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Background: Early during the current coronavirus disease 19 (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 has the effectiveness of HCQ remained questionable, but mainly based on preclinical and a few small clinical studies, HCQ is known to be potentially arrhythmogenic, especially as a result of QT prolongation., Objective: The purpose of this study was to investigate the arrhythmic effects of HCQ, as the heightened risk is especially relevant to COVID-19 patients, who are at higher risk for cardiac complications and arrhythmias at baseline., Methods: An optical mapping technique utilizing voltage-sensitive fluorescent dyes was used to determine the arrhythmic effects of HCQ in ex vivo guinea pig and rabbit hearts perfused with the upper therapeutic serum dose of HCQ (1000 ng/mL)., Results: HCQ markedly increased action potential dispersion, resulted in development of repolarization alternans, and initiated polymorphic ventricular tachycardia., Conclusion: The study results further highlight the proarrhythmic effects of HCQ., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Low-energy anti-fibrillation pacing (LEAP) has been suggested as an alternative treatment in symptomatic fibrillation patients. It significantly lowers the energy required compared with standard 1-shock defibrillation., Objective: In this study, we investigated the mechanism of arrhythmia termination by LEAP and systematically analyzed the influence of shock period and timing on the success rate of LEAP., Methods: We induced atrial and ventricular fibrillation in isolated canine hearts and applied LEAP and standard 1-shock defibrillation to terminate the arrhythmia. We simulated the arrhythmia and LEAP using a 2-dimensional bidomain human atrial model., Results: The ex vivo experiments showed successful termination of atrial fibrillation and ventricular fibrillation using LEAP, with an average 88% and 81% energy reduction, respectively, and both experiments and simulations verified that synchronization from virtual electrodes is the key mechanism for termination of arrhythmia by LEAP using modified Kuramoto phase plots and fraction of tissue excited (FTE) plots. We also observed in simulations that LEAP is more effective when the shock period is close to the dominant period and the first shock is delivered when FTE is decreasing., Conclusions: Our results support synchronization as the mechanism for arrhythmia termination by LEAP, and its effectiveness can be improved by adjusting shock period and timing., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary vein (PV) ablation plays an important role in atrial fibrillation (AF) therapy but suffers from a limited mechanistic understanding of PV arrhythmogenicity. Rapid focal activation has been suggested, but some evidence points to underlying reentry., Objective: This study was performed to evaluate how the electrophysiological properties of PVs may make them a site for reentry and to analyze specifically the roles of PV dimensions and coupling properties., Methods: A computer model designed to efficiently reproduce electrophysiological behaviors was fit to action potentials from canine left atria (LA) and PVs. To assess structural and functional arrhythmogenic determinants, an idealized PV of varying length and circumference was attached to LA tissue, and 5 seconds of activity after extrastimulation were simulated., Results: PV reentrant activity depended critically on vein size and coupling properties. With cumulative removal of transverse and longitudinal connections, sustained (n=23) or nonsustained (n=93) reentries could be observed (687 simulations) for veins 1-3 cm long and 1-2 cm in circumference. The prevalence of sustained reentry increased with PV length (8% for 1 cm vs. 22% and 31% for 2 and 3 cm, respectively; P<.05 for each). The PV circumference did not affect the incidence of sustained reentry (25%, 17%, and 21% for 1-, 1.5-, and 2-cm circumferences; P=NS), but the number of reentrant events increased from 12/201 simulations for PVs with a 1-cm circumference to 48/232 and 56/254 events for PVs with 1.5- and 2-cm circumferences, respectively (P<.05). Sustained reentry cycle lengths were approximately 200-250 ms (16/23), except for the longest PVs., Conclusion: Reentry occurs readily in PVs with realistic properties in the context of specific connection heterogeneities. Reentry properties and incidence depend on PV anisotropy and dimensions but could certainly contribute significantly to PV arrhythmogenesis.