Abstract 17030: Multi-Center Prevalent and Incident Cohorts Replicate ST2 as a Biomarker of Disease Progression in PAH and is Associated With Right Heart Failure

Abstract

Introduction: Pulmonary arterial hypertension (PAH) is defined by elevation in PA pressure (PAP) and pulmonary vascular resistance (PVR) resulting in right ventricular (RV) failure and is associated with significant morbidity and mortality. Prior studies have evaluated invasive hemodynamic and biomarker parameters of PAH progression and prognostication, including the prognostic role of ST2, a member of the IL-1 receptor family, which is upregulated in cardiopulmonary disease, including PAH. Hypothesis: Serum ST2 (sST2), is upregulated and prognostic of transplant free survival in PAH in 2 independent cohorts and is associated with parameters of RV function. Methods: The primary cohort comprised 191 largely prevalent PAH patients from the University of California San Francisco (UCSF) with 41 largely incident PAH patients from the University of Pennsylvania (Penn) in the validation cohort. The primary outcome was transplant free survival. The Presage high sensitivity ELISA was used to measure sST2. Results: The UCSF cohort was 72% female, mean age 50±15 years, 25% idiopathic & 25% connective tissue disease-PAH (CTD-PAH). Those with sST2 > median (32.5 (21.9, 53.0) U/ml) had decreased semi-quantitative RV function (p=0.0003) by echo and increased right atrial pressure ([RAP]; 11.5 vs. 8.0 mmHg, p=0.003) and decreased cardiac index ([CI]; 2.23 vs. 2.45 L/min/m2, p=0.04), vs. sST2 ≤ median. Patients with sST2 ≤ median had significantly increased survival compared to those with sST2 > median (figure). The Penn cohort was 70% female, mean age 56±11 years, 54% idiopathic & 26% CTD-PAH. Median sT2 was 34 (21.7, 45.5) U/ml with those > median having significantly increased RAP (10.5 vs. 6.2 mmHg), mean PAP (53.3 vs. 39.8 mmHg) and PVR (12.7 vs. 6.0 WU), and lower CI (2.21 vs. 3.05 L/min/m2) (all p-values<0.05). Transplant free survival was significantly higher in those with sST2 ≤ median vs. > median (figure). Conclusions: In 2 independent PAH cohorts, sST2 is predictive of survival and serves as a marker of invasive parameters of RV failure. That sST2 is associated with differences in mean PAP and PVR in the largely incident Penn cohort, as compared to the prevalent UCSF cohort, warrants further study, as does the mechanism behind the robust association of ST2 and PAH.