Multi-Chamber Reverse Remodeling and Hemodynamic Force Realignment After SGLT2 Inhibitor Initiation in Real-World Heart Failure

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) promote beneficial effects on cardiac reverse remodeling (RR) in heart failure (HF). However, most imaging evidence focuses on single chambers, mainly the left ventricle (LV) or left atrium (LA), whereas integrated biventricular and atrial remodeling remains less explored. Moreover, real-world data are limited, and myocardial-flow coupling markers, such as hemodynamic forces (HDFs), are scarcely investigated, with uncertain sex-related differences. Purpose: To evaluate multi-chamber cardiac RR after SGLT2i initiation in a real-world HF population. Secondary aims are to assess whether changes in HDFs provide additional functional insight into myocardial-flow coupling beyond conventional echocardiographic indices, and to descriptively explore sex-related differences in echocardiographic remodeling. Methods: Patients with HF and ejection fraction (EF) ≤ 45%, naive to SGLT2i and on stable guideline-directed medical therapy for ≥3 months, were enrolled. Standard and advanced echocardiography were performed at baseline and follow-up, including speckle-tracking and HDFs assessment. NYHA class and NT-proBNP were collected. Analyses were performed overall and stratified by sex. Results: Sixty-eight patients were included. After 6 months, RR was observed across all chambers: LV-RR in 33 patients (49%), right ventricular (RV) RR in 35 (52%), biventricular RR in 18 (27%), and LA-RR in 14 (21%). HDFs showed significant realignment, suggesting association with improved myocardial-flow coupling. RR effects were comparable between sexes (p > 0.05). NT-proBNP significantly decreased. Conclusions: In this real-world cohort, SGLT2i therapy was associated with significant multi-chamber RR and HDFs realignment, supporting improved myocardial-flow coupling beyond conventional indices. Exploratory sex-related analyses showed no significant differences. Larger and longer-term randomized studies are warranted.