Continuing Education Activity

Acute myocarditis is inflammation of the myocardium. It is typically seen in infants and teenagers but can occur at any age. It most commonly results from a viral illness; however, it can also be due to non-infectious etiologies. Given its variable clinical presentation, the diagnosis is frequently missed, making it difficult to quantify the true incidence of acute myocarditis. However, it is a significant source of morbidity and mortality. This activity reviews the evaluation and management of myocarditis and highlights the role of the interprofessional team in caring for patients with this condition.

Objectives:

• Describe the presentation of myocarditis.
• Explain how to evaluate a patient with suspected myocarditis.
• Review the treatment for myocarditis.
• Summarize the importance of a coordinated, interprofessional team approach to caring for patients with acute myocarditis.

Introduction

Myocarditis is inflammation of the myocardium, the cardiac muscle. Acute myocarditis is most commonly caused by a viral illness; however, it may less commonly be caused by non-infectious etiologies. Myocarditis can be further divided into acute, sub-acute, or chronic and may either affect a focal part of the myocardium or have diffuse involvement. Its clinical presentation may vary from subtle chest pain or fever to life-threatening congestive heart failure or dysrhythmia, or even death. Clinical diagnosis is often challenging, and management is usually supportive.[1][2][3]

Etiology

Causes of acute myocarditis can be separated into infectious and non-infectious. In 50% of cases, no cause can be identified; hence, myocarditis is commonly idiopathic. In patients with an identified cause, the most commonly implicated etiology is viral (similar to pericarditis), of which enteroviruses, notably Coxsackie B, are the most common. Other viral pathogens include the human immunodeficiency virus (HIV), adenovirus, and hepatitis C. Other infectious causes include parasitic (e.g., Trypanosoma cruzi), bacterial (e.g., diphtheria or tuberculosis), helminths, or fungal. Non-infectious causes of myocarditis include granulomatous inflammatory diseases (e.g., sarcoidosis or giant cell myocarditis), systemic lupus erythematosus, eosinophilic myocarditis, polymyositis and dermatomyositis, and collagen vascular disease.[4] Cases due to cocaine abuse have also been reported in the literature.[5] 

Epidemiology

Given the variable clinical presentation, clinical diagnosis is difficult. The diagnosis is frequently missed, and it is difficult to estimate the true incidence of acute myocarditis. However, the incidence is estimated to be 10 to 22 per 100,000 cases, with an estimated 1.5 million cases worldwide in 2013.[6] It also is estimated that the myocardium is involved in up to 5% of patients who develop an acute viral illness. Acute myocarditis is more common in younger adults and appears to affect both sexes and various races equally.[7][8]

Pathophysiology

It is believed that myocarditis and its complications are largely immune-mediated. For example, in infectious etiologies, the microbial agent gains entry through the respiratory or gastroenteric tract and then binds to its specific receptor in the heart. This leads to intracellular replication, resulting in cell damage and lysis. This process may result in immune dysfunction, in which molecular mimicry plays an important role and further enhances cardiac damage. If the damage is severe and prolonged, this can result in dilated cardiomyopathy.[9]

Histopathology

The histopathology of acute myocarditis is varied and depends on the organism and the extent of myocardial damage. One may see a variety of white cells, and the damage may be focal or diffuse. Necrosis with the involvement of the coronary vessels may also be seen. In long-standing cases, one may also see fibrosis. Note that endomyocardial biopsy is not routinely performed in nonfatal cases, and histopathology is generally only available in cases that are fatal.

History and Physical

The clinical presentation of acute myocarditis is highly variable, ranging from asymptomatic to subtle to cardiogenic shock and even sudden cardiac death. There are no pathognomonic clinical features. The classic presentation is similar to that of heart failure with symptoms of dyspnea, orthopnea, and leg swelling. Palpitations and syncope may also occur. In one study of clinically suspected cases, about a quarter of patients had reduced left ventricular ejection fraction (LVEF), sustained ventricular arrhythmias, or symptoms of low cardiac output.[10] When the pericardium is involved, as in myopericarditis, chest pain with features similar to pericarditis will arise. As the most common cause of myocarditis is viral, a viral prodrome (fever, arthralgia, fatigue), usually 1 to 2 weeks before the onset of heart failure symptoms, may be described by the patient. The 2013 European Society of Cardiology position statement on myocarditis breaks the presentation down to three distinct but overlapping clinical profiles: acute coronary syndrome-like (chest pain not explained by evidence supporting coronary artery disease), new-onset or worsening heart failure (in the absence of known heart failure or coronary artery disease), and life-threatening conditions (arrhythmia, cardiogenic shock, severely impaired left ventricular function).[11] Other manifestations of an infectious agent, such as dysphagia in patients with Chagas disease (caused by Trypanosoma cruzi) or neurological symptoms in patients infected with diphtheria, also may occur. In addition, patients with a non-infectious etiology often will have manifestations of their underlying systemic disease, such as skin or kidney involvement in patients with connective tissue disease. 

There are no specific physical exam findings associated with myocarditis. Physical examination may range from normal to features similar to heart failure, including S3 gallop, jugular venous distention, peripheral edema, and tachycardia. In addition, patients with ventricular dilatation may have a mitral regurgitation murmur, which is classically described as an apical pansystolic murmur. A pericardial friction rub may be appreciated, especially if there is concurrent pericarditis. Additional findings may suggest an underlying disease in non-infectious etiologies. Also, patients with eosinophilic myocarditis will have a pruritic maculopapular rash. When the pericardium is involved, a friction rub also may be heard on cardiac auscultation.

Evaluation

Diagnosis of acute myocarditis is challenging because other clinical entities may mimic the diagnosis. This is further complicated by the variable clinical presentation of acute myocarditis. Acute myocarditis should be suspected in patients with clinical signs and symptoms concerning the illness regardless of workup, especially in young patients (age 25-50) with no history of cardiac disease. Clues related to underlying etiology may support the diagnosis, such as viral prodrome or signs of connective tissue disease.[12][13][14]

Initial evaluation for acute myocarditis should include an EKG, echocardiogram, serum troponin, and  B-type natriuretic peptide (BNP). Troponin elevation, which is usually dramatic, is present in more than half of the patients. BNP is useful to assess for evidence of heart failure and ventricular stretch, which may suggest myocarditis in the right clinical picture. EKG often shows nonspecific ST changes; however, it also may show sinus tachycardia or ventricular arrhythmias (40% of patients). Also, changes consistent with pericarditis, including diffuse ST elevation, may be present in those with pericardial involvement. An echocardiogram is useful in assessing the degree of cardiac dysfunction and in helping rule out other causes, including valvular disease.

A chest radiograph is neither sensitive nor specific for myocarditis but may show an enlarged heart size, pulmonary vascular congestion, or pleural effusion. CT angiography to evaluate for other causes of chest pain may be indicated. Percutaneous coronary angiography is indicated in patients at high risk for coronary artery disease to help rule out an ischemic cause of cardiac dysfunction in the right setting. Cardiac magnetic resonance imaging seems to be promising and may help differentiate ischemic from non-ischemic etiologies of dilated cardiomyopathy. In addition, a complete blood count with differential showing eosinophilia may hint at eosinophilic myocarditis. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are usually elevated but nonspecific. Viral antibody testing can be done in the right setting; however, specificity is low and often can result in a delay in diagnosis without any change in management.

Endomyocardial biopsy, though rarely done due to its invasive nature, is the gold standard for the diagnosis of myocarditis. According to the Heart Failure Society of America, biopsy should be reserved for patients with acute deterioration of the cardiac function of unknown etiology, failing the usual medical therapy. The classic histological findings include lymphocytic infiltrates with myocyte necrosis, as described by the Dallas criteria.

Treatment / Management

Management is primarily supportive but also includes treating any identifiable cause. Patients with heart failure should receive standard treatment, including beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and diuretics if needed. Immunosuppressive therapy has not shown clinical benefit and, therefore, should not be used routinely except in patients who have underlying systemic autoimmune or granulomatous inflammatory diseases. Although viral etiology is the most commonly identified cause, the efficacy of antiviral therapy is unknown, and routine antiviral therapy is not recommended. Non-steroid anti-inflammatory agents should be avoided in the acute setting as they may impair the healing of the myocardium. In severe cases, mechanical support devices such as an intra-aortic pump or left ventricular assist devices can also be used, with consideration of heart transplants. In these instances, it is important to consider a transfer to tertiary care centers for surgical support if needed. Patients may develop dysrhythmias or left atrial or ventricular thrombus requiring anticoagulation. Finally, patients should be counseled on limiting exercise and avoiding alcohol, especially in the acute phase, as it may increase viral replication. Long-term follow-up with serial echocardiography is recommended.[15][16]

Differential Diagnosis

• Acute coronary syndrome
• Coronary artery disease
• Coronary vasospasm
• Myocardial ischemia/infarction
• Pulmonary edema
• Unstable angina
• Congestive heart failure
• Pericarditis
• Pericardial effusion

Complications

Complications of acute myocarditis result from the damage to the cardiac muscle and include heart failure, arrhythmia, myocardial infarction, and sudden cardiac arrest.

Enhancing Healthcare Team Outcomes

Acute myocarditis has many causes, and its presentation can range from asymptomatic to mild to severe. Most patients need admission due to the risk of rapid progression to life-threatening conditions, including decompensated cardiomyopathy, heart failure, ventricular dysrhythmias, and death. These patients benefit from an interprofessional team. In addition to the attending physician, the nurse and other staff are critical for serial monitoring of these patients. All patients need to be educated on the need for rest and abstaining from alcohol and tobacco. The pharmacist should educate the patient on the need to remain compliant with their medications (beta-blocker or ACE inhibitor). Most of these patients also have mild to moderate dyspnea and hence may benefit from chest physical therapy. Because of fatigue, a physical therapy consult is recommended to help build exercise endurance. Enrollment in a cardiac rehabilitation program is beneficial for most patients. Finally, the patient should be educated on a healthy lifestyle, maintaining a healthy body weight, and a low-fat diet.[17][18] [Level 5]

Outcomes

The general outcome after viral myocarditis is good. However, recovery can be long and may take 3 to 7 years. However, some patients may develop left ventricular dilatation and may need ongoing treatment for heart failure and arrhythmias. A few patients may require a heart transplant. Those who exhibit the soluble Fas ligand at presentation generally tend to have a good prognosis, whereas those who have anti-myosin autoantibodies have a worse outcome. Cardiogenic shock can occur but is rare. The mortality for acute myocarditis is about 20% at 12 months, and at four years, there is a 56% survival. Patients who require a ventricular assist device while awaiting a heart transplant generally do not fare well if the wait is more than 1 to 2 weeks.[15][19] [Level 5]