Effetto di Dapagliflozin sugli Eventi Aritmici Ventricolari nei Pazienti con Scompenso Cardiaco con Ridotta Frazione di Eiezione, Portatori di Defibrillatore Cardiaco Impiantabile

Heart failure is a complex and progressive syndrome characterized by high morbidity and mortality, in which neurohormonal activation, ventricular remodeling, and comorbidities drive clinical deterioration. In recent years, sodium–glucose cotransporter-2 inhibitors (SGLT2i) have reshaped the therapeutic landscape of heart failure, demonstrating consistent prognostic benefits across all phenotypes and suggesting potential direct and indirect antiarrhythmic effects. This PhD project aimed to evaluate the impact of dapagliflozin on ventricular arrhythmic burden (VAb) in patients with heart failure with reduced ejection fraction (HFrEF) carrying an implantable cardioverter-defibrillator (ICD), and to explore the relationship between arrhythmic reduction, functional class, and ventricular reverse remodeling. In a prospective observational study, 117 outpatients with HFrEF and ICDs treated with dapagliflozin 10 mg were enrolled. VAb (sustained VT, non-sustained VT, VF, and total ventricular arrhythmias) and ICD therapies (ATP and shocks) were compared before and after treatment. Echocardiographic parameters, NT-proBNP, NYHA class, and reverse remodeling (ΔLVEF > 15%) were also assessed. Dapagliflozin significantly reduced VAb (2.9 ± 1.8 vs 4.5 ± 2.0 events/patient/month; P = 0.01) and appropriate ATP therapies (P = 0.03). The reduction in arrhythmic events was more pronounced in NYHA III/IV patients (P = 0.001) and in those exhibiting significant reverse remodeling (P = 0.01). Two-way ANOVA demonstrated significant interactions between VTA variation and baseline NYHA class (η² = 0.553), as well as between VTA variation and ΔLVEF (η² = 0.484). In conclusion, dapagliflozin reduces ventricular arrhythmic burden in ICD carriers with HFrEF, with greater benefit in more symptomatic patients and in those achieving reverse remodeling. These findings support the hypothesis that the hemodynamic and structural effects of SGLT2 inhibition contribute substantially to short- and mid-term arrhythmic reduction.