Development of a novel method for detailed evaluation of blood flow patterns in stented segments and assessment of their role in stent thrombosis

Stents are used today to treat the blockages of the vessels of the heart in patients who have angina or suffered a heart attack. In most of these patients, stent treatment is effective and improves symptoms and life expectancy. However, there is a small proportion of patients where the stents fail and block, causing either death or a major heart attack. Studies in animals have shown that the blood flow patterns following stent implantation can predict stents that are at risk to block. However, there is lack of data about the role of blood flow on stent blockage in humans. This is because it is very difficult to create models of the vessels of the heart that have been treated with stents.
This study aims to address this problem. We will analyse images of the vessels of the heart taken by a wire that is advanced in these vessels. In these images we can see details of the vessel wall and of the stent. We will use these images to create models of the vessels treated with stents using a new method that we have developed and then we will simulate blood flow in these models to assess the flow patterns. We will do that at scale in 120 patients of whom 40 had a heart attack because of a blocked stent. We will then compare the flow patterns in stents that blocked and caused a heart attack and in vessels treated with stents that did not cause an event. We believe that this research will allow us to identify the flow patterns that can cause stent blockage. This information is important as it will help us to improve the design of future stents and also the way that we put stents so as to reduce the risk of stent blockage and future heart attacks.

Cumulative data have demonstrated that the local haemodynamic forces regulate endothelial function following stent implantation and stimulate pathophysiological mechanisms that modulate neointima proliferation and platelet activation leading to in-stent restenosis and stent thrombosis. Over the last years numerous in vivo studies have allowed us to identify haemodynamic predictors of in stent restenosis, however, there is limited clinical data today about the role of the local haemodynamic forces on stent thrombosis. This should be attributed to the low incidence of stent thrombosis and to the fact that the evaluation of the haemodynamic micro-milieu, that regulates platelet activation and thrombus formation, requires detailed reconstruction of the lumen architecture, including protruding and malapposed stent struts, which is not feasible with the conventional reconstruction techniques. In this application we aim to overcome these limitations and 1) develop an advanced methodology that relies on the separate reconstruction of the lumen and stent geometry to accurately model stented segments, 2) examine the efficacy of the advanced and of a conventional reconstruction methodology in generating geometrically correct models in bench studies and in vivo, 3) compare the haemodynamic micro-milieu estimated in models reconstructed by the advanced approach and in those derived by the conventional methodology and 4) use the advanced method to reconstruct stented segments that were thrombosed and caused events and segments that remained quiescent and examine the role of the local haemodynamic forces in stent thrombosis.