颈动脉支架成形术后再狭窄的研究进展

颈动脉支架成形术后再狭窄的研究进展定义•颈动脉支架后再狭窄(in-stentrestenosis，ISR):是指支架置入术后在支架处或支架边缘5mm范围内发生的50%的管腔狭窄.•当支架置入后发生再狭窄或参与狭窄50%时,发生缺血性卒中风险显著增高,因此,ISR是影响患者预后的重要因素.发生率•运用动脉内膜切除术或者支架成形术进行颈动脉血管重建试验(thecarotidrevascularizationusingendarterectomyorstentingsystems，CARESS)证明两者在30天(3.6％CEAVS2.1％CAS)或者1年(13.6％CEAVS10.0％CAS)的卒中和病死率没有显著差异.•有症状重度颈动脉狭窄患者内膜切除术与血管成形术比较(EndarterectomyvsAngioplastyinPatientswithSymptomaticSevereCarotidStenosis,EVA-3S)实验公布的3年随访结果显示,CAS后再狭窄发生率远远高于CEA,分别为12.5%和5%.同保护性支架血管成形术与颈动脉内膜剥脱术比较实验(Stent-ProtectedAngioplastyverusCarotidEndarterectomy,SPACE)相似.ISR机制主要机制--血管平滑肌细胞外基质沉积引起新内膜形成以及支架置入后血栓再机化.•血管壁弹性回缩；•附壁血栓形成；•血管内膜增生；•血管负性重塑(收缩性重塑,向内重塑,失代偿性重塑))。其中内膜增生是术后早期再狭窄的最主要的病理生理过程.技术因素•支架植入段外球囊压力损伤;•支架与血管壁之间存在间隙;•支架区域外残留的动脉粥样硬化病变.研究表明,球囊扩张后未覆盖的损伤区最先出现ISR.危险因素•支架置入术后残余狭窄程度(残余狭窄每增加1%,相对危险因素增高1.091)；•吸烟；•高血糖；•女性；•高龄(大于75岁);•同时置入多枚支架;•CEA史;•血管管腔直径较小;•放疗史;•支架置入术后炎症标志物水平增高;•高密度脂蛋白水平降低.分型Mehran等将ISR分为4种类型：(1)局限型：再狭窄长度≤10mm;(2)弥散型：再狭窄长度10mm;(3)增殖型：再狭窄长度10mm且超过支架一侧边缘;(4)闭塞型：支架被完全堵塞。MehranR,DangasG,AbizaidAS,Angiographicpatternsofin-stentrestenosis:classificationandimplicationsforlong-termoutcome.Circulation.1999Nov2;100(18):1872-8.ISR的预防和治疗药物预防•雷帕霉素:在阿根廷口服雷帕霉素试验（OralRapamycininARgentina,ORAR）nvc;.xzk-Ⅱ中，冠状动脉裸金属支架置入术后口服雷帕霉素14d可降低再狭窄发生率。ORAR-Ⅲ进一步显示，裸金属支架置人联合口服雷帕霉素的抗再狭窄作用与药物涂层支架相近，而且前者的花费显著较少.•抗血小板:血小板活化在ISR发生和发展过程中起着重要作用，但抗血小板药对ISR的预防作用与其对血小板功能的抑制程度并不成正比.•缬沙坦:血管紧张素Ⅱ可通过生长因子促进再狭窄发生。血管紧张素Ⅱ1型受体拮抗药能通过抑制血管紧张素Ⅱ与血管紧张素Ⅱ1型受体结合，抑制再狭窄发生.多项临床试验均显示，口服缬沙坦能降低ISR发生率.•匹格列酮:糖尿病患者在裸金属支架置入后，起到降糖和减轻ISR的作用。•他汀类药物:除具有降血脂作用外，还可改善内皮功能，具有抑制血管平滑肌增殖、迁移和预防ISR的作用.药物涂层支架(1)抗血栓作用的涂层支架：如携带肝素、磷酸胆碱、碳化物等；(2)抗增殖作用的涂层支架：包被细胞增殖抑制剂（如紫杉醇、丝裂霉素）或免疫抑制剂（如雷帕霉素、依维莫司）等.不足:药物涂层支架在阻止平滑肌细胞增殖和减少再狭窄发生的同时,也会阻止血管内皮细胞增殖。导致内皮化延迟，进而引起局部慢性炎症反应和增高远期支架内血栓形成的发生率.生物可降解支架由生物可降解或可吸收材料制成，能暂时支撑狭窄血管，达到血运重建的目的；当使命完成后便开始降解，具有异物性和血栓形成性小的特性.不足:虽然生物相容性和降解性良好，但易出现降解速度不易控制、血管内皮化延迟和远期效果不理想等问题.基因预防•研究表明，有3种miRNA，即miR-21、miR-145和miR-221，在ISR的发生过程中起着调节作用。敲除miR-21和miR-221或增加miR-145表达，能抑制支架置入后血管平滑肌细胞增殖，从而抑制新生内膜形成，预防ISR.ISR的治疗目前治疗ISR的方法很多，但尚缺乏具有明显优势的治疗方式。•经皮腔内血管成形术;•重复CAS;•支架取出后行CEA是目前应用最多的方法。•其他，如颈动脉旁路移植术、近距离放射治疗以及裸金属支架置入术等.Drug-elutingballoonangioplastyforcarotidin-stentrestenosisLiistroF1,PortoI,GrottiS,etal.Drug-elutingballoonangioplastyforcarotidin-stentrestenosis.JEndovascTher.2012Dec;19(6):729-33.Purpose:Toreportmidtermresultsof3casesinwhichdrug-elutingballoons(DEBs)weresuccessfullyusedforthemanagementofcarotidin-stentrestenosis(ISR).CaseReport:Twowomenaged68and70yearsanda68-year-oldmanwerereferredtoourinstitutionforasymptomaticseverestenosis[80%withpeaksystolicvelocity(PSV)300cm/sbyDopplerultrasoundassessment]ofindividualCarotidWallstentsimplantedintheproximalleftinternalcarotidartery(ICA).Intheangiosuite,theleftICAwasengagedinatelescopicfashionwithatriplecoaxialsystemformedbya6-Flongsheathandapreloaded5-F,125-cmdiagnosticcatheterovera0.035-inchsofthydrophilicguidewire.Underdistalfilterprotection,thelesionswerepredilatedusinga3.5x20-mmcoronaryballoonandthentreatedwithtwo1-minuteinflationsofa4x40-mmAmphirionIn.Pactpaclitaxel-elutingballoon,followedby3monthsofdualantiplatelettherapy.At12,22,and36months,respectively,thepatientsarestillasymptomatic,withduplex-documentedstentpatencyat6,12,and24months,respectively.Conclusion:DEBsareanemergingstrategyforcarotidISR,withencouragingmidtermresultsinthesepatients.Furtherexperienceinlargercohortsisneededtoconfirmthesepreliminaryobservations.ContralateralocclusionisnotaclinicallyimportantreasonforchoosingcarotidarterystentingforpatientswithsignificantcarotidarterystenosisBrewsterLP1,BeaulieuR,KasirajanK,etal.Contralateralocclusionisnotaclinicallyimportantreasonforchoosingcarotidarterystentingforpatientswithsignificantcarotidarterystenosis.JVascSurg.2012Nov;56(5):1291-4.Objective:Contralateralcarotidarteryocclusionbyitselfcarriesanincreasedriskofstroke.Carotidendarterectomy(CEA)inthepresenceofcontralateralcarotidarteryocclusionhashighreportedratesofperioperativemorbidityandmortality.Ourobjectivewastodetermineifthereisaclinicalbenefittopatientswhoreceivecarotidarterystenting(CAS)comparedtoCEAinthepresenceofcontralateralcarotidarteryocclusion.Methods:Weconductedaretrospectivemedicalchartreviewovera4.5-yearinstitutionalexperienceofpersonswithcontralateralcarotidarteryocclusionandipsilateralcarotidarterystenosiswhounderwentCASorCEA.Themainoutcomemeasureswere30-daycardiac,stroke,andmortalityrate,andmidtermmortality.Results:Ofatotalof713patientstreatedforcarotidarterystenosisduringthistimeperiod,57hadcontralateralocclusion(8%).Thirty-nineofthesepatientsweretreatedwithCAS,and18withCEA.ThemostcommonindicationsforCASwerepriornecksurgery(18),contralateralinternalcarotidocclusion(nine),andpriorneckradiation(seven).Theaverageagewas708.5forCEAand66.79.3forCAS(P.20).Bothgroupswerepredominantlymen(CEA12of18;CAS28of39;P.76),withsimilarprevalenceofsymptomaticlesions(CEA8of18,CAS20of39;P=.77).Twopatientsdiedwithin30daysintheCASgroup(5%).Nodeathsoccurredwithin30daysintheCEAgroup(P.50);themortalityrateforCASandCEAcombinedwas3.5%.Noperioperativestrokesormyocardialinfarctionoccurredi