Plasma Growth Differentiation Factor-15 is a Potential Biomarker for Pediatric Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

We aimed to investigate plasma growth differentiation factor-15 (GDF-15) levels in pediatric pulmonary arterial hypertension secondary to congenital heart disease (PAH-CHD), and assess the association with hemodynamic parameters. Plasma GDF-15 levels were measured in children with PAH-CHD (n = 46) and compared to children with CHD without PAH (n = 39). Normal individuals (n = 30) served as health control group. Plasma GDF-15 levels were significantly elevated in patients with PAH-CHD compared with those with CHD without PAH (median 1415 ng/L, interquartile range [IQR] 926.7-2111.7 ng/L vs. 890.6 ng/L, IQR 394.7-1094.3 ng/L, p < 0.01). Elevated plasma GDF-15 levels were positively related to Functional Class, uric acid, N-terminal pro-B-type natriuretic peptide (NT-proBNP), pulmonary artery systolic pressure, mean pulmonary artery pressure, pulmonary blood flow/systemic blood flow and pulmonary vascular resistance, and a lower mixed venous oxygen saturation (Sv(o2)). The area under the curve (AUC) for adding GDF-15 to NT-proBNP was not superior to the AUC of NT-pro BNP alone (AUC difference 0.0295, p = 0.324) (NT-proBNP, AUC 0.823, 95% CI 0.725-0.897; GDF-15 plus NT-proBNP, AUC 0.852, 95% CI 0.759-0.92), whereas it revealed a slightly greater specificity and positive predictive value. The diagnostic power of NT-pro BNP was not inferior to GDF-15 (AUC difference 0.0443, p = 0.43). Plasma GDF-15 levels might be a surrogate marker for pediatric PAH-CHD.