{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:19:07Z","timestamp":1790432347492,"version":"4.1.0"},"reference-count":28,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T00:00:00Z","timestamp":1613606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>With more than 25 million people affected, heart failure (HF) is a global threat. As energy production pathways are known to play a pivotal role in HF, we sought here to identify key metabolic changes in ischemic- and non-ischemic HF by using a multi-OMICS approach. Serum metabolites and mRNAseq and epigenetic DNA methylation profiles were analyzed from blood and left ventricular heart biopsy specimens of the same individuals. In total we collected serum from n = 82 patients with Dilated Cardiomyopathy (DCM) and n = 51 controls in the screening stage. We identified several metabolites involved in glycolysis and citric acid cycle to be elevated up to 5.7-fold in DCM (p = 1.7 \u00d7 10\u22126). Interestingly, cardiac mRNA and epigenetic changes of genes encoding rate-limiting enzymes of these pathways could also be found and validated in our second stage of metabolite assessment in n = 52 DCM, n = 39 ischemic HF and n = 57 controls. In conclusion, we identified a new set of metabolomic biomarkers for HF. We were able to identify underlying biological cascades that potentially represent suitable intervention targets.<\/jats:p>","DOI":"10.3390\/ijms22041999","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T05:39:28Z","timestamp":1613626768000},"page":"1999","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Energy Metabolites as Biomarkers in Ischemic and Dilated Cardiomyopathy"],"prefix":"10.3390","volume":"22","author":[{"given":"Jan","family":"Haas","sequence":"first","affiliation":[{"name":"Department of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen S.","family":"Frese","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3266-0527","authenticated-orcid":false,"given":"Farbod","family":"Sedaghat-Hamedani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham","family":"Kayvanpour","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0902-7114","authenticated-orcid":false,"given":"Rewati","family":"Tappu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rouven","family":"Nietsch","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oguz Firat","family":"Tugrul","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Wisdom","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Dietrich","sequence":"additional","affiliation":[{"name":"Siemens Healthcare GmbH, 91058 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Amr","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Weis","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3803-2679","authenticated-orcid":false,"given":"Torsten","family":"Niederdr\u00e4nk","sequence":"additional","affiliation":[{"name":"Siemens Healthcare GmbH, 91058 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Murphy","sequence":"additional","affiliation":[{"name":"MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5192-580X","authenticated-orcid":false,"given":"Thomas","family":"Krieg","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Cambridge, Addenbrooke\u2019s Hospital, Hills Road, Cambridge CB2 0QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7471-475X","authenticated-orcid":false,"given":"Marcus","family":"D\u00f6rr","sequence":"additional","affiliation":[{"name":"DZHK (German Centre for Cardiovascular Research), 17475 Greifswald, Germany"},{"name":"Department of Internal Medicine B, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5689-3448","authenticated-orcid":false,"given":"Uwe","family":"V\u00f6lker","sequence":"additional","affiliation":[{"name":"DZHK (German Centre for Cardiovascular Research), 17475 Greifswald, Germany"},{"name":"Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Fielitz","sequence":"additional","affiliation":[{"name":"DZHK (German Centre for Cardiovascular Research), 17475 Greifswald, Germany"},{"name":"Department of Internal Medicine B, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Frey","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan B.","family":"Felix","sequence":"additional","affiliation":[{"name":"DZHK (German Centre for Cardiovascular Research), 17475 Greifswald, Germany"},{"name":"Department of Internal Medicine B, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5361-0895","authenticated-orcid":false,"given":"Andreas","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics, University of Saarland, 66123 Saarbr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo A.","family":"Katus","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Meder","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), 17475 Greifswald, Germany"},{"name":"Genome Technology Center, Stanford 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