Noninvasive Hemodynamic and Echocardiographic Changes Following Vericiguat Initiation in Heart Failure With Reduced...

Vericiguat reduces cardiovascular death and heart failure (HF) hospitalization in high-risk patients with HF and reduced ejection fraction (HFrEF), but its noninvasive hemodynamic and remodelling effects in real-world practice remain incompletely characterized. We aimed to evaluate changes in noninvasive 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. Coprimary endpoints were paired 6-month changes in left ventricular ejection fraction (LVEF) and left ventricular 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 cm), or E/e' (reduction >1), without deterioration in the remaining indices. Clinical events were assessed using a 6-month landmark analysis. Among 113 patients (age 64 ± 11; median N-terminal pro B-type natriuretic peptide 1,433 pg/ml; baseline LVEF 28% ± 7.5%, average use of 4 pillars of guideline-directed medical therapy 94%), LVEF increased from 28% ± 7.5% to 29.8% ± 8% (p = 0.002); LVOT VTI from 16 ± 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 N-terminal pro B-type natriuretic peptide 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 noninvasive hemodynamic phenotyping to characterize response to soluble guanylate cyclase stimulation.