Ischemia Prevalence in 25-50% Anatomical CAD by FFR
Lesions with 25-50% diameter stenosis rarely demonstrate hemodynamic significance by FFR, with the vast majority showing FFR values >0.80 and therefore not causing ischemia.
Evidence-Based Thresholds and Physiologic Significance
The relationship between anatomical stenosis severity and functional significance is well-established but highly variable in the intermediate range:
- For stenoses <50% diameter, only 31-35% are hemodynamically significant by FFR measurement 1
- The American College of Cardiology specifically defines intermediate lesions as 50-70% diameter stenosis, which require FFR assessment before intervention 1, 2
- Stenoses in the 25-50% range fall below the traditional intermediate threshold and are generally not expected to cause flow-limiting ischemia 3
Specific Data on Mild Stenoses
The FAMOUS-NSTEMI trial provides the most direct evidence for your question:
- This study specifically enrolled patients with stenoses ≥30% diameter (broader than typical trials that use ≥50% cutoffs) 3
- The purpose was explicitly to provide data on the relationship between "mild" lesions and FFR 3
- While exact percentages for the 25-50% subgroup are not reported, the study design acknowledges these lesions as "mild" and generally not flow-limiting 3
Clinical Decision Framework
For stenoses 25-50% diameter:
- FFR measurement is generally not indicated as these lesions rarely cause ischemia 3, 1
- The threshold for considering FFR assessment begins at 50% diameter stenosis (or 40% for some European guidelines) 3, 2
- An FFR ≤0.80 defines hemodynamically significant stenosis, but this threshold is applied to intermediate (50-70%) or higher grade lesions 3, 2
Important Caveats
Serial stenoses create additive hemodynamic effects:
- Multiple lesions each measuring <50% individually may collectively cause significant flow limitation 1
- This represents a critical pitfall where visual assessment alone underestimates functional significance 1
- In patients with diffuse disease or multiple mild lesions, FFR pullback tracings can identify cumulative ischemic burden 2
Practical Clinical Implications
The 25-50% stenosis range represents anatomically non-obstructive disease:
- These patients should receive aggressive risk factor modification and optimal medical therapy 3
- Revascularization of lesions without ischemia or FFR <0.80 is not recommended (Class III recommendation) 3
- A normal functional test (including FFR >0.80) is associated with <1% annual rate of cardiac death and MI 3