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Obesity-Mediated AF and Sodium Channel Blocker Antiarrhythmics
Study Questions:
Does obesity differentially mediate response to antiarrhythmic drugs (AADs) in patients with symptomatic atrial fibrillation (AF) and in mice with diet-induced obesity (DIO) and pacing-induced AF?
Methods:
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.
Results:
A total of 311 patients were treated with a class I or III AAD for symptomatic AF. Those with obesity had greater recurrence (30%) of AF compared with those who were not obese who received sodium channel blocker antiarrhythmic drugs (6%) (p = 0.001). Both groups had similar symptomatic response to a potassium channel blocker AAD. On multivariate analysis, obesity, AAD class (class I vs. III AAD odds ratio [OR], 4.54; p = 0.001), female sex (OR, 2.31; p = 0.03), and hyperthyroidism (OR, 4.95; p = 0.02) were significant indicators of the probability of failure to respond to AADs. Pacing induced AF in 100% of DIO mice versus 30% (p < 0.001) in controls. DIO mice showed a greater reduction in AF burden when treated with sotalol compared with flecainide (85% vs. 25%; p < 0.01).
Conclusions:
Obesity differentially mediates response to AADs in patients and in mice with AF, possibly reducing the therapeutic effectiveness of sodium channel blockers.
Perspective:
Obesity is an established risk factor for AF. There is evidence supporting the notion that the cardiac sodium channel, Nav1.5 is down-regulated in obese patients with AF. The current study suggests that prescribing class I AADs in patients with AF and obesity may decrease the sodium current, and paradoxically foster AF recurrence. Class I AADs are considered first-line agents in patients with structurally normal hearts, as these medications have the least ventricular proarrhythmia. A randomized trial of class I versus class III AADs in obese patients with AF would have to be performed to confirm the suspicion that sodium channel blockers are less effective in obese patients with AF than potassium channel blockers.
Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Diet
Keywords: Anti-Arrhythmia Agents, Anticoagulants, Arrhythmias, Cardiac, Diet, High-Fat, Flecainide, Heart Failure, Hyperthyroidism, Metabolic Syndrome, Obesity, Pacemaker, Artificial, Potassium Channel Blockers, Risk Factors, Secondary Prevention, Sodium Channel Blockers, Sotalol
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