ST2 an ‘important prognostic indicator’ for pediatric PAH

Elevated soluble suppressor of tumorigenicity, or ST2, was associated with unfavorable pulmonary outcomes and significantly improved prediction of clinical worsening in pediatric patients with pulmonary arterial hypertension.

“This study shows that an FDA-approved heart failure marker, ST2, is an important prognostic indicator in pediatric pulmonary hypertension and adds to NT-proBNP. In combining [ST2] with NT-proBNP, we have better understanding of both pulmonary vascular and cardiac function and, thus, better risk prediction,” Megan Griffiths, MD, pediatric pulmonary hypertension fellow at Columbia University Medical Center, told Healio. “This is particularly important in pediatrics, where standard testing is either not feasible, like an exercise test in a small child, or is invasive and higher risk, like a cardiac catheterization.”

Researchers aanalyzed ST2 and NT-proBNP in a cross-sectional pediatric cohort from the National Biological Sample and Data Repository for PAH (n = 182; mean age, 13 years; 59% girls) and a second longitudinal pediatric cohort from the Children’s Hospital of Colorado (n = 61; mean age, 5 years; 60% girls). To predict worsening outcomes and compare results, researchers used clinical mortality models with and without ST2 and assayed pulmonary artery endothelial and smooth muscle cell ST2 expression and secretion in vitro.

In the cross-sectional cohort, ST2 was significantly associated with a 161.9 m shorter 6-minute walk distance (P = .03) and increased pulmonary vascular resistance index by 3.23 (P = .02) in an analysis adjusted for age and sex. In the longitudinal cohort, ST2 was significantly associated with a 40.9 m shorter 6-minute walk distance (P = .01), an increased pulmonary vascular resistance index of 3.78 (P < .001) and higher mean pulmonary artery pressure by 8.4 mm Hg (P < .001) compared with NT-proBNP in a similar analysis.

Use of the REVEAL Risk Score Calculator 2.0 was successful in predicting clinical worsening in the cross-sectional cohort (HR = 1.88; 95% CI, 1.2-2.9; P = .003), but including ST2 significantly improved the model (HR = 2.05; 95% CI, 1.3-3.3; P = .003).

Researchers also observed ST2 production and secretion predominately by endothelial cells in cell cultures, compared with smooth muscle cells (P < .0001).

“ST2 and NT-proBNP are clinically useful biomarkers of pediatric PAH and heart failure. NT-proBNP, an excellent marker of cardiac function, is exclusively expressed by the myocardium and responds to increased afterload from the pulmonary vascular bed,” the researchers wrote. “Right ventricular function, reflected by NT-proBNP, is a known determinant of outcomes in PAH but is often evident in later disease, as the ventricle is able to adapt to increased afterload. ST2 seems to add prognostic value in PAH, with a tighter association with key hemodynamic measures of pulmonary vascular disease, and may be a more specific and earlier marker than NT-proBNP.”

According to Griffiths, in the future, it would be important to look at whether inhibition of circulation ST2 can reduce disease severity.

“I would love to use this in a noninvasive prognostic tool to get better risk/outcomes assessment in children,” Griffiths said. “There is also ongoing research into ST2’s role in worsening cardiopulmonary disease with potential for inhibitors.”

For more information:

Megan Griffiths, MD, can be reached at mg4326@cumc.columbia.edu; Twitter: @meg6684.