Effect of Empagliflozin on Cardiac Volumes in HFrEF

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Empagliflozin was found to modestly reduce left ventricular and left atrial volumes in patients with HFrEF.

Empagliflozin was found to modestly reduce left ventricular and left atrial volumes in patients with heart failure and reduced ejection fraction (HFrEF), according to a study published in JAMA Cardiology.

In this multicenter, double-blind, placebo-controlled clinical trial, 190 patients (mean age, 64±11 years; 85.3% men) with HFrEF receiving HF therapy at Odense University Hospital and Gentofte University Hospital in Denmark were recruited between 2017 and 2019. Patients were randomly assigned at a 1:1 ratio to receive 10 mg daily empagliflozin or placebo (n=95 in each group) for 12 weeks and were assessed by echocardiography.

In this cohort, 51.1% had ischemic HFrEF, average left ventricular ejection fraction (LVEF) was 29±8%, and 12.6% had diabetes.

After adjusting for age, gender, diabetes, and atrial fibrillation, patients receiving empagliflozin vs placebo were found to have reduced: LV end-systolic volume index (reduction, 4.3 mL/m2; 95% CI, -8.5 to -0.1 mL/m2; P =.04), LV end-diastolic volume index (reduction, 5.5 mL/m2; 95% CI, -10.6 to -0.4 mL/m2; P =.03), LV mass index (reduction, 9.0 g/m2; 95% CI, -17.2 to -0.9 g/m2; P =.03), and left atrial volume index (reduction, 2.5; 95% CI, -4.8 to -0.1; P =.04).

LVEF was not affected in patients treated with empagliflozin (change, 1.2%; 95% CI, -1.2% to 3.6%; P =.32). Among patients who had not been exposed to diuretics, LVEF was improved with empagliflozin (change, 5.4%; 95% CI, 1.52-9.23%; P =.01).

Empagliflozin was associated with increased hematocrit (2.1%; 95% CI, 1.5-2.8%; P <.001) and reduced systolic blood pressure (-4.6 mmHg; 95% CI, -8.6 to -0.6 mmHg; P =.02) but did not have an effect on diastolic blood pressure (difference, 0.29; 95% CI, -2.5 to 3.0 mmHg; P =.84) or relative wall thickness (difference, 0.001%; 95% CI, -0.03% to 0.03%; P =.97).

After accounting for hematocrit change, the effect of empagliflozin treatment on left atrial volume index was no longer significant (P =.12).

Adjusting for systolic blood pressure change did not alter the association between empagliflozin treatment and LV end-diastolic volume index, but the effects of the drug on LV end-systolic volume index and left atrial volume index were no longer significant.

This study may have been limited in the selection of a young population with better functional capacity than that used in other HF trials.

These data indicated empagliflozin associated with modest reductions in cardiac volumes among patients with HFrEF.

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


Omar M, Jensen J, Ali M, et al. Associations of Empagliflozin With Left Ventricular Volumes, Mass, and Function in Patients With Heart Failure and Reduced Ejection Fraction: A Substudy of the Empire HF Randomized Clinical Trial. [published online January 6, 2021] JAMA Cardiol. doi:10.1001/jamacardio.2020.6827