{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T06:17:37Z","timestamp":1793945857518,"version":"4.8.0"},"reference-count":69,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T00:00:00Z","timestamp":1672704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation DFG","doi-asserted-by":"publisher","award":["SFB1002"],"award-info":[{"award-number":["SFB1002"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Severe aortic stenosis (AS) is a common pathological condition in an ageing population imposing significant morbidity and mortality. Based on distinct hemodynamic features, i.e., ejection fraction (EF), transvalvular gradient and stroke volume, four different AS subtypes can be distinguished: (i) normal EF and high gradient, (ii) reduced EF and high gradient, (iii) reduced EF and low gradient, and (iv) normal EF and low gradient. These subtypes differ with respect to pathophysiological mechanisms, cardiac remodeling, and prognosis. However, little is known about metabolic changes in these different hemodynamic conditions of AS. Thus, we carried out metabolomic analyses in serum samples of 40 AS patients (n = 10 per subtype) and 10 healthy blood donors (controls) using ultrahigh-performance liquid chromatography\u2013tandem mass spectroscopy. A total of 1293 biochemicals could be identified. Principal component analysis revealed different metabolic profiles in all of the subgroups of AS (All-AS) vs. controls. Out of the determined biochemicals, 48% (n = 620) were altered in All-AS vs. controls (p &lt; 0.05). In this regard, levels of various acylcarnitines (e.g., myristoylcarnitine, fold-change 1.85, p &lt; 0.05), ketone bodies (e.g., 3-hydroxybutyrate, fold-change 11.14, p &lt; 0.05) as well as sugar metabolites (e.g., glucose, fold-change 1.22, p &lt; 0.05) were predominantly increased, whereas amino acids (e.g., leucine, fold-change 0.8, p &lt; 0.05) were mainly reduced in All-AS. Interestingly, these changes appeared to be consistent amongst all AS subtypes. Distinct differences between AS subtypes were found for metabolites belonging to hemoglobin metabolism, diacylglycerols, and dihydrosphingomyelins. These findings indicate that relevant changes in substrate utilization appear to be consistent for different hemodynamic subtypes of AS and may therefore reflect common mechanisms during AS-induced heart failure. Additionally, distinct metabolites could be identified to significantly differ between certain AS subtypes. Future studies need to define their pathophysiological implications.<\/jats:p>","DOI":"10.3390\/biom13010095","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T02:51:39Z","timestamp":1672714299000},"page":"95","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Metabolomic Profiling in Patients with Different Hemodynamic Subtypes of Severe Aortic Valve Stenosis"],"prefix":"10.3390","volume":"13","author":[{"given":"Philipp","family":"Bengel","sequence":"first","affiliation":[{"name":"Clinic for Cardiology & Pneumology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manar","family":"Elkenani","sequence":"additional","affiliation":[{"name":"Clinic for Cardiology & Pneumology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo E.","family":"Beuthner","sequence":"additional","affiliation":[{"name":"Clinic for Cardiology & Pneumology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maik","family":"Pietzner","sequence":"additional","affiliation":[{"name":"MRC Epidemiology Unit, University of Cambridge, Cambridge CB2 0QQ, UK"},{"name":"Computational Medicine, Berlin Institute of Health at Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6705-3241","authenticated-orcid":false,"given":"Belal A.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Clinic for Cardiology & Pneumology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrix","family":"Pollok-Kopp","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Kr\u00e4tzner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Toischer","sequence":"additional","affiliation":[{"name":"Clinic for Cardiology & Pneumology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Puls","sequence":"additional","affiliation":[{"name":"Clinic for Cardiology & Pneumology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Fischer","sequence":"additional","affiliation":[{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"Department of Clinical Chemistry, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"Division Vascular Signaling and Cancer, German Cancer Research Center, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz","family":"Binder","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Hasenfu\u00df","sequence":"additional","affiliation":[{"name":"Clinic for Cardiology & Pneumology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5134-8347","authenticated-orcid":false,"given":"Moritz","family":"Schnelle","sequence":"additional","affiliation":[{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"},{"name":"Department of Clinical Chemistry, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1093\/eurheartj\/ehx391","article-title":"2017 ESC\/EACTS guidelines for the management of valvular heart disease","volume":"38","author":"Baumgartner","year":"2017","journal-title":"Eur. 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