ST2 is a biomarker of pediatric pulmonary arterial hypertension severity and clinical worsening.

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Pediatric pulmonary hypertension (PH) is a severe disease defined by sustained elevation of pulmonary artery pressures, and pulmonary vascular resistance (PVR). Noninvasive diagnostic and prognostic markers that are more pulmonary vascular specific have been elusive because of disease heterogeneity and patient growth.introduction RESEARCH QUESTION: Is ST2 is associated with pulmonary hemodynamic and functional changes in pediatric pulmonary hypertension? Does ST2 improve mortality risk models in pediatric pulmonary hypertension?Two pediatric cohorts (<21 years old) were assayed for ST2 and NT-ProBNP: a cross-sectional cohort from the NHLBI-funded National Biological Sample and Data Repository for PAH (PAHB, N=182), and a second longitudinal cohort from Children's Hospital of Colorado (CHC, N=61). Adjusted linear regression was used for association with clinical variables. Clinical mortality models (REVEAL score) with and without ST2 were used to predict worsening outcomes and compared. Pulmonary artery endothelial and smooth muscle cell ST2 expression and secretion were assayed in vitro.In adjusted (age, sex) analysis in the PAHB, ST2 was significantly associated with shorter six-minute walk distance (6MWD; p=0.03) and increased pulmonary vascular resistance index (PVRi; p=0.02). In adjusted longitudinal regression in the CHC cohort, ST2 was significantly associated with higher PVRi (p<0.001), shorter 6MWD (p=0.01), and higher mean pulmonary artery pressure (p<0.001). While REVEAL 2.0 score was predictive of clinical worsening in the PAH Biobank (HR 1.88), addition of ST2 significantly improved the model (HR 2.05). In cell culture, ST2 was produced and secreted predominately by endothelial cells as opposed to smooth muscle cells (p<0.0001).

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Authors: Megan Griffiths, Jun Yang, Catherine E Simpson, Dhananjay Vaidya, Melanie Nies, Stephanie Brandal, Rachel Damico, Dunbar Ivy, Eric D Austin, Michael W Pauciulo, Katie A Lutz, Erika B Rosenzweig, Russel Hirsch, Delphine Yung, William C Nichols, Allen D Everett


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