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Ornelas-Loredo A, Kany S, Abraham V, et al. Association Between Obesity-Mediated Atrial Fibrillation and Therapy With Sodium Channel Blocker Antiarrhythmic Drugs. JAMA Cardiol. 2020;5(1):57–64. doi:10.1001/jamacardio.2019.4513
Does obesity mediate response to sodium channel vs potassium channel blocker antiarrhythmic drugs in patients with atrial fibrillation and in mice with diet-induced obesity?
In this cohort study of 311 patients, those with obesity had greater recurrence (30%) of atrial fibrillation compared with those who were not obese who received sodium channel blocker antiarrhythmic drugs (6%); significant factors associated with failure to respond to antiarrhythmic drugs were use of sodium channel blockers, obesity, female sex, and hyperthyroidism. Mice with obesity showed reduced association of flecainide acetate in suppressing pacing-induced atrial fibrillation vs sotalol hydrochloride.
Possible reduced response to sodium channel blocker antiarrhythmic drugs in suppressing atrial fibrillation in patients with obesity has important clinical implications.
The association between obesity, an established risk factor for atrial fibrillation (AF), and response to antiarrhythmic drugs (AADs) remains unclear.
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.
A total of 311 patients (mean [SD] age, 65  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 < .001) in controls. Furthermore, DIO mice showed a greater reduction in AF burden when treated with sotalol compared with flecainide (85% vs 25%; P < .01).
Conclusions and Relevance
Results suggest that obesity differentially mediates response to AADs in patients and in mice with AF, possibly reducing the therapeutic effectiveness of sodium channel blockers. These findings may have implications for the management of AF in patients with obesity.
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