Abstract

Introduction: Conflicting evidence exists as to whether measuring cardiac biomarkers can help identify children at risk of developing anthracycline-mediated cardiomyopathy (ACM). The newest generations of assays can detect minute cardiac perturbations. Hypothesis: We hypothesized that exposure to anthracyclines in children causes an increase in highly- and ultra-sensitive troponin I (hsTnI and usTnI), B-type natriuretic peptide (BNP), and NT pro-BNP levels during therapy. Methods: Cardiac biomarkers were sampled at baseline, early (within 24 hours), and late (3-7 days) after every 100-150 mg/m2 of anthracycline administered, and within 30 days of the end of all chemotherapy. Biomarkers measured include TnI by fourth (“highly-sensitive”) and fifth (“ultra-sensitive”) generation assays, BNP, and NT pro-BNP. Non-parametric testing was performed to determine if peak values of each biomarker vary between anthracycline exposed and non-exposed (control) individuals. Results: Twenty-six patients (54% male, mean age 11.2 ± 6.3 yrs) with a variety of malignancies were enrolled and categorized by target cumulative anthracycline dose: Control (0mg/m 2 ), low dose (<100mg/m 2 ), middle dose (100-299mg/m 2 ), high dose (≤300mg/m 2 ). Mean peak biomarker levels are presented in Table 1. No significant differences were seen in peak values of hsTnI (p=0.51), usTnI (p=0.24), BNP (p=0.07) or NT pro-BNP (p=0.57) between control subjects and those receiving anthracyclines. Conclusions: Next generation cardiac biomarkers did not distinguish anthracycline subjects from controls while on treatment for various malignancies in this small pediatric cohort. Further study is needed to verify this finding in larger numbers of children with an assessment for differences between subgroups with different cumulative anthracycline exposures, and with follow up to determine whether such biomarkers predict long term cardiotoxicity.

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