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Heart damage from childhood treatment appears quietly and decades later. When 1,853 adult survivors were examined rather than asked, 7.4 per cent had cardiomyopathy and 28 per cent had valve disease, and most of it was new at that visit: nearly all of them had no symptoms. High blood pressure multiplied the risk of heart failure nineteenfold, which makes it the most treatable thing on the page.
Three cohorts tell this story from three angles and agree.
How common, by self-report. Among 14,358 five-year survivors of cancer diagnosed under 21 and 3,899 siblings in the Childhood Cancer Survivor Study, survivors were significantly more likely to report congestive heart failure (hazard ratio 5.9, 95 per cent confidence interval 3.4 to 9.6), myocardial infarction (5.0, 2.3 to 10.4), pericardial disease (6.3, 3.3 to 11.9) and valvular abnormalities (4.8, 3.0 to 7.6), all P below 0.001. Anthracycline exposure of 250 mg/m2 or more raised the relative hazard of congestive heart failure, pericardial disease and valvular abnormality by two to five times against no anthracycline, and cardiac radiation of 1,500 centigray or more raised hazards twofold to sixfold. The cumulative incidence continued to rise up to 30 years after diagnosis.
How common, on examination. Among 1,853 adult survivors who had received cardiotoxic therapy at least ten years earlier, median age 8 at diagnosis and 31 at evaluation, cardiomyopathy was present in 7.4 per cent, newly identified at that evaluation in 4.7; coronary artery disease in 3.8 per cent, newly identified in 2.2; valvular regurgitation or stenosis in 28.0 per cent, newly identified in 24.8; and conduction or rhythm abnormalities in 4.4 per cent. The authors note that "Nearly all survivors were asymptomatic". Prevalence rose with age, from 3 to 24 per cent among survivors aged 30 to 39 to 10 to 37 per cent among those aged 40 or more. Anthracycline doses of 250 mg/m2 or more carried an odds ratio of 2.7 (1.1 to 6.9) for cardiomyopathy and heart radiation an odds ratio of 1.9 (1.1 to 3.7).
What makes it worse, and can be changed. Among 10,724 survivors and 3,159 siblings, median age 33.7, the cumulative incidence by age 45 was 5.3 per cent for coronary artery disease, 4.8 for heart failure, 1.5 for valvular disease and 1.3 for arrhythmia. Two or more conventional cardiovascular risk factors were present in 10.3 per cent of survivors and 7.9 per cent of siblings, and risk rose with the number of them (all trends P below .001). Hypertension alone carried a rate ratio of 6.1 for coronary artery disease, 19.4 for heart failure, 13.6 for valvular disease and 6.0 for arrhythmia (all P below .01), and was independently associated with cardiac death (rate ratio 5.6, 3.2 to 9.7). Chest radiotherapy and hypertension together produced risks beyond what adding them would predict. Blood pressure is the most treatable determinant of whether a survivor develops heart failure, and it is routinely not measured at a cancer follow-up appointment.
Surveillance is harmonised. The International Guideline Harmonization Group's 2015 cardiomyopathy recommendations exist precisely because the national guidelines disagreed about who to scan and how often, and they are graded by the quality of the evidence and the benefit expected from early detection. Dexrazoxane, the one cardioprotectant with pooled randomised evidence in adults, has weaker and unpoolable evidence in children; that is set out in the cardioprotection record in this front.
What comes back, and when: the adult record on cardiotoxicity surveillance gives the recovery figures for damage found early and treated. In childhood survivors the window is different, because the injury is decades old by the time it is found and most of it is asymptomatic. The levers that remain are blood pressure, lipids, weight, smoking and activity, all of which are ordinary medicine, and the reason risk-based follow-up exists is to make sure somebody is doing it.
Anthracyclines kill cardiomyocytes through topoisomerase-2-beta-mediated DNA damage during the years in which the heart is still growing, so the adult heart is built from fewer myocytes and has less reserve rather than a visible lesion. Radiation injures valve leaflets, pericardium, coronary endothelium and the conducting system, with effects that progress for decades. Because both reduce reserve rather than cause symptoms, ordinary cardiovascular risk factors, above all hypertension, determine when the reserve runs out.
Query for this technology: (TITLE:"The heart after anthracyclines and chest radiotherapy in childhood" OR ABSTRACT:"The heart after anthracyclines and chest radiotherapy in childhood") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about The heart after anthracyclines and chest radiotherapy in childhood, not a curated reading list.
Shares International Guideline Harmonization Group for late effects of childhood cancer, Late deaths after childhood cancer, what causes them, and the proof that gentler treatment worked, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), Childhood Cancer Survivor Study (CCSS), Childhood cancers (all types) and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, The Children's Oncology Group Long-Term Follow-Up Guidelines, Childhood Cancer Survivor Study (CCSS), Wilms tumour (nephroblastoma) and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.