Virchows Archiv

, Volume 453, Issue 3, pp 233–241 | Cite as

Endomyocardial fibrosis: pathological and molecular findings of surgically resected ventricular endomyocardium

  • Silvia D’Andretta IgleziasEmail author
  • Luiz Alberto Benvenuti
  • Fiorella Calabrese
  • Vera Maria Cury Salemi
  • Ana Maria Gonçalves Silva
  • Elisa Carturan
  • Sergio Almeida de Oliveira
  • Gaetano Thiene
  • Thales De Brito
Original Article


Endomyocardial fibrosis (EMF) is a restrictive cardiomyopathy of unknown etiology prevalent in tropical regions affecting the inflow tract and apex of one or both ventricles, which show fibrous thickening of the endocardium and adjacent myocardium. Surgical treatment is recommended for patients in functional classes III or IV (New York Heart Association). The gross and histological features of the heart have been comprehensively studied in autopsies, but studies in surgical samples are still lacking. Histological and immunohistochemical features of EMF in surgical samples collected from 32 patients were described and correlated with clinical data. Polymerase chain reaction (PCR) and reverse transcription-PCR, performed on formalin fixed endomyocardial samples, were used retrospectively to detect genomes of certain cardiotropic viruses and Toxoplasma gondii. Ventricular endocardium was thickened by superficial acellular hyaline collagen fibers type I and III, with predominance of the former type. Besides fibrosis, a chronic inflammatory process and an anomalous lymphatic rich vascular pattern were observed in the deep endocardium, connected to the terminal coronary circulation of the myocardium, which might be an important pathological finding concerning EMF pathogenesis. Molecular analysis of the endomyocardium revealed high incidence of cardiotropic infective agents (6/12, 50%); however, their role in the disease pathogenesis is still controversial.


Endomyocardial fibrosis Immunohistochemistry Lymphatic vessels Surgical pathology Polymerase chain reaction 



The authors would like to thank Marcia Martins Reis for her excellent technical assistance in immunohistochemistry. This work was partially supported by the Fundação de Amparo a Pesquisa do Estado de São Paulo, process number 03/08052-8, and LIM 06, University of São Paulo Medical School.

Conflitct of interest statement

We declare that we have no conflict of interest.


  1. 1.
    Davies JNP (1948) Endocardial Fibrosis in Africans. East Afr Med J 25:10–14Google Scholar
  2. 2.
    Connor DH, Somers K, Hutt MSR et al (1967) (1968). Endomyocardial fibrosis in Uganda (Davies’ disease) Review. Part 1: Am Heart J 74: 687–709. Part 2: Am Heart J 75:107–124Google Scholar
  3. 3.
    Mady C, Pereira Barreto AC, de Oliveira SA et al (1989) Effectiveness of operative and non operative therapy in endomyocardial fibrosis. Am J Cardiol 63:1281–1282PubMedCrossRefGoogle Scholar
  4. 4.
    Oliveira SA, Pereira-Barreto ACP, Mady C et al (1990) Surgical treatment of endomyocardial fibrosis: a new approach. J Am Coll Cardiol 16:1246–1251PubMedCrossRefGoogle Scholar
  5. 5.
    Chopra P, Narula J, Talwar KK et al (1990) Histomorphologic characteristics of endomyocardial fibrosis: an endomyocardial biopsy study. Hum Pathol 21:613–616PubMedCrossRefGoogle Scholar
  6. 6.
    Somers K, Hutt MSR, Patel AK et al (1971) Endomyocardial biopsy in diagnosis of cardiomyopathies. Br Heart J 33:822–832PubMedCrossRefGoogle Scholar
  7. 7.
    Mayosi BM (2007) Contemporary trends in the epidemiology and management of cardiomyopathy and pericarditis in sub-Saharan Africa. Heart 93(10):1176–1183PubMedCrossRefGoogle Scholar
  8. 8.
    Sliwa K, Damasceno A, Mayosi BM (2005) Epidemiology and etiology of cardiomyopathy in Africa. Circulation 112:3577–3583PubMedCrossRefGoogle Scholar
  9. 9.
    Rutakingirwa M, Ziegler JL, Newton R et al (1999) Poverty and eosinophilia are risk factors for endomyocardial fibrosis (EMF) in Uganda. Trop Med Int Health 4(3):229–235PubMedCrossRefGoogle Scholar
  10. 10.
    Andy JJ (2001) Aetiology of endomyocardial fibrosis (EMF). West Afr J Med 20(3):199–207PubMedGoogle Scholar
  11. 11.
    Davies JNP, Ball JD (1955) The pathology of endomyocardial fibrosis in Uganda. Br Heart J 17:337–359PubMedCrossRefGoogle Scholar
  12. 12.
    Ijaola O, Falase AO (1990) Distribution of antibodies against coxsackie B viruses, arboviruses and Toxoplasma gondii among patients with endomyocardial fibrosis (EMF) compared with normal subjects from EMF endemic and non-endemic zones of Nigeria. Afr J Med Med Sci 19:93–103PubMedGoogle Scholar
  13. 13.
    Saiki RK, Scharf S, Faloona F et al (1985) Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle-cell anemia. Science 230:1350–1354PubMedCrossRefGoogle Scholar
  14. 14.
    Bowles NE, Ni J, Kearney DL et al (2003) Detection of viruses in myocardial tissues by polymerase chain reaction: evidence of adenovirus as a common cause of myocarditis in children and adults. J Am Coll Cardiol 42:466–472PubMedCrossRefGoogle Scholar
  15. 15.
    Bowles NE, Ni J, Marcus F et al (2002) The detection of cardiotropic viruses in the myocardium of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy. J Am Coll Cardiol 39:892–895PubMedCrossRefGoogle Scholar
  16. 16.
    Calabrese F, Angelini A, Thiene G et al (2000) No detection of enteroviral genome in the myocardium of patients with arrhythmogenic right ventricular cardiomyopathy. J Clin Pathol 53:382–387PubMedCrossRefGoogle Scholar
  17. 17.
    Calabrese F, Rigo E, Milanesi O et al (2002) Molecular diagnosis of myocarditis and dilated cardiomyopathy in children: clinicopathologic features and prognostic implications. Diagn Mol Pathol 11:212–221PubMedCrossRefGoogle Scholar
  18. 18.
    Kytö V, Vuorinen T, Saukko P et al (2005) Cytomegalovirus Infection of the heart is common in patients with fatal myocarditis. Clin Infect Dis 40:683–688PubMedCrossRefGoogle Scholar
  19. 19.
    Li Y, Peng T, Yang Y et al (2000) High prevalence of enteroviral genomic sequences in myocardium from cases of endemic cardiomyopathy (Keshan disease) in China. Heart 83:696–701PubMedCrossRefGoogle Scholar
  20. 20.
    Stanta G, Schneider C (1991) RNA extracted from paraffin-embedded human tissue is amenable to analysis by PCR amplification. Biotechniques 11:304–308PubMedGoogle Scholar
  21. 21.
    Shibata DK (1992) The polymerase chain reaction and the molecular genetic analysis of tissue biopsies. In: Herrington CS, McGee O’D (eds) Diagnostic molecular pathology. A practical approach. Oxford University Press, New York, pp 85–111Google Scholar
  22. 22.
    Ercolani L, Florence B, Denaro M et al (1988) Isolation and complete sequence of a functional human glyceraldehyde-3-phosphate dehydrogenase gene. J Biol Chem 263:1535–1541Google Scholar
  23. 23.
    Lam KM, Oldenburg N, Khan MA et al (1998) Significance of reverse transcription polymerase chain reaction in the detection of human cytomegalovirus gene transcripts in thoracic organ transplant recipients. J Heart Lung Transplant 17:555–565PubMedGoogle Scholar
  24. 24.
    Schowengerdt KO, Ni J, Denfield SW et al (1997) Association of parvovirus B19 genome in children with myocarditis and cardiac allograft rejection: diagnosis using the polymerase chain reaction. Circulation 96:3549–3554PubMedGoogle Scholar
  25. 25.
    Aretz HT (1987) Myocarditis:The Dallas Criteria. Hum Pathol 18(6):619–624PubMedCrossRefGoogle Scholar
  26. 26.
    Radhakumary C, Kumari TV, Kartha CC (2001) Endomyocardial fibrosis is associated with selective deposition of type I collagen. Indian Heart J 53:486–489PubMedGoogle Scholar
  27. 27.
    Adams DH, Lloyd AR (1997) Chemokines: leucocyte recruitment and activation cytokines. Lancet 349:490–495PubMedCrossRefGoogle Scholar
  28. 28.
    Angeli V, Ginhoux F, Llodra J et al (2006) B cell-driven lymphangiogenesis in inflamed lymph nodes enhances dendritic cell mobilization. Immunity 24:203–215PubMedCrossRefGoogle Scholar
  29. 29.
    Brockington IF, Olsen EGJ (1973) Loeffler’s endocarditis and Davies’ endomyocardial fibrosis. Am Heart J 85:308–322CrossRefGoogle Scholar
  30. 30.
    Noguchi H, Kephart GM, Colby TV et al (1992) Tissue eosinophilia and eosinophil degranulation in syndromes associated with fibrosis. Am J Pathol 140(2):521–528PubMedGoogle Scholar
  31. 31.
    Spry CJF (1986) Eosinophils in eosinophilic endomyocardial disease. Postgrad Med J 62:609–613PubMedGoogle Scholar
  32. 32.
    Olsen EGJ, Spry CJF (1985) Relation between eosinophilia and endomyocardial disease. Prog Cardiovasc Dis 27(4):241–254PubMedCrossRefGoogle Scholar
  33. 33.
    Andrade ZA, Teixeira ARL (1973) Changes in the coronary vasculature in endomyocardial fibrosis and their possible significance. Am Heart J 86(2):152–158PubMedCrossRefGoogle Scholar
  34. 34.
    Gupta PN, Valiathan M, Balakrishnan KG et al (1989) Clinical course of endomyocardial fibrosis. Br Heart J 62:450–454PubMedCrossRefGoogle Scholar
  35. 35.
    Pereira Barretto AC, Mady C, Pileggi F (1996) Longitudinal follow-up of patients not treated by surgery. Arq Bras Cardiol 67(4):285–288Google Scholar
  36. 36.
    Bestetti RB, Corbucci H, Fornitano L et al (2005) Angina-like chest pain and syncope as the clinical presentation of left ventricular endomyocardial fibrosis: a case report. Angiology 56(3):339–342PubMedCrossRefGoogle Scholar
  37. 37.
    Balakrishnan KG, Sasidharan K, Venkitachalam CG et al (1983) Coronary angiographic features in endomyocardial fibrosis. Cardiology 70:121–126PubMedGoogle Scholar
  38. 38.
    Bukhman G, Ziegler J, Parry E (2008) Endomyocardial fibrosis: still a mystery after 60 years. PLoS Negl Trop 2(2):e97 doi: 10.1371/journal.pntd.0000097 CrossRefGoogle Scholar
  39. 39.
    Valiathan SM, Kartha CC (1990) Endomyocardial fibrosis—the possible connexion with myocardial levels of magnesium and cerium—review. Int J Cardiol 28(1):1–5PubMedCrossRefGoogle Scholar
  40. 40.
    Hunt JL (2008) Molecular pathology in anatomic pathology practice. A review of basic principles. Arch Pathol Lab Med 132:248–260PubMedGoogle Scholar
  41. 41.
    Ueno H, Yokota Y, Shiotani H et al (1995) Significance of detection of enterovirus RNA in myocardial tissue by reverse transcription-polymerase chain reaction. Int J Cardiol 51:157–164PubMedCrossRefGoogle Scholar
  42. 42.
    Ni J, Bowles NE, Kim Y-H et al (1997) Viral infection of the myocardium in endocardial fibroelastosis. Molecular evidence for the role of mumps virus as an etiologic agent. Circulation 95:133–139PubMedGoogle Scholar
  43. 43.
    Keeling PJ, Tracy S (1994) Link between enteroviruses and dilated cardiomyopathy: serological and molecular data. Br Heart J 72(6 suppl):S25–29PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Silvia D’Andretta Iglezias
    • 1
    Email author
  • Luiz Alberto Benvenuti
    • 2
  • Fiorella Calabrese
    • 3
  • Vera Maria Cury Salemi
    • 2
  • Ana Maria Gonçalves Silva
    • 4
  • Elisa Carturan
    • 3
  • Sergio Almeida de Oliveira
    • 2
  • Gaetano Thiene
    • 3
  • Thales De Brito
    • 4
  1. 1.Department of PathologyUniversity of São Paulo Medical SchoolSão PauloBrazil
  2. 2.Heart Institute (InCor)University of São Paulo Medical SchoolSão PauloBrazil
  3. 3.Department of PathologyUniversity of Padua Medical SchoolPaduaItaly
  4. 4.LIM 06, Institute of Tropical MedicineUniversity of São Paulo Medical SchoolSão PauloBrazil

Personalised recommendations