The Liraglutide Effects in Atrial Fibrillation (LEAF) Study

Atrial fibrillation (AF) ablation continues to offer mediocre outcomes, particularly for persistent AF. Obesity and epicardial adipose tissue (EAT) are associated with AF and ablation outcomes. Risk factor modification (RFM), including weight loss, improves AF treatment outcomes. Liraglutide, a glucagon-like peptide-1 receptor agonist, leads to weight loss and EAT reduction.

This study sought to test the effects of adjunctive therapy with liraglutide in patients with AF undergoing ablation.

In this randomized study of overweight/obese (body mass index ≥27 kg/m²) patients with AF (80% persistent AF) who opted for catheter ablation for treatment, 28 patients were assigned to RFM and 31 to risk factor modification (plus liraglutide (RFM+L) for 3 months preablation. EAT was evaluated with serial computed tomography scans at enrollment and preablation, and serial echocardiograms up to 1-year postablation. The primary endpoint was change in left atrial epicardial adipose tissue (LAEAT) volume. Total EAT and recurrent AF at 1 year were secondary endpoints.

There were 28 patients (age 61.8 ± 10.3 years, 8 female) assigned to RFM and 31 patients (age 62.2 ± 8.6 years, 8 female) to RFM+L for 3 months preablation. Baseline characteristics were well-balanced between groups with median body mass index of 34.2-37.2 kg/m². Forty-seven (80%) had persistent AF. One patient in the RFM group and 3 in the RFM+L group opted not to proceed with ablation, and "preablation" testing was performed at the time of this decision. Overall, there were reductions in LAEAT (median -1.0 [Q1-Q3: -4.5 to 1.4] mL; P = 0.02) and weight (-2.8 ± 4.0 kg; P < 0.001) but no difference between groups. One-year freedom from AF/atrial flutter was 81% (95% CI: 62%-91%) for RFM+L and 54% (95% CI: 34%-70%) for RFM (log-rank P = 0.007). Logistic regression models showed RFM+L was associated with lower risk of 12-month recurrence (LAEAT model: OR: 0.19; 95% CI: 0.05-0.73; P = 0.015; EAT model: OR: 0.08; 95% CI: 0.01-0.40; P = 0.002). Change in EAT density was associated with lower recurrence (OR: 0.55; 95% CI: 0.36-0.84; P = 0.006).

Whereas adding liraglutide to RFM in obese patients with AF did not produce significant differences in early weight loss or LAEAT reduction, improved freedom from AF/atrial flutter was noted. Pleiotropic glucagon-like peptide-1 receptor agonist effects may provide novel pharmacologic targets for AF treatment that can substantially improve AF ablation outcomes. (Liraglutide Effect in Atrial Fibrillation [LEAF]; NCT03856632).