{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T04:15:51Z","timestamp":1791778551588,"version":"4.3.4"},"reference-count":43,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T00:00:00Z","timestamp":1717113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Almazov National Medical Research Centre of the Ministry of Health of Russian Federation","award":["075-15-2022-301"],"award-info":[{"award-number":["075-15-2022-301"]}]},{"name":"Ministry of Science and Higher Education of the Russian Federation","award":["075-15-2022-301"],"award-info":[{"award-number":["075-15-2022-301"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Myocardial fibrosis is an important factor in the progression of cardiovascular diseases. However, there is still no universal lifetime method of myocardial fibrosis assessment that has a high prognostic significance. The aim of the study was to determine the significance of ventricular endomyocardial biopsies for the assessment of myocardial fibrosis and to identify the severity of myocardial fibrosis in different cardiovascular diseases. Material and\u00a0Methods: Endomyocardial biopsies (EMBs) of 20 patients with chronic lymphocytic myocarditis (CM), endomyocardial fragments obtained during septal reduction of 21 patients with hypertrophic cardiomyopathy (HCM), and 36 patients with a long history of hypertensive and ischemic heart disease (HHD + IHD) were included in the study. The control group was formed from EMBs taken on 12\u201314 days after heart transplantation (n = 28). Also, for one patient without clinical and morphological data for cardiovascular pathology, postmortem myocardial fragments were taken from typical EMB and septal reduction sites. The relative area of fibrosis was calculated as the ratio of the total area of collagen fibers to the area of the whole biopsy. Endocardium and subendocardial fibrosis were not included in the total biopsy area. Results: The relative fibrosis area in the EMBs in the CM patient group was 5.6 [3.3; 12.6]%, 11.1 [6.6; 15.9]% in the HHD + IHD patient group, 13.4 [8.8; 16.7]% in the HCM patient group, and 2.7 [1.5; 4.6]% in the control group. When comparing the fibrosis area of the CM patients in repeat EMBs, it was found that the fibrosis area in the first EMBs was 7.6 [4.8; 12.0]%, and in repeat EMBs, it was 5.3 [3.2; 7.6]%. No statistically significant differences were found between the primary and repeat EMBs (p = 0.15). In ROC analysis, the area of fibrosis in the myocardium of 1.1% (or lower than one) was found to be highly specific for the control group of patients compared to the study patients. Conclusions: EMB in the assessment of myocardial fibrosis has a questionable role because of the heterogeneity of fibrotic changes in the myocardium.<\/jats:p>","DOI":"10.3390\/jcm13113275","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T05:58:00Z","timestamp":1717394280000},"page":"3275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Are Endomyocardial Ventricular Biopsies Useful for Assessing Myocardial Fibrosis?"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6175-8403","authenticated-orcid":false,"given":"Igor","family":"Makarov","sequence":"first","affiliation":[{"name":"Almazov National Medical Research Centre, St. Petersburg 197341, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6895-9987","authenticated-orcid":false,"given":"Daria","family":"Voronkina","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre, St. Petersburg 197341, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Gurshchenkov","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre, St. Petersburg 197341, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Ryzhkov","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre, St. Petersburg 197341, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9023-6986","authenticated-orcid":false,"given":"Anna","family":"Starshinova","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre, St. Petersburg 197341, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1878-4467","authenticated-orcid":false,"given":"Dmitry","family":"Kudlay","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Industrial Pharmacy, Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow 119991, Russia"},{"name":"Institute of Immunology FMBA of Russia, Moscow 115478, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubov","family":"Mitrofanova","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre, St. Petersburg 197341, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Karev, V., Starshinova, A.Y., Glushkova, A., Kudlay, D., and Starshinova, A. (2023). Features of Myocarditis: Morphological Differential Diagnosis in Post-COVID-19 Children. Diagnostics, 13.","DOI":"10.3390\/diagnostics13152499"},{"key":"ref_2","first-page":"88","article-title":"Myocardial fibrosis: Current aspects of the problem","volume":"89","author":"Karetnikova","year":"2017","journal-title":"Ter. Arkhiv"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1161\/CIRCULATIONAHA.111.089409","article-title":"Association between extracellular matrix expansion quantified by cardiovascular magnetic resonance and short-term mortality","volume":"126","author":"Wong","year":"2012","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/0735-1097(93)90094-H","article-title":"Which subgroup of patients with dilated cardiomyopathy would benefit from long-term beta-blocker therapy? A histologic viewpoint","volume":"21","author":"Yamada","year":"1993","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s10741-022-10247-5","article-title":"Endomyocardial biopsy in the clinical context: Current indications and challenging scenarios","volume":"28","author":"Porcari","year":"2023","journal-title":"Heart Fail. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"i1","DOI":"10.1093\/eurheartjsupp\/suae002","article-title":"The new 2023 ESC guidelines for the management of cardiomyopathies: A guiding path for cardiologist decisions","volume":"26","author":"Grasso","year":"2024","journal-title":"Eur. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Iorio, A., Luc\u00e0, F., Pozzi, A., Rao, C.M., Chimenti, C., Di Fusco, S.A., Rossini, R., Caretta, G., Cornara, S., and Giubilato, S. (2024). Anderson\u2013Fabry Disease: Red Flags for Early Diagnosis of Cardiac Involvement. Diagnostics, 14.","DOI":"10.3390\/diagnostics14020208"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s13244-023-01506-6","article-title":"Myocardial extracellular volume quantification with computed tomography-current status and future outlook","volume":"14","author":"Cundari","year":"2023","journal-title":"Insights Imaging"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.addr.2019.05.011","article-title":"Cardiac fibrosis\u2014A short review of causes and therapeutic strategies","volume":"146","author":"Hinderer","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_10","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."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.17116\/sudmed20216406143","article-title":"Causes and mechanisms of sudden cardiac death in children","volume":"64","author":"Mitrofanova","year":"2021","journal-title":"Sud.-Meditsinskaya Ekspertisa"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1161\/01.RES.5.4.357","article-title":"Quantitation of collagen in human myocardium","volume":"5","author":"Oken","year":"1957","journal-title":"Circ Res."},{"key":"ref_13","first-page":"216","article-title":"Quantification of left ventricular myocardial collagen system in children, young adults, and the elderly","volume":"72","author":"Mendes","year":"2012","journal-title":"Medicina"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107224","DOI":"10.1016\/j.carpath.2020.107224","article-title":"Morphometric characterization of collagen and fat in normal ventricular myocardium","volume":"48","author":"Miles","year":"2020","journal-title":"Cardiovasc. Pathol."},{"key":"ref_15","first-page":"309","article-title":"Myocardial fibrosis in endomyocardial biopsy specimens: Do different bioptomes affect estimation?","volume":"2","author":"Meckel","year":"1989","journal-title":"Am. J. Cardiovasc. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.jchf.2020.04.007","article-title":"Endomyocardial Biopsy Characterization of Heart Failure With Preserved Ejection Fraction and Prevalence of Cardiac Amyloidosis","volume":"8","author":"Hahn","year":"2020","journal-title":"JACC Heart Fail."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1161\/HYPERTENSIONAHA.112.196113","article-title":"Collagen cross-linking but not collagen amount associates with elevated filling pressures in hypertensive patients with stage C heart failure: Potential role of lysyl oxidase","volume":"60","author":"Querejeta","year":"2012","journal-title":"Hypertension"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1161\/HYPERTENSIONAHA.113.02654","article-title":"Association of cardiotrophin-1 with myocardial fibrosis in hypertensive patients with heart failure","volume":"63","author":"Querejeta","year":"2014","journal-title":"Hypertension"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1016\/j.jacc.2020.03.019","article-title":"Myocardial Interstitial Fibrosis in Nonischemic Heart Disease, Part 3\/4: JACC Focus Seminar","volume":"75","author":"Kovacic","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1253\/circj.CJ-11-0568","article-title":"Prognostic impact of myocardial interstitial fibrosis in non-ischemic heart failure.\u2014Comparison between preserved and reduced ejection fraction heart failure","volume":"75","author":"Aoki","year":"2011","journal-title":"Circ. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s12968-020-00674-4","article-title":"Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance","volume":"22","author":"Liu","year":"2020","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_22","first-page":"iv156","article-title":"Histological evidence of inflammatory reaction associated with fibrosis in the atrial and ventricular walls in a case-control study of patients with history of atrial fibrillation","volume":"18","author":"Mitrofanova","year":"2016","journal-title":"Europace"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s12968-016-0313-7","article-title":"Histologic validation of myocardial fibrosis measured by T1 mapping: A systematic review and meta-analysis","volume":"18","author":"Diao","year":"2016","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.jacc.2010.10.024","article-title":"Diastolic tissue Doppler indexes correlate with the degree of collagen expression and cross-linking in heart failure and normal ejection fraction","volume":"57","author":"Kasner","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Mitrofanova, L.B., Gorshkov, A.N., Lebedev, D.S., and Mikhaylov, E.N. (2014). Evidence of specialized tissue in human interatrial septum: Histological, immunohistochemical and ultrastructural findings. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113343"},{"key":"ref_26","first-page":"291","article-title":"Factors associated with reactive and reparative fibrosis of the myocardium","volume":"87","author":"Weber","year":"1992","journal-title":"Basic. Res. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1161\/CIRCRESAHA.115.306565","article-title":"Cardiac Fibrosis: The Fibroblast Awakens","volume":"118","author":"Travers","year":"2016","journal-title":"Circ. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"392","DOI":"10.31083\/j.rcm2312392","article-title":"Novel Approaches to Program Cells to Differentiate into Cardiomyocytes in Myocardial Regeneration","volume":"23","author":"Bonavida","year":"2022","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00018-013-1349-6","article-title":"The pathogenesis of cardiac fibrosis","volume":"71","author":"Kong","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"886553","DOI":"10.3389\/fcvm.2022.886553","article-title":"Cardiac Fibrosis in the Pressure Overloaded Left and Right Ventricle as a Therapeutic Target","volume":"9","author":"Schimmel","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/s41392-022-00972-6","article-title":"Signaling cascades in the failing heart and emerging therapeutic strategies","volume":"7","author":"He","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chen, G., Jiang, H., Yao, Y., Tao, Z., Chen, W., Huang, F., and Chen, X. (2022). Macrophage, a potential targeted therapeutic immune cell for cardiomyopathy. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.908790"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Nasyrov, R.A., Ivanov, D.O., Krasnogorskaya, O.L., Timchenko, V.N., Fedotova, E.P., Chepelev, A.S., Galichina, V.A., Sidorova, N.A., and Anichkov, N.M. (2023). COVID-19 in Children: Molecular Profile and Pathological Features. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242316750"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Vasichkina, E., Kofeynikova, O., Fetisova, S., Starshinova, A.Y., Sheyanova, E., Vershinina, T., Ryzhkov, A., Skripnik, A., Alekseeva, D., and Nechaeva, E. (2023). Severe Course of COVID-19 and Long-COVID-19 in Children: Difficulties in Diagnosis. Life, 13.","DOI":"10.3390\/life13030781"},{"key":"ref_35","first-page":"e981","article-title":"Possible Mechanisms of SARS-CoV2-Mediated Myocardial Injury","volume":"8","author":"Yu","year":"2023","journal-title":"Cardiovasc. Innov. Appl."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Vasichkina, E., Alekseeva, D., Kudryavtsev, I., Glushkova, A., Starshinova, A.Y., Malkova, A., Kudlay, D., and Starshinova, A. (2023). COVID-19 Heart Lesions in Children: Clinical, Diagnostic and Immunological Changes. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021147"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Mitrofanova, L.B., Makarov, I.A., Gorshkov, A.N., Runov, A.L., Vonsky, M.S., Pisareva, M.M., Komissarov, A.B., Makarova, T.A., Li, Q., and Karonova, T.L. (2023). Comparative Comparative Study of the Myocardium of Patients from Four COVID-19 Waves. Diagnostics, 13.","DOI":"10.3390\/diagnostics13091645"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s11897-023-00618-w","article-title":"Mechanism of COVID-19-Induced Cardiac Damage from Patient, In Vitro and Animal Studies","volume":"20","author":"Jones","year":"2023","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Makarov, I., Mayrina, S., Makarova, T., Karonova, T., Starshinova, A., Kudlay, D., and Mitrofanova, L. (2023). Morphological Changes in the Myocardium of Patients with Post-Acute Coronavirus Syndrome: A Study of Endomyocardial Biopsies. Diagnostics, 13.","DOI":"10.3390\/diagnostics13132212"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kudlay, D., Kofiadi, I., and Khaitov, M. (2022). Peculiarities of the T Cell Immune Response in COVID-19. Vaccines, 10.","DOI":"10.3390\/vaccines10020242"},{"key":"ref_41","first-page":"11","article-title":"Impaired cytotoxic CD8+ T cell response in elderly COVID-19 patients","volume":"11","author":"Westmeier","year":"2020","journal-title":"mBio"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Mitrofanova, L., Makarov, I., Goncharova, E., Makarova, T., Starshinova, A., Kudlay, D., and Shlaykhto, E. (2023). High Risk of Heart Tumors after COVID-19. Life, 13.","DOI":"10.3390\/life13102087"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.3389\/fimmu.2020.01142","article-title":"T Cells in Fibrosis and Fibrotic Diseases","volume":"11","author":"Zhang","year":"2020","journal-title":"Front. Immunol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/11\/3275\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:52:08Z","timestamp":1760107928000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/11\/3275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,31]]},"references-count":43,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["jcm13113275"],"URL":"https:\/\/doi.org\/10.3390\/jcm13113275","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,31]]}}}