Development Of Jing’s Valved-fenestrated Endograft System And Its Experimental Study In Animals

Background: Ascending aortic aneurysm is defined as a local abnormal expansion of the ascending aorta wall to more than 1.5 times the normal diameter.90% of patients are prone to develop into aortic rupture within 5 years without surgery.Ascending aortic aneurysm is often accompanied by aortic regurgitation.Aortic regurgitation is a kind of disease characterized by aortic valve structure damage,perforation,fibrosis,shortening and degeneration.There is no obvious clinical manifestation in the early stage of the disease,but in the late stage of the disease,the conditions will progress rapidly if symptoms appear,which will suffer severe heart failure and cause death in a short period of time.Therefore,ascending aortic aneurysm combined with aortic regurgitation is a dangerous and lethal disease.Traditional open surgery such as Bentell or Wheat(aortic valve and ascending aorta replacement with or without coronary revascularization)is the gold standard for the treatment of ascending aortic aneurysm with aortic regurgitation.Despite significant advances in open surgery-related technologies,mortality and morbidity have been significantly reduced,but many patients who are eligible for traditional aortic valve and ascending aorta replacement surgery are unable to tolerate open surgery due to factors such as advanced age and comorbidities.According to the International Register of Aortic Disease(IRAD)database,mortality was highest(58%)if conservative treatment was used alone.Therefore,minimally-invasive treatment of ascending aortic aneurysm with aortic regurgitation is important for such patients.Endovascular repair has the characteristics of small trauma,good prognosis and low mortality.It is gradually replacing traditional open surgery and has become the first line of treatment for complex aortic diseases,and widely used in abdominal aortic,descending aortic and aortic arch.Domestic and foreign scholars have begun to explore the application of intraluminal techniques to the treatment of ascending aortic dilatation;The successful application of transcatheter aortic valve implantation(TAVI)in high-risk patients has played a positive role in promoting the minimally-invasive treatment of aortic valve and ascending aortic root lesions.As we know,there are currently no successful in vivo studies of valved endograft reconstruction of the aortic valve,aortic sinus,coronary artery,and ascending aorta.Based on the clinical practice of thoracic aortic endovascular repair(TEVAR)in the treatment of ascending aortic disease and TAVI in the treatment of aortic valve disease,this study proposes an one-piece valved-fenestrated-bifurcated endografting(Jing’s valvedfenestrated endograft system)and its related delivery system and the positioning release method,using the aortic annulus and the brachiocephalic artery as an anchoring region to exclude the aneurysm from the aortic valve to the proximal region of the aortic arch,while protecting the coronary artery by fenestration and reconstructing the aortic valve,in the meantime exploring its early feasibility in healthy animal and animal disease models.Objective(1)According to the new graft design concept,Jing’s valved-fenestrated endograft system with complete structure and function was designed and manufactured to meet the needs of endovascular treatment of ascending aortic aneurysm with aortic regurgitation.(2)To construct a mature animal model of ascending aortic aneurysm with aortic regurgitation.The shape of the aneurysm,the length of anchorage zone and the degree of valve regurgitation can meet the evaluation needs of the new graft system.The animal disease model is stable for a long time.(3)To evaluate the early feasibility,safety and effectiveness of Jing’s valvedfenestrated endograft system by completing in vivo experiments on healthy animals and animal disease model experiments.Methods(1)Development of Jing’s valved-fenestrated endograft system: measuring and analyzing the anatomical data of the ascending aortic root of healthy pigs,making a Z-ring with Nitinol wire as the graft skeleton,covering the polyester membrane,each part is assembled,the corresponding position of the graft is fenestrated,the trifoliate is sutured at the proximal end of the graft,the precordial part of the bovine pericardium treated by decellularization + glutaraldehyde is used for the artificial valve,and to explore the compression and installation of new grafts and the method of localized release in vivo.(2)Animal experimental study: Adult healthy pigs were selected for in vivo experiment,introducing and releasing Jing’s valved-fenestrated endograft through apex of heart,the axial and circumferential positioning,two-stage release,and the release of the head after the graft released were completed.To evaluate the introduction mode of the graft,positioning release and withdrawal method of the delivery system,and the feasibility of Jing’s valved-fenestrated endograft system by the above experiment;(3)Construction of ascending aortic aneurysm combined with aortic regurgitation model: Adult healthy pigs were selected as experimental animals,bovine pericardial patch was used,cut and sutured to form a hollow drum,and the proximal aorta of the ascending aorta was replaced under general anesthesia.And use acupuncture to destroy the valve leaflets,construct a model of ascending aortic aneurysm combined with aortic regurgitation,and use the mature graft system and related localization release program to endovascular repair the disease model animals,through DSA,heart ultrasound,CTA to evaluat the excludsion of aneurysms,valve function,patency of branches and pathological examinations,and to assess the safety and efficacy of the graft system during and after surgeryResults(1)The anatomical parameters of the root of ascending aorta in pigs were obtained,and on this basis,a new complete-structured Jing’s valved-fenestrated endograft and its supporting transport device were developed.(2)The introduction,localization,release and withdrawal of this new graft in healthy animals were completed.Though imaging examination and specimen anatomy after surgery,the morphology and position of the graft was confirmed to be appropriated,the aortic valve was successfully reconstructed,and there was no significant change in the animal cardiac function during the follow-up period.(3)The animal model of ascending aortic aneurysm with aortic regurgitation was successfully made.Imaging examination and autopsy confirmed the successful construction of the disease model.The releasing process of new valved stent graft system was completed in animal model.Conclusion Jing’s valved-fenestrated endograft system is feasible for the treatment of ascending aortic aneurysm with aortic regurgitation.The perioperative and follow-up period results showed that the therapeutic effect was ideal.The development and related experimental research of this new graft will provide new ideas for endovascular treatment of ascending aortic aneurysm,providing a reference for future clinical trial research.