Clinical and prognostic value of endothelin-1 and big endothelin-1 expression in children with pulmonary hypertension

Objective Pulmonary arterial hypertension is known to be associated with increased expression of endothelin (ET)-1 and its precursor big ET-1. Therefore, we hypothesised that in children with pulmonary hypertension (PH) altered levels of ET-1 and big ET-1 may have clinical and prognostic impact. Methods Sixty-six children with different forms of PH (mean age 10.4 +/- 9.7 years) were included. Blood samples were taken from the pulmonary artery and a systemic artery. Levels of ET-1/big ET-1 were measured via ELISA method and compared with clinical and haemodynamic data. To assess prognostic relevance, Kaplan-Meier survival analysis was conducted with definition of end point as the composite of mortality, lung transplantation, use of intravenous prostanoids and Potts shunt creation. Results ET-1 levels ranged between 0.09 and 11.64 (mean 1.48 +/- 2.34) fmol/mL, and big ET-1 levels between 0.05 and 2.92 (mean 0.84 +/- 0.58) fmol/mL. No significant relationships were found between ET-1/big ET-1 levels and functional class as well as haemodynamic indices of PH severity. Mean follow-up after catheterisation was 63.2 +/- 44.1 months. While 31 of the 66 (47%) patients with PH reached a predefined end point, there was no significant relation between levels of ET-1/big ET-1 and patient outcome. Conclusions Although children with PH had alterations in ET-1/big ET-1 expression, which may reflect changes in net release or lung clearance, levels of ET-1/big ET-1 showed no correlation with clinical and haemodynamic parameters, and were not able to predict outcome.