asdpfo封堵器血栓形成認(rèn)識(shí)

1、asdpfo封堵器血栓形成認(rèn)識(shí)Introduction Percutaneous ASD closure (1974, King)Closure of atrial septal communications,ASD and PFOfrom an open surgical technique to percutaneous, catheter-based, closure devices Currently available devices within the United States for percutaneous closure of atrial-level defects w

2、ithin randomized controlled trialsInterventional Catheterization in Adult Congenital Heart Disease. Circulation 2007; 115;1622-1633 Complications can be unknown or under-estimated prior to general userelatively small and carefull selected patient populationshort duration of follow-uplimited indicati

3、onsTo review the rate of rare, but potentially serious complications highlighted 3 major complicationsdevice embolization (EM)device erosion (ER)thrombus formationDevice embolizationEmbolization rate AGA device 0.5%,70% of the devices successfully retrieved percutaneouslyNMT device 4% in European st

4、udies12% world-wide.Levi DS, Moore JW. Embolization and retrieval of the amplatzer septal occluder. Catheter Cardiovasc Interv. 2004;61:543547Device erosion NMT devicesonly 1 case reportAGA devices Numerous case reports In the United Statesestimated 9000 implants, 14 events were reported with confir

5、med erosions and 3 deaths 0.1% incidence of this complication, but a 20% mortality risk with it occurs Jeffrey W. Delaney, MD, Jennifer S. Li, MD, and John F. Rhodes, Congenit Heart Dis,2007,2:256264. 2-D and color Doppler TTE views of Aorto-atrial fistula. Am J Cardiol. 96: 16071609Intraoperative p

6、hoto, AGA device in place and arrow to fistula. Am J Cardiol.96: 16071609 Thrombus formationASD/PFO封堵器血栓形成的臨床診斷 封堵器血栓形成臨床診斷主要依靠超聲心動(dòng)圖，特別是經(jīng)食管超聲心動(dòng)圖（TEE）超聲心動(dòng)圖特征為封堵器表面新出現(xiàn)的非平面性異?；芈?，并且該結(jié)構(gòu)部分可隨血流而飄動(dòng) Figure ATransesophagealechocardiographyfour-chamberview:left-sided mobile thrombus attached to a StarFLEX occl

7、uder detected four Weeks after catheter closure.Figure BTransesophagealechocardiography short axis: right-andleft-sided immobile thrombus surrounding an ASDOSOccluder detected four weeks after catheter closure. Figure C Transesophageal echocardio-graphy short-axis: large mobile thrombus (3018mm) Att

8、ached to the right atrial wall (without direct contact to the ASDOS device) detected one year after catheter closure. J Am Coll Cardiol,2004,43:302-309 FigureA short transesophageal view of small mobile left-sided thrombion a StarFLEX occluder. During surgery,the absence of the left-sided thrombi. B

9、ut detection of a right-sided thrombus (8mm) not diagnosed before was removed together with the device. J Am Coll Cardiol,2004,43:302-309 對(duì)成人患者，無論超聲聲窗條件，應(yīng)常規(guī)進(jìn)行經(jīng)TEE檢查，分別在術(shù)后4周、6個(gè)月、12個(gè)月進(jìn)行對(duì)兒童患者隨訪，經(jīng)胸超聲心動(dòng)圖（TTE）已足夠ASD/PFO封堵器血栓形成的發(fā)生率 不同種類ASD/PFO封堵器血栓形成的發(fā)生率 La Rosee等描述38例ASD患者有3例（10.5%）血栓形成，60例PFO患者有8例（13.3 %

10、）血栓形成Lambert V等報(bào)道使用ASDOS封堵器139名患者中有9名血栓形成，血栓發(fā)病率6.5%Buttoned封堵器27名患者中有3名血栓形成，血栓發(fā)病率11.1%表1 單中心不同類型封堵器術(shù)后4周和6個(gè)月時(shí)TEE檢出血栓情況封堵器種類n應(yīng)檢TEE人數(shù)(n)實(shí)際TEE比例(%)血栓發(fā)生率(%,n)6個(gè)月4周6個(gè)月4周6個(gè)月Rashkind11100%100%0%0%Buttoned Device525267%69%0%0%ASDOS424266%83%3.6%(n=1)0%Angel Wings30300%97%0%3.3%(n=1)CardioSEAL272752%93%7.1%(n

11、=1)*0%Star- FLEX14211174%70%5.7%(n=6)*0%Amplatzer41837578%70%0%*0.3%(n=1)PFO-Star12712760%66%6.6%(n=5)*1.5%(n=1)Helex16113876%80%0.8%(n=1)0%J Am Coll Cardiol,2004,43:302-309 Amplatzer與CardioSEAL、Star FLEX 、PFO-Star之間血栓形成率有顯著性差異（p0.05）（資料來自Cardiovascular Center Frankfurt,SanktKatharinen, Frankfurt, G

12、ermany）最近Jeffrey 等為了回顧美國(guó)FDA從2002年開始準(zhǔn)入的種ASD/PFO封堵器（AGA和NMT）嚴(yán)重并發(fā)癥發(fā)生情況搜索了2002-2004年MEDLINE和MAUDE的AGA和NMT公司的ASD/PFO封堵器的嚴(yán)重并發(fā)癥文獻(xiàn)與數(shù)據(jù)庫資料 (MAUDE:制造商和用戶的器械使用狀況數(shù)字庫)（資料來自Congenit Heart Dis. 2007;2:256264）MEDLINE searchusing the MeSH terms“Atrial septal defect closure,” “Amplatz,” “Device closure,” and “CardioSE

13、AL”identified potential studies covering the 3-year period of device usage to be analyzedWe limited our search to articles written in Englishconcentrated on the larger case series, given that this would provide a more accurate complication rate. A total of 12 publications were selected reviewed for

14、the incidence, type, and outcome of device closure complications結(jié)果發(fā)現(xiàn)封堵器血栓形成及由此而引起的血栓栓塞是三大嚴(yán)重并發(fā)癥之一在MAUDE中NMT公司的Star- FLEX及CardioSEAL，推算的發(fā)生率為0.2%AGA公司產(chǎn)的ASO僅為0.06%。MEDLINE文獻(xiàn)中NMT公司的封堵器血栓形成發(fā)生率為： Star- FLEX5.7%、CardioSEAL7.122%AGA公司產(chǎn)的ASO僅了例表2 美國(guó)FDA的MAUDE數(shù)據(jù)庫(2002-2004年)兩種封堵器并發(fā)癥報(bào)告對(duì)比 EM, 封堵器栓塞/移位脫落； ER, 封堵器磨蝕

15、心臟/心包積液； TE, 血栓栓塞；AR, 心律失常；CVA, 腦卒中Amplatzer(R) Atrial Septal Occluder(ASO) (AGA Medical Corp., Golden Valley, MN, USA)CardioSEAL(R) Septal Occluder (CS) (NMT Medical, Inc., Boston, MA, USA)*來自廠家公布的數(shù)據(jù)，來自廠家內(nèi)部的數(shù)據(jù)封堵器來源總例數(shù)并發(fā)癥類型總例數(shù)主要類型例數(shù)相關(guān)死亡例數(shù)AGA12000*所有8873（其中34例 EM，29例 ER，6 例TE，2例AR，2 例BE）8例死亡（其中4 例ER，

16、3 例猝死，1例心臟病發(fā)作）NMT8950所有4024（其中10例 TE, 9 例EM, 5 例ER）2例死亡（其中1例CVA，1例ER）表3 MEDLINE相關(guān)文獻(xiàn)報(bào)道的并發(fā)癥匯總作者封堵器并發(fā)癥來源數(shù)量文獻(xiàn)涉及類型總數(shù)（%）主要類型相關(guān)死亡數(shù)DuASO442所有34(7.2)7（4 EM, 2 AR, 1 TE）0ChessaASO258所有23(8.9)85 EM, 2 ER, 1 TE1 NMT159所有13(8.1)55 EMHongASO49所有1(2)00LeviASO3824EM21(0.5)60WangASO197所有14(7.1)64 ER, 1 EM, 1 AR0Amin

17、ASO9000*ER14(0.1)14PreventzaASO25000*ER16(0.6)161KaulitzNMT72所有18(25)00CarminettiNMT325所有35(10.8)1212EM0KrumsdorfASO418TE000NMT169TE7(6.6)30ButeraASO153所有6(3.9)31 ER, 1 EM, 1 AR0NMT121所有6(5)33 EM0AnzaiASO36TENMT30TE5(17.6)作者封堵器并發(fā)癥來源數(shù)量文獻(xiàn)涉及類型總數(shù)（%）主要類型相關(guān)死亡數(shù)DuASO442所有34(7.2)7（4 EM, 2 AR, 1 TE）0ChessaASO

18、258所有23(8.9)85 EM, 2 ER, 1 TE1 NMT159所有13(8.1)55 EMKrumsdorfASO418TE000NMT169TE7(6.6)30NMT121所有6(5)33 EM0AnzaiASO36TENMT30TE5(17.6)ASD/PFO封堵器血栓形成的臨床危險(xiǎn)因素 術(shù)前患者的臨床因素Krumsdorf等大樣本的臨床研究表明，合并有心房顫動(dòng)或房間隔瘤是ASD和PFO封堵術(shù)患者房間封堵器血栓形成最顯著的危險(xiǎn)因素患者年齡、性別、合并凝血異常、冠心病、糖尿病或高血壓均未發(fā)現(xiàn)與封堵器血栓形成有關(guān)患者術(shù)后有關(guān)因素術(shù)后預(yù)防感染使用的抗生素品種、術(shù)后殘余分流及裝置斷裂等

19、與封堵器血栓形成亦無關(guān)表 單中心ASD/PFO封堵器血栓形成的潛在危險(xiǎn)因素分析 危險(xiǎn)因素?zé)o血栓形成病例有血栓形成病例p值心房顫動(dòng)66/980(6.2%)4/20(20%)0.05封堵術(shù)后即時(shí)殘余分流 287/980(29%)3/20(15%)NS永存房間隔瘤13/980(1.3%)4/20(20%)0.01金屬裝置斷裂 47/980(4.8%)3/20(15%)NS蛋白C缺乏8/456(1.8%)0/20(0%)NS蛋白S缺乏9/456(2%)0/20(0%)NS活化蛋白C抵抗25/456(5.5%)0/20(0%)NS平均年齡47歲48歲NS性別 男 女412/980(42%)568/980

20、(58%)9/20(45%)11/20(55%)NSNS高血壓228/980(23%)3/20(15%)NS冠心病51/980(5%)0/20(0%)NS糖尿病37/980(4%)0/20(0%)NS華法林95/980(10%)3/20(15%)NS阿斯匹林505/980(52%)6/20(30%)NS阿斯匹林+氯吡格雷380/980(39%)11/20(55%)NS魚精蛋白798/980(81%)19/20(95%)NS封堵器血栓形成的臨床轉(zhuǎn)歸 Krumsdorf等報(bào)道1000例ASD和PFO封堵術(shù)后出現(xiàn)封堵器血栓形成的病人20例17例患者血栓于周至個(gè)月內(nèi)通過內(nèi)科治療溶解12例接受華法林，1

21、例接受肝素，4例接受肝素和華法林3例需行外科摘除 1例患者的血栓粘附于Amplatzer傘的左側(cè)面1例患者血栓粘附于Star- FLEX傘的右側(cè)面例患者大血栓粘附于右房側(cè)壁 (ASDOS )J Am Coll Cardiol 2004;43:3029Thrombus on a CardioSeal occluder Left atrial thrombus formation was detected at 1 month follow-up in a 45 year old male without thrombophilia under an anticoagulation therapy

22、 with coumadine (arrow). After a short period of intravenously administered heparin, anticoagulation was changed to ASA plus Clopidogrel. At 2 months follow-up thrombus size had clearly regressed (arrows) and after additional 4 weeks it had completely resolved. (Current Pharmaceutical Design, 2006,

23、12, 1287-1291)images of large mobile thrombi on the left atrial (upper panel) and the right atrial surface (lower panel) of a StarFlex occluder in a 47 year-old female2 months after implantation. Thrombus size had increased despite broad antithrombotic regimen using a combination of anticoagulant th

24、erapy (coumadine), ASA plus Clopidogrel. The occluder was explanted surgically 9 weeks after implantation before an embolisation occurred.遲發(fā)性血栓形成Krieg等報(bào)道1例62歲男性以Amplatzer進(jìn)行PFO封堵術(shù)后8月時(shí)出現(xiàn)雙下肢小腿動(dòng)脈栓塞，隨后并發(fā)急性心肌梗死，造影發(fā)現(xiàn)右側(cè)冠狀動(dòng)脈血栓閉塞，超聲心動(dòng)圖發(fā)現(xiàn)封堵器的左房面血栓形成，腦CT發(fā)現(xiàn)急性缺血性病灶。隨即急診取出封堵器及血栓，封閉PFO，并行冠脈搭橋術(shù)，后該病人病情好轉(zhuǎn)出院Kawalsky 等報(bào)

25、道1例29歲女性以Amplatzer行繼發(fā)孔房缺封堵術(shù)2年后出現(xiàn)多發(fā)的大腦、小腦和腦干的栓塞，緊急予動(dòng)脈內(nèi)溶栓治療而療效欠佳，后經(jīng)TEE發(fā)現(xiàn)封堵器的左房面有一巨大血栓形成，這是迄今為止報(bào)道的第1例術(shù)后出現(xiàn)遲發(fā)的廣泛腦栓塞形成病例二、封堵器血栓形成的機(jī)制封堵術(shù)后患者的凝血激活與植入封堵器的內(nèi)皮化有關(guān) 動(dòng)物實(shí)驗(yàn)研究發(fā)現(xiàn)，通常封堵器植入后一個(gè)月開始內(nèi)皮化，三個(gè)月后則全部被內(nèi)皮細(xì)胞覆蓋 臨床研究發(fā)現(xiàn)，封堵術(shù)后患者的凝血系統(tǒng)的活性曾一度增高,術(shù)后3個(gè)月時(shí)降至正常水平有報(bào)道Amplatzer封堵器的鎳鈦合金和聚酯纖維暴露于血液中時(shí)都會(huì)誘導(dǎo)血小板活性和凝血系統(tǒng)活性的增強(qiáng)International Journal of Cardiology 98(2005)107112International Journal of Cardiology 98(2005)107112內(nèi)皮細(xì)胞是一個(gè)分泌多種活性物質(zhì)的器官，封堵器表面內(nèi)皮化初期，可能表達(dá)組織因子從而啟動(dòng)凝血過程，內(nèi)皮下基底膜的暴露可促使血小板粘附和聚集，激活的血小板為凝血過程提供了反應(yīng)平臺(tái)(血小板第3因子)有報(bào)道認(rèn)為，血流經(jīng)過封堵器表面產(chǎn)生的湍流使凝血系統(tǒng)的活性增高。Josep Rodes-Cabau等13發(fā)現(xiàn)術(shù)后殘余分流的存在亦提高凝血系統(tǒng)的活性。