Ornelas-Loredo A, Kany S, Abraham V, et al. - Researchers examined mediatory effect of obesity in response to sodium channel vs potassium channel blocker antiarrhythmic drugs in patients with atrial fibrillation and in mice with diet-induced obesity. They conducted an observational cohort study including 311 patients enrolled in a clinical-genetic registry. Further, they evaluated mice fed a high-fat diet for 10 weeks. The study was conducted from January 1, 2018, to June 2, 2019. They defined symptomatic response as continuation of the same antiarrhythmic drugs (AADs) for at least 3 months. Discontinuation of the AAD within 3 months of initiation because of poor symptomatic control of atrial fibrillation (AF) necessitating alternative rhythm control therapy defined nonresponse. Pacing-induced AF and suppression of AF after 2 weeks of treatment with flecainide acetate or sotalol hydrochloride were the outcome measures in DIO mice. In this cohort study, they observed greater recurrence (30%) of atrial fibrillation among those with obesity vs those who were not obese who received sodium channel blocker antiarrhythmic drugs (6%). The use of sodium channel blockers, obesity, female gender, and hyperthyroidism were the significant factors associated with failure to respond to antiarrhythmic drugs. Mice with obesity showed that flecainide acetate had reduced association in suppressing pacing-induced atrial fibrillation relative to sotalol hydrochloride. These findings suggest important clinical implications of possible reduced response to sodium channel blocker antiarrhythmic drugs in suppressing atrial fibrillation in patients with obesity.