張　路　唐　驍　符偉國　史振宇　呂　鵬　戴媛媛　王玉琦　郭大喬△

(1復旦大學附屬中山醫(yī)院血管外科-復旦大學血管外科研究所;2復旦大學附屬中山醫(yī)院放射科　上海　200032)

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腦保護下頸動脈支架成形術(shù)治療頸動脈中重度鈣化狹窄的療效分析

張路1唐驍1符偉國1史振宇1呂鵬2戴媛媛2王玉琦1郭大喬1△

(1復旦大學附屬中山醫(yī)院血管外科-復旦大學血管外科研究所;2復旦大學附屬中山醫(yī)院放射科上海200032)

目的評價腦保護下頸動脈支架成形術(shù)(carotid angioplasty and stenting,CAS)治療頸動脈中重度鈣化狹窄的安全性及有效性。方法28例頸動脈中重度鈣化狹窄患者接受了腦保護下頸動脈支架植入術(shù),均接受了術(shù)前頸動脈CT血管造影檢查及術(shù)前術(shù)后頭顱MRI檢查,評價術(shù)后新發(fā)彌散加權(quán)(diffusion weighted imaging,DWI)病灶、術(shù)后支架即刻殘余狹窄率與鈣化斑塊的關(guān)系。結(jié)果28例次CAS的即刻成功率為100%。圍手術(shù)期無死亡或心肌梗死等嚴重并發(fā)癥。術(shù)后3天內(nèi)復查頭顱MRI:新發(fā)DWI病灶15例(53.6%),均無神經(jīng)系統(tǒng)癥狀。根據(jù)術(shù)后有無新發(fā)DWI病灶,將患者分為陽性組和陰性組,比較兩組鈣化斑塊的位置、體積大小、鈣化弧度(calcium radian,CR)及Agatston鈣化評分、鈣化CT值、鈣化斑塊體積百分比和頸動脈斑塊最大厚度,差異均無統(tǒng)計學意義(P>0.05)。術(shù)后12個月內(nèi),1例患者發(fā)生手術(shù)側(cè)腦卒中,其余27例恢復良好,無短暫性腦缺血發(fā)作或腦卒中發(fā)生。術(shù)后1年復查頸動脈超聲,并隨訪頸部X線,支架內(nèi)再狹窄發(fā)生率為0,支架斷裂發(fā)生率為0。結(jié)論在實施遠端腦保護裝置的情況下,CAS對頸動脈中重度鈣化狹窄是一種安全有效的治療方法。鈣化斑塊的位置、體積大小、CR、Agatston鈣化評分、鈣化斑塊CT值、鈣化斑塊體積百分比和頸動脈斑塊最大厚度對術(shù)后新發(fā)DWI病灶的發(fā)生率無明顯影響。

頸動脈狹窄;支架;鈣化;新發(fā)DWI病灶;殘余狹窄率

在中國,腦卒中已成為死亡的首位原因[1]。頸動脈狹窄是腦卒中重要的危險因素,20%～25%腦卒中與頸動脈狹窄密切相關(guān)[2]。作為頸動脈狹窄的治療方式之一,頸動脈支架成形術(shù)(carotid angioplasty and stenting,CAS)取得了良好的效果。CAS具有微創(chuàng)的優(yōu)點,但是目前頸動脈狹窄病變的鈣化嚴重程度對于CAS療效的影響,尚無確切結(jié)論。如何選擇合適患者,對于CAS及頸動脈內(nèi)膜剝脫術(shù)這類預防性手術(shù)具有重要的意義。復旦大學附屬中山醫(yī)院血管外科自2014年6月至 2015年1月共實施127例次CAS治療顱外頸動脈狹窄,本研究回顧性分析了其中28例次頸內(nèi)動脈中重度鈣化狹窄病例,就圍手術(shù)期及中期療效分析如下。

資 料 和 方 法

病例資料CAS適應證為頸動脈直徑狹窄率超過50%的有癥狀患者,或者頸動脈直徑狹窄率超過60%的無癥狀患者[2]。入組條件為:非環(huán)狀鈣化、嚴重心肺功能不全、對側(cè)頸動脈嚴重狹窄或閉塞、頸部放療后、超過第2頸椎的高位病變或鎖骨以下的低位病變等。排除條件為:頸動脈環(huán)狀鈣化、髂動脈閉塞等頸動脈支架入路困難、嚴重腎功能不全、對比劑過敏史及患者選擇頸動脈內(nèi)膜剝脫術(shù)等。頸動脈直徑狹窄率、頸動脈殘余狹窄及頸動脈再狹窄率的計算按照北美癥狀性頸動脈狹窄內(nèi)膜切除研究(the North American Symptomatic Carotid Endarterectomy Trial,NASCET)的標準[3]。

頸動脈鈣化斑塊分布見圖1:無鈣化;外層鈣化(靠近外膜及外膜以外);中層鈣化(既不靠近管腔面,也不靠近外膜);內(nèi)層鈣化(靠近血管管腔面)。頸動脈鈣化弧度大小(calcium radian,CR)見圖2:無鈣化;CR≤30°鈣化;30°鈣化

方法術(shù)前所有入組患者行頸動脈CT血管造影和頭顱MRI,術(shù)后3天內(nèi)完成MRI。術(shù)前1周口服腸溶阿斯匹林100 mg/d和氯吡格雷75 mg/d,所有患者均行全身麻醉,經(jīng)股動脈入路。頸動脈狹窄病變的預擴張和后擴張,盡量在腦保護傘釋放到位后進行;如果頸動脈呈重度狹窄,腦保護傘無法順利通過,則應用小直徑球囊(2.5 mm～3mm)快速預擴,以便腦保護傘順利通過病變。所有患者均在路徑圖模式下釋放腦保護傘和頸動脈支架。如果殘余狹窄>30%,則行后擴。術(shù)后即刻對頸動脈及全腦血管造影,確認遠端有無栓塞及支架殘余狹窄情況。術(shù)畢連續(xù)監(jiān)測血壓心率至少24 h觀察神經(jīng)系統(tǒng)癥狀和體征,出院后繼續(xù)口服腸溶阿司匹林100 mg/d (終身)及氯吡格雷75 mg/d (至少半年)。

結(jié)　　　果

2014年6月至2015年1月,我們共實施了127例頸動脈手術(shù),其中頸動脈中重度鈣化患者28例。有癥狀患者15例,無癥狀患者13例。所有患者術(shù)中都應用遠端腦保護裝置NAV6(美國Abbott公司),共放置自膨式頸動脈支架Acculink(美國Abbott公司)28個,即刻成功率為100%(殘余狹窄<30%)。圍手術(shù)期無死亡或心肌梗死等嚴重并發(fā)癥發(fā)生。術(shù)后3天內(nèi)復查頭顱MRI,結(jié)果顯示新發(fā)DWI病灶15例(53.6%),均無神經(jīng)系統(tǒng)癥狀。1例患者于術(shù)后1個月出現(xiàn)手術(shù)側(cè)腦卒中,患側(cè)肢體肌力明顯降低(Ⅱ級),于康復治療后,肢體肌力恢復至Ⅳ級,順利出院,其余患者無癥狀性腦卒中發(fā)作。根據(jù)術(shù)后新發(fā)DWI病灶將患者分為新發(fā)DWI病灶陽性組[DWI(+)]和新發(fā)DWI病灶陰性組[DWI(-)]。兩組間在年齡、性別、伴隨基礎疾病、有無神經(jīng)系統(tǒng)癥狀、術(shù)前頸動脈狹窄率及有無預擴、后擴,心率、血壓有無下降、術(shù)前頸動脈狹窄率、術(shù)后即刻殘余狹窄率、術(shù)后復查頭顱MRI時間差異均無統(tǒng)計學意義(P>0.05,表1)。

術(shù)后DWI(+)組和DWI(-)組在CR、頸動脈斑塊的位置、鈣化斑塊體積大小、鈣化斑塊體積百分比、鈣化斑塊CT值及鈣化斑塊的最大厚度差異均無統(tǒng)計學意義(P>0.05,表2)。術(shù)后支架即刻殘余狹窄率在頸動脈斑塊的位置、鈣化斑塊體積大小、鈣化斑塊體積百分比、CR、鈣化斑塊CT值及鈣化斑塊的最大厚度差異均無統(tǒng)計學意義(P>0.05,表3)。28例患者術(shù)后1年隨訪頸動脈超聲,支架內(nèi)再狹窄率為0。術(shù)后1年隨訪頸部正側(cè)位X線,支架斷裂發(fā)生率為0。

表1　新發(fā)DWI病灶陽性組和新發(fā)DWI病灶陰性組臨床基本資料

表2　新發(fā)DWI病灶與術(shù)前頸動脈CTA測量鈣化斑塊參數(shù)的關(guān)系

表3　術(shù)后即刻殘余狹窄與鈣化斑塊之間的關(guān)系

討　　　論

目前顱外頸動脈狹窄的手術(shù)指征,主要包括動脈狹窄程度和神經(jīng)系統(tǒng)癥狀,即癥狀性頸動脈狹窄超過50%,無癥狀性頸動脈狹窄超過60%[2]。雖然數(shù)字減影血管造影仍是頸動脈狹窄診斷的金標準,但目前臨床篩選顱外頸動脈狹窄高危病變的檢測方法存在不足。從狹窄測量標準來講,血管造影測量采用北美癥狀性頸動脈內(nèi)膜切除術(shù)試驗(NACET)或者歐洲頸動脈手術(shù)試驗(European Carotid Surgery Trial,ECST)標準。但是狹窄程度并不能完全區(qū)分高危和低危病變。研究顯示輕度狹窄也可導致TIA或卒中等神經(jīng)系統(tǒng)事件,當頸動脈狹窄度0～29%時,TIA或卒中發(fā)生率為2.1%/年,當頸動脈狹窄度為30%～75%時,TIA或卒中發(fā)生率為5.7%/年[5]。從頸動脈斑塊成分和性質(zhì)評估來講,血管造影難以鑒別穩(wěn)定性斑塊和不穩(wěn)定性斑塊。頸動脈斑塊性質(zhì)是影響手術(shù)效果的因素之一,易損斑塊往往在CAS中容易發(fā)生破裂脫落,引起新發(fā)DWI病灶,隨著遠端腦保護裝置的應用,CAS后新發(fā)DWI病灶的發(fā)生率逐漸下降[6-7]。Gensicke 等[8]報道,CAS后新發(fā)DWI病灶可能增加未來腦血管事件再次發(fā)生的發(fā)生率。

以往研究顯示,嚴重鈣化狹窄是CAS的危險因素。由于頸動脈支架對頸動脈竇的壓迫,在CAS后可能導致血壓降低、心率下降,進而造成術(shù)后腦灌注不足引發(fā)缺血灶的發(fā)生[9]。在頸部X線可顯示頸動脈斑塊與CAS后的支架斷裂、扭曲密切相關(guān)[10],且Ⅲ級以上鈣化斑塊引起支架斷裂的概率是其他斑塊的4.5倍[11]。嚴重鈣化的頸動脈斑塊導致頸動脈支架的展開效果不佳,導致支架內(nèi)再狹窄的發(fā)生率較高[12]。嚴重鈣化的頸動脈狹窄,影響自膨式支架的擴張,進一步導致支架內(nèi)再狹窄,為了減少支架殘余狹窄率就需要后擴張應用更大的球囊壓力來克服斑塊的擠壓。Obeid 等[13]發(fā)現(xiàn)頸動脈支架后擴張聯(lián)合預擴張比單純預擴張使圍手術(shù)期腦卒中和死亡率增加了2.4倍。但是并非所有頸動脈鈣化病變都是CAS手術(shù)的禁忌證,如何選擇合適患者,如何詳細評估頸動脈鈣化病變,需要進一步詳細的研究。

Katano等[12]研究發(fā)現(xiàn),頸動脈支架殘余狹窄率與鈣化斑塊的鈣化評分有關(guān),認為術(shù)前頸動脈鈣化斑塊評分是術(shù)后支架殘余狹窄的唯一預測因子。Tsutsumi等[14-15]發(fā)現(xiàn)頸動脈殘余狹窄率與鈣化斑塊的體積無關(guān),但是他們發(fā)現(xiàn)斑塊CR超過278°時,支架斷裂的發(fā)生率為94.4%(17/18)。本臨床研究中,支架殘余狹窄率與鈣化斑塊的體積、位置、鈣化斑塊CT值、CR及Agatston鈣化積分均無關(guān)系,術(shù)后1年無支架斷裂發(fā)生。鈣化斑塊穩(wěn)定的因素,可能包括生物力學和炎癥兩方面,Huang等[16]利用血流動力學有限元分析發(fā)現(xiàn),鈣化成分并不像脂質(zhì)成分那樣增加纖維帽的生物力學壓力。Shaalan 等[17]發(fā)現(xiàn)纖維帽的炎性反應與斑塊的比例呈反比,這也解釋了斑塊鈣化成分越多,斑塊越穩(wěn)定的原因。本臨床研究證實,術(shù)后新發(fā)DWI病灶與CR、頸動脈斑塊的位置、鈣化斑塊體積大小、鈣化斑塊體積百分比、鈣化斑塊CT值及鈣化斑塊的最大厚度均無關(guān)系,從而也證明了鈣化成分的穩(wěn)定性。文獻報道[13]后擴張使圍手術(shù)期腦卒中率及死亡率增加,因此本組臨床研究采用充分預擴張并盡量避免支架內(nèi)后擴的原則,結(jié)果顯示預擴張或者后擴張對新發(fā)DWI病灶并無影響,分析原因,考慮本臨床研究入組患者雖為中重度頸動脈鈣化狹窄,但均為非環(huán)狀鈣化,術(shù)中不需要特別大的球囊擴張壓力來克服鈣化斑塊的擠壓,減少了斑塊碎屑脫落的風險。本臨床研究主要不足是病例數(shù)較少,尚待更大樣本量和更長的隨訪時間來驗證結(jié)果。

本組病例術(shù)后出現(xiàn)新發(fā)DWI病灶的患者都未表現(xiàn)神經(jīng)系統(tǒng)癥狀和體征,均通過CAS術(shù)后3天內(nèi)實施的頭顱MRI-DWI序列檢查發(fā)現(xiàn),分析為術(shù)中微栓子脫落所致。術(shù)中微栓子脫落可能發(fā)生在CAS的任何階段,尤其是導絲通過ICA病變及支架釋放時,脫落微栓子最多[18]。盡管術(shù)后新發(fā)腦DWI病灶沒有任何癥狀且可以部分吸收[4],但有研究表明,隱匿性DWI病灶與阿爾茲海默癥[19]、認知功能障礙[20-22]、抑郁[23-26]等有關(guān)。有研究證實這種隱匿性的腦缺血病灶使未來卒中的風險增加2～4倍[27-28]。國際頸動脈支架研究-磁共振研究中CAS術(shù)后新發(fā)腦DWI病灶的發(fā)生率為50%[4],Bijuklic 等[29]研究發(fā)現(xiàn)其發(fā)生率甚至高達87.1%。因此,本臨床研究中CAS后新發(fā)DWI病灶的發(fā)生率為53.6%(15/28),與文獻報道基本一致。

總之,對于非環(huán)狀鈣化的頸動脈狹窄,無論頸動脈斑塊的位置、CR、鈣化斑塊體積大小、鈣化斑塊體積的百分比、鈣化斑塊CT值、Agatston鈣化積分及鈣化斑塊的最大厚度,對CAS術(shù)后新發(fā)DWI病灶和支架殘余狹窄均無影響。因此,對于中重度鈣化頸動脈狹窄,遠端腦保護裝置下的CAS是安全有效的治療方法。

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E-mail:guo.daqiao@zs-hospital.sh.cn

Curative effect analysis of carotid artery stenting in the treatment of carotid angioplasty and stenting with moderate or severe calcification using the distal embolization protected device

ZHANG Lu1, TANG Xiao1, FU Wei-guo1, SHI Zhen-yu1, LYU Peng2, DAI Yuan-yuan2, WANG Yu-qi1, GUO Da-qiao1△

(1Department of Vascular Surgery,Zhongshan Hospital,Fudan University-Institute of Vascular Surgery, Fudan University,Shanghai 20032,China;2Department of Radiology,Zhongshan Hospital, Fudan University,Shanghai 200032,China)

ObjectiveTo evaluate the safety and efficacy of carotid angioplasty and stenting (CAS) in the treatment of carotid artery stenosis with moderate or severe calcification using the distal embolization protected device.MethodsTwenty-eight carotid artery stenosis patients with moderate or severe calcified plaque accepted CAS using the distal embolization protected device.Patients underwent carotid artery CT angiography before CAS,and magnetic resonance imaging of the brain pre-and post-operatively.We evaluated the relationship between calcified plaque and the rate of immediate postoperative residual stenosis as well as the postoperative new diffusion-weighted lesions.ResultsThe immediate technical success rate was 100% in 28 patients.No death or myocardial infarction occurred during the perioperative period.Fifteen cases (53.6%) of new diffusion-weighted lesions (DWI) occurred according to postoperative cranial MRI.The new diffusion-weighted lesions positive group and negative group were compared.While there was no significant difference in the calcified plaque position,volume,calcium radian(CR) and Agatston calcification score,CT calcification value,calcified plaque volume percentage and thickness between the two groups.Within 12 months after CAS,one patient suffered ischemic stroke on the side of CAS and the remaining 27 patients after CAS recovered well without transient ischemic attacks (TIA) or ischemic stroke.After 1 year,the incidence rate of carotid artery restenosis and stent fracture was zero.ConclusionsWith the distal embolization protected device,carotid artery stenting is a safe and effective treatment for carotid artery stenosis with moderate or severe calcified plaque.The location,volume,CT calcium value,the volume percentage and thickness of calcified plaque have no influence on the occurrence rate of the postoperative new diffusion-weighted lesions and restenosis.

carotid artery stenosis;stenting;calcification;new diffusion-weighted lesions;residual stenosis

R654.4

Adoi: 10.3969/j.issn.1672-8467.2016.05.006

2016-01-27;編輯:沈玲)

* This work was supported by the Foundation of Science and Technology Commission of Shanghai Municipality (074119503) and the National Natural Science Foundation of China (81570433).

上海市科委基金(074119503);國家自然科學基金(81570433)