Job A J Verdonschot1, Ping Wang2, Marc Van Bilsen3, Mark R Hazebroek3, Jort J Merken3, Els K Vanhoutte2, Michiel T H M Henkens3, Arthur Van Den Wijngaard2, Jan F C Glatz2, Ingrid P C Krapels2, Han G Brunner4, Stephane R B Heymans5, Jörgen Bierau2. 1. Department of Cardiology, Maastricht University Medical Centre, Maastricht, the Netherlands; Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, the Netherlands. Electronic address: job.verdonschot@mumc.nl. 2. Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, the Netherlands. 3. Department of Cardiology, Maastricht University Medical Centre, Maastricht, the Netherlands. 4. Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, the Netherlands; Department of Human Genetics and Donders Center for Neuroscience, Radboudumc, Nijmegen, the Netherlands. 5. Department of Cardiology, Maastricht University Medical Centre, Maastricht, the Netherlands; Department of Cardiovascular Research, University of Leuven, Belgium; Netherlands Heart Institute (ICIN), Utrecht, the Netherlands.
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.
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.
Authors: Fotios Spyropoulos; Andrea Sorrentino; Jiska van der Reest; Peiran Yang; Markus Waldeck-Weiermair; Benjamin Steinhorn; Emrah Eroglu; Seyed Soheil Saeedi Saravi; Paul Yu; Marcia Haigis; Helen Christou; Thomas Michel Journal: Am J Physiol Heart Circ Physiol Date: 2022-01-28 Impact factor: 4.733
Authors: Job A J Verdonschot; Marco Merlo; Fernando Dominguez; Ping Wang; Michiel T H M Henkens; Michiel E Adriaens; Mark R Hazebroek; Marco Masè; Luis E Escobar; Rafael Cobas-Paz; Kasper W J Derks; Arthur van den Wijngaard; Ingrid P C Krapels; Han G Brunner; Gianfranco Sinagra; Pablo Garcia-Pavia; Stephane R B Heymans Journal: Eur Heart J Date: 2021-01-07 Impact factor: 29.983
Authors: Chiara Volani; Johannes Rainer; Vinicius Veri Hernandes; Viviana Meraviglia; Peter Paul Pramstaller; Sigurður Vidir Smárason; Giulio Pompilio; Michela Casella; Elena Sommariva; Giuseppe Paglia; Alessandra Rossini Journal: Metabolites Date: 2021-03-25