Pier Paolo Bocchino, Carla Carbonaro, Guglielmo Gallone, Gianluca Galli, Giulia Gobello, Filippo Angelini, Carola Griffith Brookles, Eleonora Bertello, Stefano Pidello, Giulia De Lio, Francesco Ravera, Paolo Boretto, Carol Gravinese, Simone Frea, Claudia Raineri, Gaetano Maria De Ferrari
Vericiguat reduces cardiovascular death and heart failure (HF) hospitalization in high-risk patients with HF and reduced ejection fraction (HFrEF), but its non-invasive haemodynamic and remodelling effects in real-world practice remain incompletely characterized. We aimed to evaluate changes in non-invasive hemodynamic surrogates and cardiac remodeling parameters 6 months after vericiguat initiation in patients with HFrEF. We conducted a prospective, single-center study of consecutive patients with chronic HFrEF initiating vericiguat while receiving stable, optimized guideline-directed medical therapy (GDMT). Co-primary endpoints were paired 6-month changes in LVEF and LV outflow tract (LVOT) velocity-time integral (VTI). Echocardiograms were analyzed blinded to subsequent clinical outcomes. An exploratory "responder" phenotype was defined by improvement in ≥1 of: LVEF (increase > 2%), LVOT VTI (increase > 1.0 cm), or E/e' (reduction > 1.0), without deterioration in the remaining indices. Clinical events were assessed using a 6-month landmark analysis. Among 113 patients (age 64±11; median NT-proBNP 1433 pg/mL; baseline LVEF 28.0±7.5%, average use of 4 pillars of GDMT 94%), LVEF increased from 28.0±7.5% to 29.8±8.0% (p=0.002); LVOT VTI from 16.0±3.4 to 16.8±4.1 cm (p=0.009) at 6 months. E/e' decreased from 13.3±5.3 to 11.9±5.1 (exploratory; p=0.036), and NT-proBNP levels declined (p<0.001). Responder patients experienced fewer clinical events after the 6-month landmark (p=0.013). In conclusion, among real-world optimally treated patients with HFrEF, vericiguat initiation was associated with modest but statistically significant improvements in LVEF and LVOT VTI at 6 months. Favorable echocardiographic hemodynamic response appeared associated with improved subsequent clinical outcomes, supporting the role of non-invasive hemodynamic phenotyping to characterize response to soluble guanylate cyclase stimulation.