Basics
Description
Myocarditis is defined as inflammation of the myocardium on histologic examination. Cardiovascular complications may be significant and include myocardial dysfunction, arrhythmias, conduction abnormalities, and cardiac arrest.
Epidemiology
- True incidence of acute myocarditis is difficult to estimate because of the wide range in clinical severity, various etiologies, and underdiagnosis.
- More than 50% of pediatric cases seen are in infants <1 year of age.
- Viral myocarditis has a seasonal distribution, which varies according to the viral species.
Risk Factors
- Exposure to infectious agents, drugs, toxins, and systemic diseases
- Drug exposure
- Autoimmune disease
- Systemic disease
Pathophysiology
- Pathophysiology of myocarditis may vary based on cause (see "Etiology " ).
- Viral myocarditis is best characterized and involves a complex interaction among the virus, host immune response, and environmental factors. Three stages include (1) viral injury and innate immune response, (2) acquired host immune response, and (3) recovery or chronic cardiomyopathy.
- Inflammatory response from innate and acquired immune response may result in significant damage to the myocardium and conduction system.
- Development of autoantibodies may also play a key role in acute and chronic myocardial damage.
- Virus may cause direct damage to the myocardium independent of inflammation, secondary to cleavage of structural proteins.
- Pathogenesis of nonviral myocarditis is poorly understood.
- Regardless of the cause, symptom severity increases with worsening ventricular function and/or with worsening arrhythmias.
- Fulminant myocarditis may be characterized by both severe systolic and diastolic dysfunction.
- Progressive left ventricular systolic dysfunction may lead to hypotension, acidosis, and end-organ dysfunction.
- Left ventricular diastolic dysfunction may result in elevated left ventricular end diastolic pressures, leading to pulmonary venous and arterial hypertension, with concomitant pulmonary edema and right-sided heart failure.
Etiology
- Causes include infection, toxins, drugs, autoimmune disease, and systemic disease.
- Infectious causes include viral, bacterial, rickettsial, fungal, helminthic, spirochetal, and protozoal infections.
- Viral infection is the most common in developed countries including enteroviruses, erythroviruses, adenoviruses, and herpes viruses. Both RNA and DNA viruses have been implicated. Previously, the enteroviruses, specifically coxsackie B, were commonly seen. However, there has been a shift in the spectrum. Currently, parvovirus B19 is most commonly seen. There are growing reports of certain herpes viruses, specifically HHV6, becoming more prevalent.
- Nonviral infectious causes are far less common but must be considered especially in endemic areas, such as Central and South America where Chagas disease is prevalent.
- Nonviral myocarditis may be secondary to exposure to chemicals (arsenic and hydrocarbons), alcohol, radiation, drugs (chemotherapeutics), drug hypersensitivity, autoimmune disease such as systemic lupus erythematosus, or systemic disease such as Churg-Strauss or sarcoidosis.
- Giant cell myocarditis is a very rare form of myocarditis in children that is associated with autoimmune disease and drug hypersensitivity. These patients respond poorly to typical care and frequently require cardiac transplantation.
Diagnosis
Signs & Symptoms
- Prodromal
- Antecedent flulike illness
- Gastroenteritis
- Rheumatologic symptoms
- Fever
- Left-sided heart failure
- Exercise intolerance
- Easy fatigability
- Dyspnea
- Orthopnea
- Anorexia, loss of appetite/poor feeding, early satiety
- Emesis (especially in children)
- Right-sided heart failure
- Abdominal pain/cramping
- Swelling of abdomen/lower extremities
- Loose stools
History
- Duration of symptoms
- Travel history
- Family history
Physical Exam
Any of the following may be present:
- Pulmonary
- Rales
- Tachypnea
- Retractions
- Cardiovascular
- Jugular venous distention
- Normal to hyperdynamic precordium with or without right ventricular heave
- Lateral displacement of the point of maximal impulse (PMI)
- Tachycardia: arrhythmia (atrial and/or ventricular ectopy may be present)
- Heart sounds: accentuation of second heart sound (secondary to pulmonary artery hypertension), murmur (mitral and/or tricuspid insufficiency), gallop, and/or rub
- Abdomen: hepatomegaly, splenomegaly, ascites
- Extremities
- Weak pulses
- Poor capillary refill
- Cool extremities
Diagnostic Tests & Interpretation
- Despite limited sensitivity and specificity, endomyocardial biopsy (EMB), using the Dallas criteria for histopathologic classification, remains the gold standard for confirming the diagnosis of acute myocarditis.
- These criteria are limited in that they provide information with regard to inflammation but do not assess for the presence of viral pathogens.
- Current approaches indicate benefit in analyzing the tissue for viral DNA by polymerase chain reaction (PCR).
- EMB has inherent problems, including sample selection bias, as tissue is only obtained from the right ventricular endocardium and the possible morbidity and mortality associated with an invasive procedure.
- Electrocardiogram findings may be supportive of the diagnosis:
- Highly variable findings may include sinus tachycardia, low voltage QRS, ST segment depression/elevation, flattening or inversion of the T wave, conduction system disease including complete heart block, prolongation of the QT interval, and arrhythmias (premature atrial contractions/supraventricular tachycardia, or premature ventricular contractions/ventricular tachycardia).
Lab
- Erythrocyte sedimentation rate and C-reactive protein level may be elevated.
- Creatinine kinase MB fraction and troponin T and I levels may be elevated.
- Cultures (bacterial, viral, fungal) of blood, urine, stool, and nasopharyngeal swabs may be considered.
- Viral PCR analysis of tissue including myocardium, blood, or sputum may be considered.
- Acute and convalescent serologic studies may be considered for selected antibody studies.
Imaging
- Chest radiograph
- Cardiomegaly and varying degrees of pulmonary edema
- Possible pleural effusions
- Echocardiography
- Depressed systolic function (may be biventricular with normal to mildly dilated chamber sizes)
- Depressed diastolic function
- Focal wall motion abnormalities
- Valvular insufficiency
- Pericardial effusion
- Cardiac MRI
- Assessment of chamber size and systolic function
- Fibrosis by delayed enhancement
- Abnormal delayed enhancement and edema as seen by T2 weighting
Differential Diagnosis
- Severe left-sided obstructive heart lesions
- Mitral stenosis
- Valvular aortic stenosis
- Coarctation of the aorta
- Congenital coronary artery anomalies
- Anomalous left coronary artery from the pulmonary artery and other coronary variants
- Incessant arrhythmias
- Incessant supraventricular tachycardia
- Ventricular tachycardia
- Metabolic disorders including mitochondrial disease
- Drug use
- Cocaine or other stimulants
- Acquired disease
- Kawasaki disease
- Coronary artery disease
- Genetic syndromes
- Neuromuscular disease
- Genetically triggered cardiomyopathies
Treatment
- Initial management should be based on the clinical presentation. These include the following: bed rest and limited activity (during acute phase).
- Standard medical regimens for acute care should be based on appropriate heart failure therapies and may include the following:
- Inotropic support should be considered for patients with evidence of low cardiac output. Medication infusions may include milrinone, dopamine, and dobutamine. If epinephrine is required, mechanical support should be considered.
- Diuretics
- Afterload reduction may be considered if volume overload exists with preserved cardiac output (e.g., nitroglycerin and nitroprusside).
- Antiarrhythmics may be used in cases of hemodynamically significant arrhythmias.
- Mechanical ventilation in patients with respiratory failure secondary to myocardial failure
- Mechanical support (in patients with rapidly progressing, severe heart failure; used as a bridge to transplantation): left ventricular or biventricular assist devices, extracorporeal membrane oxygenation (ECMO)
- Rescue therapy: cardiac transplantation
- Standard medical regimens for chronic care should be based on appropriate heart failure therapies and may include the following:
- Angiotensin-converting enzyme inhibitors (ACEi)
- ²-blockers
- Angiotensin receptor blockers
- Diuretics (e.g., spironolactone for ventricular remodeling)
- Anticoagulation with unfractionated or low-molecular-weight heparin acutely and aspirin and/or Coumadin chronically for patients with severe myocardial depression and ventricular dilation
- Implantable devices may be considered for patients with conduction system disease (pacemaker) or those at risk for sudden cardiac death (implantable cardioverter-defibrillator).
Medication
- Immunosuppression: High-dose gamma globulin (2 g/kg IV immunoglobulin [Ig] over 24 hours) during the acute phase has been associated with improved recovery of left ventricular function and with a tendency for better survival during the first year after presentation.
- Steroids, azathioprine, calcineurin inhibitors, cyclosporine, cyclophosphamide, and other immunosuppressive medications have all been proposed as effective agents, although insufficient evidence of therapeutic benefit is currently available to recommend routine use.
- Antiviral therapy does not currently have an accepted role in myocarditis management.
- Use of interferon therapy is being widely studied but there continues to be a lack of demonstrable benefit.
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Clinical changes in systolic and diastolic function
- Monitoring for life-threatening arrhythmias
- Effects of the illness on other systems
- Nutritional status
- Growth
- Development
- Comorbid illnesses
Prognosis
- Prognostic data are limited by the lack of complete ascertainment of all cases of acute myocarditis, with many patients likely exhibiting mild symptoms, which spontaneously resolve.
- Prognosis is often dictated by clinical presentation and underlying etiology. However, if treated appropriately early in the course, outcome can be quite favorable.
- Prognosis is poor in patients with fulminant lymphocytic myocarditis with significant hemodynamic compromise with a mortality of >40% in adults and ’ Ό75% in children, without aggressive management strategies.
- Mortality is higher in children presenting in the neonatal period.
- Giant cell myocarditis represents a unique subgroup with a particularly poor prognosis, unless transplanted.
Complications
- Acidosis
- End-organ hypoperfusion and resultant dysfunction
- Pulmonary venous and arterial hypertension
- Pulmonary edema
- Unfavorable ventricular remodeling
- Conduction system disease including heart block
- Arrhythmias
Additional Reading
- Blauwet LA, Cooper LT. Myocarditis. Prog Cardiovasc Dis. 2010;52(4):274 " 288. [View Abstract]
- 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. 2003;42(3):473 " 476. [View Abstract]
- Foerster SR, Canter CE, Cinar A, et al. Ventricular remodeling and survival are more favorable for myocarditis than for idiopathic dilated cardiomyopathy in childhood: an outcomes study from the Pediatric Cardiomyopathy Registry. Circ Heart Fail. 2010;3(6):689 " 697. [View Abstract]
- Jefferies JL, Price JF, Morales DL. Mechanical circulatory support in childhood heart failure. Heart Fail Clin. 2010;6(4):559 " 573. [View Abstract]
- K Όhl U, Schultheiss HP. Myocarditis in children. Heart Fail Clin. 2010;6(4):483 " 496. [View Abstract]
- Moulik M, Breinholt JP, Dreyer WJ, et al. Viral endomyocardial infection is an independent predictor and potentially treatable risk factor for graft loss and coronary vasculopathy in pediatric cardiac transplant patients. J Am Coll Cardiol. 2010;56(7):582 " 592. [View Abstract]
- Wilmot I, Morales DL, Price JF, et al. Effectiveness of mechanical circulatory support in children with fulminant and persistent myocarditis. J Card Fail. 2011;17(6):487 " 494. [View Abstract]
Codes
ICD09
- 429.0 Myocarditis, unspecified
- 422.91 Idiopathic myocarditis
- 422.90 Acute myocarditis, unspecified
- 422.92 Septic myocarditis
- 422.93 Toxic myocarditis
- 422.99 Other acute myocarditis
ICD10
- I51.4 Myocarditis, unspecified
- B33.22 Viral myocarditis
- I40.9 Acute myocarditis, unspecified
- I40.0 Infective myocarditis
- I40.1 Isolated myocarditis
- I40.8 Other acute myocarditis
- I01.2 Acute rheumatic myocarditis
SNOMED
- 50920009 Myocarditis (disorder)
- 89141000 viral myocarditis (disorder)
- 46701001 Acute myocarditis (disorder)
- 64043005 Bacterial myocarditis (disorder)
- 31993003 Toxic myocarditis