Acute Myocarditis

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.

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.

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.

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).

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.

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).

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.

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.

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: $\geq$ 14 leukocytes/mm $^{2}$ (including up to 4 monocytes/mm $^{2}$ ) PLUS CD3+ T-lymphocytes $\geq$ 7 cells/mm $^{2}$ . Fulminant: >50 leukocytes/mm $^{2}$ .

No specific medical therapy exists; primary focus is supportive and symptomatic heart failure management.

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.

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.

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.

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.

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.