Jan M. Leerink MD , Elizabeth A.M. Feijen MD, PhD , Esmee C. de Baat MD , Remy Merkx MD , Helena J.H. van der Pal MD, PhD , Wim J.E. Tissing MD, PhD , Marloes Louwerens MD , Marry M. van den Heuvel-Eibrink MD, PhD , A. Birgitta Versluys MD, PhD , Elvira C. van Dalen MD, PhD , Margriet van der Heiden-van der Loo PhD , Dorine Bresters MD, PhD , Cécile M. Ronckers PhD , Andrica C.H. de Vries MD, PhD , Sebastian Neggers MD, PhD , Livia Kapusta MD, PhD , Jacqueline Loonen MD, PhD , Yigal M. Pinto MD, PhD , Leontien C.M. Kremer MD, PhD , Annelies M.C. Mavinkurve-Groothuis MD, PhD , Wouter E.M. Kok MD, PhD
{"title":"基于生物标志物的儿童癌症幸存者心脏功能障碍诊断模型","authors":"Jan M. Leerink MD , Elizabeth A.M. Feijen MD, PhD , Esmee C. de Baat MD , Remy Merkx MD , Helena J.H. van der Pal MD, PhD , Wim J.E. Tissing MD, PhD , Marloes Louwerens MD , Marry M. van den Heuvel-Eibrink MD, PhD , A. Birgitta Versluys MD, PhD , Elvira C. van Dalen MD, PhD , Margriet van der Heiden-van der Loo PhD , Dorine Bresters MD, PhD , Cécile M. Ronckers PhD , Andrica C.H. de Vries MD, PhD , Sebastian Neggers MD, PhD , Livia Kapusta MD, PhD , Jacqueline Loonen MD, PhD , Yigal M. Pinto MD, PhD , Leontien C.M. Kremer MD, PhD , Annelies M.C. Mavinkurve-Groothuis MD, PhD , Wouter E.M. Kok MD, PhD","doi":"10.1016/j.jaccao.2024.02.008","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Objectives</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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%).</p></div><div><h3>Conclusions</h3><p>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. 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Birgitta Versluys MD, PhD , Elvira C. van Dalen MD, PhD , Margriet van der Heiden-van der Loo PhD , Dorine Bresters MD, PhD , Cécile M. Ronckers PhD , Andrica C.H. de Vries MD, PhD , Sebastian Neggers MD, PhD , Livia Kapusta MD, PhD , Jacqueline Loonen MD, PhD , Yigal M. Pinto MD, PhD , Leontien C.M. Kremer MD, PhD , Annelies M.C. Mavinkurve-Groothuis MD, PhD , Wouter E.M. Kok MD, PhD\",\"doi\":\"10.1016/j.jaccao.2024.02.008\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>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.</p></div><div><h3>Objectives</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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%).</p></div><div><h3>Conclusions</h3><p>The biomarker-based diagnostic model proves effective in ruling out LV dysfunction, offering the potential to minimize unnecessary surveillance echocardiography in childhood cancer survivors. 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A Biomarker-Based Diagnostic Model for Cardiac Dysfunction in Childhood Cancer Survivors
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)
期刊介绍：
JACC: CardioOncology is a specialized journal that belongs to the esteemed Journal of the American College of Cardiology (JACC) family. Its purpose is to enhance cardiovascular care for cancer patients by publishing high-quality, innovative scientific research and sharing evidence-based knowledge.
The journal aims to revolutionize the field of cardio-oncology and actively involve and educate professionals in both cardiovascular and oncology fields. It covers a wide range of topics including pre-clinical, translational, and clinical research, as well as best practices in cardio-oncology. Key areas of focus include understanding disease mechanisms, utilizing in vitro and in vivo models, exploring novel and traditional therapeutics (across Phase I-IV trials), studying epidemiology, employing precision medicine, and investigating primary and secondary prevention.
Amyloidosis, cardiovascular risk factors, heart failure, and vascular disease are some examples of the disease states that are of particular interest to the journal. However, it welcomes research on other relevant conditions as well.
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