DESCRIPTION

Myocarditis is an inflammatory disease of heart muscle, diagnosed by histologic and/or immunologic examination. The associated myocardial damage can cause heterogeneous clinical manifestations, ranging from minimal cardiac symptoms to cardiogenic shock, arrhythmias, and sudden death.

EPIDEMIOLOGY

• Incidence is approximately 0.9 per 100,000 children.
• There is a bimodal age distribution in children with highest rates of diagnosis in infants <1 year of age and in ages 14 to 18 years.

RISK FACTORS

• Exposure to infectious agents (most commonly viral)
• Noninfectious triggers such as drugs, messenger RNA (mRNA) COVID-19 vaccines, toxins, and hypersensitivity reactions
• Autoimmune disease
• Systemic disease

PATHOPHYSIOLOGY

• Pathophysiology of myocarditis may vary based on cause but tends to follow a typical sequence of events:
  • Myocardial damage related to infectious or noninfectious insult
  • Myocyte breakdown and release of intracellular contents and proteins
  • Activation of host innate and acquired immune response
• Viral myocarditis results from interaction between the virus, host immune response, and environmental factors. Direct viral-mediated damage to cardiac myocytes, as well as inflammatory response from innate and acquired immune response, may result in significant damage to the myocardium and conduction system. Development of autoantibodies may also play a key role in acute and chronic myocardial damage. Molecular mimicry between viral and host antigens is a proposed mechanism of immune destruction of host myocardial cells.
• If there is an extensive cardiomyocyte loss, chronic secondary cardiomyopathy with heart failure may develop.
• Fulminant myocarditis is characterized by severe systolic and diastolic dysfunction and heart failure which may progress to cardiogenic shock, lactic acidosis, and end-organ dysfunction.
• Left ventricular (LV) diastolic dysfunction may result in elevated LV end-diastolic pressures, leading to pulmonary venous and arterial hypertension, with concomitant pulmonary edema and right heart failure.

ETIOLOGY

• Infectious causes include viral, bacterial, rickettsial, fungal, helminthic, spirochetal, and protozoal agents.
  • Viral infection is the most common in developed countries including enteroviruses (e.g., coxsackievirus), erythroviruses (e.g., parvovirus B19), adenoviruses, herpes viruses (e.g., human herpesvirus 6 [HHV-6], Epstein-Barr virus [EBV], cytomegalovirus [CMV]), and hepatitis C, as well as coronaviruses (e.g., SARS-CoV-2). Both RNA and DNA viruses have been implicated. The last 20 years has seen a shift in viral etiology: from enteroviruses and adenoviruses to more frequent cases of parvovirus and HHV-6.
  • Nonviral infectious causes are far less common but must be considered especially in endemic areas such as Central and South America where Chagas disease is prevalent.
• Noninfectious causes of myocarditis may be secondary to exposure to chemicals (arsenic and hydrocarbons), alcohol, radiation, vaccines (mRNA COVID-19 vaccines), drugs (particularly immune checkpoint inhibitors), as well as drug hypersensitivity, autoimmune disease such as systemic lupus erythematosus, or systemic disease such as Churg-Strauss syndrome or sarcoidosis.
• Eosinophilic myocarditis (Loeffler) is often triggered by a hypersensitivity reaction.
• Giant cell myocarditis is a very rare form of myocarditis in children often heralded by ventricular tachycardia that is associated with autoimmune disease and drug hypersensitivity. These patients respond poorly to typical care, require more aggressive immunosuppressive treatments, and may require cardiac transplantation.