The HENA-AF trial will evaluate the effects of henagliflozin on cardiac structure, function, and biomarkers of HF in patients with AF. Participants with persistent AF, enlarged left atrium, and at least another cardiovascular risk factor will be randomized to henagliflozin or placebo. Cardiac MRI will be performed at baseline and at 6 months to measure the changes in cardiac structure and function. The primary hypothesis is that henagliflozin will reduce the left atrial volume index at 6 months in patients with AF.

Atrial fibrillation (AF) is a major public health burden worldwide. Heart failure (HF) is one of the most common causes of death in patients with AF. Clinical trials have indicated that SGLT2i can reduce the risk of AF and HF in patients with diabetes, and improve the prognosis in patients with HF. However, whether SGLT2i can improve cardiac function and reduce the risk of HF in patients with AF remains unclear. The purpose of the HENA-AF trial is to evaluate the effects of henagliflozin on cardiac structure, function, and biomarkers of HF in patients with AF.

The HENA-AF trial will include approximately 100 persistent AF patients with enlarged left atrium and at least another cardiovascular risk factor. Participants will be randomized to henagliflozin or placebo. Cardiac MRI will be performed at baseline and at 6 months to measure the changes in cardiac structure and function. The primary hypothesis is that henagliflozin will reduce the left atrial volume index at 6 months in patients with AF.

Inclusion Criteria:

1. ≥18 and ≤80 years old
2. Persistent AF: ECG or Holter diagnosed AF for more than 1 month
3. LA enlargement (LAAPD ≥40mm and <60mm)
4. One or more risk factors as follows: (1) ≥65 years old; (2) LVH: echocardiographic calculation of left ventricular mass index (LVMI) male ≥115g/m2; female ≥95g/m2 (LVMI=LVM/BSA,LVM=1.04 × [(LVID+IVST+LVPWT) 3-LVID3] * 0.8 * 0.6) BSA (m2) =0.0061 * height (cm) + 0.0128 * weight (kg)-0.1529; (3) Coronary heart disease (CHD): CHD diagnosed by coronary angiography or CTA, or previous history of myocardial infarction, or revascularization (PCI, CABG); (4) Peripheral artery disease (PAD): imaging examination (ultrasound, CTA, MRA or angiography) indicates carotid or lower extremity artery stenosis >50%. Or peripheral vascular revascularization (stent or endarterectomy); (5) Obesity: BMI ≥28

Exclusion Criteria:

1. Intention of catheter ablation of AF in the next 6 months
2. Cardiovascular events (myocardial infarction, etc.) or cardiac surgery in the past 3 months
3. Clinically diagnosed heart failure (objective evidence of elevated natriuretic peptide levels and/or cardiogenic pulmonary/systemic congestion on the basis of structural and/or functional abnormalities) or left ventricular ejection fraction (LVEF) <40%
4. Type 2 diabetic patients with ASCVD or high-risk cardiovascular risk factors (ASCVD includes acute coronary syndrome, stable coronary heart disease, revascularization, ischemic cardiomyopathy, ischemic stroke, transient ischemic attack, peripheral atherosclerotic disease. High-risk cardiovascular risk factors include age ≥55 years old, coronary artery/carotid artery/lower extremity artery stenosis >50%, or left ventricular hypertrophy)
5. Type 2 diabetic patients with CKD (eGFR30-60mL/min ·1.73m2)
6. Diabetic patients who are using SGLT2i to control blood glucose
7. Type 1 diabetes
8. Severe renal insufficiency (eGFR < 30mL/ min ·1.73m2), end-stage renal disease or dialysis patients
9. Previous diabetic ketoacidosis
10. Previous allergic reactions to SGLT2i
11. Severe hypoglycemia attacks in the past 12 months
12. Pregnant
13. Life expectancy less than 1 year
14. Subjects currently participating in other interventional clinical trials
15. Cardiac MRI contraindications (previous implantation of a metal device in the body) or refusal to undergo cardiac MRI
16. The researchers determine that there are factors that will affect the subjects' compliance with the intervention. Such as alcohol abuse, drug abuse, or behavioral disorders