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

Heart failure with preserved ejection fraction (HFpEF) stands out as a complex clinical condition within cardiovascular diseases. Despite the preservation of ejection fraction, HFpEF is characterized by hemodynamic changes such as impaired diastolic function of the left ventricle (LV) and increased filling pressures. Globally, with increasing life expectancy, the prevalence of HFpEF is rising steadily due to the growing prevalence of metabolic syndromes and associated conditions. Comorbidities such as type 2 diabetes, hypertension, and obesity play a critical role in the development and progression of HFpEF. One of the main pathophysiological mechanisms of HFpEF is diastolic dysfunction (DD). This condition is associated with increased LV filling pressures, myocardial stiffness, and fibrosis processes. Additionally, complications such as right ventricular (RV) dysfunction, atrial remodeling, and pulmonary hypertension (PH) further complicate the clinical course of HFpEF. Due to diastolic dysfunction, increased left atrial (LA) pressures lead to atrial remodeling, ultimately causing atrial fibrosis and impaired atrial function. Sodium-glucose Cotransporter 2 (SGLT2) inhibitors, initially developed as pharmacological agents for diabetes treatment, have gained attention for their cardiovascular benefits and have emerged as potential therapeutic options for HFpEF management. Previous studies have demonstrated that these medications not only ensure glycemic control but also exert beneficial effects on heart and kidney functions. By inducing osmotic diuresis, SGLT2 inhibitors reduce intravascular volume, alleviating preload and afterload. This results in decreased myocardial stress in HFpEF patients. Furthermore, these drugs' antifibrotic and anti-inflammatory effects contribute to reversing myocardial remodeling. Consequently, they promote structural and functional improvements at both ventricular and atrial levels. A total of 26 patients with Type 2 diabetes mellitus (DM) and heart failure with preserved ejection fraction (HFpEF), who were monitored at the Cardiology Clinic of Pamukkale University Hospital between May 29, 2023, and May 28, 2024, were included in the study. The structural and functional cardiac data of the patients before and after treatment were compared using echocardiography and cardiac magnetic resonance imaging (CMR) techniques. The analysis conducted on the 26 included patients revealed significant improvements in structural and functional assessments of the LA using CMR after treatment. The LA volume (LAV) decreased from 78.73±21.64 mL before treatment to 71.20±22.35 mL after treatment (p<0.001). An increase was observed in LA reservoir strain values, rising from 22.3±9.4% pre-treatment to 23.0±8.3% post-treatment (p=0.010). Significant improvements were also observed in LV volume and mass. The LV end-diastolic volume (EDV) decreased from 152.27±28.92 mL pre-treatment to 139.08±28.28 mL post-treatment (p<0.001). Similarly, the LV end-systolic volume (ESV) reduced from 61.10±24.25 mL before treatment to 50.85±16.28 mL after treatment (p<0.001). The LV mass decreased from 103.46±23.03 g to 96.16±20.69 g, and the LV mass index reduced from 52.67±10.15 g/m² to 49.27±8.99 g/m² (p<0.001). Regarding the RV, the RV EDV decreased from 137.48±32.11 mL pre-treatment to 135.48±27.09 mL post-treatment (p<0.001), while the RV ESV dropped from 59.56±13.99 mL to 56.28±14.26 mL (p<0.001). The RV fractional area change (FAC) showed an increase as measured via echocardiography, though this change was not statistically significant. Tricuspid annular plane systolic excursion (TAPSE) increased from 18.3±4.65 mm before treatment to 20.54±4.22 mm after treatment (p=0.001). In diastolic dysfunction assessments, the lateral e' velocity improved from 6.77±1.66 cm/s pre-treatment to 8.17±1.98 cm/s post-treatment (p=0.010). Additionally, the E/A ratio rose from 0.83±0.38 pre-treatment to 0.85±0.27 post-treatment (p=0.002). Laboratory analysis indicated a significant reduction in the fibrosis biomarker galectin-3 (gal-3), dropping from 773.99±885.55 ng/mL pre-treatment to 502.05±535.90 ng/mL post-treatment (p=0.028). However, there was no significant change observed in the myocardial injury marker heart-type fatty acid-binding protein (H-FABP). In conclusion, this study demonstrates that SGLT2 inhibitors contribute to both structural improvements and functional enhancements in patients with HFpEF. The treatment's notable positive effects on atrial strain values and fibrosis are particularly remarkable. However, these findings need confirmation in different patient groups and long-term follow-up studies. Larger-scale randomized controlled trials would be beneficial in thoroughly evaluating the clinical efficacy and mechanisms of this therapeutic approach. Keywords: Preserved ejection fraction heart failure, SGLT2 inhibitors, Cardiac MR, Echocardiography, LA strain