Extensive Cardiac Function Analyses Using Contemporary Echocardiography in Childhood Cancer Survivors
JACC CardioOncology, vol. 5, pp. 472–485
Abstract
Childhood cancer survivors (CCS) are at risk for cardiotoxicity. We sought to assess how cardiac dysfunction measurements in CCS overlap and are differentially influenced by risk factors. This cross-sectional Dutch Childhood Cancer Survivor Study evaluated echocardiograms of 1,397 ≥5-year CCS and 277 siblings. Of CCS, n = 1,254 received cardiotoxic (anthracyclines/mitoxantrone/radiotherapy involving the heart region [RTheart]) and n = 143 received potentially cardiotoxic (cyclophosphamide, ifosfamide, or vincristine) therapy. We assessed demographic, treatment-related, and traditional cardiovascular risk factors for cardiac dysfunction using multivariable logistic regression. CCS were a median of 26.7 years after diagnosis; 49% were women. Abnormal left ventricular ejection fraction (LVEF) (defined as <52% in men, <54% in women) occurred most commonly in CCS treated with anthracyclines and RTheart combined (38%). Age/sex-specific abnormal global longitudinal strain (GLS) occurred most commonly in CCS treated with RTheart, either with (41%) or without (38%) anthracyclines. Of CCS with normal LVEF, 20.2% showed abnormal GLS. Diastolic dysfunction grade ≥II was rare. Abnormal LVEF was mainly associated with female sex, anthracycline dose, and only in women, RTheart dose. Abnormal GLS was associated with female sex, RTheart dose, diastolic blood pressure, and only in women, anthracycline dose. Cyclophosphamide, ifosfamide, and vincristine were not associated with LVEF or GLS. Compared with siblings, CCS showed higher risk of abnormal LVEF (OR: 2.9; 95% CI: 1.4-6.6) and GLS (OR: 2.1; 95% CI: 1.2-3.7), independent of (potentially) cardiotoxic treatment-related and cardiovascular risk factors. Abnormal LVEF and GLS constitute complementary measures of systolic dysfunction among long-term CCS. Their diagnostic value may differ according to cardiotoxic exposures. Also, CCS have residual, unexplained risk of cardiac dysfunction. (Early Detection of Cardiac Dysfunction in Childhood Cancer Survivors, a DCOG LATER study; NTR7481)
Authors 27
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Remy Merkx corresponding
Radboud University Medical Center · Radboud Institute for Health Sciences
Affiliation as printed
Medical Imaging/Radiology, Medical UltraSound Imaging Centre, Radboud Institute for Health Sciences, Radboud university medical center, the Netherlands
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Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Clinical and Experimental Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
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Affiliation as printed
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
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Affiliation as printed
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
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Radboud University Nijmegen · Radboud University Medical Center
Affiliation as printed
Cardiology, Radboud university medical center, Nijmegen, the Netherlands
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Affiliation as printed
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
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Affiliation as printed
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
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Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Pediatric Oncology, Amsterdam UMC, VU University, Amsterdam, the Netherlands
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Affiliation as printed
Trial- and Data Center, Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
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Erasmus MC · University Medical Center Utrecht · Princess Máxima Center · Erasmus MC - Sophia Children’s Hospital · Wilhelmina Children's Hospital
Affiliation as printed
Pediatric Oncology, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, the Netherlands
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands
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Affiliation as printed
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands
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Radboud University Nijmegen · Radboud University Medical Center
Affiliation as printed
Cardiology, Radboud university medical center, Nijmegen, the Netherlands
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Affiliation as printed
Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
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Johannes Gutenberg University Mainz · University Medical Center of the Johannes Gutenberg University Mainz · Princess Máxima Center
Affiliation as printed
Childhood Cancer Epidemiology/German Childhood Cancer Registry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
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Affiliation as printed
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
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University Medical Center Utrecht
Affiliation as printed
Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands
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University Medical Center Groningen · University of Groningen · Princess Máxima Center
Affiliation as printed
Pediatric Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
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Erasmus MC · Princess Máxima Center · Erasmus MC - Sophia Children’s Hospital
Affiliation as printed
Pediatric Oncology, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, the Netherlands
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
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Radboud University Medical Center · Radboud Institute for Health Sciences
Affiliation as printed
Medical Imaging/Radiology, Medical UltraSound Imaging Centre, Radboud Institute for Health Sciences, Radboud university medical center, the Netherlands
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Radboud University Medical Center · Radboud Institute for Health Sciences
Affiliation as printed
Medical Imaging/Radiology, Medical UltraSound Imaging Centre, Radboud Institute for Health Sciences, Radboud university medical center, the Netherlands
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Radboud University Nijmegen · Radboud University Medical Center
Affiliation as printed
Hematology, Radboud university medical center, Nijmegen, the Netherlands
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Affiliation as printed
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
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Affiliation as printed
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
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University Medical Center Utrecht · Emma Kinderziekenhuis · Princess Máxima Center · Amsterdam University Medical Centers · Wilhelmina Children's Hospital · University of Amsterdam
Affiliation as printed
Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands
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Princess Máxima Center · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Clinical and Experimental Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
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Radboud University Nijmegen · Tel Aviv University · Tel Aviv Sourasky Medical Center · Radboud University Medical Center · Amalia Kinderziekenhuis
Affiliation as printed
Pediatric Cardiology, Amalia Children's Hospital, Radboud university medical center, Nijmegen, the Netherlands
Pediatrics, Pediatric Cardiology Unit, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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