Key result
Serum sST2, galectin-3, and copeptin fail to identify pediatric myocarditis among chest pain presentations.
Why the study?
This study evaluated whether the apparent diagnostic discrimination of sST2, galectin-3, and copeptin for clinically suspected myocarditis/myopericarditis in children with chest pain depended on comparator selection.
Does serum sST2, galectin-3, and copeptin testing discriminate clinically suspected myocarditis/myopericarditis from noncardiac chest pain in children aged 6–17 years presenting with nontraumatic chest pain?
Cohort (n=88)
Blinded clinicians and adjudicators to research biomarker results
No
Does serum sST2, galectin-3, and copeptin testing discriminate clinically suspected myocarditis/myopericarditis from noncardiac chest pain in children aged 6–17 years presenting with nontraumatic chest pain?
Serum sST2, galectin-3, and copeptin failed to discriminate clinically suspected myocarditis/myopericarditis from noncardiac chest pain in children, demonstrating that high diagnostic accuracy observed when using healthy controls reflects spectrum bias rather than true clinical utility.
Biomarkers should not discriminate myocarditis from noncardiac chest pain in children; leaves open utility versus healthy controls or other contexts.
Purpose To determine whether the apparent discrimination of soluble suppression of tumorigenicity 2 (sST2), galectin-3, and copeptin in children with chest pain depended on comparator selection. The primary comparison was clinically suspected myocarditis/myopericarditis versus noncardiac chest pain within the symptomatic cohort; the patient-control comparison was secondary. Methods This prospective, single-center exploratory cohort included 66 children aged 6–17 years with nontraumatic chest pain, enrolled sequentially on predefined sampling days, and 22 contemporaneous clinically well controls. Research biomarker results were unavailable to clinicians and adjudicators. Directional areas under the receiver operating characteristic curve (AUCs) with outcome-stratified bootstrap 95% confidence intervals (CIs; 2,000 resamples) were estimated without cutoff optimization or formal between-contrast AUC testing. Results Seven symptomatic participants (10.6%) were classified as having clinically suspected myocarditis/myopericarditis and 59 as having noncardiac chest pain. In the primary comparison, AUCs were 0.47 (95% CI, 0.25–0.70) for sST2, 0.39 (0.20–0.61) for galectin-3, and 0.38 (0.18–0.60) for copeptin. In the secondary patient-control comparison, the corresponding AUCs were 0.98 (0.95–1.00), 0.98 (0.95–1.00), and 0.99 (0.97–1.00). Conclusion The biomarkers provided no evidence of clinically useful within-symptom discrimination in this small cohort. Near-perfect patient-control separation reflected comparator dependence and cannot be interpreted as diagnostic or triage accuracy for myocarditis. Clinical trial registration Not applicable this was a noninterventional observational study.
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Sahin et al. (2026) conducted a cohort in Pediatric nontraumatic chest pain and clinically suspected myocarditis/myopericarditis (n=88). Serum sST2, galectin-3, and copeptin concentrations vs. Noncardiac chest pain (primary) and clinically well controls (secondary) was evaluated on Within-symptom diagnostic discrimination (directional AUC) of sST2 for clinically suspected myocarditis/myopericarditis versus noncardiac chest pain (AUC 0.47 for sST2 (0.39 for galectin-3; 0.38 for copeptin), 95% CI 0.25-0.70, p=0.82). Serum sST2 (AUC 0.47), galectin-3 (AUC 0.39), and copeptin (AUC 0.38) failed to discriminate suspected myocarditis/myopericarditis from noncardiac chest pain in children.
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