A Clinical Approach to Inherited Arrhythmias

Abstract

In the past decade, the discovery that cases of ventricular arrhythmias and sudden cardiac death (SCD) in young individuals potentially could be caused by an unrecognized genetic substrate has defined a new subset of cardiac conditions: inherited arrhythmogenic diseases (IADs).1 Although rare in clinical practice, these diseases are more common than previously thought. They represent a challenge for the arrhythmia specialist in terms of diagnosis and clinical management. The correct diagnosis of IADs, as well as the use and interpretation of the results of genetic testing, are not straightforward and require a specific expertise such as that provided by specialized and dedicated centers. Here we will review the general issues arising from the correct interpretation of genetic testing and its indications. We also will focus on the clinical management and use of genetic information in different inherited arrhythmias. The term “channelopathies” defines a group of inherited arrhythmic syndromes caused by mutations on genes encoding for ion channel proteins and proteins that regulate ion channels.1 These mutations disrupt the balance of currents in the cardiac action potential, favoring the onset of life-threatening arrhythmias in the absence of structural heart defects. The long QT syndrome (LQTS) is a heritable channelopathy characterized by an exceedingly prolonged cardiac repolarization that may trigger ventricular arrhythmias and SCD.2 LQTS is one of the first channelopathies in which clinical and genetic features have been discovered, and a large series of patients have been collected and followed over the years.2–4 Thanks to these studies, LQTS management takes into account a patient’s genetic background and has become a paradigm for the use of genetic information applied to the clinical practice.3,4 Long QT syndrome can manifest with syncope and cardiac arrest. These commonly are triggered by adrenergic stress; however, roughly 10% …