药物洗脱支架置入术后晚期、极晚期支架内血栓形成的光学相干断层成像分析

目的:应用光学相关断层成像(OCT)分析药物洗脱支架置入术后晚期、极晚期支架内血栓形成的可能机制。方法:入选2011-01-2017-12经遵义医学院附属医院行冠状动脉(冠脉)造影明确诊断晚期、极晚期支架内血栓形成患者8例。8例患者在PCI术中均行OCT检查。回顾性分析8例患者的临床资料、PCI过程及OCT图像特征。结果:7例伴有多个心血管危险因素,2例合并轻度左心功能不全。首次支架置入至发生支架血栓的平均时间(818±651) d;双联抗血小板服用平均时间(312.8±76.3) d;低密度脂蛋白胆固醇(LDL-C)平均水平为(3.44±1.35) mmol/L,均未达到目标值;1例在术后停用双联抗血小板3个月、2例在服用双联抗血小板期间、5例在单用阿司匹林期间发生支架内血栓;6例置入依维莫司药物支架,1例行支架内非顺应性高压球囊扩张,1例行紫杉醇药物球囊治疗。OCT图像特征:7例患者支架内异质性新生内膜形成,5例为支架内新生动脉粥样硬化伴斑块破裂,2例为支架内新生动脉粥样硬化伴斑块侵蚀;1例出现严重支架贴壁不良,贴壁不良比例达66.2%;6例患者出现不同程度的支架小梁无内膜覆盖,平均为(10.4±6.2)%;5例支架内见红血栓,3例支架内见白血栓。结论:晚期、极晚期支架内血栓患者首次及再次住院多表现为急性冠脉综合征与高LDL-C水平。支架内新生动脉粥样硬化、支架贴壁不良是导致晚期、极晚期支架内血栓形成的主要原因之一。OCT的应用有助于明确晚期和极晚期支架内血栓形成的机制。     

药物洗脱支架是否会显著增加晚期支架血栓形成

药物洗脱支架(DES)较裸金属支架(BMS)明显降低了靶血管的再狭窄率和再次血运重建。因此,DES的应用被认为是继单纯球囊扩张术和BMS置入术后,冠心病介入治疗发展史上的第3个里程碑。然而,随着DES的广泛使用,晚期支架内血栓形成问题逐渐显现出来,成为人们关注的焦点。1晚期支架内血栓形成的机制研究发现与晚期支架血栓形成的发生明确相关的因素有:①DES内的化疗药物在抑制血管平滑肌细胞增殖的同时也抑制了支架内皮化;②第1代DES的聚合物不可降解,血管壁对持续存在的聚合物过敏产生局部的慢性炎症反应;③支架贴壁不良,即支架与血管壁…     

结合OCT分析DES术后晚期或晚晚期支架内血栓形成的危险因素

目的:结合光学相干断层成像技术(OCT)分析药物洗脱支架(DES)术后支架内晚期或晚晚期血栓发生的危险因素。方法:回顾性分析曾在本院或外院行药物支架术,经冠状动脉(冠脉)造影和(或)OCT确诊的发生晚期或晚晚期支架内血栓的19例患者。按年龄、性别(2∶1)匹配原则抽取曾行药物支架术,冠脉造影证实未发生支架内血栓患者38例作为对照组。对晚期或晚晚期支架内血栓的主要危险因素、冠脉造影和OCT分析。采用条件Logistic回归分析晚期或晚晚期支架内血栓形成的独立危险因素。结果:支架内血栓组糖尿病史、既往心肌梗死病史、空腹血糖、左室射血分数(LVEF)与对照组差异有统计学意义(均P0.01)。定量冠脉造影分析及OCT检查结果显示:支架内血栓组患者置入支架数目、支架长度、支架贴壁不良率、支架内皮未被覆盖率均显著高于对照组(P0.05)。条件Logistic回归分析显示:既往心肌梗死病史(OR:7.642,95%CI:1.412~41.152,P0.01)、支架长度(OR:13.285,95%CI:3.198~55.189,P0.01)、支架数量(OR:1.645,95%CI:1.106~2.447,P=0.014)、支架贴壁不良率(OR:5.132,95%CI:4.800~5.464,P=0.001)、未被覆盖支架柱比例(OR:12.549,95%CI:3.657~43.067,P0.01)、糖尿病(OR:7.256,95%CI:1.721~30.591,P0.01)为DES术后晚期或晚晚期血栓的危险因素。正常的LVEF(OR:0.714,95%CI:0.574~0.887,P=0.002)为其保护因素。结论:长支架、多支架置入、支架贴壁不良和支架内皮化不全、心肌梗死病史是晚期或晚晚期血栓的独立危险因素,正常的LVEF是其保护因素。     

光学相干断层成像评价药物洗脱支架置入术后晚期支架贴壁不良

目的 探讨药物洗脱支架(DES)置入术后晚期支架贴壁不良的特点.方法 分析32例(包括51支血管、共置入71个支架)置入DES 1年后[(14.8±5.2)个月]行光学相干断层成像(OCT)检查的患者资料,对支架节段的OCT图像每间隔0.5 mm取1帧图像进行分析,找出贴壁不良的支架金属结构,测量支架到参照血管内壁的距离及支架表面内膜厚度,分析晚期支架贴壁不良的特点.结果 OCT检查在7例(21.9%)患者中检出支架贴壁不良,其中4例合并支架段血管的正性重构,1例重叠置入支架,2例发现由血栓覆盖支架金属结构,7例患者随访期间无心脏不良事件发生.97.6%的支架金属结构完全贴壁并不同程度的内膜覆盖,2.4%的支架金属结构贴壁不良,包括1.2%的支架金属结构位于血管分支开口.位于血管分支开口的支架金属结构与其他贴壁不良支架表面的内膜覆盖厚度差异无统计学意义[(0.06±0.05)mm比(0.05±0.03)mm,P>0.05].绪论晚期支架贴壁不良见于DES置入最初的贴壁不良、血管壁正性重构、重叠置入支架以及支架金属结构位于分支血管开口;贴壁不良的支架金属结构表面亦有不同程度的内膜覆盖.     

药物洗脱支架与晚期、极晚期支架血栓

第一代药物洗脱支架在显著降低再狭窄率的同时,也带来了支架血栓尤其是晚期、极晚期支架血栓这一棘手问题.晚期、极晚期支架血栓虽然发生率较低,但一旦发生往往带来灾难性后果.晚期、极晚期支架血栓的发生机制包括血管再内皮化延迟、多聚物过敏反应、支架晚期贴壁不良及新生动脉粥样硬化斑块破裂等.第二代和第三代药物洗脱支架在安全性上可能优于第一代.生物全降解支架代表了药物洗脱支架的发展方向,有望从根本上解决药物洗脱支架的晚期和极晚期支架血栓问题.现对近年来药物洗脱支架晚期及极晚期支架血栓的发生机制及新一代药物洗脱支架的研究进展做一综述.     

药物洗脱支架术后靶病变部位再发急性ST段抬高型心肌梗死的光学相干断层成像评价

目的应用光学相干断层成像(OCT)评价冠脉药物洗脱支架术后靶病变部位再发急性ST段抬高型心肌梗死(STEMI)患者的影像特征。方法回顾性分析行药物涂层支架(DES)植入,冠脉造影(CAG)证实靶病变部位再发STEMI的15例患者。应用OCT评价罪犯血管靶病变部位影像特点。结果 15例DES术后再发STEMI患者中,罪犯血管前降支(LAD)9例,右冠脉(RCA)4例,回旋支(LCX)2例。靶病变部位影像特征:CAG均表现为支架内血栓形成,4例急性血栓形成,3例亚急性血栓形成,5例晚期血栓形成,3例极晚期血栓形成。OCT表现为3例支架边缘夹层;5例支架贴壁不良(其中2例正性血管重构继发获得性贴壁不良);2例病变覆盖不全;2例支架内新生粥样硬化斑块(NAP)形成伴破裂;2例支架内皮化不全;1例表现仅为血栓形成。结论支架边缘夹层、贴壁不良、覆盖不全以及支架内NAP破裂均可导致支架术后靶病变部位再发STEMI,OCT对该类患者治疗有指导意义。     

采用光学相干断层成像评价无再狭窄药物洗脱支架内膜增生

目的应用冠状动脉血管内光学相干断层成像技术(optical coherence tomography,OCT)评价造影随访无再狭窄的药物洗脱支架(drug eluting stent,DES)内皮增生情况。方法从北京安贞医院2007年9月至2008年9月连续入选DES术后无症状而接受冠状动脉造影复查无明显再狭窄的患者18例,所有患者接受OCT检查,比较不同的DES植入时间、不同DES组之间,每组支架小梁血管内膜增生情况。结果共分析4709个支架小梁,其中被内皮完全覆盖的支架小梁个数4173个(88.6%),被内皮部分覆盖的个数是33个(0.7%),暴露的小梁个数382个(8.1%);贴壁不良的小梁个数121个(2.6%),覆盖支架小梁的内膜的平均厚度是0.099mm,内膜厚度100μm的小梁个数2378个(50.5%);不同药物洗脱支架之间内膜增生厚度、支架小梁内膜覆盖及晚期支架贴壁不良差异有统计学意义;与DES植入时间12个月相比,植入时间12个月血管内膜增生厚度有明显增加趋势(0.1183mm比0.0875mm;P=0.001);支架内膜无覆盖比率分别是:1.7%比6.8%(P0.05);贴壁不良比率是:2.1%比0.5%(P0.001)。结论通过OCT分析16个月左右的药物洗脱支架血管内膜厚度,总的来说90.1%的支架小梁有内膜覆盖,但是仍然有高达9.9%的无内膜覆盖,支架类型、支架置入时间之间内膜覆盖、支架贴壁有一定差异;同时支架植入大于12个月的支架贴壁不良比率高于不足12个月的,提示更晚期的支架贴壁不良情况存在,对于药物洗脱支架的随访时间应该更长,双联抗血小板治疗疗程也许应该更长。     

药物促进冠脉支架置入术后血管再内皮化

经皮冠状动脉球囊扩张和支架置入术是目前治疗冠心病的重要手段。早期的冠脉支架为金属裸支架（BMS）,由于BMS置入术后冠状动脉的再狭窄率较高,药物涂层支架（DES）应运而生。DES通过抑制血管内膜的增生降低支架置入术后再狭窄,但同时也带来了内皮延迟愈合,内皮化延迟是支架内晚期血栓发生的基础,晚期血栓常可带来非常严重的后果。目前已知很多药物可促进血管再内皮化,预防晚期血栓的发生。本文将重点就晚期血栓发生的机制、常见促进再内皮化的药物如粒细胞集落刺激因子、过氧化物酶体增殖物激活受体激动剂、促红细胞生成素、雌激素、他汀的机制及研究现状进行综述。     

支架内血栓形成病例的临床特点分析

目的:分析支架内血栓形成病例的临床特点并探讨其原因.方法:收集自2007-04至2008-06的所有支架内血栓的患者,共12例.其中男性10例,女性2例.1例置入金属裸支架,其余11例均为药物涂层支架.分析入选病例的临床特点,冠状动脉病变特征.结果:12例患者中,亚急性血栓5例;晚期血栓4例;极晚期血栓3例.分析病变特点及血栓形成原因显示:在早期血栓形成的5例中4例为原发性支架贴壁不良、支架膨胀不良、未完全覆盖病变;1例为糖尿病、长病变、完全闭塞病变.在晚期和极晚期血栓形成的7例病例中3例因为停用了波立维;2例有支架内严重再狭窄;1例为正性重构、获得性贴壁不良;1例为糖尿病、小血管病变,且支架中段扩张不充分不除外贴壁不良的因素.结论:支架内血栓是金属裸支架和药物涂层支架置入术后很少发生但非常严重的并发症.急性的支架内血栓可能与贴壁不良有关.晚期支架内血栓在病因学上是多因素的,主要与双联抗血小板药物治疗依从性相关.     

PCI术后冠状动脉支架内血栓形成原因分析及对策

目的探讨冠状动脉介入术后支架内血栓形成的相关原因及对策,进一步提高其诊治水平。方法回顾性分析13例支架内血栓形成患者的临床及冠状动脉造影特点及处理措施。结果支架贴壁、膨胀不良、未完全覆盖病变,分叉病变,停服阿斯匹林、氯吡格雷和（或）药物抵抗等为支架内血栓形成的主要原因。结论急性和亚急性支架内血栓形成可能与技术因素有关支架贴壁不良等;晚期和极晚期支架内血栓可能与支架再狭窄、双联抗血小板药物治疗不当有关。强化抗血小板治疗、血栓抽吸导管负压抽吸,反复球囊扩张或重新置入支架是支架内血栓形成的主要治疗方法。     

Stent thrombosis of drug eluting stent: pathological perspective

Although, the first-generation drug eluting stents (DES) have significantly reduced rates of restenosis compared to bare metal stents (BMS), an increased risk of late stent thrombosis (LST) has emerged as a major concern. Pathologic studies of patients dying from late DES thrombosis demonstrates delayed arterial healing characterized by persistent fibrin deposition and poor endothelialization as the primary substrate. However, recent thorough investigations revealed additional mechanisms of stent thrombosis such as hypersensitivity reaction, excessive fibrin deposit with malapposition, or neoatherosclerosis, which are associated with device-specific components and the majority of very late stent thrombosis is likely associated with these abnormal vascular responses. Therefore, although the incidence of stent thrombosis following DES implantation is similar in each period, the underlying mechanisms of this complication may vary. In the current review, the mechanisms of stent thrombosis in the DES era will be discussed using the data from autopsy studies that have been published.     

Incomplete arterial healing 8 years after the implantation of sirolimus‐eluting stent. In vivo visualization by optical coherence tomography

The time course of complete arterial healing after drug eluting stent implantation is unknown. We present a case of incomplete endothelialization and late stent malapposition identified by optical coherence tomography 8 years after a sirolimus‐eluting stent implantation, which was not related with any adverse clinical event. © 2011 Wiley Periodicals, Inc.     

西罗莫司洗脱支架术后极晚期血栓形成四例分析

目的回顾性分析西罗莫司洗脱支架术后发生极晚期支架内血栓形成患者的临床资料。方法2002年10月至2005年8月,共612例患者置入835枚西罗莫司洗脱支架,其中4例患者（0．65％）于2006年1至8月发生极晚期支架内血栓形成,导致急性前壁ST段抬高的心肌梗死再次入院。回顾性分析该4例患者的临床情况、抗血小板药物应用情况、造影结果以及PCI过程等相关资料。结果4例患者均为男性,年龄40～69岁,血栓发生时间为术后31～37个月。患者第一次支架术后服用氯吡格雷7～12个月,其中1例患者血栓发生前18个月停用阿司匹林。支架置入部位均为前降支,急诊造影提示支架内闭塞,局部可见明显血栓征象,前向血流TIMI0级,均再次行PCI治疗后存活。结论药物洗脱支架术后可以发生极晚期血栓形成,药物洗脱支架术后的远期随访问题值得重视。     

Late acquired stent malapposition detected by optical coherence tomography examination

Late stent malapposition may play a role in stent thrombosis, but the results of several intravascular ultrasound and few optical coherence tomography (OCT) studies are still controversial. We present a case of late acquired stent malapposition after drug eluting stent implantation, identified by follow-up OCT examination at 12 months, which was not related with any adverse clinical event.     

Very Late Stent Thrombosis 11 Years after Implantation of a Drug-Eluting Stent

Very late stent thrombosis is an infrequent yet potentially fatal complication associated with drug-eluting stents. We report the case of an 88-year-old man who sustained an ST-segment-elevation myocardial infarction 11 years after initial sirolimus-eluting stent implantation. Optical coherence tomograms of the lesion showed that the focal incomplete endothelialization of the stent struts was the likely cause; neointimal formation, neoatherosclerosis, and late stent malapposition might also have contributed.To our knowledge, this is the longest reported intervening period between stent insertion and the development of an acute coronary event secondary to very late stent thrombosis. The associated prognostic and therapeutic implications are considerable, because they illuminate the uncertainties surrounding the optimal duration of antiplatelet therapy in patients who have drug-eluting stents. Clinicians face challenges in treating these patients, particularly when competing medical demands necessitate the discontinuation of antiplatelet therapy. In addition to the patient''s case, we discuss factors that can contribute to very late stent thrombosis.     

Erosion/malapposition of a sirolimus eluting stent – Optical coherence tomography image – A case report

The presence of erosion/malapposition of a Sirolimus eluting stent was clearly visualized using Optical Coherence Tomography (OCT) imaging. The presence of erosion/malapposition and the absence of neointimal hyperplasia after 10 months of sirolimus eluting stent could constitute a potential thrombogenic substrate for late stent thrombosis.     

急性冠脉综合征患者药物洗脱支架雷帕霉素CypherTM植入后的不良反应分析

目的:分析雷帕霉素药物洗脱支架CypherTM植入后对急性冠脉综合征患者近、远期的不良反应.方法: 选择接受CypherTM治疗的冠心病患者83例,在支架植入术后9个月内全部接受门诊随访及冠脉造影,了解支架内急性和亚急性血栓、边缘效应、贴壁不良现象、支架处动脉瘤发生率及相应的不良心脏事件(MACE)发生情况.结果:83例患者共植入支架112个,植入成功率为98.8%(82/83).29例(34.9%)接受冠脉造影,MACE9例,发生率10.8%(9/83),其中,1例术中发生猝死,1例术后3d因亚急性血栓造成再发心肌梗死,其余7例在出院后1～3 月内发生心绞痛,皆经造影证实为血栓形成,再次成功靶血管血运重建8例;其余20例无症状患者造影发现支架边缘狭窄(无血栓)2例,总再狭窄为13.3%(11/83);无动脉瘤发生.9例MACE中,有弥漫病变5例,其中4例植入长支架,1例植入重叠支架,其余为简单病变;29例患者共发现贴壁不良现象5例,皆发生MACE,其中4例为弥漫病变植入长支架,1例为简单病变.结论:急性或亚急性血栓形成是药物支架CypheTM植入后出现的主要不良反应,可能与弥漫病变植入长、重叠支架引起贴壁不良有关.     

Very late thrombosis after drug-eluting stents.

Stent thrombosis is a rare but potentially fatal complication of percutaneous treatment of coronary disease. Its occurrence after drug eluting stent (DES) placement has raised concerns, especially when it occurs late after the stent implantation. The mechanisms of late thrombosis after DES have yet to be completely understood. By means of serial angiography and intravascular (IVUS) images we described a relatively new and unusual vessel response to drug-eluting stents (e.g. huge positive remodeling in all vessel extension), leading to impressive late-acquired incomplete stent apposition and finally causing stent thrombosis and acute myocardial infarction. After describing the two cases, one after Cypher stent implantation and one after Taxus stent implantation, we briefly reviewed the literature available on stent thrombosis with special emphasis on its late occurrence.     

Neo-atherosclerosis in very late stent thrombosis of drug eluting stent

Background

Recent studies have described neo-atherosclerosis, developing inside the stent, as cause of very late stent thrombosis.

Case report

A 59-year-old man, with family history of coronary artery disease, presented to our Department because of anterior ST-segment elevation myocardial infarction. Two years before he had underwent percutaneous coronary intervention with multiple drug-eluting stents (DES) implantation on proximal-mid left anterior descending artery (LAD), and mid-right coronary artery (RCA), respectively. The angiogram revealed stent thrombosis with total occlusion of proximal LAD. Multiple passages with manual thrombus-aspiration catheter were successfully performed with improvement in TIMI flow. Optical Coherence Tomography (OCT) imaging revealed fully expanded stents without areas of inappropriate apposition to vessel wall; and mild to moderate intimal hyperplasia throughout the stented segment, with full covered stent struts; areas of ulcerated and ruptured plaque within the proximal struts of stented segment was depicted with intraluminal protruding material. Thus, an additional bare metal stent (BMS) was deployed inside and overlapping the previous in order to seal this plaque. OCT post procedure revealed optimal stent expansion and apposition, without residual protruding material. At 9-month follow-up patient was alive and free from symptoms. Coronary angiogram revealed patency of implanted stents without significant restenosis.

Conclusions

Neo-atherosclerosis with thrombosis on top of ruptured necrotic plaque core may play a role in the pathophysiology of very late stent thrombosis in both BMS and DES. Our report highlights the role OCT to assess the mechanism of VLST.