{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:38:42Z","timestamp":1785425922318,"version":"3.56.0"},"reference-count":20,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara"},{"id":[{"id":"https:\/\/ror.org\/00afdp487","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Severe mitral regurgitation (MR) is associated with chronic atrial stretch, chamber enlargement, pulmonary pressure elevation, and atrial fibrosis, yet the relationship between tissue inflammatory\/profibrotic signaling, histologically quantified fibrosis, and echocardiographic remodeling remains incompletely characterized. This study aimed to compare biatrial tissue remodeling in patients with severe MR undergoing mitral valve surgery with a practical non-valvular surgical comparator group undergoing isolated coronary artery bypass grafting (CABG). Methods: This single-center, observational, cross-sectional comparative study included 36 elective cardiac-surgery patients: 22 with severe MR and 14 undergoing isolated CABG without significant valvular disease. Left- and right-atrial tissue samples were collected intraoperatively. IL-6, TNF-\u03b1, and TGF-\u03b2 expression was assessed by quantitative real-time PCR using pooled atrial samples stratified by atrial side and study group, whereas atrial fibrosis was quantified histologically on individual tissue specimens using Masson\u2019s trichrome staining and digital image analysis. Clinical, laboratory, and echocardiographic parameters were compared between groups, and exploratory associations were assessed with cautious interpretation. Results: Compared with the CABG comparator group, patients with severe MR showed a pooled molecular profile compatible with higher aggregate atrial expression of IL-6, TNF-\u03b1, and TGF-\u03b2; because qPCR was performed on pooled tissue preparations, these molecular findings were interpreted descriptively and were not used for patient-level inferential statistics. Histologically quantified fibrosis was significantly increased in severe MR in both the left atrium (29.69 \u00b1 12.26% vs. 12.17 \u00b1 4.56%, p &lt; 0.0001) and the right atrium (25.25 \u00b1 11.33% vs. 9.01 \u00b1 4.46%, p &lt; 0.0001). The MR group also showed more pronounced echocardiographic remodeling, including larger estimated left atrial volume, higher pulmonary artery systolic pressure, and greater right ventricular diameter. Exploratory individual-level analyses were restricted to histological fibrosis and echocardiographic variables. Conclusions: Severe MR was associated with marked echocardiographic remodeling and significantly greater histologically quantified biatrial fibrosis compared with a CABG surgical comparator group. Pooled qPCR findings support an aggregate inflammatory\/profibrotic signal, but they should be interpreted descriptively because individual-level molecular variability could not be assessed. These findings are hypothesis-generating and do not establish causality.<\/jats:p>","DOI":"10.3390\/diagnostics16142183","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:55:21Z","timestamp":1783990521000},"page":"2183","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biatrial Inflammatory and Profibrotic Remodeling in Severe Mitral Regurgitation: A Comparative Tissue and Echocardiographic Study Versus CABG Comparator Group"],"prefix":"10.3390","volume":"16","author":[{"given":"Adrian-Grigore","family":"Merce","sequence":"first","affiliation":[{"name":"Doctoral School Medicine\u2013Pharmacy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Efimie Murgu Sq. No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Department of Cardiology, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Advanced Research Center, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Multidisciplinary Doctoral School, \u201cVasile Goldi\u0219\u201d Western University of Arad, 310025 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1298-9090","authenticated-orcid":false,"given":"Daniel-Dumitru","family":"Ni\u0219ulescu","sequence":"additional","affiliation":[{"name":"Doctoral School Medicine\u2013Pharmacy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Efimie Murgu Sq. No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Department of Cardiology, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Advanced Research Center, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Multidisciplinary Doctoral School, \u201cVasile Goldi\u0219\u201d Western University of Arad, 310025 Arad, Romania"},{"name":"Department of Histology, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, 310025 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8510-6653","authenticated-orcid":false,"given":"Anca","family":"Hermenean","sequence":"additional","affiliation":[{"name":"Department of Histology, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, 310025 Arad, Romania"},{"name":"\u201cAurel Ardelean\u201d Institute of Life Sciences, \u201cVasile Goldi\u0219\u201d Western University of Arad, 310025 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana-Maria","family":"Burciu","sequence":"additional","affiliation":[{"name":"Doctoral School Medicine\u2013Pharmacy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Efimie Murgu Sq. No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Discipline of Radiology and Medical Imaging, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Sq. No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9501-5530","authenticated-orcid":false,"given":"Iulia-Raluca","family":"Munteanu","sequence":"additional","affiliation":[{"name":"Doctoral School Medicine\u2013Pharmacy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Efimie Murgu Sq. No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Department of Cardiology, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Advanced Research Center, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian-Petru","family":"Merce","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Advanced Research Center, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Department of Cardiovascular Surgery, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9003-456X","authenticated-orcid":false,"given":"Daniel-Miron","family":"Brie","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Advanced Research Center, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anik\u00f3","family":"Morno\u0219","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Advanced Research Center, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7378-7787","authenticated-orcid":false,"given":"Drago\u0219 Constantin","family":"Cozma","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Advanced Research Center, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Cardiology Department, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Sq. No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5998-2932","authenticated-orcid":false,"given":"Raluca","family":"Coifan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Advanced Research Center, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Cardiology Department, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Sq. No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6096-9601","authenticated-orcid":false,"given":"Cristian","family":"Morno\u0219","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Advanced Research Center, Institute of Cardiovascular Diseases Timi\u0219oara, 300310 Timi\u0219oara, Romania"},{"name":"Cardiology Department, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Sq. No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4635","DOI":"10.1093\/eurheartj\/ehaf194","article-title":"2025 ESC\/EACTS Guidelines for the Management of Valvular Heart Disease","volume":"46","author":"Praz","year":"2025","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3892","DOI":"10.1038\/s41598-023-31163-0","article-title":"Left Atrial Size Predicts Outcome in Severe but Asymptomatic Mitral Regurgitation","volume":"13","author":"Zilberszac","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.jtcvs.2019.08.040","article-title":"Preoperative Left Atrial Volume Index Is Associated with Postoperative Outcomes in Mitral Valve Repair for Chronic Mitral Regurgitation","volume":"160","author":"Balachandran","year":"2020","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1093\/eurheartj\/ehm199","article-title":"Left Atrial Remodelling in Mitral Regurgitation\u2014Methodologic Approach, Physiological Determinants, and Outcome Implications: A Prospective Quantitative Doppler-Echocardiographic and Electron Beam-Computed Tomographic Study","volume":"28","author":"Bellamy","year":"2007","journal-title":"Eur. Heart J."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Stassen, J., van Wijngaarden, A.L., Wu, H.W., Palmen, M., Tomsic, A., Delgado, V., Bax, J.J., and Marsan, N.A. (2022). Left Atrial Remodeling after Mitral Valve Repair for Primary Mitral Regurgitation: Evolution over Time and Prognostic Significance. J. Cardiovasc. Dev. Dis., 9.","DOI":"10.3390\/jcdd9070230"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jmu.2016.09.003","article-title":"Role of Left Atrial Reservoir Strain Rate in Left Atrial Remodeling in Severe Mitral Regurgitation","volume":"25","author":"Yang","year":"2017","journal-title":"J. Med. Ultrasound"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.amjcard.2012.10.049","article-title":"Usefulness of Atrial Deformation Analysis to Predict Left Atrial Fibrosis and Endocardial Thickness in Patients Undergoing Mitral Valve Operations for Severe Mitral Regurgitation Secondary to Mitral Valve Prolapse","volume":"111","author":"Cameli","year":"2013","journal-title":"Am. J. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"El Mathari, S., Kluin, J., Hopman, L.H.G.A., Bhagirath, P., Oudeman, M.A.P., Vonk, A.B.A., Nederveen, A.J., Eberl, S., Klautz, R.J.M., and Chamuleau, S.A.J. (2023). The Role and Implications of Left Atrial Fibrosis in Surgical Mitral Valve Repair as Assessed by CMR: The ALIVE Study Design and Rationale. Front. Cardiovasc. Med., 10.","DOI":"10.3389\/fcvm.2023.1166703"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7278","DOI":"10.1038\/s41598-020-64308-6","article-title":"Regulation of Left Atrial Fibrosis Induced by Mitral Regurgitation by SIRT1","volume":"10","author":"Zhang","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jelectrocard.2021.11.031","article-title":"Mitral Valve Regurgitation Is Associated with Left Atrial Fibrosis in Patients with Atrial Fibrillation","volume":"70","author":"Wu","year":"2022","journal-title":"J. Electrocardiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Bouwmeester, S., van Loon, T., Ploeg, M., Mast, T.P., Verzaal, N., van Middendorp, L.B., Strik, M., van Nieuwenhoven, F.A., Dekker, L.R., and Prinzen, F.W. (2022). Left Atrial Remodeling in Mitral Regurgitation: A Combined Experimental-Computational Study. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0271588"},{"key":"ref_12","first-page":"101327","article-title":"Atrial Fibrillation in Human Patients Is Associated with Increased Collagen Type V and TGFbeta1","volume":"50","author":"Kostin","year":"2024","journal-title":"Int. J. Cardiol. Heart Vasc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3892\/ijmm.2020.4842","article-title":"Atrial Fibrosis Underlying Atrial Fibrillation","volume":"47","author":"Li","year":"2021","journal-title":"Int. J. Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1016\/j.jacc.2014.02.555","article-title":"Atrial Remodeling and Atrial Fibrillation: Recent Advances and Translational Perspectives","volume":"63","author":"Nattel","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Pang, Z., Ren, Y., and Yao, Z. (2025). Interactions between Atrial Fibrosis and Inflammation in Atrial Fibrillation. Front. Cardiovasc. Med., 12.","DOI":"10.3389\/fcvm.2025.1578148"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1080\/14017430802651803","article-title":"Activated Nuclear Factor-\u03baB and Increased Tumor Necrosis Factor-Alpha in Atrial Tissue of Atrial Fibrillation","volume":"43","author":"Qu","year":"2009","journal-title":"Scand. Cardiovasc. J."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Rosca, C.I., Sharma, A., Nisulescu, D.-D., Otiman, G., Duda-Seiman, D.-M., Morariu, S.I., Lighezan, D.F., and Kundnani, N.R. (2023). Prevalence of Cardio-Embolic Brain Complications in Permanent and Paroxysmal Atrial Fibrillation Patients. Healthcare, 11.","DOI":"10.3390\/healthcare11020175"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Rosca, C.I., Lighezan, D.F., Nisulescu, D.-D., Sharma, A., Neagu, M.N., Nistor, D., Georgescu, D., and Kundnani, N.R. (2023). Metabolic Syndrome: A Strange Companion of Atrial Fibrillation; A Blessing in Disguise from the Neuropsychiatric Point of View. Biomedicines, 11.","DOI":"10.3390\/biomedicines11072012"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.jacc.2018.06.048","article-title":"Myocardial Fibrosis in Patients with Primary Mitral Regurgitation with and Without Prolapse","volume":"72","author":"Kitkungvan","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/nature01323","article-title":"Inflammation in Atherosclerosis","volume":"420","author":"Libby","year":"2002","journal-title":"Nature"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/14\/2183\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T01:03:40Z","timestamp":1783991020000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/14\/2183"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,13]]},"references-count":20,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["diagnostics16142183"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16142183","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,13]]}}}