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 (FFRADN) and papaverine (FFRPAP) in 326 patients (326 vessels). FFRADN overestimation was calculated as FFRADN - FFRPAP. We explored determinants of low Pd/Pa - high FFRADN discordance (Pd/Pa ≤ 0.92 and FFRADN > 0.80) versus high Pd/Pa - low FFRADN discordance (Pd/Pa > 0.92 and FFRADN ≤ 0.80). Reclassification of functional significance was defined as FFRADN > 0.80 and FFRPAP ≤ 0.80. Multivariable analysis identified FFRADN overestimation (p = 0.002) and heart rate at baseline (p = 0.048) as independent determinants of the low Pd/Pa-high FFRADN discordance. In the low Pd/Pa-high FFRADN group (n = 26), papaverine produced a further decline in the FFR value in 21 vessels (81%) compared with FFRADN, 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.