What are the causes of myocarditis?

Causes of Myocarditis

Viral infections are the most common cause of myocarditis in developed countries, with enteroviruses (particularly Coxsackie B), adenoviruses, and parvovirus B19 being the predominant pathogens. 1, 2

Infectious Causes

Viral Pathogens (Most Common)

• Enteroviruses, especially Coxsackie B virus, remain the leading viral cause in North America and are responsible for both acute and fulminant presentations 1, 2
• Parvovirus B19 and human herpes virus 6 are the most frequently identified viruses in Western Europe and can lead to chronic myocarditis through viral persistence in myocardial tissue 3, 2
• Adenoviruses are particularly important in pediatric and adolescent populations 1, 2
• SARS-CoV-2 (COVID-19) has emerged as a major cause, with autopsy studies showing myocarditis in 7.2% of COVID-19 deaths and some cardiac inflammation in 47.8% 1, 4
• Influenza virus is another common viral trigger 5
• Herpes simplex virus can cause both acute and chronic myocarditis 4

Other Infectious Agents

• Bacterial infections including Lyme disease (Borrelia burgdorferi), which causes carditis in 0.3-8% of infected individuals with varying degrees of AV block 1
• Protozoal infections, particularly Chagas disease (Trypanosoma cruzi), which is a major cause in Central and South America with one-third of seropositive individuals developing chronic cardiac disease 3
• Fungal, spirochete, rickettsia, and metazoa infections 1
• HIV causes chronic cardiomyopathy in 8% of asymptomatic individuals 3

Autoimmune and Inflammatory Causes

Systemic Autoimmune Diseases

• Systemic lupus erythematosus causes chronic myocardial inflammation as part of systemic autoimmune processes 1, 3, 5
• Rheumatoid arthritis shows focal late gadolinium enhancement on cardiac MRI in 46-55% of patients, indicating chronic myocardial injury 3
• Systemic sclerosis demonstrates chronic myocardial involvement with fibrosis in 17-53% of patients 3
• Polyarteritis nodosa, hypersensitivity vasculitis, Takayasu syndrome, polymyositis, and Reiter's syndrome 1

Specific Inflammatory Subtypes

• Giant cell myocarditis is an aggressive autoimmune disorder that typically affects young individuals and is usually fatal if untreated, requiring multidrug immunosuppression 1, 3, 2
• Cardiac sarcoidosis frequently presents as chronic myocarditis and often affects the heart without clinical evidence of extracardiac disease 3
• Eosinophilic myocarditis results from overproduction of eosinophils leading to myocardial damage through infiltration and inflammatory cytokine release 1

Hypersensitivity and Drug-Related Causes

Medications and Vaccines

• Immune checkpoint inhibitors used in cancer treatment 5
• mRNA COVID-19 vaccines rarely cause myocarditis, with highest rates in male adolescents aged 12-17 years after the second dose (incidence as high as 50 cases/100,000) 2, 5
• Smallpox vaccine 5
• Sulfonamides 1
• Chemotherapy agents including adriamycin and cyclophosphamide 1

Toxic Exposures

• Cocaine, heroin, amphetamines, and alcohol 1
• Heavy metals including lead, arsenic, cobalt, and phosphorus 1
• Radiation exposure 1
• Ethylene glycol 1

Hypersensitivity Reactions

• Drug allergies (particularly medications and vaccinations) 1
• Hypereosinophilic syndrome with eosinophils >1500/μL 1
• Neoplastic processes 1
• Parasitic infections leading to eosinophilia 1

Metabolic and Nutritional Causes

Nutritional Deficiencies

• Protein, thiamine, and selenium deficiency 1

Electrolyte Disorders

• Hypocalcemia, hypophosphatemia, hyponatremia, and hypokalemia 1

Endocrine Diseases

• Diabetes mellitus 1
• Thyroid disease (both hypothyroidism and hyperthyroidism) 1
• Hypoparathyroidism with hypocalcemia 1
• Pheochromocytoma and acromegaly 1

Genetic and Storage Diseases

• Pompe disease (glycogen storage disease type II) caused by deficiency in lysosomal enzyme α-1-4-glucosidase, affecting 1 in 40,000 births 1
• Anderson-Fabry disease, an X-linked disorder with deficiency in lysosomal hydrolase α-galactosidase A, with cardiac manifestations presenting at mean age 32 years in males and 40 years in females 1

Other Causes

• Peripartum cardiomyopathy 1
• Tachycardia-induced from incessant supraventricular tachyarrhythmias or atrial fibrillation with rapid ventricular rates 1
• Sleep apnea syndrome 1
• Whipple's disease and L-carnitine deficiency 1

Important Clinical Considerations

The pathogenesis of myocarditis consists of three overlapping phases: acute injury (often viral), host innate and acquired immunologic response, and finally recovery or transition to scar and dilated cardiomyopathy. 1

Risk factors that increase susceptibility include male sex (68% of COVID-19 myocarditis cases occur in men), advanced age, underlying cardiovascular disease, obesity, diabetes, hypertension, and immunosuppression. 1, 4, 6

A critical pitfall is that endomyocardial biopsy yields only 5-10% positive results when strict histologic criteria are applied, even in patients with recent-onset systolic dysfunction and heart failure. 1 However, biopsy remains the gold standard when life-threatening clinical course requires consideration of immunosuppression. 4