Sodium-Glucose Cotransporter-2 Inhibitor Use and Lower Left Atrial Epicardial Adipose Tissue Volume Across Metabolic Phenotypes in Atrial Fibrillation.

BACKGROUND: Epicardial adipose tissue (EAT) is implicated in atrial fibrillation (AF), yet pharmacologic strategies to modify EAT remain incompletely defined. OBJECTIVE: We evaluated whether sodium-glucose cotransporter-2 inhibitor (SGLT2i) use is associated with lower left atrial EAT volume (LA-EATV) in AF ablation candidates and whether this association varies across metabolic phenotypes. METHODS: In this single-center retrospective study, consecutive AF ablation candidates with analyzable preprocedural contrast-enhanced computed tomography (CECT) were included. Two prespecified multivariable linear regression models (continuous and binary covariates) were constructed, and 1:2 propensity score matching (PSM) was performed. Interaction analyses across metabolic phenotypes were also performed. RESULTS: Of 1,321 candidates, 1,133 had analyzable CECT data. In both multivariable models, SGLT2i use was associated with lower log-transformed LA-EATV (β = -0.274, p = 0.01 and β = -0.296, p = 0.009, respectively), corresponding to approximately 25% lower LA-EATV. The inverse association was also observed in the propensity score-matched cohort (β = -0.314, 95% confidence interval -0.585 to -0.044; p = 0.023). Significant interactions were observed for triglyceride (TG) level and body mass index (BMI). The association was stronger in patients with TG ≥175 mg/dL and attenuated in those with BMI ≥25 kg/m2. The strongest phenotype-stratified association was observed in patients with hypertriglyceridemia but without obesity (p = 0.01). CONCLUSION: SGLT2i use was associated with lower LA-EATV in patients with AF after multivariable adjustment. Exploratory findings suggested that the strength of this association may vary according to metabolic phenotype, but these hypothesis-generating observations require confirmation in larger studies.