Background

Emerging evidence suggests that pediatric and adult dilated cardiomyopathy (DCM) represent distinct diseases. Few diagnostic tools exist for pediatric cardiologists to assess clinical status and prognosis. We hypothesized that pediatric DCM would have a unique biomarker profile compared to adult DCM and controls.

Methods

We utilized a DNA aptamer array (SOMAScan) to compare biomarker profiles between pediatric and adult DCM. We simultaneously measured 1310 plasma proteins and peptides from 39 healthy children (mean age 3 years, interquartile range (IQR) 1–14), 39 ambulatory subjects with pediatric DCM (mean age 2.7 years, IQR 1–13), and 40 ambulatory adults with DCM (mean age 53 years, IQR 46–63).

Results

Pediatric and adult DCM patients displayed distinct biomarker profiles, despite similar clinical characteristics. We identified 20 plasma peptides and proteins that were increased in pediatric DCM compared to age- and sex-matched controls. Unbiased multidimensionality reduction analysis suggested previously unrecognized heterogeneity among pediatric DCM subjects. Biomarker profile analysis identified four subgroups of pediatric DCM with distinguishing clinical characteristics.

Conclusions

These findings support the emerging concept that pediatric and adult DCM are distinct disease entities, signify the need to develop pediatric-specific biomarkers for disease prognostication, and challenge the paradigm that pediatric DCM should be viewed as a single disease.

Impact

• Pediatric and adult DCM patients displayed distinct biomarker profiles, despite similar clinical characteristics and outcomes.

• Our findings suggest that pediatric DCM may be a heterogeneous disease with various sub-phenotypes, including differing biomarker profiles and clinical findings.

• These data provide prerequisite information for future prospective studies that validate the identified pediatric DCM biomarkers, address their diagnostic accuracy and prognostic significance, and explore the full extent of heterogeneity amongst pediatric DCM patients.

中文翻译：

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儿童和成人扩张型心肌病通过不同的生物标志物特征来区分

背景

新的证据表明，儿童和成人扩张型心肌病 (DCM) 代表着不同的疾病。儿科心脏病专家评估临床状态和预后的诊断工具很少。我们假设与成人 DCM 和对照相比，儿科 DCM 具有独特的生物标志物特征。

方法

我们利用 DNA 适体阵列 (SOMAScan) 来比较儿童和成人 DCM 之间的生物标志物概况。我们同时测量了 39 名健康儿童（平均年龄 3 岁，四分位数范围 (IQR) 1-14）、39 名患有儿科 DCM 的流动受试者（平均年龄 2.7 岁，IQR 1-13）和 40 名流动成人的 1310 种血浆蛋白和肽。 DCM（平均年龄 53 岁，IQR 46-63）。

结果

尽管临床特征相似，但儿童和成人 DCM 患者表现出不同的生物标志物特征。我们发现，与年龄和性别匹配的对照组相比，儿科 DCM 中的 20 种血浆肽和蛋白质有所增加。无偏多维还原分析表明儿科扩张型心肌病受试者之间存在先前未被认识的异质性。生物标志物概况分析确定了具有独特临床特征的儿科 DCM 的四个亚组。

结论

这些发现支持了儿童和成人扩张型心肌病是不同疾病实体的新兴概念，表明需要开发儿科特异性生物标志物用于疾病预测，并挑战了儿童扩张型心肌病应被视为单一疾病的范式。

影响

• 尽管临床特征和结果相似，但儿童和成人 DCM 患者表现出不同的生物标志物特征。

• 我们的研究结果表明，儿科扩张型心肌病可能是一种异质性疾病，具有多种亚表型，包括不同的生物标志物特征和临床表现。

• 这些数据为未来的前瞻性研究提供了必要的信息，这些研究验证了已确定的儿科 DCM 生物标志物，解决了其诊断准确性和预后意义，并探索了儿科 DCM 患者的全部异质性。