Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease associated with increased cardiovascular morbidity and mortality. Myocardial fibrosis, a key pathological consequence of prolonged inflammation, contributes to diastolic dysfunction and the development of heart failure with preserved ejection fraction (HFpEF) in RA patients. Understanding its pathophysiology, early detection, and potential therapeutic strategies is crucial for improving patient outcomes. In this study we explore the underlying mechanisms of myocardial fibrosis in RA, focusing on immune-mediated pathways, oxidative stress, and extracellular matrix dysregulation, with concise look at the impact of immunosuppressive therapy on cardiac remodeling and role of speckle-tracking echocardiography (STE) in detecting subclinical myocardial fibrosis, emphasizing global longitudinal strain (GLS) as a promising surrogate marker. Key words Rheumatoid arthritis " Myocardial fibrosis " Diastolic dysfunction " Cardiovascular disease surveillance " Strain echocardiography.

Faculty of Medicine Comenius University in Bratislava and 5th Department of Internal Medicine University Hospital Bratislava Ružinov Bratislava Slovak Republic

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Chen J, Norling LV, Cooper D. Cardiac Dysfunction in Rheumatoid Arthritis: The Role of Inflammation. Cells. 2021;10:881. doi: 10.3390/cells10040881. PubMed DOI PMC

Özkan U, Kakilli N, Gürdoğan M, Taştekin N, Birtane M. Rheumatoid arthritis and cardiovascular comorbidities. Explor Musculoskeletal Dis. 2023;1:264–288. doi: 10.37349/emd.2023.00028. DOI

Davis JM, 3rd, Lin G, Oh JK, Crowson CS, Achenbach SJ, Therneau TM, Matteson EL, et al. Five-year changes in cardiac structure and function in patients with rheumatoid arthritis compared with the general population. Int J Cardiol. 2017;240:379–385. doi: 10.1016/j.ijcard.2017.03.108. PubMed DOI PMC

Alexandre A, Sá-Couto D, Brandão M, Cabral S, Fonseca T, Costa RQ, Marinho A, Vasconcelos C, et al. Subclinical left ventricular dysfunction in rheumatoid arthritis: findings from the prospective Porto-RA cohort. Clin Res Cardiol. 2024 doi: 10.1007/s00392-024-02548-6. PubMed DOI PMC

Schau T, Gottwald M, Arbach O, Seifert M, Schöpp M, Neuß M, Butter C, Zänker M. Increased Prevalence of Diastolic Heart Failure in Patients with Rheumatoid Arthritis Correlates with Active Disease, but Not with Treatment Type. J Rheumatol. 2015;42:2029–2037. doi: 10.3899/jrheum.141647. PubMed DOI

Paulus WJ, Zile MR. From Systemic Inflammation to Myocardial Fibrosis. Circ Res. 2021;128:1451–1467. doi: 10.1161/CIRCRESAHA.121.318159. PubMed DOI PMC

Kuneš J, Hojná S, Mráziková L, Montezano A, Touyz RM, Maletínská L. Obesity, Cardiovascular and Neurodegenerative Diseases: Potential Common Mechanisms. Physiol Res. 2023;72(Suppl 2):S73–S90. doi: 10.33549/physiolres.935109. PubMed DOI PMC

Park E, Griffin J, Bathon JM. Myocardial Dysfunction and Heart Failure in Rheumatoid Arthritis. Arthritis Rheumatol. 2022;74:184–199. doi: 10.1002/art.41979. PubMed DOI PMC

Borsky P, Fiala Z, Andrys C, Beranek M, Hamakova K, Kremlacek J, Malkova A, et al. C-reactive protein, chemerin, fetuin-A and osteopontin as predictors of cardiovascular risks in persons with psoriasis vulgaris. Physiol Res. 2021;70:383–391. doi: 10.33549/physiolres.934654. PubMed DOI PMC

Grillet B, Pereira RVS, Van Damme J, Abu El-Asrar A, Proost P, Opdenakker G. Matrix metalloproteinases in arthritis: towards precision medicine. Nat Rev Rheumatol. 2023;19:363–377. doi: 10.1038/s41584-023-00966-w. PubMed DOI

Kotake S, Yago T, Kobashigawa T, Nanke Y. The Plasticity of Th17 Cells in the Pathogenesis of Rheumatoid Arthritis. J Clin Med. 2017;6:67. doi: 10.3390/jcm6070067. PubMed DOI PMC

Maggi L, Mazzoni A, Cimaz R, Liotta F, Annunziato F, Cosmi L. Th17 and Th1 Lymphocytes in Oligoarticular Juvenile Idiopathic Arthritis. Front Immunol. 2019;10:450. doi: 10.3389/fimmu.2019.00450. PubMed DOI PMC

Silverman GJ, Carson DA. Roles of B cells in rheumatoid arthritis. Arthritis Res Ther. 2003;5(Suppl 4):S1–S6. doi: 10.1186/ar1010. PubMed DOI PMC

da Fonseca LJS, Nunes-Souza V, Goulart MOF, Rabelo LA. Oxidative Stress in Rheumatoid Arthritis: What the Future Might Hold regarding Novel Biomarkers and Add-On Therapies. Oxid Med Cell Longev. 2019;2019:7536805. doi: 10.1155/2019/7536805. PubMed DOI PMC

Luo P, Xu W, Ye D, Chen W, Ying J, Liu B, Li J, et al. Metabolic Syndrome Is Associated With an Increased Risk of Rheumatoid Arthritis: A Prospective Cohort Study Including 369,065 Participants. J Rheumatol. 2024;51:360–367. doi: 10.3899/jrheum.2023-0349. PubMed DOI

Firestein GS. Pathogenesis of rheumatoid arthritis: the intersection of genetics and epigenetics. Trans Am Clin Climatol Assoc. 2018;129:171–182. PubMed PMC

Nguyen MN, Kiriazis H, Gao XM, Du XJ. Cardiac Fibrosis and Arrhythmogenesis. Compr Physiol. 2017;7:1009–1049. doi: 10.1002/j.2040-4603.2017.tb00771.x. PubMed DOI

Zeller CB, Appenzeller S. Cardiovascular disease in systemic lupus erythematosus: the role of traditional and lupus related risk factors. Curr Cardiol Rev. 2008;4:116–122. doi: 10.2174/157340308784245775. PubMed DOI PMC

Lazzerini PE, Laghi-Pasini F, Boutjdir M, Capecchi PL. Cardioimmunology of arrhythmias: the role of autoimmune and inflammatory cardiac channelopathies. Nat Rev Immunol. 2019;19:63–64. doi: 10.1038/s41577-018-0098-z. PubMed DOI

Gulati A, Jabbour A, Ismail TF, Guha K, Khwaja J, Raza S, Morarji K, et al. Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. JAMA. 2013;309:896–908. doi: 10.1001/jama.2013.1363. PubMed DOI

Draghi A, Borch TH, Radic HD, Chamberlain CA, Gokuldass A, Svane IM, Donia M. Differential effects of corticosteroids and anti-TNF on tumor-specific immune responses: implications for the management of irAEs. Int J Cancer. 2019;145:1408–1413. doi: 10.1002/ijc.32080. PubMed DOI

Szappanos Á, Hajas Á, Hartyánszky I, Jr, Kádár K, Kuthi L, Hartyánszky I, Merkely B, Nagy AI. Severe cardiovascular manifestation of ASIA syndrome triggered by silicone breast implants. Rheumatology (Oxford) 2025;64:1550–1552. doi: 10.1093/rheumatology/keae564. PubMed DOI

Lazou A, Ikonomidis I, Bartekova M, Benedek T, Makavos G, Palioura D, Cabrera Fuentes H, Andreadou I. Chronic inflammatory diseases, myocardial function and cardioprotection. Br J Pharmacol. 2020;177:5357–5374. doi: 10.1111/bph.14975. PubMed DOI PMC

Padjen I, Crnogaj MR, Anić B. Conventional disease-modifying agents in rheumatoid arthritis - a review of their current use and role in treatment algorithms. Reumatologia. 2020;58:390–400. doi: 10.5114/reum.2020.101400. PubMed DOI PMC

Roubille C, Coffy A, Rincheval N, Dougados M, Flipo RM, Daurès JP, Combe B. Ten-year analysis of the risk of severe outcomes related to low-dose glucocorticoids in early rheumatoid arthritis. Rheumatology (Oxford) 20212;60:3738–3746. doi: 10.1093/rheumatology/keaa850. PubMed DOI

Barnabe C, Martin B-J, Ghali WA. Systematic review and meta-analysis: Anti-tumor necrosis factor α therapy and cardiovascular events in rheumatoid arthritis. Arthritis Care Res (Hoboken) 2011;63:522–529. doi: 10.1002/acr.20371. PubMed DOI

Slezák J, Kura B, Frimmel K, Zálešák M, Ravingerová T, Viczenczová C, Okruhlicová Ľ, Tribulová N. Preventive and therapeutic application of molecular hydrogen in situations with excessive production of free radicals. Physiol Res. 2016;65(Suppl 1):S11–S28. doi: 10.33549/physiolres.933414. PubMed DOI

Roubille C, Richer V, Starnino T, McCourt C, McFarlane A, Fleming P, Siu S, et al. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Ann Rheum Dis. 2015;74:480–489. doi: 10.1136/annrheumdis-2014-206624. PubMed DOI PMC

Setoguchi S, Schneeweiss S, Avorn J, Katz JN, Weinblatt ME, Levin R, Solomon DH. Tumor necrosis factor-α antagonist use and heart failure in elderly patients with rheumatoid arthritis. Am Heart J. 2008;156:336–341. doi: 10.1016/j.ahj.2008.02.025. PubMed DOI PMC

Coletta AP, Clark AL, Banarjee P, Cleland JGF. Clinical trials update: RENEWAL (RENAISSANCE and RECOVER) and ATTACH. Eur J Heart Fail. 2002;4:559–561. doi: 10.1016/S1388-9842(02)00121-6. PubMed DOI

Bozkurt B, Torre-Amione G, Warren MS, Whitmore J, Soran OZ, Feldman AM, Mann DL. Results of Targeted Anti-Tumor Necrosis Factor Therapy With Etanercept (ENBREL) in Patients With Advanced Heart Failure. Circulation. 2001;103:1044–1047. doi: 10.1161/01.CIR.103.8.1044. PubMed DOI

Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation. 2003;107:3133–3140. doi: 10.1161/01.CIR.0000077913.60364.D2. PubMed DOI

Singh S, Fumery M, Singh AG, Singh N, Prokop LJ, Dulai PS, Sandborn WJ, Curtis JR. Comparative Risk of Cardiovascular Events With Biologic and Synthetic Disease-Modifying Antirheumatic Drugs in Patients With Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. Arthritis Care Res (Hoboken) 2020;72:561–576. doi: 10.1002/acr.23875. PubMed DOI PMC

Feng R, Liu H, Chen Y. Baricitinib represses the myocardial fibrosis via blocking JAK/STAT and TGF-β1 pathways in vivo and in vitro. BMC Cardiovasc Disord. 2025;25:65. doi: 10.1186/s12872-025-04517-x. PubMed DOI PMC

Hasni SA, Gupta S, Davis M, Poncio E, Temesgen-Oyelakin Y, Carlucci PM, Wang X, et al. Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus. Nat Commun. 2021;12:3391. doi: 10.1038/s41467-021-23361-z. PubMed DOI PMC

Buch MH, Mallat Z, Dweck MR, Tarkin JM, O’Regan DP, Ferreira V, Youngstein T, Plein S. Current understanding and management of cardiovascular involvement in rheumatic immune-mediated inflammatory diseases. Nat Rev Rheumatol. 2024;20:614–634. doi: 10.1038/s41584-024-01149-x. PubMed DOI

Fardet L, Petersen I, Nazareth I. Risk of cardiovascular events in people prescribed glucocorticoids with iatrogenic Cushing’s syndrome: cohort study. BMJ. 2012;345:e4928. doi: 10.1136/bmj.e4928. PubMed DOI PMC

Ridker PM, Everett BM, Pradhan A, MacFadyen JG, Solomon DH, Zaharris E, Mam V, et al. Low-Dose Methotrexate for the Prevention of Atherosclerotic Events. N Engl J Med. 2019;380:752–762. doi: 10.1056/NEJMoa1809798. PubMed DOI PMC

Sitia S, Tomasoni L, Turiel M. Speckle tracking echocardiography: A new approach to myocardial function. World J Cardiol. 2010;2:1–5. doi: 10.4330/wjc.v2.i1.1. PubMed DOI PMC

Neradilova C, Gregorovicova M, Kovanda J, Kvasilova A, Melenovsky V, Nanka O, Sedmera D. “Form follows function”: the developmental morphology of the cardiac atria. Physiol Res. 2024;73(Suppl 3):S697–S714. doi: 10.33549/physiolres.935503. PubMed DOI PMC

Abou R, van der Bijl P, Bax JJ, Delgado V. Global longitudinal strain: clinical use and prognostic implications in contemporary practice. Heart. 2020;106:1438–1444. doi: 10.1136/heartjnl-2019-316215. PubMed DOI

Chadalavada S, Rauseo E, Sanghvi M, Lee AM, Amir-Khalili A, Chirvasa M, Banik S, et al. Diabetes worsens the adverse association between myocardial diffuse fibrosis and left ventricular strain. Eur Heart J. 2024;45(Suppl 1):ehae666.252. doi: 10.1093/eurheartj/ehae666.252. DOI

Witt UE, Müller ML, Beyer RE, Wieditz J, Salem S, Hashemi D, Chen W, et al. A simplified approach to discriminate between healthy subjects and patients with heart failure using cardiac magnetic resonance myocardial deformation imaging. Eur Heart J Imaging Methods Pract. 2024;2:qyae093. doi: 10.1093/ehjimp/qyae093. PubMed DOI PMC

Abdelrahman Elkassas LS, Raief Mosaad BM, Ibrahim AS. Advanced Myocardial Characterization in Hypertrophic Cardiomyopathy: Feasibility of CMR-based Feature Tracking Strain Analysis. QJM-Int J Med. 2024;117(Suppl 1):hcae070.568. doi: 10.1093/qjmed/hcae070.568. DOI

Hu X, Bao Y, Zhu Y, Zheng K, Zhang J, Zhou W, Deng Y, Liu Y. Predicting Left Ventricular Myocardial Fibrosis in Patients with Hypertrophic Cardiomyopathy by Speckle Tracking Automated Functional Imaging. Ultrasound Med Biol. 2023;49:1309–1317. doi: 10.1016/j.ultrasmedbio.2023.01.020. PubMed DOI

Li Y, Liu J, Cao Y, Han X, Shao G, Zhou X, Gu J, et al. Predictive values of multiple non-invasive markers for myocardial fibrosis in hypertrophic cardiomyopathy patients with preserved ejection fraction. Sci Rep. 2021;11:4297. doi: 10.1038/s41598-021-83678-z. PubMed DOI PMC

Reiber JHC. Global longitudinal strain (GLS) Int J Cardiovasc Imaging. 2022;38:269–270. doi: 10.1007/s10554-022-02556-5. PubMed DOI

Harper AR, Patel HC, Lyon AR. Heart failure with preserved ejection fraction. Clin Med (Lond) 2018;18(Suppl 2):S24–S29. doi: 10.7861/clinmedicine.18-2-s24. PubMed DOI PMC

Regitz-Zagrosek V, Kararigas G. Mechanistic Pathways of Sex Differences in Cardiovascular Disease. Physiol Rev. 2017;97:1–37. doi: 10.1152/physrev.00021.2015. PubMed DOI

Metsios GS, Stavropoulos-Kalinoglou A, Kitas GD. The role of exercise in the management of rheumatoid arthritis. Expert Rev Clin Immunol. 2015;11:1121–1130. doi: 10.1586/1744666X.2015.1067606. PubMed DOI

Metsios GS, Stavropoulos-Kalinoglou A, Veldhuijzen van Zanten JJ, Nightingale P, Sandoo A, Dimitroulas T, Kitas GD, Koutedakis Y. Individualised exercise improves endothelial function in patients with rheumatoid arthritis. Ann Rheum Dis. 2014;73:748–751. doi: 10.1136/annrheumdis-2013-203291. PubMed DOI

Cooney JK, Law RJ, Matschke V, Lemmey AB, Moore JP, Ahmad Y, Jones JG, et al. Benefits of exercise in rheumatoid arthritis. J Aging Res. 2011;2011:681640. doi: 10.4061/2011/681640. PubMed DOI PMC

Sköldstam L, Hagfors L, Johansson G. An experimental study of a Mediterranean diet intervention for patients with rheumatoid arthritis. Ann Rheum Dis. 2003;62:208–214. doi: 10.1136/ard.62.3.208. PubMed DOI PMC

Montoya T, Sánchez-Hidalgo M, Castejón ML, Rosillo M, González-Benjumea A, Alarcón-de-la-Lastra C. Dietary Oleocanthal Supplementation Prevents Inflammation and Oxidative Stress in Collagen-Induced Arthritis in Mice. Antioxidants (Basel) 2021;10:650. doi: 10.3390/antiox10050650. PubMed DOI PMC