Diagnosis of Myocarditis

Essential Diagnostic Tests

The European Society of Cardiology recommends that all patients with suspected myocarditis undergo 12-lead ECG to look for QRS width >120 ms, PR-segment depression, and diffuse ST-elevation, which suggests associated pericarditis, or low voltage with thickened LV walls, which suggests myocardial edema 1
The European Society of Cardiology suggests that transthoracic echocardiography be used to assess for wall motion abnormalities, wall thickening, and ventricular function in patients with suspected myocarditis 2, 3, 4, 5
Cardiac biomarkers, including troponins, creatine kinase, erythrocyte sedimentation rate, and C-reactive protein, should be measured in patients with suspected myocarditis, as elevated levels can indicate myocardial injury 2, 3, 4, 5

Diagnostic Criteria

The European Society of Cardiology references the Caforio criteria, which require clinically suspected myocarditis if ≥1 clinical presentation AND ≥1 diagnostic criterion from different categories are present, excluding angiographically detectable coronary disease or other known cardiovascular causes 1, 6
The Caforio criteria include clinical presentations such as arrhythmias or heart block, which are associated with myocarditis 2, 3, 4, 5

Cardiac Magnetic Resonance Imaging

The European Society of Cardiology recommends that cardiac magnetic resonance (CMR) imaging be used to confirm acute myocarditis, even before endomyocardial biopsy, as it is highly sensitive and can detect characteristic patterns such as epicardial or mid-wall delayed gadolinium enhancement (DGE) 2, 3, 4, 5
CMR imaging can also detect myocardial edema using T2-weighted sequences, and early post-gadolinium T1-weighted sequences can increase diagnostic accuracy 1, 6

Endomyocardial Biopsy Indications

The European Society of Cardiology recommends that endomyocardial biopsy be performed in patients with life-threatening disease course, such as acute fulminant myocarditis with refractory ventricular tachyarrhythmias in severe acute heart failure 2, 3, 4, 5
Endomyocardial biopsy is also indicated in patients with hemodynamically compromising sustained ventricular arrhythmias or aborted cardiac arrest, and in patients with suspected giant cell myocarditis or sarcoidosis 4, 1, 6

Clinical Phenotyping for Risk Stratification

The European Society of Cardiology distinguishes two critical clinical settings: acute fulminant myocarditis and chronic inflammatory cardiomyopathy, which have different prognoses and treatment approaches 2, 3, 4, 5
Acute fulminant myocarditis is characterized by refractory malignant ventricular tachyarrhythmias with severe acute heart failure, and has an adverse short-term prognosis with early death from multisystem failure 2, 3, 4, 5

Warning Signs Requiring Hospital Admission

Patients with ventricular arrhythmias or heart block in acute myocarditis require prolonged ECG monitoring and mandatory hospital admission, as they are at high risk of sudden cardiac death 2, 3, 4, 5
Progressive wall motion abnormalities with deteriorating LV function, persistent or fluctuating troponin concentrations, widening QRS complex, and frequent non-sustained ventricular arrhythmias may precede sustained life-threatening arrhythmia, and require close monitoring and hospital admission 5

Diagnostic Approach to Myocarditis

Diagnostic Methods

The American Heart Association and American College of Cardiology recommend that endomyocardial biopsy is the definitive diagnostic method for myocarditis, providing histopathologic and molecular biological confirmation of myocardial inflammation 7, 8, 9
Endomyocardial biopsy is the only method that provides definitive histopathologic confirmation of myocarditis through direct tissue analysis, immunohistochemical evaluation, and viral genome detection 7
The American College of Cardiology states that definitive confirmation of specific causes of myocarditis requires histopathologic and molecular biological evaluation of myocardial tissue samples 10, 11, 12, 13

Role of Imaging

Cardiac MRI provides strong noninvasive evidence for myocardial inflammation with 78% sensitivity and 88% specificity 10, 11, 12, 13
The European Society of Cardiology gives Cardiac MRI a Class I indication for assessment of myocarditis 10, 11, 12
Cardiac MRI is particularly useful for regions not accessible to endomyocardial biopsy and for excluding alternate diagnoses 10, 11, 12

Diagnostic Criteria

The 2018 Lake Louise Criteria indicate myocardial inflammation when Cardiac MRI demonstrates at least one T2-based criterion plus at least one T1-based criterion 10, 11, 12, 13
This combination increases specificity for acute myocardial inflammation 10, 12, 13

Limitations of Endomyocardial Biopsy

Endomyocardial biopsy has low sensitivity due to sampling error, as inflammation may be patchy and missed by limited tissue sampling 8, 9
Endomyocardial biopsy is not routinely required for clinical management in most cases 7

Diagnosing Myocarditis

Essential Exclusion Criteria

The American Heart Association recommends that myocarditis can be effectively ruled out if all of the following are absent: no cardiac symptoms, normal troponin levels, normal ECG, and normal echocardiography 14, 15
The American College of Cardiology suggests that the absence of cardiac symptoms such as chest pain, dyspnea, palpitations, syncope, or new-onset fatigue is essential in ruling out myocarditis 14, 15
Normal troponin levels, defined as cardiac troponin I or T within normal limits, are crucial in excluding myocarditis 14, 15
A normal ECG, characterized by no ST-segment changes, T-wave abnormalities, conduction delays, arrhythmias, or low voltage, is necessary to rule out myocarditis 14, 16
Normal echocardiography, defined as no wall motion abnormalities, preserved ventricular function, no wall thickening, and no pericardial effusion, is essential in excluding myocarditis 14, 16

Systematic Diagnostic Approach to Rule Out Myocarditis

The American Heart Association recommends a systematic diagnostic approach to rule out myocarditis, starting with initial clinical assessment, followed by obtaining 12-lead ECG and cardiac biomarkers, and then performing echocardiography 14, 15
The European Society of Cardiology suggests that cardiac biomarkers, such as elevated troponin T or I, strongly suggest myocardial injury and should be considered in the diagnostic approach 14, 15
The American College of Cardiology recommends that echocardiography be performed to assess regional or global wall motion abnormalities, left or right ventricular systolic/diastolic dysfunction, increased wall thickness, pericardial effusion, and intracavitary thrombi 14, 16

Critical Pitfalls to Avoid

The American Heart Association warns that relying on a single normal test to rule out myocarditis is insufficient, as troponin can be normal in subacute or chronic presentations, ECG may be normal in up to 10% of cases, and echocardiography has lower sensitivity than CMR 14
The American College of Cardiology suggests that alternative diagnoses, such as acute coronary syndrome, Takotsubo cardiomyopathy, acute pericarditis, dilated cardiomyopathy, valvular disease, congenital heart disease, and hyperthyroidism, should be considered when myocarditis cannot be ruled out 14, 15

Special Considerations

The American Heart Association recommends that patients with immune checkpoint inhibitor therapy be approached with caution, as normal cardiac enzymes cannot always rule out myocarditis, and these patients can have life-threatening myocarditis with associated myasthenia gravis or myositis 17, 14
The European Society of Cardiology suggests that 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 14

Diagnostic Approach for Suspected Myocarditis

Initial Diagnostic Workup

The American College of Cardiology and the American Heart Association recommend that 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 18, 19
The American College of Cardiology recommends that all patients with suspected myocarditis require three immediate tests, including 12-lead ECG to identify QRS width >120 ms, PR-segment depression with diffuse ST-elevation, or low voltage with thickened LV walls, cardiac biomarkers including troponin I or T, and transthoracic echocardiography to assess for regional/global wall motion abnormalities, systolic or diastolic dysfunction, ventricular dilatation, increased wall thickness, pericardial effusion, or intracavitary thrombi 18, 19

Advanced Diagnostic Imaging

The European Society of Cardiology has given cardiac MRI a Class I indication for myocarditis assessment and should be performed in hemodynamically stable patients 20
The 2018 Updated Lake Louise Criteria require BOTH ≥1 T2-based criterion (myocardial edema) and ≥1 T1-based criterion (myocardial injury) for the diagnosis of myocarditis, as recommended by the American College of Cardiology and the European Society of Cardiology 19, 21

Endomyocardial Biopsy Indications

The American College of Cardiology recommends that endomyocardial biopsy is indicated (Class I) in specific scenarios, including acute fulminant myocarditis with hemodynamic compromise, new-onset heart failure with dilated ventricle and new ventricular arrhythmias, or refractory sustained ventricular tachyarrhythmias, as recommended by the American Heart Association 18, 19
Pre-procedural CMR localization of inflammatory changes reduces sampling errors and improves diagnostic yield, as recommended by the American College of Cardiology 19

Inflammatory Marker Thresholds for Acute Myocarditis in Influenza A

Diagnostic Thresholds

Marked elevation of both ESR and CRP strongly supports acute myocarditis – ESR typically > 60 mm/hr and CRP > 3.0 mg/dL (often > 7.0 mg/dL); normal values of both markers essentially rule out acute myocarditis except in rare isolated chorea cases. Evidence level: expert consensus 22
ESR > 60 mm/hr is the preferred cutoff for myocarditis, although some experts consider an ESR > 30 mm/hr still consistent with the diagnosis. Evidence level: expert consensus 22
CRP must exceed the upper limit of normal, and in acute myocarditis it commonly reaches > 7.0 mg/dL (or higher). Evidence level: expert consensus 22

Interpretation of Marker Patterns

Concurrent ESR > 60 mm/hr and CRP > 7.0 mg/dL defines a pattern consistent with acute myocarditis and warrants immediate cardiac evaluation (e.g., ECG and echocardiography). Evidence level: expert consensus 22
Normal or minimally elevated ESR and CRP together make acute myocarditis highly unlikely when accompanied by normal troponin, ECG, and echocardiography. Evidence level: expert consensus 22

Pre‑treatment Considerations

ESR, CRP, and cardiac troponins should be measured before starting corticosteroid therapy, because steroids can rapidly suppress these inflammatory markers and obscure diagnostic interpretation. Evidence level: expert consensus 23