Although most cases of myocarditis (ie, inflammation of the heart muscles) have a viral etiology, many nonviral causes are also recognized,  and indeed, a number of common infectious illnesses of childhood may be associated with myocarditis in pediatric patients.  In addition, myocarditis can be a manifestation of hypersensitivity or can be secondary to a drug reaction. The severity of myocarditis varies from relatively asymptomatic disease to fulminant, severe disease with a rapid, progressive, downhill course. (See Etiology, Clinical, and Workup.)
Epidemiologically, myocarditis appears to be sporadic. The most common cause is thought to be coxsackievirus B, but the condition can also arise from bacterial, parasitic, fungal, toxic, and drug-related causes. (See Treatment and Medications.)
With clinically significant myocarditis present (regardless of cause), myocardial function is reduced in the presence of and as a result of extensive interstitial inflammation and/or injury. Systolic function of the left ventricle with concomitant dilatation of the heart and cardiac enlargement occurs. The overall result is an attendant reduction in cardiac output.
In addition, progressive congestive heart failure (CHF) with increased left ventricular end-diastolic volume and pressure results in an increase in left atrial pressure, which is transmitted into the pulmonary venous system. This may also result in pulmonary edema secondary to increased pulmonary arterial hydrostatic forces.
Finally, during the healing stages of myocarditis, fibroblasts may replace existing myocytes with resultant scar formation. Chronic CHF may result. An autopsy sample that shows scarring in the ventricles is seen below.
Causes of myocarditis, including nonviral causes, include the following:
Rickettsial - Rickettsia rickettsii, R tsutsugamushi
Bacterial organisms/infections - Klebsiella species, Leptospira species, Salmonella species, Brucella species, Legionella pneumophila, meningococci, clostridia, streptococci (scarlet fever), staphylococci, pneumococci, tuberculosis, syphilis, tetanus
Protozoa and protozoal infections - Trypanosoma cruzi (Chagas disease), toxoplasmosis, amebiasis
Other parasites and parasitic infections - Toxocara canis, schistosomiasis, heterophyiasis, cysticercosis, echinococci, visceral larva migrans
Fungal infections - Actinomycosis, coccidioidomycosis, histoplasmosis, candidiasis
Toxic etiology - Scorpion envenomations, diphtheria
Drugs - Cyclophosphamide, phenylbutazone, acetazolamide, amphotericin B, indomethacin, tetracycline, isoniazid, methyldopa, phenytoin, penicillin, sulfonamides
Hypersensitivity/autoimmune - Rheumatoid arthritis, rheumatic fever, ulcerative colitis, systemic lupus erythematosus (SLE), Kawasaki syndrome, dermatomyositis
Other - Sarcoidosis, scleroderma, idiopathic, giant cell, peripartum myocarditis
Although rare, some of the more common causes of nonviral myocarditis are discussed below in greater detail.
Chagas disease is caused by a protozoal infestation with T cruzi. It is very uncommon in North America but can affect as much as half the population in endemic areas, such as South America. Acute infection can cause protracted heart failure and death. Endomyocardial biopsy and microscopic examination typically demonstrate organisms, neutrophils, lymphocytes, macrophages, and eosinophils.
Giant cell myocarditis
In giant cell myocarditis, giant cells are present in the myocardium with or without granulomas. This type may be evidenced with tuberculosis, syphilis, rheumatoid arthritis, or rheumatic heart disease, or with fungal or parasitic infections. The characteristic cell is probably histiocytic in origin and is usually found in nonviral myocarditis. Similar cells have been noted in patients with myocarditis associated with drugs such as phenylbutazone. This type of myocarditis may not be specific but, rather, may represent a final common pathologic pathway.
Systemic lupus erythematosus
Patients with SLE may have myocardial fibrinoid lesions in the connective tissue, with an accompanying cellular reaction. This reaction may also affect the valves, most notably the mitral and aortic valves.  Although the predominant cardiac manifestation of SLE is pericarditis, myocardial involvement with CHF can occur. The treatment of choice is corticosteroids.
Kawasaki disease may include myocardial involvement, which usually occurs in the acute phase; it can occur independent of any coronary artery involvement and usually resolves completely. In some cases, however, the diffuse myocarditis may be severe and may lead to heart failure and death. Although the pathophysiologic mechanisms that occur in Kawasaki disease are not known, a generalized autoimmune disorder is suspected.
Dermatomyositis, a multisystem (probably autoimmune) disease, is characterized by diffuse, nonsuppurative inflammation of skeletal muscle and skin. However, cardiac involvement, including a loss of striations, fragmentation, and vascularization of muscle fibers, has been reported. The interstitium may also show a variable amount of edema. Tachycardia and conduction abnormalities are described, but heart failure is uncommon. Long-term therapy with prednisone is beneficial in most cases. Children have a good long-term prognosis, as most recover, and medication may be discontinued in 1-2 years.
Myocarditis is not common in children. A multi-institutional analysis of 35 academic children’s hospitals belonging to the Pediatric Health Information System noted 216 patients with myocarditis in 2005. 
The actual frequency of the disease may be higher, however, because clinicians do not recognize all cases of myocarditis. Several autopsy series found a much higher incidence of myocarditis than has been noted in clinical practice, although the clinical relevance of this is not clear.
Evidence suggests that a percentage of patients undergoing endomyocardial biopsy for unexplained ventricular arrhythmias or ventricular dysfunction have findings suggestive of myocarditis.
The prognosis for myocarditis varies and depends on age, etiology, and severity at the time of presentation. The mortality rate in newborn infants is high (75%) in some reports. Older infants and children have a better prognosis, with mortality rates ranging from 10-25% in clinically recognizable cases. Some studies have suggested complete recovery in as many as 50% of the cases.
Perhaps as many as 25-35% of patients who present with clinical myocarditis may be left with a significant chronic dilated cardiomyopathy and may require cardiac transplantation.
The cause of myocarditis certainly may affect prognosis. For example, patients with conduction abnormalities or arrhythmias secondary to diphtheric myocarditis tend to have a poor prognosis.
In a retrospective analysis of clinical and magnetic resonance imaging (MRI) prognostic factors from 58 pediatric myocarditis cases (nonviral and viral) over a 5-year period, Sachdeva et al found that risk factors for poor outcomes included an ejection fraction below 30% on presentation, peak brain natriuretic peptide levels above 10,000 ng/L, and late enhancements on cardiac MRI. 
What would you like to print?