BackgroundCurrently, acute ischemic stroke is still a leading cause of mortality and morbidity. Approximately 2 years ago, mechanical thrombectomy was proven beneficial as a revolutionary new therapy for stroke in the MR‐CLEAN trial (A Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). However, the mechanisms by which the thrombectomy device, or stent‐retriever, interacts with the thrombus are largely unknown. A better understanding could lead to improved efficacy of mechanical thrombectomy devices.Methods and ResultsSeven stent‐retrievers with thrombi still entrapped were collected directly after thrombectomy. The stent‐retrievers were studied using micro computed tomography, followed by scanning electron microscopy and light microscopy. Two independent observers rated interaction type and thrombus surface structure (porous filamentous or dense) at the interaction sites.A total of 79 interaction sites between thrombus and stent‐retriever were categorized. Thrombus‐stent‐retriever interaction was found to be adhesive (n=44; 56%) or mechanical (n=35; 44%). Adhesive interaction was most frequently observed at interaction sites with a dense surface, compared with interaction sites with a porous filamentous fibrin surface (38/58; 66% versus 6/21; 29%, P=0.011).ConclusionsThe interaction between thrombus and stent‐retriever was predominantly adhesive, not mechanical. Adhesive interaction was strongly associated with the presence of a dense thrombus surface without a porous filamentous fibrin network.

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Introduction: Safety and efficacy of novel drug-eluting coronary stents (DES) are often preclinically tested using healthy swine coronary models. These only show fibrotic neointima (NI) response, while in humans we also observe uncovered struts and minimal NI thickening. Therefore, healthy swine models only allow limited conclusions. Hypothesis: In an adult familial hypercholesterolemia (FH) swine model, NI healing after coronary DES implantation mimics the range of human NI responses to DES. Methods: Adult FH swine (n=6 French Bretoncelles-Meishan) were given a high fat diet for 12 months to develop coronary atherosclerosis. DES (n=14) were implanted under guidance of OCT at sites of confirmed atherosclerotic plaque. Swine were sacrificed at 28 days follow-up (FU). Serial OCT imaging was performed before, after and 28 days FU. Lumen area, stent area, plaque burden (PB) and NI burden were evaluated for each time point and frame and averaged per stent. PB prior to stenting was evaluated using coronary side branches as references. The percentage uncovered struts at FU was assessed on a strut-by-strut basis. Results: The NI response showed uncovered struts, minimal coverage and fibrotic NI thickening. We found an association between baseline lesion PB and FU findings (Figure). Low PB (<40%) prior to stenting resulted in a thick NI at FU, reminiscent of healthy coronary models. In contrast, high PB (>40%) resulted in thin NI coverage and more uncovered struts at FU, uniquely showing similarities to human responses. Conclusions: In this adult FH swine model, the NI response presents the whole spectrum that is seen in humans, from uncovered struts, to minimal, to fibrotic intimal thickening. Interestingly, pre-existing coronary atherosclerotic PB is negatively associated with NI thickness and strut coverage after DES implantation. This underscores the importance of advanced disease, versus healthy, animal models for safety and efficacy testing of DES.

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Background Despite the efficacy of novel drug eluting stents (DES) in preventing restenosis, this complication still occurs, as do neo-atherosclerosis development and poor stent strut coverage that are associated with stent thrombosis. Safety and efficacy of novel coronary stents are preclinically being tested using an established porcine coronary model. However, the use of young healthy animal only allow limited conclusions to be drawn on the long-term effects, as the artieries do not reflect human pathology of advanced atherosclerosis. A key unresolved question is whether and how the presence, size and composition of pre-existing atherosclerotic plaque affect neointimal healing. Purpose The objective of this study is to understand the role of atherosclerotic plaque in neointimal response following DES placement in a large animal model of coronary artery disease by using optical coherence tomography (OCT) analysis. Methods The study was approved by the animal ethics committee. Familial hypercholesterolemia (FH) swine (n=6 Bretoncelles-Meishan) were given a high fat diet for 12 months to develop atherosclerosis. Stents (n=14) were implanted in n=14 coronary arteries under guidance of OCT with a stent-artery ratio of 1.1:1 at sites of atherosclerotic plaque, and animals were sacrificed after 28 days. Two types of Sirolimus eluting stents with different release profiles were implanted. Serial OCT pullbacks were taken before and after stent placement and after 28 days (follow-up), quantitatively analyzed and compared using dedicated software. The lumen area, stent area, plaque size (calculated as external elastic lamina (EEL) area - lumen area) and neointima (calculated as stent area – lumen area) were evaluated for each frame and averaged per stent. The plaque burden before stent implantation was evaluated at the same site of stent placement using coronary side branches as reference. Results The graph shows the association between the pre-existing plaque size before stenting and neointima formation after 28 days. Surprisingly, more pre-existing plaque size resulted in less neointima (P&lt;0.01). There was one outlier, a stent with long dissection and extensive malapposition at baseline which showed an excessive tissue response at follow-up. The response in this animal model shows similarity to human vessel response as both regions with thin neointima formation as well as poor strut coverage were observed for both stent types. Conclusion The novel model of adult FH swine shows long-term vessel response to DES, that is similar to human response. This work shows that pre-existing atherosclerotic plaque affects the neointima after DES implantation. This insight highlights the necessity to use relevant disease models for safety and efficacy testing. Plaque size and neointima relation Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Netherlands Organisation for Health Research and Development (ZonMw)