Use of cardiac biomarkers in neonatology

In cardiology, B-type natriuretic peptide and the amino terminal segment of its prohormone (NT-proBNP) are important biomarkers. The importance of these peptides as markers for heart disease in pediatric cardiology is reviewed. The peptide levels are dependent on age, assay, and possibly gender. The normal value range and upper limits for infants and children are needed. To determine reference values, data were combined from four studies that measured NT-proBNP levels in normal infants and children using the same electrochemiluminescence assay. The age intervals for the upper limits of normal were chosen for intervals in which no age-dependent change was observed. Statistical analysis was performed on log-transformed data. A total of 690 subjects (47% males) ages birth to 18 years were included in the review. The levels of NT-proBNP were highest in the first days of life, then showed a marked decline in the first week or weeks. The peptide levels continued to decline gradually with age (r = 0.43; p < 0.001). Male and female levels differed only for children ages 10 to 14 years. However, the upper limit of normal did not differ between the boys and girls in any age group. The findings lead to the conclusion that B-type natriuretic peptide (BNP) and NT-proBNP are important markers for heart disease in pediatric cardiology. The levels of NT-proBNP are highest in the first days of life and decrease drastically thereafter. A mild gradual decline occurs with age throughout childhood. Girls have somewhat higher levels of NT-proBNP during puberty.

Right ventricular failure is a leading cause of death in patients with chronic pulmonary hypertension (PH). We checked whether detection of cardiac troponin T (cTnT), a specific marker of myocyte injury, could be useful in prognostic stratification of those patients. Initial evaluation of 56 clinically stable patients (age 41+/-15 years) with pulmonary arterial (51 patients) or inoperable chronic thromboembolic (5 patients) PH (mean pulmonary arterial pressure 60+/-18 mm Hg) included cTnT test, allowing detection of its serum levels > or =0.01 ng/mL [cTnT(+)]. cTnT was detectable in 8 of 56 (14%) patients (mean+/-SD, 0.034+/-0.022; range, 0.010 to 0.077 ng/mL). Despite similar pulmonary hemodynamics, they had higher heart rate (92+/-15 versus 76+/-14 bpm, P=0.004), lower mixed venous oxygen saturation (50+/-10% versus 57+/-9%, P=0.04), and higher serum N-terminal pro-B-type natriuretic peptide (4528+/-3170 versus 2054+/-2168 pg/mL, P=0.03) and walked less during the 6-minute walk test (298+/-132 versus 396+/-101 m, P=0.02). Cumulative survival estimated by Kaplan-Meier curves was significantly worse at 24 months in cTnT(+) compared with cTnT(-) (29% versus 81%, respectively, log-rank test P=0.001). Multivariate analysis revealed cTnT status (hazard ratio, 4.89; 95% CI, 1.18 to 20.29; P=0.03), 6-minute walk test (hazard ratio, 0.93 for each 10 m; P=0.01), and pulmonary vascular resistance (hazard ratio, 1.13; P=0.01) as independent markers of mortality. All 3 cTnT(+) patients who survived the follow-up period converted to cTnT(-) during treatment. Detectable cTnT is a so-far ignored independent marker of increased mortality risk in patients with chronic precapillary PH, supporting the role of progressive myocyte injury in the vicious circle leading to hemodynamic destabilization.