Myocarditis

Definition

• Goldman-Cecil Medicine, Ch. 47
• Robbins & Kumar Basic Pathology

Epidemiology

• Incidence is difficult to estimate because presentation ranges from asymptomatic ECG changes to hemodynamic collapse and sudden death.
• Population prevalence estimates: 1 in 100,000 to 1 in 10,000.
• Postmortem studies identify myocarditis in up to 12% of young victims of sudden cardiac death.
• Some degree of subclinical myocarditis is detected in nearly 10% of routine autopsies.
• Up to 5% of patients with viral illness may exhibit some form of myocarditis.

Etiology

Viral (most common in Western world)

• Enteroviruses (Coxsackievirus A and B) historically predominated
• Parvovirus B19 and human herpesvirus 6 (HHV-6) are now increasingly detected
• Others: adenovirus, H1N1 influenza, SARS-CoV-2, CMV, HIV, Epstein-Barr, hepatitis C, rubella, varicella-zoster, RSV, rabies

Protozoal

• Trypanosoma cruzi (Chagas disease) - the most common infective myocarditis worldwide, endemic in Central/South America; about 300,000 infected individuals live in the US. Cardiac involvement occurs in the vast majority; 10% die in the acute phase, with others developing progressive CHF and arrhythmia 10-20 years later.
• Toxoplasma gondii - especially in immunocompromised hosts

Bacterial

• Corynebacterium diphtheriae, Mycoplasma pneumoniae, Salmonella, Staphylococcus, Mycobacterium, meningococcus, Borrelia burgdorferi (Lyme disease - occurs in ~5% of Lyme patients, usually self-limited conduction system disease)

Spirochetal

• Treponema pallidum, Borrelia, Leptospira

Fungal

• Aspergillus, Candida, Cryptococcus, Histoplasma

Parasitic

• Trichinella spiralis (most common helminthic cause), Echinococcus, Taenia solium

Immune-mediated / Non-infectious

• Systemic autoimmune diseases: SLE, systemic sclerosis, polymyositis/dermatomyositis, sarcoidosis, eosinophilic granulomatosis with polyangiitis (EGPA)
• Giant cell myocarditis (rare, often fulminant)
• Drug hypersensitivity (hypersensitivity myocarditis): penicillin, sulfonamides, tetracycline, methyldopa - characterized by eosinophilic infiltrates
• mRNA COVID-19 vaccination: rare, especially in male adolescents and young adults, more often after the second dose, typically within one week; most cases recover uneventfully
• Heart transplant rejection

Pathogenesis

1. Acute stage: direct cytotoxicity, focal myocyte necrosis
2. Subacute stage: rise in humoral factors, autoimmune injury
3. Chronic stage: diffuse myocardial fibrosis, potential progression to dilated cardiomyopathy (DCM)

• ROSEN's Emergency Medicine, Ch. 68

Morphology / Histopathology

• Viral myocarditis: edema, interstitial inflammatory infiltrates (predominantly lymphocytic, often patchy), and myocyte injury
• Hypersensitivity myocarditis: interstitial and perivascular infiltrates with lymphocytes, macrophages, and a high proportion of eosinophils

Endomyocardial biopsy showing myocarditis: dense lymphocytic infiltrate between myocardial fibers. (ROSEN's Emergency Medicine, Fig. 68.3)

• Robbins & Kumar Basic Pathology, p. 375

Clinical Presentation

Differential Diagnosis

• Acute myocardial infarction (most important)
• Other infectious processes with cardiac involvement
• Takotsubo cardiomyopathy
• Dilated cardiomyopathy
• Arrhythmogenic cardiomyopathy

Diagnostic Workup

ECG

• Sinus tachycardia (most common)
• Widened QRS, low voltages
• Prolonged QT interval
• AV block
• ST/T-wave changes that may simulate an AMI pattern but extend beyond the distribution of a single coronary artery

Biomarkers

• Troponin may be elevated (timing is variable; a negative troponin does not exclude the diagnosis)
• WBC, CRP, ESR: not diagnostically useful
• Serologic studies: rising antibody titers to specific pathogens; PCR on tissue

Echocardiography

• Reduced LVEF, global hypokinesis, regional wall motion abnormalities not following coronary anatomy
• May be normal or show modest changes
• Pericardial effusion may coexist

Cardiac MRI (CMR) - key non-invasive modality

1. T2-weighted imaging: subepicardial or myocardial edema
2. Early gadolinium enhancement: inflammatory hyperemia
3. Late gadolinium enhancement (LGE): non-ischemic pattern - typically subepicardial, most often in the lateral and/or inferior wall

Acute myocarditis on CMR. (A) T2-weighted STIR short-axis image: subepicardial hyperintense area (arrow) in the inferior wall. (B) Late enhancement image: contrast uptake in a non-ischemic subepicardial pattern. Emergency coronary angiography was negative. (Grainger & Allison's Diagnostic Radiology, Fig. 14.29)

Coronary Angiography

• Usually shows normal arteries; performed to exclude obstructive CAD when ACS cannot be ruled out by history/ECG alone

Endomyocardial Biopsy

• Still the gold standard for formal diagnosis
• Limited by variable sensitivity and specificity due to patchy inflammation and sampling error
• MRI guidance can improve yield by targeting abnormal regions
• Biopsy may identify alternative causes (e.g., giant cell myocarditis, amyloid) or confirm inflammatory etiology
• Not routinely performed; reserved for cases where the result will change management

Management

Heart Failure

• Diuretics: furosemide (10 mg IV initially in diuretic-naive patients)
• Vasodilators: nitroglycerine for CHF symptom relief
• Inotropes: dobutamine (2 mcg/kg/min) for severe hemodynamic compromise
• ACE inhibitors (e.g., lisinopril): long-term benefit, especially in Chagas-related heart failure
• Mechanical circulatory support: VADs (temporary/percutaneous) as a bridge to recovery or transplant; ECMO for refractory cases
• Cardiac transplantation: for non-recovery, though outcomes are worse than transplant for other indications (lower 1-year survival, higher rejection rates)

Rhythm Management

• Rate and rhythm control as needed
• Amiodarone (600 mg/day) for ventricular dysrhythmias
• ICD consideration in patients with persistent ventricular arrhythmias

Activity Restriction

• Athletes with myocarditis should not compete until signs of inflammation have resolved and LV function has normalized - exercise worsens myocarditis in animal models

Immunosuppression

• No proven benefit in viral myocarditis in clinical trials
• May be appropriate for autoimmune causes (SLE, giant cell myocarditis, sarcoidosis)
• Corticosteroids, azathioprine, cyclosporine have been studied without consistent benefit in viral disease

Specific Causes

• Chagas disease: benzmidazole (ages 2-12 yr: 5-8 mg/kg/day x 60 days), nifurtimox (8-15 mg/kg/day depending on age)
• Drug hypersensitivity: withdraw the offending agent
• Autoimmune disease: optimize immunosuppressive therapy

Prognosis and Complications

• 10-20% rate of major adverse cardiac events overall
• Complications: ventricular dysrhythmias, LV aneurysm, CHF, progression to dilated cardiomyopathy (DCM)
• Myocarditis accounts for up to 16% of adult DCM cases and up to 46% in children
• Fulminant presentation in children has a higher rate of in-hospital death, transplantation, and persistent LV dysfunction compared with non-fulminant disease
• Patients are at elevated risk for sudden cardiac death (SCD), including those who are asymptomatic

Recent Evidence (PubMed 2024-2026)

• A 2024 systematic review and meta-analysis in JAMA Oncology (PMID 39172480) found that immune checkpoint inhibitor-related cardiotoxicity - including myocarditis - is increasingly recognized in cancer patients and carries a high mortality rate.
• A 2025 systematic review (PMID 38221509) in ESC Heart Failure examined autopsy findings in fatal COVID-19 vaccine-induced myocarditis cases, confirming histopathological evidence of myocarditis in these rare events.