Biomarkers to diagnose ventricular dysfunction in childhood cancer survivors: A systematic review

Jan M. Leerink*, Simone J. Verkleij, Elizabeth A.M. Feijen, Annelies M.C. Mavinkurve-Groothuis, Milanthy S. Pourier, Kaisa Ylänen, Wim J.E. Tissing, Marloes Louwerens, Marry M. Van Den Heuvel, Eline Van Dulmen-Den Broeder, Andrica C.H. De Vries, Cecile M. Ronckers, Heleen J.H. Van Der Pal, Livia Kapusta, Jacqueline Loonen, Louise Bellersen, Yigal M. Pinto, Leontien C.M. Kremer, Wouter E.M. Kok

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Objective: To systematically review the literature and assess the diagnostic value of biomarkers in detection of late-onset left ventricular (LV) dysfunction in childhood cancer survivors (CCS) treated with anthracyclines. Methods: We systematically searched the literature for studies that evaluated the use of biomarkers for detection of LV dysfunction in CCS treated with anthracyclines more than 1 year since childhood cancer diagnosis. LV dysfunction definitions were accepted as an ejection fraction <50% or <55% and/or a fractional shortening <28%, <29% or <30%. Contingency tables were created to assess diagnostic accuracies of biomarkers for diagnosing LV dysfunction. Results: Of 1362 original studies screened, eight heterogeneous studies evaluating four different biomarkers in mostly asymptomatic CCS were included. In four studies, an abnormal N-terminal pro-B-type natriuretic peptide (NT-proBNP, cut-off range 63-125 ng/L) had low sensitivity (maximally 22%) and a specificity of up to 97% for detection of LV dysfunction. For troponin levels, in five studies one patient had an abnormal troponin value as well as LV dysfunction, while in total 127 patients had LV dysfunction without troponin elevations above cut-off values (lowest 0.01 ng/mL). Two studies that evaluated brain natriuretic peptide and nitric oxide were underpowered to draw conclusions. Conclusions: In individual studies, the diagnostic value of NT-proBNP for detection of LV dysfunction in CCS is limited. Troponins have no role in detecting late-onset LV dysfunction with cut-off values as low as 0.01 ng/mL. Further study on optimal NT-proBNP cut-off values for rule out or rule in of LV dysfunction is warranted.

Original languageEnglish
Pages (from-to)210-216
Number of pages7
Issue number3
StatePublished - 1 Feb 2019


FundersFunder number
Dutch Heart FoundationCVON2015-21
Dutch heart FoundationcVOn2015-21


    • cardiac imaging and diagnostics
    • heart failure
    • systemic review


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