A computational study of stenting-caused arterial damage and its contribution to in-stent restenosis

Atherosclerosis is a progressive vascular disease, in which the arterial wall thickens compared to its healthy condition. Percutaneous coronary intervention is a minimally invasive, endovascular procedure to treat atherosclerosis, for which a stent is usually deployed at the diseased part of artery to open the blocked vessel. However, the stenting procedure may cause injury (damage) to the vessel wall, resulting in neointimal hyperplasia which is the major contribution to in-stent restenosis. This thesis aims to assess the stenting-induced arterial damage and its contribution to tissue growth after percutaneous coronary intervention. In particular, a range of model subroutines were developed to study the effects of stent-, procedure- and vessel-related factors on tissue damage in the media layer and the development of in-stent restenosis.

Using the finite element method, this study presents a mechanistic approach to evaluate the tissue damage caused by stenting and the development of in-stent restenosis in an artery following stent implantation. Hyperelastic models with damage, verified with experimental results, are used to describe the level of tissue damage in arterial layers and plaque caused by stenting. A tissue-growth model, associated with vessel damage, is adopted to describe the growth behaviour of a media layer after stent implantation. Change of lumen diameter with time is used to quantify the development of in-stent restenosis in the vessel after stenting. The effects of pre- and post-dilations on the stenting outcomes are investigated for a polymeric stent. Patient-specific modelling of stent deployment is also simulated to study the effect of stent overlapping on the outcome of percutaneous coronary intervention.

The simulation results showed that the larger the artery expansion achieved during inflation the higher the damage introduced to the media layer, leading to an increased level of in-stent restenosis. Softening of the plaque and the artery, due to the pre-dilation, can facilitate the subsequent stent-deployment process, but increases the rate of in-stent restenosis. The post-stenting dilation is effective to achieve further expansion of the artery but causes additional damage to the artery and an increased rate of in-stent restenosis. The plaque in the patient-specific artery is proved to be heavily calcified according to simulation results and the optical coherency tomography image. Single stent produced smaller lumen area, less damage to the media layer and a lower rate of in-stent restenosis than overlapped stents. While non-overlapped stents produced smaller lumen area when compared to overlapped stents, but caused more damage to the medial layer and a higher rate of in-stent restenosis.

In summary, this research demonstrated that stent designs and materials strongly affect the stenting-induced damage in the media layer and the subsequent development of in-stent restenosis. The linear correlation of the stenting-induced damage in the media layer and the rate of in-stent restenosis can be used to predict the level of in-stent restenosis developed after percutaneous coronary intervention, including complex clinical procedures such as stent overlapping. Both the pre- and post-dilations increase the rate of the in-stent restenosis. To minimise the in-stent restenosis, a non-compliant balloon is recommended for post-dilation when required. Additionally, to balance the postprocedural and long-term outcomes of stenting, the simulation results recommend the use of a single stent or multiple stents with minimum overlapping for treatment of a long lesion.