SGLT2 inhibitors effects on cardiac function and plasma biomarkers of diabetic patients with preserved ejection fraction

BACKGROUND Sodium-glucose cotransporter inhibitors (SGLT2i) have proven a reduction in cardiovascular events in diabetic patients with and without heart failure (HF), as well as in non-diabetic patients with HF. The mechanisms underlying this benefit are not well known, with contradicting data on the changes that SGLT2i produce on cardiac function and structure. METHODS Between October 2020 and October 2021, 31 diabetic patients without prior history of SGLT2i use with normal ejection fraction (> 50%), glycated hemoglobin < 6.5%, renal clearance rate of > 60 ml/min/1.73 m2 and sinus rhythm were prospectively included. In all of them, SGLT2i were started. At inclusion and 6-months follow-up, different clinical, ECG, analytical and echocardiographic (standard, 3D and speckle tracking) variables were recorded. RESULTS The average age of our population was 66.4 years (± 8.4). 90% were male, 71% were hypertensive, and 77.4% were dyslipidemic. 77.4% of patients had a history of ischemic heart disease, and 10% had vascular disease in other territories. At the time of inclusion, 80.6% of the population was treated with ACEI or ARB, 54.8% with beta-blockers, 29% with diuretics, and 93.5% with statins. After an average follow-up period of 6.6 months (± 0.8), an average reduction of 9.9 g/m2 (± 4.5, p = 0.048) in 3D-estimated left ventricle mass was observed. An increase in absolute left ventricle global longitudinal strain (LVGLS) of 0.74 (± 0.35, p = 0.05) was observed, as well as an increase in isovolumetric relaxation time (IVRT) of 9.8 ms (± 4.8, p = 0.05). Moreover, we observed a significant reduction in ANP (p = 0.008) and CK-MB levels (p = 0.006), after SGLT2i treatment. No relevant differences in LV dimensions and volumes were observed, as well as in the evaluated RV parameters and other biomarkers. CONCLUSIONS It is necessary to understand the mechanism underlying the clinical benefit of these drugs. This will allow us to better understand its effect in patients with HF. Our data shows that the use of SGLT2i is associated with cardiac improvements, both structural (myocardial mass) and functional (IVRT, LVGLS), in a population of patients with normal ejection fraction.