{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T01:46:52Z","timestamp":1790214412028,"version":"4.1.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2017,2,20]],"date-time":"2017-02-20T00:00:00Z","timestamp":1487548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"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"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dilated cardiomyopathy (DCM) is the most common cardiomyopathy and causes left ventricular enlargement and contractile dysfunction, with a poor prognosis. The mechanisms underlying the disease process have not been precisely identified, but recent evidence has suggested that the activation of myocardial inflammation is involved in the deterioration associated with the condition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Biopsy samples from 182 consecutive DCM patients were immunohistochemically stained with antibodies specific to CD3 (T lymphocytes), CD68 (whole macrophages), and CD163 (M2 macrophages), and each type of infiltrating cell was counted. Masson's trichrome staining was used to determine the collagen area fraction (CAF) in each sample. Patients were followed up for 6.9\u2009\u00b1\u20092.4\u2009years, and their clinical data were obtained for analysis. Median (interquartile range) numbers of myocardial CD3, CD68, and CD163-cell infiltrates were 8.1 (4.0\u201314.2)\/mm2, 22.3 (12.1\u201336.0)\/mm2, and 6.5 (2.0\u201314.0)\/mm2, respectively. Patients with higher counts of infiltrating CD3-, CD68-, and CD163-positive cells had significantly poorer outcomes (P\u2009=\u20090.007, P\u2009=\u20090.011, and P\u2009=\u20090.022, respectively). A high CD163-positive infiltrate count was independently associated with worse outcome in multivariate Cox regression analysis (hazard ratio 1.77, P\u2009=\u20090.004), and multivariate linear regression analysis revealed that the CD163 cell count was an independent determinant of CAF (P\u2009&amp;lt;\u20090.001).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>It was found that DCM with increased myocardial immune activation was associated with poor long-term outcome. The association between M2 macrophages and collagen formation suggests the phenotypic polarization of macrophages toward M2 may be associated with ventricular remodelling in DCM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.767","type":"journal-article","created":{"date-parts":[[2017,2,20]],"date-time":"2017-02-20T01:52:52Z","timestamp":1487555572000},"page":"490-498","source":"Crossref","is-referenced-by-count":84,"title":["Clinical Impact of the Presence of Macrophages in Endomyocardial Biopsies of Patients with Dilated Cardiomyopathy"],"prefix":"10.1093","volume":"19","author":[{"given":"Takafumi","family":"Nakayama","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center , 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Sugano","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center , 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuro","family":"Yokokawa","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center , 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Nagai","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center , 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taka-aki","family":"Matsuyama","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Cerebral and Cardiovascular Center , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Ohta-Ogo","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Cerebral and Cardiovascular Center , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Cerebral and Cardiovascular Center , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatsue","family":"Ishibashi-Ueda","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Cerebral and Cardiovascular Center , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Nakatani","sequence":"additional","affiliation":[{"name":"Department of Transplantation, National Cerebral and Cardiovascular Center , Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Ohte","sequence":"additional","affiliation":[{"name":"Department of Cardio-Renal Medicine and Hypertension, Nagoya City University \u00a0","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Yasuda","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center , 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihisa","family":"Anzai","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center , 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,2,20]]},"reference":[{"key":"2026011721182353800_ejhf767-bib-0001","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1056\/NEJM200004133421502","article-title":"Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy","volume":"342","author":"Felker","year":"2000","journal-title":"N Engl J Med"},{"key":"2026011721182353800_ejhf767-bib-0002","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1161\/01.CIR.99.8.1091","article-title":"From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future","volume":"99","author":"Kawai","year":"1999","journal-title":"Circulation"},{"key":"2026011721182353800_ejhf767-bib-0003","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1161\/CIRCULATIONAHA.108.769489","article-title":"Predictors of outcome in patients with suspected myocarditis","volume":"118","author":"Kindermann","year":"2008","journal-title":"Circulation"},{"issue":"Suppl O","key":"2026011721182353800_ejhf767-bib-0004","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1093\/eurheartj\/16.suppl_O.100","article-title":"Immunohistochemistry in dilated cardiomyopathy","volume":"16","author":"Kuhl","year":"1995","journal-title":"Eur Heart J"},{"key":"2026011721182353800_ejhf767-bib-0005","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1161\/CIRCRESAHA.114.304951","article-title":"Lack in treatment options for virus-induced inflammatory cardiomyopathy: can iPS-derived cardiomyocytes close the gap?","volume":"115","author":"Van Linthout","year":"2014","journal-title":"Circ Res"},{"issue":"Suppl O","key":"2026011721182353800_ejhf767-bib-0006","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1093\/eurheartj\/16.suppl_O.168","article-title":"Treatment of chronic myocarditis with corticosteroids","volume":"16","author":"Kuhl","year":"1995","journal-title":"Eur Heart J"},{"key":"2026011721182353800_ejhf767-bib-0007","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1161\/01.CIR.103.22.2681","article-title":"Immunohistological changes in dilated cardiomyopathy induced by immunoadsorption therapy and subsequent immunoglobulin substitution","volume":"103","author":"Staudt","year":"2001","journal-title":"Circulation"},{"key":"2026011721182353800_ejhf767-bib-0008","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1161\/01.CIR.104.1.39","article-title":"Randomized, placebo-controlled study for immunosuppressive treatment of inflammatory dilated cardiomyopathy: two-year follow-up results","volume":"104","author":"Wojnicz","year":"2001","journal-title":"Circulation"},{"key":"2026011721182353800_ejhf767-bib-0009","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1093\/eurheartj\/ehp249","article-title":"Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: the TIMIC study","volume":"30","author":"Frustaci","year":"2009","journal-title":"Eur Heart J"},{"key":"2026011721182353800_ejhf767-bib-0010","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1016\/j.jacc.2007.09.008","article-title":"The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology","volume":"50","author":"Cooper","year":"2007","journal-title":"J Am Coll Cardiol"},{"key":"2026011721182353800_ejhf767-bib-0011","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nri978","article-title":"Alternative activation of macrophages","volume":"3","author":"Gordon","year":"2003","journal-title":"Nat Rev Immunol"},{"key":"2026011721182353800_ejhf767-bib-0012","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.jaut.2009.09.012","article-title":"Alternatively activated macrophages in infection and autoimmunity","volume":"33","author":"Fairweather","year":"2009","journal-title":"J Autoimmun"},{"key":"2026011721182353800_ejhf767-bib-0013","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1100\/2011\/213962","article-title":"Macrophage polarization in health and disease","volume":"11","author":"Cassetta","year":"2011","journal-title":"Sci World J"},{"key":"2026011721182353800_ejhf767-bib-0014","doi-asserted-by":"crossref","first-page":"816460","DOI":"10.1155\/2015\/816460","article-title":"Understanding the mysterious M2 macrophage through activation markers and effector mechanisms","volume":"2015","author":"Roszer","year":"2015","journal-title":"Mediators Inflamm"},{"key":"2026011721182353800_ejhf767-bib-0015","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1161\/CIRCULATIONAHA.111.052126","article-title":"Regulatory role of dendritic cells in postinfarction healing and left ventricular remodelling","volume":"125","author":"Anzai","year":"2012","journal-title":"Circulation"},{"key":"2026011721182353800_ejhf767-bib-0016","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1161\/CIRCRESAHA.111.300502","article-title":"Matrix metalloproteinase-28 deletion exacerbates cardiac dysfunction and rupture after myocardial infarction in mice by inhibiting M2 macrophage activation","volume":"112","author":"Ma","year":"2013","journal-title":"Circ Res"},{"key":"2026011721182353800_ejhf767-bib-0017","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.114.000839","article-title":"Decreased myocardial dendritic cells is associated with impaired reparative fibrosis and development of cardiac rupture after myocardial infarction in humans","volume":"3","author":"Nagai","year":"2014","journal-title":"J Am Heart Assoc"},{"key":"2026011721182353800_ejhf767-bib-0018","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S1388-9842(99)00047-1","article-title":"Familial dilated cardiomyopathy: clinical features in French families","volume":"1","author":"Mangin","year":"1999","journal-title":"Eur J Heart Fail"},{"key":"2026011721182353800_ejhf767-bib-0019","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1016\/j.echo.2005.10.005","article-title":"Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology","volume":"18","author":"Lang","year":"2005","journal-title":"J Am Soc Echocardiogr"},{"key":"2026011721182353800_ejhf767-bib-0020","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1253\/circj.CJ-15-0663","article-title":"Prognostic Impact of Functional Mitral Regurgitation in Patients Admitted With Acute Decompensated Heart Failure","volume":"80","author":"Wada","year":"2016","journal-title":"Circ J"},{"key":"2026011721182353800_ejhf767-bib-0021","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/ejhf.464","article-title":"Significance of myocardial tenascin-C expression in left ventricular remodelling and long-term outcome in patients with dilated cardiomyopathy","volume":"18","author":"Yokokawa","year":"2016","journal-title":"Eur J Heart Fail"},{"key":"2026011721182353800_ejhf767-bib-0022","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1093\/eurheartj\/eht210","article-title":"Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases","volume":"34","author":"Caforio","year":"2013","journal-title":"Eur Heart J"},{"issue":"Suppl C","key":"2026011721182353800_ejhf767-bib-0023","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1093\/eurheartj\/15.suppl_C.62","article-title":"Immunohistological characterization of infiltrating lymphocytes in biopsies of patients with clinically suspected dilated cardiomyopathy","volume":"15","author":"Kuhl","year":"1994","journal-title":"Eur Heart J"},{"key":"2026011721182353800_ejhf767-bib-0024","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1253\/jcj.65.797","article-title":"Myocardial inflammatory cell infiltrates in cases of dilated cardiomyopathy as a determinant of outcome following partial left ventriculectomy","volume":"65","author":"Kanzaki","year":"2001","journal-title":"Jpn Circ J"},{"key":"2026011721182353800_ejhf767-bib-0025","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1097\/00005792-199907000-00005","article-title":"The spectrum of dilated cardiomyopathy. The Johns Hopkins experience with 1,278 patients","volume":"78","author":"Felker","year":"1999","journal-title":"Medicine"},{"key":"2026011721182353800_ejhf767-bib-0026","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1136\/hrt.75.3.295","article-title":"Immunohistological evidence for a chronic intramyocardial inflammatory process in dilated cardiomyopathy","volume":"75","author":"Kuhl","year":"1996","journal-title":"Heart"},{"key":"2026011721182353800_ejhf767-bib-0027","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1369\/jhc.5A6871.2006","article-title":"AM-3\u2009K, an anti-macrophage antibody, recognizes CD163, a molecule associated with an anti-inflammatory macrophage phenotype","volume":"54","author":"Komohara","year":"2006","journal-title":"J Histochem Cytochem"},{"key":"2026011721182353800_ejhf767-bib-0028","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1007\/s10753-015-0214-1","article-title":"Elevated endomyocardial biopsy macrophage-related markers in intractable myocardial diseases","volume":"38","author":"Hayashi","year":"2015","journal-title":"Inflammation"},{"key":"2026011721182353800_ejhf767-bib-0029","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1007\/s10753-014-9941-y","article-title":"Macrophages regulate renal fibrosis through modulating TGFbeta superfamily signalling","volume":"37","author":"Shen","year":"2014","journal-title":"Inflammation"},{"key":"2026011721182353800_ejhf767-bib-0030","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/nri2748","article-title":"Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells","volume":"10","author":"Glass","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"2026011721182353800_ejhf767-bib-0031","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s00059-005-2730-5","article-title":"Inflammatory dilated cardiomyopathy (DCMI)","volume":"30","author":"Maisch","year":"2005","journal-title":"Herz"},{"key":"2026011721182353800_ejhf767-bib-0032","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.ejphar.2009.12.019","article-title":"Left ventricular enlargement in coxsackievirus-B3 induced chronic myocarditis \u2013 ongoing inflammation and an imbalance of the matrix degrading system","volume":"630","author":"Rutschow","year":"2010","journal-title":"Eur J Pharmacol"},{"key":"2026011721182353800_ejhf767-bib-0033","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1080\/08916930500484906","article-title":"Autoimmunity in coxsackievirus B3 induced myocarditis","volume":"39","author":"Huber","year":"2006","journal-title":"Autoimmunity"},{"key":"2026011721182353800_ejhf767-bib-0034","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.ahj.2007.02.013","article-title":"Detection of viral genome in the myocardium: lack of prognostic and functional relevance in patients with acute dilated cardiomyopathy","volume":"153","author":"Kuethe","year":"2007","journal-title":"Am Heart J"},{"key":"2026011721182353800_ejhf767-bib-0035","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1159\/000443375","article-title":"Clinical significance of viral genome persistence in the myocardium of patients with dilated cardiomyopathy","volume":"58","author":"Nowalany-Kozielska","year":"2015","journal-title":"Intervirology"},{"key":"2026011721182353800_ejhf767-bib-0036","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1093\/eurheartj\/ehv727","article-title":"Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases","volume":"37","author":"Pinto","year":"2016","journal-title":"Eur Heart J"},{"key":"2026011721182353800_ejhf767-bib-0037","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1056\/NEJM198910193211601","article-title":"A prospective, randomized, controlled trial of prednisone for dilated cardiomyopathy","volume":"321","author":"Parrillo","year":"1989","journal-title":"N Engl J Med"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fejhf.767","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/19\/4\/490\/66330532\/eurjhf_19_4_490.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/19\/4\/490\/66330532\/eurjhf_19_4_490.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T02:19:48Z","timestamp":1768702788000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/19\/4\/490\/8418786"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,20]]},"references-count":37,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2017,2,20]]},"published-print":{"date-parts":[[2017,4,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ejhf.767","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,4]]},"published":{"date-parts":[[2017,2,20]]}}}