The duration of the QT interval is the surface electrocardiographic representation of action potential (AP) repolarization in the ventricle. Prolongation of the QT interval implies a prolongation of AP duration in a significant number of ventricular myocytes and has been associated with an increased risk of the polymorphic tachycardia torsade de pointes (TdP) and sudden death. Relative prolongation of the QT interval occurs normally in females compared with males. 1 Pathologic QT-interval prolongation may result from a genetic abnormality that produces an overt abnormality on the electrocardiogram (ECG) of a person at rest (eg, as seen in the congenital long-QT syndrome [LQTS]). 2, 3 It may also be caused by electrical remodeling in response to atrioventricular node blockade, 4 tachycardia, 5 cardiac hypertrophy and failure, 6 or by the administration of drugs that prolong APs in ventricular myocytes. A combination of genetic predisposition, environmental stress, and pharmacologic effect may play an especially important role in the clinical problem of sudden death as a result of QT-interval prolongation.

A variety of drugs have been implicated in prolonging the QT interval and causing life-threatening arrhythmias. Indeed, some agents, such as cisapride7, 8 and terfenadine, 9 have been restricted or withdrawn from clinical use because their risk for triggering TdP was believed to outweigh their therapeutic benefits. A hypothesis may shed light on common risk factors for TdP as well as its apparently unpredictable development in some patients: given that multiple, often re-