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

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.

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.

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.