Effects of SGLT-2 inhibitors on cardiac MRI changes and biomarkers in patients with heart failure with preserved ejection fraction

Abstract Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome associated with diastolic dysfunction, left atrial (LA) impairment, and atrial remodeling (1). Despite the preserved systolic function, HFpEF patients often experience elevated left ventricular (LV) filling pressures, myocardial fibrosis, and altered atrial mechanics, all contributing to worsening outcomes (2). Sodium-glucose cotransporter 2 (SGLT2) inhibitors, originally developed for glycemic control in diabetes mellitus, have recently emerged as promising therapeutic agents in HFpEF due to their pleiotropic cardiovascular effects (3). The primary aim of this study is to evaluate the impact of SGLT2 inhibitors on diastolic function, left atrial function, and atrial remodeling in HFpEF patients using echocardiography and cardiac magnetic resonance (CMR) imaging. Additionally, the study seeks to contribute to understanding HFpEF pathophysiology by analyzing circulating biomarkers (galectin-3 and heart-type fatty acid-binding protein (H-FABP)) which reflect myocardial fibrosis and injury, respectively. A total of 26 patients with HFpEF and type 2 diabetes mellitus who were followed at our Hospital between May 29, 2023, and May 28, 2024, were included in the study. Echocardiographic and CMR imaging assessments were performed before and after treatment with SGLT2 inhibitors. Blood samples were collected at both time points for biomarker evaluation. Post-treatment imaging showed significant reductions in LA volüme index (from 40,6±12,9 mL to 36,9±13,8 ml/m², p0.028) and improvements in LA reservoir strain (from 22.3±9.4% to 23.0±8.3%, p=0.010). LV volumes and mass also decreased significantly, including a reduction in LV end-diastolic volume index (152.27±28.92 mL to 139.08±28.28 mL, p0.001) and LV mass index (52.67±10.15 g/m² to 49.27±8.99 g/m², p0.001). TAPSE values increased (18.3±4.65 mm to 20.54±4.22 mm, p=0.001), indicating improved RV function (Table 1). Diastolic parameters improved, such as lateral e' velocity (6.77±1.66 to 8.17±1.98 cm/s, p=0.010) and E/A ratio (0.83±0.38 to 0.85±0.27, p=0.002) (Table 2). A significant decline in galectin-3 levels was observed (773.99±885.55 ng/mL to 502.05±535.90 ng/mL, p=0.028), while H-FABP levels remained unchanged. In conclusion, SGLT2 inhibitors demonstrated beneficial effects on structural and functional cardiac parameters in patients with HFpEF, particularly in improving left atrial mechanics and reducing fibrosis. These findings support their role in HFpEF management, although further studies with larger cohorts and longer follow-up are needed to validate and expand upon these results.Comparison of cardiac MRI findings in pa Comparison of echocardiographic paramete