Dapagliflozin Effects on Left Ventricular Remodeling and Filling Pressures in Heart Failure With Reduced Ejection Fraction

Aims: The benefits of sodium glucose cotransporter 2 inhibitors in patients with heart failure with reduced ejection fraction (HFrEF) have been clearly demonstrated in randomized clinical trials. However, the mechanisms of the observed beneficial effects remain incompletely understood. This study aimed to assess morphofunctional cardiac changes following dapagliflozin introduction in stable outpatients with HFrEF and to investigate whether these changes were determinants of the improved clinical outcome. Methods: In this multicenter, prospective observational study, 300 consecutive HFrEF patients ≥18 years old on optimized medical therapy and eligible for dapagliflozin therapy were enrolled between April 2022 and January 2023. Laboratory and echocardiographic assessments were performed at baseline and after a median of 6 months. Results: Following dapagliflozin initiation, 47% of patients achieved a target of improvement in left ventricular end-diastolic volume (Δ EDVi < −10%) and/or end-systolic volume (Δ ESVi < –15%) and/or ejection fraction (Δ EF% > 10%) at 6 months. The proportion of patients with elevated left ventricular filling pressures decreased from 26% to 3% at 6 months (P < .001). The combination of left ventricular remodeling and filling pressures improvements was associated with absence of heart failure–related hospitalizations and significant natriuretic peptide reduction at 12 months. Conclusions: Dapagliflozin determined left ventricular remodeling and improved left ventricular filling pressures in a high proportion of patients with stable HFrEF patients already on optimized medical therapy. These improvements were associated with absence of heart failure–related hospitalizations and a significant natriuretic peptide reduction at 12 months.