Ablation of atrial fibrillation in Brugada syndrome patients with an implantable cardioverter defibrillator to prevent inappropriate shocks resulting from rapid atrial fibrillation

International Journal of Cardiology 168 (2013) 5273–5276

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Ablation of atrial fibrillation in Brugada syndrome patients with an implantable cardioverter defibrillator to prevent inappropriate shocks resulting from rapid atrial fibrillation☆ Akinori Sairaku a,b,⁎,1, Yukihiko Yoshida a,1, Yukiko Nakano b,1, Yasuki Kihara b,1 a b

Department of Cardiology, Nagoya Daini Red Cross Hospital, Nagoya, Japan Department of Cardiology, Graduate School of Medicine, Hiroshima University, Hiroshima, Japan

a r t i c l e

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Article history: Received 1 May 2013 Received in revised form 17 July 2013 Accepted 3 August 2013 Available online 15 August 2013 Keywords: Ablation Atrial fibrillation Brugada syndrome Implantable cardioverter defibrillator Inappropriate shock Ventricular fibrillation

a b s t r a c t Background: Inappropriate shocks resulting from atrial tachyarrhythmias are highly problematic for patients with an implantable cardioverter defibrillator (ICD). We aimed to determine the effectiveness of catheter ablation of atrial fibrillation (AF) in preventing inappropriate shocks due to rapid AF in patients diagnosed with Brugada syndrome (BS) who were implanted with an ICD. Methods: We performed AF ablation in 5 BS patients with ICDs who experienced inappropriate shocks caused by rapid paroxysmal AF and in a BS patient scheduled to determine an indication of an ICD implantation who frequently experienced rapid AF. Results: Although 2 patients underwent a 2nd ablation procedure because of AF recurrences, 5 of the 6 patients were finally free from AF after their last procedure during a median follow-up period of 43.2 months. No further inappropriate shocks caused by rapid AF occurred after the 1st ablation session in any of the patients. A patient developed a ventricular fibrillation storm during his electrophysiological study following the ablation procedure, and then was implanted with an ICD. Conclusions: AF ablation in BS patients may be reasonable to prevent inappropriate ICD shocks resulting from rapid AF. However, ventricular extrastimuli just after the ablation had better be avoided in them. © 2013 Elsevier Ireland Ltd. All rights reserved.

1. Introduction An implantable cardioverter defibrillator (ICD) is the only acceptable therapy to prevent sudden cardiac death (SCD) in patients with Brugada syndrome (BS) who are considered to be at high risk [1]. However, occasional delivery of inappropriate shocks is an Achilles' heel of ICD therapy, and many efforts have been made to prevent that [2,3]. It is known that atrial fibrillation (AF) is sometimes observed with a prevalence of 10–20% in BS patients, and rapid AF can lead to inappropriate shock events [1,4]. Some antiarrhythmic drugs (AADs) for AF however favor the development of fatal ventricular arrhythmias in those patients [5]. In addition, AADs have only limited effect on preventing the occurrence of AF. During the past decade, catheter ablation of AF has rapidly evolved. Because the validity and safety of the ablation of AF have become widely recognized, its indications have recently been extended. Therefore, given the difficulty of treating AF with AADs in those patients, ☆ Disclosure: This work is not supported by any external funding. ⁎ Corresponding author at: Department of Cardiology, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Tel.: +81 82 257 5540; fax: +81 82 257 5169. E-mail address: [email protected] (A. Sairaku). 1 These authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. 0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.08.016

we came up with a strategy of ablating AF in BS patients who experienced inappropriate ICD shocks due to rapid AF or in those who were expected to suffer from it. In the present study we reported BS patients with ICDs who underwent AF ablation to prevent inappropriate shocks. 2. Methods 2.1. Patients We retrospectively reviewed the electrophysiology laboratory database at Nagoya Daini Red Cross Hospital and Hiroshima University Hospital from 2009 to 2012 to identify BS patients with an ICD who underwent AF ablation to prevent inappropriate shocks resulting from rapid AF. This study was approved by the Institutional Research Board of each hospital. 2.2. ICD An ICD was implanted in the patients with a class I or IIa indication [1]. Single- or dualchamber ICDs were implanted depending on the physician's preference. A single ventricular fibrillation (VF) zone was programmed with a lower detection rate of 200 bpm in the Hiroshima University Hospital and 188 bpm in the Nagoya Daini Red Cross Hospital. 2.3. Catheter ablation The details of the double Lasso catheter-guided extensive encircling pulmonary vein (PV) isolation performed in the present study have been described elsewhere [6]. In brief, two 7-French decapolar circumferential catheters (Lasso, Biosense Webster,

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Table 1 Clinical characteristics of the study patients.

Age at ICD implantation (years) Clinical event Family history of SCD Spontaneous type 1 ECG Inducible VT/VF Indication for ICD implantation SCN5A mutation Duration of AF (years) Left atrial diameter (mm) ICD type No. of appropriate shocks No. of inappropriate shocks

Patient 1

Patient 2

Patient 3

Patient 4

Patient 5

Patient 6

67 Aborted SCD – – + Class I N/A 6 35 Dual chamber 3 4

63 VT + + + Class I N/A 1 38 Single chamber 0 1

55 Syncope – + + Class I N/A 0.5 37 Dual chamber 0 1

28 Aborted SCD + – – Class I + 5 31 Single chamber 2 1

29 None – + + Class IIa – 4 32 Dual chamber 0 3

52 Syncope + – + Class IIa – 4 41 N/A N/A N/A

ICD = implantable cardioverter device, SCD = sudden cardiac death, VT = ventricular tachycardia, ECG = electrocardiogram, N/A = not applicable, VF = ventricular fibrillation, AF = atrial fibrillation. Diamond Bar, CA, USA) were placed within the ipsilateral superior and inferior PVs. After constructing 3-dimensional electroanatomical maps using a non-fluoroscopic navigation system (CARTO, Biosense Webster), circumferential ablation lines were created around the left- and right-sided ipsilateral PVs. Before September 2010, a non-irrigated ablation catheter with a 4-mm tip (Navistar, Biosense Webster) was used to create the circumferential lesions at a maximum power of 30 W and maximum electrode–tissue interface temperature of 55 °C, and after that a 3.5-mm irrigated tip catheter (ThermoCool, Biosense Webster) was used at a maximum power of 35 W. The endpoint of the PV isolation was either the elimination or dissociation of the PV potentials recorded from the circular catheters placed within the PVs and exit block from the PVs. Finally, the cavotricuspid isthmus was ablated with an endpoint of bi-directional conduction block. In patients who needed a second procedure, the PVs were checked for reconnections and the cavotricuspid isthmus was checked for the integrity of the block line; and, if necessary, additional ablation was performed in the same manner as the initial session.

2.4. Follow-up The patients were scheduled to be followed up at the outpatient clinic 3, 6, 9, and finally 12 months after the procedure to check for any AF recurrences defined in the current guidelines [7]. Twelve lead electrocardiograms (ECG) were obtained at all clinical visits, and 24-hour Holter monitoring was performed at 3-month intervals during the followup period. When a recurrence of AF occurred after the blanking period [7], the patients were offered a second ablation procedure. The ICD was checked every 6 months even after completion of the follow-up. 2.5. Statistical analysis The continuous variables were summarized as means ± standard deviation or medians with interquartile ranges, and categorical variables as proportions.

Fig. 1. Recordings from an ICD on the same day in patient no. 4 showing an episode of an appropriate shock for ventricular fibrillation (A), and an inappropriate shock due to paroxysmal atrial fibrillation with a rapid ventricular rate (B). CD = cardioversion, CE = charge end, VR = ventricular refractory sense, VS = ventricular sense.

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Table 2 Findings during the 1st ablation procedure.

Ablation catheter Total procedural duration (min) Total radiofrequency energy (J)

Patient 1

Patient 2

Patient 3

Patient 4

Patient 5

Patient 6

Non-irrigation 230 43842

Non-irrigation 141 39417

Non-irrigation 110 25218

Irrigation 127 48021

Irrigation 146 34182

Non-irrigation 343 83235

3. Results We identified 104 BS patients who were implanted with an ICD to prevent SCD. The mean age of the patients at implantation of the ICD was 48 ± 14 years, and 97.1% of them were male. Twenty (19.2%) of the patients had paroxysmal AF. Among them, we found 6 (5.8%) patients who experienced or were expected to experience one or more episodes of inappropriate shocks resulting from rapid AF and then underwent AF ablation to prevent the unfavorable incidents. The clinical profile of the 6 BS patients is reported in Table 1. The median age of the patients at implantation of the ICD was 53.5 years [28.8, 64.0]. All of them were male, were not prescribed with any AADs, and did not have any structural heart disease. Five patients who were already implanted with an ICD had a median of 1.0 [1.0, 3.5] inappropriate shocks resulting from rapid paroxysmal AF (Fig. 1). A remaining patient (patient no. 6) who was scheduled to receive an electrophysiological study to determine an indication for an ICD implantation, experienced frequent episodes of symptomatic paroxysmal AF with a ventricular rate ranging from 180 to 200 bpm. The 1st ablation procedures were successfully completed in all 6 patients. The morphology of the ST segment in the V1 and V2 leads was the same before and after the procedure in all the patients. The findings during the ablation procedure are detailed in Table 2. During the electrophysiological study undertaken in one patient (patient no. 6) following the ablation procedure, triple extrastimuli from the right ventricular apex at 500/240/220/200 ms induced a VF storm. Cardio-pulmonary resuscitation with an oral intubation was promptly started, and the VF was never terminated until the 7th electrical cardioversion attempt was applied (Fig. 2). A dual-chamber ICD was then implanted 7 days after the electrophysiological procedure in the patient. A recurrence of AF occurred in 2 patients (patient nos. 1 and 3), 32 and 60 months after the 1st ablation session, respectively, and therefore

they underwent a 2nd ablation session. The ICD recorded asymptomatic episodes of paroxysmal AF with a short duration even after the blanking period of the 2nd session in one of them (patient no. 3), however, he did not experience any further inappropriate shocks after the ablation. The remaining 5 patients remained free from AF without any AADs during a median follow-up period of 43.2 [19.9, 74.4] months after their last session. 4. Discussion To the best of our knowledge, we for the first time reported an attempt to prevent inappropriate shocks by ablating rapid paroxysmal AF in BS patients with an ICD. Bordachar et al. [4]. suggested in their work that most atrial arrhythmias observed in BS patients may be of a PV origin. Further, Yamada et al. [8]. reported an excellent outcome of AF ablation in patients with a Brugada ECG. Those support our finding that 5 of the 6 BS patients achieved long-term freedom from AF after their last ablation session. Quinidine has been known to have a potential action to prevent SCD in BS patients as well as a therapeutic effect on AF [9], yet as it stands both of them are considered to be limited [1]. Some incidences of inappropriate shocks due to rapid paroxysmal AF may possibly be prevented by means of initiating AADs other than quinidine or rate control medications, or by reprogramming the ICD [2]. However, those attempts may rather lead to an increase in the episodes of fatal ventricular arrhythmias [1], or even underdetection of them [10]. Bordachar et al. [4]. also suggested that BS patients with paroxysmal atrial arrhythmias may be at a higher risk for SCD compared to those without. When taking those together, the non-radical managements to reduce inappropriate shocks due to rapid AF might further increase the risk of SCD in the BS patients. Therefore, considering the higher rate of freedom from AF

Fig. 2. Ventricular fibrillation was induced by triple extrastimuli from the right ventricle just after the ablation procedure in patient no.6, and repeated attempts of electrical cardioversion were required to terminate it.

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after the ablation procedure in the present series, it may be a reasonable approach to prevent inappropriate shocks. PV isolation is known to reduce parasympathetic activity in human hearts [11]. Therefore, considering that an increase in the vagal tone contributes to the occurrence of ventricular arrhythmias in BS patients [1], the ablation procedure used in the present series is presumed to have made the ventricular arrhythmias less likely to be induced. Instead, we actually encountered an electrical storm occurring during the electrophysiological study following the ablation procedure in a BS patient. The precise mechanism is unclear, however, we provide a possible explanation for the phenomenon as follows. Both sympathetic and parasympathetic nerves are eliminated by radiofrequency applications to the PV antrum which is the most densely innervated area in the human atria, and the latter are destroyed with a greater proportion than the former, consequently disrupting the sympathovagal balance [12]. BS is known to be characterized by an autonomic imbalance with reduced adrenergic nerve activity [13]. Thus, the PV isolation may have further unbalanced the autonomic tone in the BS patient, and may therefore have made it easy to induce and sustain VF. In addition, the patient received many more radiofrequency energy applications to his atria during the procedure than the others, which perhaps played an unpredictable role in the occurrence of the VF storm. 4.1. Limitations Because of the rareness of BS patients requiring an implantation of the ICD, we studied only a small number of patients. To emphasize the importance of our results, a large-scaled study is needed. 4.2. Conclusions AF ablation may be an acceptable therapeutic strategy to prevent inappropriate ICD shocks resulting from rapid paroxysmal AF in high risk BS patients. However, ventricular extrastimuli just after the ablation procedure had better not be carried out. Acknowledgment The authors thank John Martin for his grammatical assistance.

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