{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T05:17:21Z","timestamp":1787980641669,"version":"build-2784847793"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T00:00:00Z","timestamp":1766188800000},"content-version":"vor","delay-in-days":1566,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Nippon Medical School Alumni","award":["2018-01"],"award-info":[{"award-number":["2018-01"]}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K08460"],"award-info":[{"award-number":["20K08460"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K16026"],"award-info":[{"award-number":["17K16026"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K08460"],"award-info":[{"award-number":["20K08460"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K16026"],"award-info":[{"award-number":["17K16026"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The aim of the present study was to consider whether the ultrastructural features of cardiomyocytes in dilated cardiomyopathy can be used to guide genetic testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Endomyocardial biopsy and whole-exome sequencing were performed in 32 consecutive sporadic dilated cardiomyopathy patients [51.0 (40.0\u201364.0) years, 75% men] in initial phases of decompensated heart failure. The predicted pathogenicity of ultrarare (minor allele frequency \u22640.0005), non-synonymous variants was determined using the American College of Medical Genetics guidelines. Focusing on 75 cardiomyopathy-susceptibility and 41 arrhythmia-susceptibility genes, we identified 404 gene variants, of which 15 were considered pathogenic or likely pathogenic in 14 patients (44% of 32). There were five sarcomeric gene variants (29% of 17 variants) found in five patients (16% of 32), involving a variant of MYBPC3 and four variants of TTN. A patient with an MYBPC3 variant showed disorganized sarcomeres, three patients with TTN variants located in the region encoding the A-band domain showed sparse sarcomeres, and a patient with a TTN variant in encoding the I-band domain showed disrupted sarcomeres. The distribution of diffuse myofilament lysis depended on the causal genes; three patients with the same TMEM43 variant had diffuse myofilament lysis near nuclei (P = 0.011), while two patients with different DSP variants had lysis in the peripheral areas of cardiomyocytes (P = 0.033).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Derangement patterns of myofilament and subcellular distribution of myofilament lysis might implicate causal genes. Large-scale studies are required to confirm whether these ultrastructural findings are related to the causative genes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.13596","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T05:42:16Z","timestamp":1630906936000},"page":"5178-5191","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Myocardial Ultrastructure can Augment Genetic Testing for Sporadic Dilated Cardiomyopathy with Initial Heart Failure"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8214-2736","authenticated-orcid":false,"given":"Tsunenori","family":"Saito","sequence":"first","affiliation":[{"name":"Smidt Heart Institute, Cedars-Sinai Medical Center , 8700 Beverly Blvd, Los Angeles, CA, 90048 ,","place":["USA"]},{"name":"Department of Cardiovascular Medicine, Nippon Medical School Graduate School , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko Saito","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Neurology, Japanese Red Cross Medical Center , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Mozawa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Nippon Medical School Graduate School , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Adachi","sequence":"additional","affiliation":[{"name":"Division of Morphological and Biomolecular Research, Graduate School of Medicine, Nippon Medical School , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Division of Morphological and Biomolecular Research, Graduate School of Medicine, Nippon Medical School , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotoka","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute, Cedars-Sinai Medical Center , 8700 Beverly Blvd, Los Angeles, CA, 90048 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiichiro","family":"Oka","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Nippon Medical School Graduate School , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Department of Hygiene and Public Health, Nippon Medical School Graduate School , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eitaro","family":"Kodani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Nippon Medical School Tama Nagayama Hospital , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuniya","family":"Asai","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Nippon Medical School Chiba Hokusoh Hospital , Chiba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoichi","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Nippon Medical School Graduate School , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Nippon Medical School Graduate School , Tokyo ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta A.","family":"Gottlieb","sequence":"additional","affiliation":[{"name":"Smidt Heart Institute, Cedars-Sinai Medical Center , 8700 Beverly Blvd, Los Angeles, CA, 90048 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,9,6]]},"reference":[{"key":"2026012114192281800_ehf213596-bib-0001","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1093\/eurheartj\/ehs397","article-title":"Diagnostic work-up in cardiomyopathies: bridging the gap between clinical phenotypes and final diagnosis. 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