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A Biomarker-Based Diagnostic Model for Cardiac Dysfunction in Childhood Cancer Survivors.
Leerink, Jan M; Feijen, Elizabeth A M; de Baat, Esmee C; Merkx, Remy; van der Pal, Helena J H; Tissing, Wim J E; Louwerens, Marloes; van den Heuvel-Eibrink, Marry M; Versluys, A Birgitta; van Dalen, Elvira C; van der Heiden-van der Loo, Margriet; Bresters, Dorine; Ronckers, Cécile M; de Vries, Andrica C H; Neggers, Sebastian; Kapusta, Livia; Loonen, Jacqueline; Pinto, Yigal M; Kremer, Leontien C M; Mavinkurve-Groothuis, Annelies M C; Kok, Wouter E M.
Afiliación
  • Leerink JM; Amsterdam UMC, University of Amsterdam, Heart Center, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands.
  • Feijen EAM; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
  • de Baat EC; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
  • Merkx R; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
  • van der Pal HJH; Radboud University Medical Center, Department of Medical Imaging, Nijmegen, the Netherlands.
  • Tissing WJE; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
  • Louwerens M; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
  • van den Heuvel-Eibrink MM; Beatrix Children's Hospital, Department of Pediatric Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Versluys AB; Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
  • van Dalen EC; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
  • van der Heiden-van der Loo M; Department of Pediatric Oncology, Erasmus Medical Center, Rotterdam, the Netherlands.
  • Bresters D; University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, the Netherlands.
  • Ronckers CM; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
  • de Vries ACH; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
  • Neggers S; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
  • Kapusta L; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
  • Loonen J; Willem Alexander Children's Hospital/Leiden University Medical Center, Leiden, the Netherlands.
  • Pinto YM; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
  • Kremer LCM; Carl von Ossietzky University of Oldenburg, Oldenburg, Germany.
  • Mavinkurve-Groothuis AMC; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
  • Kok WEM; Department of Pediatric Oncology, Erasmus Medical Center, Rotterdam, the Netherlands.
JACC CardioOncol ; 6(2): 236-247, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38774012
ABSTRACT

Background:

Childhood cancer survivors at risk for heart failure undergo lifelong echocardiographic surveillance. Previous studies reported the limited diagnostic accuracy of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) in detecting left ventricular (LV) dysfunction. However, potential enhanced diagnostic accuracy through the combination of biomarkers and clinical characteristics has been suggested.

Objectives:

The aim of this study was to develop and internally validate a diagnostic model that combines cardiac biomarkers with clinical characteristics for effectively ruling in or ruling out LV dysfunction in childhood cancer survivors.

Methods:

A multicenter cross-sectional study included 1,334 survivors (median age 34.2 years) and 278 siblings (median age 36.8 years). Logistic regression models were developed and validated through bootstrapping, combining biomarkers with clinical characteristics.

Results:

Abnormal NT-proBNP levels were observed in 22.1% of survivors compared with 5.4% of siblings, whereas hs-cTnT levels exceeding 10 ng/L were uncommon in both survivors (5.9%) and siblings (5.0%). The diagnostic models demonstrated improvement upon the addition of NT-proBNP and hs-cTnT to clinical characteristics, resulting in an increased C statistic from 0.69 to 0.73 for LV ejection fraction (LVEF) <50% and a more accurate prediction of more severe LV dysfunction, with the C statistic increasing from 0.80 to 0.86 for LVEF <45%. For LVEF <50% (prevalence 10.9%), 16.9% of survivors could be effectively ruled out with high sensitivity (95.4%; 95% CI 90.4%-99.3%) and negative predictive value (97.5%; 95% CI 94.6%-99.7%). Similarly, for LVEF <45% (prevalence 3.4%), 53.0% of survivors could be ruled out with moderate to high sensitivity (91.1%; 95% CI 79.2%-100%) and high negative predictive value (99.4%; 95% CI 98.7%-100%).

Conclusions:

The biomarker-based diagnostic model proves effective in ruling out LV dysfunction, offering the potential to minimize unnecessary surveillance echocardiography in childhood cancer survivors. External validation is essential to confirm these findings. (Early Detection of Cardiac Dysfunction in Childhood Cancer Survivors; A DCOG LATER Study; https//onderzoekmetmensen.nl/nl/trial/23641).
Palabras clave

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: JACC CardioOncol Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: JACC CardioOncol Año: 2024 Tipo del documento: Article País de afiliación: Países Bajos