Physicians' Academy for Cardiovascular Education

Effect of SGLT2i on hemodynamics in patients with HFrEF

Effect of Empagliflozin on Hemodynamics in Patients With Heart Failure and Reduced Ejection Fraction

Literature - Omar M, Jensen J, Frederiksen PH, et al. - J Am Coll Cardiol. 2020 Dec 8;76:2740-2751. doi: 10.1016/j.jacc.2020.10.005.

Introduction and methods

SGLT2 inhibition significantly improves CV outcomes in patients with type 2 diabetes with or without a history of HF [1-4]. Also extended studies with SGLT2i treatment in patients with HFrEF showed a risk reduction in CV death and hospitalization for HF [5,6]. However, the mechanism of SGLT2i leading to improved CV outcomes remains unknown. Possible hypothetical mechanisms for these positive outcomes based on preclinical data are reverse cardiac remodeling, alternation in plasma volume, myocardial substrate switch, and effects on myocardial mitochondrial function [7-9].

Increased left ventricular (LV) filling pressure coexists with inadequate cardiac output (CO) in rest or during exercise is a characteristic of HFrEF [10]. Thus, the relationship between LV filling pressure and CO gives insight into the hemodynamic adaptation of the heart during exercise. This study assessed the effects of SGLT2i treatment on hemodynamics in patients with HFrEF by examining the ratio of pulmonary capillary wedge pressure (PCWP) to cardiac index (CI) at rest and during exercise.

This study is part of the investigator initiated double-blind, placebo-controlled, randomized trial Empire HF. Patients with HFrEF were included from March 6, 2018, to September 10, 2019, from the Odense University Hospital, Odense, Denmark. Patients with stable HFrEF, New York Heart Association (NYHA) functional class II to III symptoms and LVEF ≤40% were recruited. Patients (n=70; 18 to 85 years) were randomized (1:1) to empagliflozin (10 mg once daily), added to the patient’s standard HF treatment, or matching placebo. Patients underwent right heart catherization (RHC) during rest and exercise to measure the PCWP and transthoracic echocardiography at rest to determine LV volume. PCWP was measured as the average of ≥3 cardiac cycles at rest and >10 cardiac cycles with exercise. CO was divided by body surface area to calculate the CI. The primary outcome was PCWP to CI ratio at maximal exercise after a 12 weeks follow-up. Secondary endpoints included the between-group changes in ratio of PCWP to CI and the individual components at all stages of exercise.

Main results


This investigator-initiated study showed that 12 weeks of empagliflozin treatment in patients with HFrEF had no effect on the PCWP to CI ratio at rest or during exercise compared to placebo. There was, however, a significant treatment-effect of empagliflozin on PCWP over the full range of exercise loads, suggesting a reduction in LV pressure in these patients.


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