| Background: Atrial fibrillation is a common arrhythmia, which can cause serious complication including ischemia stroke, putting a huge medical and economic burden on our country. Oral antithrombotic drug is a safe and effective strategy for preventing stroke in patients of atrial fibrillation. Among those oral antithrombotic drugs, Warfarin is most commonly used, which is easily affected by food and other drugs, also needs frequent monitoring of INR because of narrow therapy window, and holds a high risk of major bleeding. Many newly-developed oral antithrombotic drugs no longer need monitoring of INR, but still could induce serious bleeding. Patients of high risk for bleeding could hardly endure the strategy of oral antithrombotic drugs. It has been discovered that more than 90% of thrombus formation happens at the site of left atrial appendage(LAA). LAA occlusion is found to be a safe and effective strategy for preventing stroke in atrial fibrillation in many studies. There have been several devices for LAA occlusion, including ACP、WATCHMAN and LAmbre, which respectively holds many advantages and flaws also, the latter affecting the safety and effectiveness of LAA occlusion. This technique has been ongoing for a long period in China, but till now only the LAmbre device(HongKong) has been applied to clinical. Our center has carried out studies of LAA occlusion for several years, and is hammering at inventing a new LAA occlusion device, along with Pushi Medical Corps(ShangHai), which has very strong strength for occluder development and production.Objective: To develop a novel device for LAA occlusion system, and to evaluate its mechanical property, its safety and effectiveness for LAA occlusion in animal experimentation(canine), in an attempt to lay a foundation for subsequent clinical trials.Methods: 1. The development of a novel device for LAA occlusion and its experimentation in vitro: inspired by the features and clinical trial results of the LAA occlusion devices used in clinical at the moment, we aim at making some improvements and developing a novel device for LAA occlusion.(1) On the basis of the classical double-disk LAA occluder, we make some improvements, including the bowl-shaped LAA disk, no-polyester fiber membrane design, pykno-knited by thin filament, loop-shaped and directional variable barbs, capacity to be fully retrieved, and the proper camber of delivery sheath.(2) The production of the novel LAA occlusion is fulfilled by Pushi Medical Corps(ShangHai).(3) The experimentation in vitro for LAA occlusion system: firstly to evaluate the mechanical property of the new device, including its compressibility, elastic recovery, capacity load of hydrostatic pressure, secondly to carry out experimentation in vitro of the LAA occlusion system. 2. Animal experimentation of the LAA occlusion system in canine model:(1) LAA occlusion procedure includes the following steps: anesthesia of canine, femoral vein puncture, atrial septal puncture, LAA angiography, measurement of the LAA parameters, and the positioning and releasing of the occluder.(2) After the procedure, canines are administrated by sequential therapy of LMWH for 3 days, aspirin and clopidogrel both for 3 months, and then aspirin alone till the last follow-up.(3) Follow up: while the canines died during the procedure are dissected instantly for gaining experience, other canines are scheduled to follow-up visits at 1, 3, 6 months after the procedure, including the general condition, ECG and chest fluoroscopy, trans-esophageal echocardiography(TEE), LAA angiography, observation of gross specimens and pathological sections, in an attempt to gain information of effectiveness, such as endothelialization and complete closure of LAA, and also the safety concerns, including pericardial effusion, device embolism, affecting the adjoining structures and so on.Results: 1. The development of a novel device for LAA occlusion and its experimentation in vitro:(1) The novel device for LAA occlusion has two plates, the left atria plate and LAA plate, jointed by a thin waist, which permits a small range of motion. The LAA plate is bowl-shaped, anchored in the LAA; the left atria plate covers the orifice of LAA, blocking up blood flow. There are four pairs of loop-shaped directional variable barbs on the LAA plate. The occluder is pykno-knited by thin filament, without polyester fiber membrane in the plate. The camber of head end of the delivery sheath is about 100°, proper for the orifice of LAA. According to the size of LAA of canine, the devices range from 16 mm to 22 mm in the diameter of the LAA plate.(2) The production of the LAA occlusion system is accomplished by Pushi Medical Corps(ShangHai).(3) The experimentation in vitro for LAA occlusion system: the device has good mechanical property, including its compressibility and elastic recovery capacity. The plate without membrane in it can endure hydrostatic pressure of 45-60cmH2 O, more than sufficient for the pressure in LAA even under pathological conditions. Devices of 16-22 mm can be easily pushed through, released and retrieved within a 8F delivery sheath for at least 5 times, without damaging the barbs or delivery sheath. In the test in vitro with canine hearts, the delivery sheath is in good position for LAA orifice, and we did not notice any injuries to the LAA wall by the barbs on the LAA plate during retrieving the device. 2. Animal experimentation of the LAA occlusion system in canine model:(1) during the procedure 3 of 15 canines died, of cardiac tamponade caused by atrial septal puncture, device embolism caused by improper choice of occluder, and anesthesia too deep, respectively. The success rate of the procedure is 80%(12/15). Among those canines alive, the rate of complete closure immediately after the procedure is 75%(9/12), while the other 3 canines show a small amount of residual shunt.(2) Follow-up: the 12 canines are fed in good general condition until the last follow-up date. ECG is normal, and chest fluoroscopy shows no dislocation or deformation of the occluder. TEE and LAA angiography show complete closure of LAA in all canines, including the 3 canines with a small amount of residual shunt immediately after the procedure. Gross specimens show prosperous endothelialization in all canines. Endothelial cells are in an orderly arrangement under light microscope. TEE shows a canine with moderate mitral insufficiency, in which canine TEE or gross specimen shows no direct contact of the device and the mitral valve. We consider the moderate mitral insufficiency may not be device-related.Conclusion: The novel system for LAA occlusion is original designed, including bowl-shaped LAA disk, no-polyester fiber membrane design, loop-shaped and directional variable barbs, and so on. Animal experimentation shows it is safe and effective in LAA occlusion. No serious complication occurred during perioperative period, except that 1 canine died of device embolism because we lacked of experience at the beginning of our experiment and chose a smaller device. The rate of complete closure of LAA immediately after the procedure is 75%, and grows up to 100% at 1, 3, 6months after the procedure. We believe that with the increase of experience and the improvements of the device, the novel device will show better property of safety and effectiveness in subsequent animal experiments and clinical trials. |
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