Physician-induced torsade de pointes - Therapeutic implications

Torsade de pointes (TdP) is a clinico-electrocardiographic syndrome characterized by an abnormally prolonged QT interval and the occurrence of potentially life-threatening ventricular tachyarrhythmias. Two mayor causes can be distinguished: congenital and acquired long QT syndrome. Whereas the former has recently been identified as an ion channelopathy, the mechanisms underlying acquired long QT syndrome are far from being understood. It has been suggested that patients with the acquired form of the disease may suffer from a clinically hidden form of the congenital variant. However, recent studies have yielded only a small number of individual cases in whom genetic analyses revealed the presence of an ion channel gene mutation. Since acquired long QT syndrome is most often induced by drugs prolonging myocardial repolarization, it is largely an iatrogenic disease. In order to prevent unwitting exposure to risk, physicians prescribing agents that may prolong repolarization need to be aware of the typical clinico-electrocardiographic characteristics of drug-induced TdP, and its diagnosis and management. A clearer delineation of the risk factors predisposing to abnormal prolongation of repolarization, and a more precise quantification of the torsadogenic potency of individual drugs appear mandatory in order to prevent or at least minimize the occurrence of this potentially fatal adverse effect of certain drugs.