Abstract
BackgroundCardiovascular disease is the leading nonmalignant cause of late deaths in childhood cancer survivors. Cardiovascular disease and cardiac dysfunction can remain asymptomatic for many years, but eventually lead to progressive disease with high morbidity and mortality. Early detection and intervention are therefore crucial to improve outcomes.ObjectiveIn our study, we aim to assess the prevalence of preclinical cardiac dysfunction in adult childhood cancer survivors using conventional and speckle tracking echocardiography; determine the association between cardiac dysfunction and treatment-related risk factors (anthracyclines, alkylating agents, steroids, cardiac radiation) and modifiable cardiovascular risk factors (abdominal obesity, hypertension); investigate the development of cardiac dysfunction longitudinally in a defined cohort; study the association between cardiac dysfunction and other health outcomes like pulmonary disease, endocrine disease, renal disease, quality of life, fatigue, strength and endurance, and physical activity; and gain experience conducting a clinical study of childhood cancer survivors that will be extended to a national, multicenter study of cardiac complications.MethodsFor this retrospective cohort study, we will invite ≥5-year childhood cancer survivors who were treated at the University Children's Hospital Bern, Switzerland with any chemotherapy or cardiac radiation since 1976 and who are ≥18 years of age at the time of the study for a cardiac assessment at the University Hospital Bern. This includes 544 childhood cancer survivors, of whom about half were treated with anthracyclines and/or cardiac radiation and half with any other chemotherapy. The standardized cardiac assessment includes a medical history focusing on signs of cardiovascular disease and its risk factors, a physical examination, anthropometry, vital parameters, the 1-minute sit-to-stand test, and echocardiography including 2-dimensional speckle tracking.ResultsWe will invite 544 eligible childhood cancer survivors (median age at the time of the study, 32.5 years; median length of time since diagnosis, 25.0 years) for a cardiac assessment. Of these survivors, 300 (55%) are at high risk, and 244 (45%) are at standard risk of cardiac dysfunction.ConclusionsThis study will determine the prevalence of preclinical cardiac dysfunction in Swiss childhood cancer survivors, inform whether speckle tracking echocardiography is more sensitive to cardiac dysfunction than conventional echocardiography, and give a detailed picture of risk factors for cardiac dysfunction. The results will help improve primary treatment and follow-up care of children with cancer.Trial RegistrationClinicalTrials.gov NCT03790943; https://clinicaltrials.gov/ct2/show/NCT03790943International Registered Report Identifier (IRRID)DERR1-10.2196/17724
Highlights
Survival of childhood cancer has improved, and the number of childhood cancer survivors (CCS) has greatly increased during recent decades [1,2]
This study will determine the prevalence of preclinical cardiac dysfunction in Swiss childhood cancer survivors, inform whether speckle tracking echocardiography is more sensitive to cardiac dysfunction than conventional echocardiography, and give a detailed picture of risk factors for cardiac dysfunction
Studies from North America, Germany, and The Netherlands have assessed survivors exposed to cardiotoxic cancer therapy, in whom a prevalence of subclinical cardiac dysfunction ranging from 6% to 27% was identified via conventional echocardiography [7,8,9,10]
Summary
Survival of childhood cancer has improved, and the number of childhood cancer survivors (CCS) has greatly increased during recent decades [1,2]. Cardiovascular disease is the leading nonmalignant cause of death among CCS [3] with a cumulative incidence that increases up to 30 years after cancer diagnosis [6]. Studies from North America, Germany, and The Netherlands have assessed survivors exposed to cardiotoxic cancer therapy, in whom a prevalence of subclinical cardiac dysfunction ranging from 6% to 27% was identified via conventional echocardiography [7,8,9,10]. This suggests that many CCS have impaired cardiac function that might progress to clinical heart failure later in life. Detection and intervention are crucial to improve outcomes
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