Transthoracic Reverse Occlusion Of Left Atrial Appendage:Instruments Development And Experimental Study

Background:Atrial fibrillation is the most common sustained arrhythmia,which has a large number of patients. According to conservative estimates there are more than 8 millions patients with atrial fibrillation in our country at present. The most serious consequence of atrial fibrillation is stroke, which brings heavy burden to society and family for its high disability rate and high death rate. Left atrial appendage plays a fatal role in the incidence of stroke especially in patients with nonvalvular atrial fibrillation, whose 91% thrombus formation are in left atrial appendage. This is the theoretical basis of treatment including left atrial appendage resection, suture separation, thoracoscopic ligation and transcatheter closure for the prevention of stroke in patients with atrial fibrillation.However, surgical resection of left atrial appendage was only suitable for simultaneously in cardiac operation because of its large trauma and long recovery time.what’s more, there was often residual root after resection of the left atrial appendage. Short-term and long-term failure rate suture separation were higher, and if the operation failured thrombosis risk wouid rise, thoracoscopic ligation using auxiliary equipment improved the success rate of left atrial appendage closure, but the clinical application is limited because of complex operation and a certain proportion of releasing rate postoperation. In all closure devices of transcatheter occlusion of left atrial appendage, there were two types of occlusion methods:One is the "piston", such as Wacthman devices and PLATTO devices, which can not be easy to closured for left atrial appendage like chicken wings or cauliflower. Another is "coverage", such as Amplatzer Cardiac Plug (ACP) and LAmbre devices, which would be influence adjacent structures, such as pulmonary vein, mitral valve etc, because needing to choose the larger occluder to completely cover the long and narrow opening of appendage, devices wound increase the sealing disc coverage. In addition, the barbs of device may injury cavity wall leading to chronic perforation, oppression circumflex branch etc. And for whose left atrial appendages with a shallow cavity like a basin, it can not be closed transcatheter because there was no suitable "landing zone". At the same time, the occluder were woven with metal materials, its safety still uncertain because of lack of long-term follow-up data, such as wearning and eroding surrounding tissue accompanied by heart beating.The surgical and interventional methods were combined to make a research on the hot issue of left atrial appendage occlusion in this study, which attempted to solve two problems:First, we created a new operation----transthoracic reverse occlusion of left atrial appendage. Second, we designed two kinds of different materials of the occluder and conveying systems, and then evaluated the feasibility, effectiveness and safety by transthoracic reverse occlusion of left atrial appendage through in vitro and animal experiments. Our aim is laid an experimental foundation for the next animal experimental study of thoracoscopic occlusion of left atrial appendage. The experimental contents are summarized as follows:Objectives:To design metal left atrial appendage occluder and absorbable left atrial appendage occluder and transportation system for transthoracic reverse occlusion; To evaluate the feasibility, effectiveness and safety by in vitro experiments and animal experiments, and provide an experimental foundation for the next step study with video assisted thoracoscopic of left atrial appendage reverse occlusion.Methods:(1) Application anatomy of the experimental canine:Take 15 fresh canine heart specimens, then we dissected and measured the following 12 anatomical parameters: including atrial appendage lateral extend length; outside diameter of 1/3; lateral root long diameter, short diameter, perimeter of the loop; the shortest distance from the atrial appendage edge of the opening to the left superior pulmonary vein, the left inferior pulmonary vein, and the edge of the mitral valve; 1/3 the thickness of atrial appendage; the long diameter, short diameter and perimeter of atrial appendage opening. (2) The design of nickel titanium alloy left atrial appendage occluder and conveying systems and in vitro animal experiment:Designing nickel titanium alloy LAA occluder like "wine cup" and conveying system, there were the 9 fresh dog heart specimens in vitro experiments to identify the feasibility of transcatheter closure of the left atrial appendage occlusion. (3) The design of absorbable left atrial appendage occluder and conveying systems and in vitro animal experiment:Designing absorbable LAA occluder like "double disc" and conveying system, there were the 6 fresh dog heart specimens in vitro experiments to identify the feasibility of transcatheter closure of the left atrial appendage occlusion. (4) Experimental study of transthoracic reverse occlusion using nickel titanium alloy left atrial appendage occluder:This study contained 9 healthy canines. We first made left atrial appendage angiography, then exposed and hanged the left atrial appendage through mini-thoracotomy and measured the diameter of left atrial appendage opening. After we made a fried in the up of 1/3 atrial appendage, punctured the fried to establishment an half track of "outside-puncture point-left atrial-left ventricular", we chosed the occluder whose diameter was larger than the opening about 25% to occlude it, then made left atrial appendage angiography again at the end of the operation. X-ray fluoroscopy, ECG, left artrial appendage angiography, non selective coronary angiography, and transesophageal echocardiography was performed at 24 hours、1 week、8 weeks respectively on two dogs after device implantation during postoperative follow-up. After had been done there works, dogs were sacrificed to observe occluder position. (5) Experimental study of transthoracic reverse occlusion using absorbable left atrial appendage occluder. This study contained 7 healthy canines. Operation process was the same with the metal occluder animal experiment. X-ray fluoroscopy, ECG, left artrial appendage angiography, non selective coronary angiography, and transesophageal echocardiography was performed at 24 hours、8 weeks respectively on two dogs after device implantation during postoperative follow-up. After had been done there works, dogs were sacrificed to observe occluder position.Results:(1) Application anatomy about transthoracic reverse occlusion of the experimental canine:Left atrial appendage of canine was the narrow cavity with a blind end similar to a niche. Its anatomic parameters are as follows:atrial appendage lateral extend length was (37.1±1.80)mm; outside diameter of 1/3 was (16.0±1.45)mm; lateral root long diameter, short diameter, perimeter of the loop was (15.8±0.97)mm,(7.0±0.84) mm,(37.0±2.24)mm respectively,; the shortest distance from the atrial appendage edge of the opening to the left superior pulmonary vein, the left inferior pulmonary vein, and the edge of the mitral valve was (5.92±0.92)mm,(7.5±0.79)mm,(8.4±0.67)mm respectively; 1/3 the thickness of atrial appendage was (12.3±1.23) mm; the long diameter, short diameter and perimeter of atrial appendage opening was (15.8±0.92)mm, (6.9±0.85) mm, (36.5±2.88)mm respectively. (2) The design of nickel titanium alloy left atrial appendage occluder and conveying systems and in vitro animal experiment:The overall appearance of occluder was "wine cup", there were two disk, and three layers of polyester film to block the blood flow, Atrial appendage side disk diameter had three kinds types including 16mm,18mm and 20mm, while atrial appendage lateral disk diameter was 16mm, each type had waist high 8mm,10mm respectively. The conveying system comprises 9F delivery sheath, expansion sheath, preload sheath and a pushing cable. Delivery sheath has scale which can be use to grasp the depth into the left atrial appendage, and expansion sheath head end had smooth transition shape which exposed only about 0.8cm when inserted into the delivery sheath to prevent damaging internal tissue of heart. In vitro, the occluder can be smoothly loaded, transported and released through 9F sheath. In vitro occlusion experiment of 10 canines,9 cases were successful, it showed that after the completion of the occlusion of atrial appendage occlude located stably in the central of left atrial appendage opening, the distance from its edge to the left inferior pulmonary vein, the left superior pulmonary vein and mitral edge were more than 3mm, so there was no influence on theirs blood flow. The ideal point of puncture should be located in 1/3 long axis of left atrial appendage outside.1 case was failure because of poor puncture point. (3) The design of absorbable left atrial appendage occluder and conveying systems and in vitro animal experiment:The overall appearance of occluder was "double disc", it consists of a framework filled with two pieces of Poly-L-lactic acid (PLA) fabrics. The framework was woven from polydioxanone (PDO), Atrial appendage side disk diameter had two kinds of types including 20mm and 22mm, while atrial appendage lateral disk diameter was 10mm, each type had waist high 8mm,10mm respectively. The conveying system comprises 14F delivery sheath, expansion sheath, preload sheath and a pushing cable. Delivery sheath has scale which can be use to grasp the depth into the left atrial appendage, and expansion sheath head end had smooth transition shape which exposed only about 0.8cm when inserted into the delivery sheath to prevent damaging internal tissue of heart. In vitro, the occluder can be smoothly loaded, transported and released through 14F sheath. The released occlude can restore the shape after loading sustained 15minutes. like-riveting structure of occlude tail can be undergo (5.2±0.75) effective delivering and releasing without destroying. In vitro occlusion experiment of 6 canines, all cases were successful, it showed that after the completion of the occlusion of atrial appendage occlude located stably in the central of left atrial appendage opening, the distance from its edge to the left inferior pulmonary vein, the left superior pulmonary vein and mitral edge were more than 3mm, so there was no influence on theirs blood flow. The position of occluder does not move when it was stretched. (4) Experimental study of transthoracic reverse occlusion using nickel titanium alloy left atrial appendage occluder:Of 9 canines, operation was successful in 8 cases (Operation success was defined as canine can be removed the ventilator smoothly after complete operation and experimental animal can survive for 24 hours) The success rate was 88.89%. One dog (Number Al) died of hemorrhage during the operation, the others survived. Follow up data from X-ray fluoroscopy, ECG, left atrial appendage angiography, non selective coronary angiography, transesophageal echocardiography, and sacrificing general observation indicated occluders location were good, they did not affect the left superior pulmonary vein, the left inferior pulmonary vein and mitral blood flow, circumflex branch would not be squeezed, the occluders had been basically endothelialization 8 weeks after operation in 5 dogs. But 1 dog (Number A7) was killed 8 weeks after operation had hilge thrombus in atrial, which may be related to inadequate anticoagulation. There are 2 dogs are still at follow-up and be in good condition so far. (5) Experimental study of transthoracic reverse occlusion using absorbable left atrial appendage occluder:Of 7 canines, operation was successful in 6 cases The success rate was 85.71%. One dog (Number B2) died of anesthesia during the operation, the others survived. Follow up data from X-ray fluoroscopy, ECG, left atrial appendage angiography, non selective coronaty angiography, transesophageal echocardiography, and sacrificing general observation indicated occluders location were good, they did not affect the left superior pulmonary vein, the left inferior pulmonary vein and mitral blood flow, circumflex branch would not be squeezed, the occluders had been fully endothelialization 8 weeks after operation in 4 dogs. There are 2 dogs are still at follow-up and be in good condition so far.Conclusions:Transthoracic reverse occlusion of left atrial appendage using metal occluder and absorbable occlude is is feasible, safe and effective. It is applicable to any form of left atrial appendage and there are no complications such as occlude abscission, effecting blood reflux of pulmonary veins and the mitral valve function, etc. Some complications rarely happen including residual shunt and extrusion circumflex artery. The main disadvantage is slightly larger trauma and slower recovery. Compared with the metal occluder, the absorbable occluder has better endothelialization and biocompatibility and would not be permanently retained foreign body. This study showed that we can carry on to the next animal experimental study of thoracoscopic reverse occlusion of left atrial appendage.