Figure 2.

Mechanisms of QT prolongation and TdP. Prolongation of the QT interval on the electrocardiogram results from the prolongation of the action potential duration (APD) of ventricular myocytes, brought in this case by hydroxychloroquine (HCQ), chloroquine (CQ), azithromycin (AZI) or lopinavir-ritonavir (LOPI), hence by their association. They all reduce outward potassium currents during phase 3 of the action potential. Such reduction of net outward current augments the APD, which translates in an increased QT interval on the ECG. It also facilitates the development of early afterdepolarizations (EADs) associated with calcium influx, because of the delay in repolarisation and a membrane still relatively electropositive. These EADs can lead to extrasystoles which may trigger complex ventricular reentries such as Torsades de Pointes. The prolonged QT reflects the underlying arrhythmogenic substrate resulting from an increased dispersion of the repolarization. The development of early afterdepolarizations and TdP usually occurs with drugs that block I_Kr, the rapid component of the potassium current I_K A factor of particular importance for the genesis of TdP is a particular predisposition of individual patients aggravated by the presence of risk factors (hypokalemia, hypomagnesemia, feminine gender, bradycardia, multiple drugs prolonging the QT…), which reduce the repolarization reserve [27].