Abstract

A progressively increasing number of non-cardiac agents prolong cardiac repolarization predisposing to polymorphic ventricular tachycardia, termed torsade de pointes (TdP), and sudden cardiac death. Drug-induced QT interval prolongation is considered the most frequent cause of withdrawal or relabeling of marketed drugs. Although the exact mechanisms are incompletely understood, the majority of these agents exhibit direct electrophysiological effects on the rapidly activating delayed rectifier potassium current. Additionally, pharmacokinetic interactions with drugs known to inhibit cytochrome P450 isoenzymes may enhance the torsadogenic potential of these agents. Genetic analyses have identified the subclinical congenital form in 5-10% of patients with drug-induced long QT syndrome. The likelihood of drug-induced long QT syndrome is difficult to be predicted in routine clinical practice. However, clinical history may reveal well-established risk factors that act as “effect amplifiers” making an otherwise relatively safe drug dangerous with regard to risk for TdP. The current review describes the underlying mechanisms of drug-induced QT interval prolongation and TdP as well as the risk factors that predispose to this potentially life-threatening conditions.