Dottorato in FISIOPATOLOGIA ED IMAGING CARDIO-TORACO-VASCOLARE

Titolo della tesi: Vericiguat therapy in heart failure with reduced ejection fraction: insights from a multiparametric analysis

Background: Vericiguat, a soluble guanylate cyclase stimulator, improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF) and recent worsening. However, evidence regarding its direct impact on HF pathophysiology remains unclear. Methods: This prospective single-center observational study enrolled 70 consecutive outpatients with chronic HFrEF and a recent worsening episode. All patients received guideline-directed medical therapy plus Vericiguat and were evaluated at baseline (T0) and after 12 months (T1). The primary endpoints were the variation in TAPSE/sPAP ratio and quantitative LVEF. Results: After 12 months, Vericiguat significantly improved the TAPSE/sPAP ratio from 0.58 (±0.22) to 0.74 (±0.20) mm/mmHg (p<0.001), indicating enhanced right ventricular–pulmonary arterial coupling. Similarly, LVEF improved from 31 % (±8) to 35.4 (±9) (p<0.001), accompanied by a reduction in left ventricular end-diastolic volume (p=0.001) and end-systolic volume (p<0.001), consistent with left ventricular reverse remodeling. No baseline variable independently predicted TAPSE/sPAP and LVEF improvement in multivariate analysis, suggesting a class-wide therapeutic effect. NT-proBNP levels significantly decreased (p<0.001), while renal function and hemoglobin showed mild declines (p=0.006 and p=0.005, respectively), without clinically significant adverse events. Conclusion: In patients with HFrEF and recent worsening, Vericiguat was associated with significant improvement in both right ventricular–pulmonary arterial coupling and left ventricular systolic function. These findings indicate favorable hemodynamic and remodeling effects, despite the advanced stage of disease.