Physicians' Academy for Cardiovascular Education

SGLT2i improves LV structure and function in nondiabetic patients with HFrEF

Randomized Trial of Empagliflozin in Nondiabetic Patients With Heart Failure and Reduced Ejection Fraction

Literature - Santos-Gallego CG, Vargas-Delgado AP, Requena-Ibanez JA, et al. - J Am Coll Cardiol. 2021;77:243-255. doi: 10.1016/j.jacc.2020.11.008.

Introduction and methods

Large clinical trials have demonstrated improved HF outcomes by SGLT2 inhibitors in patients with T2DM as well as patients with HFrEF [1-6]. The early benefits of SGLT2i in clinical outcomes, however, cannot be explained solely by the glucose-lowering effects of SGLT2 inhibitors, since the hypoglycemic activity of the compound is comparable to other glucose-lowering drugs that do not improve HF [7].

In nondiabetic porcine models of HF, empagliflozin significantly improved adverse left ventricular (LV) remodeling, decreased LV volumes and LV hypertrophy, reduced neurohormonal activation, and improved cardiac diastolic and systolic function compared to control group [8,9]. Based upon these results, the EMPA-TROPISM (are the “Cardiac Benefits” of Empagliflozin Independent of Its Hypoglycemic Activity) trial was designed to translate the preclinical data from the HF porcine models to human nondiabetic patients with HFrEF [10].

This study assessed the effects of empagliflozin on LV function and volumes, functional capacity, and quality of life (QoL) in HFrEF patients without T2DM.

The EMPA-TROPISM trial is a single-site, double-blind, randomized, placebo-controlled trial that included nondiabetic patients (>18 years) with HF (New York Heart Association [NYHA] functional class II and III), LVEF<50%, and stable symptoms and medical therapy within the last 3 months. Patients (n=84) were randomized (1:1) to receive empagliflozin 10 mg daily or matching placebo. The primary endpoint was between-groups change in left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV). Secondary endpoints include the between-groups changes in peak oxygen consumption (VO₂) and cardiac pulmonary adaptation. Other endpoints were LV mass, LVEF, LV sphericity index, oxygen uptake efficiency slope (OUES), minute ventilation per carbon dioxide production (VCO₂), distance in the 6-min walk test, and QoL. Follow-up was 6 months after randomization.

Main results


The EMPA-TROPISM trial showed that a 6-month daily administration of empagliflozin benefits nondiabetic patients with HFrEF by reducing LV volume, decreasing LV hypertrophy, improving LVEF, and a less spherical LV with less pronounced architectural remodeling, compared to placebo. In addition, empagliflozin improved functional capacity and QoL in these patients.


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Find this article online at J Am Coll Cardiol Watch a video by Carlos Santos-Gallego on this study

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