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Diagnostic tools for early detection of cardiac dysfunction in childhood cancer survivors: Methodological aspects of the Dutch late effects after childhood cancer (LATER) cardiology study - 18/12/19

Doi : 10.1016/j.ahj.2019.10.010 
Jan M. Leerink, MD a, 1, E. Lieke A.M. Feijen, PhD b, c, , 1 , Helena J.H. van der Pal, MD, PhD b, Wouter E.M. Kok, MD, PhD a, Annelies M.C. Mavinkurve-Groothuis, MD, PhD b, Livia Kapusta, MD, PhD d, e, Yigal M. Pinto, MD, PhD a, Angela H.E.M. Maas, MD, PhD f, Louise Bellersen, MD, PhD f, Arco J. Teske, MD, PhD b, g, Cécile M. Ronckers, PhD b, c, Marloes Louwerens, MD, PhD h, Elvira C. van Dalen, MD, PhD b, Eline van Dulmen-den Broeder, MD, PhD i, Lilian Batenburg, MD, PhD b, p, Margriet van der Heiden-van der Loo, PhD k, Marry M. van den Heuvel-Eibrink, MD, PhD b, Flora E. van Leeuwen, PhD l, Andrica C.H. de Vries, MD, PhD m, Gert Weijers, PhD n, Chris L. de Korte, PhD n, Jacqueline J. Loonen, MD, PhD o, Sebastian J.C.M.M. Neggers, MD, PhD j, A.B. Birgitta Versluys, MD, PhD b, Wim J.E. Tissing, MD, PhD p, Leontien C.M. Kremer, MD, PhD b, c

on behalf of the LATER Study Group

a Amsterdam UMC, University of Amsterdam, Heart Center; Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands 
b Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands 
c Amsterdam UMC, University of Amsterdam, Department of Pediatric Oncology, Amsterdam, The Netherlands 
d Radboud University Medical Center, Amalia Children's Hospital, Department of Pediatric Cardiology, Nijmegen, The Netherlands 
e Tel Aviv University, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Department of Pediatrics, Pediatric cardiology unit, Tel Aviv, Israel 
f Radboud University Medical Center, Department of Cardiology, Nijmegen, The Netherlands 
g University Medical Centre Utrecht, Department of Cardiology, Utrecht, The Netherlands 
h Leiden University Medical Center, Department of Internal Medicine, Utrecht, The Netherlands 
i Amsterdam UMC, VU University, Department of Pediatric Oncology, Amsterdam, The Netherlands 
j Erasmus University Medical Center, Department of Internal Medicine, Rotterdam, The Netherlands 
k Dutch Childhood Oncology Group – Late Effects after Childhood Cancer (LATER) registry, Utrecht, The Netherlands 
l Netherlands Cancer Institute, Department of Epidemiology, Amsterdam, The Netherlands 
m Department of Pediatric Oncology, Erasmus Medical Center, Rotterdam, The Netherlands 
n Radboud University Medical Center, Medical Ultrasound Imaging Center, Department of Radiology and Nuclear Medicine, Nijmegen, The Netherlands 
o Radboud University Medical Center, Department of Hematology, Nijmegen, The Netherlands 
p University Medical Center Groningen, Beatrix Children's Hospital, Department of Pediatric Oncology, Groningen, The Netherlands 

Reprint requests: Dr. E.A.M. Feijen, Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.Princess Máxima Center for Pediatric OncologyHeidelberglaan 25Utrecht3584 CSThe Netherlands

Abstract

Background

Cancer therapy-related cardiac dysfunction and heart failure are major problems in long-term childhood cancer survivors (CCS). We hypothesize that assessment of more sensitive echo- and electrocardiographic measurements, and/or biomarkers will allow for improved recognition of patients with cardiac dysfunction before heart failure develops, and may also identify patients at lower risk for heart failure.

Objective

To describe the methodology of the Dutch LATER cardiology study (LATER CARD).

Methods

The LATER CARD study is a cross-sectional study in long-term CCS treated with (potentially) cardiotoxic cancer therapies and sibling controls. We will evaluate 1) the prevalence and associated (treatment related) risk factors of subclinical cardiac dysfunction in CCS compared to sibling controls and 2) the diagnostic value of echocardiography including myocardial strain and diastolic function parameters, blood biomarkers for cardiomyocyte apoptosis, oxidative stress, cardiac remodeling and inflammation and ECG or combinations of them in the surveillance for cancer therapy-related cardiac dysfunction. From 2017 to 2020 we expect to include 1900 CCS and 500 siblings.

Conclusions

The LATER CARD study will provide knowledge on different surveillance modalities for detection of cardiac dysfunction in long-term CCS at risk for heart failure. The results of the study will enable us to improve long-term follow-up surveillance guidelines for CCS at risk for heart failure.

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Plan


 Netherlands Trial Registry (NTR) number 7481.
 Funding: Dutch Heart Foundation Grant [CVON2015–21]. Kika/ODAS Grant 171 ‘DCOG LATER program’.
 The LATER Study Group also includes the following collaborative authors:
MA Grootenhuis (Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands)
JG den Hartogh (Dutch Childhood Cancer Parent Organization (VOKK), Nieuwegein)
H van Santen (Wilhelmina Children's hospital, University Medical Center Utrecht, Utrecht, The Netherlands)



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