Vessel specific discrepancies between visual assessment and resting and hyperemic physiological indices

Introduction Visual estimation of coronary artery disease (CAD) often correlates poorly with functional severity (1). We aimed to evaluate the impact of systematic physiological assessment—incorporating resting full-cycle ratio (RFR), fractional flow reserve (FFR), hydrostatic pressure correction, and pressure predicted microvascular resistance reserve (ppMRR)—on lesion characterization and therapeutic decision-making. Methods We prospectively analyzed 144 intermediate lesions in 114 patients in the Ready registry (2) across three centers. Distal pressure values were refined using individual hydrostatic pressure correction in cases with significant height differences between the catheter tip and the sensor of the pressure wire. Lesions were categorized as non-significant, focal, diffuse, or mixed based on distal RFR and pullback-derived pressure gradients (ΔRFR). Microvascular function was assessed using ppMRR, which integrates visual area stenosis with pressure-derived parameters. Pressure values were defined in most cases, allowing for the investigation of their correlation with resting and hyperemic parameters. Results Therapy recommendations (OMT vs. intervention) based on visual assessment demonstrated poor agreement with both FFR (52.1%, kappa=0.058) and RFR (54.2%, kappa=0.053), frequently overestimating stenosis severity. Reclassification was substantial: diagnostic categorization changed in 65.3% of cases when switching from visual to combined physiological assessment. The application of hydrostatic pressure correction further altered the classification in 25.0% of the total cohort; however, this impact was significantly more pronounced in the LAD (36.2%) compared to non-LAD vessels (4.0%, p < 0.001). Physiological profiles were highly vessel-specific. The LAD exhibited a significantly higher burden of positive physiology (79.8%) compared to the CX (47.8%, p=0.004) and RCA (33.3%, p<0.001). Correspondingly, RFR/FFR discordance was more frequent in the LAD than in non-LAD vessels (33% vs. 16%, p=0.047). Microvascular function differed significantly across phenotypes. The FFR+/RFR- discordant group demonstrated significantly higher ppMRR (3.99 ± 1.81) than both the double-positive (2.96 ± 0.97, p=0.04) and the FFR-/RFR+ groups (2.78 ± 1.02, p=0.01). Overall, microvascular dysfunction (ppMRR < 2.5) was present in 40.6% of cases, with the highest prevalence in the RFR+/FFR- discordant phenotype. Conclusion Visual assessment is frequently inaccurate for defining CAD significance and pattern. Systematic physiological assessment is essential for precise lesion evaluation. Differences in microvascular function (ppMRR) may underlie RFR/FFR discordance. Our findings reinforce that the LAD is a 'different animal' in coronary physiology.