How accurate are Instantaneous Wave-Free Ratio (IFR) or Fractional Flow Reserve (FFR) measurements in patients with severe aortic stenosis?

FFR and iFR Accuracy in Severe Aortic Stenosis

Both FFR and iFR demonstrate reduced accuracy in patients with severe aortic stenosis, with FFR showing more stable measurements but both indices requiring cautious interpretation and potentially adjusted thresholds in this population.

Key Diagnostic Performance Issues

FFR Performance in Severe AS

• FFR values remain relatively stable before and after transcatheter aortic valve implantation (TAVI), making it the more reliable index in this population 1
• In the NOTION-3 substudy, FFR measurements showed no significant change from baseline to 6 months post-TAVI (0.84 vs 0.86, P=0.72), with only 22% lesion reclassification rate 1
• FFR demonstrated poor diagnostic accuracy (65%) specifically in lesions with severe obstructions in AS patients, though accuracy improved post-TAVI 2
• The standard FFR threshold of ≤0.80 may need adjustment to 0.82 to optimally detect hemodynamically significant lesions (iFR≤0.89) in AS patients 3

iFR Performance in Severe AS

• iFR shows significant individual variation after TAVI despite unchanged mean values, with 15% of lesions crossing the 0.89 threshold post-valve replacement 2
• Mean iFR values remained identical before and after TAVI (0.89±0.12 vs. 0.89±0.12, P=0.66), but individual measurements varied widely and erratically 2
• iFR improved significantly from 0.88 at baseline to 0.92 at 6-month follow-up post-TAVI (P=0.003), resulting in a 64% to 33% reduction in positive lesions and higher reclassification rate compared to FFR 1
• The optimal iFR cut-off value in AS patients may be substantially lower at 0.73 rather than the standard 0.89 threshold 4

Clinical Decision Algorithm

When to Use FFR vs iFR in AS Patients

1. For pre-TAVI coronary assessment requiring stable measurements: prioritize FFR over iFR 1

   • FFR shows lower reclassification rates (22% vs 64%) at follow-up 1
   • FFR measurements are less influenced by the hemodynamic changes induced by valve replacement 2

2. If iFR is used in AS patients, apply adjusted thresholds:

   • Consider using iFR ≤0.73 rather than ≤0.89 as the ischemic threshold 4
   • Recognize that standard iFR thresholds may overestimate lesion severity in AS 4

3. Expect higher variation with greater transaortic gradients:

   • Higher iFR variation correlates with larger transaortic gradient drops after TAVI 2
   • Patients with very severe AS (mean gradient ≥60 mmHg) will have less reliable iFR measurements 2

Integration with Guideline Recommendations

• The 2024 ESC guidelines recommend FFR or iFR for intermediate stenoses (40-90% diameter) to guide revascularization decisions 5
• Both indices are Class I, Level A recommendations for assessing hemodynamic significance when non-invasive tests are inconclusive 5
• However, these guideline recommendations were not specifically validated in severe AS populations 5

Critical Pitfalls and How to Avoid Them

Pitfall #1: Using Standard Thresholds Without Adjustment

• The standard iFR threshold of ≤0.89 significantly overestimates ischemia in AS patients 4
• The optimal FFR threshold shifts from ≤0.80 to ≤0.82 in AS populations 3
• Solution: Apply population-specific cut-offs (FFR ≤0.82, iFR ≤0.73) when assessing AS patients 3, 4

Pitfall #2: Assuming iFR Stability Across Valve Intervention

• Individual iFR values show erratic variation post-TAVI despite stable mean values 2
• 15% of lesions cross the diagnostic threshold after valve replacement 2
• Solution: If revascularization decisions are deferred based on iFR, remeasure post-TAVI before finalizing management 2

Pitfall #3: Ignoring the Severity of AS When Interpreting Results

• Higher transaortic gradients correlate with greater iFR measurement variability 2
• Diagnostic accuracy is particularly poor (65%) in severely obstructed lesions 2
• Solution: Exercise greater caution with iFR interpretation in patients with mean gradients >60 mmHg 2

Comparative Diagnostic Accuracy

• Overall agreement between FFR and iFR in AS patients is good (Intraclass Correlation Coefficient 0.83) 3
• FFR has 97.7% accuracy in detecting iFR≤0.89 using adjusted threshold of 0.82 3
• iFR has 97.4% accuracy in detecting FFR≤0.80 using adjusted threshold of 0.88 3
• However, these accuracy metrics apply only when using adjusted, AS-specific thresholds rather than standard cut-offs 3

Practical Advantages and Limitations

FFR Advantages in AS

• More stable measurements across valve intervention 1
• Lower reclassification rates reduce uncertainty in management decisions 1
• Better validated in severe AS populations 1

iFR Theoretical Advantages

• No adenosine requirement eliminates hyperemic agent contraindications 5
• Diastolic-phase calculation theoretically better suited to AS flow patterns 4
• However, these theoretical benefits are offset by higher measurement variability in practice 2, 1

Long-term Outcome Concerns

• Meta-analyses show 2% absolute increase in all-cause mortality at 5 years with iFR-guided management compared to FFR, though not specifically in AS populations 5, 6
• This mortality difference was not associated with increased MI or revascularization rates 5, 6