{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T05:04:14Z","timestamp":1773291854727,"version":"3.50.1"},"reference-count":29,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"unspecified","delay-in-days":70,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["2646098"],"award-info":[{"award-number":["2646098"]}],"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":["JP19H03442"],"award-info":[{"award-number":["JP19H03442"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["24ek0109683h0002"],"award-info":[{"award-number":["24ek0109683h0002"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013642","name":"Japan Heart Foundation","doi-asserted-by":"publisher","award":["Grant on Dilated Cardiomyopathy"],"award-info":[{"award-number":["Grant on Dilated Cardiomyopathy"]}],"id":[{"id":"10.13039\/501100013642","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Open Heart"],"accepted":{"date-parts":[[2025,2,24]]},"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Among patients with dilated cardiomyopathy (DCM), myocardial inflammation and fibrosis are risk factors for poor clinical outcomes. Here, we investigated the combined prognostic value of these two factors, as evaluated using myocardial biopsy samples.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This retrospective and multicentre study included patients with DCM\u2014defined as LVEF of \u226445% and left diastolic diameter of &gt;112% of predicted value, without evidence of secondary or ischaemic cardiomyopathy. In myocardial biopsy samples, inflammatory cells were counted using immunohistochemistry, and Masson\u2019s Trichrome staining was performed to quantify the myocardial fibrosis as collagen area fraction (CAF). Higher myocardial inflammation was defined as leucocytes of \u226514\/mm\u00b2, including \u22644 monocytes\/mm\u00b2, with CD3<jats:sup>+<\/jats:sup> T lymphocytes of\u22657\/mm\u00b2. Greater myocardial fibrosis was defined as CAF of&gt;5.9% by the Youden\u2019s index. The primary endpoint was cardiac death or left ventricular assist device implantation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 255 DCM patients were enrolled (average age, 53.1 years; 78% males). Within this cohort, the mean LVEF was 28.0%, mean CAF was 10.7% and median CD3<jats:sup>+<\/jats:sup> cell count was 8.3\/mm<jats:sup>2<\/jats:sup>. During the median follow-up period of 2688 days, 46 patients met the primary endpoint. Multivariable Cox proportional hazard analyses revealed that CD3<jats:sup>+<\/jats:sup> cell count and CAF were independent determinants of the primary endpoint. Kaplan\u2013Meier analysis showed that patients with both higher myocardial inflammation and greater fibrosis had the worst prognosis (log-rank p&lt;0.001). When myocardial inflammation was graded as one of three degrees: T lymphocytes of &lt;13\/mm\u00b2 (low); 13 of 13.1\u201323.9\/mm\u00b2 (moderate); and T lymphocytes of \u226524\u2009\/mm\u00b2 (high), patients with moderate inflammation exhibited a superior survival rate when CAF was \u22645.9%, but a worse survival rate when CAF was &gt;5.9%.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Having both biopsy-proven higher myocardial inflammation and greater fibrosis predicted the worst clinical prognosis in patients with DCM.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/openhrt-2025-003250","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T06:54:39Z","timestamp":1741848879000},"page":"e003250","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical impact of combined assessment of myocardial inflammation and fibrosis using myocardial biopsy in patients with dilated cardiomyopathy: a multicentre, retrospective cohort study"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3529-6238","authenticated-orcid":false,"given":"Takafumi","family":"Nakayama","sequence":"first","affiliation":[{"name":"Department of Cardiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiko Ohta","family":"Ogo","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Cerebral and Cardiovascular Center, Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuo","family":"Sugano","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Keiyu Hospital, Yokohama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuro","family":"Yokokawa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromitsu","family":"Kanamori","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6395-5072","authenticated-orcid":false,"given":"Yoshihiko","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Cerebral and Cardiovascular Center, Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiaki","family":"Hiroe","sequence":"additional","affiliation":[{"name":"Department of Cardiology, National Center for Global Health and Medicine, Shinjuku-ku, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kinta","family":"Hatakeyama","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Cerebral and Cardiovascular Center, Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hatsue","family":"Ishibashi-Ueda","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Cerebral and Cardiovascular Center, Suita, Japan"},{"name":"Department of Pathology, Hokusetsu General Hospital, Takatsuki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8845-3626","authenticated-orcid":false,"given":"Kazufumi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Center for Advanced Heart Failure, Okayama University Hospital, Okayama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaoru","family":"Dohi","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihisa","family":"Anzai","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan"},{"name":"Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoko","family":"Imanaka-Yoshida","sequence":"additional","affiliation":[{"name":"Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu, 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inflammation predicts adverse outcome in patients with cardiac AL amyloidosis","volume":"20","author":"Siegismund","year":"2018","journal-title":"Eur J Heart Fail"},{"key":"2025081709560304000_12.1.e003250.16","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.118.009052","article-title":"Immune-Mediated Myocarditis in Fabry Disease Cardiomyopathy","volume":"7","author":"Frustaci","year":"2018","journal-title":"J Am Heart Assoc"},{"key":"2025081709560304000_12.1.e003250.17","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.ijcard.2022.05.068","article-title":"Clinical impact of the pathological quantification of myocardial fibrosis and infiltrating T lymphocytes using an endomyocardial biopsy in patients with hypertrophic cardiomyopathy","volume":"362","author":"Shintani","year":"2022","journal-title":"Int J 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fibrosis beforehand in dilated cardiomyopathy?","volume":"11","author":"Amemiya","year":"2024","journal-title":"ESC Heart Fail"},{"key":"2025081709560304000_12.1.e003250.28","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1253\/circj.CJ-18-0063","article-title":"Inflammatory Mechanisms of Cardiovascular Remodeling","volume":"82","author":"Anzai","year":"2018","journal-title":"Circ J"},{"key":"2025081709560304000_12.1.e003250.29","doi-asserted-by":"publisher","DOI":"10.1038\/nri3800"}],"container-title":["Open 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