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

Abstract

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). 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. Clinical Trial: Prospectively registered in ClinicalTrials.gov, Identifier: NCT03790943, registration