What are the diagnostic criteria for cardiac sarcoidosis?

Diagnostic Criteria for Cardiac Sarcoidosis

Cardiac sarcoidosis diagnosis requires three components: compatible clinical/imaging findings, histopathologic confirmation of nonnecrotizing granulomas (from cardiac or extracardiac tissue), and exclusion of alternative causes—with cardiac MRI being the preferred initial imaging modality over echocardiography or PET for suspected cases. 1

Core Diagnostic Framework

The diagnosis of cardiac sarcoidosis follows the general sarcoidosis diagnostic triad but with cardiac-specific manifestations 1:

1. Compatible Clinical Presentation

Highly Probable Cardiac Features 1:

• Treatment-responsive cardiomyopathy or atrioventricular node block with no other risk factors
• Spontaneous or inducible ventricular tachycardia in patients without traditional risk factors
• New-onset third-degree AV block in young or middle-aged adults

Probable Cardiac Features 1:

• Reduced left ventricular ejection fraction with no identifiable risk factors (detected by echocardiography or MRI)
• Increased inflammatory activity in the heart on MRI, PET, or gallium scanning

2. Imaging Criteria

Cardiac MRI with Late Gadolinium Enhancement (LGE) is the preferred initial test 1:

• CMR-LGE has direct histopathological correlation with cardiac sarcoidosis 1
• The absence of CMR-LGE predicts no serious cardiac events for at least 3 years 1
• The extent of LGE correlates with risk of future major adverse cardiac events 1
• Prevalence of CMR-LGE abnormalities approaches the autopsy-confirmed prevalence of cardiac sarcoidosis 1

When CMR is unavailable or inconclusive, dedicated cardiac PET is recommended 1:

• Requires dietary preparation to suppress physiologic myocardial glucose uptake 1
• Provides both diagnostic and prognostic information 1

Transthoracic echocardiography has lower sensitivity and should not be relied upon as the primary diagnostic modality 1.

3. Histopathologic Confirmation

Endomyocardial biopsy has limited sensitivity (only 19.2% diagnostic yield) 2:

• Noncaseating granulomas are the definitive finding 1
• Higher yield (36.4%) in patients with dilated cardiomyopathy-like presentation versus only 6.7% in those with isolated conduction disturbances 2
• Negative biopsy does not exclude cardiac sarcoidosis 2

Extracardiac tissue sampling is often more practical 3:

• Definitive histopathological diagnosis for sarcoidosis was established in 86.6% of cardiac sarcoidosis patients through extracardiac sites 3
• Compact, tightly formed collections of epithelioid histiocytes and multinucleated giant cells with minimal to no necrosis favor sarcoidosis 1

4. Exclusion of Alternative Diagnoses

Critical exclusions before confirming diagnosis 4, 5:

• Tuberculosis must be actively excluded through microbiological testing, molecular testing, and BAL analysis, as both present with granulomatous inflammation but require opposite treatments 4
• Tuberculosis shows caseating granulomas versus nonnecrotizing granulomas in sarcoidosis 4
• Other granulomatous conditions including fungal infections, giant cell myocarditis, and dilated cardiomyopathy must be considered 6

Established Diagnostic Criteria Sets

Three major criteria systems exist for cardiac sarcoidosis 3:

1. Japanese Ministry of Health and Welfare (JMHW) criteria - includes CMR as a minor diagnostic criterion 1, 3
2. Heart Rhythm Society (HRS) criteria - relies on either CMR or cardiac PET for diagnosis 1, 3
3. World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) criteria - categorizes as highly probable, probable, or possible cardiac involvement 3

All three criteria perform comparably, with JMHW and WASOG performing equally well even in tuberculosis-endemic settings 3.

Recommended Diagnostic Algorithm

For patients with extracardiac sarcoidosis and suspected cardiac involvement 1:

• First-line: Cardiac MRI with LGE for both diagnostic and prognostic information
• Second-line: Dedicated cardiac PET if CMR unavailable or results inconclusive
• Avoid relying on transthoracic echocardiography alone due to lower sensitivity

For patients presenting with cardiac symptoms without known sarcoidosis 1:

• Evaluate for highly specific features (treatment-responsive cardiomyopathy, unexplained VT, new AV block in young adults)
• Obtain cardiac MRI with LGE
• Pursue extracardiac tissue diagnosis when possible (higher yield than endomyocardial biopsy)
• Actively exclude tuberculosis and other infections

Critical Pitfalls

Do not withhold treatment based on negative endomyocardial biopsy 2:

• Patients with sarcoidosis and significant cardiac involvement should be treated despite negative myocardial biopsies given the low 19.2% diagnostic yield 2

Sensitivity and specificity of imaging are biased estimates 1:

• Both CMR and PET are components of the reference standards used in diagnostic criteria, making true test performance difficult to assess 1

Tuberculosis misdiagnosis is potentially fatal 4:

• Misdiagnosing TB as sarcoidosis leads to immunosuppression when antimicrobial therapy is needed 4
• Always perform microbiological exclusion before initiating corticosteroid therapy 4