The Complementary Value of Absolute Coronary Flow in the Assessment of Patients with Ischaemic Heart Disease (the COMPAC-Flow Study)

Abstract

Fractional flow reserve (FFR) is the current gold-standard invasive assessment of coronary artery disease (CAD). FFR reports coronary blood flow (CBF) as a fraction of a hypothetical and unknown normal value. Although used routinely to diagnose CAD and guide treatment, how accurately FFR predicts actual CBF changes remains unknown. Here we compared fractional CBF with the absolute CBF (aCBF in mL/min), measured with a computational method during standard angiography and pressure-wire assessment, on 203 diseased arteries (143 patients). We found a substantial correlation between the two measurements (r 0.89, Cohen's Kappa 0.71). Concordance between fractional and absolute CBF reduction was high when FFR was >0.80 (91%), but reduced when FFR was ≤0.80 (81%), 0.70-0.80 (68%) and, particularly 0.75-0.80 (62%). Discordance was associated with coronary microvascular resistance, vessel diameter and mass of myocardium subtended, all factors to which FFR is agnostic. Assessment of aCBF complements FFR, and may be valuable to assess CBF, particularly in cases within the FFR 'grey-zone'.

Figure 1. The relationship between fractional and absolute coronary blood flow reduction.

Concordance between fractional and absolute CBF reduction is indicated by the labels according to the FFR range. Concordance means significant FFR (≤0.80) and significant reduction in aCBF (≥23 mL/min), or insignificant FFR (>0.80) and insignificant reduction in aCBF (<23 mL/min). The horizontal and leftward vertical dashed lines reflect the thresholds for physiological significance for FFR and aCBF. The asterisks indicate statistical significance for differences in concordance (z scores) compared with the FFR>0.80 group at, the P<0.05* and P<0.01** level (exact P values [2 tailed] are 0.021 for the ≤0.80 group, <0.001 for the 0.70-0.80 and 0.75-0.80 groups and 0.02 for the ≤0.70 group, unadjusted for multiple comparisons). No replicates.

Figure 2. Box and whisker plots demonstrating the difference between concordant (white boxes) and discordant (shaded boxes) cases in each FFR subgroup on the basis of absolute microvascular resistance (panel A), vessel diameter (panel B) and myocardial jeopardy (panel C).

The direction of these differences are associated with discordance between absolute and fractional coronary blood flow changes. Concordance was 100% in the FFR <0.70 group; hence the absence of a plot for this subgroup. The box defines the interquartile range, the line and x indicate the median and mean, and the bars represent variability outside the upper and lower quartiles excluding outliers. Asterisks indicate statistical significance at the P≤0.05 level (P values for panel a are all <0.001, for panel b are 0.03 and 0.02, and for panel c are 0.018, 0.019 and 0.021 respectively, calculated in Rstudio (two-sided Mann Whitney U) with no adjustment for multiple comparisons). The numbers in grey indicate N for each group, in each comparison (no replicates).