Myocarditis in Emergency Medicine
- Author: David S Howes, MD; Chief Editor: David FM Brown, MD more...
Background
Myocarditis is clinical syndrome characterized by inflammation of myocytes resulting from infectious, toxic, and autoimmune etiologies. Ongoing viral infection, myocardial destruction, and adverse remodeling can lead to persistent ventricular dysfunction and 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 have lead to a much greater understanding of the pathophysiology of fulminant myocarditis in which susceptible patients uptake viral RNA and develop a cytotoxic necrosis and rapid (1-2 d) cell death without the appearance of any interstitial infiltrate. In both animal models and these patients, a rapid progression to severe ventricular dysfunction and cardiovascular collapse occurs.[1]
In the more typical course of the disease, 4-14 days after viral infection, cells produce an immune response including macrophage activation and cytokine expression and develop an histologically apparent infiltrate of mononuclear cells. In this subacute viral-clearing phase, natural killer cells target myocardium expressing the viral RNA and continue myocyte necrosis. Tumor necrosis factor is involved in rapidly clearing virus and signals additional proinflammatory cells, activates endothelial cells, and has direct negative inotropic effects. In the latter stages of the subacute process, cytotoxic T lymphocytes infiltrate myocytes and trigger lysis of these cells by presenting virus fragments via the histocompatibility complex on the surface of the myocyte membrane. Neutralizing antiviral antibodies also develop to assist in the clearing of virus.[2]
In the chronic phases, the deleterious effects of either inadequate or inappropriately abundant immune response can lead to the 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.[1] As a prototype of inadequate immune response, human patients with HIV are a subgroup known to do poorly, with a high rate of progression to fulminant heart failure, and polymerase chain reaction (PCR) of endomyocardial biopsy samples show a persistent expression of viral genome, both HIV and others.[3]
On the opposite extreme of immune activity, overabundant T cells may continue activity into the chronic phase, causing tissue destruction and ventricular dysfunction manifesting as chronic heart failure. Ongoing study has demonstrated the presence of antimyosin autoantibodies and other immunomodulators long after initial viral infection and has demonstrated a worsened clinical prognosis from this persistent immune response directed at myocytes.[4, 5]
Epidemiology
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 myocarditis,[6] 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 of myocarditis play a more important role, with Chagas disease from the parasite Trypanosoma cruzi infecting approximately 18 million people with 50,000 annual deaths. Worldwide the true frequency of disease in its less severe forms is even more difficult to appreciate.[4]
Mortality/Morbidity
Because of difficulty in diagnosing myocarditis, 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, myocarditis is fulminant and leads rapidly to cardiovascular collapse and shock sometimes requiring mechanical support. Paradoxically, if these patients survive the first 3-4 weeks of illness they have near 100% recovery and far fewer long-term complications compared with those patients with more indolent courses.[7, 8]
Mortality for clinically significant and biopsy-proven myocarditis varies widely. Patients who initially have and then subsequently clear virus as demonstrated by polymerase chain reaction of endomyocardial biopsy tissue have excellent recovery with a return to normal or near-normal left ventricular function and overall mortality less than 4%.[9]
Patients with persistent viral genome expression and/or antimyosin autoantibodies show limited recovery of left ventricular (LV) function, decreased stroke volume index, and more stiffness of the ventricle with the resultant long-term morbidity of heart failure and a mortality of nearly 25%.[3]
Sex
The male-to-female ratio for myocarditis is 1.5:1.
Age
The average age of patients with myocarditis is 42 years. In younger patients with sudden cardiac death, as much as 20% of cases may be related to myocarditis.
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