Echocardiographic evaluation of cardiac remodelling in a cohort of patients with heart failure and reduced ejection fraction treated with dapagliflozin

Abstract

Abstract Background Several mechanisms have been proposed to explain SGLT2 inhibitors’ (SGLT2i) beneficial effects in patients with heart failure (HF), but their exact mode of action in this setting is not fully understood. Pivotal randomised clinical trials regarding this class of drugs in HF setting have not reported echocardiographic data regarding potential cardiac positive remodelling. Objectives To assess the effects of dapagliflozin treatment initiation on cardiac remodelling in patients with HF and reduced ejection fraction (HFrEF), with a focus on left ventricular performance and atrial volumetry. Methods In this retrospective observational study, we analysed data from 94 patients with HFrEF in whom dapagliflozin had been prescribed as part of HF treatment optimization. Inclusion criteria were: age > 18 years; ongoing optimal medical therapy (OMT) for HF according to 2021 ESC HF guidelines (except for SGLT2i); transthoracic echocardiogram within 30 days of baseline assessment demonstrating a left ventricular (LV) ejection fraction (EF) <40%; comprehensive assessment at 6 months with clinical, laboratory and echocardiographic data. Results Patients (mean age 71.7 ± 9.8, 76% males, coronary artery disease as HFrEF main aetiology in 66%) showed significant cardiac remodelling after dapagliflozin initiation, specifically in terms of stroke volume index (SVi, +9.7 ml/m2, p<0.001), LVEF (+5.1%, p<0.001), LV end-diastolic volume (LV EDV) index (-8.4 ml/m2, p<0.001), left atrial (LA) volume index (-3.9 ml/m2, p=0.026), and LV mass index (LVMi, -12.9 gr/m2, p=0.004). BNP tended to significantly decrease (-168.6 ng/L, p=0.025). Percentage of patients with an indication for ICD implantation in primary prevention went from 36.2% to 8.5%, p<0.001. We did not observe significant differences in terms of mitral regurgitation (MR) grading at follow-up (in particular, the proportion of patients with severe MR remained approximately stable: 7% vs 4%, p=0.86). We did not observe any change in diastolic function measured by E/e’ ratio (mean difference -0.6; 95% CI -2.2 to 0.9, p=0.41). Conclusions Treatment with dapagliflozin resulted in positive remodelling in our cohort of patients with HFrEF in terms of chamber volumes, contractility parameters (and this was not explained by an improvement in MR severity) and LVMi. There was a significant decrease in natriuretic peptide as well as in the proportion of patients with primary prevention ICD indication. Our findings highlight the need of further data to fully elucidate the exact mechanism that leads to LA and LV positive remodelling with SGLT2i.Figure 1.Change in TTE Parameters