Treatment of Coronary In-Stent Restenosis: A Systematic Review

Coronary stent implantation has significantly improved percutaneous coronary intervention and enabled the management of early complications of plain balloon angioplasty. However, a new complication has accompanied these improvements: in-stent restenosis (ISR) arising from neointimal hyperplasia. ISR after coronary angioplasty is currently one of the main limitations of this method, leading to the recurrence of exertional angina pectoris or acute coronary syndromes. The clinical incidence of ISR after bare-metal stent (BMS) implantation is approximately 20%–35%. The use of drug-eluting stents (DES) has led to a further decrease in the occurrence of ISR to 5%–10%. Evidence resulting from controlled clinical studies suggests that DES and drug-eluting balloon catheters (DEB) provide the best clinical and angiographic results in the treatment of ISR. We undertook a systematic review of the pathophysiology, diagnostics and treatment options for BMS- and DES-ISR. We discuss recent randomised studies, comparing different DES or DEB used for BMS or DES-ISR treatment, as well as the use of new biovascular scafolds and the topic of scafold restenosis.     

药物洗脱支架术后冠状动脉造影随访无再狭窄患者光学相干断层成像检查结果分析

Objective:To evaluate neointimal coverage after Drug Eluting Stent implantation without no restenosis during angiographic follow up by using optical coherence tomography(OCT).Methods:18 case enrolled into this project who received angiography follow up and OCT checkout.Results:1.Totally,4709 struts were analyzed and 88.6% were completely covered with neointimal,and 0.7% were partly covered and 8.1% were uncovered.The rate of late malapposition of struts was 2.6%.The average neointimal hyperplasia thickness...     

Advantages and disadvantages of biodegradable platforms in drug eluting stents

Coronary angioplasty with drug-eluting stent(DES)implantation is currently the most common stent procedure worldwide.Since the introduction of DES,coronary restenosis as well as the incidence of target vessel and target lesion revascularization have been significantly reduced.However,the incidence of very late stent thrombosis beyond the first year after stent deployment has more commonly been linked to DES than to baremetal stent(BMS)implantation.Several factors have been associated with very late stent thrombosis after DES implantation,such as delayed healing,inflammation,stent mal-apposition and endothelial dysfunction. Some of these adverse events were associated with the presence of durable polymers,which were essential to allow the elution of the immunosuppressive drug in the first DES designs.The introduction of erodable polymers in DES technology has provided the potential to complete the degradation of the polymer simultaneously or immediately after the release of the immunosuppressive drug,after which a BMS remains in place.Several DES designs with biodegradable(BIO)polymers have been introduced in preclinical and clinical studies, including randomized trials.In this review,we analyze the clinical results from 6 observational and randomized studies with BIO polymers and discuss advantages and disadvantages of this new technology.     

Vessel healings after stenting with different polymers in STEMI patients

Background Different stents implantation in ST-segment elevation myocardial infarction (STEMI) patients may influence the long term prognosis by affecting vessel healings after stenting. The aim of this study was to evaluate the vessel healings after implantation of drug eluting stents (DES) with biodegradable or durable polymer or of bare-metal stents (BMS) in patients with acute STEMI. Methods This study included 50 patients, who underwent follow up angiogram and optical coherence tomography (OCT) assessment about one year after percutaneous coronary intervention (PCI) for STEMI. According to the initial stents types, these patients were classified to durable (n = 19) or biodegradable polymer sirolimus-eluting stents (n = 15), or BMS (n = 16) groups. The conditions of stent struts coverage and malapposition were analyzed with OCT technique. Results A total of 9003 struts were analyzed: 3299, 3202 and 2502 from durable or biodegradable polymer DES, or BMS, respectively. Strut coverage rate (89.0%, 94.9% and 99.3%, respectively), malapposition presence (1.7%, 0.03% and 0 of struts, respectively) and average intimal thickness over struts (76 ± 12 μm, 161 ± 30 μm and 292 ± 29 μm, respectively) were significantly different among different stent groups (all P < 0.001). Conclusions Vessel healing status in STEMI patients is superior after implantation of biodegradable polymer DES than durable polymer DES, while both are inferior to BMS     

A novel polymer-free dual-drug eluting stent with nanotechonology

Durable polymers used for first-generation drug-eluting stents potentially contribute to persistent inflammation and late stent thrombosis. BICARE （Lepu Medical Technology Co., Ltd, Beijing, China） is a novel polymer-free stent system with nanotechnology and elutes rapamycin （1.6 μg/mm2） and probucol （0.8 μg/mm2）. The millpores on the surface of the stents were produced by nanotechnology. Studies on in-vitro release profile and the preliminary feasibility and safety of the BICARE stent were conducted. The results of release profile study demonstrated the ability of dual-drug polymer-free loading stents to release rapamycin and probucol in a controlled and sustained manner. The preliminary feasibility and safety of BICARE dual-drug polymer-free stent are demonstrated firstly in human study. Optical coherence tomography （OCT） findings indicated excellent stent strut coverage at 4-month. Further pivotal randomized trial will confirm if this early results could translate into longer term safety and efficacy benefits.     

Relationship between hyperhomocysteine and long-term outcome of coronary artery disease patients after drug-eluting stent implantation

<正>Objective To explore the relationship between hyperhomocysteinemia(H-Hcy)and long-term outcome of coronary artery disease(CAD)patients after drug-eluting stent(DES)implantation in a single centre.Methods A total of 1 408 consecutive patients implanted with DES in our department between March 2011 and January 2013     

Unusual penetration of plastic biliary stent in a large ampullary carcinoma: A case report

Endoscopic biliary stenting is a well-established treatment of choice for many obstructive biliary disorders.Commonly used plastic endoprostheses have a higher risk of clogging and dislocation.Distal stent migration is an infrequent complication.Duodenum is the most common site of a migrated biliary stent.Intestinal perforation can occur during the initial insertion or endoscopic or percutaneous manipulation,or as a late consequence of stent placement.A 52-year-old male who presented with obstructive jaundice underwent endoscopic retrograde cholangiopancreatography(ERCP) with plastic stent placement.However,jaundice did not improve and he then underwent ERCP which revealed the plastic stent penetrating the ampullary tumor into the duodenal wall causing malfunction of the stent.A new plastic stent was inserted and the patient underwent Whipple’s operation.He is currently doing well after the operation.     

Longitudinal stent compression of everolimus-eluting stent: A report of 2 cases

Second generation drug eluting stents(DES) have shown better safety and efficacy in comparison to first generation DES,because of thinner struts,nondurable polymers and coating with better anti-proliferative drugs.The newer DES with cobalt alloy base have demonstrated a greater trackability,deliverability,conformability,flexibility and radio-opacity.However,these thin strut stents have a downside of poor longitudinal axial strength,and therefore get easily deformed/ compressed at their end with a slight trauma during exchange of various catheters.We hereby report two cases of "longitudinal stent compression(LSC)" of everolimus-eluting stent,which happened during percutaneous coronary intervention of right coronary artery.Both the cases were successfully managed with non-compliant balloon dilatation.Various reasons for LSC and its management are discussed in the article.     

The incremental risk of noncardiac surgery on adverse cardiac events following coronary stenting

Background Recent coronary stent placement and noncardiac surgery contribute to the risk of adverse cardiac events, but the relative contributions of these two factors have not been quantified.Objectives This research was designed to determine the incremental risk of noncardiac surgery on myocardial infarction(MI) and coronary revascularization following coronary stenting.Methods A U.S. retrospective cohort study of patients receiving coronary stents at Veterans Affairs medical centers between 2000 and 2010 was used to match patients undergoing noncardiac surgery within 24 months of stent placement to two patients with stents not undergoing surgery. Patients were matched on stent type and cardiac risk factors present at the time of stent placement. A composite endpoint of MI and / or cardiac revascularization for the 30-day interval post-surgery was calculated. Adjusted risk differences(RD) were compared across time periods following stent implantation, using generalized estimating equations.Results We matched 20,590 surgical patients to 41,180 nonsurgical patients. During the 30-day interval following noncardiac surgery, the surgical cohort had higher rates of the composite cardiac endpoint(3.1% vs. 1.9%;RD: 1.3%; 95% confidence interval: 1.0% to 1.5%). The incremental risk of noncardiac surgery adjusted for surgical characteristics ranged from 3.5% immediately following stent implantation to 1% at 6 months, after which it remained stable out to 24 months. Factors associated with a significant reduction in risk following surgery more than 6 months post-stent included elective inpatient procedures(ΔRD: 1.8%; P = 0.01), highrisk surgery(ΔRD: 3.7%; P = 0.01), and drug-eluting stent(DES)(ΔRD: 1.3%; P = 0.01).Conclusions The incremental risk of noncardiac surgery on adverse cardiac events among post-stent patients is highest in the initial 6 months following stent implantation and stabilizes at 1.0% after 6 months. Elective, high-risk,inpatient surgery, and patients with DES may benefit most from delay from a 6-month delay after stent placement.(From: Journal of the American College of Cardiology Volume 64, Issue 25, 30 December 2014, Pages 2730-2739)     

Stent displacement in endoscopic pancreatic pseudocyst drainage and endoscopic management

A pancreatic pseudocyst(PPC)is a collection of pancreatic fluid enclosed by a non-epithelialized,fibrous or granulomatous wall.Endoscopic pancreatic pseudocyst drainage(PPD)has been widely used clinically to treat PPCs.The success and complications of endoscopic PPD are comparable with surgical interventions.Stent displacement is a rare complication after endoscopic PPD.Almost all the complications of endoscopic PPD have been managed surgically,and there is rare report involving the endoscopic treatment of intraperitoneal stent displacement.We report here a case of stent displacementafter endoscopic ultrasound-and fluoroscopy-guided PPD in a 41-year-old female patient with a PPC in the tail of the pancreas.The endoscopic treatment was successfully performed to remove the displaced stent.The clinical course of the patient was unremarkable.The cyst had significantly reduced and disappeared by 12 wk.We found that both endoscopic ultrasound and fluoroscopy should be used during endoscopic PPD to avoid stent displacement.The displaced stent can be successfully treated by endoscopic removal.     

Evaluation by optical coherence tomography of neointimal coverage of sirolimus-eluting stent three months after implantation

Confirming complete neointimal coverage after implantation of a drug-eluting stent is clinically important because incomplete stent coverage is responsible for late thrombosis and sudden cardiac death. Optical coherence tomography is a high-resolution (approximately 10 microm) imaging technique capable of detecting a thin layer of neointimal hyperplasia (NIH) inside a sirolimus-eluting stent (SES) and stent malapposition. This investigation evaluated stent exposure and malapposition 3 months after SES implantation using optical coherence tomography in a different clinical presentations, such as acute coronary syndrome (ACS) and non-ACS. Motorized optical coherence tomographic pullback (1 mm/s) was performed at 3-month follow-up to examine consecutive implanted 31 SESs in 21 lesions in 21 patients (9 with ACS and 12 with non-ACS). NIH thickness inside each strut and percent NIH area in each cross section were measured. In total, 4,516 struts in 567-mm single-stented segments were analyzed. Overall, NIH thickness and percent NIH area were 29 +/- 41 microm and 10 +/- 4%, respectively. Rates of exposed struts and exposed struts with malapposition were 15% and 6%, respectively. These were more frequent in patients with ACS than in those with non-ACS (18% vs 13%, p <0.0001; 8% vs 5%, p <0.005, respectively). In conclusion, neointimal coverage over a SES at 3-month follow-up is incomplete in ACS and non-ACS. Our study suggests that dual antiplatelet therapy might be continued >3 months after SES implantation.     

Comparison of neointimal coverage by optical coherence tomography of a sirolimus-eluting stent versus a bare-metal stent three months after implantation

No detailed data regarding neointimal coverage of bare-metal stents (BMSs) at 3 months after implantation was reported to date. This investigation was designed to evaluate the neointimal coverage of BMSs compared with sirolimus-eluting stents (SESs) using optical coherence tomography. A prospective optical coherence tomographic follow-up examination was performed 3 months after stent implantation for patients who underwent BMS (n = 16) or SES implantation (n = 24). Neointimal hyperplasia (NIH) thickness on each stent strut and percentage of NIH area in each cross section were measured. Malapposition of stent struts to the vessel wall and the existence of in-stent thrombi were also evaluated. There were 5,076 struts of SESs and 2,875 struts of BMSs identified. NIH thickness and percentage of NIH area in the BMS group were higher than in the SES group (351 +/- 248 vs 31 +/- 39 mum; p <0.0001; 45.0 +/- 14% vs 10.0 +/- 4%; p <0.0001, respectively). The frequency of uncovered struts was higher in the SES group than the BMS group (15% vs 0.1%; p <0.0001). Malapposed struts were observed more frequently in the SES group than the BMS group (15% vs 1.1%; p <0.0001). In conclusion, there was no difference in incidence of in-stent thrombus between the 2 groups (14% vs 0%; p = 0.23). The present study showed almost all BMS struts to be well covered at a 3-month follow-up, suggesting that patients receiving BMS stents may not require dual-antiplatelet therapy >3 months after implantation.     

光学相干断层成像评价不同类型药物洗脱支架置入术后的内膜覆盖

目的 应用光学相干断层成像(OCT)对比不同类型药物洗脱支架(DES)置入后的内膜覆盖情况.方法 入选62例在我院置入DES(15.3±5.7)个月后行OCT检查的患者,依据置入支架类型分为Cypher支架组(病例数=26,支架数=57)、Endeavor支架组(病例数=17,支架数=23)和Firebird支架组(病...     

Neointimal coverage of zotarolimus-eluting stent at 1, 2, and 3 months’ follow-up: an optical coherence tomography study

Incomplete neointimal coverage and malapposed struts after stenting are associated with increased risk of stent thrombosis. We aimed to evaluate neointimal coverage early after Resolute zotarolimus-eluting stent (R-ZES) implantation using optical coherence tomography (OCT). A total of 20 patients with de novo native coronary lesions with R-ZES were enrolled. Among these patients, 20 stented lesions in 19 patients were evaluated at 1, 2, and 3 months after R-ZES implantation. The strut apposition and neointimal coverage were evaluated by OCT. Neointimal hyperplasia (NIH) thickness and percentage of covered struts and the proportion of incompletely apposed struts were measured at 1-mm intervals. The mean percentages of covered stent struts were over 85 % within 3 months (88.4 ± 6.3 % at 1 month, 95.5 ± 5.5 % at 2 months, 93.6 ± 3.5 % at 3 months). The percentages of incompletely apposed struts were not significantly different among the groups (4.4 ± 4.2 % at 1 month, 1.9 ± 1.9 % at 2 months, 3.1 ± 2.2 % at 3 months, p = 0.51). Mean NIH thickness (38.9 ± 8.1 μm at 1 month, 70.6 ± 18.8 μm at 2 months, 54.1 ± 5.9 at 3 months, p = 0.0016) was thickest in the 2 months group. Most of all OCT findings within 2 months demonstrated neointimal coverage with low signal intensity. The neointimal coverage of ZES-R was over 85 % within 3 months. These data may support shorter requirement of dual antiplatelet therapy duration with R-ZES.     

First-in-Man Evaluation of a Sirolimus-Eluting Stent With Abluminal Fluoropolymeric/Triflusal Coating With Ultrathin Struts by OCT at 9 Months' Follow-Up: The PROMETHEUS Study

ObjectivesWe sought to investigate stent healing and neointimal hyperplasia with ihtDEStiny drug-eluting stent (DES) by optical coherence tomography (OCT) examination conducted 9 months after implantation.BackgroundThe currently used DES present certain features that have been linked separately to their better performance in terms of efficacy and safety.MethodsFirst-in-man, prospective and multicenter study including patients treated with ihtDEStiny stent undergoing OCT examination at 9 months follow up. The ihtDEStiny stent is a sirolimus eluting stent with an oval shape ultrathin struts (68 μm) and an abluminal coating of a fluoropolymer containing the antiplatelet agent triflusal. Primary endpoint was the percentage of obstruction of the in-stent volume by the neointima.ResultsIn 58 patients (63 lesions) in-stent late lumen loss was 0.11 ± 0.23 mm (95% CI 0.05–0.16) with only in 6% of stents being > 0.5 mm and in-segment binary stenosis was 1.6%. In OCT mean neointima volume obstruction was 10.5 ± 6.9% with a mean neointima thickness of 110.9 ± 89.8 μm. The proportion of uncovered struts was 2.5%, malapposed struts 1.1% and malapposed/uncovered struts 0.7% and no subclinical thrombi detected. Mean incomplete stent apposition area was 0.1 ± 0.1 mm². At 12 months target lesion revascularization rate was 3% and no stent thrombosis was reported.ConclusionsIn this study the ihtDEStiny stent has shown a very low degree of neointimal proliferation associated with a low rate of uncovered/malapposed struts and total absence of subclinical thrombi at 9 months follow up.     

Angioscopic Findings after Drug-Eluting Stent Implantation

In-stent restenosis is the Achilles' heel of standard or bare-metal stent (BMS) implantation, occurring in 10-40% of the patients. Drug-eluting stent (DES) are supposed to inhibit inflammation and neointimal growth and, subsequently, in-stent restenosis. The neointimal proliferation inside the stent is recognized as lumen late loss on angiograms or as an obstruction area (or volume) on intravascular ultrasound (IVUS) in chronic phase. Coronary angioscopy provides direct visualization of the lumen and is capable of macroscopic pathologic diagnosis of atherosclerotic plaques and intracoronary thrombi. This modality is also able to supply detailed information on stent coverage with neointimal hyperplasia. The neointimal growth inside the stent is evaluated as white neointimal coverage over the stent struts. Angioscopic view inside the DES is quite different from that inside the BMS. In this article, the difference in angioscopic findings between the DES and the BMS is shown.     

Difference in neointimal coverage at chronic stage between bare metal stent and sirolimus-eluting stent evaluated at stent-strut level by optical coherence tomography

Compared with the bare metal stent (BMS), suppression of neointimal growth in the sirolimus-eluting stent (SES) reduced restenosis at the cost of more exposed struts that could impose the risk of stent thrombosis. The present study was conducted to analyze neointimal coverage patterns of stents at a strut-level after implantation of BMS or SES with the use of optical coherence tomography (OCT). We enrolled 35 patients and analyzed neointimal coverage of every strut from 41 stents (BMS: n = 8, SES: n = 33) by using OCT at follow-up of the stent implantation. All of the 371 struts from eight BMSs were covered with ≥100 μm of neointima, while 19.8 and 3.5 % of 3,478 struts from 33 SESs were uncovered (neointimal thickness of <10 μm) and malapposed, respectively. The histogram of neointimal thickness showed basically normal distribution in BMS but skewed in SES. No regional difference in neointimal thickness was observed in BMS (proximal, 535.7 ± 25.2 μm; body, 532.4 ± 17.0 μm; distal, 485.8 ± 27.0 μm). In SES, however, the body segment showed thinner neointima [median 40 μm (interquartile range (IQR) 10–90 μm)] than proximal [60 μm (IQR 10–140 μm), p < 0.001] or distal [50 μm (IQR 10–110 μm), p < 0.001] segment, while uncovered and malapposed struts were more frequent in the proximal and body segments. In conclusion, SES, compared with BMS, showed more suppressed neointimal growth with regional variation: neointimal thickness was the least in the body part while the ratio of exposed and malapposed struts was minimal in the distal segment. OCT was useful for a strut-level analysis of neointimal coverage over the whole stent.     

光学相干断层成像比较猪冠状动脉西罗莫司洗脱支架与佐他莫司洗脱支架置入后早期新生内膜覆盖情况

目的应用光学相干断层成像(OCT)比较西罗莫司洗脱支架(SES)与佐他莫司洗脱支架(ZES)置入后1月内新生内膜覆盖情况。方法 18只中华小型猪平均分为3组,每只猪分别在前降支和右冠状动脉随机置入SES和ZES支架各一枚,3组实验动物分别在第7天、14天、28天进行OCT检查,测量新生内膜厚度、支架内面积、管腔内面积、新生内膜面积、面积狭窄百分比和新生内膜覆盖率,比较ZES与SES置入后1月内新生内膜覆盖情况。结果 OCT测量结果显示,支架置入7天和14天时,ZES与SES两种支架丝表面新生内膜厚度和新生内膜覆盖率均存在显著统计学差异(P<0.001)。同样支架术后28天时ZES与SES支架丝表面新生内膜厚度存在显著统计学差异(244.3±282.3μmvs136.3±91.1μm,P<0.001),新生内膜覆盖率存在显著差异(94.88%±2.93%vs90.96%±4.35%,P=0.008)。结论在支架置入后1个月内,ZES与SES比较新生内膜增生更显著,支架丝表面新生内膜覆盖率更高。     

Preliminary observations using optical coherence tomography to assess neointimal coverage of a metal stent in a porcine model

BackgroundConcerns surrounding late stent thrombosis have prompted the development of novel imaging techniques to assess neointimal coverage. Recent clinical studies have evaluated optical coherence tomography (OCT) to evaluate neointimal coverage, but pathologic correlation in an animal model is lacking. We assessed the hypothesis that OCT could accurately assess early neointimal coverage in a porcine model.MethodsOCT imaging of bare metal stents in each coronary artery was performed at implantation (n=6), Day 4 (n=3), and Day 20 (n=3), and images were evaluated at three cross-sections per stented segment. Neointimal strut coverage was categorized by OCT as covered or uncovered, and neointimal thickness was determined (Day 20). Pathological correlation was obtained using scanning electron microscopy (SEM) to assess strut coverage (Day 4) and histomorphometry to quantify neointimal thickness (Day 20).ResultsAt Day 4, OCT imaging detected 28 (26%) of 109 uncovered struts, and the ratio of uncovered/total strut area by SEM was 31%. All imaging modalities showed complete coverage at Day 20. Mean (±SE) neointimal thickness at Day 20 was 109±6 μm by OCT (n=116 struts) and 93±5 μm by pathology (n=68). Mean neointimal thickness on a segment-by-segment basis determined by OCT correlated with mean histomorphometric analysis (Reviewer 1: r=.74, P=.092 and Reviewer 2: r=0.60, P=.212).ConclusionsDay 4 represents an important time point for the assessment of early neointimal coverage in the porcine model. OCT imaging accurately assesses the extent and thickness of early neointimal coverage with good pathologic correlation. OCT represents a promising imaging modality for the in vivo assessment of neointimal coverage.