What is the appropriate workup for a patient with suspected myocarditis?

Workup for Myocarditis

Initial Clinical Assessment and Immediate Actions

All patients with suspected myocarditis require immediate cardiac troponin measurement, 12-lead ECG, and transthoracic echocardiography, as these three tests form the diagnostic foundation and should be obtained urgently. 1

Essential Laboratory Testing

• Cardiac troponin (I or T) must be obtained immediately—troponin I is preferred when skeletal muscle disease coexists, as it is more specific for cardiac injury 1, 2
• Creatine kinase (CK) and CK-MB should be measured, as reported cases invariably show elevations 1
• Brain natriuretic peptide (BNP) is essential—levels >500 pg/mL indicate significant concern and will be elevated in cases with decreased ejection fraction 1, 2
• Inflammatory markers including erythrocyte sedimentation rate and C-reactive protein, though nonspecific, can support the diagnosis 1

Critical caveat: Normal cardiac enzymes cannot reliably exclude myocarditis, making comprehensive evaluation essential even with reassuring initial biomarkers 2

Electrocardiographic Findings to Identify

The ECG should be scrutinized for 1, 3:

• Conduction abnormalities: First- to third-degree AV block, bundle branch block, or intraventricular conduction delay (QRS >120 ms predicts higher risk of death or transplantation) 1
• ST-segment and T-wave changes: Diffuse ST elevation and PR depression suggest associated pericarditis 1
• Arrhythmias: Atrial fibrillation, ventricular tachycardia/fibrillation, sinus arrest, or frequent premature beats 1
• Low voltage: Especially with thickened LV walls on echo suggests myocardial edema 1
• QTc prolongation 2

Echocardiographic Assessment

Transthoracic echocardiography must evaluate for 1:

• Regional or global systolic/diastolic dysfunction with or without ventricular dilatation 1
• Wall motion abnormalities (global or regional) 1
• Increased wall thickness secondary to edema 1
• Pericardial effusion 1
• Intracavitary thrombi 1
• Decreased left or right ventricular ejection fraction 1

Advanced Imaging: Cardiac MRI

Cardiac MRI is the preferred advanced imaging modality and should be performed if clinical syndrome suggests myocarditis, cardiac troponin is elevated, or ECG shows abnormalities. 1, 2, 3

Cardiac MRI findings diagnostic for myocarditis include 1, 3:

• Late gadolinium enhancement (LGE) in epicardial or mid-wall pattern (subendocardial pattern suggests ischemia instead) 1
• Myocardial edema on T2-weighted sequences 1
• Updated Lake Louise Criteria or native T1-mapping abnormalities 3

LGE is the strongest independent predictor of sudden cardiac death and mortality, making cardiac MRI crucial for risk stratification 4, 5

Endomyocardial Biopsy Indications

Endomyocardial biopsy remains the gold standard but is reserved for specific high-risk scenarios: 1, 3

Perform biopsy when patients have 1:

• Requirement for inotropic support or mechanical circulatory support
• Mobitz type 2 second-degree or higher heart block
• Sustained or symptomatic ventricular tachycardia
• Failure to respond to guideline-based therapy
• Rapidly deteriorating cardiac function
• Suspected giant cell myocarditis (requires specific immunosuppression)
• Fulminant presentation with hemodynamic compromise
• Evaluation for cardiac transplantation candidacy 3

Important principle: When clinical suspicion is high, treatment should be offered empirically before confirmatory biopsy results are obtained 1

Critical Monitoring Requirements

Because of the possibility of life-threatening arrhythmias or heart block, early cardiology involvement and continuous telemetry monitoring must be instituted immediately. 1, 4

• Transfer to advanced heart failure center capable of mechanical circulatory support if hemodynamic instability exists 4
• Active, ongoing cardiology consultation to discuss risk/benefit of treatments 2

Essential Exclusions Before Diagnosis

Acute coronary syndrome and stress-induced cardiomyopathy must be excluded, especially in patients with chest pain, heart failure, or new arrhythmia. 1, 3

This may require 1:

• Cardiac stress testing
• Coronary angiography (to exclude coronary stenosis ≥50%) 1

Additional Workup Considerations

When Immune Checkpoint Inhibitor-Related Myocarditis is Suspected

Evaluate for concurrent conditions that frequently co-occur 1, 2:

• Myositis: Check CK, aldolase, ESR, CRP (median CK 2650 IU/L in myositis) 2
• Myasthenia gravis: Present in 12.5% of cases—look for ptosis, diplopia, bulbar symptoms (dysphagia, dysarthria, dysphonia) 2
• Respiratory muscle weakness: Assess pulmonary function 1, 2

Viral Serology and Other Testing

• Viral serology is generally not recommended as routine testing provides only circumstantial evidence and lacks correlation with myocardial viral presence 3
• Consider HIV testing in appropriate clinical contexts, as HIV-associated cardiomyopathy remains relevant 1

Diagnostic Criteria Summary

Myocarditis is clinically suspected when ≥1 clinical presentation (chest pain, dyspnea, fatigue, palpitations, syncope) combines with ≥1 diagnostic criterion from different categories (ECG changes, elevated troponin, imaging abnormalities) in the absence of obstructive coronary disease or other explanatory causes. 1, 3

Common Pitfalls to Avoid

• Do not rely on normal troponin alone—only 34% of histologically confirmed acute myocarditis cases had elevated troponin I in older assays (high-sensitivity assays may improve detection) 1
• Do not delay treatment waiting for biopsy confirmation when clinical suspicion is high 1
• Do not miss concurrent myositis or myasthenia gravis in immune checkpoint inhibitor patients—these significantly worsen prognosis 1, 2
• Do not discharge patients with suspected myocarditis without telemetry monitoring and cardiology evaluation—arrhythmias can be life-threatening 1, 4