Effects of Sodium-Glucose Cotransporter 2 Inhibitor on Vascular Endothelial and Diastolic Function in Heart Failure With Preserved Ejection Fraction　― Novel Prospective Cohort Study ―

Background: Pathogenesis of heart failure with preserved ejection fraction (HFpEF) may involve endothelial dysfunction and abnormal vascular structure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have beneficial cardiovascular effects and may improve vascular function in patients with HFpEF. Methods and Results: We recruited 184 patients with type 2 diabetes and HFpEF (mean age, 66.0±14.4 years) who were scheduled for treatment with SGLT2 inhibitors, had transthoracic echocardiogram to identify diastolic function, and flow-mediated dilation (FMD) to evaluate endothelial function, and assessed cardio-ankle vascular index (CAVI) and carotid intima-media thickness as indices of vascular function and vascular structure, respectively. Body weight, systolic blood pressure, diastolic blood pressure, triglycerides, remnant lipoprotein cholesterol, fasting plasma glucose, hemoglobin A1c, urinary albumin/creatinine ratio, and insulin resistance (IR) decreased, hematocrit and FMD increased significantly, and CAVI decreased significantly, after 12-week treatment (P<0.05). Short-term SGLT2 inhibitors improved diastolic function, significantly reducing the mitral ratios of septal E/early septal annular tissue Doppler velocity (P=0.003) and lateral E/early lateral e' (P=0.044). On multiple regression statistically significant associations were seen between ∆mean E/e' and ∆FMD, ∆CAVI, and ∆IR. Conclusions: SGLT2 inhibitors can improve diastolic function in patients with type 2 diabetes, suggesting that current treatment policies for diabetes should be re-examined. Further prospective studies with larger sample sizes could provide mechanistic insights into the benefits of SGLT2 inhibitors.