Is physiology testing, such as Fractional Flow Reserve (FFR) or instant wave-free ratio (iFR), reliable in patients with severe aortic stenosis?

Reliability of Physiology Testing in Severe Aortic Stenosis

Fractional Flow Reserve (FFR) is more reliable than instantaneous wave-free ratio (iFR) for assessing coronary lesions in patients with severe aortic stenosis, though neither has been formally validated in this population and both have important limitations related to altered hemodynamics.

Key Physiological Concerns in Severe AS

The fundamental challenge is that severe aortic stenosis profoundly alters coronary hemodynamics in ways that affect pressure-based indices:

• Coronary flow reserve (CFR) is reduced in AS patients even with normal coronary arteries due to myocardial hypertrophy and abnormal microvascular function 1
• FFR assumptions may be violated because the calculation assumes constant minimal microvascular resistance during hyperemia, but AS causes heterogeneous microcirculatory responses 1
• Neither FFR nor iFR has been validated in populations with severe AS, as these patients were typically excluded from landmark trials 2, 3

FFR Performance in Severe AS

FFR demonstrates superior reliability compared to iFR in this population:

• FFR shows good correlation with myocardial perfusion imaging (SPECT) in AS patients, with an area under the curve of 0.91 and negative predictive value of 95% for detecting ischemia 4
• FFR values remain stable before and after transcatheter aortic valve implantation (TAVI), with no significant change at 6-month follow-up (0.84 vs 0.86, p=0.72), suggesting measurements are not substantially distorted by the valve stenosis 5
• FFR-guided management is safe with no increase in major adverse cardiac events, death, myocardial infarction, or revascularization rates up to 5 years compared to angiography-guided treatment 6
• Low reclassification rate after TAVI: only 22% of lesions were FFR-positive before TAVI versus 30% after (p=0.219), indicating reasonable stability 5

iFR Performance in Severe AS

iFR shows significant limitations in the AS population:

• Poor agreement with myocardial perfusion imaging: iFR demonstrated only 59% agreement with SPECT compared to FFR's 85% (p=0.014) 4
• High false-positive rate: 39% of iFR measurements were false positives (negative SPECT but iFR <0.89) compared to only 12% for FFR (p=0.011) 4
• Significant reclassification after TAVI: RFR (resting full-cycle ratio, similar to iFR) improved significantly from 0.88 to 0.92 (p=0.003) after valve replacement, with 64% of lesions positive before TAVI dropping to 33% after (p=0.003), indicating substantial measurement instability 5
• Lower ischemic threshold may be needed: Using an iFR cutoff of 0.82 instead of the standard 0.89 improved agreement with SPECT to 73% 4

Practical Hybrid Approach

A tailored strategy combining both indices can optimize decision-making:

• Use iFR for initial screening with extreme values: iFR >0.93 has 98.4% negative predictive value to exclude FFR-significant stenosis, and iFR <0.83 has 91.3% positive predictive value to identify FFR-significant stenosis 3
• Reserve FFR for intermediate iFR values (0.83-0.93) to confirm functional significance 3
• This hybrid approach spares 63% of patients from adenosine while maintaining 97% agreement with FFR lesion classification 3

Clinical Decision Algorithm

When assessing coronary lesions in severe AS:

1. Measure iFR first in intermediate lesions (40-90% diameter stenosis) 3
2. If iFR >0.93: Defer revascularization (high confidence) 3
3. If iFR <0.83: Proceed with revascularization (high confidence) 3
4. If iFR 0.83-0.93: Perform FFR with adenosine for definitive assessment 3
5. Use FFR ≤0.80 as the treatment threshold rather than relying on iFR alone 5, 4

Important Caveats

• Aortic valve area matters: Diagnostic accuracy of all pressure-based indices decreases significantly when aortic valve area is <0.60 cm² 7
• Timing considerations: If possible, perform physiological assessment after TAVI rather than before, as this eliminates the confounding effects of the valve stenosis 5
• Long-term mortality concern: Meta-analyses show a 2% absolute increase in all-cause mortality at 5 years with iFR-guided management compared to FFR in general populations, though the mechanism remains unclear 2, 8
• FFR still superior to angiography alone: Despite limitations, FFR-guided decisions result in appropriate downgrading of disease severity and reduced unnecessary bypass grafting without increasing adverse events 6