Non-Invasive Hemodynamic And Echocardiographic Changes Following Vericiguat Initiation In Heart Failure With Reduced Ejection Fraction: A Prospective Registry Study.

Abstract

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.