Diagnosis and management challenges of in-stent restenosis in coronary arteries

Over the course of the 3 decades, percutaneous coronary intervention(PCI) with stent implantation transformed the practice of cardiology. PCI with stenting is currently the most widely performed procedure for the treatment of symptomatic coronary disease. In large trials, drugeluting stents(DES) have led to a significant reduction in in-stent restenosis(ISR) rates, one of the major limitations of bare-metal stents. Due to these favorable findings, DES was rapidly and widely adopted enabling more complex coronary interventions. Nevertheless, ISR remains a serious concern as late stent complications. ISR mainly results from aggressive neointimal proliferation and neoatherosclerosis. DES-ISR treatment continues to be challenging complications for interventional cardiologists.

Influence of increased epicardial adipose tissue volume on 1-year in-stent restenosis in patients who received coronary stent implantation

Epicardial 脂肪质的织物(吃) 显著地与冠的动脉粥样硬化患者匾，心脏的事件和冠的心疾病的临床的预后的形成和作文被联系。但是，是否增加了吃免职可以影响 in-stent 狭窄(ISR ) 的发生当前是不清楚的。这研究把冠的计算断层摄影术 angiography ( CCTA )用作一个平均数调查是否增加了吃体积与为怀疑的冠的动脉疾病的评估经历了64片 CCTA 检查的 364 个病人全部的 ISR.MethodsA 被联系，并且随后第一次经历了经皮的冠的干预(一种总线标准)，然后为一年里的 ISR 检查的接受冠的 angiography ( CA )后续，回顾地在这研究被包括。吃体积被 CCTA 检查测量。CA 后续在 9 和 15 个月之间被获得。ISR 作为 stent 片断或 peri-stent 片断变窄的 50% 钠直径是 dened。吃体积有或没有 ISR 在病人之间被比较， ISR 的另外的著名预言者是 compared.ResultsEAT 没有 ISR ，体积 signicantly 与那些相比与 ISR 在病人被增加( 154.5 ?潃据畬楳湯??汥敤汲?华??千瀠瑡敩瑮?楷桴???瑳条摥倠?洠杩?戠?湡漠瑰浩污猠牴瑡来?獡潳楣瑡摥眠瑩?敲畤散?潬杮琭牥?慣摲慩?敤瑡?牯??潣灭牡摥眠瑩?湯?楴敭倠?猠牴瑡来?

Drug-eluting balloons versus new generation drug-eluting stents for the management of in-stent restenosis: an updated meta-analysis of randomized studies

Background New-generation drug-eluting stents (DES) was more effective in the treatment of in-stent restenosis (ISR) compared with the first-generation DES. Drug-eluting balloons (DEB) and new-generation DES had been available strategies in treatment of bare-metal stents/DES ISR (BMS/DES-ISR). Six new randomized trials have recently examined the angiographic outcomes and one-year clinical outcomes of DEB and new generation DES in BMS/DES-ISR. However, the optimal management for BMS/DES-ISR lesions remains controversial. Methods We searched the randomized clinical trials evaluating the angiographic outcomes and one-year clinical outcomes of DEB and new-generation DES in patients with BMS/DES-ISR. The primary endpoints were the angiographic outcomes, including the minimal luminal diameter (MLD), diameter stenosis %(DS%), late lumen loss (LLL), and binary restenosis (BR). Results A total of six randomized clinical trials with 1177 BMS/DES-ISR patients were included in our meta-analysis. For angiographic outcomes, there were significantly less MLD and more DS% with DEB compared to new-generation DES (MLD: MD =?0.18, 95% CI:?0.31– ?0.04, P < 0.001;DS%: MD = 5.68, 95% CI: 1.00–10.37, P < 0.001). Moreover, for one-year clinical outcomes, DEB was associated with a significant increase risk in target lesion revascularization (TLR)(RR = 2.93, 95% CI: 1.50–5.72, P = 0.002). However, DEB was associated with higher risks of major adverse cardiac event, target vessel revascularization, TLR, BR, and more DS% only in DES-ISR group. Conclusions DEB and new-generation DES have the similar clinical efficacy for the treatment of BMS-ISR. However, DES showed more MLD, less DS%, and a decreased risk of TLR for the treatment of DES-ISR.

Recent advances in cardiovascular stent for treatment of in-stent restenosis:Mechanisms and strategies

Treatments of atherogenesis,one of the most common cardiovascular diseases(CVD),are continuously being made thanks to innovation and an increasingly in-depth knowledge of percutaneous transluminal coronary angioplasty(PTCA),the most revolutionary medical procedure used for vascular restoration.Combined with an expanding balloon,vascular stents used at stricture sites enable the long-time restoration of vascular permeability.However,complication after stenting,in-stent restenosis(ISR),hinders the advancement of vascular stents and are associated with high medical costs for patients for decades years.Thus,the development of a high biocompatibility stent with improved safety and efficiency is urgently needed.This review provides an overview of current advances and potential technologies for the modification of stents for better treatment and prevention of ISR.In particular,the mechanisms of in-stent restenosis are investigated and summarized with the aim to comprehensively understanding the pathogenesis of stent complications.Then,according to different therapeutic functions,the current stent modification strategies are reviewed,including polymeric drug eluting stents,biological friendly stents,prohealing stents,and gene stents.Finally,the review provides an outlook of the challenges in the design of stents with optimal properties.Therefore,this review is a valuable and practical guideline for the development of cardiovascular stents.

Comparison of the efficacy of drug-eluting balloon for de novo lesions and in-stent restenosis lesions of the femoropopliteal arteries

Objective:To compare the efficacy of drug-eluting balloons for de novo and in-stent restenosis(ISR)for lesions of the femoropopliteal arteries during 12-month follow-up.Materials and methods:A retrospective analysis of 66 patients was performed.These patients had lower extremity atherosclerosis obliterans and were treated with drug-eluting balloons from June 2016 to June 2017.All the lesions were femoropopliteal,including 47 de novo lesions and 19 ISR lesions.Clinical results were followed up at 6 months and 12 months postoperatively.The primary patency rate,target lesion revascularization,Rutherford classification,ankle-brachial index,amputation rate and mortality were compared between the two groups.Results:All the 66 patients underwent the treatment of femoropopliteal artery lesions with unilateral limbs.The surgical success rates were 100%.No adverse events such as acute ischemia or amputation occurred in the hospital.There was no difference between the two groups'Rutherford classification and the ankle-brachial index at the 6-month follow-up(p>0.05).At the 12-month follow-up,the de novo group's Rutherford classification was lower than the ISR group(p=0.026),and the ankle-brachial index of the ISR group was lower(0.66±0.033 vs 0.52±0.056,p=0.036).There was no difference between the patency rate of the de novo group and the ISR group(93.6%vs 84.2%,p=0.229)at the 6-month follow-up.However,the ISR group patency rate was lower at the 12-month follow-up(63.2%vs 85.1%,p=0.048).As for revascularization there was no significant difference between the two groups at the 6-month follow-up(4.2%vs 10.5%,p=0.334),but a higher rate occurred in the ISR group at the 12-month follow-up(26.3%vs 6.4%,p=0.025).There were no significant differences in the mortality or amputation rate between the two groups(p>0.05).Conclusions:Drug-eluting balloons were effective in treating both de novo lesions and ISR lesions in the atherosclerotic femoropopliteal artery,but the 12-month follow-up results of ISR lesions were less favorable than the de novo lesions.

Increased serum TREM-1 level is associated with in-stent restenosis,and activation of TREM-1 promotes inflammation,proliferation and migration in vascular smooth muscle cells

Background and Objective In-stent restenosis(ISR)remains a major limitation of percutaneous coronary intervention despite improvements in stent design and pharmacological agents,whereas the mechanism of ISR has not been fully clarified.In the present study,we sought to investigate the potential association of serum soluble TREM-1(sTREM-1)levels with the incidence of ISR.The role of TREM-1 was evaluated in cultured vascular smooth muscle cells(VSMCs).

Intracoronary brachytherapy for the treatment of recurrent drugeluting stent in-stent restenosis:A systematic review and metaanalysis

BACKGROUND We performed a meta-analysis on observational studies since randomized control trials are not available.We studied intracoronary brachytherapy(ICBT)and recurrent drug eluting stent in-stent restenosis(DES-ISR)to evaluate the procedural success,target lesion revascularization(TLR),incidence of myocardial infarction(MI)and all-cause mortality at 2 years follow-up.AIM To perform meta-analysis for patients undergoing ICBT for recurrent DES-ISR.METHODS We performed a systematic search of the PubMed/MEDLINE,Cochrane and DARE databases to identify relevant articles.Studies were excluded if intracoronary brachytherapy was used as a treatment modality for initial ISR and studies with bare metal stents.We used a random-effect model with DerSimonian&Laird method to calculate summary estimates.Heterogeneity was assessed using I2 statistics.RESULTS A total of 6 observational studies were included in the final analysis.Procedural angiographic success following intra-coronary brachytherapy was 99.8%.Incidence of MI at 1-year was 2%and 4.1%at 2-years,respectively.The incidence of TLR 14.1%at 1-year and 22.7%at 2-years,respectively.All-cause mortality at 1-and 2-year follow-up was 3%and 7.5%,respectively.CONCLUSION Given the observational nature of the studies included in the analysis,heterogeneity was significantly higher for outcomes.While there are no randomized controlled trials or definitive guidelines available for recurrent ISR associated with DES,this analysis suggests that brachytherapy might be the alternative approach for recurrent DES-ISR.Randomized controlled trials are required to confirm results from this study.

Finite Element Simulation of In-Stent Restenosis with Tissue Growth Model

In this study, a finite element simulation of in-stent restenosis (ISR) is conducted to simulate the deployment and expansion of a stent in an occluded artery with a contact model and a mechanics-based growth model. A tissue growth model based on the multiplicative decomposition of deformation is applied to investigate the growth of the plaque and artery wall upon the stent’s implantation. Due to the high stresses at the contact points between the stent struts and the tissue, further tissue injury or restenosis is observed. The simulation results show that after the stent deployment, the von Mises stress is significantly larger in the plaque compared to the artery wall, especially in the region that is in contact with the stent. However, the growth of the plaque and artery tends to even out the stress concentration over time. The tissue growth is found to be more significant near the inner wall than the outer layer. A 0.77 mm restenosis is predicted, which agrees with published clinical observations. The features of the artery growth are carefully analyzed, and the underlying mechanism is discussed. This study is the first attempt to apply finite element analysis to artery restenosis, which establishes a framework for predicting ISR’s occurrence and severity. The results also provide insights into understanding the underlying mechanism of in-stent restenosis.

Clinical study about the effect of Simiao Yong'an Decoction on preventing in-stent restenosis and regulating inflammation and oxidative stress after lower extremity stent angioplasty stenting

Objective:To study the effect of Simiao Yong'an Decoction on the prevention of in-stent restenosis and the regulation of inflammation and oxidative stress after lower extremity stent angioplasty.Methods:A prospective study was conducted on 60 ASO patients who underwent lower extremity stent angioplasty in our hospital between January 2014 and January 2018.The patients were randomly divided into observation group receiving postoperative Simiao Yong'an Decoction combined with antiplatelet drug treatment and control group receiving postoperative antiplatelet drug treatment.The conditions of in-stent restenosis were followed up,and the indicators of coagulation,inflammation and oxidative stress were detected.Results:The incidence of in-stent restenosis in observation group 1 year after operation was significantly lower than that in control group;6 months and 12 months after operation,the ankle brachial index(ABI)levels,minimal lumen diameter(MLD)levels at the stent and superoxide dismutase(SOD)contents of observation group were significantly higher than those of control group,whereas D-dimer(D-D)and fibrinogen degradation product(FDP)levels as well as P-selectin,C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),malondialdehyde(MDA)and inducible nitric oxide synthase(iNOS)contents were significantly lower than those of control group.Conclusions:Simiao Yong'an Decoction can prevent the in-stent restenosis and inhibit the inflammation and oxidative stress after lower extremity stent angioplasty.

Construction and Analysis of an LncRNA-miRNA-mRNA Network Based on Competitive Endogenous RNA Reveal miRNAs Potentially Involved in In-stent Restenosis after Percutaneous Coronary Intervention

Objective:Percutaneous coronary intervention is one of the most common procedures used for the invasive treatment of patients with coronary heart disease;the incidence of in-stent restenosis(ISR)after percutaneous coronary intervention is 5%to 15%.In this study,a competitive endogenous RNA(ceRNA)network was constructed to investigate potential mechanisms involved in ISR.Methods:The expression data for differentially expressed microRNAs(DEmiRNAs)and messenger RNAs(mRNAs)between patients with and without ISR were obtained using limma package.Long noncoding RNAs(lncRNAs)were predicted based on the DEmiRNAs using the miRDB,miRTarBase,and TargetScan databases.An ISR-specific ceRNA network was subsequently constructed and investigated.To verify the key miRNAs of ceRNA,patients with and without ISR were enrolled from Guangdong Provincial Hospital of Chinese Medicine between January 2017 and December 2018(n=8,respectively);plasma was collected from all enrolled patients.Results:Based on the raw data obtained from the Gene Expression Omnibus database,472 DEmiRNAs and 304 differentilly expressed messenger RNAs between patients with and without ISR were identified.A ceRNA network was constructed by combining 270 IncRNAs,3 miRNAs(miR-125,miR-140,and miR-206),and 4 mRNAs(STRADB,TKT,PCTP,and BTG2).The hub genes of the ceRNA network of ISR included the following:miR-125,miR-206,miR-140,PCDHB9,CASC2,BAK1P1,CSPG4P3Y,CSPG4P4Y,STRCP1,and GRIP2.Verification of miRNAs of ceRNA also showed that the expression of miR-206 was upregulated in patients with ISR vs.those without ISR(P<0.05).In contrast,the expression of miR-140 and miR-125 was downregulated in patients with ISR vs.those without ISR(P<0.05).Conclusions:This study constructed noncoding RNA-related ceRNA networks for ISR.The results indicated that miR-206,miR-125,and miR-140 may be biomarkers of ISR.

Role of plasma C-reactive protein in predicting in-stent restenosis in patients with stable angina after coronary stenting

Background The role of plasma high sensitivity C-reactive protein （hs-CRP） in in-stent restenosis （ISR） remains controversial. We investigated plasma hs-CRP level at both admission and follow-up in patients with stable angina （SA）after successful coronary stenting in order to clarify the predictive value of hs-CRP for ISR.Methods We summarized 303 consecutive chronic SA patients with coronary drug-eluting stent （DES） implantation.The ISR was analyzed by quantitative coronary analysis （QCA） at a mean follow-up of 8 months, and the patients were divided into two groups according to the detected ISR as ISR group （n=48） and non-ISR group （n=255）. Plasma hs-CRP was examined at both admission and 8-month follow-up in all patients, standard medication continued throughout the investigation period.Results QCA presented that 48 patients （15.8%） suffered from ISR at follow-up. The basic clinical characteristics were similar between the two groups, while plasma hs-CRP was higher in ISR group than that in non-ISR group at both admission and follow-up, P 〈0.001 respectively. Multivariate regression analysis indicated that plasma hs-CRP level at either admission or follow-up could independently predict ISR occurrence （OR=5.581, 95% Cl 2.532-12.302, P〈0.001and OR=6.299, 95% CI 2.722-14.577, P 〈0.001, respectively）.Conclusions Our data indicate that plasma hs-CRP level may independently predict ISR at both admission and follow-up in SA patients with coronary DES implantation, which implies that a chronic, sustained systemic inflammatory response might be involved in ISR pathogenesis.

Inflammation inhibitory effects of sirolimus and paclitaxel-eluting stents on interleukin-1β-induced coronary artery in-stent restenosis in pigs

Background Coronary artery in-stent restenosis （ISR） and late stent thrombosis remain as important complications of stenting. The inflammation reactions to sirolimus and paclitaxel-eluting stents were investigated in a swine stenosis model induced by interleukin （IL）-1β.Methods Mini pigs （n=12; 2-3 months old and weighing 25-30 kg） were subjected to thoracotomy. Segments （10 mm）of the mid left anterior descending coronary artery and left circumflex coronary artery were exposed and aseptically wrapped with a cotton mesh soaked with IL-1β （5 μg）. After 2 weeks, the animals were anesthetized and quantitative coronary arteriography （QCA） was performed. The stenosis sites were randomized into three groups for stent insertion： a sirolimus-eluting stent （SES） group （FirebirdTM, n=7）, a paclitaxel-eluting stent （PES） group （TAXUSTM, n=9）, and a bare-metal stent （BMS） group （YINYITM, Dalian Yinyi Biomaterials Development Co., Ltd, China, n=8）. The three different stents were randomly implanted into stenosis segments. Expression of monocyte chemoattractant protein-1 （MCP-1）, tumor necrosis factor-alpha （TNF-α）, P-selectin and vascular cell adhesion molecule-1 （VCAM-1） was determined by reverse transcription-coupled polymerase chain reaction （RT-PCR）.Results QCA showed severe stenosis in IL-1β treated segments. The SES and PES groups showed lower 1-month angiographic late lumen loss （LLL） within the stent and the lesion compared with BMS （P 〈0.05） by follow-up QCA. The SES showed lower LLL than that of PES in reducing 1-month inflammation lesions in pigs by follow-up QCA （（0.15±0.06）mm vs. （0.33±0.01） mm, P 〈0.0001）. The neointimal hyperplasia areas in SES and PES showed lower than those of BMS （SES （11.6±1.7） mm2, PES （27.2±1.6） mm2 vs. BMS （76.2±1.3） mm2, P 〈0.0001）. The mRNA expression of MCP-1 by RT-PCR in SES and PES showed lower than that of BMS at 30 days after stenting （SES 0.20±0.03, PES 0.48±0.49 vs.BMS 0.58±0.07, P 〈0.05）. Levels of VCAM-1 in SES were significantly lower than those of PES and BMS （SES 0.35±0.08 vs. PES 0.65±0.13, BMS 0.70±0.06, P 〈0.05）. Histochemical immunostaining of vessel walls showed lower inflammatory chemokine MCP-1 expression in the SES and PES groups compared with BMS.Conclusion SESs were superior in reducing 1-month angiographic LLL in inflammation lesions in pigs, strongly suggesting that SESs can suppress inflammatory reactions in ISR at multiple points.

A novel mechanism of inhibiting in-stent restenosis with arsenic trioxide drug-eluting stent: Enhancing contractile phenotype of vascular smooth muscle cells via YAP pathway

Objective:Arsenic trioxide(ATO or As2O3)has beneficial effects on suppressing neointimal hyperplasia and restenosis,but the mechanism is still unclear.The goal of this study is to further understand the mechanism of ATO's inhibitory effect on vascular smooth muscle cells(VSMCs).Methods and results:Through in vitro cell culture and in vivo stent implanting into the carotid arteries of rabbit,a synthetic-to-contractile phenotypic transition was induced and the proliferation of VSMCs was inhibited by ATO.F-actin filaments were clustered and the elasticity modulus was increased within the phenotypic modulation of VSMCs induced by ATO in vitro.Meanwhile,Yes-associated protein(YAP)nuclear translocation was inhibited by ATO both in vivo and in vitro.It was found that ROCK inhibitor or YAP inactivator could partially mask the phenotype modulation of ATO on VSMCs.Conclusions:The interaction of YAP with the ROCK pathway through ATO seems to mediate the contractile phenotype of VSMCs.This provides an indication of the clinical therapeutic mechanism for the beneficial bioactive effect of ATO-drug eluting stent(AES)on in-stent restenosis(ISR).

Clinical characteristics of early and late drug-eluting stent in-stent restenosis and mid-term prognosis after repeated percutaneous coronary intervention

Background:The mechanism and characteristics of early and late drug-eluting stent in-stent restenosis(DES-ISR)have not been fully clarified.Whether there are different outcomes among those patients being irrespective of their repeated treatments remain a knowledge gap.Methods:A total of 250 patients who underwent initial stent implantation in our hospital,and then were readmitted to receive treatment for the reason of recurrent significant DES-ISR in 2016 were involved.The patients were categorized as early ISR(<12 months;E-ISR;n=32)and late ISR(≥12 months;L-ISR;n=218).Associations between patient characteristics and clinical performance,as well as clinical outcomes after a repeated percutaneous coronary intervention(PCI)were evaluated.Primary composite endpoint of major adverse cardiac events(MACEs)included cardiac death,non-fatal myocardial infarction(MI),or target lesion revascularization(TLR).Results:Most baseline characteristics are similar in both groups,except for the period of ISR,initial pre-procedure thrombolysis in myocardial infarction,and some serum biochemical indicators.The incidence of MACE(37.5%vs.5.5%;P<0.001)and TLR(37.5%vs.5.0%;P<0.001)is higher in the E-ISR group.After multivariate analysis,E-ISR(odds ratio[OR],13.267;[95%CI 4.984-35.311];P<0.001)and left ventricular systolic dysfunction(odds ratio[OR],6.317;[95%CI 1.145-34.843];P=0.034)are the independent predictors for MACE among DES-ISR patients in the mid-term follow-up of 12 months.Conclusions:Early ISR and left ventricular systolic dysfunction are associated with MACE during the mid-term follow-up period for DES-ISR patients.The results may benefit the risk stratification and secondary prevention for DES-ISR patients in clinical practice.

Long-term outcomes of percutaneous coronary intervention for in-stent chronic total occlusion

Background:The development of the technique has improved the success rate of percutaneous coronary intervention(PCI)for instent chronic total occlusion(IS-CTO).However,long-term outcomes remain unclear.The present study sought to investigate long-term outcomes of PCI for IS-CTO.Methods:A total of 474 IS-CTO patients were enrolled at two cardiac centers from 2015 to 2018 retrospectively.These patients were allocated into either successful or failed IS-CTO PCI groups.The primary endpoint(major adverse cardiac events[MACE])consisted of recurrent angina pectoris(RAP),target-vessel myocardial infarction(MI),heart failure,cardiac death,or ischemia-driven target-vessel revascularization(TVR)at follow-up.Multivariable Cox regression analysis was used to investigate the association between treatment appropriateness and clinical outcomes.Results:A total of 367 patients were successfully treated with IS-CTO PCI while 107 patients had failed recanalization.After a median follow-up of 30 months(interquartile range:17-42 months),no significant difference was observed between the two groups for the following parameters:cardiac death(successful PCIvs.failed PCI:0.9%vs.2.7%;adjusted hazard ratio[HR]:1.442;95%confidence interval[CI]:0.21-9.887;P=0.709),RAP(successful PCIvs.failed PCI:40.8%vs.40.0%;adjusted HR:1.025;95%CI:0.683-1.538;P=0.905),heart failure(successful PCIvs.failed PCI:6.1%vs.2.7%;adjusted HR:0.281;95%CI:0.065-1.206;P=0.088),target-vessel related MI(successful PCIvs.failed PCI:1.5%vs.2.7%;adjusted HR:1.150;95%CI:0.221-5.995;P=0.868),MACE(successful PCIvs.failed PCI:44.2%vs.45.3%;adjusted HR:1.052;95%CI:0.717-1.543;P=0.797).More patients were free of angina in the successful IS-CTO PCI group compared with failed PCI in the first(80.4%vs.60%,P<0.01)and second years(73.3%vs.60.0%,P=0.02)following up.Successful IS-CTO PCI had a lower incidence of MACE in the first and second years(20.2%vs.40.0%,P<0.01;27.9%vs.41.3%,P=0.023)compared with failed PCI.After a median follow-up of 30 months,the reocclusion rate was 28.5%and TVR was 26.1%in the successful IS-CTO PCI group.Receiving>18 months of dual antiplatelet therapy(DAPT)was an independent predictor of decreased risk of TVR(HR:2.682;95%CI:1.295-5.578;P=0.008)or MACE(without TVR)(HR:1.898;95%CI:1.036-3.479;P=0.038)in successful IS-CTO PCI.Conclusions:After a median follow-up of 30 months,the successful IS-CTO PCI group had MACE similar to that of the failed PCI group.However,the successful IS-CTO PCI group had improved angina symptoms and were free from requiring coronary artery bypass grafting in the first or second years.To decrease MACE,DAPT was found to be essential and recommended for at least 18 months for IS-CTO PCI.

Efficacy and safety of drug-eluting stent implantation for the treatment of in-stent restenosis occurring within bare-metal stent and drug-eluting stent

Objective:Although drug-eluting stent(DES) implantation is the primary treatment modality for bare-metal stent(BMS) in-stent restenosis(ISR),little is known about the efficacy and safety profile of DES in the treatment of DES-ISR.The goal of this study was to compare the clinical outcomes following DES treatment for BMS-ISR and DES-ISR.Methods:Rates of major adverse cardiac events(MACE) were compared in 97 consecutive patients who underwent DES implantation for the treatment of ISR(56 BMS-ISR and 41 DES-ISR) from January 2004 to December 2008.Results:Baseline clinical and procedural characteristics were comparable,except that the DES used in the BMS-ISR group was longer and had a larger diameter.The length of follow-up was(28.60±1.96) and(20.34±1.54) months for the BMS-ISR and DES-ISR groups,respectively.One patient(1.8%) experienced non-cardiac mortality and one(1.8%) had target-vessel revascularization(TVR) in the BMS-ISR group.In the DES-ISR group,three patients(7.3%) died of sudden death with a documented acute ST-segment elevation myocardial infarction,and three suffered TVR(7.3%).Kaplan-Meier analysis indicated that cumulative survival probability and MACE-free probability were both significantly lower for the DES-ISR group(log rank test P=0.047 and P=0.005,respectively).In Cox regression analysis,DES-ISR remained an independent predictor for future MACE occurrence after adjustment for other factors(compared with BMS-ISR,risk ratio(RR)=8.743,95% confidence interval(CI) 1.54-49.54,P=0.014).Switching to a different type of DES to treat DES-ISR did not improve the prognosis.Conclusion:DES-ISR patients had a poorer prognosis than BMS-ISR patients after DES therapy.

Clinical outcome after management of unprotected left main in-stent restenosis after bare metal or drug-eluting stents

Background Implantation of either bare metal stent （BMS） or drug-eluting stent （DES） has been used in every day practice for patients with unprotected left main stenosis （UPLMS）. There are still a lack of data regading the subsequent results of UPLMS in-stent restenosis （ISR）. The present study aimed at determing the clinical outcome of UPLMS ISR patients after implantation of either BMS or DES.Methods Patients with UPLMS ISR after stenting were included. The primary endpoint was the cumulative major adverse cardiac events （MACE）, including cardiac death, myocardial infarction （Ml）, and target vessel revascularization （TVR）.Results UPLMS ISR rate was 14.8% （n=73, 15.7% after BMS, 14.5% for DES） after average of （3.89±2.01） years （range from 1 to 10.5 years） follow-up. Angiographic follow-up between 6-8 months was available in 85.3%. Of these,repeat percutaneous coronary intervention （PCI） was used in 62 （84.9%） patients, with medicine only in 9 （12.4%） and coronary artery bypass graft （CABG） in 2 （2.7%）. Most repeat PCI patients were with unstable angina （87.0%）, and had decreased left ventricular ejection fraction （（42.58±5.12）%）, fewer focal/ostial left circumflex branch （LCX） lesions, in relative to medicine only group. After （31.9±23.3） months, the MACE, Ml, TVR and cardiac death were 31.5%, 1.4%, 24.1% and 8.2%, respectively. Definite and possible stent thrombosis occurred in 1 （1.4%） patient.Conclusions Medical therapy for asymptomatic isolated ostial LCX was safe. Repeat PCI for UPLMS ISR was associated with acceptable early and short-term clinical outcome. Further study was needed to elucidate the role of CABG in treating UPLMS ISR.

Simulation of vessel tissue remodeling with residual stress:an application to in-stent restenosis

We present a numerical procedure to model the artery wall remodeling stimulated by stenting considering varying degree of residual stresses.This framework sets up biological remodeling with the existence of residual stress.Previous studies suggest that the residual stress originates from the growth and remodeling of the premature tissue.Meanwhile,it is known that tissue remodeling can happen under mechanical loading.However,none of the existing research studies the impact of residual stress on the mechanical-driven growth of biomaterials.To fill this gap,we build a numerical framework that couples the residual stress with a growth model,and examine its impact on tissue remodeling.The proposed approach is applied to in-stent restenosis,where the tissue remodeling process is modeled with finite element method,and the residual stress is generated geometrically using open angle method.The result shows that residual stress reverses the radial distribution of stress concentration,which is ameliorated by tissue remodeling.The thickening of vessel wall tends to increase with residual stress,which links to more severe in-stent restenosis.The results demonstrate the important interplay between residual stress and tissue remodeling.The findings suggest that residual stress should be considered in the future simulation of tissue remodeling.

The value of serum levels of aldosterone in predicting in-stent restenosis after coronary stent implantation

In recent years,Percutaneous coronary intervention(PCI) as an effective treatment for coronary heart disease has been widely carried out in China.However,people is still confronted with the problem that the incidence of in-stent restenosis (ISR) after PCI.Some risk factors of coronary heart disease have been obviously known,but the in-dependent predictor factors for the ISR has not been clear.Clarifying risk factors for ISR to establish interfering meas-ures may be a new direction for PCI treatment in the future.At present,it has been reported that aldosterone (ALD) may be involved in ISR.In order to further investigate the relationship between the serum ALD levels and ISR,our re-search was to determine the ALD and other serum markers to explore the impact factors of ISR.Methods We meas-ured serum ALD,high sensitivity C-reactive protein (hs-CRP) ,adiponectin (ADP) and other indicators in 258 pa-tients with coronary stenting,and made routine follow-up for 6-9 months to perform coronary angiography.According to the results of coronary angiography,all patients were divided into restenosis group and non-restenosis group.We an-alyzed the relationship between ALD,other indicators and ISR to explore whether serum ALD was an independent risk factor ISR.Results Serum ALD levels were significantly higher in restenosis group than non-restenosis group.Logis-tic regression analysis showed that diabetes,ALD,hs-CRP and complex lesions were also independent risk factors for ISR (P < 0.05) ,while the ADP was as a protective factor for ISR (P < 0.05) .Conclusions ALD is one of inde-pendent risk factors for ISR after undergoing coronary stent implantation in patients.It has the possibility of becoming one new method in this medical field.

Stenting for Aorto-Ostial In-Stent Restenosis via Side Strut of an Excessively Protruding Stent Guided by Intracoronary Imaging

To the Editor:A 54-year-old man was admitted for progressive chest pain.Four years ago,the patient had surgical aortic valve replacement (SAVR),and preoperative multislice computed tomography (MSCT)showed no coronary stenosis.A year after SAVR,he presented with chest pain,and coronary angiogram revealed an isolated ostial left main coronary artery (LMCA) stenosis [Figure 1a].A 4.0mm × 18.0mm stent (Medtronic Vascular, Santa Rosa,CA,USA)was implanted without a high-pressure postdilation [Figure 1b].The patient was discharged on aspirin, ticagrelor (replaced with clopidogrel after 3months),and statins. Unfortunately,the stent was found to protrude into the aorta by approximately 10mm by MSCT at 4-month follow-up [Figure 1c].