{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T02:46:04Z","timestamp":1783565164294,"version":"3.55.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>In hypertrophic cardiomyopathy (HCM), the mechanisms through which pathogenic sarcomere variants (G+) lead to left ventricular hypertrophy (LVH) are not understood.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>\n              VANISH (Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy) was a multicenter, double-blind, placebo-controlled, randomized trial testing valsartan\u2019s ability to attenuate phenotypic progression in early sarcomeric (G+LVH+) and subclinical HCM (G+LVH\u2012). The outcome was a composite z-score reflecting change in cardiac remodeling from baseline to year 2 (end of study). Baseline and year 2 blood samples were used to quantify 276 proteins using a proximity extension assay (Olink, Sweden). We explored relative differences in protein abundance between early and subclinical HCM at baseline. In addition, we compared proteomic changes between baseline and year 2 in subclinical HCM participants who experienced phenotypic conversion to early HCM (convertors) versus nonconvertors; early HCM participants receiving valsartan versus placebo; and in association with changes in the phenotypic progression z-score. Comparisons were made using the\n              <jats:italic toggle=\"yes\">t<\/jats:italic>\n              -test, Mann-Whitney\n              <jats:italic toggle=\"yes\">U<\/jats:italic>\n              test, linear mixed models, and generalized linear models, correcting for multiple testing using a 5% false discovery rate\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>Circulating proteins were analyzed in 192 participants (32 subclinical and 160 early HCM [81 allocated to valsartan]). NT-proBNP (N-terminal pro-B-type natriuretic peptide) differentiated early from subclinical HCM and tracked with phenotypic progression in early HCM (1-unit worsening in z-score associated with a 27% increase in NT-proBNP [95% CI, 17\u201337%]). Some extracellular matrix remodeling proteins showed a higher abundance (eg, tissue-type plasminogen activator) in early compared with subclinical HCM or tracked with disease progression (decorin) in early HCM. Some growth factors had a higher relative abundance in early HCM (eg, fibroblast growth factor-21). While no individual protein was able to distinguish phenotypic convertors from nonconvertors, multiprotein panels including lipocalin 2, lectin-like oxidized low-density lipoprotein receptor 1, and either NT-proBNP or interleukin-17 receptor A, could distinguish these groups.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>NT-proBNP was the most informative protein, showing a higher abundance in early compared with subclinical HCM and tracking with the phenotypic progression z-score in early-stage HCM. Studying pathways involving growth factors and extracellular matrix remodeling may yield additional insights into the mechanisms behind disease progression in sarcomevere variant carriers and early HCM.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>REGISTRATION:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT01912534.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.124.012393","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T09:00:27Z","timestamp":1746781227000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Proteomic Analysis of Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) Clinical Trial"],"prefix":"10.1161","volume":"18","clinical-trial-number":[{"clinical-trial-number":"nct01912534","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5826-9617","authenticated-orcid":true,"given":"Constantin-Cristian","family":"Topriceanu","sequence":"first","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (C.-C.T., A.C.P., C.E.S., N.K.L., C.Y.H.)."},{"name":"UCL Institute of Cardiovascular Science, University College London, United Kingdom (C.-C.T., J.C.M., G.C.)."},{"name":"Unit for Lifelong Health and Ageing at UCL, University College London, United Kingdom (C.-C.T., G.C.)."},{"name":"Cardiac MRI Unit, Barts Heart Centre, London, United Kingdom (C.-C.T., J.C.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0834-206X","authenticated-orcid":true,"given":"Christoffer Rasmus","family":"Vissing","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Denmark (C.R.V., A.A.R., H.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8665-3309","authenticated-orcid":true,"given":"Anna","family":"Axelsson Raja","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Denmark (C.R.V., A.A.R., H.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9802-7188","authenticated-orcid":true,"given":"Sharlene M.","family":"Day","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia (S.M.D., A.T.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4855-9260","authenticated-orcid":true,"given":"Mark W.","family":"Russell","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor (M.W.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Zahka","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Foundation, OH (K.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7782-5540","authenticated-orcid":true,"given":"Alexandre C.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (C.-C.T., A.C.P., C.E.S., N.K.L., C.Y.H.)."},{"name":"Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of S\u00e3o Paulo Medical School, Brazil (A.C.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7941-0947","authenticated-orcid":true,"given":"Steven D.","family":"Colan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Boston Children\u2019s Hospital, MA (S.D.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9254-3202","authenticated-orcid":true,"given":"Anne M.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD (A.M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-7337","authenticated-orcid":true,"given":"Charles","family":"Canter","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, St Louis, MO (C.C., R.G.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7249-3727","authenticated-orcid":true,"given":"Richard G.","family":"Bach","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, St Louis, MO (C.C., R.G.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8721-3022","authenticated-orcid":true,"given":"Matthew T.","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, CA (M.T.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8284-0673","authenticated-orcid":true,"given":"Joseph W.","family":"Rossano","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Philadelphia, PA (J.W.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9669-8495","authenticated-orcid":true,"given":"Anjali T.","family":"Owens","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia (S.M.D., A.T.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1116-2286","authenticated-orcid":true,"given":"Luisa","family":"Mestroni","sequence":"additional","affiliation":[{"name":"University of Colorado Anschutz Medical Campus, Aurora, CO (L.M., M.R.G.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9043-0810","authenticated-orcid":true,"given":"Matthew R. G.","family":"Taylor","sequence":"additional","affiliation":[{"name":"University of Colorado Anschutz Medical Campus, Aurora, CO (L.M., M.R.G.T.)."}],"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":"UCL Institute of Cardiovascular Science, University College London, United Kingdom (C.-C.T., J.C.M., G.C.)."},{"name":"Cardiac MRI Unit, Barts Heart Centre, London, United Kingdom (C.-C.T., J.C.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5662-0642","authenticated-orcid":true,"given":"Gabriella","family":"Captur","sequence":"additional","affiliation":[{"name":"UCL Institute of Cardiovascular Science, University College London, United Kingdom (C.-C.T., J.C.M., G.C.)."},{"name":"Unit for Lifelong Health and Ageing at UCL, University College London, United Kingdom (C.-C.T., 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