Hemodynamic Insights into Combined Fractional Flow Reserve and Instantaneous Wave-Free Ratio Assessment Through Quantitative [¹⁵O]H₂O PET Myocardial Perfusion Imaging

In patients evaluated for obstructive coronary artery disease (CAD), guidelines recommend using either fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) to guide coronary revascularization decision-making. The hemodynamic significance of lesions with discordant FFR and iFR measurements is debated. This study compared [¹⁵O]H₂O PET–derived absolute myocardial perfusion between vessels with concordant and discordant FFR and iFR measurements. Methods: We included 197 patients suspected of obstructive CAD who had undergone [¹⁵O]H₂O PET perfusion imaging and combined FFR/iFR interrogation in 468 vessels. Resting myocardial blood flow (MBF), hyperemic MBF, and coronary flow reserve (CFR) were compared among 4 groups: FFR low/iFR low (n = 79), FFR high/iFR low (n = 22), FFR low/iFR high (n = 22), and FFR high/iFR high (n = 345). Predefined [¹⁵O]H₂O PET thresholds for ischemia were 2.3 mL·min⁻¹·g⁻¹ or less for hyperemic MBF and 2.5 or less for CFR. Results: Hyperemic MBF was lower in the concordant low (2.09 ± 0.67 mL·min⁻¹·g⁻¹), FFR high/iFR low (2.41 ± 0.80 mL·min⁻¹·g⁻¹), and FFR low/iFR high (2.40 ± 0.69 mL·min⁻¹·g⁻¹) groups compared with the concordant high group (2.91 ± 0.84 mL·min⁻¹·g⁻¹) (P < 0.001, P = 0.004, and P < 0.001, respectively). A lower CFR was observed in the concordant low (2.37 ± 0.76) and FFR high/iFR low (2.64 ± 0.84) groups compared with the concordant high group (3.35 ± 1.07, P < 0.01 for both). However, for vessels with either low FFR or low iFR, quantitative hyperemic MBF and CFR values exceeded the ischemic threshold in 38% and 49%, respectively. In addition, resting MBF exhibited a negative correlation with iFR (P < 0.001) and was associated with FFR low/iFR high discordance compared with concordant low FFR/low iFR measurements, independent of clinical and angiographic characteristics, as well as hyperemic MBF (odds ratio [OR], 0.41; 95% CI, 0.26–0.65; P < 0.001). Conclusion: We found reduced myocardial perfusion in vessels with concordant low and discordant FFR/iFR measurements. However, FFR/iFR combinations often inaccurately classified vessels as either ischemic or nonischemic when compared with hyperemic MBF and CFR. Furthermore, a lower resting MBF was associated with a higher iFR and the occurrence of FFR low/iFR high discordance. Our study showed that although combined FFR/iFR assessment can be useful to estimate the hemodynamic significance of coronary lesions, these pressure-derived indices provide a limited approximation of [¹⁵O]H₂O PET–derived quantitative myocardial perfusion as the physiologic standard of CAD severity.