卵圆孔未闭封堵术：争论与发展(中英文)

卵圆孔未闭封堵术：争论与发展May9,2009AndrewD.Michaels,MD,MAS,FACC,FAHADirector,CardiacCatheterizationLaboratoryandInterventionalCardiologyUniversityofUtah,SaltLakeCity,Utah胎儿循环•胎儿期，氧合血液由脐静脉经下腔静脉进入右房•血流由下腔静脉经过Eustachian瓣流到卵圆窝.出生后房间隔发育宫内出生后Hagen,Scholz.MayoClinProc1984;59:17-20.人口的75％人口的25%PFO相关临床综合症•体位相关呼吸困难Platypneaorthodeoxia•减压病/高原性肺水肿•脑血管事件/TIA•偏头痛PlatypnoeaOrthodeoxia•罕见•直立体位引起的呼吸困难，伴有低氧血症•机制：右向左房间分流Aigneretal.EurJCardiothorSurg2008;33:268.Medinaetal.Circulation2001;104:741.PlatypneaOrthodeoxia•1949年至今已有文献报道近100例•PFO常伴有:主动脉瘤胸廓畸形肺切除术后•约50例已接受封堵术减压病•对230名无症状潜水者进行研究•27%有PFO•需要减压舱治疗者:19%有PFO2%无PFOTortietal.EurHeartJ2004;25:1014-20.隐匿性脑卒中•40岁男性，突发失语•既往史无特殊.无明显脑卒中病因.•TEE:发现房间隔瘤与PFO.•常见伴发症:50%隐匿性脑卒中患者有PFO.推测机制:•静脉血栓反常性体循环栓塞症.•PFO通道内原位血栓形成造成栓塞血栓流经PFO首例PFO伴血栓形成报道于1876.既往通过超声心动图及术中见到嵌顿于PFO的血栓.但无法观察到小栓子的流程。服用阿司匹林的PFO患者脑血管事件/TIA复发率较高Masetal.NEJM2001;345:1740-6.•581名患者有隐匿性脑卒中•均接受阿司匹林治疗华法林－阿司匹林复发性脑卒中研究Mohretal.NEJM2001;345:1444-51.•N=2206缺血性脑血管事件(56%腔梗;25%隐匿性;13%大血管性)•随机接受阿司匹林325mg或华法林治疗•结论:抗血小板及抗凝治疗有效（无效）率相当。药物治疗vs.PFO封堵术Windeckeretal.JACC2004;44:750-8.•308名隐匿性脑卒中伴PFO患者•随机接受药物治疗或PFO封堵术治疗药物治疗vs.PFO封堵术:观察性研究的荟萃分析Khairyetal.AnnIntMed2003;139:753-60.药物治疗(6个研究)N=8953.8-12.0%4.9PFO封堵术(10个研究)N=13550-4.9%3.01年脑卒中/TIA复发率死亡/脑卒中/TIA事件/100人年PFO封堵器PFOASDAmplatzerPFOSTARFlexAmplatzerASOCardioSEALHelexAmplatzerCribiformASD左房伞植入右房伞植入植入前植入后偏头痛与PFO的关系•12％人口患有偏头痛(女性18%;男性6%)•偏头痛患者中存在PFO的占：48%的偏头痛伴视觉先兆123%的偏头痛不伴视觉先兆20%正常人•隐匿性脑卒中伴PFO患者中偏头痛发生率52%有偏头痛伴视觉先兆271%封堵术后症状缓解3•偏头痛患者较正常人MRI检查病变阳性率高13倍41.Anzola.Neurology1999;52:1622-5.2.Sztajzel.CVDiseases2002;13:102-6.3.Wilmshurst.Lancet2000;356:1648-51.4.Kruit.JAMA2004;294:427-34.卵圆孔未闭与偏头痛之间可能的病理生理相关性•经过PFO的微小栓子可引起偏头痛.•体液因子（如5－HT)免受肺降解,引起偏头痛.MIST研究结果DowsonA,etal.Circulation2008;117:1397-404.无偏头痛发作患者,n03131.0偏头痛发作频率/月,mean±SD4.82±2.443.23±1.804.51±2.173.53±2.130.14MIDAS总评分,median(range)36(3–108)17(0–270)34(2–189)18(0–240)0.88头痛天数/3月(MIDAS),median(range)27(0–70)18(0–90)30(5–80)21(0–80)0.79HIT-6总评分,mean±SD67.2±4.759.5±9.366.2±5.158.5±8.60.77术前术前术后术后Pvalue手术组(n=74)假手术组(n=73)偏头痛随机临床试验•NMTMedicalclosedMISTII(January24,2008).•PREMIUM(AGAMedical)及ESCAPE(StJudeMedical)仍在进行中.PFO封堵器技术现况与展望•目前封堵器技术的局限性大型，永久性植入物.远期并发症：心率失常，炎症，糜烂，血栓形成，过敏反应.•未来的封堵器技术小型封堵器.生物可吸收(BioSTAR).可缝合封堵器.射频消融.Mullenetal.Circulation2006;114:1962-7.结论•目前隐匿性脑卒中的药物治疗疗效欠佳.研究提示存在高危复发脑卒中的亚组.尚无随机临床试验支持任何药物治疗•经皮PFO封堵术可能成为隐匿性脑卒中预防的主要干预手段.安全.非随机临床试验资料提示对可有效预防脑卒中.•有待关于脑卒中与偏头痛的进一步临床研究结果.结论PatentForamenOvaleClosure:ControversiesandAccomplishmentsMay9,2009AndrewD.Michaels,MD,MAS,FACC,FAHADirector,CardiacCatheterizationLaboratoryandInterventionalCardiologyUniversityofUtah,SaltLakeCity,UtahFetalCirculation•Duringfetallife,oxygenatedbloodreturningfromtheumbilicalveinenterstheRAthroughtheIVC.•BloodflowisdirectedbytheEustachianvalvefromtheIVCtothefossaovalisandthroughthePFO.Post-NatalSeptalDevelopmentInUteroAfterBirthHagen,Scholz.MayoClinProc1984;59:17-20.75%ofPopulation25%ofPopulationClinicalSyndromesAssociatedwithPFO•Platypneaorthodeoxia•Decompressionsickness/high-altitudepulmonaryedema•CVA/TIA•MigrainePlatypnoeaOrthodeoxia•Uncommonsyndrome•Dyspneainducedbyuprightposture,withassociatedhypoxemia•Mechanism:right-to-leftinteratrialshuntingAigneretal.EurJCardiothorSurg2008;33:268.Medinaetal.Circulation2001;104:741.PlatypneaOrthodeoxia•~100casesinliteraturesince1949•PFOassociatedwith:AorticaneurysmChestdeformityPost-pneumonectomy•~50haveundergonedeviceclosureDecompressionSickness•230asymptomaticdiverssurveyed•27%hadaPFO•Decompressionchamberrequired:19%withaPFO2%withoutaPFOTortietal.EurHeartJ2004;25:1014-20.CryptogenicStrokeCase•40yomanwithsuddenaphasia.•Nomedicalhistory.Noobviouscauseofstroke.•TEE:atrialseptalaneurysmandPFO.•Associations:50%ofpeoplewithcryptogenicstrokehaveaPFO.Presumedmechanism:•Paradoxicalembolismofvenousthrombus.•In-situthrombosiswithinPFOtunnelwithembolization.ThrombusintransitthroughPFOFirstcaseofPFOwiththrombusdescribedin1876.ThrombuscaughtinPFOhasbeenseenbyechoandatsurgery.However,passagesofsmallemboliareimpossibletoprove.HigherCVA/TIARecurrenceRateinPatientswithPFO+ASAMasetal.NEJM2001;345:1740-6.•581patientswithcryptogenicstroke•AlltreatedwithaspirinWarfarin-AspirinRecurrentStrokeStudyMohretal.NEJM2001;345:1444-51.•N=2206withischemicCVA(56%lacunar;25%cryptogenic;13%largevessel)•RandomizedtoASA325mgvsWarfarin•Conclusion:Antiplateletandanticoagulanttherapyequally(in)effectiveMedicalTherapyvs.PFOClosureWindeckeretal.JACC2004;44:750-8.•N=308withcryptogenicCVAandPFO•RandomizedtomedicaltherapyorPFOclosureMedicalTherapyvs.PFOClosure:Meta-AnalysisofObservationalStudiesKhairyetal.AnnIntMed2003;139:753-60.MedicalTherapy(6studies)N=8953.8-12.0%4.9PFOClosure(10studies)N=13550-4.9%3.0RecurrentCVA/TIA1-YearDeath/CVA/TIAEvents/100ptyrsPFODevicesPFOASDAmplatzerPFOSTARFlexAmplatzerASOCardioSEALHelexAmplatzerCribiformASDLeftAtrialDiscDeploymentRightAtrialDiscDeploymentPrePostAssociationBetweenMigraineandPFO•Migraineheadacheaffects12%ofpopulation(18%F;6%M)•IncidenceofPFOinpatientswithmigraine48%ifmigrainewithaura123%ifmigrainewithoutaura