Abstract
Fulminant myocarditis is an inflammatory process that occurs in the myocardium and causes acute-onset heart failure. If patients with fulminant myocarditis are aggressively supported in a timely manner, nearly all can have an excellent recovery. In this Review, we discuss the clinical and histological distinguishing features of fulminant myocarditis and contrast this disease entity with nonfulminant myocarditis. The epidemiology, pathophysiology, clinical presentation, methods of diagnosis, management options and prognosis of fulminant myocarditis are reviewed in detail.
Key Points
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Myocarditis could account for up to 10% of acute-onset heart failure cases; viral infections are responsible in the majority of instances
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The pathophysiology of myocarditis involves both direct, virally mediated myocyte injury and immune-mediated tissue injury
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Patients with fulminant myocarditis often present with cardiogenic shock and multiorgan failure; several clinical and laboratory findings enable the practicing physician to differentiate fulminant from nonfulminant myocarditis
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Endomyocardial biopsy serves a critical role in the management of fulminant myocarditis and is an essential diagnostic tool to help differentiate myocarditis from giant cell myocarditis and necrotizing eosinophilic myocarditis
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Patients with fulminant myocarditis should be managed with aggressive inotropic support with or without placement of an intra-aortic balloon pump; if the patient does not respond rapidly to aggressive supportive therapy, insertion of a ventricular assist device should be considered at an early stage
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With aggressive supportive care, complete ventricular recovery occurs in the majority of patients with fulminant myocarditis; however, even after ventricular recovery, standard heart-failure medications should be administered indefinitely
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References
Feldman AM et al. (2000) Myocarditis. N Engl J Med 343: 1388–1398
Magnani JW et al. (2006) Myocarditis: current trends in diagnosis and treatment. Circulation 113: 876–890
Herskowitz A et al. (1993) Demographic features and prevalence of idiopathic myocarditis in patients undergoing endomyocardial biopsy. Am J Cardiol 71: 982–986
McCarthy RE III et al. (2000) Long-term outcome of fulminant myocarditis as compared with acute (nonfulminant) myocarditis. N Engl J Med 342: 690–695
Mason JW et al. (1995) A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators. N Engl J Med 333: 269–275
Hufnagel G et al. (2000) The European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases (ESETCID). First epidemiological results. Herz 25: 279–285
Drory Y et al. (1991) Sudden unexpected death in persons less than 40 years of age. Am J Cardiol 68: 1388–1392
Phillips M et al. (1986) Sudden cardiac death in Air Force recruits. A 20-year review. JAMA 256: 2696–2699
Grumbach IM et al. (1999) Adenoviruses and enteroviruses as pathogens in myocarditis and dilated cardiomyopathy. Acta Cardiol 54: 83–88
Why HJ et al. (1994) Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy. Circulation 89: 2582–2589
Liu P et al. (1996) Viral myocarditis: balance between viral infection and immune response. Can J Cardiol 12: 935–943
Martino TA et al. (1998) Cardiovirulent coxsackieviruses and the decay-accelerating factor (CD55) receptor. Virology 244: 302–314
Liu P et al. (2000) The tyrosine kinase p56lck is essential in coxsackievirus B3-mediated heart disease. Nat Med 6: 429–434
Leiden JM (1997) The genetics of dilated cardiomyopathy—emerging clues to the puzzle. N Engl J Med 337: 1080–1081
Towbin JA (1998) The role of cytoskeletal proteins in cardiomyopathies. Curr Opin Cell Biol 10: 131–139
Badorff C et al. (1999) Enteroviral protease 2A cleaves dystrophin: evidence of cytoskeletal disruption in an acquired cardiomyopathy. Nat Med 5: 320–326
Silver MA et al. (1989) Coronary microvascular narrowing in acute murine coxsackie B3 myocarditis. Am Heart J 118: 173–174
Kawai C (1999) From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future. Circulation 99: 1091–1100
Huber AR et al. (1989) Disruption of the subendothelial basement membrane during neutrophil diapedesis in an in vitro construct of a blood vessel wall. J Clin Invest 83: 1122–1136
Harlan JM et al. (1981) Neutrophil-mediated endothelial injury in vitro mechanisms of cell detachment. J Clin Invest 68: 1394–1403
Lee JK et al. (1998) A serine elastase inhibitor reduces inflammation and fibrosis and preserves cardiac function after experimentally-induced murine myocarditis. Nat Med 4: 1383–1391
Chow LH et al. (1992) Enteroviral infection of mice with severe combined immunodeficiency. Evidence for direct viral pathogenesis of myocardial injury. Lab Invest 66: 24–31
Kamijo R et al. (1994) Requirement for transcription factor IRF-1 in NO synthase induction in macrophages. Science 263: 1612–1615
Liu P et al. (1995) The role of transgenic knockout models in defining the pathogenesis of viral heart disease. Eur Heart J 16 (Suppl O): 25–27
Seko Y et al. (1990) Expression of major histocompatibility complex class I antigen in murine ventricular myocytes infected with coxsackievirus B3. Circ Res 67: 360–367
Kaya Z et al. (2001) Contribution of the innate immune system to autoimmune myocarditis: a role for complement. Nat Immunol 2: 739–745
Ono K et al. (1998) Cytokine gene expression after myocardial infarction in rat hearts: possible implication in left ventricular remodeling. Circulation 98: 149–156
Felker GM et al. (2000) Echocardiographic findings in fulminant and acute myocarditis. J Am Coll Cardiol 36: 227–232
Dec GW Jr et al. (1985) Active myocarditis in the spectrum of acute dilated cardiomyopathies. Clinical features, histologic correlates, and clinical outcome. N Engl J Med 312: 885–890
Smith SC et al. (1997) Elevations of cardiac troponin I associated with myocarditis. Experimental and clinical correlates. Circulation 95: 163–168
Kato S et al. (2004) Risk factors for patients developing a fulminant course with acute myocarditis. Circ J 68: 734–739
Lee CH et al. (2006) Predictive factors of a fulminant course in acute myocarditis. Int J Cardiol 109: 142–145
Vignola PA et al. (1984) Lymphocytic myocarditis presenting as unexplained ventricular arrhythmias: diagnosis with endomyocardial biopsy and response to immunosuppression. J Am Coll Cardiol 4: 812–819
Cooper LT Jr et al. (1997) Idiopathic giant-cell myocarditis—natural history and treatment. Multicenter Giant Cell Myocarditis Study Group Investigators. N Engl J Med 336: 1860–1866
Cooper LT et al. (2005) Biventricular assist device placement and immunosuppression as therapy for necrotizing eosinophilic myocarditis. Nat Clin Pract Cardiovasc Med 2: 544–548
Herzog CA et al. (1984) Acute necrotising eosinophilic myocarditis. Br Heart J 52: 343–348
Midei MG et al. (1990) Peripartum myocarditis and cardiomyopathy. Circulation 81: 922–928
Zaidi AR et al. (2007) Outcome of heart transplantation in patients with sarcoid cardiomyopathy. J Heart Lung Transplant 26: 714–717
Cooper LT Jr (2000) Giant cell myocarditis: diagnosis and treatment. Herz 25: 291–298
Kilgallen CM et al. (1998) A case of giant cell myocarditis and malignant thymoma: a postmortem diagnosis by needle biopsy. Clin Cardiol 21: 48–51
Daniels PR et al. (2000) Giant cell myocarditis as a manifestation of drug hypersensitivity. Cardiovasc Pathol 9: 287–291
Cooper LT Jr (2005) Giant cell and granulomatous myocarditis. Heart Fail Clin 1: 431–437
Newman LS et al. (1997) Sarcoidosis. N Engl J Med 336: 1224–1234
Hilfiker-Kleiner D et al. (2007) A cathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy. Cell 128: 589–600
Hochman JS et al. (2001) One-year survival following early revascularization for cardiogenic shock. JAMA 285: 190–192
Pinamonti B et al. (1988) Echocardiographic findings in myocarditis. Am J Cardiol 62: 285–291
Mendes LA et al. (1994) Right ventricular dysfunction: an independent predictor of adverse outcome in patients with myocarditis. Am Heart J 128: 301–307
Lieback E et al. (1996) Clinical value of echocardiographic tissue characterization in the diagnosis of myocarditis. Eur Heart J 17: 135–142
Carvalho JS et al. (1996) Prognostic value of posterior wall thickness in childhood dilated cardiomyopathy and myocarditis. Eur Heart J 17: 1233–1238
Hiramitsu S et al. (2001) Transient ventricular wall thickening in acute myocarditis: a serial echocardiographic and histopathologic study. Jpn Circ J 65: 863–866
Gagliardi MG et al. (1991) Usefulness of magnetic resonance imaging for diagnosis of acute myocarditis in infants and children, and comparison with endomyocardial biopsy. Am J Cardiol 68: 1089–1091
Gagliardi MG et al. (1999) MRI for the diagnosis and follow-up of myocarditis. Circulation 99: 458–459
Mahrholdt H et al. (2004) Cardiovascular magnetic resonance assessment of human myocarditis: a comparison to histology and molecular pathology. Circulation 109: 1250–1258
Liu PP et al. (2005) Cardiovascular magnetic resonance for the diagnosis of acute myocarditis: prospects for detecting myocardial inflammation. J Am Coll Cardiol 45: 1823–1825
Hung MY et al. (2007) Use of gallium 67 scintigraphy to differentiate acute myocarditis from acute myocardial infarction. Tex Heart Inst J 34: 305–309
Cooper LT et al. (2007) The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Circulation 116: 2216–2233
Chow LH et al. (1989) Insensitivity of right ventricular endomyocardial biopsy in the diagnosis of myocarditis. J Am Coll Cardiol 14: 915–920
Hauck AJ et al. (1989) Evaluation of postmortem endomyocardial biopsy specimens from 38 patients with lymphocytic myocarditis: implications for role of sampling error. Mayo Clin Proc 64: 1235–1245
Aretz HT et al. (1987) Myocarditis. A histopathologic definition and classification. Am J Cardiovasc Pathol 1: 3–14
Shanes JG et al. (1987) Interobserver variability in the pathologic interpretation of endomyocardial biopsy results. Circulation 75: 401–405
Lieberman EB et al. (1991) Clinicopathologic description of myocarditis. J Am Coll Cardiol 18: 1617–1626
Acker MA (2001) Mechanical circulatory support for patients with acute-fulminant myocarditis. Ann Thorac Surg 71 (Suppl): S73–S76
Dipla K et al. (1998) Myocyte recovery after mechanical circulatory support in humans with end-stage heart failure. Circulation 97: 2316–2322
Zafeiridis A et al. (1998) Regression of cellular hypertrophy after left ventricular assist device support. Circulation 98: 656–662
Reiss N et al. (1996) Management of acute fulminant myocarditis using circulatory support systems. Artif Organs 20: 964–970
Kawahito K et al. (1998) Usefulness of extracorporeal membrane oxygenation for treatment of fulminant myocarditis and circulatory collapse. Am J Cardiol 82: 910–911
Bavaria JE et al. (1990) Effect of circulatory assist devices on stunned myocardium. Ann Thorac Surg 49: 123–128
Matsumori A et al. (1999) High doses of digitalis increase the myocardial production of proinflammatory cytokines and worsen myocardial injury in viral myocarditis: a possible mechanism of digitalis toxicity. Jpn Circ J 63: 934–940
Houel R et al. (1999) Myocardial recovery after mechanical support for acute myocarditis: is sustained recovery predictable. Ann Thorac Surg 68: 2177–2180
Parrillo JE et al. (1989) A prospective, randomized, controlled trial of prednisone for dilated cardiomyopathy. N Engl J Med 321: 1061–1068
Miric M et al. (1996) Long-term follow up of patients with dilated heart muscle disease treated with human leucocytic interferon alpha or thymic hormones initial results. Heart 75: 596–601
Wojnicz R et al. (2001) Randomized, placebo-controlled study for immunosuppressive treatment of inflammatory dilated cardiomyopathy: two-year follow-up results. Circulation 104: 39–45
Gullestad L et al. (2001) Immunomodulating therapy with intravenous immunoglobulin in patients with chronic heart failure. Circulation 103: 220–225
McNamara DM et al. (2001) Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy. Circulation 103: 2254–2259
Maisch B et al. (2004) Treatment of inflammatory dilated cardiomyopathy and (peri)myocarditis with immunosuppression and i.v. immunoglobulins. Herz 29: 624–636
Bergelson JM et al. (1997) Isolation of a common receptor for coxsackie B viruses and adenoviruses 2 and 5. Science 275: 1320–1323
Liu PP et al. (2001) Advances in the understanding of myocarditis. Circulation 104: 1076–1082
Neu N et al. (1987) Cardiac myosin induces myocarditis in genetically predisposed mice. J Immunol 139: 3630–3636
Neu N et al. (1987) Autoantibodies specific for the cardiac myosin isoform are found in mice susceptible to coxsackievirus B3-induced myocarditis. J Immunol 138: 2488–2492
Wang Y et al. (2000) Nasal administration of cardiac myosin suppresses autoimmune myocarditis in mice. J Am Coll Cardiol 36: 1992–1999
Acknowledgements
Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.The authors would like to acknowledge Dr Thomas E Rogers, Professor in Pathology at University of Texas Southwestern Medical Center, Dallas, TX, USA, for his invaluable help in obtaining the histologic images of endomyocardial biopsy slides.
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Gupta, S., Markham, D., Drazner, M. et al. Fulminant myocarditis. Nat Rev Cardiol 5, 693–706 (2008). https://doi.org/10.1038/ncpcardio1331
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DOI: https://doi.org/10.1038/ncpcardio1331
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