Aims The present analysis addresses the potential clinical and physiologic significance of discordance in severity of coronary artery disease between the angiogram and fractional flow reserve (FFR) in a large and unselected patient population. Methods and results Between September 1999 and December 2011, FFR and percent diameter stenosis (DS) as assessed by quantitative coronary angiography were obtained in 2986 patients (n ¼ 4086 coronary stenoses), in whom at least one stenosis was of

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... iate angiographic severity. Fractional flow reserve correlated slightly but significantly with DS [20.38 (95% CI: 20.41; 20.36); P , 0.001]. The sensitivity, specificity, and diagnostic accuracy of a ≥50% DS for predicting FFR ≤ 0.80 were 61% (95% CI: 59; 63), 67% (95% CI: 65; 69), and 0.64 (95% CI: 0.56; 0.72), respectively. In different anatomical settings, sensitivity and specificity showed marked variations between 35 to 74% and 58 to 76%, respectively, resulting in a discordance in 35% of all cases for these thresholds. For an angiographic threshold of 70% DS, the diagnostic performance by the Youden's index decreased from 0.28 to 0.11 for the overall population. Conclusion The data confirm that one-third of a large patient population shows discordance between angiogram ≥50%DS and FFR ≤0.8 thresholds of stenosis severity. Left main stenoses are often underestimated by the classical 50% DS cut-off compared with FFR. This discordance offers physiologic insights for future trials. It is hypothesized that the discordance between angiography and FFR is related to technical limitations, such as imprecise luminal border detection by angiography, as well as to physiologic factors, such as variable minimal microvascular resistance. ---