Fractional Flow Reserve vs. Instantaneous Wave-Free Ratio Discordance

Study Questions:

What are the coronary flow characteristics of angiographically intermediate stenosis, which have discordant fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) values?


This was a post hoc analysis of the combined pressure and Doppler flow velocity registry (IDEAL study). The authors divided the patients into the following groups: FFR+/iFR+ (108 vessels, 91 patients), FFR–/iFR+ (28 vessels, 24 patients), FFR+/iFR– (22 vessels, 22 patients), FFR–/iFR– (208 vessels, 154 patients), and unobstructed vessel group (201 vessels, 153 patients). In addition to FFR and iFR values, coronary flow velocity was measured using intracoronary Doppler at baseline (cm/s) and with hyperemia (cm/s). Coronary flow reserve (CFR) was velocity during hyperemia divided by velocity during baseline.


A total of 366 vessels with intermediate stenosis (40-70% on angiography) and 201 unobstructed vessels underwent analysis. There was a higher prevalence of diabetes in the FFR-/iFR+ compared to FFR+/iFR- discordant groups (41% vs. 14%, p = 0.03). FFR and iFR correlated with each other in 86% of the stenosed vessels. There was discordance in 14% of the stenosed cases. Among patients with discordant FFR and iFR, when FFR was positive and iFR was negative, hyperemic flow velocity and CFR were not significantly different compared to FFR–/iFR– and the unobstructed group. On the other hand, when stenosis were discordant with –FFR and +iFR, hyperemic flow velocity and CFR were similar to the FFR+/iFR+ group [28.2 (IQR, 20.5-39.7) cm/s vs. 23.5 (IQR, 16.4-34.9) cm/s and 1.44 (IQR, 1.29-1.85) vs. 1.39 (IQR, 1.06-1.88), respectively (p = 0.09 and p = 0.46, respectively)].


Among patients with angiographically intermediate stenosis, discordance in FFR and iFR was in part due to hyperemic flow velocity, CFR, and prevalence of diabetes. In patients with FFR+/iFR– stenosis, hyperemic flow velocities may be overestimated, resulting in lower FFR values and similar flow characteristics as angiographically unobstructed vessels. iFR-based classification may be more closely related to hyperemic flow velocity and CFR.


This paper attempts to better understand discordance between iFR and FFR values using CFR as the gold standard. Although there are ample limitations such as the role of diabetes and the absence of correlation to clinical outcomes, the analysis sheds light on possible mechanisms by which FFR might be falsely flow limiting. This may be due to the effect of diabetes and adenosine on the microvasculature and hyperemic flow velocity. Most importantly, there continues to be good correlation between FFR and iFR. However, when there is discordance, iFR may be a more reliable measure.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Vascular Medicine, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Nuclear Imaging

Keywords: Adenosine, Constriction, Pathologic, Coronary Angiography, Coronary Stenosis, Diabetes Mellitus, Fractional Flow Reserve, Myocardial, Hyperemia, Microvessels, Secondary Prevention

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