Effect of sodium-glucose type 2 cotransporter inhibitorson cardiac structure and function in patients with normal ejection fraction

Abstract Introduction 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 heart failure with reduced and preserved ejection fraction (EF). 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 EF (>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, 77.4% were dyslipidemic, 22.6% were obese and 87.1% were current or former smokers. 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 After an average follow-up period of 6.6 months (±0.8), medication had to be withdrawn in 5 patients (in 3 of them due to repeated genital or urinary infections, and in 2 of them because of patient choice). An average reduction of 0.89 mm (±0.24, p = 0.001) in myocardial thickness was observed, as well as a reduction in the 3D-estimated left ventricle mass of 9.9 g/m2 (±4.5, p = 0.03), and in the E/é ratio of 1.4 (±4.5, p = 0.02). 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). An increase in LA strain and indexed volume was noted, although differences did not achieve statistical significance. No relevant differences in LV dimensions and volumes were observed, as well as in the evaluated RV parameters (picture 1). 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, E/e'), in a population of patients with normal EF.