Myocarditis

Myocarditis is an inflammatory disease of the myocardium that most often affects young individuals and is the cause of approximately 10% of sudden deaths in young adults. The disease is most commonly caused by viral infections (e.g., parvovirus B19, coxsackievirus), but it may also be seen in patients with acute rheumatic fever or autoimmune diseases (e.g., systemic lupus erythematosus, vasculitic syndromes). Patients may be asymptomatic or present with new-onset chest pain, arrhythmias, and/or new-onset heart failure. Severe cardiac inflammation may lead to fulminant myocarditis characterized by cardiogenic shock, hemodynamically significant arrhythmias (e.g., heart block, ventricular tachycardia), and multiorgan failure. Diagnostic testing should include ECG, inflammatory markers and cardiac biomarkers, transthoracic echocardiography (TTE), and possibly diagnostic confirmation with endomyocardial biopsy. Management of myocarditis involves supportive measures and targeted treatment of any underlying disease as indicated. Most adults with viral myocarditis make a full recovery, but there is a small risk of the condition progressing to dilated cardiomyopathy. The prognosis is especially poor for infants.

The exact incidence is unknown.

• 1–5% of viral infections are estimated to have cardiac involvement.
• Often occurs in young patients (average age ∼ 40 years)
• In ∼ 10% of sudden deaths in young adults, myocarditis is diagnosed in the post-mortem examination. ^[1]

Epidemiological data refers to the US, unless otherwise specified.

Infectious ^[2]

• Viral
  • Most commonly implicated: coxsackie B1-B5 (picornavirus), parvovirus B19, human herpesvirus 6 (HHV-6), adenovirus, HCV, HIV
  • Other viruses: EBV, CMV, echovirus, H1N1 influenza A
• Bacterial
  • Group A β-hemolytic Streptococcus (acute rheumatic fever)
  • Corynebacterium diphtheriae (diphtheria)
  • Borrelia burgdorferi (borreliosis)
  • Mycobacterium (tuberculosis)
  • Mycoplasma pneumoniae
• Fungal (Candida, Aspergillus)
• Parasitic
  • Protozoan: Toxoplasma gondii, Trypanosoma cruzi (Chagas disease, common in South America)
  • Helminthic: Trichinella, Echinococcus

Noninfectious ^[3]

• Connective tissue diseases; (e.g., systemic lupus erythematosus, sarcoidosis, dermatomyositis, polymyositis)
• Vasculitis syndromes (e.g., Kawasaki disease)
• Toxic myocarditis
  • Toxins (e.g., carbon monoxide poisoning, black widow venom)
  • Medications (e.g., sulfonamides; , immune checkpoint inhibitors), chemotherapy (e.g., anthracycline, doxorubicin)
  • Alcohol, cocaine
  • Radiation therapy

• Often asymptomatic, but may range from acute, fulminant cases to chronically active or persistent myocarditis
• Preceding (1–2 weeks) flulike symptoms; (fever, arthralgia, myalgia, upper respiratory tract infections): indicate possible viral cause
• Fatigue, weakness, dyspnea; , nausea, vomiting ^[4]
• Cardiac arrhythmias: sinus tachycardia (often dissonantly high in relation to patient's body temperature); , ventricular extrasystoles with palpitations or syncope, heart block with bradyarrhythmia
• Chest pain: indicates pericardial involvement (perimyocarditis)
• Acute decompensated congestive heart failure with dilated cardiomyopathy (see “Symptoms of left heart failure” and “Symptoms of right heart failure”)
• Cardiogenic shock in fulminant cases
• Auscultation findings
  • Brief systolic murmurs
  • Heart failure: S3 and S4 gallops
  • Pericarditis: pericardial friction rub
• In infants and young children: poor feeding, irritability, respiratory distress, and failure to thrive

The clinical manifestation of myocarditis is heterogeneous and nonspecific, ranging from asymptomatic courses to fulminant cardiac decompensation.
References:^[3][5]

Approach ^[1][6][7]

• Suspect myocarditis in patients with:^[8]
  • Clinical features, e.g., chest pain, arrhythmia, new-onset heart failure
  • Typical patient factors: young age, no ASCVD risk factors, recent potential trigger (e.g., URI), and/or acute pericarditis
• Admit to hospital and consult a specialist early (e.g., cardiology, critical care).
• Obtain a minimal diagnostic workup for all patients.
  • 12-lead ECG
  • Routine laboratory studies
  • TTE
• Consider indications for:
  • Additional laboratory studies
  • Advanced imaging
  • Endomyocardial biopsy

Suspect myocarditis in patients without ASCVD risk factors who present with chest pain, arrhythmias, and/or heart failure not explained by another disease.

12-lead ECG ^[1][7]

ECG findings in myocarditis are often abnormal but nonspecific, and may include :

• Sinus tachycardia
• Arrhythmias
  • Frequent atrial or ventricular premature beats
  • Supraventricular arrhythmia, e.g., atrial fibrillation
  • Ventricular arrhythmia, e.g., ventricular fibrillation
• Conduction abnormalities, e.g., AV block, bundle branch block
• Repolarization abnormalities
  • Nonspecific ST-segment changes
  • Diffuse, concave ST elevations
  • T-wave changes, e.g., T-wave inversion
• Low QRS voltage due to pericardial effusion or myocardial edema
• Abnormal Q waves

Laboratory studies ^[6][7]

Obtain routine studies for all patients. Additional studies to determine the underlying cause of myocarditis should be guided by clinical suspicion.

• Routine studies
  • ↑ Cardiac biomarkers
    • CK, CK-MB
    • Troponin T, troponin I
    • BNP, NT-proBNP
  • ↑ ESR, CRP
  • CBC: leukocytosis
• Additional studies ^[6]
  • For Infectious causes, e.g.:
    • Blood cultures in patients with fever
    • HIV testing
    • Hepatitis panel
    • Diagnostics for Lyme disease
  • For noninfectious causes, e.g.:
    • ANAs for connective tissue diseases
    • Toxins for toxic myocarditis
  • Serologies are not routinely recommended. ^[7]

Imaging ^[7][9][10]

Initial imaging

• X-ray and/or CT chest
  • Commonly ordered to evaluate chest pain (not specifically indicated for the evaluation of myocarditis)
  • Chest x-ray is often performed as an initial test in patients with fulminant myocarditis. ^[6]
  • Findings are nonspecific, e.g., cardiac enlargement, pulmonary edema, pleural effusions.
• Echocardiography
  • Obtain for all patients with suspected myocarditis.
  • Supportive findings
    • Global or regional wall motion abnormality (systolic or diastolic)
    • Reduced ejection fraction
    • Ventricular dilation
    • Increased wall thickness
    • Pericardial effusion
    • Complications, e.g., endocavitary thrombus
  • May also identify alternative noninflammatory causes of acute heart failure (e.g., valvular dysfunction)

Advanced imaging ^[6][7][10]

• Cardiac MRI
  • May be used in stable patients to:
    • Evaluate for suspected myocarditis
    • Identify sites for endomyocardial biopsy
  • Findings
    • Functional and structural abnormalities similar to TTE findings
    • Myocardial edema, pericardial effusion, capillary hyperemia
    • Diffuse, late gadolinium enhancement
• Coronary angiography: Consider in all patients to exclude coronary artery disease.

Cardiac MRI should not delay endomyocardial biopsy in patients with fulminant myocarditis or subacute presentation who have not responded to standard care for arrhythmia and/or congestive heart failure within 1–2 weeks. ^[6]

Endomyocardial biopsy (EMB) ^{[6][7][8][11]}

• There is no consensus on when EMB should be performed; specialist consultation is recommended.
• Consider in all patients with suspected myocarditis, especially:
  • Patients with fulminant myocarditis
  • If results are expected to influence treatment
• Procedure: cardiac catheterization with ≥ 3 tissue biopsy samples taken
• Sample analysis includes:
  • Histopathology may show focal necrosis with lymphocytic infiltration.
  • Immunohistology
  • Viral PCR: possible detection of viral DNA or RNA ^[7][12]

EMB is considered the gold standard test for diagnostic confirmation and can identify the underlying cause of myocarditis.

• See “Differential diagnosis of chest pain.”
• Pericarditis
• Myocardial infarction

The differential diagnoses listed here are not exhaustive.

Approach ^{[1][7][8][12]}

For hemodynamically unstable patients, see “Management of fulminant myocarditis.”

• Admit for inpatient management for continuous cardiac monitoring.
• Start symptomatic treatment as needed.
• Identify and treat the underlying cause.
  • Review and consider stopping medications that can cause toxic myocarditis. ^[6][9]
  • Initiate targeted therapy as indicated under specialist guidance (e.g., rheumatology).
• Recommend avoiding aerobic activity for 3–6 months after diagnosis.
• Follow-up at regular intervals using clinical assessment, ECG, and TTE findings.

Symptomatic treatment ^[1][8][11]

• Pain management: Reserve NSAIDs for patients with perimyocarditis and normal LV function.
• Management of acute heart failure: Follow standard management recommendations.
• Management of arrhythmias
  • Life-threatening arrhythmias can occur at any stage but often resolve after several weeks.
    • Temporary measures may be necessary, e.g., temporary cardiac pacing, wearable cardioverter-defibrillator.
    • Consider indications for a permanent cardiac implantable electronic device only after the resolution of the acute phase.
  • See “Management of tachycardia” and “Management of bradycardia” for details.

Use NSAIDs with caution as they can increase sodium retention, exacerbate renal hypoperfusion, and may increase mortality in patients with myocarditis. ^[1][6]

Treatment of the underlying cause ^[1][11]

• Consider under specialist guidance and tailor to the patient.
• Treatment may include:
  • Systemic immunomodulators, e.g., for giant cell myocarditis, cardiac sarcoidosis
  • Antiviral therapy
  • Antibiotic therapy, e.g., for Lyme carditis
  • Intravenous immunoglobulins

All treatment should be guided by a specialist.

Management of fulminant myocarditis ^[6]

Fulminant myocarditis is a rare and life-threatening syndrome of severe myocardial inflammation.

• Clinical features may include:
  • Rapidly progressive acute heart failure
  • Hemodynamically significant arrhythmias (e.g., Mobitz type II, ventricular tachycardia)
  • Cardiogenic shock with features of end-organ damage
• Follow ABCDE approach.
• Admit to cardiac or intensive care unit for management of cardiogenic shock.
• Obtain diagnostics for myocarditis as soon as possible without delaying stabilization, including markers of end-organ damage:
  • ABG/VBG, lactate
  • LFTs
  • BMP
• Specific treatment depends on the cause and may include high-dose steroids.
• Consider consultation for heart transplantation.

Immediately consult cardiology and initiate management of acute heart failure and cardiogenic shock. Maintain a low threshold for beginning treatment of refractory acute heart failure (e.g., with mechanical circulatory support). ^[13]

• Progression to dilated cardiomyopathy (∼ 15% of cases)
• Heart failure or sudden cardiac death; : probably due to ventricular tachycardia or fibrillation (common in adults < 40 years old)
• Acute and/or persistent arrhythmias
• Atrioventricular block
• Intracardiac thrombi formation, which can result in systemic embolization
• Concurrent pericarditis (perimyocarditis) that may lead to cardiac tamponade (associated with large pericardial effusions)

References:^[5]

We list the most important complications. The selection is not exhaustive.

• Viral myocarditis: Most adults make a full recovery; however, progression to dilated cardiomyopathy may occur. ^[14]
  • However, prognosis is very poor for infants (75% lethality rate).
  • Lethality rate for children is 25% and another 25% may develop chronic heart failure complications.
• Markers of poor prognosis ^[5]
  • Poor ventricular function, left bundle-branch block, low ejection fraction
  • Persistent viral genome (in the myocardium)
  • Persistent, chronic myocarditis ^[9]