SGLT2 inhibitors and endothelial function in dilated cardiomyopathy with HFrEF: a 12-month sex-based analysis
A Cersosimo, L Amore, R Rovelli, L Teresi, N Pierucci, G Arabia, M Metra, E VizzardiAbstract
Background
Dilated cardiomyopathy (DCM) is a major cause of heart failure with reduced ejection fraction (HFrEF) and is associated with high morbidity and mortality. Endothelial dysfunction is a key pathophysiological mechanism contributing to disease progression and adverse outcomes in HFrEF. Sodium–glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated substantial prognostic benefits in HFrEF regardless of diabetic status; however, potential sex-related differences in their vascular effects remain poorly characterized, particularly in patients with DCM.
Purpose
This study aimed to investigate the longitudinal effects of SGLT2i therapy on endothelial function in patients with DCM and HFrEF, with a specific focus on potential sex-related differences in endothelial response.
Methods
In this observational, longitudinal, single-center study, patients with DCM and HFrEF initiating SGLT2i therapy between March 2021 and August 2022 were enrolled. Endothelial function was assessed using peripheral arterial tonometry, expressed as the reactive hyperemia index (RHI), measured at baseline and after 12 months of treatment. Sex-based analyses were performed to compare baseline endothelial function, longitudinal changes in RHI, and treatment response between men and women.
Results
A total of 89 patients were included (57% male; age 75±8 years). Mean baseline left ventricular ejection fraction was 32.9 ± 7.9%, and 76% of patients were in NYHA functional class II–III. Ischemic etiology was present in 55% of cases. Overall, endothelial function significantly improved after 12 months of SGLT2i therapy, with RHI increasing from 1.15 to 1.64 (ΔRHI = +0.49; p < 0.0001). This improvement was observed in both men (from 1.15 to 1.65; ΔRHI = +0.50; p < 0.0001) and women (from 1.15 to 1.61; ΔRHI = +0.46; p < 0.0001). No significant sex-related differences were detected in baseline RHI values or in the magnitude of endothelial improvement at follow-up, indicating a comparable vascular response to SGLT2i therapy between sexes.
Conclusions
In patients with DCM and HFrEF, SGLT2 inhibitor therapy is associated with a significant improvement in endothelial function over 12 months. Importantly, this vascular benefit appears to be independent of sex, supporting the concept of sex-neutral pleiotropic effects of SGLT2i on vascular health. These findings reinforce the role of SGLT2i as a foundational therapy in HFrEF and suggest that their endothelial benefits may contribute to improved cardiovascular outcomes in both men and women.For image description, please refer to the figure legend and surrounding text.