Physiologic mechanism of discordance between instantaneous wave-free ratio and fractional flow reserve: Insight from ¹³N-ammonium positron emission tomography

Background: Invasive physiologic indices, such as fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR), are used in clinical practice. We sought to evaluate the physiological mechanism of discordance between iFR and FFR using ¹³N-ammonia positron emission tomography (PET)-derived quantitative parameters.

Methods: Data from 113 patients, who underwent both ¹³N-ammonia PET and invasive FFR and iFR measurement, were analyzed. Coronary circulatory indices, such as myocardial blood flow (MBF), coronary flow reserve (CFR), microvascular resistance, and trans-stenosis resistance were compared between patients with discordant results (low FFR despite high iFR) and those with concordant abnormal results (low FFR and low iFR), using cut-off values of FFR≤0.80 and iFR<0.90, respectively.

Results: Among the 113 patients, 39 (34.5%) showed concordant abnormal results in FFR and iFR measurement, and 17 (15.0%) showed discordant results between FFR and iFR (low FFR and high iFR). In comparison of coronary circulatory indices between discordant group and concordant abnormal group, both showed similar resting MBF (p=0.360), however, the discordant group showed higher hyperemic MBF and CFR, compared with the concordant abnormal group (p=0.003 and p<0.001, respectively). Trans-stenosis resistance was lower in the discordant group, in both resting and hyperemic status (p<0.001 for both). Although the discordant group showed higher resting microvascular resistance, these patients showed significantly higher reduction of microvascular resistance at hyperemia.

Conclusions: Patients with low FFR despite high iFR showed significant differences in microvascular resistance, trans-stenosis resistance, absolute MBF, and CFR compared to those with concordant abnormal results between FFR and iFR.