Endothelial dysfunction versus early atherosclerosis: a study with high resolution imaging

Abstract

Purpose: Endothelial dysfunction has been shown to be of prognostic significance in predicting major coronary events. Characterization of microstructural changes of the vessel wall in coronary segment with endothelial dysfunction may have potential prognostic importance for detection of ischemic heart disease (IHD). Methods: We studied 5 patients with IHD, found to have normal or near normal angiograms. These patients received graded doses of intracoronary acetylcholine (10-6, 10-5 and 10-4 mol/L over 3 minutes at 10 minutes intervals) to assess endothelial dysfunction. Epicardial endothelial dysfunction was defined as >30% epicardial vessel diameter reduction during testing. An intracoronary bolus dose of 1000 μg of nitroglycerin was administered to relieve vasoconstriction; IVUS was performed 10 minutes after relief of vasoconstriction and OCT 20 minutes later. The OCT imaging wire was positioned at the site, and 1 cm proximal and distal to of the observed coronary vasomotor abnormality. Each OCT image was analyzed by two independent observers who were blinded to the results. Using OCT imaging, the intima is identified by a signal-rich layer near to the lumen, the media by a signal-poor middle layer, and the adventitia by a signal-rich outer layer. Loss of layered architecture reflects early sign of atherosclerosis. Results: A total of 7 coronary segments showed vasoconstriction. Wall morphology was evaluated by IVUS. Subjects with normal smooth coronaries exhibited a thickness of the coronary wall<1mm. We obtained a total of 83 OCT images. There were 49 images of dysfunctional sites and 34 of the control segments. Of the 49 images of dysfunctional sites, 9 (19.4%) showed the usual layer structure of a normal artery (three-layer structure: intima, media and adventitia), and the remaining 40 (81.6%) showed early structural changes (single intimal thickened layer up to 380 micron). 16 of these 40 images revealed small signal-poor regions compatible with lipid deposits. Imaging of the control segments showed the usual three-layer structure in 5 (14.7%) images, small signal-poor regions in 14 (41.2%) images, and early structural changes in the remaining 15 (44.1%) images. Conclusions: Our findings indicate that endothelial dysfunction and early atherosclerosis, although related in many coronary segments, may exist separately. Functional alterations can be identified safely at a stage when atherosclerotic lesions are not detectable by any imaging technique. Acetylcholine testing may be useful in designing early effective interventions that restore endothelial function.