617 Effects of SGLT2 inhibitors on left and right ventricular function in a real-world diabetic population
Authors: Kotinas Alexios S. , Gitto Mauro , Terzi Riccardo , Oliva Angelo , Zagoreo Jorgele , Reimers Bernhard , Stefanini Giulio G. , Mirani Marco , Favacchio Giuseppe , Condorelli Gianluigi , Panico Cristina 
Published: December 2021

Abstract

Aims
Heart failure (HF) is a pandemic and despite improvements in therapy, the mortality rate has remained unacceptably high. Sodium glucose cotransporter-2 inhibitors (SGLT2i) have emerged as a promising new class of glucose-lowering drugs, reducing HF-related outcomes across all ejection fraction ranges in clinical trials. However, few studies have assessed their efficacy using echocardiography imaging in a real-world setting.

Methods and results
Type 2 diabetes mellitus (T2DM) patients treated with SGLT2i from 2015 to 2020 were enrolled in a retrospective observational study. Clinical, biochemical, and echocardiographic data at baseline and 6 and 12 months after treatment initiation were collected. Of the 459 patients screened, 312 (68%) patients completed 1 year of SGLT2i therapy. Side effects were developed in 92 (20%) patients leading them to stop treatment pre-maturely, while 55 (12%) were lost to follow-up. From the 312 patients who completed 1 year of treatment, 83 patients had echocardiography data before initiation and after either 6 or 12 months of treatment and were included in the data analysis. Sample’s average age was 65.78 ± 8.53 years, 23 (27.7%) were females, and the mean BMI was 32.10 ± 6.29 kg/m2. At baseline patients had Hb1Ac 7.94 ± 1.80% and the mean duration of diabetes was 11.19 ± 8.54 years. 59 (71.1%) patients were asymptomatic (NYHA I) at baseline. The mean left ventricular ejection fraction (LVEF) at baseline was 48.40 ± 10.89%, while mean left ventricular end-diastolic volume (LVEDV) was 127.96 ± 41.84 ml. Mean pulmonary artery systolic pressure (PASP) was 33.63 ± 7.89 mmHg and mean tricuspid annular plane systolic excursion (TAPSE) was 20.18 ± 4.17 mm before treatment started. Mean E/e′ ratio at baseline was 9.75 ± 3.50. Mean septal wall thickness before therapy was initiated was 12.05 ± 1.80 mm while mean anterior wall thickness was 11.22 ± 1.52 mm. Almost all of the patients had at least one cardiovascular risk factor, hypertension being the most common (77, 92.8%), while 53 (63.9%) patients had a history of coronary artery disease (CAD), of which 42 (50.6%) had suffered a myocardial infarction. All-cause HF was present in 31 (37.3%) patients (19 HFrEF, 7 HFmrEF, 5 HFpEF). After a mean of 12.94 ± 7.91 months of SGLT2i treatment, left ventricular function was improved as LVEF was increased to 50.62 ± 10.04% (+2.22%, P = 0.018), while LVEDV was reduced to 123.24 ± 41.41 ml (−4.72 ml, P = 0.052). A trend towards improvement of the right ventricular function was also observed as TAPSE increased to 21.45 ± 3.92 mm (+1.27 mm, P = 0.076). PASP remained rather stable (−0.83 mm, P = 0.620), as well as the E/e′ ratio (−0.11, P = 0.857). Septal wall thickness was found unchanged (−0.16 mm, P = 0.449), as well as the anterior wall thickness (−0.63 mm, P = 0.143). After 1 year of treatment the number of asymptomatic patients remained stable (60, P = 0.863).

Conclusions
SGLT2i improved left ventricular systolic function in a sample of real-world diabetic patients, as shown by the changes in LVEF and LVEDV. A trend towards right ventricular function improvement was also recorded, demonstrated by the TAPSE increase. These findings highlight SGLT2i action on ventricular function and might be hypothesis generating to further elucidate their cardiovascular mechanism of action, beyond their already noted diuretic effect.