AUTHOR AND EDITOR INFORMATION

Section 1 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• References

INTRODUCTION

Section 2 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• References

Background

Myocarditis is an inflammatory disease of the myocardium with a wide range of clinical presentation, from subtle to devastating. It is diagnosed by established histologic, immunologic, and immunochemical criteria. Myocarditis is described as "an inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes."¹ It usually manifests in an otherwise healthy person and can result in rapidly progressive (and often fatal) heart failure and arrhythmia. In the clinical setting, myocarditis is synonymous with inflammatory cardiomyopathy.

Lieberman proposed the following alternative clinicopathologic classification:²

• Fulminant myocarditis - Follows a viral prodrome; distinct onset of illness comprising severe cardiovascular compromise with ventricular dysfunction and multiple foci of active myocarditis; either resolves spontaneously or results in death
• Acute myocarditis - Less distinct onset of illness, with established ventricular dysfunction; may progress to dilated cardiomyopathy
• Chronic active myocarditis - Less distinct onset of illness, with clinical and histologic relapses; development of ventricular dysfunction associated with chronic inflammatory changes (including giant cells)
• Chronic persistent myocarditis - Less distinct onset of illness; persistent histologic infiltrate with foci of myocyte necrosis without ventricular dysfunction despite symptoms (eg, chest pain, palpitations)

These terms are still used to describe the clinical presentation and progression of myocarditis, particularly in the absence of ongoing histologic evaluation.

For related information, see Medscape's Heart Failure and Cardiac Rhythm Management Resource Center.

Pathophysiology

Myocarditis is likely caused by a wide variety of infectious organisms, autoimmune disorders, and exogenous agents, with genetic and environmental predisposition. Most cases are presumed to be caused by a common pathway of host-mediated, autoimmune-mediated injury, although direct cytotoxic effects of the causative agent and damages due to cytokine expression in the myocardium may play some role in myocarditis etiology. Damage occurs through the following mechanisms:

• Direct cytotoxic effect of the causative agent
• Secondary immune response, which can be triggered by the causative agent
• Cytokine expression in the myocardium (eg, tumor necrosis factor-alpha, nitric oxide synthase)
• Aberrant induction of apoptosis

Myocardial damage has 2 main phases, as follows:

• Acute phase (first 2 wk): Myocyte destruction is a direct consequence of the offending agent, which causes cell-mediated cytotoxicity and cytokine release, contributing to myocardial damage and dysfunction. Detection of the causal agent is uncommon during this stage.
• Chronic phase (>2 wk): Continuing myocyte destruction is autoimmune in nature, with associated abnormal expression of human leukocyte antigen (HLA) in myocytes (and in the case of viral myocarditis, persistence of viral genome in myocardium).

In viral myocarditis, viral isolates differ in tissue tropism and virulence. For example, coxsackievirus A9 is a self-limiting myocarditis, whereas coxsackievirus B3 causes severe myocarditis resulting in a high mortality rate. The induction of the coxsackie-adenovirus receptor (CAR) and the complement deflecting protein decay accelerating factor (DAF, CD55) may allow efficient internationalization of the viral genome. Viral replication may lead to further disruption of metabolism and perturbation of inflammation and its response. Vasospasm induced by endothelial cell viral infection may also contribute to further damage.³

New evidence of dystrophin disruption by expression of enteroviral protease 2A points to yet another unique pathogenic mechanism.⁴ In contrast, some viruses (such as parvovirus B19) may focus on pericapillary depositions, contributing to diastolic dysfunction rather than direct myocyte destruction. Regardless, viral persistence provides the necessary stimuli for autoimmune or other inflammatory responses.

Frequency

United States

Frequency is difficult to ascertain, owing to the wide variation of clinical presentation. Incidence is usually estimated at 1-10 cases per 100,000 persons. Incidence of positive right ventricular biopsy findings in patients with suspected myocarditis is highly variable (ranging from 0-80%). According to estimates, as many as 1-5% of patients with acute viral infections may have involvement of the myocardium.

International

• A population study in Finland found that, in nearly a study of 700,000 healthy young male military recruits, 98 cases had myocarditis mimicking myocardial ischemia, 1 case presented as sudden death, and 9 cases presented as recent-onset dilated cardiomyopathy.⁵
• A Japanese 20-year series of 377,841 autopsies found idiopathic, nonspecific, interstitial, or viral myocarditis in only 0.11% of individuals.⁶

Mortality/Morbidity

Most patients with mild symptoms recover completely without any residual cardiac dysfunction, with a third subsequently developing dilated cardiomyopathy.^{7, 8, 9}

• In the Myocarditis Treatment Trial, the 1-year mortality rate was 20% and the 4-year mortality rate was 56% in a population with symptomatic heart failure presentation and left ventricular ejection fraction lower than 45% at baseline.¹⁰
• For untreated giant cell myocarditis, median survival from symptom onset is only 5.5 months, and the 1-year mortality rate is 80% (includes death and transplant).¹¹
• Mortality rate for postpartum cardiomyopathy at 1 year also can be as high as 50%.

Race

No particular predominance is noted except for peripartum cardiomyopathy (a specific form of myocarditis that appears to have a higher incidence in patients of African descent).

Sex

Incidence is similar between males and females, although young males are particularly susceptible.

Age

Patients are usually fairly young. The median age of patients affected with lymphocytic myocarditis is 42 years.

• Patients with giant cell myocarditis may be older (mean age 58 years), but this condition usually does not discriminate with respect to age, sex, or presenting symptoms.
• Other susceptible groups include immunocompromised individuals, pregnant women, and children (particularly neonates).

CLINICAL

Section 3 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• References

History

Clinical history is of acute decompensation of heart failure in a person with no other underlying cardiac dysfunction or with low cardiac risk. The diagnosis is usually presumptive, based on patient demographics and the clinical course (eg, spontaneous recovery following supportive care).

• Patients may present with mild symptoms of chest pain (in concurrent pericarditis), fever, sweats, chills, and dyspnea.
• In viral myocarditis, patients may present with a history of recent (within 1-2 wk) flulike syndrome of fevers, arthralgias, and malaise or pharyngitis, tonsillitis, or upper respiratory tract infection.
• Population studies suggest that adults may present with few symptoms, rather than the acute toxic state of cardiogenic shock or frank heart failure (fulminant myocarditis) that is often associated with myocarditis.
• Symptoms of palpitations, syncope, or even sudden cardiac death may develop, due to underlying ventricular arrhythmias or atrioventricular block (especially in giant cell myocarditis).
• Adults may present with heart failure years after initial index event of myocarditis (as many as 12.8% of patients with idiopathic dilated cardiomyopathy had presumed prior myocarditis in one case series).

Physical

Patients with myocarditis usually present with signs and symptoms of acute decompensation of heart failure (eg, tachycardia, gallop, mitral regurgitation, edema) and pericardial friction rub in those with concomitant pericarditis. Specific findings in special cases are as follows:

• Sarcoid myocarditis - Lymphadenopathy, also with arrhythmias, sarcoid involvement in other organs (up to 70%)
• Acute rheumatic fever (usually affects heart in 50-90%) - Associated signs such as erythema marginatum, polyarthralgia, chorea, subcutaneous nodules (Jones criteria)
• Hypersensitive/eosinophilic myocarditis - Pruritic maculopapular rash and history of using offending drug
• Giant cell myocarditis - Sustained ventricular tachycardia in rapidly progressive heart failure¹²
• Peripartum cardiomyopathy - Heart failure developing in the last month of pregnancy or within 5 months following delivery

Causes

Approximately 50% of the time, myocarditis is classified as idiopathic, although a viral etiology is often suspected but unproved, even with sophisticated immunohistochemical and genomic studies. Recent studies on patients with idiopathic dilated cardiomyopathy found evidence of viral particles in endomyocardial biopsy specimens in up to two thirds of the patients.¹³

• Viral - Enterovirus, coxsackie B, adenovirus, influenza, cytomegalovirus, poliomyelitis, Epstein-Barr virus, HIV-1, viral hepatitis, mumps, rubeola, varicella, variola/vaccinia, arbovirus, respiratory syncytial virus, herpes simplex virus, yellow fever virus, rabies, parvovirus
• Rickettsial - Scrub typhus, Rocky Mountain spotted fever, Q fever
• Bacterial - Diphtheria, tuberculosis, streptococci, meningococci, brucellosis, clostridia, staphylococci, melioidosis, Mycoplasma pneumoniae, psittacosis
• Spirochetal - Syphilis, leptospirosis/Weil disease, relapsing fever/Borrelia, Lyme disease
• Fungal - Candidiasis, aspergillosis, cryptococcosis, histoplasmosis, actinomycosis, blastomycosis, coccidioidomycosis, mucormycosis
• Protozoal - Chagas disease, toxoplasmosis, trypanosomiasis, malaria, leishmaniasis, balantidiasis, sarcosporidiosis
• Helminthic - Trichinosis, echinococcosis, schistosomiasis, heterophyiasis, cysticercosis, visceral larva migrans, filariasis
• Bites/stings - Scorpion venom, snake venom, black widow spider venom, wasp venom, tick paralysis
• Drugs (usually causing hypersensitivity myocarditis)
• • Chemotherapeutic drugs - Doxorubicin and anthracyclines, streptomycin, cyclophosphamide, interleukin-2, anti-HER-2 receptor antibody/Herceptin
  • Antibiotics - Penicillin, chloramphenicol, sulfonamides
  • Antihypertensive drugs - Methyldopa, spironolactone
  • Antiseizure drugs - Phenytoin, carbamazepine
  • Amphetamines, cocaine, catecholamines
• Chemicals - Hydrocarbons, carbon monoxide, arsenic, lead, phosphorus, mercury, cobalt
• Physical agents (radiation, heatstroke, hypothermia)
• Acute rheumatic fever
• Systemic inflammatory disease - Giant cell myocarditis, sarcoidosis, Kawasaki disease, Crohn disease, systemic lupus erythematosus, ulcerative colitis, Wegener granulomatosis, thyrotoxicosis, scleroderma, rheumatoid arthritis
• Peripartum cardiomyopathy
• Posttransplant cellular rejection

DIFFERENTIALS

Section 4 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• References

WORKUP

Section 5 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• References

Lab Studies

• Complete blood count - Leukocytosis (may demonstrate eosinophilia)
• Elevated erythrocyte sedimentation rate (and other acute phase reactants such as C-reactive protein)
• Rheumatologic screening - To rule out systemic inflammatory diseases
• Elevated cardiac enzymes (creatine kinase or cardiac troponins)
• • These are an indicator for cardiac myonecrosis. Cardiac troponin (troponin I or T), in particular, is elevated in at least 50% of patients with biopsy-proven myocarditis. They may also help identify those with resolution of viral myocarditis.
  • The test has 89% specificity and 34% sensitivity and increases more frequently than creatine kinase MB subunits (elevated in only 5.7% of patients with biopsy-proven myocarditis).
• Serum viral antibody titers for viral myocarditis
• • Common viral antibody titers available for clinical evaluation include coxsackievirus group B, HIV, cytomegalovirus, Ebstein-Barr virus, hepatitis virus family, and influenza viruses. Titers increase 4-fold or more with gradual fall during convalescence (nonspecific), hence requiring serial testing.
  • Antibody titer test is rarely indicated in the diagnosis of viral myocarditis or any dilated cardiomyopathies, owing to its low specificity and the delay of rising viral titers, which would have no impact on therapeutic decisions.
  • The presence of viral genome in endomyocardial biopsy samples have been sought to be the criterion standard for viral persistence; however, it lacks specificity as the presence of viral genome can also be present in healthy controls. The most common viral genomes found include parvovirus and herpes simplex.

Imaging Studies

• Echocardiography: This is performed to exclude other causes of heart failure (eg, valvular, amyloidosis, congenital) and to evaluate the degree of cardiac dysfunction (usually diffuse hypokinesis and diastolic dysfunction). It also may allow gross localization of the extent of inflammation (ie, wall motion abnormalities, wall thickening, pericardial effusion). In addition, echocardiography may distinguish between fulminant and acute myocarditis by identifying near-normal left ventricular diastolic dimensions and increased septal thickness in fulminant myocarditis (versus increased left ventricular diastolic dimensions and normal septal thickness in acute myocarditis), with marked improvement in systolic function in time.
• Cardiac angiography: This is often indicated to rule out coronary ischemia as a cause of new-onset heart failure, especially when clinical presentation mimics acute myocardial infarction. It usually shows high filling pressures and reduced cardiac outputs.
• Gadolinium-enhanced MRI: This imaging technique is used for assessment of the extent of inflammation and cellular edema, although it is still nonspecific. Delayed-enhanced MRI has also been used to quantify the amount of scarring that occurred following acute myocarditis.
• Nuclear imaging: Antimyosin scintigraphy (using antimyosin antibody injections) can identify myocardial inflammation with high sensitivity (91-100%) and negative predictive power (93-100%) but has low specificity (31-44%) and low positive predictive power (28-33%). In contrast, gallium scanning is used to reflect severe myocardial cellular infiltration and has a good negative predictive value, although specificity is low. Positron emission tomography (PET) scanning has been used in selected cases (eg, sarcoidosis) to assess the degree and location of inflammation.

Other Tests

• Electrocardiogram - Often nonspecific (eg, sinus tachycardia, nonspecific ST or T-wave changes)
• • Occasionally, heart block (atrioventricular block or intraventricular conduction delay), ventricular arrhythmia, or injury patterns with ST- or T-wave changes mimicking myocardial ischemia or pericarditis (pseudoinfarction pattern) may indicate poorer prognosis.
  • Arrhythmia is common in Chagas heart disease. The following may be seen: right bundle-branch block with or without bifascicular block (50%), complete heart block (7-8%), atrial fibrillation (7-10%), and ventricular arrhythmia (39%).

Procedures

• Endomyocardial biopsy (EMB): This is the criterion standard for diagnosis of myocarditis, although it still has limited sensitivity and specificity, as inflammation can be diffuse or focal. Routine EMB in establishing diagnosis of myocarditis rarely is helpful clinically, however, since histologic diagnosis seldom has an impact on therapeutic strategies, unless giant cell myocarditis is suspected.^{14, 15} The risk of adverse events approaches 6% (including complications with 2.7% on sheath insertion and 3.3% on the biopsy procedure), including 0.5% probability of perforation.¹⁵
• Because of sampling technique, sensitivity may increase with multiple biopsies (50% for 1 biopsy, 90% for 7 biopsies). The standard is to obtain at least 4 or 5 biopsies, although false-negative rates still may be as high as 55%.
• False-positive rates are also high, owing to small numbers of normally occurring lymphocytes in the myocardium and the difficulty in distinguishing between lymphocytes and other cells (such as eosinophils in hypersensitive/eosinophilic myocarditis).
• Wide interobserver variability in histologic interpretations is also a factor.
• Noncaseating granulomas for sarcoid myocarditis are found in only 5% of cases by biopsies, and in as many as 27% in autopsy series.
• Persisting viral mRNA can be found in only 25-50% of patients with biopsy-proven acute myocarditis, and persistent viral mRNA often confers a poor prognosis. Recent epidemiological results from the European Study on the Epidemiology and Treatment of Cardiac Inflammatory Disease (ESETCID) database found that only 11.8% of patients with suspected acute or chronic myocarditis and reduced ejection fractions had detectable viral genomes in biopsy samples.¹⁶

Histologic Findings

Biopsy specimens from EMB should reveal the simultaneous findings of lymphocyte infiltration and myocyte necrosis.

Staging

The Dallas classification (1987) and the World Health Organization (WHO) Marburg classification (1996) are commonly used.¹

• Cell types - Lymphocytic, eosinophilic, neutrophilic, giant cell, granulomatous, or mixed
• Amount - None (grade 0), mild (grade 1), moderate (grade 2), or severe (grade 3)
• Distribution - Focal (outside vessel lumen), confluent, diffuse, or reparative (in fibrotic areas)
• Dallas classification (1987)
• • Initial biopsy
  • • Myocarditis - Myocardial necrosis, degeneration, or both, in the absence of significant coronary artery disease with adjacent inflammatory infiltrate with or without fibrosis
    • Borderline myocarditis - Inflammatory infiltrate too sparse or myocyte damage not apparent
    • No myocarditis
  • Subsequent biopsy
  • • Ongoing (persistent) myocarditis with or without fibrosis
    • Resolving (healing) myocarditis with or without fibrosis
    • Resolved (healed) myocarditis with or without fibrosis
• WHO Marburg criteria (1996) defines myocarditis as a minimum of 14 infiltrating leukocytes/mm², preferably T cells (CD45RO), with as many as 4 macrophages possibly included.¹⁶

TREATMENT

Section 6 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• References

Medical Care

Treatment of myocarditis includes supportive therapy for symptoms of acute heart failure with use of diuretics, nitroglycerin/nitroprusside, and angiotensin-converting enzyme (ACE) inhibitors (see Pulmonary Edema, Cardiogenic). Inotropic drugs (eg, dobutamine, milrinone) may be necessary for severe decompensation, although they are highly arrhythmogenic. Long-term treatment follows the same medical regimen, including ACE inhibitors, beta-blockers, and aldosterone receptor antagonists. However, in some instances, some of these drugs cannot be implemented initially because of hemodynamic instability.

• Withdrawal of the offending agent is called for, if applicable (eg, cardiotoxic drugs, alcohol). Treat underlying infectious or systemic inflammatory etiology. Nonsteroidal anti-inflammatory agents should be avoided in the acute phase, as their use may impede myocardial healing and actually exacerbate the inflammatory process and increase the risk of mortality.
• Anticoagulation may be advisable as a preventive measure, as in other causes of heart failure, although no definitive evidence is available.
• Antiarrhythmics can be used cautiously, although most antiarrhythmic drugs have negative inotropic effects that may aggravate heart failure.
• • Supraventricular arrhythmias should be converted electrically.
  • High-grade ventricular ectopy and ventricular tachyarrhythmia should be treated cautiously with beta-blockers and antiarrhythmics.
  • Patients are usually very sensitive to digoxin and should use it with caution and in low doses. (Digoxin increases expression of proinflammatory cytokines and mortality rate in animal models.)
  • Complete heart block is an indication for temporary transvenous pacing.
  • Implantable defibrillators rarely are indicated in lymphocytic myocarditis unless extensive scarring has occurred. In the case of frequent nonsustained or polymorphic ventricular ectopy or tachyarrhythmia, temporary or wearable defibrillator support (eg, LifeVest) may be considered.
• This condition carries a low threshold for ventilatory and circulatory support (such as intra-aortic balloon pump) because of the rapidly progressive course of decompensation and the potential for reversal. In extreme cases, circulatory support with a ventricular assist device or percutaneous circulatory support (such as TandemHeart or Impella) has been reported.
• Immunosuppression has not been demonstrated to change the natural history of infectious myocarditis. Three large-scale prospective clinical trials on immunosuppressive strategies have been performed in patients with myocarditis, none of which showed significant benefits (National Institutes of Health [NIH] prednisone trial¹⁷, Myocarditis Treatment Trial¹⁰, and Intervention in Myocarditis and Acute Cardiomyopathy [IMAC] trial¹⁸). Empirical treatment with immunosuppression for systemic autoimmune disease, especially in giant cell myocarditis and sarcoid myocarditis, is often given based on evidence from small series.^{11, 19}
• Ongoing studies will determine if antiviral agents, immunosuppressants, or immunoabsorption therapies are beneficial in specific patient populations, although some small series have provided preliminary evidence that demonstrated their potential efficacies.

Surgical Care

• Left ventricular assistive devices (LVADs) and extracorporeal membrane oxygenation (ECMO) may be indicated for short-term circulatory support if needed for cardiogenic shock.
• Cardiac transplantation
• • Survival rates have not been shown to be decreased in patients with acute myocarditis, although retrospective observations have been made that more posttransplant acute rejections and subsequent posttransplant vasculopathy may occur in these patients.
  • Transplantation has been shown to be particularly beneficial to those with biopsy-proven giant cell myocarditis; the 5-year survival rate after transplantation was 71%, despite a 25% incidence of posttransplantation recurrence, as seen in 9 of 34 patients in the Multicenter Giant Cell Myocarditis study.

Consultations

• Cardiothoracic surgery
• Infectious disease and/or rheumatology consultations

Diet

Low-sodium diet similar to that of heart failure management

Activity

Bedrest and avoidance of athletic activities are recommended from anecdotal experiences (with lower incidence of arrhythmia).

MEDICATION

Section 7 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• References

In general, treatment of both acute and chronic myocarditis is aimed at reducing congestion and improving cardiac hemodynamics in heart failure, as well as providing supportive therapy with the hopes of prolonging survival (see Treatment). Treatment of heart failure follows the same treatment regimen regardless of the underlying cause (ie, ACE inhibitors, beta-adrenergic blockers).

Intensive immunosuppressive therapy (eg, corticosteroids, azathioprine, cyclosporine, muromonab-CD3/OKT3) has been shown to have some benefit only in small-scale clinical studies in treatment of giant cell myocarditis and has not been validated in large clinical trials. At this time, immunosuppressive therapy is not recommended for myocarditis until clear evidence is available from the results of multicenter trials.

Drug Category: Vasodilators

Reduce systemic vascular resistance, allowing more forward flow and improving cardiac output. This in turn improves myocardial oxygen supply, resulting in dilatation of epicardial and collateral vessels, improving blood supply to the ischemic myocardium.

Drug Category: ACE inhibitors

Following stabilization of heart failure symptoms, initiation of ACE inhibitors is the standard of care to delay disease progression in heart failure. Beta-adrenergic antagonists should be used only following resolution of congestive symptoms and clinical stabilization of the patient's condition.

Drug Category: Diuretics

Reduce preload. The initial drop in cardiac output produced by diuresis causes a compensatory increase in peripheral vascular resistance. With continuing diuretic therapy, the extracellular fluid volume and plasma volume return almost to pretreatment levels, and peripheral vascular resistance falls below its pretreatment baseline.

FOLLOW-UP

Section 8 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• References

Further Inpatient Care

Further outpatient care consists of largely supportive care, with slow rehabilitation and implementation of evidence-based medical therapy. Repeat assessment with echocardiography may be helpful to determine the persistency of cardiac dysfunction.

Further Outpatient Care

• Ongoing chronic inflammation may cause dilated cardiomyopathy and subsequent heart failure. Patients with a history of myocarditis should be monitored at intervals of 1-3 months initially, with gradual return of physical activity.
• Any evidence of residual cardiac dysfunction or remodeling should be treated in the same manner as chronic heart failure. The role of medical therapy in those with complete resolution of cardiac structure and performance within a short time is less well established, although conservatively, most would still receive ACE inhibitors or beta-blockers at a minimum.

Transfer

Transfer to tertiary care center with heart failure/transplant expertise may be warranted in fulminant cases where surgical support may be necessary.

Deterrence/Prevention

• Vaccination should reduce the incidence of myocarditis caused by measles, rubella, mumps, poliomyelitis, and influenza. Development of vaccines for other cardiotropic viruses may prevent viral myocarditis in the future.

Complications

• Cardiogenic shock may occur in fulminant cases of myocarditis.
• Severe heart block requiring permanent pacemaker placement occurred in 1% of patients in the Myocarditis Treatment trial.

Prognosis

• Patients who have survived fulminant myocarditis have a good prognosis. In a study of 147 cases of myocarditis monitored for an average of 5.6 years, 93% of the 15 patients with fulminant disease were alive without transplant 11 years after biopsy, compared with 45% of the 132 patients with less severe disease. Left ventricular dilation was not as severe in the fulminant cases as in the nonfulminant ones^{20, 21}.
• Expression of soluble Fas and Fas ligands at initial presentation appears to be a good serologic marker to predict the prognosis of acute myocarditis, while antimyosin autoantibodies are associated with development of worse cardiac dysfunction in chronic myocarditis.²²
• Predictors of death or need for heart transplantation after acute myocarditis in multivariate analyses include syncope, low ejection fraction, and left bundle-branch block, all indicators of advanced cardiomyopathy.²³

Patient Education

Patients should be advised of the current understanding of the natural history of myocarditis and the strengths and limitations of different diagnostic testing and therapeutic options. Overall, neurohormonal agents are given in a similar manner as in patients presenting with new-onset heart failure. Serial assessment is needed to determine the potential resolution of acute myocarditis, and during the early recovery period, strenuous exercise and digoxin should be avoided. Data regarding the risks of relapse with drug withdrawal following recovery is not available, so it is generally not recommended in practice. 

MISCELLANEOUS

Section 9 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• References

Medical/Legal Pitfalls

• High clinical suspicion of acute myocarditis is required for young and otherwise healthy individuals who develop heart failure with a rapid deteriorating course.
• Young patients presenting with cardiogenic shock with classic ECG changes of myocardial infarction but febrile may suffer from pseudomyocardial infarction, which is consistent with myocarditis. These people certainly need cardiac catheterization to rule out ischemic causes, despite the possibility of myocarditis.
• Close follow-up care is needed for patients who survive acute myocarditis, despite full initial recovery, as persistent chronic inflammation may lead to subsequent dilated cardiomyopathy and heart failure.
• Giant cell myocarditis has a more aggressive course and may require prompt surgical support (LVAD, transplant).

Special Concerns

A new entity of transient cardiac dysfunction has evolved, known as takotsubo cardiomyopathy or transient apical ballooning syndrome. It is characterized by severe hypokinesis of the anteroapical and inferoapical regions of the heart for unclear reason, and often with complete resolution. Many cases have been associated with a psychological or stressful event. Some have suggested a myocarditis nature of the condition, but the precise understanding of this syndrome remains unclear.

FURTHER READING

Section 10 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• References

Ellis CR, Di Salvo T. Myocarditis: basic and clinical aspects. Cardiol Rev. 2007 Jul-Aug;15(4):170-7.

Frishman WH, Zeidner J, Naseer N. Diagnosis and management of viral myocarditis. Curr Treat Options Cardiovasc Med. 2007 Dec;9(6):450-64.

Heart failure Society of America (HFSA). 2006 HFSA Comprehensive Heart Failure Practie Guidelines Section 16: Myocarditis - Current Treatment. J Card Fail. 2006 Feb; 12(1 suppl): e120-2. Available at http://www.heartfailureguidelines.org/.

ACKNOWLEDGMENTS

Section 11 of 12  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• References

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author James B Young, MD to the development and writing of this article.

REFERENCES

Section 12 of 12

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Further Reading
• Acknowledgments
• References

1. Aretz HT, Billingham ME, Edwards WD, et al. Myocarditis. A histopathologic definition and classification. Am J Cardiovasc Pathol. Jan 1987;1(1):3-14. [Medline].
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3. Bowles NE, Towbin JA. Molecular aspects of myocarditis. Curr Opin Cardiol. May 1998;13(3):179-84. [Medline].
4. Badorff C, Knowlton KU. Dystrophin disruption in enterovirus-induced myocarditis and dilated cardiomyopathy: from bench to bedside. Med Microbiol Immunol (Berl). May 2004;193(2-3):121-6. [Medline].
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6. Wakafuji S, Okada R. Twenty year autopsy statistics of myocarditis incidence in Japan. Jpn Circ J. Dec 1986;50(12):1288-93. [Medline].
7. D'Ambrosio A, Patti G, Manzoli A, et al. The fate of acute myocarditis between spontaneous improvement and evolution to dilated cardiomyopathy: a review. Heart. May 2001;85(5):499-504. [Medline].
8. Dec GW Jr, Palacios IF, Fallon JT, et al. Active myocarditis in the spectrum of acute dilated cardiomyopathies. Clinical features, histologic correlates, and clinical outcome. N Engl J Med. Apr 4 1985;312(14):885-90. [Medline].
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10. Mason JW, O'Connell JB, Herskowitz A, et al. A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators. N Engl J Med. Aug 3 1995;333(5):269-75. [Medline].
11. Cooper LT Jr, Berry GJ, Shabetai R. Idiopathic giant-cell myocarditis--natural history and treatment. Multicenter Giant Cell Myocarditis Study Group Investigators. N Engl J Med. Jun 26 1997;336(26):1860-6. [Medline].
12. Rosenstein ED, Zucker MJ, Kramer N. Giant cell myocarditis: most fatal of autoimmune diseases. Semin Arthritis Rheum. Aug 2000;30(1):1-16. [Medline].
13. Kuhl U, Pauschinger M, Noutsias M, et al. High prevalence of viral genomes and multiple viral infections in the myocardium of adults with "idiopathic" left ventricular dysfunction. Circulation. Feb 22 2005;111(7):887-93. [Medline].
14. Karatolios K, Pankuweit S, Maisch B. Diagnosis and treatment of myocarditis: the role of endomyocardial biopsy. Curr Treat Options Cardiovasc Med. December 2007;9:473-81. [Medline].
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Article Last Updated: Sep 2, 2008