Cellular basis of drug-induced torsades de pointes

Abstract

Striking QT prolongation and the morphologically distinctive ventricular tachycardia torsades de pointes can occur in up to 5% of patients treated with certain antiarrhythmic drugs. This adverse drug reaction also occurs, albeit far less frequently, during therapy with a range of drugs not used for cardiovascular indications; examples include certain antibiotics, antipsychotics and antihistamines. The common mechanism for drug-induced torsades de pointes is inhibition of a specific repolarizing potassium current, I(Kr). The key question facing clinicians, regulators and those who develop drugs is why torsades de pointes only occurs in some patients exposed to I(Kr) block. This paper reviews the clinical, cellular, molecular and genetic features of the arrhythmia that may provide an answer to this question and proposes future studies in this area.