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
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.
JACC CardioOncol. 2024 Apr 16;6(2):236-247. doi: 10.1016/j.jaccao.2024.02.008. eCollection 2024 Apr.
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.
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.
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.
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%).
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).
有心力衰竭风险的儿童癌症幸存者需接受终身超声心动图监测。既往研究报道，N端前脑钠肽（NT-proBNP）和高敏心肌肌钙蛋白T（hs-cTnT）在检测左心室（LV）功能障碍方面诊断准确性有限。然而，有研究提示，联合生物标志物和临床特征可能会提高诊断准确性。
本研究旨在开发并内部验证一种诊断模型，该模型将心脏生物标志物与临床特征相结合，以有效判断或排除儿童癌症幸存者的LV功能障碍。
一项多中心横断面研究纳入了1334例幸存者（中位年龄34.2岁）和278例同胞（中位年龄36.8岁）。通过自抽样法开发并验证逻辑回归模型，将生物标志物与临床特征相结合。
22.1%的幸存者NT-proBNP水平异常，而同胞中这一比例为5.4%；hs-cTnT水平超过10 ng/L在幸存者（5.9%）和同胞（5.0%）中均不常见。诊断模型在临床特征基础上加入NT-proBNP和hs-cTnT后有改善，左心室射血分数（LVEF）<50%时，C统计量从0.69增加到0.73，对更严重LV功能障碍的预测更准确，LVEF<45%时，C统计量从0.80增加到0.86。对于LVEF<50%（患病率10.9%），16.9%的幸存者可通过高灵敏度（95.4%；95%CI：90.4%-99.3%）和阴性预测值（97.5%；95%CI：94.6%-99.7%）有效排除。同样，对于LVEF<45%（患病率3.4%），53.0%的幸存者可通过中度至高灵敏度（91.1%；95%CI：79.2%-100%）和高阴性预测值（99.4%；95%CI：98.7%-100%）排除。
基于生物标志物的诊断模型在排除LV功能障碍方面有效，有可能减少儿童癌症幸存者不必要的监测性超声心动图检查。外部验证对于证实这些发现至关重要。（儿童癌症幸存者心脏功能障碍的早期检测；荷兰儿童肿瘤学组后续研究；https://onderzoekmetmensen.nl/nl/trial/23641）
