{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:59:52Z","timestamp":1791910792120,"version":"4.3.4"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","license":[{"start":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T00:00:00Z","timestamp":1693872000000},"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":["Circulation"],"published-print":{"date-parts":[[2023,9,5]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>In hypertrophic cardiomyopathy (HCM), myocyte disarray and microvascular disease (MVD) have been implicated in adverse events, and recent evidence suggests that these may occur early. As novel therapy provides promise for disease modification, detection of phenotype development is an emerging priority. To evaluate their utility as early and disease-specific biomarkers, we measured myocardial microstructure and MVD in 3 HCM groups\u2014overt, either genotype-positive (G+LVH+) or genotype-negative (G\u2212LVH+), and subclinical (G+LVH\u2212) HCM\u2014exploring relationships with electrical changes and genetic substrate.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>This was a multicenter collaboration to study 206 subjects: 101 patients with overt HCM (51 G+LVH+ and 50 G\u2212LVH+), 77 patients with G+LVH\u2212, and 28 matched healthy volunteers. All underwent 12-lead ECG, quantitative perfusion cardiac magnetic resonance imaging (measuring myocardial blood flow, myocardial perfusion reserve, and perfusion defects), and cardiac diffusion tensor imaging measuring fractional anisotropy (lower values expected with more disarray), mean diffusivity (reflecting myocyte packing\/interstitial expansion), and second eigenvector angle (measuring sheetlet orientation).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              Compared with healthy volunteers, patients with overt HCM had evidence of altered microstructure (lower fractional anisotropy, higher mean diffusivity, and higher second eigenvector angle; all\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) and MVD (lower stress myocardial blood flow and myocardial perfusion reserve; both\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). Patients with G\u2212LVH+ were similar to those with G+LVH+ but had elevated second eigenvector angle (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001 after adjustment for left ventricular hypertrophy and fibrosis). In overt disease, perfusion defects were found in all G+ but not all G\u2212 patients (100% [51\/51] versus 82% [41\/50];\n              <jats:italic>P<\/jats:italic>\n              =0.001). Patients with G+LVH\u2212 compared with healthy volunteers similarly had altered microstructure, although to a lesser extent (all diffusion tensor imaging parameters;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001), and MVD (reduced stress myocardial blood flow [\n              <jats:italic>P<\/jats:italic>\n              =0.015] with perfusion defects in 28% versus 0 healthy volunteers [\n              <jats:italic>P<\/jats:italic>\n              =0.002]). Disarray and MVD were independently associated with pathological electrocardiographic abnormalities in both overt and subclinical disease after adjustment for fibrosis and left ventricular hypertrophy (overt: fractional anisotropy: odds ratio for an abnormal ECG, 3.3,\n              <jats:italic>P<\/jats:italic>\n              =0.01; stress myocardial blood flow: odds ratio, 2.8,\n              <jats:italic>P<\/jats:italic>\n              =0.015; subclinical: fractional anisotropy odds ratio, 4.0,\n              <jats:italic>P<\/jats:italic>\n              =0.001; myocardial perfusion reserve odds ratio, 2.2,\n              <jats:italic>P<\/jats:italic>\n              =0.049).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Microstructural alteration and MVD occur in overt HCM and are different in G+ and G\u2212 patients. Both also occur in the absence of hypertrophy in sarcomeric mutation carriers, in whom changes are associated with electrocardiographic abnormalities. Measurable changes in myocardial microstructure and microvascular function are early-phenotype biomarkers in the emerging era of disease-modifying therapy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.123.063835","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T23:01:11Z","timestamp":1689721271000},"page":"808-818","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":59,"title":["Microstructural and Microvascular Phenotype of Sarcomere Mutation Carriers and Overt Hypertrophic Cardiomyopathy"],"prefix":"10.1161","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1467-5490","authenticated-orcid":true,"given":"George","family":"Joy","sequence":"first","affiliation":[{"name":"Barts Heart Centre, Barts Health NHS Trust, London, UK (G.J., I.P., P.V., R.K.H., H.K., A.B., M.L., K.S., S.A.M., M.O., C.M., R.H.D., P.D.L., J.C.M., L.R.L.)."},{"name":"Institute of Cardiovascular Science (G.J.. M.W., I.P., R.K.H., F.C., A.B., M.L., K.S., M.O., C.M., R.H.D., P.D.L., G.C., J.C.M., L.R.L.), University College London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher I.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Sciences Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, UK (C.I.L., I.T., A.D., J.E.S., E.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2079-1455","authenticated-orcid":true,"given":"Matthew","family":"Webber","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Science (G.J.. M.W., I.P., R.K.H., F.C., A.B., M.L., K.S., M.O., C.M., R.H.D., P.D.L., G.C., J.C.M., L.R.L.), University College London, UK."},{"name":"Medical Research Council Unit for Lifelong Health and Ageing (M.W., I.P., F.C., R.H.D., G.C.), University College London, UK."},{"name":"Centre for Inherited Heart Muscle Conditions, Department of Cardiology, Royal Free London NHS Foundation Trust, UK (M.W., F.C., G.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8546-5023","authenticated-orcid":true,"given":"Iain","family":"Pierce","sequence":"additional","affiliation":[{"name":"Barts Heart Centre, Barts Health NHS Trust, London, UK (G.J., I.P., P.V., R.K.H., H.K., A.B., M.L., K.S., S.A.M., M.O., C.M., R.H.D., P.D.L., J.C.M., L.R.L.)."},{"name":"Institute of Cardiovascular Science (G.J.. M.W., I.P., R.K.H., F.C., A.B., M.L., K.S., M.O., C.M., R.H.D., P.D.L., G.C., J.C.M., L.R.L.), University College London, UK."},{"name":"Medical Research Council Unit for Lifelong Health and Ageing (M.W., I.P., F.C., R.H.D., G.C.), University College London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irvin","family":"Teh","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Sciences Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, UK (C.I.L., I.T., A.D., J.E.S., E.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"McGrath","sequence":"additional","affiliation":[{"name":"Imaging Department, Royal Brompton &amp; Harefield Hospitals, London, UK (L.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Velazquez","sequence":"additional","affiliation":[{"name":"Barts Heart Centre, Barts Health NHS Trust, London, UK (G.J., I.P., P.V., R.K.H., H.K., A.B., M.L., K.S., S.A.M., M.O., C.M., R.H.D., P.D.L., J.C.M., L.R.L.)."},{"name":"Cardiology Clinical and Academic Group, St. Georges University of London and St. Georges University Hospitals NHS Foundation Trust, UK (P.V., M.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2110-5234","authenticated-orcid":true,"given":"Rebecca K.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Barts Heart Centre, Barts Health NHS Trust, London, UK (G.J., I.P., P.V., R.K.H., H.K., A.B., M.L., K.S., S.A.M., M.O., C.M., R.H.D., P.D.L., J.C.M., L.R.L.)."},{"name":"Institute of Cardiovascular Science (G.J.. M.W., I.P., R.K.H., F.C., A.B., M.L., K.S., M.O., C.M., R.H.D., P.D.L., G.C., J.C.M., L.R.L.), University College London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huafrin","family":"Kotwal","sequence":"additional","affiliation":[{"name":"Barts Heart Centre, Barts Health NHS Trust, London, UK (G.J., I.P., P.V., R.K.H., H.K., A.B., M.L., K.S., S.A.M., M.O., C.M., R.H.D., P.D.L., J.C.M., L.R.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1134-3036","authenticated-orcid":true,"given":"Arka","family":"Das","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Sciences Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, UK (C.I.L., I.T., A.D., J.E.S., E.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Chan","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Science (G.J.. M.W., I.P., R.K.H., F.C., A.B., M.L., K.S., M.O., C.M., R.H.D., P.D.L., G.C., J.C.M., L.R.L.), University College London, UK."},{"name":"Medical Research Council Unit for Lifelong Health and Ageing (M.W., I.P., F.C., R.H.D., G.C.), University College London, UK."},{"name":"Centre for Inherited Heart Muscle Conditions, Department of Cardiology, Royal Free London NHS Foundation Trust, UK (M.W., F.C., G.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Bakalakos","sequence":"additional","affiliation":[{"name":"Barts Heart Centre, Barts Health NHS Trust, London, UK (G.J., I.P., P.V., R.K.H., H.K., A.B., M.L., K.S., S.A.M., M.O., C.M., R.H.D., P.D.L., J.C.M., L.R.L.)."},{"name":"Institute of Cardiovascular Science (G.J.. M.W., I.P., R.K.H., F.C., A.B., M.L., K.S., M.O., C.M., R.H.D., P.D.L., G.C., J.C.M., L.R.L.), University College London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1831-7853","authenticated-orcid":true,"given":"Massimiliano","family":"Lorenzini","sequence":"additional","affiliation":[{"name":"Barts Heart Centre, Barts Health NHS Trust, London, UK (G.J., I.P., P.V., R.K.H., H.K., A.B., M.L., K.S., S.A.M., M.O., C.M., R.H.D., P.D.L., J.C.M., L.R.L.)."},{"name":"Institute of Cardiovascular Science (G.J.. M.W., I.P., R.K.H., F.C., A.B., M.L., K.S., M.O., C.M., R.H.D., P.D.L., G.C., J.C.M., L.R.L.), University College London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1966-1880","authenticated-orcid":true,"given":"Konstantinos","family":"Savvatis","sequence":"additional","affiliation":[{"name":"Barts Heart Centre, Barts Health NHS Trust, London, UK (G.J., I.P., P.V., R.K.H., H.K., A.B., M.L., K.S., S.A.M., M.O., C.M., R.H.D., P.D.L., J.C.M., L.R.L.)."},{"name":"Institute of Cardiovascular Science (G.J.. M.W., I.P., R.K.H., F.C., A.B., M.L., K.S., M.O., C.M., R.H.D., P.D.L., G.C., J.C.M., L.R.L.), University College London, UK."},{"name":"William Harvey Research Institute, Queen Mary University London, UK (K.S., S.A.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1031-4084","authenticated-orcid":true,"given":"Saidi A.","family":"Mohiddin","sequence":"additional","affiliation":[{"name":"Barts Heart Centre, Barts Health NHS Trust, London, UK (G.J., I.P., P.V., R.K.H., H.K., A.B., M.L., K.S., S.A.M., M.O., C.M., R.H.D., P.D.L., J.C.M., L.R.L.)."},{"name":"William Harvey Research Institute, Queen Mary University London, UK (K.S., S.A.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5390-1596","authenticated-orcid":true,"given":"Peter W.","family":"Macfarlane","sequence":"additional","affiliation":[{"name":"Electrocardiology Section, School of Health and Wellbeing, University of Glasgow, UK (P.W.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5773-0344","authenticated-orcid":true,"given":"Michele","family":"Orini","sequence":"additional","affiliation":[{"name":"Barts Heart Centre, Barts Health NHS Trust, London, UK (G.J., I.P., P.V., R.K.H., H.K., A.B., M.L., K.S., S.A.M., M.O., C.M., R.H.D., P.D.L., J.C.M., L.R.L.)."},{"name":"Institute of Cardiovascular Science (G.J.. M.W., I.P., R.K.H., F.C., A.B., M.L., K.S., M.O., C.M., R.H.D., P.D.L., G.C., J.C.M., L.R.L.), University College London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0245-7090","authenticated-orcid":true,"given":"Charlotte","family":"Manisty","sequence":"additional","affiliation":[{"name":"Barts Heart Centre, Barts Health NHS Trust, London, UK (G.J., I.P., P.V., R.K.H., H.K., A.B., M.L., K.S., S.A.M., M.O., C.M., R.H.D., P.D.L., J.C.M., L.R.L.)."},{"name":"Institute of Cardiovascular Science (G.J.. M.W., I.P., R.K.H., F.C., A.B., M.L., K.S., M.O., C.M., R.H.D., P.D.L., G.C., J.C.M., L.R.L.), University College London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9875-6070","authenticated-orcid":true,"given":"Peter","family":"Kellman","sequence":"additional","affiliation":[{"name":"National Heart, Lung, and Blood Institute, National Institutes of Health, DHHS, Bethesda, MD (P.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhodri H.","family":"Davies","sequence":"additional","affiliation":[{"name":"Barts Heart Centre, Barts Health NHS Trust, London, UK (G.J., I.P., P.V., R.K.H., H.K., A.B., M.L., K.S., S.A.M., M.O., C.M., R.H.D., P.D.L., J.C.M., L.R.L.)."},{"name":"Institute of Cardiovascular Science (G.J.. M.W., I.P., R.K.H., F.C., A.B., M.L., K.S., M.O., C.M., R.H.D., P.D.L., G.C., J.C.M., L.R.L.), University College London, UK."},{"name":"Medical Research Council Unit for Lifelong Health and Ageing (M.W., I.P., F.C., R.H.D., G.C.), University College London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9055-9267","authenticated-orcid":true,"given":"Pier D.","family":"Lambiase","sequence":"additional","affiliation":[{"name":"Barts Heart Centre, Barts Health NHS Trust, London, UK (G.J., I.P., P.V., R.K.H., H.K., A.B., M.L., K.S., S.A.M., M.O., C.M., R.H.D., P.D.L., J.C.M., L.R.L.)."},{"name":"Institute of Cardiovascular Science (G.J.. M.W., I.P., R.K.H., F.C., A.B., M.L., K.S., M.O., C.M., R.H.D., P.D.L., G.C., J.C.M., L.R.L.), University College London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1475-2329","authenticated-orcid":true,"given":"Christopher","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Cardiovascular Innovation Research Centre, HVTI, Cleveland Clinic, OH (C.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0999-5684","authenticated-orcid":true,"given":"Jurgen E.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Sciences Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, UK (C.I.L., I.T., A.D., J.E.S., E.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8962-3524","authenticated-orcid":true,"given":"Maite","family":"Tome","sequence":"additional","affiliation":[{"name":"Cardiology Clinical and Academic Group, St. Georges University of London and St. Georges University Hospitals NHS Foundation Trust, UK (P.V., M.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5662-0642","authenticated-orcid":true,"given":"Gabriella","family":"Captur","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Science (G.J.. M.W., I.P., R.K.H., F.C., A.B., M.L., K.S., M.O., C.M., R.H.D., P.D.L., G.C., J.C.M., L.R.L.), University College London, UK."},{"name":"Medical Research Council Unit for Lifelong Health and Ageing (M.W., I.P., F.C., R.H.D., G.C.), University College London, UK."},{"name":"Centre for Inherited Heart Muscle Conditions, Department of Cardiology, Royal Free London NHS Foundation Trust, UK (M.W., F.C., G.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Dall\u2019Armellina","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Sciences Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, UK (C.I.L., I.T., A.D., J.E.S., E.D.)."}],"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, Barts Health NHS Trust, London, UK (G.J., I.P., P.V., R.K.H., H.K., A.B., M.L., K.S., S.A.M., M.O., C.M., R.H.D., P.D.L., J.C.M., L.R.L.)."},{"name":"Institute of Cardiovascular Science (G.J.. 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