Empagliflozin Improves Right Ventricular Remodeling and Right Ventricular Systolic Function in Non-Diabetic Hfref: Insights from Porcine and Human Studies

Background On top of improving heart failure outcomes, we and others have demonstrated that SGLT2 inhibitors induce reverse cardiac remodeling in HFrEF. However, these studies have focused on the left ventricle, while no information is available on the potential benefits of SGLT2i on the right ventricle (RV). Therefore, our objective is to investigate the effect of empagliflozin on RV remodeling and RV systolic function in non-diabetic HFrEF Methods Animal study: HFrEF was induced by means of proximal LAD occlusions for 2 hours in non-diabetic pigs. Pigs were then randomized to empagliflozin 10mg daily or placebo for 2 months (8/group). Pigs were evaluated with cardiac MRI. We previously reported that empagliflozin reduces LV volumes and improve LVEF (Santos-Gallego, JACC 2019) Human study : The EMPATROPISM clinical trial ((NCT03485222) randomized non-diabetic HFrEF patients to empagliflozin 10mg daily or placebo. All patients were evaluated with MRI. We previously reported that empagliflozin reduces LV volumes, while also improving peakVO2, LVEF, and quality of life (Santos-Gallego, JACC 2021) Results Animal study: Both groups were similar at baseline (RVESV 16.1±3.2 vs 15.8±2.1mL; RVEF 51.9±5.6 vs 52.7±4.7%; p=NS). Cardiac MRI showed that empagliflozin-treated pigs exhibited smaller RVEDV and RVESV at 2 months compared with control. Also treated animals exhibited better RVEF and better right ventriculoarterial coupling (Ees/Ea) vs control (Table) Human study: Both groups were similar at baseline (RVESV 87.4±35.6 vs 76.4±32.4 mL; RVEF 47.1±7.9 vs 49.2±9.1%; p=NS). Cardiac MRI showed that empagliflozin-treated patients experienced a reduction in RVESV vs placebo. Furthermore, empagliflozin-treated patients exhibited improvement in RVEF and in right ventriculoarterial coupling (Ees/Ea) vs control (Table) Conclusions Empagliflozin improves right ventricular remodeling and right ventricular systolic function in non-diabetic HFrEF