Multimodal evidence chain of iron overload, inflammation, and dysfunction: an integrated predictive model of early cardiac injury in pediatric transfusion-dependent β-thalassemia.
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INTRODUCTION: Despite standardized transfusion and chelation therapy, children with transfusion-dependent β-thalassemia (TDT) remain at high risk for cardiac dysfunction due to iron overload. Conventional ejection fraction assessment lacks sensitivity for early injury. This study evaluated multimodal indicators to develop a robust early-warning model. METHODS: A prospective cohort of 128 TDT children (3-16 years) underwent cardiac magnetic resonance (CMR) T2* imaging, echocardiography with global longitudinal strain (GLS), and measurement of circulating biomarkers including high-sensitivity cardiac troponin I (hs-cTnI), B-type natriuretic peptide (BNP), interleukin-6, and tumor necrosis factor-α. Children were classified into dysfunction and normal groups based on LVEF and GLS. Logistic regression identified predictors, and ROC analysis validated the integrated model. RESULTS: The dysfunction group demonstrated reduced GLS, ventricular remodeling, elevated hs-cTnI and BNP, and significantly shorter T2* values compared with controls (p < 0.001). Inflammatory cytokines were also upregulated. Multivariate analysis identified hs-cTnI, BNP, and T2* as independent predictors. The combined three-factor model achieved excellent discrimination (AUC 0.914), outperforming single markers, with preserved calibration following bootstrap validation. CONCLUSION: By linking iron overload, myocardial injury, inflammation, and structural dysfunction, this study proposes a clinically feasible integrated model for early cardiac risk detection in pediatric TDT. The approach supports precision monitoring and prevention of heart failure.