myocarditis myocarditis myocarditis, also known as inflammatory cardiomyopathy, is an acquired cardiomyopathy due to inflammation of the heart muscle. 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. myocarditisother namesinflammatory cardiomyopathy (infectious)a microscope image of myocarditis at autopsy in a person with acute onset of heart failurespecialtyinfectious disease, cardiologysymptomsshortness of breath, chest pain, decreased ability to exercise, irregular heartbeatcomplicationsheart failure due to dilated cardiomyopathy, cardiac arrestdurationhours to monthscausesusually viral infection, also bacterial infections, certain medications, autoimmune disordersdiagnostic methodelectrocardiogram, blood troponin, heart mri, heart biopsytreatmentmedications, implantable cardiac defibrillator, heart transplantmedicationace inhibitors, beta blockers, diuretics, corticosteroids, intravenous immunoglobulinprognosisvariablefrequency2.5 million with cardiomyopathy (2015)deaths354,000 with cardiomyopathy (2015) 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 (ecg), 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 (ivig) 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: symptoms notes signs notes chest pain often described as sharp or stabbing in nature fever especially when infectious, e.g., from parvovirus b19 shortness of breath worse when lying down or in a prone position dull heart sounds muffling occurs with inflammation, especially with pericarditis palpitations feeling like one's heart is beating forcefully abnormal heart rhythm determined using an electrocardiogram dizziness or fainting can reflect inadequate blood flow to the brain damage to heart cells seen 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. these different etiologies are detailed below. recent study from israel conludes that natural covid-19-infection is not associated with myocarditis. 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 genetic information such as coxsackie viruses (especially coxsackie b3 and b5). 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. viral: adenovirus, parvovirus b19, coxsackie virus, rubella virus, polio virus, epstein-barr virus, hepatitis c virus, influenza virus and severe acute respiratory syndrome coronavirus 2 (sars‑cov‑2, causing covid-19) protozoan: trypanosoma cruzi and toxoplasma gondii (causing chagas disease and toxoplasmosis, respectively) bacterial: brucella, corynebacterium diphtheriae, neisseria gonorrhoeae, haemophilus influenzae, actinomyces, tropheryma whipplei, vibrio cholerae, borrelia burgdorferi, leptospira, rickettsia, mycoplasma pneumoniae fungal: aspergillus parasitic: ascaris, echinococcus granulosus, paragonimus westermani, schistosoma, taenia solium, trichinella spiralis, visceral larva migrans, wuchereria bancrofti immune conditions allergic reaction (e.g., to acetazolamide or amitriptyline) kawasaki disease autoimmunity (scleroderma, lupus, sarcoidosis, and systemic vasculitides) toxic shock syndrome drug reactions and toxins anthracyclines and other forms of chemotherapy antipsychotics including clozapine alcohol stimulants such as mephedrone and cocaine arsenic carbon monoxide snake venom heavy metals (copper or iron) vaccination myocarditis and pericarditis can be a rare side effect of some vaccines like the smallpox vaccine. myocarditis can be a rare side-effect of the covid-19 mrna vaccines. the fda and european medicines agency estimates the risk of myocarditis after the covid-19 vaccine as 1 case per 100,000 of those who are vaccinated. the risk of myocarditis after covid-19 vaccination was observed to be highest in males between 16–29 years of age, and after receiving the second dose of the mrna covid-19 vaccine. for this high-risk group, incidence of myocarditis has been reported to be more than 1 case per 10,000. physical injuries electric shock hyperpyrexia, and radiation mechanism 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 (viruses with a high affinity for the heart muscle) 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 (myocytes) 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 (car) and decay-accelerating factor (daf). 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 (cbvs) 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 (heart muscle cell) 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 (heart muscle) 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 (and frequently other organs). diagnosis diffuse st elevation in a young male due to myocarditis and pericarditis lymphocytic myocarditis (white arrow points to a lymphocyte), commonly showing myocyte necrosis (black arrow), seen as hypereosinophilic cytoplasm with loss of striations. endomyocardial biopsy specimen with extensive eosinophilic infiltrate involving the endocardium and myocardium (hematoxylin and eosin stain) myocarditis refers to an underlying process that causes inflammation and injury of the heart. it does not refer to inflammation of the heart as a consequence of some other insult. many secondary causes, such as a heart attack, can lead to inflammation of the myocardium and therefore the diagnosis of myocarditis cannot be made by evidence of inflammation of the myocardium alone. myocardial inflammation can be suspected on the basis of elevated inflammatory markers including c-reactive protein (crp), erythrocyte sedimentation rate (esr), or an increased igm (serology) against viruses known to affect the myocardium. markers of myocardial damage (troponin or creatine kinase cardiac isoenzymes) are elevated. the crp and esr are sometimes elevated in myocarditis but they are not specific as they may be elevated due to many other causes. similarly, ck may be elevated in myocarditis but is also non-specific, as it may be elevated in myositis (skeletal muscle injury). high sensitivity troponin is usually elevated in myocarditis and this marker is very specific to myocardial (heart muscle) injury. myocardial inflammation may also be suspected based on ecg findings, but these findings are not specific to myocarditis. the ecg finding most commonly seen in myocarditis is sinus tachycardia with non-specific st or t wave changes. but other findings that may be seen in perimyocarditis (a combination of pericarditis and myocarditis) include pr segment depression, pr segment depression with associated st segment elevation, diffuse st segment elevation (in a pericarditis pattern). st segment elevation was seen in 62% of people with myocarditis. the presence of q waves, a widened qrs complex, prolongation of the qt interval, high degree av nodal blockade, and ventricular tachyarrhythmias are associated with a poor prognosis when seen on ecg in people with myocarditis. the gold standard is the biopsy of the myocardium, in general done in the setting of angiography. a small tissue sample of the endocardium and myocardium is taken and investigated. the cause of the myocarditis can be only identified by a biopsy. endomyocardial biopsy samples are assessed for histopathology (how the tissue looks like under the microscope): myocardial interstitium may show abundant edema and inflammatory infiltrate, rich in lymphocytes and macrophages. focal destruction of myocytes explains the myocardial pump failure. in addition samples may be