History and exam

Key diagnostic factors

common

presence of risk factors

Risk factors include HIV and other infections, smallpox vaccination, autoimmune/immune-mediated diseases, and peri-partum and postnatal periods.

viral syndrome (prior)

A viral prodrome of fever, myalgias, respiratory symptoms, or gastroenteritis in the 2-3 weeks preceding initial presentation is common in patients presenting with myocarditis, including in children.

autoimmune disease

Many autoimmune diseases are associated with myocarditis.[26]

infectious disease

Many infectious diseases are associated with myocarditis.

uncommon

drugs and toxins

Known causative drugs and toxins include anthracyclines (e.g., doxorubicin, daunorubicin, epirubicin, idarubicin), fluoropyrimidines (e.g., fluorouracil, capecitabine), immunotherapies (e.g., ipilimumab, tremelimumab, nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, and trastuzumab), arsenic, zidovudine, carbon monoxide, ethanol, iron, interleukin-2, cocaine, amphetamine, smallpox or mpox vaccine, SARS-CoV-2 (COVID-19) mRNA vaccine (may occur with other types of COVID-19 vaccines), catecholamines (e.g., adrenaline, noradrenaline, dopamine), cyclophosphamide, heavy metals (copper, iron, lead), radiation, antibiotics (penicillins, cephalosporins, sulfonamides), amphotericin B, thiazide diuretics, anticonvulsants (carbamazepine, phenytoin, phenobarbital), digoxin, lithium, amitriptyline, clozapine, snake venom, bee venom, black widow spider venom, scorpion venom, and wasp venom.

Other diagnostic factors

common

age <50 years

Patients with myocarditis tend to be younger (<50 years) than those presenting with more common cardiac conditions such as acute coronary syndrome.

chest pain

Occurs in 35% of patients presenting with myocarditis and can be typical, atypical, or positional in nature.[4][16]​ Occurs in up to 42% of children with myocarditis.[15]

dyspnoea

Common symptom in adult patients with myocarditis.

Present in approximately one quarter of children with myocarditis.[15]

orthopnoea

Myocarditis manifesting as new-onset congestive heart failure (CHF) frequently causes orthopnoea.

fatigue

Common complaint in patients presenting with myocarditis.[16] Occurs in up to 70% of children with myocarditis.[15]

palpitations

Often described by adult patients presenting with myocarditis.

Occurs in approximately 16% of children with myocarditis.[15]

rales

Typical finding in patients with CHF secondary to myocarditis.

elevated neck veins

Secondary to volume overload. Common in CHF caused by myocarditis.

S3 gallop

Frequently accompanies myocarditis manifested as CHF.[16]

sinus tachycardia

As a compensatory means to increase cardiac output, one of the first signs to develop in patients presenting with CHF caused by myocarditis. Occurs in up to 57% of children with myocarditis.[15]

atrial and ventricular arrhythmias

Include refractory arrhythmias and malignant rhythms such as sustained ventricular tachycardia. Are often present during the acute presentation of myocarditis. Occur in up to 45% of children with myocarditis.[15] Sustained tachyarrhythmias were found to be associated with a 2.3-fold increase in death in a series of children with acute myocarditis.[21]​​

tachypnoea

Present in up to 60% of children with myocarditis; more common in younger children and infants.[15]

hepatomegaly

Present in up to 50% of children with myocarditis.[15]

uncommon

syncope

Syncope caused by ventricular arrhythmias is a rare but possible presenting symptom of myocarditis. Occurs in up to 10% of children with myocarditis.[15]

fever

Present in up to 58% of children with myocarditis at or prior to presentation.[15]

gastrointestinal issues

Nausea/vomiting or abdominal pain may be present in up to 48% of children with myocarditis, with diarrhoea observed in approximately 8%.[15]

rhinorrhoea

Present in up to 44% of children with myocarditis.[15]

cough

Present in up to 44% of children with myocarditis.[15]

S3 and S4 summation gallop

Occasionally presents in the setting of myocarditis with CHF.

pericardial friction rub

Myocarditis often extends to the pericardium (myopericarditis) and can cause an audible pericardial friction rub.

peripheral hypoperfusion

As evidenced by renal failure, elevated serum lactate, or other sign of end-organ damage, can be associated with myocarditis-induced cardiogenic shock.

hypotension

Myocarditis can present as profound left ventricular systolic dysfunction resulting in hypotension.

altered sensorium

Altered mental status, particularly in the elderly, can be the first apparent sign of myocarditis-induced CHF, even in the setting of normal blood pressure.

lymphadenopathy

Focal or diffuse lymphadenopathy can be present in patients with sarcoidosis-associated myocarditis.

respiratory distress

Present in up to 47% of children with myocarditis.[15]

Risk factors

strong

infection (non-HIV)

Many viral, bacterial, and fungal infections have been implicated in the pathogenesis of myocarditis.[25][33]​ The most common cause of myocarditis worldwide is Trypanosoma cruzi with an estimated 18 million people infected.[7] In the US, adenoviruses and enteroviruses, such as Coxsackie B, are believed to be the predominant cause.[45] In Germany, parvovirus B19 is the organism most prevalently isolated from endomyocardial biopsy, while in Japan, hepatitis C virus is most commonly implicated.[46][47] Case reports have implicated SARS-CoV-2 infection as a potential aetiological agent during the COVID-19 pandemic.[29]

HIV infection

HIV disease places a person at very high risk of developing myocarditis. In a postmortem study of patients with AIDS, 67% were found to have biopsy-confirmed myocarditis.[46] Also, prospective data suggest that the yearly incidence of developing myocarditis is 1.6% in asymptomatic HIV-positive patients; this incidence increases among patients with CD4 counts <400 cells/mm³.[47]

autoimmune/immune-mediated diseases

systemic lupus erythematosus, scleroderma, and other immune-mediated diseases such as sarcoidosis place patients at markedly increased risk of developing myocarditis.[48][49][50]

peripartum and postnatal periods

There is a strong association between women in the peripartum or postnatal period and the development of myocarditis.[4][51]

weak

drugs and toxins

Hypersensitivity myocarditis is associated with many medications.[30][31][32][52][53][54]​​

Drugs and toxic exposures that are known to cause myocarditis include anthracyclines (e.g., doxorubicin, daunorubicin, epirubicin, idarubicin), fluoropyrimidines (e.g., fluorouracil, capecitabine), immunotherapies (e.g., ipilimumab, tremelimumab, nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, and trastuzumab), arsenic, zidovudine, carbon monoxide, ethanol, iron, interleukin-2, cocaine, amphetamine, smallpox or mpox vaccine, SARS-CoV-2 (COVID-19) mRNA vaccine (may occur with other types of COVID-19 vaccines), catecholamines (e.g., adrenaline, noradrenaline, dopamine), cyclophosphamide, heavy metals (copper, iron, lead), radiation, antibiotics (penicillins, cephalosporins, sulfonamides), amphotericin B, thiazide diuretics, anticonvulsants (carbamazepine, phenytoin, phenobarbital), digoxin, lithium, amitriptyline, clozapine, snake venom, bee venom, black widow spider venom, scorpion venom, and wasp venom.

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