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.     

Brachytherapy for rental artery in-stent restenosis

Percutaneous transluminal angioplasty with stenting is now an established modality for treatment of atherosclerotic renal artery stenosis. However, the rate of restenosis can be as high as 20%. While intravascular brachytherapy has proven efficacy in coronary artery in-stent stenosis, its role in the treatment of renal artery in-stent stenosis is not well understood. We report a case of recurrent in-stent renal artery stenosis treated successfully by brachytherapy with excellent follow up results at 22 months.     

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.     

Rotational atherectomy for in-stent restenosis: acute and long-term results of the first 100 cases

Objectives. This study evaluated the clinical safety and long-term results of rotational atherectomy (RA) followed by low-pressure balloon dilatation (percutaneous transluminal coronary angioplasty [PTCA]) for the treatment of in-stent restenosis (ISR).Background. In-stent restenosis is associated with a high incidence of recurrence after interventional treatment. Because ISR is due to neointimal hyperplasia, rotational ablation may be a more effective treatment than PTCA.Methods. Between November 1995 and November 1996, 100 consecutive patients with first-time ISR were treated by RA. Quantitative coronary angiography and intravascular ultrasound (IVUS) were used to analyze the acute procedural results. The incidence of repeat in-stent restenosis and target vessel revascularization (TVR) at follow-up was determined.Results. Procedural success without any major in-hospital complications was achieved in 100% of cases. Slow flow was observed in 3% and creatine kinase-MB enzyme elevation >3× normal occurred in 2%. The mean burr-to-artery ratio was 0.68 ± 0.18 and adjuvant balloon dilatation was performed at 4.2 ± 2.1 atm. Minimum luminal diameter increased from 0.86 ± 0.28 mm to 1.89 ± 0.21 mm after RA and to 2.56 ± 0.29 mm after adjunct PTCA. Quantitative IVUS analysis showed that 77% of the luminal gain occurred due to rotational ablation of the restenotic tissue and only 23% occurred after adjunct balloon dilation, and further stent expansion did not contribute to the luminal enlargement. At a mean follow-up of 13 ± 5 months, repeat in-stent restenosis occurred in 28% of patients with TVR of 26%. Univariate predictors of repeat restenosis were burr-to-artery ratio <0.6, ISR in <90 days of stenting, ostial lesion, stent for a restenotic lesion and diffuse type ISR.Conclusions. Rotational atherectomy is a safe and feasible technique for treatment of ISR and is associated with a relatively low recurrent restenosis in comparison to historical controls of balloon angioplasty.     

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.     

Provisional stenting strategies: systematic overview and implications for clinical decision-making

Coronary stents reduce the rates of abrupt closure, emergency coronary artery bypass graft surgery and restenosis, but do not prevent myocardial infarction or death at six months. The financial burden of increased stent use and the difficulty in managing in-stent restenosis have provided the impetus to develop provisional stenting strategies. Patients at low risk for restenosis after balloon angioplasty may not derive additional benefit from stent implantation and may be successfully managed with percutaneous transluminal coronary angioplasty (PTCA) alone. Numerous patient, lesion and procedural predictors of restenosis have been identified. Postprocedural assessment using quantitative coronary angiography, intravascular ultrasound (IVUS), coronary flow velocity reserve (CVR) or fractional flow reserve (FFR) may further enhance the ability to predict adverse outcomes after PTCA. Several studies have been performed to investigate the feasibility of provisional stenting strategies using various modalities to identify low risk patients who could be managed with PTCA alone. An optimal or "stent-like" angiographic result after PTCA is associated with favorable clinical outcomes. Preliminary results of studies using IVUS or CVR to guide provisional stenting appear promising. Angiography alone may be inadequate to identify truly low risk patients and may need to be combined with clinical factors, assessment of recoil, IVUS or physiologic indexes. Strategies that avoid unnecessary stenting in even a small proportion of patients may have large impacts on health care costs. Provisional stenting may potentially reduce costs and rates of in-stent restenosis without compromising the quality of health care delivery.     

Vascular stenting in normal and atherosclerotic rabbits. Studies of the intravascular endoprosthesis of titanium-nickel-alloy

Percutaneous transluminal balloon angioplasty would be more effective if the rate of recurrent stenosis were reduced. To evaluate the prevention of restenosis after percutaneous transluminal angioplasty, intravascular endoprosthetic stents of titanium-nickel-alloy were implanted transluminally in seven normal and 21 atherosclerotic rabbits. In normal rabbits, a 3.5-mm diameter stent was implanted in the aorta and a 2.5-mm diameter stent in the right iliac artery, which were followed with serial angiograms from 6 weeks (n = 7) to 8 months (n = 4). There was a mean stenosis of 13.1% in the 2.5-mm and 13.6% in the 3.5-mm stent. There was no significant narrowing compared with the adjacent control segments of artery; histopathology showed a thin, fibrous neointima with smooth muscle cells. Each atherosclerotic rabbit was balloon dilated at two separate stenotic sites; each site was 2.0 cm in length. The aortic site (with 28.8 +/- 13.8% mean stenosis [+/- SD]) was dilated with a 3.5-mm balloon, and the iliac site (with 36.5 +/- 14.2% stenosis) was dilated with a 2.5-mm balloon. In each site, an intravascular stent of corresponding diameter and 7-mm length was implanted in one half of the dilated segment, assigned randomly, and the other half served as the angioplasty control. Angiographically observed restenosis rates and the corresponding histopathology were similar in the atherosclerotic segments that had angioplasty alone versus the atherosclerotic segments that had angioplasty plus stenting. The mean neointimal thickness in the aortas and iliac arteries, respectively, measured 247 +/- 181 microns (+/- SD) and 218 +/- 77 microns after 6 weeks (n = 8) versus 321 +/- 168 and 308 +/- 189 microns after 20 weeks (n = 5, p = NS). At 20 weeks follow-up, there was 29.1 +/- 29.8% (median, 16.4%) stenosis in the aortic stent versus 38.9 +/- 24.1% (median, 34.0%) stenosis in the percutaneous transluminal angioplasty control segment of aorta (n = 5, p = NS) and 81.4 +/- 25.5% stenosis in the iliac artery stent versus 89.3 +/- 15.3% stenosis in the PTA control segment of the right iliac artery (n = 5, p = NS). Comparing stenotic arterial segments treated with angioplasty alone with angioplasty plus intravascular stenting in the atherosclerotic rabbits showed that there was no significant difference in either the histopathologic changes or the restenosis rates.     

Endovascular brachytherapy for treatment of bilateral renal artery in-stent restenosis.

Percutaneous transluminal angioplasty of renal artery stenosis is an attractive alternative to surgical therapy. However, even with endovascular stenting, the overall rate of restenosis is 21%. While brachytherapy for coronary in-stent restenosis has proven efficacy, its use for renal artery in-stent restenosis has not been formally evaluated. We report a case of bilateral in-stent renal artery restenosis treated with endovascular brachytherapy.     

Drug-eluting stent implantation for treatment of recurrent renal artery in-stent restenosis.

Percutaneous renal artery stenting has become the treatment of choice for renal artery stenosis. In-stent restenosis (ISR) still remains a persistent problem. Drug eluting stents have significantly reduced the incidence of ISR in coronary arteries. We report a case in which recurrent renal ISR was successfully treated with paclitaxel-eluting stent implantation, using intravascular ultrasound guidance, with maintained stent patency at 6 months.     

Carotid artery in-stent restenosis in a patient with contralateral total occlusion, resolved with drug-eluting stenting

A 70-year-old male patient with 90% stenosis of the right carotid artery and total occlusion of the left carotid artery underwent right carotid stenting. Two weeks after the procedure, the patient experienced grand mal seizures, and had angioplasty after 6 and 11 months, respectively, for recurrent in-stent restenosis. During drug-eluting stent deployment, the patient developed acute stent thrombosis, but he recovered quickly and completely after local thrombolysis and balloon angioplasty. For the 1 year of follow up to date, the patient has been symptom-free and without restenosis. At 6 months from the last-mentioned study, the patient was admitted for intermittent claudication, fatigability and severe hypertension. A Doppler study of the carotid stent showed normal velocities, and the the neurological exam was similar to the previous one. Angiography confirmed bilateral ostial stenosis of the renal arteries and we performed bilateral renal stenting at that time.     

颅内外血管狭窄术后支架内再狭窄的研究进展

支架置入术是目前治疗颅内外血管狭窄的常用治疗方法之一,但支架内再狭窄(ISR)是术后亟需解决的主要问题,其形成机制复杂,影响因素众多,需要神经介入医师综合评估支架术后ISR的发生风险.该文就ISR形成机制、影响因素、临床治疗等进行综述,为临床工作提供参考.     

Intravascular ultrasound-guided cutting balloon angioplasty for renal artery stent restenosis

Renal artery stenting is the procedure of choice for treating atherosclerotic renal artery stenosis; it improves the acute results of percutaneous balloon angioplasty and has a better long-term outcome, particularly a reduced risk of restenosis. However, the treatment of renal artery stent restenosis is not well established and it is challenging because of limited therapeutic options. A novel technique of treating renal artery stent restenosis using cutting balloon angioplasty guided by intravascular ultrasound is presented.     

光学干涉断层成像系统对冠心病病变特征的评价

目的:初步探讨光学干涉断层成像(OCT)系统评价冠心病病变特征的价值。方法:分析在2005年12月行冠状动脉造影检查的同时接受OCT检查的5例冠心病患者的OCT影像特征。结果:2例不稳定型心绞痛患者中,1例右冠状动脉中段成角病变狭窄99%,OCT清晰显示血栓、钙化、纤维帽厚度及脂质斑块,介入治疗后OCT检查示支架贴壁良好,血栓消失;1例前降支狭窄50%,OCT探测到清晰的附壁血栓、最薄处纤维帽及斑块破裂。3例介入治疗后患者中,1例回旋支中远段支架内狭窄75%、2例前降支支架内狭窄50%,OCT检查精确定量再狭窄程度63.33%~87.25%,增生基质主要为纤维样组织,可见少许脂质样基质,其中回旋支支架内狭窄患者OCT检查时发生支架远段冠状动脉夹层,行回旋支远段支架置入术治疗。结论:OCT系统在评价冠心病病变特征和介入治疗结果方面具有较好的应用价值。     

First use of cryoplasty to treat in-stent renal artery restenosis

Atherosclerotic renal artery stenosis is the most common cause of renovascular hypertension. Primary treatment of renal artery stenosis includes renal artery balloon angioplasty and, in some cases, renal artery stenting. However, in-stent restenosis occurs in 11% to 39% of patients thus treated. Herein, we report the case of a 76-year-old woman whose left-sided renal artery stenosis had been treated by means of renal artery stenting. She later presented at our institution with flash pulmonary edema that was caused by in-stent restenosis. We successfully treated the patient with cutting-balloon angioplasty and cryoplasty of the in-stent restenosis. To our knowledge, this is the 1st report of the use of cryotherapy to treat in-stent renal artery stenosis.     

老年高血压肾动脉狭窄患者介入治疗的长期疗效分析

目的评价经皮肾动脉成形术血运重建对肾动脉狭窄老年高血压患者的血压、肾功能等方面中远期的影响及术后支架内再狭窄的相关因素。方法选择合并有高血压的肾动脉狭窄患者199例;经肾动脉成形术重建肾动脉血运。术后平均随访(19±11)个月,观察患者血压、降压药物、肾功能的变化,并对支架内再狭窄进行相关分析。结果 199例患者中,肾动脉成形术成功率97.5%。病变动脉管腔直径狭窄率由(73±11)%降至(12±10)%。术后随访138例患者血压下降明显,收缩压由(161±26)mm Hg(1mm Hg=0.133 kPa)降至(1 37±16)mm Hg,舒张压由(85±1 5)mm Hg降至(77±11)mm Hg,差异有统计学意义(P<0.01);口服降压药物品种明显减少,由平均(2.4±1.2)种降至(1.8±0.9)种(P<0.01);患者手术前后肌酐水平无显著差异,但对术前有肾功能不全患者估测的肾小球滤过率改善差异有统计学意义;术后24个月发生支架内再狭窄14例,非开口病变是再狭窄的危险因素。结论老年高血压肾动脉狭窄患者经皮肾动脉成形术的手术成功率高,并有助于此类患者血压的长期控制,特别是部分肾功能不全患者肾小球率过滤可能会有改善,支架内再狭窄与病变部位相关。     

Drug-eluting stent for recurrent mesenteric artery in-stent restenosis.

PURPOSE: To report the use of a drug-eluting stent (DES) for treatment of symptomatic in-stent restenosis (ISR) in the superior mesenteric artery (SMA). CASE REPORT: A 79-year-old woman suffering from chronic renal failure and needing dialysis was admitted for vomiting, postprandial abdominal pain, and weight loss for 3 months. Computed tomographic angiography (CTA) documented massive calcification of the vascular bed, mainly in the aorta, and a very tight ostial stenosis of the SMA. A 4.5-x20-mm Genesis stent was deployed at the ostium, with good angiographic result and immediate symptomatic benefit. After 3 months, symptoms recurred; angiography demonstrated ISR. Percutaneous angioplasty with a 4-x15-mm cutting balloon was performed. The patient remained asymptomatic for only 2 months; recurrent ISR at this time was treated with a 3.5-x24-mm coronary TAXUS Express paclitaxel-eluting coronary stent deployed inside the previously implanted stent. Under prolonged double antiplatelet regimen, the patient was asymptomatic at the 8-month follow-up; CTA demonstrated patency of the SMA. CONCLUSION: Considering the high rate of restenosis and the periprocedural complications described with endovascular treatment of SMA stenosis, a drug-eluting stent may be a good option not only for the treatment of restenosis but also in de novo lesions, at least when the vessel diameter is <4.5 mm.     

Endovascular treatment of in-stent restenosis after carotid artery stenting: immediate and midterm results.

PURPOSE: To evaluate the immediate and midterm outcome and analyze the debris captured after repeat endovascular intervention for the treatment of in-stent restenosis after carotid artery stenting (CAS). METHODS: Thirty-one consecutive patients (27 men; mean age 63.7+/-13.0 years, range 53- 81) underwent repeat endovascular intervention (balloon angioplasty and provisional stenting) for the treatment of 32 in-stent restenoses following CAS. RESULTS: Procedural success was achieved in all patients. An additional stent was implanted in 10 (31%) cases. No procedural complication was observed. Filter analysis was performed in 17 (53%) procedures; on 12 (71%), macroscopically visible material was captured. The histomorphometric analysis performed on 6 (19%) filters showed fibrin nets entrapping erythrocytes, leucocytes, platelets, and in 2 cases, fibrous hypercellular tissue fragments. At 30 days and during follow-up (mean 17+/-5 months), no deaths, transient ischemic attacks, or strokes were observed. In 1 (3.1%) patient, asymptomatic recurrence of ISR was found on Doppler ultrasonography and successfully treated with balloon angioplasty. CONCLUSION: Repeat endovascular intervention using balloon angioplasty with provisional stenting and routine cerebral protection appears to be a feasible, safe, and clinically effective strategy for the treatment of in-stent restenosis after CAS.     

Serial intravascular ultrasound assessment of the efficacy of intracoronary gamma radiation for preventing recurrent in-stent restenosis

Intracoronary stents reduce restenosis compared with balloon angioplasty. However, a major limitation of stenting is in-stent restenosis, which occurs in 10% to 40% of the patients depending upon risk factors. Serial intravascular ultrasound studies have shown that in-stent restenosis is primarily due to neointimal hyperplasia. Treatment of in-stent restenosis is challenging and recurrence rates are high regardless of interventional technique used. Several randomized clinical trials with intracoronary ionizing radiation using both beta (b) and gamma (g) emitters following primary catheter-based intervention have demonstrated a significant reduction in recurrence. The majority of these studies have used both serial angiographic and serial intravascular ultrasound endpoints to assess the efficacy of intracoronary radiation to prevent recurrence after the treatment of in-stent restenosis. As different mechanism of postradiation restenosis may operate in the original lesion segment, the ballooned segment and the actual irradiated segment, these imaging techniques have also helped to document any long-term affects of radiation including aneurysm formation, edge effects, geographical miss, and the presence or absence of remodeling. The angiographic results have correlated well with intravascular ultrasound results after radiation therapy and at follow-up. Thus, a combination of both serial intravascular ultrasound and careful angiography, which documents balloon, stent, and radiation source positioning, can fully assess the effectiveness of this modality of treatment.     

Pulmonary Vein Stenting for the Treatment of Acquired Severe Pulmonary Vein Stenosis after Pulmonary Vein Isolation: Clinical Implications after Long-Term Follow-Up of 4 Years

Introduction: Severe pulmonary vein stenosis (PVS) after catheter ablation of atrial fibrillation (AF) is a well-recognized complication with a further reported incidence of 1.3%. The preferred therapy for symptomatic PVS is pulmonary vein (PV) angioplasty, but this treatment modality is followed by restenosis in 44–70%. Whether there is additional long-term benefit from PVS stenting is uncertain. The aim of this study was the evaluation of the long-term success after PV stenting of severe stenosis.
Methods and Results: Ten patients (pts) with 13 PVS were prospectively evaluated. PV stenting was performed with Palmaz Genesis stents. Magnetic resonance imaging (MRI), lung perfusion scans, and CT-scans were performed before, directly after, and every 12 months thereafter. Primary endpoint of the study was the occurrence of restenosis after PV stenting. After a median follow-up of 47.7 (IQRs 25/75 47.2–48.5) months, the primary endpoint was achieved in 3 out of 13 PVs (23% of the treated PVs). We observed two in-stent restenosis 2 and 4 years after PV stenting. These pts experienced onset of dyspnea some weeks before. After an additional balloon angioplasty, the in-stent restenosis was resolved. In one asymptomatic patient, we observed an occlusion of the PV stent 13 months poststenting. Normalization of lung perfusion was noted 4 years after PV stenting versus directly poststenting in all pts without in-stent restenosis (n = 7).
Conclusion: PVS stenting with stent sizes ≥10 mm seems to be an adequate therapy modality for treatment of severe acquired PVS. Late in-stent restenosis after PVS stenting can occur. The normalization of the initially disturbed lung perfusion scan is possible and remains stable, even 4 years after PVS stenting.     

Sirolimus-eluting stent in chronic total occlusion: the SICTO study

Coronary stenting can significantly reduce the restenosis and reocclusion rates after successful balloon angioplasty for chronic total occlusions (CTO). Nevertheless, recanalization of CTO remains among the worst predictors for in-stent restenosis and reocclusion. This multicenter, nonrandomized study assessed the safety and effectiveness of the CYPHER sirolimus-eluting stent in reducing angiographic in-stent late loss in totally occluded native coronary arteries. A total of 25 eligible patients were treated with the CYPHER sirolimus-eluting stent. Baseline clinical and angiographic data were collected and 6-month follow-up angiography and intravascular ultrasound (IVUS) were performed. Clinical follow-up was required at 30 days, 6, 12, 18, and 24 months. Study stent implantation was successful in all patients, with a mean stent length of 28.4 +/- 11 mm. Six-month angiographic outcomes showed that mean lumen diameter stenosis did not change (2.22 +/- 0.56 mm postprocedure; 2.26 +/- 0.60 mm at 6 months follow-up; P = NS). Similarly, mean percent diameter stenosis did not change significantly (15.7 +/- 8.6% postprocedure, 19.3 +/- 11% at follow-up; P = NS). The absolute late lumen loss was -0.03 +/- 0.28 mm with a 6-month in-stent restenosis rate of 0%. IVUS follow-up revealed in-stent obstruction volume of only 4.9 +/- 6.8%. Long-term clinical follow-up showed target lesion revascularization at 12 months was only 4%, with target vessel revascularization of only 12%. The CYPHER sirolimus-eluting stent was safe and effective in the treatment of CTO compared to historical data with bare metal stents.