Drug-induced torsades de pointes and implications for drug development.

Torsades de pointes is a potentially lethal arrhythmia that occasionally appears as an adverse effect of pharmacotherapy. Recently developed understanding of the underlying electrophysiology allows better estimation of the drug-induced risks and explains the failures of older approaches through the surface ECG. This article expresses a consensus reached by an independent academic task force on the physiologic understanding of drug-induced repolarization changes, their preclinical and clinical evaluation, and the risk-to-benefit interpretation of drug-induced torsades de pointes.

Development of drugs that alter ventricular repolarization.

Many drugs are found to alter ventricular repolarization, as manifest by T-wave and U-wave changes on the surface electrocardiogram. These changes have frequently been associated with malignant ventricular arrhythmias. There is no perfectly sensitive and specific way of anticipating such arrhythmias, but some clinical and preclinical screening methods are better than others.