1、颈动脉支架成形术后再狭窄的研究进展,淄博市第一人民医院 张涛,定义,颈动脉支架后再狭窄( in-stent restenosis，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(the carotid revascularization using endarterectomy or stenting systems，CARESS)证明两者在30天(3.6CEA VS 2.1CAS)或者1年
2、(13.6CEA VS 10.0CAS)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(Endarterectomy vs Angioplasty in Patients with Symptomatic Severe Carotid Stenosis,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-Protected Angioplasty verus Carotid Endarterectomy,SPACE)相似.,ISR机制,主要机制-血管平
3、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,
4、Mehran等将ISR分为4种类型：(1)局限型：再狭窄长度10 mm;(2)弥散型：再狭窄长度10 mm;(3)增殖型：再狭窄长度10 mm且超过支架一侧边缘;(4)闭塞型：支架被完全堵塞。,Mehran R, Dangas G, Abizaid AS,Angiographic patterns of in-stent restenosis: classification and implications for long-term outcome.Circulation. 1999 Nov 2;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
5、（Oral Rapamycin in ARgentina, ORAR） n vc;.xzk-中，冠状动脉裸金属支架置入术后口服雷帕霉素14 d可降低再狭窄发生率。ORAR-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:血管紧张素可通过生长因子促进再狭窄发生。血管紧张素1型受体拮抗药能通过抑制血管紧张素与血管紧张素1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
6、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
7、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.
8、,Drug-eluting balloon angioplasty 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 in which drug-eluting balloons (DEBs) were succ
9、essfully 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 asymptomatic severe stenosis 80% with peak systolic velocity (PSV) 300cm/s by Doppler ultrasound assessment of individual Caro
10、tid Wallstents implanted in the proximal left internal carotid artery (ICA). In the 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. Unde
11、r distal 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 dual antiplatelet therapy. At 12, 22, and 36 months,respectively, the patients a
12、re still asymptomatic, with duplex-documented stent patency at 6, 12, and 24 months, respectively.,Conclusion:,DEBs are an emerging strategy for carotid ISR, with encouraging midterm results in these patients. Further experience in larger cohorts is needed to confirm these preliminary observations.,
13、Contralateral occlusion is not a clinically important reason for 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 artery stenting for pa
14、tients 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 endarterectomy(CEA) in the presence of contralateral carotid artery occlusion has high reported rates of periop
15、erative morbidity and mortality. Our objective was to determine if there is a clinical benefit to patients who receive carotid 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 in
16、stitutional experience of persons with contralateral 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 of 713 patients treated for carotid art
17、ery 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 were prior neck surgery (18), contralateral internal carotid occlusion (nine), and prior neck radiation (seven). The av
18、erage age was 70 8.5 for CEA and 66.7 9.3 for CAS (P .20). Both groups were predominantly men (CEA 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
19、days in the CEA group (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 29.416 months (CEA) and 2814.4 months (CAS; range, 1.5-48.5 months),
20、 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 restenosis 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 of contralateral carotid artery occlusion as a selection criterion for CAS over CEA in the absence of other indications.,Thanks！,
