Sodium-glucose co-transporter-2 inhibitors improve cardiac structure but most studies suggest no change in left ventricular (LV) systolic function at rest. Whether sodium-glucose co-transporter-2 inhibitors improve LV contractile reserve is unknown. We investigated the effect of empagliflozin on LV contractile reserve in patients with heart failure (HF) and reduced ejection fraction.

Prespecified sub-study of the Empire HF trial, a double-blind, placebo-controlled, and randomized trial. Patients with LV ejection fraction (LVEF) ≤ 40% on guideline-directed HF therapy were randomized (1:1) to empagliflozin 10 mg or placebo for 12 weeks. The treatment effect on contractile reserve was assessed by low dose dobutamine stress echocardiography.

In total, 120 patients were included. The mean age was 68 (SD 10) years, 83% were male, and the mean LVEF was 38 (SD 10) %. Respectively 60 (100%) and 59 (98%) patients in the empagliflozin and placebo groups completed stress echocardiography. No statistically significant effect of empagliflozin was observed for the contractile reserve assessed by LV-GLS (adjusted mean absolute change, empagliflozin vs placebo, 0.7% [95% confidence interval {CI} –0.5 to 2.0, P = .25]) or LVEF (adjusted mean absolute change, empagliflozin vs placebo, 2.2% [95% CI –1.4 to 5.8, P = .22]) from baseline to 12 weeks. LV-GLS contractile reserve was associated with accelerometer-measured daily activity level (coefficient –24 accelerometer counts [95% CI –46 to –1.8, P = .03]).

Empagliflozin for 12 weeks added to guideline-directed HF therapy did not improve LV contractile reserve in patients with HF and reduced ejection fraction.