Anne-Marie Koop

8 283 INTRODUCTION Over the past decades, survival of children with congenital heart disease (CHD) and pulmonary hypertension (PH) has improved markedly due to advances in treatment strategies. This increased survival has led to an expanding population of children and grown-up patients with congenital heart disease (GUCH). 1,2 However, in many patients residual lesions are present, which lead to deterioration of cardiac and physical function over time. Overload of the right ventricle (RV), either primary or residual, leading to chronic cardiac adaptation, is an important determinant in the development of RV failure in patients with CHD and PH. RV adaptation to abnormal loading includes cardiac remodelling processes, such as hypertrophy, inflammation and fibrosis, that precede deterioration of ventricular function. 1,3 Identifying abnormal load and consequent remodelling processes in early stages of the disease could optimize timing of (re-)interventions aimed at preservation of cardiac function. In acquired left ventricular (LV) disease, blood-derived biomarkers have shown to be of value in clinical practice. 4–6 Ventricular adaptation and remodelling is a process of injury and repair, which includes myocardial stretch and injury, inflammation, metabolic changes and connective tissue deposition. These processes are accompanied by elevated plasma levels of compounds from the various involved pathways. 6–9 Biomarkers as N-Terminal pro-B-Type natriuretic peptide (NT- proBNP), midregional proadrenomedullin (MR-proADM) and neprilysin are known to be released in abnormal loading conditions and to address activation of renin angiotensin-aldosterone system (RAAS). Increases in NT-proBNP will stimulate natriuresis, diuresis andvasodilation, andMR-proADMhas natriuretic andvasodilatory effects in response to activation of the sympathetic nervous system. 10 Serum levels of galectin-3, growth differentiation factor-15 (GDF-15) and myeloperoxidase (MPO) have been suggested to reflect ventricular remodelling characterized by oxidative stress, inflammation and fibrosis. 11–16 Endothelin-1 (ET-1) is a vasoconstrictive and inotropic agent with alsomitogenic abilities, released both intra- and extracardiacally, initially serving cardiovascular adaptation. 17 Troponin T, a myofilament, is released to the bloodstream when cardiomyocyte injury and decay occurs. These biomarkers are likely to be of value, not only in patients with LV-diseases, but also in those with a stressed RV. To date, however, these biomarkers have been insufficiently studied in adaptive processes of the RV in children with CHD or PH. 18–24 In this study a multi-biomarker approach was chosen for the characterization of RV adaptation and remodelling in response to abnormal loading in children with various congenital heart defects or PH. A selected set of plasma biomarkers was used related to various pathophysiological processes involved in cardiac adaptation and remodelling. We investigated the biomarkers profiles in children with different types and degree of RV overload in relation to echocardiographic RV function