Biological Serum Markers in the Management of Pediatric Pulmonary Arterial Hypertension

Abstract

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...

Paediatric pulmonary hypertension: monitoring progress and identifying unmet needs

“…A Dutch study also investigated the prognostic utility of Nterminal pro-BNP (NT-proBNP) in 29 children with PAH [48]. Higher NT-proBNP levels were associated with higher WHO functional class (r50.34, p50.04) and increased mortality rates (Chi-squared59.93, p50.002).…”

What Levels of Uric Acid and NT-Probnp Predict Outcomes of Eisenmenger Syndrome in Children?

“…Serum uric acid levels were also correlated with right atrial pressure, NYHA functional class, six-minute walk test, cardiac index, cardiac output, and survival (24,25). Van Albada et al (11) found the strongest correlations between serum uric acid and mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac index. In our study, no correlation was shown between uric acid level and NYHA functional class or six-minute walk test (Table 3).…”

“…Also, it is not feasible and is less validated in young children (9,10). Certain biomarkers, such as BNP, serum creatinine, and uric acid, have been used in PHT (11,12). The most important feature of this study and its main difference from other studies is that it uses the largest Eisenmenger pediatric population to date to investigate the roles of NT-proBNP and uric acid in comparison with hemodynamic data (noninvasive and invasive) in children.…”

N-terminal-pro brain natriuretic peptide levels in children with allergic rhinitis

“…Although studies are lacking in children, data indicate that NT-proBNP can be used to monitor treatment effects and predict mortality in pediatric PAH (20). A study by Oran et al (18) found that increased PAP and serum prohormone concentrations were reversible after surgery in 20 children with adenotonsillar hypertrophy.…”