BackgroundThe cardiovascular (CV) benefits of sodium-glucose transport protein 2 inhibitors have been attributed, in part, to cardiac reverse remodelling. The EMPA-HEART CardioLink-6 study reported that sodium-glucose cotransporter-2 inhibition for 6 months with empagliflozin was associated with a significant reduction in left ventricular mass indexed to body surface area (LVMi). In this sub-analysis, we evaluated whether baseline LVMi may influence how empagliflozin affects cardiac reverse remodelling.MethodsA total of 97 patients with type 2 diabetes and coronary artery disease were randomized to empagliflozin (10 mg/d) or matching placebo for 6 months. The study cohort was divided into those whose baseline LVMi was ≤ 60 g/m2and those who had a baseline LVMi > 60 g/m2. Subgroup comparisons were conducted using a linear regression model adjusted for baseline values (ANCOVA) that included an interaction term between LVMi subgroup and treatment.ResultsBaseline LVMi was 53.3 g/m2(49.2–57.2) and 69.7 g/m2(64.2–76.1) for those with baseline ≤ 60 g/m2(n = 54) and LVMi > 60 g/m2(n = 43) respectively. The adjusted difference of LVMi regression between those randomized to empagliflozin and placebo were − 0.46 g/m2(95% CI: −3.44, 2.52,p= 0.76) in the baseline LVMi ≤ 60 g/m2subgroup and − 7.26 g/m2(95% CI: −11.40, −3.12,p= 0.0011) in the baseline LVMi > 60 g/m2subgroup (p-for-interaction = 0.007). No significant associations were found between baseline LVMi and 6-month change in LV end systolic volume-indexed (p-for-interaction = 0.086), LV end diastolic volume-indexed (p-for-interaction = 0.34), or LV ejection fraction (p-for-interaction = 0.15).ConclusionsPatients with higher LVMi at baseline experienced greater LVM regression with empagliflozin.