卵圆孔未闭封堵术的争论和发展PPT课件

卵圆孔未闭封堵术的争论和发展胎儿循环 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.EurJCardiothorSurg2019;33:268.Medinaetal.Circulation2019;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.EurHeartJ2019;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。服用阿司匹林的PFO患者脑血管事件/TIA复发率较高Masetal.NEJM2019;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.NEJM2019;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.JACC2019;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.AnnIntMed2019;139:753-60.1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CLOSUREoriginally1600patients,nowFDAallowedreductionto900.Enrolled>700.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4 Anzola.Neurology2019;52:1622-5. Sztajzel.CVDiseases2019;13:102-6. Wilmshurst.Lancet2000;356:1648-51. Kruit.JAMA2019;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.Circulation2019;117:1397-404.术前术前术后术后Pvalue手术组(n=74)假手术组(n=73) 无偏头痛发作患者,n 0 3 1 3 1.0 偏头痛发作频率/月,mean±SD 4.82±2.44 3.23±1.80 4.51±2.17 3.53±2.13 0.14      MIDAS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) 0.79      HIT-6总评分,mean±SD 67.2±4.7 59.5±9.3 66.2±5.1 58.5±8.6 0.77     偏头痛随机临床试验 NMTMedicalclosedMISTII(January24,2019). 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.Circulation2019;114:1962-7.Metallicwiresandsyntheticfabrics.BioSTARusesacellularporcineintestinalcollagenlayermatrixmountedonaSTAR-flexdevice.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%ofPopulation 25%ofPopulationClinicalSyndromesAssociatedwithPFO Platypneaorthodeoxia Decompressionsickness/high-altitudepulmonaryedema CVA/TIA MigrainePlatypnoeaOrthodeoxia Uncommonsyndrome Dyspneainducedbyuprightposture,withassociatedhypoxemia Mechanism:right-to-leftinteratrialshuntingAigneretal.EurJCardiothorSurg2019;33:268.Medinaetal.Circulation2019;104:741.PlatypneaOrthodeoxia ~100casesinliteraturesince1949 PFOassociatedwith: Aorticaneurysm Chestdeformity Post-pneumonectomy ~50haveundergonedeviceclosureDecompressionSickness 230asymptomaticdiverssurveyed 27%hadaPFO Decompressionchamberrequired: 19%withaPFO 2%withoutaPFOTortietal.EurHeartJ2019;25:1014-20.CryptogenicStrokeCase 40yomanwithsuddenaphasia. Nomedicalhistory.Noobviouscauseofstroke. TEE:atrialseptalaneurysmandPFO. Associations: 50%ofpeoplewithcryptogenicstrokehaveaPFO. Presumedmechanism: Paradoxicalembolismofvenousthrombus. In-situthrombosiswithinPFOtunnelwithembolization.ThrombusintransitthroughPFOFirstcaseofPFOwiththrombusdescribedin1876.ThrombuscaughtinPFOhasbeenseenbyechoandatsurgery.However,passagesofsmallemboliareimpossibletoprove.HigherCVA/TIARecurrenceRateinPatientswithPFO+ASAMasetal.NEJM2019;345:1740-6. 581patientswithcryptogenicstroke AlltreatedwithaspirinWarfarin-AspirinRecurrentStrokeStudyMohretal.NEJM2019;345:1444-51. N=2206withischemicCVA(56%lacunar;25%cryptogenic;13%largevessel) RandomizedtoASA325mgvsWarfarin Conclusion:Antiplateletandanticoagulanttherapyequally(in)effectiveMedicalTherapyvs.PFOClosureWindeckeretal.JACC2019;44:750-8. N=308withcryptogenicCVAandPFO RandomizedtomedicaltherapyorPFOclosureMedicalTherapyvs.PFOClosure:Meta-AnalysisofObservationalStudiesKhairyetal.AnnIntMed2019;139:753-60.RecurrentCVA/TIA1-YearDeath/CVA/TIAEvents/100ptyrs MedicalTherapy(6studies)N=895 3.8-12.0% 4.9 PFOClosure(10studies)N=1355 0-4.9% 3.0PFODevicesPFOASDAmplatzerPFOSTARFlexAmplatzerASOCardioSEALHelexAmplatzerCribiformASDLeftAtrialDiscDeploymentRightAtrialDiscDeploymentPrePostCLOSUREoriginally1600patients,nowFDAallowedreductionto900.Enrolled>700.AssociationBetweenMigraineandPFO Migraineheadacheaffects12%ofpopulation(18%F;6%M) IncidenceofPFOinpatientswithmigraine 48%ifmigrainewithaura1 23%ifmigrainewithoutaura 20%incontrols IncidenceofmigraineincryptogenicstrokewithPFO 52%hadmigrainewithaura2 71%hadsuppressionpost-closure3 Migrainepatientshave13timeshigherincidenceofMRIlesions4 Anzola.Neurology2019;52:1622-5. Sztajzel.CVDiseases2019;13:102-6. Wilmshurst.Lancet2000;356:1648-51. Kruit.JAMA2019;294:427-34.PotentialPathophysiologicAssociationBetweenPFOandMigraine MicroembolismthroughPFOtriggersmigraine. Humoralfactors(i.e.,serotonin)escapepulmonarydegradation,triggeringmigraine.PublishedMISTResultsDowsonA,etal.Circulation2019;117:1397-404.BaselineBaselinePostPostPvalueImplant(n=74)Sham(n=73) Patientswithnomigraineattacks,n 0 3 1 3 1.0 Frequencyofmigraineattacks/mo,mean±SD 4.82±2.44 3.23±1.80 4.51±2.17 3.53±2.13 0.14      TotalMIDASscore,median(range) 36(3–108) 17(0–270) 34(2–189) 18(0–240) 0.88      Headached/3mo(MIDAS),median(range) 27(0–70) 18(0–90) 30(5–80) 21(0–80) 0.79      HIT-6totalscore,mean±SD 67.2±4.7 59.5±9.3 66.2±5.1 58.5±8.6 0.77     MigraineRandomizedClinicalTrials NMTMedicalclosedMISTII(January24,2019). PREMIUM(AGAMedical)andESCAPE(StJudeMedical)stillenrolling.CurrentandFuturePFODeviceTechnologies LimitationsofCurrentDeviceTechnologies Large,permanentimplants. Latecomplications:arrhythmia,inflammation,erosions,thrombus,allergicreactions. FutureDeviceTechnologies Smallerprofiledevices. Bioabsorbable(BioSTAR). Suture-baseddevices. Radiofrequencyablation.Mullenetal.Circulation2019;114:1962-7.Metallicwiresandsyntheticfabrics.BioSTARusesacellularporcineintestinalcollagenlayermatrixmountedonaSTAR-flexdevice. Currentmedicaltherapyinsufficientforpatientswithcryptogenicstroke. Subgroupsathigh-riskforrecurrentCVAareidentifiable. NoRCTdatainsupportofanytreatment. PercutaneousPFOclosureislikelytobecomeacornerstoneofcryptogenicCVAprevention. Safe. Non-randomizeddatasuggestsefficacyforCVAprevention. AwaitclinicaltrialresultsforCVAandmigraine.ConclusionsCLOSUREoriginally1600patients,nowFDAallowedreductionto900.Enrolled>700.Metallicwiresandsyntheticfabrics.BioSTARusesacellularporcineintestinalcollagenlayermatrixmountedonaSTAR-flexdevice.CLOSUREoriginally1600patients,nowFDAallowedreductionto900.Enrolled>700.Metallicwiresandsyntheticfabrics.BioSTARusesacellularporcineintestinalcollagenlayermatrixmountedonaSTAR-flexdevice.