Long-term Subclinical Cardiotoxicity of Modern Cardiotoxic Treatment Protocols in Childhood Cancer Survivors Assessed by Cardiovascular Magnetic Resonance T1 Mapping and Circulatory Biomarkers

Childhood cancer survivors (CCS) are at increased risk of developing heart disease due to the cardiotoxic effects of oncological treatment. This study aimed to investigate the long-term cardiotoxic effects of cancer therapy in CCS using a multimodal approach combining cardiac magnetic resonance (CMR) imaging and circulating blood biomarkers. A total of 117 CCS (mean age 24.7 ± 5.2 years), at least five years post-treatment and in complete remission, were prospectively enrolled. All participants underwent CMR, including T1 mapping, and blood analysis for biomarkers of endothelial damage and oxidative stress. Parameters were compared with sex- and age-matched healthy control groups. Anthracycline treatment was administered in 82.9% of CCS (mean cumulative doxorubicin equivalent dose 231.7 ± 92.0 mg/m²). Left ventricular ejection fraction and mitral annular plane systolic excursion were significantly reduced in CCS compared to controls (59.0 ± 5.5% vs. 67.2 ± 6.9%, p < 0.001; 12.5 ± 1.7 mm vs. 13.9 ± 2.2 mm, p = 0.001). Late gadolinium enhancement was detected in four CCS. No significant differences in global native T1 relaxation time or extracellular volume were observed. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels remained within normal limits but correlated with native T1, ECV, and MAPSE. Levels of myeloperoxidase, big endothelin-1, and ischemia-modified albumin were significantly higher than in controls. Subclinical myocardial changes were detected in long-term CCS using CMR and circulating biomarkers. These findings support the utility of a multimodal approach for the early identification of individuals at increased cardiovascular risk after childhood cancer treatment.