Fatal arrhythmias: Another reason why doctors remain cautious about chloroquine/hydroxychloroquine for treating COVID-19

Abstract: Background Early during the current COVID-19 pandemic, hydroxychloroquine (HCQ) received a significant amount of attention as a potential antiviral treatment, such that it became one of the most commonly prescribed medications for COVID-19 patients. However, not only the effectiveness of HCQ has remained questionable, and mainly based on pre-clinical, and a few small clinical studies, but also HCQ is known to be potentially arrhythmogenic, especially as a result of QT prolongation. Objective To investigate the arrhythmic effects of HCQ as the heightened risk is especially relevant as COVID-19 patients are at a higher risk of cardiac complications and arrhythmias at baseline. Methods Here, we use the optical mapping technique, using voltage-sensitive fluorescent dyes, to illustrate the arrhythmic effects of hydroxychloroquine in ex-vivo guinea pig and rabbit hearts perfused with the upper therapeutic serum doses of HCQ (up to 1000ng/ml). Results We observe that HCQ markedly increases the action potential dispersion and results in the development of repolarization alternans and initiate polymorphic ventricular tachycardia. Conclusions These results further highlight the proarrhythmic effects of HCQ.