BASICS
DESCRIPTION
- Inflammatory disease of myocardium. Viral infection is the most common cause. Other etiologies include infectious pathogens, autoimmune diseases, hypersensitivity reactions, systemic eosinophilic syndromes, and toxic reactions to drugs.
- Clinical presentation varies widely from mild chest discomfort or dyspnea, to shock, heart failure, and sudden cardiac death.
- Definitive diagnosis requires histologic or immunohistologic confirmation.
- Treatment is multifaceted and depends on the cause and severity of the disease. Options include basic pharmacologic therapy for left ventricular dysfunction, vasopressor and inotropic support for hemodynamic compromise, immunomodulatory, immunosuppressive, antiviral therapy, extracorporeal membrane oxygenation, ventricular assist devices, and heart transplant for severely compromised patients.
- Often there is a resolution of disease with supportive care. Unresolved disease may lead to chronic dilated cardiomyopathy (DCM) with risk of increased morbidity and mortality.
EPIDEMIOLOGY
- Male > female
- Infant mortality as high as 75% (1)
- Child mortality as high as 25% (1)
Incidence
Unknown, given that endomyocardial biopsy is infrequent due to risks and lack of histologic standard (2)
Prevalence
- Large prospective study implicated myocarditis as the cause of DCM in 9.6% of cases (3).
- Based on prospective postmortem data, myocarditis is associated with sudden cardiac death in young adults at rates between 4% and 20% (3).
- In HIV-related deaths, myocarditis is the most common cardiac finding on autopsy (50% prevalence) (2).
ETIOLOGY AND PATHOPHYSIOLOGY
Three-phase progression (3):
- Acute injury/infection: direct or indirect myocyte injury from pathogen or toxin and initiation of innate immune response
- Subacute phase/myocardial inflammation: acquired immune system activation with immune dysregulation. T-cell response, B-cell activation, and possible antibody cross-reaction with endogenous myocardial epitopes (molecular mimicry) lead to myocytolysis and worsening inflammatory response.
- Chronic: progression to DCM; immune response downregulation and development of fibrosis in the myocardium
- Viral
- Coxsackie B, cytomegalovirus, HIV and adenovirus most common
- Bacterial
- Staphylococcus, Streptococcus, Mycoplasma
- Fungal
- Aspergillus, Candida, Coccidioides, Cryptococcus
- Protozoal
- Trypanosoma cruzi, Entamoeba histolytica
- Parasitic
- Schistosomiasis, larva migrans, trichinosis
- Spirochetal
- Borrelia burgdorferi, leptospirosis, syphilis
- Immunologic
- Giant cell, sarcoidosis, Kawasaki disease, systemic lupus erythematosus (SLE)
- Hypersensitivity reactions
- Cephalosporins, lithium, diuretics, sulfonamides
- Systemic hypereosinophilic syndromes
- Toxins
- Ethanol, cocaine, heavy metals, carbon monoxide
RISK FACTORS
- Prior hypersensitivity reactions
- Autoimmune disease
- Drug or toxin exposure
- Living in or traveling to an area endemic to specific pathogens
- Eosinophilic syndromes
DIAGNOSIS
The diagnosis of myocarditis is based on a combination of clinical, laboratory, and imaging findings (see "Diagnostic Tests & Interpretation " ):
- Wide range of clinical presentations, from asymptomatic with ECG abnormalities to cardiogenic shock or sudden death
- Fulminant myocarditis: severe hemodynamic compromise, distinct viral prodrome, abrupt onset. Echocardiography demonstrates nondilated wall thickening, hypocontractile left ventricle. Best long-term prognosis among patients presenting with heart failure (2)
- Subacute myocarditis: less severe presentation but worse long-term prognosis due to increased likelihood of chronic DCM
HISTORY
- Most patients are asymptomatic.
- Presentation types: acute coronary syndrome-like symptoms, new-onset heart failure, life-threatening arrhythmias, and chronic heart failure (4).
- Viral prodrome (fever, malaise, myalgias, upper respiratory and/or GI symptoms) within previous 2 weeks, although incidence is highly variable (5).
- Exertional dyspnea (72%)
- Chest pain or discomfort (32%)
- Palpitations
- Decreased exercise tolerance
- Syncope (predictor of increased mortality)
- Children have a more fulminant presentation and are frequently initially misdiagnosed with asthma, pneumonia, or sepsis (1).
- Important to distinguish:
- Fulminant myocarditis: abrupt onset (<3 days) with 2-week viral prodrome, hemodynamic compromise, good prognosis with supportive care
- Subacute myocarditis: unclear onset, rare hemodynamic compromise, frequently requires cardiac transplant; increased mortality
- High-risk presentations (2):
- Heart failure with eosinophilia
- Giant cell myocarditis (at high risk of death or need for cardiac transplant)
- Heart failure + dilated left ventricle + new ventricular arrhythmia, heart block, or poor response to treatment over 2 weeks
- Coexistence with cardiac amyloidosis or hypertrophic cardiomyopathy can worsen prognosis.
PHYSICAL EXAM
- Arrhythmias (18%)
- Friction rub (concurrent pericarditis) or gallop
- Increased jugular venous distention
- Decreased pulse pressure
- Hypotension or cardiogenic shock
- In children, the most common findings are tachycardia, tachypnea, retractions, and grunting.
DIFFERENTIAL DIAGNOSIS
- Aortic dissection
- Pericarditis
- Acute myocardial infarction
- Pulmonary embolus
- Congestive heart failure
- Sepsis
- Cardiomyopathy (dilated, restrictive, hypertrophic, transient stress [Takotsubo])
- Pericardial effusion
- Pneumonia
DIAGNOSTIC TESTS & INTERPRETATION
- Lab tests, ECG, and echocardiography are insensitive and frequently nonspecific but in combination may yield important diagnostic information.
- ECG findings (6,7)[C]
- Nonspecific T-wave changes (most common)
- Sinus tachycardia
- Supraventricular/ventricular arrhythmia
- Atrioventricular conduction delay
- Diffuse ST elevation and PR depression
- QRS duration >120 ms, including left bundle branch block, predicts increased mortality.
- QTc prolongation >440 ms
- Signs of acute myocardial infarction
- Chest x-ray may reveal cardiac enlargement and/or pulmonary congestion.
- Echocardiography to evaluate for valvular disease, hypertrophic or restrictive cardiomyopathy; identifies DCM
- Endomyocardial biopsy (EMB) is the gold standard of diagnosis but is infrequently indicated (<5% of cases warrant biopsy). Higher yield if obtained <4 weeks after symptom onset (2)[B].
- EMB may be useful when a particular cause is suspected, and confirmation will alter the treatment plan. The risk of a serious complication from biopsy is <1% in experienced centers (6)[B].
- Biopsy is recommended if common causes of dilated cardiomyopathy are excluded and one of the following exists (5,7)[C]:
- New-onset heart failure of <2-week duration with normal size or dilated left ventricle and hemodynamic compromise
- Ventricular arrhythmias or progressive conduction disease
- Heart failure with rash, fever, or eosinophilia
- History of collagen vascular disease
- Amyloidosis, sarcoidosis, hemochromatosis
- Suspected giant cell myocarditis, indicated by poor response to usual care within 1 to 2 weeks or high-grade block
- Rapidly progressive cardiomyopathy
Initial Tests (lab, imaging)
- Cardiac biomarkers
- Creatine kinase: low predictive value
- Troponin I or T: high specificity (89 " 94%), low sensitivity 30 " 50%; sensitivity improves when symptom duration <4 weeks (3,5).
- B-type naturetic peptide (BNP): high sensitivity and specificity in predicting heart failure from myocarditis or DCM (1,7).
- Viral serology (6)[C]
- Not useful; associated viruses highly prevalent in many populations
- Myocarditis may occur after acute viral phase has resolved.
- Other biomarkers such as erythrocyte sedimentation rate/C-reactive protein (ESR/CRP) are not recommended due to poor sensitivity and specificity.
- Noninvasive imaging (3,4,5,6 and 7)[C]
- Cardiac MRI
- 80% sensitive; detects myocardial inflammation; cannot detect acute versus chronic
- Identifies patients who may benefit from biopsy, may localize biopsy site, and evaluates disease progression
- Gadolinium late enhancement, T1-weighted
- T2-weighted imaging demonstrates myocardial edema.
- Echocardiography (6)
- Fulminant: normal chamber size, increased septal thickness due to edema
- Acute: left ventricle dilation, normal wall thickness
- Right ventricle dilation occurs in 23% of EMB-proven myocarditis; predictive of death or need for cardiac transplantation (3)
Diagnostic Procedures/Other
- Cardiac catheterization if symptoms or ECG findings suggest acute myocardial infarction
- Viral polymerase chain reaction (PCR) using EMB specimen
Test Interpretation
Dallas criteria (histopathologic definition of myocarditis):
- Inflammatory cellular infiltrate with myocyte necrosis
- Limited by sampling error due to patchy nature of disease (>17 samples required to diagnose 80% cases) and intraobserver variability (3,7)
- Immunohistochemistry (CD3, CD68, human leukocyte antigen) improves sensitivity (6).
TREATMENT
- Largely supportive, with specific treatment aimed at heart failure and underlying etiologies
- Cardiac pacing for symptomatic AV blocks (Type II or III, i.e., Lyme, Chagas) (2)
- American College of Cardiology/American Heart Association recommendations for the treatment of left ventricular systolic dysfunction: diuretics, ²-adrenergic blockers, ACE inhibitors, and angiotensin II receptor blockers as indicated (5)[A,B]
- Avoid NSAIDs: associated with increased mortality (2)[C].
- Drug-induced hypersensitivity: Withdraw agent.
- Systemic hypereosinophilic syndrome: Treat underlying disorder.
- Cardiac sarcoidosis: Corticosteroids are recommended regardless of cardiac dysfunction severity.
- Kawasaki disease: intravenous immune globulin (IVIG) (7)[B]
- Hepatitis C: may respond to interferon (IFN) (2)[C]
- Systemic autoimmune (SLE, scleroderma, polymyositis, giant cell myocarditis): Immunosuppressants may be beneficial.
- Investigational treatment options (3,6):
- Immunosuppression: In biopsy negative for virus, cardiac function improved in 88%.
- Antiviral (IFN- ²), immunoadsorptive treatments
- Consider intra-aortic balloon pump, left ventricular assist device, or extracorporeal membrane oxygenation for severe myocarditis as a temporizing measure or bridge to heart transplantation (rescue therapy) (2)[C].
- Due to rapid deterioration, identification of giant cell myocarditis prompts mechanical circulatory support or a heart transplant (poor prognosis: median survival of 5.5 months from onset).
- Amyloidosis is a negative prognostic factor for a heart transplant.
MEDICATION
See "Congestive Heart Failure " for management of heart failure aspects.
ISSUES FOR REFERRAL
All myocarditis patients should be referred to a cardiologist.
ADDITIONAL THERAPIES
Limit physical activity in the acute setting. Exercise training may improve clinical status for patients with current or prior symptoms of heart failure and reduced left ventricular ejection fraction (6)[B].
SURGERY/OTHER PROCEDURES
- Intra-aortic balloon pump
- Implantable cardioverter-defibrillator
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
- Admit all patients with suspected myocarditis for supportive care, etiology-specific treatment as appropriate, and cardiologic evaluation.
- Particularly concerning presentations:
- Hemodynamic compromise
- Arrhythmia
- Uncorrected high BP
- Acute myocardial ischemia
- Severe infection
- Syncope
- Cardiopulmonary monitoring and support
- Vasopressors or inotropes, if indicated
- ECG, echocardiogram, cardiac catheterization
- Intra-aortic balloon pump, ventricular assist device
Discharge Criteria
- Hemodynamically stable
- Medical workup completed
- Outpatient medication plan and follow-up arranged
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Regular follow up for at least 3 years due to possible recurrence
DIET
Salt restriction with heart failure
PATIENT EDUCATION
- Most cases are expected to resolve without severe morbidity or mortality.
- Patients must adhere to medication and diet plans to avoid worsening of heart failure.
PROGNOSIS
- Spontaneous improvement in 50 " 57%
- 3- to 5-year survival of 56 " 83% (varies with cause)
- Acute fulminant: 93% survival at 11 years
- Acute nonfulminant: 45% survival at 11 years
COMPLICATIONS
- If previous history of myocarditis or idiopathic cardiomyopathy, may have chronic myocardial persistence of virus, leading to progressive left ventricular deterioration
- 21% develop DCM at mean follow-up 3 years (6).
REFERENCES
11 Freedman SB, Haladyn JK, Floh A, et al. Pediatric myocarditis: emergency department clinical findings and diagnostic evaluation. Pediatrics. 2007;120(6):1278 " 1285.22 Cooper LTJr. Myocarditis. N Engl J Med. 2009;360(15):1526 " 1538.33 Elamm C, Fairweather D, Cooper LT. Pathogenesis and diagnosis of myocarditis. Heart. 2012;98(11):835 " 840.44 Biesbroek PS, Beek AM, Germans T, et al. Diagnosis of myocarditis: current state and future perspectives. Int J Cardi. 2015;191:211 " 219.55 Magnani JW, Dec GW. Myocarditis: current trends in diagnosis and treatment. Circulation. 2006;113(6):876 " 890.66 Kindermann I, Barth C, Mahfoud F, et al. Update on myocarditis. J Am Coll Cardiol. 2012;59(9):779 " 792.77 Canter CE, Simpson KP. Diagnosis and treatment of myocarditis in children in the current era. Circulation. 2014;129(1):115 " 128.
ADDITIONAL READING
- Anzini M, Merlo M, Sabbadini G, et al. Long-term evolution and prognostic stratification of biopsy-proven active myocarditis. Circulation. 2013;128(22):2384 " 2394.
- Jessup M, Abraham WT, Casey DE, et al. 2009 focused update: ACCF/AHA guidelines for the diagnosis and management of heart failure in adults. Circulation. 2009;119(14):1977 " 2016.
- Schultz JC, Hilliard AA, Cooper LTJr, et al. Diagnosis and treatment of viral myocarditis. Mayo Clin Proc. 2009;84(11):1001 " 1009.
CODES
ICD10
- I51.4 Myocarditis, unspecified
- B33.22 Viral myocarditis
- I40.9 Acute myocarditis, unspecified
- I40.0 Infective myocarditis
- I40.8 Other acute myocarditis
- I40.1 Isolated myocarditis
- I01.2 Acute rheumatic myocarditis
ICD9
- 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
SNOMED
- Myocarditis (disorder)
- viral myocarditis (disorder)
- Acute myocarditis (disorder)
- Bacterial myocarditis (disorder)
- Toxic myocarditis
CLINICAL PEARLS
- Most patients recover with only supportive care. However, unresolved disease may lead to chronic DCM with a high risk of increased morbidity and mortality.
- An EMB should be reserved for high-risk presentations and/or where it is suspected to change the management plan.
- General heart failure treatment guidelines are applicable to patients with heart failure due to myocarditis.