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Childhood cancer survivors are at high risk of developing congestive heart failure (CHF) compared with the general population, and there is a dose-dependent increase in CHF risk by anthracycline dose. The mechanism by which this occurs has not been fully elucidated. Metabolomics, the comprehensive profile of small-molecule metabolites, has the potential to provide insight into the pathogenesis of disease states and discover diagnostic markers for therapeutic targets. We performed echocardiographic testing and blood plasma metabolomic analyses (8 pathways; 354 metabolites) in 150 asymptomatic childhood cancer survivors previously treated with anthracyclines. Median time from cancer diagnosis to study participation was 12.4 years (2.6–37.9 years); 64% were treated for a hematologic malignancy; median anthracycline dose was 350 mg/m2 (25–642 mg/m2). Thirty-five (23%) participants had cardiac dysfunction—defined as left ventricular end-systolic wall stress >2SD by echocardiogram. Plasma levels of 15 compounds in three metabolic pathways (carbohydrate, amino acid, and lipid metabolism) were significantly different between individuals with cardiac dysfunction and those with normal systolic function. After adjusting for multiple comparisons, individuals with cardiac dysfunction had significantly lower plasma carnitine levels [relative ratio (RR), 0.89; P < 0.01] in relation to those with normal systolic function. These findings may facilitate the development of primary prevention (treatment of carnitine deficiency before/during anthracycline administration) and secondary prevention strategies (screening and treatment in long-term survivors) in patients at highest risk for CHF. Cancer Epidemiol Biomarkers Prev; 23(6); 1109–14. ©2014 AACR.

XLSX file - 51KB, List of final set of 354 named biochemicals included in the metabolomic analyses.

PDF file - 98KB, Supplementary Figure 1: Visualization of Data Normalization. Supplementary Table 1: Description of Metabolon QC Samples. Supplementary Table 2: Metabolon QC Standards.

Background: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth. Methods: We retrospectively collected data on patients Results: We report on 139 adolescents and young adults with 140 episodes of suspected myocarditis (49 confirmed, 91 probable) at 26 centers. Most patients were male (n=126, 90.6%) and White (n=92, 66.2%); 29 (20.9%) were Hispanic; and the median age was 15.8 years (range, 12.1–20.3; interquartile range [IQR], 14.5–17.0). Suspected myocarditis occurred in 136 patients (97.8%) after the mRNA vaccine, with 131 (94.2%) after the Pfizer-BioNTech vaccine; 128 (91.4%) occurred after the second dose. Symptoms started at a median of 2 days (range, 0–22; IQR, 1–3) after vaccination. The most common symptom was chest pain (99.3%). Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%), or no anti-inflammatory therapies (8.6%). Twenty-six patients (18.7%) were in the intensive care unit, 2 were treated with inotropic/vasoactive support, and none required extracorporeal membrane oxygenation or died. Median hospital stay was 2 days (range, 0–10; IQR, 2–3). All patients had elevated troponin I (n=111, 8.12 ng/mL; IQR, 3.50–15.90) or T (n=28, 0.61 ng/mL; IQR, 0.25–1.30); 69.8% had abnormal ECGs and arrhythmias (7 with nonsustained ventricular tachycardia); and 18.7% had left ventricular ejection fraction Conclusions: Most cases of suspected COVID-19 vaccine myocarditis occurring in persons