Insufficient adenosine-induced hyperemia is a major determinant of discordance between non-hyperemic pressure ratio and fractional flow reserve

Adenosine occasionally overestimates fractional flow reserve (FFR) values (i.e., insufficient adenosine-induced hyperemia), leading to low non-hyperemic pressure ratios (NHPR)–high FFR discordance. We investigated the impact of insufficient adenosine-induced hyperemia on NHPR–FFR discordance and the reclassification of functional significance. We measured resting distal-to-aortic pressure ratio (Pd/Pa) and FFR by using adenosine (FFR(ADN)) and papaverine (FFR(PAP)) in 326 patients (326 vessels). FFR(ADN) overestimation was calculated as FFR(ADN) − FFR(PAP). We explored determinants of low Pd/Pa − high FFR(ADN) discordance (Pd/Pa ≤ 0.92 and FFR(ADN) > 0.80) versus high Pd/Pa − low FFR(ADN) discordance (Pd/Pa > 0.92 and FFR(ADN) ≤ 0.80). Reclassification of functional significance was defined as FFR(ADN) > 0.80 and FFR(PAP) ≤ 0.80. Multivariable analysis identified FFR(ADN) overestimation (p = 0.002) and heart rate at baseline (p = 0.048) as independent determinants of the low Pd/Pa–high FFR(ADN) discordance. In the low Pd/Pa–high FFR(ADN) group (n = 26), papaverine produced a further decline in the FFR value in 21 vessels (81%) compared with FFR(ADN), and the reclassification was observed in 17 vessels (65%). Insufficient adenosine-induced hyperemia is a major determinant of the low resting Pd/Pa–high FFR discordance. Physicians should bear in mind that the presence of low NHPR–high FFR discordance may indicate a false-negative FFR result.