Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been found to significantly reduce heart failure hospitalization (HHF) and cardiovascular (CV) mortality in different patient populations including those with type 2 diabetes (T2D), heart failure (HFrEF and HFpEF) and chronic kidney disease (CKD). Furthermore, SGLT2 inhibition has been found to improve renal function and to reduce kidney failure in these patient populations. Limited data exists on the use of SGLT2 inhibition in patients with acute decompensated heart failure. In this study we examined early and more delayed effects of empagliflozin treatment on hemodynamic parameters (primary endpoint: cardiac index)) and renal function including parameters of acute kidney injury in patients with decompensated heart failure.

Methods: In this prospective, placebo-controlled, double-blind, exploratory study, patients with acute decompensated heart failure with or without diabetes were randomized to empagliflozin 10 mg or placebo for a period of 30 days. Hemodynamic, laboratory and urinary parameters were assessed after 6 hours, 1 day, 3 days, 7 days and 30 days of treatment.

Results: Baseline characteristics were not different in the empagliflozin (n=10) and placebo (n=9) group. Empagliflozin led to a significant increase in urinary glucose excretion throughout the study  (baseline: 37 ± 15 mg/24 hours; day 1: 14565 ± 8663 mg/24 hours; p=0.001). Treatment with empagliflozin had no effect on the primary endpoint of cardiac index nor on systemic vascular resistance index at any time point. Still, empagliflozin significantly reduced parameters of acute kidney injury (the product of TIMP-2 and IGFBP7 measured by NephroCheck® as indicators of tubular kidney damage) which became significant after 3 days of treatment (placebo: 1.1 ± 1.1; empagliflozin: 0.3 ± 0.2; p=0.02) and remained significant at the 7 day timepoint (placebo: 2.5 ± 3.8; empagliflozin: 0.3 ± 0.2; p=0.003).

Conclusions: Empagliflozin treatment does not affect hemodynamic parameters but significantly reduces acute kidney injury in patients with acute heart failure.