A Biomarker-Based Diagnostic Model for Cardiac Dysfunction in Childhood Cancer Survivors.

Autor:	Leerink JM; Amsterdam UMC, University of Amsterdam, Heart Center, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands.; Princess Máxima Center for Pediatric Oncology, Utrecht, 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; Radboud University Medical Center, Department of Medical Imaging, Nijmegen, the Netherlands., van der Pal HJH; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Tissing WJE; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Beatrix Children's Hospital, Department of Pediatric Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Louwerens M; Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands., van den Heuvel-Eibrink MM; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Department of Pediatric Oncology, Erasmus Medical Center, Rotterdam, the Netherlands.; University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, the Netherlands., Versluys AB; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., van Dalen EC; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., van der Heiden-van der Loo M; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Bresters D; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Willem Alexander Children's Hospital/Leiden University Medical Center, Leiden, the Netherlands., Ronckers CM; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Carl von Ossietzky University of Oldenburg, Oldenburg, Germany., de Vries ACH; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Department of Pediatric Oncology, Erasmus Medical Center, Rotterdam, the Netherlands., Neggers S; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Department of Medicine, Section Endocrinology, Erasmus Medical Center, Rotterdam, the Netherlands., Kapusta L; Radboud University Medical Center, Department of Pediatric Cardiology, Amalia Children's Hospital, Nijmegen, the Netherlands.; Pediatrics, Pediatric Cardiology Unit, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel., Loonen J; Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands., Pinto YM; Amsterdam UMC, University of Amsterdam, Heart Center, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands., Kremer LCM; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.; University Medical Center Utrecht, Wilhelmina Children's Hospital, Utrecht, the Netherlands.; Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Amsterdam, the Netherlands., Mavinkurve-Groothuis AMC; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands., Kok WEM; Amsterdam UMC, University of Amsterdam, Heart Center, Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands.
Jazyk:	angličtina
Zdroj:	JACC. CardioOncology [JACC CardioOncol] 2024 Apr 16; Vol. 6 (2), pp. 236-247. Date of Electronic Publication: 2024 Apr 16 (Print Publication: 2024).
DOI:	10.1016/j.jaccao.2024.02.008
Abstrakt:	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). Competing Interests: This research was supported by the Dutch Heart Foundation (CVON2015-21) and Stichting Kinderen Kankervrij/ODAS Stichting. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. (© 2024 The Authors.)
Databáze:	MEDLINE
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