Myocarditis


Myocarditis is inflammation of the cardiac muscle. Myocarditis can progress to inflammatory cardiomyopathy when there is associated ventricular remodeling and cardiac dysfunction due to chronic inflammation. Symptoms can include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat. The duration of problems can vary from hours to months. Complications may include heart failure, due to dilated cardiomyopathy or cardiac arrest.
Myocarditis is most often due to a viral infection. Other causes include bacterial infections, certain medications, toxins and autoimmune disorders. A diagnosis may be supported by an electrocardiogram, increased troponin, heart MRI, and occasionally a heart biopsy. An ultrasound of the heart is important to rule out other potential causes, such as heart valve problems.
Treatment depends on both the severity and the cause. Medications such as ACE inhibitors, beta blockers, and diuretics are often used. A period of no exercise is typically recommended during recovery. Corticosteroids or intravenous immunoglobulin may be useful in certain cases. In severe cases, an implantable cardiac defibrillator or heart transplant may be recommended.
In 2013, about 1.5 million cases of acute myocarditis occurred. While people of all ages are affected, the young are most often affected. It is slightly more common in males than females. Most cases are mild. In 2015, cardiomyopathy, including myocarditis, resulted in 354,000 deaths, up from 294,000 in 1990. The initial descriptions of the condition are from the mid-1800s.

Signs and symptoms

The signs and symptoms associated with myocarditis are varied, and relate either to the actual inflammation of the myocardium or to the weakness and dysfunction of the heart muscle that is secondary to the inflammation. While myocarditis may develop over periods ranging from hours to months, patients typically present with signs and symptoms that resemble heart failure, including the following:
SymptomsNotesSignsNotes
Chest painOften described as sharp or stabbing in natureFeverEspecially when infectious, e.g., from parvovirus B19
Shortness of breathWorse when lying down or in a prone positionDull heart soundsMuffling occurs with inflammation, especially with pericarditis
PalpitationsFeeling like one's heart is beating forcefullyAbnormal heart rhythmDetermined using an electrocardiogram
Dizziness or faintingCan reflect inadequate blood flow to the brainDamage to heart cellsSeen as elevated troponin and inflammation on imaging

Since myocarditis is often due to a viral illness, many patients experience symptoms consistent with a recent viral infection including a fever, rash, loss of appetite, abdominal pain, vomiting, diarrhea, joint pains, and easily becoming tired. Additionally, myocarditis is often associated with pericarditis, and many people with myocarditis present with signs and symptoms that suggest myocarditis and pericarditis at the same time.
Children primarily present with the aforementioned symptoms associated with a viral infection. Later stages of the illness can involve the respiratory system and lead to increased work of breathing. These are often mistaken for asthma.
Myocarditis can be distinguished as either fulminant or acute based on the severity of symptoms on presentation, as well as the time course over which symptoms develop and persist. This categorization can help predict the treatment, outcomes, and complications of myocarditis.
Fulminant myocarditis is defined as sudden and severe myocarditis that is associated with signs and symptoms of heart failure while at rest. More specifically, fulminant myocarditis is characterized by a distinct, rapid onset of severe heart failure symptoms, such as shortness of breath and chest pain, that develop over the course of hours to days. Additionally, treatment requires the use of medications or mechanical devices to improve heart function.
Acute non-fulminant myocarditis has a less distinct onset in contrast to fulminant myocarditis, and evolves over days to months. While the symptoms of acute myocarditis overlap with those of fulminant myocarditis, they do not typically occur at rest, and treatment does not require the use of mechanical circulatory support.

Causes

While many causes of myocarditis are known, there are many cases in which a causative agent cannot be identified. In Europe and North America, viruses are common culprits. Worldwide, however, the most common cause is Chagas disease, an illness endemic to Central and South America that results from infection with the protozoan Trypanosoma cruzi. Overall, myocarditis can be caused by infections, immune conditions, toxins, drug reactions, and physical injuries to the heart.

Infections

The most common causes of myocarditis are infectious organisms. Viral infections are the most common cause in developed countries, with a majority of cases being caused by those with single-stranded RNA genomes, such as Coxsackie viruses. Globally, Chagas disease is the leading cause of myocarditis, which results from infection with the protozoan Trypanosoma cruzi. Bacteria can also result in myocarditis, although it is rare in patients with normal heart function and without a preexisting immunodeficiency. A list of the most relevant infectious organisms is below.
Most forms of myocarditis involve the infiltration of heart tissues by one or two types of pro-inflammatory blood cells, lymphocytes and macrophages plus two respective descendants of these cells, NK cells and macrophages. Eosinophilic myocarditis is a subtype of myocarditis in which cardiac tissue is infiltrated by another type of pro-inflammatory blood cell, the eosinophil. Eosinophilic myocarditis is further distinguished from non-eosinophilic myocarditis by having a different set of causes and recommended treatments.
The pathophysiology of viral myocarditis is not well understood, but it is believed to involve cardiotropic viruses gaining entry to cardiac muscle cells, usually via binding to a transmembrane receptor. Over approximately the next 1–7 days the virus replicates and causes inflammation leadings to necrosis and apoptosis of cardiac muscle cells and activation of the innate immune system. Over the next 1–4 weeks, viral replication continues with subsequent activation of the acquired immune system leading to T cell infiltration and the formation of antibodies, including possibly auto-antibodies. Over the next few months to years, this process either resolves and concludes with viral clearance or it may progress to cause permanent heart damage such as dilated cardiomyopathy, ventricular dysfunction or other cardiomyopathies. Coxsackie B, specifically B3 and B5, has been found to interact with coxsackievirus-adenovirus receptor and decay-accelerating factor. However, other proteins have also been identified that allow Coxsackieviruses to bind to cardiac cells. The natural function of CAR and mechanism that the Coxsackievirus uses to infect the cardiac muscle is still unknown. The mechanism by which coxsackie B viruses trigger inflammation is believed to be through the recognition of CBV virions by Toll-like receptors.
The binding of many types of coronaviruses, including the SARS-CoV-2 virus, through ACE2 receptors present in heart muscle may be responsible for direct viral injury leading to myocarditis. In a study done during the 2002-2004 SARS outbreak, SARS viral RNA was detected in the autopsy of heart specimens in 35% of the patients in the Toronto, Canada area who had died due to SARS. It was also observed that an already diseased heart has increased expression of ACE2 receptor contrasted to healthy individuals which may lead to greater viral infiltration in the heart muscle. Hyperactive immune responses in COVID-19 patients may lead to the initiation of the cytokine storm. This excess release of cytokines may lead to myocardial injury. In addition to direct cardiac myocyte damage due to SARS-CoV-2 viral infiltration and inflammation, there are other suspected mechanisms that COVID-19 may indirectly cause myocarditis. During COVID-19, the other indirect mechanisms thought to contribute to myocarditis include: oxygen supply-demand mismatch to the heart muscle leading to myocardial injury; microvascular thrombi, or blood clots in the small blood vessels of the heart causing injury; the systemic hyperinflammatory state in Covid-19 leading to heart muscle injury; or the virus causing indirect damage to the heart by inducing auto-immune mediated damage to the heart muscle.