[Effects of antimalarial drugs and cardiomyocytes. Pathogenic approach and new therapeutic recommendations].

The cardiotoxicity of halofantrine was a major concern during the past decade. Other old antimalarials (quinine, mefloquine, etc.) and more recent drugs may carry a similar risk. Studies of ventricular repolarization and myocardial cells can throw light on these adverse effects. Studies of QT dispersion measured on the surface electrocardiogram and of QT dynamicity and variability (QT/RR slope) during long-term Holter recording help to identify patients at risk of drug-induced ventricular arrhythmia. Such electrocardiographic investigations have shown that quinine, mefloquine and artemisinin derivatives do not alter ventricular repolarization. In contrast, halofantrine significantly increases QT dispersion and the QT regression slope. At the cellular level, most major antimalarial drugs inhibit potassium channels, which are regulated by the LQT1 and HERG genes responsible for the congenital long-QT syndrome. We propose new recommendations for the use of these drugs in the treatment and prevention of malaria.