Empagliflozin Reduces Myocardial Extracellular Volume in Patients With Type 2 Diabetes and Coronary Artery Disease

OBJECTIVES This study sought to evaluate the effects of empagliflozin on extracellular volume (ECV) in individuals with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD). BACKGROUND Empagliflozin has been shown to reduce left ventricular mass index (LVMi) in patients with T2DM and CAD. The effects on myocardial ECV are unknown. METHODS This was a prespecified substudy of the EMPA-HEART (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes) CardioLink-6 trial in which 97 participants were randomized to receive empagliflozin 10 mg daily or placebo for 6 months. Data from 74 participants were included: 39 from the empagliflozin group and 35 from the placebo group. The main outcome was change in left ventricular ECV from baseline to 6 months determined by cardiac magnetic resonance (CMR). Other outcomes included change in LVMi, indexed intracellular compartment volume (iICV) and indexed extracellular compartment volume (iECV), and the fibrosis biomarkers soluble suppressor of tumorgenicity (sST2) and matrix metalloproteinase (MMP)-2. RESULTS Baseline ECV was elevated in the empagliflozin group (29.6 +/- 4.6%) and placebo group (30.6 +/- 4.8%). Six months of empagliflozin therapy reduced ECV compared with placebo (adjusted difference: -1.40%; 95% confidence interval [CI]: -2.60 to -0.14%; p = 0.03). Empagliflozin therapy reduced iECV (adjusted difference: -1.5 ml/m(2); 95% CI: -2.6 to -0.5 ml/m(2); p = 0.006), with a trend toward reduction in iICV (adjusted difference: -1.7 ml/m(2); 95% CI: -3.8 to 0.3 ml/m(2); p = 0.09). Empagliflozin had no impact on MMP-2 or sST2. CONCLUSIONS In individuals with T2DM and CAD, 6 months of empagliflozin reduced ECV, iECV, and LVMi. No changes in MMP-2 and sST2 were seen. Further investigation into the mechanisms by which empagliflozin causes reverse remodeling is required. (C) 2021 Published by Elsevier on behalf of the American College of Cardiology Foundation.

Automated summary

The study shows that empagliflozin treatment for 6 months can reduce ECV, iECV, and LVMi in individuals with T2DM and CAD, with no impact on MMP-2 and sST2. Further research on the mechanisms of empagliflozin-induced reverse remodeling is needed.