Viral Myocarditis

Inflammation of the myocardium caused by viral infection, most often parvovirus B19, human herpesvirus 6, enteroviruses (coxsackie B), adenovirus, influenza, SARS-CoV-2, cytomegalovirus, Epstein-Barr virus, hepatitis C and HIV. Incidence is about 10 to 22 per 100,000 per year, and it causes sudden death in young adults.

• Mechanism: viral entry and direct injury, followed by an immune response (T cells, cytokines, autoantibodies) that causes further myocyte damage and fibrosis. Persistent virus or autoimmunity can lead to dilated cardiomyopathy.
• Natural history: about half recover completely within 2 to 4 weeks, about 25% develop persistent ventricular dysfunction, and about 12 to 25% progress to dilated cardiomyopathy, transplantation or death. Fulminant myocarditis (shock, left ventricular ejection fraction usually less than 30%) has high early mortality, but survivors have a good long term outcome.

• Preceded by a viral illness 1 to 4 weeks earlier in many cases: fever, myalgia, cough, diarrhoea. Presentations: chest pain, dyspnoea, palpitations, fatigue, syncope, acute heart failure, cardiogenic shock, or sudden death.
• Signs: tachycardia, S3 gallop, murmur of functional mitral regurgitation, raised jugular venous pressure, crackles, peripheral oedema, hypotension in severe cases.
• Differential diagnosis: acute coronary syndrome and myocardial infarction with non-obstructed arteries, Takotsubo syndrome, pericarditis, peripartum cardiomyopathy, giant cell myocarditis, eosinophilic myocarditis, sarcoidosis, rheumatic carditis, Chagas disease, sepsis cardiomyopathy, drug toxicity, and thyrotoxicosis.
• Complications: heart failure, ventricular tachycardia and fibrillation, high grade atrioventricular block, sudden death, cardiogenic shock, intracardiac thrombus and embolism, and dilated cardiomyopathy.

• High sensitivity troponin (raised in most), CRP, ESR, natriuretic peptide, full blood count with eosinophil count, urea, creatinine, thyroid stimulating hormone, HIV test, and viral testing as indicated.
• ECG: diffuse ST-T changes, ST elevation, QRS widening, bundle branch block, atrioventricular block, ventricular arrhythmia. Continuous monitoring is needed.
• Echocardiography: reduced ejection fraction, regional wall motion abnormality, wall thickening from oedema, small effusion, and ventricular thrombus.
• Coronary angiography or CT coronary angiography to exclude obstructive coronary disease.
• Cardiac MRI: myocardial oedema (T2 signal, T1 and T2 mapping) and late gadolinium enhancement in a subepicardial or mid-wall pattern, supporting the diagnosis without biopsy.
• Endomyocardial biopsy (with histology, immunohistochemistry and viral genome testing) is indicated for fulminant presentation, haemodynamic compromise, new heart failure with rapid deterioration, ventricular arrhythmia or high grade atrioventricular block, or failure to improve within 1 to 2 weeks, to exclude giant cell and eosinophilic myocarditis.

• General: admit for monitoring (telemetry for at least 48 to 72 hours with troponin elevation or any arrhythmia), bed rest in the acute phase, and avoid strenuous exercise for 3 to 6 months (competitive athletes should not return until ejection fraction, biomarkers, Holter and exercise test are all normal). Avoid NSAIDs and high dose steroids in uncomplicated viral myocarditis, because they may worsen outcome.
• Heart failure therapy once stable:
  • Ramipril 1.25 to 2.5 mg daily, titrated every 1 to 2 weeks to 10 mg daily; or sacubitril/valsartan 24/26 mg twice daily titrated to 97/103 mg twice daily (never together with an ACE inhibitor). Monitor potassium and creatinine.
  • Bisoprolol 1.25 mg daily titrated to 10 mg daily (or metoprolol succinate 25 to 200 mg daily) once euvolaemic and not in shock.
  • Spironolactone 12.5 to 25 mg daily, up to 50 mg, if potassium is less than 5.0 mmol/L and eGFR is greater than 30.
  • Dapagliflozin 10 mg daily or empagliflozin 10 mg daily; evidence in myocarditis specifically is limited.
  • Furosemide 20 to 80 mg daily orally (IV for congestion).
• Arrhythmia:
  • Ventricular arrhythmia: correct potassium to 4.5 mmol/L or more and magnesium (2 g IV magnesium sulfate over 10 minutes if low), use amiodarone 150 mg IV over 10 minutes then 1 mg/min for 6 hours and 0.5 mg/min thereafter, and avoid class I antiarrhythmics.
  • High grade atrioventricular block: temporary pacing; permanent pacing if block persists beyond 1 to 2 weeks.
  • Implantable defibrillators are deferred for 3 to 6 months unless life threatening arrhythmia persists; a wearable defibrillator can bridge.
  • Atrial fibrillation: rate control with bisoprolol or digoxin 0.125 to 0.25 mg daily; anticoagulation when indicated.
• Fulminant myocarditis: intensive care, inotropes (dobutamine 2.5 to 10 micrograms/kg/min, or milrinone 0.25 to 0.5 micrograms/kg/min), and early mechanical circulatory support (venoarterial ECMO, percutaneous ventricular assist device, intra aortic balloon pump) as a bridge to recovery, transplantation or durable assist device.
• Anticoagulation: warfarin to INR 2.0 to 3.0 for 3 to 6 months for left ventricular thrombus, or for atrial fibrillation with risk factors.
• Immunosuppression only for confirmed non-viral causes: giant cell myocarditis (methylprednisolone 1 g IV daily for 3 days, then prednisolone 1 mg/kg/day with ciclosporin or tacrolimus and azathioprine 1 to 2 mg/kg/day), eosinophilic myocarditis (prednisolone 1 mg/kg/day), cardiac sarcoidosis, and myocarditis with autoimmune disease. Do not give immunosuppression for active viral infection (viral genome on biopsy).
• Antiviral and immunoglobulin therapy have unproven benefit in adults (evidence limited).
• Special groups:
  • Children: higher risk of fulminant disease; immunoglobulin 2 g/kg has been used but evidence is limited; dose heart failure drugs by weight.
  • Pregnancy: avoid ACE inhibitors, sacubitril/valsartan, spironolactone and SGLT2 inhibitors; use metoprolol and diuretics; the risk of deterioration is high.
  • HIV: start antiretroviral therapy and screen for opportunistic causes.
  • Athletes: restrict sport for 3 to 6 months.
• Red flags: syncope, sustained ventricular tachycardia, high grade block, shock, rising troponin, new heart failure.
• Follow up: echocardiography at 1, 3, 6 and 12 months; cardiac MRI at 3 to 6 months; Holter and exercise test before return to sport; continue heart failure drugs for at least 6 to 12 months after recovery.