Association between Obesity-Mediated Atrial Fibrillation and Therapy with Sodium Channel Blocker Antiarrhythmic Drugs

Abstract

Importance: The association between obesity, an established risk factor for atrial fibrillation (AF), and response to antiarrhythmic drugs (AADs) remains unclear. Objective: To test the hypothesis that obesity differentially mediates response to AADs in patients with symptomatic AF and in mice with diet-induced obesity (DIO) and pacing induced AF. Design, Setting, and Participants: An observational cohort study was conducted including 311 patients enrolled in a clinical-genetic registry. Mice fed a high-fat diet for 10 weeks were also evaluated. The study was conducted from January 1, 2018, to June 2, 2019. Main Outcomes and Measures: Symptomatic response was defined as continuation of the same AAD for at least 3 months. Nonresponse was defined as discontinuation of the AAD within 3 months of initiation because of poor symptomatic control of AF necessitating alternative rhythm control therapy. Outcome measures in DIO mice were pacing-induced AF and suppression of AF after 2 weeks of treatment with flecainide acetate or sotalol hydrochloride. Results: A total of 311 patients (mean [SD] age, 65 [12] years; 120 women [38.6%]) met the entry criteria and were treated with a class I or III AAD for symptomatic AF. Nonresponse to class I AADs in patients with obesity was less than in those without obesity (30% [obese] vs 6% [nonobese]; difference, 0.24; 95% CI, 0.11-0.37; P =.001). Both groups had similar symptomatic response to a potassium channel blocker AAD. On multivariate analysis, obesity, AAD class (class I vs III AAD [obese] odds ratio [OR], 4.54; 95% Wald CI, 1.84-11.20; P =.001), female vs male sex (OR, 2.31; 95% Wald CI, 1.07-4.99; P =.03), and hyperthyroidism (OR, 4.95; 95% Wald CI, 1.23-20.00; P =.02) were significant indicators of the probability of failure to respond to AADs. Pacing induced AF in 100% of DIO mice vs 30% (P