Influence of growth and metabolic markers on hs-troponin T and NT-proBNP levels in healthy children.

Background and objectives: As part of the LIFE Child study, we previously described the associations between N-terminal-pro-hormone brain natriuretic peptide (NT-proBNP) and hs-troponin T (hs-TnT) levels and an individual's sex, age and pubertal status, as well as with body mass index (BMI) and serum lipid levels. For NT-proBNP, we found inverse associations with advancing puberty, increasing BMI and serum lipid levels. These findings led us to further question the putative influences of the developing individual's metabolic and growth status as represented by levels of insulin-like growth factor-1 (IGF-1) and IGF-1-binding protein-3 (IGF-BP3) as well as hemoglobin A1c (HbA1c) and Cystatin C (CysC). Material and methods: Serum values, medical history and anthropometric data provided by 2522 children aged 0.25-18 years were collected and analyzed as per study protocol. Results: A strong negative association between NT-proBNP values and IGF-1, IGF-BP3 and HbA1c levels was identified. For IGF-BP3, this interaction was modulated by sex and age, for HbA1c only by age. For hs-TnT, a positive association was found with IGF-BP3, IGF-1 and CysC. The association between hs-TnT and IGF-1 was sex dependent. The association between CysC and hs-TnT was stronger in girls, but the interaction with age was only seen in boys. Between hs-TnT and HbA1c, the association was significantly negative and modulated by age. Conclusion: Based on our large pediatric cohort, we could identify age- and sex-dependent interactions between the metabolic status represented by IGF-1, IGF-BP3, CysC and HbA1c levels and the cardiac markers NT-proBNP and hs-TnT.

Age-Dependent Reference Values for hs-Troponin T and NT-proBNP and Determining Factors in a Cohort of Healthy Children (The LIFE Child Study).

This study aimed to provide reliable pediatric reference values for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitive Troponin T (hsTnT) obtained from a population of well children and investigate for associations with sex, pubertal status, body mass index (BMI), and serum lipid levels. We analyzed hsTnT and NT-proBNP values obtained from 4826 samples provided by 2522 children aged 0.25-18 years participating in a prospective longitudinal population-based cohort study, "LIFE child" in Leipzig, Germany (Poulain et al., Eur J Epidemiol 32:145-158, 2017). NT-proBNP values decreased throughout childhood from values over 400 ng/L at 3 months to 138 ng/L in females and 65 ng/L in males by 18 years of age. Values dropped rapidly with advancing pubertal stage. We found a strong association between lower NT-proBNP values and higher BMI or elevated serum lipids, the latter effect being more pronounced in males. For hsTnT levels, approximately half of the measurements were below the detection limit. However, 76% of those aged 3 months and 21% of those aged 6 months had values exceeding the adult cut-off limit. Females had slightly higher levels in the first 2 years of life but this was reversed during puberty. In males, there was an upward trend from pubertal stage 2 onward. We identified a positive association between hsTnT and BMI but a negative association with low-density lipoprotein (LDL) cholesterol and triglyceride levels in boys but not in girls. Based on a large number of healthy children, we have established reliable reference values for NT-proBNP and hsTnT for use in everyday clinical practice. We have also identified important associations between certain metabolic and cardiac markers.Clinical Trial Registration ClinicalTrial.gov (NCT02550236).

Does obesity have an effect on the ECG in children?

This review summarizes current data on influences of childhood obesity on the 12-lead electrocardiogram (ECG). Studies on obese adults showed a higher risk of cardiovascular complications and also, partly pathological, ECG alterations. Data on ECG alterations in obese children is rare. In current studies, no pathological findings were found. All alterations, which mimic the later pathological phenomena in obese adults, were within normal ranges. Studies reported significantly longer P-wave time and P-wave dispersion (Pd) in obese children [Üner A, Dogan M, Epcacan Z, Epçaçan S. The effect of childhood obesity on cardiac functions. J Pediatr Endocr Met 2014;27:261-71.], no correlation of heart rate, P-wave, or QT dispersions (QTd) [Akyüz A, Alpsoy S, Akkoyun DC, Nalbantoǧlu B, Tülübaș F, et al. Effect of overweight on P-wave and QT dispersions in childhood. Turk Kardiyol Dern Ars 2013;41:515-21.], significantly higher QTd in obese children [Yildirim S, Binnetoglu FK, Battal F, Aylanc H, Nazan Kaymaz N, et al. Relation between QT variables and left ventricular geometry in athletes and obese children. Acta Med Port 2016;29:95-100.], no significant association between obesity and QTc interval (QTc), but longer PR intervals, wider QRS duration and left axis shifting of frontal P-wave, QRS and T-wave axes [Sun G, Li Y, Zho X, Guuo X, Zhang X, et al. Association between obesity and ECG variables in children and adolescents: a cross-sectional study. Exp Ther Med 2013;6:1455-62.], significant prolongation of QTc, T peak-to-end, and QTd in the obese children [Paech C, Liebold A, Gebauer RA, Wagner F, Vogel M, et al. Relative QT interval prolongation and electrical inhomogeneity of cardiac repolarization in childhood obesity. Prog Pediatr Cardiol 2017;47:64-7.], slight shift to the left in the QRS axis (with no changes in the P axis), increased amplitudes of the left-sided leads in obese children, and no correlation of the heart rate with the weight [Paech C, Anhalt M, Gebauer RA, Wagner F, Vogel M, et al. New normal limits for pediatric ECG in childhood obesity? Influence of childhood obesity on the ECG. Prog Pediatr Cardiol 2018;48:119-23.]. Altogether, the study results are inconsistent. Clearly, pathological phenomena in the ECG of obese children were not reported: only preliminary stages like QTc prolongation within the norm were found. The pathological alterations seen in adult obese patients are not (yet) seen in childhood. The slight changes reported in childhood obesity are likely to manifest later and to develop into pathological phenomena in obese adults and, therefore, might increase the risk of cardiovascular events like arrhythmia and sudden cardiac death in adulthood.

Symptomatic myocardial bridging: a frequently occurring coronary variation can cause severe myocardial ischaemia in affected children with underlying cardiac conditions.

Myocardial bridging is a congenital coronary artery anomaly in which the coronary artery has a partly "tunnelled" intramyocardial course. This tunnelling leads to compression of the affected vessel segment during ventricular systole. It is considered to be a benign variation of the norm in about 25% of the population caused by an aberrancy of embryologic coronary development. The bridging is also thought to cause severe cardiac conditions in a few of those affected. The series of six young patients presented here is the largest series so far to report on symptomatic myocardial bridging in children with different underlying heart diseases. All patients recently presented to our centre with signs of myocardial ischaemia. They subsequently underwent coronary angiography, which revealed myocardial bridging of the ramus interventricularis anterior. In all patients, therapy with ß blockers was started to reduce heart rate and myocardial contractility. ß Blocker treatment was also given in order to prolong diastole and improve coronary artery blood flow. Two patients underwent surgical exposure of the involved coronary segment: a 2-year-old boy because of recurrent, severe myocardial ischaemia in combination with a reduction of general health, changes in ST-segments, and the presence of a dilative cardiomyopathy; and a 13-year-old girl because of evidence of myocardial ischaemia during exercise testing after surviving sudden cardiac death. Surgery was successful and recovery was complete and uneventful. The presented series shows that myocardial bridging can be symptomatic and may require urgent treatment and even surgical intervention in early childhood in rare cases.