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.

A KCNQ1 mutation causes a high penetrance for familial atrial fibrillation.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia, and its incidence is expected to grow. A genetic predisposition for AF has long been recognized, but its manifestation in these patients likely involves a combination of rare and common genetic variants. Identifying genetic variants that associate with a high penetrance for AF would represent a significant breakthrough for understanding the mechanisms that associate with disease.

Advances in the management of atrial fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia worldwide, increasing in incidence with the aging population. Substantial morbidity and mortality accompany its diagnosis. Management should focus on rate and rhythm management, on reducing thromboembolic risk, and also potentially on targeting the mechanisms responsible for its perpetuation.

Unexplained sudden death, focussing on genetics and family phenotyping.

Purpose Of Review: Unexplained sudden death and the sudden arrhythmic death syndrome (SADS) affect a small but significant proportion of young and apparently healthy individuals. This review revisits the causes underlying such deaths and the investigational strategies that identify surviving family who may be at risk.

Recent Findings: Recent epidemiological data is available from case series or government records.

Drug-induced arrhythmia: pharmacogenomic prescribing?

Drug-induced Torsades de Pointes is a rare, unpredictable, and life-threatening serious adverse event. It can be caused by both cardiac and non-cardiac drugs and has become a major issue in novel drug development and for the regulatory authorities. This review describes the problem, predisposing factors, and the underlying genetic predisposition as it is understood currently.

Characterization of early repolarization during ajmaline provocation and exercise tolerance testing.

Background: Early repolarization (ER) in the inferior electrocardiogram leads is associated with idiopathic ventricular fibrillation, but the majority of subjects with ER have a benign prognosis. At present, there are no risk stratifiers for asymptomatic ER.

Objective: To examine the response to ajmaline provocation and exercise in potentially high-risk subjects with ER and without a definitive cardiac diagnosis.

Next generation diagnostics in inherited arrhythmia syndromes : a comparison of two approaches.

Next-generation sequencing (NGS) provides an unprecedented opportunity to assess genetic variation underlying human disease. Here, we compared two NGS approaches for diagnostic sequencing in inherited arrhythmia syndromes. We compared PCR-based target enrichment and long-read sequencing (PCR-LR) with in-solution hybridization-based enrichment and short-read sequencing (Hyb-SR).

Common variation in the NOS1AP gene is associated with drug-induced QT prolongation and ventricular arrhythmia.

Objectives: This study sought to determine whether variations in NOS1AP affect drug-induced long QT syndrome (LQTS).

Background: Use of antiarrhythmic drugs is limited by the high incidence of serious adverse events including QT prolongation and torsades de pointes. NOS1AP gene variants play a role in modulating QT intervals in healthy subjects and severity of presentation in LQTS.

Specificity of elevated intercostal space ECG recording for the type 1 Brugada ECG pattern.

Background: Right precordial (V1-3) elevated electrode placement ECG (EEP-ECG) is often used in the diagnosis of Brugada syndrome (BrS). However, the specificity of this has only been studied in smaller studies in Asian populations. We aimed to study this in a larger European population.

Early repolarisation: controversies and clinical implications.

Early repolarisation was previously considered a benign variant but in recent years has emerged as a marker of risk for sudden death. In part, this appears to reflect a change in the definition. ECG territory, degree of J-point elevation and ST-segment morphology are associated with different degrees of risk for subsequent ventricular arrhythmia.

A large candidate gene survey identifies the KCNE1 D85N polymorphism as a possible modulator of drug-induced torsades de pointes.

Background: Drug-induced long-QT syndrome (diLQTS) is an adverse drug effect that has an important impact on drug use, development, and regulation. We tested the hypothesis that common variants in key genes controlling cardiac electric properties modify the risk of diLQTS.

Methods And Results: In a case-control setting, we included 176 patients of European descent from North America and Europe with diLQTS, defined as documented torsades de pointes during treatment with a QT-prolonging drug.

Prevalence of the type 1 Brugada electrocardiogram in Caucasian patients with suspected coronary spasm.

Aims: Sporadic cases have reported the coexistence of coronary spasm and Brugada syndrome. However, the prevalence of the Brugada phenotype in coronary spasm is unknown, particularly in non-Japanese populations. In this study, we sought to examine the prevalence of the type 1 Brugada electrocardiogram (ECG) in a large European patient population undergoing intracoronary provocation testing for suspected coronary spasm.

The nonlinear structure of the desmoplakin plakin domain and the effects of cardiomyopathy-linked mutations.

Desmoplakin is a cytoplasmic desmosomal protein that plays a vital role in normal intercellular adhesion. Mutations in desmoplakin can result in devastating skin blistering diseases and arrhythmogenic right ventricular cardiomyopathy, a heart muscle disorder associated with ventricular arrhythmias, heart failure, and sudden death. The desmoplakin N-terminal region is a 1056-amino-acid sequence of unknown structure.

Sudden death and ion channel disease: pathophysiology and implications for management.

The underlying aetiology of sudden arrhythmic death syndrome is predominantly inherited cardiac disease, and 'channelopathies' (cardiac ion channel disease) are the most common detectable cause of death. This heterogeneous group includes Brugada syndrome, long QT syndrome and catecholaminergic polymorphic ventricular tachycardia. Common features include variable penetrance, sudden death due to ventricular arrhythmias, and the absence of structural heart disease.

Low prevalence of risk markers in cases of sudden death due to Brugada syndrome relevance to risk stratification in Brugada syndrome.

Objectives: The objective of this study was to determine the prevalence of conventional risk factors in sudden arrhythmic death syndrome (SADS) probands with Brugada syndrome (BrS).

Background: Patients with BrS and previous aborted sudden cardiac death (SCD) are at high risk of recurrent events. Other universally accepted clinical features associated with higher risk include unheralded syncope and the presence of a spontaneous type 1 electrocardiogram (ECG).

The phenotype standardization project: improving pharmacogenetic studies of serious adverse drug reactions.

The ability to predict the risk for serious drug-induced adverse reactions first requires a large patient database for characterization and validation of genetic markers. The Phenotype Standardization Project (PSP) was initiated to standardize phenotypic definitions, thereby facilitating much-needed recruitment without sacrificing the reliability of patient classification. Three phenotypes have been considered in this initial phase: drug-induced liver injury, drug-induced skin injury, and drug-induced torsade de pointes.