Assessment of Proarrhythmic Risk for Class III Antiarrhythmic Drug in Atrium

drug-induced arrhythmias have attracted less attention in the atrium, but they still have hazards that cannot be ignored and are associated with increased morbidity and mortality and decreased physical function and quality of life. There is clinical evidence that antiarrhythmic drugs (AADs) of class III, when used clinically for arrhythmia treatment, have a proarrhythmic risk in the atrium. However, the risk has not been systematically studied. In this paper, we aim to evaluate the relative risk of six class III AADs in causing atrial arrhythmias under SR and AF conditions. To achieve this, we first construct modeling populations of atrial cells from patients with SR or AF, and then simulate the effects of 6 class III AADs on these two populations. Finally, we systematically assess the relative risks of the six drugs under SR and AF conditions using the rate of arrhythmias induced by each drug in the population as metrics. Our results suggest that class III AADs do have the potential to induce atrial arrhythmias. Among the six drugs, vernakalant has the highest risk of proarrhythmic response in SR population, following by dronedarone and dofetilide. Ibutilide and sotalol show relatively intermediate risks, and amiodarone has the lowest risk. In AF population, dronedarone has the highest risk, vernakalant, dofetilide and ibutilide show relatively intermediate risks. Amiodarone and sotalol have relatively low risks. Comprehensive multicenter trials confirm the reliability of our results.