A large number of causes of myocarditis have been identified, but often a cause cannot be found. 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 is due to infection by the protozoan "Trypanosoma cruzi". Many of the causes listed below, particularly those involving protozoa, fungi, parasites, allergy, autoimmune disorders, and drugs are also causes of eosinophilic myocarditis.

The exact incidence of myocarditis is unknown. However, in series of routine autopsies, 1–9% of all patients had evidence of myocardial inflammation. In young adults, up to 20% of all cases of sudden death are due to myocarditis.

Among patients with HIV, myocarditis is the most common cardiac pathological finding at autopsy, with a prevalence of 50% or more.

HIV is a major cause of cardiomyopathy – in particular dilated cardiomyopathy. Dilated cardiomyopathy can be due to pericardial effusion or infective endocarditis, especially in intravenous drug users which are common in the HIV population. However, the most researched causes of cardiomyopathy are myocardial inflammation and infection caused by HIV-1. Toxoplasma gondii is the most common opportunistic infectious agent associated with myocarditis in AIDS. Coinfection with viruses (usually, coxsackievirus B3 and cytomegalovirus) seems to have an important affect in myocarditis. HIV-1 infection produces additional virus and cytokines such as TNF-α. This induces cardiomyocyte apoptosis. TNF-α causes a negative inotropic effect by interfering with the intracellular calcium ion concentrations. The intensity of the stains for TNF-α and iNOS of the myocardium was greater in patients with HIV associated cardiomyopathy, myocardial viral infection and was inversely correlated with CD4 count with antiretroviral therapy having no effect. Cardiac autoimmunity affects the pathogenesis of HIV-related heart disease as HIV-infected patients with dilated cardiomyopathy are more likely to have cardiac-specific autoantibodies than HIV-infected patients with healthy hearts and HIV-negative controls. Many patients with HIV have nutritional deficiencies which have been linked to left ventricular dysfunction. HIV-infected patients with encephalopathy are more likely to die of congestive heart failure than are those without encephalopathy. HAART has reduced the incidence of myocarditis thus reducing the prevalence of HIV-associated cardiomyopathy. Intravenous immunoglobulins (IVIGs) can also help patients with HIV-associated myocarditis.

The prognosis of eosinophilic myocarditis is anywhere from rapidly fatal to extremely chronic or non-fatal. Progression at a moderate rate over many months to years is the most common prognosis. In addition to the speed of inflammation-based heart muscle injury, the prognosis of eosinophilc myocarditis may be dominated by that of its underlying cause. For example, an underlying malignant cause for the eosinophilia may be survival-limiting.

Intensive cardiac care and immunosuppressives including corticosteroids are helpful in the acute stage of the disease. Chronic phase has, mainly debility control and supportive care options.

Signs and symptoms such as malabsorption and diarrhoea respectively, may occur with HIV infection causing many HIV patients to have nutritional deficiencies and altered levels of vitamin B12, carnitine, and growth and thyroid hormones - all have been associated with left ventricular dysfunction. A lowered BMI in HIV patients is also associated with cardiomyopathy.

Carditis is the inflammation of the heart or its surroundings. The plural of carditis is carditides.

It is usually studied and treated by specifying it as:

- Pericarditis is the inflammation of the pericardium

- Myocarditis is the inflammation of the heart muscle

- Endocarditis is the inflammation of the endocardium

- Pancarditis is the inflammation of the entire heart: the epicardium, the myocardium and the endocardium

- Reflux carditis refers to a possible outcome of esophageal reflux (also known as GERD), and involves inflammation of the esophagus/stomach mucosa

Autoimmune heart diseases are the effects of the body's own immune defense system mistaking cardiac antigens as foreign and attacking them leading to inflammation of the heart as a whole, or in parts. The commonest form of autoimmune heart disease is rheumatic heart disease or rheumatic fever.

Pericarditis may be caused by viral, bacterial, or fungal infection.

In the developed world viruses are believed to be the cause of about 85% of cases. In the developing world tuberculosis is a common cause but it is rare in the developed world.

Viral causes include coxsackievirus, herpesvirus, mumps virus, and HIV among others.

Pneumococcus or tuberculous pericarditis are the most common bacterial forms. Anaerobic bacteria can also be a rare cause. Fungal pericarditis is usually due to histoplasmosis, or in immunocompromised hosts Aspergillus, Candida, and Coccidioides. The most common cause of pericarditis worldwide is infectious pericarditis with tuberculosis.

Idiopathic giant-cell myocarditis (IGCM) is a cardiovascular disease of the muscle of the heart (myocardium).

The condition is rare; however, it is often fatal and there is no proven cure because of the unknown nature of the disorder.

IGCM frequently leads to death with a high rate of about 70% in first year. A patient with IGCM typically presents with symptoms of heart failure, although some may present initially with ventricular arrhythmia or heart block. Median age from the time the disease is diagnosed to the time of death is approximately 6 months. 90% of patients are either deceased by the end of 1 year or have received a heart transplant. Diagnosis is made by endomyocardial biopsy during heart catheterization. Biopsy shows multinucleated giant cells and thus the name. While previously cases universally required heart transplantation, recent studies show that two thirds of patients can survive past one year with high doses of immunosuppressants such as prednisone and cyclosporine. The transplanted heart has a high chance of disease recurrence. Compared to lymphocytic (presumed viral) myocarditis, giant cell myocarditis is much more severe with much more rapid progression.

It is suggested to be caused by T-lymphocytes.

About 30% of people with viral pericarditis or pericarditis of an unknown cause have one or several recurrent episodes.

Myopericarditis is a combination of both myocarditis and pericarditis appearing in a single individual, namely inflammation of both the pericardium and the heart muscle. It can involve the presence of fluid in the heart. Myopericarditis refers primarily to a pericarditis with lesser myocarditis, as opposed to a perimyocarditis, though the two terms are often used interchangeably. Both will be reflected on an ECG. Myo-pericarditis usually involves inflammation of the pericardium, or the sac covering the heart.

The ACAM2000 smallpox vaccine has been known to cause myopericarditis in some people.

There are many causes of eosinophilia that may underlie eosinophilic myocarditis. These causes are classified as primary (i.e. a defect intrinsic to the eosinophil cell line), secondary (induced by an underlying disorder that stimulates the proliferation and activation of eosinophils), or idiopathic (i.e. unknown cause). Non-idiopathic causes of the disorder are sub-classified into various forms of allergic, autoimmune, infectious, or malignant diseases and hypersensitivity reactions to drugs, vaccines, or transplanted hearts. While virtually any cause for the elevation and activation of blood eosinophils must be considered as a potential cause for eosinophilic myocarditis, the follow list gives the principal types of eosinophilia known or thought to underlie the disorder.

Primary conditions that may lead to eosinophilic myocarditis are:

- Clonal hypereosinophilia.

- Chronic eosinophilic leukemia.

- The idiopathic hypereosinophilic syndrome.

Secondary conditions that may lead to eosinophilic myocarditis are:

- Infections agents:

- Parasitic worms: various "Ascaris, Strongyloides, Schistosoma, filaria, Trematoda", and "Nematode" species. Parasitic infestations often cause significant heart valve disease along with myocarditis and the disorder in this setting is sometimes termed Tropical endomyocardial fibrosis. While commonly considered to be due to the cited parasites, this particular form of eosinophilic myocarditis may more often develop in individuals with other disorders, e.g. malnutrition, dietary toxins, and genetic predisposition, in addition to or place of round worm infestation.

- Infections by protozoa: various "Toxoplasma gondii, Trypanosoma cruzi, trichinella spiralis, Entamoeba", and "Echinococcus" species.

- Viruses: While some viral infections (e.g. HIV) have been considered causes of eosinophilic endocarditis, a study of 20 patients concluded that viral myocarditis lacks the characteristic of eosinophil-induced damage in hearts taken during cardiac transplantation.

- Allergic and autoimmune diseases such as severe asthma, rhinitis, or urticarial, chronic sinusitis, aspirin-induced asthma, allergic bronchopulmonary aspergillosis, chronic eosinophilic pneumonia, Kimura's disease, polyarteritis nodosa, eosinophilic granulomatosis with polyangiitis (i.e. Churg-Strauss syndrome), and rejection of transplanted hearts.

- Malignancies and/or premalignant hematologic conditions not due to a primary disorder in eosinophils such as Gleich's syndrome, Lymphocyte-variant hypereosinophilia Hodgkin disease, certain T-cell lymphomas, acute myeloid leukemia, the myelodysplastic syndromes, systemic mastocytosis, chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, myelofibrosis, chronic myelomonocytic leukemia, and T-lymphoblastic leukemia/lymphoma-associated or myelodysplastic–myeloproliferative syndrome-associated eosinophilias; IgG4-related disease and Angiolymphoid hyperplasia with eosinophilia as well as non-hematologic cancers such as solid tumors of the lung, gastrointestinal tract, and genitourinary tract.

- Hypersensitivity reactions to agents include:

- Antibiotics/anti-viral agents: various penicillins (e.g. penicillin, ampicillin), cephalosporins (e.g. cephalosporin), tetracyclins (e.g. tetracycline), sulfonamides (e.g. sulfadiazine, sulfafurazole), sulfonylureas, antituburcular drugs (e.g. isoniazid, 4-aminosalicylic acid), linezolid, amphotericin B, chloramphenicol, streptomycin, dapsone, nitrofurantoin, metronidazole, nevirapine, efavirenz, abacavir, nevirapine.

- Anticonvulsants/Antipsychotics/antidepressants: phenindione, phenytoin, phenobarbital, lamotrigine, lamotrigine, clozapine, valproic acid, carbamazepine, desipramine, fluoxetine, amitriptyline, olanzapine.

- Anti-inflammatory agents: ibuprofen, indomethacin, phenylbutazone, oxyphenbutazone, acetazolamide, piroxicam, diclofenac.

- Diuretics: hydrochlorothiazide, spironolactone, chlortalidone.

- ACE inhibitors: captopril, enalapril.

- Other drugs: digoxin, ranitidine, lenalidomide, methyldopa, interleukin 2, dobutamine, acetazolamide.

- Contaminants: Unidentified contaminants inrapeseed oil cause the toxic oil syndrome and in commercial batches of the amino acid, L-tryptophan, cause the eosinophilia–myalgia syndrome.

- Vaccinations: Tetanus toxoid, smallpox, and diphtheria/pertussis/tetanus vaccinations.

Although in many cases no cause is apparent, dilated cardiomyopathy is probably the result of damage to the myocardium produced by a variety of toxic, metabolic, or infectious agents. It may be due to fibrous change of the myocardium from a previous myocardial infarction. Or, it may be the late sequelae of acute viral myocarditis, such as with Coxsackie B virus and other enteroviruses possibly mediated through an immunologic mechanism.

Other causes include:

- Chagas disease, due to "Trypanosoma cruzi". This is the most common infectious cause of dilated cardiomyopathy in Latin America

- Pregnancy. Dilated cardiomyopathy occurs late in gestation or several weeks to months postpartum as a peripartum cardiomyopathy. It is reversible in half of cases.

- Alcohol abuse (alcoholic cardiomyopathy)

- Nonalcoholic toxic insults include administration of certain chemotherapeutic agents, in particular doxorubicin (Adriamycin), and cobalt.

- Thyroid disease

- Inflammatory diseases such as sarcoidosis and connective tissue diseases

- Tachycardia-induced cardiomyopathy

- Muscular dystrophy

- Tuberculosis - 1 to 2% of TB cases.

- Autoimmune mechanisms

Recent studies have shown that those subjects with an extremely high occurrence (several thousands a day) of premature ventricular contractions (extrasystole) can develop dilated cardiomyopathy. In these cases, if the extrasystole are reduced or removed (for example, via ablation therapy) the cardiomyopathy usually regresses.

Syphilitic aortitis (SA) is inflammation of the aorta associated with the tertiary stage of syphilis infection. SA begins as inflammation of the outermost layer of the blood vessel, including the blood vessels that supply the aorta itself with blood, the vasa vasorum. As SA worsens, the vasa vasorum undergo hyperplastic thickening of their walls thereby restricting blood flow and causing ischemia of the outer two-thirds of the aortic wall. Starved for oxygen and nutrients, elastic fibers become patchy and smooth muscle cells die. If the disease progresses, syphilitic aortitis leads to an aortic aneurysm. Unlike atherosclerosis, which typically manifests in older people, syphilitic aortitis typically affects those under the age of 50. It has become rare in the developed world with the advent of penicillin treatments after World War II.

Although the disease is more common in African-Americans than in Caucasians, it may occur in any patient population.

Molecular mechanisms underlying the coxsackievirus induced dilated cardiomyopathy is largely unknown. However, both direct viral cytotoxicity and secondary host immune responses may lead to the eventual pathogenesis.

Cardiomyopathies are either confined to the heart or are part of a generalized systemic disorder, both often leading to cardiovascular death or progressive heart failure-related disability. Other diseases that cause heart muscle dysfunction are excluded, such as coronary artery disease, hypertension, or abnormalities of the heart valves. Often, the underlying cause remains unknown, but in many cases the cause may identifiable. Alcoholism, for example, has been identified as a cause of dilated cardiomyopathy, as has drug toxicity, and certain infections (including Hepatitis C). On the other hand, molecular biology and genetics have given rise to the recognition of various genetic causes. For example, mutations in the cardiac desmosomal genes as well as in the DES gene may cause arrhythmogenic right ventricular cardiomyopathy (ARVC).

A more clinical categorization of cardiomyopathy as 'hypertrophied', 'dilated', or 'restrictive', has become difficult to maintain because some of the conditions could fulfill more than one of those three categories at any particular stage of their development. The current American Heart Association definition divides cardiomyopathies into primary, which affect the heart alone, and secondary, which are the result of illness affecting other parts of the body. These categories are further broken down into subgroups which incorporate new genetic and molecular biology knowledge.

With early treatment, rapid recovery from the acute symptoms can be expected, and the risk of coronary artery aneurysms is greatly reduced. Untreated, the acute symptoms of Kawasaki disease are self-limited ("i.e." the patient will recover eventually), but the risk of coronary artery involvement is much greater. Overall, about 2% of patients die from complications of coronary vasculitis. Patients who have had Kawasaki disease should have an echocardiogram initially every few weeks, and then every one or two years to screen for progression of cardiac involvement.

Laboratory evidence of increased inflammation combined with demographic features (male sex, age less than six months or greater than eight years) and incomplete response to IVIG therapy create a profile of a high-risk patient with Kawasaki disease. The likelihood that an aneurysm will resolve appears to be determined in large measure by its initial size, in which the smaller aneurysms have a greater likelihood of regression. Other factors are positively associated with the regression of aneurysms, including being younger than a year old at the onset of Kawasaki disease, fusiform rather than saccular aneurysm morphology, and an aneurysm location in a distal coronary segment. The highest rate of progression to stenosis occurs among those who develop large aneurysms. The worst prognosis occurs in children with giant aneurysms. This severe outcome may require further treatment such as percutaneous transluminal angioplasty, coronary artery stenting, bypass grafting, and even cardiac transplantation.

A relapse of symptoms may occur soon after initial treatment with IVIG. This usually requires rehospitalization and retreatment. Treatment with IVIG can cause allergic and nonallergic acute reactions, aseptic meningitis, fluid overload and, rarely, other serious reactions. Overall, life-threatening complications resulting from therapy for Kawasaki disease are exceedingly rare, especially compared with the risk of nontreatment. Also, evidence indicates Kawasaki disease produces altered lipid metabolism that persists beyond the clinical resolution of the disease.

Kawasaki disease affects boys more than girls, with people of Asian ethnicity, particularly Japanese and Korean people, most susceptible, as well as people of Afro-Caribbean ethnicity. The disease was rare in Caucasians until the last few decades, and incidence rates fluctuate from country to country.

Currently, Kawasaki disease is the most commonly diagnosed pediatric vasculitis in the world. By far, the highest incidence of Kawasaki disease occurs in Japan, with the most recent study placing the attack rate at 218.6 per 100,000 children <5 years of age (about one in 450 children). At this present attack rate, more than one in 150 children in Japan will develop Kawasaki disease during their lifetimes.

However, its incidence in the United States is increasing. Kawasaki disease is predominantly a disease of young children, with 80% of patients younger than five years of age. About 2,000-4,000 cases are identified in the U.S. each year (9 to 19 per 100,000 children younger than 5 years of age).

In the United Kingdom, estimates of incidence rate vary because of the rarity of Kawasaki disease. However, it is believed to affect fewer than one in every 25,000 people. Incidence of the disease doubled from 1991 to 2000, however, with four cases per 100,000 children in 1991 compared with a rise of eight cases per 100,000 in 2000.

In the continental United States, Kawasaki Disease is more common during the winter and early spring, boys with the disease outnumber girls by ≈1.5–1.7:1, and 76% of affected children are <5 years of age.

Inflammatory involvement of tertiary syphilis begins at the adventitia of the aortic arch which progressively causes obliterative endarteritis of the vasa vasorum. This leads to narrowing of the lumen of the vasa vasorum, causing ischemic injury of the medial aortic arch and then finally loss of elastic support and dilation of the vessel. Dissection of the aortic arch is rare due to medial scarring. As a result of this advanced disease process, standard methods of angiography/angioplasty may be impossible for those with suspected coronary heart disease. However, these patients may be candidates for diagnostic CT as a less invasive modality. This disorder is also known eponymously as Heller-Döhle syndrome.

Coxsackievirus shows a cardiac tropism partly due to the high expression of coxsackievirus and adenoviris receptors (CAR) in cardiomyocytes. Coxsackievirus B genome is approximately 7.4 Kb and translated as a polycistronic polyprotein. Upon translation, the polyprotein is cleaved by two essential viral proteases, 2A and 3C. The viral protease 2A cleaves the proteins in a sequence specific manner. These viral proteases can also act on host proteins exerting negative effects on the residing cell. Enteroviral protease 2A can cleave the cytoskeletal dystrophin protein in cardiomyocytes disrupting the dystrophin glycoprotein (DCG) complex. The cleavage site of dystrophin by protease 2A occurs in the hinge 3 region of the protein resulting a disruption of DCG complex and loss of sarcolemma integrity and increasing myocyte permeability. This eventually results in similar cardiac deformities observed in dilated cardiomyopathy caused by hereditary defects in dystrophin in DMD patients. Additionally, dystrophin deficiency has been shown to increase the severity in dilated cardiomyopathy in a mouse model for DMD. The increased susceptibility of dystrophin deficient heart to coxsackievirus-induced dilated cardiomyopathy is attributed to more efficient release of the virus from infected cells resulting an increased in viral-mediated cytopathic effects.

Viral induced dilated cardiomyopathy can be characterized using different methods. A recent study showed in coxsackievirus infected heart proteome, increased levels of fibrotic extracellular matrix proteins and reduced amounts of energy-producing enzymes can be observed suggesting they could be characteristic in enteroviral cardiomyopathy.

There are notable differences between the hereditary dilated cardiomyopathy in DMD and acute coxsackieviral-mediated cardiomyopathy.

1. The amount of virally infected cardiomyocytes varies in different stages of the disease. In a mouse model, at the acute stage (7 days after infection with coxsackievirus B3) approximately 10% of the myocytes are infected and could affect overall cardiac function. In chronic murine infection, the percentage of infected cardiomyocytes are much lower.

2. Unlike in the DMD, in coxsackievirus induced cardiomyopathy, acute cleavage of dystrophin in cardiomyocytes is unlikely to induce any prompt compensatory mechanism since host cell translation mechanism is defective in the infected cells.

Treatment may include suggestion of lifestyle changes to better manage the condition. Treatment depends on the type of cardiomyopathy and condition of disease, but may include medication (conservative treatment) or iatrogenic/implanted pacemakers for slow heart rates, defibrillators for those prone to fatal heart rhythms, ventricular assist devices (VADs) for severe heart failure, or ablation for recurring dysrhythmias that cannot be eliminated by medication or mechanical cardioversion. The goal of treatment is often symptom relief, and some patients may eventually require a heart transplant.

Viral cardiomyopathy occurs when viral infections cause myocarditis with a resulting thickening of the myocardium and dilation of the ventricles. These viruses include Coxsackie B and adenovirus, echoviruses, influenza H1N1, Epstein-Barr virus, rubella (German measles virus), varicella (chickenpox virus), mumps, measles, parvoviruses, yellow fever, dengue fever, polio, rabies and the viruses that cause hepatitis A and C.

A review cites references to 31 different diseases and other stresses associated with the EFE reaction. These include infections, cardiomyopathies, immunologic diseases, congenital malformations, even electrocution by lightning strike. EFE has two distinct genetic forms, each having a different mode of inheritance. An x-linked recessive form, and an autosomal recessive form have both been observed.