Metabolic Profiling Associates with Disease Severity in Nonischemic Dilated Cardiomyopathy

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.