Comparison between sirolimus-eluting stents and intracoronary catheter-based beta radiation for the treatment of in-stent restenosis

We report the outcomes of patients who had in-stent restenosis (IRS) that was treated with intravascular brachytherapy (IVBT) or sirolimus-eluting stent (SES) implantation. The benefit of IVBT for treating ISR is well documented. SES implantation decreases first-time ISR and, in preliminary reports, has been used to treat ISR. Fifty consecutive patients who had ISR were treated; the first 25 patients underwent SES implantation and the next 25 patients were treated with IVBT using a beta-Cath System (a 40-mm strontium-90/yttrium-90 source). Quantitative angiographic and intravascular ultrasound follow-up were performed at 5.2 +/- 1.1 and 12.1 +/- 1.2 months; clinical follow-up was performed at 15 months. SES deployment and IVBT were successful in all patients. At 12-month follow-up, 8 patients who underwent IVBT had angiographic recurrence (4 in the stent and 4 at the stent edge); only 1 patient who underwent SES implantation developed recurrent ISR. At 12 months, in-stent late luminal loss was similar between the SES and IVBT groups (0.35 +/- 0.45 vs 0.34 +/- 0.46 mm, p = 0.9); however, in-stent net luminal gain was higher in the SES group than in the IVBT group (1.32 +/- 0.13 vs 0.57 +/- 0.19 mm, p <0.0001), and in-lesion late luminal loss was higher in the IVBT group (0.48 +/- 0.32 vs 0.16 +/- 0.42 mm, p = 0.004). At 12 months, intravascular ultrasound stent volume obstruction was higher after IVBT versus than after SES implantation (38.7% vs 6.7%, p <0.0001). At 15-month clinical follow-up, 64% and 96% (p <0.01) of patients who underwent IVBT and SES implantation, respectively, were free of major adverse cardiac events. In conclusion SES implantation for the treatment of ISR was effective and superior to catheter-based IVBT in preventing recurrent neointimal proliferation and angiographic restenosis at 1-year follow-up.     

Covered stent for the treatment of recurrent bilateral renal artery in-stent restenosis

The optimal treatment for renal artery in-stent restenosis (ISR) is not well established. Reintervention with different strategies including balloon angioplasty, cutting-balloon angioplasty, additional stenting with bare-metal, drug-eluting or covered stents and brachytherapy are effective in achieving immediate angiographic success. However, recurrent ISR rates are high irrespective of treatment strategy. We present a case describing the use of a covered stent for the treatment of recurrent bilateral renal artery ISR after bare-metal and drug-eluting stent implantation and cutting-balloon angioplasty.     

Sirolimus-eluting stent for treatment of complex in-stent restenosis: the first clinical experience

OBJECTIVES: In this study, we assess the value of sirolimus eluting stent (SES) implantation in patients with complex in-stent restenosis (ISR). BACKGROUND: The treatment of ISR remains a therapeutic challenge, since many pharmacological and mechanical approaches have shown disappointing results. The SESs have been reported to be effective in de-novo coronary lesions. METHODS: Sixteen patients with severe, recurrent ISR in a native coronary artery (average lesion length 18.4 mm) and objective evidence of ischemia were included. They received one or more 18 mm Bx VELOCITY SESs (Cordis Waterloo, Belgium). Quantitative angiographic and three-dimensional intravascular ultrasound (IVUS) follow-up was performed at four months, and clinical follow-up at nine months. RESULTS: The SES implantation (n = 26) was successful in all 16 patients. Four patients had recurrent restenosis following brachytherapy, and three patients had totally occluded vessels preprocedure. At four months follow-up, one patient had died and three patients had angiographic evidence of restenosis (one in-stent and two in-lesion). In-stent late lumen loss averaged 0.21 mm and the volume obstruction of the stent by IVUS was 1.1%. At nine months clinical follow-up, three patients had experienced four major adverse cardiac events (two deaths and one acute myocardial infarction necessitating repeat target vessel angioplasty). CONCLUSIONS: The SES implantation in patients with severe ISR lesions effectively prevents neointima formation and recurrent restenosis at four months angiographic follow-up.     

Comparison of sirolimus versus paclitaxel eluting stents for treatment of coronary in-stent restenosis

In patients with in-stent restenosis (ISR) inside bare metal stents, drug-eluting stents reduce the recurrence of restenosis compared with balloon angioplasty. However, few data are available about this therapeutic modality in the case of diffuse restenosis. The aim of this study was to evaluate the immediate and mid-term outcome of sirolimus- and paclitaxel-eluting stent implantation in diffuse ISR and determine the predictors of clinical and angiographic restenosis recurrence. A series of 161 consecutive patients with 194 diffuse ISR lesions (>10 mm) treated with drug-eluting stent implantation were evaluated. Major adverse cardiac events were defined as death, myocardial infarction, and the need for target lesion revascularization. During a mean follow-up of 8.2 +/- 3.4 months, the cumulative incidence of major adverse cardiac events was 19% in the SES group and 24% in the PES group (p = 0.56). Angiographic follow-up was performed in 80% of the lesions. The overall restenosis rate was 22% and was not significantly different between lesions treated with sirolimus-eluting (20%) or paclitaxel-eluting (25%, p = 0.55) stents. The incidence of restenosis was higher in diabetics (32%) than in nondiabetics (16%, odds ratio 2.5, 95% confidence interval 1.1 to 5.5, p = 0.02). By multivariate analysis, diabetes was confirmed to be the only independent predictor of recurrent restenosis (odds ratio 3.53, 95% confidence interval 1.39 to 9.02, p = 0.008). In conclusion, drug-eluting stent implantation for diffuse ISR is associated with acceptable clinical and angiographic results. The association of diffuse restenosis and diabetes mellitus is an unfavorable condition leading to a high risk of recurrence.     

Recurrent in-stent restenosis is not associated with the angiotensin-converting enzyme D/I, angiotensinogen Thr174Met and Met235Thr, and the angiotensin-II receptor 1 A1166C polymorphism

Although great progress has been made in reducing renarrowing of the lumen after stenting of coronary arteries, a considerable number of patients develop recurrent in-stent stenosis. Several studies suggest that neointimal proliferation is the crucial pathophysiological process underlying restenosis after stenting. The renin-angiotensin-aldosterone system (RAS) has been implicated in the development of neointimal hyperplasia. We tested the hypothesis that polymorphisms of the RAS genes are associated with recurrent in-stent restenosis (ISR). Coronary stent implantation was performed in 272 patients with clinical symptoms or objective signs of ischemia. At follow-up angiography 6 months after stenting, 81 patients (29.8%) revealed in-stent restenosis. These patients underwent balloon angioplasty and were scheduled for a further 6 months of follow up. One year after initial stenting of the coronary artery, 39 patients displayed no significant angiographic ISR, whereas 42 patients developed recurrent in-stent restenosis (RISR). The survey of specific functional polymorphisms of the RAS, namely the angiotensin-I converting enzyme (ACE) D/I, the angiotensinogen (AGT) T174M and M235T, and A1166C of the angiotensin-II receptor 1 (AGTR1), revealed that the incidence RISR in the high-risk cohort was not associated with any of the polymorphisms examined in this study.     

Sirolimus-eluting stents for the prevention of restenosis in a worst-case scenario of diffuse and recurrent in-stent restenosis.

For recurrent in-stent restenosis (ISR), surgical revascularization or brachytherapy is still the principal therapeutic options. The present investigation explores the efficacy of a sirolimus-eluting stent to prevent restenosis in these lesions with a high risk of recurrence. In 22 consecutive patients with a recurrent and diffuse ISR, a sirolimus-eluting stent was implanted to cover the restenotic lesion. All patients were followed clinically for at least 1 year and underwent a repeat angiography after 7 months. A quantitative coronary angiographic analysis was done. The target vessel failure was 14% in the sirolimus-eluting stent group, with an angiographic late loss of only 0.39 +/- 0.54. No subacute stent thrombosis was observed, and the 1-year event-free survival was 86%. The three cases with restenosis were all focal and could be successfully treated by additional drug-eluting stent implantation. This study showed the efficacy of a sirolimus-eluting stent for the prevention of restenosis in a worst-case scenario of recurrent and diffuse ISR. The observed restenosis rate is lower than that reported after brachytherapy and suggests that sirolimus-eluting stents are a promising treatment option for ISR.     

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.     

Multiple Stent Fractures After Everolimus-Eluting Stent Implantation Causing Acute Myocardial Infarction: A Case Report

Stent fracture is an uncommon complication of drug-eluting stent implantation, but it has a clinical significance because of its potential association with adverse cardiac events such as in-stent restenosis, target lesion revascularization, and stent thrombosis. Multiple stent fractures account for a small proportion, but they may lead to more serious complications. Newer generation drug-eluting stents are designed for improved safety and efficacy compared with early generation drug-eluting stents. Multiple stent fractures after newer generation drug-eluting stent implantation are a rare case.We report a case of 25-year-old male who presented with acute myocardial infarction caused by multiple stent fractures after everolimus-eluting stents implantation and was treated by balloon angioplasty.Physicians should be aware of the possibility of multiple stent fractures even after newer generation drug-eluting stent implantation.     

血浆脑钠尿肽水平与冠状动脉支架植入术后再狭窄有关

目的:探讨冠心病患者血浆脑钠尿肽(BNP)水平与冠状动脉支架内再狭窄的关系。方法:选择317例接受冠状动脉支架植入术(PCI)以及术后1年内再次接受冠状动脉造影(CAG)检查的患者,分为再狭窄和无再狭窄组,分别在PCI术前、出院前和复查CAG前测定血浆BNP水平,两组患者分别比较相应的BNP水平。结果:再狭窄组PCI术前、出院前及复查CAG前的BNP水平与无再狭窄组分别进行比较,差异有统计学意义(P0.05),多因素logistic回归分析结果,血浆BNP水平是预测再狭窄的独立危险因子(均P0.01)。结论:血浆BNP水平与PCI术后再狭窄密切相关,有可能作为再狭窄的有用预测指标。     

Late restenosis following placement of a sirolimus eluting stent for in-stent restenosis

Drug eluting stents (DES) are rapidly replacing intravascular brachytherapy for the treatment of bare metal in-stent restenosis (ISR). To date, there are no long-term follow up data supporting this practise. We report symptomatic repeat in-stent restenosis occurring 27 months after sirolimus eluting stent deployment for de novo in-stent restenosis. This case suggests that in a subgroup of patients with ISR, as with brachytherapy, the drug eluting stent may be simply delaying rather than inhibiting the restenotic process.     

药物洗脱支架治疗后冠状动脉再狭窄相关因素的分析

目的探讨药物洗脱支架治疗后冠状动脉再狭窄与临床和造影的相关因素。方法入选416例冠状动脉造影(CAG)资料完整的冠心病患者,男性328例,女性88例,共置入支架470枚,按照CAG结果分为再狭窄组59例和无再狭窄组357例,平均造影随访时间(7．91±2．37)个月。结果再狭窄组CAG示61枚支架发生再狭窄(13．0％),女性、既往冠状动脉旁路移植术(CABG)病史、慢性闭塞(CTO)病变病史、最大球囊释放压力、置入支架长度与术后再狭窄相关(P<0．05);置入支架血管直径与再狭窄高度相关(OR=0．61,95％CI:0．43～0．82,P< 0．01)。结论女性、既往CABG病史、CTO病变、血管直径、置入支架长度是支架术后再狭窄的危险因素,而糖尿病史等与再狭窄无关。     

Treatment of in-stent restenosis.

Although in-stent restenosis is the result of neointimal hyperplasia, mechanical problems (e.g. stent underexpansion) that occurred during implantation may result in restenosis at follow-up. The treatment of in-stent restenosis, begins with identification of these occult mechanical problems. Thereafter, in-stent restenosis can be treated with PTCA, atheroablation, or additional stent implantation; it is nuclear which technique is superior. Not all in-stent restenosis lesions have a similar risk of recurrence. Recurrence appears to depend on several markers of biologic activity: focal vs diffuse in-stent restenosis, the first episode vs recurrent in-stent restenosis, and early vs late recurrence. Vascular brachytherapy has emerged as the most promising way to treat high-risk lesion subsets.     

Frequency of stent fracture as a cause of coronary restenosis after sirolimus-eluting stent implantation

Stent fracture (SF) was suggested as a cause of restenosis after sirolimus-eluting stent (SES) implantation. This study was performed to evaluate the incidence and characteristics of SF to determine its contribution to restenosis in patients with in-stent restenosis (ISR) after SES implantation. From May 2003 to February 2006, SESs were used for percutaneous coronary intervention in 868 patients with 1,109 coronary narrowings. Follow-up coronary angiography was performed in 366 patients (42%), and 26 ISR lesions were observed. These patients were enrolled in this study. SF was divided into 3 types as avulsion, collapse, and partial based on the findings of fluoroscopy, coronary angiography, and intravascular ultrasound study. Of 26 patients with ISR lesions, SF was identified in 10. SF types were avulsion (5 patients), collapse (2 patients), and partial (3 patients). SF was identified at the midshaft (7 patients) and overlap sites (3 patients) of stents. SF was not observed in the 30 patients with ISR after bare-metal Bx Velocity stent implantation. Four patients with SF were treated with paclitaxel-eluting stents. In conclusion, SF is 1 of the leading causes of ISR after SES implantation. Careful fluoroscopic examination is necessary at the time of follow-up angiography to identify this problem.     

Diffuse in-stent restenosis of CYPHER? stent due to hypersensitivity reaction confirmed by pathohistological findings

The use of drug-eluting stents (DES) reduces the risk of repeat revascularization without increase of death and myocardial infarction compared to standard bare metal stents. However, in-stent restenosis (ISR) after DES implantation still occurs. Here, we report a rare case with a diffuse ISR after CYPHER^? stent implantation because of chronic inflammation and hypersensitivity reactions, confirmed by pathohistological findings.     

雷帕霉素涂层支架治疗老年人冠心病的疗效及再狭窄的随访分析

目的 观察雷帕霉素涂层冠状动脉Cypher支架治疗老年冠心病患者的临床疗效及再狭窄情况。方法 2002年11月至2005年5月在我院心导管室接受Cypher支架治疗的328例60岁以上的老年冠心病患者，观察术后即刻效果，随访6个月记录心脏性死亡、心肌梗死、再次血管重建事件，并进行冠状动脉造影复查。328例中，ST段抬高的急性心肌梗死66例，非ST段抬高的急性心肌梗死21例，不稳定心绞痛149例，稳定型心绞痛92例。结果 支架植入成功率99．1％（325／328），住院期间无死亡。随访6个月出现急性和亚急性血栓各1例，晚期血栓致心肌梗死2例，心力衰竭死亡1例，进行血管重建术7例。住院其间主要心脏不良事件发生率0．6％（2／328），6个月心脏不良事件发生率3．7％（12／328）。术后6个月84例患者冠状动脉造影复查显示，再狭窄率为8．3％（7／84），支架内为2．4％（2／84），靶病变重建率为5．9％（5／84）。结论 应用Cypher支架治疗老年人冠心病是安全和有效的，主要心脏不良事件发生率低，支架内再狭窄率和靶病变重建率明显低于普通金属支架。     

Angiographic and intravascular ultrasound findings of the late catch-up phenomenon after intracoronary beta-radiation for the treatment of in-stent restenosis

We report one-year angiographic and intravascular ultrasound (IVUS) outcomes of in-stent restenosis (ISR) patients treated with intravascular brachytherapy (IVBT). The benefit of IVBT for treating ISR is well documented. However, few data exist on significant angiographic and intravascular ultrasonic in-stent lumen deterioration beyond the habitual 6-month analysis after the index radiation procedure or so-called late catch-up process in the treatment of ISR. Twenty-five consecutive patients with ISR were treated with IVBT using the Beta-Cath System (a 40 mm 90 Sr per 90 gamma source). Quantitative angiographic and IVUS analysis was performed in all of them at 6 and 12 months. IVBT was successful in all patients. Four patients (16%) developed recurrent angiographic binary restenosis at 6-month follow-up, all located within the adjacent reference segments, with 2 being associated with geographical miss. An additional 4 patients (16%) presented with recurrent ISR at 12-month follow-up, all within the stented segment. Significant in-stent lumen loss (0.16 +/- 0.42 mm to 0.34 +/- 0.46 mm; p = 0.008) and in-stent intimal hyperplasia growth (+11.2 +/- 0.48 mm3; p = 0.03) was observed between 6 and 12 months. Intracoronary beta-radiation for the treatment of ISR was associated with significant luminal deterioration (late catch-up) within the stents between 6 and 12 months due to an important late progression of in-stent intimal hyperplasia.     

Three-year follow-up after rotational atherectomy for the treatment of diffuse in-stent restenosis: predictors of major adverse cardiac events.

Restenosis remains the major limitation of coronary stent implantation, especially in diffuse forms of in-stent restenosis. In this study, rotablation (RA) with adjunct angioplasty of in-stent restenosis was performed in 84 patients. Clinical follow-up and control angiography were obtained 6-month postprocedure. The rate of recurrent restenosis after rotablation for in-stent restenosis at 6-month angiographic follow-up was 45%, resulting in a rate of major adverse cardiac events of 35%. At 3-year follow-up, the cumulative event-free survival rate was 57% for the entire population. The only predictor of MACE at 3-year clinical follow-up by multivariate logistic regression analysis was in-stent lesion length. RA for the treatment of diffuse in-stent restenosis is thereby characterized by high procedural success rates and recurrent angiographic restenosis in 45% of patients with diffuse lesions. Major adverse cardiac events occur most likely within the first 6 months postprocedure. Three years after rotablation of in-stent restenosis, 43% of patients had experienced at least one major adverse cardiac event. Cathet Cardiovasc Intervent 2001;53:334-340.     

The evolving role of inflammatory biomarkers in risk assessment after stent implantation

The main adverse reactions to coronary stents are in-stent restenosis (ISR) and stent thrombosis. Along with procedural factors, individual susceptibility to these events plays an important role. In particular, inflammatory status, as assessed by C-reactive protein levels, predicts the risk of ISR after bare-metal stent implantation, although it does not predict the risk of stent thrombosis. Conversely, C-reactive protein levels fail to predict the risk of ISR after drug-eluting stent (DES) implantation, although they appear to predict the risk of stent thrombosis. Of note, DES have abated ISR rates occurring in the classical 1-year window, but new concern is emerging regarding late restenosis and thrombosis. The pathogenesis of these late events seems to be related to delayed healing and allergic reactions to polymers, a process in which eosinophils seem to play an important role by enhancing restenosis and thrombosis. The identification of high-risk individuals based on biomarker assessment may be important for the management of patients receiving stent implantation. In this report, we review the evolving role of inflammatory biomarkers in predicting the risk of ISR and stent thrombosis.     

Mechanisms of acute lumen gain and recurrent restenosis after rotational atherectomy of diffuse in-stent restenosis: a quantitative angiographic and intravascular ultrasound study.

OBJECTIVES: This quantitative angiographic and intravascular ultrasound study determined the mechanisms of acute lumen enlargement and recurrent restenosis after rotational atherectomy (RA) with adjunct percutaneous transluminal coronary angioplasty in the treatment of diffuse in-stent restenosis (ISR). BACKGROUND: In-stent restenosis remains a significant clinical problem for which optimal treatment is under debate. Rotational atherectomy has become an alternative therapeutic approach for the treatment of diffuse ISR based on the concept of "tissue-debulking." METHODS: Rotational atherectomy with adjunct angioplasty of ISR was used in 45 patients with diffuse lesions. Quantitative coronary angiographic (QCA) analysis and sequential intravascular ultrasound (IVUS) measurements were performed in all patients. Forty patients (89%) underwent angiographic six-month follow-up. RESULTS: Rotational atherectomy lead to a decrease in maximal area of stenosis from 80+/-32% before intervention to 54+/-21% after RA (p < 0.0001) as a result of a significant decrease in intimal hyperplasia cross-sectional area (CSA). The minimal lumen diameter after RA remained 15+/-4% smaller than the burr diameter used, indicating acute neointimal recoil. Additional angioplasty led to a further decrease in area of stenosis to 38+/-12% due to a significant increase in stent CSA. At six-month angiographic follow-up, recurrent restenosis rate was 45%. Lesion and stent length, preinterventional diameter stenosis and amount of acute neointimal recoil were associated with a higher rate of recurrent restenosis. CONCLUSIONS: Rotational atherectomy of ISR leads to acute lumen gain by effective plaque removal. Adjunct angioplasty results in additional lumen gain by further stent expansion and tissue extrusion. Stent and lesion length, severity of ISR and acute neointimal recoil are predictors of recurrent restenosis.     

外周血Toll样受体4及TNF-α与冠状动脉支架置入术后再狭窄的关系

目的:支架术后再狭窄(in-stent restenosis,ISR)是影响冠状动脉介入疗效的主要问题,本研究探讨外周血Toll样受体4(toll like receptor4,TLR4)及TNF-α与冠状动脉支架置入术后再狭窄的相关性。方法:入选135例稳定型心绞痛患者,冠状动脉造影示单支血管病变,并成功置入支架,术后6~12个月复查冠状动脉造影,将患者分为支架术后再狭窄组和无再狭窄组,采用流式细胞技术测定支架置入术前及术后5~7d外周血单核细胞TLR4的表达量,同时用酶联免疫吸附试验法(ELISA)检测血清中TNF-α的浓度。结果:复查冠状动脉造影发现14例患者发生支架内再狭窄,占10.4%,无再狭窄组121例,占89.6%。组间比较:术前TLR4及TNF-α的表达水平在两组间差异无统计学意义。分别为:TLR4[(144.20±52.99)vs.(117.40±61.9),P0.05],TNF-α[(34.32±11.97)vs.(27.47±14.47)ng/L;P0.05];术后5~7d两组患者TLR4与TNF-α表达均升高,且再狭窄组升高更明显:TLR4[(182.20±61.59)vs.(125.10±61.9),P0.01],TNF-α(52.62±19.04)vs.(32.63±13.71)ng/L,P0.01)。再狭窄组术后TLR4和TNF-α均升高,与支架置入术前相比差异有统计学意义;术后血清中TNF-α的浓度与外周血单核细胞中TLR4表达的平均荧光强度呈正相关。结论:冠状动脉支架置入术后外周血TLR4及TNF-α的表达均升高,且再狭窄组升高更明显,与无再狭窄组比较,差异有统计学意义。推测TLR4及TNF-α介导的炎症反应与支架术后再狭窄相关。