What is EBV-Associated Myopericarditis?
The Epstein-Barr virus (EBV) is a common virus, which is part of the herpesvirus family. It’s made up of double-stranded DNA enclosed by proteins. The virus is spread through close contact between people who can catch the virus and people who carry the virus without showing any symptoms. The main way it spreads is through body fluids, primarily saliva, but it can also be transmitted during stem cell and organ transplants and blood transfusions.
The virus can lead to severe and sometimes fatal diseases in people with weaker immune systems, including chronic EBV disease, a condition which results in an over-activation of the immune system, certain autoimmune conditions, and various types of cancers such as Hodgkin lymphoma, non-Hodgkin lymphoma, nasopharyngeal cancer, and Burkitt lymphoma.
While less common, the Epstein-Barr virus can also cause heart-related issues. These can result from direct damage by the virus to our cells or by an immune response causing injury to our cells. People with compromised immune systems are particularly likely to experience these complications, which can include changes to the coronary artery (the artery supplying blood to the heart), aneurysms (a lump in the wall of an artery), worsening coronary artery disease, inflammation of the heart muscles and outer lining of the heart, issues with heart valves, and high blood pressure in the lungs. If not treated quickly and effectively, these complications can be deadly.
What Causes EBV-Associated Myopericarditis?
EBV, or Epstein-Barr Virus, is covered in an outer layer of proteins which are crucial for the virus to attach to and enter specific cells in our body, mainly B-cells (a type of white blood cell) and epithelial cells (skin cells and cells that line the body’s surfaces). The virus then tricks the B-cells into duplicating its genetic code. This turns the B-cells into memory B-cells, which can either circulate in your blood or stay dormant until an external factor stimulates them to become active.
Various cells, such as B lymphocytes (another name for B-cells), T lymphocytes (another type of white blood cell), epithelial cells, and muscle cells can host the EBV. The virus is unique because, unlike the herpes simplex (HSV) or the cytomegalovirus (CMV), it can transform B-cells without causing obvious damage to them. The EBV can lie dormant in these cells, so factors like a weakened immune system may reactivate the virus and bring about symptoms. These can include infectious mononucleosis (mono), the “kissing disease”, and certain autoimmune diseases, where the immune system mistakenly attacks healthy cells.
Having a weakened immune system, like in organ transplant recipients or in other people with compromised immunity, is associated with aggressive disorders where the lymph cells (white blood cells found in lymph, a fluid in the circulatory system) multiply too quickly. This was first observed in tissue samples from patients with lymphoma, a type of cancer, which contained the EBV.
Risk Factors and Frequency for EBV-Associated Myopericarditis
Most adults worldwide, about 90% to 95%, have been infected with the Epstein-Barr Virus (EBV). A study in the United States found that about 66.5% of children and teenagers aged 6 to 19 have experienced this infection. For younger kids, aged 6 to 8, the rate was around 54%, while for older teens, aged 18 to 19, it was up to 82.9%. Out of all these children and teenagers, those of Mexican-American descent had a higher rate of EBV infection than their non-Hispanic black and white peers.
In countries with low to mid-range income levels, the estimated number of people with EBV ranged from 92.1% to 94.8%, with the highest rates seen in people over 40 years old. In the United Kingdom, a similar study found a rate of 85.3%, with girls getting the infection at a younger age than boys.
Other factors that can raise the rate of EBV infection are being white, having a lower body mass index, not smoking, living in a big family, having a lower income, having parents with less education, experiencing maternal deprivation early in life, and being born in a foreign country.
On the other hand, myopericarditis, a heart-related condition, is rarely seen in children and teenagers, with about 1 to 2 cases per 100,000 individuals. Its connection to EBV is not clearly understood yet because the evidence is based on observational studies or case reports, not larger, clinical trials. However, some studies have found higher levels of inflammation and EBV-related proteins in patients with heart attacks. Furthermore, in a study of 142 patients with heart enlargement and signs of myocarditis, 9 patients were found to have EBV DNA.
Signs and Symptoms of EBV-Associated Myopericarditis
People with conditions related to the heart can experience a wide range of symptoms, from no symptoms at all to severe ones that can lead to sudden death due to serious heart failure or irregular heart rhythms. The nature and intensity of these symptoms can tell a lot about the severity of the condition. In particular, people who have symptoms of heart failure from the start are more likely to need a heart transplant and are at a higher risk of dying from heart-related issues.
Most of the time, the symptoms are similar to those of a common cold, which can include:
- Fever
- Fatigue
- Cough
- Discomfort while swallowing (odynophagia)
- Chest pain located in front of the heart (precordial chest pain)
- Feeling of the heart racing (palpitations)
- Generalized muscle pain (polymyalgia)
- Feeling of lack of energy (asthenia)
- Mild, non-spreading chest discomfort
- Shortness of breath
- Dizziness
- Decreased ability to exercise
Note that these symptoms do not appear during rest. Sometimes, myocarditis (inflammation of the heart muscle), which can occur in both children and adults, may be predicted by a viral prodrome.
If the person’s pericardium (the sac that surrounds the heart) is mostly involved, they might describe the pain as sharp, gets worse with coughing or deep breaths, and gets better when they lean forward. On the other hand, if the heart muscle is significantly involved, the pain might be continuous, which can make it difficult to differentiate it from pain due to inadequate blood supply to the heart, especially among those with cardiovascular risk factors.
They might also show common signs of heart failure such as shortness of breath, trouble breathing when lying down, swelling in the lower legs, and fatigue. Less common symptoms include irregular heart rhythms, fainting, and sudden cardiac arrest.
A physical examination may reveal a variety of findings such as fever, a rubbing sound heard over the heart (pericardial friction rub), and signs of heart failure. Other findings may include swollen neck lymph nodes and swollen tonsils with white patches. Interestingly, symptoms like an enlarged liver or spleen are usually not present. Signs of a systemic illness that might be involved in causing the condition may include autoimmune disorders, systemic lupus erythematosus, recent vaccinations, chemotherapy, and immune checkpoint inhibitor therapy.
The appearances of these symptoms can sometimes suddenly develop into life-threatening problems. Myopericarditis (inflammation of both the heart muscle and the pericardium) can lead to a variety of clinical courses, from death due to severe systolic dysfunction or ventricular arrhythmias to gradual decline into dilated cardiomyopathy (a condition where the heart’s ability to pump blood is decreased). After being discharged from the hospital, it is very important to closely follow-up these patients for several weeks, especially those who are at risk of developing heart failure.
Testing for EBV-Associated Myopericarditis
Atypical lymphocytes are usually found in increased numbers in people testing for Epstein-Barr virus (EBV), a common virus which can cause diseases like mononucleosis. Serological tests, which detect antibodies in the blood, can tell if one has ever been exposed to the virus. However, the results from these tests don’t usually change treatment plans, which is why they aren’t generally used for diagnosis. There are specific tests for EBV, like a heterophile antibody test which can detect antibodies related to EBV. Though these tests do occasionally give false positives due to cross-reacting with other viral infections, autoimmune disorders or cancers, they’re generally a good, quick and affordable first step due to their high sensitivity and specificity.
Given some of the challenges in diagnosing EBV infection with antibody tests alone, Polymerase Chain Reaction (PCR) methods are accurately detecting EBV. This DNA-detecting method has a strong sensitivity and specificity among kids with infectious mononucleosis – a disease caused by EBV. Not only that, PCR can detect as low as 50 copies of EBV DNA per reaction when used on tissues, which is why it’s the primary method of detecting EBV in tissue samples now.
Myopericarditis can lead to high levels of inflammatory markers that can be found in your blood. Your doctor may ask for a comprehensive blood analysis to rule out other issues such as thyroid disorders, hepatitis and to assess your kidney function.
An electrocardiogram can show characteristic patterns in pericarditis which includes a widespread concave elevation. There can also be general or localized shifts, arrhythmias involving irregular heartbeats or short periods of ventricular arrhythmias.
Pericardial effusion of fluid around the heart could be visible on a chest X-ray. This fluid, constriction or squeezing of the heart can usually be confirmed by an echocardiogram.
The characteristics of myocarditis, inflammation of the heart muscle, on an echocardiogram are not specific but it is an important part of the routine examination which may show a minimally or non-functioning heart with minimal or no pericardial effusion. It can show varying results, like a dilated, enlarged heart, hypertrophy or enlargement and various other patterns.
When there’s suspicion of blocked coronary arteries, coronary angiography is used to confirm this. It isn’t typically needed for young patients with myopericarditis symptoms but might be needed in individuals with potential blockage of arteries in their hearts. For these individuals, non-invasive testing is challenging, so sometimes they need a heart catheter to rule out acute coronary syndrome, limited blood flow to the heart.
Cardiac MRI is a good choice for assessing people suspected of myocarditis. The Lake Louis criteria uses T1 and T2 criteria which show abnormalities in the heart tissue. These changes are often associated with higher rates of mortality, including sudden cardiac death.
In some severe cases, Endomyocardial biopsy (EMB), a procedure in which a small piece of the heart muscle is removed and examined, is needed. This is typically done in cases where standard treatment doesn’t help and if the patient’s condition is deteriorating. There are specific guidelines for when an EMB is recommended in myocarditis. It is the gold standard for diagnosis of the disease since it gives definitive results. It’s generally used for patients with heart failure that’s sudden and new, heart failure with enlarged heart and abnormal heart rhythms.
Treatment Options for EBV-Associated Myopericarditis
Usually, most patients affected by myopericarditis (inflammation of the heart muscle and the surrounding membrane) recover fully, and long-term complications are rare. The current treatment methods for this condition, primarily caused by viruses, are supportive.
The treatment varies significantly based on the patient’s stability. Patients whose vital signs are unstable and who present a life-threatening condition should be urgently transferred to specialized medical facilities. These facilities must have the necessary resources to monitor heart function and carry out procedures like cardiac biopsies (a procedure to remove and examine heart tissue) and heart surgeries. In cases where the patient’s condition is critical, a device to assist heart and lung function may be needed temporarily until the patient recovers or until a heart transplant can be done. While in some desperate situations, a heart transplant might be considered, doctors usually prefer to wait and see if the patient can recover on their own first.
For patients who experience stable but persistent heart failure, various types of medications are recommended, including diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers. If these treatments don’t relieve heart failure symptoms, doctors might consider adding another class of drugs called aldosterone antagonists.
Sometimes, the initial symptoms of myopericarditis can mirror those of pericarditis (inflammation of the lining around the heart). If the heart’s pumping function remains unaffected, anti-inflammatory drugs can be used as a primary treatment. If there’s considerable inflammation of the heart muscle, doctors are cautious about using anti-inflammatories, as they may worsen the heart’s pumping action. In such cases, these drugs are given at low doses.
Arrhythmias, irregular heart rhythms, and heart blocks (interrupted or slow electrical signals in the heart) are possible complications of acute myocarditis. Stable patients experiencing a fast heartbeat, which doesn’t affect their vital organs, may be treated with beta-blockers. For sustained irregular heart rhythms, amiodarone and dofetilide are alternatives. For patients with heart blocks, a temporary pacemaker might be used initially, followed by the potential need for a permanent pacemaker. Patients with chronic heart conditions may also benefit from a device called an implantable cardioverter-defibrillator once they are out of the acute phase of the illness.
Physical activity should be curtailed during the acute phase of myocarditis. Patients are also advised to stay away from competitive sports for 3 to 6 months post-illness. Regular follow-ups including check-ups, echocardiograms and Holter monitoring (a continuous recording of your heart’s electrical activities) are recommended.
Currently, no approved antiviral therapies are available, but vaccines could be a future possibility. Intravenous immunoglobulin, proteins that function as antibodies, may be used in certain cases where standard treatments for heart failure do not work and inflammation is driven by autoantibodies (antibodies that attack one’s own proteins).
The use of immunosuppressants, medications that reduce the body’s immune response, is still under study for treating myocarditis. These could include steroids alone or combined with drugs such as azathioprine or cyclosporine A. The effectiveness of other medications for this condition is still largely unknown. Most reports highlight the treatment outcomes of chronic cases with no viral involvement.
What else can EBV-Associated Myopericarditis be?
In simple terms, cardiovascular magnetic resonance imaging plays a crucial role in differentiating between different causes of acute coronary syndromes, essentially sudden, severe heart conditions. This becomes significant due to the unclear and similar signs and symptoms that may look like other diseases, such as myopericarditis, a condition that affects the heart muscle and the sac around the heart. For example, if a patient had symptoms due to the reactivation of the Epstein-Barr virus, doctors can rule out acute coronary syndrome.
Chagas Heart Disease is primarily caused by a parasite called Trypanosoma cruzi. It’s considered the most common cause of infectious myocarditis, an inflammation of the heart muscle, across the globe, but it primarily affects people in the Americas. This condition has two phases: the acute phase, which shows up shortly after infection and sticks around for 4-8 weeks, and the chronic phase, which can stretch over 10-30 years. The PCR test is the most effective way to diagnose Chagas disease in the acute phase. In about one-third of cases, the chronic phase shifts from having no symptoms to exhibiting symptoms.
Pericarditis, a swelling and irritation of the pericardium, the thin sac-like membrane surrounding your heart, often comes with pericardial effusion or excess fluid around the heart. This could eventually turn into cardiac tamponade, a serious condition where mounting fluid in the pericardial cavity puts pressure on the heart, affecting its function.
What to expect with EBV-Associated Myopericarditis
It’s crucial to distinguish between acute myopericarditis and pericarditis. Acute myopericarditis involves inflammation of both the heart muscle and the outer heart lining, while pericarditis only involves the outer lining. Common viruses, such as parvovirus B19, adenovirus, herpes viruses, hepatitis viruses, HIV, and enteroviruses, can trigger this inflammation, causing acute pericarditis and myocarditis.
Interestingly, the Epstein-Barr Virus (EBV), which is commonly known for causing mononucleosis or “mono,” rarely causes these heart conditions in people with healthy immune systems. However, the severity and outcomes of EBV-caused heart inflammation can differ greatly among patients due to the different ways it presents and how it interacts with the patient’s immune system.
Some of the most serious risks involve heart failure, particularly with severe onset cases. In general, if patients experience severe heart failure, persistent irregular heartbeats, a reduced ability of the heart to pump blood (measured as a left ventricular ejection fraction below 50%), or require certain medications (inotropic agents or vasopressors) or mechanical heart assistance, they’re at greater risk for poor outcomes related to their heart health.
Possible Complications When Diagnosed with EBV-Associated Myopericarditis
The complications resulting from the interaction between the Epstein-Barr Virus (EBV) and the host’s immune system can vary greatly. However, complications known to result from viral (including EBV) heart issues include:
- Enlargement of the arteries that supply blood to the heart
- Abnormal bulges in these coronary arteries
- Heart valve diseases
- Heart attacks
- Pulmonary hypertension, a condition of high blood pressure in the lungs
- Dysfunction of the heart’s main pumping chamber (left ventricle)
- Failure of the right chamber of the heart (right ventricle)
- Irregular heartbeats
- Fatal outcomes resulting from the previous issues
Preventing EBV-Associated Myopericarditis
Persons suffering from an infection called EBV should be informed that the illness could potentially lead to a variety of complications. These complications could be silent, showing no symptoms or could even end up being life-threatening. Some serious outcomes include the enlargement of the blood vessels supplying the heart, problems with the heart’s valves, and heart failure. However, it is important to note that these severe complications can be avoided with proper and prompt treatment.
EBV is mainly spread through close contact with someone who already has the infection, specifically through their saliva. This is why practicing regular preventative measures like good personal hygiene and awareness can help stop the virus from spreading.
Patients who develop a condition called myopericarditis, an inflammation of the heart muscle and the surrounding sac, may become hemodynamically unstable. This term means their heart might struggle to pump blood throughout the body. In such cases, urgent referral to a specialized heart center is necessary. Other patients may show symptoms that follow similar patterns to heart failure, in which case their treatment will follow heart failure protocols.
Patients who have heart failure are at higher risk of experiencing negative heart-related complications. Therefore, constant monitoring and proper medical care are crucial to their wellbeing. Timely and thorough heart check-ups are key to detecting possible complications early and providing suitable interventions.
In summary, it is very important to educate patients about possible complications of EBV infection, emphasize the significance of preventing transmission, ensure early referrals for those severely affected and implement the correct management plan. All these combined can lead to better health outcomes and a lower risk of complications.
