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1、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Platypneao
2、rthodeoxia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.PlatypneaOrthodeoxia1949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PFO2%无PFOTortietal.EurHeartJ2004;25
3、: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首例首例 PFO伴血栓形成报道于伴血栓形成报道于1876.既往通过超声心动图及术中见到嵌顿于既往通过超声心动图及术中见到嵌顿于PFO的血栓的血栓.但无法观察到小栓子的流程。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
4、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=1
5、3550-4.9%3.01年脑卒中年脑卒中/TIA复发率复发率死亡死亡/脑卒中脑卒中/TIA事件事件/100 人年人年PFO封堵器PFOASDAmplatzerPFOSTARFlexAmplatzerASOCardioSEALHelexAmplatzerCribiformASD左房伞植入左房伞植入右房伞植入右房伞植入植入前植入前植入后植入后偏头痛与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%的偏头痛伴视觉先兆123%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%有偏头痛伴视觉先兆271%封堵术后症状缓解3偏头痛患者较正常
6、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5HT)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,meanSD4.822.443
7、.231.804.512.173.532.130.14MIDAS总评分,median(range)36(3108)17(0270)34(2189)18(0240)0.88头痛天数/3月(MIDAS),median(range)27(070)18(090)30(580)21(080)0.79HIT-6总评分,meanSD67.24.759.59.366.25.158.58.60.77术前术前术后术后Pvalue手术组手术组 (n=74)假手术组假手术组(n=73)偏头痛随机临床试验NMTMedicalclosedMISTII(January24,2008).PREMIUM(AGAMedical)
8、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Pat
9、entForamenOvaleClosure:ControversiesandAccomplishmentsMay9,2009AndrewD.Michaels,MD,MAS,FACC,FAHADirector,CardiacCatheterizationLaboratoryandInterventionalCardiologyUniversityofUtah,SaltLakeCity,UtahFetalCirculationDuringfetallife,oxygenatedbloodreturningfromtheumbilicalveinenterstheRAthroughtheIVC.B
10、loodflowisdirectedbytheEustachianvalvefromtheIVCtothefossaovalisandthroughthePFO.Post-NatalSeptalDevelopmentInUteroAfterBirthHagen,Scholz.MayoClinProc1984;59:17-20.75%ofPopulation25%ofPopulationClinicalSyndromesAssociatedwithPFOPlatypneaorthodeoxiaDecompressionsickness/high-altitudepulmonaryedemaCVA
11、/TIAMigrainePlatypnoeaOrthodeoxiaUncommonsyndromeDyspneainducedbyuprightposture,withassociatedhypoxemiaMechanism:right-to-leftinteratrialshuntingAigneretal.EurJCardiothorSurg2008;33:268.Medinaetal.Circulation2001;104:741.PlatypneaOrthodeoxia100casesinliteraturesince1949PFOassociatedwith:Aorticaneury
12、smChestdeformityPost-pneumonectomy50haveundergonedeviceclosureDecompressionSickness230asymptomaticdiverssurveyed27%hadaPFODecompressionchamberrequired:19%withaPFO2%withoutaPFOTortietal.EurHeartJ2004;25:1014-20.CryptogenicStrokeCase40yomanwithsuddenaphasia.Nomedicalhistory.Noobviouscauseofstroke.TEE:
13、atrialseptalaneurysmandPFO.Associations:50%ofpeoplewithcryptogenicstrokehaveaPFO.Presumedmechanism:Paradoxicalembolismofvenousthrombus.In-situthrombosiswithinPFOtunnelwithembolization.ThrombusintransitthroughPFOFirst case of PFO with thrombus described in 1876.Thrombus caught in PFO has been seen by
14、 echo and at surgery.However, passages of small emboli are impossible to prove.HigherCVA/TIARecurrenceRateinPatientswithPFO+ASAMasetal.NEJM2001;345:1740-6.581patientswithcryptogenicstrokeAlltreatedwithaspirinWarfarin-AspirinRecurrentStrokeStudyMohretal.NEJM2001;345:1444-51.N=2206withischemicCVA(56%l
15、acunar;25%cryptogenic;13%largevessel)RandomizedtoASA325mgvsWarfarinConclusion:Antiplateletandanticoagulanttherapyequally(in)effectiveMedicalTherapyvs.PFOClosureWindeckeretal.JACC2004;44:750-8.N=308withcryptogenicCVAandPFORandomizedtomedicaltherapyorPFOclosureMedicalTherapyvs.PFOClosure:Meta-Analysis
16、ofObservationalStudiesKhairyetal.AnnIntMed2003;139:753-60.MedicalTherapy(6studies)N=8953.8-12.0%4.9PFOClosure(10studies)N=13550-4.9%3.0Recurrent CVA/TIA1-YearDeath/CVA/TIAEvents/100 pt yrsPFODevicesPFOASDAmplatzerPFOSTARFlexAmplatzerASOCardioSEALHelexAmplatzerCribiformASDLeft Atrial Disc DeploymentR
17、ight Atrial Disc DeploymentPrePostAssociationBetweenMigraineandPFOMigraineheadacheaffects12%ofpopulation(18%F;6%M)IncidenceofPFOinpatientswithmigraine48%ifmigrainewithaura123%ifmigrainewithoutaura20%incontrolsIncidenceofmigraineincryptogenicstrokewithPFO52%hadmigrainewithaura271%hadsuppressionpost-c
18、losure3Migrainepatientshave13timeshigherincidenceofMRIlesions41.Anzola.Neurology1999;52:1622-5.2.Sztajzel.CVDiseases2002;13:102-6.3.Wilmshurst.Lancet2000;356:1648-51.4.Kruit.JAMA2004;294:427-34.PotentialPathophysiologicAssociationBetweenPFOandMigraineMicroembolismthroughPFOtriggersmigraine.Humoralfa
19、ctors(i.e.,serotonin)escapepulmonarydegradation,triggeringmigraine.PublishedMISTResultsDowsonA,etal.Circulation2008;117:1397-404.Patientswithnomigraineattacks,n03131.0Frequencyofmigraineattacks/mo,meanSD4.822.443.231.804.512.173.532.130.14TotalMIDASscore,median(range)36(3108)17(0270)34(2189)18(0240)
20、0.88Headached/3mo(MIDAS),median(range)27(070)18(090)30(580)21(080)0.79HIT-6totalscore,meanSD67.24.759.59.366.25.158.58.60.77BaselineBaselinePostPostPvalueImplant (n=74)Sham (n=73)MigraineRandomizedClinicalTrialsNMTMedicalclosedMISTII(January24,2008).PREMIUM(AGAMedical)andESCAPE(StJudeMedical)stillen
21、rolling.CurrentandFuturePFODeviceTechnologiesLimitationsofCurrentDeviceTechnologiesLarge,permanentimplants.Latecomplications:arrhythmia,inflammation,erosions,thrombus,allergicreactions.FutureDeviceTechnologiesSmallerprofiledevices.Bioabsorbable(BioSTAR).Suture-baseddevices.Radiofrequencyablation.Mul
22、lenetal.Circulation2006;114:1962-7.Currentmedicaltherapyinsufficientforpatientswithcryptogenicstroke.Subgroupsathigh-riskforrecurrentCVAareidentifiable.NoRCTdatainsupportofany treatment.PercutaneousPFOclosureislikelytobecomeacornerstoneofcryptogenicCVAprevention.Safe.Non-randomizeddatasuggestsefficacyforCVAprevention.AwaitclinicaltrialresultsforCVAandmigraine.Conclusions
