Abstract
BackgroundCardiovascular disease (CVD) is the leading non-malignant cause of death in childhood cancer survivors. Heightened risk of CVD is often attributable to treatment with anthracycline chemotherapy. Anthracycline-mediated cardiac injury may lie latent for years following cessation of treatment and is therefore often not detected until disease is advanced and aggressive therapy is required. Symptomatic CVD may be preceded by subclinical cardiac and vascular dysfunction. This study aimed to determine whether such dysfunction could be detected in healthy, anthracycline-treated survivors of childhood leukaemia.MethodsCardiac magnetic resonance imaging (cMRI) with late gadolinium enhancement and endothelial function were used to characterise pre-clinical stages of CVD. Twenty-two long-term (>5 years survival; age 21 ± 3 years) childhood leukaemia survivors were assessed. All survivors were asymptomatic and had normal resting echocardiography. To exclude potential confounding effects of radiotherapy, no survivors had received this treatment. Twenty-two similarly aged (25 ± 3 years) gender-matched controls were recruited for comparison.ResultsLeft ventricular ejection fraction was lower in the survivors (55.0 ± 4.6%) compared to the controls (59.4 ± 6.2%; p = 0.010). Further, five survivors (23%) had clinically reduced (<50%) left ventricular ejection fraction. Normalised left ventricular end systolic volume was augmented in survivors (40.0 ± 9.1 mL·m2 vs. 34.5 ± 7.5 mL·m2; p = 0.038). Cardiac MRI did not show any late gadolinium enhancement. High resolution, ultrasound-derived flow mediated dilation was impaired in survivors (6.7 ± 2.1% vs. 8.60 ± 1.91%, p = 0.005).ConclusionsWe detected subclinical changes in cardiovascular structure and function indicative of early disease in anthracycline-treated childhood leukaemia survivors with normal echocardiography. Early detection and characterisation of underlying disease allows for timely intervention and improved outcomes in this at-risk population.
Highlights
Cardiovascular disease (CVD) is the leading non-malignant cause of death in childhood cancer survivors
Anthracycline chemotherapy has been identified as an independent risk-factor for CVD, with studies showing that almost half of exposed survivors will develop injury to the heart [6,7,8,9]
Our findings suggest that there is minimal fibrosis involved in the early remodelling process raising the question as to whether there is any value in including late gadolinium enhancement into Cardiac magnetic resonance imaging (cMRI) follow-up
Summary
Cardiovascular disease (CVD) is the leading non-malignant cause of death in childhood cancer survivors. The current five-year survival rate for childhood cancer in developed countries is approaching 85% [1,2,3]. These gains come at a cost – the long-term impact of malignancy and its treatment is substantial, with 62% of survivors developing a chronic health condition within 17 years of diagnosis [4]. There are currently very few effective ways of detecting subclinical cardiac dysfunction in survivors [10] This emphasises the need to find effective follow-up screening measures that will allow for early detection of underlying abnormalities before they become too advanced and difficult to treat
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