Epicardial Adipose Tissue-Targeted DApagliflozin for Reducing Electrical Remodeling in Atrial Fibrillation (EAT-DARE-AF)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Atrial Fibrillation (AF)
• Intervention / Treatment: Drug: Dapagliflozin (10Mg Tab) along with standard medical therapy

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Shanghai Chest Hospital
    • Contact: Mu Qin, Dr; Email: qinmuae@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-80 years;

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:

• Duration of persistent AF >5 years;

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control
Experimental: Dapagliflozin; Dapagliflozin 10 mg per day for 3 months after initial catheter ablation	Drug: Dapagliflozin (10Mg Tab) along with standard medical therapy; Dapagliflozin 10 mg per day for 3 months after initial catheter ablation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Atrial fibrillation burden at 3 months after ablation	Atrial fibrillation burden is defined as the percent of time spent in atrial tachyarrhythmia (atrial fibrillation, atrial flutter, or atrial tachycardia) episodes detected by 7-day single-lead ECG patches at 3 months after ablation.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of quality of life at 3 months	Changes of quality of life from baseline to 3 months after ablation evaluated by the Atrial Fibrillation Effect on Quality of Life (AFEQT) questionnaire.	3 months
Atrial fibrillation recurrence during 3 months after ablation	Atrial fibrillation recurrence is defined as the first recurrence of any atrial tachyarrhythmia (atrial fibrillation, atrial flutter, or atrial tachycardia) lasting 30 seconds or longer detected by ECG during 3 months after ablation.	3 months
Atrial fibrillation recurrence during 1 year after ablation	Atrial fibrillation recurrence is defined as the first recurrence of any atrial tachyarrhythmia (atrial fibrillation, atrial flutter, or atrial tachycardia) lasting 30 seconds or longer detected by ECG during 1 year after ablation.	1 year

Collaborators and Investigators

• Sponsor: Shanghai Chest Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 29, 2025
• First Submitted That Met QC Criteria: December 29, 2025
• First Posted (Estimated): January 12, 2026

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: December 29, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Atrial Fibrillation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Pathological Conditions, Signs and Symptoms; Atrial Fibrillation; Pharmaceutical Preparations; Dosage Forms; Tablets; dapagliflozin
• Other Study ID Numbers: EAT-DARE-AF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No