Serum sST2 and MR-ProADM in pediatric acute rheumatic fever: association with cardiac involvement and clinical risk stratification.
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BACKGROUND: Acute rheumatic fever (ARF) remains a major cause of acquired heart disease in children, particularly in low- and middle-income countries. Cardiac involvement is the main determinant of long-term morbidity and mortality; however, early evaluation relies heavily on echocardiography, which may not always be readily accessible. Therefore, there is a need for adjunctive biomarkers to support clinical assessment and risk stratification. METHODS: This case-control study included 38 pediatric patients diagnosed with ARF and 38 age- and sex-matched healthy controls. Serum levels of soluble suppression of tumorigenicity-2 (sST2) and mid-regional pro-adrenomedullin (MR-ProADM) were measured using enzyme-linked immunosorbent assay. Cardiac involvement was assessed by echocardiography and further categorized as mild or no involvement vs. moderate-to-severe involvement. Nonparametric tests, receiver operating characteristic (ROC) analysis, and multivariate logistic regression were performed. RESULTS: Both sST2 and MR-ProADM levels were significantly higher in patients with ARF compared to controls (p < 0.001 and p = 0.046, respectively). sST2 demonstrated good discriminative performance for distinguishing ARF from controls (AUC: 0.81), whereas MR-ProADM showed moderate performance (AUC: 0.67). When evaluating clinically relevant cardiac involvement, both biomarkers showed acceptable discriminative ability (AUC: 0.732 for sST2 and 0.707 for MR-ProADM). In multivariate analysis, sST2 was independently associated with moderate-to-severe cardiac involvement (OR: 1.02, 95% CI: 1.002-1.042, p = 0.033), while MR-ProADM showed a borderline association. CONCLUSION: sST2 and MR-ProADM are elevated in pediatric ARF and reflect systemic inflammatory and cardiovascular processes. While they are not substitutes for echocardiographic evaluation, sST2 in particular may provide additional information in identifying patients with more clinically significant cardiac involvement. These biomarkers may serve as supportive tools for clinical assessment and early risk stratification, especially in resource-limited settings.