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

Uzelac, Ilija; Iravanian, Shahriar; Ashikaga, Hiroshi; Bhatia, Neal K.; Herndon, Conner; Kaboudian, Abouzar; Gumbart, James C.; Cherry, Elizabeth M.; Fenton, Flavio H.

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.