Diagnosing Preclinical Cardiac Dysfunction in Swiss ChildhoodCancer Survivors: Protocol for a Single-Center Cohort Study

BACKGROUND Cardiovascular 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 outcome. OBJECTIVE In our study, we aim to 1) assess the prevalence of preclinical cardiac dysfunction in adult childhood cancer survivors using conventional and speckle tracking echocardiography, 2) 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), 3) investigate the development of cardiac dysfunction longitudinally in a defined cohort, 4) study the association between cardiac dysfunction and other health outcomes like pulmonary, endocrine, and renal diseases, quality of life, fatigue, strength and endurance, and physical activity, and 5) gain experience conducting a clinical study of childhood cancer survivors that will be extended to a national, multicenter study of cardiac complications. METHODS For 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 and/or cardiac radiation since 1976 and who are ≥18 years of age at time of study for a cardiac assessment at the University Hospital Bern. This includes overall 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 an echocardiography including 2-dimensional speckle tracking. RESULTS We will invite 544 eligible childhood cancer survivors for a cardiac assessment with a median age at study of 32.5 years and a median times since diagnosis of 25.0 years. Three hundred survivors (55%) are at high risk and 244 survivors (45%) are at standard risk for cardiac dysfunction. CONCLUSIONS The results of this study will show 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 suffering from cancer. CLINICALTRIAL Prospectively registered in ClinicalTrials.gov, Identifier: NCT03790943, registration