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

TL;DR

This study finds that childhood cancer survivors show early heart damage from past treatments, using advanced imaging and blood tests.

Contribution

The study introduces a multimodal approach combining CMR T1 mapping and biomarkers to detect subclinical cardiotoxicity in childhood cancer survivors.

Findings

CCS had reduced left ventricular ejection fraction and MAPSE compared to controls.

Biomarkers like myeloperoxidase and ischemia-modified albumin were elevated in CCS.

NT-proBNP levels correlated with CMR parameters but remained within normal limits.

Abstract

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.

The online version contains supplementary material available at 10.1007/s12012-026-10098-8.

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