Efficacy of Dapagliflozin on Catheter Ablation Outcomes in Persistent Atrial Fibrillation Patients With Increased Epicardial Adipose Tissue
Efficacy of Dapagliflozin on Catheter Ablation Outcomes in Persistent Atrial Fibrillation Patients With Increased Epicardial Adipose Tissue
Persistent atrial fibrillation (PeAF) is associated with a high risk of recurrence following catheter ablation despite advances in ablation technology and strategies. Beyond electrophysiological mechanisms, increasing evidence suggests that atrial structural and inflammatory remodeling plays a pivotal role in the initiation and maintenance of AF, particularly in persistent forms.
Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot located between the myocardium and visceral pericardium. EAT shares a common microcirculation with the underlying atrial myocardium and exerts paracrine and vasocrine effects through the secretion of pro-inflammatory cytokines, adipokines, and profibrotic mediators. Increased EAT volume or thickness has been consistently associated with AF burden, atrial fibrosis, left atrial enlargement, and a higher risk of AF recurrence after catheter ablation.
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated pleiotropic cardiovascular benefits beyond glucose lowering, including reduction in visceral adiposity, attenuation of systemic and local inflammation, and favorable effects on cardiac remodeling. Observational studies and randomized trials in patients with diabetes or heart failure suggest that SGLT2i therapy reduces incident AF and AF recurrence after ablation. However, the effect of SGLT2i in non-diabetic, non-heart failure patients-particularly those with increased EAT as a distinct pathophysiological substrate-remains unclear.This trial is designed to evaluate whether dapagliflozin, administered peri-ablation, can reduce atrial arrhythmia recurrence in PeAF patients with increased EAT but without class I indications for SGLT2i. This targeted approach aims to provide mechanistic and clinical evidence supporting metabolic-inflammatory modulation as an adjunctive strategy to catheter ablation.
Inclusion Criteria:
Diagnosis of persistent atrial fibrillation (continuous AF >7 days and ≤5 years);
Planned first-time catheter ablation for AF;
No class I indications for dapagliflozin, defined as:
No diabetes mellitus;
No history of heart failure (HFrEF, HFmrEF, or HFpEF);
No chronic kidney disease (eGFR ≥60 mL/min/1.73 m²);
Evidence of increased epicardial adipose tissue on cardiac CT or cardiac MRI, defined according to pre-specified imaging thresholds;
Ability to provide written informed consent.
Exclusion Criteria:
Left atrial anteroposterior diameter >50 mm on transthoracic echocardiography;
Prior AF catheter ablation or surgical ablation;
Current or recent (within 3 months) use of any SGLT2 inhibitor;
Severe structural heart disease (e.g., hypertrophic cardiomyopathy, rheumatic valvular disease, dilated cardiomyopathy);
Contraindications to catheter ablation (e.g., left atrial thrombus, active infection);
Estimated glomerular filtration rate <60 mL/min/1.73 m²;
Type 1 diabetes or history of diabetic ketoacidosis;
Pregnancy or breastfeeding;
Any condition deemed by investigators to make study participation inappropriate.