How do you rule out myocarditis as a differential diagnosis?

How to Rule Out Myocarditis as a Differential Diagnosis

To rule out myocarditis, you must systematically exclude the combination of cardiac symptoms, elevated troponin, and characteristic findings on ECG/imaging while ensuring coronary artery disease is not the cause. 1

Essential Exclusion Criteria

Myocarditis can be effectively ruled out if ALL of the following are absent: 1, 2

• No cardiac symptoms: absence of chest pain (pericarditic or pseudoischemic), dyspnea, palpitations, syncope, or new-onset fatigue 1
• Normal troponin levels: cardiac troponin I or T within normal limits 1
• Normal ECG: no ST-segment changes, T-wave abnormalities, conduction delays, arrhythmias, or low voltage 1
• Normal echocardiography: no wall motion abnormalities, preserved ventricular function, no wall thickening, no pericardial effusion 1

Systematic Diagnostic Approach to Rule Out Myocarditis

Step 1: Initial Clinical Assessment

Look for specific cardiac symptoms that suggest myocarditis: 1

• Acute chest pain (pericarditic or mimicking MI)
• New-onset dyspnea (days to 3 months) or worsening dyspnea
• Palpitations or syncope
• Unexplained fatigue with or without heart failure signs

If the patient is completely asymptomatic, you need ≥2 diagnostic criteria from different categories to suspect myocarditis. 1

Step 2: Obtain 12-Lead ECG and Cardiac Biomarkers

ECG findings that would support myocarditis (and thus prevent ruling it out): 1, 2

• First- to third-degree AV block or bundle branch block
• ST-segment elevation without reciprocal depression, or diffuse ST/T-wave changes
• Prolonged QRS duration (>120 ms)
• New Q waves, low voltage, or frequent premature beats
• Ventricular or supraventricular arrhythmias

Cardiac biomarkers: 1

• Elevated troponin T or I (preferably high-sensitivity assay above 99th percentile) strongly suggests myocardial injury
• Normal troponin does NOT completely rule out myocarditis but makes it significantly less likely 1

Step 3: Echocardiography

Perform transthoracic echocardiography to assess: 1, 2

• Regional or global wall motion abnormalities (often in non-coronary distribution)
• Left or right ventricular systolic/diastolic dysfunction
• Increased wall thickness (suggesting edema)
• Pericardial effusion
• Intracavitary thrombi

Normal echocardiography with normal function and no structural abnormalities significantly reduces the likelihood of myocarditis. 1

Step 4: Exclude Coronary Artery Disease

Critical caveat: You cannot diagnose myocarditis if significant coronary disease is present. 1

• In men >50 years and women >55 years with cardiac symptoms and elevated troponin, coronary angiography or CT angiography should be performed to exclude coronary stenosis ≥50% 1
• Myocarditis presents with chest pain and troponin elevation mimicking acute MI but with normal coronary arteries 1

Step 5: Cardiac MRI (If Initial Tests Are Equivocal)

Cardiac MRI is the most sensitive non-invasive test and should be performed in hemodynamically stable patients when suspicion remains: 1, 2

Classic CMR findings that confirm myocarditis (preventing exclusion): 1, 2

• Increased T2 signal (myocardial edema/inflammation)
• Increased native T1 signal (fibrosis or inflammation)
• Non-ischemic late gadolinium enhancement pattern (epicardial or mid-wall, not subendocardial)
• Regional wall motion abnormalities in non-coronary distribution

The 2018 Lake Louise Criteria require ≥1 T2-based criterion PLUS ≥1 T1-based criterion to diagnose myocardial inflammation. 2

Normal CMR with no edema, no late gadolinium enhancement, and normal T1/T2 mapping effectively rules out acute myocarditis. 1, 2

Definitive Exclusion Algorithm

Myocarditis is effectively ruled out when: 1, 2

1. No qualifying clinical presentation (no cardiac symptoms, or symptoms explained by other conditions)
2. AND normal troponin levels
3. AND normal ECG (or ECG changes explained by other conditions)
4. AND normal echocardiography (normal ventricular function, no wall motion abnormalities, no structural changes)
5. AND/OR normal cardiac MRI (if performed, showing no edema, no characteristic late gadolinium enhancement, normal T1/T2)

Critical Pitfalls to Avoid

Do not rely on a single normal test to rule out myocarditis: 1

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

Recognize that sampling error limits endomyocardial biopsy: 2, 3

• Biopsy has low sensitivity due to patchy inflammation
• A negative biopsy does not definitively exclude myocarditis
• Biopsy is reserved for life-threatening presentations or when specific etiologies (giant cell, eosinophilic) are suspected 1, 2

Consider alternative diagnoses that can mimic myocarditis: 1

• Acute coronary syndrome (must exclude with angiography in appropriate age groups)
• Takotsubo cardiomyopathy
• Acute pericarditis without myocardial involvement
• Dilated cardiomyopathy from other causes
• Valvular disease, congenital heart disease, hyperthyroidism

In patients with immune checkpoint inhibitor therapy, normal cardiac enzymes cannot always rule out myocarditis: 1

• These patients can have life-threatening myocarditis with associated myasthenia gravis or myositis
• Maintain high suspicion even with borderline findings
• Check creatine kinase if myositis is suspected 1

When Myocarditis Cannot Be Ruled Out

If ≥1 clinical presentation AND ≥1 diagnostic criterion from different categories are present, myocarditis remains in the differential and requires further evaluation with cardiac MRI or consideration of endomyocardial biopsy. 1, 2

Patients with ventricular arrhythmias, heart block, or progressive ventricular dysfunction require hospital admission and intensive monitoring regardless of other findings, as they are at high risk for sudden cardiac death. 2, 4