TY - JOUR
T1 - Effect of Empagliflozin on Hemodynamics in Patients With Heart Failure and Reduced Ejection Fraction
AU - Omar, Massar
AU - Jensen, Jesper
AU - Frederiksen, Peter H.
AU - Kistorp, Caroline
AU - Videbæk, Lars
AU - Poulsen, Mikael Kjær
AU - Möller, Sören
AU - Ali, Mulham
AU - Gustafsson, Finn
AU - Køber, Lars
AU - Borlaug, Barry A.
AU - Schou, Morten
AU - Møller, Jacob Eifer
N1 - Funding Information:
This study is a separate part of the empagliflozin in heart failure patients with reduced ejection fraction (Empire HF) randomized, double-blinded, placebo-controlled trial ( 12 ). The study protocol and statistical analysis plan are available in the Appendix, respectively. The Empire HF trial tested the effect of empagliflozin on brain natriuretic peptide after 12 weeks of treatment and failed to detect a reduction ( 13 ). The current study examined 70 patients, enrolled from March 6, 2018, to September 10, 2019, at a single tertiary center (Odense University Hospital, Denmark) ( Supplemental Figure 1 ). The trial was designed, conducted, and reported complied with the Declaration of Helsinki; was approved by the ethics committee in Denmark (reference number 61738); and was conducted according to Good Clinical Practice. All patients provided written informed consent. The study was designed and conducted without any interference or financial support from the manufacturer of empagliflozin.
Publisher Copyright:
© 2020 American College of Cardiology Foundation
PY - 2020/12/8
Y1 - 2020/12/8
N2 - 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.
AB - 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.
KW - SGLT2 inhibitor
KW - exercise
KW - heart failure reduced ejection fraction
KW - hemodynamics
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U2 - 10.1016/j.jacc.2020.10.005
DO - 10.1016/j.jacc.2020.10.005
M3 - Article
C2 - 33272368
AN - SCOPUS:85096482653
SN - 0735-1097
VL - 76
SP - 2740
EP - 2751
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 23
ER -