頸動(dòng)脈支架成形術(shù)后再狹窄的研究進(jìn)展

1、頸動(dòng)脈支架成形術(shù)后再狹窄的研究進(jìn)展,淄博市第一人民醫(yī)院 張濤,定義,頸動(dòng)脈支架后再狹窄( in-stent restenosis，ISR):是指支架置入術(shù)后在支架處或支架邊緣5mm范圍內(nèi)發(fā)生的>50%的管腔狹窄.當(dāng)支架置入后發(fā)生再狹窄或參與狹窄>50%時(shí),發(fā)生缺血性卒中風(fēng)險(xiǎn)顯著增高,因此,ISR是影響患者預(yù)后的重要因素.,發(fā)生率,運(yùn)用動(dòng)脈內(nèi)膜切除術(shù)或者支架成形術(shù)進(jìn)行頸動(dòng)脈血管重建試驗(yàn)(the carotid revascu

2、larization using endarterectomy or stenting systems，CARESS)證明兩者在30天(3.6％CEA VS 2.1％CAS)或者1年(13.6％CEA VS 10.0％CAS)的卒中和病死率沒(méi)有顯著差異.有癥狀重度頸動(dòng)脈狹窄患者內(nèi)膜切除術(shù)與血管成形術(shù)比較(Endarterectomy vs Angioplasty in Patients with Symptomatic Severe

3、Carotid Stenosis,EVA-3S)實(shí)驗(yàn)公布的3年隨訪結(jié)果顯示,CAS后再狹窄發(fā)生率遠(yuǎn)遠(yuǎn)高于CEA,分別為12.5%和5%.同保護(hù)性支架血管成形術(shù)與頸動(dòng)脈內(nèi)膜剝脫術(shù)比較實(shí)驗(yàn)(Stent-Protected Angioplasty verus Carotid Endarterectomy,SPACE)相似.,ISR機(jī)制,主要機(jī)制--血管平滑肌細(xì)胞外基質(zhì)沉積引起新內(nèi)膜形成以及支架置入后血栓再機(jī)化.血管壁彈性回縮；附壁血栓形成

4、；血管內(nèi)膜增生；血管負(fù)性重塑(收縮性重塑,向內(nèi)重塑,失代償性重塑))。 其中內(nèi)膜增生是術(shù)后早期再狹窄的最主要的病理生理過(guò)程.,技術(shù)因素,支架植入段外球囊壓力損傷;支架與血管壁之間存在間隙;支架區(qū)域外殘留的動(dòng)脈粥樣硬化病變.研究表明,球囊擴(kuò)張后未覆蓋的損傷區(qū)最先出現(xiàn)ISR.,危險(xiǎn)因素,支架置入術(shù)后殘余狹窄程度(殘余狹窄每增加1%,相對(duì)危險(xiǎn)因素增高1.091)；吸煙；高血糖；女性；高齡(大于75歲);同時(shí)置入多枚支

5、架;CEA史;血管管腔直徑較小;放療史;支架置入術(shù)后炎癥標(biāo)志物水平增高;高密度脂蛋白水平降低.,分型,Mehran等將ISR分為4種類(lèi)型：(1)局限型：再狹窄長(zhǎng)度≤10 mm;(2)彌散型：再狹窄長(zhǎng)度>10 mm;(3)增殖型：再狹窄長(zhǎng)度>10 mm且超過(guò)支架一側(cè)邊緣;(4)閉塞型：支架被完全堵塞。,Mehran R, Dangas G, Abizaid AS,Angiographic patterns o

6、f in-stent restenosis: classification and implications for long-term outcome.Circulation. 1999 Nov 2;100(18):1872-8.,ISR的預(yù)防和治療,藥物預(yù)防,雷帕霉素:在阿根廷口服雷帕霉素試驗(yàn)（Oral Rapamycin in ARgentina, ORAR） n vc;.xzk-Ⅱ中，冠狀動(dòng)脈裸金屬支架置入術(shù)后口服雷帕霉素14

7、d可降低再狹窄發(fā)生率。ORAR-Ⅲ進(jìn)一步顯示，裸金屬支架置人聯(lián)合口服雷帕霉素的抗再狹窄作用與藥物涂層支架相近，而且前者的花費(fèi)顯著較少.抗血小板: 血小板活化在ISR發(fā)生和發(fā)展過(guò)程中起著重要作用，但抗血小板藥對(duì)ISR的預(yù)防作用與其對(duì)血小板功能的抑制程度并不成正比.纈沙坦:血管緊張素Ⅱ可通過(guò)生長(zhǎng)因子促進(jìn)再狹窄發(fā)生。血管緊張素Ⅱ1型受體拮抗藥能通過(guò)抑制血管緊張素Ⅱ與血管緊張素Ⅱ1型受體結(jié)合，抑制再狹窄發(fā)生.多項(xiàng)臨床試驗(yàn)均顯示，口服纈沙坦能

8、降低ISR發(fā)生率.匹格列酮:糖尿病患者在裸金屬支架置入后，起到降糖和減輕ISR的作用。他汀類(lèi)藥物:除具有降血脂作用外，還可改善內(nèi)皮功能，具有抑制血管平滑肌增殖、遷移和預(yù)防ISR的作用.,藥物涂層支架,(1)抗血栓作用的涂層支架：如攜帶肝素、磷酸膽堿、碳化物等；(2)抗增殖作用的涂層支架：包被細(xì)胞增殖抑制劑（如紫杉醇、絲裂霉素）或免疫抑制劑（如雷帕霉素、依維莫司）等.不足:藥物涂層支架在阻止平滑肌細(xì)胞增殖和減少再狹窄發(fā)生的 同時(shí)

9、,也會(huì)阻止血管內(nèi)皮細(xì)胞增殖。導(dǎo)致內(nèi)皮化延遲，進(jìn)而引起局部慢性炎癥反應(yīng)和增高遠(yuǎn)期支架內(nèi)血栓形成的發(fā)生率.,生物可降解支架,由生物可降解或可吸收材料制成，能暫時(shí)支撐狹窄血管，達(dá)到血運(yùn)重建的目的；當(dāng)使命完成后便開(kāi)始降解，具有異物性和血栓形成性小的特性.不足:雖然生物相容性和降解性良好，但易出現(xiàn)降解速度不易控制、血管內(nèi)皮化延遲和遠(yuǎn)期效果不理想等問(wèn)題.,基因預(yù)防,研究表明，有3種miRNA，即miR-21、miR-145和miR-221，在IS

10、R的發(fā)生過(guò)程中起著調(diào)節(jié)作用。敲除miR-21和miR-221或增加miR-145表達(dá)，能抑制支架置入后血管平滑肌細(xì)胞增殖，從而抑制新生內(nèi)膜形成，預(yù)防ISR.,ISR的治療,目前治療ISR的方法很多，但尚缺乏具有明顯優(yōu)勢(shì)的治療方式。經(jīng)皮腔內(nèi)血管成形術(shù);重復(fù)CAS;支架取出后行CEA是目前應(yīng)用最多的方法。其他，如頸動(dòng)脈旁路移植術(shù)、近距離放射治療以及裸金屬支架置入術(shù)等.,Drug-eluting balloon angioplasty

11、 for carotid in-stent restenosis,Liistro F1, Porto I, Grotti S,et al.Drug-eluting balloon angioplasty for carotid in-stent restenosis.J Endovasc Ther. 2012 Dec;19(6):729-33.,Purpose:,To report midterm results of 3 cases

12、in which drug-eluting balloons (DEBs) were successfully used for the management of carotid in-stent restenosis (ISR).,Case Report:,Two women aged 68 and 70 years and a 68-year-old man were referred to our institution for

13、 asymptomatic severe stenosis [>80% with peak systolic velocity (PSV) >300cm/s by Doppler ultrasound assessment] of individual Carotid Wallstents implanted in the proximal left internal carotid artery (ICA). In the

14、 angiosuite, the left ICA was engaged in a telescopic fashion with a triple coaxial system formed by a 6-F long sheath and a preloaded 5-F, 125-cm diagnostic catheter over a 0.035-inch soft hydrophilic guidewire. Under d

15、istal filter protection, the lesions were predilated using a 3.5x20-mm coronary balloon and then treated with two 1-minute inflations of a 4x40-mm Amphirion In.Pact paclitaxel-eluting balloon, followed by 3 months of dua

16、l antiplatelet therapy. At 12, 22, and 36 months,respectively, the patients are still asymptomatic, with duplex-documented stent patency at 6, 12, and 24 months, respectively.,Conclusion:,DEBs are an emerging strategy fo

17、r carotid ISR, with encouraging midterm results in these patients. Further experience in larger cohorts is needed to confirm these preliminary observations.,,Contralateral occlusion is not a clinically important reason f

18、or choosing carotid artery stenting for patients with significant carotid artery stenosis,Brewster LP1, Beaulieu R, Kasirajan K,et al.Contralateral occlusion is not a clinically important reason for choosing carotid arte

19、ry stenting for patients with significant carotid artery stenosis.J Vasc Surg. 2012 Nov;56(5):1291-4.,Objective:,Contralateral carotid artery occlusion by itself carries an increased risk of stroke. Carotid endarterectom

20、y(CEA) in the presence of contralateral carotid artery occlusion has high reported rates of perioperative morbidity and mortality. Our objective was to determine if there is a clinical benefit to patients who receive car

21、otid artery stenting (CAS)compared to CEA in the presence of contralateral carotid artery occlusion.,Methods:,We conducted a retrospective medical chart review over a 4.5-year institutional experience of persons with con

22、tralateral carotid artery occlusion and ipsilateral carotid artery stenosis who underwent CAS or CEA. The main outcome measures were 30-day cardiac, stroke, and mortality rate, and midterm mortality.Results: Of a total o

23、f 713 patients treated for carotid artery stenosis during this time period, 57 had contralateral occlusion (8%). Thirty-nine of these patients were treated with CAS, and 18 with CEA. The most common indications for CAS w

24、ere prior neck surgery (18), contralateral internal carotid occlusion (nine), and prior neck radiation (seven). The average age was 70 8.5 for CEA and 66.7 9.3 for CAS (P .20). Both groups were predominantly men (CEA

25、12 of 18; CAS 28 of 39; P .76), with similar prevalence of symptomatic lesions (CEA 8 of 18, CAS 20 of 39; P= .77). Two patients died within 30 days in the CAS group (5%). No deaths occurred within 30 days in the CEA gr

26、oup (P .50); the mortality rate for CAS and CEA combined was 3.5%. No perioperative strokes or myocardial infarction occurred in either group.Two transient ischemic attacks occurred after CAS. At mean follow-up of 29.4＋

27、16 months (CEA) and 28＋14.4 months (CAS; range, 1.5-48.5 months), seven deaths occurred in the CAS group and one in the CEA group (17.9% vs5.5%; P= .40). There were two reinterventions in the CAS group for in-stent rest

28、enosis and there were no reoperations in the CEA group.,Conclusions:,Although CEA and CAS can both be performed with good perioperative results and acceptable midterm mortality, the observed outcomes do not support use o