Effect of Empagliflozin on Pulmonary Capillary Wedge Pressure in HFrEF

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Researchers’ goal was to determine empagliflozin’s impact on the central hemodynamic parameters of patients with heart failure with reduced ejection fraction.

Empagliflozin therapy for 12 weeks resulted in a significant reduction of pulmonary capillary wedge pressure (PCWP), across all exercise loads, compared with placebo, among patients with stable euvolemic heart failure and reduced ejection fraction (HFrEF), according to a study published in the Journal of the American College of Cardiology. Treatment did not, however, significantly improve patients’ cardiac index (CI) or the PCWP/CI ratio, regardless of activity level.

While sodium-glucose cotransporter-2 inhibitors such as empagliflozin are known to improve clinical outcomes in HFrEF patients, the precise mechanism behind this benefit remains uncertain. Investigators sought to characterize the impact of this medication on the central hemodynamic parameters of patients with HFrEF, in a first of its kind study.

In this subanalysis of the randomized, double-blinded, placebo-controlled Empire HF trial (ClinicalTrials.gov ID NCT03198585), 70 individuals (mean age, 57 years; mean left ventricular [LV] EF, 26%; 12 [17%] diagnosed with type 2 diabetes mellitus [T2DM]) with HFrEF on guideline-driven HF therapy were enrolled between March 2018 and September 2019. Participants were randomized to receive either empagliflozin 10 mg (n = 35; mean age, 59±8 years; 91% male) or placebo (n = 35; mean age, 56±11 years; 89% male) once per day for 12 weeks.

Hemodynamic stress testing via right heart catheterization was conducted at rest and during exercise, at baseline and again after 12 weeks. The primary study endpoint was the peak exercise PCWP/CI ratio at the 12-week follow-up.

No significant between-group treatment effect was detected on peak PCWP/CI (mean change from placebo, -0.15 mm Hg/L/min/m2; 95% CI, -1.63 to 1.34 mm Hg/L/min/m2; P =.846). However, across the full range of exercise loads, there was a significant reduction in PCWP (and therefore LV filling pressure) in the empagliflozin group vs the placebo group (mean change from placebo, -2.40 mm Hg; 95% CI, -3.96 to -0.84 mm Hg; P =.003). In contrast, comparing empagliflozin to placebo revealed no significant treatment effect on or reduction in CI between the groups (mean change from placebo, -0.09 L/min/m2; 95% CI, -0.14 to 0.32 L/min/m2; P =.448) across the exercise load range. Results were consistent in those with and without T2DM.

There were no discontinuations of the study drug over 12 weeks, and no fatalities during the study, with the study drug generally well tolerated. A total of 3 serious adverse events were reported – 2 in the empagliflozin group and 1 in the placebo group – though none were deemed related to treatment.

Study limitations included potentially reduced power, possible type 2 error, small sample size, lack of power to estimate PCWP/CI individual effects, and difficult assessment of PCWP during exercise.

“These findings suggest that empagliflozin may have a favorable effect on reducing cardiac filling pressure after 12 weeks of treatment in patients with stable HFrEF,” noted the authors.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Omar M, Jensen J, Frederiksen PH, et al. Effect of empagliflozin on hemodynamics in patients with heart failure and reduced ejection fraction. J Am Coll Cardiol. 2020;76(23):2740-2751. doi: 10.1016/j.jacc.2020.10.005