Continuing Education Activity

The terms pericarditis refers to inflammation of the pericardium and myocarditis. Both can occur together in clinical practice, and hence the term myopericarditis is used. Sometimes myopericarditis is used interchangeably with perimyocarditis. Myopericarditis is used when there are primarily pericarditis symptoms with evidence of the involvement of the myocardium as evidenced by cardiac biomarker elevation or imaging studies revealing normal wall motion. If there is evidence of regional wall motion abnormalities with reduced ventricular function, the term perimyocarditis has been used. This activity reviews the evaluation of myopericarditis and the role of the medical team in treating this condition.

Objectives:

• Review the frequency of myopericarditis.
• Outline the evaluation of patients with suspected myopericarditis.
• Summarize the treatment options available for a patient diagnosed with myopericarditis.
• Explain strategies to optimize care coordination among interprofessional team members to improve outcomes for patients affected by myopericarditis.

Introduction

The terms pericarditis refers to inflammation of the pericardium and myocarditis. Both can occur together in clinical practice, and hence the term myopericarditis is used.

Sometimes myopericarditis is used interchangeably with perimyocarditis. Myopericarditis is used when there are primarily pericarditis symptoms with evidence of the involvement of the myocardium as evidenced by cardiac biomarker elevation or imaging studies revealing normal wall motion.[1] If there is evidence of regional wall motion abnormalities with reduced ventricular function, the term perimyocarditis has been used.

Etiology

The majority of cases of myopericarditis are idiopathic as no definitive cause is identified even after extensive work up. Causes are divided into infectious and non-infectious causes. Most of the infectious causes are viral, and they are often attributed to the following viruses:

Infectious Causes

• Viruses: Coxsackievirus, adenoviruses, herpes viruses, echovirus, Ebstein-Barr virus, cytomegalovirus, influenza virus, hepatitis C virus, parvovirus B19
• Bacterial: Mycobacterium tuberculosis, Streptococcus, Staphylococcus, Haemophilus, Legionella, Mycoplasma
• Fungal: Histoplasma, Aspergillus, Blastomyces, coccidioidomycosis
• Parasites: Toxoplasma, amebic, Chaga disease

Non-Infectious Causes

Drugs (cardiotoxic effects or hypersensitivity reactions): procainamide, isoniazid, hydralazine, alcohol, anthracycline, heavy metals

• Post-radiation to the chest cavity
• Systemic inflammatory diseases: Lupus, rheumatoid arthritis, scleroderma, Sjogren, mixed connective tissue  disease
• Other inflammatory conditions: Granulomatosis, inflammatory bowel disease
• Metastatic cancers: Especially lung cancer, breast cancer, melanoma
• Primary cardiac tumors: Rhabdomyosarcoma
• Metabolic: Hypothyroidism, Renal failure/uremia
• Vaccine-associated myopericarditis

Epidemiology

The exact incidence and prevalence of myopericarditis have not been established. Acute pericarditis is the admitting diagnosis in 0.1% of hospital admissions. A study of military recruits estimated the incidence of myocarditis is around 17 per 100,000 persons.[2][3] Vaccine-associated myocarditis has been reported in 0.01% of military recruits following smallpox vaccination.

History and Physical

Clinical features depend on the degree of the inflammation of the pericardium, myocardium, and acuity of the illness. The clinical presentation can differ from a subtle, self-limiting illness to severe cardiogenic shock and death.

Early symptoms included precordial chest pain, fatigue, dyspnea, palpitations, and fever. Patients may give symptoms suggestive of a viral prodrome (a runny nose, arthralgia, low-grade fever) 1 to 2 weeks preceding the presentation. In predominant pericardial involvement, they can describe the pain as sharp, worse with a cough or inspiration and relieved by sitting forward. If there is significant myocardial involvement, there may be a continuous pain, and sometimes, it is hard to differentiate from myocardial ischemia pain, especially in people with cardiovascular risk factors. They may also have predominant heart failure symptoms such as shortness of breath, orthopnea, pedal edema, and fatigue. Rare symptoms include arrhythmias, syncope, and sudden cardiac arrest. Physical examination findings can be variable, but common findings may include fever, pericardial friction rub and features of heart failure. Look for other signs of systemic illness which may contribute to the etiology.

Evaluation

Laboratory studies

Myopericarditis can result in elevation of markers of inflammation like erythrocyte sedimentation rate, C-reactive protein, white blood cell and cardiac biomarkers suggesting myocardial involvement. All the patients should also have routine blood work to rule out thyroid pathology, hepatitis, and renal function. Workup with serological markers is undertaken in patients with persistent symptoms or associated with signs of such illness. Routine viral serologies are unlikely to be helpful in the diagnostics process as the results from these studies rarely alter the treatment.

Electrocardiogram

Typical ECG findings of pericarditis include diffuse concave ST-segment elevation and PR depression. Depending on the degree of myocardial involvement, these classic changes may or may not be present with diffuse T-wave changes or inversions. Even though ST-segment changes are diffuse in most cases, it is not uncommon to see localized ECG changes (inferolateral or anterolateral) depending on the degree of the involvement. Common arrhythmias include supraventricular or ventricular ectopic beats or non-sustained ventricular arrhythmias.

Chest Radiography

Chest x-ray is normal in most of the self-limiting and minor forms of the disease or may reveal an enlarged cardiac silhouette suggesting significant fluid accumulation in the pericardial space in some patients. There may be signs of heart failure as well in some very sick patients.

Echocardiogram

An echocardiogram is routinely performed and in most patients may be normal with normal heart function with a trace or no significant pericardial effusion. Researchers have described increased pericardial brightness as a marker of the pericardial inflammation, but this is a non-specific finding with limited specificity.

Some patients may have significant pericardial fluid accumulation with or without hemodynamic compromise (tamponade physiology). An echocardiogram will also assess the left and right ventricular function and associated valvular heart disease abnormalities.[4] Patients with reduced left ventricular function are preferably managed in tertiary centers, and these patients have high morbidity and mortality.

Coronary Angiography

Coronary angiography is not indicated in young patients with typical features of myopericarditis, but in patients with risk factors for atherosclerotic cardiovascular disease it may be difficult to differentiate from myocardial ischemia based on non-invasive tests and would need cardiac catheterization to rule out acute coronary syndrome.

Cardiac Magnetic Resonance Imaging

Cardiac magnetic resonance imaging (CMR) can be a very good diagnostic test in these patients to assess the degree of myocardial and pericardial involvement.  In patients with myopericarditis, subepicardial or mid-myocardial inflammatory changes are seen along with myocardial edema in different vascular territories, as opposed to subendocardial or transmural myocardial enhancement in one arterial territory in acute coronary syndrome. CMR will also assess the left ventricular function. Pericarditis can be diagnosed on CMR by the presence of noncalcified pericardial thickening with pericardial effusion.

Endomyocardial Biopsy

Endomyocardial biopsy may be needed in a few selective sick patients, who exhibit clinical signs of continued deterioration despite standard supportive care. In these patients, endomyocardial biopsy is recommended if it may alter treatment options, for example for giant cell arteritis).

Diagnosis

The diagnosis of myopericarditis is suspected based on the history of pleuro-pericarditis chest pain, findings on the clinical exam like pericardial friction rub associated with typical changes of EKG and elevated cardiac biomarkers. Elevated markers of inflammation will support the diagnosis of myopericarditis and echocardiogram is done to assess the left ventricular function and pericardial involvement. In patients with atherosclerotic risk factors, they will need cardiac catheterization to rule out obstructive epicardial coronary artery disease. Cardiac magnetic resonance imaging is a useful test to assess the degree of myocardial involvement especially in patients with hemodynamic instability or symptoms of heart failure or cardiac arrhythmias.

Diagnostic Criteria

Acute pericarditis is diagnosed in the presence of 2 or more of the following features: Pleuro-pericarditis chest pain, pericardial friction rub on the exam, ECG changes (diffuse concave ST-segment elevation and PR depression), or pericardial effusion.[5]

Myopericarditis is diagnosed in the presence of one additional feature: Elevated cardiac biomarkers, presumed new Left ventricular systolic dysfunction based on echocardiography or CMR, myocardial inflammation by CMR.

Treatment / Management

The overall prognosis of this condition is very good with no long-term sequelae in most patients.[6] Limited data are available to guide the treatment of myopericarditis. If the presenting illness has more of pericarditis symptoms with preserved left ventricular function, Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first line of drugs used. But in patients with significant myocardial involvement, caution is suggested with NSAIDS, as they can worsen the myocardial function. In these patients, minimal doses of NSAIDs are used to achieve symptomatic relief. In patients with significant pericardial effusion associated with pericardial tamponade, percutaneous or surgical drainage is recommended for hemodynamic stabilization. In patients with signs and symptoms of heart failure with myocardial involvement, standard heart failure therapy with beta blockers and angiotensin-converting enzyme inhibitors and/or diuretics are recommended. Colchicine is used routinely in patients with pericarditis, but its role in myopericarditis is not well established. Corticosteroids are usually used in specific conditions like giant cell myocarditis or recurrent pericarditis. Activity restriction is recommended for up to 3 months in patients with myocardial involvement, and in people that take part in competitive contact sports activities; prolonged physical exertion restriction may be needed on an individual basis.

Vaccine-Associated Myopericarditis

Symptoms and signs of myopericarditis occurring within 30 days of a vaccine are defined as vaccine-associated myopericarditis in the absence of other pathology. These symptoms have reported following smallpox vaccine, and the incidence is about 0.01%.[7] Diagnostic tests and treatment are similar to what has been described above. Most patients will make a spontaneous recovery, but a small fraction of patients with highly-active viral infection as evidenced by polymerase chain reaction (PCR) may need treatment with vaccinia immune globulin.

Differential Diagnosis

• Alcoholic cardiomyopathy

• Cardiac tamponade

• Cardiogenic shock

• Chagas disease

• Cocaine-related  cardiomyopathy

• Coronary artery atherosclerosis

• Dilated cardiomyopathy

• Hypertrophic cardiomyopathy

• Interstitial pulmonary fibrosis

• Neurogenic pulmonary edema

• Peripartum cardiomyopathy

• Restrictive cardiomyopathy

• Sudden cardiac death

• Unstable angina

• Ventricular tachycardia

Pearls and Other Issues

In patients with risk factors for atherosclerotic vascular disease, it can be confused with the acute coronary syndrome.

Patients usually present with complaints of chest pain, shortness of breath, fever and on examination may have a pericardial friction rub.

Laboratory tests will be positive for markers of inflammation like erythrocyte sedimentation rate, C-reactive protein, and white cell count. 

Cardiac biomarkers will be elevated in patients with myopericarditis. An electrocardiogram may have changes of pericarditis, but in patients with significant pericardial effusion and myocarditis, typical changes may not be seen. 

An echocardiogram is routinely performed to assess the degree of pericardial effusion and left the ventricular function.

Cardiac magnetic resonance imaging may provide, additional information to quantify the extent of inflammation in the myocardium.

Patients with predominant pericarditis features are treated with high dose non-steroidal anti-inflammatory drugs, while in patients with predominant myocarditis features, these drugs have to be used with caution.

Enhancing Healthcare Team Outcomes

An interprofessional approach to myopericarditis is recommended.

Myopericarditis is not an uncommon problem and is usually of viral in etiology. The condition has diverse presentations and hence is best managed in an interprofessional team that includes an intensivist, cardiologist, radiologist, infectious disease specialist, physical therapist, and an internist. Even though most cases of myopericarditis have a good prognosis, the clinical focus should be on identifying the patients with large pericardial effusions or patients with significantly lowered systolic function as these patients need aggressive medical therapies to prevent morbidity and mortality. In the absence of data from randomized trials, treatment recommendations of myopericarditis are based on expert opinion.