AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Myocarditis is an inflammatory disorder of the myocardium with necrosis of the myocytes and associated inflammatory infiltrate. It is usually caused by a viral infection, particularly adenovirus and enterovirus infections (eg, coxsackievirus), although many infectious organisms commonly seen in infants and children have been implicated. Occasionally, myocarditis may be a manifestation of drug hypersensitivity or toxicity. Although the utility of myocardial biopsy is debated, suspected myocarditis can be classified into the following 3 types based on pathologic findings as defined in the Dallas Criteria (1987):

• Active myocarditis - Characterized by abundant inflammatory cells and myocardial necrosis
• Borderline myocarditis - Characterized by an inflammatory response that is too sparse for this type to be labeled as active myocarditis; degeneration of myocytes not demonstrated with light microscopy
• Nonmyocarditis

If an active or borderline inflammatory process is found, follow-up biopsies can be subclassified into ongoing, resolving, or resolved myocarditis.

Pathophysiology

Myocarditis generally results in a decrease in myocardial function, with concomitant enlargement of the heart and an increase in the end-diastolic volume caused by increased preload. Normally, the heart compensates for dilation with an increase in contractility (Starling law), but because of inflammation and muscle damage, a heart affected with myocarditis is unable to respond to the increase in volume. In addition, inflammatory mediators, such as cytokines and adhesion molecules, as well as apoptotic mechanisms are activated. The progressive increase in left ventricular end-diastolic volume increases left atrial, pulmonary venous, and arterial pressures, resulting in increasing hydrostatic forces. These increased forces lead to both pulmonary edema and congestive heart failure. Without treatment, this process may progress to end-stage cardiac failure and death.

Frequency

International

Myocarditis is a rare disease. The World Health Organization reports that incidence of cardiovascular involvement after enteroviral infection is 1-4%, depending on the causative organism. Incidence varies greatly among countries and is related to hygiene and socioeconomic conditions. Availability of medical services and immunizations also affect incidence. Occasional epidemics of viral infections have been reported with an associated higher incidence of myocarditis. Enteroviruses, such as coxsackievirus and echovirus, and adenoviruses, particularly types 2 and 5, are the most commonly involved organisms.

Mortality/Morbidity

Studies give a wide spectrum of mortality and morbidity statistics. With suspected coxsackievirus B, the mortality rate is higher in newborns (75%) than in older infants and children (10-25%). Complete recovery of ventricular function has been reported in as many as 50% of patients. Some patients develop chronic myocarditis (ongoing or resolving) and/or dilated cardiomyopathy and may eventually require cardiac transplantation.

Race

No racial predilection exists.

Sex

No sex predilection exists in humans, but some research in laboratory animals suggests that the disease may be more aggressive in males than in females. Certain strains of female mice had a reduced inflammatory process when treated with estradiol. In other studies, testosterone appeared to increase cytolytic activity of T lymphocytes in male mice.

Age

No age predilection exists. Younger patients, especially newborns and infants, and immunocompromised patients may have increased susceptibility to myocarditis.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Clinical presentation varies considerably. In mild forms, there are few or no symptoms. In severe cases, patients may present with acute cardiac decompensation and progress to death.
• • Heart failure: This is the most common presenting picture in all ages. The condition of patients who present with heart failure may rapidly deteriorate even with supportive care. Neonates and young children have higher mortality rates than older patients. Rapid supportive care with blood pressure support, afterload reduction, and control of arrhythmia may prevent early death.
  • Chest pain: Although rare in young children, this may be the initial presentation for older children, adolescents, and adults. Chest pain may be due to myocardial ischemia or concurrent pericarditis.
  • Arrhythmia: Patients can present with any type of dysrhythmia, including atrioventricular conduction disturbances. Sinus tachycardia is typical and the rate is faster than expected for the degree of fever present, which is typically low-grade. Junctional tachycardia is also seen and can be difficult to control medically.
  • Dilated cardiomyopathy: The debate continues over whether myocarditis progresses to dilated cardiomyopathy. Many investigators believe that dilated cardiomyopathy is a direct result of a previously burned-out myocarditis episode.
• Initial symptoms in infants include the following:
• • Irritability
  • Lethargy
  • Periodic episodes of pallor
  • Fever
  • Hypothermia
  • Tachypnea
  • Anorexia
  • Failure to thrive
• Older children present with similar symptoms and may experience lack of energy and general malaise.
• Parents may refer to a recent, nonspecific, flulike illness, gastrointestinal symptoms, poor feeding, or rapid breathing.

Physical

• Signs of diminished cardiac output, such as tachycardia, weak pulse, cool extremities, decreased capillary refill, and pale or mottled skin may be present.
• Heart sounds may be muffled, especially in the presence of pericarditis. An S₃ may be present, and a heart murmur caused by atrioventricular valve regurgitation may be heard.
• Hepatomegaly may be present in younger children.
• Rales may be heard in older children.
• Jugular venous distention and edema of the lower extremities may be present.
• Neonates
• • Neonates may seem irritable, be in respiratory distress, and exhibit signs of sepsis.
  • Somnolence, hypotonia, and seizures can be associated if the CNS is involved.
  • Hypothermia or hyperthermia, oliguria, elevated liver enzymes and elevated blood urea nitrogen and creatinine caused by direct viral damage and/or low cardiac output may be present.
• Infants
• • Signs include failure to thrive, anorexia, tachypnea, tachycardia, wheezing, and diaphoresis with feeding.
  • In severe cases, low cardiac output may progress to acidosis and death.
  • End organ damage may develop because of direct viral infestation or because of low cardiac output.
  • CNS involvement may also develop.
• Adolescents
• • Presentation may be similar to that of younger children but with a more prominent decrease in exercise tolerance, lack of energy, malaise, chest pain, low-grade fever, arrhythmia, and cough.
  • End-organ damage and low cardiac output may be present.

Causes

• Infecting organisms include the following:
• • Coxsackievirus types A and B, especially type B, are the most common viral causes of myocarditis.
  • Adenovirus (types 2 and 5 most common)
  • Cytomegalovirus
  • Echovirus
  • Epstein-Barr virus
  • Hepatitis C virus
  • Herpes virus
  • Human immunodeficiency virus
  • Influenza and parainfluenza
  • Measles
  • Mumps, associated with endocardial fibroelastosis (EFE)
  • Parvovirus B19
  • Poliomyelitis virus
  • Rubella
  • Varicella
• Murine model
• • The coxsackievirus and adenovirus receptor acts as the receptor for the four most common viruses causing human myocarditis: type C (type 2 and type 5) adenovirus and coxsackievirus B3 and B4.
  • Coxsackievirus B serotypes 1-6 have been associated with human myocarditis, but the most serious cases have been attributed to types 3 and 4.
  • In 1973, Lerner and Wilson developed an animal model of myocarditis using mice inoculated with coxsackievirus B3. This model was characterized by an early and a late phase. Following inoculation of the mice with the virus, there was initial replication of the virus with maximum replication within 3-5 days. By day 5, focal myocyte necrosis was evident. On day 7, most mice showed no further inflammation and no organisms could be recovered; however, some mice showed ongoing worsening inflammation similar to that seen in humans.
  • The primary response to the early phase of viral infection is the release of natural killer (NK) cells, which lyse infected myocytes. This helps clear the virus from the system.
  • NK cells also induce expression of major histocompatibility complex antigens on myocytes by releasing cytokines, which prepare the NK cells to interact with T lymphocytes. Animal models depleted of NK cells develop a more severe form of myocarditis.
  • The late phase or second wave of T lymphocytes (CD4, CD8) begins approximately 1 week after the mouse has been inoculated with the virus. T lymphocytes can injure cells in the following 3 ways:
    • Stimulation of cytotoxic T cells
    • Production of antibody and antibody-dependent myotoxicity
    • Direct antibody and complement formation
  • These ongoing processes are considered genetically mediated autoimmune processes. Two different strains of cytolytic T cells have been recognized; one strain attacks virus-infected myocytes and the other strain attacks uninfected cells.
  • Enzymatic cleavage by viral proteins of cytoskeletal proteins appears to play a role in development of dilated cardiomyopathy.
  • Apoptosis appears to play a role in the development of dilated cardiomyopathy.
  • Various kinds of autoantibodies have been found in as many as 60% of patients with myocarditis. These include complement-fixing antimyolemmal antibodies, complement-fixing antisarcolemmal antibodies, antimyosin heavy chain antibodies, and anti–alpha myosin antibodies. Although their role in the disease is not completely understood, their presence may serve as a marker for diagnosing myocarditis in the future.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Medial necrosis of the coronary arteries
Shock

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Complete blood count with differential
• • Acute anemia of any origin may cause heart failure, and chronic anemia exacerbates heart failure; both respond to blood transfusion.
  • The presence of lymphocytosis or neutropenia supports diagnosis of a viral infection.
• Blood cultures: Ruling out any bacterial infection is important.
• Sedimentation rate and C-reactive protein: These nonspecific markers of inflammation usually are elevated. However, a normal value does not rule out myocarditis, particularly in the presence of congestive heart failure, which may lower the sedimentation rate.
• Viral cultures: Nasopharyngeal and rectal swabs may help identify etiology.
• Viral titers: A 4-fold increase in a specific titer from the acute to convalescent phase is strong evidence of infection.
• In situ hybridization
• • This process identifies viral RNA in myocardial tissue of patients believed to have myocarditis.
  • The incidence of false-negative results is high.
• Polymerase chain reaction (PCR)
• • PCR is used to find the viral genome in myocardial cells.
  • It is rapid, sensitive, and may become the test of choice for the diagnosis of viral myocarditis.
• Creatinine kinase–MB isoenzyme (CK-MB): These markers of myocardial damage are elevated most commonly when associated elevation of the ST segment on the ECG is present.
• Lactate dehydrogenase isoenzyme 1: This may be elevated in idiopathic myocarditis.
• Troponin I
• • This is another indicator of myocardial damage.
  • It is usually elevated up to a month after infection but is not specific for this disease.

Imaging Studies

• Echocardiography
• • This is the most cost-effective test used for evaluation of myocardial function.
  • It is sensitive but not specific.
  • Findings include the following:
    • Global hypokinesis (the most common finding)
    • Increased left ventricular end diastolic and systolic dimensions
    • Left ventricular dysfunction, primarily systolic with decreased ejection fraction and shortening fraction
    • Segmental wall motion abnormalities
    • Pericardial effusion
• Chest radiography
• • Cardiomegaly and pulmonary edema may be depicted.
  • Incidentally noted cardiomegaly on chest radiograph may be the initial presentation.
• Radionuclide imaging
• • This may be helpful as a screening tool.
  • Gallium citrate Ga 67 myocardial scintigraphy is useful to reveal chronic inflammatory processes. It is a sensitive test but is limited by its low specificity and predictive value.
  • Indium In 111 antimyosin antibody imaging is highly sensitive for myocardial necrosis, but has a high incidence of false-positive results. However, absence of antimyosin uptake is highly predictive of a negative biopsy (92-98%).
  • Myocardial perfusion imaging with technetium Tc 99m–labeled labeled methoxyisobutyl isonitrile single-photon emission computed tomography (99mTc-MIBI SPECT) is usually a tool used to evaluate the severity of myocardial ischemia. Because the uptake and clearance of 99mTc-MIBI is affected by cell viability and membrane integrity, clinicians have recently used it as a marker for the severity of myocardial necrosis and inflammation in patients with myocarditis, with results comparable to those obtained with enzymatic cell damage markers.

Other Tests

• Electrocardiography (ECG)
• • In some patients with mild cardiac involvement, ECG changes may be the only abnormal findings suggestive of myocarditis.
  • Low-voltage QRS (<5 mm throughout the limb leads) is the classic pattern. Pseudoinfarction patterns with pathologic Q waves and poor progression of R waves in the precordial leads may also be present.
  • T-wave flattening or inversion is a common finding associated with small or absent Q waves in V₅ and V₆.
  • Left ventricular hypertrophy with strain may be present.
  • Other nonspecific findings include prolonged PR segment and prolonged QT interval.
  • Sinus tachycardia is the most common finding. Premature ventricular contractions and atrial tachycardias have been reported. Junctional tachycardia is common and may worsen congestive heart failure. Occasional second- and third-degree atrioventricular block may be present, requiring temporary pacing.
  • Ventricular tachycardia is commonly associated and may be the initial presentation.
• Other techniques are under investigation to determine a specific viral etiology of myocarditis, such as immunohistochemical stains, inflammatory mediators, and autoantibody measurements.

Procedures

• Endomyocardial biopsy
• • Biopsy is the criterion standard for the diagnosis of myocarditis. Myocardial biopsy establishes diagnosis and classifies disease stage.
  • Biopsy is a relatively safe and effective way to sample heart muscle in older children; however, a risk of perforation in sick or younger infants exists.
  • The utility of endomyocardial biopsy is controversial because of the possibility of a high false-negative result rate and because no proven therapy exists, even when a positive biopsy is obtained.
  • Some advocate using radionuclide imaging techniques as screening tools before considering endomyocardial biopsy.
• Biopsy specimens may be useful for PCR diagnosis of viral etiology.

Histologic Findings

Gross evaluation of the heart reveals flabby and pale muscle with petechiae. Ventricular muscle is usually thin and may be hypertrophied. Heart valves and the endocardium are not usually involved, but in cases of chronic myocarditis, they might appear as they appear in endocardial fibroelastosis. Some experts believe that endocardial fibroelastosis is a result of viral myocarditis.

The microscopic hallmark of acute myocarditis is focal or diffuse interstitial infiltrate of mononuclear cells, lymphocytes, plasma cells, and eosinophils. Viral particles are rarely seen unless searched with special techniques (ie, PCR). Necrosis and disarrangement of the myocytes are typical and often are seen with coxsackievirus infection. In the chronic and healing stages, myocytes are replaced by fibroblasts (scar tissue).

In adenoviral myocarditis, less severe infiltrate can be seen histologically than is seen in cases of enteroviral infection.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• General care
• • In the acute phase, the patient should be admitted to the hospital even if only mild signs of respiratory distress or congestive heart failure are present. Rapid progression to overt heart failure and/or hemodynamic collapse may occur.
  • Medical care is aimed at minimizing hemodynamic demands of the body. No specific proven therapy is available to prevent the myocardial damage, but maintenance of tissue perfusion is the goal to avoid further complications. Normal arterial blood oxygen levels should be maintained with supplemental oxygen as needed.

Consultations

Cardiologist

Diet

A low-salt diet is recommended for patients with congestive heart failure.

Activity

• Bed rest is necessary during the acute phase of the illness and may slow the intramyocardial replication of the virus.
• Activity is permitted as partial or complete recovery is achieved.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

If congestive heart failure is present, digitalis may be useful in maintaining adequate function. Diuretics can be given concomitantly to remove excess extracellular fluid and to decrease preload. Caution should be exercised since removal of fluid may cause low cardiac output and shock. It may be necessary to keep a higher venous-filling pressure to maintain an adequate cardiac output. Intracardiac pressure monitoring can facilitate maintenance of adequate filling pressures.

Inotropic agents are used when cardiac output cannot be maintained by less invasive measures. Dopamine, dobutamine, inamrinone (formerly amrinone), and milrinone are the most commonly used vasopressors.

Afterload reduction is most important in treating acute myocarditis and is used when hypotension is not present. This decreases the workload for the compromised myocardium and can allow patients to recover from the acute phase of illness. Agents that reduce afterload improve cardiac output by decreasing systemic arterial resistance. Intravenous medications such as nitroprusside, inamrinone, and milrinone can be replaced with oral ACE inhibitors when the patient stabilizes.

The use of immunosuppressive agents for the treatment of viral myocarditis is still controversial. Some animal studies revealed an exacerbation of viral cytotoxicity when treated with immunosuppressive agents. Other small series in humans have shown that the conditions of patients improve when the patients are treated with these agents. The Multicenter Myocarditis Treatment Trial aimed to establish differences in outcome among 3 treatment modalities. A total of 111 patients were randomized into 1 of the 3 following groups:

1. Prednisone/azathioprine
2. Prednisone/cyclosporine
3. Conventional therapy without immunosuppression

Findings revealed left ventricular function and survival were not significantly different among the 3 groups.

Intravenous gamma globulin may be important in the treatment of acute myocarditis. It has been associated with improved left ventricular function and improved survival.

New therapeutic agents are being studied as candidates for the treatment of myocarditis. These include agents that inhibit the virus entrance to the cells; antiviral agents that inhibit translation, transcription, or both; and interferon, among others. However, these strategies are still in early stages and, although they have promising results, some time may go by before they are widely accepted. Pleconaril, an investigational agent that inhibits viral attachment to host cell receptors, has a broad antienteroviral activity and, in clinical trials, has demonstrated benefit in children with enteroviral meningitis. This medicine is being tested in children with myocarditis.

Conventional management includes digoxin, diuretics, and afterload reduction. Severe cases with hemodynamic compromise may require intravenous inotropic agents, afterload reduction, vasodilators, and anticoagulation.

Drug Category: Cardiac glycosides

These may improve left ventricular function by increasing myocardial contraction by inhibiting the sodium/potassium adenosine triphosphatase (ATPase) pump. This leads to sodium accumulation within the myocyte, which stimulates the sodium-calcium exchange. The increased intracellular calcium increases the force of contraction.

Drug Category: Diuretics

Hypoperfusion of the kidneys causes retention of sodium and water, which produces peripheral and pulmonary edema. Diuretics decrease the intravascular volume overload.

Drug Name	Chlorothiazide (Diuril)
Description	This is a thiazide diuretic. If given with furosemide, it may decrease hypercalciuria. Inhibits sodium reabsorption at the distal tubule in the kidney.
Adult Dose	500 mg to 2 g/d PO qd or divided bid 100-500 mg/d IV qd or divided bid
Pediatric Dose	<6 months: 20-40 mg/kg/d PO divided bid; 2-8 mg/kg/d IV divided bid >6 months: 20 mg/kg/d PO divided bid; 4 mg/kg/d IV divided bid
Contraindications	Documented hypersensitivity; anuria
Interactions	Thiazide diuretics may decrease the effectiveness of anticoagulants, antigout agents, and sulfonylureas; effectiveness may be decreased by bile acid sequestrants, methenamine, and NSAIDs; thiazide diuretics may increase the toxicity of allopurinol, anesthetics, antineoplastics, calcium salts, diazoxide, digitalis, lithium, loop diuretics, methyldopa, muscle relaxants, and vitamin D; amphotericin B and anticholinergics may increase the toxicity of thiazide diuretics.
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Safety of IV use in children has not been established; this drug can produce electrolyte imbalance; not to be given SC or IM

Drug Name	Spironolactone (Aldactone)
Description	Potassium-sparing diuretic. Acts on the distal convoluted tubule of the kidney as an aldosterone antagonist.
Adult Dose	100-200 mg/d PO qd or divided bid
Pediatric Dose	2-3 mg/kg/d PO divided bid/tid
Contraindications	Documented hypersensitivity; hyperkalemia; hyponatremia; severe renal impairment; Addison disease
Interactions	ACE inhibitors, cyclosporine, or potassium supplements increase risk of hyperkalemia; may increase the risk of digoxin toxicity; avoid salt substitutes or natural licorice
Pregnancy	D - Unsafe in pregnancy
Precautions	May cause electrolyte imbalance, especially hyperkalemia; concomitant use with indomethacin or ACE inhibitors may cause hyperkalemia; main adverse effects are GI upset, hyponatremia, hyperkalemia, hepatotoxicity, lethargy, confusion, impotence and gynecomastia; spironolactone is carcinogenic in rodents

Drug Category: Angiotensin-converting enzyme (ACE) inhibitors

Cardiac output and systemic resistance determine blood pressure. When systemic resistance is decreased with afterload reduction, myocardial shortening and stroke volume improve. Therefore, cardiac output can be maintained at a lower heart rate with lower myocardial oxygen demand. ACE inhibitors decrease production of angiotensin II, a potent vasoconstrictor. High levels of angiotensin II have also been associated with cellular damage in patients with myocarditis.

Drug Category: Adrenergic agonist agents (inotropic agents)

Dopamine is a precursor to epinephrine, thus augmenting endogenous release of catecholamines. Also stimulates specific dopamine receptors. Dobutamine does not promote release of endogenous epinephrine. Dobutamine predominantly augments myocardial contractility via beta1 stimulation.

Drug Name	Dobutamine (Dobutrex)
Description	Stimulates beta1-adrenergic receptors. It has less alpha1 stimulation than dopamine; therefore, it produces less increase in systemic vascular resistance.
Adult Dose	2-15 mcg/kg/min continuous IV drip
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; subaortic stenosis
Interactions	Beta-adrenergic blockers antagonize effects of dobutamine; general anesthetics may increase toxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Treat hypovolemia before infusion; treat extravasation promptly with SC administration of phentolamine (Regitine); administration through a central vein is recommended; do not use umbilical artery for infusion; may decrease central venous pressure (CVP) and wedge pressure

Drug Category: Cyclic adenosine monophosphate (c-AMP) phosphodiesterase inhibitors

Inotropic effects occur by inhibiting c-AMP phosphodiesterase, which increases the cellular levels of c-AMP. The sodium-potassium pump is not affected, as with digitalis. Vasodilatory activity is related to the direct relaxation effect on vascular smooth muscle.

Drug Name	Milrinone (Primacor)
Description	Bipyridine positive inotropic effect and vasodilator with little chronotropic activity. Different in mode of action from both digitalis glycosides and catecholamines.
Adult Dose	Loading dose: 50 mcg/kg (undiluted) IV over 10-15 min Maintenance dose: 0.375-0.75 mcg/kg/min IV; titrate to effect
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Milrinone precipitates in presence of furosemide
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Like any other inotropic agent, this drug may aggravate outflow tract obstructions; use with caution in patients with a history of ventricular arrhythmias, atrial flutter, or atrial fibrillation; ventricular arrhythmias, supraventricular arrhythmias, hypotension, and headaches are some of the more common adverse drug reactions

Drug Category: Immunomodulatory agents

Immune globulin is a purified preparation of gamma globulin. It is derived from large pools of human plasma and is comprised of 4 subclasses of antibodies, approximating the distribution of human serum.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Discharge when stable on oral medications.

Further Outpatient Care

• Monitor medication doses and adverse effects.
• Serial echocardiograms are useful to follow ventricular function.

In/Out Patient Meds

• Medications include the following, when indicated:
• • Digitalis
  • Afterload reduction agents
  • Diuretics
  • Antiarrhythmics
  • Anticoagulants

Transfer

• Transfer to a facility with intensive and cardiology care may be required.

Deterrence/Prevention

• Limit patient activity until recovered.
• Avoid negative inotropes.
• Be aware of the possibility of further decrease in ventricular function.

Complications

• Arrhythmia
• Congestive heart failure
• Thromboembolism
• Further decrease in ventricular function
• Dilated cardiomyopathy

Prognosis

• Studies give a wide spectrum of mortality and morbidity statistics.
• With suspected coxsackievirus B, mortality rate is higher in newborns (75%) than in older infants and children (10-25%).
• Complete recovery of ventricular function has been reported in as many as 50% of patients.
• Some patients develop chronic myocarditis (ongoing or resolving) and/or dilated cardiomyopathy. Those who develop dilated cardiomyopathy may require a heart transplant.

Patient Education

• Restrict activity based on performance after the acute phase.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to make a diagnosis

Special Concerns

• Viral myocarditis may be a fatal disease during pregnancy; however, pregnant women are not at a higher risk of developing viral myocarditis compared with the general population.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Abzug MJ. Presentation, diagnosis, and management of enterovirus infections in neonates. Paediatr Drugs. 2004;6(1):1-10. [Medline].
• Aretz HT, Billingham ME, Edwards WD, et al. Myocarditis. A histopathologic definition and classification. Am J Cardiovasc Pathol. Jan 1987;1(1):3-14. [Medline].
• Aretz HT. Myocarditis: the Dallas criteria. Hum Pathol. Jun 1987;18(6):619-24. [Medline].
• Aretz HT. Diagnosis of myocarditis by endomyocardial biopsy. Med Clin North Am. Nov 1986;70(6):1215-26. [Medline].
• Balaji S, Wiles HB, Sens MA, Gillette PC. Immunosuppressive treatment for myocarditis and borderline myocarditis in children with ventricular ectopic rhythm. Br Heart J. Oct 1994;72(4):354-9. [Medline].
• Bowles NE, Ni J, Kearney DL, et al. Detection of viruses in myocardial tissues by polymerase chain reaction. evidence of adenovirus as a common cause of myocarditis in children and adults. J Am Coll Cardiol. Aug 6 2003;42(3):466-72. [Medline].
• Calabrese F, Thiene G. Myocarditis and inflammatory cardiomyopathy: microbiological and molecularbiological aspects. Cardiovasc Res. Oct 15 2003;60(1):11-25. [Medline].
• Camargo PR, Snitcowsky R, da Luz PL, et al. Favorable effects of immunosuppressive therapy in children with dilated cardiomyopathy and active myocarditis. Pediatr Cardiol. Mar-Apr 1995;16(2):61-8. [Medline].
• Camerini F, Salvi A, Sinagra G. Endomyocardial biopsy in dilated cardiomyopathy and myocarditis: which role?. Int J Cardiol. Apr 1991;31(1):1-8. [Medline].
• Drucker NA, Newburger JW. Viral myocarditis: diagnosis and management. Adv Pediatr. 1997;44:141-71. [Medline].
• Drucker NA, Colan SD, Lewis AB, et al. Gamma-globulin treatment of acute myocarditis in the pediatric population. Circulation. Jan 1994;89(1):252-7. [Medline].
• Friedman RA, Schowengerdt KO Jr, Towbin JA. Myocarditis. In: The Science and Practice of Pediatric Cardiology. Lippincott Williams & Wilkins;1999:1777-1794.
• Karjalainen J. Clinical diagnosis of myocarditis and dilated cardiomyopathy. Scand J Infect Dis Suppl. 1993;88:33-43. [Medline].
• Kawai C. From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future. Circulation. Mar 2 1999;99(8):1091-100. [Medline].
• Lerner AM, Wilson FM. Virus myocardiopathy. Prog Med Virol. 1973;DA - 19730608:63-91. [Medline].
• Lewis AB. Myocarditis. In: Moss and Adams: Heart Disease in Infants, Children, and Adolescents. 5th ed. Lippincott Williams & Wilkins;1995:1381-1390.
• Liu Z, Yuan J, Yanagawa B, et al. Coxsackievirus-induced myocarditis: new trends in treatment. Expert Rev Anti Infect Ther. Aug 2005;3(4):641-50. [Medline].
• Mason JW, O''Connell JB, Herskowitz A, et al. A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators. N Engl J Med. Aug 3 1995;333(5):269-75. [Medline].
• Pankuweit S, Ruppert V, Eckhardt H, et al. Pathophysiology and aetiological diagnosis of inflammatory myocardial diseases with a special focus on parvovirus B19. J Vet Med B Infect Dis Vet Public Health. Sep-Oct 2005;52(7-8):344-7. [Medline].
• Robinson JL, Hartling L, Crumley E, et al. A systematic review of intravenous gamma globulin for therapy of acute myocarditis. BMC Cardiovasc Disord. Jun 2 2005;5(1):12. [Medline].
• Stewart MJ, Blum MA, Sherry B. PKR's protective role in viral myocarditis. Virology. Sep 15 2003;314(1):92-100. [Medline].
• Sun Y, Ma P, Bax JJ, et al. 99mTc-MIBI myocardial perfusion imaging in myocarditis. Nucl Med Commun. Jul 2003;24(7):779-83. [Medline].
• Taketomo CK, Hodding JH, Kraus DM. Pediatric Dosage Handbook 1999-2000. 6th ed. Lexi-Comp Inc;1999.
• Wheeler DS, Kooy NW. A formidable challenge: the diagnosis and treatment of viral myocarditis in children. Crit Care Clin. Jul 2003;19(3):365-91. [Medline].

Article Last Updated: Mar 24, 2006