A Novel Nitinol Occluder For Occluding Left Atrial Appendage Of Canines:An Animal Experimental Study

Background: Atrial fibrillation(AF)is one of the most common cardiac arrhythmia and the most serious complication is cerebral embolism.It can cause a high disability or mortality rate and severely affect the quality of patients' life,and cause a heavy economic burden to family and society.It increases the risk of cerebral embolism for patients five-fold.AF treatmeat strategies include cardioversion(pharmacologic cardioversion,current electrical cardioversion),maintenance of sinus rhythm,controlling too fast ventricular rate,anticoagulation therapy and radiofrequency ablation.Drugs can make some AF mainly paroxysmal atrial fibrillation cardioversion to sinus rhythm,while it is complex for persistent AF cardioversion and the success rate is relatively low,as it needs for regular anticoagulation therapy before cardioversion and the recurrence rate is high after cardioversion.In recent years,Radiofrequency ablation of atrial fibrillation has developed rapidly,the success rate of paroxysmal atrial fibrillation is about 80% while the success rate of persistent atrial fibrillation is 50%.Atrial fibrillation patients are required routine multislice computed tomography and transesophageal echocardiography examination before underwent radiofrequency ablation to exclude left atrial thrombus and to rule out contraindications to operation.The consistency of two examination methods detecting thrombus is reported variously.For recurrence paroxysmal and persistent atrial fibrillation,anticoagulant therapy for preventing cerebral embolism is especially important.Warfarin is classical anticoagulant drug of vitamin K antagonists,and its therapeutic window is narrow.It needs for regular monitoring the prothrombin time international standardization ratio and it is easy to be affected by food and other drugs,which results in poor compliance during patients taking warfarin and high interrupt rate.Novel oral anticoagulants have some advantages compared to warfarin and it does not require regular monitoring coagulation function.The disadvantage of novel oral anticoagulants is that it is short for the corresponding antagonists and patients with high bleeding risk are still not suitable for the use of these drugs and the price is relatively expensive.Studies have shown that the source of thrombus in patients with non-valvular atrial fibrillation is 91% rooted in left atrial appendage.The left atrial appendage transcatheter closure operation is an effective measure to prevent thrombus in left atrial appendage of atrial fibrillation patients.At present,left atrial appendage closure system in current clinical application includes Watchman,Amplatzer Cardiac Plug,LARIAT and LAMBRE occluder,the former three systems are imported occluders.The imported occluders are relatively expensive and it is hard to afford by domestic patients.Our center intends to develop a novel left atrial appendage closure system on the researcher and development basis of past left atrial appendage closure system.Objective: 1.To discuss the value of multislice spiral computed tomography(MSCT)and transesophageal echocardiography(TEE)in evaluating left atrial thrombus in patients with atrial fibrillation;To observe left atrial appendage(LAA)morphology in patients with atrial fibrillation and provide the basis for developing a novel nitinol occlude.2.To develop a novel nitinol LAA occluder and evaluate feasibility,efficacy and safety of left atrial appendadge occluder by animal experiments in canine model.Methods: 1.To collect hospitalized atrial fibrillation patients undergoing radiofreqrency ablation from January 1st 2014 to June 30 th 2015 in Department of Cardiology in our hospital,during hospitalization underwent MSCT and TEE examination,then collect the results of the two examination methods for detecting thrombosis,to compare the sensitivity and specificity of the two examination methods;2.To select clean healthy 14 dogs and puncture atrial septal and occlude left atrial appendage of canines through femoral vein.After operation immediately,1 month,3 and 6 months,to observe the experimental results by radiography,TEE and anatomy,such as thrombus,neoplasm and endothelialization on the surface of occluder.(1)The design of novel nitinol LAA occluder and delivery system: the double-disc structures with the disc in LAA which is conical columnar basal structure and the disc in left atrial covering the opening of LAA.The occluder were wovened densely by filaments with multi-direction and muti-angle implanting barbs.The occluder can be withdrawn after releasing and can adapt to different morphologies of left atrial appendage.The delivery system was improved on the basis of atrial septal defects delivery system and the head angle of delivery sheath was larger.(2)Left atrial appendage closure experimental process: including pre-experimental anesthesia,femoral vein catheter,atrial septal puncture process,left atrial appendage angiography,the measurement for left atrial appendage neck,the selection,delivery and release of occluder,and post-release angiography for confirmation process finally;(3)Postoperative treatment: dogs after the opetation received enoxaparin 20 mg subcutaneously 1/12 hours for 3 days and took aspirin 3-5mg/(kg·d)and clopidogrel 1.25mg/(kg·d)until one month,three and six months of experimental nodes respectively;(3)The efficacy and safety evaluation: The experimental dogs which were executed at 1 month,3 and 6 months respectively after successful closure.To observe general conditions of experimental dogs,electrocardiogram,left atrial appendage and coronary angiography,transesophageal echocardiography examination,the gross anatomy and endothelial condition on the surface of the left atrial disc of the occluder.To evaluate the feasibility of occluder implantation comprehensively and evaluate its biocompatibility furtherly.By analyzing the experimental procedure-related complications such as pericardial tamponade,apparatus related thrombotic events,the influence to the adjacent structures of left atrial appendage to evaluate its safety.Results: The comparative study of the value of MSCT and TEE in detecting left atrial thrombus: To observe altogether 202 cases of atrial fibrillation patients,124 male cases and 88 female cases,MSCT detecting 190 cases were consistent with TEE,among which 6 cases were detecting thrombus formation and the remainder 184 cases were not found thrombus,the diagnostic accordance rate was 94.1%.8 cases were detected thrombus positive or suspected positive,which was different from the TEE test results.It was shown congestion performance in 1 case,cloudy shadow in 1 case,flocculent echo in 1 case and no significant thrombus in 5 cases in the left atrial and left atrial appendage by TEE examination.Another 4 cases,1 case was detected as left atrial anterosuperior wall thrombus and the other 3 cases were detected as a little thrombus in the left atrial appendage,while the MSCT detected no thrombus.The TEE was regarded as gold standard,the sensitivity was 60% for MSCT detecting thrombus,the specificity was 95.8%,the positive predictive value was 42.9%,the negative predictive value was 97.9%,the positive likelihood ratio was 14.4 and the negative likelihood ratio was 0.42.After fourfold table paired chi-square test,?2=45.936,P<0.01 and ?=46.9%;The morphology for MSCT detecting left atrial appendage is cauliflower shape in 20 cases(9.9%),cactus shape in 61 cases(30.2%),chicken wing shape in 81 cases(40.1%)and vane shape in 40 cases(19.8%).Among 6 cases which were detected by two methods thrombus formatiom the morphology of left atrial appendage of 4 cases is cauliflower,persistent atrial fibrillation is 4 cases,mean left atrial volume is 124.25 ±12.42 ml which is more than other three groups in left atrial volume.A novel nitinol occluder for occluding left atrial appendage of canines: an animal experimental study: Among 14 experimental dogs,11 dogs were successfully implanted occluder instantly and the success rate of instantly closure was 78.6%,the occluders of 2 cases were a little small,the occluder of 1 case was a little large which may compress left circumflex leading to dog's death and 1 case was died of puncture site bleeding which led to large hematoma;Among 14 experimental dogs,in 2 cases were caused pericardial effusion during the atrial septal puncture process and terminated operation,the occluder in 1 case dropped into left ventricle leading to dog's death due to the dog's heart too small.The experimental dogs were executed according to the experimental nodes,the surface of occluders was covered by fibrous tissue cells and there were sparsely endothelial cells growth on the surface by pathological examination after 1 month;it was visible that the surface of occluders was completely covered with endothelial cells after 6 months.There was no embolism or infarction on liver,kidney and spleen by macrography examination.1 month,3 months and 6 months after the operation,it was visible by TEE examination that the shape and location of occluders were good and LAA was completely occluded and there was no thrombus in left atrial.1 month after the operation,1 case examined by TEE was shown the occluder slightly affected anterior mitral valve.Conclusion: 1.MSCT detected left atrial thrombus rate was high in accordance with TEE,and the former had higher negative predictive value and the latter had a higher advantage over identifying blood stagnation and thrombus;The patients who were persistent atrial fibrillation,cauliflower type left atrial appendage and left atrial volume increasing were more prone to have left atrial thrombus.2.It was simple and feasible to use novel nitinol LAA occluder to occlude LAA of canines and the incidence rate of thrombus was low on the surface of occluders.