Drug-Induced QT Interval Prolongation: Mechanisms, Risk Factors, Genetics and Clinical Management

Abstract

Long QT syndrome LQTS characterized by prolongation of the QT interval, may occur as congenital or drug-induced forms. Drug-induced QT interval prolongation DI-QTP is closely associated with severe ventricular arrhythmias [especially torsade de pointes TdP ] and sudden cardiac death. In particular, development of DI-QTP is generally associated with multiple risk factors. Cardiac and non-cardiac drugs may cause QT interval prolongation QTP and TdP. Most of the QT-prolonging drugs act by blocking the rapid component of the delayed rectifier potassium channel whereas a smaller number of drugs act by modifying Ca2+ and Na+ currents. In addition, pharmacokinetic drug interactions are among the reasons of DI-QTP. The corrected QT interval QTc according to heart rate by Bazett’s formula is the most commonly used. Genetic susceptibility is another important issue in predicting DI-QTP and TdP risk. Silent mutations and/or polymorphisms associated with cardiac ion channels may cause a risk for DI-QTP. Firstly, for treatment, drugs that cause QTP should be stopped rapidly, electrolyte abnormalities and other pathologies should be rapidly corrected. Intravenous magnesium sulphate, overdrive pacing, isoproterenol and plasma alkalinisation via sodium bicarbonate are the main useful treatments for DI-QTP and related TdP therapy. Class 1B antiarrhythmic drugs and intravenous potassium are thought to may be effective in TdP.The purpose of this article is to review the underlying mechanisms of QTP, risk factors and genetics of DI-QTP, how to measurement of QT interval and treatment of acquired LQTS.Key-words: Drugs, QT interval, QT prolongation and torsade de pointes