| Background: The incidence of aortic stenosis was increased significantly with thedevolopment of aging population. Valve calcification and degenerative stenosis of the aorticvalve are arised in more than40%of80-year-old elderly. The incidence of AS in thepeople over the age of75is4.6%, AS has been the major disease second only tohypertension and coronary heart disease in America. The traditional treatment methods foraortic stenosis is surgery valve replacement. However, about30-50%patients with severecomplications can not recieve surgical treatment.In2002, Cribier et al.launched transcatheter aortic valve replacement surgerysuccessfully. Following this, the equipment and technology of transcatheter aortic valvereplacement gained attention gradually, the concept of transcatheter valve replacement hadbeen accepted by the experts. At present, dozens of valve stented have been used in animalexperiments or clinical application, however only Edwards and CoreValve valved stentsystem have been used the most widely.Since the TAVR device was used into clinical, more than35,000cases has beencompleted in the world. The Partner studies have shown that: the1year survival rate ofTAVR is similar with surgery for those severe aortic valve disease patients at high risk whocan not recieve the surgical treatment. In addition, TAVR can also be treated the patients withaortic bioprosthesis failure. This technology is mature and develop ing complementary andalternative treatment for SAVR.Beginning in2010, some AS patients had been treated with the Corevalve and Edwardsprosthetic valved stents at Zhongshan Hospital and Changhai Hospital respectively in China.The TAVR procedures have been performed at some hospitals in Beijing later. However, thistechnology is still not carried out widely in our country on account of high cost and withoutratification by SFDA. In addition, few patients can afford the high medical costs to receivedTAVR treatment with the valved stents which imported abroad. Therefore, the research ofvalved stents localization is imperative. But the progress of localization is slow relatively, nohomemade devices for TAVR has been applied in clinical. We had developed aself-expandable pulmonary valved stent and aortic valved stent since2006. We havedeveloped a transcatheter nitinol self-expanding aortic valved stent system for TAVR with theLepu(Beijing) Medical Device Co., Ltd.since2010, and carried out the experimental study with this device.Objectives: To evaluate the feasibility and safety of transcatheter replacement of aorticvalve of goats with a new-type self-expanding valved stent, test the function of the stent, andprovide experimental data for further studies.Methods:(1)Applied anatomy and imaging of transcatheter aortic valve replacementTwenty adult human heart specimens and twenty fresh healthy hircine hearts weredissected and measured. Observe the anatomic position of aortic valves and the relationshipbetween the aortic valves and adjacent structure firstly. The perimeter of aortic valve annulus,the length of aortic valve free margin and attachment margin were measured respectively. Thearea of valve leaflet, the distance from coronary ostium to sinus bottom and the length ofascending aorta were also measured. Six healthy goats were also used for measurement ofheart anatomy in vivo; The diameter of aortic annulus, left ventricular myocardium thickness,left ventricular end-diastolic volume, left ventricular end-systolic volume, and left ventricularejection fraction were evaluated by transthoracic echocardiography; Left ventriculography wasperformed to determine the best projecting position for aortic sinus imaging; The catheterdelivery system of16F and18F was inserted through the femoral artery, the left iliac arteryand the infrarenal aorta respectively, the diameter of which was measured at baseline.(2) Development of the self-expanded valved stent and delivery systemA diamond-shape meshes stent was engraved from domestic straight nickel-titaniumalloy tubes by laser and been formed the valved stent with three parts those were aortic part,left ventricular outflow tract part and waist part by heat treatment. Fresh porcine pericardiumwas shaked continuously in a0.01%trypsin solution for24hours, then cross-linked with a0.6%glutaraldehyde solution at4°C for36hours, and then was immersed in2%L-glutamicacid solution for24hours to remove toxicity of glutaraldehyde. The processed porcinepericardium was trimmed into leafets and sutured by hand into the stent. The delivery systemconsists of an outer sheath,an inner dilator, control handle. The outside diameter of deliverysystem is14-French. The valved stent can be intaken into the sheath with preloading assistdevices.(3) Experiments of new TAVR device in vitroInsert the shealth loaded valved stent into a translucent silicone tube with a metal ring by DSA, release the vavled stent when the prosthetic annulus overlapped with the metal ring onthe tube. measure the distance from the prosthetic annulus to the metal ring after releasing.The data was been divided into3groups(Group A, Group B and Group C). Group B, Group Ccompared with Group A.(4) The effect of pacing frequency on transaortic valve pressure gradients in goatsSix healthy adult goats randomly chosen for the study were tested under generalanesthesia. A temporary pacing lead connected with a temporary pacemaker be sent to theright ventricle through the femoral vein. The pacing frequency range from150beats/min to350beats/min by increment of25beats/min. The aortic systolic, diastolic and meanpressure were measured at different pacing frequency and the pressure gradients in aortic werecalculated.(5) Experimental study of transcatheter aortic valved stent implantationSixteen healthy goats was selected to replace the aortic valve in situ through the internalcarotid artery or infrarenal aorta with the new TAVR device under DSA,and were followedup for12months after procedure. ECG, imaging and hemodynamic examination wereundergone at the time of immediate postoperative period,3months,6months and12months, and some goats were killed to for gross anatomy and pathology examination. The"valve-in-valve" technique was used to remedy goats which the first valved stent implantedincorrectly..(6) Development of retractable aortic valved stent systemDeveloping two kinds of transcatheter retractable nitinol self-expanding aortic valvestents and the supporting delivery devices. It's structure was connected with rivet. The valvedstent was made up of four parts which were aorta, bottom, waist and extension part.Delivering and releasing of the valved stent were controlled by cable. Preliminary experimentsof the devices were test in both vitro and vivo.Results:(1) The perimeter of aortic valve annulus of adult and canines in vitro were (69.56±3.48)mm and (59.43±7.51) mm respectively, the length of aortic valve free margin were (29.17±2.21) mm and (21.33±2.75) mm respectively, the length of attachment margin were (23.45±2.66) mm and (18.20±2.36) mm respectively, the distance from lower edge of left coronaryartery to valve annulus (15.51±1.13) mm and (10.30±0.89) mm respectively, the distance from lower edge of right coronary artery to valve annulus (12.88±0.87) mm and (8.36±1.24) mmrespectively. The diameter of hircine aortic annulus and aorta in vivo by imaging was(19.24±2.67) mm and (18.02±3.37)mm respectively. The diameter of the femoral artery, theleft internal carotid artery and the infrarenal aorta was (5.33±2.39) mm,(7.20±1.65) mm and(8.24±2.77) mm respectively. The18F catheter delivery system could be easily insertedthrough the infrarenal aorta.(2) The valved stent consists of three parts: the aortic part, waist part and left ventricularoutflow tract part. The aortic part is inflate, the waist part is thin relatively and the leftventricular outflow tract is slightly cone-shape. The valved stents were been divided fourspecifications as18,20,22and24mm of four specifications in accordance with diameter of thewaist and the shape of valve is completely imitated native valve. The valved stent can beintaking into the16F sheath designed specially with the supporting device, and be implantedin vivo through the vessel. The releasing is controlled by the operating handle. Experiments invitro showed the delivery sheath worked reliably. The pre-loaded supporting device loadedvalve effectively. The repeated deployment was smoothly, and the valved stent appeared nodamage.(3) The valved stents had been released successfully30times by DSA(success ratio100%), of which23times are accurate(76.67%). the prosthetic annulus overlapped the metalring4times, no come up to the the metal ring5times(average value-2.00±1.00mm) andsurpassed the metal ring21times(average value2.84±2.56mm). The average value of inclinethe base overall is2.03±3.05, Group A is3.60±4.14, Group B is1.90±2.60(95%CI: P＞0.05)and Group C is0.6±1.07(95%CI: P＜0.05).(4) The transaortic valve systolic pressure gradient rised with the acceleration of thepacing rate. When the pacing rate accelerated to250-300beats/min, the pressure gradientrised from-25.00±3.90mmHg to11.17±10.85~13.50±3.89mmHg. Diastolic transvalvularsystolic pressure gradient declined with the acceleration of the pacing rate. When the pacingrate accelerated to250-300beats/min, the pressure gradient was in the43.83±2.93~47.00±3.03mmHg, showing a lower decline rate of50.11%(P <0.01,95%CI).(5) Of sixteen goats, two die of stents implanted were too large and improper position.One died of right coronary artery was blockaged by stent, and this goat lived for3hours afterprocedure. One died of vascular complications. The position of valved stents is too high in2 goats in first implantation, then they were remedied by "valve-in-valve " technique. Thevalved stent'position of first implantation is too high, then it was retracted and deployed in thedescending aorta, then another stent was implanted in situ successfully. Nine goats weresurvive. The mean aortic annulus diameter was (18.25±1.59) mm on fluoroscopymeasurements at baseline. The mean aortic stent diameter was (22.60±0.97) mm, theprocedure time was (98.60±16.21) min. Imaging inspection showed that the aortic prostheticvalves working properly and cardiac function of the goats were regular in postoperativeimmediacy,3months,6months and12months. The ECG showed no evidence of conductionblock and other arrhythmias. The tissue specimen of postoperative immediacy,3months and12months showed that the valve stents were in good position. A layer of transparentendometrial tissue covering the stent surface on the anatomical specimens after12months.The endothelial cells covered on the valve stents were mature and compact under scanningelectron microscope.(6) The new retractable valved stent consists of four parts: the aortic part, waist part, leftventricular outflow tract part and extension part. The nut on the top of extension part can beconnected with the cable which can push and deploy the valved stent. Delivery systemconsists of the sheath, the inner core, cable and hemostatic valve. The diameter of sheath is16French. Experiment showed that the new valve stent can be deployed and retractedsmoothly witn the supporting delivery devices, the valved stents had no damage afterdeployed repeatly.Conclusions: The self-designed aortic valved stent was implanted into the native aorticannulus of canines successfully, which has good structural stability and excellentbiocompatibility. The study shows that the new-type valved stent and delivery system weresafe, feasible and efficient. The results support the further investigation of the aortic valvedstent for possible use in clinical.
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