Implantable cardioverter‐defibrillator in Brugada syndrome: Long‐term follow‐up

Abstract Background Brugada syndrome (BrS) is associated with sudden cardiac death (SCD). Although implantable cardioverter‐defibrillator (ICD) implantation is recommended, the long‐term outcomes and follow‐up data with regard to ICD complications have led to controversy. Hypothesis In the present study, we described the data assimilated in a total of 11 studies, analyzing the outcome in 747 BrS patients receiving ICD. Methods Data were performed and analyzed after a systematic review of literature compiled from a thorough database search (PubMed, Web of Science, Cochrane Library, and Cinahl). Results The mean age of patients receiving ICD was (43.1 ± 13.4, 82.5% males, 46.6% spontaneous BrS type I). Around 15.3% of the patients were admitted due to SCD and 10.4% suffered from atrial arrhythmia. Appropriate shocks were documented in 18.1% of the patients over a mean follow‐up period of 82.3 months (47.5‐110.4). The following complications were recorded: lead failure and fracture (5.4%), lead perforation (0.7%), lead dislodgement (1.7%), infection (3.9%), pain (0.4%), subclavian vein thrombosis (0.3%), pericardial effusion (0.1%), endocarditis (0.1%), psychiatric problems (1.5%), pneumothorax (0.7%). Inappropriate shocks were documented in 18.1% of the patients. The management of inappropriate shocks was achieved by pulmonary vein isolation (0.5%), drug treatment with sotalol (1.3%) or sotalol with beta‐blocker (0.3%) and hydroquinidine (0.1%). Conclusions ICD therapy in BrS is associated with relevant ICD‐related complications including a substantial risk of inappropriate shocks more frequently in symptomatic BrS patients.


| INTRODUCTION
Type I Brugada syndrome (BrS) is presented by a right bundle branch block (RBBB) and coved ST-segment elevation in precordial leads (V1-V3), and its clinical relevance lies in the fact that patients have a pronounced risk to develop malignant tachyarrhythmias. 1,2 The prevalence of BrS is estimated to be 5/10 000 inhabitants with a higher prevalence in Japan and Philippines as compared to western countries. Not considering accidents, BrS is the leading cause of death in men <40 years old, particularly in countries where the syndrome is endemic. Fever and sodium-channel blockers could potentially unmask BrS, which have led to an expert consensus advising patients with BrS to avoid these drugs and express caution during clinical states such as fever and infections. 3 Due to the high risk of sudden cardiac death (SCD), it has been recommended that BrS-patients with a previous episode of sudden cardiac arrest, or those showing inducibility of a sustained ventricular arrhythmia during an electrophysiological study be treated with an implantable cardioverter-defibrillator (ICD). 4 However, ICD is not always feasible or adequate for every patient.
Although alternative treatments including hydroquinine (HQ) treatment and catheter ablation therapy have demonstrated efficacy in recurrent ventricular arrhythmias, 5 patients who have experienced a prior cardiac arrest or syncopal events secondary to ventricular tachycardia/ventricular fibrillation should undergo ICD implantation. 6,7 ICD implantation for primary prevention in BrS patients is controversial. 6,8 The aim of the present study is to observe the long-term outcome and complication rate of BrS patients, who have received transvenous ICD implantation for primary and secondary prevention.

| METHODS
In this analysis, we included all patients diagnosed with BrS and treated with transvenous ICD implantation 2007 and 2018. A total of 747 BrS patients described in 11 research papers, were recruited for our analysis.
BrS was diagnosed only in the presence of a type 1 Brugada pattern on the electrocardiogram (ECG) (coved type), either at baseline or after the administration of a sodium channel blocking agent. The definition of type 1 ECG pattern was the presence of a terminal r 0 -wave with a J-point elevation of at least 0.2 mV, with a slowly descending ST-segment followed by a negative T-wave in ≥1 right precordial lead (V 1 -V 3 ). ECG is placed in the fourth, third, or second intercostal space.
Sodium channel blockers were administered intravenously over a 10-minutes period to unmask the diagnostic ECG pattern of BrS in case of a non-type 1 ECG pattern at baseline. Programming of ICDs of included studies is summarized in Table S1. Patients were followed annually in a dedicated cardiogenetic outpatient clinic and every 6 to 12 months in the ICD clinic (unless shorter periods of follow-up were required).

| Data collection of different studies
Demographic and clinical data including age at diagnosis, gender, family history of SCD or BrS, symptoms before diagnosis, such as atrial arrhythmias and syncope, results of drug testing, affected genotype, electrophysiological study including ventricular stimulation were followed-up and evaluated. Baseline ICD-related data included type of ICD. The indication for ICD implantation was reviewed in different studies, with emphasis on basal ECG characteristics, history of recurrent syncope, inducible VT of VF during programmed ventricular stimulation (PVS), family history of SD, and history of VF or aborted cardiac arrest.

| Statistics
Data are presented as mean ± SD for continuous variables with a nor-

| ICD-related complications
The rates of appropriate ICD shocks (18.5%) were similar as compared    Table 1 and Figure 2B. Also 3.2% of the patients suffered from an electrical storm. We have compared the data of inappropriate ICD shocks regarding in asymptomatic and symptomatic patients. Asymptomatic BrS patients suffered more significantly from lower rate of inappropriate shocks (Figure 3 A,B). On the other hand, appropriate ICD shocks were significantly more documented in symptomatic patients (Figure 4 A,B).

| Management of complications
Pulmonary vein isolation was carried out in 0.5% of the patients.   Although only 15.3% of patients were admitted due to aborted out of hospital cardiac arrest and these received ICD implantations for secondary prevention, asymptomatic patients receiving ICDs for primary prevention also suffered from life-threatening arrhythmias, which were terminated by appropriate ICD shocks. However, further insights in risk stratification strategies are necessary in BrS to avoid ICD-related complications.

| Study limitation
This study provides registry data dominated by retrospective studies and, although the authors clinically evaluated all patients, clinical assessment and treatment algorithm was not uniform and consecutively ICD indications were homogeneous throughout the study. Only

| CONCLUSIONS
Regarding a relevant risk of device-related complications with a higher rate of inappropriate ICD shocks in symptomatic BrS patients special care during regular follow-up in specialized cardiogenetic centers may allow the reduction in the number of adverse events.

ACKNOWLEDGMENTS
We would like to thank the Hector Stiftung and DZHK (German Center for Cardiovascular Research).