Noninvasive prognostic biomarkers for left heart failure as predictors of survival in pulmonary arterial hypertension

Abstract Background Three biomarkers, soluble suppression of tumorigenicity 2 (ST2), galectin 3 (Gal3), and the N-terminal brain natriuretic peptide prohormone (NT-proBNP) are approved for noninvasive risk assessment in left heart failure, and small observational studies have shown their prognostic utility in heterogeneous pulmonary hypertension cohorts. We examined associations between these biomarkers and disease severity and survival in a large cohort of patients with Group I pulmonary arterial hypertension (PAH). We hypothesized that additive use of biomarkers in combination would improve the prognostic value of survival models. Methods Biomarker measurements and clinical data were obtained from 2,017 adults with Group I PAH. Associations between biomarker levels and clinical variables, including survival times, were examined with multivariable regression models. Likelihood ratio tests and Akaike Information Criteria were used to compare survival models. Results Higher ST2 and NT-proBNP were associated with higher pulmonary pressures and vascular resistance and lower 6 minute walk distance. Higher ST2 and NT-proBNP levels were associated with increased risk of death (hazard ratios 2.79, 95% CI 2.21-3.53, p Conclusions ST2 and NT-proBNP are strong, noninvasive prognostic biomarkers in PAH. Despite its prognostic value in left heart failure, Gal3 was not predictive in PAH. Adding ST2 to survival models significantly improves model predictive capacity. Future studies are needed to develop multimarker assays that improve noninvasive risk stratification in PAH.