Exploring Hemodynamic Differences in Patients With Discordant FFR-iFR Using Reservoir-Excess Pressure Analysis

Physiology-guided coronary revascularization using fractional flow reserve (FFR) and/or instantaneous wave-free ratio (iFR) improves outcomes compared with angiography alone. However, when FFR and iFR are measured simultaneously, discordance occurs in 15%-20% of lesions and is associated with heterogeneous clinical outcomes, while the underlying hemodynamic mechanisms are not fully captured by conventional pressure tracings. Reservoir-excess pressure analysis (REPA), which decomposes arterial pressure into reservoir pressure (Pr) and excess pressure (Pxs), and quantifies the diastolic rate constant (DRC), may offer additional pathophysiological insight into these differences. Elevated DRC and Pxs with reduced Pr may indicate systemic hyperperfusion accompanied by lower aortic compliance.

The objective of this study was to characterize pressure-derived hemodynamics (i.e., REPA) and identify mechanisms related to FFR/iFR discordance in coronary arteries with angiographically intermediate stenoses.

This secondary analysis included 249 unique lesions with intermediate coronary artery stenoses (visually estimated diameter stenosis of 40%-70%) from 223 patients in the international, multicenter DEFINE-FLOW study. FFR was defined as hyperemic Pd/Pa and iFR as resting Pd/Pa during the wave-free period. Established thresholds (FFR ≤ 0.80 and iFR ≤ 0.89) were used to define concordant and discordant stenoses. REPA was performed on ensemble-averaged proximal aortic pressure waveforms at rest to derive Pr, Pxs, and related parameters (Figure 2).

REPA parameters demonstrated distinct hemodynamic profiles across groups. FFR-/iFR+ cases showed significantly higher Pxs (7.53 [4.97, 10.12] mmHg) and DRC (3.00 [2.06, 3.52]) and lower IntPr/IntPxs (11.73 [9.57, 17.00]) compared with FFR+/iFR- (Pxs: 5.19 [4.21, 6.89] mmHg, DRC: 2.28 [1.69, 2.51], IntPr/IntPxs: 17.90 [14.23, 19.87]) and FFR-/iFR- (Pxs: 5.38 [4.03, 7.17] mmHg, DRC: 2.20 [1.67, 2.91], IntPr/IntPxs: 17.03 [12.76, 21.21]) cases. Notably, both Pxs and DRC values were highest and IntPr/IntPxs was lowest in FFR-/iFR+ cases. Pxs was an independent predictor of FFR-/iFR+ discordance among cases with FFR > 0.80; higher aortic Pxs was associated with lower iFR values and a greater likelihood of an abnormal iFR classification (OR: 1.230; 95% CI: 1.026-1.473; p = 0.025). In contrast, higher hAPV (OR: 1.187; 95% CI: 1.100-1.281; p < 0.001) and lower bAPV (OR: 0.751; 95% CI: 0.644-0.875; p < 0.001), which together reflect a higher CFR, were independent predictors of FFR+/iFR- discordance.

Weaker proximal aortic reservoir function and higher aortic Pxs are associated with abnormal iFR in lesions with normal FFR, whereas higher CFR is associated with normal iFR in lesions with abnormal FFR. Systemic hemodynamics, including proximal aortic reservoir behavior, may provide additional mechanistic insight into altered coronary pressure hemodynamics and improve the pathophysiological understanding of FFR-iFR discordance that may affect revascularization decisions in chronic coronary syndromes.