Variability of Coronary Physiology (FFR/iFR) in Diffuse Tandem Lesions

Physiology guided revascularization has been shown to improve clinical outcomes vs. conventional angiography. However, after percutaneous coronary intervention (PCI) residual pressure gradients may persist, and multiple studies have linked these to persistent angina. This is why adequate physiological assessment is required, both before and after procedure. 

The physiological assessment of coronary artery disease (CAD) has evolved from evaluating the hemodynamic severity of single stenosis lesions to more comprehensive, longitudinal pressure mapping using pullback. This technique will anticipate revascularization impact on serial or diffuse disease (with pressure drift presence). However, the predictive value of translesional pressure gradients (ΔFFR o ΔiFR) had not been systematically assessed so far. 

The SERIAL was a randomized multicenter trial carried out in four UK centers including 87 patients with at least one significant focal lesion and a second one or a diffusely diseased segment in the same vessel. Participates were randomized 1:1 to FFR or iFR guided PCI. They all underwent pre and post-PCI pullback assessment, mainly to assess the difference between predicted post-PCI ΔFFR or ΔiFR value vs real post intervention ΔFFR or ΔiFR value. As secondary outcome, the study looked at predictive accuracy of FFRcalc model (a formula accounting for lesion interaction).  

Mean patient age was 67, 31% had diabetes and 74% presented stable angina. The most frequently assessed artery was the anterior descending (64%). Mean baseline FFR and iFR values were 0.71 and 0.82 respectively, with 13% discordance.

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It was shown that both ΔFFR and ΔiFR systematically overestimated the hemodynamic benefit of treating one single target lesion. Mean prediction error was 12% for FFR and 4% for iFR (p<0.001). Also, applying ischemia binary thresholds (FFR ≤ 0.80, iFR ≤ 0.89) resulted in misclassification of residual ischemia in over one third of cases (36% and 34%, respectively). The use of the FFRcalc new parameter reduced error margin (14% misclassification), though it tended to underestimate the benefit and showed greater variability upon serial assessment. 

These findings from a randomized design challenge the value of pullback pressure gradient as a reliable, sole predictive tool, especially in common scenarios such as serial of diffuse CAD. 

Conclusion

The SERIAL, first head-to-head trial on diffuse lesions, has shown predicting post-PCI physiological outcomes using ΔFFR or ΔiFR in serial disease is inaccurate due to overestimation. FFRcalc might offer better diagnostic performance; however, the safest strategy still is post intervention physiological assessment. 

Original Title: Randomized Comparison of Fractional Flow Reserve and Instantaneous Wave Free Ratio in Serial Disease.

Reference: Li Kam Wa, M, Ezad, S, Modi, B. et al. Randomized Comparison of Fractional Flow Reserve and Instantaneous Wave Free Ratio in Serial Disease. J Am Coll Cardiol Intv. 2025 Jul, 18 (13) 1617–1627. https://doi.org/10.1016/j.jcin.2025.05.033.