Continuing Education Activity
Myocarditis is an inflammatory process of the myocardium. It can present in the acute, subacute, or chronic phase with either focal or diffuse involvement of the myocardium. In the United States and other developed countries, viral infections are most frequently the cause of myocarditis. In developing countries, rheumatic carditis, Chagas disease, and complications related to advanced HIV/AIDS also provide important causes of myocarditis. Myocarditis is diagnosed based on clinical presentation. Diagnosis is classically confirmed by endomyocardial biopsy. This activity reviews the evaluation and management of myocarditis and highlights the role of the interprofessional team in managing patients with this condition.
- Explain the pathophysiology of myocarditis.
- Describe the signs and symptoms of a patient with myocarditis.
- Summarize the management of the patients diagnosed with myocarditis.
- Explain the importance of coordination among interprofessional team members to improve outcomes for patients affected by viral myocarditis.
Myocarditis is an inflammatory process of the myocardium. It can present as an acute, subacute, or chronic disease process and may present with either focal or diffuse involvement of the myocardium. In symptomatic patients, the presentation can be highly variable from generalized fatigue, malaise, chest pain, congestive heart failure (CHF), cardiogenic shock, arrhythmias, and even cardiac arrest.
In the United States and other developed countries, viral infections are most frequently the cause of myocarditis. In developing countries, rheumatic carditis, Chagas disease, and complications related to advanced HIV/AIDS also provide important causes of myocarditis. Other causes include toxic myocarditis, which is related to drugs that may cause an insidious form of the disease.
Myocarditis is diagnosed based on clinical presentation. Diagnosis is classically confirmed by endomyocardial biopsy (EMB) via established histologic, immunologic, and immunohistochemical criteria.
Myocarditis can occur in an otherwise healthy person and quickly result in progressive heart failure. Myocarditis may be acute (first 2 weeks) or chronic (lasting more than 2 weeks).
The etiology is thought to be caused by a variety of infectious and non-infectious causes. Among the infectious causes, viruses are presumed to be the most common pathogen. In North America and Europe the most frequently implicated viruses include enteroviruses, including coxsackievirus. Parvovirus B-19 and human herpesvirus 6 are frequent culprits as well. Other pathogens that have been implicated include various bacteria, fungi, protozoa, and helminths. Other common but non-infectious causes of myocarditis include autoimmune disorders such as systemic lupus erythematosus (SLE), Wegener’s granulomatosis, and giant cell arteritis. In almost 50-80% of cases, no cause is ever found. In some of these patients, viral particles may be found in biopsy specimens.
- It is believed that the damage to the myocardium occurs in the following ways:
- Direct damage by the offending agent
- Secondary immune response triggered by the offending agent
- Expression of cytokines in the myocardium which lead to an inflammatory process
- Premature or aberrant induction of apoptosis
The incidence of myocarditis is approximately 1.5 million cases worldwide per year. Incidence is usually estimated between 10 to 20 cases per 100,000 persons. The overall incidence is unknown and probably underdiagnosed. In the United States, the frequency of myocarditis is difficult to ascertain as many cases are subclinical. In community-based populations, the prevalence and outcomes of myocarditis are unknown as epidemiologic studies suggest that the majority of Coxsackie B virus infections, an important cause of myocarditis are subclinical, thus following a benign course.
According to some estimates, 1% to 5% of all patients with acute viral infections may involve the myocardium.
The majority of patients are young and healthy. Individuals who are susceptible include children, pregnant women, and those who are immunocompromised.
Myocarditis begins with the direct invasion of an infectious agent and its subsequent replication within or around the myocardium causing myonecrosis.
This leads to the destruction of the cardiac tissue from the infiltration and replication of the infectious agent. Later, the host cellular immune responds and the cytotoxic effects of host immunity are activated by the offending agent.
There may also be a toxic effect of exogenous or endogenous chemicals produced by the systemic pathogen directly on the myocyte.
Three stages of the disease process:
- Acute: defined by direct viral cytotoxicity and focal or diffuse necrosis of the myocardium
- Subacute: defined by an increase in autoimmune-mediated injury with activated T cells and B cells and subsequent antibody production creating cardiac autoantibodies along with inflammatory proteins. There are higher concentrations of anti-b-myosin antibodies in patients with myocarditis with dilated cardiomyopathy than in control groups.
- Chronic: defined by diffuse myocardial fibrosis and cardiac dysfunction that may lead to dilated cardiomyopathy and its sequelae such as CHF, ventricular dysrhythmias, and abnormal ECG findings.
Endomyocardial biopsy (EMB) typically is recommended after other causes of heart failure such ischemic heart disease, valvular lesions, and other causes of cardiomyopathy have been excluded. Endomyocardial biopsy is recommended should the likelihood of the results change management or impact prognosis. Classic histologic examination of the endomyocardial biopsy will reveal cellular infiltrates, which are usually histiocytic and mononuclear with or without associated myocyte damage. Specific findings include eosinophilic, granulomatous, and giant cell myocarditis. The infiltrates are highly variable, often associated with varying degrees myonecrosis. With subacute and chronic myocarditis, interstitial fibrosis may result from the previous insult of the myocardial cytoskeleton.
Toxic drug-induced myocarditis is a term used to describe myocarditis caused by illicit drugs or drugs used as part of chronic medical management. Many drugs such as cocaine, phenothiazines, alcohol, TCA antidepressants, and lithium to name a few, are known to cause myocarditis over time. Frequently, toxic myocarditis will run an insidious course resulting in CHF and dilated cardiomyopathy, often irreversible.
Myocarditis is also a common autopsy finding in patients with cocaine abuse. While the mechanism is largely unknown, many largely believe it is due to its increased sympathomimetic effect, severe oxidative stress, and even metabolite interactions with ion channels. Myocarditis may account for the myocardial anatomic changes that predispose the patient to ventricular dysrhythmias associated with sudden death.
History and Physical
Patients typically will present with a 7-14 day history of a flu-like illness, including fever, malaise, myalgia, vomiting, and diarrhea.
- Adults will typically present with dyspnea, chest pain, and arrhythmias. Vital signs will be abnormal, including fever, tachycardia, tachypnea, and sometimes hypotension. No single sign or symptom will be specific to make the diagnosis, but a presentation with chest pain or CHF often indicates a poor prognosis.
- Children will often present with grunting respirations and intercostal retractions. Infants will often present with fulminant syndrome, fever, hypoxia with cyanosis, respiratory distress/failure, and even cardiac arrest. Much like adults, long-term prognosis correlates with the severity of their initial presentation.
The physical exam may reveal the following:
- Sarcoid myocarditis may present with heart block and associated lymphadenopathy
- Giant cell myocarditis may present with ventricular tachycardia and heart failure
- Acute rheumatic fever mat present with chorea, erythema marginatum, polyarthritis, and subcutaneous nodules.
Physical findings may include an S3, rales, gallop, tachycardia and dependent edema.
Most patients will present with abnormal ECG that are widely variable. This included sinus tachycardia, widened QRS patterns, low voltage, prolonged QT, variable atrioventricular (AV) blocks, and even acute myocardial infarction (AMI) pattern.
Cardiac markers, such as troponin, may be elevated, but during which course of the disease process is mostly unknown. Higher levels of troponin likely correlate with more myocardial damage as it is indicative of myonecrosis, but negative values do not rule out the diagnosis. Other tests that should be ordered include complete blood count (CBC), erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP). The white count, ESR, and CRP may be elevated but are not diagnostic in any way.
Viral antibody titers should also be ordered and should include coxsackievirus group B, HIV, CMV, Ebstein-Barr virus, hepatitis and influenza viruses. Titers will typically increase by four-fold during the acute phase with gradual fall with the progression of the disease process. Serial titers may be helpful.
Cardiac ECHO should be ordered and may show nonspecific findings such as reduced left the ventricular function, global hypokinesis, and even regional wall motion abnormalities.
Contrast MRI or nuclear studies can show the extent of the inflammation and cellular edema, although this may still be non-specific.
Endomyocardial biopsy (EMB), while considered the “gold standard” for diagnosis, is rarely utilized as it has limited sensitivity and specificity, as inflammation across the myocardium may be diffuse or focal in myocarditis. More importantly, histologic diagnosis rarely has an impact on therapeutic approaches. However, if a patient is deteriorating and no cause if found, the Heart Failure Society of America does recommend a myocardial biopsy.
In some patients, cardiac catheterization may be required to rule out coronary artery disease.
Treatment / Management
Patients who presently acutely need to be managed with supplemental oxygen and optimization of fluid status. Beta-blockers should be avoided in those with heart block and heart failure. Patients with a heart block may require a temporary pacemaker. Some patients may require an AICD.
Those patients with heart failure often require diuretics and inotropic support. Log term treatment with ACE inhibitors is recommended. All cardiotoxic drugs should be withheld. NSAIDs should be withheld as they impede the healing of the myocardium and exacerbate the inflammatory process. Some patients may require anticoagulation. The use of antiarrhythmics requires good clinical judgment as many of these agents also have negative inotropic effects that may aggravate heart failure.
Treatment, for the most part, is supportive and aimed at preserving left ventricular function and can range from a simple limitation of activity to rhythm and CHF management, ventricular assist devices, and even cardiac transplantation down the road. Multicenter trials evaluating immunosuppressive therapies have shown no benefit at this time. In the chronic stage, CHF symptoms tend to predominate, and standard pharmacologic treatments for CHF are indicated.
Some patients may benefit from short-term use of the intra-aortic balloon pump and or ventricular assist device. Cardiac transplantation is an option if a donor can be found.
Patients with mild symptoms do improve spontaneously but recovery can take months. Repeat assessment with echocardiograms is necessary. Patients who continue to do poorly should be referred to a tertiary care center where transplant and assist device services are available.
- Coronary artery anomalies
- Endocardial fibroelastosis
- Genetics of von Gierke disease
- Genetics of glycogen-storage disease type II
- Medial necrosis of coronary arteries
The prognosis of patients with myocarditis depends on the severity of the inflammatory process and presentation of symptoms. Patients with severe disease have a poor prognosis without a transplant. Patients with mild myocarditis usually have a good outcome. Poor prognostic factors include low ejection fraction, left bundle branch block, and syncope. The most common cause of death is cardiogenic shock. Others may develop varying degrees of heart block that require permanent pacing. The highest mortality rates are seen in postpartum cardiomyopathy.
The long-term prognosis was usually good, with a 3 to 5-year survival ranging from 56 to 83%, respectively. Patients with acute fulminant myocarditis have an excellent long-term prognosis of 93% at 11 years once they survive the acute illness.
Postoperative and Rehabilitation Care
Long-term follow-up every 3 months is needed as recovery can take months or years. The patient should be advised against intense physical activity.
Deterrence and Patient Education
Patients should be educated about vaccination against measles, rubella, polio, influenza, and mumps.
Those with heart failure should be told to eat a low salt diet and avoid strenuous activities.
Pearls and Other Issues
All patients diagnosed or suspected to have acute myocarditis should be admitted to the hospital and be monitored for hemodynamic instability. Immediate complications of myocarditis include ventricular dysrhythmias, left ventricular aneurysm, CHF, and dilated cardiomyopathy. The mortality rate is up to 20% at 1 year and 50% at 5 years. Despite optimal medical management, overall mortality has not changed in the last 30 years.
Enhancing Healthcare Team Outcomes
The diagnosis and management of viral myocarditis are complex and is best done with an interprofessional team that includes a cardiologist, intensivist, nurse practitioner, cardiac surgeon, internist, and infectious disease expert. In most cases, the patient initially presents to the primary care clinicians and nurse practitioner. These professionals should be aware of myocarditis and make the appropriate referral to a cardiologist on a timely basis.
Once the diagnosis is made, the treatment is largely supportive. All symptomatic patients need ICU monitoring. Immediate complications of myocarditis include ventricular dysrhythmias, left ventricular aneurysm, CHF, and dilated cardiomyopathy.
The majority of patients are followed as outpatients by the primary care or the cardiologist and the need to obtain serial echocardiograms cannot be understated. The pharmacist should educate the patient on a low salt diet and refrain from intense physical activity. The pharmacist should also ensure that the patient is on no medication that adversely affects heart function. Close communication between the interprofessional team is vital to ensure good outcomes. [Level 5]