Abstract
BACKGROUND: It is difficult to cover aneurysm-like ventricular septal defect (VSD) of large inlet and multiple outlets completely with symmetrical type occluders or eccentric type occluders.
OBJECTIVE: To investigate the feasibility of A4B2 occluder devices for covering aneurysm-like VSD, and to observe the effects of proper occluders selected according to pseudoaneurysm size on covering aneurysm-like VSD.
DESIGN: Case analysis.
SETTING: the First Hospital of Hebei Medical University.
PARTICIPANTS: From August 2004 to May 2006, 226 patients with the pseudoaneurysm of perimembranous VSD, who underwent interventional therapy in the First Hospital of Hebei Medical University, were recruited in the study. According to the results of the left ventricular angiography, 36 patients of pseudoaneurysm of perimembranous VSD with large inlet and multiple outlets were closured with A4B2 occluder devices. According to the results of the left ventricular angiography, the mean diameter of the left inlet of VSD was (10.6±8.7) mm (ranged from 8 to 21 mm), the mean diameter of the right outlet of VSD was (3.1±2.9) mm (ranged from 2 to 8 mm). Main materials: Occluder device and delivery mechanism were offered by Shanghai Shape Memory Alloy Materials Company and Beijing Starway Medical Technology Inc. They were processed into double disks using nickel-titanium shape memory alloy wires by a special technology to close VSD by a transcatheter approach. The size of the occluder was denoted with the diameter of the waist, and the size ranged from 4 to 16 mm in the present study.
METHODS: All the occluders were transferred by a 7-10 F transferring sheath from right heart system, and the mean diameter of the occluders was (6.36±2.48) mm (ranged from 4 to 16 mm). Fifteen minutes after the procedure, left ventricular angiography and transthoracic echocardiography (TTE) were performed again to evaluate the efficacy. After the procedure, electrocardiogram (ECG) monitoring lasted for 5 successive days in all patients, and ECG and TTE were performed 1, 3, 6 and 12 months later.
MAIN OUTCOME MEASURES: Residual shunt, arrhythmia and valve function as well as blood compatibility.
RESULTS: Sixteen cases were closured by placing the occluders into left inlet of VSD, 16 cases were closured by placing the occluders into the pseudoaneurysm completely, and 4 cases were closured at the outlet of the defects. The results of the left ventricular angiography and TTE that performed fifteen minutes after the procedure demonstrated that 32 cases were completely closured and slightly residual shunts (< 3 mm) was found in other 4 patients. And confirmed by TTE, the residual shunts completely disappeared in 2 of the 3 patients 24 hours later while in the other one in 1 month after the procedure. Temporary left bundle branch block was found in 3 cases while temporary right bundle branch block was found in 2 cases, and all of them recovered within one week. Without severe complications, all of the 36 patients were treated successfully with A4B2 (thin waist shape) occluder devices made in China. Critical appraisal in blood compatibility of the implantation materials used in this research had been performed. The hemolysis ratio was less than 5%, the platelet adhesion was less, and the blood coagulation function ,the immune system response（immunoglobulin and complement）and the re-endothelialization of material surface were all normal.
CONCLUSION: Transcatheter interventional therapy with domestic A4B2 occluder devices for VSD with pseudoaneurysm is safe, effective, promising, and has fewer complications. The key to the procedure is to select suitable occluders and suitable positions where to plant them according to the size, morphologic characteristics, position, and maturity of the pseudoaneurysm.

INTRODUCTION

The pseudoaneurysm is a specific type of perimembranous ventricular septal defect (VSD), and it is the key stage of the spontaneous closure of the perimembranous VSD [1-2]. Since the complex morphologic characteristics, the decentralizing position, the multiple outlets, the relationship between the defect and the adjacent tissues and the conglutinating degree of the pseudoaneurysm, it is difficult to cover the defect completely with symmetrical occluders or eccentric shape occluders[3-10]. So we should take all of the above into account when performing operations. Since 2004, 226 patients with the pseudoaneurysm of perimembranous VSD were treated and A4B2 occluder devices were used successfully in 36 patients who were with large inlet and multiple or small outlet pseudoaneurysm.

SUBJECTS AND METHODS

Subjects
From August 2004 to May 2006, 226 patients with the pseudoaneurysm of perimembranous VSD were enrolled in this research. According to the results of left ventricular angiography, 36 patients of pseudoaneurysm of perimembranous VSD with large inlet and multiple or small outlets, including 16 males and 20 females, with a mean age of (6.0±2.6) years (ranged from 2.5 to 18 years ), an average body weight of (20.58±8.55) kg (ranged from 12 to 60 kg) and an average body height of (88.6±10.4) cm
(ranged from 60 to 171 cm), were closured with A4B2 occluder devices. According to the results of the left ventricular angiography, the mean diameter of the left inlet of VSD was (10.6±8.7) mm (ranged from 8 to 21 mm), and the mean diameter of the right outlet of VSD was (3.1±2.9) mm (ranged from 2 to 8 mm). The distance from the border of the defect (left ventricular side) to the aortic valve was (2.6±0.8) mm (0-4 mm). All subjects were diagnosed as pseudoaneurysm of perimembranous VSD by the disease history, physical examinations, chest X-ray film, electrocardiogram (ECG) and transthoracic echocardiography (TTE) and were all accorded with the indications of transcatheter closure. Informed consents for the treatments and laboratory measurements were obtained from the legal guardians of patients and patients over 18 years old.

Occluder devices and transferring equipments
All kinds of A4B2 occluders used in the present study were offered by Shanghai Shape Memory Alloy Materials Company and Beijing Starway Medical Technology Inc. The new type of occluder was woven by silk of nickel-titanium memory alloy, then the meshwork of the alloy was made into double-plate shape with a cylindrical waist through a heat-set. The diameters of the two plates were different. The diameter of right plate was greater than that of waist by 4 mm, the diameter of left plate was greater than that of waist by 8 mm, and the cylindrical waist was 2 mm. Working as an impermeable barrier, the mesh was filled with polymeric materials. The size of the occluder was denoted with the diameter of the waist and the size ranged from 4 to 16 mm in the present study. The transferring system of the occluder was composed of transfering sheath (7-10 F), dilating tube, borne catheter, and push screw.

Closure methods [11-13]
Chloramines ketone was used in the basic anaesthesia in children while 1% lidocaine was used in the local anesthesia in adults. Then the right femoral artery and femoral vein were punctured, and pigtail catheter was pushed into the left ventricular through the femoral artery. Left ventricular angiography at the angle of left anterior oblique (LAO) 40°- 60°and CRU 20°-25° was performed in order to realize the size, morphologic characteristics, position, the relationship between the defect and the adjacent tissues and the conglutinating degree of the pseudoaneurysm. After left ventricular angiography, through the femoral artery, Judkins right coronary artery catheter or reformative pigtail catheter was transferred into the left ventricle, and through the VSD into the right ventricle, and arrived at the pulmonary artery or superior vena cava at last. Then the snare was transferred through the femoral vein, hitched the leading wire and then pulled it out of the body. As above, the path from femoral vein to femoral artery was founded. Along with the leading wire, a 7-10 F transferring sheath was delivered to the ascending aorta. With the help of pushing the catheter into the artery system, the leading wire with the catheter and transferring sheath were delivered into the apex of the left ventricular together, then the leading wire and dilating tube were pulled out. The occluder was connected with the push screw and pulled into the borne catheter and the borne catheter was inserted into the transferring sheath. With the guidance of fluoroscopy, the transferring sheath was pushed into the left ventricle, then the left plate was opened, pulled back gently and backed on the left ventricular side of the defects. When meeting resistance, TTE was performed to observe the position of the occluder in order to define that the left plate was stocked on the left ventricular side of the defect fast. Then the transferring sheath was pulled back and the right plate was opened. When we confirmed that the murmur disappeared by auscultation, left ventricular angiography and TTE were performed again in order to confirm that there was no residual shunt while the opening and closure of the aortic valve and tricuspid valve were not influenced. After the push screw was contrarotated, the occluder was released. During the procedure, heparin (100 U/kg) was injected intravenously. After the procedure, ECG monitoring lasted for 5 successive days, antibiotics and dexamethasone (200 μg/kg·d) were injected intravenously for 3 to 5 days and aspirin(3 mg/kg·d) was taken orally for 3 months. ECG and TTE were performed before and at 1, 3, 6 and 12 months after discharge.

Statistical analysis
SPSS 12.0 software package was used to perform statistical analysis. All the measurement data were expressed by Mean±SD. Paired t-test was used for the comparison between two groups. P < 0.05 was considered significant.

RESULTS

According to the results of the left ventricular angiography, 36 out of 226 patients of the pseudoaneurysm of perimembranous VSD whose pseudoaneurysm was of large inlet and multiple or small outlets were closured with A4B2 occluder devices.

The size of implanted occluders
According to the size, morphologic characteristics, position, and maturity of the pseudoaneurysm, suitable occluders with a mean diameter (6.36±2.48) mm (ranged from 4 to 16 mm) were selected.
The position where occluders were implanted
Sixteen cases were closured by placing the occluders into left inlet of VSD, 16 cases were closured by placing the occluders into the pseudoaneurysm completely, and 4 cases were closured at the outlet of the defects (Figures 1, 2).

The operation time for occlusion
The mean time of fluoroscopy was (15.2±8.8) minutes (ranged from 10 to 65 minutes) while the mean total time of the procedure was (42.5±16.2) minutes (ranged from 30 to 125 minutes). All 36 patients were treated successfully with A4B2 occluder devices.

The immediate efficacy after occlusion
The results of the left ventricular angiography and TTE that performed fifteen minutes after the procedure (occlusion) demonstrated that 32 cases were completely closured, slightly residual shunts (< 3 mm) were found in other 4 patients with multiple outlets, of which 3 cases were closured by placing the occluders into the pseudoaneurysm completely and 1 case was closured at the outlet of the defect. And confirmed by TTE, the residual shunts completely disappeared in 2 of the 3 patients 24 hours later while the residual shunt flow completely disappeared in the other one patient in 1 month after the procedure.

TTE, ECG and chest X-ray film changes after occlusion
After therapy, left ventricular end-diastolic pressure (LVEDP) decreased from (11.6±2.6) mm Hg to (6.7±3.2) mm Hg and the difference was significant (t = 5.61, P < 0.001). TTE that performed 24 hours after the procedure showed that the left ventricular end-diastolic diameter (LVEDD) decreased from (49.5±7.8) mm to (46.2±7.8) mm and the difference was significant (t = 3.85, P = 0.002). Chest X-ray film showed that the ratio for cardiac and thoracic size(C/T) decreased from (0.50±0.03) to (0.46±0.03) and the difference was significant (t = 4.98, P < 0.001).

Intraoperative complications
Temporary left bundle branch block was found in 3 cases while temporary right bundle branch block was found in 2 cases, and all of them were recovered in one week.

Biological compatibility of material and tissues
Critical appraisal in blood compatibility of the implantation materials used in this research had been performed. The hemolysis ratio was less than 5%, the platelet adhesion was less, and the blood coagulation function, the immune system response (immunoglobulin and complement) and the re-endothelialization of material surface were all normal.

DISCUSSION

The pseudoaneurysm of VSD is a kind of membrane structure that the perimembranous VSD protrudes to the right ventricular and communicates with it. The protruding part is made up of cuspis septails of tricuspid valve, cuspis anterior of tricuspid valve or chordae tendineae. The conglutinating hyperplastic tissue appears semicircle and irregular projecture locating at perimembranous interventricular septum. The wall of the pseudoaneurysm is thicker and its motion is restrictive. The conglutinating cuspis septails protrudes to the right ventricular gently. It is safe, without traumas and has a higher diagnosing rate that the pseudoaneurysm of VSD examined by TTE, so TTE can be selected as a first diagnosing means. The size, morphologic characteristics, position, the relationship between the defect and the adjacent tissues and the conglutinating degree of the pseudoaneurysm can be defined by the left ventricular angiography. According to the results of the left ventricular angiography, the pseudoaneurysm of VSD can be defined as funnelform, cystiform, cauliflower shape or tubular shape [14].
As for the pseudoaneurysm of perimembranous VSD with large inlet and multiple or small outlets, its complex morphologic characteristics, decentralizing position, multiple outlets, the relationship between the defect and the adjacent tissues and the conglutinating degree of the pseudoaneurysm lead to more considerations of the technique when performing operations. It is difficult to cover the multiple outlets of the pseudoaneurysm completely with symmetrical occluders or eccentric shape occluders. If selecting symmetrical occluder of large diameter, since the outspreading of the occluder waist is restricted, the two plates of the occluder will be squeezed into sphericity so that the closure location will be squeezed seriously and it is easy to cause the stenosis of the ventricular outflow tract. If selecting A4B2 occluder, its larger left plate can cover the multiple outlets completely while its thin waist can match the diameter of the outlet and its plates can outspread adequately, so the inlet of the defect can be covered completely. At the same time, the shape of the occluder can recover well, no more cardiac cavity will be occupied and no stenosis of the ventricular outflow tract will be caused. The clinical application also showed that the immediate effect of this type of occluder on closuring the pseudoaneurysm of VSD was better.
In our opinion, the key to the procedure is to select suitable occluders and suitable position where to plant them. First, in order to confirm the closure location, the accurate judgement of the conglutinating degree of the pseudoaneurysm and the distance from the border of the defect (left ventricular side) to the aortic valve by TTE and angiography is needed. Second, different kinds of A4B2 occluders must be selected according to the size, morphologic characteristics, position, the difference of the inlet diameter and the outlet diameter, and the quantity and distance of the outlets. If the conglutinating degree of the pseudoaneurysm is lower, we must closure the inlet of the pseudoaneurysm in order to avoid the occluder transferring or falling off. If the conglutinating degree of the pseudoaneurysm is higher, the occluder cannot transfer or fall off whether the inlet, the outlet or the body of the pseudoaneurysm is closured. If the distance from the border of the defect(left ventricular side) to the aortic valve is equal or more than 2.0 mm, we should try our best to close the inlet of the defect. If the distance is less than 2.0 mm, we should put the upper side of the occluder nearby the aortic valve and the inferior part of the occluder in the left ventricular, so the defect can be closured completely and the dilation of the pseudoaneurysm can be avoided after the procedure. If the superior border of the defect is nearby the aortic valve, we should close the body or outlet of the pseudoaneurysm in order to avoid influencing the aortic valve. At this time, if the pseudoaneurysm has multiple outlets and the directions of the outlets are different, especially there are some outlets at the superior border of the pseudoaneurysm or the distance of the outlets is far, closure of multiple outlets can be ensured without residual shunt flow and without transferring of the occluder by closure of pseudoaneurysm than closure of outlet [15].
About the occluder selecting, we should select different kinds of A4B2 occluders according to the size, morphologic characteristics, closing position, inlet diameter and outlet diameter, the quantity and distance of the defect. In principle, the type of occluder(the diameter of the occluder waist), must be equal or 1-2 mm larger than the diameter of the outlet. If we close the inlet of the pseudoaneurysm, ordinarily, the diameter of the left plate should be 2-4 mm larger than the inlet diameter of the defect. If closing the outlet of the pseudoaneurysm, we should try our best to transfer the transferring sheath through the biggest outlet. For the defect with multiple outlets, we should cover all the outlets with the left plate to closure the defect completely. We should select the occluder type by the maximal distance between the biggest outlet and the other outlets. To estimate whether the occluder is suitable, we should observe not only whether the defect was closured completely but also whether the two plates of the occluder outspread enough under the guidance of the TTE and fluoroscopy [16-18]. Since the border of the left plate is larger, it must be considered that whether the occluder influences the aortic valve after the planting of the occluder. The distance from the pseudoaneurysm to the aortic valve and the diameter of the cystiform must be measured accurately before the procedure. The ascending aorta angiography should be performed before and after the procedure generally in order to evaluate whether the occluder influences the function of the aortic valve [11,19-20].
In the present study, all 36 patients were treated successfully with A4B2 occluder devices. Perhaps due to the connecting area between the occluder and the left septum are larger for the larger left plate, temporary left bundle branch block was found in 3 cases, and temporary right bundle branch block in 2 cases, and all of them recovered within one week. In one word, transcatheter interventional therapy with domestic A4B2 occluder devices for VSD with pseudoaneurysm is safe, effective, promising and has fewer complications. The key to the procedure is to select suitable occluders and suitable positions where to plant them according to the size, morphologic characteristics, position, and maturity of the pseudoaneurysm.

REFERENCES

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确定封堵部位选择合适封堵器封堵膜部
瘤型室间隔缺损的效果☆

解启莲，赵增仁，王 军，高 磊，闫宝勇，王 震，张密林，周 谨，樊文峰，刘坤申
河北医科大学第一医院，河北省石家庄市 050031
解启莲☆，男，1968年生，安徽省六安市人，汉族，博士，副主任医师，副教授，主要从事先天性心脏病介入治疗与研究。
摘要
背景：对于大入口多出口的膜部瘤型室间隔缺损，如果采用对称型或偏心型室间隔缺损封堵器，有时难以完全封堵。
目的：观察A4B2封堵器封堵膜部瘤型室间隔缺损的可行性，根据膜部瘤大小选择合适封堵器对封堵效果的影响。
设计：病例分析。
单位：河北医科大学第一医院。
对象：2004-08/2006-05拟在河北医科大学第一医院行介入治疗的室间隔缺损伴膜部瘤形成226例患者中，对造影术显示膜部瘤为大入口多出口的36例患者应用A4B2封堵器封堵治疗。36例室间隔缺损伴膜部瘤形成患者,造影测量室缺左室面破口（入口）直径平均为（10.6±8.7）mm (8~21 mm), 右室面均有多个出口，最大右室面破口（出口）直径平均为（3.1±2.9）mm (2~8 mm)。主要材料：封堵器与输送装置由上海形状记忆合金材料有限公司和北京华医圣杰科技有限公司生产。采用医用镍钛形状记忆合金等材料，经特殊工艺加工制作成双盘形，专用于先天性心脏病室间隔缺损的封堵治疗。封堵器的型号大小以腰部直径来表示,可选型号为4~16 mm。
方法：①应用7~10 F输送鞘管从右心系统送入相应封堵器。②选择不同型号A4B2封堵器, 置入封堵器直径为4~16 mm,平均(6.3±2.4) mm。③封堵后15 min重复左心室造影和经胸心脏超声检查,观察封堵的即刻效果。封堵后1，3，6，12个月定期进行心电图、心脏超声检查。
主要观察指标：封堵后有无残余分流、心律失常以及心脏各瓣膜功能是否受到影响。
结果：①封堵膜部瘤左室面破口16例，封堵器完全置于瘤体内封堵瘤体16例，封堵膜部瘤右室面破口4例。②36例患者封堵后15 min左心室造影、经胸心脏超声检查显示32例完全封堵,3例造影示少量分流(< 3 mm),（其中2例发生在封堵器完全置于瘤体内；1例发生在封堵膜部瘤右室面破口封堵后），其中2例24 h后心脏超声复查无残余分流，1例1个月后超声复查无残余分流。③术中并发左、右束支传导阻滞分别为3例和2例,均为一过性，1周内恢复。④封堵器置入体内后血小板黏附较少，凝血功能检查、免疫系统反应（免疫球蛋白、补体）、 材料表面再内皮化反应均正常，未发生炎症等宿主反应。无封堵器脱落等材料反应发生。
结论：经导管采用A4B2封堵器治疗膜部瘤型室间隔缺损，关键在于对膜部瘤大小、形态、位置及膜部瘤组织粘连牢固程度判断并以此来确定封堵部位及选择合适的封堵器。
关键词：经导管封堵；室间隔缺损, 膜部瘤型；封堵器；植入材料；血液相容性；心血管植入物
中图分类号: R318 文献标识码: A 文章编号: 1673-8225(2008)13-02591-05
解启莲，赵增仁，王军，高磊，闫宝勇，王震，张密林，周谨，樊文峰，刘坤申.确定封堵部位选择合适封堵器封堵膜部瘤型室间隔缺损的效果[J].中国组织工程研究与临床康复，2008，12(13):2591-2595
[www.zglckf.com/zglckf/ejournal/upfiles/08-13/13k-2591(ps).pdf]
（Edited by Ding C/Song LP/Wang L）