Dapagliflozin reduces epicardial adipose tissue in patients with heart failure with reduced ejection fraction and type 2 diabetes

Abstract Introduction Epicardial adipose tissue (EAT) accumulation is associated with adverse outcome in heart failure with preserved ejection fraction, however its role in HF with reduced ejection fraction (HFrEF) is less clear. The relationship between EAT thickness and their impact on patients who have diabetes and heart failure remains unclear. SGLT2 inhibitors such as dapagliflozin improve outcomes in heart failure and diabetes, however their mechanism of benefit is not well understood. The aim of our study was to assess whether dapagliflozin reduced EAT in patients with type 2 diabetes and HFrEF. Methods We performed an analysis of individuals with type 2 diabetes and HFrEF who were randomised to receive either dapagliflozin or a placebo for 12 months as part of the REFORM trial. Participants had cardiac magnetic resonance (CMR) scans at baseline and at 12 months. Epicardial fat was measured utilizing 4-chamber cine images to quantify adipose tissue between the myocardium and the visceral layer of the pericardium. This assessment was carried out using the single end-diastolic image, with measurements conducted by evaluators blinded to the randomisation status of participants. Results 47 participants completed the stud. At baseline, not only EAT thickness and BMI level (placebo: 33, dapagliflozin 32, p=0.49) but also heart rate (74.39 bpm vs. 77.61 bpm, p=0.35), systolic blood pressure (132.75 mmHg vs. 135.00 mmHg, p=0.63), diastolic blood pressure (71.39 mmHg vs. 74.04 mmHg, p=0.33) and age (67 vs. 66, p=0.79) were comparable between the two groups. 23 randomised to placebo and 24 to dapagliflozin. Baseline EAT was similar in both groups (placebo: 11.54 cm², dapagliflozin 11.74 cm², p=0.414). After 12 months of treatment dapagliflozin caused a significant reduction in EAT compared to placebo (1.21 cm² vs. 0.09 cm², p=0.007). Conclusion Dapagliflozin significantly reduced epicardial adipose tissue compared to placebo in patients with type 2 diabetes and HFrEF. The reduction in EAT may play a role in the beneficial effects of dapagliflozin in heart failure patients.4 Ch CMRBox plot