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

Abstract

Background: 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.