Hyperemic vs non-hyperemic indexes discordance: Role of epicardial and microvascular resistance (HyperDisco Study)

Background: Literature reports a 20 % discordance between hyperemic (FFR) and non-hyperemic indexes (NHi) of coronary stenosis lesions. This work aims to develop and test clinically, a formula relating FFR and NHi (including iFR, RFR and Pd/Pa) to study their discordance. Methods: We conducted a prospective, single-center, clinical study enrolling all patients undergoing full coronary physiology assessment with Coroventis CoroFlow Cardiovascular System (Abbott Vascular, St. Paul, Minnesota) to validate the developed formula: FFR/NHi=IMR/BMRBSR+BMR/HSR+IMR where IMR(BMR) is the hyperemic (basal) microvascular resistance and HSR(BSR) is the hyperemic (basal) stenosis resistance. Results: A total of 51 patients were enrolled, 72 % male, average age 67.4 ± 8.9. Mean hemodynamic data were: FFR 0.87 ± 0.07, iFR 0.93 ± 0.05, RFR 0.91 ± 0.05, Pd/Pa 0.92 ± 0.05, BMR 76.6 ± 51.6 mmHg*s, IMR 28.4 ± 22.8 mmHg*s, BSR 5.5 ± 4.7 mmHg, HSR 3.8 ± 2.9 mmHg*s, coronary flow reserve (CFR) 2.9 ± 1.6, resistive reserve ratio (RRR) 3.3 ± 2.0. Lin's Concordance and Bland Altman analysis showed an optimal correlation between measured and estimated data. Sensitivity analysis showed that: (1) FFR can underestimate epicardial stenosis severity leading to FFR- vs NHi + discordance in case of elevated IMR, (2) NHi can overestimate epicardial stenosis severity leading to FFR- vs NHi + in the case of low BMR, (3) if BSR > HSR, FFR- vs NHi + discordance can occur, while if BSR < HSR, FFR+ vs NHi- discordance can occur. Conclusion: (1) NHi can be more reliable in case of elevated IMR; (2) FFR-CFR combination can be more reliable for low BMR occurring to compensate an epicardial stenosis; (3) NHi-CFR combination can be more reliable when BSR > HSR, while FFR-CFR combination can be more reliable when BSR < HSR. The combination between pressure and flow indexes (FFR-CFR or NHi-CFR) is more reliable when compensatory mechanisms occur.