Diagnosis of Myocarditis

1. Clinical Presentation

• Acute myocarditis: Gradual onset, moderate ventricular dysfunction
• Fulminant myocarditis: Abrupt onset within 2 weeks of viral illness; hemodynamic compromise, hypotension, global hypofunction on echo, thickened ventricular walls (edema)
• Giant cell myocarditis: Progressive heart failure, arrhythmias, or heart block refractory to standard therapy; survival < 6 months without immunosuppression
• Chronic active myocarditis: Insidious onset, older adults, eventually resembles restrictive or dilated cardiomyopathy

— Braunwald's Heart Disease, pp. 263–278

2. Diagnostic Criteria — Three-Tiered Classification

3. Biomarkers

• Elevated in myocarditis, predominantly in fulminant and acute presentations
• High-sensitivity troponin T has superior predictive value for acute myocarditis when MI is excluded
• Higher troponin levels correlate with lower LVEF and greater severity
• Sensitivity was low with older assays; improved with high-sensitivity assays

• CK-MB >29.5 ng/mL predicts in-hospital death (sensitivity 83%, specificity 73%) in adult acute/fulminant myocarditis
• NT-proBNP: Elevated in acute DCM due to myocarditis; declines rapidly with recovery
• CRP, ESR, leukocyte count: Elevated but non-specific
• IL-10 and soluble Fas: Associated with increased risk of death in adults
• Anti-heart antibodies: Predict increased risk of death/transplant, but tests are not standardized
• Circulating viral antibody titers: Do NOT correlate with tissue viral genomes — rarely of diagnostic use

— Braunwald's Heart Disease, p. 270; Fuster and Hurst's The Heart, p. 1459

4. Electrocardiography

• Sinus tachycardia (most common)
• Nonspecific repolarization changes (ST-T wave abnormalities)
• PR-segment depression + diffuse ST elevation → suggests myopericarditis
• QRS duration >120 ms and Q waves → associated with high risk of cardiac death or need for transplant
• Ventricular premature complexes and arrhythmias (including VT, heart block)

5. Echocardiography

• Dilated cardiomyopathy pattern: Dilated, spherical ventricle with reduced systolic function (chronic)
• Fulminant myocarditis pattern: Small or normal chamber size with reversible ventricular hypertrophy/thickening (due to myocardial edema)
• Segmental wall motion abnormalities: May mimic acute MI/STEMI (important differential)
• Right ventricular dysfunction: Less common but indicates poor prognosis

6. Cardiac MRI (CMR) — Lake Louise Criteria

1. T2-based criteria: Regional or global increased T2 signal (myocardial edema)
2. T1-based criteria: Increased T1 signal and/or extracellular volume (ECV) + late gadolinium enhancement (LGE) in a non-ischemic pattern

• Pericardial effusion on CMR
• Systolic LV dysfunction
• Pericardial LGE (myopericarditis)

— Braunwald's Heart Disease, p. 278, Table 55.1 (Lake Louise Criteria)

7. Endomyocardial Biopsy (EMB)

• Active myocarditis: Inflammatory infiltrate of the myocardium with necrosis and/or degeneration of adjacent myocytes not typical of ischemic damage
• Borderline myocarditis: Infiltrate present without myocyte necrosis (requires repeat biopsy)
• No myocarditis: No inflammatory infiltrate

• Sampling error — patchy inflammation may be missed
• Average diagnostic yield ~10% in DCM (range 0.5–67%)
• Right ventricular sampling is standard; LV EMB may be performed if needed

• Immunohistochemistry: Detection of activated lymphocytes/macrophages (CD3+, CD68+) with >14 inflammatory cells/mm² is considered positive
• PCR for viral genomes: B19V, adenovirus, CMV, enterovirus, EBV, HSV 1/2/6, influenza A/B
• Higher B19V copy numbers or evidence of active viral replication required for significance

• New unexplained heart failure with hemodynamic compromise (fulminant)
• New unexplained heart failure with arrhythmias, heart block, or failure to respond to standard therapy within 1–2 weeks
• Suspected giant cell or eosinophilic myocarditis (requires tissue diagnosis for immunosuppression)

— Fuster and Hurst's The Heart, 15th Ed.; Braunwald's Heart Disease, pp. 270–278

8. Nuclear Imaging (¹⁸F-FDG-PET)

• Sensitivity ~46%, specificity ~81% for clinically suspected myocarditis
• Not recommended for routine use; may add functional information to structural imaging
• FDG accumulates in inflammatory cells — useful adjunct in sarcoid-related myocarditis
• Hybrid PET/MRI or PET/CT approaches are being developed to expand diagnostic yield

9. Differential Diagnosis

• Acute MI / ACS: Myocarditis causes chest pain without evolving ischemic ECG changes; normal coronary arteries on angiography (MINOCA pattern)
• Dilated cardiomyopathy: May be endpoint of myocarditis; biopsy distinguishes active inflammation
• Pericarditis/myopericarditis: PR depression, positional chest pain, pericardial rub, pericardial effusion
• Takotsubo cardiomyopathy: Regional wall motion pattern, stress precipitant

Summary Diagnostic Algorithm

Suspected myocarditis
        ↓
Clinical history + symptoms + viral prodrome
        ↓
ECG + Echocardiography + Troponin/CK-MB/NT-proBNP
        ↓
Cardiac MRI (Lake Louise Criteria)
   → T2 edema + T1/LGE in non-ischemic pattern = Probable myocarditis
        ↓
Endomyocardial Biopsy (if: fulminant, hemodynamic compromise,
  arrhythmia/heart block, refractory to treatment, suspected giant cell
  or eosinophilic myocarditis)
   → Dallas criteria + Immunohistochemistry + PCR = Definite myocarditis

Sources: Braunwald's Heart Disease, 2 Vol Set — A Textbook of Cardiovascular Medicine; Fuster and Hurst's The Heart, 15th Edition