Serum ACE Level Sensitivity for Cardiac Sarcoidosis
Serum ACE levels have extremely poor sensitivity for diagnosing cardiac sarcoidosis and should not be relied upon for this purpose. While the 2020 American Thoracic Society guidelines do not specifically address serum ACE testing for cardiac sarcoidosis screening or diagnosis, the available evidence demonstrates that this biomarker is inadequate for detecting cardiac involvement 1.
Diagnostic Performance
The sensitivity of serum ACE for cardiac sarcoidosis is approximately 6.7% in biopsy-proven cases, making it essentially useless as a diagnostic tool for cardiac involvement 2. This contrasts sharply with its performance in systemic sarcoidosis, where sensitivity ranges from 42-78% depending on the cut-off value used 3, 4, 5.
Key Evidence Points:
In isolated or predominant cardiac sarcoidosis, only 3 out of 45 patients (6.7%) had elevated serum ACE levels, even during the active phase of disease 2
Serum ACE elevation is more common when pulmonary involvement is present, suggesting that cardiac-predominant disease does not significantly elevate this marker 2
For general sarcoidosis (not cardiac-specific), sensitivity ranges from 59-78% when using optimized cut-off values, but this does not translate to cardiac involvement 3, 4, 5
Recommended Diagnostic Approach for Cardiac Sarcoidosis
The American Thoracic Society provides clear guidance on appropriate testing modalities 1:
Screening in Asymptomatic Patients:
Baseline ECG is recommended as the only routine screening test for patients with extracardiac sarcoidosis without cardiac symptoms (sensitivity 9%, specificity 97%) 1
TTE and 24-hour Holter monitoring are NOT recommended for routine screening due to insufficient sensitivity (25% and 50% respectively) 1
Diagnostic Testing When Cardiac Involvement is Suspected:
Cardiac MRI with late gadolinium enhancement (LGE) is the preferred first-line test with sensitivity of 75-100% and specificity of 75-77% 1
Cardiac PET scanning is the alternative when MRI is unavailable or inconclusive, showing abnormalities in 52% of patients with sarcoidosis 1
Important Clinical Caveats
Several factors further limit the utility of serum ACE in cardiac sarcoidosis:
ACE inhibitor therapy significantly reduces serum ACE levels, creating false-negative results in patients on these common cardiovascular medications 6
Different ACE inhibitors affect levels variably, with zofenopril causing less suppression than perindopril, enalapril, or ramipril 6
Normal ACE levels do not exclude active cardiac sarcoidosis, as demonstrated by the 93.3% of biopsy-proven cases with normal values 2
Alternative inflammatory markers (ESR and hs-CRP) are more sensitive for detecting active cardiac sarcoidosis, though they lack specificity 2
Clinical Bottom Line
Do not order serum ACE levels to diagnose or screen for cardiac sarcoidosis. Instead, use ECG for initial screening in asymptomatic patients with known extracardiac sarcoidosis, and proceed directly to cardiac MRI (or cardiac PET if MRI unavailable) when cardiac involvement is suspected based on symptoms, ECG abnormalities, or clinical presentation 1. The extremely low sensitivity of serum ACE (6.7%) makes it clinically irrelevant for cardiac sarcoidosis evaluation, even though it may have some utility in monitoring systemic disease activity 2.