Impact of Microvascular Resistance on Coronary Hemodynamic Diagnostic Indices: A Multiscale Simulation Study.

PURPOSE: Coronary diagnostic indices-fractional flow reserve (FFR) and coronary flow reserve (CFR)-disagree in up to 30% of cases, complicating diagnosis and revascularization decisions. Microvascular health likely drives this discordance, but its isolated effect is challenging to quantify in vivo and is often confounded by anatomical factors in computational studies. METHODS: Here, we integrated three-dimensional computational fluid dynamics (CFD) with a lumped-parameter network of the coronary microvasculature, systematically varying hyperemic microvascular resistance (HMR) across physiological ranges while keeping epicardial lesion geometry fixed. We simulated nine left coronary artery models with varying lesion locations (LAD/LCx), lengths (1.2/2.5 cm), and stenosis severities (0/45/60%). Each model was evaluated under four hyperemic microvascular resistance states, yielding 36 hyperemic simulations for the FFR, HMR, and HSR analyses. An additional resting simulation was performed for each coronary artery model, yielding nine resting simulations, and 45 simulations in total. Pressure and velocity fields were used to calculate FFR, CFR, HMR, and hyperemic stenosis resistance (HSR), enabling quantification of global relationships and local sensitivities near clinical thresholds (FFR=0.8; CFR=2). RESULTS: Increasing HMR elevated FFR and reduced CFR for identical lesions, suggesting that coronary flow is primarily governed by HMR rather than stenosis severity. Higher HMR modestly increased the arterial wall area exposed to low wall shear stress at bifurcations. Near the clinical thresholds, the local associations of FFR with HMR and HSR were comparable in magnitude, whereas CFR was more strongly associated with HMR than HSR. Cases with low FFR (<0.50) remained hemodynamically significant irrespective of HMR. Both modes of FFR-CFR discordance were reproduced by varying HMR in otherwise identical geometries, demonstrating that HMR alone can significantly change lesion hemodynamic significance. CONCLUSION: Our findings support reporting HMR alongside FFR and CFR to enhance clinical interpretation and improve physiological accuracy in CFD-based coronary assessment.