Long-term SGLT2 inhibitor therapy improves myocardial strain and diastolic function in HFpEF: a retrospective study linking functional recovery to reduced myocardial fibrosis

Background The pathophysiological mechanisms of heart failure with preserved ejection fraction (HFpEF) are complex, with myocardial fibrosis being one of its core features, closely associated with diastolic dysfunction and poor prognosis. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have shown clinical benefits in patients with HFpEF; however, their effects on myocardial strain and diastolic function, as well as their relationship with the reduction of myocardial fibrosis, remain unclear. Objective To evaluate the effects of long-term SGLT2i treatment (≥6 months) on left ventricular global longitudinal strain (GLS), diastolic function parameters, and serum fibrosis markers in patients with HFpEF, and to explore the potential mechanisms, through a retrospective cohort study. Methods A total of 185 patients with HFpEF diagnosed at our hospital between June 2023 and January 2025 were consecutively enrolled and divided into an SGLT2i group ( n = 93) and a control group ( n = 92) based on whether they received SGLT2i treatment. Demographic data, echocardiographic parameters (GLS, LVEF, E/e’, LAVI, LVMI, TRV), and serological indicators (NT-proBNP, PⅢNP, GDF-15) were collected at baseline and during follow-up (median 12 months). The primary endpoint was the change in GLS ( Δ GLS); secondary endpoints included changes in diastolic function parameters, rates of biomarker change, and heart failure rehospitalization rate. Independent sample t-tests, Mann–Whitney U tests, and chi-square tests were used to compare intergroup differences; Pearson correlation analysis was performed to assess the correlation between Δ GLS and Δ PⅢNP, Δ NT-proBNP; multivariate linear regression analysis was used to identify independent influencing factors of GLS improvement; Kaplan–Meier method was used to evaluate rehospitalization-free survival. Results Baseline characteristics were balanced and comparable between the two groups (all P > 0.05). After 6 months of treatment, GLS improved significantly ( Δ GLS: −2.49% ± 0.54% vs. −0.44% ± 0.52%, P < 0.001). NT-proBNP decreased by 30.4% vs. 9.7% ( P < 0.001), PⅢNP by 15.1% vs. 5.8% ( P < 0.001), and GDF-15 by 20.5% vs. 8.6% ( P < 0.001). During the follow-up period, the heart failure rehospitalization rate in the SGLT2i group was significantly lower than that in the control group (24.7% vs. 55.4%, P < 0.001), and rehospitalization-free survival was significantly higher (Log-rank P < 0.001). In the overall population, Δ GLS was significantly positively correlated with Δ PⅢNP (r = 0.554, P < 0.001). Multivariate regression analysis showed that SGLT2i treatment was an independent predictor of GLS improvement ( β = −2.05, P < 0.001). Conclusion Long-term SGLT2i treatment can significantly improve myocardial strain, diastolic function, and clinical outcomes in patients with HFpEF, and its effects are closely related to the reduction of myocardial fibrosis markers, suggesting that the anti-fibrotic effect may be an important mechanism of SGLT2i cardioprotection.