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Obesity Predisposes Anthracycline-Treated Survivors of Childhood and Adolescent Cancers to Subclinical Cardiac Dysfunction

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Abstract

Anthracyclines are effective chemotherapeutics used in approximately 60% of pediatric cancer cases but have a well-documented risk of cardiotoxicity. Existing cardiotoxicity risk calculators do not include cardiovascular risk factors present at the time of diagnosis. The goal of this study is to leverage the advanced sensitivity of strain echocardiography to identify pre-existing risk factors for early subclinical cardiac dysfunction among anthracycline-exposed pediatric patients. We identified 115 pediatric patients with cancer who were treated with an anthracycline between 2013 and 2019. Peak longitudinal left ventricular strain was retroactively calculated on 495 surveillance echocardiograms via the TOMTEC AutoSTRAIN software. Cox proportional hazards models were employed to identify risk factors for abnormal longitudinal strain (> − 16%) following anthracycline treatment. High anthracycline dose (≥ 250 mg/m2 doxorubicin equivalents) and obesity at the time of diagnosis (BMI > 95th percentile-for-age) were both significant predictors of abnormal strain with hazard ratios of 2.79, 95% CI (1.07–7.25), and 3.85, 95% CI (1.42–10.48), respectively. Among pediatric cancer survivors, patients who are obese at the time of diagnosis are at an increased risk of sub-clinical cardiac dysfunction following anthracycline exposure. Future studies should explore the incidence of symptomatic cardiomyopathy 10–15 years post-treatment among patients with early subclinical cardiac dysfunction.

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Funding

IAG is supported by the National Institutes of Health TL1-TR002555. AB is supported by the National Institutes of Health R38-HL143612 and Duke Pediatric Research Scholars. MER and MATH are supported by the National Institutes of Health P30 CA016672 and Cancer Prevention Research Institute (IIRCCA RP108166). National Institutes of Health (K08-HL136839 and R01-HL160654), Doris Duke Charitable Foundation (CSDA-2020098), John Taylor Babbitt Foundation, The Hartwell Foundation, Additional Ventures, Y.T. and Alice Chen Pediatric Genetics and Genomics Research Center.

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Authors and Affiliations

  1. Duke University School of Medicine, Durham, NC, USA

    Ian A. George

  2. Duke Department of Pediatrics, Division of Cardiology, Duke University School of Medicine, Durham, NC, USA

    BriAnna Souder, Amy Berkman, David H. Noyd, M. Jay Campbell, Piers C. A. Barker, Andrew W. McCrary & Andrew P. Landstrom

  3. Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Amy Berkman

  4. Seattle Children’s Hospital, Seattle, WA, USA

    David H. Noyd

  5. Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Michael Roth

  6. Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Michelle A. T. Hildebrandt

  7. Department of Medicine, Duke University and Duke Cancer Institute, Durham, NC, USA

    Kevin C. Oeffinger

  8. Duke University Medical Center, Box 3090, Durham, NC, 27710, USA

    Andrew W. McCrary

  9. Duke University Medical Center, Box 2652, Durham, NC, 27710, USA

    Andrew P. Landstrom

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Ian A. George, Andrew P. Landstrom and Andrew W. McCrary. The first draft of the manuscript was written by Ian A. George and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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George, I.A., Souder, B., Berkman, A. et al. Obesity Predisposes Anthracycline-Treated Survivors of Childhood and Adolescent Cancers to Subclinical Cardiac Dysfunction. Pediatr Cardiol (2024). https://doi.org/10.1007/s00246-024-03423-x

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