What is the diagnostic approach for a patient with suspected myocarditis?

Diagnostic Approach for Suspected Myocarditis

Myocarditis should be clinically suspected when a patient presents with ≥1 clinical symptom (chest pain, dyspnea, palpitations, syncope) AND ≥1 diagnostic abnormality from different categories (ECG changes, elevated troponin, imaging abnormalities), after excluding coronary artery disease with ≥50% stenosis. 1

Initial Diagnostic Workup

Mandatory First-Line Tests

All patients with suspected myocarditis require three immediate tests: 2

• 12-lead ECG to identify QRS width >120 ms (predicts higher mortality/transplant risk), PR-segment depression with diffuse ST-elevation (suggests pericarditis), or low voltage with thickened LV walls (suggests myocardial edema) 1, 2

• Cardiac biomarkers including troponin I or T, creatine kinase, erythrocyte sedimentation rate, and C-reactive protein 1, 2. Note that troponin was elevated in only 34% of biopsy-proven acute myocarditis cases in the US Myocarditis Treatment Trial, so normal troponin does NOT exclude myocarditis, particularly in subacute presentations 1, 2

• Transthoracic echocardiography to assess for regional/global wall motion abnormalities, systolic or diastolic dysfunction, ventricular dilatation, increased wall thickness, pericardial effusion, or intracavitary thrombi 1, 2

Critical Exclusion Step

Coronary angiography must be performed to exclude obstructive coronary disease (≥50% stenosis) before confirming myocarditis diagnosis, especially in patients with infarct-like presentation. 1

Advanced Diagnostic Imaging

Cardiac MRI - The Definitive Noninvasive Test

Cardiac MRI has Class I indication from the European Society of Cardiology for myocarditis assessment and should be performed in hemodynamically stable patients. 1, 2

The 2018 Updated Lake Louise Criteria require BOTH: 1

• ≥1 T2-based criterion (myocardial edema): T2-weighted imaging showing myocardium >2X signal intensity compared to skeletal muscle, or T2 mapping 1

• ≥1 T1-based criterion (myocardial injury): Late gadolinium enhancement (LGE) in epicardial or mid-wall pattern (NOT endocardial/subendocardial which suggests ischemia), or T1 mapping, or early gadolinium enhancement indicating hyperemia 1

CMR has 78% sensitivity and 88% specificity for myocardial inflammation and is particularly valuable for detecting inflammation in regions not accessible to biopsy. 2

Endomyocardial Biopsy Indications

Endomyocardial biopsy is the definitive diagnostic method but is NOT routinely required for clinical management in most cases. 2

Biopsy is indicated (Class I) in these specific scenarios: 1, 2

• Acute fulminant myocarditis (<2 weeks) with hemodynamic compromise requiring inotropes or mechanical circulatory support 1

• New-onset heart failure (2 weeks to 3 months) with dilated ventricle AND new ventricular arrhythmias, AV block II-III, or failure to respond to standard therapy within 1-2 weeks 1

• Refractory sustained ventricular tachyarrhythmias or aborted cardiac arrest 2

• Suspected giant cell myocarditis (sensitivity 80-85%) or cardiac sarcoidosis 1, 2

Pre-procedural CMR localization of inflammatory changes reduces sampling errors and improves diagnostic yield. 1 The sensitivity increases when immunoperoxidase stains (anti-CD3, anti-CD68, anti-HLA) are used 1

Risk Stratification and Mandatory Hospital Admission

These patients require immediate hospital admission with continuous ECG monitoring: 2, 3

• Any ventricular arrhythmias or heart block 2
• Hemodynamic instability or signs of acute heart failure 2, 3
• Progressive wall motion abnormalities with deteriorating LV function 2
• Persistent or fluctuating troponin concentrations 2
• Widening QRS complex or frequent non-sustained ventricular tachycardia 2

Patients with fulminant myocarditis (severe dysfunction with refractory arrhythmias) should be evaluated at an advanced heart failure center for potential mechanical circulatory support. 2, 3

Ruling Out Myocarditis

Myocarditis can be effectively ruled out ONLY when ALL four criteria are met: 2

1. No cardiac symptoms (no chest pain, dyspnea, palpitations, syncope, fatigue)
2. Normal troponin levels
3. Normal ECG (no ST changes, T-wave abnormalities, conduction delays, arrhythmias, low voltage)
4. Normal echocardiography (no wall motion abnormalities, preserved function, no wall thickening, no effusion)

Critical Pitfalls to Avoid

Never rely on a single normal test to exclude myocarditis: 2

• Troponin can be normal in subacute/chronic presentations 2
• ECG may be normal in up to 10% of cases 2
• Echocardiography has lower sensitivity than CMR 2

Special caution for patients on immune checkpoint inhibitor therapy: normal cardiac enzymes cannot rule out myocarditis, as these patients can develop life-threatening myocarditis with associated myasthenia gravis or myositis. 2

Diagnostic Algorithm Summary

1. Initial assessment: ECG + troponin + echocardiography 2
2. If abnormal: Exclude coronary disease with angiography 1
3. If coronaries normal: Perform cardiac MRI using 2018 Lake Louise Criteria 1
4. If high-risk features present: Hospital admission with continuous monitoring 2, 3
5. If life-threatening presentation: Consider endomyocardial biopsy 1, 2

The diagnostic window for optimal CMR sensitivity is within a few weeks from symptom onset, as inflammatory changes evolve and may resolve. 1