• George Giannakoulas, Sophia-Anastasia Mouratoglou, Michael A Gatzoulis, and Haralambos Karvounis.
• First Cardiology Department, AHEPA Hospital, Aristotle University of Thessaloniki, St. Kyriakidi 1, 54636, Thessaloniki, Greece; Royal Brompton Biomedical Research Unit NIHR, National Heart and Lung Institute, Imperial College, London, United Kingdom. Electronic address: giannak@med.auth.gr.
• Int. J. Cardiol. 2014 Jul 1;174(3):618-23.

BackgroundThe development of pulmonary arterial hypertension (PAH) in patients with congenital heart disease (CHD) is multifactorial with a number of biomarkers serving as mediators of neurohormonal activation [B-type natriuretic peptide (BNP) and its N-terminal-pro-fragment (NT-proBNP)], endothelial dysfunction [asymmetric dimethylarginine (ADMA)] and cellular proliferation [vascular endothelial growth factor (VEGF)].MethodsWe systematically reviewed the literature for trials studying the role of these biomarkers in the clinical evaluation, prognosis and management of patients with PAH related to CHD (CHD-PAH).ResultsTwenty-six studies were included in the systematic review, involving a total of 1113 patients with CHD-PAH. These patients had higher BNP, NT-proBNP and ADMA levels and higher VEGF expression when compared with healthy controls. Baseline and serial values of plasma levels of natriuretic peptides were shown to be significant predictors of survival. ADMA concentration was elevated in patients with CHD-PAH when compared with patients with simple CHD without PAH, whereas VEGF expression was particularly high in patients with CHD and persistent PAH after corrective surgery of the underlying heart disease.ConclusionRight heart dysfunction, endothelial inflammation and proliferation are mirrored by plasma levels of the corresponding biomarkers among patients with CHD-PAH. There is early evidence to suggest that natriuretic peptides, in particular, may be a simple and effective tool for determining prognosis and timing for therapeutic interventions in patients with CHD-PAH.Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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