Two studies recently published in JACC: Cardiovascular Interventions provide fresh insights into coronary physiology, suggesting that angiography-derived fractional flow reserve (FFR) may be a practical alternative to wire-based FFR, while highlighting the prognostic significance of definite discordance between FFR and nonhyperemic pressure ratios (NHPR).

In the PROVISION trial, revascularization guided by angiography-derived FFR was noninferior to pressure wire-based FFR in a randomized comparison of the two strategies among patients with stable coronary artery disease (CAD). Across 13 Japanese centers, 401 patients (mean age, 72 years; 29% women) were randomized 1:1 to either strategy.

Revascularization was performed in 41% of angiography-derived cases vs. 38% of wire-based cases (absolute difference, 3.5%; p for noninferiority=0.049). Angiography-derived FFR reduced median radiation exposure (28.3 Gy∙cm² vs. 34.8 Gy∙cm²) but took longer (9 min. vs. 8 min.) compared with wire-based FFR.

Results at one year showed that major adverse cardiovascular events (MACE), including cardiac death, any MI or ischemia-driven target vessel revascularization, occurred in 8.4% of angiography-derived cases vs. 10.1% of wire-based cases (hazard ratio [HR], 0.84; p=0.591).

"We should still be cognizant that each step taken toward developing a completely simulated FFR assessment has required incremental compromises on accuracy and fidelity," cautions Damien Collison, MB, BCh, MD, in an accompanying editorial comment. "Whatever risks that may hold for patients will only be identified and fully understood through longer-term follow-up of large, randomized trials with particular focus on the discordant cases where FFR and angiography-derived FFR disagree."

A separate post hoc analysis of the J-PRIDE registry suggests that clinically important prognostic information may be present when FFR and NHPR results diverge, particularly in cases of definite discordance.

Investigators Yasutsugu Shiono, MD, PhD, et al., classified 3,200 Japanese CAD patients (median age, 73 years; 25% women) into six categories based on FFR and NHPR results, distinguishing between clear-cut and borderline agreement or discordance around established physiological thresholds: FFR–/NHPR– (G1, n=990), definite FFR+/NHPR+ (G2, n=1,036), marginal discordant FFR+/NHPR– (G3, n=441), definite discordant FFR+/NHPR– (G4, n=201), marginal discordant FFR–/NHPR+ (G5, n=416) and definite discordant FFR–/NHPR+ (G6, n=116). After accounting for the borderline values around FFR and NHPR cutoffs, only about half of the lesions initially classified as discordant remained definitely discordant.

Results showed that compared with G1, the two groups with definite discordance, G4 and G6, had higher risk of MACE, including all-cause mortality, any MI and any revascularization (adjusted HR [aHR], 1.98; p=0.029 and aHR, 2.18; p=0.013, respectively). G6, definite discordant FFR–/NHPR+, had a higher risk of all-cause mortality as well (aHR, 2.57; p=0.017).

Older age, female sex, diabetes, anemia, lower BMI, end-stage renal dysfunction requiring hemodialysis, aortic stenosis and left ventricular hypertrophy were all significant predictors of definite discordant FFR–/NHPR+.

In an accompanying editorial comment, Bon-Kwon Koo, MD, PhD, FACC, points out that relying solely on FFR or NHPR can lead to different treatment decisions in nearly one of five patients. "Discordance should not be viewed simply as a disagreement between [two] numbers, nor as an opportunity to declare a winner between the [two] indices," Koo writes, instead calling it "a signal that the coronary circulation is more complex than a binary threshold can capture."