Excerpt from Myocarditis

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Background

Myocarditis is collection of diseases of infectious, toxic, and autoimmune etiologies characterized by inflammation of the heart. Subsequent myocardial destruction can lead to dilated cardiomyopathy.

Myocarditis is an elusive illness to study, diagnose, and treat because the clinical presentation may range from nearly asymptomatic to overt heart failure requiring transplantation; a myriad of causes exist, and it is occasionally the unrecognized culprit in cases of sudden death.

Pathophysiology

Myocarditis is defined as inflammatory changes in the heart muscle and is characterized by myocyte necrosis.

Animal models of viral myocarditis have lead to a much greater understanding of the pathophysiology of acute, severe myocarditis and correlate with the findings in susceptible patients who apparently uptake viral RNA and develop a cytotoxic necrosis and rapid (1-2 d) cell death without the appearance of the interstitial infiltrate usually associated with myocarditis.

Over 4-14 days, those cells that survive the initial insult, in response to macrophage activation and cytokine expression, develop the classic, histologically apparent infiltration of mononuclear cells. In this subacute viral-clearing phase, natural killer cells target myocardium expressing viral RNA and continue myocyte necrosis. Tumor necrosis factor is also involved in rapidly clearing virus, but its involvement results in the further recruitment of inflammatory cells, activates endothelial cells, and has negative inotropic effects. In the latter stages of the subacute process, cytotoxic T lymphocytes infiltrate the myocardium and direct lysis of cardiocytes, which present virus fragments via the histocompatibility complex on the surface of myocyte membrane. Neutralizing antiviral antibodies also develop to assist in the clearing of virus.

In the chronic phases, the deleterious effects of either inadequate or inappropriately abundant immune response can lead to the unfortunate long-term sequelae of dilated cardiomyopathy and heart failure. In animal models of insufficient immune response, viral replication can continue and cause chronic destruction of myocytes. Biopsy results of patients with acute myocarditis who develop dilated cardiomyopathy demonstrate changes consistent with those seen in polymerase chain reaction (PCR) amplifying RNA from enteroviruses. On the opposite spectrum of immune activity, overabundant T cells may continue activity into the chronic phase and also may cause tissue destruction and heart failure.

Frequency

United States

The true incidence of myocarditis is unknown because many cases are asymptomatic, and some symptoms related to significant morbidity may not be appropriately credited. One major urban US medical examiners office attributed 1.3% of sudden and unexpected deaths to myocarditis¹, consistent with other autopsy studies that demonstrate evidence of myocardial inflammation in 1-1.5% of deaths. In the United States, viral and medication-related cases are the most commonly identified causes.

International

Internationally other etiologies (ie, Chagas disease, diphtheria) play a greater role than in the United States, and true frequency of disease is even more difficult to appreciate.

Mortality/Morbidity

Because of its difficulty in diagnosis, the large number of cases that likely never come to medical attention, and its previously underappreciated role in sudden dysrhythmic death, morbidity and mortality data are difficult to construct.

• Rarely, acute myocarditis is fulminant and leads rapidly to death. 
• Mortality for clinically significant and biopsy proven myocarditis varies widely. Recent studies have demonstrated death to be as low as 4% of cases for patients without heart failure and with no persistent viral genome expression. On the opposite end of the spectrum, in patients with persistent viral genome expression, myocarditis related mortality may be as high as 25%.
• The appropriate delicate balance of the immune response to viral invasion of myocytes indicates that a certain number of individuals, perhaps with genetic predispositions, will advance to dilated cardiomyopathy and heart failure, the most common long-term sequelae in those patients who do not recover completely.

Sex

The male-to-female ratio is 1.5:1.

Age

The average age of patients with myocarditis is 42 years. It is a prominent cause of sudden cardiac death in young adults, accounting for 8-12% of such deaths.

Please click here to view the full topic text: Myocarditis