Instantaneous Wave-Free Ratio (iFR)
Definition
iFR is a resting pressure-wire index that measures the ratio of distal coronary pressure to aortic pressure during a specific diastolic period (the "wave-free period") when microvascular resistance is naturally low and stable. Unlike FFR, iFR does not require adenosine administration. A value ≤0.89 is considered hemodynamically significant (ischemic); normal is >0.89.
Key Concepts
Physiology
- iFR exploits the naturally low microvascular resistance during mid-to-late diastole (wave-free period) — the same pressure gradient physiology as FFR but without pharmacologic hyperemia
- Normal iFR >0.89 indicates non-flow-limiting stenosis; iFR ≤0.89 indicates hemodynamically significant stenosis warranting revascularization
- iFR and FFR are concordant in ~80% of lesions; discordance most common in intermediate lesions (0.75–0.80 FFR / 0.86–0.93 iFR)
Advantages over FFR in STEMI
- Does not require adenosine — avoids adenosine-related side effects (AV block, chest pain, dyspnea)
- Adenosine response is diminished in STEMI due to elevated baseline flow, potentially producing false-negative FFR values
- Shorter procedure time; can be performed at the same sitting as primary PCI without additional pharmacologic preparation (sources/iFR-PPCI-iMODERN-NEJM-2026, rating: very high)
iFR in STEMI — Specific Caveats
- Elevated resting flow in STEMI may produce false-positive iFR values (lower iFR than true physiologic significance): reported mean difference 0.01 (not significant) and false-positive rate ~11%
- This effect is small but may contribute to higher revascularization rates in iFR-guided vs MRI-guided strategies (sources/iFR-PPCI-iMODERN-NEJM-2026, rating: very high)
iFR vs Cardiac Stress MRI — iMODERN Trial
- iMODERN (NEJM 2026): First RCT comparing immediate iFR-guided PCI vs deferred MRI-guided PCI for nonculprit lesions in STEMI (n=1,146)
- iFR identified ischemia in 44.9% of lesions; MRI identified ischemia in 20.2% of patients — approximately 2× difference
- Primary composite (death/recurrent MI/HF hospitalization) at 3 years: 9.3% vs 9.8% (HR 0.95; P=0.81) — no superiority for immediate iFR
- The iFR arm had lower HF hospitalization (HR 0.24) and stroke/TIA (HR 0.36), but higher stent thrombosis (1.7% vs 0.6%)
- The difference in lesion detection rates is attributed to fundamentally different targets: iFR measures epicardial pressure drop; MRI assesses myocardial perfusion territory (sources/iFR-PPCI-iMODERN-NEJM-2026, rating: very high)
iFR vs FFR — Existing Evidence
- DEFINE-FLAIR and iFR-SWEDEHEART trials (NEJM 2017): iFR and FFR equivalent for MACE at 1 year in stable CAD
- iFR-guided deferral of revascularization is safe when iFR >0.89 (MACE ~4% at 1 year — comparable to FFR deferral)
- FFR-guided complete revascularization in STEMI/very-high-risk NSTEMI was also neutral at 4.8 years (FULL REVASC, NEJM 2024; HR 0.93, P=0.53), consistent with the iMODERN finding — both physiologic tools appear insufficient to improve hard outcomes when used to guide nonculprit PCI in ACS (sources/ffrpci-mi-fullrevasc-nejm-2024, rating: very high)
Contradictions / Open Questions
- Overdetection vs clinical significance: iFR detects roughly twice as many ischemic lesions as MRI in the STEMI context — yet this does not translate to superior outcomes. Whether iFR systematically overdiagnoses or MRI systematically underdiagnoses remains debated (sources/iFR-PPCI-iMODERN-NEJM-2026, rating: very high)
- STEMI physiology: Elevated resting flow in STEMI may make iFR unreliable in the acute setting — ideally reassessed after hemodynamic stabilization (weeks later), though this defeats the practical advantage of immediate guidance
- Ideal cutoff in STEMI: The ≤0.89 threshold was validated in stable CAD; optimal iFR threshold in acute STEMI may differ given altered physiology
Connections
- Related to concepts/Multivessel-PCI-STEMI-Timing — iFR used as guidance modality in iMODERN
- Related to concepts/Intracoronary-Imaging-Guided-PCI — physiologic and imaging guidance are complementary tools in PCI decision-making
- Related to entities/Chronic-Coronary-Disease — iFR primarily validated in stable/chronic CAD settings