Plasma HGF and OPN as Potential Biomarkers of Pulmonary Arterial Hypertension in Congenital Heart Disease

Objectives: Pulmonary arterial hypertension in congenital heart disease (PAH-CHD) is the most common type of PAH and increases morbidity and mortality in patients with CHD. Right heart catheterization (RHC) is the standard method to diagnose PAH. However, RHC is an invasive and complicated method with relatively high cost. Noninvasive, feasible, and cost-efficient methods are urgently needed. The objective of this study was to evaluate three potential biomarkers of PAH-CHD: Hepatocyte growth factor (HGF), osteopontin (OPN), and suppression of tumorigenicity 2 (ST2). Methods: Plasma samples were collected from patients with CHD (n = 46) and healthy individuals (n = 22) and divided into four groups according to the severity of PAH. The levels of HGF, OPN, and ST2 were then analyzed using an enzyme-linked immunosorbent assay. Correlations between HGF, OPN, ST2, and clinical parameters of PAH-CHD were analyzed. Results: The plasma HGF levels in the moderate to the severe group were significantly higher than those in the mild group, nonPAH group, and healthy control group (p < 0.05). Derived from a receiver operating characteristic (ROC) curve analysis, a cut-off value of 356.75 ng/ml for the HGF concentration was able to predict PAH-CHD with 53% sensitivity and 89% specificity. The HGF level was positively related to pulmonary arterial systolic pressure (PASP) (r = 0.36, p < 0.05) and pulmonary vascular resistance (PVR) (r = 0.36, p < 0.05). Plasma OPN levels in the mild group were significantly higher than other groups and positively correlated with the pulmonary-systemic shunt ratio (Qp/Qs) (r = 0.33, p < 0.05). There was no statistically significant between-group difference in plasma soluble ST2 (sST2) levels. Conclusion: The plasma HGF level was elevated in PAH-CHD patients and can be used as a potential biomarker. The plasma OPN level was positively correlated with the Qp/Qs.