title: Mechanisms of drug-induced proarrhythmia in clinical practice.
abstract: Drug-induced proarrhythmia represents a great challenge for those involved in the development of novel pharmaceuticals and in the regulatory bodies for drug approval as well as for the prescribing clinicians. Our understanding of the mechanisms that underlie drug-induced proarrhythmia has grown dramatically over the last two decades. A growing number of cardiac and non-cardiac agents have been shown to alter cardiac repolarization predisposing to fatal cardiac arrhythmias such as ventricular tachycardia or ventricular fibrillation and sudden cardiac death. These agents may induce the phenotype of long QT syndrome and less commonly of short QT syndrome and Brugada syndrome (BS). Although, genetic susceptibility underlie drug-induced proarrhythmia in certain cases, current data are limited regarding this topic. The present review surveys the current published literature on the mechanisms and the offending medical agents that predispose to drug-induced long QT syndrome, short QT syndrome and BS. Drug-induced proarrhythmia should be considered as a predictor of sudden cardiac death and should prompt critical re-evaluation of the risks and benefits of the suspicious medication. Survivors of drug-induced proarrhythmia and family members require careful examination and possibly genetic testing for the presence of a channelopathy. Treating physicians are advised to follow the lists of agents implicated in drug-induced proarrhythmia in order to minimize the risk of arrhythmia and sudden cardiac death.
authors.affiliation: Arkadia Konstantopoulou, Spyros Tsikrikas, Dimitrios Asvestas, Konstantinos P Letsas, Second Department of Cardiology, Laboratory of Cardiac Electrophysiology, Evangelismos General Hospital of Athens, 10676 Athens, Greece.
authors.forename: Arkadia
authors.initials: A
authors.lastname: Konstantopoulou
authors.forename: Spyros
authors.initials: S
authors.lastname: Tsikrikas
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Asvestas
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Korantzopoulos
authors.forename: Konstantinos P
authors.initials: KP
authors.lastname: Letsas
keywords: Brugada syndrome; Drugs; Long QT syndrome; Short QT syndrome; Sudden cardiac death