An antiarrhythmic approach to hydroxychloroquine-induced QT prolongation

Abstract

Derivatives of quinolone, namely quinidine, quinine and hydroxychloroquine (HCQ, hydroxylated form of aminoquinone), have been used for decades in the treatment of different diseases, including malaria, rheumatological diseases, cardiac arrhythmias and, most recently, the new coronavirus disease 2019 (COVID-19). Although quinidine is no longer widely used for the termination and prevention of arrhythmias, quinine and HCQ are still in common use for rheumatological diseases and malaria. Their common side-effects, QT prolongation and a risk of proarrhythmia, have re-emerged as a result of the widespread use of HCQ in the treatment of COVID-19. In fact, they all show the main electrophysiological aspects of class Ia antiarrhythmic drugs. This antiarrhythmic effect is mainly characterised by the inhibition of fast Na channels and to a lesser extent by K-channel inhibition. However, this class I antiarrhythmic effect is accompanied by a proarrhythmic effect by prolonging the QT interval, thereby facilitating the occurrence of torsades de pointes or ventricular arrhythmias. Therefore, being a derivative of quinolone, like quinidine, and manifesting class Ia antiarrhythmic drug effects, HCQ has been given all the attention regarding the