Impact of overestimation of fractional flow reserve by adenosine on anatomical-functional mismatch

Adenosine occasionally results in overestimation of fractional flow reserve (FFR) values, compared with other hyperemic stimuli. We aimed to elucidate the association of overestimation of FFR by adenosine with anatomically significant but functionally non-significant lesions (anatomical-functional mismatch) and its influence on reclassification of functional significance. Distal-to-aortic pressure ratio (Pd/Pa) was measured using adenosine (Pd/Pa-ADN) and papaverine (Pd/Pa-PAP) in 326 patients (326 vessels). The overestimation of FFR was calculated as Pd/Pa-ADN-Pd/Pa-PAP. The anatomical-functional mismatch was defined as diameter stenosis > 50% and Pd/Pa-ADN > 0.80. Reclassification was indicated by Pd/Pa-ADN > 0.80 and Pd/Pa-PAP <= 0.80. The mismatch (n = 72) had a greater overestimation of FFR than the non-mismatch (n = 99): median 0.02 (interquartile range 0.01-0.05) versus 0.01 (0.00-0.04), p = 0.014. Multivariable analysis identified the overestimation of FFR (p = 0.003), minimal luminal diameter (p = 0.001), and non-left anterior descending artery (LAD) location (p < 0.001) as determinants of the mismatch. Reclassification was indicated in 29% of the mismatch and was more frequent in the LAD than in the non-LAD (52% vs. 20%, p = 0.005). The overestimation of FFR is an independent determinant of anatomical-functional mismatch. Anatomical-functional mismatch, specifically in the LAD, may suggest a false-negative result.