Definition & Epidemiology
- Inflammatory heart disease associated with cardiac dysfunction.
- Characterized by myocardial injury and subsequent host immune system activation.
- Incidence: 1–1.95/100,000/year in children.
- High mortality rate in severe cases; frequent cause of terminal heart failure requiring mechanical circulatory support (MCS) or transplant.
Pathophysiology
Disease progression involves three distinct phases:
- Phase 1 (Invasion): Pathogenic trigger (virus/bacteria) invades myocardium. Causes direct myocardial necrosis and apoptosis.
- Phase 2 (Subacute): Activation of innate immune system (natural killer cells, macrophages, T-cells). T-cell mediated elimination of virus-infected cardiomyocytes causes further degradation.
- Phase 3 (Healing): Fibrosis of damaged myocardium. Virus persistence and ongoing immune reaction cause loss of functional structure. Possible transition into Dilated Cardiomyopathy (DCM).
- Age-dependent spread: Diffuse pancarditis in infants/toddlers. Focal myocardial involvement in adolescents.
Etiology
| Category | Specific Agents/Causes |
|---|---|
| Viral (Most Common) | Coxsackieviruses (A/B), Echovirus, Adenovirus, Parvovirus B19, Epstein-Barr virus (EBV), Cytomegalovirus (CMV), Influenza A/B, Human herpes virus-6 (HHV-6), SARS-CoV-2 (COVID-19). |
| Vaccine-Associated | mRNA COVID-19 vaccination, Smallpox vaccine. |
| Bacterial/Other Infectious | Diphtheria (toxic myocarditis with circulatory collapse), Beta-hemolytic streptococcus (Rheumatic fever), Borrelia burgdorferi (Lyme disease), Trypanosoma cruzi (Chagas disease), Fungal infections. |
| Immune/Autoimmune | Kawasaki disease, Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis, Churg-Strauss syndrome, Hypereosinophilic syndrome, Giant cell myocarditis. |
| Toxic/Drug-Induced | Anthracyclines, Immune checkpoint inhibitors, Cocaine, Heavy metals (copper, iron), Venoms. |
| Genetic Predisposition | 12% of affected children carry pathogenic autosomal recessive variants in cardiac genes (BAG3, DSP, LMNA, MYH7, TTN), predisposing vulnerable myocardium to inflammation. |
Clinical Presentation
Presentation is highly heterogeneous and strongly age-dependent.
| Age Group | Characteristic Clinical Findings |
|---|---|
| Infants & Toddlers (<2 years) | Fulminant presentation. Fever, apathy, feeding intolerance, sweating, gastrointestinal symptoms. Overt heart failure: respiratory distress, tachycardia, hypotension, gallop rhythm, cardiac murmur, cardiogenic shock. |
| Older Children & Adolescents | Insidious or acute. Chest pain (predominant), respiratory distress, palpitations, easy fatigability, syncope/near-syncope. Often exhibit preserved or mildly depressed left ventricular (LV) function. |
| General/Advanced Signs | Hepatomegaly, peripheral edema, pulmonary wheezes/rales, apical systolic murmur (mitral insufficiency), pericardial friction rub (if myopericarditis). |
Diagnostic Evaluation
Laboratory Studies
- Cardiac Biomarkers: Troponin T/I frequently elevated. Indicates myocardial injury/inflammation. Low sensitivity (71%) and specificity (86%) for pediatric myocarditis diagnosis. Poor prognostic correlation with LV function.
- Heart Failure Markers: BNP/NT-proBNP useful to assess ventricular dysfunction severity and predict clinical course.
- Viral Testing: Viral genome detection via Polymerase Chain Reaction (PCR) (blood, tracheal secretions, stool) preferred. Serology obsolete.
Electrocardiogram (ECG)
- Abnormal in 93% of cases. Highly nonspecific.
- Sinus tachycardia (46%) out of proportion to fever/pain.
- Bradycardia with AV block (22%), Right bundle branch block.
- Repolarization changes, nonspecific ST-segment and T-wave changes (mimicking ischemia).
- Low-voltage QRS (indicates myocardial edema or effusion damping).
Imaging (Chest X-Ray & Echocardiography)
- CXR: Cardiomegaly (in 60%), pulmonary venous congestion, pulmonary edema, pleural effusions.
- Echocardiography: Diminished ventricular systolic function, chamber enlargement, mitral insufficiency, pericardial effusion. Diastolic dysfunction may precede systolic impairment.
Cardiac Magnetic Resonance Imaging (CMR)
- Noninvasive reference standard.
- Detects edema, hyperemia, capillary leak, and myocyte necrosis.
- Late Gadolinium Enhancement (LGE) pattern: typically subepicardial or midwall (inferolateral LV wall, basal septum). Differentiates from ischemic defects (subendocardial).
| Lake Louise Criteria (CMR) | Description |
|---|---|
| Original Criteria (2009) | Requires 2 of 3: (1) T2-weighted edema, (2) Early Gadolinium Enhancement (EGE) hyperemia, (3) LGE necrosis/scar. |
| Revised Criteria (2019) | Requires “2 of 2” combination: - T1-based criterion: Prolonged T1 time, increased extracellular volume, or LGE presence. - T2-based criterion: Increased T2 relaxation time or increased T2-weighted signal intensity. |
Endomyocardial Biopsy (EMB)
- Reserved for new-onset cardiomyopathy, suspected giant cell myocarditis, or clinical deterioration.
- Complications: Perforation, pericardial tamponade, hemopericardium, arrhythmia.
| Histological Criteria | Definition |
|---|---|
| Dallas Criteria | Histological evidence of inflammatory infiltrates associated with myocyte degeneration/necrosis of nonischemic origin. Limited by sampling bias/interobserver variability. |
| World Heart Federation (WHF) | Quantitative immunohistochemistry: 14 leukocytes/mm (including up to 4 monocytes/mm) PLUS CD3+ T-lymphocytes 7 cells/mm. Fulminant: >50 leukocytes/mm. |
Differential Diagnosis
- Anomalous Left Coronary Artery from Pulmonary Artery (ALCAPA).
- Idiopathic Dilated Cardiomyopathy (DCM).
- Carnitine deficiency / Inborn errors of metabolism.
- Kawasaki disease.
- Endocardial Fibroelastosis (EFE).
- Acute pericarditis / Myopericarditis.
Management
No specific medical therapy exists; primary focus is supportive and symptomatic heart failure management.
Medical Therapy
- Heart Failure: Angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, loop diuretics, aldosterone antagonists. Contraindicated in fulminant cardiovascular collapse.
- Inotropes: Milrinone, levosimendan. Use caution due to proarrhythmic potential.
- Antiarrhythmics: Amiodarone for significant atrial/ventricular arrhythmias.
Mechanical Circulatory Support
- Intensive care admission, mechanical ventilation.
- Extracorporeal Membrane Oxygenation (ECMO) or Ventricular Assist Device (VAD) indicated for cardiogenic shock as a bridge to recovery or cardiac transplantation.
Immunomodulating & Antiviral Therapy
- Intravenous Immunoglobulin (IVIG): 1–2 g/kg over 24–48 hours. May reduce in-hospital mortality and improve myocardial inflammation, though evidence remains debated.
- Corticosteroids/Immunosuppressants: Controversial. May increase viral replication. Considered useful specifically in virus-negative inflammation, giant cell myocarditis, or cardiac sarcoidosis.
- Antivirals: Ganciclovir or Valganciclovir strictly for confirmed CMV myocarditis.
Sports Clearance & Activity Restriction
- Strict restriction from competitive sports and strenuous physical activity during acute phase.
- Clearance criteria to resume sports (minimum 3–6 months post-illness):
- Normal ventricular systolic function.
- Normalization of serum markers (injury, inflammation, heart failure).
- Absence of clinically relevant arrhythmias on Holter monitor and graded exercise ECG.
- Absence of active inflammation on CMR.
Prognosis & Follow-up
- Variable clinical course. Newborns with symptomatic enteroviral myocarditis face 75% mortality.
- 10–50% of patients recover full ventricular function; remainder progress to chronic DCM or require transplantation.
- Poor Prognostic Risk Factors:
- Female gender,
- age <2 years,
- LVEF <30% at presentation,
- presence of extensive septal LGE on CMR.
- COVID-19 mRNA vaccine-associated myocarditis demonstrates excellent prognosis with full recovery typically noted by 90 days. Follow-up echocardiography required.