythmias and the interval between the last tachyarrhythmia attack and its measurement. It is difficult to evaluate such factors affecting the BNP level. Lastly, the recurrence of antegrade conduction via Kent bundle was confirmed by 12-lead ECG. However, that of retrograde conduction was judged indirectly, according to the absence of AVRT. Clinical implications Currently, PVI is established as the treatment for AF, and more recently is suggested even for the first-line treatment of paroxysmal AF [26]. It is largely effective and safe, with the risk of complications ranging around 4.5–9% [26–28]. For patients in whom freedom from AF can be expected after Kent bundle ablation alone, PVI would not be required and would prevent the risk of unnecessary complications. On the basis of the results of the present study, we suggest a strategy that uses BNP 40 pg/ml to identify the subset of WPW patients in whom AF ablation in addition to Kent bundle ablation would prevent the recurrence of AF. Conclusion Among patients with WPW syndrome and AF, Kent bundle ablation alone may have a sufficient clinical impact to prevent further recurrence of AF in select patients. Screening of the BNP level would help to decide the strategy to manage those patients. A prospective investigation with more patients is required to elucidate the exact relationship between the BNP level and post-ablation AF. Funding This research received no grant from any funding agency in the public, commercial, or not-for-profit sectors. Disclosures Authors declare that there is no conflict of interest. References [1] Sharma AD, Klein GJ, Guiraudon GM, Milstein S. Atrial fibrillation in patients with Wolff-Parkinson-White syndrome: incidence after surgical ablation of the accessory pathway. Circulation 1985;72:161–9. [2] Robinson K, Rowland E, Krikler DM. Wolff-Parkinson-White syndrome: atrial fibrillation as the presenting arrhythmia. Br Heart J 1988;59:578–80. [3] Oddsson H, Edvardsson N, Walfridsson H. Episodes of atrial fibrillation and atrial vulnerability after successful radiofrequency catheter ablation in patients with Wolff, Parkinson, White syndrome. Europace 2002;4:201–6. [4] Borregaard R, Lukac P, Gerdes C, Møller D, Mortensen PT, Pedersen L, Nielsen JC, Jensen HK. Radiofrequency ablation of accessory pathways in patients with the Wolff-Parkinson-White syndrome: the long-term mortality and risk of atrial fibrillation. Europace 2015;17:117–22. [5] Pappone C, Santinelli V, Manguso F, Augello G, Santinelli O, Vicedomini G, Gulletta S, Mazzone P, Tortoriello V, Pappone A, Dicandia C, Rosanio S. A randomized study of prophylactic catheter ablation in asymptomatic patients with the Wolff-Parkinson-White syndrome. N Engl J Med 2003;349:1803–11. [6] Haissaguerre M, Fischer B, Labbe´ T, Leme´tayer P, Montserrat P, d’Ivernois C, Dartigues JF, Warin JF. Frequency of recurrent atrial fibrillation after catheter ablation of overt accessory pathways. Am J Cardiol 1992;69:493–7. [7] Dagres N, Clague JR, Kottkamp H, Hindricks G, Breithardt G, Borggrefe M. Impact of radiofrequency catheter ablation of accessory pathways on the
Please cite this article in press as: Kawabata M, et al. The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation. J Cardiol (2016), http://dx.doi.org/ 10.1016/j.jjcc.2016.01.007
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Contents lists available at ScienceDirect
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Original article
The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation Mihoko Kawabata (MD, PhD)a,*, Masahiko Goya (MD, PhD)a, Takamitsu Takagi (MD)b, Shu Yamashita (MD)c, Shinsuke Iwai (MD)d, Masahito Suzuki (MD)e, Tomomasa Takamiya (MD)f, Tomofumi Nakamura (MD)f, Tatsuya Hayashi (MD)g, Atsuhiko Yagishita (MD)c, Takeshi Sasaki (MD, PhD)a, Yoshihide Takahashi (MD, PhD)g, Yuhichi Ono (MD)h, Hitoshi Hachiya (MD, PhD)b, Yasuteru Yamauchi (MD, PhD)c, Kenichiro Otomo (MD, PhD)h, Junichi Nitta (MD, PhD)e, Kaoru Okishige (MD, PhD)d, Mitsuhiro Nishizaki (MD, PhD, FJCC)f, Yoshito Iesaka (MD, PhD)b, Mitsuaki Isobe (MD, PhD, FJCC)i, Kenzo Hirao (MD, PhD)a a
Heart Rhythm Center, Tokyo Medical and Dental University, Tokyo, Japan Cardiovascular Center, Tsuchiura Kyodo Hospital, Ibaraki, Japan c Department of Cardiology, Musashino Red Cross Hospital, Tokyo, Japan d Division of Cardiology, Yokohama-City Minato Red Cross Hospital, Yokohama, Japan e Department of Cardiology, Saitama Red Cross Hospital, Saitama, Japan f Department of Cardiology, Yokohama Minami Kyosai Hospital, Yokohama, Japan g Department of Cardiology, National Disaster Medical Center, Tokyo, Japan h Department of Cardiology, Ome Municipal General Hospital, Tokyo, Japan i Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 20 October 2015 Received in revised form 28 December 2015 Accepted 10 January 2016 Available online xxx
Background: Atrial fibrillation (AF) often coexists with Wolff-Parkinson-White (WPW) syndrome. We compared the efficacy of Kent bundle ablation alone and additional AF ablation on accompanying AF, and examined which patients would still have a risk of AF after successful Kent bundle ablation. Methods: This retrospective multicenter study included 96 patients (56 15 years, 72 male) with WPW syndrome and AF undergoing Kent bundle ablation. Some patients underwent simultaneous pulmonary vein isolation (PVI) for AF. The incidence of post-procedural AF was examined. Results: Sixty-four patients underwent only Kent bundle ablation (Kent-only group) and 32 also underwent PVI (+PVI group). There was no significant difference in the basic patient characteristics between the groups. Additional PVI did not improve the freedom from residual AF compared to Kent bundle ablation alone (p = 0.53). In the Kent-only group, AF episodes remained in 25.0% during the follow-up (709 days). A univariate analysis showed that age 60 years, left atrial dimension 38 mm, B-type natriuretic peptide (BNP) 40 pg/ml, and concomitant hypertension were predictive factors for residual AF. However, in the multivariate analysis, only BNP 40 pg/ml remained as an independent predictive factor (HR = 17.1 and CI: 2.3–128.2; p = 0.006). Conclusions: Among patients with WPW syndrome and AF, Kent bundle ablation alone may have a sufficient clinical impact of preventing recurrence of AF in select patients. Screening the BNP level would help decide the strategy to manage those patients. ß 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Keywords: Wolff-Parkinson-White syndrome Atrial fibrillation Catheter ablation B-type natriuretic peptide
* Corresponding author at: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Tel.: +81 358035231; fax: +81 358030131. E-mail address: [email protected] (M. Kawabata). http://dx.doi.org/10.1016/j.jjcc.2016.01.007 0914-5087/ß 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Kawabata M, et al. The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation. J Cardiol (2016), http://dx.doi.org/ 10.1016/j.jjcc.2016.01.007
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Introduction Atrial fibrillation (AF) often occurs in patients with WolffParkinson-White (WPW) syndrome and its incidence is considerably higher than that in the general population, with citations ranging 9–38% [1–4]. Of special concern is that in patients with WPW syndrome, AF can degenerate into ventricular fibrillation, resulting in sudden death [5]. Some older studies reported that successful Kent bundle ablation also suppressed AF in WPW syndrome patients with AF [1,6], but recent studies indicate that this is not necessarily true [3,4,7–9]. Recently, catheter ablation has been widely accepted as a treatment option for symptomatic paroxysmal AF [10] and in clinical practice, ablation of Kent bundle and AF are frequently performed during the same session [11]. However, few reports have assessed the efficacy of additional AF ablation in preventing residual AF in such patients, or its necessity [12]. It is important to distinguish those in whom Kent bundle ablation is sufficient to control AF episodes from those who need further ablation of AF. Therefore, the purpose of this study was twofold: (1) to compare the efficacy of performing Kent bundle ablation only and additional AF ablation on the post-procedural AF incidence in these patients, and (2) to identify which subset of patients would still have a high risk of AF after the successful elimination of Kent bundle. Methods Study population and data collection This study was a retrospective multicenter study. The cohort of patients referred to 8 centers (Tokyo Medical and Dental University, Ome Municipal General Hospital, National Disaster Medical Center, Saitama Red Cross Hospital, Tsuchiura Kyodo Hospital, Musashino Red Cross Hospital, Yokohama-City Minato Red Cross Hospital, and Yokohama Minami Kyosai Hospital) for radiofrequency ablation of WPW syndrome from January 2008 through May 2013 was analyzed. Before the ablation, symptomatic AF was documented with 12-lead electrocardiograms (ECGs), and/or 24-h Holter recordings in all patients. Some patients underwent simultaneous first pulmonary vein isolation (PVI) for AF. Whether additional PVI was to be performed was decided by each physician. Patients who had undergone PVI beforehand were excluded from this study. Data collection included the clinical characteristics, demographic data, and electrophysiological data based on an analysis of the medical records. The left ventricular ejection fraction (LVEF) and left atrial dimension (LAD) were assessed by echocardiography. The B-type natriuretic peptide (BNP) level was measured prior to the electrophysiological (EP) study and ablation. EP study and ablation Invasive EP study and Kent bundle ablation were performed in all patients. Stimulation was performed to determine the shortest cycle length of 1:1 conduction via Kent bundle, and the effective refractory periods (ERP) of Kent bundle and right atrium. Incremental constant pacing was performed until 2:1 conduction block over Kent bundle was achieved. The ERP was defined as the longest interval between the last basic pacing cycle stimulus and a single extrastimulus that produced no excitation. In the EP study prior to Kent bundle ablation, the stimulation protocol was basic, i.e. without infusion of isoproterenol (ISP) and was not specifically intended to induce AF. AF inducibility was defined as occurring when AF with a duration of at least 1 min was induced.
The procedural endpoint of Kent bundle ablation was defined as the elimination of the Kent bundle conduction even after ISP infusion. The endpoint of AF ablation was PVI, which was defined as bidirectional conduction block between the left atrium and PVs. After completing the PVI, adenosine triphosphate was injected during ISP infusion to unmask any dormant conduction, which was eliminated by additional radiofrequency applications [13]. Clinical follow-up Patients were prescribed no antiarrhythmic medications after their procedure. The schedule of the outpatient follow-up was determined by each physician depending on the clinical status of the patient. Data on post-ablation AF were obtained from the patients’ medical charts. In those who had ceased being followed at the hospital where they had received the ablation, a questionnaire or telephone interview was performed to update the long-term outcome database in 2013–2014. In the survey, the patients were asked whether they had any symptoms suggesting tachyarrhythmia, which were palpitations (with or without a regularity of the heart beat), syncope, or dizziness. If they had such symptoms, they were encouraged to visit the centers to check up on the existence of arrhythmias. They were also asked whether they had had any arrhythmic events confirmed by their physicians, or whether they had current medications suggesting AF recurrence. Post-ablation AF was assumed when confirmed by 12-lead ECGs, 24-h Holter recordings, or records of the events by the patient’s portable ECG. For this analysis, we excluded any patients who were lost to follow-up. Ethical considerations All enrolled patients gave their written informed consent. This study was carried out in accordance with the Principles of the Declaration of Helsinki. The institutional clinical research ethics committees of all participating institutions approved the study protocol. Statistical analysis All data are expressed as the mean SD or numbers and percentages of patients. Data were censored if the patient had AF episodes after the elimination of Kent bundle. Differences in continuous variables were analyzed with an unpaired Student’s t-test. The Chi-square test or Fisher’s exact test was used to test for independence in contingency tables. The survival curve illustrating the freedom from post-procedural AF was assessed by the Kaplan– Meier method. To compare the survival curves between the groups, a log-rank test and Cox proportional hazards regression were used. A logistic regression analysis was used to compare the risk of postprocedural AF. The results were presented as hazard ratios (HRs) with 95% confidence intervals (CIs). A value of p < 0.05 was considered statistically significant. SPSS version 11.0.1 software (SPSS Inc., Chicago, IL, USA) was used for all statistical analyses. Results Clinical characteristics of the cohort A total of 104 WPW syndrome patients with clinically documented AF underwent Kent bundle ablation. Eight patients were lost during the follow-up and were excluded from the analysis, resulting in a population of 96 patients. The population ranged in age between 21 and 85 years, averaging 56 15 years, and 72 (75.0%) were male. Ninety-four (97.9%) patients had paroxysmal AF. There were 20 (20.8%) patients who had undergone
Please cite this article in press as: Kawabata M, et al. The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation. J Cardiol (2016), http://dx.doi.org/ 10.1016/j.jjcc.2016.01.007
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electrical cardioversion for hemodynamically unstable pseudoventricular tachycardia. At baseline, structural heart disease and comorbid hypertension (HT) were diagnosed in 6.3% and 33.3% of the patients, respectively. Their mean LAD was 35 7 mm, and the BNP level was 79.0 134 pg/ml. The patients were divided into two groups: the ‘Kent-only group’ consisting of the 64 patients who underwent Kent bundle ablation without PVI and the ‘+PVI group’ consisting of 32 patients who underwent Kent bundle ablation and PVI during the same session. Both groups were similar in terms of the demographic parameters and electrophysiological findings (Table 1). The suppression of AF after the elimination of Kent bundle – comparison between subgroups with or without additional PVI Kent bundle ablation was successful in all patients, with no recurrence of the Kent bundle conduction. During the follow-up (median 709 days), AF was detected in 22 of 96 patients (22.9%), including 16 of 64 in the Kent-only group (25.0%) and 6 of 32 in the +PVI group (18.8%). Kaplan–Meier analysis demonstrated that the freedom from post-procedural AF after 3 months was 87.5%, after 1 year 85.5%, and after 5 years 64.6% in the Kent-only group, while in the +PVI group it was 90.6% after 3 months, 87.1% after 1 year, and 77.8% after 5 years. The additional PVI did not improve the freedom from residual AF compared to Kent bundle ablation alone (p = 0.53, Fig. 1). Both patients with non-paroxysmal AF belonged to the +PVI group. The Kaplan–Meier analyses were similar even after excluding those with non-paroxysmal AF (p = 0.41). The predictive factors for AF recurrence after Kent bundle ablation alone – analysis of the Kent-only group A univariate analysis showed that older age (p = 0.008), larger LAD (p = 0.045), higher BNP level (p = 0.028), and concomitant HT (p = 0.044) were significantly related to residual AF (Table 2). The ROC curves showed that, exceeding age of 60 years, LAD of 38 mm, or BNP level of 40 pg/ml abruptly increased the risk of residual AF. In the EP findings, the shortest pacing cycle length for both the antegrade and retrograde 1 to 1 conduction via Kent bundle was
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significantly longer in those with residual AF (p = 0.029 and 0.017). Whether retrograde conduction via Kent bundle was present or AF was inducible during the session, did not influence the presence of residual AF after the Kent elimination. When the four univariate predictive demographic factors, age 60 years, LAD 38 mm, BNP 40 pg/ml, and concomitant HT, were evaluated using a multivariate analysis, BNP 40 pg/ml was the only independent predictor of residual AF (HR = 17.1 and CI: 2.3–128.2; p = 0.006, Table 3). In the Kent-only group we excluded 17 patients whose BNP level had not been measured before the ablation, leaving us with only 29 without and 18 with BNP 40 pg/ml. The Kaplan–Meier curves for the freedom from AF after the ablation in the 3 groups, namely, the Kent-only group with and without BNP 40 pg/ml and the +PVI group, showed that the Kent-only group with BNP 40 pg/ ml had a significantly worse outcome than the other two groups (p = 0.005, vs. the +PVI group and p = 0.0005, vs. the Kent-only group without BNP 40 pg/ml; Fig. 2). Among patients with BNP 40 pg/ml, there were 18 in the Kentonly group and 12 in the +PVI group. The Kaplan–Meier curves for the freedom from AF after the ablation in both categories revealed that the additional PVI significantly improved the outcome (p = 0.01; Fig. 3). Discussion In this retrospective multicenter study, we showed that in patients with WPW syndrome and AF, adding PVI to Kent bundle ablation suppressed AF no better than Kent bundle ablation alone (p = 0.53). In the Kent-only group, AF episodes were still observed in 25.0% of patients after Kent bundle ablation during a follow-up with a median of 709 days. The univariate analysis showed that age 60 years old, LAD 38 mm, BNP 40 pg/ml, and concomitant HT were predictive factors for post-procedural AF. However, in the multivariate analysis, only BNP 40 pg/ml remained as an independent predictive factor. The prevalence of WPW syndrome is estimated to be approximately 0.9–3% in the general population [14]. Paroxysmal AF often coexists with WPW syndrome, with a reported incidence
Table 1 Clinical characteristics of the cohort.
Gender (male/female) Age, years CAD, % Hypertension, % Valvular disease, % CHADS2 score LAD, mm LVEF, % BNP, pg/ml Paroxysmal atrial fibrillation, % Basic electrophysiological characteristics Presence of antegrade conduction via Kent bundle, % Presence of retrograde conduction via Kent bundle, % Left/right-sided Kent bundle Antegrade ERP of Kent bundle, ms Shortest pacing cycle length with 1:1 antegrade conduction of Kent bundle, ms Retrograde ERP of Kent bundle, ms Shortest pacing cycle length with 1:1 retrograde conduction of Kent bundle, ms AVRT CL, ms RA ERP, ms Shortest R–R interval during AF, ms Incidence of inducible AVRT, % Patients with multiple Kent bundle, %
Kent-only group (n = 64)
+PVI group (n = 32)
p-Value
45/19 54 15 5 30 3 0.58 0.89 35.4 7.3 (n = 51) 62.3 8.8 (n = 51) 71.0 118 (n = 47) 0
27/5 58 13 0 41 3 0.78 0.83 35.3 6.0 (n = 26) 63.4 11.9 (n = 26) 94.7 164 (n = 24) 6
0.10 0.22 0.29 0.20 0.74 0.28 0.95 0.64 0.49 0.11
69 84 47/17 269 41 292 50 294 75 307 80 337 57 236 44 283 83 56 3
66 72 24/8 332 102 (n = 16) 463 263 (n = 14) 295 51 (n = 15) 311 45 (n = 14) 339 45 272 72 (n = 24) 307 112 61 0
0.47 0.15 0.36 0.20 0.14 0.98 0.87 0.86 0.13 0.29 0.41 0.44
(n = 31) (n = 30) (n = 45) (n = 43) (n = 45)
AF, atrial fibrillation; AVRT, atrioventricular reentrant tachycardia; BNP, B-type natriuretic peptide; CAD, coronary artery disease; CL, cycle length; ERP, effective refractory period; LAD, left atrial dimension; LVEF, left ventricular ejection fraction; n = number of patients; PVI, pulmonary vein isolation; RA, right atrial.
Please cite this article in press as: Kawabata M, et al. The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation. J Cardiol (2016), http://dx.doi.org/ 10.1016/j.jjcc.2016.01.007
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Fig. 1. The incidence of atrial fibrillation (AF) after Kent bundle ablation in Wolff-Parkinson-White patients with AF, grouped by whether or not they underwent additional pulmonary vein isolation (PVI) simultaneously (the +PVI group and the Kent-only group). The additional PVI did not improve the freedom from residual AF compared to Kent bundle ablation alone (p = 0.53).
Table 2 Univariate analysis for residual AF after Kent bundle ablation alone.
Gender (male/female) Age, years CAD, % Hypertension, % Valvular disease, % CHADS2 score LAD, mm (n = 51) LVEF, % (n = 51) BNP, pg/ml (n = 47) Basic electrophysiological characteristics Presence of antegrade conduction via Kent bundle, % Presence of retrograde conduction via Kent bundle, % Left/right-sided Kent bundle Antegrade ERP of Kent bundle, ms (n = 31) Shortest pacing cycle length with 1:1 antegrade conduction of Kent bundle, ms (n = 30) Retrograde ERP of Kent bundle, ms (n = 45) Shortest pacing cycle length with 1:1 retrograde conduction of Kent bundle, ms (n = 43) AVRT CL, ms RA ERP, ms (n = 45) Shortest R-R interval during AF, ms Incidence of inducible AVRT, % Incidence of inducible AF, % Patients with multiple Kent bundle, %
Residual AF (n = 16)
No. AF (n = 48)
p-Value
11/5 63 14 13 50 6 0.88 1.0 38.5 8.7 (n = 15) 59.7 10.0 (n = 15) 146 143 (n = 13)
34/14 52 15 2 23 2 0.48 0.83 34.0 6.3 (n = 36) 63.4 8.1 (n = 36) 42.5 94.2 (n = 34)
0.55 0.008 0.15 0.044 0.44 0.12 0.045 0.17 0.028
50 88 13/3 245 25 (n = 4) 336 62 (n = 4)
75 88 34/14 273 42 (n = 27) 283 43 (n = 26)
0.06 1.00 0.32 0.22 0.029
331 108 (n = 10) 358 109 (n = 8)
284 61 (n = 35) 289 59 (n = 35)
0.08 0.017
334 40 226 31 (n = 12) 303 81 63 56 0
338 63 239 47 (n = 33) 276 83 54 33 4
0.88 0.36 0.29 0.40 0.09 0.55
AF, atrial fibrillation; AVRT, atrioventricular reentrant tachycardia; BNP, B-type natriuretic peptide; CAD, coronary artery disease; CL, cycle length; ERP, effective refractory period; LAD, left atrial dimension; LVEF, left ventricular ejection fraction; n = number of patients; RA, right atrial.
Table 3 Multivariate analysis for the predictors of residual AF after Kent bundle ablation alone. Risk factors Age 60 years LAD 38 mm BNP 40 pg/ml Hypertension
Odds ratio
95% confidence interval
p-Value
3.46 2.73 17.1 2.90
0.46–25.9 0.35–21.3 2.28–128.2 0.38–22.2
0.23 0.34 0.006 0.31
AF, atrial fibrillation; BNP, B-type natriuretic peptide; LAD, left atrial dimension.
of 9–38% [1–4]. AF with rapid conduction over Kent bundle can deteriorate into ventricular fibrillation, causing sudden death [5]. In WPW patients, the risk of sudden death is estimated to be 0.15% per patient-year [15], and it can be the initial presentation. Several potential mechanisms responsible for the occurrence of AF in WPW syndrome patients have been reported [16,17]. The majority is thought to be non-PV related, and is attributed to spontaneous degeneration of atrioventricular reciprocating tachycardia (AVRT) into AF, the electrical properties of Kent bundle, the effects of Kent bundle on the atrial architecture, and intrinsic atrial
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Fig. 2. The post-procedural atrial fibrillation (AF)-free Kaplan–Meier curves of the 3 groups, including the pulmonary vein isolation (+PVI) group and the Kent-only group with or without B-type natriuretic peptide (BNP) 40 pg/ml. The Kent-only group with BNP 40 pg/ml had a significantly worse outcome than the other two groups (p = 0.005, vs. the +PVI group and p = 0.0005, vs. the Kent-only group without BNP 40 pg/ml).
Fig. 3. The post-procedural atrial fibrillation (AF)-free Kaplan–Meier curves of the patients with B-type natriuretic peptide (BNP) 40 pg/ml, grouped by whether or not they underwent additional pulmonary vein isolation (PVI) simultaneously (the +PVI group and the Kent-only group). The additional PVI significantly improved the freedom from residual AF compared to Kent bundle ablation alone (p = 0.01).
vulnerability; however, Derejko et al. suggested a potential role of the PVs also in patients with WPW syndrome and AF [8]. When such patients are scheduled to undergo Kent bundle ablation, the question arises as to how to address the accompanying AF. The reported effects of successful catheter ablation of Kent bundle on the incidence of AF are diverse. Previous studies reported that the rate of AF remission was 9–42% with Kent bundle ablation alone [3,4,7–9]. A recent study showed that the addition of PVI after successful ablation of paroxysmal supraventricular tachycardia (of
which 29 were patients with Kent bundle) reduced the AF recurrence rate, but the difference did not reach a statistical significance (p = 0.20) [12]. Our results in 96 patients with Kent bundle were similar to theirs, strengthening the notion that PVI may not be necessary in all patients with WPW syndrome and AF. Nevertheless, it would be useful if the subset of patients in whom AF ablation would be beneficial could be identified among patients undergoing Kent bundle ablation. So far, the literature suggests that the age is a factor affecting AF incidence in post Kent
Please cite this article in press as: Kawabata M, et al. The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation. J Cardiol (2016), http://dx.doi.org/ 10.1016/j.jjcc.2016.01.007
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bundle ablation patients. In particular, a significantly higher risk has been reported among patients aged 50 years or more [3,4,7]. Our patients who still had AF after elimination of Kent bundle were older, had larger LAD, higher BNP level, and higher concomitant HT incidence. These overlap with the AF risk factors identified in the Framingham study for the general population [18]. With respect to comorbidities, Borregaard et al. reported that the WPW group had a higher prevalence of heart failure, HT, valvular heart disease, ischemic heart disease, and congenital heart disease compared to the general population, all of which are associated with AF [4]. Among the risk factors we identified by the univariate analysis, we found that BNP 40 pg/ml was the only independent predictive factor. The BNP level is widely used to facilitate the diagnosis and guide the heart failure therapy [19]. A higher level of BNP is related to AF [20,21] and it could predict an AF risk in the general population [22]. It also has been reported to be a risk factor for the recurrence of AF after PVI [23]. To the best of our knowledge, this is the first report finding a relationship between the BNP level and remaining AF after elimination of Kent bundle in WPW patients. On the other hand, in line with the evidence from previous studies, there are some conditions other than heart failure associated with elevated BNP levels, including LV hypertrophy, tachycardia, right ventricular overload, myocardial ischemia, hypoxemia, renal dysfunction, advanced age, liver cirrhosis, sepsis, history of HT, and infection [20,24]. In some of our patients, the BNP level might have been elevated because of rapid ventricular response during AVRT, or concomitant HT, and not directly associated with AF itself. However, we think BNP 40 pg/ml might be a simple and useful index for differentiating patients who could benefit from additional PVI during Kent bundle ablation for AF prevention. Limitations of the study The main limitation was the retrospective nature of our study. The post-ablation follow-up, and details of the ablation procedure, such as the patients’ sedation state, and which company’s catheters, programmable stimulator, electrophysiology work station, three-dimensional mapping system, radiofrequency energy supply or settings were used, etc. were determined according to the discretion of each participating center. Therefore, they were diverse and not uniform in detail among the patients. The indication for PVI in the same session of Kent bundle ablation also depended on each center, and was determined by the AF burden or patients’ symptoms. However, the baseline characteristics of the ‘Kent-only group’ and ‘+PVI group’ were similar. Moreover, the fundamentals of our procedures were common and widely accepted in real clinical practice. We missed some preprocedural data because of the retrograde fashion of this study. To assess the impact of the BNP level on the freedom from AF after the ablation, we excluded 17 patients in the Kent-only group whose BNP levels were missing, which may have biased the results. Second, the follow-up did not allow the complete detection of asymptomatic AF episodes, which may have led to an underestimation of the true incidence of AF. It has been reported that episodes of subclinical AF are almost eight times as common as episodes of clinical AF [25]. In general, patients who received AF ablation receive careful follow-up because of relatively high recurrence rate, but those who received Kent bundle ablation did less carefully because of high success rate. If it would be less intensive in the Kent-only group, the recurrence rate must be underestimated. The diverse follow-up across the centers might influence the detection of post-ablation AF. Third, it might be difficult for patients to differentiate AVRT from AF precisely when they experience palpitations. Therefore, the AF burden before Kent bundle ablation, which is thought to be
influential in the prognosis of AF, or the style of AF occurrence, whether AVRT degenerated into AF, or atrial premature contractions triggered AF, could not be evaluated accurately. This time we could not find the EP characteristics which might have be related to the persistence of AF after Kent bundle ablation. Fourth, although we found that BNP 40 pg/ml was a predictive factor for residual AF, the BNP level might fluctuate. It might be related to the frequency of the tachyarrhythmias and the interval between the last tachyarrhythmia attack and its measurement. It is difficult to evaluate such factors affecting the BNP level. Lastly, the recurrence of antegrade conduction via Kent bundle was confirmed by 12-lead ECG. However, that of retrograde conduction was judged indirectly, according to the absence of AVRT. Clinical implications Currently, PVI is established as the treatment for AF, and more recently is suggested even for the first-line treatment of paroxysmal AF [26]. It is largely effective and safe, with the risk of complications ranging around 4.5–9% [26–28]. For patients in whom freedom from AF can be expected after Kent bundle ablation alone, PVI would not be required and would prevent the risk of unnecessary complications. On the basis of the results of the present study, we suggest a strategy that uses BNP 40 pg/ml to identify the subset of WPW patients in whom AF ablation in addition to Kent bundle ablation would prevent the recurrence of AF. Conclusion Among patients with WPW syndrome and AF, Kent bundle ablation alone may have a sufficient clinical impact to prevent further recurrence of AF in select patients. Screening of the BNP level would help to decide the strategy to manage those patients. A prospective investigation with more patients is required to elucidate the exact relationship between the BNP level and post-ablation AF. Funding This research received no grant from any funding agency in the public, commercial, or not-for-profit sectors. Disclosures Authors declare that there is no conflict of interest. References [1] Sharma AD, Klein GJ, Guiraudon GM, Milstein S. Atrial fibrillation in patients with Wolff-Parkinson-White syndrome: incidence after surgical ablation of the accessory pathway. Circulation 1985;72:161–9. [2] Robinson K, Rowland E, Krikler DM. Wolff-Parkinson-White syndrome: atrial fibrillation as the presenting arrhythmia. Br Heart J 1988;59:578–80. [3] Oddsson H, Edvardsson N, Walfridsson H. Episodes of atrial fibrillation and atrial vulnerability after successful radiofrequency catheter ablation in patients with Wolff, Parkinson, White syndrome. Europace 2002;4:201–6. [4] Borregaard R, Lukac P, Gerdes C, Møller D, Mortensen PT, Pedersen L, Nielsen JC, Jensen HK. Radiofrequency ablation of accessory pathways in patients with the Wolff-Parkinson-White syndrome: the long-term mortality and risk of atrial fibrillation. Europace 2015;17:117–22. [5] Pappone C, Santinelli V, Manguso F, Augello G, Santinelli O, Vicedomini G, Gulletta S, Mazzone P, Tortoriello V, Pappone A, Dicandia C, Rosanio S. A randomized study of prophylactic catheter ablation in asymptomatic patients with the Wolff-Parkinson-White syndrome. N Engl J Med 2003;349:1803–11. [6] Haissaguerre M, Fischer B, Labbe´ T, Leme´tayer P, Montserrat P, d’Ivernois C, Dartigues JF, Warin JF. Frequency of recurrent atrial fibrillation after catheter ablation of overt accessory pathways. Am J Cardiol 1992;69:493–7. [7] Dagres N, Clague JR, Kottkamp H, Hindricks G, Breithardt G, Borggrefe M. Impact of radiofrequency catheter ablation of accessory pathways on the
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Please cite this article in press as: Kawabata M, et al. The impact of B-type natriuretic peptide levels on the suppression of accompanying atrial fibrillation in Wolff-Parkinson-White syndrome patients after accessory pathway ablation. J Cardiol (2016), http://dx.doi.org/ 10.1016/j.jjcc.2016.01.007
