Five-year outcomes from the two major trials indicated higher mortality with instantaneous wave-free ratio (iFR)-guided revascularization compared to fractional flow reserve (FFR)-guidance, despite similar outcomes in deferred patients. This discrepancy likely comes from discordant revascularization decisions.

To precisely assess the characteristic differences, including microvascular function, between resting full-cycle ratio (RFR)-guided and FFR-guided strategies, we performed virtual randomization, specially targeting discordant lesions, to simulate RFR-guided and FFR-guided groups. Microvascular resistance reserve (MRR) was utilized to assess microvascular function independently of epicardial stenosis.

Methods and Results

We retrospectively analyzed 837 intermediate lesions in 620 patients, from our institutional physiological database, with a median follow-up of 6.9 years. Using thresholds of FFR ≤ 0.80 and RFR ≤ 0.89, lesions were categorized into concordant-high (n = 280), high-RFR/low-FFR (n = 105), low-RFR/high-FFR (n = 93), and concordant-low (n = 359) groups. Discordant and concordant lesions were virtually randomized into RFR- and FFR-guided groups. Patients were followed for 6.9 (4.6–9.1) years. Age, sex, percentage diameter stenosis, and MRR differed significantly between the RFR/FFR discordant groups. After randomization, no significant characteristic-based differences were observed between both concordant and discordant virtual RFR/FFR-guided groups. Compared with the patients with FFR-guided would-be-revascularized lesions, those with RFR-guided would-be-revascularized lesions with discordant RFR/FFR results had significantly lower MRR, higher age, and tended to be female. MRR significantly predicted all-cause death in the total and would-be-revascularized cohorts, but not in deferred patients.

Conclusions

In discordant lesions of virtually randomized RFR- and FFR-guided strategies, RFR-guided would-be-revascularized lesions were associated with impaired microvascular function (low MRR) compared with FFR-guided would-be-revascularized lesions, which may underlie the reported increased mortality in iFR-guided revascularized patients.

Conflicts of Interest

The authors declare no conflicts of interest.

Open Research

Data Availability Statement

All anonymous data supporting this manuscript can be shared by contacting the corresponding author.

Supporting Information

Filename	Description
ccd31517-sup-0001-Supplemental_Figure_1.tif3.5 MB	Supporting Figure S1. ROC curve analysis for predicting abnormal MRR (< 2.5).
ccd31517-sup-0002-Supplemental_Figure_2.tif1.7 MB	Supporting Figure S2. Distribution of MRR in classification based on RFR and FFR cut-off values.
ccd31517-sup-0003-Supplemental_Figure_3A.tif728.1 KB	Supporting Figure S3. Kaplan-Meier analysis of clinical events in patients with preserved and impaired MRR in the total cohort. A. All-cause death, N = 110.
ccd31517-sup-0004-Supplemental_Figure_3B.tif706.6 KB	B. Death and myocardial infarction, N = 145.
ccd31517-sup-0005-Supplemental_Figure_3C.tif746 KB	C. Myocardial infarction, heart failure, all-cause death, target vessel failure, nontarget vessel failure, N = 250.
ccd31517-sup-0006-Supplemental_Figure_4A.tif1.1 MB	Supporting Figure S4. Kaplan-Meirer analysis for all-cause death in the preserved and impaired MRR groups in the revascularized and deferred lesion cohort after randomization. A. Revascularized lesions, N = 459.
ccd31517-sup-0007-Supplemental_Figure_4B.tif1 MB	B. Deferred lesions, N = 378.
ccd31517-sup-0008-Supplementary_Files_0305.docx39.3 KB	Supporting Files 0305.docx.

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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Volume106, Issue1

July 1, 2025

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Physiological Insight Into the Discordance Between Non-Hyperemic Pressure Ratio-Guided and Fractional Flow Reserve-Guided Revascularization

ABSTRACT

Background

Methods and Results

Conclusions

Conflicts of Interest

Open Research

Data Availability Statement

Supporting Information

References

Citing Literature

References

Information

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Physiological Insight Into the Discordance Between Non-Hyperemic Pressure Ratio-Guided and Fractional Flow Reserve-Guided Revascularization

ABSTRACT

Background

Methods and Results

Conclusions

Conflicts of Interest

Open Research

Data Availability Statement

Supporting Information

References

Citing Literature

References

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