Myocarditis

History

• Antecedent infection is common but may have been unrecognized by the patient
  • Nearly any virus (and less commonly, a wide variety of other pathogens) may cause myocarditis; symptoms vary widely and may include fever, headache, respiratory symptoms, and/or rash ^c1c2c3c4
• Recent use of new drug associated with myocarditis or recent vaccine administration (especially tetanus) may suggest hypersensitivity as the mechanism of myocardial inflammation
• Patient may have a known autoimmune or inflammatory disease associated with myocarditis, or suggestive symptoms may be present (eg, rash, joint pain or swelling, preexisting respiratory symptoms, ocular symptoms suggesting uveitis) ^c5c6
• Presentation varies greatly and ranges from mild chest pain and palpitations to cardiogenic shock and ventricular arrhythmia with sudden death
  • Classic presentation is acute, nonfulminant syndrome occurring within 1 to 4 weeks after onset of a viral syndrome ^r1
    • Symptoms may be nonspecific
      • Fatigue; decreased exercise tolerance ^c7
      • Dyspnea with exertion ^c8
      • Palpitations ^c9
      • Chest pain at rest ^c10
      • Unexplained syncope ^c11
    • May present with de novo congestive heart failure, especially in middle-aged or older adults ^c12
  • Fulminant myocarditis presents with rapid onset of heart failure, progressing to cardiogenic shock
    • When associated with prodromal viral infection, usually occurs within 2 weeks of infection ^r15
    • Severe heart failure symptoms develop abruptly over 1 to 2 days ^r1
    • May present with sustained arrhythmias ^c13
• Presentation in children varies with age
  • Newborns and infants are typically more severely affected than older children and adults and are more likely to present with circulatory shock and acute dilated cardiomyopathy ^r18c14c15d1
  • Less severe, nonspecific presentations include fussiness, lethargy, fever, poor feeding and feeding difficulties, vomiting, and difficulty breathing ^c16c17c18c19
  • Children older than 2 years may have chest pain, abdominal pain, myalgias, cough, and lethargy ^r9c20c21c22

Physical examination

• Patients with acute, nonfulminant myocarditis present with a range of manifestations; patients may appear well with normal findings on physical examination or may have physical signs of myocarditis
  • Rapid or irregular pulse, or both ^c23c24
  • In infants, tachypnea and diaphoresis during feeding with poor weight gain ^c25c26c27
  • In children, tachycardia, tachypnea, and abnormal respiratory examination results are most common when myocarditis is the ultimate diagnosis; fever may be present ^c28c29c30
  • If congestive heart failure develops, expected findings may include:
    • Elevated jugular venous pressure ^c31
    • Rales and wheezes ^c32c33
    • S₃ gallop ^c34
    • Hepatomegaly ^c35
    • Peripheral edema ^c36
• Expected findings with development of fulminant myocarditis:
  • Cardiopulmonary examination reflects heart failure and pulmonary edema ^c37c38
  • New cardiac murmur (mitral or tricuspid regurgitation) may appear ^c39
  • Altered mental status, tachycardia, hypotension, and evidence of poor distal perfusion with cardiogenic shock ^c40c41

Causes

• Myocardial inflammation resulting from a wide range of inciting events
  • Viral infection is the most common antecedent event; cases without other identified cause are usually considered to be secondary to undocumented viral infection ^c42
    • Mechanism is an immune response leading to organ dysfunction
    • Common viral causes include adenoviruses, enteroviruses (especially coxsackievirus), parvoviruses (especially B19V), influenza viruses, measles virus, and human herpesvirus 6 ^{c43c44c45c46c47c48c49c50c51}
    • Less common viral infections include cytomegalovirus, HSV, hepatitis C virus, HIV, and Epstein-Barr virus ^c52c53c54c55
    • Has been associated with COVID-19 and COVID-19 vaccines. Frequency and prognostic impact of COVID-19–mediated myocarditis is uncertain ^r19
  • Other infectious agents
    • Bacterial infection as a cause is less common than viral infection
      • Staphylococcus, Streptococcus, Pneumococcus, Meningococcus, Gonococcus, Salmonella, Brucella, and Nocardia species; Corynebacterium diphtheriae, Haemophilus influenzae, Mycobacterium tuberculosis, and Mycoplasma pneumoniae^{c56c57c58c59c60c61c62c63c64}
      • Spirochetal infections, especially Borrelia burgdorferi (Lyme carditis) and Leptospira species ^c65c66
      • Rickettsial infections, including Rickettsia rickettsii, Rickettsia tsutsugamushi, and Coxiella burnetii^c67c68c69
    • Fungal infection
      • Aspergillus, Actinomyces, Blastomyces, Candida, Coccidioides, Cryptococcus, Histoplasma, Mucormycoses, and Sporothrix ^{c70c71c72c73c74c75c76c77}
    • Parasitic infection (associated with eosinophilic myocarditis)
      • Trypanosoma cruzi, Toxoplasma gondii, Trichinella spiralis, Echinococcus granulosus, and Taenia solium ^{c78c79c80c81c82}
      • Entamoeba and Leishmania species ^c83c84
  • Exposure to myocardial toxins
    • Chemotherapeutic agents (eg, anthracyclines, cyclophosphamide) ^c85
    • Stimulants (eg, amphetamines [excluding amphetamine salts used to treat attention-deficit/hyperactivity disorder], cocaine) ^c86c87
    • Catecholamine excess related to pheochromocytoma ^c88
    • Heavy metals ^c89
    • Physical agents (eg, radiation, electric shock) ^c90c91
  • Hypersensitivity states
    • Drug-induced
      • Associated with use of antiseizure agents (primarily carbamazepine) and antipsychotics (primarily clozapine) as well as a number of antibiotics ^c92c93
        • Most cases of myocarditis develop early in the course of drug use; when related to clozapine use, manifestations may occur up to 2 years after initiation of drug therapy ^r9
        • Amongst antibiotics, minocycline and β-lactam antibiotics are most frequently associated ^c94
      • Associated with use of immune checkpoint inhibitors (treatment with anti-PD1, anti-CTLA4, or both) for cancer therapy ^c95c96c97
        • Most cases occur early in therapy, after 1 or 2 doses ^r20
    • Vaccine-induced; noted after tetanus and smallpox vaccines in case reports ^c98c99
  • Myocardial inflammation may occur as a component of many systemic autoimmune, inflammatory, and other systemic disease states
    • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) ^c100
    • Granulomatosis with polyangiitis (Wegener granulomatosis) ^c101d2
    • Hypereosinophilic syndrome ^c102
    • Systemic lupus erythematosus ^c103d3
    • Scleroderma ^c104
    • Polymyositis ^c105d4
    • Sarcoidosis ^c106d5
    • Behçet disease ^c107d6
    • Rheumatoid arthritis ^c108d7
    • Kawasaki disease ^c109d8
    • Inflammatory bowel disease ^c110d8
    • Myasthenia gravis ^c111d9
    • Type 1 diabetes mellitus ^c112d10
    • Thyrotoxicosis ^c113d11
    • Malignancy ^c114

Risk factors and/or associations

Primary diagnostic tools

• Suspect myocarditis based on clinical presentation after exclusion of alternate causes for presenting manifestations
  • Most common presentation patterns include chest pain, arrhythmia, heart failure, or all 3
  • Other conditions with similar patterns of presentation include angiographically significant coronary artery disease, valvular heart disease, congenital heart disease, and hypertensive cardiomyopathy
• First line evaluation for patients who present with clinically suspected myocarditis
  • The following initial evaluation is recommended for all patients: ^r1
    • 12-lead ECG; consider Holter monitor ^r1c125c126
    • Chest radiograph ^c127
    • Transthoracic echocardiogram ^r1c128
    • Inflammatory biomarkers (ie, erythrocyte sedimentation rate and C-reactive protein; WBC count) ^{r1c129c130c131}
    • Cardiac troponin level ^r1c132
  • The following tests may be recommended in consultation with cardiologist based on individual clinical presentation:
    • Cardiac MRI ^r1c133
    • Focused laboratory evaluation ^r1
      • Brain natriuretic peptide or NT-proBNP (N-terminal-proBNP) when heart failure is suspected but uncertain ^r1c134
      • Routine viral serologies are not recommended; however, serologies to identify suspected hepatitis C virus infection, suspected rickettsial infection, Lyme disease in endemic areas, and HIV in high-risk patients are recommended ^{r1c135c136c137c138}
      • Testing for associated systemic disease if suggested by presentation (eg, autoimmune disorder such as systemic lupus erythematosus) ^c139
• Clinical diagnosis of myocarditis can be made with the following clinical criteria: ^r1
  • 1 or more compatible clinical presentations, and
  • 1 or more additional diagnostic criteria (ie, a newly abnormal compatible ECG or Holter monitor result, elevated cardiac troponin level, functional or structural abnormality on cardiac imaging, or specific pattern on cardiac MRI)
  • If asymptomatic (ie, compatible clinical presentation is absent), must meet 2 diagnostic criteria from different categories (ECG, laboratory, imaging)
• Guidelines differ regarding some aspects of second-tier evaluation for patients with clinical myocarditis, particularly indications for confirmatory endomyocardial biopsy ^c140
  • European guidelines recommend that all patients who fulfill the criteria for clinically suspected myocarditis also undergo the following evaluations: ^r1
    • Coronary angiography (to exclude ischemic heart disease) ^c141
      • Important when clinical presentation is compatible with acute coronary syndrome
    • Endomyocardial biopsy for definitive diagnosis ^c142
      • Considered the gold standard for diagnosis and, in some cases, can identify underlying cause
  • American College of Cardiology/American Heart Association guidelines recommend the following: ^r3r7
    • Noninvasive diagnostic criteria can be used to diagnose suspected or probable acute myocarditis when diagnosis is suspected and endomyocardial biopsy is infeasible or not clearly indicated ^r3
    • Biopsy is strongly recommended (Class I recommendation) only for patients with severe presentation in the following scenarios: ^r7
      • Patients with new-onset heart failure of less than 2 weeks' duration associated with a normal-sized or dilated left ventricle and hemodynamic compromise
      • New-onset heart failure of 2 weeks' to 3 months' duration associated with a dilated left ventricle and new ventricular arrhythmias, second- or third-degree heart block, or failure to respond to usual care within 1 to 2 weeks
  • American College of Cardiology Foundation/American Heart Association heart failure guidelines recommend endomyocardial biopsy when seeking a specific diagnosis that will likely influence therapy ^r21
    • Biopsy is suggested for most patients with presentation consistent with giant cell myocarditis, eosinophilic myocarditis, and myocarditis associated with a systemic autoimmune/inflammatory condition (eg, systemic lupus erythematosus, cardiac sarcoid) because immunosuppressive therapy may be beneficial ^r22

Laboratory

• Laboratory studies are indicated for all patients with suspected myocarditis to support diagnosis ^r1
  • Markers of inflammation and infection
    • Erythrocyte sedimentation rate, C-reactive protein levels, or both ^r1c143c144
      • May be elevated with myocarditis
      • Nonspecific, often elevated with acute pericarditis as well
    • WBC count ^r23c145
      • Eosinophilia suggests possibility of underlying hypersensitivity reaction (eg, to a drug) or another type of eosinophilic myocarditis; however, peripheral eosinophilia is absent in 25% of patients with eosinophilic myocarditis ^r17
  • Troponin levels ^r1c146
    • Troponin I and troponin T may be elevated in adults and children with acute myocarditis ^r9c147c148
  • Brain natriuretic peptide or NT-proBNP (N-terminal-proBNP) levels ^r1c149
    • Often elevated
    • Can help to distinguish respiratory symptoms of cardiac (versus pulmonary) origin, if elevated

Imaging

• Chest radiograph ^c150
  • Appearance may be normal or show cardiomegaly and pulmonary vascular congestion if heart failure is present
• Cardiovascular MRI ^c151
  • Indicated for clinically stable patients to support diagnosis of myocarditis ^r1r4
  • Requires breath-holding sequences; infants and young children (and those who are severely ill) require intubation and mechanical ventilation
  • Can support but not definitively exclude diagnosis; may not detect less severe forms of disease ^r8
  • Best for identifying acute, active inflammation and less well established for identifying chronic myocarditis ^r1
    • Highest sensitivity exists for diagnosis of acute inflammation if performed within 2 weeks of symptom onset ^r18
  • Utility is limited in patients with frequent ventricular and atrial arrhythmias ^r24
  • Use Lake Louise criteria; consensus-based recommendation for modification of original criteria is available^r4r1
    • Strong evidence with increased specificity for myocardial inflammation exists when study shows both myocardial edema and other markers of inflammatory myocardial injury
    • Findings consistent with myocardial inflammation include: ^r4
      • Myocardial edema
      • Markers of inflammatory myocardial injury
        • T1-based criteria include:
          • Increased myocardial T1 relaxation time
          • Increased extracellular volume
          • Late gadolinium enhancement
            • Correlates with a greater risk of assist device implantation, transplant, or death in both children^r25 and adults ^r4
        • T2-based criteria include:
          • Global or regional increase of myocardial T2 relaxation time
          • Increased signal intensity in T2-weighted images
        • Note that presence of positive T1- and T2-based markers increases specificity for diagnosing acute myocardial inflammation; however, having only 1 marker may still support a diagnosis of acute myocardial inflammation but with less specificity ^r4
    • Supportive evidence includes presence of left ventricle dysfunction or pericardial effusion ^r4
  • Indications for repeating cardiovascular MRI in 1 to 2 weeks include: ^r1
    • Failure to meet full criteria
    • No criteria met in patient presenting with very recent onset of symptoms with strong clinical suspicion for myocarditis

Functional testing

• 12-lead ECG ^r1c152
  • Indicated for all patients with clinically suspected myocarditis ^r1
  • Neither specific nor sensitive for myocarditis ^r1
  • Findings typically abnormal ^r1
  • Most common findings in acute phase of clinical myocarditis are nonspecific and include: ^r18
    • Sinus tachycardia with low-voltage QRS complexes
    • T-wave changes (T-wave inversion)
  • Other findings may include:
    • ST-T segment elevation is typically concave and diffuse without reciprocal changes ^r1
    • ST segment depression may occur ^r1
    • New Q waves ^r4
    • Reduced R wave height ^r1
    • PR depression may resemble findings associated with acute myocardial infarction or pericarditis
  • Conduction delays and arrhythmias are common, occurring in more than half of patients ^r8r9
    • Conduction delays may include first- to third-degree atrioventricular block, bundle branch block, intraventricular conduction delay (wide QRS) ^r1
    • Arrhythmias may include frequent premature ventricular contractions, supraventricular tachycardia, sinus arrest, atrial fibrillation, ventricular tachycardia or fibrillation, and asystole ^r1
    • Atrioventricular conduction delay in the context of mild left ventricular dilation suggests Lyme carditis (often associated with complete heart block), cardiac sarcoidosis, or giant cell myocarditis ^r1r26
    • Myocarditis due to Trypanosoma cruzi may be associated with complete heart block
  • Negative predictors for survival include QRS prolongation, northwest axis deviation, and new left bundle branch block ^r1
• Holter monitor ^c153
  • Consider if there are symptoms or ECG signs of arrhythmia
    • Tachyarrhythmias are often nonsustained and typically do not cause hemodynamic compromise except in fulminant disease ^r9
    • Reported ventricular arrhythmia occurrence is more frequent in myocarditis due to HIV, Borrelia burgdorferi in Lyme disease, Corynebacterium diphtheriae, Trypanosoma cruzi, giant cell myocarditis, and cardiac sarcoid ^r22
    • Conversely, ventricular arrhythmias are rare in myocarditis associated with systemic lupus erythematosus and other systemic autoimmune diseases ^r22
• Transthoracic echocardiogram ^r1c154
  • Indicated for all patients with clinically suspected myocarditis as a useful measurement tool of cardiac chamber sizes, wall thickness, and systolic and diastolic function ^r1
    • Although it is not diagnostic of myocarditis, it can assess for other causes of heart failure
  • Findings vary and may include:
    • Regional wall motion abnormalities
    • Diastolic dysfunction with preserved ejection fraction
    • Global ventricular dysfunction
    • Ventricular thrombi (up to 25% of patients) ^r9
    • Pericardial effusion
  • Marked left ventricular dilation and normal wall thickness is often noted in patients with acute myocarditis
  • Nondilated, thickened, and hypocontractile left ventricle is often noted in patients with fulminant myocarditis
    • Right ventricular dysfunction is uncommon; however, when present, it is a strong predictor of the need for heart transplant ^r9

Procedures

Other diagnostic tools

• Clinical diagnostic criteria
  • Classically, diagnosis has been considered definitive only with histologic and immunohistochemical evidence from endomyocardial biopsy
  • European Society of Cardiology Working Group on Myocardial and Pericardial Diseases noninvasive diagnostic criteria for clinically suspected myocarditis include: ^r1
    • At least 1 clinical presentation with at least 1 of the specific diagnostic criteria or at least 2 specific diagnostic criteria from different categories if patient is asymptomatic
      • Clinical presentations
        • Acute chest pain, either pericarditic or pseudoischemic
        • New onset of or worsening dyspnea at rest or during exercise and/or fatigue, with or without other signs of heart failure
        • Palpitation or unexplained arrhythmia symptoms
        • Syncope
        • Aborted sudden cardiac death
        • Unexplained cardiogenic shock
      • Specific diagnostic criteria
        • Category 1: newly abnormal ECG finding or Holter/stress test features or both, with any of the following:
          • Atrioventricular block (first-, second-, or third-degree) or bundle branch block
          • ST-T wave changes (ST elevation or non-ST elevation, T-wave inversion)
          • Reduced R wave height
          • Abnormal Q waves
          • Intraventricular conduction delay
          • Sinus arrest
          • Low voltage, frequent premature beats
          • Ventricular tachycardia, ventricular fibrillation, or asystole
          • Supraventricular tachycardia
          • Atrial fibrillation
        • Category 2: elevated troponin T or troponin I levels (indicating myocardial cytolysis)
        • Category 3: functional and structural abnormalities on cardiac imaging
          • Regional wall motion or global systolic or diastolic function abnormality; may be accompanied by:
            • Ventricular dilation
            • Increased wall thickness
            • Pericardial effusion
            • Endocavitary thrombi
        • Category 4: edema or classical myocarditis pattern on late gadolinium enhancement on cardiac MRI

Most common

• Newborns, infants, and younger children ^r18
  • Critical coarctation of the aorta ^r29c156
    • Congenital narrowing of the proximal thoracic aorta (typically as stenosis in the juxtaductal position), hypoplasia of the transverse aortic arch, or stenosis of the abdominal aorta ^c157
    • Heart failure results during ductal closure when coarctation is significantly stenotic owing to acute development of left ventricular outflow obstruction; manifestations closely resemble those of myocarditis ^c158
    • Decreased femoral arterial pulse volume compared with right brachial artery, raised upper limb blood pressures compared with lower limb, and differential cyanosis raise concern of coarctation of the aorta
    • Response to prostaglandin infusion is consistent with a ductal-dependent congenital heart lesion
    • Differentiate and diagnose with transthoracic echocardiography
  • Anomalous origin of the left coronary artery from pulmonary artery ^r30c159
    • Congenital abnormality in which the left coronary artery arises from the pulmonary artery rather than the aorta
    • Manifestations often develop with decrease in pulmonary arterial resistance in the first few weeks of life, presenting with symptoms and signs of congestive heart failure similar to myocarditis
    • Diagnoses are difficult to differentiate on clinical grounds alone; ancillary studies (eg, echocardiogram) are often required to aid in differentiation
    • Differentiate with echocardiography and identification of anomalous origin of the coronary artery; angiography is the gold standard for diagnostic confirmation
  • Sepsis ^r31c160d12
    • Presents similarly in neonates and infants, with nonspecific manifestations such as tachypnea, respiratory distress, tachycardia, poor perfusion, lethargy, fussiness, and poor feeding; cardiac and other organ dysfunction may develop
    • Sepsis may be more likely to result in temperature instability and abnormally high or low WBC indices than myocarditis; however, depending on underlying cause, fever may be a manifestation of myocarditis
    • Diagnoses are difficult to differentiate on clinical grounds alone; ancillary studies (eg, echocardiogram, cultures) are often required to aid in differentiation
    • Diagnose sepsis with blood cultures and clinical course (eg, response to empiric antibiotics)
  • Hypoglycemia ^r32c161
    • Presents similarly in neonates and infants, with nonspecific manifestations such as tachypnea, tachycardia, lethargy, fussiness, and poor feeding
    • Diagnoses are difficult to differentiate on clinical grounds alone; ancillary studies (eg, serum glucose) are required to aid in differentiation
    • Diagnose hypoglycemia by serum glucose level
    • Plasma glucose level defining hypoglycemia is not rigorously agreed on in the first 72 hours of life; levels below about 45 mg/dL are generally considered abnormal, ^r33especially when accompanied by symptoms of hypoglycemia; by 72 hours of life, normal glucose levels reach 60 to 100 mg/dL
• Older children and adults ^r18
  • Pericarditis ^r34c162d13
    • Acute or chronic inflammation of the pericardium, most commonly caused by a virus
      • Other causes include nonviral infections, autoimmune diseases, uremia, previous myocardial infarction, cardiac surgery, malignancies, radiation, medications, and trauma
    • Presentation may be similar to myocarditis with difficulty breathing, chest pain, and diminished cardiac output secondary to pericardial effusion and tamponade ^r1
    • Characteristic chest pain associated with pericarditis may help differentiate conditions; chest pain exacerbated by cough, inspiration, and supine positioning that improves with leaning forward suggests pericarditis ^r35
    • Presence of a pericardial friction rub is pathognomonic for pericarditis but not universally appreciable on examination; presence of pulsus paradoxus suggests tamponade or constrictive pericarditis; Beck triad (ie, hypotension, increased jugular venous pressure, muffled heart sounds) suggests tamponade physiology ^r35
    • Acute pericarditis may be diagnosed with 2 of 4 manifestations: chest pain, pericardial friction rub, characteristic ECG findings (diffuse ST elevation and PR depression), and pericardial effusion on echocardiogram
    • Cardiac MRI may be required to differentiate the 2 conditions if diagnosis remains uncertain
  • Cardiomyopathy ^r36r37c163d1
    • Heterogeneous group of myocardial disorders, typically characterized by either ventricular hypertrophy or dilation
    • Potential causes of cardiomyopathy are diverse and include hypertensive, genetic (familial), inflammatory, metabolic, endocrine, toxic, and infiltrative processes
    • Presentation reflects underlying pathology; dilated cardiomyopathy typically presents as heart failure or reduced cardiac output, whereas hypertrophic cardiomyopathy may present with chest pain, syncope, arrhythmias, or sudden death
    • ECG findings are often abnormal and may vary depending on cause; typical findings include left ventricular hypertrophy, various left atrial abnormalities, possibly pathologic Q waves, and arrhythmia (eg, atrial fibrillation)
    • Differentiate by clinical presentation and cardiac evaluation beginning with ECG and echocardiography; confirmation of underlying cause involves a focused secondary evaluation guided by clinical presentation
  • Acute coronary syndromes ^c164d14
    • Group of clinical symptoms associated with acute myocardial ischemia, including unstable angina and myocardial infarction (ST-elevation myocardial infarction and non-ST-segment elevation myocardial infarction), usually resulting from coronary artery disease ^r38
    • Presenting patterns in patients with angina that mimic myocarditis include chest pain, dyspnea, syncope, and fatigue ^r1r38
    • ECG findings (eg, ST-segment elevation or depression, T-wave inversion, Q waves) may be similar between conditions; findings in patients with myocarditis may be diffuse or reflect coronary or noncoronary distribution pattern ^r2
    • Cardiac troponin levels may be elevated in both conditions
    • Differentiate by clinical presentation, clinical course, and ancillary test findings, including echocardiogram; cardiac MRI; and radionucleotide testing, coronary angiography, or both, depending on individual presentation ^r39
    • Diagnostic confirmation of myocardial infarction usually involves a combination of factors, including consistent clinical presentation, ECG findings, supportive biomarker profile, and imaging studies ^r40
  • Endocarditis ^r41c165d15
    • Infectious or noninfectious (eg, lupus, malignancy) development of cardiac vegetations usually involving cardiac valves ^d3
    • May present similarly with congestive heart failure; fever may be present
    • In contrast to patients with myocarditis, there may be evidence of major (arterial) embolization of vegetations as well as other classic stigmata of endocarditis (eg, Janeway lesions, conjunctival hemorrhage, Osler nodes, Roth spots). Murmur is suggestive of endocarditis
    • Differentiate by clinical presentation and ancillary testing; cardiac imaging with echocardiogram differentiates conditions
    • Diagnosis of endocarditis is based on Duke criteria; blood cultures remain critical to diagnosis of infectious endocarditis

Admission criteria

Admit hemodynamically stable patients who are asymptomatic or mildly symptomatic and suspected of having myocarditis; initiate clinical monitoring until a definitive diagnosis is reached ^r1

• Condition may progress quickly to cardiopulmonary emergency even if systolic function is initially preserved

Recommendations for specialist referral

• Consult cardiologist for all patients with myocarditis for further diagnostic and treatment recommendations
• Patients with fulminant myocarditis should be managed by a cardiologist and team of other physicians with expertise in critical care in a facility with ventricular assist device and extracorporeal membrane oxygenation capability ^r1
• Consider consultation with an infectious disease specialist in patients with suspected underlying infectious cause for diagnostic and treatment recommendations
• Consult a rheumatologist to direct appropriate immunosuppressive therapy for patients with underlying systemic autoimmune and inflammatory disease processes

Drug therapy

• IV immunoglobulin ^c166
  • Consider for viral myocarditis in children (often given routinely despite lack of convincing evidence of efficacy) ^r1
    • Immune Globulin (Human) Solution for injection; Neonates: 2 g/kg IV as a single dose.
    • Immune Globulin (Human) Solution for injection; Infants, Children, and Adolescents: 2 g/kg IV as a single dose.

Nondrug and supportive care

Discontinue any drug implicated as a possible cause of hypersensitivity myocarditis

Instruct all patients to restrict physical activity throughout the acute phase of illness ^r1c167

• Regardless of age, sex, and left ventricular function, athletes with myocarditis (probable or confirmed) should not participate in competitive or leisure sports until: ^r10
  • Resolution of all symptoms, and:
  • Results of retesting are normal (resting echocardiogram, 24-hour Holter monitoring, and an exercise ECG) performed no less than 3 to 6 months after the initial illness, and: ^r10
  • European guidelines recommend that the nonparticipation period should be 6 months from onset of illness ^r1
• Nonathletes should also restrict physical activity for at least 6 months ^r1r10
• Reassess the patient after resolution of clinical presentation before releasing them to resume competitive sports ^r1