Histology and immunohistology of myocarditis

  • Annalisa Angelini
  • Fiorella Calabrese
  • Gaetano Thiene
Part of the Progress in Inflammation Research book series (PIR)


The contemporary definition and classification of cardiomyopathies by the American Heart Association recently listed myocarditis (inflammatory cardiomyopathy) among the primary cardiomyopathies (predominantly involving the heart) as opposed to the secondary forms (mainly involving the heart in the setting of generalized systemic disease). Endomyocardial biopsy (EMB) is still considered the gold standard for the in vivo diagnosis of myocarditis, its sensibility and specificity being increased by the application of immunohistochemistry and morphometric analysis. Obtaining tissue samples from multiple areas of the ventricles greatly increases the sensibility of EMB in detecting myocarditis since the process could be focal, regional or diffuse. Dallas criteria, recognizing inflammatory infiltrates with necrosis and/or degeneration of the adjacent myocytes (not typical of the ischemic damage associated with coronary artery disease)as the key for diagnosis, should be complemented by the introduction of new criteria that should include: clinical presentation, histopathology, immunohistochemistry, morphometry, viral polymerase chain reaction, cardiac antibodies assessment, and imaging findings.


Dilate Cardiomyopathy Endomyocardial Biopsy Idiopathic Dilate Cardiomyopathy Inflammatory Cell Infiltrate Viral Myocarditis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, Moss AJ, Seidman CE, Young JB (2006) Contemporary definition and classification of the cardiomyopathies: An American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 113(14): 1807–16CrossRefPubMedGoogle Scholar
  2. 2.
    Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O’Connell J, Olsen E, Thiene G, Goodwin J, Gyarfas I, Martin I, Nordet P (1996) Report of the 1995 WHO/ ISFC task force on the definition of cardiomyopathies. Circulation 93: 841–842PubMedGoogle Scholar
  3. 3.
    Aretz HT (1987) Myocarditis: The Dallas criteria. Hum Pathol 18: 619–624CrossRefPubMedGoogle Scholar
  4. 4.
    Skouri HN, Dec GW, Friedrich MG, Cooper LT (2006) Noninvasive imaging in myocarditis. J Am Coll Cardiol 48: 2085–93CrossRefPubMedGoogle Scholar
  5. 5.
    Mahrholdt H, Wagner A, Deluigi CC, Kispert E, Hager S, Meinhardt G, Vogelsberg H, Fritz P, Dippon J, Bock CT et al (2006) Presentation, patterns of myocardial damage, and clinical course of viral myocarditis. Circulation 114: 1581–90CrossRefPubMedGoogle Scholar
  6. 6.
    Mahrholdt H, Goedecke C, Wagner A, Meinhardt G, Athanasiadis A, Vogelsberg H, Fritz P, Klingel K, Kandolf R, Sechtem U (2004) Cardiovascular magnetic resonance assessment of human myocarditis: A comparison to histology and molecular pathology. Circulation 109: 1250–8CrossRefPubMedGoogle Scholar
  7. 7.
    Muller S, Muller P, Meyer R, Volkmann H, Gottschild D, Thoss K, Kalhofer G, Wessel G (1985) Myocardial bioptic findings in correlation with TL-201 imaging and hemodynamic parameters in patients with latent cardiomyopathies suspected of having myocarditis. Heart Vessels Suppl 1: 111–5CrossRefPubMedGoogle Scholar
  8. 8.
    Salvi A, Di Lenarda A, Dreas L, Silvestri F, Camerini F (1989) Immunosuppressive treatment in myocarditis. Int J Cardiol 22: 329–38CrossRefPubMedGoogle Scholar
  9. 9.
    Hammond EH, Menlove RL, Anderson JL (1987) Predictive value of immunofluorescence and electron microscopic evaluation of endomyocardial biopsies in the diagnosis and prognosis of myocarditis and idiopathic dilated cardiomyopathy. Am Heart J 114:1055–65CrossRefPubMedGoogle Scholar
  10. 10.
    Bolte HD, Ludwig B, Schultheiss HP (1984) Viral myocarditis: Symptomatology, clinical diagnosis and hemodynamics. Internist (Berl) 25(3): 143–9Google Scholar
  11. 11.
    Magnani JW, Danik HJ, Dec GW Jr, DiSalvo TG (2006) Survival in biopsy-proven mocarditis: A long term retrospective analysis of the histopathologic, clinical, and hemodynamic predictors. Am Heart J 151: 463–470CrossRefPubMedGoogle Scholar
  12. 12.
    Gore I, Saphir O (1947) Myocarditis: A classification of 1402 cases. Am Heart J 34:827–831CrossRefPubMedGoogle Scholar
  13. 13.
    Fenoglio JJ Jr, Ursell PC, Kellogg CF, Drusin RE, Weiss MB (1983) Diagnosis and classification of myocarditis by endomyocardial biopsy. N Engl J Med 301: 12–18CrossRefGoogle Scholar
  14. 14.
    Lieberman EB, Hutchins GM, Herskowitz A, Rose NR, Baughman KL (1991) Clinicopathologic description of myocarditis. J Am Coll Cardiol 18: 1617–26CrossRefPubMedGoogle Scholar
  15. 15.
    Angelini A, Crosato M, Boffa GM, Calabrese F, Calzolari V, Chioin R, Daliento L, Thiene G (2002) Active versus borderline myocarditis: Clinicopathological correlates and prognostic implications. Heart 87: 210–215CrossRefPubMedGoogle Scholar
  16. 16.
    Hauck AJ, Kearney DL, Edwards WD (1989) Evaluation of postmortem endomyocardialbiopsy specimens from 38 patients with lymphocytic myocarditis: Implications for role of sampling error. Mayo Clin Proc 64: 1235–1245PubMedGoogle Scholar
  17. 17.
    Angelini A, Calzolari V, Calabrese F, Boffa GM, Maddalena F, Chioin R, Thiene G (2000) Myocarditis mimicking acute myocardial infarction: Role of endomyocardial biopsy in the differential diagnosis. Heart 84: 245–50CrossRefPubMedGoogle Scholar
  18. 18.
    Edwards WD, Holmes DR, Reeders GS (1982) Diagnosis of active lymphocytic myocarditis by endomyocardial biopsy: Quantitative criteria for light microscopy. Mayo Clin Proc 57: 419–425PubMedGoogle Scholar
  19. 19.
    Linder J, Cassling RS, Rogler WC, Wilson JE, Markin RS, Sears TD, McManus BM (1985) Immunohistochemical characterization of lymphocytes in uninflamed ventricular myocardium. Implications for myocarditis. Arch Pathol Lab Med 109: 917–921PubMedGoogle Scholar
  20. 20.
    Schnitt SJ, Ciano PS, Schoen FJ (1987) Quantitation of lymphocytes in endomyocardial biopsies: Use and limitations of antibodies to leukocyte common antigen. Hum Pathol 18: 796–801CrossRefPubMedGoogle Scholar
  21. 21.
    Tazelaar HD, Billingham ME (1986) Myocardial lymphocytes: Fact, fancy or myocarditis? Am J Cardiovasc Pathol 1: 47–49Google Scholar
  22. 22.
    Kuhl U, Noutsias M, Seeber B, Schultheiss HP (1996) Immunohistological evidence for a chronic intramyocardial inflammatory process in dilated cardiomyopathy. Heart 75: 295–300CrossRefPubMedGoogle Scholar
  23. 23.
    Maisch B, Herzum M, Hufnagel G, Schonian U (1996) Immunosuppressive and immunomodulatory treatment for myocarditis. Curr Opin Cardiol 11: 310–324CrossRefPubMedGoogle Scholar
  24. 24.
    Billingham ME (1989) Acute myocarditis: Is sampling error a contraindication for diagnostic biopsies? J Am Coll Cardiol 14: 921–922CrossRefPubMedGoogle Scholar
  25. 25.
    Edwards WD Holmes DR, Reeders GS (1982) Diagnosis of active lymphocytic myocarditis by endomyocardial biopsy: Quantitative criteria for light microscopy. Mayo Clin Proc 57: 419–425PubMedGoogle Scholar
  26. 26.
    Edwards WD (1984) Myocarditis and endomyocardial biopsy. Cardiol Clin 2: 647–656PubMedGoogle Scholar
  27. 27.
    Chow LH, Radio SJ, Sears TD, McManus BM (1989) Insensitivity of right ventricular endomyocardial biopsy in the diagnosis of myocarditis. J Am Coll Cardiol 14: 915–920CrossRefPubMedGoogle Scholar
  28. 28.
    Hauck AJ, Edwards ED (1992) Histopathologic examination of tissues obtained by endomyocardial biopsy. In: Fowles RE (ed): Cardiac biopsy. Mount Kisco, Futura, 95Google Scholar
  29. 29.
    Thiene G, Bartoloni G, Poletti A, Boffa GM (1996) Tecniche, indicazioni ed utilità della biopsia endomiocardica. In: Baroldi G, Thiene G (eds): Biopsia endomiocardica, Piccin, Padova, 5–45Google Scholar
  30. 30.
    Burke AP, Farb A, Robinowitz M, Virmani R (1991) Serial sectioning and multiple level examination of endomyocardial biopsies for the diagnosis of myocarditis. Mod Pathol 4: 690–693PubMedGoogle Scholar
  31. 31.
    Frustaci A, Bellocci F, Olsen EG (1994) Results of biventricular endomyocardial biopsy in survivors of cardiac arrest with apparently normal hearts. Am J Cardiol 74: 890–895CrossRefPubMedGoogle Scholar
  32. 32.
    Herskowitz A, Ahmed-Ansari A, Neumann DA, Beschorner WE, Rose NR, Soule LM, Burek CL, Sell KW, Baughman KL (1990) Induction of major histocompatibility complex antigens within the myocardium of patients with active myocarditis: A nonhistologic marker of myocarditis. J Am Coll Cardiol 15: 624–632CrossRefPubMedGoogle Scholar
  33. 33.
    Kuhl U Seeberg B, Schultheiss HP, Strauer BE (1994) Immunohistological characterization of infiltrating lymphocytes in biopsies of patients with clinically suspected dilated cardiomyopathy. Eur Heart J 15 Suppl. C: 62–67PubMedGoogle Scholar
  34. 34.
    Kuhl U, Noutsias M, Schultheiss HP (1995) Immunohistochemistry in dilated cardiomyopathy. Eur Heart J 16: SO: 100–106PubMedGoogle Scholar
  35. 35.
    Wojnicz R, Nowalany-Kozielska E, Wojciechowska C, Glanowska G, Wilczewski P, Niklewski T, Zembala M, Polonski L, Rozek MM, Wodniecki J (2001) Randomized, placebo-controlled study for immunosuppressive treatment of inflammatory dilated cardiomyopathy: Two-year follow-up results. Circulation 104: 39–45CrossRefPubMedGoogle Scholar
  36. 36.
    Friedrich MG, Strohm O, Schulz-Menger J, Marciniak H, Luft FC, Dietz R (1998) Contrast media-enhanced magnetic resonance imaging visualizes myocardial changes in the course of viral myocarditis. Circulation 97: 1802–9PubMedGoogle Scholar
  37. 37.
    Mestroni L, Rocco C, Gregori D, Sinagra G, Di Lenarda A, Miocic S, Vatta M, Pinamonti B, Muntoni F, Caforio AL et al (1999) Familial dilated cardiomyopathy: Evidence for genetic and phenotypic heterogeneity. J Am Coll Cardiol 34: 181–90CrossRefPubMedGoogle Scholar
  38. 38.
    Jin O, Sole MJ, Butany JW, Chia WK, McLaughlin PR, Liu P, Liew CC (1990) Detection of enterovirus RNA in myocardial biopsies from patients with myocarditis and cardiomyopathy using gene amplification by polymerase chain reaction. Circulation 82: 8–16PubMedGoogle Scholar
  39. 39.
    Chapman NM, Tracy S, Gauntt CJ, Fortmueller U (1990) Molecular detection and identification of enteroviruses using enzymatic amplification and nucleic acid hybridization. J Clin Microbiol 28: 843–50PubMedGoogle Scholar
  40. 40.
    Weiss LM, Liu XF, Chang KL, Billingham ME (1992) Detection of enteroviral RNA in idiopathic dilated cardiomyopathy and other human cardiac tissues. J Clin Invest 90: 156–9CrossRefPubMedGoogle Scholar
  41. 41.
    Grasso M, Arbustini E, Silini E, Diegoli M, Percivalle E, Ratti G, Bramerio M, Gavazzi A, Vigano M, Milanesi G (1992) Search for Coxsackievirus B3 RNA in idiopathic dilated cardiomyopathy using gene amplification by polymerase chain reaction. Am J Cardiol 69: 658–64CrossRefPubMedGoogle Scholar
  42. 42.
    Petitjean J, Kopecka H, Freymuth F, Langlard JM, Scanu P, Galateau F, Bouhour JB, Ferriere M, Charbonneau P, Komajda M (1993) Detection of enterovirus in endomyocardial biopsy by molecular approach. J Med Virol 41: 260CrossRefPubMedGoogle Scholar
  43. 43.
    Hilton DA, Variend S, Pringle JH (1993) Demonstration of Coxsackie virus RNA in formalin-fixed tissue sections from childhood myocarditis cases by in situ hybridization and the polymerase chain reaction. J Pathol 170: 45–51CrossRefPubMedGoogle Scholar
  44. 44.
    Martin AB, Webber S, Fricker FJ, Jaffe R, Demmler G, Kearney D, Zhang YH, Bodurtha J, Gelb B, Ni J, Bricker T, Towbin JA (1994) Acute myocarditis. Rapid diagnosis by PCR in children. Circulation 90: 330–339PubMedGoogle Scholar
  45. 45.
    Pauschinger M, Bowles NE, Fuentes-Garcia FJ, Pham V, Kuhl U, Schwimmbeck PL, Schultheiss HP, Towbin JA (1999) Detection of adenoviral genome in the myocardium of adult patients with idiopathic left ventricular dysfunction. Circulation 99: 1348–54PubMedGoogle Scholar
  46. 46.
    Calabrese F, Valente M, Thiene G, Angelini A, Testolin L, Biasiolo MA, Soteriou B, Livi U, Palù G (1999) Enteroviral genome in native hearts may influence outcome of patients who undergo cardiac transplantation. Diagn Mol Pathol 8: 39–46CrossRefPubMedGoogle Scholar
  47. 47.
    Chimenti C, Calabrese F, Thiene G, Pieroni M, Maseri A, Frustaci A (2001) Inflammatory left ventricular microaneurysms as a cause of apparently idiopathic ventricular tachyarrhythmias. Circulation 104: 168–173PubMedGoogle Scholar
  48. 48.
    Calabrese F, Rigo E, Milanesi O, Boffa GM, Angelini A, Valente M, Thiene G (2002) Molecular diagnosis of myocarditis and dilated cardiomyopathy in children. Clinicopathologic features and prognostic implications. Diagn Mol Pathol 11: 212–221CrossRefPubMedGoogle Scholar
  49. 49.
    Calabrese F, Thiene G (2003) Myocarditis and inflammatory cardiomyopathy: Microbiological and molecular biological aspects. Cardiovasc Res 60: 11–25CrossRefPubMedGoogle Scholar
  50. 50.
    Kuhl U, Pauschinger M, Noutsias M, Seeberg B, Bock T, Lassner D, Poller W, Kandolf R, Schultheiss HP (2005) High prevalence of viral genomes and multiple viral infections in the myocardium of adults with “idiopathic” left ventricular dysfunction. Circulation 22; 111: 887–93CrossRefGoogle Scholar
  51. 51.
    McKenna WJ, Davies MJ (1995) Immunosuppression for myocarditis. N Engl J Med 333: 312–313CrossRefPubMedGoogle Scholar
  52. 52.
    Mason JW, O’connell JB, Herskowitz A, Rose NR, McManus BM, Billingham ME, Moon TE and the myocarditis treatment trial investigators (1995) A clinical trial of immunosuppressive therapy for myocarditis. N Engl J Med 333: 269–275CrossRefPubMedGoogle Scholar
  53. 53.
    Tazelaar HD, Billingham ME (1987) Myocardial lymphocytes. Fact, fancy, or myocarditis? Am J Cardiovasc Pathol 147–50Google Scholar
  54. 54.
    Davies MJ, Ward DE (1992) How can myocarditis be diagnosed and should it be treated? Br Heart J 68: 346–347CrossRefPubMedGoogle Scholar
  55. 55.
    Baughman K (2006) Diagnosis of myocarditis: Death of Dallas criteria. Circulation 113: 593–5CrossRefPubMedGoogle Scholar
  56. 56.
    Magnani JD, Dec GW (2006) Myocarditis: Current trends in diagnosis and treatment. Circulation 113: 876–890CrossRefPubMedGoogle Scholar

Copyright information

© Springer Basel 2010

Authors and Affiliations

  • Annalisa Angelini
    • 1
  • Fiorella Calabrese
    • 1
  • Gaetano Thiene
    • 1
  1. 1.Department of Medico-diagnostic Sciences and Special Therapies, Special Pathological AnatomyUniversity of Padua Medical SchoolPadovaItaly

Personalised recommendations