How to prevent sudden death in patients with inherited arrhythmia syndromes or cardiomyopathies

Abstract

Inherited arrhythmogenic myocardial diseases are distinctively characterized by the genetically determined increased risk of ventricular fibrillation and sudden arrhythmic death, predominantly in young people.1 They include either genetic heart muscle diseases manifesting clinically with ventricular arrhythmias related to structural ventricular abnormalities (ie, hypertrophic, dilated, and arrhythmogenic right ventricular cardiomyopathy [ARVC]), or channelopathies presenting as a primarily electrical myocardial dysfunction (ie, genetic defects on cardiac ion channels, including long and short QT syndromes, Brugada syndrome, Lenegre disease, and catecholaminergic polymorphic ventricular tachycardia). Common clinical manifestations include syncopal episodes and cardiac arrest precipitated by ventricular fibrillation. Studies on genotype-phenotype correlations led to identification of health gene carriers in every condition. Programmed ventricular stimulation, which has been designed to reproduce scar-related reentrant ventricular tachycardia in postmyocardial infarction patients, is scarcely useful in a patients with inherited arrhythmogenic diseases, with or without structural abnormalities, and risk stratification mostly relies on the severity of spontaneous clinical presentation. An implantable cardioverter defibrillator (ICD) is the definitive lifesaving therapeutic option in most affected patients, whereas β-blockers may have a limited role for the management of adrenergic-dependent arrhythmias. The recent development of molecular genetics, with the discovery of a genetic role in these myocardial disorders of previously unknown origin, raised the need for a new classification that goes beyond the phenotype.2Accordingly, in the new definition/classification proposed by the American Heart Association,3 all these genetically determined diseases, either structural or primarily electrical, sharing the high risk of arrhythmic sudden death, are included among the listing of inherited cardiomyopathies, regardless of their phenotype. The session focused on arrhythmia mechanisms and prevention of sudden death in patients with arrhythmogenic genetic cardiomyopathies.