冠状动脉内支架置入术后再狭窄与炎症反应

再狭窄已成为冠状动脉内支架置入术后存在的主要问题,支架对血管壁的持续刺激,激活血小板、中性粒细胞、单核巨噬细胞、T淋巴细胞等炎症细胞,合成和分泌多种炎症因子,诱发炎症反应,导致血管平滑肌细胞的迁移和增殖、细胞外基质的堆积、新生内膜形成、血管重构,引起再狭窄。本研究就冠状动脉支架内再狭窄与炎症反应做一综述。     

冠脉支架植入术后炎症反应对再狭窄影响的研究进展

<正>《中国心血管病报告2017》中指出我国现今冠心病的患病人数为1100万,死亡率逐年上升,发病趋于年轻化。经皮冠状动脉介入术(PCI)是目前治疗冠状动脉粥样硬化性心脏病的最佳方案~([1])。从30年前法国进行了世界上第一例人体冠脉支架植入术至今,支架内再狭窄(ISR)仍然是PCI术后长期生存中亟需解决的问题~([2]),尽管技术水平逐年发展,发生率仍有10%。其中,术后持续存在的炎症反应成为冠脉支架术后再狭窄的重要原因之一。本文阐述炎症反应在冠脉支架再狭窄中的研究进展,相信不久的将来人们通过进一步抑制炎症作用为高危冠脉支架植入术后的患者带来福音。     

冠状动脉支架内再狭窄的炎症机制和抗炎治疗

冠状动脉支架内再狭窄严重制约了支架置入术的发展,越来越多的证据表明炎症反应参与了从早期的血管损伤到最终的内膜增生等整个再狭窄过程,并发挥了关键性作用。本文试述炎症及相关炎症因子在再狭窄过程中的作用及抗炎治疗的应用。     

炎症反应在冠脉支架置入术后再狭窄中的研究进展

炎症反应通过刺激内膜增生在支架置入术后再狭窄的过程中发挥重要作用。支架置入术后局部和系统炎症反应的强度和持续时间直接与患者的预后有关。治疗应该通过抗增生、局部药物释放等方法直接增加局部对促增生炎性刺激的抵抗力和减少机体炎症反应的强度和持续时间。     

CXCL16及其受体与冠状动脉粥样硬化的关系

近年来,经皮冠状动脉介入治疗已成为冠心病的有效治疗手段。然而,支架植入后再狭窄的出现严重限制了临床预后。多种机制因素参与支架内再狭窄的发生发展过程。CXCL16及其受体在炎症反应中扮演重要角色,本文就CXCL16及其受体与支架内再狭窄的形成机制进行综述。     

药物涂层支架在冠心病介入治疗中的临床应用

冠状动脉(下简称冠脉)内支架术已成为目前经皮冠脉介入治疗的最常用的疗法,≥85％冠脉最初(de novo)病变在接受介入治疗时,使用了支架术。但普通裸支架术后再狭窄仍高达20％～40％。最近的研究表明,药物涂层支架在预防再狭窄中具有独特的应用价值。     

冠状动脉支架术后再狭窄发生机制及介入治疗进展

冠状动脉支架术后再狭窄的发生机制主要为新生内膜的增殖。为降低再狭窄的发生率，人们尝试了多种介入治疗方法，其中血管内放射治疗和药物涂层支架是较有效方法。本拟对再狭窄的发生机制和血管内放射及药物涂层支架治疗再狭窄作一综述。     

冠状动脉药物涂层支架后再狭窄与炎症反应的相关性

药物涂层支架的应用使冠心病的介入治疗有了长足进展,但是支架再狭窄仍是不容忽视的问题。现就支架后的炎症反应和再狭窄的关系,药物涂层支架对于抑制炎症和降低再狭窄发生率的作用机理进行综述。     

冠状循环内白介素-6浓度与冠状动脉支架置入术后再狭窄的关系

炎症与冠心病的关系日益受到人们的重视 ,已有报道局部或全身炎症反应在动脉粥样硬化及其并发症的发生、发展中起重要作用 [1]。炎症标记物白介素 - 6 (IL- 6 )和 C-反应蛋白 (CRP)在急性心肌梗死患者中增高 [2 ] ,而 IL- 6为 CRP在肝脏合成的主要诱导物 ,其与冠状动脉支架置入术后再狭窄的关系鲜见报道。本研究检测行 PTCA及冠状动脉支架置入术的冠心病患者 PTCA术前和术后即刻冠状循环内IL- 6、CRP浓度的变化 ,了解其与支架置入术后再狭窄的关系。1　资料与方法1 .1　临床资料　 2 0 0 0年 4月至 2 0 0 2年 6月 ,在我院住院的行…     

冠状动脉粥样硬化性心脏病患者择期支架植入术前血浆超敏C反应蛋白水平对术后6个月支架内再狭窄及12个月急性冠脉事件发生的预测价值

目的 探讨冠状动脉粥样硬化性心脏病(简称冠心病)患者支架植入术前血浆超敏C反应蛋白(hs-CRP)水平与术后6个月支架内再狭窄及12个月急性冠脉事件发生的关系.方法 选择2007年10月～2010年2月我院住院的行经皮冠状动脉介入治疗(PCI)的冠心病患者358例,通过测定支架植入术前患者血浆hs-CRP水平,初步采用Logistic回归分析冠心病患者术前hs-CRP水平和PCI术后6个月后支架内再狭窄和随访12个月急性冠脉事件发生的关系.结果 血浆hs-CRP水平和PCI术后随访12个月急性冠脉事件高度相关(OR=2.21,P ＜0.01);血浆hs-CRP水平和PCI术后6个月支架内再狭窄无明显相关(OR=1.17,P ＞0.05).结论 冠心病患者支架植入术前血浆hs-CRP水平和PCI术后急性冠脉事件的发生密切相关,但是和PCI术后支架内再狭窄无明显相关,支架植入术前血浆hs-CRP水平对PCI术后急性冠脉事件的发生有较好的预测价值.     

Predictors of diffuse and aggressive intra-stent restenosis

OBJECTIVES: This study was performed to investigate the causes of diffuse and aggressive intra-stent restenosis. BACKGROUND: Although restenosis is usually considered to be a dichotomous variable, there is clinical relevance to the severity of restenosis. It is not known which variables are predictive of diffuse or aggressive intra-stent restenosis. METHODS: A consecutive series of 456 coronary lesions with in-stent restenosis was evaluated for the type of restenosis using quantitative coronary angiography. Restenosis was defined as > or = 50% diameter stenosis at follow-up angiography, diffuse restenosis as a follow-up lesion length > or = 10 mm and aggressive restenosis as either an increase in lesion length from the original lesion or a restenotic narrowing tighter than the original. Clinical, anatomic and procedural characteristics were evaluated for lesions associated with these types of restenosis. RESULTS: Diffuse restenosis was associated with a smaller reference artery diameter, longer lesion length, female gender, longer stent length and the use of coil stents. Aggressive restenosis was more common in women, with the use of Wallstents and with long stent to lesion length ratios. Aggressive restenosis occurred earlier and was more closely associated with symptoms and myocardial infarctions than nonaggressive restenotic lesions. CONCLUSIONS: Markers for diffuse restenosis were also important markers for the presence of any restenosis. A long stent to lesion length ratio is an important marker for aggressive restenosis. When severe forms of in-stent restenosis occur, they tend to present earlier and with more symptoms, including myocardial infarction. More careful consideration of the type of in-stent restenosis may aid in identifying when alternative strategies may be useful.     

血清叶酸与冠状动脉支架内再狭窄关系的研究

目的探讨冠状动脉支架内再狭窄与血清叶酸水平的关系。方法选择资料齐全的86例冠心病支架术后患者,根据造影结果分再狭窄组与非再狭窄组。运用放射免疫法测定血清叶酸浓度。对支架术后两组血清叶酸水平进行对比分析。结果两组在年龄、性别、高血压的发生率无统计学意义,但吸烟、合并糖尿病者再狭窄发生率明显高于非再狭窄者(P<0.01),再狭窄组血清叶酸明显低于非再狭窄组(P<0.05)。结论资料提示:年龄、性别、高血压等对支架的再狭窄无明显影响,吸烟、糖尿病患者再狭窄发生率明显增加;且支架内再狭窄者叶酸水平明显降低。     

Re-angioplasty of in-stent restenosis versus balloon restenoses--a matched pair comparison

BACKGROUND: Despite different biological mechanisms involved in the restenotic process of in-stent restenosis and restenosis after balloon angioplasty alone, the occurrence of a second restenosis has been reported in the same range. There are no data available comparing the outcome after re-angioplasty of such lesions. We analyzed in a matched pair comparison the clinical outcome and angiographic long-term result of patients with balloon angioplasty of a first in-stent restenosis versus patients with balloon re-angioplasty of a first balloon restenosis. METHODS: Both groups consisted of 74 lesions matched by treated vessel, lesion location differentiated in proximal and non-proximal, and angiographic appearance of coronary artery disease differentiated in singular stenosis, diffuse or mixed pattern. Clinical follow-up was 100%. Angiographic follow-up was 78.4% after median 174 days. RESULTS: Angiographic restenosis rate in matched pairs of patients (n=46/74) was significantly higher in the balloon restenosis group (41.3%, n=19/46) compared to the in-stent restenosis group (21.7%, n=10/46, p<0.042). There was no death or myocardial infarction. After clinical follow-up, target lesion revascularization rate was significantly lower in the in-stent restenosis group compared to the balloon restenosis group (12.1%, n=9/74 versus 27.0%, n=20/74; difference between groups 14.9%, 95% confidence interval 2.0-27.3%, p<0.023). Multivariate logistic regression analysis revealed as predictors for a second restenosis unstable angina pectoris, non-proximal lesion, restenosis after balloon angioplasty and the occurrence of the first restenosis within 90 days after initial intervention. CONCLUSION: Clinical and angiographic outcome after balloon angioplasty of a first in-stent restenosis was significantly better compared with balloon re-angioplasty of a first balloon restenosis.     

Balloon angioplasty for the treatment of coronary in-stent restenosis: immediate results and 6-month angiographic recurrent restenosis rate

Objectives. The purpose of this prospective study was to evaluate the immediate results and the 6-month angiographic recurrent restenosis rate after balloon angioplasty for in-stent restenosis.Background. Despite excellent immediate and mid-term results, 20% to 30% of patients with coronary stent implantation will present an angiographic restenosis and may require additional treatment. The optimal treatment for in-stent restenosis is still unclear.Methods. Quantitative coronary angiography (QCA) analyses were performed before and after stent implantation, before and after balloon angioplasty for in-stent restenosis and on a 6-month systematic coronary angiogram to assess the recurrent angiographic restenosis rate.Results. Balloon angioplasty was performed in 52 patients presenting in-stent restenosis. In-stent restenosis was either diffuse (≥ 10 mm) inside the stent (71%) or focal (29%). Mean stent length was 16 ± 7 mm. Balloon diameter of 2.98 ± 0.37 mm and maximal inflation pressure of 10 ± 3 atm were used for balloon angioplasty. Angiographic success rate was 100% without any complication. Acute gain was lower after balloon angioplasty for in-stent restenosis than after stent implantation: 1.19 ± 0.60 mm vs. 1.75 ± 0.68 mm (p = 0.0002). At 6-month follow-up, 60% of patients were asymptomatic and no patient died. Eighteen patients (35%) had repeat target vessel revascularization. Angiographic restenosis rate was 54%. Recurrent restenosis rate was higher when in-stent restenosis was diffuse: 63% vs. 31% when focal, p = 0.046.Conclusions. Although balloon angioplasty for in-stent restenosis can be safely and successfully performed, it leads to less immediate stenosis improvement than at time of stent implantation and carries a high recurrent angiographic restenosis rate at 6 months, in particular in diffuse in-stent restenosis lesions.     

Management of drug-eluting stent restenosis

In-stent restenosis has been a longstanding problem after percutaneous coronary intervention. The introduction of the drug-eluting stent (DES) successfully reduced the rate of restenosis; however, it is not completely diminished. Although restenosis occurs less frequently compared to the bare-metal stent (BMS), DES restenosis remains a familiar problem due to the increasing total number of implanted DESs as well as the targeting of more complex lesions. In addition, worse outcomes after repeat revascularization compared to BMS restenosis are reported in DES restenosis. Management of DES restenosis is an emerging issue, which requires careful evaluation of the restenosed lesion, together with cautious determination of therapeutic strategy. In this review, available repeat revascularization procedures for DES restenosis as well as possible impacting factors on the outcomes are discussed.     

Long-term angiographic follow-up after successful repeat balloon angioplasty for in-stent restenosis

BACKGROUND: Coronary stent implantation is associated with improved angiographic short-term and mid-term clinical outcome. However, restenosis rate still remains between 20 and 30%. HYPOTHESIS: The purpose of the study, performed as a prospective angiographic follow-up to detect restenosis, was to evaluate the immediate and the 6-month angiographic results of repeat balloon angioplasty for in-stent restenosis. METHODS: From April 1996 to September 1997, 335 stenting procedures performed in 327 patients underwent prospectively 6-month control angiography. Of the 96 lesions that showed in-stent restenosis (> 50% diameter stenosis) (29%), 72 underwent balloon angioplasty. RESULTS: The primary success rate was 100%. Follow-up angiogram at a mean of 6.9 +/- 2.4 months was obtained in 54 patients. Recurrent restenosis was observed in 24 of the 55 stents (44%). Repeat intervention for diffuse and body location in-stent restenosis before repeat intervention was associated with significantly higher rates of recurrent restenosis (p < 0.001 and p < 0.05, respectively). Of the 19 patients who underwent further balloon angioplasty (100% success rate), coronary angiography was performed in 18 (95%) at a mean of 8.2 +/- 2.0 months and showed recurrent restenosis in 12 patients (67%). Further repeat intervention for diffuse and severe in-stent restenosis before the second repeat intervention was associated with significantly higher rates of further recurrent restenosis (p < 0.05 and p < 0.005, respectively). CONCLUSIONS: Although balloon angioplasty can be safely, successfully, and repeatedly performed after stent restenosis, it carries a progressively high recurrence of angiographic restenosis rate during repeat 6-month follow-ups. The subgroup of patients with diffuse, severe, and/or body location in-stent restenosis proved to be at higher risk of recurrent restenosis.     

Utility of myocardial fractional flow reserve for prediction of restenosis following sirolimus-eluting stent implantation

Drug-eluting stents reduce restenosis due to neointimal growth suppression. Considering long-term outcomes, it is both difficult and important to predict drug-eluting stent restenosis. Thus, this study was designed to examine the utility of myocardial fractional flow reserve (FFR) as a predictor of sirolimus-eluting stent (SES) restenosis. Thirty-three patients (35 lesions) were enrolled. Upon completion of SES implantation, FFR was obtained under hyperemia. At 8 months of follow-up, coronary angiography revealed that five lesions had restenosis. Percent diameter stenosis (restenosis 68.7 ± 12.8% vs. non-restenosis 68.7 ± 12.4%, p = 0.78) and lesion length (restenosis 15.8 ± 9.4 mm vs. non-restenosis 14.4 ± 9.2 mm, p = 0.60) were similar. At post-intervention, percent diameter stenosis (restenosis 16.4 ± 6.1% vs. non-restenosis 14.0 ± 7.4%, p = 0.48) and minimum stent area (restenosis 6.01 ± 1.08 mm2 vs. non-restenosis 6.27 ± 1.85 mm2, p = 0.92) were also equivalent. However, proximal edge lumen area was smaller (restenosis 4.24 ± 1.40 mm2 vs. non-restenosis 7.73 ± 2.64 mm2, p = 0.004) and FFR was lower in the restenosis group (restenosis 0.81 ± 0.12 vs. non-restenosis 0.92 ± 0.06, p = 0.029). SES patients with restenosis had a lower FFR post stent deployment, suggesting the decreased FFR may be a useful predictor for SES restenosis.     

冠状动脉支架术后病人发生再狭窄的危险因素分析

目的　探讨冠状动脉支架术后再狭窄的危险因素。方法　回顾性分析我院行冠状动脉内支架植入术并进行冠状动脉造影复查随访的 49例病人的临床和造影资料。用单因素和Logistic多因素逐步回归分析方法分析了病人临床特征及冠状动脉造影特征等 2 9个变量与再狭窄的关系。结果　复查冠状动脉造影时间 ,再狭窄组明显短于无再狭窄组。再狭窄组病人合并有糖尿病史比例较无狭窄组明显增多。Logistic回归分析 :再狭窄与复查造影时间、术前心肌梗死溶栓试验 (TIMI)血流、支架直径、支架植入后病变处管腔血流速度呈显著负相关 ;与糖尿病史、美国心脏病学会和美国心脏病协会 (ACC AHA)冠状动脉病变分类呈显著正相关。结论　冠状动脉支架术后病人发生再狭窄多在术后 6个月以内。糖尿病史 ,术前TIMI血流分级 ,支架直径 ,ACC AHA病变分型 ,支架植入后病变处管腔血流速度为支架植入术后再狭窄的独立危险因素。     

血管抑肽(Angiopeptin)预防PTCA后及/或支架内再狭窄

血管抑肽（angiopeprin)，一种人工合成的环八肽，生长抑素（somatostatin)的类似物，在动物实验证实可抑制动脉损伤后的内膜增生、预防PTCA（经皮穿刺冠状动脉扩张成型术）后再狭窄，然而，预防PTCA后再狭窄的临床试验则有不同的结果。我们简要复习了近年文献，讨论了血管抑肽在预防PTCA后及支架内再狭窄的作用，分析了血管抑肽的给药途径与给药方法以及动物实验与临床试验的结果及其可能的原因。     

Cost-efficacy modeling of functional testing with perfusion imaging to detect asymptomatic restenosis following percutaneous transluminal coronary angioplasty.

The objective of this study was to perform a theoretical cost-efficacy analysis on the use of routine functional testing with perfusion imaging to identify patients with asymptomatic restenosis following percutaneous transluminal coronary angioplasty (PTCA) procedures. Approximately 50% of patients with restenosis following PTCA are asymptomatic. Routine functional testing is commonly performed at 3 to 6 months to identify these patients. The cost-efficacy associated with this strategy is unknown. Theoretical models were constructed based on assumed costs for functional testing (U.S. $1,300) and coronary angiography (U.S. $3,000). Restenosis rates were assumed to be 40%, and half of patients with restenosis were assumed to be asymptomatic. To provide a range of costs to identify a patient with asymptomatic restenosis, three scenarios were constructed based on the diagnostic test characteristics of functional testing. Sensitivity analyses were performed using a range of costs for functional testing, restenosis rates, and proportion of patients with restenosis who are asymptomatic. Depending on the diagnostic accuracy of functional testing, it costs $8,200 to $22,400 to identify an asymptomatic patient with restenosis following PTCA. The cost to identify a patient with asymptomatic restenosis varies inversely with the rates of restenosis. When restenosis rates are < 20%, the cost to identify a patient with asymptomatic restenosis exceeds $10,000. Similarly, the cost to identify a patient with asymptomatic restenosis increases when the proportion of patients with asymptomatic restenosis decreases. The cost, associated with the use of routine functional testing for the identification of asymptomatic patients with restenosis appears exorbitant. However, a formal study is warranted to determine the cost-efficacy of such a strategy. Cathet. Cardiovasc. Intervent. 48:352-356, 1999.