Chloroquine and hydroxychloroquine side effects on cardiovascular system
Another essential aspect to be discussed is about chloroquine cardiovascular side effects since this is one of the promising drugs that have been tested in COVID-19 patients. It is well-reported that long-term chloroquine use may increase depolarization length duration and Purkinje fiber\souts refractory period31-34, ultimately leading to atrioventricular nodal and/or His system malfunction31.
As an antimalarial drug, both chloroquine and hydroxychloroquine (HCQ) are accumulated in lysosomes, directly inhibiting phospholipase activity, inducing cytoplasmic inclusion body formation, increasing lysosomal pH and causing protein inactivity31,35. Due to these properties, drug-induced atrial and ventricular arrhythmias have been associated with their use31-35. The most usual electrocardiographic alteration is fascicular block, which can lead to advanced types of atrioventricular block, generally associated with syncope36.
HCQ can also induce QT interval prolongation, an extremely rare but potential fatal side effect, due to the risk of induced polymorphic ventricular tachycardia and SCD. The proposed mechanism by which HCQ causes QT interval prolongation is not well understood. In 2015, Capel et al. demonstrated, in guinea pig sinoatrial node myocytes, an inhibitory effect of the HCQ on the hyperpolarization-activated current ion channels (also known as “funny current” channels), along with delayed rectifier potassium currents, and L-type calcium ion currents37. Inhibitory effects on pacemaker cells were shown to cause delayed rates in depolarization leading to decreased heart rates. These findings may correlate with a proposed mechanism by which refractory action potentials in cardiac myocytes may lead to prolongation of QT interval due to delayed depolarization and repolarization from abnormal ion currents38. QT prolongation in individual medical therapy is not always predictable, dose adjustments and/or additional monitoring of electrocardiograms may be appropriate in some cases. HCQ proarrhythmic risk must be monitored in patients with underlying cardiovascular or renal disorders, and high caution should be posed in the case of electrolyte imbalance, dysrhythmias or concurrent use of QTc-prolonging drugs38.