Myocarditis

Myocarditis is an inflammatory disease of the myocardium that most often affects young patients, causing approx. 10% of sudden deaths in young adults. The disease is commonly caused by viral infections (e.g., parvovirus B19, coxsackievirus) or acute rheumatic fever, but may also manifest in patients with systemic conditions such as systemic lupus erythematosus or vasculitic syndromes. Adult patients are commonly asymptomatic or present with nonspecific symptoms, including fever, fatigue, and weakness. Some patients also experience cardiac signs that vary in severity from chest pain and arrhythmias to heart failure or sudden cardiac death. Infants and children typically have a more severe presentation. Inflammation may also spread and lead to concurrent pericarditis. Myocarditis should be suspected in patients with a history of flulike symptoms and new evidence of ECG abnormalities, such as sinus tachycardia or concave ST-segment elevations. Further diagnostic tests may show elevated cardiac enzymes and cardiac enlargement in chest x-rays. If the diagnosis is uncertain, a myocardial biopsy may also be indicated. Initial management of myocarditis involves supportive measures and treatment of any underlying diseases (e.g., antibiotic therapy). Cardiac symptoms usually require additional medication, including amiodarone for arrhythmias or beta-blockers for congestive heart failure. Whereas most adults with viral myocarditis make a full recovery, there is a small risk of the condition progressing to dilated cardiomyopathy. The prognosis is especially poor for infants and small children.

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)
  • Medication (e.g., sulfonamides), 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]

Patients suspected of myocarditis should have an ECG and laboratory tests conducted to support the diagnosis. Ultimately, if the diagnosis is unclear, a biopsy may be indicated to help determine treatment.

ECG/24-hour Holter monitoring

Although ECG abnormalities due to myocardial inflammation are very nonspecific and may only manifest temporarily, myocarditis should be suspected if the following findings are observed:

• Sinus tachycardia
• Arrhythmias: atrial or ventricular ectopic beats, complex ventricular arrhythmia, atrial tachycardia
• Repolarization abnormalities
  • Nonspecific T-wave and ST-segment changes ^[1]
  • Possible ST-segment elevations may mimic myocardial infarction ^[1]
• Heart block: right bundle branch block, complete heart block, AV block
• Rule out myocardial infarction: loss of R wave and pathological Q wave specific to myocardial infarction, not found in myocarditis
• Pericardial effusion: low voltage (low R-wave with poor progression)

Laboratory findings

• ↑ Cardiac enzymes (CK, CK-MB, troponin T)
• ↑ ESR (and CRP)
• Leukocytosis
• ↑ BNP
• Virus serology

Imaging

• Chest x-ray and CT: cardiac enlargement, pulmonary congestion, pleural effusions
• Echocardiography
  • Findings often unremarkable
  • Ventricles: dilation, diffuse hypokinesia, reduced ejection fraction, impaired contractility, regional wall motion abnormalities
  • Pericardial effusion: localized or circumferential fluid surrounding the ventricles
  • Exclusion of other possible etiologies of heart failure (e.g., heart defects)

Myocardial biopsy

• Via cardiac catheterization of the left heart and MRI-supported biopsy
  • Indications
    • New onset heart failure, severe arrhythmias, resistance to treatment
    • Only performed if previous diagnostics are inconclusive and a definitive diagnosis of myocarditis might influence treatment
  • Results
    • Possible detection of viral DNA/RNA
    • Immunohistochemical detection of inflammation: Focal necrosis with lymphocytic infiltration most often has a viral etiology

References:^[1][5][6]

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

The differential diagnoses listed here are not exhaustive.

• Supportive therapy
  • Inpatient surveillance (cardiac monitoring, oxygen administration, management of fluid status)
  • Rest; avoid physical activity
  • Analgesic drugs if required
• Causative treatment
  • Antibiotic therapy for bacterial myocarditis
  • Antimycotic therapy (fluconazole, amphotericin B) for fungal infections
• Treatment of complications
  • Congestive heart failure: (e.g., management of fluid accumulation with diuretics, beta blockers , ACE inhibitors)
  • Treatment of cardiac arrhythmias (e.g., amiodarone)
  • Heart transplantation

References:^[5][6][7]

• 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. ^[8]
  • 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]