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Clinical Value of the Quantitative Flow Ratio to Predict Long-term Target Vessel Failure in Patients with in-stent restenosis after Drug-coated Balloon Angioplasty

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Current Medical Science 2024年第3期44卷 561-567页

作者： Xiang-qi WU Long-bo LI Wei YOU Zhi-ming WU Lei ZHAO Zhi-hui WANG Pei-na MENG Bin LIU Fei YE Department of Cardiology Nanjing First HospitalNanjing Medical UniversityNanjing210006China Department of Cardiology The Second Hospital of Jilin UniversityJilin130000China

Objective The study sought to investigate the clinical predictive value of quantitative flow ratio(QFR)for the long-term target vessel failure(TVF)outcome in patients with in-stent restenosis(ISR)by using drug-coated balloon(DCB)treatment after a long-term follow-up.Methods This was a retrospective study.A total of 186 patients who underwent DCB angioplasty for ISR in two hospitals from March 2014 to September 2019 were enrolled.The QFR of the entire target vessel was measured offline.The primary endpoint was TVF,including target vessel-cardiac death(TV-CD),target vessel-myocardial infarction(TV-MI),and clinically driven-target vessel revascularization(CD-TVR).Results The follow-up time was 3.09±1.53 years,and 50 patients had TVF.The QFR immediately after percutaneous coronary intervention(PCI)was significantly lower in the TVF group than in the no-TVF group.Multivariable Cox regression analysis indicated that the QFR immediately after PCI was an excellent predictor for TVF after the long-term follow-up[hazard ratio(HR):5.15×10−5(6.13×10−8−0.043);P<0.01].Receiver-operating characteristic(ROC)curve analysis demonstrated that the optimal cut-off value of the QFR immediately after PCI for predicting the long-term TVF was 0.925(area under the curve:0.886,95%confidence interval:0.834–0.938;sensitivity:83.40%,specificity:88.00;P<0.01).In addition,QFR≤0.925 post-PCI was strongly correlated with the TVF,including TV-MI and CD-TVR(P<0.01).Conclusion The QFR immediately after PCI showed a high predictive value of TVF after a long-term follow-up in ISR patients who underwent DCB angioplasty.A lower QFR immediately after PCI was associated with a worse TVF outcome.

关键词： percutaneous coronary intervention in-stent restenosis target vessel failure quantitative flow ratio

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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

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Cardiology Discovery 2023年第4期3卷 239-248页

作者： Xiao Jin Bingxin Wu Li Han Xiaofeng Zhu Department of Traditional Chinese Medicine The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong 510630China Department of Cardiology Second Affiliated Hospital of Guangzhou University of Chinese Medicine(Guangdong Provincial Hospital of Chinese Medicine)GuangzhouGuangdong 510120China

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.

关键词： Percutaneous coronary intervention in-stent restenosis Competitive endogenous RNA Gene Expression Omnibus datasets

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

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Chinese Medical Journal 2020年第22期133卷 2674-2681页

作者： Jian-Feng Zheng Ting-Ting Guo Yuan Tian Yong Wang Xiao-Ying Hu Yue Chang Hong Qiu Ke-Fei Dou Yi-Da Tang Jin-Qing Yuan Yong-Jian Wu Hong-Bing Yan Shu-Bin Qiao Bo Xu Yue-Jin Yang Run-Lin Gao Department of Cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Department of Cardiology Urumqi Friendship HospitalUrumqiXinjiang 830049China

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.

关键词： in-stent restenosis Neointimal hyperplasia Risk factors Drug-eluting stent

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

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Chinese Medical Journal 2011年第6期124卷 845-850页

作者： XU Yan-lu LI Jian-jun XU Bo ZHU Cheng-gang YANG Yue-jin CHEN Ji-lin QIAO Shu-bin YUAN Jin-qing QIN Xue-wen MA Wei-hua YAO Min LIU Hai-bo WU Yong-jian CHEN Jue YOU Shi-jie DAI Jun XIA Ran GAO Run-lin Department of Cardiology Fuwai Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100037 China

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.

关键词： high sensitivity C-reactive protein inflammation stable angina in-stent restenosis

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

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Chinese Medical Journal 2010年第7期123卷 794-799页

作者： CHEN Shao-liang XU Bo Gary Mintz YE Fei ZHANG Jun-jie KAN Jing SUN Xue-wen ZHANG Ai-ping CHEN Jin-guo QIAN Jun Kwan Tak W Department of Cardiology Nanjing First Hospital Nanjing Medical University Nanjing Jiangsu 210006 China Department of Cardiology Fu Wai Cardiovascular Hospital Beijing 100047 China Cardiovascular Research Foundation New York USA Department of Cardiology Nanjing First Hospital Nanjing Medical University Nanjing Jiangsu 210006 China Department of Cardiology Huainan Oriental Hospital Huainan Anhui 340015 China Department of Cardiology Huainan People's Hospital Huainan Anhui 340016 China Department of Cardiology Chuzhou People's Hospital Chuzhou Anhui 420055 China Department of Cardiology Maanshan Central Hospital MaanshanAnhui 330076 China Department of Cardiology Beth Israel Hospital New York USA

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.

关键词： unprotected left main stenosis in-stent restenosis percutaneous coronary intervention

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

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Chinese Medical Journal 2010年第17期123卷 2405-2409页

作者： ZHOU Xu-chen HUANG Rong-chong ZHANG Bo YIN Da LIANG Bin WANG Shao-peng GUAN Qi-gang SUN Xi-zhuo MIAO Zhi-lin HE Xue-zhi HAN Feng-tong CHENG Ying ZHANG Li ZENG Ding-yin Department of Cardiology First Affiliated Hospital of Dalian Medical University Dalian Liaoning 116011 China Department of Cardiology First Affiliated Hospital of China Medical University Shenyang Liaoning 110001 China Department of Cardiology Dalian Central Hospital Dalian Liaoning 116000 China

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 v

关键词： interleukin-1β sirolimus paclitaxel drug-eluting stent inflammation in-stent restenosis

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

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Chinese Journal of Chemical Engineering 2021年第9期34卷 12-29页

作者： Hang Yao Yuwei He Jinrong Ma Lang Jiang Jingan Li Jin Wang Nan Huang Key Laboratory of Advanced Technology for Materials of the Education Ministry School of Materials Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China Department of Chemical Engineering University of WashingtonSeattle 98195USA Department of Pharmaceutics School of PharmacyFudan University&Key Laboratory of Smart Drug DeliveryMinistry of EducationShanghai 201203China School of Materials Science and Engineering Zhengzhou UniversityZhengzhou 450000China

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.

关键词： Cardiovascular stent modification in-stent restenosis Late stent thrombosis Re-endothelialization Inflammatory modulation

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

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International Journal of Smart and Nano Materials 2019年第1期10卷 11-27,I0002页

作者： Jie Cheng Lucy T.Zhang Department of Mechanical Aerospace and Nuclear Engineering Rensselaer Polytechnic InstituteTroyNYUSA

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.

关键词： Residual stress remodeling growth model in-stent restenosis

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

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World Journal of Cardiology 2021年第4期13卷 95-102页

作者： Irtqa Ilyas Ashish Kumar Devina Adalja Mariam Shariff Rupak Desai Yasar Sattar Saraschandra Vallabhajosyula Nageshwara Gullapalli Rajkumar Doshi Department ofInternal Medicine University of Nevada Reno School of MedicineRenoNV 89509United States Department of Critical Care Medicine Saint John's Medical College HospitalBangalore 560034KarnatakaIndia Department of Internal Medicine GMERS Gotri Medical CollegeVadodara 380021GujaratIndia Department of Cardiology Atlanta VA Medical CenterDecaturGA 30033United States Department of Internal Medicine Icahn School of Medicine at Mount Sinai ElmhurstNew YorkNY 11373United States Interventional Cardiology Emory UniversityAtlantaGA 30322United States

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.

关键词： Intracoronary brachytherapy in-stent restenosis Meta-analysis Drug eluting stent Systematic review Brachytherapy

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

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Laparoscopic, Endoscopic and Robotic Surgery 2019年第3期2卷 59-64页

作者： Yuefeng Zhu Guohua Hu Xueying Ke Kai Liang Department of Vascular Surgery Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China

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 t

关键词： Lower extremity atherosclerosis obliterans De novo lesions in-stent restenosis Drug-eluting balloon

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