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

Background: Vericiguat reduces major adverse events in patients with heart failure with reduced ejection fraction (HFrEF) and recent worsening. However, its effects on cardiac function and cardio-pulmonary coupling remain insufficiently characterized. Methods: In this observational, prospective, single-centre study, we enrolled consecutive patients with HFrEF and a recent worsening episode despite GDMT. We performed a comprehensive clinical, biomarkers, and echocardiographic evaluation at baseline (T0) and at 12-month follow-up (T1). The primary endpoint of the study was to assess the impact of Vericiguat on the variation of TAPSE/sPAP ratio and quantitative LVEF from T0 to T1. Results: We enrolled 60 HFrEF patients with a recent worsening episode. Mean age was 72.6±10.6 years; mean LVEF was 31% (±8). At 12 months, significant improvements in LVEF (p<0.001), LVEDV (p=0.001), LVESV (p<0.001), TAPSE (p=0.01), TTG (p<0.001), sPAP (p<0.001), TAPSE/sPAP ratio (p<0.001), NT-proBNP (p<0.001) and NYHA class (p=0.02) have been observed. A clear inverse association has been observed between sPAP and TAPSE/sPAP variation (r=-0.697; p<0.001). A significant reduction in eGFR (p=0.006) and mean haemoglobin (p=0.005) has been also observed. At multivariate analysis, Vericiguat therapy was independently associated with improvement in both TAPSE/sPAP ratio (β=0.137; 95%CI 0.072–0.202; p=0.001) and LVEF (β=4.55; 95%CI 2.95–6.15; p=0.001). Conclusions: In a real-world cohort of worsening HFrEF patients, Vericiguat therapy was independently associated with improvement in both TAPSE/sPAP ration and LVEF after 12 months of therapy, supporting its potential hemodynamic and cardiopulmonary benefits leading to the well-known outcome reduction.