Impact of SGLT2 inhibitors on endothelial function and echocardiographic parameters in dilated cardiomyopathy

Abstract

Background: Dilated cardiomyopathy (DCM) is a common cause of heart failure with reduced ejection fraction (HFrEF) in industrialized countries and a major contributor to morbidity and mortality. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated significant benefits in HFrEF management; however, their impact on endothelial function in this patient population remains less explored. This study aims to evaluate the effects of SGLT2i on endothelial function and echocardiographic parameters in patients with DCM.

Methods: This observational, longitudinal, monocentric study enrolled patients with DCM and HFrEF. Endothelial function was assessed using peripheral arterial tonometry (EndoPAT) at baseline, 6 months, and 12 months following the initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i). The enrollment period spanned from November 2021 to November 2022. The primary endpoint was the change in reactive hyperemia index (RHI) over time. In addition, a subgroup analysis was conducted to compare the effects of different SGLT2i agents (empagliflozin vs. dapagliflozin) and DCM etiology (ischemic vs. idiopathic) on endothelial function.

Results: A total of 102 patients were included, predominantly male (72%), with a median age of 75 years and an average baseline left ventricular ejection fraction (LVEF) of 32.9 ± 7.9%. NYHA class II/III was observed in 76% of participants, and ischemic etiology accounted for 53% of DCM cases. The baseline RHI value was 1.15 ± 0.34. At 6 months, it significantly increased to 1.40 ± 0.34 (P < 0.0001), reflecting an absolute change of 0.25 ± 0.03 (ΔRHI baseline - 6 months). Between 6 and 12 months, the RHI showed a further significant increase to 1.69 ± 0.36 (P < 0.0001), with an additional change of 0.29 ± 0.03 (ΔRHI 6 - 12 months). The overall change in RHI from baseline to 12 months (ΔRHI baseline - 12 months) was 0.54 ± 0.04 (P < 0.0001). No significant differences in RHI were observed between patients treated with dapagliflozin and those receiving empagliflozin (P = 0.589), nor between different DCM etiologies (ischemic vs. idiopathic, P = 0.463). The enhancement in RHI was associated with a reduction in the incidence of hospitalization for heart failure (AUC 0.783, P < 0.001). Progressive improvement in left ventricular function was observed through echocardiographic parameters. Although EDV and ESV showed a decreasing trend (EDV: 176.2 ± 64.9 to 167.6 ± 31.1 ml, P = 0.335; ESV: 124.5 ± 52.7 to 116.8 ± 24.6 ml, P = 0.606), these changes were not statistically significant. LVEF improved significantly from 32.9 ± 7.9% at baseline to 36.8 ± 5.5% at 6 months and 37.1 ± 4.9% at 12 months (P < 0.001). The E/A ratio declined from 1.5 ± 0.5 to 1.1 ± 0.3 (P = 0.023) and the E/E' ratio decreased from 18.1 ± 5.1 to 11.1 ± 2.8 (P = 0.027).Left atrial volume significantly decreased from 108 to 100 ml (P = 0.041), and pulmonary artery systolic pressure dropped from 44 to 39 mmHg at 6 months and 35 mmHg at 12 months (P < 0.001).

Conclusion: SGLT2i therapy significantly improves endothelial function in patients with DCM suggesting a potential vascular benefit beyond their well established cardioprotective effects.

Keywords: EndoPAT; dilated cardiomyopathy; echocardiography; endothelial function; heart failure; heart failure with reduced ejection fraction; sodium-glucose cotransporter-2 inhibitors.

Graphical abstract

Fig. 1

A patient basal RHI (a) and 12 months after SGLT2i therapy (b).

Fig. 2

Basal, 6- and 12-month RHI values after SGLT2i therapy.

Fig. 3

Reactive hyperemia index values in SGLT2i-treated patients.

Fig. 4

Reactive hyperemia index values in patients according to dilated cardiomyopathy etiology.

Fig. 5

Correlation between reactive hyperemia index improvement and the probability of hospitalization for heart failure.