【作者】 张蕾；

【导师】 周达新；

【作者基本信息】 复旦大学 ， 内科学， 2012， 硕士

【摘要】 第一部分经导管封堵室间隔缺损对心脏传导功能影响的研究背景和目的：室间隔缺损(ventricular septal defect, VSD)约占先天性心脏病(congenital heart disease, CHD,简称先心病)的20%-30%。近年来随着VSD封堵器的改进和国产化,VSD经导管封堵治疗处于快速发展的阶段。但封堵术后心脏节律异常尤其是传导阻滞并发症不容忽视,也是安全性争议的主要焦点之一。文献报道传导阻滞发生率为1.9%-31.6%。本研究旨在使用心脏电生理检查(electrophysiological study, EPS)方法来评价VSD经导管封堵对心脏传导功能的影响。材料和方法：以2011年3月至2012年3月在复旦大学附属中山医院心血管内科住院并接受经导管封堵治疗的66例VSD患者为研究对象,其中包括：单纯膜周部VSD (perimembranous VSD, PMVSD)47例,单纯肌部VSD (muscular VSD.MVSD)6例,嵴内型VSD (intracristal VSD, icVSD)6例,VSD外科修补术后残余分流(residual shunt, RS)5例,心肌梗死(myocardial infarction,MI)后室间隔穿孔2例,根据左心室造影结果将患者分为PMVSD组和非PMVSD组,对每一位患者个体化选择介入治疗方案,植入封堵器均为中国产。在封堵器放置前及放置后记录心腔内希氏束电图(His bundle electogram, HBE),测定PR间期、QRS波时限、A-H间期、希氏束电位(H波)以及H-V间期,并于术后即刻、术后24小时、48小时、1个月、3个月、6个月随访体表心电图(electrocardiogram, ECG),记录心律失常事件。结果：66例患者共59例成功完成了经导管封堵术,成功率为89.3%。体表心电图PR间期封堵前后无显著差异(P=0.091),而QRS波时限有封堵后明显延长(P=0.003)；封堵前后心腔内电生理测的A-H间期、H波宽度及H-V间期分别为：82.4±16.9和88.8±19.4ms、19.6±2.5和20.5±2.5ms、45.3±7.0ms和48.7±7.8ms,前后差异均具有统计学意义(P值分别为：0.000、0.008及0.000);但PMVSD组和非PMVSD组相比,只有H-V间期延长值具有统计学差异(P=0.037)。术后随访1～12个月(2.17±2.11个月)。23例(39.7%)术后新发有心律失常包括：Ⅰ度房室传导阻滞(atrioventricular block, AVB)3例,左前分支阻滞(left anterior hemiblock.LAH)1例,完全性左束支阻滞(complete left bundle-branch block, CLBBB)1例,完全性右束支阻滞(complete right bundle-branch block,CRBBB)7例,不完全性右束支阻滞(incomplete leftbundle-branch block, IRBBB)5例,Ⅰ度AVB合并CRBBB1例,阵发性加速性房室交界性自主心律(paroxysmal accelerated atrioventricular junction rhythm)3例,房性早搏(atrial premature beats)1例,房室交界性早搏(atrioventricular junction premature beats)1例。除1例患者术后1年心电图仍为阵发性加速性房室交界性自主心律外,其余22例心律失常均恢复。无封堵器移位、高度房室传导阻滞、溶血、瓣膜及腱索损伤等严重并发症及电生理检查相关并发症。其中H-V间期延长大于3.5ms可作为术后发生节律异常的预测因子,其敏感性71.4%,特异性71.1%,优势比(odds ratio, OR)=6.14。但就PMVSD组而言,HV间期延长大于2.5ms即可作为术后发生节律异常的预测因子,其敏感性77.8%,特异性66.7%,OR=7.0。结论：使用国产封堵器经导管封堵治疗室间隔缺损是安全有效的措施,经导管封堵治疗室间隔缺损对心脏传导系统的影响主要位于房室结以下传导束,一过性心脏传导系统的损伤是常见的并发症；术中行心腔内EPS不增加并发症风险,H-V间期延长>3.5ms可作为术后近期发生传导阻滞的预测因子。第二部分室间隔缺损经导管封堵术后节律异常的临床研究背景和目的：室间隔缺损(ventricular septal defect, VSD)经导管封堵治疗成功率高,介入治疗和围手术期并发症在3%左右,其中心脏节律异常是常见并发症。该研究旨在回顾性分析封堵术后节律异常的临床危险因素及防治措施。材料和方法：2011年3月至2012年3月在复旦大学附属中山医院心血管内科住院并成功完成经导管封堵治疗的59例VSD,包括：单纯膜周部VSD(perimembranous VSD, PMVSD)44例,单纯肌部VSD(muscular VSD, MVSD)5例,嵴内型VSD(intracristal VSD, icVSD)4例,VSD外科修补术后残余分流4例,心肌梗死后室间隔穿孔2例,植入封堵器均为中国产。在封堵前、封堵后即刻、封堵后24h、48h、1个月、3个月、6个月随访体表ECG,记录心脏节律异常事件。结合临床资料、经胸超声心动图(transthoracic echocardiography,TTE)、心血管造影资料及随访结果,分析封堵术后并发节律异常的类型、相关因素及转归。结果：23例(39.7%)术后新发有心律失常包括：Ⅰ度房室传导阻滞(atrioventricular block, AVB)3例,左前分支阻滞(left anterior hemiblock,LAH)1例,完全性左束支阻滞(complete left bundle-branch block, CLBBB)1例,完全性右束支阻滞(complete right bundle-branch block,CRBBB)7例,不完全性右束支阻滞(incomplete left bundle-branch block, IRBBB)5例,Ⅰ度AVB合并CRBBB1例,阵发性加速性房室交界性自主心律(paroxysmal accelerated atrioventricular junction rhythm)3例,房性早搏(atrial premature beats)1例,房室交界性早搏(atrioventricular junction premature beats)1例,除1例患者术后1年心电图仍为阵发性加速性房室交界性自主心律外,其余22例心律失常均恢复,总恢复率为95.7%。发生节律异常组与未发生节律异常组相比,在VSD类型、距三尖瓣距离、距主动脉瓣距离及肺动脉压力方面均有差异(P<0.05),而年龄、BMI、VSD大小、有无膜部瘤、封堵器类型、大小、生产厂家、有无残余分流、操作持续时间、透视时间等因素方面无显著差异(P>0.05)。由于肺动脉压力与VSD的大小相关,不能作为单独的危险因素；进一步对是否是膜周部VSD、距TV距离、距AV距离行Logistic回归分析,这3项因素与术后传导阻滞的发生均无相关性(P值分别为0.212,0.066及0.6)。但对PMVSD单独分析,对距TV距离,距AV距离以及VSD大小进行Logistic回归分析,发现距三尖瓣的距离与术后传导阻滞的发生最有相关性(P=0.021)。对距三尖瓣距离对不发生传导阻滞事件绘制受试者工作特性曲线(receiver operative characteristic curve, ROC曲线),曲线下面积为0.732,95%CI为0.587-878,P值为0.008。根据ROC曲线来确定与三尖瓣距离值预测封堵术后发生传导阻滞的最佳阈值为12.5mm,其预测的灵敏度为76.7%,特异性为61.1%,正确性为70.8%,阳性预测值为61.1%,阴性预测值为76.7%,OR=5.16。结论：节律异常是VSD封堵治疗术后近期常见的并发症,但多能恢复为窦性心律。术前超声心动图准确测量VSD距三尖瓣距离十分必要,但并发心律失常具体与哪些因素有关、与远期预后是否相关尚需要进一步研究。更多还原

【Abstract】 Part one:Study on the Impact of Cardiac Conductin Function following Transcatheter Closure of Ventricular Septal DefectsBackground and objective:Ventricular septal defect(VSD) accounts for about20%-30%of congenital heart disease.Transcatheter closure of VSDs has experienced a stage of rapid development during the past decade owing to the improvement and nationalization of the VSD occluder in China.The cases of transcatheter closure of VSDs had increased dramatically in the recent few years.however the complication of atrioventricular block(AVB) has to be taken into consideration and has become one of the safety disputes.The incidence of AVB reported in literature was1.9%-31.6%.In this study the impact of transcatheter closure of VSDs on the cardiac conduction dunction was evaluated by invasive cardiac electrophysiological (EPS) methods,seeking high rick factor of post-closure arrhythmia especially AVB.Material and methods:From March2011to March2012,66patients underwent transcather closure of VSD in Zhongshan Hospital affiliated to Fudan University.According to history and left ventricular angiography,patients were confirmed as follows:47cases of perimembranous VSDs.5cases of muscular VSDs,7cases of intracristal VSDs,5cases of residual shunts after VSD surgical repair,2cases of ventricular septal rupture after myocardial infarction.All patients were devided into two groups which were PMVSD group and nonPMVSD group.Body surface electrocardiogram(ECG) and His bundle electogram(HBE) were taken pre-and post-implatation of occluders which were made in China.PR interval、QRS complex interval.A-H interval,His duration and H-V interval were measured.Surface ECG was performed at the24th hour,48th hour,lst month,3nd month and6th month after the procedure for each patient who had successful closure of VSD.Results:The defects were successfully closed in59/66patients (success rate of89.3%).No significant change for PR interval on surface ECG was observed before and after closure (P=0.091). But the QRS complex interval showed a significant prolongation(P=0.003).As for the invasive EPS parameters,A-H interval、His duration and H-V interval showed the similar significant difference pre-and post-procedure,which were82.4±16.9vs88.8±19.4ms(P=0.000)、19.6±2.5vs20.5±2.5ms(P=0.008).45.3±7.0ms vs48.7±7.8ms(P=0.000) respectively.But only H-V prolongation has significant difference in PMVSD group compared with nonPMVSD group.Follow-up duration after closure was1-12months,there were23cases(39.7%) of new-onset of arrhythmia including:3cases of I degree atrioventricular block(AVB),l case of left anterior hemiblock(LAH),l case of complete left bundle-branch block(CLBBB),7cases of complete right bundle-branch block(CRBBB),5cases of incomplete right bundle-branch block(IRBBB),l cases of I degree AVB combined with CRBBB,3cases of paroxysmal accelerated atrioventricular junction rhythm.1case of atrial premature beat,l cases of atrioventricular junction premature beat.Except1case sustained paroxysmal accelerated atrioventricular junction rhythm1year after closure,other22cases of arrhythmia recovered.No occluder displacement、high degree AVB、hemolysis、valve and chordate tendineae injury and other serious complications related to electrophysiological study were noted.H-V interval prolongation more than3.5ms can be used as a predictor of postoperative conduction disturbance with sensitivity of71.4%, specificity of70.1%and odds ratio (OR) of6.14. As for PMVSD group, H-V interval prolongation more than2.5ms can be used as a predictor with sensitivity of77.8%, specificity of66.7%and OR of7.0.Conclusion:Transcatheter closure of VSDs with occluder made in China is a safe and effective option with limited complications.The impact on cardiac conduction system lies mainly in the conductive bundle beneath the atrioventricular node.Transient injury of cardiac conduction system is a common complication.H-V interval prolongation if more than3.5ms can be used as a predictor of postoperative conduction disturbance.Intracardiac EPS does not increase the risk of complications. Part two:The Clinical Study of Rhythm Disturbance after Transcatheter Closure of Ventricular Septal Defects.Background and objective:Transcatheter closure of ventricular septal defect has a high success rate with perioperative complications rate around3%.The heart rhythm abnormalities are common complications.The aim of this study was to retrospectively analysis the clinical risk factors and prevention measures of rhythm disturbance after transcatheter closure.Material and methods:From March2011to March2012,59patients had successful completion of transcatheter occlusion of VSDs in cardiovascular department of Zhongshan Hospital Affiliated to Fudan University.The clinical types of VSDs are as follows:simple perimembranous VSD(PMVSD) in44cases,simple muscular VSD (MVSD) in5patients, intracristal VSD (icVSD) in4cases, residual shunts after surgical repair of VSDs in4cases, post myocardial infarction ventricular septal perforation in2cases. The occluders implanted were produced in China.Surface ECGs were taken before and after the procedure immediately.and follow-up at the24th hour,48th hour,lst month,3nd month.and6th month after closure.Heart rhythm abnormality events were noted combined with data of clinical,ultrasonic cardiography.angiocardiography,to analysis the risk factors and prognosis of rhythm disturbance.Results:There were23cases(39.7%) of new-onset of arrhythmia including:3cases of I degree atrioventricular block(AVB).l case of left anterior hemiblock(LAH),l case of complete left bundle-branch block(CLBBB).7cases of complete right bundle-branch block(CRBBB),5cases of incomplete right bundle-branch block(IRBBB).l cases of I degree AVB combined with CRBBB.3cases of paroxysmal accelerated atrioventricular junction rhythm,1case of atrial premature beat,l cases of atrioventricular junction premature beat.Except1case sustained paroxysmal accelerated atrioventricular junction rhythm1year after closure,other22cases of arrhythmia recovered(total recover rate95.7%).Between rhythm disturbance group and non-rhythm disturbance group, there were significant differences in the respect of VSD type, distance from VSD rim to aortic valve and tricuspid valve, pulmonary pressure (P<0.05).While no significant differences were observed in aspect of age,body mass index(BMI),VSD size, membranous aneurysm, the type, size and manufacturer of occluder,residual shunts,procedure and fluoroscopy time(P>0.05). Pulmonary pressure was mainly related to the size and shunts of VSDs,so it was excluded from the risk factors.Further Logistic regression analysis of VSD type (PMVSD or nonPMVSD), distance from VSD rim to aortic valve and tricuspid valve revealed that these three factors had no correlation with postoperative rhythm disturbance (P value was0.212,0.066and0.6respectively). But for PMVSD group,Logistic regression analysis of VSD size,distance from VSD rim to aortic valve and tricuspid valve showed the most closely correlation between the latter and postoperative rhythm disturbance (P=0.021). Receiver operating characteristics curve (ROC curve) about the distance from VSD rim to tricuspid valve and incidence of no postoperative rhythm disturbance indicated that the area under the curve was0.732(with95%CI:0.587-878,P=0.008).According to the ROC curve,the cut-off point of the distance value prediction was12.5mm with the sensitivity of76.7%, specificity of61.1%, accuracy of70.8%, the positive predictive value of61.1%,the negative predictive value of76.7%and OR of5.16.Conclusion:The rhythm disturbance was common complication short term after transcatheter closure of VSDs,while mosty could recover to sinus rhythm.Preoperative accurate measurement of the distance from VSD rim to tricuspid valve using ultrasonic cardiography is very necessary.But what factors are exactly related to postoperative arrhythmia,and whether rhythm abomormalities affect the prognosis still need further study.更多还原