Immunosuppressive treatment of inflammatory cardiomyopathy patients

  • Andrea Frustaci
  • Cristina Chimenti
Part of the Progress in Inflammation Research book series (PIR)


Inflammatory cardiomyopathy, defined as myocarditis associated with cardiac dysfunction is a main cause of heart failure. The acknowledgment of the underlying histological and molecular substrate may significantly contribute to improve the treatment of the disease that can be so devastating to require cardiac transplantation. Immunosuppression has been recognized as an effective therapeutic option for eosinophilic, giant cell, granulomatous myocarditis and for lymphocytic myocarditis associated with connective tissue disorders and with rejection of the transplanted heart. Treatment of idiopathic lymphocytic myocarditis particularly in its chronic form is still debated. Recent studies suggest that a negative PCR analysis of endomyocardial tissue for viral genomes and the detection of autoimmune markers, as HLA up-regulation and anti-heart autoantibodies, identify responders to immunosuppression improving the patients’ outcome even in an advanced stage of the disease. Recovery of cardiac function in responders to immunosuppression is associated with inhibition of cell death and with newly synthesized contractile material.


Immunosuppressive Treatment Endomyocardial Biopsy Cardiac Sarcoidosis Acute Myocarditis Giant Cell 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.
    Richardson P, McKenna W, Bristow M, Maisch B, Mautner B, O’Connell J, Olsen E, Thiene G, Goodwin J, Gyarfas I et al (1996) Report of the 1995 WHO/ISFC task force on the definition and classification of cardiomyopathies. Circulation 93: 841–842PubMedGoogle Scholar
  2. 2.
    Feldman AM, McNamara D (2000) Myocarditis. N Engl J Med 343: 1388–98CrossRefPubMedGoogle Scholar
  3. 3.
    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: 168–73PubMedGoogle Scholar
  4. 4.
    Narula J, Khaw BA, Dec GW Jr, Palacios IF, Southern JF, Fallon JT, Strauss HW, Haber E, Yasuda T (1993) Brief report: Recognition of acute myocarditis masquerading as acute myocardial infarction. N Engl J Med 328;100–104CrossRefPubMedGoogle Scholar
  5. 5.
    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
  6. 6.
    Frustaci A, Chimenti C, Maseri A (1999) Global bi-ventricular dysfunction in patients with symptomatic coronary artery disease may be caused by myocarditis. Circulation 99: 1295–1299PubMedGoogle Scholar
  7. 7.
    Frustaci A, Verardo R, Caldarulo M, Acconcia MC, Russo MA, Chimenti C (2007) Myocarditis in hypertrophic cardiomyopathy patients presenting acute clinical deterioration. Eur Heart J 28: 733–740CrossRefPubMedGoogle Scholar
  8. 8.
    Mason JW, O’ Connell JB, Herskowitz A, Rose NR, McManus BM, Billingham ME, Moon TE (1995) A clinical trial of immunosuppressive therapy for myocarditis. N Engl J Med 333: 269–75CrossRefPubMedGoogle Scholar
  9. 9.
    Aretz HT, Billingham ME, Edwards WD, Factor SM, Fallon JT, Fenoglio JJ, Olsen EG, Schoen FJ (1987) Myocarditis. A histopatologic definition and classification. Am J Cardiovasc Pathol 1: 3–14PubMedGoogle Scholar
  10. 10.
    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: 62–7PubMedGoogle Scholar
  11. 11.
    Pauschinger M, Bowles NE, Fuentes-Garcia F, Pham V, Kuhl U, Schwimmbeck PL, Schultheiss HP, Towbin JA et al (1999) Detection of adenoviral genome in the myocardium of adult patients with idiopathic left ventricular dysfunction. Circulation 99: 1348–54PubMedGoogle Scholar
  12. 12.
    Pauschinger M, Doerner A, Kuehl U, Schwimmbeck PL, Poller W, Kandolf R, Schultheiss HP (1999) Enteroviral RNA replication in the myocardium of patients with left ventricular dysfunction and clinically suspected myocarditis. Circulation 99: 889–95PubMedGoogle Scholar
  13. 13.
    )Noutsias M, Fechner H, de Jonge H, Wang X, Dekkers D, Houtsmuller AB, Pauschinger M, Bergelson J, Warraich R, Yacoub M et al (2001) Human coxsackie-adenovirus receptor is colocalized with integrins alpha(v)beta(3) and alpha(v)beta(5) on the cardiomyocyte sarcolemma and upregulated in dilated cardiomyopathy: Implications for cardiotropic viral infections. Circulation 104: 275–80PubMedGoogle Scholar
  14. 14.
    Badorff C, Lee GH, Lamphear BJ, Martone ME, Campbell KP, Rhoads RE, Knowlton KU (1999) Enteroviral protease 2A cleaves dystrophin: Evidence of cytoskeletal disruption in an acquired cardiomyopathy. Nat Med 5: 320–6CrossRefPubMedGoogle Scholar
  15. 15.
    Gjerdrum LM, Lielpetere I, Rasmussen LM, Bendix K, Hamilton-Dutoit S (2001) Laserassisted microdissection of membrane-mounted paraffin sections for polymerase chain reaction analysis. Identification of cell populations using immunohistochemistry and in situ hybridization. J Mol Diagn 3: 105–110CrossRefPubMedGoogle Scholar
  16. 16.
    Chimenti C, Russo A, Pieroni M, Calabrese F, Verardo R, Thiene G, Russo MA, Maseri A, Frustaci A (2004) Intramyocyte detection of Epstein-Barr virus genome by laser capture microdissection in patients with inflammatory cardiomyopathy. Circulation 110: 3534–9CrossRefPubMedGoogle Scholar
  17. 17.
    Chan KY, Iwahara M, Benson LN, Wilson GJ, Freedom RM (1991) Immunosuppressive therapy in the management of acute myocarditis in children; a clinical trial. J Am Coll Cardiol 17: 458–460CrossRefPubMedGoogle Scholar
  18. 18.
    Matitiau A, Perez-Atayde A, Sanders SP, Sluysmans T, Parness IA, Spevak PJ, Colan SD (1994) Infantile dilated cardiomyopathy. Relation of outcome to left ventricular mechanics, hemodynamics, and histology at the time of presentation. Circulation 90: 1310–8PubMedGoogle Scholar
  19. 19.
    Lee KJ, McCrindle BW, Bohn DJ, Wilson GJ, Taylor GP, Freedom RM, Smallhorn JF, Benson LN (1999) Clinical outcomes of acute myocarditis in childhood. Heart 82: 226–33PubMedGoogle Scholar
  20. 20.
    Kleinert S, Weintraub RG, Wilkinson JL, Chow CW (1997) Myocarditis in children with dilated cardiomyopathy: Incidence and outcome after dual therapy immunosuppression. J Heart Lung Transplant 16: 1248–54PubMedGoogle Scholar
  21. 21.
    Parrillo JE, Cunnion RE, Epstein SE, Parker MM, Suffredini AF, Brenner M, Schaer GL, Palmeri ST, Cannon RO, Alling D et al (1989) A prospective, randomized, controlled trial of prednisone for dilated cardiomyopathy. N Engl J Med 321: 1061–8CrossRefPubMedGoogle Scholar
  22. 22.
    Kuhl U, Schultheiss HP (1995) Treatment of chronic myocarditis with corticosteroids. Eur Heart J 16Suppl O: 168–72PubMedGoogle Scholar
  23. 23.
    Frustaci A, Gentiloni N, Chimenti C, Natale L, Gasbarrini G, Maseri A et al (1998) Necrotizing myocardial vasculitis in Churg-Strauss syndrome: Clinicohistologic evaluation of steroids and immunosuppressive therapy. Chest 114: 1484–9CrossRefPubMedGoogle Scholar
  24. 24.
    Badorff C, Schwimmbeck PL, Kuhl U, Gerhold M, Stein H, Schultheiss HP (1997) Cardiac sarcoidosis: Diagnostic validation by endomyocardial biopsy and therapy with corticosteroids. Z Kardiol 86: 9–14CrossRefPubMedGoogle Scholar
  25. 25.
    Cooper LT Jr, Berry GJ, Shabetai R (1997) Idiopathic giant-cell myocarditis-natural history and treatment. Multicenter Giant Cell Myocarditis Study Group Investigators. N Engl J Med 336: 1860–6CrossRefPubMedGoogle Scholar
  26. 26.
    Frustaci A, Chimenti C, Pieroni M, Gentiloni N (2000) Giant cell myocarditis responding to immunosuppressive therapy. Chest 117: 905–907CrossRefPubMedGoogle Scholar
  27. 27.
    Frustaci A, Gentiloni N, Caldarulo M (1996) Acute myocarditis and left ventricular aneurysm as presentations of systemic lupus erythematosus. Chest 109: 282–4CrossRefPubMedGoogle Scholar
  28. 28.
    Billingham ME (1997) Can histopathology guide immunosuppression for cardiac allograft rejection in the light of new techniques? Transplant Proc 29: 35S–36SCrossRefPubMedGoogle Scholar
  29. 29.
    Dec GW Jr, Palacios IF, Fallon JT, Aretz HT, Mills J, Lee DC, Johnson RA (1985) Active myocarditis in the spectrum of acute dilated cardiomyopathies. Clinical features, histologic correlates, and clinical outcome. N Engl J Med 312: 885–90CrossRefPubMedGoogle Scholar
  30. 30.
    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
  31. 31.
    Frustaci A Chimenti C, Calabrese F, Pieroni M, Thiene G, Maseri A (2003) Active lymphocytic myocarditis: Virologic and immunologic profile of responders vs nonresponders to immunosuppressive therapy. Circulation 107: 857–63CrossRefPubMedGoogle Scholar
  32. 32.
    Frustaci A, Chimenti C, Pieroni M, Salvatori L, Morgante E, Sale P, Ferretti E, Petrangeli E, Gulino A, Russo MA (2006) Cell death, proliferation and repair in human myocarditis responding to immunosuppressive therapy. Mod Pathol 19: 755–65PubMedGoogle Scholar
  33. 33.
    Kuhl U, Pauschinger M, Schwimmbeck PL, Seeberg B, Lober C, Noutsias M, Poller W, Schultheiss HP (2003) Interferon-beta treatment of patients with enteroviral and adenoviral cardiomyopathy causes effective virus clearance and long-term clinical improvement. Circulation 107: 2793–8CrossRefPubMedGoogle Scholar
  34. 34.
    Martin AB, Webber S, Fricker FJ, Jaffe R, Demmler G, Kearney D, Zhang YH, Bodurtha J, Gelb B, Ni J et al (1994) Acute myocarditis. Rapid diagnosis by PCR in children. Circulation 90: 330–9PubMedGoogle Scholar

Copyright information

© Springer Basel 2010

Authors and Affiliations

  • Andrea Frustaci
    • 1
  • Cristina Chimenti
    • 1
  1. 1.Department of Cardiovascular and Respiratory SciencesLa Sapienza UniversityRomeItaly

Personalised recommendations