This comprehensive review explains that myocarditis—inflammation of the heart muscle—can range from mild symptoms that resolve on their own to life-threatening heart failure. The condition is most often triggered by common viral infections but can also result from medications, autoimmune disorders, or rare inflammatory diseases. Key findings show that while most patients recover fully, some develop chronic heart failure, and specific clinical features help identify those needing specialized care like heart biopsy or immunosuppressive therapy.

Understanding Myocarditis: Causes, Symptoms, and Treatment Options

Table of Contents

• Introduction: What is Myocarditis?
• How Myocarditis is Defined and Diagnosed
• Symptoms and Clinical Presentation
• Common and Rare Causes
• How Myocarditis Develops in the Body
• Diagnostic Approaches and Testing
• Prognosis and Clinical Outcomes
• Treatment Strategies and Management
• Limitations of Current Knowledge
• Patient Recommendations and Next Steps
• Source Information

Introduction: What is Myocarditis?

Myocarditis is an inflammatory condition of the heart muscle that can affect patients of all ages. This comprehensive medical review explains that the condition presents with a wide spectrum of symptoms, ranging from mild breathing difficulties or chest pain that resolves without specific treatment to cardiogenic shock and death. The most significant long-term complication is dilated cardiomyopathy with chronic heart failure, where the heart becomes enlarged and weakened.

Most cases of myocarditis result from common viral infections, but specific forms may develop from other pathogens, toxic drug reactions, hypersensitivity responses, or rare inflammatory disorders like giant-cell myocarditis and cardiac sarcoidosis. The prognosis and treatment approach vary significantly depending on the underlying cause, and clinicians must carefully evaluate clinical and hemodynamic data to determine when to refer patients for specialized testing including endomyocardial biopsy.

How Myocarditis is Defined and Diagnosed

The standard Dallas pathological criteria for diagnosing myocarditis require the presence of an inflammatory cellular infiltrate with or without associated heart muscle cell death (myocyte necrosis) on conventionally stained heart tissue sections. However, these criteria have several limitations including variability in interpretation among pathologists, lack of prognostic value, and low sensitivity due to sampling error—since inflammation might be patchy and missed in small biopsy samples.

These limitations have led to alternative pathological classifications using cell-specific immunoperoxidase stains for surface antigens including anti-CD3, anti-CD4, anti-CD20, anti-CD68, and anti-human leukocyte antigen. These immunostaining techniques provide greater sensitivity and may offer better prognostic information than conventional staining methods.

Emerging research suggests that noninvasive cardiac magnetic resonance imaging (MRI) may provide an alternative diagnostic method without the risks associated with heart biopsy. Regions of myocarditis have been shown to correlate closely with areas of abnormal signal on cardiac MRI. The lack of consensus about the value of invasive studies like endomyocardial biopsy, combined with the generally good prognosis for patients with mild acute dilated cardiomyopathy from suspected myocarditis, has led to recommendations that biopsy should be considered based on the likelihood of finding specific treatable disorders.

Clinicopathological criteria can help distinguish between fulminant lymphocytic myocarditis and acute lymphocytic myocarditis, providing prognostically useful information beyond purely pathological classifications. Fulminant lymphocytic myocarditis typically has a distinct onset with viral symptoms within 2 weeks before cardiovascular symptoms and hemodynamic compromise, yet generally has a good prognosis. In contrast, acute lymphocytic myocarditis frequently lacks a distinct onset and hemodynamic compromise but more often results in death or need for cardiac transplantation.

Symptoms and Clinical Presentation

Myocarditis presents with highly variable symptoms, making diagnosis challenging. Acute myocarditis is frequently first diagnosed as nonischemic dilated cardiomyopathy in patients with symptoms that have been present for a few weeks to several months. The manifestations range from subclinical disease (showing no noticeable symptoms) to sudden death, with various presentations including:

• New-onset atrial or ventricular arrhythmias (abnormal heart rhythms)
• Complete heart block (electrical conduction failure)
• Acute myocardial infarction-like syndrome with normal coronary arteries

Cardiac symptoms are diverse and may include fatigue, decreased exercise tolerance, palpitations, precordial chest pain, and syncope (fainting). Chest pain in acute myocarditis can result from associated pericarditis (inflammation of the heart's outer lining) or occasionally from coronary artery spasm.

Although a viral prodrome with fever, muscle aches, and respiratory or gastrointestinal symptoms is classically associated with myocarditis, reported symptoms vary significantly. In the European Study of the Epidemiology and Treatment of Inflammatory Heart Disease, which screened 3,055 patients with suspected acute or chronic myocarditis:

• 72% had dyspnea (shortness of breath)
• 32% had chest pain
• 18% had arrhythmias

Most studies report a slight preponderance of myocarditis in male patients, possibly due to a protective effect of natural hormone variations on immune responses in women. Children often present more severely than adults, with more fulminant (sudden and severe) presentations. Because of this wide spectrum, clinicians must consider myocarditis in the differential diagnosis of many cardiac syndromes.

Common and Rare Causes

Viral and postviral myocarditis remain major causes of acute and chronic dilated cardiomyopathy. Seroepidemiologic and molecular studies have linked coxsackievirus B to outbreaks of myocarditis from the 1950s through the 1990s. The spectrum of viruses detected in heart biopsy samples has shifted over time—from coxsackievirus B to adenovirus in the late 1990s, and more recently to parvovirus B19 and other viruses according to reports from the United States and Germany.

In Japan and in serologic studies in the United States, hepatitis C virus has also been linked to myocarditis and dilated cardiomyopathy. Many other viruses have been associated less frequently with myocarditis, including Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6. These numerous observations linking viruses with myocarditis have led to ongoing treatment trials of antiviral therapy in patients with virus-associated cardiomyopathy.

Beyond viruses, other infectious causes should be considered:

• Lyme disease caused by Borrelia burgdorferi can cause myocarditis, particularly in patients with travel history to endemic areas or tick bites, especially if they have atrioventricular conduction abnormalities
• Trypanosoma cruzi infection (Chagas disease) in rural Central and South America can present as acute myocarditis or chronic cardiomyopathy, sometimes with specific electrical conduction abnormalities
• HIV-infected patients show myocarditis as the most common cardiac finding at autopsy, with prevalence of 50% or more

Drug-induced hypersensitivity reactions and systemic hypereosinophilic syndromes can cause specific myocarditis that often responds to withdrawal of the offending agent or treatment of the underlying disorder. Numerous medications have been implicated, including some anticonvulsants, antibiotics, and antipsychotics.

Eosinophilic myocarditis is characterized by a predominantly eosinophilic infiltrate in the heart muscle and may occur with systemic diseases like hypereosinophilic syndrome, Churg-Strauss syndrome, cancer, and parasitic infections. A rare but aggressive form called acute necrotizing eosinophilic myocarditis has an acute onset and high mortality rate.

Two idiopathic disorders deserve special attention:

• Giant-cell myocarditis is an acute disorder with high risk of death or need for cardiac transplantation, associated with autoimmune disorders, thymoma, and drug hypersensitivity
• Cardiac sarcoidosis should be suspected in patients with chronic heart failure, dilated cardiomyopathy and new ventricular arrhythmias, or heart block that doesn't respond to standard care

How Myocarditis Develops in the Body

Most information about the molecular pathogenesis of viral and autoimmune myocarditis comes from animal models rather than human studies. In these models, viruses enter heart muscle cells or macrophages through specific receptors and coreceptors. For example, the human Coxsackie adenovirus receptor serves as the entry point for coxsackievirus B and adenoviruses 2 and 5.

The innate immune response is essential for early host defense during infection. Viruses and certain host proteins can trigger this response through mechanisms involving toll-like receptors and pattern-recognition receptors in patients with tissue injury. The development of myocarditis requires MyD88, a key protein in dendritic-cell toll-like receptor signaling.

Coxsackievirus B infection up-regulates toll-like receptor 4 on macrophages, stimulates the maturation of antigen-presenting cells, leads to proinflammatory cytokine release, and decreases regulatory T-cell function. The production of increased levels of type 1 helper T (Th1) and type 2 helper T (Th2) cytokines that occurs 6 to 12 hours into an innate immune response is associated with the development of cardiomyopathy.

CD4+ T lymphocytes are key mediators of cardiac damage in experimental autoimmune myocarditis. Both CD4+ and CD8+ T cells are important in coxsackievirus B myocarditis models. Circulating T cells that have low avidity for self antigens are normally harmless but can cause immune-mediated heart disease if stimulated with large amounts of self antigens.

Autoantibodies to various cardiac antigens are common in suspected or confirmed lymphocytic myocarditis and dilated cardiomyopathy. Streptococcal M protein and coxsackievirus B share epitopes with cardiac myosin, and cross-reactive antibodies may result from this antigenic mimicry. After viral clearance, cardiac myosin may provide an ongoing source of antigen in chronic myocarditis, stimulating persistent inflammation through autoimmune mechanisms.

Diagnostic Approaches and Testing

Biomarkers of cardiac injury are elevated in a minority of patients with acute myocarditis but may help confirm the diagnosis. Troponin I has high specificity (89%) but limited sensitivity (34%) in diagnosing myocarditis. Clinical and experimental data suggest that increased levels of cardiac troponin I are more common than increased levels of creatine kinase MB in acute myocarditis.

A few serologic and imaging biomarkers have been associated with poor clinical outcomes. For example, relatively high serum levels of Fas ligand and interleukin-10 may predict increased risk of death, though these assays are not widely available for clinical use.

In acute myocarditis, the electrocardiogram may show sinus tachycardia with nonspecific ST-segment and T-wave abnormalities. Occasionally, the changes resemble those of an acute myocardial infarction and may include ST-segment elevation, ST-segment depression, and pathologic Q waves. Pericarditis is not uncommon in association with myocarditis.

Echocardiography typically shows impaired heart function, often with dilation of the left ventricle. Regional wall-motion abnormalities or perfusion defects not matching coronary artery distributions may also be seen in noninfectious disorders like cardiac sarcoidosis and arrhythmogenic right ventricular cardiomyopathy.

Prognosis and Clinical Outcomes

The true incidence of myocarditis in the community remains unknown because endomyocardial biopsy is used infrequently due to perceived risks and lack of a widely accepted sensitive histologic standard. However, viral genomes are more common in cardiac tissue from patients with chronic dilated cardiomyopathy than in those with valvular or ischemic cardiomyopathy, supporting the concept that viral myocarditis leads to substantial disease burden in the community.

Myocarditis is an important cause of sudden death and childhood cardiomyopathy. A recent long-term study of pediatric myocarditis demonstrated that the greatest burden may not be apparent for 6 to 12 years after diagnosis when children die or require cardiac transplantation for chronic dilated cardiomyopathy.

The prognosis varies significantly by myocarditis type:

• Fulminant lymphocytic myocarditis has a distinct onset with viral prodrome within 2 weeks before symptoms and hemodynamic compromise but generally good prognosis
• Acute lymphocytic myocarditis frequently lacks distinct onset and hemodynamic compromise but more often results in death or need for cardiac transplantation
• Giant-cell myocarditis carries poor prognosis with high likelihood of death or need for cardiac transplantation
• Most patients with mild acute dilated cardiomyopathy from suspected myocarditis have relatively mild disease that resolves with few short-term sequelae

Certain clinical clues help identify patients at higher risk for poor outcomes, including rash, fever, peripheral eosinophilia, or temporal relation with recently initiated medications.

Treatment Strategies and Management

Treatment of myocarditis varies according to the cause and severity. General supportive care forms the foundation of management, including:

• Management of heart failure symptoms with standard medications
• Monitoring and treatment of arrhythmias
• In severe cases, intravenous inotropic agents or mechanical circulatory support

For specific types of myocarditis, targeted approaches include:

• Hypersensitivity myocarditis: Identification and withdrawal of the offending medication, with possible corticosteroid use
• Giant-cell myocarditis: Immunosuppressive therapy, though prognosis remains poor with high likelihood of needing cardiac transplantation
• Cardiac sarcoidosis: Corticosteroids for biopsy-proven cases
• Lyme myocarditis: Appropriate antibiotic therapy

Ongoing clinical trials are investigating antiviral therapy for virus-associated cardiomyopathy and immunosuppression for inflammatory forms. The prominent role of T lymphocytes in experimental models supports the rationale for anti-T-cell therapy in severe human cardiomyopathy with prominent autoimmune features.

For children with myocarditis, possible use of corticosteroids or intravenous immune globulin (IVIG) may be considered, though evidence remains limited.

Limitations of Current Knowledge

Several important limitations affect our understanding and management of myocarditis. First, the Dallas pathological criteria have significant variability in interpretation among pathologists and limited prognostic value. The low sensitivity due to sampling error means some cases may be missed entirely.

Prognostic data on heart transplantation and survival are limited to relatively few patients since both fulminant and acute lymphocytic myocarditis are rare conditions. Most information about molecular pathogenesis comes from rodent models and isolated cell systems rather than human tissue studies, limiting direct application to patient care.

The true incidence of myocarditis in the community remains unknown because endomyocardial biopsy is performed infrequently. Seroepidemiologic data are difficult to interpret due to the heterotopic effect of enteroviruses, which may cause an anamnestic antibody response to other coxsackievirus B strains.

Additionally, it remains unclear why the great majority of infections with "cardiotropic" viruses—including enterovirus, adenovirus, and parvovirus B19—do not cause cardiomyopathy, suggesting important genetic and environmental determinants of virulence that are not yet fully understood.

Patient Recommendations and Next Steps

If you suspect you might have myocarditis or have been diagnosed with the condition, here are important steps to consider:

1. Seek immediate medical attention if you experience chest pain, significant shortness of breath, palpitations, or fainting—especially if these symptoms follow a viral illness
2. Provide complete medication history to your healthcare providers, as some drugs can cause hypersensitivity myocarditis
3. Share any history of tick bites, travel to Lyme-endemic areas, or potential exposure to other infectious causes
4. Follow up regularly with cardiovascular specialists, as myocarditis can have long-term consequences even after initial recovery
5. Report any new symptoms promptly, including fatigue, decreased exercise tolerance, or heart rhythm abnormalities
6. Discuss with your doctor whether referral to a specialist for advanced testing like cardiac MRI or endomyocardial biopsy might be appropriate for your situation

For patients diagnosed with myocarditis, adherence to prescribed treatments and activity restrictions is crucial. Most patients with mild cases recover fully, but some may develop chronic heart failure requiring ongoing management. Participation in clinical trials may be an option for those with severe or treatment-resistant forms of the disease.

Source Information

Original Article Title: Myocarditis
Author: Leslie T. Cooper, Jr., M.D.
Publication: The New England Journal of Medicine
Date: April 9, 2009
Volume and Issue: 360;15
Pages: 1526-1538

This patient-friendly article is based on peer-reviewed research from a comprehensive medical review published in one of the world's leading medical journals. The original work was authored by an expert from the Division of Cardiovascular Diseases at Mayo Clinic, Rochester, MN.