Abnormal Fractional Flow Reserve in Nonobstructive Coronary Artery Disease

Background The basis of discordance between invasive coronary angiographic (ICA) anatomic stenosis and fractional flow reserve (FFR) is not fully understood. We analyzed coronary computed tomography angiography (CTA) characteristics of ICA-verified nonobstructive lesions in the proximal or midleft anterior descending artery with FFR ≤0.8, that is, anatomy-physiology mismatch. Methods and Results CTA and ICA were performed in 108 patients. FFR was measured during intravenous ATP (180 μg/[kg·min]) infusion. CTA-verified plaque characteristics between 53 consecutive ICA-FFR mismatch (ICA-quantitative coronary angiography <50%, FFR≤0.8) and 55 ICA-FFR match (ICA-quantitative coronary angiography<50%, FFR>0.8) vessels were compared. CTA-verified vessel area (20.7±6.7 versus 16.9±4.8 mm²; P=0.0007), positive area remodeling index (ARI; 1.38±0.23 versus 1.06±0.11; P<0.0001), %plaque area (64.7±12.7 versus 57.4±8.5%; P<0.0007), jeopardized myocardial mass (46.2±18.5 versus 37.1±14.3 g; P= 0.006), and the prevalence of low attenuation plaque (45.3% versus 9.1%; P<0.0001) at the minimum lumen area were significantly higher in the ICA-FFR mismatch than the match group. By receiver operation curve analysis, the areas under the curve for positive area remodeling index, %plaque area and jeopardized myocardial mass were 0.921, 0.681, and 0.641, respectively, for the diagnosis of mismatch (cutoff values 1.13, 66% and 58.7 g, respectively). The sensitivity and specificity of area remodeling index >1.13 for predicting ICA-FFR mismatch were 88.7% and 78.2%, respectively. Conclusions In the absence of anatomically significant stenosis, abnormal FFR is more frequently encountered in patients with CTA-derived positive remodeling, larger plaque burden, and low attenuation plaque. These findings contribute to a better understanding of how FFR-based decision-making might translate into demonstrated superior clinical outcomes.