Treatment of Patients With HFrEF With Empagliflozin Associated With Improved Systolic Function and LV Volume, Mass

Treatment of nondiabetic patients with heart failure with reduced ejection fraction (HFrEF) with empagliflozin was found to improve left ventricular (LV) volume, mass, and systolic function as well as functional capacity and quality of life, according to a study published in the Journal of the American College of Cardiology.

In this double-blind, placebo-controlled trial (Are the “Cardiac Benefits” of Empagliflozin Independent of Its Hypoglycemic Activity [EMPA-TROPISM]; Identifier: NCT03485222), 84 nondiabetic patients with HFrEF (mean age, 62±12.1 years; 64% men; 50% Hispanic/Latino) were randomly assigned to receive the sodium-glucose cotransporter 2 inhibitor (SGLT2i) empagliflozin —(10 mg daily) or placebo for 6 months. The study’s primary endpoint was change in LV end-diastolic and end-systolic volume assessed with cardiac magnetic resonance. Secondary end points included changes in LV mass, LV ejection fraction, peak oxygen consumption in the cardiopulmonary exercise test, 6-min walk test, and quality of life.

Treatment with empagliflozin vs placebo was associated with significant reductions in: LV end-diastolic volume (–25.1±26.0 mL vs –1.5 ± 25.4 mL, respectively; P <.001), LV end-systolic volume (–26.6±20.5 mL vs –0.5±21.9 mL, respectively; P <.001), LV mass (–17.8±31.9 g vs 4.1±13.4 g, respectively; P <.001), and LV sphericity, and with improvements in LV ejection fraction (6.0±4.2 vs –0.1±3.9, respectively; P <.001).

Participants who received empagliflozin vs placebo had significant improvements in: peak O2 consumption (1.1±2.6 mL/min/kg vs –0.5±1.9 mL/min/kg, respectively; P =.017), oxygen uptake efficiency slope (111±267 vs –145±318, respectively; P <.001), 6-min walk test (81±64 m vs –35±68 m, respectively; P <.001), and quality of life (Kansas City Cardiomyopathy Questionnaire–12: 21±18 vs 2±15, respectively; P <.001).

“Of utmost importance, empagliflozin-treated patients exhibited improvement in functional capacity (using both maximal exercise in cardiopulmonary exercise testing and submaximal exercise in 6-min walk test) and increase in quality of life compared with the placebo arm,” noted the study authors.

Study limitations include its single-site nature, relatively small number of patients, and high dropout rate in the cardiopulmonary exercise testing.

”[T]hese data suggest the benefits of SGLT2i in the treatment of patients [with HFrEF] independently of their diabetic status,” concluded the study authors.

Disclosures: This research was supported by an independent grant from Boehringer Ingelheim, who provided both drug and financial support for the study. One of the authors reported affiliations with pharmaceutical and medical device companies. Please see the original reference for a full list of disclosures.


Santos-Gallego CG, Vargas-Delgado AP, Requena-Ibanez JA, et al. Randomized trial of empagliflozin in nondiabetic patients with heart failure and reduced ejection fraction. J Am Coll Cardiol. 2021;77(3):243-255.