What tests are recommended for diagnosing autoimmune myocarditis?

Diagnostic Tests for Autoimmune Myocarditis

The recommended diagnostic workup for autoimmune myocarditis should include cardiac biomarkers (troponin, creatine kinase), inflammatory markers, autoantibodies, electrocardiogram, echocardiography, and cardiac MRI as the cornerstone tests. 1, 2

Initial Laboratory Evaluation

Cardiac-Specific Tests

• Cardiac biomarkers:
  • Troponin (preferably troponin I in cases with skeletal muscle involvement) 1
  • Creatine kinase (CK) 1, 2
  • Aldolase 1
  • LDH 2

Inflammatory Markers

• Erythrocyte sedimentation rate (ESR) 1, 2
• C-reactive protein (CRP) 1, 2
• White blood cell count 1

Autoantibody Testing

• Myocarditis-specific autoantibodies:

  • Anti-cardiac myosin antibodies 3, 4
  • Anti-TIF1γ (associated with severe disease) 2
  • Anti-MDA5 (associated with interstitial lung disease) 2
  • Anti-NXP2 (associated with calcinosis) 2
  • Anti-SRP (associated with necrotizing autoimmune myopathy) 2
  • Anti-Jo-1, anti-PL-7, anti-PL-12 (myositis-associated antibodies) 1, 2

• Additional autoantibody testing:

  • Antinuclear antibodies (ANA) 1
  • Anti-AChR and anti-striational antibodies (to evaluate possible concomitant myasthenia gravis) 1

Cardiac Imaging and Functional Assessment

Non-Invasive Imaging

• Electrocardiogram (ECG) - to detect:

  • ST-segment elevation
  • T-wave changes
  • Conduction abnormalities
  • Arrhythmias 1, 2

• Echocardiography - to assess:

  • Ventricular function and dimensions
  • Wall motion abnormalities
  • Wall thickness (may be increased due to edema)
  • Pericardial effusion 1, 2

• Cardiac MRI (CMR) - gold standard non-invasive test:

  • T2-weighted sequences to detect myocardial edema
  • T1-weighted sequences with gadolinium to detect hyperemia
  • Late gadolinium enhancement to detect myocardial fibrosis/necrosis 1

Invasive Testing

• Endomyocardial biopsy - considered the definitive diagnostic test:
  • Histological examination for inflammatory infiltrates
  • Immunohistochemistry for characterization of inflammatory cells
  • PCR for viral genome detection 1

Additional Considerations

Concomitant Evaluation

• Pulmonary assessment:

  • Pulmonary function tests with CO diffusion
  • Chest X-ray or HRCT (especially if interstitial lung disease suspected) 2

• Neuromuscular assessment:

  • Electromyography (EMG) if diagnosis is uncertain or overlap with neuromuscular disorders is suspected 2
  • MRI of affected muscles with T2-weighted/STIR sequences 2

Diagnostic Algorithm

1. First-line testing:

   • Cardiac biomarkers (troponin, CK)
   • Inflammatory markers (ESR, CRP)
   • ECG
   • Echocardiography

2. Second-line testing:

   • Cardiac MRI (if available)
   • Autoantibody panel (cardiac-specific and myositis-specific)

3. Confirmatory testing:

   • Endomyocardial biopsy (particularly in life-threatening cases or when diagnosis remains uncertain)

Important Clinical Considerations

• Myocarditis may present with chest pain (82-95% of cases), dyspnea (19-49%), or syncope (5-7%) 5
• Mortality rates are significantly higher when myocarditis occurs with concurrent myositis (approximately 20% vs. less than 10% in isolated myocarditis) 1
• Cardiac involvement should always be assessed in patients with suspected myositis, as the combination significantly worsens prognosis 1
• In immune checkpoint inhibitor-related myocarditis, symptoms typically occur early (median 25 days after treatment initiation) 1

Pitfalls to Avoid

• Do not rely solely on cardiac enzymes - normal cardiac enzyme levels cannot always rule out myocarditis 1
• Do not overlook cardiac involvement in patients with myositis - this combination significantly increases mortality risk 1, 2
• Do not delay cardiac MRI - it is the most sensitive non-invasive test for confirming acute myocarditis 1
• Do not miss associated conditions - check for concurrent myasthenia gravis or interstitial lung disease which may occur alongside autoimmune myocarditis 1

By following this comprehensive diagnostic approach, clinicians can effectively identify autoimmune myocarditis and initiate appropriate treatment to improve patient outcomes.