Low FFR equal to low ischemia: Really?

We read with great interest the elegant work by JM Lee et al. [ [1] ]. They evaluated the physiologic mechanism of discordance between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) using 13N-ammonia positron emission tomography (13NH3-PET) to estimate coronary circulation indices. The authors show that in 15% of the analyzed population there is a discordant result between FFR and iFR (low FFR and high iFR). Noteworthy, this subgroup of patients showed significantly lower proportion of PET-defined myocardial ischemia. In fact, the authors used a previously validated cut-off for PET-defined myocardial ischemia, namely CFR <2.0 and hyperemic MBF ≤1.84 ml/min/g. Unfortunately, the same authors demonstrated that this cut-off was correlated with an FFR value ≤0.75 [ [2] ]. The optimal threshold for a FFR ≤0.80 was CFR <2.12 and hyperemic MBF ≤1.99 ml/min/g. In the present work, patients in the discordant group had a median FFR of 0.77 (25th–75th quartile: 0.76–0.78) and a mean hyperemic MBF of 1.94 ± 0.45 ml/min/g. Thus, it is obvious that discordant patients showed lower ischemia since they used two different ischemia definitions in respect to the same technology. FFR was considered positive when ≤0.80, PET-ischemia value was considered positive with a threshold based on FFR ≤0.75 and almost no patient in the discordant group had an FFR value ≤0.75. Thus, we are struggling to understand the methodology and the clinical implications of these results. In fact as previously reported by Johnson et al. [ [3] ] FFR is a continuous marker of ischemia, and the benefit gained from treating FFR lesions ≤0.80 is widely validated.