Assessment of the functional significance of left anterior descending coronary artery (LAD) stenosis of intermediate severity (IS) is challenging. A direct comparison of fractional flow reserve (FFR), instantaneous wave-free ratio (IFR), and non-invasive coronary flow reserve (CFR) has never been performed. Our objective was to test the usefulness of noninvasive CFR by comparison to invasive FFR and IFR in patients with LAD stenosis of angiographic IS and stable coronary artery disease.

58 stable consecutive patients (mean age, 68±10 years; with angiographic proximal or mid LAD stenosis of IS (40-70% diameter stenosis on quantitative coronary angiography), no previous anterior myocardial infarction, were prospectively studied. They underwent iFR which was calculated as a trans-lesion pressure ratio during a specific period of baseline diastole, FFR with intracoronary bolus adenosine (150μg), and CFR using intravenous adenosine (140μg/kg/min over 2min) in the distal part of the LAD, the same day. CFR was defined as hyperemic peak diastolic LAD flow velocity divided by baseline flow velocity, and FFR was defined as distal pressure divided by mean aortic pressure during maximal hyperemia.

The mean values of iFR, FFR, and CFR were 0.88±0.07, 0.81±0.08, and 2.4±0.6 respectively. A significant correlation was found between CFR and FFR (r=0.72, curvilinear relationship), FFR and IFR (r=0.63, linear relationship), and between CFR and IFR (r=0.44) (all, p<0.01). Using a ROC curve analysis, the best cut-off to detect a significant lesion based on FFR assessment (FFR<0.8, n=16) was iFR≤0.86 with a sensitivity (Se) of 75%, specificity (Sp) of 81%, AUC 0.8±0.05; and CFR≤2 with a Se of 82%, Sp of 85%, AUC 0.9±0.03, (all, p<0.001). Based on these cut-offs, discordant results between CFR and FFR were observed in 9 cases (accuracy 84%), between CFR and iFR in 14 cases (accuracy 76%), and between iFR and FFR in 11 cases (accuracy 81%).

In stable patients with LAD stenosis of IS, non-invasive CFR is a useful tool to detect a significant lesion based on FFR. Furthermore, CFR is better correlated to FFR than to iFR, and its accuracy seems as good as iFR in this setting.