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

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.

Ascophyllum nodosum and Fucus vesiculosus ameliorate restenosis via improving inflammation and regulating the PTEN/PI3K/AKT signaling pathway

Restenosis is a common complication following coronary angioplasty.The traditional use of seaweeds for health benefits has increasingly been explored,however few studies exist reporting its protective effects on the development of restenosis and gut dysbiosis.The aim of this study was to investigate the potential of seaweed extracts(SE) of Ascophyllum nodosum and Fucus vesiculosus in inhibiting intimal hyperplasia in a rat model of restenosis and its underlying mechanisms in macrophages and vascular smooth muscle cells(vSMCs).16S rRNA sequencing was done to investigate the regulatory effect of SE on the gut microbiome of injured rats.As indicated by the results,SE significantly inhibited the progression of intimal hyperplasia in vivo,attenuated inflammation in macrophages and could inhibit the proliferation,dedifferentiation and migration of vSMCs.It was observed through immunoblotting assays that treatment with SE significantly upregulated PTEN expression in macrophages and inhibited the upregulation of PI3K and AKT expression in vSMCs.Meanwhile,according to the 16S rRNA gene sequencing analysis,supplementation with SE modulated gut microbiota composition in injured rats.In conclusion,SE could ameliorate intimal hyperplasia by inhibiting inflammation and vSMCs proliferation through the regulation of the PTEN/PI3K/AKT pathway and modulating the gut microbiome.

Prospective randomized study to evaluate and compare the post-procedural sexual function in patients undergoing semi-rigid ureterorenoscopy for distal ureteric stones in three different operating room settings

Objective:To evaluate and compare the effect of semi-rigid ureterorenoscopy on post-procedural sexual function with three different operating room settings.Methods:In this prospective randomized study,consecutive sexually active patients with normal pre-operative sexual function undergoing uncomplicated semi-rigid ureterorenoscopy for distal ureteric stones were randomized into three groups,with three different operating room settings.Procedure-related anxiety and sexual function were assessed pre-operatively using Amsterdam Preoperative Anxiety and Information Scale and Brief Sexual Function Inventory(in males)and Female Sexual Function Index-6(in females),respectively.All the participants were stented following the procedure,and the stent was removed after 3 weeks.Post-procedural sexual function and general discomfort were assessed and compared between three groups at 1 week,3 weeks,and 12 weeks.The effect of surgery-related anxiety,preoperative sexual function,age,and general discomfort(including stent-related discomfort)on post-procedural sexual function were analyzed using multiple regression analysis.A p-value of less than 0.05 was considered statistically significant.Results:Totally,327 eligible patients were randomized into three groups.The group of patients who underwent the procedural with a screen separating the operating area from the patient vision,while the patient could watch the endoscopy through a separate monitor,had better post-procedural sexual function compared to those who had total vision of the operating area as well as to those whose eyes were blocked.This difference was statistically significant.This post-procedural reduction in sexual function could not be attributed to in situ stent alone.Conclusions:Our study showed that semi-rigid ureterorenoscopy can have significant negative effect on sexual function,which can be reduced with proper preoperative counseling and an ideal operating room settings.

Clinical and angiographic characteristics of asymptomatic restenosis after PCI

Objective To analyze the clinical and angiographic characteristics associated with asymptomatic versus symptomatic restenosis after percutaneous coronary intervention(PCI).Methods One hundred and sixty eight patients who underwent percutaneous revascularization and 6 month follow up angiography were recruited from 2001 to 2002, in which Fifty nine patients with angiographic restenosis ( ≥50% diameter stenosis) were analyzed. Multivariate analysis evaluated 24 clinical and angiographic variables, comparing those with and without angina. Results Restenosis occurred in 32 patients with clinical silence (55%) and 27 patients with angina. Male sex ( P =0.03 ), absence of antianginal therapy with nitrates ( P =0.002 ) ,greater reference diameter after the procedure ( P =0.04 ), greater reference diameter at follow up (P=0.01), and less lesion severity at 6 months ( P =0.04 ) were univariate predictors of asymptomatic restenosis. By multivariate analysis, only male, greater reference diameter at follow up, and less lesion severity at 6 months were associated with restenosis without angina.Conclusions Approximately half of patients with angiographic restenosis have no symptoms. The only multivariate predictors of silent restenosis at 6 months were male sex, greater reference diameter at follow up, and less lesion severity on follow up angiography.

Experimental Study of Adenovirus Vector Mediated-hVEGF_(165) Gene on Prevention of Restenosis after Angioplasty

This study evaluated the effects of adenovirus vector mediated human vascular endothelial growth factor-165 (hVEGF 165) gene on prevention of restenosis after angioplasty. Rabbit models of bilateral carotid artery injury were established by balloon denudation. The recombinant adenoviruses containing hVEGF 165 cDNA was directly injected into left side of the injured carotid arteries. On day 3 and week 3 after transfection the expression of VEGF was observed by RT-PCR and immunohistochemistry. The thrombokinesis, reendothelialization (rET) and intimal hyperplasia in carotid arteries were evaluated by computerized image analysis system 3 weeks after gene transfer. The changes in the VEGF gene-treated side were compared with the control side. Our results showed that 3 days and 3 weeks after hVEGF 165 gene transfer the VEGF mRNA and antigen expression were detected in vivo. 3 weeks after the transfer, the carotid artery rET was markedly better in the VEGF gene-treated group compared with the control. The thrombokinesis, intima area/media area (I/M), maximal intimal and medial thicknesses (IT max and MT max) demonstrated a statistically significant decrease in arteries treated with VEGF gene as compared with the control group. It is concluded that VEGF gene transfer could be achieved by intra-arterial injection of recombinant adenoviruses. It might accelerate the restoration of endothelial integrity, inhibit thrombokinesis and attenuate intimal hyperplasia in the injured arteries after VEGF gene transfer. This procedure could be useful in preventing restenosis after angioplasty.

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.

Treatment of coronary in-stent restenosis： a systematic review

Coronary stem 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.

Correlation of restenosis after rabbit carotid endarterectomy and inflammatory cytokines

Objective:To establish rabbit model of restenosis after carotid endartereclomy surgery,and to study tissue inflammatory cytokines(TNF-α,IL-61 involved in restenosis.Methods:A total of 32 rabbits were randomly divided into two groups:model group and control group.The right common carotid artery in rabbits was damaged by carotid endar terectomy in model group.The tissues were harvested at different time points respectively,the pathological changes of the vascular wall after operation were observed at different time points.The changes of expression of tissue vascular wall inflammatory cytokines(TNF-α.IL-6)at different lime points after the surgery was observed by RT-PCR,and the changes of serum inflammatory cytokines(TNT-α,IL-6)were detected by F.I.1SA.Results:The new intima appeared after 7 days of the injury and reached the peak on 28 d which is uneven and significantly thicker than the control group(P<0.01).The tissue inflammatory cytokines(TNF-α,IL-6)were significantlv increased after the rabbit common carotid artery injury,which was significant difference compared with normal control group(P<0.05).Conclusions:The tissue inflammatory factors significantly increase after the rabbit carotid artery injury,which suggests the mutual concurrent effects of inflammatory cytokines can result in the proliferation of vascular restenosis.

Andrographolide inhibits NF-KB activation and attenuates neointimal hyperplasia in arterial restenosis

The NF-kB transcription factors modulate the expression of tissue factor （TF）, E-selectin （CD62E） and vascular cell adhesion molecule-1 （VCAM-1）, which are essential for thrombosis and inflammation. We have previously shown that andrographolide （Andro） covalently modifies the reduced cysteine^62 of p50-a major subunit of NF-kB transcription factors, thus blocking the binding of NF-kB transcription factors to the promoters of their target genes, preventing NF-kB activation and inhibiting inflammation in vitro and in vivo. Here we report that Andro, but not its inactive structural analog 4H-Andro, significantly suppressed the proliferation of arterial neointima （-60% reduction） in a murine model of arterial restenosis. Consistently, p50^-/- mice manifested attenuated neointimal hyperplasia upon arterial ligation. Notably, the same dosage of Andro did not further reduce neointimal formation in p50^-/- mice, which implicates the specificity of Andro on p50 for treating experimental arterial restenosis. The upregulation of NF-kB target genes, including TF, E-selectin and VCAM-1, and the increased deposition of leukocytes （mainly CD68^＋ macrophages） were clearly detected within the injured arterial walls, all of which were significantly abolished by treatment with Andro or genetic deletion of p50. The expression ofTF, E-selectin and VCAM-I was also markedly upregulated in the patient sample of thrombotic vasculitis, indicating the clinical relevance of NF-kB activation in the pathogeneses of occlusive arterial diseases. Our data thus indicate that, by the downregulation of the NF-kB target genes that are critical in thrombosis and inflammation, specific inhibitors of p50, such as Andro, may be therapeutically valuable for preventing and treating thrombotic arterial diseases, including neointimal hyperplasia in arterial restenosis.

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.

Matrix metalloproteinase 9 level as an indicator for restenosis following cervical and intracranial angioplasty and stenting

Cervical and intracranial angioplasty and stenting is an effective and safe method of reducing the risk of ischemic stroke, but it may be affected by in-stent restenosis. The present study in-vestigated serum level of matrix metalloproteinase 9 as a predictor of restenosis after 40 patients underwent cervical and/or intracranial angioplasty and stenting. Results showed that resteno-sis occurred in 30% （3/10） of patients when the serum level of matrix metalloproteinase 9 at 3 days after surgery was 2.5 times higher than preoperative level. No restenosis occurred when the serum level of matrix metalloproteinase 9 at 3 days after surgery was not 2.5 times higher than preoperative level. Restenosis occurred in 12% （2/17） of patients when the serum level of matrix metalloproteinase 9 was higher than preoperative level for more than 30 days after surgery, but only occurred in 4% （1/23） of patients when the serum level of matrix metalloproteinase 9 was higher than preoperative level for less than 30 days after surgery. However, the differences observed were not statistically signiifcant （P 〉 0.05）. Experimental ifndings indicate that when the serum level of matrix metalloproteinase 9 is 2.5 times higher than preoperative level at 3 days after cervi-cal and intracranial angioplasty and stenting, it may serve as a predictor of in-stent restenosis.

New predictors of in-stent restenosis in patients with diabetes mellitus undergoing percutaneous coronary intervention with drug-eluting stent

Background Percutaneous coronary intervention （PCI） had become the major therapeutic procedure for coronary artery disease （CAD）, but the high rate of in-stent restenosis （ISR） still remained an unsolved clinical problem in clinical practice. Increasing evidences suggested that diabetes mellitus （DM） was a major risk factor for ISR, but the risk predictors of ISR in CAD patients with DM had not been well characterized. The aim of this study was to investigate the clinical and angiographic characteristic predictors significantly associated with the occurrence of ISR in diabetic patients following coronary stenting with drug-eluting stent （DES）. Methods A total of 920 patients with diabetes who diagnosed CAD and underwent coronary DES implantation at Beijing Anzhen Hospital in China were consecutively enrolled from January 2012 to December 2012. Of these, 440 patients underwent the second angiography within ≥ 6 months due to the progression of treated target lesions. Finally, 368 of these patients who met the inclusion and exclusion criteria were followed up by angiography after baseline PCI. According to whether ISR was detected at follow-up angiography, patients were divided into the ISR group （n = 74） and the non-ISR group （n = 294）. The independent predictors of ISR in patients with DM were explored by multivariate Cox＇s proportional hazards regression models. Results A total of 368 patients （260 women and 108 men） with a mean ages of 58.71 ± 10.25 years were finally enrolled in this study. Of these, ISR occurred in 74/368 diabetic patients （20.11%） by follow-up angiography. Univariate analysis showed that most baseline characteristics of the ISR and non-ISR group were similar. Patients in the ISR group had significantly higher serum very low density lipoprotein cholesterol （VLDL-C）, triglyceride （TG） and uric acid （UA） levels, more numbers of target vessel lesions, higher prevalence of multi-vessel disease, higher SYNTAX score, higher rate of previous but lower rate of drinking compared with patients in the non-ISR group. The independent predictors of ISR in patients with DM after DES implantation included VLDL-C （HR = 1.85, 95% CI： 1.24-2.77, P = 0.002）, UA （per 50 μmol/L increments, HR = 1.19, 95% CI： 1.05 1.34, P = 0.006）, SYNTAX score （per 5 increments, HR = 1.34, 95% CI： 1.03-1.74, P = 0.031） and the history ofPCI （HR = 3.43, 95% CI： 1.57-7.80, P = 0.003） by the multivariate Cox＇s proportional hazards regression analysis. Conclusions The increased serum VLDL-C and UA level, higher SYNTAX score and the history of previous PCI were independent predictors of ISR in patients with DM after coronary DES implantation. It provided new evidence for physi- cians to take measures to lower the risk oflSR for the better management of diabetic patients after PCI.

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

Background Epicardial adipose tissue （EAT） is significantly associated with the formation and composition of coronary atherosclerotic plaque, cardiac events and the clinical prognosis of coronary heart disease. But, whether increased EAT deposition may affect the incidence of in-stent restenosis （ISR） is currently unclear. This study used coronary computed tomography angiography （CCTA） as a mean to investigate whether increased EAT volume was associated with ISR. Methods A total of 364 patients who underwent 64-slice CCTA examination for the evaluation of suspected coronary artery disease, and subsequently underwent percutaneous coronary intervention （PCI） for the first time, and then accepted coronary angiography （CA） follow-up for ISR examination in one year, were retrospectively included in this study. EAT volume was measured by CCTA examination. CA follow-up was obtained between 9 and 15 months. ISR was defined as 〉 50% kuninal diameter narrowing of the stent segment or peri-stent segment. EAT volume was compared between patients with and without ISR and additional well-known predictors of ISR were compared. Results EAT volume was significantly increased in patients with ISR compared with those without ISR （154.5 ± 74.6 mL vs. 131.0 ± 52.2 mL, P 〈 0.001）. The relation between ISR and EAT volume remained significant after adjustment for conventional cardiovascular risk factors and angiographic parameters. Conclusions EAT volume was related with ISR and may provide additional information for future ISR.

Aggressive restenosis after percutaneous intervention in two coronary loci in a patient with human immunodeficiency virus infection

A 54-year-old black African woman, 22 years human immunodeficiency virus(HIV)-positive, presented with an acute coronary syndrome. She was taking two nucleoside reverse transcriptase inhibitors and two protease inhibitors. Viral load and CD4 count were stable. Angiography revealed a right coronary artery lesion, which was treated with everolimus eluting stent. She also underwent balloon angioplasty to the first diagonal. She re-presented on three different occasions and technically successful coronary intervention was performed. The patient has reported satisfactory compliance with dual anti platelet therapy throughout. She was successfully treated with surgical revascularisation. The patient did not experience any clinical recurrence on follow up. This case demonstrates exceptionally aggressive multifocal and recurrent instent restenosis in a patient treated for HIV infection, raising the possibility of an association with HIV infection or potentially components of retro viral therapy.

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.

Restenosis after recanalization for Budd-Chiari syndrome: Management and long-term results of 60 patients

BACKGROUND Budd-Chiari syndrome is defined as hepatic venous outflow tract obstruction.For Asian Budd-Chiari syndrome patients,the major treatment modality is recanalization(percutaneous transluminal angioplasty with or without stent implantation).The cumulative 1-,5-,and 10-year primary patency rates and survival rates are reported to be excellent or satisfactory,but the long-term outcome of patients with restenosis(the most common complication after recanalization)is unknown.AIM To explore the treatment strategy for restenosis in patients with Budd-Chiari syndrome after interventional therapy and to evaluate the long-term follow-up results.METHODS The clinical data and follow-up results of 60 patients with restenosis after interventional therapy from November 1983 to December 2013 were retrospectively analyzed.RESULTS Sixty patients with restenosis were retrospectively divided into a percutaneous transluminal angioplasty(PTA)group(40 patients)and a PTA+stent group(20 patients)according to the primary recanalization method.For the patients with restenosis in the PTA group,13 refused treatment,and 27 received further treatment;among these patients,five had a second restenosis,two had a third restenosis,and one had a fourth restenosis.For the patients with restenosis in the PTA+stent group,nine refused treatment,ten received PTA alone,and the other received PTA+stent implantation.Among the patients who received further treatment,five had a second restenosis,three had a third restenosis,and one had a fourth restenosis.The 1-,5-,10-,20-,and 25-year cumulative survival rates of the 38 patients who received further treatment after restenosis were 100%,78.3%,78.3%,70.5%,and 70.5%,respectively;however,for the 22 patients who refused treatment,the survival rates were 72.7%,45.9%,30.6%,10.2%,and unavailable,respectively(P<0.001).CONCLUSION Long-term follow-up after interventional therapy is very important.Active treatment for patients with restenosis can improve prognosis,and minimally invasive treatment strategies for restenosis allows to obtain satisfactory results.

Restenosis of a drug eluting stent on the previous bioresorbable vascular scaffold successfully treated with a drug-coated balloon: A case report

BACKGROUND The in-stent restenosis(ISR)rates are reportedly inconsistent despite the increased use of second-generation drug eluting stent(DES).Although bioresorbable vascular scaffold(BVS)have substantial advantages with respect to vascular restoration,the rate of scaffold thrombosis is higher with BVS than with DES.Optimal treatment strategies have not been established for DES-ISR to date.CASE SUMMARY We report on a case of a 60-year-old man patient with acute coronary syndrome.He had a history of ST-segment elevation myocardial infarction associated with very late scaffold thrombosis and treated with a DES.Coronary angiography revealed significant stenosis,suggesting DES-ISR on the previous BVS.Optical coherence tomography(OCT)identified a plaque rupture and a disrupted scaffold strut in the neointimal proliferation of DES.To treat the DES-ISR on the previous BVS,we opted for a drug-coated balloon(DCB)after a balloon angioplasty using a semi-compliant and non-compliant balloon.The patient did not experience adverse cardiovascular events on using a DCB following the use of intensive dual antiplatelet therapy and statin for 24 mo.CONCLUSION This case highlights the importance of OCT as an imaging modality for characterizing the mechanism of target lesion failure.The use of a DCB following the administration of optimal pharmacologic therapy may be an optimal strategy for the treatment and prevention of recurrent BVS thrombosis and DES-ISR.

The Mechanical Study of Vascular Endothelial Growth Factor on the Prevention of Restenosis after Angioplasty

The mechanism of vascular endothelial growth factor (VEGF) on the prevention of restenosis after angioplasty was investigated. The cultured vascular endothelial cells (VEC) were incubated with the conditioned medium (CM) from vascular smooth muscle cells (VSMC) infected with recombinant adenoviruses containing the hVEGF 165 gene. To observe the effects of VEGF on proliferation and NO, ET, 6-keto-PGF1α secretion of VEC, WST-1 method, Griess method and radioimmunoassay were used respectively. The PDGF-B mRNA transcription in VECs was detected by RT-PCR. It was showed that NO, 6-keto-PGF1α and OD value were markedly increased in a dose-dependent manner in the VEGF-treated groups as compared with those in the control group, while ET and PDGF-B mRNA were significantly decreased in the VEGF-treated groups (P<0.05 or P<0.01). Adenovirus vector mediated hVEGF 165 gene could promote the proliferation of VECs and improve NO, PGI 2 secretion, inhibit ET secretion and PDGF-B mRNA transcription in the VECs. The above results offered further theoretical evidence for VEGF on the prevention of restenosis after angioplasty.

Incidence, Predictors, Treatment, and Long-Term Prognosis of Patients with Restenosis after Long Drug-Eluting Stent Implantation for Coronary Arteries

Background: Few data on the clinical course and management of patients experiencing restenosis after implantation of long drug-eluting stents treatment for coronary arteries was available. Objectives: The aim of this study was to evaluate the incidence, predictors, and long-term outcomes of patients with in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) with long (33 mm & 38 mm) drug-eluting stents (DES) for long lesions in coronary arteries including left anterior descending artery (LAD), Lt circumflex artery (Lt Cx), right coronary artery (RCA), obtuse marginal artery (OM) & posterior descending artery (PDA). Methods: Between July 2009 and October 2010, 421 long DES had being implanted in 421 consecutive patients with significant coronary artery stenosis, with 371 patients (88%) undergoing routine follow up, clinical follow up done by exercise stress test at 6 & 12 months after stenting for 126 patients (34%), in 124 patients (33.5%) follow up was done by Computed Tomography angiography & 121 patients (32.5%) with clinically driven angiographic follow-up. A major adverse cardiac event was defined as the composite of death, myocardial infarction (MI), or target-lesion revascularization (TLR) within 15 months. Results: All patients who underwent clinical follow up were asymptomatic. The overall incidence of angiographic (CT or conventional) ISR with long (33 mm & 38 mm) DES was 4% (15 out of 371 stents) with 8 (53.3%) focal-type and 7 (46.7%) with diffuse-type ISR. Six patients (40%) under-went repeated PCI, seven (46.7%) underwent bypass surgery, and 2 (13.3%) were treated medically. During long-term follow-up (ranging from 12 - 26 months), there were no deaths, 3 (0.8%) MI, and 13 (3.5%) repeated target-lesion revascularization (PCI or CABG) cases. The incidence of major adverse cardiac event was 5.3% in the medical group, 10.1% in the repeated PCI group, and 21.4% in the bypass surgery group. Multivariate analysis showed that the occurrence of DES-ISR did not affect the risk of death or MI. Conclusions: The incidence of ISR was 4% after long DES stenting for coronary arteries. The long-term clinical prognosis of patients with long DES-ISR associated with coronary artery stenting might be benign, if the patient has optimal treatment.

Local drug-delivery balloon for proliferative occlusive in-stent restenosis after drug-eluting stent

Drug-coated balloon has been developed as an alternative to drug-eluting stents for in-stent restenosis but the performance of drug infusion balloon in such setting has not been previously described. We present a case of particularly aggressive in-stent restenosis after drug eluting stent implantation treated with a new kind of drug infusion balloon developed in order to overcome the impossibility to inflate regular drug-coated balloon for several dilatation.