Standard Therapy Plus Empagliflozin Did Not Affect LV Global Longitudinal Strain in HFrEF

senior, elderly man taking prescription medication
Investigators sought to determine the effect of empagliflozin on LV contractile reserve in patients with HFrEF.

Left ventricular (LV) contractile reserve was not improved among patients with heart failure with reduced ejection fraction (HFrEF) after 12 weeks of empagliflozin in addition to guideline-directed heart failure (HF) therapy. These findings were published in American Heart Journal.

This study analyzed data from the Empire HF ( identifier: NCT03198585) trial which was an investigator-initiated, double-blind, placebo-controlled study of empagliflozin among patients with stable, chronic HFrEF. Patients (N=120) with HFrEF were recruited at 4 outpatient clinics in Denmark between 2017 and 2019. In addition to guideline-directed therapy, patients were randomly assigned in a 1:1 ratio to receive 10 mg oral empagliflozin or placebo for 12 weeks. The prespecified endpoint was change in LV contractile reserve from baseline.

The empagliflozin and placebo cohorts comprised 78% and 87% men; aged mean 68±10 and 67±10 years; BMI was 29±4.4 and 30±5.0; 95% and 98% were White; and 78% and 83% had New York Heart Association Functional Class II, respectively.

At baseline, the average absolute response between stress and rest in LV global longitudinal strain (GLS) was -3.0% (P <.0001) and -2.7% (P <.0001) among the intervention and placebo cohorts. At 12 weeks, similar responses were observed (absolute response, -2.9% vs -3.3%; both P <.0001). Similarly, LVEF changed from 12% to 8.8% among placebo recipients and 13% to 11% among empagliflozin recipients (all P <.0001).

Compared between cohorts, neither the change from baseline in LV-GLS (adjusted mean absolute change [AMAC], 0.7%; 95% CI, -0.5% to 2.0%; P =.25) nor LVEF (AMAC, 2.2%; 95% CI, -1.4% to 5.8%; P =.22) differed significantly.

The LV-GLS contractile reserve was observed to associate with accelerometer-measured daily activity levels (coefficient, -24; 95% CI, -46 to -1.8 accelerometer counts, P =.03).

These trends were generally consistent across age, gender, BMI, HF-related symptoms, and other comorbidities or drug use.

The major limitation of this study was the use of a stress stimulus of 20 μg/kg/min dobutamine instead of 10 μg/kg/min dobutamine. This stress stimulus was selected due to the high proportion of patients using beta-blocker therapy which has been established to counteract the effect of dobutamine.

“Empagliflozin 10 mg once daily for 12 weeks in addition to guideline-directed HF therapy did not substantially improve left ventricular contractile reserve in patients with stable, chronic HFrEF as compared to placebo,” the study authors wrote. “Future studies should focus on small changes in the metabolism and contractility of the myocardium with other imaging modalities during treatment with SGLT2 inhibitors.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Jensen J, Omar M, Ali M, et al. The effect of empagliflozin on contractile reserve in heart failure: Prespecified sub-study of a randomized, double-blind, and placebo-controlled trial. Am Heart J. Published online June 5, 2022. doi:10.1016/j.ahj.2022.04.008