Novel cardiac biomarkers predict short-term outcome in interventional treatment of tricuspid regurgitation

Background
Interventional treatment of severe tricuspid regurgitation (TR) is evolving, yet identifying patients who may benefit from such interventions remains a challenge. Established cardiac biomarkers, like N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP), often do not correlate with disease severity and can be unreliable in cases of comorbid conditions such as cardiorenal syndrome. New biomarkers, including soluble urokinase plasminogen activator receptor (suPAR) and Growth Differentiation Factor 15 (GDF-15), have emerged but are not yet routinely used clinically. Elevated suPAR levels may indicate systemic immune activation and chronic inflammation, both of which are associated with adverse cardiac remodeling and endothelial dysfunction. In TR, increased GDF-15 levels have been linked to right ventricular wall stress and fibrosis, indicating maladaptive remodeling. This study aimed to evaluate the predictive value of suPAR and GDF-15 for rehospitalization due to decompensated heart failure and all-cause mortality within three months post-intervention, hypothesizing that these novel biomarkers would outperform NT-proBNP.

Methods
In this single-center prospective cohort study, data from patients undergoing edge-to-edge repair or heterotopic minimal invasive tricuspid valve intervention were analyzed. Blood samples were taken before the intervention. NT-proBNP was determined in the routine laboratory and measurements of suPAR and GDF-15 were obtained using commercially available ELISA kits. Receiver operator characteristics with calculation of the area under the curve (AUC) were performed to illustrate the predictive value of each biomarker for the combined endpoint rehospitalization and mortality. We defined an AUC of 0.60-0.69 as poor, 0.70-0.79 as fair, 0.80-0.89 as good, and 0.90-1.00 as excellent in terms of predictive value. AUC-ROC comparison was performed (Hanley and McNeil). AUC-ROC for suPAR and GDF-15 were categorized into low, medium and high-risk categories and compared using the chi-square test to evaluate survival rates and visualized with Kaplan-Meier curves.

Results
Data from 60 consecutive patients were analyzed. Among them, 47 underwent edge-to-edge repair (TriClip n=9; Pascal n=38), while 13 had heterotopic minimally invasive tricuspid valve interventions (TricValve; n=13). The mean age was 80.3 years (SD 7.3), with 48.3% male. Baseline characteristics of the patients are shown in Table 1.
Rehospitalization for decompensated heart failure occurred in 12 patients (20%), and mortality within three months was 10%. suPAR demonstrated a good prognostic value (AUC 0.888, SE 0.055, 95% CI 0.779 – 0.997, p < 0.001), as did GDF-15 (AUC 0.869, SE 0.067, 95% CI 0.737 – 1.000, p < 0.001), compared to a fair performance of NT-proBNP (AUC 0.739, SE 0.074, 95% CI 0.593 – 0.884, p = 0.008). The predictive values for biomarkers assessed are shown in Figure 1.The AUC differences indicated significant superiority of suPAR (z-score 2.142, p = 0.016) and GDF-15 (z-score 2.191, p = 0.014) over NT-proBNP. Kaplan-Meier Curves for suPAR and GDF-15 are shown in Figure 2.

Conclusion
In this pilot study, suPAR and GDF-15 showed a superior predictive value for rehospitalization and three-month all-cause mortality compared to the established biomarker NT-proBNP.