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

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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
JournalHeart
Volume105
Issue number3
Early online date2018
DOIs
Publication statusPublished - 1 Feb 2019

Cite this

Leerink, J. M., Verkleij, S. J., Feijen, E. A. M., Mavinkurve-Groothuis, A. M. C., Pourier, M. S., Ylänen, K., ... Kok, W. E. M. (2019). Biomarkers to diagnose ventricular dysfunction in childhood cancer survivors: A systematic review. Heart, 105(3), 210-216. https://doi.org/10.1136/heartjnl-2018-313634
Leerink, Jan M. ; Verkleij, Simone J. ; Feijen, Elizabeth A. M. ; Mavinkurve-Groothuis, Annelies M. C. ; Pourier, Milanthy S. ; Ylänen, Kaisa ; Tissing, Wim J. E. ; Louwerens, Marloes ; van den Heuvel, Marry M. ; van Dulmen-den Broeder, Eline ; de Vries, Andrica C. H. ; Ronckers, Cecile M. ; van der Pal, Heleen J. H. ; Kapusta, Livia ; Loonen, Jacqueline ; Bellersen, Louise ; Pinto, Yigal M. ; Kremer, Leontien C. M. ; Kok, Wouter E. M. / Biomarkers to diagnose ventricular dysfunction in childhood cancer survivors: A systematic review. In: Heart. 2019 ; Vol. 105, No. 3. pp. 210-216.
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title = "Biomarkers to diagnose ventricular dysfunction in childhood cancer survivors: A systematic review",
abstract = "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.",
author = "Leerink, {Jan M.} and Verkleij, {Simone J.} and Feijen, {Elizabeth A. M.} and Mavinkurve-Groothuis, {Annelies M. C.} and Pourier, {Milanthy S.} and Kaisa Yl{\"a}nen and Tissing, {Wim J. E.} and Marloes Louwerens and {van den Heuvel}, {Marry M.} and {van Dulmen-den Broeder}, Eline and {de Vries}, {Andrica C. H.} and Ronckers, {Cecile M.} and {van der Pal}, {Heleen J. H.} and Livia Kapusta and Jacqueline Loonen and Louise Bellersen and Pinto, {Yigal M.} and Kremer, {Leontien C. M.} and Kok, {Wouter E. M.}",
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Leerink, JM, Verkleij, SJ, Feijen, EAM, Mavinkurve-Groothuis, AMC, Pourier, MS, Ylänen, K, Tissing, WJE, Louwerens, M, van den Heuvel, MM, van Dulmen-den Broeder, E, de Vries, ACH, Ronckers, CM, van der Pal, HJH, Kapusta, L, Loonen, J, Bellersen, L, Pinto, YM, Kremer, LCM & Kok, WEM 2019, 'Biomarkers to diagnose ventricular dysfunction in childhood cancer survivors: A systematic review' Heart, vol. 105, no. 3, pp. 210-216. https://doi.org/10.1136/heartjnl-2018-313634

Biomarkers to diagnose ventricular dysfunction in childhood cancer survivors: A systematic review. / Leerink, Jan M.; Verkleij, Simone J.; Feijen, Elizabeth A. M.; Mavinkurve-Groothuis, Annelies M. C.; Pourier, Milanthy S.; Ylänen, Kaisa; Tissing, Wim J. E.; Louwerens, Marloes; van den Heuvel, Marry M.; van Dulmen-den Broeder, Eline; de Vries, Andrica C. H.; Ronckers, Cecile M.; van der Pal, Heleen J. H.; Kapusta, Livia; Loonen, Jacqueline; Bellersen, Louise; Pinto, Yigal M.; Kremer, Leontien C. M.; Kok, Wouter E. M.

In: Heart, Vol. 105, No. 3, 01.02.2019, p. 210-216.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Biomarkers to diagnose ventricular dysfunction in childhood cancer survivors: A systematic review

AU - Leerink, Jan M.

AU - Verkleij, Simone J.

AU - Feijen, Elizabeth A. M.

AU - Mavinkurve-Groothuis, Annelies M. C.

AU - Pourier, Milanthy S.

AU - Ylänen, Kaisa

AU - Tissing, Wim J. E.

AU - Louwerens, Marloes

AU - van den Heuvel, Marry M.

AU - van Dulmen-den Broeder, Eline

AU - de Vries, Andrica C. H.

AU - Ronckers, Cecile M.

AU - van der Pal, Heleen J. H.

AU - Kapusta, Livia

AU - Loonen, Jacqueline

AU - Bellersen, Louise

AU - Pinto, Yigal M.

AU - Kremer, Leontien C. M.

AU - Kok, Wouter E. M.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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.

AB - 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.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/30158136

U2 - 10.1136/heartjnl-2018-313634

DO - 10.1136/heartjnl-2018-313634

M3 - Article

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SP - 210

EP - 216

JO - Heart

JF - Heart

SN - 1355-6037

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Leerink JM, Verkleij SJ, Feijen EAM, Mavinkurve-Groothuis AMC, Pourier MS, Ylänen K et al. Biomarkers to diagnose ventricular dysfunction in childhood cancer survivors: A systematic review. Heart. 2019 Feb 1;105(3):210-216. https://doi.org/10.1136/heartjnl-2018-313634