Why the study?
Obese patients with AF represent a heterogeneous population, and whether distinct patient phenotypes exhibit differential treatment responses to catheter ablation versus lifestyle modification plus antiarrhythmic drugs is unknown.
Does catheter ablation improve freedom from atrial arrhythmias compared to lifestyle modification plus antiarrhythmic drugs across different phenotypes in obese patients with atrial fibrillation?
RCT (n=122)
Open-label
1:1
Yes
Does catheter ablation improve freedom from atrial arrhythmias compared to lifestyle modification plus antiarrhythmic drugs across different phenotypes in obese patients with atrial fibrillation?
Odds Ratio: 3.98 (95% CI 1.01–15.57)
Absolute Event Rate: 88.5% vs 65.9%
Absolute Risk Reduction: 22.6%
p-value: p=0.047
Obese patients with atrial fibrillation exhibit phenotype-dependent treatment responses to catheter ablation, with benefit primarily concentrated in those displaying structural remodeling without marked metabolic or inflammatory derangement.
Supports phenotype-specific ablation benefit in obese AF; leaves open prospective validation before guiding therapy.
Background: The PRAGUE-25 trial demonstrated catheter ablation (CA) superiority over lifestyle modification plus antiarrhythmic drugs (LFM + AAD) in obese patients with atrial fibrillation (AF). However, obese AF patients represent a heterogeneous population with varying pathophysiological substrates. We hypothesized that distinct patient phenotypes may exhibit differential treatment responses. Methods: This post-hoc analysis applied hierarchical cluster analysis (Ward's D2 method, Euclidean distance) to 122 PRAGUE-25 patients with complete data using six delta (12-month minus baseline) echocardiographic and metabolic variables (Δ-LAVI, Δ-LVEDD, Δ-NT-proBNP, Δ-triglycerides, Δ-leukocytes, Δ-platelets). Treatment effects within each phenotype were compared using Fisher's exact test and odds ratios with 95% confidence intervals. Results: = 3.45, p = 0.178), CA superiority was statistically significant only in the Intermediate phenotype (OR 3.98, 95% CI: 1.01-15.57, p = 0.047; AF freedom 88.5% CA vs 65.9% LFM + AAD). In the Metabolic and Advanced Neurohormonal/Inflammatory phenotypes (45% of patients), no statistically significant treatment difference was observed; however, wide confidence intervals preclude conclusions of treatment equivalence in these underpowered subgroups. These findings appear to be primarily driven by the Intermediate Remodeling phenotype. Conclusions: These hypothesis-generating findings suggest phenotype-dependent treatment response heterogeneity in obese atrial fibrillation. As cluster membership can only be determined retrospectively, prospective validation using baseline predictor models is required before clinical application.
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Ranič et al. (2026) conducted an RCT in Obese atrial fibrillation (n=122). Catheter ablation vs. Lifestyle modification plus antiarrhythmic drugs (LFM + AAD) was evaluated on Freedom from atrial fibrillation, atrial flutter, or atrial tachycardia at the scheduled 12-month visit in the Intermediate Remodeling phenotype (Cluster 2) (OR 3.98, 95% CI 1.01-15.57, p=0.047).
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