TY - JOUR
T1 - Extensive Cardiac Function Analyses Using Contemporary Echocardiography in Childhood Cancer Survivors
T2 - A DCCSS LATER Study
AU - Merkx, Remy
AU - Leerink, Jan M.
AU - Feijen, E. (Lieke) A. M.
AU - de Baat, Esmée C.
AU - Bellersen, Louise
AU - Bresters, Dorine
AU - van Dalen, Elvira C.
AU - van Dulmen-den Broeder, Eline
AU - van der Heiden-van der Loo, Margriet
AU - van den Heuvel-Eibrink, Marry M.
AU - Kok, Judith L.
AU - Louwerens, Marloes
AU - Maas, Angela H. E. M.
AU - Neggers, Sebastian J. C. M. M.
AU - Ronckers, C. cile M.
AU - Teepen, Jop C.
AU - Teske, Arco J.
AU - Tissing, Wim J. E.
AU - de Vries, Andrica C. H.
AU - Weijers, Gert
AU - de Korte, Chris L.
AU - Loonen, Jacqueline
AU - Mavinkurve-Groothuis, Annelies M. C.
AU - van der Pal, Helena J. H.
AU - Kremer, Leontien C. M.
AU - Kok, Wouter E. M.
AU - Dutch LATER Study Group
AU - Kapusta, Livia
N1 - Funding Information: The authors thank the other members of the DCOG LATER consortium (Birgitta Versluys, Martha Grootenhuis, Flora van Leeuwen, Lideke van der Steeg, Geert Janssens, Hanneke van Santen, Margreet Veening, Jaap den Hartogh, Saskia Pluijm, Lilian Batenburg, Hanneke de Ridder, Nynke Hollema, Lennart Teunissen, Anke Schellekens), and all physicians, research nurses, sonographers, data managers, and participating patients, parents, and siblings for their contributions. Publisher Copyright: © 2023 The Authors
PY - 2023/8/1
Y1 - 2023/8/1
N2 - Background: Childhood cancer survivors (CCS) are at risk for cardiotoxicity. Objectives: We sought to assess how cardiac dysfunction measurements in CCS overlap and are differentially influenced by risk factors. Methods: 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. Results: 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. Conclusions: 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.
AB - Background: Childhood cancer survivors (CCS) are at risk for cardiotoxicity. Objectives: We sought to assess how cardiac dysfunction measurements in CCS overlap and are differentially influenced by risk factors. Methods: 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. Results: 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. Conclusions: 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.
KW - cancer survivors
KW - cardiotoxicity
KW - child
KW - echocardiography
KW - global longitudinal strain
KW - left ventricular dysfunction
UR - http://www.scopus.com/inward/record.url?scp=85166974491&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jaccao.2023.06.003
DO - https://doi.org/10.1016/j.jaccao.2023.06.003
M3 - Article
C2 - 37614574
SN - 2666-0873
VL - 5
SP - 472
EP - 485
JO - JACC: CardioOncology
JF - JACC: CardioOncology
IS - 4
ER -