A new study provides fresh insights on the physiological patterns influencing discordance between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) in coronary artery disease (CAD). The study, published online in JACC: Cardiovascular Interventions, suggests that the pullback pressure gradient index (PPGi) can objectively categorize CAD as either focal or diffuse. “Our findings demonstrate that the physiological pattern of CAD is a critical determinant in FFR/iFR discordance,” said the authors of the paper. “This highlights the importance of objective tools like PPGi in guiding treatment decisions.” Role of CAD patterns Led by Pruthvi C. Revaiah, MD from the University of Galway in Ireland, the team’s key findings go into further detail of the role of CAD patterns in this discordance. Using PPGi, a metric based on angiography-based virtual pressure pullback curves, the research team determined whether the disease was predominantly focal (≥0.75) or diffuse (<0.75). They found that FFR+/iFR- cases were significantly associated with focal CAD (76.3%), while FFR-/iFR+ cases were predominantly linked to diffuse CAD (96.3%). These results emphasize how disease patterns influence physiological indices. PPGi utilization “Predominantly focal disease pattern quantified objectively by PPGi derived from angiography-based virtual pressure pullback curve was significantly associated with FFR+/iFR−, while predominantly diffuse disease pattern was significantly associated with FFR−/iFR+,” the authors of the paper concluded. Christopher C.Y. Wong, MBBS, PhD, from Stanford University School of Medicine in Palo Alto, California, and William F. Fearon, MD, from the VA Palo Alto Health Care System, California, commended the study’s strength in utilizing the PPGi to objectively classify CAD as either focal or diffuse. In their accompanying editorial comment, the commentators suggest that focal CAD was more amenable to targeted interventions like stenting, while diffuse CAD often leads to worse outcomes. This includes residual angina and procedural complications. They add that in cases of discordance, operators should prioritize FFR for borderline iFR lesions, while deferring percutaneous coronary intervention (PCI) if FFR is negative. Study methodology The study enrolled 355 patients (390 vessels; age 68±10 years; male 249 (70%)) with chronic coronary syndrome who had ≥1 epicardial coronary artery lesion with 40% to 90% diameter stenosis by visual assessment on invasive coronary angiography. These patients also had analyzable FFR, iFR, and PPGi derived from quantitative flow ratio. Cutoffs for hemodynamic significance were FFR ≤0.80 and iFR ≤0.89. Vessels were classified as FFRþ/iFRþ (n=103 [26.4%]), FFR/iFRþ (n=27 [6.9%]), FFRþ/iFR (n=38 [9.7%]), and FFR/iFR (n=222 [57%]) groups. Sources: Revaiah PC, Tsai TY, Chinhenzva A, et al. Physiological Disease Pattern as Assessed by Pull Back Pressure Gradient Index in Vessels With FFR/iFR Discordance. JACC Cardiovasc. Interv. 2025. (Article in Press). Wong CCY, Fearon WF. Pulling Back to See the Forest From the Trees: Insights Into FFR and iFR Discordance. JACC Cardiovasc. Interv. 2025. (Article in Press). Image Credit: PH alex aviles – stock.adobe.com