Myocarditis – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

Inflammatory disease of myocardium, most commonly from viral infection. Other etiologies include infectious pathogens, autoimmune disease, drug-induced hypersensitivity reactions, systemic eosinophilic syndromes, and toxins.Clinical presentation varies widely from mild chest discomfort or dyspnea, to shock, heart failure, and sudden cardiac death.Range of treatment is broad and dependent upon the cause and severity of disease, from basic pharmacologic therapy for left ventricular dysfunction, to vasopressor and inotropic support for hemodynamic compromise, to ventricular assist devices, extracorporeal membrane oxygenation, or heart transplant for severely compromised patients.While more often there is resolution of disease with supportive or directed care, unresolved disease may lead to chronic dilated cardiomyopathy with high risk of increased morbidity and mortality.

Epidemiology

Male > FemaleInfant mortality as high as 75%Child mortality as high as 25% (1)

Incidence

Unknown

Prevalence

Large prospective study implicated myocarditis as cause of dilated cardiomyopathy in 9% of cases (2)Based on prospective postmortem data, myocarditis is associated with sudden cardiac death in young adults at rates between 8.6% and 12% (2).In human immunodeficiency virus (HIV)–related deaths, myocarditis is the most common cardiac finding on autopsy (50% prevalence).

Risk Factors

Community viral endemic or other infectionHypersensitivity reactionAutoimmune diseaseDrug or toxin exposureTravel to area endemic to specific pathogensEosinophilic syndromes

Pathophysiology

3-phase progression:

Acute direct or indirect myocyte injury from pathogen or toxin and initiation of innate immune responseAcquired immune system activation with immune dysregulation. T cell response, B cell activation, possible antibody cross-reaction with endogenous myocardial epitopes (molecular mimicry) leads to myocytolysis or worsening inflammatory response.Progression to persistent cardiomyopathy and either chronic infection or eventual recovery

Etiology

Viral: Enteroviruses (coxsackie B particularly) are the most common cause of myocarditis overall (and found in 32% of viral-mediated myocarditis).Bacterial: Staphylococcus, Streptococcus, MycobacterialFungal: Aspergillus, Candida, Coccidioides, CryptococcusProtozoal: Parasitic: Schistosoma, Larva migrans, TrichinellaImmunologic: Giant cell, sarcoidosis, Kawasaki diseaseDrug-induced hypersensitivity reactions: Antibiotics, anticonvulsants, antipsychoticsSystemic hypereosinophilic syndromesToxins:

Diagnosis

Histopathologic (Dallas criteria): Inflammatory cellular infiltrate with myocyte necrosisNo longer gold standard due to (2): Sampling error (>17 samples required to diagnose 80% cases)Intraobserver variabilityIn hypersensitivity myocarditis, diagnostic in only 10–20% casesClinicopathological classification: Fulminant: Severe hemodynamic compromise, distinct viral prodrome, abrupt onset. Echocardiography: Nondilated wall thickening, hypocontractile left ventricle. Best long-term prognosis among those patients presenting with heart failure (3).Subacute: Less severe presentation, but worse long-term prognosis due to increased likelihood of developing chronic dilated cardiomyopathyImmunohistochemistry: Immunoperoxidase staining of human leukocyte antigensViral PCRNoninvasive imaging (MRI, nuclear imaging, echocardiography)

History

Viral prodrome (fever, malaise, myalgias, upper respiratory, and/or gastrointestinal symptoms) within previous 2 weeks. Reported viral prodrome incidence highly variable (2).Exertional dyspnea (72%)Chest pain or discomfort (32%)Decreased exercise tolerancePalpitationsSyncope (predictor of increased mortality)Wide range of clinical presentations: From asymptomatic with electrocardiogram (EKG) abnormalities to cardiogenic shock or sudden deathMost patients presenting with acute dilated cardiomyopathy have mild disease (3).Children have a more fulminant presentation and are frequently initially misdiagnosed with asthma, pneumonia, or sepsis (1).Important to distinguish: Acute lymphocytic: Unclear onset, rare hemodynamic compromise, frequently requires cardiac transplant; increased mortalityFulminant lymphocytic: Abrupt onset (<3 days) with 2-week viral prodrome, hemodynamic compromise, good prognosis with supportive careHigh-risk presentations (3): Heart failure with eosinophiliaGiant cell myocarditis (high risk of death or cardiac transplant)Heart failure + dilated left ventricle + new ventricular arrhythmia, heart block, or poor response to treatment over 2 weeksCo-existence with cardiac amyloidosis or hypertrophic cardiomyopathy can worsen prognosis.Clinical suspicion for high morbidity/mortality presentation should prompt endomyocardial biopsy.

Physical Exam

Arrhythmias (18%)Friction rub (concurrent pericarditis)Increased jugular venous pressureHypotensionDecreased pulse pressureHemodynamic collapse/cardiogenic shockPulmonary hypertension, bundle branch block, EF <40% predict increased mortalityIn children, most common findings are tachycardia, tachypnea, intercostal retractions, grunting

Diagnostic Tests & Interpretation

Lab tests, EKG, and echocardiography are insensitive and frequently nonspecific.Cardiac catheterization and chest x-ray to evaluate alternative diagnosesEKG findings (3)[C]: Sinus tachycardiaVentricular arrhythmiaAtrioventricular conduction blockDiffuse ST-segment elevation and PR-segment depressionSigns of acute myocardial infarction (ST segment elevations in =2 leads, T-wave inversions, ST segment depressions, pathologic Q waves)Echocardiography to rule out causes of heart failure. Identifies global or focal left ventricular abnormality, dilated cardiomyopathyEndomyocardial biopsy (EMB) is infrequently indicated (<5% of cases warrant biopsy). Higher yield if within <4 weeks of symptom onset (3)[B].EMB may be useful when a particular cause is suspected and confirmation will alter treatment plan. The risk of serious complication from biopsy is <1% in centers experienced with technique.Biopsy recommended if common causes of dilated cardiomyopathy are excluded and 1 of the following is present (2)[C]: Ventricular arrhythmias or progressive conduction diseaseHeart failure with rash, fever, or eosinophiliaHistory of collagen vascular diseaseAmyloidosis, sarcoidosis, hemochromatosisSuspected giant cell myocarditis (poor prognosis: Median survival of 5.5 months from onset)Rapidly progressive cardiomyopathyHigher yield if within <4 weeks of symptom onsetAmyloidosis disfavors heart transplantDue to rapid deterioration, identification of giant cell disease prompts mechanical circulatory support or heart transplant

Lab

Initial lab tests

Cardiac enzymes: Creatine kinase: Low predictive valueTroponin I or T: 30–50% sensitive, 90% specific, 80–90% positive predictive value (2) for myocardial injuryMyocyte-specific major histocompatibility complex antigens: 80–85% sensitive and specific (2)Erythrocyte sedimentation rate not recommended: Poor sensitivity and specificity

Imaging

Noninvasive imaging (2,4):

Cardiac MRI: May be a viable alternative to biopsy, identifies patients that may benefit from biopsy, guides biopsy, evaluates disease progressionGadolinium late enhancement and T2-weightedEchocardiography: Segmental wall abnormalities and nondilated wall thickeningGadolinium enhanced spin-echo, segmented inversion recovery gradient-echo pulse sequenceUltrasonic tissue characterization =90% specificNuclear imaging with antimyosin antibodies: Gallium67 for myocyte inflammationIndium11 for myocyte necrosis

Diagnostic Procedures/Surgery

Cardiac catheterization may be required if symptoms or EKG findings suggest acute myocardial infarction.

Pathological Findings

See Dallas Criteria above

Differential Diagnosis

Aortic dissectionPericarditisAcute myocardial infarctionPulmonary embolusCongestive heart failureSepsisCardiomyopathies (dilated, restrictive, hypertrophic, transient stress [Takotsubo disease])Pericardial effusionPneumonia

Treatment

Hemodynamic and cardiovascular supportive care. Additional management based on presentation or suspected underlying cause (3).>50% spontaneously recover.In suspected acute viral myocarditis, advise patient to limit physical activity because it may increase viral replication and worsen condition (4)[C].Follow latest American College of Cardiology/American Heart Association recommendations for treatment of left ventricular systolic dysfunction, utilizing diuretics, ß-adrenergic blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers as indicated (2)[B].Aldosterone antagonist (selectively used for NYHA class III or IV symptoms) (2)[B]Nonsteroidal anti-inflammatory drugs are associated with increased mortality (3)[C].Drug-induced hypersensitivity: Withdraw agentSystemic hypereosinophilic syndrome: Treat underlying disorder.Kawasaki disease: Intravenous immunoglobulinHepatitis C: May respond to interferon therapy (3)[C]Systemic autoimmune (SLE, scleroderma, polymyositis, giant cell myocarditis): Immunosuppressants may be beneficial (2)[C].Consider intra-aortic balloon pump or left ventricular assist device for severe myocarditis as a temporizing measure or bridge to heart transplantation (rescue therapy) (3)[C].

Medication

See Congestive Heart Failure topic for management of heart-failure aspects.

Additional Treatment

Limit physical activity in the acute setting, but exercise training may improve clinical status in patients with current or prior symptoms of heart failure and reduced left ventricular ejection fraction (5)[B].

Surgery/Other Procedures

Intra-aortic balloon pumpImplantable cardioverter-defibrillator

In-Patient Considerations

Initial Stabilization

Cardiopulmonary monitoring and supportVasopressors or inotropes if indicatedEKG, echocardiogram, cardiac catheterizationIntra-aortic balloon pump, ventricular assist device

Admission Criteria

Hemodynamic compromiseArrhythmiaUncorrected high blood pressureAcute myocardial ischemiaSevere infectionSyncope

Discharge Criteria

Hemodynamically stableMedical workup completedOutpatient 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.Follow-up for as long as 3 years may be required.Adhere to medication and diet plan to avoid worsening of heart failure.

Prognosis

Spontaneous improvement in 50–57%3- to 5-year survival of 56–83%Acute fulminant presentation: 93% survival at 11 yearsAcute nonfulminant presentation: 45% survival at 11 years (4)

Complications

If previous history of myocarditis or idiopathic cardiomyopathy, may have chronic myocardial persistence of virus leading to progressive left ventricular deteriorationUp to 50% develop dilated cardiomyopathy.

References

1. Freedman SB, Haladyn JK, Floh A, et al. Pediatric myocarditis: emergency department clinical findings and diagnostic evaluation. Pediatrics. 2007;120:1278–85.

2. Magnani JW, Dec GW et al. Myocarditis: current trends in diagnosis and treatment. Circulation. 2006;113:876–90.

3. Cooper LT et al. Myocarditis. N Engl J Med. 2009;360:1526–38.

4. Dennert R, Crijns HJ, Heymans S et al. Acute viral myocarditis. Eur Heart J. 2008

5. Hunt SA, Abraham WT, Chin MH, et al. American College of Cardiology/American Heart Association 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult.Circulation. 2005;112:e154–235.

Additional Reading

Jessup M, Abraham WT, Casey DE, Feldman MA. 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults. Circulation. 2009;119:1977–2016.

Codes

Snomed

50920009 myocarditis (disorder)89141000 viral myocarditis (disorder)64043005 bacterial myocarditis (disorder)31993003 toxic myocarditis (disorder)46701001 acute myocarditis (disorder)

ICD9

429.0 Myocarditis, unspecified422.90 Acute myocarditis, unspecified422.91 Idiopathic myocarditis422.92 Septic myocarditis422.93 Toxic myocarditis

Clinical Pearls

Most patients recover with only supportive care; however, unresolved disease may lead to chronic dilated cardiomyopathy with high risk of increased morbidity and mortality.Endomyocardial biopsy should be reserved for high-risk presentations and/or where it is suspected the information may change management.General heart failure treatment guidelines are applicable to patients with heart failure due to myocarditis.