Serial Measurements of N-Terminal Pro-B-Type Natriuretic Peptide Serum Level for Monitoring Pulmonary Arterial Hypertension in Children

Objective To assess the association between serially measured N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum levels and disease severity in children with pulmonary arterial hypertension (PAH), and to assess its predictive value for death or (heart-)lung transplantation. Study design This was a longitudinal cohort study of the Dutch National Network for Pediatric Pulmonary Hypertension conducted between 2003 and 2017. Data on NT-proBNP and disease severity markers (World Health Organization Functional Class [WHO-FC], 6-minute walking distance [6MWD], and tricuspid annular plane systolic excursion [TAPSE]) were collected every 3 to 6 months from 82 children with PAH. The outcome measure was death or (heart-)lung transplantation. Also, NT-proBNP levels over time were compared between survivors and nonsurvivors. Results The median patient age was 8.8 years (IQR, 4.6-13.5 years), and 61% were female. The median duration of follow-up was 4.8 years (IQR, 1.9-10.0 years). At all times during the course of disease, higher NT-proBNP levels were associated with higher WHO-FC (β = 0.526; 95% CI, 0.451-0.600), lower 6MWD z-score (β = −0.587; 95% CI, −0.828 to −0.346), lower TAPSE z-score (β = −0.783; 95% CI, −1.016 to −0.549), and elevated risk of death or (heart-)lung transplantation (hazard ratio 16.61; 95% CI, 7.81-35.33). Compared with survivors, nonsurvivors had NT-proBNP levels that were higher at first measurement and increased exponentially over time (P = .005). Changes in NT-proBNP serum level over time were predictive of outcome. Conclusions Throughout the disease course of pediatric PAH, serial measurements of NT-proBNP are associated with disease severity and transplant-free survival. Monitoring NT-proBNP levels over time provides important prognostic information that can support clinical decision making in combination with other established prognostic markers.