Microvascular resistance reserve: insights into discordant resting and hyperemic epicardial coronary physiology

Discordance between resting and hyperemic epicardial physiology is commonbut mechanistically unclear. Microvascular resistance reserve (MRR), a novelindex of vasodilatory capacity, may provide insight. We aimed to characterizethe prevalence and microvascular substrate of FFR/RFR discordance, andwhether MRR is independently associated with discordant phenotypes.

We retrospectively analyzed 891 vessels from 723 consecutive patients with paired resting full-cycle ratio (RFR) and fractional flow reserve (FFR) measurements (June 2018-October 2024). Vessels were categorized as concordant or discordant. An operator-selected subset of 210 underwent coronary flow reserve (CFR), index of microvascular resistance (IMR), and MRR assessment. Multivariable logistic regression identified predictors of each discordant phenotype (FFR-/RFR+ and FFR+/RFR-).

Discordance was present in 195 vessels (22%); 121 (13.6%) FFR-/RFR+ and 74 (8.3%) FFR+/RFR-. Discordance was more common in the LAD (25% vs. 17%, OR 1.68, 95% CI 1.20-2.36, p = 0.003), driven predominantly by the FFR-/RFR+ phenotype (OR 2.43, 95% CI 1.56-3.78, p < 0.001). In the microvascular subset (n = 210), reduced CFR (OR 0.77, 95% CI 0.59-0.97, p = 0.039) and reduced MRR (OR 0.81, 95% CI 0.65-0.97, p = 0.037) were independently associated with the FFR-/RFR+ phenotype, while neither predicted the FFR+/RFR- phenotype. However, among 45 discordant vessels with microvascular data, MRR provided greater discrimination than CFR (AUC 0.712, 95% CI 0.539-0.884 vs. 0.608, 95% CI 0.434-0.783, p = 0.018).

These exploratory, hypothesis-generating findings suggest that impaired microvascular vasodilatory reserve, expressed predominantly as elevated resting flow, may contribute mechanistically to the FFR-/RFR+ phenotype.