What is the full workup for suspected immune checkpoint inhibitor (ICI) myocarditis?

Comprehensive Workup for Suspected Immune Checkpoint Inhibitor Myocarditis

The full workup for suspected immune checkpoint inhibitor (ICI) myocarditis must include cardiac biomarkers (troponin and BNP), ECG, echocardiography, and cardiac MRI, with prompt cardiology consultation for any abnormal findings. 1

Initial Diagnostic Evaluation

Laboratory Testing

• Cardiac biomarkers:
  • Troponin I or T (elevated in >90% of cases)
  • Brain natriuretic peptide (BNP) or N-terminal pro-BNP
  • Total creatine kinase (CK)
  • CK-MB

Cardiac Testing

• 12-lead ECG - Look for:

  • New conduction abnormalities
  • QTc prolongation
  • ST-T wave changes
  • Arrhythmias

• 2D Echocardiography - Evaluate:

  • Left ventricular function (may be normal despite myocarditis)
  • Wall motion abnormalities
  • Pericardial effusion

• Cardiac MRI - Gold standard for non-invasive diagnosis:

  • Look for myocardial edema
  • Late gadolinium enhancement
  • Increased T1/T2 signal

Additional Testing

• Chest imaging (X-ray or CT) to exclude:

  • Pulmonary embolism
  • Pneumonitis
  • Pulmonary edema

• Fasting lipid profile - Important to distinguish between atherosclerosis-related troponin elevation and potential myocarditis 1

Advanced Diagnostic Procedures

Endomyocardial Biopsy

• Consider when diagnosis remains uncertain after non-invasive testing
• Particularly important in severe cases or when alternative diagnoses are being considered

Additional Testing for Associated Conditions

• Autoimmune panel - Patients with pre-existing autoimmune disease have higher risk of severe myocarditis 2
• Anti-acetylcholine receptor antibodies - Associated with concurrent myasthenia gravis and more severe presentations 2

Timing Considerations

• Highest risk period is within first 1-2 months of ICI therapy
• Median time to onset is 16 days (range 1-196 days) after ICI initiation 3
• Typically develops after approximately 2 cycles of ICI therapy (range 1-13 cycles) 3

Risk Stratification

• Higher risk factors for severe myocarditis:
  • Pre-existing autoimmune disease (45% vs 6% in non-severe cases)
  • Higher troponin levels (42-fold ULN vs 3.55-fold ULN in non-severe cases)
  • Presence of anti-acetylcholine receptor antibodies
  • Combination ICI therapy (higher risk than monotherapy) 2

Monitoring Protocol

• Baseline cardiac evaluation before ICI therapy initiation
• Serial ECGs and cardiac biomarker testing during treatment, particularly in high-risk patients
• Immediate evaluation for any cardiac symptoms during ICI therapy

Management Considerations

• Patients with suspected or confirmed myocarditis should be admitted for cardiac monitoring
• Confirmed cases require immediate discontinuation of ICI therapy and high-dose corticosteroids (1 mg/kg methylprednisolone IV) 1
• Mortality rate is approximately 48%, with potentially better outcomes when additional immunosuppressive agents beyond steroids are used 3

Common Pitfalls to Avoid

• Missing the diagnosis: ICI myocarditis can present with normal ejection fraction
• Delayed treatment: Early intervention is critical as condition can rapidly deteriorate
• Inadequate monitoring: Serial troponin measurements are essential even in asymptomatic patients
• Overlooking concurrent immune-related adverse events: Particularly myasthenia gravis, which can complicate treatment 4
• Using infliximab: This may increase risk of death from cardiovascular causes and should be avoided 3

Remember that ICI myocarditis is a medical emergency with high mortality risk, requiring prompt diagnosis and aggressive management with cardiology involvement.