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

Christina Schindera, Claudia Elisabeth Kuehni, Mladen Pavlovic, Eva Simona Haegler-Laube, Daniel Rhyner, Nicolas Waespe, Jochen Roessler, Thomas Suter, Nicolas Xavier von der Weid, Christina Schindera, Claudia Elisabeth Kuehni, Mladen Pavlovic, Eva Simona Haegler-Laube, Daniel Rhyner, Nicolas Waespe, Jochen Roessler, Thomas Suter, Nicolas Xavier von der Weid

Abstract

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 outcomes.

Objective: In 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.

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 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.

Results: We 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.

Conclusions: 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. The results will help improve primary treatment and follow-up care of children with cancer.

Trial registration: ClinicalTrials.gov NCT03790943; https://ichgcp.net/clinical-trials-registry/NCT03790943.

International registered report identifier (irrid): DERR1-10.2196/17724.

Keywords: Switzerland; alkylating agents; anthracyclines; cardiac radiation; cardiotoxicity; echocardiography; speckle tracking; steroids; strain.

Conflict of interest statement

Conflicts of Interest: JR reports personal fees from SOBI, Roche, and Pierre Fabre for advisory board membership, which is independent of the submitted work.

©Christina Schindera, Claudia Elisabeth Kuehni, Mladen Pavlovic, Eva Simona Haegler-Laube, Daniel Rhyner, Nicolas Waespe, Jochen Roessler, Thomas Suter, Nicolas Xavier von der Weid. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 10.06.2020.

Figures

Figure 1
Figure 1
Responsible teams in the study of preclinical diagnosis of cardiac dysfunction in childhood cancer survivors.
Figure 2
Figure 2
Study design and risk group stratification of childhood cancer survivors.
Figure 3
Figure 3
Recruitment of childhood cancer survivors eligible for the study, current as of October 1, 2019.

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