Department of Cardiology, Maastricht University Medical Centre, Maastricht, the Netherlands; Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, the Netherlands.
Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, the Netherlands.
J Card Fail. 2020 Mar;26(3):212-222. doi: 10.1016/j.cardfail.2019.09.004. Epub 2019 Sep 18.
Metabolomic profiling may have diagnostic and prognostic value in heart failure. This study investigated whether targeted blood and urine metabolomics reflects disease severity in patients with nonischemic dilated cardiomyopathy (DCM) and compared its incremental value on top of N-terminal prohormone of brain natriuretic peptide (NT-proBNP).
A total of 149 metabolites were measured in plasma and urine samples of 273 patients with DCM and with varying stages of disease (patients with DCM and normal left ventricular reverse remodeling, n = 70; asymptomatic DCM, n = 72; and symptomatic DCM, n = 131). Acylcarnitines, sialic acid and glutamic acid are the most distinctive metabolites associated with disease severity, as repeatedly revealed by unibiomarker linear regression, sparse partial least squares discriminant analysis, random forest, and conditional random forest analyses. However, the absolute difference in the metabolic profile among groups was marginal. A decision-tree model based on the top metabolites did not surpass NT-proBNP in classifying stages. However, a combination of NT-proBNP and the top metabolites improved the decision tree to distinguish patients with DCM and left ventricular reverse remodeling from symptomatic DCM (area under the curve 0.813 ± 0.138 vs 0.739 ± 0.114; P = 0.02).
Functional cardiac recovery is reflected in metabolomics. These alterations reveal potential alternative treatment targets in advanced symptomatic DCM. The metabolic profile can complement NT-proBNP in determining disease severity in nonischemic DCM.
代谢组学分析可能在心力衰竭的诊断和预后方面具有价值。本研究旨在探究针对血液和尿液的代谢组学分析是否能够反映非缺血性扩张型心肌病（DCM）患者的疾病严重程度，并比较其与 N 端脑钠肽前体（NT-proBNP）相比是否具有额外的诊断价值。
共检测了 273 例 DCM 患者（DCM 并左心室逆重构正常组，n=70；无症状 DCM 组，n=72；有症状 DCM 组，n=131）的血液和尿液样本中的 149 种代谢物。酰基肉碱、唾液酸和谷氨酸是与疾病严重程度最相关的代谢物，这一点通过单生物标志物线性回归、稀疏偏最小二乘判别分析、随机森林和条件随机森林分析不断得到验证。然而，各组间代谢谱的差异很小。基于顶级代谢物的决策树模型在进行分组分类时并不优于 NT-proBNP。但是，将 NT-proBNP 和顶级代谢物结合起来，可以提高决策树区分 DCM 并左心室逆重构与有症状 DCM 的能力（曲线下面积 0.813±0.138 比 0.739±0.114；P=0.02）。
心脏功能的恢复在代谢组学上有所反映。这些变化揭示了晚期有症状 DCM 中潜在的替代治疗靶点。代谢谱可补充 NT-proBNP 来确定非缺血性 DCM 的疾病严重程度。
