Circulating High Mobility Group Box-1 Does Not Predict Pulmonary Arterial Hypertension in Children with Congenital Heart Disease: A Prospective Cohort Study

Abstract

Objectives: Pulmonary arterial hypertension (PAH) is a devastating complication of pediatric congenital heart disease (CHD). A recent study has identified the protein high mobility group box-1 (HMGB1) as a diagnostic tool in adults with CHD-associated PAH. HMGB1 levels in adults with CHD-associated PAH correlated with mean pulmonary artery pressure and pulmonary vascular resistance, and HGMB1 levels fell in response to sildenafil therapy. We wanted to assess if HGMB1 was a biomarker of pediatric CHD-PAH.

Design: Prospective cohort study.

Setting: Quaternary pediatric academic hospital PARTICIPANTS: Children ≤18 years with CHD with and without known pulmonary hypertension. Controls were children undergoing dental or urologic surgery with no known heart disease.

Interventions: Pulmonary hemodynamics, echocardiographic assessment, and biomarker measurement. Controls had biomarker measurement only.

Measurements and main results: Patients with CHD-PAH had mean pulmonary vascular resistance index of 10 Wood units/m². Neither HGMB1 nor N-terminal pro-brain-type natriuretic peptide levels were significantly different between the groups. Neither marker correlated with pulmonary hypertension.

Conclusions: Unlike in adults, HGMB1 is not a biomarker of PAH in pediatric CHD. Further work will continue to explore for biomarkers for this high-risk population.

Keywords: HMGB1 protein; biomarkers; cardiac catheterization; child; heart defects, congenital; hemodynamics; humans; pulmonary arterial hypertension.