Prognostic Impact and Structural Recovery in HFrEF Patients on Vericiguat with PH and Tricuspid Regurgitation: Results from the VERISEC Registry

Introduction and aim

Right heart involvement is a critical prognostic factor in heart failure with reduced ejection fraction (HFrEF). This study evaluated the clinical course, 1-year outcomes, and echocardiographic remodeling of patients initiating Vericiguat in a real-world setting, stratified by the presence of pulmonary hypertension (PH) and tricuspid regurgitation (TR).

Methods

We analyzed 835 patients from the VERISEC registry (VERIcicguat in Spanish Real-world Clinical practice), a prospective, multicenter study involving 41 specialized heart failure units. Patients were categorized into three groups based on their baseline right-heart status before vericiguat treatment: 1) neither PH nor moderate-to-severe TR; 2) either PH or moderate-to-severe TR; and 3) both PH (regardless of grade) and moderate-to-severe TR. Analysis focused on Vericiguat titration and safety, 1-year survival using Kaplan-Meier curves, and 12-month echocardiographic changes, incorporating the TAPSE/PH ratio as a surrogate marker of right ventricular-pulmonary arterial (RV-PA) coupling.

Results

The study population had a mean age of 71.3 years (78% male), with 48% showing right-sided heart involvement. Patients with combined PH and TR presented higher clinical complexity, including lower systolic blood pressure and a higher proportion in NYHA class III/IV (Table 1). Despite this, Vericiguat showed high tolerability across the spectrum; 60% of the highest-risk group (PH+TR) successfully reached the 10 mg target dose, with no significant differences in discontinuation rates compared to lower-risk groups (p=0.090).

At 12-month follow-up, significant reverse remodeling was documented among survivors. Specifically, 51.3% of patients with significant TR at baseline improved by at least one grade, and 38.9% of those with right ventricular (RV) dilatation achieved normalization of cavity size. Additionally, mean TAPSE increased from 17.5 to 18.2 mm. Regarding clinical events, the combination of PH and TR was a powerful predictor of mortality, with a 1-year survival rate of 81.3% compared to 93.7% in patients without either condition (Log-rank p<0.001) (Figure 1). Both RV dilatation and a lower TAPSE/PH ratio (10.9 in deceased vs. 12.9 in survivors) were confirmed as independent predictors of cardiovascular death (p=0.010).

Conclusions

In clinical practice, the combination of PH and TR identifies a high-risk HFrEF phenotype. In these patients, Vericiguat is well-tolerated, allowing for successful up-titration even in these complex patients. Notably, a substantial proportion of survivors experience significant right-heart reverse remodeling, with reduced tricuspid regurgitation and normalized right ventricular dimensions. These findings suggest that Vericiguat may facilitate right-sided structural recovery by improving pulmonary vascular resistance and RV-PA coupling.Table 1.PH and TR ImpactFigure 1.Survival by PH and TR Phenotypes