Evaluation of endothelin-1 and Von Willebrand factor as biomarkers of pulmonary hypertension in children with congenital heart disease

ABSTRACT

This study was done to delineate the role of endothelin-1 [ET-1] and von willebrand factor [vWF] in the pathophysiology of pulmonary hypertension [PHT] secondary to congenital heart disease. Forty-three children [29 males, 14 females] with cyanotic and acyanotic congenital heart diseases were enrolled in this study. Their age ranged between 4 months 5.10 year. Plasma ET-1 levels and vWFAg activity were assayed by enzyme linked immunosorbent assay. Enrolled children were divided into three groups according to pulmonary artery pressure [PAP]. Group 1 with normal PAP [children with mild PHT [PAP 31-49 mmHg] [n=14]; group III with moderate or severe PHT [PAP >/= 50mmHg] [n=14]. Twelve perfectly matched healthy children were enrolled as a control group. The results of the present study showed that plasma ET-1 levels in group I were significantly higher than that in control group [P<0.001], on the other hand no significant differences were noted in vWF Ag% in both groups. Plasma endothelin-1 and vWFAg were significantly elevatd in all groups with PHT Vs controls [P<0.001 and P<0.001]. Plasma endothelin-1 and vWF Ag% were significantly elevated in group III Vs both group II and I [P<0.001]. plasma endothelin-1 and vWFAg% were significantly elevated in group II Vs group I [P<0.001 and P<0.001]. Plasma ET-1 levels and vWFAg% positively correlated with pulmonary artery pressure in group II and III [P<0.001 and P0.001]. Elevated ET-1 and vWF may contribute directly to development of pulmonary hypertension in children with congenital heart diseases. ET-1 and vWF estimation could be used as non-invasive early markers of pulmonary hypertension in such children, particularly in post-operative evaluation. Our data are in keeping with evidence of significant coagulation abnormalities in pulmonary hypertension and the need for chronic anticoagulant therapy may increase survival in children with pH. These facts opened the door for exploring therapeutic anti-ET-1 and anti- vWF agents in the treatment of pulmonary hypertension in children