Effect of Empagliflozin on Hemodynamics in Patients With Heart Failure and Reduced Ejection Fraction

Massar Omar*, Jesper Jensen, Peter H. Frederiksen, Caroline Kistorp, Lars Videbæk, Mikael Kjær Poulsen, Sören Möller, Mulham Ali, Finn Gustafsson, Lars Køber, Barry A. Borlaug, Morten Schou, Jacob Eifer Møller

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review


Background: Inhibition of the sodium-glucose cotransporter-2 (SGLT2i) improves outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF), but the mechanism by which they improve outcomes remains unclear. Objectives: This study aimed to investigate the effects of sodium-glucose cotransporter-2 inhibitor empagliflozin on central hemodynamics in patients with HF and HFrEF. Methods: This investigator-initiated, double-blinded, placebo-controlled, randomized trial enrolled 70 patients with HFrEF from March 6, 2018, to September 10, 2019. Patients were assigned to empagliflozin of 10 mg or matching placebo once daily on guideline-driven HF therapy for 12 weeks. The primary outcome was ratio of pulmonary capillary wedge pressure (PCWP) to cardiac index (CI) at peak exercise after 12 weeks. Patients underwent right-heart catheterization at rest and during exercise at baseline and 12-week follow-up. Results: Patients with HFrEF, mean age of 57 years, mean left-ventricular ejection fraction, 26%, and 12 (17%) with type 2 diabetes mellitus were randomized. There was no significant treatment effect on peak PCWP/CI (−0.13 mm Hg/l/min/m2; 95% confidence interval: −1.60 to 1.34 mm Hg/l/min/m2; p = 0.86). Considering hemodynamics over the full range of exercise loads, PCWP was significantly reduced (−2.40 mm Hg; 95% confidence interval: −3.96 to −0.84 mm Hg; p = 0.003), but not CI (−0.09 l/min/m2; 95% confidence interval: −0.14 to 0.32 l/min/m2; p = 0.448) by empagliflozin. This was consistent among patients with and without type 2 diabetes. Conclusions: Among patients with stable HFrEF, empagliflozin for 12 weeks reduced PCWP compared with placebo. There was no significant improvement in neither CI nor PCWP/CI at rest or exercise.

Original languageEnglish
JournalJournal of the American College of Cardiology
Issue number23
Pages (from-to)2740-2751
Publication statusPublished - 8. Dec 2020


  • exercise
  • heart failure reduced ejection fraction
  • hemodynamics
  • SGLT2 inhibitor


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