Characterization and Management of Arrhythmic Events in Young Patients With Brugada Syndrome.

BACKGROUND: Information on young patients with Brugada syndrome (BrS) and arrhythmic events (AEs) is limited. OBJECTIVES: The purpose of this study was to describe their characteristics and management as well as risk factors for AE recurrence. METHODS: A total of 57 patients (age ≤20 years), all with BrS and AEs, were divided into pediatric (age ≤12 years; n = 26) and adolescents (age 13 to 20 years; n = 31). RESULTS: Patients' median age at time of first AE was 14 years, with a majority of males (74%), Caucasians (70%), and probands (79%) who presented as aborted cardiac arrest (84%). A significant proportion of patients (28%) exhibited fever-related AE. Family history of sudden cardiac death (SCD), prior syncope, spontaneous type 1 Brugada electrocardiogram (ECG), inducible ventricular fibrillation at electrophysiological study, and SCN5A mutations were present in 26%, 49%, 65%, 28%, and 58% of patients, respectively. The pediatric group differed from the adolescents, with a greater proportion of females, Caucasians, fever-related AEs, and spontaneous type-1 ECG. During follow-up, 68% of pediatric and 64% of adolescents had recurrent AE, with median time of 9.9 and 27.0 months, respectively. Approximately one-third of recurrent AEs occurred on quinidine therapy, and among the pediatric group, 60% of recurrent AEs were fever-related. Risk factors for recurrent AE included sinus node dysfunction, atrial arrhythmias, intraventricular conduction delay, or large S-wave on ECG lead I in the pediatric group and the presence of SCN5A mutation among adolescents. CONCLUSIONS: Young BrS patients with AE represent a very arrhythmogenic group. Current management after first arrhythmia episode is associated with high recurrence rate. Alternative therapies, besides defibrillator implantation, should be considered.

Abnormally high risk of stroke in Brugada syndrome.

BACKGROUND: The present study sought to evaluate the incidence of cerebrovascular events in a large cohort of patients with Brugada syndrome (BrS) analysing possible predictors, clinical characteristics and prognosis of cardioembolic events secondary to atrial fibrillation. METHODS: A total of 671 consecutive patients (age 42.1 ±â€Š17.0 years; men 63%) with a diagnosis of BrS were retrospectively analysed over a mean follow-up period of 10.8 ±â€Š5.5 years. The diagnosis of ischemic stroke was made according to the AHA/ASA guidelines using computed tomography (CT) and angio-CT in the emergency department. RESULTS: Among 671 patients with BrS, 79 (11.8%) had atrial fibrillation. The incidence of cardioembolic stroke in patients with BrS and atrial fibrillation was 13.9% (11 events). These patients had a low CHA2DS2Vasc score (82%, 0 and 1). Patients with transient ischemic attack/stroke were more frequently asymptomatic (91 vs. 25%; P < 0.0001) and older (59.4 ±â€Š11.2 vs. 43.9 ±â€Š16.7; P = 0.004) as compared with those without cerebrovascular events. CONCLUSION: The incidence of cardioembolic stroke in patients with BrS and atrial fibrillation was unexpectedly high. The cerebrovascular accidents were often the presenting clinical manifestation and were significantly associated with asymptomatic atrial fibrillation and older age. CHADS2 and CHA2DS2Vasc scores did not predict the unexpectedly high risk of thromboembolic events in this group of patients. The use of more invasive diagnostic tools might be useful in order to increase the rate of atrial fibrillation detection.

Prevalence and Electrocardiographic and Electrophysiological Characteristics of Idiopathic Ventricular Arrhythmias Originating From Intramural Foci in the Left Ventricular Outflow Tract.

BACKGROUNDS: Idiopathic ventricular arrhythmias (VAs) originating from the left ventricular outflow tract (LVOT) sometimes require catheter ablation from both the endocardial and epicardial sides for their elimination, suggesting the presence of intramural VA foci. This study investigated the prevalence and electrocardiographic and electrophysiological characteristics of these idiopathic intramural LVOT VAs when compared with the idiopathic endocardial and epicardial LVOT VAs. METHODS AND RESULTS: We studied 82 consecutive VAs with origins in the aortomitral continuity (n=30), LV summit (n=34), and intramural site (n=18). The maximum deflection index (the time to the maximum deflection in the precordial leads/QRS duration) was the largest in LV summit VAs (0.52±0.07), smallest in aortomitral continuity VAs (0.45±0.06), and midrange in intramural VAs (0.49±0.05). The electrocardiographic and electrophysiological characteristics of the intramural LVOT VAs were similar to those of the aortomitral continuity VAs. The intramural LVOT VAs exhibited a significantly smaller R-wave amplitude ratio in leads III to II, and ratio of the Q-wave amplitude in leads aVL to aVR, and a significantly earlier and later local ventricular activation time relative to the QRS onset at the His bundle and successful ablation sites than the LV summit VAs, respectively. CONCLUSIONS: Intramural sites account for a significant proportion of LVOT VAs. The electrocardiographic and electrophysiological characteristics of the idiopathic intramural LVOT VAs were midrange between those of the idiopathic endocardial and epicardial LVOT VAs, and more similar to those of the idiopathic endocardial LVOT VAs than those of the idiopathic epicardial LVOT VAs.

High prevalence of concealed Brugada syndrome in patients with atrioventricular nodal reentrant tachycardia.

BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) may coexist with Brugada syndrome (BrS). OBJECTIVES: The present study was designed to determine the prevalence of drug-induced type 1 Brugada ECG pattern (concealed BrS) in patients presenting with clinical spontaneous AVNRT and to investigate their electrocardiographic, electrophysiological, and genetic characteristics. METHODS: Ninety-six consecutive patients without any sign of BrS on baseline electrocardiogram undergoing electrophysiological study and ablation for symptomatic, drug-resistant AVNRT and 66 control subjects underwent an ajmaline challenge to unmask BrS. Genetic screening was performed in 17 patients displaying both AVNRT and BrS. RESULTS: A concealed BrS electrocardiogram was uncovered in 26 of 96 patients with AVNRT (27.1%) and in 3 of 66 control subjects (4.5%) (P ≤ .001). Patients with concealed BrS were predominantly female patients (n=23 [88.5%] vs n=44 [62.9%], P = .015), had higher prevalence of chest pain (n=10 [38.5%] vs n=13 [18.6%], p=0.042), migraine headaches (n=10 [38.5%] vs n=10 [14.2%], p=0.008), and drug-induced initiation and/or worsening of duration and/or frequency of AVNRT (n=4 [15.4%] vs n=1 [1.4%], p=0.006) as compared to patients with AVNRT without BrS. Genetic screening identified 19 mutations or rare variants in 13 genes in 13 of 17 patients with both AVNRT and BrS (yield = 76.5%). Ten of these 13 genotype-positive patients (76.9%) harbored genetic variants known or suspected to cause a loss of function of cardiac sodium channel current (SCN5A, SCN10A, SCN1B, GPD1L, PKP2, and HEY2). CONCLUSION: Our results suggest that spontaneous AVNRT and concealed BrS co-occur, particularly in female patients, and that genetic variants that reduce sodium channel current may provide a mechanistic link between AVNRT and BrS and predispose to expression of both phenotypes.

Brugada syndrome: an update.

More than 20 years have passed since the description of Brugada syndrome as a clinical entity. The original case series depicted patients who all had coved ST-segment elevation in the right precordial leads, associated with a high risk of sudden death and no apparent structural heart disease. As subsequent registry data were published, it became apparent that the spectrum of risk is wide, with the majority of patients classified as low risk. Two consensus documents have been published that will continue to be updated. Despite intense research efforts, many controversies still exist over its pathophysiology and the risk stratification for sudden death. Management continues to be challenging with a lack of drug therapy and high complication rates from implantable cardioverter defibrillators. In this review, we highlight the current state-of-the-art therapies and their controversies.

Brugada syndrome: two decades of progress.

Two decades ago, a series of 8 idiopathic ventricular fibrillation patients who each had an abnormal ECG (right bundle branch block with coved-type ECG), but otherwise had normal hearts were described by Brugada and Brugada. Since then, the clinical entity has become known as Brugada syndrome (BS). Shortly thereafter, mutations of the SCN5A gene that encodes for the α-subunit of the sodium channel were found, galvanizing the field of ion channelopathies following in the footsteps of the breakthrough in long QT syndrome. Over the past 20 years, extensive research in this field has produced major progress toward better understanding of BS and the gaining of knowledge of the genetic background, pathophysiology and new management. Two consensus reports were published to help define the diagnostic criteria, risk stratification and management of BS patients. However, there are controversies. In this review, we will share our experiences of BS patients in Thailand and discuss advances in many aspects of the syndrome (ie, genetics and pathophysiology) and some of these pertinent controversies, as well as new treatment of the syndrome with catheter ablation.

Syncope in Brugada syndrome patients: prevalence, characteristics, and outcome.

BACKGROUND: The report from the 2nd Consensus Committee on BrS suggests that all patients with syncope without a "clear extracardiac cause" should have an implantable cardioverter-defibrillator (ICD). However, a clear extracardiac cause for syncope may be difficult to prove. OBJECTIVE: The purpose of this study was to characterize syncope in patients with Brugada syndrome (BrS). METHODS: All patients diagnosed with BrS at our institution between 1999 and 2010 were enrolled in a prospective registry. Patients with suspected arrhythmic syncope (group 1) were compared to patients with nonarrhythmic syncope (group 2) and to patients with syncope of doubtful origin (group 3). RESULTS: Of 203 patients with BrS, 57 (28%; 44 male, age 46 ± 12 years) experienced at least 1 syncope. Group 1 consisted of 23 patients, all of whom received an ICD. In group 2 (17 patients), 3 received an ICD because of a positive electrophysiologic study. In group 3 (17 patients), 6 received an implantable loop recorder and 6 received an ICD. After mean follow-up of 65 ± 42 months, 14 patients in group 1 remained asymptomatic, 4 had recurrent syncope, and 6 had appropriate ICD therapy. In group 2, 9 patients remained asymptomatic and 7 had recurrent neurocardiogenic syncope. In group 3, 7 remained asymptomatic and 9 had recurrent syncope. One patient from each group died from a noncardiac cause. CONCLUSION: In the present study, syncope occurred in 28% of patients with BrS. The ventricular arrhythmia rate was 5.5% per year in group 1. In 30%, the etiology of the syncope was questionable. No sudden cardiac death occurred in groups 2 and 3.