1、頸動脈支架成形術后再狹窄的頸動脈支架成形術后再狹窄的研究進展研究進展定義頸動脈支架后再狹窄( in-stent restenosis，ISR):是指支架置入術后在支架處或支架邊緣5mm范圍內發生的50%的管腔狹窄.當支架置入后發生再狹窄或參與狹窄50%時,發生缺血性卒中風險顯著增高,因此,ISR是影響患者預后的重要因素.發生率運用動脈內膜切除術或者支架成形術進行頸動脈血管重建試驗(the carotid revascularization using endarterectomy or stenting systems，CARESS)證明兩者在30天(3.6CEA VS 2.1CAS)或者1年

2、(13.6CEA VS 10.0CAS)的卒中和病死率沒有顯著差異.有癥狀重度頸動脈狹窄患者內膜切除術與血管成形術比較(Endarterectomy vs Angioplasty in Patients with Symptomatic Severe Carotid Stenosis,EVA-3S)實驗公布的3年隨訪結果顯示,CAS后再狹窄發生率遠遠高于CEA,分別為12.5%和5%.同保護性支架血管成形術與頸動脈內膜剝脫術比較實驗(Stent-Protected Angioplasty verus Carotid Endarterectomy,SPACE)相似.ISR機制 主要機制-血管平滑

3、肌細胞外基質沉積引起新內膜形成以及支架置入后血栓再機化.血管壁彈性回縮；附壁血栓形成；血管內膜增生；血管負性重塑(收縮性重塑,向內重塑,失代償性重塑)。 其中內膜增生是術后早期再狹窄的最主要的病理生理過程.技術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;支架區域外殘留的動脈粥樣硬化病變.研究表明,球囊擴張后未覆蓋的損傷區最先出現ISR.危險因素支架置入術后殘余狹窄程度(殘余狹窄每增加1%,相對危險因素增高1.091)；吸煙；高血糖；女性；高齡(大于75歲);同時置入多枚支架;CEA史;血管管腔直徑較小;放療史;支架置入術后炎癥標志物水平增高;高密度脂蛋白水平降低.分型Mehran等

4、將ISR分為4種類型：(1)局限型：再狹窄長度10 mm;(2)彌散型：再狹窄長度10 mm;(3)增殖型：再狹窄長度10 mm且超過支架一側邊緣;(4)閉塞型：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.ISRISR的預防和治療的預防和治療藥物預防雷帕霉素:在阿根廷口服雷帕霉素試驗（O

5、ral Rapamycin in ARgentina, ORAR） n vc;.xzk-中，冠狀動脈裸金屬支架置入術后口服雷帕霉素14 d可降低再狹窄發生率。ORAR-進一步顯示，裸金屬支架置人聯合口服雷帕霉素的抗再狹窄作用與藥物涂層支架相近，而且前者的花費顯著較少.抗血小板: 血小板活化在ISR發生和發展過程中起著重要作用，但抗血小板藥對ISR的預防作用與其對血小板功能的抑制程度并不成正比.纈沙坦:血管緊張素可通過生長因子促進再狹窄發生。血管緊張素1型受體拮抗藥能通過抑制血管緊張素與血管緊張素1型受體結合，抑制再狹窄發生.多項臨床試驗均顯示，口服纈沙坦能降低ISR發生率.匹格列酮:糖尿病患者

6、在裸金屬支架置入后，起到降糖和減輕ISR的作用。他汀類藥物:除具有降血脂作用外，還可改善內皮功能，具有抑制血管平滑肌增殖、遷移和預防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胞增殖和減少再狹窄發生的 同時,也會阻止血管內皮細胞增殖。導致內皮化延遲，進而引起局部慢性炎癥反應和增高遠期支架內血栓形成的發生率.生物可降解支架由生物可降解或可吸收材料制成，能暫時支撐狹窄血管，達到血運重建的目的；當使命完成后便開始降解，具

7、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，但易出現降解速度不易控制、血管內皮化延遲和遠期效果不理想等問題.基因預防研究表明，有3種miRNA，即miR-21、miR-145和miR-221，在ISR的發生過程中起著調節作用。敲除miR-21和miR-221或增加miR-145表達，能抑制支架置入后血管平滑肌細胞增殖，從而抑制新生內膜形成，預防ISR.ISR的治療 目前治療ISR的方法很多，但尚缺乏具有明顯優勢的治療方式。經皮腔內血管成形術;重復CAS;支架取出后行CEA是目前應用最多的方法。其他，如頸動脈旁路移植術、近距離放射治療以及裸金屬支架置入術等.Drug-elut

8、ing balloon angioplasty for carotid in-stent restenosisLiistro 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 successfully use

9、d 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 Carotid Wallstent

10、s 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. Under distal filt

11、er 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 are still asym

12、ptomatic, 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.Contralateral o

13、cclusion is not a clinically important reason for choosing carotid artery stenting for patients with significant carotid artery stenosisBrewster LP1, Beaulieu R, Kasirajan K,et al.Contralateral occlusion is not a clinically important reason for choosing carotid artery stenting for patients with sign

14、ificant carotid artery stenosis.J Vasc Surg. 2012 Nov;56(5):1291-4. Objective: 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 perioperati

15、ve 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: Methods: We conducted a retrospective medical chart review over a 4.5-year

16、 institutional 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

17、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 were prior neck surgery (18), contralateral internal carotid occlusion (nine), and prior neck radiation (seven). The

18、 average 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 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 o