Appropriate parameters are needed for the monitoring of children with pulmonary arterial hypertension (PAH). Various biologic markers seem to be of use in adults with PAH. No data are available on their value in children with PAH. In this study, the relation between serum markers, functional parameters, and hemodynamic variables in pediatric PAH and their ability to predict survival is determined. Serum N-terminal pro brain natriuretic peptide (NT-proBNP), uric acid, norepinephrine, and epinephrine were measured and correlated with invasive hemodynamics, functional parameters, and outcome in 29 pediatric patients with PAH who visited a tertiary reference center for pediatric PAH between 1997 and 2005. NT-proBNP correlated with functional class (R ϭ 0.36; p ϭ 0.03) and 6-min walking distance (6MWD) (R ϭ Ϫ0.53; p Ͻ 0.001). Uric acid correlated with mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac index (R ϭ 0.63, p ϭ 0.01; R ϭ 0.71, p ϭ 0.03, and R ϭ Ϫ0.65, p ϭ 0.007, respectively). After initiation of treatment, NT-proBNP decreased. This decrease correlated with an increased 6MWD. Finally, norepinephrine and NT-proBNP levels were highly predictive for mortality. In this series of children with PAH, biologic markers were correlated with hemodynamics and functional capacity, as parameters of disease severity. The data indicate that these markers can be used to monitor treatment effects and predict mortality in pediatric PAH. (Pediatr Res 63: 321-327, 2008) P ulmonary arterial hypertension (PAH) is a chronic, progressive, and usually fatal disease. It is characterized by proliferation of pulmonary vascular cells and obliteration of small pulmonary arteries, leading to increased pulmonary vascular resistance and eventually right heart failure and death. PAH may present at any age, from infancy into high age. In the last decade, new pharmacological therapies have been developed that improve hemodynamics, exercise capacity, and survival in these patients. For optimal clinical decision-making, it has become of growing importance to accurately assess disease severity, effectiveness of therapy, and prognosis in the individual patient with PAH.Several correlates of disease severity and survival have been described in adults with PAH. Hemodynamic and functional capacity parameters are currently the cornerstones in characterizing disease progression. Invasively obtainable hemodynamic parameters have been shown to represent disease severity and to predict survival (1). Noninvasive parameters for functional capacity are used for the assessment of clinical condition, severity of disease, and effectiveness of therapy. Six-min walking distance (6MWD) has been shown to correlate well with World Health Organization (WHO) functional class, and also with hemodynamic parameters (2). Further, maximal cardiopulmonary exercise testing can be safely performed in these patients using specific guidelines, and is used with increasing frequency (3).In pediatric patients with PAH, the use of these paramete...

Chronic increased pulmonary blood flow is considered a pre-requisite for the induction of advanced vascular lesions in pulmonary arterial hypertension in congenital heart defects. The aim of the present study was to characterise the effects of increased pulmonary flow induced by an aortocaval shunt in the monocrotaline rat model for pulmonary hypertension in terms of survival, haemodynamics, pathology and histology.Male Wistar rats were injected with monocrotaline followed by the creation of an abdominal aortocaval shunt. Animals were sacrificed when displaying symptoms of weight loss or dyspnoea, 4-5 weeks after the creation of the shunt.Echocardiography identified increased ventricular dimensions in shunted rats and right ventricular hypertrophy in monocrotaline-treated rats. At similar pulmonary artery pressures, shunted monocrotaline rats displayed higher morbidity and mortality, increased pulmonary-tosystemic artery pressure ratios and increased right ventricular hypertrophy compared with nonshunted monocrotaline rats. Histological assessment demonstrated increased number and diameter of pre-acinar pulmonary arteries. Intra-acinar vessel remodelling and occlusion occurred to a similar extent in shunted and nonshunted monocrotaline rats.In conclusion, increased pulmonary blood flow in monocrotaline-induced pulmonary hypertension is associated with increased morbidity, mortality, and unfavourable haemodynamic and cardiac effects. These effects could be attributed to more pronounced right heart failure rather than to altered intra-acinar pulmonary vessel remodelling. KEYWORDS: Animal model, congenital heart disease, plexogenic arteriopathy, pulmonary arterial hypertension, pulmonary vascular histopathology, right heart failure P atients with congenital heart disease associated with systemic-to-pulmonary shunts, increasing both pulmonary blood flow and pressure, develop characteristic pulmonary vascular lesions as concentric-laminar intimal fibrosis and plexiform lesions. These vascular lesions are characterised by vascular smooth muscle and endothelial cell proliferation. In contrast, in patients with congenital heart defects and isolated increased pulmonary artery pressure (PAP), these lesions almost never develop [1,2]. The current authors hypothesise that, in congenital heart defects, increased pulmonary blood flow, in addition to increased pressure, is a pre-requisite for the development of the hallmark lesions of advanced pulmonary arterial hypertension.Animal models with an isolated increase in PAP, e.g. induced by the toxic alkaloid monocrotaline, show pulmonary vascular remodelling, but fail to display the more advanced lesions as described previously [3-5].The role of increased pulmonary blood flow has been explored in animal models [6]. In rat models with isolated increased flow [7,8], a moderate increase in pulmonary pressure and medial hypertrophy has been observed, but only after a prolonged period of exposure.When the additional effect of flow was explored in existing rat models for pul...

Pulmonary hypertension associated with congenital systemic-to-pulmonary shunts has been classified, in the Evian-Venice classification, as Pulmonary Arterial Hypertension, which includes a heterogeneous group of conditions. Emerging options for treatment of patients with pulmonary arterial hypertension are related to those with the idiopathic form of the disease, but may also improve quality of life and survival in patients with pulmonary arterial hypertension associated with congenital cardiac disease. Despite the evident similarities in pulmonary vascular disease, it is important also to recognise the differences between patients in whom pulmonary arterial hypertension is the consequence of systemic-to-pulmonary shunts as opposed to those with other conditions. Patients with pulmonary hypertension associated with congenital cardiac disease themselves constitute a heterogeneous population, in which generalisation may be hazardous. Specific considerations need to be given to the type of cardiac diagnosis, the prognosis and evolution of pulmonary vascular disease, and the circulatory physiology before embarking on new strategies for medical treatment in the individual patient. In this review, we highlight the features that require specific attention in these patients. In addition, we discuss briefly the data currently available on the effectiveness of the new anti-proliferative drugs in patients with the Eisenmenger syndrome.