Abstract 17157: The SGLT2 Inhibitor Empagliflozin Ameliorates Interstitial Myocardial Fibrosis and Aortic Stiffness in Non-Diabetic Patients With Heart Failure With Reduced Ejection Fraction: A Secondary Analysis of the EMPATROPISM Trial

Background: SGLT2 inhibitors (SGLT2i) improve prognosis in HFrEF patients. We recently demonstrated in a porcine model of non-diabetic HFrEF that empagliflozin (EMPA) ameliorates adverse cardiac remodeling and improves LV systolic function. However, the effect of EMPA on interstitial myocardial fibrosis (IMF) and aortic stiffness has not yet been studied Hypothesis: Empagliflozin ameliorates IMF and aortic stiffness in non-diabetic HFrEF patients Methods: The EMPATROPISM clinical trial (NCT 03485222) investigated the efficacy and safety of EMPA in non-diabetic HFrEF patients. 84 patients were randomized to EMPA 10mg daily for 6 months or placebo on top of optimal medical treatment, and were evaluated with cardiac magnetic resonance (CMR). IMF was assessed by CMR using extracellular volume (ECV) by T1 mapping. Aortic stiffness was quantified by pulse wave velocity (PWV) by CMR. The primary endpoint was change in LVEDV. Prespecified secondary endpoints were changes in ECV (ΔECV) and PWV (ΔPWV) at 6 months between both arms Results: 80 patients completed the follow up period. There were no differences at baseline in LVEDV (220±75 vs 209±68mL for EMPA vs placebo, p=0.5) or LVEF (36±8 vs 37±8%, p=0.7). There were no differences at baseline in both groups in either ECV or PWV (Table). In the primary endpoint, EMPA-treated patients showed decrease in LVEDV and increase in LVEF (ΔLVEDV -25±25 vs -1±25mL, p Conclusions: In HFrEF patients without diabetes, treatment with empagliflozin ameliorates IMF and aortic stiffness. This may explain the benefits of SGLT2i in HFrEF even in the absence of diabetes