Cardiac sarcoidosis: epidemiology, etiology, pathogenesis and pathomorphology (literature review)

The review presents an analysis of current literature data on cardiac sarcoidosis (CS), the frequency of which varies widely in the structure of systemic sarcoidosis – from 3 to 39%. Many authors have noted a general upward trend in the prevalence and incidence of both systemic and CS, with variations depending on geographical region and ethnicity. It is suggested that the clinical phenotypes of CS differ depending on ethnic predisposition and sex. The role of human leukocyte antigen (HLA) polymorphism and specific alleles in the development of cardiac involvement in sarcoidosis has been investigated. The possible influence of infectious agents (Cutibacterium acnes, Mycobacterium tuberculosis, etc.) as an initiating factor in the development of the disease is considered. Non-caseating epithelioid granulomas, a specific morphological feature of sarcoidosis, can be localized in any part of the myocardium, leading to rhythm and conduction disturbances, the development of ventricular aneurysms, and heart failure. Multinucleated giant cells are detected in non-caseating epithelioid granulomas in no more than 20% of CS cases, and the absence of this specific pathomorphological feature does not rule out cardiac involvement in sarcoidosis. The staging of granulomatous inflammation supports the use of surrogate histopathological signs, including microgranulomas, clusters of M1-macrophages, signs of lymphangiogenesis, confluent fibrosis and fatty infiltration of the myocardium.

1. Chuchalin AG, Avdeev SN, Ajsanov ZR, Baranova OP, Borisov SE, Geppe NA. Sarcoidosis: federal clinical guidelines for diagnosis and treatment. Russian Pulmonology Journal. 2022; 32(6): 806–833. (In Russ.). doi: 10.18093/0869-0189-2022-32-6-806-833

2. Sharma R, Kouranos V, Cooper LT, Metra M, Ristic A, Heidecker B, et al. Management of cardiac sarcoidosis. European heart journal. 2024; 45(30): 2697–2726. doi: 10.1093/eurheartj/ehae356

3. Hamzeh N, Steckman DA, Sauer WH, Judson MA. Pathophysiology and clinical management of cardiac sarcoidosis. Nature reviews. Cardiology. 2015; 12(5): 278–288. doi: 10.1038/nrcardio.2015.22

4. Birnie DH, Nery PB, Ha AC, Beanlands RS. Cardiac sarcoidosis. Journal of the American College of Cardiology. 2016; 68(4): 411–21. doi: 10.1016/j.jacc.2016.03.605

5. Vizel’ AA, Vizel’ IYu, Amirov NB. Epidemiology of sarcoidosis in the Russian Federation. The Bulletin of Contemporary Clinical Medicine. 2017; 10(5): 66–73. (In Russ.). doi: 10.20969/VSKM.2017.10(5).66-73

6. Hena KM. Sarcoidosis epidemiology: race matters. Frontiers in immunology. 2020; 11: 537382. doi: 10.3389/fimmu.2020.537382

7. Serçe Unat D. Epidemiology and etiology of sarcoidosis. Shedding light on sarcoidosis – the path from etiology to prognosis. Intech Open Journals. 2025; 1-18. doi: 10.5772/intechopen.1011795

8. Miyashita K, Hashimoto K, Maeda S, Suda T. Current epidemiological and clinical features of sarcoidosis in Japan: a nationwide claims data study. Cureus. 2025; 17(5): e83328. doi: 10.7759/cureus.83328

9. Tan JL, Fong HK, Birati EY, Han Y. Cardiac Sarcoidosis. The American journal of cardiology. 2019; 123(3): 513–522. doi: 10.1016/j.amjcard.2018.10.021

10. Santulli G. Cardiac Sarcoidosis: updated insights on epidemiology and diagnostic criteria. American journal of cardiology. 2023; 204: 425–427. doi: 10.1016/j.amjcard.2023.07.123

11. Farina N, De Luca G, Peretto G, Bartoli A, Esposito A, Matucci-Cerinic M, et al. Cardiac sarcoidosis: clinical insights, diagnosis, and management strategies. Reviews in cardiovascular medicine. 2025; 26(2): 26605. doi: 10.31083/RCM26605

12. Shabalin VV, Grinshtejn YuI. Cardiac sarcoidosis: modern diagnostics and therapy. Russian Journal of Cardiology. 2020; 25(11): 4052. (In Russ.). doi: 10.15829/1560-4071-2020-4052

13. Cheng RK, Kittleson MM, Beavers CJ, Birnie DH, Blankstein R, Bravo PE, et al. Diagnosis and management of cardiac sarcoidosis: a scientific statement from the American Heart Association. Circulation. 2024; 149(21): e1197– e1216. doi: 10.1161/CIR.0000000000001240

14. Kawai H, Sarai M, Kato Y, Naruse H, Watanabe A, Matsuyama T, et al. Diagnosis of isolated cardiac sarcoidosis based on new guidelines. ESC heart failure. 2020; 7(5): 2662–2671. doi: 10.1002/ehf2.12853

15. Mankad P, Mitchell B, Birnie D, Kron J. Cardiac sarcoidosis. Current cardiology reports. 2019; 21(12): 152. doi: 10.1007/s11886-019-1238-1

16. Trisvetova EL, Iudina OA, Smolensky AZ, Cherstvyi ED. Diagnosis of isolated cardiac sarcoidosis. Russian Journal of Archive of Pathology. 2019; 81(1): 57–64. (In Russ.). doi: 10.17116/patol20198101157

17. Majrina SV, Ryzhkova DV, Mitrofanova LB, Ryzhkov AV, Murtazalieva PM, Moiseeva OM. Modern approaches to the diagnosis and treatment of cardiac sarcoidosis: results of a cohort study. Russian Journal of Cardiology. 2023; 28(5): 23–30. (In Russ.). doi: 10.15829/1560-4071-2023-5301

18. Smedema JP, Ainslie G, Crijns HJGM. Review: Contrast-enhanced magnetic resonance in the diagnosis and management of cardiac sarcoidosis. Progress in cardiovascular diseases. 2020; 63(3): 271–307. doi: 10.1016/j.pcad.2020.03.011

19. Baughman RP, Field S, Costabel U, Crystal RG, Culver DA, Drent M, et al. Sarcoidosis in America. Analysis based on health care use. Annals of the American Thoracic Society. 2016; 13(8): 1244–1252. doi: 10.1513/AnnalsATS.201511-760OC

20. Salonen J, Kaarteenaho R. National retrospective registry survey on the epidemiology of sarcoidosis in Finland 2002−2022. BMJ open respiratory research. 2024; 11(1): e002461. doi: 10.1136/bmjresp-2024-002461

21. Fidler LM, Balter M, Fisher JH, To T, Stanbrook MB, Gershon A. Epidemiology and health outcomes of sarcoidosis in a universal healthcare population: a cohort study. The European respiratory journal. 2019; 54(4): 1900444. doi: 10.1183/13993003.00444-2019

22. Arkema EV, Grunewald J, Kullberg S, Eklund A, Askling J. Sarcoidosis incidence and prevalence: a nationwide register-based assessment in Sweden. The European respiratory journal. 2016; 48(6): 1690–1699. doi: 10.1183/13993003.00477-2016

23. Freeman AM, Weinberger HD. Cardiac sarcoidosis: key concepts in pathogenesis, disease management, and interesting cases. Springer International Publishing: Imprint: Springer. 2015; 176. doi: 10.1007/978-3-319-14624-9

24. Park JE, Kim YS, Kang MJ, Kim CJ, Han CH, Lee SM, et al. Prevalence, incidence, and mortality of sarcoidosis in Korea, 2003–2015: A nationwide population-based study. Respiratory medicine. 2018; 144S: S28–S34. doi: 10.1016/j.rmed.2018.03.028

25. Arkema EV, Cozier YC. Sarcoidosis epidemiology: recent estimates of incidence, prevalence and risk factors. Current opinion in pulmonary medicine. 2020; 26(5): 527– 534. doi: 10.1097/MCP.0000000000000715

26. Yoon HY, Kim HM, Kim YJ, Song JW. Prevalence and incidence of sarcoidosis in Korea: a nationwide population-based study. Respiratory research. 2018; 19(1): 158. doi: 10.1186/s12931-018-0871-3

27. Wu CH, Chung PI, Wu CY, Chen YT, Chiu YW, Chang YT, et al. Comorbid autoimmune diseases in patients with sarcoidosis: a nationwide case-control study in Taiwan. The Journal of dermatology. 2017; 44(4): 423– 430. doi: 10.1111/1346-8138.13654

28. Vizel’ AA, Vizel’ IYu. Sarkoidosis: basic provisions of the project of federal clinical recommendations. Therapy. 2019; 5(31): 20–26. (In Russ.). doi: 10.18565/therapy.2019.5.20-26

29. Vizel’ IYu, Vizel’ AA. Characteristic of sarcoidosis register in the Republic of Tatarstan. The Bulletin of Contemporary Clinical Medicine. 2015; 8(5): 18–26. (In Russ.).

30. Vereckei A, Besenyi Z, Nagy V, Radics B, Vágó H, Jenei Z, et al. Cardiac sarcoidosis: a comprehensive clinical review. Reviews in cardiovascular medicine. 2024; 25(2): 37. doi: 10.31083/j.rcm2502037

31. Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet PY, Müller-Quernheim J. Sarcoidosis. Lancet. 2014; 383(9923): 1155–67. doi: 10.1016/S0140-6736(13)60680-7

32. Ueberham L, Hagendorff A, Klingel K, Paetsch I, Jahnke C, Kluge T, et al. Pathophysiological gaps, diagnostic challenges, and uncertainties in cardiac sarcoidosis. Journal of the American Heart Association. 2023; 12(6): e027971. doi: 10.1161/JAHA.122.027971

33. De Bortoli A, Birnie DH. Diagnosis and treatment of cardiac sarcoidosis. Circulation journal. 2023; 87(4): 471– 480. doi: 10.1253/circj.CJ-22-0671

34. Rubio-Rivas M, Corbella X. Clinical phenotypes and prediction of chronicity in sarcoidosis using cluster analysis in a prospective cohort of 694 patients. European journal of internal medicine. 2020; 77: 59–65. doi: 10.1016/j.ejim.2020.04.024

35. Schupp JC, Freitag-Wolf S, Bargagli E, Mihailović-Vučinić V, Rottoli P, Grubanovic A, et al. Phenotypes of organ involvement in sarcoidosis. The European respiratory journal. 2018; 51(1): 1700991. doi: 10.1183/13993003.00991-2017

36. Han YS, Rivera-Grana E, Salek S, Rosenbaum JT. Distinguishing uveitis secondary to sarcoidosis from idiopathic disease: cardiac implications. JAMA ophthalmology. 2018; 136(2): 109–115. doi: 10.1001/jamaophthalmol.2017.5466

37. Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. The New England journal of medicine. 2007; 357(21): 2153– 2165. doi: 10.1056/NEJMra071714

38. Iwai K, Takemura T, Kitaichi M, Kawabata Y, Matsui Y. Pathological studies on sarcoidosis autopsy. II. Early change, mode of progression and death pattern. Acta pathologica japonica. 1993; 43(7–8): 377–385. doi: 10.1111/j.1440-1827.1993.tb01149.x

39. Gilotra NA, Griffin JM, Pavlovic N, Houston BA, Chasler J, Goetz C. Sarcoidosis-related cardiomyopathy: current knowledge, challenges, and future perspectives state-of-the-art review. Journal of cardiac failure. 2022; 28(1): 113–132. doi: 10.1016/j.cardfail.2021.06.016

40. Rybicki BA, Iannuzzi MC, Frederick MM, Thompson BW, Rossman MD, Bresnitz EA, et al. Familial aggregation of sarcoidosis. A case-control etiologic study of sarcoidosis (ACCESS). American journal of respiratory and critical care medicine. 2001; 164(11): 2085–2091. doi: 10.1164/ajrccm.164.11.2106001

41. Te HS, Perlman DM, Shenoy C, Steinberger DJ, Cogswell RJ, Roukoz H, et al. Clinical characteristics and organ system involvement in sarcoidosis: comparison of the University of Minnesota cohort with other cohorts. BMC pulmonary medicine. 2020; 20(1): 155. doi: 10.1186/s12890-020-01191-x

42. Markevitz N, Epstein Shochet G, Levi Y, Israeli-Shani L, Shitrit D. Sarcoidosis in Israel: clinical outcome status, organ involvement, and long-yerm follow-up. Lung. 2017; 195(4): 419–424. doi: 10.1007/s00408-017-0015-4

43. Mehta D, Lubitz SA, Frankel Z, Wisnivesky JP, Einstein AJ, Goldman M, et al. Cardiac involvement in patients with sarcoidosis: diagnostic and prognostic value of outpatient testing. Chest. 2008; 133(6): 1426–1435. doi: 10.1378/chest.07-2784

44. Kandolin R, Lehtonen J, Airaksinen J, Vihinen T, Miettinen H, Ylitalo K, et al. Cardiac sarcoidosis: epidemiology, characteristics, and outcome over 25 years in a nationwide study. Circulation. 2015; 131(7): 624–632. doi: 10.1161/CIRCULATIONAHA.114.011522

45. Lehtonen J, Uusitalo V, Pöyhönen P, Mäyränpää MI, Kupari M. Cardiac sarcoidosis: phenotypes, diagnosis, treatment, and prognosis. European heart journal. 2023; 44(17): 1495–1510. doi: 10.1093/eurheartj/ehad067

46. Mathai SV, Patel S, Jorde UP, Rochlani Y. Epidemiology, pathogenesis, and diagnosis of cardiac sarcoidosis. Methodist DeBakey cardiovascular journal. 2022; 18(2): 78– 93. doi: 10.14797/mdcvj.1057

47. Kysperska K, Kuchynka P, Palecek T. Cardiac sarcoidosis: from diagnosis to treatment. Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2021; 165(4): 347–359. doi: 10.5507/bp.2021.057

48. Markatis E, Afthinos A, Antonakis E, Papanikolaou IC. Cardiac sarcoidosis: diagnosis and management. Reviews in cardiovascular medicine. 2020; 21(3): 321–338. doi: 10.31083/j.rcm.2020.03.102

49. Neves FS, Pereira IA, Sztajnbok F, Neto NSR. Sarcoidosis: a general overview. Advances in rheumatology. 2024; 64(1): 57. doi: 10.1186/s42358-024-00381-z

50. Rybicki BA, Sinha R, Iyengar S, Gray-McGuire C, Elston RC, Iannuzzi MC. Genetic linkage analysis of sarcoidosis phenotypes: the sarcoidosis genetic analysis (SAGA) study. Genes and immunity. 2007; 8(5): 379–386. doi: 10.1038/sj.gene.6364396

51. Chen ES, Moller DR. Etiologies of sarcoidosis. Clinical reviews in allergy and immunology. 2015; 49(1): 6–18. doi: 10.1007/s12016-015-8481-z

52. Manovitskaya NV, Bogush LS, Davidovskaya EI, Manovitskaya VO, Yakubenya ON. The role of some genetic factors in the development of sarcoidosis (review). Recept = Prescription. 2024; 27(6): 870–881. (In Russ.). doi: 10.34883/PI.2024.27.6.003

53. Darlington P, Melin J, Rivera N, Grunewald J, Eklund A, Kullberg S. Peripheral blood lymphopenia in sarcoidosis associates with HLA-DRB1 alleles but not with lung immune cells and organ involvement. Clinical and experimental immunology. 2023; 13; 213(3): 357–362. doi: 10.1093/cei/uxad052

54. Rivera NV, Ronninger M, Shchetynsky K, Franke A, Nöthen MM, Müller-Quernheim J, et al. High-density genetic mapping identifies new susceptibility variants in sarcoidosis phenotypes and shows genomic-driven phenotypic differences. American journal of respiratory and critical care medicine. 2016; 193(9): 1008–1022. doi: 10.1164/rccm.201507-1372OC

55. Eldhagen P, Bobbio E, Darlington P, Grunewald J, Eklund A, Polte CL, et al. Phenotypic and HLA-DRB1 allele characterization of Swedish cardiac sarcoidosis patients. International journal of cardiology. 2022; 359: 108–112. doi: 10.1016/j.ijcard.2022.04.006

56. Rybicki BA, Maliarik MJ, Poisson LM, Sheffer R, Chen KM, Major M, et al. The major histocompatibility complex gene region and sarcoidosis susceptibility in African Americans. American journal of respiratory and critical care medicine. 2003; 167(3): 444–449. doi: 10.1164/rccm.2112060

57. Suzuki H, Ota M, Meguro A, Katsuyama Y, Kawagoe T, Ishihara M, et al. Genetic characterization and susceptibility for sarcoidosis in Japanese patients: risk factors of BTNL2 gene polymorphisms and HLA class II alleles. Investigative ophthalmology and visual science. 2012; 53(11): 7109–7115. doi: 10.1167/iovs.12-10491

58. Sikorova K, Osoegawa K, Kocourkova L, Strnad A, Petrkova J, Fernández-Viña MA, et al. Association between sarcoidosis and HLA polymorphisms in a Czech population from Central Europe: focus on a relationship with clinical outcome and treatment. Frontiers in medicine. 2023; 10: 1094843. doi: 10.3389/fmed.2023.1094843

59. Takashige N, Naruse TK, Matsumori A, Hara M, Nagai S, Morimoto S, et al. Genetic polymorphisms at the tumour necrosis factor loci (TNFA and TNFB) in cardiac sarcoidosis. Tissue antigens. 1999; 54(2): 191–193. doi: 10.1034/j.1399-0039.1999.540211.x

60. Darlington P, Haugom-Olsen H, von Sivers K, Wahlström J, Runold M, Svjatoha V, et al. T-cell phenotypes in bronchoalveolar lavage fluid, blood and lymph nodes in pulmonary sarcoidosis-indication for an airborne antigen as the triggering factor in sarcoidosis. Journal of internal medicine. 2012; 272(5): 465–471. doi: 10.1111/j.1365-2796.2012.02543.x

61. Shah HH, Zehra SA, Shahrukh A, Waseem R, Hussain T, Hussain MS, et al. Cardiac sarcoidosis: a comprehensive review of risk factors, pathogenesis, diagnosis, clinical manifestations, and treatment strategies. Frontiers in cardiovascular medicine. 2023; 10: 1156474. doi: 10.3389/fcvm.2023.1156474

62. Homma JY, Abe C, Chosa H, Ueda K, Saegusa J, Nakayama M, et al. Bacteriological investigation on biopsy specimens from patients with sarcoidosis. The Japanese journal of experimental medicine. 1978; 48(3): 251–255.

63. Song Z, Marzilli L, Greenlee BM, Chen ES, Silver RF, Askin FB, et al. Mycobacterial catalase-peroxidase is a tissue antigen and target of the adaptive immune response in systemic sarcoidosis. The Journal of experimental medicine. 2005; 201(5): 755–767. doi: 10.1084/jem.20040429

64. Ungprasert P, Crowson CS, Matteson EL. Seasonal variation in incidence of sarcoidosis: a population-based study, 1976–2013. Thorax. 2016; 71(12): 1164–1166. doi: 10.1136/thoraxjnl-2016-209032

65. Vihlborg P, Bryngelsson IL, Andersson L, Graff P. Risk of sarcoidosis and seropositive rheumatoid arthritis from occupational silica exposure in Swedish iron foundries: a retrospective cohort study. BMJ Open. 2017; 7(7): e016839. doi: 10.1136/bmjopen-2017-016839

66. Fazio JC, Viragh K, Houlroyd J, Gandhi SA. A review of silicosis and other silica-related diseases in the engineered stone countertop processing industry. Journal of occupational medicine and toxicology. 2025; 20(1): 9. doi: 10.1186/s12995-025-00455-8

67. Hena KM, Murphy S, Zhang Y, Shao Y, Kazeros A, Reibman J. Clinical evaluation of sarcoidosis in community members with World Trade Center dust exposure. International journal of environmental research and public health. 2019; 16(7): 1291. doi: 10.3390/ijerph16071291

68. Lagana SM, Parwani AV, Nichols LC. Cardiac sarcoidosis: a pathology-focused review. Archives of pathology and laboratory medicine. 2010; 134(7): 1039–1046. doi: 10.5858/2009-0274-RA.1

69. Chuchalin AG, Vizel’ AA, Il’kovich MM, Avdeev SN, Amirov NB, Baranova OP, et al. Diagnosis and treatment of sarcoidosis. Summary of federal conciliative clinical recommendations. Part I. Classification, etiopathogenesis, clinic. The Bulletin of Contemporary Clinical Medicine. 2014; 7(45): 62–70. (In Russ.).

70. Terasaki F, Azuma A, Anzai T, Ishizaka N, Ishida Y, Isobe M, et al. JCS 2016 Guideline on diagnosis and treatment of cardiac sarcoidosis – digest version. Circulation journal. 2019; 83(11): 2329–2388. doi: 10.1253/circj.CJ-19-0508

71. Kato S, Sakai Y, Okabe A, Kawashima Y, Kuwahara K, Shiogama K, et al. Histology of cardiac sarcoidosis with novel considerations arranged upon a pathologic basis. Journal of clinical medicine. 2022; 11(1): 251. doi: 10.3390/jcm11010251

72. Honda Y, Nagai T, Ikeda Y, Sakakibara M, Asakawa N, Nagano N, et al. Myocardial immunocompetent cells and macrophage phenotypes as histopathological surrogates for diagnosis of cardiac sarcoidosis in Japanese. Journal of the American Heart Association. 2016; 5(11): e004019. doi: 10.1161/JAHA.116.004019

73. Oe Y, Ishibashi-Ueda H, Matsuyama TA, Kuo YH, Nagai T, Ikeda Y, et al. Lymph vessel proliferation on cardiac biopsy may help in the diagnosis of cardiac sarcoidosis. Journal of the American Heart Association. 2019; 8(2): e010967. doi: 10.1161/JAHA.118.010967

74. Locke LW, Crouser ED, White P, Julian MW, Caceres EG, et al. IL-13-regulated macrophage polarization during granuloma formation in an in vitro human sarcoidosis model. American journal of respiratory cell and molecular biology. 2019; 60(1): 84–95. doi: 10.1165/rcmb.2018-0053OC

75. Cha MJ, Seo JW, Oh S, Park EA, Lee SH, Kim MY, et al. Indirect pathological indicators for cardiac sarcoidosis on endomyocardial biopsy. Journal of pathology and translational medicine. 2020; 54(5): 396–410. doi: 10.4132/jptm.2020.06.10

76. Serei VD, Fyfe B. The many faces of cardiac sarcoidosis. American journal of clinical pathology. 2020; 153(3): 294–302. doi: 10.1093/ajcp/aqz169