Cardiac remodeling is an adverse phenomenon linked to heart failure (HF) progression. Cardiac remodeling could represent the real therapeutic goal in the treatment of patients with HF and reduced ejection fraction (HFrEF), being potentially reversed through different pharmacotherapies. Currently, there are well-established drugs such as ACEi/ARBs and β-blockers with anti-remodeling effects. More recently, ARNI effects on cardiac remodeling were also demonstrated; additional potential benefits of gliflozins remain non clearly demonstrated. To evaluate possible changes in cardiac remodeling in patients with HFrEF/HFmrEF in treatment with ARNI or ARNI plus SGLT2i and the potential benefit on cardiac remodeling of adding SGLT2i to ARNI. Between June 2021 and August 2023, 100 consecutive patients with HFrEF/HFmrEF underwent conventional and advanced echocardiography (TDI, 2DSTE): patients were therefore divided into three groups according to therapy with neither ARNI nor SGLT2i, just ARNI or both. After 3 months, all patients underwent echocardiographic follow-up. After a 3 months of therapy, significant improvements were observed for LVEF, LVEDD, LVEDV, LVESV, LV mass, E/e', LV GLS, TAPSE (ANOVA p< 0.01 in all cases), RV S' velocity (ANOVA p< 0.001).The trend in favor of additional treatment with SGTL2i over ARNI remained statistically significant even after multivariable analysis (p< 0.001 for LVEF, LVEDD; p< 0.01 for LV GLS, TAPSE, TRVS; p< 0.05 for LV mass). SGLT2i therapy when added to the standard treatment for HFrEF and HFmrEF is associated with an improved biventricular function and ventricular dimensions at follow-up.

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2i) improve outcomes in heart failure (HF), but baseline characteristics associated with left ventricular (LV) changes after their initiation in routine practice are incompletely defined. Methods: In this retrospective two-centre study, 101 patients with HF (94 HFrEF, 6 HFmrEF, 1 HFpEF) initiating an SGLT2i underwent echocardiography at baseline and 6 months. For the purposes of this study, LV reverse remodelling was defined as a simultaneous reduction in LV end-diastolic (LVEDV) and end-systolic volume (LVESV); LVESV reductions ≥10% and ≥15% were used as stringent definitions. Associations were explored with Firth logistic regression adjusted for age and baseline LVEF. Death or HF hospitalisation after the 6-month visit was analysed in relation to 6-month changes (landmark analysis). Results: Median LVEF increased from 28.8% at baseline to 31.6% at 6 months, and the medians of individual paired changes in LVEDV and LVESV were −13.0% and −16.3% (all p < 0.001). The operational definition was met by 74 patients (73.3%) and an LVESV reduction ≥15% by 56 (55.4%). Higher BMI and larger baseline LVEDV were associated with LV volume reduction, and lower TAPSE with LVEF response, LVESV reduction ≥15% and NYHA improvement. No statistically significant association was observed between 6-month changes in LVEF or LV volumes and subsequent death or HF hospitalisation; confidence intervals were wide. Conclusions: In this uncontrolled cohort, SGLT2i initiation was followed by modest LV volume reduction and a small LVEF increase. These associations are exploratory and hypothesis-generating.