{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T05:36:08Z","timestamp":1784007368909,"version":"3.55.0"},"reference-count":77,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Hypertrophic cardiomyopathy (HCM) is defined clinically by pathological left ventricular hypertrophy. We have previously developed a plasma proteomics biomarker panel that correlates with clinical markers of disease severity and sudden cardiac death risk in adult patients with HCM. The aim of this study was to investigate the utility of adult biomarkers and perform new discoveries in proteomics for childhood-onset HCM.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>Fifty-nine protein biomarkers were identified from an exploratory plasma proteomics screen in children with HCM and augmented into our existing multiplexed targeted liquid chromatography-tandem\/mass spectrometry-based assay. The association of these biomarkers with clinical phenotypes and outcomes was prospectively tested in plasma collected from 148 children with HCM and 50 healthy controls. Machine learning techniques were used to develop novel pediatric plasma proteomic biomarker panels.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Four previously identified adult HCM markers (aldolase fructose-bisphosphate A, complement C3a, talin-1, and thrombospondin 1) and 3 new markers (glycogen phosphorylase B, lipoprotein a and profilin 1) were elevated in pediatric HCM. Using supervised machine learning applied to training (n=137) and validation cohorts (n=61), this 7-biomarker panel differentiated HCM from healthy controls with an area under the curve of 1.0 in the training data set (sensitivity 100% [95% CI, 95\u2013100]; specificity 100% [95% CI, 96\u2013100]) and 0.82 in the validation data set (sensitivity 75% [95% CI, 59\u201386]; specificity 88% [95% CI, 75\u201394]). Reduced circulating levels of 4 other peptides (apolipoprotein L1, complement 5b, immunoglobulin heavy constant epsilon, and serum amyloid A4) found in children with high sudden cardiac death risk provided complete separation from the low and intermediate risk groups and predicted mortality and adverse arrhythmic outcomes (hazard ratio, 2.04 [95% CI, 1.0\u20134.2];\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.044).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>In children, a 7-biomarker proteomics panel can distinguish HCM from controls with high sensitivity and specificity, and another 4-biomarker panel identifies those at high risk of adverse arrhythmic outcomes, including sudden cardiac death.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.123.004448","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T05:00:47Z","timestamp":1717736447000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Novel Multiplexed Plasma Biomarker Panel Has Diagnostic and Prognostic Potential in Children With Hypertrophic Cardiomyopathy"],"prefix":"10.1161","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5662-0642","authenticated-orcid":true,"given":"Gabriella","family":"Captur","sequence":"first","affiliation":[{"name":"UCL MRC Unit for Lifelong Health &amp; 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Rare Cardiovascular Disease, Institute of Cardiovascular Science, London, United Kingdom (E.F., A.B., I.H., G.N., J.P.K.)."},{"name":"Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United Kingdom (E.F., A.B., I.H., G.N., J.P.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3629-4464","authenticated-orcid":true,"given":"Annabelle","family":"Barnes","sequence":"additional","affiliation":[{"name":"Centre for Paediatric Inherited &amp; Rare Cardiovascular Disease, Institute of Cardiovascular Science, London, United Kingdom (E.F., A.B., I.H., G.N., J.P.K.)."},{"name":"Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United Kingdom (E.F., A.B., I.H., G.N., J.P.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enpei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Translational Mass Spectrometry Research Group, UCL Institute of Child Health, London, United Kingdom (I.D., E.Z., W.E.H., K.M.)."},{"name":"UCL Medical School, University College London, London, United Kingdom (E.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7820-4474","authenticated-orcid":true,"given":"Imogen","family":"Heenan","sequence":"additional","affiliation":[{"name":"Centre for Paediatric Inherited &amp; Rare Cardiovascular Disease, Institute of Cardiovascular Science, London, United Kingdom (E.F., A.B., I.H., G.N., J.P.K.)."},{"name":"Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United Kingdom (E.F., A.B., I.H., G.N., J.P.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2064-237X","authenticated-orcid":true,"given":"Gabrielle","family":"Norrish","sequence":"additional","affiliation":[{"name":"Centre for Paediatric Inherited &amp; Rare Cardiovascular Disease, Institute of Cardiovascular Science, London, United Kingdom (E.F., A.B., I.H., G.N., J.P.K.)."},{"name":"Centre for Inherited Cardiovascular Diseases, Great Ormond Street Hospital, London, United Kingdom (E.F., A.B., I.H., G.N., J.P.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8071-1491","authenticated-orcid":true,"given":"James C.","family":"Moon","sequence":"additional","affiliation":[{"name":"Barts Heart Centre, the Cardiovascular Magnetic Resonance Unit, London, United Kingdom (J.C.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3383-3984","authenticated-orcid":true,"given":"Perry M.","family":"Elliott","sequence":"additional","affiliation":[{"name":"Barts Heart Centre, the Inherited Cardiovascular Diseases Unit, St Bartholomew\u2019s Hospital, London, United Kingdom (P.M.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2106-8760","authenticated-orcid":true,"given":"Wendy E.","family":"Heywood","sequence":"additional","affiliation":[{"name":"Translational Mass Spectrometry Research Group, UCL Institute of Child Health, London, United Kingdom (I.D., E.Z., W.E.H., K.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0763-8288","authenticated-orcid":true,"given":"Kevin","family":"Mills","sequence":"additional","affiliation":[{"name":"Translational Mass Spectrometry Research Group, UCL Institute of Child Health, London, United Kingdom (I.D., E.Z., W.E.H., K.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0014-9927","authenticated-orcid":true,"given":"Juan Pablo","family":"Kaski","sequence":"additional","affiliation":[{"name":"Centre for Paediatric Inherited &amp; 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