Atherosclerotic plaque characteristics improve diagnosis of ischemia for non-obstructive coronary artery lesions: a direct comparison to fractional flow reserve

Abstract

Purpose: Fractional flow reserve (FFR) at the time of invasive coronary angiography (ICA) is the gold standard for determining lesion-specific ischemia, and identifies ischemia in a significant proportion of lesions considered anatomically non-obstructive. Beyond luminal stenosis severity, coronary CT angiography (CT) enables evaluation of atherosclerotic plaque characteristics (APCs) that include positive remodeling (PR), low attenuation plaque (LAP) and spotty intra-plaque calcification (SC). The relationship of these APCs to ischemia in non-obstructive coronary lesions has not been evaluated to date. Methods: 252 patients from 17 centers in 5 countries were prospectively enrolled. Patients underwent CT and ICA, with clinically indicated FFR performed for 407 coronary lesions. CTs were evaluated by an independent core laboratory in blinded fashion, with ≥50% and <50% stenosis considered obstructive and non-obstructive, respectively. Presence of APCs within coronary lesions by CT was defined as: (1) PR, maximal lesion diameter/reference diameter ≥1.10; (2) LAP, any intra-plaque voxel <30 HU; and (3) SC, nodular calcified plaque ≤3 mm. Coronary lesion-specific ischemia was defined by an FFR ≤0.8. Results: For FFR-interrogated coronary lesions, 195 of 407 (48%) were non-obstructive by CT. FFR-defined ischemia was present in 33 of 195 (17%) lesions, with a mean FFR value of 0.75±0.07. Amongst non-obstructive lesions that caused ischemia, 24 (73%), 9 (27%) and 8 (24%) exhibited PR, LAP and SC, respectively; with at least 1 APC present in 24 (73%) of lesions. In multivariable analyses, the presence of PR [Odds ratio (OR) 6.6, 95% confidence interval (CI) 2.4-17.9, p<0.0001)] was associated with lesion-specific ischemia while LAP (OR 1.0, 95% CI 0.3-3.2, p=0.9) and SC (OR 1.4, 95% CI 0.5-4.5, p=0.5) were not. A dose-response relationship was observed for increasing risk of ischemia for non-obstructive coronary lesions possessing 1 (OR 4.5, p=0.006), 2 (OR 11.8, p<0.001) and 3 (OR 4.0, p=0.1) APCs. Conclusion: The presence of positive arterial remodeling and increasing numbers of APCs enhances diagnosis of non-obstructive coronary lesions that cause ischemia.