Serial measurements of serum NT-proBNP as markers of left ventricular systolic function and remodeling in children with heart failure

Background: Increasing serum levels of N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) are associated with worsening heart failure (HF) in adults. We determined whether changes in NT-proBNP level are associated with changes in symptoms and left ventricular (LV) systolic function and remodeling in children with HF secondary to dilated cardiomyopathy. Methods: We retrospectively examined associations between serum NT-proBNP levels and NYHA/Ross functional class, LV systolic and diastolic diameter (LVSD-z and LVDD-z), LV ejection fraction (LVEF), and LV shortening fraction (LVSF-z) using generalized linear mixed models. Fluctuation in functional class of subjects was also modeled using logistic regression and receiver operating characteristic (ROC) curves. Results: In 36 children (14 males), a 10-fold increase in NT-proBNP serum levels was associated (P < .001) with a 9.8% decrease in LVEF, a 3.25-unit drop in LVSF-z, a 1.53-unit increase in LVDD-z, a 2.64-unit increase in LVSD-z, and an increased odds of being in functional class III/IV (OR 85.5; 95% CI, 10.9 to 671.0). An NT-proBNP level greater than 1000 pg/mL identified children constantly or intermittently in functional class III-IV with 95% sensitivity and 80% specificity. The reliability of a single NT-proBNP value was 0.61, but the means for two and three NT-proBNP values were 0.76 and 0.82, respectively. Conclusions: In children with HF, NT-proBNP is associated with cardiac symptoms and indices of LV systolic dysfunction and remodeling. NT-proBNP >1000 pg/mL identifies highly symptomatic children. Within subject serial measurements of NT-proBNP are needed for a reliable and accurate determination of disease status and/or course.