Evaluating Wall Shear Stress Indices to Uncover Stimuli for Restenosis and Malapposition in Stented Coronary Arteries
Date of Award
Master of Science (MS)
LaDisa, John F.
The cause of coronary artery neointimal thickening leading to restenosis in ~10% of drug-eluting stents is unknown. Although research suggests adverse values of traditional wall shear stress (WSS) indices may contribute, studies to date have not accounted for stent geometry, which dictates local WSS patterns influencing drug concentration. Recently proposed WSS indices such as WSS variability and WSS exposure time (WSSET) may shed further light on restenosis or, the opposite effect, resorption. The objective of this investigation was to locally evaluate traditional and recently proposed post-stenting metrics and their respective impact on restenosis or resorption. This study used de-identified data from 29 patients, randomized to thin-strut Promus Element, thin-strut Xience Prime, or thick-strut Nobori stents. All patients underwent optical coherence (OCT) and coronary computed tomography (CT) angiography post-stenting as well as at a 9-month follow-up. WSS metrics were calculated from computational fluid dynamics simulations of patient-specific 3D arteries, reconstructed by the fusion of OCT and CT angiography data, and normalized to WSS in the proximal unstented region. The change in lumen area (CLA) from post-stenting to follow-up was calculated using co-registered OCT pairs (469 pairs), corresponding to OCT imaging locations. The WSS results were compared with CLA using two-step cluster analysis. Results showed that low WSS is a precursor to neointimal thickening, resulting in restenosis, confirming previous research. The Nobori stent was most prominent in the cluster with low WSS, potentially induced by the large radial thickness of the Nobori stent. Furthermore, high WSSET showed a relationship to restenosis. The combination of TAWSS combined with post-stenting WSS variability was shown to be directly related to CLA, which characterized vessel resorption. When vessel resorption occurs, regions of malapposition, uncovered struts or malapposed struts may develop. These are undesirable features, which potentially result in late stent thrombosis. In all, the results from this collection of multiple local analyses provide insight into potential predictive indices of local artery restenosis and resorption after stenting. If confirmed through future prospective studies, these indices may improve the efficacy of drug-eluting stents, thereby improving the quality of life for patients with coronary artery disease.