Drug-Induced QT Interval Prolongation and Torsade De Pointes:Identification of Risk Factors

A progressively increasing number of non-cardiacagents prolong cardiac repolarization predisposingto polymorphic ventricular tachycardia, termed tor-sade de pointes (TdP), and sudden cardiac death.Drug-induced QT interval prolongation is consideredthe most frequent cause of withdrawal or relabelingof marketed drugs. Although the exact mechanismsare incompletely understood, the majority of theseagents exhibit direct electrophysiological effects onthe rapidly activating delayed rectifier potassiumcurrent. Additionally, pharmacokinetic interactionswith drugs known to inhibit cytochrome P450 iso-enzymes may enhance the torsadogenic potentialof these agents. Genetic analyses have identifiedthe subclinical congenital form in 5-10% of patientswith drug-induced long QT syndrome. The likelihoodof drug-induced long QT syndrome is difficult to bepredicted in routine clinical practice. However, clini-cal history may reveal well-established risk factorsthat act as “effect amplifiers” making an otherwiserelatively safe drug dangerous with regard to risk forTdP. The current review describes the underlyingmechanisms of drug-induced QT interval prolonga-tion and TdP as well as the risk factors that predis-pose to this potentially life-threatening conditions.