Metabolic Profiling Associates with Disease Severity in Nonischemic Dilated Cardiomyopathy

Job A J Verdonschot; Ping Wang; Marc Van Bilsen; Mark R Hazebroek; Jort J Merken; Els K Vanhoutte; Michiel T H M Henkens; Arthur Van Den Wijngaard; Jan F C Glatz; Ingrid P C Krapels; Han G Brunner; Stephane R B Heymans; Jörgen Bierau

doi:10.1016/j.cardfail.2019.09.004

Metabolic Profiling Associates with Disease Severity in Nonischemic Dilated Cardiomyopathy

Job A J Verdonschot^*, Ping Wang, Marc Van Bilsen, Mark R Hazebroek, Jort J Merken, Els K Vanhoutte, Michiel T H M Henkens, Arthur Van Den Wijngaard, Jan F C Glatz, Ingrid P C Krapels, Han G Brunner, Stephane R B Heymans, Jörgen Bierau

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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 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).

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.

Original language	English
Pages (from-to)	212-222
Number of pages	11
Journal	Journal of Cardiac Failure
Volume	26
Issue number	3
DOIs	https://doi.org/10.1016/j.cardfail.2019.09.004
Publication status	Published - Mar 2020

Keywords

Metabolomics
dilated cardiomyopathy
disease severity
heart failure
HEART-FAILURE
GLUTATHIONE HOMEOSTASIS
SIALIC-ACID
EXCRETION
DIAGNOSIS
PLASMA

Access to Document

10.1016/j.cardfail.2019.09.004Licence: CC BY-NC-ND

Cite this

Verdonschot, J. A. J., Wang, P., Van Bilsen, M., Hazebroek, M. R., Merken, J. J., Vanhoutte, E. K., Henkens, M. T. H. M., Van Den Wijngaard, A., Glatz, J. F. C., Krapels, I. P. C., Brunner, H. G., Heymans, S. R. B., & Bierau, J. (2020). Metabolic Profiling Associates with Disease Severity in Nonischemic Dilated Cardiomyopathy. Journal of Cardiac Failure, 26(3), 212-222. https://doi.org/10.1016/j.cardfail.2019.09.004

@article{1a2e64d7628548929bff93d05d1f6e23,

title = "Metabolic Profiling Associates with Disease Severity in Nonischemic Dilated Cardiomyopathy",

abstract = "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 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).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.",

keywords = "Metabolomics, dilated cardiomyopathy, disease severity, heart failure, HEART-FAILURE, GLUTATHIONE HOMEOSTASIS, SIALIC-ACID, EXCRETION, DIAGNOSIS, PLASMA",

author = "Verdonschot, {Job A J} and Ping Wang and {Van Bilsen}, Marc and Hazebroek, {Mark R} and Merken, {Jort J} and Vanhoutte, {Els K} and Henkens, {Michiel T H M} and {Van Den Wijngaard}, Arthur and Glatz, {Jan F C} and Krapels, {Ingrid P C} and Brunner, {Han G} and Heymans, {Stephane R B} and J{\"o}rgen Bierau",

year = "2020",

month = mar,

doi = "10.1016/j.cardfail.2019.09.004",

language = "English",

volume = "26",

pages = "212--222",

journal = "Journal of Cardiac Failure",

issn = "1071-9164",

publisher = "Churchill Livingstone Inc Medical Publishers",

number = "3",

}

Verdonschot, JAJ , Wang, P, Van Bilsen, M, Hazebroek, MR, Merken, JJ, Vanhoutte, EK , Henkens, MTHM, Van Den Wijngaard, A, Glatz, JFC, Krapels, IPC , Brunner, HG , Heymans, SRB & Bierau, J 2020, 'Metabolic Profiling Associates with Disease Severity in Nonischemic Dilated Cardiomyopathy', Journal of Cardiac Failure, vol. 26, no. 3, pp. 212-222. https://doi.org/10.1016/j.cardfail.2019.09.004

TY - JOUR

T1 - Metabolic Profiling Associates with Disease Severity in Nonischemic Dilated Cardiomyopathy

AU - Verdonschot, Job A J

AU - Wang, Ping

AU - Van Bilsen, Marc

AU - Hazebroek, Mark R

AU - Merken, Jort J

AU - Vanhoutte, Els K

AU - Henkens, Michiel T H M

AU - Van Den Wijngaard, Arthur

AU - Glatz, Jan F C

AU - Krapels, Ingrid P C

AU - Brunner, Han G

AU - Heymans, Stephane R B

AU - Bierau, Jörgen

PY - 2020/3

Y1 - 2020/3

N2 - 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 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).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.

AB - 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 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).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.

KW - Metabolomics

KW - dilated cardiomyopathy

KW - disease severity

KW - heart failure

KW - HEART-FAILURE

KW - GLUTATHIONE HOMEOSTASIS

KW - SIALIC-ACID

KW - EXCRETION

KW - DIAGNOSIS

KW - PLASMA

U2 - 10.1016/j.cardfail.2019.09.004

DO - 10.1016/j.cardfail.2019.09.004

M3 - Article

C2 - 31541741

SN - 1071-9164

VL - 26

SP - 212

EP - 222

JO - Journal of Cardiac Failure

JF - Journal of Cardiac Failure

IS - 3

ER -