Elsevier

Progress in Cardiovascular Diseases

Volume 52, Issue 4, January–February 2010, Pages 274-288
Progress in Cardiovascular Diseases

Myocarditis

https://doi.org/10.1016/j.pcad.2009.11.006Get rights and content

Abstract

Myocarditis is an uncommon, potentially life-threatening disease that presents with a wide range of symptoms in children and adults. Viral infection is the most common cause of myocarditis in developed countries, but other etiologies include bacterial and protozoal infections, toxins, drug reactions, autoimmune diseases, giant cell myocarditis, and sarcoidosis. Acute injury leads to myocyte damage, which in turn activates the innate and humeral immune system, leading to severe inflammation. In most patients, the immune reaction is eventually down-regulated and the myocardium recovers. In select cases, however, persistent myocardial inflammation leads to ongoing myocyte damage and relentless symptomatic heart failure or even death. The diagnosis is usually made based on clinical presentation and noninvasive imaging findings. Most patients respond well to standard heart failure therapy, although in severe cases, mechanical circulatory support or heart transplantation is indicated. Prognosis in acute myocarditis is generally good except in patients with giant cell myocarditis. Persistent, chronic myocarditis usually has a progressive course but may respond to immunosuppression.

Section snippets

Definition

The Dallas criteria were proposed in 1986 to provide a histopathologic classification for the diagnosis of myocarditis. These criteria require that an inflammatory cellular infiltrate with or without associated myocyte necrosis be present on conventionally stained myocardial tissue sections. Although these criteria have been used for more than 20 years, they are limited by variability in expert interpretation, lack of prognostic value, discrepancy with other markers of viral infection and

Incidence and natural history of myocarditis

The true incidence of myocarditis has been difficult to determine because clinical presentations vary widely, and EMB is rarely used due to perceived risks and lack of a widely accepted and sensitive histologic standard. Autopsy reports have revealed varying estimates of the incidence of myocarditis according to the population studied, with estimates ranging from 0.12% to 12%.10, 11, 12, 13, 14 The Myocarditis Treatment Trial reported the incidence of biopsy-documented myocarditis in patients

Adults

The clinical presentation of acute myocarditis in adults is highly variable, ranging from subclinical disease to fulminant heart failure. A viral prodrome including fever, rash, myalgias, arthralgias, fatigue, and respiratory or gastrointestinal symptoms frequently, but not always, precedes the onset of myocarditis by several days to a few weeks. Patients may present with chest pain, dyspnea, palpitations, fatigue, decreased exercise tolerance, or syncope. Chest pain in acute myocarditis may

Electrocardiogram

Although widely used as a screening tool, the sensitivity of electrocardiogram (ECG) for myocarditis is only 47%.44 The most common ECG findings are nonspecific T-wave changes. Occasionally, the ECG changes may mimic acute myocardial infarction or pericarditis with ST-segment elevation, ST-segment depression, PR depression, and pathologic Q waves.45, 46 In referral populations, new-onset supraventricular or ventricular arrhythmias occur in up to 55% of patients.47 These tachyarrhythmias are

Infectious

A variety of infectious and noninfectious diseases can cause myocarditis (Table 2). Viral infection is the most common cause in Western Europe and North America, with adenovirus and enterovirus (including coxsackievirus) historically being the most frequently identified viruses.16, 67, 71 Recently, the most commonly detected viral genomes in EMB samples were parvovirus B-19 and human herpesvirus-6. Serologic studies, predominantly in Japan, have linked the hepatitis C virus to myocarditis and

Host factors

Factors that determine susceptibility to viral myocarditis are not fully known, although a variety of factors such as malnutrition, pregnancy, sex hormones,21 and age have been implicated. Genetic host factors, including major histocompatibility haplotype,100 HLA-DQ locus,101 and CD45 polymorphisms,102 may be important determinants of early viral infection. Other host factors including selenium deficiency,103 vitamin E deficiency,103 and mercury exposure104, 105 have been reported to increase

Heart failure therapy

Most patients with acute myocarditis presenting with DCM respond well to standard heart failure therapy including diuretics, angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, and the introduction of β-blockers such as bisoprolol, metoprolol succinate, or carvedilol once they are clinically stable. Digoxin should be used with caution and only in low doses in patients with viral myocarditis because administration of digoxin in high doses to mice with viral-induced

Prognosis

Prognosis is excellent for adult patients with acute lymphocytic myocarditis with mild symptoms and preserved left ventricular ejection fraction, as most of them spontaneously improve without residual sequelae. In contrast, the Myocarditis Treatment Trial demonstrated that symptomatic adult patients who present with heart failure symptoms and a left ventricular ejection fraction less than 45% at baseline have a 4-year mortality of 56%.17 These results were obtained before the routine use of β

Prevention

Specific strategies for the prevention of myocarditis have yet to be determined. To the extent that they have eliminated the diseases, vaccination against measles, mumps, rubella, poliomyelitis, and influenza has made myocarditis secondary to these diseases quite rare and raises the question of whether vaccinations against other cardiotropic viruses may prevent myocarditis in the future. Murine models have demonstrated that vaccination is protective against viral infection and prevents

Summary and future directions

Myocarditis is a potentially life-threatening disease that primarily affects children and young adults with sometimes devastating consequences, including sudden death. The primary long-term consequences are DCM and chronic heart failure. Although much progress has been made in recent years in the diagnosis, pathophysiology, and treatment of this disease, numerous questions remain and indicate the need for further investigation. Noninvasive strategies for confirming the diagnosis of myocarditis,

Statement of Conflict of Interest

The authors declare that there are no conflicts of interest.

References (188)

  • PieroniM. et al.

    High prevalence of myocarditis mimicking arrhythmogenic right ventricular cardiomyopathy differential diagnosis by electroanatomic mapping-guided endomyocardial biopsy

    J Am Coll Cardiol

    (2009)
  • BassoC. et al.

    Arrhythmogenic right ventricular cardiomyopathy

    Lancet

    (2009)
  • MorgeraT. et al.

    Electrocardiography of myocarditis revisited: clinical and prognostic significance of electrocardiographic changes

    Am Heart J

    (1992)
  • VignolaP.A. et al.

    Lymphocytic myocarditis presenting as unexplained ventricular arrhythmias: diagnosis with endomyocardial biopsy and response to immunosuppression

    J Am Coll Cardiol

    (1984)
  • DecG.W. et al.

    Viral myocarditis mimicking acute myocardial infarction

    J Am Coll Cardiol

    (1992)
  • GreenwoodR.D. et al.

    The clinical course of primary myocardial disease in infants and children

    Am Heart J

    (1976)
  • NishiiM. et al.

    Serum levels of interleukin-10 on admission as a prognostic predictor of human fulminant myocarditis

    J Am Coll Cardiol

    (2004)
  • LauerB. et al.

    Cardiac troponin T in patients with clinically suspected myocarditis

    J Am Coll Cardiol

    (1997)
  • PinamontiB. et al.

    Echocardiographic findings in myocarditis

    Am J Cardiol

    (1988)
  • NieminenM.S. et al.

    Echocardiography in acute infectious myocarditis: relation to clinical and electrocardiographic findings

    Am J Cardiol

    (1984)
  • MendesL.A. et al.

    Right ventricular dysfunction: an independent predictor of adverse outcome in patients with myocarditis

    Am Heart J

    (1994)
  • JamesK.B. et al.

    Left ventricular diastolic dysfunction in lymphocytic myocarditis as assessed by Doppler echocardiography

    Am J Cardiol

    (1994)
  • FelkerG.M. et al.

    Echocardiographic findings in fulminant and acute myocarditis

    J Am Coll Cardiol

    (2000)
  • LaissyJ.P. et al.

    MRI of acute myocarditis: a comprehensive approach based on various imaging sequences

    Chest

    (2002)
  • Abdel-AtyH. et al.

    Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: comparison of different approaches

    J Am Coll Cardiol

    (2005)
  • MatsumoriA. et al.

    Myocarditis and heart failure associated with hepatitis C virus infection

    J Card Fail

    (2006)
  • HerskowitzA. et al.

    Myocarditis and cardiotropic viral infection associated with severe left ventricular dysfunction in late-stage infection with human immunodeficiency virus

    J Am Coll Cardiol

    (1994)
  • PuglieseA. et al.

    Impact of highly active antiretroviral therapy in HIV-positive patients with cardiac involvement

    J Infect

    (2000)
  • TaliercioC.P. et al.

    Myocarditis related to drug hypersensitivity

    Mayo Clin Proc

    (1985)
  • DilberE. et al.

    Acute myocarditis associated with tetanus vaccination

    Mayo Clin Proc

    (2003)
  • CassimatisD.C. et al.

    Smallpox vaccination and myopericarditis: a clinical review

    J Am Coll Cardiol

    (2004)
  • DanielsP.R. et al.

    Giant cell myocarditis as a manifestation of drug hypersensitivity

    Cardiovasc Pathol

    (2000)
  • OkuraY. et al.

    A clinical and histopathologic comparison of cardiac sarcoidosis and idiopathic giant cell myocarditis

    J Am Coll Cardiol

    (2003)
  • YazakiY. et al.

    Comparison of clinical features and prognosis of cardiac sarcoidosis and idiopathic dilated cardiomyopathy

    Am J Cardiol

    (1998)
  • BaughmanK.L.

    Diagnosis of myocarditis: death of Dallas criteria

    Circulation

    (2006)
  • MaischB. et al.

    Definition of inflammatory cardiomyopathy (myocarditis): on the way to consensus. A status report

    Herz

    (2000)
  • KindermannI. et al.

    Predictors of outcome in patients with suspected myocarditis

    Circulation

    (2008)
  • MahrholdtH. et al.

    Cardiovascular magnetic resonance assessment of human myocarditis: a comparison to histology and molecular pathology

    Circulation

    (2004)
  • GutberletM. et al.

    Suspected chronic myocarditis at cardiac MR: diagnostic accuracy and association with immunohistologically detected inflammation and viral persistence

    Radiology

    (2008)
  • CooperL.T. et al.

    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

    (2007)
  • WakafujiS. et al.

    Twenty year autopsy statistics of myocarditis incidence in Japan

    Jpn Circ J

    (1986)
  • CarnielE. et al.

    Fatal myocarditis: morphologic and clinical features

    Ital Heart J

    (2004)
  • KytoV. et al.

    Incidence of fatal myocarditis: a population-based study in Finland

    Am J Epidemiol

    (2007)
  • GravanisM.B. et al.

    Incidence of myocarditis. A 10-year autopsy study from Malmo, Sweden

    Arch Pathol Lab Med

    (1991)
  • DoolanA. et al.

    Causes of sudden cardiac death in young Australians

    Med J Aust

    (2004)
  • HahnE.A. et al.

    The Myocarditis Treatment Trial: design, methods and patients enrollment

    Eur Heart J

    (1995)
  • KuhlU. et al.

    High prevalence of viral genomes and multiple viral infections in the myocardium of adults with “idiopathic” left ventricular dysfunction

    Circulation

    (2005)
  • MasonJ.W. et al.

    A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators

    N Engl J Med

    (1995)
  • CaforioA.L. et al.

    A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis

    Eur Heart J

    (2007)
  • LydenD.C. et al.

    Coxsackievirus B-3-induced myocarditis. Effect of sex steroids on viremia and infectivity of cardiocytes

    Am J Pathol

    (1987)
  • Cited by (0)

    Statement of Conflict of Interest: see page 284.

    Author's note: Substantial content in this review article is drawn from Cooper LT Jr. Myocarditis. N Engl J Med 2009;9;360(15):1526-38.

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