Abstract 13819: Is an Adult Familial Hypercholesterolemia, Swine Model Suited to Test Safety and Efficacy of Drug-eluting Coronary Stents?

• Published in: Circulation (New York, N.Y.) N.Y.), 2020-11, Vol.142 (Suppl_3 Suppl 3), p.A13819-A13819
• Main Authors: Razzi, Francesca, Regar, Evelyn, Dijkstra, Jouke, Witberg, Karen, Ligthart, Jurgen, ramlal, sharad A, Stam, Mathijs, Krabbendam-Peters, Ilona, Hoogendoorn, Ayla, Wentzel, Jolanda J, van Soest, Gijs, Van Esch, Jan, Duncker, Dirk J, van Steijn, Volkert, Van Beusekom, Heleen M
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.142.suppl_3.13819

IntroductionSafety 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. HypothesisIn an adult familial hypercholesterolemia (FH) swine model, NI healing after coronary DES implantation mimics the range of human NI responses to DES. MethodsAdult 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. ResultsThe 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%) resulted in thin NI coverage and more uncovered struts at FU, uniquely showing similarities to human responses. ConclusionsIn 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.