Nonviral Myocarditis

What is Nonviral Myocarditis?

The term “myocarditis” was first used by a German doctor, Joseph Friedrich Sobernheim, back in 1837. The word basically means “inflammation of the myocardium,” which is the muscular tissue of the heart. But, for a long time, doctors weren’t quite sure what should and shouldn’t be classified as myocarditis. In the 19th and early 20th century, this term was used broadly to describe a lot of heart diseases that didn’t involve heart valves, including conditions we now know as heart diseases related to high blood pressure and poor blood supply to the heart.

Even after we identified heart disease due to poor blood supply as a separate condition, the term “myocarditis” was still used interchangeably with other heart muscle diseases. This confusion was in part because myocarditis could manifest in many different ways, from general symptoms like fever, muscle aches, and decreased exercise capacity to severe conditions like sudden cardiac arrest and circulatory failure.

It was not until 1995 that the World Health Organization and the International Society and Federation of Cardiology grouped the various heart muscle diseases and defined myocarditis as “an inflammation disease of the heart muscle, diagnosed by specific histological, immunological, and immunohistochemical criteria.” However, because the test to diagnose myocarditis, called an endomyocardial biopsy, is not often performed, we still don’t know exactly how common this condition is.

Myocarditis can range from being mild and improving on its own with minimal impact on heart function, to suddenly becoming serious with severe circulatory failure needing medication or mechanical support. When myocarditis comes with heart dysfunction, the condition is known as inflammatory cardiomyopathy.

What Causes Nonviral Myocarditis?

Myocarditis is an inflammation of the heart muscle (myocardium). It is often caused by viruses, like the enterovirus Coxsackie B, as well as parvovirus B19, adenovirus, influenza A virus, human herpesvirus, Epstein–Barr virus, cytomegalovirus, hepatitis C virus, and HIV.

There are also non-viral causes of myocarditis. These can be broadly grouped into three categories: infectious, immune-mediated, and toxic.

Infectious causes of myocarditis can include:

– Bacteria such as group A Streptococci, which can cause rheumatic myocarditis (heart inflammation linked to rheumatic fever) as well as others like Corynebacterium diphtheriae, Mycobacterium, and Mycoplasma pneumoniae.
– Spirochetes, which are a type of bacteria, like Borrelia burgdorferi, which causes Lyme myocarditis, and affects heart rhythm.
– Protozoa, single-celled organisms, like Trypanosoma cruzi, which causes Chagas’ disease.
– Parasites such as Tenia solium (cause of cysticercosis) and Trichinella (which causes a disease called trichinosis).
– Fungi like Aspergillus and Candida, as well as Histoplasma and Cryptococcus.
– Diseases like Q fever and Rocky Mountain spotted fever, caused by a specific type of bacteria known as Rickettsia.

Immune-mediated causes of myocarditis happen when the body’s own immune system attacks the heart. This may be due to:

– Autoimmune diseases, which are conditions where the body’s immune system attacks its own tissues. These include lesions like giant cell myocarditis and diseases like systemic lupus erythematosus.
– Hypersensitivity reactions, which are overreactions of the immune system, to drugs like penicillin or furosemide, or after a reaction to vaccines.
– Rejection of a transplanted heart.

Toxic causes of myocarditis typically involve substances that can damage the heart. This may include:

– Drugs like amphetamines, cocaine, and certain chemotherapy and antipsychotic medications.
– Heavy metals like copper, iron, and lead.
– Metabolic causes such as certain types of tumors that cause excess hormone production, or nutritional deficiencies (such as thiamine deficiency, known as beriberi).

Each type of myocarditis has different treatments, usually aimed at addressing the underlying cause and relieving symptoms. It is always important to seek medical advice if you suspect myocarditis.

Risk Factors and Frequency for Nonviral Myocarditis

Myocarditis, an inflammation of the heart muscle, is a leading cause of sudden death and nonischemic dilated cardiomyopathy, especially among young people. It’s considered the third leading cause of sudden cardiac death in competitive athletes according to the American Heart Association and the American College of Cardiology. Notably, for children under 18, it’s the most frequently identified cause of dilated cardiomyopathy. The exact prevalence is difficult to establish as myocarditis is likely under-reported. Studies suggest that the death rate among young people due to myocarditis ranges between 2 to 42%.

Young children and newborns are more often affected by a severe form of myocarditis, triggered by viral infections, while acute lymphocytic and giant cell myocarditis are more frequently seen in adults with a median age of 43. Men are slightly more likely to develop myocarditis than women, which some researchers believe might be due to natural hormonal differences affecting the immune response.

While viral myocarditis is common, there are many non-viral causes as well. In developed regions, diseases such as rheumatic heart disease and tertiary syphilis are rare, mainly due to better healthcare and early administration of antibiotics. However, in regions with poor sanitation, enteric pathogens and parasitic infestations are more common, and diphtheritic myocarditis mostly affects populations with insufficient immunization coverage.

Certain pathogens are more common in specific geographic regions. These include:

• Borrelia burgdorferi, Babesia, and Anaplasma species found in Ixodes ticks in the northeastern United States
• Trypanosoma cruzi predominantly found in rural areas of Central and South America
• Coccidioides immitis frequently found in the southwestern United States and northern Mexico
• Histoplasma capsulatum, which is prevalent in the central and eastern United States, especially the Ohio and Mississippi river valley
• Blastomyces dermatitidis common in eastern North America, particularly around the St. Lawrence and Mississippi river systems

Signs and Symptoms of Nonviral Myocarditis

Myocarditis, or inflammation of the heart muscle, can cause a variety of symptoms that range from no symptoms at all to severe, life-threatening conditions. It can cause mild issues like fever and muscle aches, more severe symptoms that can resemble a heart attack, and even heart failure or dangerous heart rhythms.

The European Society of Cardiology categorizes myocarditis symptoms into four main groups:

• Symptoms that mimic a heart attack, often following a respiratory or gastrointestinal illness by approximately 1-4 weeks.
• Sudden or worsening heart failure that’s been happening for less than 3 months, with no known causes of heart failure or blocked arteries. Symptoms can include feeling out of breath, heart palpitations, swelling in the feet, fatigue, and chest discomfort.
• Chronic heart failure with symptoms that have lasted more than 3 months, with no known heart failure causes or blocked arteries.
• Life-threatening conditions like severe heart rhythms or cardiogenic shock with a significantly reduced ability of the heart to pump blood.

The patient might also show signs and symptoms of the disease causing the myocarditis. For instance, a patient with Chagas’ disease may experience swelling at the infection site, fever, muscle pain, a rash, and swelling of the eyelid. In the chronic phase, this disease might cause difficulty swallowing, constipation, or orthostatic hypotension. Lyme carditis can present symptoms like a rash, flu-like symptoms, joint pain, facial paralysis, or neuropathy.

In 1991, Liebermann et al. created a classification using clinical presentations to differentiate between different types of myocarditis. Fulminant myocarditis has a sudden onset within to two to three days and may require circulatory support, but typically resolves on its own. Other types of myocarditis, such as giant cell myocarditis and cardiac sarcoidosis, might have a more drawn out course but can result in worsened outcomes. They can cause continuous dangerous heart rhythms, high degree heart blocks, and progressively worsening heart failure that may not respond to treatment.

Testing for Nonviral Myocarditis

Myocarditis is a condition that can cause changes in a patient’s electrocardiogram (EKG), the tool used to measure the electrical activity of the heart. This could cause the heart’s ST-segment, which shows the heart’s electrical conduction, to elevate in a particular shape and pattern. Some specific types of myocarditis, like Lyme carditis, giant cell myocarditis, and cardiac sarcoidosis, often lead to AV blocks or bundle branch blocks, which are abnormalities in the heart’s electrical conduction system. Patients with a longer QRS duration – the time it takes for an electrical signal to travel through the lower heart chambers – are at a greater risk of needing a heart transplant or dying if myocarditis is suspected.

There are certain cardiac biomarkers, like types of proteins called troponin T and troponin I, that may increase in the blood if myocarditis is present, but these increases aren’t specific to myocarditis. Patients with heart failure symptoms might also have higher levels of a hormone called brain natriuretic peptide (BNP), and they may have increased levels of acute phase reactants like ESR or CRP, which are proteins that increase in response to inflammation.

An ultrasound of the heart, also known as an echocardiogram, might show abnormal functioning of the ventricles (the lower heart chambers) with or without abnormalities in the wall motion of the heart. The size of the ventricular chambers can increase in both acute and chronic myocarditis, but the heart muscle may behave differently. In acute cases, the heart muscle may be normal or even thickened, while in chronic cases, the muscle often thins and scars.

To diagnose myocarditis, we must look for certain signs. In acute myocarditis, there will be types of antibodies called IgM, but in chronic microbial myocarditis, different types of antibodies called IgG will be present. Analysis of a biopsy from the heart muscle itself can also yield the most definitive proof of myocarditis.

In patients who are suspected to have myocarditis, a type of scan called a cardiac MRI could be of great help. There are certain features that are looked for in these cases and if two out of the three are found then the results can confirm myocarditis. If myocarditis is still suspected but the scan doesn’t meet these criteria, then the scan may need to be repeated after 1-2 weeks.

Each case of suspected myocarditis is unique and should be watched closely. All patients with this condition should be admitted to the hospital for monitoring, with daily EKGs and a transthoracic echocardiogram (ultrasound of the heart). The doctors may also consider arteries examination to rule out blockages in blood vessels. If the patient is stable then a cardiac MRI can be done for deeper analysis. In severe cases, a biopsy from the heart muscle may be taken for immediate examination.

Treatment Options for Nonviral Myocarditis

The treatment of myocarditis, which is an inflammation of the heart muscle, can be focused on treating symptoms or addressing the underlying cause. When treating symptoms, doctors usually manage heart failure and irregular heart rhythms following current medical recommendations.

For patients experiencing severe symptoms, intensive care may be needed. This can include medical support to maintain heart function, the use of devices to assist heart function, or extracorporeal membrane oxygenation (ECMO) – oxygenation of blood outside the body – in severe cases. If the heart is not responding to treatment, a heart transplant may be considered. For patients whose heart is not functioning properly but who are not critically ill, drugs that regulate blood pressure and heart rhythm, along with diuretics to rid the body of excess fluids, may be recommended, following current heart failure guidelines.

Myocarditis patients may experience abnormal heart rhythms that can rapidly progress into life-threatening situations. That’s why there may be a need for temporary or permanent devices to manage heart rhythms. Doctors may use medication to treat irregular heart rhythms or, in some cases, a device may be implanted to monitor and correct heart rhythms. This device can act as a stop-gap treatment until the heart recovers or a heart transplant is performed. They can also use a method called radio-frequency catheter ablation to manage recurrent irregular heart rhythms. A wearable device is another option to help control temporary arrhythmias. In certain cases, a defibrillator may be needed if heart function is significantly reduced.

In terms of addressing the underlying cause of myocarditis, appropriate antibiotic therapy is used for infectious causes. If the myocarditis was caused by a reaction to drugs or toxins, stopping the use of the agent usually resolves the symptoms. For cases of autoimmune myocarditis, where the body’s immune system attacks its own tissues, treatment can vary from patient to patient. Typically, these treatments suppress the immune response. Doctors may also administer a type of therapy called intravenous immunoglobulins (IVIG), where antibodies from healthy people are given to the patient, to those who don’t respond to typical treatments.

Non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided as they’ve shown no benefit and could potentially worsen the condition. Patients should also avoid physical activity due to a higher risk for sudden cardiac death.

What else can Nonviral Myocarditis be?

Myocarditis, an inflammation of the heart muscle, can be tricky to diagnose because it often looks like other health issues. Here are some conditions that doctors need to rule out when diagnosing myocarditis:

• Acute coronary syndrome (heart attack)
• Valvular disease (problems with the heart valves)
• Infective endocarditis (infection in the heart’s interior lining)
• Cardiac tamponade (pressure on the heart caused by fluid accumulation)
• Pericarditis (inflammation of the sac surrounding the heart)
• Arrhythmogenic right ventricular cardiomyopathy (a rare type of heart disease that can cause heart failure)
• Hypertrophic cardiomyopathy (thickened heart muscle)
• Cardiac amyloidosis (abnormal proteins in the heart tissue)
• Ischemic cardiomyopathy (heart muscle disease caused by narrowed arteries)
• Coronary artery vasospasm (a temporary tightening of the muscles within the arteries of your heart)
• Peripartum cardiomyopathy (heart failure towards the end of pregnancy or in the months after delivery)
• Ventricular tachycardia (a fast heart rate)
• Interstitial pulmonary fibrosis (scarring of the lungs)
• High altitude-induced pulmonary edema (fluid in the lungs caused by high altitudes)

Because myocarditis can mirror these conditions, doctors need to be very thorough in their examination and testing to ensure an accurate diagnosis.

What to expect with Nonviral Myocarditis

The outcome of myocarditis, an inflammation of the heart muscle, can vary depending on the specific type and cause of the condition. For example, if myocarditis is caused by a virus, it usually gets better on its own over time. More severe cases, known as fulminant myocarditis, can initially require intense treatment but usually get better in the end. However, if the virus continues to be active in the body, as detected by a test called PCR, the condition may not improve as well.

At the same time, a type of myocarditis known as acute lymphocytic myocarditis, which includes causes related to the body’s immune response, normally has less favorable outcomes compared to fulminant myocarditis. Another variant, giant cell myocarditis, tends to be associated with poor outcomes and is often connected with severe heart complications which can sometimes require heart transplant surgery. Even after a heart transplant, giant cell myocarditis can come back, but thankfully it usually responds well to treatment.

Eosinophilic myocarditis, another form of the condition, demonstrates variable outcomes. Some forms of this type which are induced by reactions to drugs, parasites, or an overactive immune response can improve with stopping the drug, taking anti-parasite medication, or with steroid therapy respectively. However, there’s an aggressive form of this condition called acute necrotizing eosinophilic myocarditis that is associated with higher death rates.

Certain factors like the presence of functional disturbances in both ventricles of the heart at the time of diagnosis, can predict a worse outcome for myocarditis. Dysfunction in the right ventricle of the heart is a particularly good predictor of poor outcomes. Furthermore, myocarditis can make existing heart conditions like cardiac amyloidosis and hypertrophic cardiomyopathy worse. Some studies have found that high levels of certain proteins, sFas and sFasL, present during the diagnosis, may indicate a higher risk of death.

Possible Complications When Diagnosed with Nonviral Myocarditis

The immediate complications after developing myocarditis (inflammation of the heart muscle) can be quite serious and include conditions such as cardiogenic shock (a condition where your heart can’t pump enough blood to meet your body’s needs), ventricular arrhythmias (abnormal heart rhythms), and even sudden cardiac death. If myocarditis does not resolve, it can become even worse, leading to conditions such as dilated cardiomyopathy (a disease of the heart muscle where it becomes stretched and thin), heart failure with reduced ability to pump blood (reduced ejection fraction), areas of weak and inactive heart muscle (focal hypokinesis), and ventricular aneurysms.

These heart muscle weaknesses may further lead to the formation of blood clots within the heart (intracardiac thrombi) causing further complications such as a stroke or heart attack. Up to 30% of patients with a proven myocarditis case may develop dilated cardiomyopathy. In some cases, a certain type of myocarditis called eosinophilic myocarditis may cause tough, fibrous tissue in the inner lining of the heart (endocardial fibrosis) leading to heart valve diseases.

Common Complications:

• Cardiogenic shock
• Ventricular arrhythmias
• Sudden cardiac death
• Progression to dilated cardiomyopathy
• Heart failure with reduced ejection fraction
• Focal hypokinesis
• Ventricular aneurysms
• Intracardiac thrombi that can cause stroke or heart attack
• Endocardial fibrosis leading to valvular diseases (typically in eosinophilic myocarditis)

Preventing Nonviral Myocarditis

Patients should be informed about the progression of their disease and what they can expect in the future. These patients have a higher chance of sudden death, therefore they should not take part in physical activities until the disease has completely cleared up (acute myocarditis), or until 6 months after their symptoms started. This advice is the same for everyone, regardless of whether they are athletes or not, their age, gender, how severe their disease is, or what treatment they are receiving. Athletes in particular should have a health check-up before they can begin playing competitive sports again, and they should continue to have these health check-ups every 6 months.