Chicago—A causal link has been established in past research between obesity and atrial fibrillation (AF), according to a new study, but how and why obesity affects response to antiarrhythmic drugs (AADs) remains unclear.

The report published in JAMA Cardiology sought 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.

University of Illinois at Chicago researchers led the observational cohort study. It included 311 patients enrolled in a clinical-genetic registry and had a second component involving mice fed a high-fat diet for 10 weeks. The study was conducted from January 1, 2018, to June 2, 2019.

For the study, symptomatic response was defined as continuation of the same AAD for at least 3 months, while nonresponse was defined as discontinuation of the AAD within 3 months because of poor symptomatic control of AF requiring alternative rhythm- control therapy.

At the same time, outcome measures in DIO mice were defined as pacing-induced AF and suppression of AF after 2 weeks of treatment with flecainide acetate or sotalol hydrochloride.

The 311 patients, who had a mean age of 65 years and were 38.6% female, were treated for symptomatic AF with a class I or III AAD.

Results indicate that patients with obesity had greater recurrence (30%) of AF compared with those without obesity who received sodium channel blocker antiarrhythmic drugs (6%). Both groups had similar symptomatic response to a potassium channel blocker AAD, however, researchers note.

On multivariate analysis, significant indicators of the probability of failure to respond to AADs were:
• AAD class (class I vs III AAD [obese] odds ratio [OR], 4.54; 95% Wald CI, 1.84-11.20; P = .001),
• Female versus 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).

The study found that pacing-induced AF occurred in 100% of DIO mice versus 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),” the authors add.

“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,” the authors conclude. “These findings may have implications for the management of AF in patients with obesity.”

“This is the first time anyone has shown that there is a differential response to antiarrhythmic drugs for AFib,” pointed out senior author Dawood Darbar, MBChB, MD, professor and head of cardiology at the UIC College of Medicine.

“As 50% of the patients in our AFib Registry are obese, this provided us with a unique opportunity to determine whether obesity affected response to drug treatment for AFib. Our study provides new information that physicians can use to guide their decisions for obese patients with AFib.”

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