Experiments and simulations to quantify the arrhythmic effects of Hydroxychloroquine (HCQ) and azithromycin (AZM) in the treatment of COVID19.*

Early during the current coronavirus disease 19(COVID-19) pandemic, hydroxychloroquine (HCQ) received a significant amount of attention as a potential antiviral treatment, and became one of the most commonly prescribed medications for COVID-19 patients. However, not only its effectiveness was questionable, but there were serious potential arrhythmogenic effects, especially as the concentrations used were higher than when commonly prescribed for malaria or and autoimmune conditions.
We show how we can use optical mapping and methods from nonlinear dynamics to quantify the arrhythmic effects of drugs in the heart with a combined approach of theory, experiments and computer simulations. We will identify a period doubling bifurcation that develops on the cell voltage (action potential) due to HCQ blocking certain potassium ion channels. We describe numerically and then experimentally the complex, disorganized patterns of electrical activation that develop due to this bifurcation in space. We demonstrate the arrhythmic substrate that develops due to HCQ and its combination with AZM and identify the physical mechanism.