Is intravascular imaging (IVI) indicated in patients with suspected coronary artery disease (CAD) and ambiguous vessels showing discordance between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) measurements?

Intravascular Imaging for FFR/iFR Discordance

When FFR and iFR measurements are discordant in ambiguous coronary vessels, intravascular imaging (IVUS or OCT) is not specifically indicated to resolve the discordance—instead, prioritize additional physiological assessment with coronary flow reserve (CFR) and microvascular resistance measurements to determine the true hemodynamic significance and guide revascularization decisions. 1

Understanding FFR/iFR Discordance

The 2024 ESC guidelines establish that both FFR (≤0.80) and iFR (≤0.89) are Class I, Level A recommendations for assessing intermediate stenoses, but they do not provide specific guidance for managing discordant results 1. The guidelines acknowledge that FFR and iFR can yield different results in the same lesion, with important clinical implications 1.

Key physiological insights:

• Discordant FFR/iFR measurements occur in approximately 20% of intermediate lesions, reflecting different hemodynamic states (hyperemic vs. resting) 2
• FFR low/iFR high discordance is associated with lower resting myocardial blood flow, independent of hyperemic flow 2
• FFR high/iFR low discordance suggests preserved hyperemic capacity despite resting flow limitations 2

Recommended Approach: Combined Pressure-Flow Assessment

The optimal strategy for resolving FFR/iFR discordance involves adding coronary flow measurements rather than anatomic imaging:

Primary Recommendation: CFR and Microvascular Assessment

• Measure CFR using thermodilution or Doppler techniques (abnormal if <2.0-2.5) to assess overall coronary vasodilatory capacity 1
• Calculate IMR (abnormal if ≥25 units) to evaluate microvascular resistance 1, 3, 4
• Determine hyperaemic stenosis resistance (HSR) by measuring pressure gradient divided by flow for comprehensive diagnostic assessment 1

Clinical Decision Algorithm Based on Combined Assessment

Concordant normal FFR and CFR (both normal):

• Excellent prognosis—defer revascularization 1
• No role for intravascular imaging 1

Discordant FFR and CFR:

• Abnormal FFR but normal CFR: Good clinical outcome up to 5 years if left untreated—defer revascularization 1
• Normal FFR but abnormal CFR with normal IMR: Suggests diffuse epicardial disease causing "low-flow" ischemia—consider medical optimization 1
• Normal FFR but abnormal CFR with elevated IMR (≥25): Indicates microvascular dysfunction—initiate medical therapy targeting microcirculation 1, 3, 4

Concordant abnormal FFR and CFR:

• Similar prognosis to concordant abnormal results—proceed with revascularization 1

Limited Role of Intravascular Imaging for Discordance

The guidelines do not recommend intravascular imaging specifically to resolve FFR/iFR discordance. IVUS is indicated only in specific anatomic scenarios:

When IVUS Should Be Considered

• Left main stenosis evaluation: IVUS should be considered (Class IIa, Level B) for intermediate left main stenoses regardless of physiological measurements 1
• Complex lesion PCI guidance: IVUS is recommended (Class I, Level A) when performing PCI on anatomically complex lesions including left main, bifurcations, and long lesions 1
• Post-PCI optimization: IVUS may be considered to identify high-risk patients or lesions amenable to additional treatment 1

Why IVUS Does Not Resolve Physiological Discordance

• IVUS minimum lumen area (MLA) shows only moderate correlation with FFR (r=0.34) 5
• MLA thresholds (<2.8 mm² for FFR <0.75; <3.2 mm² for FFR <0.8) have limited sensitivity (69-80%) and specificity (68-80%) 5
• Anatomic measurements cannot distinguish between epicardial stenosis severity and microvascular dysfunction, which is the primary cause of FFR/iFR discordance 2, 1
• IVUS provides structural information but cannot assess the functional hemodynamic significance that differs between FFR and iFR 6

Critical Pitfalls to Avoid

Do not assume anatomic severity predicts physiological significance:

• In the PRIME-FFR and FAME studies, 31% of 40-49% stenoses were hemodynamically significant by FFR 1
• Visual angiographic assessment correlates poorly with FFR/iFR measurements 1

Do not ignore microvascular contribution:

• Patients with discordant FFR/iFR often have underlying microvascular dysfunction that IVUS cannot detect 2, 1
• Elevated IMR (≥25 units) indicates structural microvascular disease requiring different management than epicardial stenosis 3, 4

Do not perform systematic imaging of all vessels:

• Systematic wire-based pressure assessment of all vessels is Class III (not recommended) 1
• Selective assessment of intermediate lesions only is the recommended approach 1

Practical Clinical Implementation

When encountering FFR/iFR discordance in an intermediate stenosis:

1. Measure CFR immediately using continuous or bolus thermodilution during the same procedure 1
2. Calculate IMR to assess microvascular function (Pd × mean transit time during hyperemia) 1, 4
3. Apply the decision algorithm:
   • If CFR normal (≥2.0): Defer revascularization regardless of FFR 1
   • If CFR abnormal with normal IMR: Consider diffuse disease, optimize medical therapy 1
   • If CFR abnormal with elevated IMR: Diagnose microvascular dysfunction, initiate targeted medical therapy 3, 4
   • If both FFR and CFR abnormal: Proceed with revascularization 1

Reserve IVUS for:

• Left main stenoses where anatomic assessment complements physiology 1
• Guiding complex PCI procedures after the decision to revascularize has been made 1
• Post-PCI optimization to ensure adequate stent expansion 1

Evidence Quality Considerations

The 2024 ESC guidelines represent the most current evidence (Class I, Level A for FFR/iFR) 1. The recommendation for combined pressure-flow assessment is supported by Class IIa, Level B evidence 1. Recent PET perfusion studies demonstrate that FFR/iFR combinations frequently misclassify ischemia compared to quantitative myocardial blood flow, with 38-49% of vessels with low FFR or iFR exceeding ischemic thresholds 2. This underscores the importance of comprehensive physiological assessment rather than relying on anatomic imaging to resolve discordance.