{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:14:48Z","timestamp":1791090888304,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["91818602"],"award-info":[{"award-number":["91818602"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["CVON2014-40 DOSIS"],"award-info":[{"award-number":["CVON2014-40 DOSIS"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["95105003"],"award-info":[{"award-number":["95105003"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["09150182010020"],"award-info":[{"award-number":["09150182010020"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dutch Cardiovascular Alliance","award":["2020B005, Double-Dose"],"award-info":[{"award-number":["2020B005, Double-Dose"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hypertrophic Cardiomyopathy (HCM) is a common inherited heart disease with poor risk prediction due to incomplete penetrance and a lack of clear genotype\u2013phenotype correlations. Advanced imaging techniques have shown altered myocardial energetics already in preclinical gene variant carriers. To determine whether disturbed myocardial energetics with the potential to serve as biomarkers are also reflected in the serum metabolome, we analyzed the serum metabolome of asymptomatic carriers in comparison to healthy controls and obstructive HCM patients (HOCM). We performed non-quantitative direct-infusion high-resolution mass spectrometry-based untargeted metabolomics on serum from fasted asymptomatic gene variant carriers, symptomatic HOCM patients and healthy controls (n = 31, 14 and 9, respectively). Biomarker panels that discriminated the groups were identified by performing multivariate modeling with gradient-boosting classifiers. For all three group-wise comparisons we identified a panel of 30 serum metabolites that best discriminated the groups. These metabolite panels performed equally well as advanced cardiac imaging modalities in distinguishing the groups. Seven metabolites were found to be predictive in two different comparisons and may play an important role in defining the disease stage. This study reveals unique metabolic signatures in serum of preclinical carriers and HOCM patients that may potentially be used for HCM risk stratification and precision therapeutics.<\/jats:p>","DOI":"10.3390\/cells10112950","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T22:21:08Z","timestamp":1635805268000},"page":"2950","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Distinct Metabolomic Signatures in Preclinical and Obstructive Hypertrophic Cardiomyopathy"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9401-6190","authenticated-orcid":false,"given":"Maike","family":"Schuldt","sequence":"first","affiliation":[{"name":"Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8287-3707","authenticated-orcid":false,"given":"Beau","family":"van Driel","sequence":"additional","affiliation":[{"name":"Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sila","family":"Alg\u00fcl","sequence":"additional","affiliation":[{"name":"Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahana Y.","family":"Parbhudayal","sequence":"additional","affiliation":[{"name":"Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands"},{"name":"Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4461-4293","authenticated-orcid":false,"given":"Daniela Q. C. M.","family":"Barge-Schaapveld","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"G\u00fc\u00e7l\u00fc","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"},{"name":"Department of Cardiology, Isala Zwolle, 8025 AB Zwolle, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Genetics, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Michels","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Thorax Center, Erasmus Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette F.","family":"Baas","sequence":"additional","affiliation":[{"name":"Department of Genetics, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"van de Wiel","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Data Science, Amsterdam UMC, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Nieuwdorp","sequence":"additional","affiliation":[{"name":"Department of Internal and Vascular Medicine, Amsterdam UMC, Universiteit van Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeni","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Internal and Vascular Medicine, Amsterdam UMC, Universiteit van Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjeerd","family":"Germans","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0960-6263","authenticated-orcid":false,"given":"Judith J. M.","family":"Jans","sequence":"additional","affiliation":[{"name":"Department of Genetics, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5224-5788","authenticated-orcid":false,"given":"Jolanda","family":"van der Velden","sequence":"additional","affiliation":[{"name":"Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.jacc.2015.01.019","article-title":"New Perspectives on the Prevalence of Hypertrophic Cardiomyopathy","volume":"65","author":"Semsarian","year":"2015","journal-title":"J. Am. Coll. 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