Metabolic Profiling Associates with Disease Severity in Nonischemic Dilated Cardiomyopathy
Metabolic Profiling Associates with Disease Severity in Nonischemic Dilated Cardiomyopathy
复制标题
DOI：
10.1016/j.cardfail.2019.09.004
复制
发表时间：
2020-03-01
影响因子：
6
通讯作者：
Bierau, Joergen
中科院分区：
文献类型：
--
作者：
J Verdonschot, Job A.;Wang, Ping;Bierau, Joergen
背景：代谢组学分析可能对心力衰竭有诊断和预后价值。本研究探讨靶向血、尿代谢组学在反映非缺血性扩张型心肌病(DCM)患者病情严重程度中的作用，并比较其在脑利钠肽N末端前激素原(NT-proBNP)基础上的增量值。方法和结果：检测273例DCM患者血浆和尿液中149种代谢物，其中DCM伴正常左室逆重构患者70例，无症状DCM患者72例，有症状DCM患者131例。如单生物标记物线性回归、稀疏偏最小二乘判别分析、随机森林和条件随机森林分析反复揭示的那样，酰基肉碱、唾液酸和谷氨酸是与疾病严重程度相关的最独特的代谢物。然而，不同组之间代谢谱的绝对差异是微乎其微的。基于顶级代谢物的决策树模型在分类阶段没有超过NTproBNP。然而，NT-ProBNP和顶级代谢物的组合改善了决策树，以区分扩张型心肌病并左室逆重构患者和症状性扩张型心肌病患者(曲线下面积0.813+/-0.138比0.739+/-0.114；P=0.02)。这些改变揭示了晚期症状性扩张型心肌病潜在的替代治疗靶点。代谢谱可以补充NT-proBNP来确定非缺血性DCM的疾病严重程度。
Background: 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).Methods and Results: 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 NTproBNP 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).Conclusion: 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.