冠脉支架内再狭窄发生机制及防治研究进展

冠心病介入治疗已经成为冠心痛的重要治疗方法.但是支架内再狭窄是冠心病介入医师不得不面对的一个问题.近年来随着关于ISR发生的病理生理学基础研究细胞信号转导等基础研究的深入,有关各种针对其发生机制的相关防治方法不断发展.各种涂层支架、冠脉内放射治疗、基因治疗以及口服药物治疗为解决ISR提供了各种方法.本文就冠脉支架术后支架内再狭窄的发生机制及诊治进展进行了综述.     

下肢动脉硬化闭塞症血管成形术的疗效观察

目的:探讨血管成形术治疗下肢动脉硬化闭塞症的临床应用价值。方法:对我院78例下肢动脉硬化闭塞患者的临床资料进行回顾性分析。78例患者(98条血管)术前经CTA诊断后,行腔内血管成形术(PTA)和血管支架植入术治疗,治疗后随访1~18个月,分析踝/肱指数(ABI)、血管内径、皮温及足背动脉搏动的变化。结果:成功完成77例(98.7%)患者、97条(99.0%)患肢的PTA和支架植入术,除1例下肢动脉完全闭塞患者导丝未能成功通过病变导致介入失败外,其余病例经介入治疗后均开通,术中所有病例均未发生血肿、血管壁破裂、穿孔或内支架移位,远端血管血栓栓塞等并发症。术后,患者下肢缺血症状消失或明显减轻,踝/肱指数(ABI)由术前(0.39±0.23)恢复至(0.86±0.26),下肢血管内径及足背动脉搏动均明显改善。结论:PTA和血管支架植入术是一种治疗下肢动脉硬化闭塞症安全有效的方法,成功率高,并发症少,再狭窄率低。     

外周动脉疾病治疗进展

外周动脉疾病(PAD)与心血管疾病(CV)的发病率和死亡率有着密切的联系。ACCF/AHA指南建议无症状和症状性PAD患者戒烟并应用抗血小板/抗凝药物。对于存在严重肢体缺血(CLI)的PAD患者应考虑接受腔内与开放保肢手术治疗。即便存在CLI的PAD患者接受如上治疗,有时仍无法为患肢提供足够的血流灌注以消除症状。为建立有效血供,许多研究已经深入细胞治疗层面。内皮干细胞、单核细胞和骨髓间充质干细胞在临床应用中得到了很好的研究。血管内皮生长因子、成纤维细胞生长因子和肝细胞生长因子(HGF)也被应用于PAD患者,以诱导血管生成。其中,HGF最有优势,因为它可诱导血管生成却不伴有反应性血管炎及血管通透性增高。同时,血管腔内治疗器械及技术,如药物涂层球囊等也获得较快发展。本文将PAD治疗进展综述如下。     

药物洗脱支架植入后再狭窄的研究进展

随着药物洗脱支架(Drug Eluting Stent,DES)的出现,再狭窄的问题得到进一步的有效控制.然而,药物洗脱支架也存在较低的再狭窄率,由于应用药物洗脱支架治疗人数非常多,这一比率就不容忽视.本文将阐述DES支架内再狭窄发生的病理生理学机制、临床表现、形态学特征以及处理策略.     

DES早期支架内血栓的形成和防治

目前,冠状动脉内支架植入术是冠心病血运重建的主要方法,支架置入可显著减少再狭窄和靶血管血运重建.虽然支架术后支架内血栓形成少见,但预后差,临床上可表现为急性心肌梗死或猝死.是药物洗脱支架的潜在危险,预防支架内血栓形成是冠状动脉粥样硬化性心脏病介入领域的研究热点和难点,因此,支架内血栓的形成、防治问题仍然值得我们关注与探讨.本文阐明了早期支架内血栓的影响因素,预防,观察方法及治疗措施.使用新一代的药物洗脱支架有望减少支架内血栓的发生.     

冠状动脉弥漫性长病变治疗的研究进展

冠心病目前已经成为全球性关注的健康问题,为当今人类一大灾难性疾病。既往研究表明,冠状动脉弥漫性长病变占冠心病总患者约20%,冠状动脉弥漫性长病变患者其动脉粥样硬化的病变范围更加广泛,病变呈弥漫性,而且更多累及左主干,常常伴有血管直径小,血管成角、钙化、扭曲等特点,而且多发生于高龄、糖尿病患者中,以上特点又决定了冠状动脉弥漫性长病变成为冠心病治疗的又一难题。因此,有效的预防与治疗冠状动脉弥漫性长病变,已成为目前的关注重点与热点,本文概述了冠状动脉弥漫性长病变临床治疗中的常用方法以及各方法的疗效与优劣之势,多年临床实践经验表明PCI治疗仍占有主导位置,虽然目前冠状动脉弥漫性长病变的介入治疗应用药物洗脱支架的已经取得良好的临床效果,在很大程度降低了心血管事件发生率和再次血管重建率,但药物洗脱支架支架治疗冠状动脉弥漫性长病变的远期疗效仍在评估中。     

血管成形术介入治疗糖尿病下肢血管病变的临床效果分析

目的:探讨经皮腔内血管成形术(PTA)联合支架植入术治疗糖尿病下肢血管病变的临床效果及安全性。方法:选择2008年3月至2011年12月在我院内分泌科接受治疗的2型糖尿病合并糖尿病足的患者36例,将其随机分为观察组(19例)和对照组(17例)。观察组19例患者中,14例行PTA术,4例行PTA+腔内支架植入术,1例行截肢术;对照组17例患者,全部采用传统方法进行治疗。观察和比较两组患者术后的糖尿病下肢血管病变的特点、临床效果及并发症的发生情况。结果:观察组19例患者,共40条靶血管,实施PTA手术的成功率为87.5%。采用两种治疗方法 2周或4周后,患者的临床症状和体征均得到一定程度的缓解,且均未观察到明显的不良反应。与对照组相比,接受介入治疗的患者,其临床症状的缓解率明显升高,其中在2周时介入治疗对麻木和紫绀症状的缓解尤其显著,和对照组之间有统计学差异(P0.05)。结论:血管成形术介入治疗糖尿病下肢血管病变是一种安全可靠的方法,治疗效果好,安全性高,值得临床推广。     

药物洗脱支架治疗急性心肌梗死患者临床随访观察

目的:探讨药物洗脱支架在急性心肌梗死(AMI)入住我院CCU后行急诊经皮冠状动脉介入治疗(PCI)的安全性和有效性.方法:选择2007年1月至2007年12月因急性心肌梗死入住我院CCU的220例急性心肌梗死患者,其中于发病12小时内行急诊手术治疗的患者200例,急诊手术仅处理梗死相关血管的靶病变,均植入药物洗脱支架,评价手术成功率、并发症、随访期间心脏不良事件发生率、再狭窄率等.结果:200例患者急诊手术治疗均获得成功,植入支架数量为1.41±0.711枚,未发生与介入治疗有关的严重并发症,住院期间发生心源性死亡2例,非心源性死亡1例,无院内支架内血栓形成、再次心梗,临床随防7.3±1.9(5-15)个月,136例患者复查了冠状动脉造影,造影随访率72.3%,随访终点内死亡5例(死亡率2.66%),含心源性死亡3例,非心源性死亡2例,其中再发心肌梗死1例,6例患者进行了再次靶血管血运重建(3.19%).结论:药物洗脱支架在急性心肌梗死患者行急诊PCI治疗中安全可行,且院内、术后7个月随访观察显示疗效显著,并明显降低靶血管再狭窄率.     

冠心病患者经皮冠状动脉介入治疗术后支架内再狭窄的相关危险因素分析

目的:探究冠心病(CHD)患者经皮冠状动脉介入治疗(PCI)术后支架内再狭窄(ISR)的相关危险因素。方法:选取2014年6月～2017年6月期间我院收治的行PCI的CHD患者200例为研究对象,术后随访一年再行冠脉造影检测,根据患者是否发生ISR分为观察组(38例,发生ISR)和对照组(162例,未发生ISR),收集并比较两组患者基线资料及生化指标,采用多因素logistic回归分析CHD患者PCI术后发生ISR的危险因素。结果:观察组吸烟、饮酒、高血压、糖尿病的人数占比、病程及支架直径均高于对照组,差异有统计学意义(P0.05)。观察组脂蛋白(a)[LP(a)]、纤维蛋白原(FIB)及尿酸(UA)水平显著高于对照组,总胆红素(TBIL)水平显著低于对照组,差异有统计学意义(P0.05)。多因素logistic回归分析显示,吸烟、糖尿病、支架直径(小)以及高水平LP(a)、低水平UA为CHD患者行PCI术后发生ISR的危险因素。结论:CHD患者行PCI术后发生ISR的危险因素有吸烟、糖尿病、支架直径以及高水平LP(a)、低水平UA,因此在PCI术中应尽可能选用较大的支架,同时戒烟、控制血糖有利于预防ISR的发生,定期检测血清LP(a)、UA水平变化,并采取有效的医疗与保健措施能够减少ISR的发生风险。     

新型可降解涂层冠脉药物洗脱支架荣获国家技术发明二等奖

由中科院院士、复旦大学附属中山医院心内科主任葛均波教授自主研制的"新型可降解涂层冠脉药物洗脱支架",荣获国家技术发明二等奖。应用新型涂层材料——聚乳酸类材料,作为药物载体确保药物支架逐步稳定释放。应用"非对称性涂层技术",仅在支架与血管壁接触的侧面涂上药物载体。这样既克服了传     

Modeling the transport of drugs eluted from stents: physical phenomena driving drug distribution in the arterial wall

Despite recent data that suggest that the overall performance of drug-eluting stents (DES) is superior to that of bare-metal stents, the long-term safety and efficacy of DES remain controversial. The risk of late stent thrombosis associated with the use of DES has also motivated the development of a new and promising treatment option in recent years, namely drug-coated balloons (DCB). Contrary to DES where the drug of choice is typically sirolimus and its derivatives, DCB use paclitaxel since the use of sirolimus does not appear to lead to satisfactory results. Since both sirolimus and paclitaxel are highly lipophilic drugs with similar transport properties, the reason for the success of paclitaxel but not sirolimus in DCB remains unclear. Computational models of the transport of drugs eluted from DES or DCB within the arterial wall promise to enhance our understanding of the performance of these devices. The present study develops a computational model of the transport of the two drugs paclitaxel and sirolimus eluted from DES in the arterial wall. The model takes into account the multilayered structure of the arterial wall and incorporates a reversible binding model to describe drug interactions with the constituents of the arterial wall. The present results demonstrate that the transport of paclitaxel in the arterial wall is dominated by convection while the transport of sirolimus is dominated by the binding process. These marked differences suggest that drug release kinetics of DES should be tailored to the type of drug used.     

A Thermal Analogy for Modelling Drug Elution from Cardiovascular Stents

Restriction of blood flow by the narrowing or occlusion of arteries is one of the most common presentations of cardiovascular disease. One treatment involves the introduction of a metal scaffold, or stent, designed to prevent recoil and to provide structural stability to the vessel. On the occasions that this treatment is ineffective, failure is usually associated with re-invasion of tissue. This can be prevented by local delivery of drugs which inhibit tissue growth. The drug might be delivered locally in a polymer coating on the stent. This paper develops and explores the use of a thermal analogue of the drug delivery process and the associated three-dimensional convection–diffusion equation to model the spatial and temporal distribution of drug concentration within the vessel wall. This allows the routine use of commercial finite element analysis software to investigate the dynamics of drug distribution, assist in the understanding of the treatment process and develop improved delivery systems. Two applications illustrate how the model might be used to investigate the effects of controllable or measurable parameters on the progression of the process. It is demonstrated that the geometric characteristics of the stent can have significant impact on the homogeneity of the dosing in the vessel wall.     

Current perspectives of biodegradable drug-eluting stents for improved safety

The introduction of the drug-eluting stent (DES) proved to be an important step forward in reducing the rates of restenosis and target lesion revascularization after percutaneous coronary intervention (PCI). However, the rapid implementation of DES in standard practice and the expansion of the indications for PCI to high-risk patients and complex lesions also introduced a new problem. DES in-stent restenosis (ISR) occurs in 3 ?? 20% of patients, depending on the patient, lesion characteristics and the DES type. The initial commercially available DES used a stainless steel platform coated with a permanent polymer to provide a controlled release of an anti-restenotic drug. The platform, polymer and drug are all targets for improvement. More advanced metallic and fully biodegradable stent platforms are currently under investigation. The permanent polymer coating, a likely contributor to adverse events, is being superseded by biocompatible and bioabsorbable alternatives. New drugs and drug combinations are also a research goal, as interventional cardiologists and the industry strive towards a safer anti-restenotic DES. This paper reviews the benefits, risks, and current status of biodegradable drug-eluting stents.     

A thermal analogy for modelling drug elution from cardiovascular stents

Restriction of blood flow by the narrowing or occlusion of arteries is one of the most common presentations of cardiovascular disease. One treatment involves the introduction of a metal scaffold, or stent, designed to prevent recoil and to provide structural stability to the vessel. On the occasions that this treatment is ineffective, failure is usually associated with re-invasion of tissue. This can be prevented by local delivery of drugs which inhibit tissue growth. The drug might be delivered locally in a polymer coating on the stent. This paper develops and explores the use of a thermal analogue of the drug delivery process and the associated three-dimensional convection-diffusion equation to model the spatial and temporal distribution of drug concentration within the vessel wall. This allows the routine use of commercial finite element analysis software to investigate the dynamics of drug distribution, assist in the understanding of the treatment process and develop improved delivery systems. Two applications illustrate how the model might be used to investigate the effects of controllable or measurable parameters on the progression of the process. It is demonstrated that the geometric characteristics of the stent can have significant impact on the homogeneity of the dosing in the vessel wall.     

Correlating Coating Characteristics with the Performance of Drug-Coated Balloons – A Comparative In Vitro Investigation of Own Established Hydrogel- and Ionic Liquid-Based Coating Matrices

Drug-coated balloons (DCB), which have emerged as a therapeutic alternative to drug-eluting stents in percutaneous cardiovascular intervention, are well described with regard to clinical efficacy and safety within a number of clinical studies. In vitro studies elucidating the correlation between coating additive and DCB performance are however rare but considered important for the understanding of DCB requirements and the improvement of established DCB. In this regard, we examined three different DCB-systems, which were developed in former studies based on the ionic liquid cetylpyridinium salicylate, the body-own hydrogel hyaluronic acid and the pharmaceutically well-established hydrogel polyvinylpyrrolidone, considering coating morphology, coating thickness, drug-loss, drug-transfer to the vessel wall, residual drug-concentration on the balloon surface and entire drug-load during simulated use in an in vitro vessel model. Moreover, we investigated particle release of the different DCB during simulated use and determined the influence of the three coatings on the mechanical behavior of the balloon catheter. We could show that coating characteristics can be indeed correlated with the performance of DCB. For instance, paclitaxel incorporation in the matrix can reduce the drug wash-off and benefit a high drug transfer. Additionally, a thin coating with a smooth surface and high but delayed solubility can reduce drug wash-off and decrease particle burden. As a result, we suggest that it is very important to characterize DCB in terms of mentioned properties in vitro in addition to their clinical efficacy in order to better understand their function and provide more data for the clinicians to improve the tool of DCB in coronary angioplasty.     

Numerical modelling of mass transport in an arterial wall with anisotropic transport properties

Coronary artery disease results in blockages or narrowing of the artery lumen. Drug eluting stents (DES) were developed to replace bare metal stents in an effort to combat re-blocking of the diseased artery following treatment. The numerical models developed within this study focus on representing the changing trends of drug delivery from an idealised DES in an arterial wall with an anisotropic ultra-structure. To reduce the computational burden of solving coupled physics problems, a model reduction strategy was adopted. Particular focus has been placed upon adequately modelling the influence of strut compression as there is a paucity of numerical studies that account for changes in transport properties in compressed regions of the arterial wall due to stent deployment. This study developed an idealised numerical modelling framework to account for the changes in the directionally dependent porosity and tortuosities of the arterial wall as a result of radial strut compression. The results show that depending on the degree of strut compression, trends in therapeutic drug delivery within the arterial wall can be either increased or decreased. The study highlights the importance of incorporating compression into numerical models to better represent transport within the arterial wall and suggests an appropriate numerical modelling framework that could be utilised in more realistic patient specific arterial geometries.     

Improving smooth muscle cell exposure to drugs from drug-eluting stents at early time points: a variable compression approach

The emergence of drug-eluting stents (DES) as a viable replacement for bare metal stenting has led to a significant decrease in the incidence of clinical restenosis. This is due to the transport of anti-restenotic drugs from within the polymer coating of a DES into the artery wall which arrests the cell cycle before restenosis can occur. The efficacy of DES is still under close scrutiny in the medical field as many issues regarding the effectiveness of DES drug transport in vivo still exist. One such issue, that has received less attention, is the limiting effect that stent strut compression has on the transport of drug species in the artery wall. Once the artery wall is compressed, the stents ability to transfer drug species into the arterial wall can be reduced. This leads to a reduction in the spatial therapeutic transfer of drug species to binding sites within the arterial wall. This paper investigates the concept of idealised variable compression as a means of demonstrating how such a stent design approach could improve the spatial delivery of drug species in the arterial wall. The study focused on assessing how the trends in concentration levels changed as a result of artery wall compression. Five idealised stent designs were created with a combination of thick struts that provide the necessary compression to restore luminal patency and thin uncompressive struts that improve the transport of drugs therein. By conducting numerical simulations of diffusive mass transport, this study found that the use of uncompressive struts results in a more uniform spatial distribution of drug species in the arterial wall.     

Stent expansion in curved vessel and their interactions: a finite element analysis

Coronary restenosis after angioplasty has been reduced by stenting procedure, but in-stent restenosis (ISR) has not been eliminated yet, especially in tortuous vessels. In this paper, we proposed a finite element method (FEM) to study the expansion of a stent in a curved vessel (the CV model) and their interactions. A model of the same stent in a straight vessel (the SV model) was also studied and mechanical parameters of both models were researched and compared, including final lumen area, tissue prolapse between stent struts and stress distribution. Results show that in the CV model, the vessel was straightened by stenting and a hinge effect can be observed at extremes of the stent. The maximum tissue prolapse of the CV model was more severe (0.079 mm) than the SV model (0.048 mm); and the minimum lumen area of the CV was decreased (6.10 mm(2)), compared to that of the SV model (6.28 mm(2)). Tissue stresses of the highest level were concentrated in the inner curvature of the CV model. The simulations offered some explanations for the clinical results of ISR in curved vessels and gave design suggestions of the stent and balloon for tortuous vessels. This FEM provides a tool to study mechanisms of stents in curved vessels and can improve new stent designs especially for tortuous vessels.     

Angina pectoris: interventional therapies and treatment of restenosis

Angina pectoris is a clinical syndrome of symptoms caused by myocardial ischaemia due to oxygen demand exceeding supply. The most common cause is coronary artery stenosis due to progressive atherosclerotic disease. Angina has a prevalence of approximately 5% and increases with age. Despite improvements in treatment there remains a yearly mortality of 2-3%. A major advance in the treatment of symptomatic angina was the introduction of percutaneous transluminal coronary angioplasty (PTCA). This initial enthusiasm was dampened by significant numbers developing symptomatic restenosis from vascular elastic recoil and neointimal hyperplasia (NI). The widespread introduction of stent deployment following the initial angioplasty reduced the rates of elastic recoil but failed to prevent NI and may actually stimulate it. Currently, there is much interest in mechanisms that alter cell proliferation thereby decreasing NI. Techniques include brachytherapy, photodynamic therapy and drug-eluting stents. Provisional data for these new stents, which slowly release medication that inhibits cell turnover, are very good with few occurrences of restenosis. Results from larger randomised trials are awaited.