# Understanding Myocarditis: Causes, Symptoms, Diagnosis, and Treatment

Myocarditis is an inflammation of the heart muscle that ranges from a mild, self-limiting illness to a life-threatening emergency requiring mechanical heart support or transplantation. This patient-friendly guide, based on a comprehensive review published in the *New England Journal of Medicine*, explains how doctors define, diagnose, and treat myocarditis—including the specific symptoms to watch for, the viruses and other triggers responsible, and what the latest research says about who recovers fully and who faces long-term complications like dilated cardiomyopathy and heart failure.

# Understanding Myocarditis: Causes, Symptoms, Diagnosis, and Treatment

## Table of Contents

- Key Points
- What Is Myocarditis?
- How Doctors Define Myocarditis
- Symptoms and How Common Myocarditis Is
- What Causes Myocarditis?
- How Myocarditis Damages the Heart
- How Myocarditis Is Diagnosed
- Clinical Scenarios: A Guide to Diagnosis and Prognosis
- What This Means for Patients
- Study Limitations
- Recommendations for Patients
- Frequently Asked Questions
- Source Information

## Key Points

- Myocarditis is heart muscle inflammation that can be mild or life-threatening, with symptoms ranging from fatigue to cardiogenic shock.
- Viral infections like coxsackievirus B, adenovirus, and parvovirus B19 are major causes; nonviral causes include Lyme disease, Chagas, and HIV.
- Diagnosis often uses troponin I, ECG, MRI, and biopsy, but a normal troponin does not rule out myocarditis.
- Prognosis varies: fulminant lymphocytic myocarditis often has good recovery with support, but giant-cell myocarditis has poor outcomes.
- Long-term risks include dilated cardiomyopathy and heart failure, sometimes appearing years later, especially in children.

## What Is Myocarditis?

Myocarditis is an inflammatory condition of the heart muscle (the myocardium) that can affect people of all ages. It is a challenging diagnosis because it can look like many other heart conditions. In fact, the symptoms range from mild shortness of breath or chest pain that resolves on its own—without any specific treatment—all the way to cardiogenic shock (a condition where the heart cannot pump enough blood to meet the body's needs) and even death.

The most common long-term consequence of myocarditis is dilated cardiomyopathy with chronic heart failure. Dilated cardiomyopathy is a condition in which the heart's main pumping chamber (the left ventricle) becomes enlarged and weakened, making it harder for the heart to pump blood efficiently.

This review article was written by Dr. Leslie T. Cooper, Jr., from the Division of Cardiovascular Diseases at the Mayo Clinic in Rochester, Minnesota. It was published in the *New England Journal of Medicine* on April 9, 2009, and it provides a practical, up-to-date approach to evaluating and treating patients with suspected myocarditis. As the author notes, the prognosis and treatment vary significantly depending on the underlying cause, and doctors often use clinical and hemodynamic (blood flow) data to decide when a patient should be referred to a specialist for an endomyocardial biopsy (a procedure in which a small sample of heart tissue is taken for examination).

## How Doctors Define Myocarditis

The traditional method for diagnosing myocarditis is called the **Dallas pathological criteria**. According to these criteria, myocarditis is present when a conventional stained heart-tissue sample shows an inflammatory cellular infiltrate (immune cells invading the heart tissue)—with or without associated myocyte necrosis (death of heart muscle cells).

However, these Dallas criteria have important limitations:

-
**Variability in interpretation:** Different pathologists may read the same sample differently.
-
**Lack of prognostic value:** The criteria do not reliably predict how well a patient will do.
-
**Low sensitivity:** The test often misses cases of myocarditis—partly due to sampling error, since the biopsy needle may miss the inflamed areas of the heart.

Because of these limitations, researchers have developed alternative pathological classifications that rely on cell-specific immunoperoxidase stains for surface antigens, such as anti-CD3, anti-CD4, anti-CD20, anti-CD68, and anti–human leukocyte antigen. These are special staining techniques that label different types of immune cells (T lymphocytes, B lymphocytes, and macrophages) to make them visible under a microscope. Criteria based on immunoperoxidase staining have greater sensitivity than the Dallas criteria and may also carry prognostic value—meaning they can help predict patient outcomes.

There is also growing interest in noninvasive diagnostic methods. Preliminary studies suggest that **cardiac magnetic resonance imaging (MRI)** may offer an alternative way to diagnose myocarditis without the risks of biopsy. Regions of myocarditis have been reported to correlate closely with regions of abnormal signal on cardiac MRI. However, there is not yet a consensus on how much value invasive studies such as endomyocardial biopsy provide.

Because the overall prognosis is generally good for patients with mild, acute dilated cardiomyopathy who have suspected myocarditis, recent recommendations have shifted. Instead of biopsying every patient, doctors are now advised to consider endomyocardial biopsy primarily when there is a likelihood of finding **specific treatable disorders**.

One of the most useful approaches combines clinical and pathological information. Using **clinicopathological criteria**, doctors can distinguish between two distinct forms of lymphocytic myocarditis:

-
**Fulminant lymphocytic myocarditis:** This form has a distinct onset, usually with a viral prodrome (early symptoms like fever, muscle aches, or respiratory/gastrointestinal symptoms) within 2 weeks before the onset of heart symptoms. It causes hemodynamic compromise (the heart struggles to pump blood), but—perhaps surprisingly—it generally has a good prognosis if the patient survives the acute phase with aggressive support.
-
**Acute lymphocytic myocarditis:** This form often lacks a distinct onset and may or may not involve hemodynamic compromise. However, it more frequently results in death or the need for cardiac transplantation.

Two important caveats apply to these clinicopathological criteria. First, even though patients with fulminant lymphocytic myocarditis frequently recover, they are quite ill and typically need treatment with intravenous inotropic agents (medications that strengthen the heart's contractions) or mechanical circulatory support (devices like ventricular assist devices that help the heart pump). Second, because both forms of myocarditis are rare, the prognostic data on heart transplantation and survival are limited to relatively few patients.

## Symptoms and How Common Myocarditis Is

Acute myocarditis is frequently first diagnosed as nonischemic dilated cardiomyopathy—that is, an enlarged and weakened heart that is *not* caused by blocked coronary arteries. This diagnosis often comes after symptoms have been present for a few weeks to several months. But the manifestations of myocarditis are incredibly varied, ranging from subclinical disease (no noticeable symptoms at all) to sudden death.

Some patients present with new-onset atrial or ventricular arrhythmias (irregular heart rhythms), complete heart block (a condition where the electrical signals between the upper and lower chambers of the heart are completely blocked), or an acute myocardial infarction–like syndrome (symptoms that mimic a heart attack, including chest pain and ECG changes, but without blocked arteries).

Cardiac symptoms are variable and may include:

- Fatigue
- Decreased exercise tolerance
- Palpitations (feeling like your heart is racing or skipping beats)
- Precordial chest pain (pain in the front of the chest over the heart)
- Syncope (fainting)

Chest pain in acute myocarditis can result from an associated pericarditis (inflammation of the sac surrounding the heart) or, occasionally, from coronary-artery spasm (a temporary tightening of the arteries that supply blood to the heart muscle).

Although a viral prodrome with fever, myalgia (muscle aches), and respiratory or gastrointestinal symptoms is classically associated with myocarditis, the reported symptoms are highly variable. In the **European Study of the Epidemiology and Treatment of Inflammatory Heart Disease**, researchers screened 3,055 patients with suspected acute or chronic myocarditis. Here is what they found:

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

Most studies of acute myocarditis report a slight preponderance in male patients. This may be due to a protective effect of natural hormone variations on immune responses in women. The clinical presentation in children differs from that in adults—children often have a more fulminant (sudden and severe) presentation.

Because of this wide spectrum of clinical presentations, doctors need to consider myocarditis in the differential diagnosis (the list of possible causes) for many cardiac syndromes. This is particularly important because most people who present with acute dilated cardiomyopathy and myocarditis have relatively mild disease that resolves with few short-term sequelae (after-effects). However, certain clinical clues point to a higher risk for a more difficult course. These include:

-
**Rash, fever, peripheral eosinophilia** (an elevated count of eosinophils, a type of white blood cell), or a **temporal relationship with recently initiated medications**—these suggest a possible hypersensitivity myocarditis (an allergic-type reaction to a drug).
-
**Giant-cell myocarditis** should be considered in patients with acute dilated cardiomyopathy associated with thymoma (a tumor of the thymus gland), autoimmune disorders, ventricular tachycardia (a dangerously fast heart rhythm), or high-grade heart block.
-
**Cardiac sarcoidosis** should be suspected in patients with chronic heart failure, dilated cardiomyopathy plus new ventricular arrhythmias, second-degree or third-degree heart block, or who do not respond to standard care.

The true incidence of myocarditis in the community is unknown. Endomyocardial biopsy is used infrequently because of perceived risks and the lack of a widely accepted, sensitive histologic (tissue) standard. Seroepidemiologic data (studies of antibodies in populations) are difficult to interpret because of the heterotypic (cross-reactive) effect of enteroviruses, which may cause an amnestic antibody response to other coxsackievirus B strains—meaning a previous infection with one virus can falsely elevate antibody levels to a related virus.

That said, the observation that viral genomes (genetic material from viruses) are more common in cardiac tissue from patients with chronic dilated cardiomyopathy than in tissue from patients with valvular or ischemic cardiomyopathy supports the concept that viral myocarditis leads to a substantial disease burden in the community.

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

## What Causes Myocarditis?

### Viral Infections

Viral and postviral myocarditis remain major causes of acute and chronic dilated cardiomyopathy. Seroepidemiologic and molecular studies linked **coxsackievirus B** to outbreaks of myocarditis from the 1950s through the 1990s. The spectrum of viruses detected in endomyocardial biopsy samples has shifted over time:

- In the late 1990s: **coxsackievirus B → adenovirus**

- In the past 5 years (relative to the 2009 publication): **parvovirus B19** and other viruses, according to reports from the United States and Germany

In Japan, and in a serologic study in the United States, **hepatitis C virus** was also linked to myocarditis and dilated cardiomyopathy. Many other viruses have been associated less frequently with myocarditis, including:

- Epstein–Barr virus (the virus that causes mononucleosis)
- Cytomegalovirus
- Human herpesvirus 6

The large number of observations linking viruses to myocarditis has led to ongoing treatment trials of antiviral therapy in patients with virus-associated cardiomyopathy.

### Other Infectious Causes

Beyond viruses, several other infectious causes deserve consideration in patients with acute or chronic cardiomyopathy:

-
**Borrelia burgdorferi (Lyme disease):** Myocarditis can result from this tick-borne infection. Patients with Lyme myocarditis are occasionally coinfected with ehrlichia or babesia (other tick-borne organisms). Lyme myocarditis should be suspected in patients with a history of travel to endemic regions or a tick bite, particularly if they also have atrioventricular conduction abnormalities (problems with the electrical system of the heart).
-
**Trypanosoma cruzi (Chagas disease):** In rural Central and South America, this parasitic infection can present as acute myocarditis or chronic cardiomyopathy, sometimes with right bundle-branch block or left anterior fascicular block (specific ECG abnormalities). Echocardiography or contrast ventriculography may reveal a left ventricular apical aneurysm (a bulge in the lower tip of the heart's pumping chamber), regional wall-motion abnormalities, or diffuse cardiomyopathy.
-
**HIV (human immunodeficiency virus):** Myocarditis is the most common cardiac pathological finding at autopsy of patients infected with HIV, with a prevalence of **50% or more**. Cardiomyopathy in HIV patients may be caused by inhibition of cardiac contractility by HIV type 1 glycoprotein 120, coinfections, or antiviral medications.

### Drug-Induced Hypersensitivity and Eosinophilic Myocarditis

Drug-induced hypersensitivity reactions and systemic hypereosinophilic syndromes (conditions with abnormally high levels of eosinophils) can cause a specific form of myocarditis. This often responds to withdrawal of the offending agent or to treatment of the underlying disorder, though adjuvant corticosteroid therapy is often required.

Numerous medications have been implicated in hypersensitivity myocarditis, including:

- Some anticonvulsants (seizure medications)
- Some antibiotics
- Some antipsychotics

**Eosinophilic myocarditis** is characterized by a predominantly eosinophilic infiltrate in the myocardium. It may occur in association with systemic diseases such as:

- The hypereosinophilic syndrome
- The Churg–Strauss syndrome (a rare autoimmune condition causing inflammation of blood vessels)
- Löffler's endomyocardial fibrosis (a condition causing thickening and scarring of the heart lining)
- Cancer
- Parasitic, helminthic (worm), or protozoal infections

Eosinophilic myocarditis has also been reported after vaccination for several diseases, including smallpox. Clinical manifestations include congestive heart failure, endocardial and valvular fibrosis (scarring of the heart lining and valves), and endocardial thrombi (blood clots inside the heart).

A rare disorder, **acute necrotizing eosinophilic myocarditis**, is an aggressive form with an acute onset and a high death rate.

### Giant-Cell Myocarditis and Cardiac Sarcoidosis

Two idiopathic (of unknown cause) and histologically similar disorders—**giant-cell myocarditis** and **cardiac sarcoidosis**—are rare but important causes of cardiomyopathy.

Giant-cell myocarditis is an acute disorder with a high risk of death or need for cardiac transplantation. It is considered primarily autoimmune in nature because of its association with a variety of autoimmune disorders, thymoma, and drug hypersensitivity. Giant-cell myocarditis is sometimes distinguished from the much more common postviral myocarditis by the presence of ventricular tachycardia, heart block, and a downhill clinical course despite optimal clinical care.

Patients who present with apparently chronic dilated cardiomyopathy yet with **new ventricular arrhythmias**, **second-degree or third-degree heart block**, or **no response to optimal care** are more likely to have cardiac sarcoidosis—a granulomatous myocarditis (inflammation with formation of granulomas, which are clusters of immune cells).

### Myocarditis Alongside Other Heart Conditions

Myocarditis can occur together with other cardiomyopathies and may worsen the clinical course. For example:

- The prognosis in **cardiac amyloidosis** (a condition where abnormal proteins build up in the heart) is much worse if histologic evidence of myocarditis is present.
- Myocarditis has been associated with clinical deterioration in **hypertrophic cardiomyopathy** (a condition where the heart muscle becomes abnormally thick), and in such cases, evidence of a persistent viral genome may be found in the myocardium.
- A high percentage of patients with **arrhythmogenic right ventricular cardiomyopathy or dysplasia** (a genetic condition affecting the heart muscle) have associated myocarditis. Some of these cases are linked to viral infection, though the prognostic value of this is not known.

Researchers have also reported that active coxsackievirus B infection was present in **up to 40%** of patients who died of acute myocardial infarction (heart attack). In these patients, the involved cardiomyocytes showed evidence of cytoskeletal disruption (damage to the internal structure of heart muscle cells).

## How Myocarditis Damages the Heart

Most of what we know about the molecular pathogenesis (the biological mechanisms by which the disease develops) of viral and autoimmune myocarditis comes from rodent models and isolated cell systems, rather than from studies of human tissue. In these models, viruses appear to enter cardiac myocytes (heart muscle cells) or macrophages through specific receptors and coreceptors.

For example, the receptor for coxsackievirus B and adenoviruses 2 and 5 is the **human Coxsackie adenovirus receptor**. A coreceptor that plays a role in viral entry for serotypes B1, B2, and B5 is the **coxsackievirus B coreceptor decay-accelerating factor**—and it appears that differential binding to this coreceptor influences viral virulence (how aggressive the virus is).

The virulence of coxsackievirus B is also modified by:

- Variations in its viral genome
- Host factors, such as **selenium deficiency** and **mercury exposure**

A better understanding of the genetic and environmental determinants of virulence is needed to understand why the great majority of infections with "cardiotropic" (heart-preferring) viruses—including enterovirus, adenovirus, and parvovirus B19—do not cause cardiomyopathy.

The **innate immune response** (the body's first-line, non-specific defense against infection) is essential early during an infection. Viruses, streptococcal M protein, and certain host proteins can trigger this response through several 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 (cells that show foreign proteins to the immune system)
- Leads to proinflammatory cytokine release
- Decreases regulatory T-cell function

The production of increased levels of type 1 helper T (Th1) and type 2 helper T (Th2) cytokines, which occurs **6 to 12 hours** into the innate immune response, is associated with the development of cardiomyopathy. In other words, the *nature* of the initial immune response can determine what happens later with the more specific T-cell and B-cell responses. It is not yet known whether an autoreactive immune response (where the immune system attacks the body's own tissues) will lead to viral clearance and normal heart function, or ultimately progress to chronic immune-mediated cardiomyopathy, in any given patient.

**CD4+ T lymphocytes** (a type of white blood cell) are key mediators of cardiac damage in experimental autoimmune myocarditis. Circulating T cells that have a low avidity (weak attraction) for self-antigens are normally harmless, but they can cause immune-mediated heart disease if stimulated with large amounts of self-antigens. T-cell responses associated with the production of both Th1 and Th2 cytokines have been implicated in the pathogenesis of myocarditis after viral infection. More recently, a third T-helper subgroup—**Th17 cells**, which produce **interleukin-17**—has also been implicated in myocarditis. Both CD4+ and CD8+ T cells are important in a murine (mouse) model of coxsackievirus B myocarditis.

The prominent role of T lymphocytes in multiple models of experimental myocarditis supports the rationale for using **anti–T-cell therapy** in severe human cardiomyopathy with prominent autoimmune features.

Circulating CD4+ T cells are normally kept in check by at least one subgroup of regulatory T cells (Treg). Research by Ono and colleagues demonstrated that a subgroup of regulatory T cells that express CD4, the transcription factor forkhead box p3 (FOXP3), and a high level of the corticosteroid-induced tumor necrosis factor receptor can influence the course of autoimmune myocarditis. **CD4+CD25+FOXp3+ T cells** are also important negative regulators of inflammation in coxsackievirus B myocarditis. Notably, regulatory T-cell subgroups have not yet been studied in human myocarditis—this is a gap in our knowledge.

**Autoantibodies** (antibodies that attack the body's own tissues) to a variety of cardiac antigens are common in suspected or histologically confirmed lymphocytic myocarditis and dilated cardiomyopathy. Streptococcal M protein and coxsackievirus B share epitopes (the specific parts of an antigen that antibodies recognize) with cardiac myosin, an intracellular protein in heart muscle cells. Cross-reactive antibodies may result in the production of autoantibodies through this **antigenic mimicry**—the body mistakes its own proteins for the invader. After the virus is cleared, cardiac myosin may provide an endogenous (internal) source of antigen in chronic myocarditis and stimulate chronic inflammation through autoimmune mechanisms. Studies over the past decade have also described cross-reactivity between cardiac myosin and **laminin**, a protein on the surface of human cells.

## How Myocarditis Is Diagnosed

### Biomarkers (Blood Tests)

Biomarkers of cardiac injury are elevated in a minority of patients with acute myocarditis but may help confirm the diagnosis. **Troponin I**—a protein released into the blood when heart muscle is damaged—has high specificity (**89%**) but limited sensitivity (**34%**) in the diagnosis of myocarditis. In plain terms, if troponin I is elevated, it strongly suggests heart muscle damage; but a normal level does not rule out myocarditis, because the test misses about two-thirds of cases.

Clinical and experimental data suggest that increased levels of cardiac troponin I are more common than increased levels of **creatine kinase MB** (another marker of heart muscle damage) 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** (a protein involved in cell death signaling) may predict an increased risk of death
- Relatively high serum levels of **interleukin-10** (an anti-inflammatory cytokine) may also predict an increased risk of death

However, these assays are not widely available in clinical practice.

### Electrocardiography (ECG)

In acute myocarditis, the electrocardiogram (a test that records the electrical activity of the heart) may show **sinus tachycardia** (a fast heart rate originating from the normal pacemaker) with nonspecific ST-segment and T-wave abnormalities. Occasionally, the ECG changes are suggestive of an acute myocardial infarction (heart attack) and may include:

- ST-segment elevation
- ST-segment depression
- Pathologic Q waves

Pericarditis (inflammation of the sac around the heart) can also produce ECG changes that overlap with those of myocarditis, and the two conditions often occur together.

## Clinical Scenarios: A Guide to Diagnosis and Prognosis

The review article includes a valuable table outlining seven distinct clinical scenarios for the diagnosis of myocarditis. Each scenario combines the duration of illness, the pathological findings likely on biopsy, the expected prognosis, and the recommended treatment approach. Here is a plain-language explanation of each scenario:

1.
**Heart-attack-like syndrome with normal coronary arteries (illness lasting hours to days):** Biopsy typically shows active lymphocytic myocarditis or, rarely, necrotizing eosinophilic myocarditis or giant-cell myocarditis. If lymphocytic myocarditis is present on biopsy, the prognosis is good. Treatment is supportive (managing symptoms and supporting heart function).
1.
**Heart failure with normal-sized or dilated left ventricle and hemodynamic compromise (illness lasting less than 2 weeks):** Biopsy usually shows active lymphocytic myocarditis or, less commonly, necrotizing eosinophilic myocarditis or giant-cell myocarditis. The prognosis is good in fulminant lymphocytic myocarditis, but acute care often requires inotropic medications (drugs that strengthen the heart's contractions) or mechanical circulatory support (devices that help the heart pump). Treatment is supportive, with possible use of corticosteroids or intravenous immune globulin (IVIG) in children.
1.
**Heart failure with dilated left ventricle plus new ventricular arrhythmias, high-degree heart block, or lack of response to usual care within 1 to 2 weeks (illness lasting weeks to months):** Biopsy may reveal giant-cell myocarditis, eosinophilic myocarditis, or lymphocytic myocarditis. The prognosis is poor, with a high likelihood of death or need for cardiac transplantation if giant-cell myocarditis is found. Treatment is variable, guided by the histopathological (tissue) results.
1.
**Heart failure with dilated left ventricle without new ventricular arrhythmias or high-degree heart block (illness lasting weeks to months):** Nonspecific changes are most likely on biopsy, with viral genomes present in **25 to 35%** of patients and lymphocytic myocarditis (by Dallas criteria) in about **10%**. The prognosis is good in the first several years, but there is a risk of late disease progression with heart failure and cardiomyopathy. Treatment is supportive; research into genomic predictors of risk is ongoing.
1.
**Heart failure with eosinophilia (elevated eosinophil count in the blood; illness of any duration):** Biopsy shows eosinophilic or hypersensitivity myocarditis, or eosinophilic endomyocarditis. The prognosis is poor. Treatment is supportive, including identification and treatment of the underlying cause; corticosteroids may be used for hypersensitivity myocarditis.
1.
**Heart failure with dilated left ventricle plus new ventricular arrhythmias, high-degree heart block, or lack of response to usual care within 1 to 2 weeks (illness lasting more than several months):** Biopsy may show cardiac sarcoidosis (idiopathic granulomatous myocarditis) or a specific infection (e.g., *Trypanosoma cruzi* or *Borrelia burgdorferi*); nonspecific changes are most likely. If sarcoidosis is confirmed on biopsy, there is an increased risk of needing a pacemaker or implantable cardioverter–defibrillator (ICD). Treatment is supportive, with corticosteroids for biopsy-proven cardiac sarcoidosis.
1.
**Heart failure with dilated left ventricle without new ventricular arrhythmias or high-degree heart block (illness lasting more than several months):** Nonspecific changes are most likely, but sensitive immunostaining reveals increased numbers of inflammatory cells in up to **40%** of patients, and viral genomes are present in **25 to 35%**. The prognosis depends on functional class (how limited the patient is in daily activities), ejection fraction (the percentage of blood the heart pumps out with each beat), and the presence or absence of inflammation and viral genomes on biopsy. Treatment is supportive; antiviral treatment and immunosuppression are under investigation.

## What This Means for Patients

For patients and families facing a possible myocarditis diagnosis, several key messages emerge from this review.

**First, the prognosis varies widely—but many patients do well.** The most common scenario—a patient with mild, acute dilated cardiomyopathy and suspected myocarditis—carries a generally good short-term prognosis. Many patients recover with supportive care alone. However, the long-term picture matters: some patients, especially children, may not show the full burden of the disease for 6 to 12 years, when they may develop progressive heart failure or require transplantation.

**Second, the cause matters enormously.** Viral myocarditis is most common and often self-limiting, but giant-cell myocarditis carries a poor prognosis and demands aggressive, early treatment. Hypersensitivity myocarditis (from medications) may improve dramatically once the offending drug is stopped. Cardiac sarcoidosis requires specific treatment with corticosteroids and monitoring for rhythm problems that might need a pacemaker or ICD.

**Third, biopsy decisions are now more targeted.** Rather than biopsying everyone, cardiologists increasingly use clinical clues to decide who should undergo endomyocardial biopsy. The goal is to identify the specific treatable disorders—like giant-cell myocarditis, eosinophilic myocarditis, or cardiac sarcoidosis—where knowing the diagnosis changes treatment. The presence of ventricular arrhythmias, heart block, or failure to respond to standard care within 1 to 2 weeks should prompt consideration of biopsy.

**Fourth, the immune system is central to the disease—both as a defender and as a potential source of harm.** Understanding that the disease involves T-cell responses (including Th1, Th2, and Th17 cells) and autoantibodies directed against heart proteins like cardiac myosin explains why researchers are testing both antiviral and immunosuppressive therapies. It also suggests that patients with severe cardiomyopathy and prominent autoimmune features might benefit from therapies that target T cells—though these remain investigational.

## Study Limitations

It is important to understand what this review could and could not establish. The article is a narrative review, not a new clinical trial, so it synthesizes existing research rather than presenting new data.

The review notes several critical limitations in the field:

-
**The true incidence of myocarditis is unknown**, because endomyocardial biopsy is infrequently used and there is no widely accepted, sensitive histologic standard for diagnosis.
-
**The Dallas pathological criteria are limited** by variability in interpretation, lack of prognostic value, and low sensitivity due to sampling error.
-
**Most knowledge about pathogenesis comes from animal models and isolated cell systems**, not from human tissue. Regulatory T-cell subgroups, for example, have not yet been studied in human myocarditis.
-
**Prognostic data on rare forms of myocarditis** (like fulminant lymphocytic and giant-cell myocarditis) are limited to relatively few patients.
-
**The diagnostic value of cardiac MRI** and the clinical utility of biopsy remain subjects of debate, without consensus.
-
**The article was published in 2009**, so it does not include advances from the past 15+ years, including updated consensus criteria for cardiac MRI (the Lake Louise criteria), newer antiviral and immunosuppressive trial results, or modern understanding of COVID-19–related myocarditis.

## Recommendations for Patients

Based on the information in this review, here are practical recommendations for patients and their families:

1.
**Seek prompt medical evaluation for persistent symptoms.** If you have unexplained shortness of breath, chest pain, palpitations, or fainting—especially after a recent viral illness with fever and muscle aches—see a doctor. While most cases are mild, some require rapid, aggressive treatment.
1.
**Mention recent medications.** If you develop heart symptoms shortly after starting a new medication (including anticonvulsants, antibiotics, or antipsychotics) and have a rash or fever, inform your doctor. Drug-induced hypersensitivity myocarditis may improve when the offending medication is withdrawn.
1.
**Report tick bites or travel to endemic areas.** Lyme disease myocarditis and Chagas disease have specific treatments, and early diagnosis improves outcomes. Tell your doctor about any travel to rural Central or South America or exposure to ticks.
1.
**Understand what your test results mean.** A normal troponin level does *not* rule out myocarditis (the test has only 34% sensitivity). An ECG may look like a heart attack even when your coronary arteries are normal. These are known limitations that your cardiologist will keep in mind.
1.
**Ask about endomyocardial biopsy if you have warning signs.** If you have dilated cardiomyopathy with new ventricular arrhythmias, high-grade heart block, or no response to standard care within 1 to 2 weeks, discuss with your specialist whether a biopsy is appropriate to look for treatable conditions like giant-cell myocarditis or cardiac sarcoidosis.
1.
**Be aware of long-term follow-up needs.** Even if you recover from the acute episode, myocarditis can lead to dilated cardiomyopathy and heart failure years later—particularly in children, where the burden may not appear for 6 to 12 years. Ongoing follow-up with a cardiologist is important.
1.
**Watch for medication side effects if you have HIV.** Patients with HIV are at high risk for myocarditis (prevalence of 50% or more at autopsy), and both the virus and some antiviral medications can affect the heart. Discuss cardiac monitoring with your HIV specialist.

## Frequently Asked Questions

### What causes myocarditis?

Viral infections are a major cause, including coxsackievirus B, adenovirus, parvovirus B19, and hepatitis C virus. Other infectious causes include Lyme disease, Chagas disease, and HIV. Drug-induced hypersensitivity reactions, autoimmune conditions, and rare disorders like giant-cell myocarditis and cardiac sarcoidosis can also cause myocarditis. The trigger determines treatment and prognosis.

### What are the symptoms of myocarditis?

Symptoms are highly variable. Some people have no symptoms. Others experience fatigue, decreased exercise tolerance, palpitations, chest pain, fainting, or shortness of breath. Chest pain may come from associated pericarditis or coronary artery spasm. A viral prodrome with fever, muscle aches, and respiratory or gastrointestinal symptoms often occurs before heart symptoms.

### How is myocarditis diagnosed?

Doctors may use blood tests like troponin I, ECG, cardiac MRI, and endomyocardial biopsy. Troponin I has high specificity but low sensitivity, so a normal level does not rule out myocarditis. Biopsy uses the Dallas criteria or immunoperoxidase staining. Biopsy is recommended mainly when treatable conditions like giant-cell myocarditis or cardiac sarcoidosis are suspected.

### What is the prognosis for myocarditis?

Prognosis varies widely. Many patients with mild acute dilated cardiomyopathy and suspected myocarditis recover with supportive care. Fulminant lymphocytic myocarditis often has a good prognosis if the patient survives the acute phase. However, acute lymphocytic myocarditis more often leads to death or transplantation. Giant-cell myocarditis has a poor prognosis. Long-term complications include dilated cardiomyopathy and heart failure.

### What treatments are available for myocarditis?

Treatment is mostly supportive, managing symptoms and supporting heart function. This may include inotropic medications or mechanical circulatory support for severe cases. Corticosteroids are used for hypersensitivity myocarditis and biopsy-proven cardiac sarcoidosis. Intravenous immune globulin may be used in children. Stopping the offending drug is essential for drug-induced hypersensitivity myocarditis. Antiviral and immunosuppressive therapies are under investigation.

### When is an endomyocardial biopsy needed?

Biopsy is not recommended for every patient. Doctors consider biopsy when there is a likelihood of finding specific treatable disorders. It should be considered if you have dilated cardiomyopathy with new ventricular arrhythmias, high-grade heart block, or no response to standard care within 1 to 2 weeks. Biopsy can diagnose giant-cell myocarditis, eosinophilic myocarditis, or cardiac sarcoidosis.

### Can myocarditis cause long-term heart damage?

Yes. The most common long-term consequence is dilated cardiomyopathy with chronic heart failure. Some patients, especially children, may not show the full burden of disease for 6 to 12 years, when they might develop progressive heart failure or need transplantation. Even after recovery from the acute episode, ongoing follow-up with a cardiologist is important.

## Source Information

**Original Article Title:** T h e n e w e ng l a n d j o u r na l o f m e dic i n e

**Publication:** *The New England Journal of Medicine*, 2009; Volume 360, pages 1526–1538. Published April 9, 2009.

**Copyright:** © 2009 Massachusetts Medical Society. All rights reserved.

**Note:** This patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and is not a substitute for professional medical advice, diagnosis, or treatment. Always consult your physician or a qualified healthcare provider with questions about your medical condition.


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