Action potential and QT prolongation not sufficient to cause Torsade de Pointes: role of action potential triangulation.

摘要

Syncope and sudden death resulting from Torsade de Pointes (TdP) are very uncommon but major adverse drug effects. Prolongation of the QT interval is the most widely used marker of this potential. Minimal prolongation of the QT interval has been the basis for termination of drug development programs, the imposition of significant restrictions on prescription or withdrawal of drugs from the market. In the absence of drug treatment or electrolyte abnormality, QT interval prolongation is a common finding in clinical elec-trocardiography. In this setting, syncope and sudden death are largely restricted to individuals with inherited mutations of cardiac ion channel genes. Roden and Hondeghem have summarized compelling arguments that simple QT interval prolongation is a poor marker for proarrhythmic susceptibility. The many shortcomings of the long QT-proarrhythmia hypothesis include: 1. Drugs that produce the same QT interval prolongation do not pose equivalent proarrhythmic risk. Proarrhythmia is rare with amiodarone treatment, but common with quini-dine. The QT interval is normal in a majority of patients in some series of drug-induced proarrhythmia. 2. Among the congenital syndromes associated with abnormal repolarization, the short QT syndrome poses the greatest risk.