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

IF 12 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology Pub Date : 2024-04-01 DOI:10.1016/j.jaccao.2024.02.008

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

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引用次数: 0

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)

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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

背景有心力衰竭风险的儿童癌症幸存者需要终生接受超声心动图监测。以前的研究表明，N-末端前 B 型钠尿肽（NT-proBNP）和高敏心肌肌钙蛋白 T（hs-cTnT）在检测左心室功能障碍方面的诊断准确性有限。本研究旨在开发并在内部验证一种诊断模型，该模型结合了心脏生物标记物和临床特征，可有效排除或排除儿童癌症幸存者的左心室功能障碍。结果在22.1%的幸存者中观察到NT-proBNP水平异常，而在5.4%的兄弟姐妹中观察到NT-proBNP水平异常，而hs-cTnT水平超过10 ng/L在幸存者（5.9%）和兄弟姐妹（5.0%）中均不常见。将 NT-proBNP 和 hs-cTnT 加入临床特征后，诊断模型得到了改善，使 LV 射血分数（LVEF）为 50%时的 C 统计量从 0.69 增加到 0.73，并能更准确地预测更严重的 LV 功能障碍，LVEF 为 45% 时的 C 统计量从 0.80 增加到 0.86。对于 LVEF <50%（发病率为 10.9%），可以有效排除 16.9% 的幸存者，具有较高的灵敏度（95.4%；95% CI：90.4%-99.3%）和阴性预测值（97.5%；95% CI：94.6%-99.7%）。同样，对于 LVEF <45%（发病率为 3.4%），53.0% 的幸存者可被排除，灵敏度为中高水平（91.1%；95% CI：79.2%-100%），阴性预测值为高水平（99.4%；95% CI：98.7%-100%）。要证实这些发现，外部验证至关重要。(儿童癌症幸存者心功能障碍的早期检测；DCOG LATER 研究；https://onderzoekmetmensen.nl/nl/trial/23641）

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来源期刊

Jacc: Cardiooncology Multiple-

CiteScore

12.50

自引率

6.30%

发文量

106

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.