Department of Otolaryngology-Head & Neck Surgery, Indiana University School of Medicine, 1300 W. Michigan St, Suite 400, Indianapolis, IN, 46202, USA.
Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN, USA.
Metabolomics. 2021 Oct 3;17(10):95. doi: 10.1007/s11306-021-01846-8.
Children and young adults with single ventricle (SV) heart disease frequently develop heart failure (HF) that is intractable and difficult to treat. Our understanding of the molecular and biochemical reasons underlying this is imperfect. Thus, there is an urgent need for biomarkers that predict outcome and provide a rational basis for treatment, and advance our understanding of the basis of HF.
We sought to determine if a metabolomic approach would provide biochemical signatures of HF in SV children and young adults. If significant, these analytes might serve as biomarkers to predict outcome and inform on the biological mechanism(s) of HF.
We applied a multi-platform metabolomics approach composed of mass spectrometry (MS) and nuclear magnetic resonance (NMR) which yielded 495 and 26 metabolite measurements respectively. The plasma samples came from a cross-sectional set of young SV subjects, ages 2-19 years with ten control (Con) subjects and 16 SV subjects. Of the SV subjects, nine were diagnosed as congestive HF (SVHF), and 7 were not in HF. Metabolomic data were correlated with clinical status to determine if there was a signature associated with HF.
There were no differences in age, height, weight or sex between the 3 cohorts. However, statistical analysis of the metabolomic profiles using ANOVA revealed 44 metabolites with significant differences between cohorts including 41 profiled by MS and 3 by NMR. These metabolites included acylcarnitines, amino acids, and bile acids, which distinguished Con from all SV subjects. Furthermore, metabolite profiles could distinguish between SV and SVHF subjects.
These are the first data to demonstrate a clear metabolomic signature associated with HF in children and young adults with SV. Larger studies are warranted to determine if these findings are predictive of progression to HF in time to provide intervention.
患有单心室（SV）心脏病的儿童和青少年经常会出现心力衰竭（HF），这种心力衰竭难以治疗且顽固。我们对其潜在的分子和生化原因的了解并不完善。因此，迫切需要有能预测预后的生物标志物，为治疗提供合理的依据，并深入了解 HF 的基础。
我们试图确定代谢组学方法是否能为 SV 儿童和青少年的 HF 提供生化特征。如果有显著差异，这些分析物可能作为预测预后的生物标志物，并为 HF 的生物学机制提供信息。
我们采用了一种多平台代谢组学方法，包括质谱（MS）和核磁共振（NMR），分别获得了 495 和 26 种代谢产物的测量值。这些血浆样本来自一组交叉的年轻 SV 受试者，年龄在 2 至 19 岁之间，有 10 名对照（Con）受试者和 16 名 SV 受试者。在 SV 受试者中，有 9 名被诊断为充血性 HF（SVHF），7 名没有 HF。将代谢组学数据与临床状况相关联，以确定是否存在与 HF 相关的特征。
3 组之间的年龄、身高、体重或性别均无差异。然而，使用 ANOVA 对代谢组学图谱进行的统计分析显示，有 44 种代谢物在队列之间存在显著差异，其中 41 种通过 MS 分析，3 种通过 NMR 分析。这些代谢物包括酰基肉碱、氨基酸和胆汁酸，它们将 Con 与所有 SV 受试者区分开来。此外，代谢物图谱可以区分 SV 和 SVHF 受试者。
这些是首批证明与 SV 儿童和青少年 HF 相关的明确代谢组学特征的研究数据。需要进行更大规模的研究，以确定这些发现是否能预测 HF 的进展，以便及时进行干预。
