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Percutaneous coronary interventions have progressed through the era of plain balloon dilation, bare-metal stent insertion to drug-eluting stent treatment, which has significantly reduced the acute occlusion and restenosis rates of target vessels and improved patient prognosis, making drug-eluting stents the mainstream interventional treatment for coronary artery disease. In recent years, drug-coated balloons (DCBs) have become a new treatment strategy for coronary artery disease, and the drugs used in the coating and the coating technology have progressed in the past years. Without permanent implant, a DCB delivers antiproliferative drugs rapidly and uniformly into the vessel wall via the excipient during a single balloon dilation. Many evidence suggests that DCB angioplasty is an effective measure for dealing with in-stent restenosis and de novo lesions in small coronary vessels. As more clinical studies are published, new evidence is emerging for the use of DCB angioplasty in a wide range of coronary diseases, and the indications are expanding internationally. Based on the latest research from China and elsewhere, the Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon has updated the previous DCB consensus after evidence-based discussions and meetings in terms of adequate preparation of in-stent restenosis lesions, expansion of the indications for coronary de novo lesions, and precise guidance of DCB treatment by intravascular imaging and functional evaluation. [ABSTRACT FROM AUTHOR]

Vascular smooth muscle cells (VSMCs) proliferation is a critical event that contributes to the pathogenesis of vascular remodeling such as hypertension, restenosis, and pulmonary hypertension. Increasing evidences have revealed that VSMCs proliferation is associated with the activation of receptor tyrosine kinases (RTKs) by their ligands, including the insulin-like growth factor receptor (IGFR), fibroblast growth factor receptor (FGFR), epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptor (PDGFR). Moreover, some receptor tyrosinase inhibitors (TKIs) have been found and can prevent VSMCs proliferation to attenuate vascular remodeling. Therefore, this review will describe recent research progress on the role of RTKs and their inhibitors in controlling VSMCs proliferation, which helps to better understand the function of VSMCs proliferation in cardiovascular events and is beneficial for the prevention and treatment of vascular disease. [ABSTRACT FROM AUTHOR]

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Objective. The aim of this study is to evaluate the clinical efficacy of Tongxinluo capsules in preventing coronary restenosis based on meta-analysis and network pharmacology research methods and to preliminarily explore its intervention mechanism. Methods. First, through meta-analysis, we comprehensively searched databases such as CNKI, Wanfang, PubMed, the Cochrane Library, and Web of Science to find out the randomized controlled trials of Tongxinluo capsules in the treatment of coronary restenosis until February, 2022. According to the Cochrane Library, risk bias assessment tools were used to evaluate the included literature and Review Manager 5.2 software was used to conduct statistical analysis of the included studies. Then, based on network pharmacology, through TCMSP database and BATMAN-TCM database screening, the chemical components of Tongxinluo capsules and their related effects, symptom, and common targets were analyzed. String net was used to construct protein-protein interaction (PPI) network, and R3.6.1 software was used to carry out GO biological process enrichment analysis and KEGG signaling pathway enrichment analysis to clarify key pathways. Results. The meta-analysis finally included 10 RCTs with a total of 1318 subjects. Meta-analysis results showed that Tongxinluo capsules combined with conventional cardiovascular drugs could significantly improve the clinical efficacy of preventing in-stent restenosis and the clinical efficacy of preventing angina pectoris. There was no significant difference in the clinical efficacy of preventing myocardial infarction. Network pharmacology obtained a total of 101 chemical components and 149 targets through the online database. The results of network analysis showed that the targets were mainly involved in receptor ligand activity, carboxylic acid binding, steroid hormone receptor activity, and other related action pathways and were also involved in AGE-RAGE signaling pathway, cell senescence signaling pathway, and other related pathways. Conclusion. Tongxinluo capsules combined with conventional cardiovascular drugs can improve the clinical efficacy of preventing in-stent restenosis and angina pectoris and have a significant effect on reducing inflammatory factors. The comprehensive result of the effect is mainly through the participation of receptor ligand activity, carboxylic acid binding, steroid hormone receptor activity, and other ways to achieve the purpose of treating coronary restenosis. [ABSTRACT FROM AUTHOR]

Context • In-stent restenosis (ISR) is a common clinical complication after carotid artery stenting (CAS) and a major risk for a stent’s fatigue life. Duplex ultrasound (DUS) is widely used for the preliminary evaluation and follow-up of extracranial carotid artery disease, but DUS stenosis grading is mainly based on the original or nonsurgical carotid artery. That grading may not be applicable to carotid artery stenosis after CAS. Objective • The study intended to investigate the predictive value of quantitative analysis of results from the DUS examination in the evaluation of ISR following CAS. Design • The research team designed a control analysis of result samples. Setting • The study took place in the Ultrasound Department at the Affiliated Yantai Yuhuangding Hospital of Qingdao University in Yantai, Shandong, China. Participants • Participants were 103 patients who underwent carotid artery stenting (CAS) between March 2017 and April 2018 at the hospital. Outcome Measures • The study used Doppler DUS and digital subtraction angiography (DSA) of the carotid artery at 12 months postoperatively to analyze the consistency of DUS and DSA in the evaluation of ISR. Taking the results of the DSA examination as the standard, the research team analyzed the differences between those results and the indicators from the DUS examination for participants with different severities of stenosis. The research team plotted the receiver operating characteristic curve (ROC) and evaluated the diagnostic efficiency of DUS indicators in the determination of restenosis, including diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. Results • The DSA examination showed that stenosis severity was 0%-30% for 51 participants, 31%-50% for 27 participants, 51%-80% for 16 participants, and >80% for 9 participants. The DUS showed that stenosis severity was 0%-30% for 35 participants, 31%-50% for 38 participants, 51%-80% for 22 participants, and >80% for 8 participants. The consistency was found to be Kappa (ĸ)=0.74. Taking the DSA as the standard, the peak systolic velocity (PSV), end diastolic velocity (EDV), peak systolic velocity of the internal carotid artery/peak systolic velocity of the common carotid artery (PSVICA/PSVCCA) significantly increased in participants with a stenosis severity of 51-80% and >80%, compared with those with a stenosis severity of <50%, and the difference was statistically significant (P<.05). The ROC curve showed that the area under curve (AUC) of the PSV predicting restenosis at a >50% severity was significantly higher than those of the EDV and PSVICA/PSVCCA (P<.05). Where the optimal cut-off-off point for the PSV was 195 cm/s, the ROC curve showed that the AUC of the PSV predicting restenosis at an >80% severity was significantly higher than that of the EDV and PSVICA/PSVCCA (P < .05). Where the optimal cut-off point for the PSV was 280 cm/s, the PSV had significantly higher diagnostic accuracy, sensitivity, and positive predictive value than the EDV and PSVICA/PSVCCA in evaluating the restenosis at a severity of >50% and >80%. Conclusions • Doppler DUS can effectively evaluate restenosis after carotid artery stenting (CAS), where a PSV ≥195 cm/s and 280 cm/s can be used as the reference indicators for >50% and >80% restenosis. [ABSTRACT FROM AUTHOR]

Background Calcification has been proven to be a marker of atherosclerosis and is related to an increased risk of ischemic stroke. Additionally, calcification was reported to be prevalent in patients with stenotic lesions of the intracranial vertebral artery. Thus, reliable imaging facilities for evaluating plaque calcification have remarkable significance in guiding stenting and predicting patient outcomes. Optical coherence tomography (OCT) has a unique advantage in its ability to detect calcium and to achieve three-dimensional volumetric calcium characterization. Methods From March 2017 to September 2018, seven cases of calcified lesions with intracranial vertebral artery stenosis were investigated using OCT, before and after the placement of an Apollo balloon-mounted stent. Transcranial color-coded duplex sonography was performed to identify restenosis with a mean follow-up time of 13.3 months in this case series. Results All calcified lesions were evaluated quantitatively and qualitatively using OCT. Among all cases, five had macrocalcifications and two had spotty calcifications. Severe in-stent restenosis was observed in two cases, both with macrocalcifications. Conclusions This study suggests a potential relationship between macrocalcifications and the risk of in-stent restenosis of the intracranial vertebral artery. These preliminary findings obtained from a limited sample should be verified by prospective large-scale studies. [ABSTRACT FROM AUTHOR]

Cilostazol, a phosphodiesterase III inhibitor, has vasodilating and antiplatelet properties with a low rate of bleeding complications. It has been used over the past 25 years for improving intermittent claudication in patients with peripheral artery disease (PAD). Cilostazol also has demonstrated efficacy in patients undergoing percutaneous revascularization procedures for both PAD and coronary artery disease. In addition to its antithrombotic and vasodilating actions, cilostazol also inhibits vascular smooth muscle cell proliferation via phosphodiesterase III inhibition, thus mitigating restenosis. Accumulated evidence has shown that cilostazol, due to its "pleiotropic" effects, is a useful, albeit underutilized, agent for both coronary artery disease and PAD. It is also potentially useful after ischemic stroke and is an alternative in those who are allergic or intolerant to classical antithrombotic agents (eg, aspirin or clopidogrel). These issues are herein reviewed together with the pharmacology and pharmacodynamics of cilostazol. Large studies and meta-analyses are presented and evaluated. Current guidelines are also discussed, and the spectrum of cilostazol's actions and therapeutic applications are illustrated. [ABSTRACT FROM AUTHOR]

Drug eluting stents (DES) have revolutionised interventional cardiology and currently represent the standard for percutaneous coronary interventions (PCI). However, due to several limitations, new strategies are required, especially in very complex lesions. Drug-coated balloons (DCB) offer an attractive therapeutic alternative, and have already obtained a Class I recommendation for the treatment of in stent restenosis (ISR) with Level A of evidence. Moreover, the role of DCB has been tested in several other settings, such as de novo large vessel disease, multivessel disease or very complex lesions, with promising results regarding safety and effectiveness. In this context, a hybrid strategy consisting in the use of a DES and DCB with the aim of reducing the amount of metal implanted and minimising the risk of ISR and stent thrombosis could become the solution for very complex lesions. Several important studies already demonstrated very good angiographic results in terms of late lumen loss and restenosis for this approach in bifurcation lesions. Moreover, for long diffuse coronary disease similar rates of MACE, TVR, and TLR at 2-year follow-up in comparison to a DES-alone strategy were found. What is more, the use of this strategy in high-bleeding risk patients could safely permit the practitioners to reduce the DAPT duration, as data is suggesting. As our daily practice already strongly incorporated this strategy and with more data expected from important trials, it is our strong believe that the hybrid approach can become a standard treatment choice in the near future. [ABSTRACT FROM AUTHOR]

In-stent restenosis (ISR) is the main factor affecting the outcome of percutaneous coronary intervention (PCI), and its main pathological feature is neointimal hyperplasia. Huotan Jiedu Tongluo decoction (HTJDTLD) is an effective traditional Chinese medicine (TCM) prescription for the treatment of vascular stenosis diseases. However, the precise anti-ISR mechanism of HTJDTLD remains unclear. Here, we investigated whether HTJDTLD can inhibit the excessive activation of endoplasmic reticulum stress (ERS) and reduce the level of autophagy factors through regulating the PERK-eIF2α-ATF4 pathway, thereby inhibiting the proliferation of the intima of blood vessels damaged by balloon injury (BI) and preventing the occurrence of ISR. In this study, a 2F Fogarty balloon was used to establish a common carotid artery (CCA) BI model in male Sprague-Dawley rats. Then, HTJDTLD (16.33 g/kg/d) or atorvastatin (1.19 mg/kg/d) was administered by gavage. Four weeks later, hematoxylin-eosin (HE) and Masson staining of the injured CCA were performed to observe the histological changes in the CCA. Immunohistochemistry (IHC) was used to assess the proliferation and dedifferentiation of vascular smooth muscle cells (VSMCs) in the CCA. Western blotting and RT-PCR were used to measure the expression of ERS- and autophagy-related proteins and mRNAs in the CCA. The results indicated that HTJDTLD significantly alleviated BI-induced carotid artery intimal hyperplasia and fibrosis and reduced the neointimal area (NIA) and NIA/medial area (MA) ratio. In addition, HTJDTLD inhibited the proliferation and dedifferentiation of VSMCs, reduced the expression of proliferating cell nuclear antigen (PCNA), and increased the smooth-muscle-α-actin- (SMα-actin-) positive area. HTJDTLD also significantly reduced the expression of the ERS-related factors: GRP78, p-PERK/PERK, p-eIF2α/eIF2α, ATF4, and CHOP. In addition, the expression of the autophagy-related factors, Beclin1, LC3B, and ATG12, was significantly decreased. In addition, in vitro experiments showed that HTJDTLD inhibited the above-mentioned ERS signal molecules in human umbilical vein endothelial cells (HUVEC) and rat aortic smooth muscle cells (A7R5) induced by tunicamycin (TM) and played a crucial role in protecting cells from damage. HTJDTLD may be a very promising drug for the treatment of ISR. [ABSTRACT FROM AUTHOR]

Aim: To evaluate whether high‐intensity interval training (HIIT) was superior to low‐intensity training or usual care among patients after percutaneous coronary intervention. The hypothesis was that HIIT would help patients after percutaneous coronary intervention (PCI) improve cardiopulmonary function, lipid profiles and in‐stent restenosis. Design: A systematic review and meta‐analysis were conducted according to the Preferred Reporting Items for Systematic Review and Meta‐analysis (PRISMA)2009 Checklist. Methods: Randomized controlled trials (RCTs) focusing on HIIT programme in patients after PCI were searched in Cochrane Library, Web of Science Core Collection, EMbase, PubMed, China National Knowledge Infrastructure (CNKI) and SinoMed from the inception to 24 March 2020. Standard Mean difference (SMD) and 95% confidence intervals (CI) were performed to summarize the effect sizes. Results: Six RCTs (247 patients) met the criteria. HIIT programme had a statistically significant effect on raising left ventricular ejection function (LVEF) (SMD = 0.38, 95%CI [0.03, 0.73], I2 = 3%), VO2peak (SMD = 0.94, 95%CI [0.61, 1.28], I2 = 0%), as well as improving the serum level of high‐density lipoprotein (SMD = 0.55, 95%CI [0.06, 1.03], I2 = 0%) and late luminal loss (SMD = −0.65, 95%CI [−1.07, −0.23], I2 = 0%). But HIIT had no prominent effect on improving heart rate (SMD = −0.04, 95%CI [−0.29, 0.21], I2 = 0%). Summarily, HIIT programme appears to be favourable for CAD patients after PCI by improving cardiopulmonary function, such as LVEF and VO2peak, as well as reducing late luminal loss in per stented arteries. Nevertheless, HIIT has no advantage for adjusting heart rate. More researches with rigorous methods are warranted to explore the controversy about lipid profiles. [ABSTRACT FROM AUTHOR]

Background: Although percutaneous coronary intervention (PCI) had become widely employed therapeutic procedure for coronary artery disease, stent restenosis limited the benefits of this revascularization and the question how to prevent such events remained unresolved. While numerous empirical observations suggested Tongguan Capsules (通冠胶囊), a patented Chinese Medicine, could decrease frequency and duration of angina pectoris attacks, evidence supporting its efficacy on restenosis remained inadequate. Objective: This trial was designed to determine whether Tongguan Capsules would reduce restenosis rate in patients after successful stent implantation. Methods: Approximately 400 patients undergoing percutaneous coronary stent deployment were enrolled and randomized to control group or Tongguan Capsules (4.5 g/d) for 3 months. All patients received standard anti-platelet, anti-coagulation and lipid-decreasing treatments, concurrently. The primary clinical endpoint was the 12-month incidence of the major adverse cardiovascular events (defined as cardiac death, myocardial infarction, and recurrence of symptoms requiring additional revascularization). The angiographic end point was restenosis rate at 6 months. Conclusion: This study would provide important evidence for the use of Tongguan Capsules in patients after stent implantation in combination with routine therapies, which may significantly reduce incidence of the restenosis so as to potentially improve the clinical outcomes. (registration number: ChiCTR-TRC- ChiCTR-IIR-17011407) [ABSTRACT FROM AUTHOR]

Background: In patients receiving stents for symptomatic non-thrombotic iliac vein lesions, many clinicians prescribe anti-thrombotic medications. Whether or not anti-coagulation post-venous stenting improves stent patency is unknown. The aim of this investigation is to determine whether prophylactic post-operative anti-thrombotic therapy improves stent patency and/or prevents in-stent restenosis. Methods: The medical records and venous ultrasounds for 389 patients stented for non-thrombotic iliac vein lesions were retrospectively reviewed. Patients were categorized into three anti-thrombotic regimens: Clopidogrel, Aspirin and Clopidogrel, and Apixaban or Rivaroxaban. Patients were routinely assessed for restenosis and stent patency at 6, 26, and 52 weeks and treated with anti-thrombotics for 90 days. Results: Freedom from in-stent restenosis at 6, 26, and 52 weeks were Clopidogrel (91.50, 82.91, 80.95%), Aspirin and Clopidogrel (88.68, 80.03, 80.03%), and Apixaban or Rivaroxaban (91.03, 85.11, 83.18%). Primary patencies were Clopidogrel (98.77, 98.77, 98.10%), Aspirin and Clopidogrel (100, 95.74, 95.74%), and Apixaban or Rivaroxaban (98.70, 98.70, 96.71%). There were no statistically significant differences. Conclusions: The type of post-operative anti-thrombotic therapy for non-thrombotic iliac vein lesions does not appear to improve stent patency or prevent the development of in-stent restenosis. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to evaluate the effects of rehabilitation exercise on coronary artery of the patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). Methods: We searched Medline, EMBASE, Cochrane CENTRAL databases, ISI Web of Science databases, Chinese Biological Medicine Data Base, Chinese knowledge resources, and Wan Fang database. Two researchers independently screened the literature databases, and assessed methodological qualities using the Physiotherapy Evidence Database scale and extracted data. Results: The coronary restenosis rate in rehabilitation exercise group was 10.8% (23/212), and that in the control group was 21% (48/229). Patients with rehabilitation exercise showed a significant reduction in restenosis rate, compared to the control group ((pooled OR: 0.46, 95% CI: 0.26–0.82, p < 0.01); heterogeneity: Chi2=3.86, df =5 (p = 0.57); I2=0%). In addition, the late luminal loss per stent in the rehabilitation exercise group was significantly smaller than that in the control group ((pooled MD: –0.33, 95% CI: –0.52 to –0.13, p < 0.01); heterogeneity: Chi2=0.27, df =1 (p = 0.60); I2=0%). Conclusions: Appropriate rehabilitation exercise reduces the incidence of coronary restenosis after PCI in patients with CHD and contributes to a significant reduction in late luminal loss in the stented coronary segment. Appropriate rehabilitation exercise can reduce the incidence of coronary restenosis after percutaneous coronary intervention in patients with coronary heart disease. Appropriate rehabilitation exercise contributes to a reduction in late luminal loss in the stented coronary segment. [ABSTRACT FROM AUTHOR]

Purpose. To explore the effect of vascular stress changes on endothelial function recovery and vascular restenosis inhibition, under the condition of dynamic degradation process of the degradable stent. Methods. Fitting the material parameters of the hyperelastic vascular constitutive relationship, the stress distribution of the intima of the blood vessel before the stent was implanted and during the dynamic degradation was calculated by numerical simulation. In vitro culture experiments were carried out, and the stretch ratios of the silicone chamber were set to 0%, 5%, 10%, and 15%, respectively, to simulate the effects of different degradation stages on the growth state of endothelial cells. Results. After the stent was completely degraded, the circumferential intimal stress (strain) of the vessel was recovered to 0.137 MPa, 5.5%, which was close to the physiological parameters (0.122 MPa, 4.8%) before stent implantation. In vitro experiments showed that the endothelial cell survival rate was the highest under the condition of circumferential stress (strain) of 0.1 MPa, 5%, and all adhesion growth could be achieved. Conclusions. With the occurrence of degradation process of the stent, the circumferential stress (strain) of the intima was recovered to a range close to physiological parameters, which promotes the growth of endothelial cells. The recovery of intimal function can effectively inhibit the process of vascular restenosis. The results can provide a theoretical basis and experimental platform for the study of coronary intervention for the treatment of vascular restenosis. [ABSTRACT FROM AUTHOR]

Major advances in coronary interventional techniques and pharmacotherapy as well as the use of drug-eluting stents (DESs) have considerably reduced the risk of in-stent restenosis (ISR). However, ISR remains a major clinical challenge. Inflammation and platelet activation are important processes that underlie the pathophysiology of ISR. Parameters related to blood cells, entailing both cell count and morphology, are useful markers of the inflammatory response and platelet activation in clinical practice. Recent studies have highlighted several new combined or derived parameters related to blood cells that independently predict ISR after DES implantation. The neutrophil/lymphocyte ratio, an inflammatory marker, is regarded as a predictor of the risk of ISR and the stability of atherosclerotic plaques. The mean platelet volume, a widely used platelet activation parameter, has been shown to be a predictor of the risk of ISR and the efficacy of antiplatelet therapy. Other markers considered include the platelet/lymphocyte ratio, red blood cell distribution width, and platelet distribution width. This review provides an overview of these parameters that may help stratify the risk of coronary angiographic and clinical outcomes related to ISR. [ABSTRACT FROM AUTHOR]

Background: Metformin is the most commonly used drug for type 2 diabetes. Research has shown that metformin also has a protective effect on endothelium by decreasing endothelial vascular reactivity. We hypothesize that metformin will decrease restenosis/reintervention rates in patients receiving lower extremity non–drug-eluting stents (nDESs) in the superficial femoral artery(SFA) and/or popliteal artery. Materials/Methods: Retrospective study was performed on 187 patients from October 2012 to December 2015 who received an nDES in the SFA and/or popliteal artery. Patients were divided into 3 groups (Table 1) and compared against for duplex based restenosis (>60%) rates, limb loss rates, and reintervention rates. Each patient's Trans-Atlantic-Inter-Society-Consensus II (TASC-II) class was collected. Postoperative duplex was performed 1 week after the procedure, then every 3 months for the first year, then, every 6 months to check for patency. IBM-SPSS-22 was used for all analyses. Results: Average age of the patients was 64.65 ± 73.4 years. 101 patients had 101 procedures performed on the left lower extremity; 86 patients had 86 procedures performed on the right lower extremity; 123 patients were male and 64 were female. Average length of follow-up was 13.1±9.7 months. Most common indication for intervention was claudication, followed by critical limb threatening ischemia. Restenosis and reintervention by groups can be seen in Table 1. No patients experienced limb loss. There were no statistically significant differences between any of the 3 groups and their limb loss, restenosis, or reintervention rates. Conclusions: Despite having multiple proven effects in improving certain clinical outcomes and a proven protective effect on endothelium by decreasing endothelial vascular reactivity, metformin does not appear to reduce restenosis or reintervention rates in patients receiving lower extremity nDESs in the SFA and/or popliteal artery. [ABSTRACT FROM AUTHOR]

Current endovascular surgical technology requires the development and introduction of new methods allowing the drawbacks of existing technologies to be overcome. These methods include combined approaches to recanalization of arteries and prevention of instent restenosis, which can be achieved by combining minimally invasive techniques. It is proposed that the reliability and efficacy of these methods, increasing comfort and radiation safety of the surgeon, can be ensured by introducing new robotic systems into endovascular surgery. [ABSTRACT FROM AUTHOR]

Abstract Nitric oxide (NO) is a highly potent, yet short-lived bioactive molecule with a broad spectrum of physiological functions. Continuous and controllable in situ generation of NO from vascular stent surface can effectively prevent restenosis and thrombosis after its implantation. In this study, inspired by the adhesion and protein cross-linking in the mussel byssus, through immersing the stents into an aqueous solution with dopamine (DA) and copper ions (CuII), we developed a one-step metal-catecholamine assembled strategy to prepare a durable in situ NO-generating biomimetic coating (DA-CuII). Due to the high NO catalytic efficacy and robust chelation of CuII into the DA-CuII network, the coated stents exhibited excellent hemocompatibility. The coating also catalytically decomposed endogenous S-nitrosothiols (RSNOs) from fresh blood, and locally generated NO for over 30 days with a flux comparable to its physiological range (0.5–4 × 10−10 mol × cm−2 × min−1). Moreover, the optimized biomimetic coatings displayed specific cell selectivity to significantly enhance endothelial cell (EC) growth while substantially inhibit smooth muscle cell (SMC) growth and migration. This feature impressively promoted regeneration of a new endothelial cell layer after stent implantation, hence improved the anti-thrombogenic and anti-restenosis qualities of vascular stents in vivo. We envision that our long-term in situ NO-generating coatings could serve as biosurfaces for long-term prevention of stent thrombosis and restenosis. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Abstract Polymeric bioresorbable stents (BRSs) can eliminate the long-term stent restenosis by degrading after vascular remolding and have been recommended for the congenital heart disease treatment. However, the mechanical weakness remains one of main inferiorities of their applications. So, the aim of this study was to develop mechanically reinforced bioresorbable stents (MRBSs) based on poly(p -dioxanone) (PPDO) monofilaments and braiding technology. Axial runners were introduced and MRBSs showed greatly higher compression force and relatively lower viscous performance, as well as longer mechanical stability during degradation, compared with controls. Besides, stent compression behaviors were analyzed experimentally and numerically to investigate their deformation mechanisms. The results showed increased contacting points and friction force among yarns in MRBSs. Also, the skeleton formed in MRBSs attributed to higher yarn bending degree, strain energy and better structure stability during compression. Combined with the non-linear PPDO material stress-strain ratio and thermodynamic theory, yarn based stent compression modes were discussed. In addition, the autocatalysis and nonrandom chain scission degradation behaviors of MRBSs were revealed. [ABSTRACT FROM AUTHOR]

Highlights • The effect of stenosis eccentricity on drug distribution and wall shear stress is studied. • Plaque rupture and thrombosis occur essentially in the proximal zone of the deployment area where the wall shear stress is higher. • Higher wall shear stress is observed in the vessel with eccentric poststenting geometry. • There is no meaningful difference between in-stent restenosis in vessels with concentric or eccentric post-stenting geometries. Abstract Atherosclerosis in the coronary arteries is one of the leading causes of death in the world. Percutaneous coronary interventions (PCI) associated with the implantation of drug eluting stents (DES) is one of the most common forms of revascularization in patients with atherosclerotic coronary artery disease. The use of DES is considered as an effective tool to reduce restenosis after PCI. However despite all the progress made in DES procedures, the rate of restenosis remains relatively high. Mathematical modeling and numerical simulation are believed to play an essential role in identifying zones with a higher risk of in-stent restenosis. In this work the local delivery of a therapeutic agent, from a stent implanted in a coronary artery, is mathematically modeled and numerically simulated. The mathematical model includes the diffusion of the dissolved drug in the biodegradable polymeric coating of the stent, the diffusion and convection of the drug with reversible binding in the viscoelastic arterial wall with plaques of different morphology and the local hemodynamics. The study is an attempt to detect zones with a higher risk of in-stent restenosis and their relation to plaque eccentricity. The location of zones with highest risk of thrombosis and plaque rupture is also addressed. The results are in agreement with claims presented in clinical papers. [ABSTRACT FROM AUTHOR]

Background Antiproliferative drugs in drug eluting stents (DES) are associated with complications due to impaired re-endothelialization. Additionally, adventitial neovascularization has been suggested to contribute to in-stent restenosis (ISR). Since Vascular Endothelial Growth Factors (VEGFs) are the key mediators of angiogenesis, we investigated feasibility and efficacy of local gene therapy for ISR utilizing soluble decoy VEGF receptors to reduce biological activity of adventitial VEGFs. Method Sixty-nine adult WHHL rabbit aortas were subjected to endothelial denudation. Six weeks later catheter-mediated local intramural infusion of 1.5x10e10 pfu adenoviruses encoding soluble VEGF Receptor-1 (sVEGFR1), sVEGFR2, sVEGFR3 or control LacZ and bare metal stent implantation were performed in the same aortic segment. Marker protein expression was assessed at 6d in LacZ cohort. Immunohistochemistry, morphometrical analyses and angiography were performed at d14, d42 and d90. Results Transgene expression was localized to adventitia. All decoy receptors reduced the size of vasa-vasorum at 14d, AdsVEGFR2 animals also had reduced density of adventitial vasa-vasorum, whereas AdsVEGFR3 increased the density of vasa-vasorum. At d42, AdsVEGFR1 and AdsVEGFR2 reduced ISR (15.7 ± 6.9% stenosis, P < 0.01 and 16.5 ± 2.7%, P < 0.05, respectively) vs. controls (28.3 ± 7.6%). Moreover, AdsVEGFR-3 treatment led to a non-significant trend in the reduction of adventitial lymphatics at all time points and these animals had significantly more advanced neointimal atherosclerosis at 14d and 42d vs. control animals. Conclusions Targeting adventitial neovascularization using sVEGFR1 and sVEGFR2 is a novel strategy to reduce ISR. The therapeutic effects dissipate at late follow up following short expression profile of adenoviral vectors. However, inhibition of VEGFR3 signaling accelerates neoatherosclerosis. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the efficacy of drug-coated balloon (DCB) for calcified coronary lesions.Background: Calcified coronary lesions is associated with poor clinical outcomes after revascularization. Recently, DCB is emerging as an alternative strategy for de novo coronary lesions. However, reports describing the efficacy of DCB for calcified coronary lesions are limited.Methods: A total of 81 patients (96 lesions) who electively underwent DCB treatment for de novo coronary lesions were enrolled: 46 patients (55 lesions) in the calcified group and 35 patients (41 lesions) in the non-calcified group. Angiographic follow-up data and clinical outcomes after the procedure were evaluated.Results: The diameter of the DCB used was 2.5 ± 0.5 mm. No bail-out stenting was observed after DCB treatment. Rotational atherectomy was used in 82% of lesions in the calcified group. Follow-up angiography (median, 6.5 months after intervention) was performed for 59 patients (30 in the calcified group and 29 in the non-calcified group). Late lumen loss and rates of restenosis were comparable between the groups (0.03 mm in the calcified group vs -0.18 mm in the non-calcified group, P = 0.093 and 13.9% vs 3.03%, P = 0.095, respectively). The survival rates for target lesion revascularization free survival and major adverse cardiac events at 2 years were comparable between the groups (85.3% vs 93.4%, P = 0.64 and 81.4% vs 88.5%, P = 0.57, respectively).Conclusion: Calcified coronary lesions might dilute the effect of DCB. However, clinical outcomes in the calcified group were similar to those in the non-calcified group. [ABSTRACT FROM AUTHOR]

Objective. To examine the effects and safety of oral compound Chinese medicine (CCM) plus routine western medicine (RWM) in in-stent restenosis (ISR). Methods. Various electronic databases (CBM, CNKI, VIP, Wanfang, PubMed, EMBASE, and Cochrane Library) were searched until April 2017. The quality of the included studies was evaluated, and meta-analyses were performed using RevMan5.3 and STATA 12.0 software. Moreover, funnel plot and Egger’s publication bias plots were analysed to identify publication bias and adverse reactions were reported. A sensitive analysis was carried out according to the quality score. Results. In all, 40 RCTs involving 4536 patients were selected for this review. The pooled estimates of three studies showed that the benefit to the number of ISRs (NoR) was more substantial for CCM plus RWM than for RWM alone (RR 0.24, 95% CI 0.10 to 0.57, P=0.001;I2=0%, P=0.81). The rate of ISR was significantly lower for CCM plus RWM than for the same RWM alone (RR 0.44, 95% CI 0.37 to 0.53, P<0.00001; I2=0%, P=0.95). CCM plus RWM benefitted the rate of ISR when a CM placebo plus RWM was used as the control intervention (RR 0.34, 95% CI 0.20 to 0.57, P<0.0001; I2=0%, P=0.95). The difference of adverse reactions was not significant. For secondary outcomes, the CCM plus RWM group did not reduce the rates of revascularization and cardiac death, but it did reduce the rate of recurrent angina over the results observed in the RWM alone group. In addition, funnel plot and Egger’s publication bias plot indicated that there was publication bias. The association between the use of CCM plus RWM and RWM alone remained significant after the sensitivity analysis excluding studies with low quality score (quality score ⩽ 4) with a pooled RR of 0.41 (95% CI, 0.34–0.50). Conclusion. Oral CCM plus RWM clearly benefitted patients with percutaneous coronary intervention (PCI) because it prevented and treated ISR better than was observed for either RWM alone or a CM placebo plus RWM. [ABSTRACT FROM AUTHOR]

The activity of glucagon-like peptide 1 (GLP-1R) is essential for preventing restenosis following vascular injury; however, the mechanism of dysfunctional GLP-1R glycosylation and ways to enhance the activity of GLP-1R on vascular surfaces in diabetic patients are poorly understood. In the present study, we investigated the N-glycosylation level and role of stress-associated endoplasmic reticulum protein 1 (SERP1) in preventing restenosis following carotid injury in diabetic rats. Our results showed that N-glycosylation levels in both rat aortic endothelial cells (RAOECs) and rat vascular smooth muscle cells (VSMCs) decreased gradually following glucose treatment in a concentration dependant manner. Furthermore, co-immunoprecipitation (Co-IP) analyses indicated that SERP1 could interact with GLP-1R in RAOECs and VSMCs. Moreover, SERP1 enhanced GLP-1R N-glycosylation and increased the production of phosphorylated endothelial nitric oxide synthase (eNOS) as well as proliferation of RAOECs. SERP1 also increased phosphorylated adenosine monophosphate activated protein kinase (AMPK) and decreased the migration of VSMCs. Importantly, intima media thickness (IMT) and neointimal hyperplasia were alleviated in the carotid artery of diabetic rats injected with SERP1 following balloon injury. We also found an increase in re-endothelialization and a decrease in VSMC proliferation in the carotid artery of diabetic rats injected with SERP1. In summary, the remarkable effects of SERP1 on reducing restenosis following vascular injury may contribute to future advancements in the treatment of diabetic vascular complications. [ABSTRACT FROM AUTHOR]

Peripheral vascular disease (PVD) is a prevalent vascular disease that affect a large number of patients. The establishment of optimal treatments to mitigate the intimal hyperplasia (IH)-induced restenosis would help relieve the health burden of the PVD. Ribonucleotide reductase M2 (RRM2) is critical to cellular migration and proliferation. We have previously demonstrated that suppression of RRM2 expression could substantially inhibit hepatocellular carcinoma cell proliferation and migration. We hereby developed RRM2 small interfering RNA (siRNA)-loaded cell penetrating peptides-conjugated liposome-polycation-DNA complex (LPD) (RRM2-CLPD), aiming to inhibit the migration and proliferation of vascular smooth muscle cells (VSMCs) crucial for IH. RRM2-CLPD is of a small size (∼150 nm) and high siRNA encapsulation efficiency (∼90%). Further, we demonstrated that RRM2-CLPD could significantly inhibited RRM2 gene and protein expression by ∼80%. Notably, RRM2-CLPD was able to effectively bind to VSMCs, resulting in significant cellular proliferation and migration inhibition. Taken together, RRM2-CLPD represent a very promising treatment for IH. [ABSTRACT FROM AUTHOR]

Endovascular intervention is a mainstay treatment of peripheral artery disease (PAD) in addition to aggressive risk factor modification and exercise programs in patients with favorable anatomy or in those who are considered too high risk for surgical intervention. Treatment with percutaneous transluminal angioplasty (PTA) and bare metal stents (BMS) has been limited by high rates of in-stent restenosis (ISR) requiring repeat revascularization. Drug-eluting stents (DES), developed and designed to reduce ISR, offer a promising solution to the current challenges in endovascular management of PAD. Several randomized clinical trials have shown improved short- and mid-term outcomes with DES as compared with both PTA and BMS. Herein we provide an up-to-date review of the current literature on DES use in PAD. [ABSTRACT FROM AUTHOR]

Objective: In-stent restenosis (ISR) is a feared complication after coronary stent implantation. Drug-coated balloon (DCB) is being promoted as a treatment option for ISR. However, the benefit-risk ratio of DCB length has not been investigated. Longer DCBs release more anti-proliferative drug to the vessel wall; however, they are associated with a higher lesion length and vessel injury. Hypothesis: DCB length is associated with clinical outcome. Methods: We analyzed 286 consecutive Pantera Lux (Biotronik, active component Paclitaxel) DCB-treated patients between April 2009 and June 2012. Of them, 176 patients were treated using a 15-mm DCB and 109 were treated using a 20-mm DCB. Baseline characteristics and major adverse cardiac events (MACE; death, myocardial infarction, and target lesion revascularization) during initial hospital stay and a 2-year follow-up period were obtained. Results: Patients characteristics such as cardiovascular risk factors, prior diseases, co-medication, clinical presentation, target vessel, and left ventricular function did not differ between the groups. MACE during hospital course was similar [1.7% vs. 2.8%, relative risk (RR) 1.6, 95% confidence interval (CI) 0.3-7.9, p=0.554]. Likewise, at 2-year follow-up, MACE did not differ between the groups (23.2% vs. 27.5%, RR 1.2, 95% CI 0.6-1.5, p=0.408). Conclusion: DCB length was not associated with clinical outcome during a 2-year follow-up period. [ABSTRACT FROM AUTHOR]

Background Pattern of DCB restenosis and associated outcomes in facing complex femoropopliteal lesions remain uncertain. Methods Data were retrospectively collected from dual centers in Taiwan on patients who underwent treatment with DCBs for femoropopliteal lesions between 2013 and 2016. The restenosis pattern was categorized by the index-treated length. Clinical outcomes and time to DCB restenosis were retrospectively analyzed. Cox proportional hazards model identified restenosis predictors. Results We recruited a total of 164 patients (91 men; median age 73 years) into the final analysis. The mean lesion length was 204.0 ± 109.2 mm. Of them, 45% total occlusions, 28% severe calcification and 15% in-stent restenosis were treated. Fifty-five patients have DCB restenosis (28 focal and 27 diffuse-occlusive patterns) over a 55-month follow-up. The median restenosis time emerged as a bimodal pattern with a significant difference between the diffuse-occlusive and focal restenosis group (225 vs. 484 days, P  = 0.01). The 1-year patency rate after reintervention for DCB restenosis also was different between both restenosis group (29% vs. 65%, P  = 0.017). The anticipated timing of escape for diffuse-occlusive or focal restenosis was 687 and 1068 days, respectively. Independent factors were lesion length ( P  = 0.049) for diffuse-occlusive restenosis and lumen gain of the popliteal artery for focal restenosis ( P  = 0.034). Conclusions This study demonstrated time to DCB failure emerged as a bimodal pattern of distribution and associations of restenosis pattern to subsequent outcomes after the repeated intervention. Exemption from late catchup restenosis required 3-year observation instead of the 1-year mark for conventional treatment. [ABSTRACT FROM AUTHOR]

Although nitinol is widely used in percutaneous cardiovascular interventions, a causal relationship between nickel released from implanted cardiovascular devices and adverse systemic or local biological responses has not been established. The objective of this study was to investigate the relationship between nitinol surface processing, in-vivo nickel release, and biocompatibility. Nitinol stents manufactured using select surface treatments were implanted into the iliac arteries of minipigs for 6 months. Clinical chemistry profile, complete blood count, serum and urine nickel analyses were performed periodically during the implantation period. After explant, stented arteries were either digested and analyzed for local nickel concentration or fixed and sectioned for histopathological analysis of stenosis and inflammation within the artery. The results indicated that markers for liver and kidney function were not different than baseline values throughout 180 days of implantation regardless of surface finish. In addition, white blood cell, red blood cell, and platelet counts were similar to baseline values for all surface finishes. Systemic nickel concentrations in serum and urine were not significantly different between processing groups and comparable to baseline values during 180 days of implantation. However, stents with non-optimized surface finishing had significantly greater nickel levels in the surrounding artery compared to polished stents. These stents had increased stenosis with potential for local inflammation compared to polished stents. These findings demonstrate that proper polishing of nitinol surfaces can reduce in-vivo nickel release locally, which may aid in minimizing adverse inflammatory reactions and restenosis. Statement of significance Nitinol is a commonly used material in cardiovascular medical devices. However, relationships between nitinol surface finishing, in-vivo metal ion release, and adverse biological responses have yet to be established. We addressed this knowledge gap by implanting single and overlapped nitinol stents with different surface finishes to assess systemic impact on minipigs (i.e. serum and urine nickel levels, liver and kidney function, immune and blood count) over the 6 month implantation period. In addition, nickel levels and histopathology in stented arteries were analyzed on explant to determine relationships between surface processing and local adverse tissue reactions. The findings presented here highlight the importance of surface processing on in-vivo nickel release and subsequent impact on local biological response for nitinol implants. [ABSTRACT FROM AUTHOR]

Importance: The effect of ticagrelor with or without aspirin on saphenous vein graft patency in patients undergoing coronary artery bypass grafting (CABG) is unknown.Objective: To compare the effect of ticagrelor + aspirin or ticagrelor alone vs aspirin alone on saphenous vein graft patency 1 year after CABG.Design, Setting, and Participants: Randomized, multicenter, open-label, clinical trial among 6 tertiary hospitals in China. Eligible patients were aged 18 to 80 years with indications for elective CABG. Patients requiring urgent revascularization, concomitant cardiac surgery, dual antiplatelet or vitamin K antagonist therapy post-CABG, and who were at risk of serious bleeding were excluded. From July 2014 until November 2015, 1256 patients were identified and 500 were enrolled. Follow-up was completed in January 2017.Interventions: Patients were randomized (1:1:1) to start ticagrelor (90 mg twice daily) + aspirin (100 mg once daily) (n = 168), ticagrelor (90 mg twice daily) (n = 166), or aspirin (100 mg once daily) (n = 166) within 24 hours post-CABG. Neither patients nor treating physicians were blinded to allocation.Main Outcomes and Measures: Primary outcome was saphenous vein graft patency 1 year after CABG (FitzGibbon grade A) adjudicated independently by a committee blinded to allocation. Saphenous vein graft patency was assessed by multislice computed tomographic angiography or coronary angiography.Results: Among 500 randomized patients (mean age, 63.6 years; women, 91 [18.2%]), 461 (92.2%) completed the trial. Saphenous vein graft patency rates 1 year post-CABG were 88.7% (432 of 487 vein grafts) with ticagrelor + aspirin; 82.8% (404 of 488 vein grafts) with ticagrelor alone; and 76.5% (371 of 485 vein grafts) with aspirin alone. The difference between ticagrelor + aspirin vs aspirin alone was statistically significant (12.2% [95% CI, 5.2% to 19.2%]; P < .001), whereas the difference between ticagrelor alone vs aspirin alone was not statistically significant (6.3% [95% CI, -1.1% to 13.7%]; P = .10). Five major bleeding episodes occurred during 1 year of follow-up (3 with ticagrelor + aspirin; 2 with ticagrelor alone).Conclusions and Relevance: Among patients undergoing elective CABG with saphenous vein grafting, ticagrelor + aspirin significantly increased graft patency after 1 year vs aspirin alone; there was no significant difference between ticagrelor alone and aspirin alone. Further research with more patients is needed to assess comparative bleeding risks.Trial Registration: clinicaltrials.gov Identifier: NCT02201771. [ABSTRACT FROM AUTHOR]

Background: Drug eluting stents reduce the risk of in-stent restenosis but delay healing of the vascular wall. Recent data on late and very late stent thrombosis after drug-eluting stent (DES) implantation have raised concerns about the long-term safety. High lipophilicity of paclitaxel promotes rapid cellular uptake and prolongs its action. This makes paclitaxel a very promising candidate for local drug therapy intended to inhibit the proliferative and migratory processes involved in restenosis following PCI.Objectives: In a prospective randomized trial, we compared the efficacy of the new catheter based delivery of fluid paclitaxel after bare metal stenting with that of drug eluting stents in patients at high risk for in-stent restenosis.Methods and Results: We conducted a prospective, randomized trial comparing the local delivery of fluid paclitaxel after bare metal stent implantation (DDB+BMS group) with the implantation of drug eluting stent (DES group) (1:1) in 68 patients at high risk for in-stent restenosis. The primary end points were in-stent late lumen loss and binary restenosis rate ›50%. Secondary end points were procedure success and composite clinical end points (major adverse cardiac events and revascularization of the target lesion) 6months after intervention. At 6months, follow-up angiography showed an in-stent late lumen loss of 1.0±1.3mm in (DDB+BMS group) versus 0.94±1.3mm in DES group (P=.743) without statistically significant difference in the cumulative overall rate of major cardiac events between both groups. DES subgroup analysis showed in-stent late lumen loss of 0.09±0.3mm in everolimus eluting stent (EES) subgroup patients that was statistically significant in comparison with (DDB+BMS group, n=30) (P=.033) and paclitaxel eluting stent (PES, n=19) subgroup patients (P=.006).Target lesion revascularization was 0% in EES subgoup patients, 36.7% in DDB+BMS group patients and 47.7% in PES subgroup patients (P=.026).Conclusion: Paclitaxel either in fluid form used in drug delivery balloons or in polymerized form used in drug eluting stents was ineffective in reducing neointimal proliferation, in-stent restenosis, and clinical events. EES was superior compared with PES and catheter based delivery of fluid paclitaxel after bare metal stent implantation regarding primary and secondary end points. [ABSTRACT FROM AUTHOR]

Background: Angiotensin receptor blockers (ARBs) are known for its anti-inflammatory and anti-proliferative effects. The aim of the study was to evaluate long-term effects of ARBs on morphologic characteristics of stent restenosis in patients with coronary artery disease requiring stent implantation by optical coherence tomography (OCT).Methods: Patients with coronary artery disease having history of drug-eluting stent implantation (n = 407) were analyzed on the basis of ARB therapy as the ARB group (n = 162) and the non-ARB group (n = 245). Neointimal characterizations were performed at lesions with diameter stenosis >30% with OCT in each group. Major adverse cardiovascular events (MACEs), lumen area, stent area, neointimal area, neointimal thickness, nonapposed struts, uncovered struts, and intraluminal mass between two groups were also observed.Results: More patients in the ARB group revealed homogeneous and layered neointimal pattern (44.9% vs. 35.6%, P < 0.001, and 16.8% vs. 10.6%, P < 0.001, respectively), and whereas patients in the non-ARB group revealed heterogeneous neointimal pattern (1.1% vs. 7.6%, P < 0.001). Mean neointimal area (1.09 ± 1.00 mm2 vs. 1.38 ± 1.24 mm2) and mean neointimal thickness (140.6 ± 112.0 μm vs. 189.6 ± 423.1 μm) with OCT were smaller in the ARB group when compared to the non-ARB group. Percentage of covered stents was significantly higher in the ARB group when compared to the Non-ARB group (97.3% vs. 92.6%, P = 0.015). Other factors such as follow-up % diameter stenosis, late lumen loss, binary restenosis, MACEs, various neointimal characteristics analyzed by image analyzing software did not show significant differences.Conclusion: The use of ARBs after drug-eluting stent implantation demonstrated difference in neointimal characteristics, less amount of neointimal area and fewer number of uncovered stent struts during the follow-up OCT, indicating the anti-proliferative and anti-inflammatory effects of ARBs. [ABSTRACT FROM AUTHOR]

Background: BioFreedom is a polymer- and carrier-free drug-coated stent that delivers Biolimus A9 to the vessel wall. Our purpose was to evaluate the efficacy and safety of this DCS in patients with short-duration dual antiplatelet therapy.Methods: The BioFreedom US IDE feasibility trial was a single-arm, open-label, prospective study of patients requiring stenting of de novo lesions. Patients received 3 months of DAPT, repeat angiography at 9 months, and clinical follow-up at multiple intervals. A subgroup also underwent intravascular ultrasound (IVUS) interrogation. The primary safety end point was major adverse cardiac events, defined as a composite of cardiac death, myocardial infarction, target lesion revascularization, or stent thrombosis. The primary efficacy end point, in-stent late lumen loss at 9 months, was compared with a historical control from a first-generation paclitaxel-eluting stent.Results: A total of 72 patients from 10 sites received BioFreedom DCS implanted in 83 de novo lesions. At 9 months, the incidence of composite MACE was 8.4%, and TLR was 1.5%. Short DAPT was safe without occurrence of stent thrombosis. The primary end point of LLL was 0.32±0.53 mm. Paired IVUS analyses comparing postprocedural with 9-month measurements showed low in-stent neointimal volume obstruction (5.39±5.28%) and low neointimal hyperplasia (7.43±8.04 mm3).Conclusions: This study's angiography and IVUS assessments demonstrated that the BioFreedom DCS has anti-restenotic efficacy similar to first-generation DES. In the absence of concerning safety signals, this DCS should be considered effective and safe for patients who require a shorter duration of DAPT. [ABSTRACT FROM AUTHOR]

Since the first coronary angioplasty on Sept 16, 1977, the field of percutaneous coronary intervention has evolved rapidly. Now marking its 40th anniversary, percutaneous coronary intervention has become one of the most common medical procedures worldwide. Much of this progress has been due to the iteration and improvement of angioplasty technologies. Balloon angioplasty was limited by unpredictable procedural outcomes due to vessel dissection and recoil, and a high rate of restenosis. The introduction of stents resulted in more stable early results and lower rates of restenosis, although early stent thrombosis and neointimal hyperplasia causing vessel renarrowing were key limitations. Drug-eluting stents delivering antiproliferative agents significantly lowered the rates of restenosis, permitting widespread use of percutaneous coronary intervention in more advanced and complex disease. Although fully bioresorbable scaffolds have the potential to further improve long-term outcomes, they have not yet achieved results equivalent to those of conventional metallic drug-eluting stents in the early years after implantation. Progress in catheter technology did not occur in isolation, and the success of percutaneous coronary intervention is also due to important advances in intracoronary imaging, and adjunct pharmacotherapy-each of which is reviewed in other papers in this Series. [ABSTRACT FROM AUTHOR]

Background Neointimal hyperplasia, which is caused by dysfunction of vascular smooth muscle cells and vascular endothelial cells (VECs), is a foundation for later development of vein grafted occlusion. This study investigates whether neointimal hyperplasia could be prevented by the application of paeonol, a phenolic compound having functions of anti-inflammatory, anti-oxidant, and anti-proliferative. Methods Autologous jugular veins, which engrafted to carotid arteries in rabbits, were enveloped with paeonol or left untreated. After 0, 2, and 3 wk, vein grafts were respectively harvested. Proliferating cell nuclear antigen, vascular cell adhesion molecule l (VCAM-1), and intercellular cell adhesion molecule 1 were assessed with immunohistochemistry and Western blot. VECs apoptosis was also detected with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling assay. Results Paeonol treatment reduced early neointimal hyperplasia by 42%-46% ( P < 0.001) and early medial hyperplasia by 18%-22% ( P < 0.001) compared with the controls. Immunohistochemical and Western blot results show a significant downregulation of proliferating cell nuclear antigen ( P < 0.001) and VCAM-1 ( P < 0.001) in paeonol treatment group in the second and third weeks. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling analysis discovered that VECs apoptosis was also reduced by the paeonol treatment in the second and third weeks ( P < 0.001). Conclusions Paeonol could prevent vein graft early restenosis by suppressing intimal and medial hyperplasia via inhibition of vascular smooth muscle cells proliferation, VCAM-1 expression, and anti-apoptosis of VECs in grafted veins. [ABSTRACT FROM AUTHOR]

Background: Drug-eluting stents (DESs) were considered as ground-breaking technology promising to eradicate restenosis and the necessity to perform multiple revascularization procedures subsequent to percutaneous coronary intervention. Soon after DESs were released on the market, however, there were reports of a potential increase in mortality and of early or late thrombosis. In addition, DESs are far more expensive than bare-metal stents (BMSs), which has led to their limited use in many countries. The technology has improved over the last few years with the second generation of DESs (DES-2). Moreover, costs have come down and an improved safety profile with decreased thrombosis has been reported. Objective: Perform a cost–benefit analysis of DES-2s versus BMSs in the context of a publicly funded university hospital in Quebec, Canada. Methods: A systematic review of meta-analyses was conducted between 2012 and 2016 to extract data on clinical effectiveness. The clinical outcome of interest for the cost–benefit analysis was target-vessel revascularization (TVR). Cost units are those used in the Quebec health-care system. The cost–benefit analysis was based on a 2-year perspective. Deterministic and stochastic models (discrete-event simulation) were used, and various risk factors of reintervention were considered. Results: DES-2s are much more effective than BMSs with respect to TVR rate ratio (i.e., 0.29 to 0.62 in more recent meta-analyses). DES-2s seem to cause fewer deaths and in-stent thrombosis than BMSs, but results are rarely significant, with the exception of the cobalt–chromium everolimus DES. The rate ratio of myocardial infraction is systematically in favor of DES-2s and very often significant. Despite the higher cost of DES-2s, fewer reinterventions can lead to huge savings (i.e., -$479 to -$769 per patient). Moreover, the higher a patient’s risk of reintervention, the higher the savings associated with the use of DES-2s. Conclusion: Despite the higher purchase cost of DES-2s compared to BMSs, generalizing their use, in particular for patients at high risk of reintervention, should enable significant savings. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the inhibitory effect of sirolimus coating on the occurrence of restenosis and thrombosis with heparinized stents. Heparin and dopamine were conjugated by chemical bonding and anchored on the stent surface by a mussel-inspired adhesion mechanism. Subsequently, sirolimus was coated with poly lactic-glycolic acid on the heparinized stent surface. The heparin was well attached to the surface, and the surface was smooth after sirolimus coating. The smoothness of the surface was maintained after expansion of the stent. The amount of sirolimus released from the stent was 67.3% ± 4.55% within 7 days, followed by continual release up to day 28. The proliferation of smooth muscle cells was successfully arrested (51.3% ± 2.25% at 7 days of culture) by sirolimus released from the stent. Platelet adhesion was clearly prevented in the heparin-coated group (78.0 ± 8.00/1.8 cm2) compared to that in the heparin noncoated group (5.0 ± 1.00/1.8 cm2). Animal studies showed that the heparin and sirolimus-coated stent group had no obvious inflammatory response and no change in the fibrin score compared to those in the other groups. However, restenosis clearly decreased in the heparin and sirolimus-coated group (12.3% ± 3.54%) compared to the bare-metal stent group (27.5% ± 8.52%) and the heparin-coated group (25.3% ± 11.79%). These results suggest that heparinized surface-based sirolimus coating may be a useful approach for the prevention of restenosis and stent thrombosis. [ABSTRACT FROM AUTHOR]

The optimal duration and type of antiplatelet therapy after implantation of a drug-eluting stent (DES) remains uncertain. At the time of the first-in-man implantation of the sirolimus DES in 1999, the protocol-defined dual antiplatelet therapy (DAPT) duration was only 2 months. Subsequently, DAPT duration was extended to 1 year on the basis of anecdotal historical data, and this practice was then incorporated into clinical guidelines. For >1 decade, trialists have sought to compare the safety and efficacy of abbreviated (<6 months) and prolonged (>12 months) DAPT regimens. However, the body of evidence is limited by the heterogeneity of end points, time of randomization, and bleeding criteria used in each trial. Pharmaceutical advances led to the introduction of new ADP-receptor antagonists, which are thought to be more effective than clopidogrel. The ADP-receptor antagonists moved the focus from the optimal duration of DAPT to the potential efficacy of single antiplatelet therapy after DES implantation. In this Review, we summarize the current evidence on the duration of DAPT and the risk of bleeding and adverse cardiac events after DES implantation, and describe the pitfalls of trial interpretation. The ongoing, prospective trials to test single antiplatelet therapy after DES implantation are also discussed. [ABSTRACT FROM AUTHOR]

In-stent restenosis is one of the most serious modes of failure of cardiovascular stent implant. Although drug-eluting stents have been proven to reduce in-stent restenosis, the nonspecific inhibitory effects of anti-proliferative drugs, such as rapamycin, result in delayed re-endothelialization and fatal late stent thrombosis. Although many studies have focused on promoting rapid re-endothelialization, a feasible method of reducing excessive extracellular matrix (ECM) production and cell proliferation might provide a promising way to efficiently inhibit the restenosis in vivo. In this study, we constructed a surface-mediated gene delivery system through a layer-by-layer assembly of protamine sulfate (PrS) and a functional plasmid DNA (pDNA) encoding short hairpin RNA to downregulate the expression of transforming growth factor-β1 (TGF-β1), aiming to inhibit cell proliferation and reduce excessive ECM production. We demonstrated that (PrS/pDNA) films were successfully constructed with good stability under physiological conditions. The (PrS/pDNA) films were able to transfect fibroblasts, thus reducing the secretion of fibronectin and collagen and inhibiting cell proliferation in vitro . Further in vivo experiments showed that the transfection of arterial tissue led to significant local downregulation of TGF-β1 and ECM proteins and inhibited neointimal hyperplasia. These functional gene delivery films avoid the use of non-specific drugs and may serve as part of a new strategy for targeting in-stent restenosis in the field of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Purpose Ostial restenosis is a common cause of failures in paranasal sinus surgery. The aim of the current study was to investigate the use of low-dose-rate brachytherapy to prevent neo-ostial restenosis in an animal model. Methods and Materials In 14 rabbits, maxillary neo-ostia were created and measured. One side each was stented with a regular silicone stent, the other side was either not stented ( n = 7) or stented with a phosphorous-32 implanted stent depositing a low-dose radiation of 15 Gy ( n = 7) within 1 week, after which all stents were removed. After a period of additional 12 weeks of recovery, the animals were sacrificed, the neo-ostia were again measured, and the areas and histopathologic changes compared in between the groups. Results After 15-Gy stenting, the mean ostial areas were even slightly enlarged by 5.1% compared to the area at stent removal, whereas a significant reduction in area, indicating a process of restenosis, by 56.1% or 54.0% was seen in the control groups with no stent and normal stent, respectively. Furthermore, no indication for adverse histopathologic radiation effects was seen in the 15-Gy group. Conclusions Low-dose-rate brachytherapy with phosphorous-32 doped silicone stents showed promising results in the prevention of neo-ostium restenosis in this proof-of-concept study, indicating that further preclinical and clinical testing may be warranted. [ABSTRACT FROM AUTHOR]

Bio-inorganic films and drug-eluting coatings are usually used to improve the hemocompatibility and inhibit restenosis of vascular stent; however, above bio-performances couldn't combine together with single materials. In the present study, we reported a simple approach to fabricate a metal film with the aim of imparting the stent with good blood compatibility and accelerating endothelialization. The films with various ratios of Cu and Ti were prepared through the physical vapor deposition. Phase structure and element composition were investigated by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), respectively. The releasing volume of copper ion in Cu/Ti film was determined by immersing test. The hemolysis ratio, platelet adhesion and clotting time were applied to evaluate the hemocompatibility. The proliferative behaviors of endothelial cells and smooth muscle cells under certain copper concentration were investigated in vitro and in vivo. Results indicated that copper-titanium films exhibited good hemocompatibility in vitro; however, the increase of Cu/Ti ratio could lead to increasing hemolysis ratio. Endothelial cells displayed more proliferative than smooth muscle cells when the copper concentration was < 7.5 μg/ml, however both cells tended to apoptosis to some degree when the copper concentration was increased. The complete endothelialization of the film with low copper in vivo was observed at the 2nd week, indicating that the copper-titanium film with the lower copper concentration could promote endothelialization. Therefore, the inorganic copper-titanium film could be potential biomaterials to improve blood compatibility and accelerating endothelialization of vascular stents. [ABSTRACT FROM AUTHOR]

Background: The paclitaxel drug coated balloon (DCB) is an established treatment for bare metal stent (BMS) in-stent restenosis (ISR) in native coronary arteries. The evidence of DCB-application for drug eluting stent (DES) ISR both in native coronaries and saphenous vein grafts (SVG) is limited. Aim of our study was to compare the differential efficacy of DCB for treatment of BMS- and DES-ISR in native coronary vessels and SVGs.Methods and Results: N = 135 DCB-treated patients with available follow up (FU) angiography were included in this retrospective study. Patients received treatment between April 2009 and March 2013 at 2 tertiary care hospitals in Germany. DCB was applied in BMS-ISR (n = 65; 48%) and DES-ISR (n = 70; 52%). DCB-treated lesions were located in native coronary arteries (n = 110; 81%; BMS-ISR: n = 58; 53%; DES-ISR: n = 52; 47%) and SVGs (n = 25; 19%; BMS-ISR: n = 7, 28%; DES-ISR: n = 18, 72%). Median FU was 12 months. Endpoints were binary restenosis and target lesion revascularization (TLR). Binary restenosis (29% vs. 57%; P < 0.01) and TLR (18% vs. 46%; P < 0.01) were significantly more frequent in DES-ISR versus BMS-ISR. In SVGs, TLR was required in 72% (DES-ISR) versus 14% (BMS-ISR); P = 0.02. In the Kaplan-Meier-analysis freedom from both endpoints was significantly decreased in the DES-lesions both in the total population (binary restenosis P < 0.01; TLR P < 0.01) and native coronaries (binary restenosis P = 0.02; TLR P = 0.04).Conclusions: DCB treatment is less effective in DES-ISR than in BMS-ISR. The diminished efficacy of DCB treatment is even more pronounced in DES-ISR located within degenerated SVGs. [ABSTRACT FROM AUTHOR]

Background: Drug-coated balloons (DCB) have been used to treat de novo small vessel coronary disease (SVD), with promising results and shorter dual antiplatelet therapy (DAPT) duration compared to drug-eluting stents (DES). We compared safety and effectiveness of the two treatments at 1 year.Methods: We reviewed 3,613 angioplasty cases retrospectively from 2011 to 2013 and identified 335 patients with SVD treated with device diameter of ≤2.5 mm. DCB-only angioplasty was performed in 172 patients, whereas 163 patients were treated with second-generation DES.Results: DCB patients had smaller reference vessel diameter (2.22 ± 0.30 vs. 2.44 ± 0.19 mm, P < 0.001) and received smaller devices (median diameter 2.25 vs. 2.50 mm, P < 0.001) compared to the DES group. DES-treated vessels had larger acute lumen gain (1.71 ± 0.48 mm) than DCB (1.00 ± 0.53 mm, P < 0.001). Half the patients had diabetes mellitus. While there were more patients presenting with acute coronary syndrome (ACS) in the DCB group (77.9% vs. 62.2%, P = 0.013), they received shorter DAPT (7.4 ± 4.7 vs. 11.8 ± 1.4 months, P < 0.001) than the DES group. The 1-year composite major adverse cardiac event rate was 11.6% in the DCB arm and 11.7% in the DES arm (P = 1.000), with target lesion revascularization rate of 5.2% and 3.7%, respectively, (P = 0.601).Conclusions: In this high-risk cohort of patients, DCB-only angioplasty delivered good clinical outcome at 1 year. The results were comparable with DES-treated patients, but had the added benefit of a shorter DAPT regime. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the effectiveness of intravenous steroid pulse therapy following balloon dilatation for esophageal stenosis and stricture in children.Methods: The study enrolled six children, including three with congenital esophageal stenosis and three with anastomotic strictures after surgery for esophageal atresia, all of whom were treated by balloon dilatation combined with high-dose intravenous methylprednisolone pulse therapy. Methylprednisolone was injected intravenously at a dose of 20 mg/kg/day for 2 days, starting from the day of dilatation, followed by 10 mg/kg/day for 2 days, for a total of 4 days.Results: Esophageal stricture recurred in all three patients with congenital esophageal stenosis despite repeated balloon dilatation without methylprednisolone. However, the symptoms of dysphagia improved and did not recur after systemic steroid pulse therapy following balloon dilatation. Symptoms also resolved in all three patients with anastomotic strictures following balloon dilatation with systemic steroid pulse therapy. All six patients remained asymptomatic after 6-21 months follow-up, with no complications.Conclusion: Intravenous methylprednisolone pulse therapy following balloon dilatation is safe and effective for the treatment of esophageal stenosis and strictures in children. [ABSTRACT FROM AUTHOR]

Background Stent design and technological modifications to allow for anti-proliferative drug elution influence restenosis rates following percutaneous coronary intervention (PCI). We aimed to investigate whether peri-procedural administration of corticosteroids or the use of thinner strut cobalt alloy stents would reduce rates of binary angiographic restenosis (BAR) after PCI. Methods This was a two centre, mixed single and double blinded, randomised controlled trial using a factorial design. We compared (a) the use of prednisolone to placebo, starting at least six hours pre-PCI and continued for 28 days post-PCI, and (b) cobalt chromium (CoCr) to stainless steel (SS) alloy stents, in patients admitted for PCI. The primary end-point was BAR at six months. Results 315 patients (359 lesions) were randomly assigned to either placebo (n = 145) or prednisolone (n = 170) and SS (n = 160) or CoCr (n = 160). The majority (58%) presented with an ACS, 11% had diabetes and 287 (91%) completed angiographic follow up. BAR occurred in 26 cases in the placebo group (19.7%) versus 31 cases in the prednisolone group (20.0%) respectively, p = 1.00. For the comparison between SS and CoCr stents, BAR occurred in 32 patients (21.6%) versus 25 patients (18.0%) respectively, p = 0.46. Conclusion Our study showed that treating patients with a moderately high dose of prednisolone for 28 days following PCI with BMS did not reduce the incidence of BAR. In addition, we showed no significant reduction in 6 month restenosis rates with stents composed of CoCr alloy compared to SS ( http://www.isrctn.com/ISRCTN05886349 ). [ABSTRACT FROM AUTHOR]

Objectives: The BASE-ACS trial demonstrated non-inferiority of titanium-nitride-oxide-coated bioactive stents (BAS), versus everolimus-eluting stents (EES), for major adverse cardiac events (MACE) at 1- and 2-year follow-up, in patients with acute coronary syndrome (ACS). We presented the 4-year outcome of the BASE-ACS trial.Design: We randomized 827 patients with ACS to receive either BAS (417) or EES (410). MACE was a composite of cardiac death, non-fatal myocardial infarction (MI) or ischemia-driven target lesion revascularization (TLR) at 12-month follow-up. Analyses were performed by intention to treat. Follow-up was planned at 12 months, and yearly thereafter for 5 years.Results: Four-year clinical follow-up was completed in 753 (91.1%) patients. At 4 years, BAS were non-inferior to EES for MACE (14.7% versus 17.8%, respectively; p = 0.24 for superiority; p = 0.001 for non-inferiority). Non-fatal MI was less frequent with BAS (5.0% versus 9.2%, respectively; p = 0.025). Cardiac death and ischemia-driven TLR were comparable (2.9% versus 3.5%, and 8.6% versus 9.2%; p = 0.62 and p = 0.80, respectively). Independent predictors of MACE were calcified lesions (HR 1.54, p = 0.021), the number of vessels treated (HR 1.53, p = 0.025), and reference vessel diameter (HR 0.54, p = 0.006).Conclusions: In patients presenting with ACS, BAS was associated with a clinical outcome non-inferior to EES at 4-year follow-up. [ABSTRACT FROM AUTHOR]

The transradial approach is increasingly used for percutaneous coronary intervention (PCI), and we therefore aimed to compare the clinical outcomes after transradial intervention (TRI) and transfemoral intervention (TFI) in all patients undergoing PCI. Among 6,973 patients enrolled in a nationwide, prospective, multicenter registry (February 2013 to September 2013), 1,860 underwent TRI (n = 1,445, 77.7%) and TFI (n = 415, 22.3%). Bleeding and major adverse cardiac events (MACE; death, myocardial infarction, revascularization, or stent thrombosis) were compared. Bleeding occurred in 42 patients (2.3%) and was significantly less likely in the TRI versus TFI group (overall cohort: 1.5% vs 4.8%, p = 0.001; propensity score-matched: n = 728, 2.7% vs 5.2%, p = 0.048). Multivariate regression revealed that TRI was negatively associated with bleeding (odds ratio 0.42, 95% CI 0.21 to 0.83, p = 0.013). MACE occurred in 152 patients (8.2%). Kaplan-Meier estimates showed higher MACE-free survival rates in the TRI versus TFI group (overall cohort: 93.3% vs 86.7%, log-rank p = 0.026; propensity score-matched: 91.8% vs 86.5%, log-rank p = 0.04). Cox proportional analysis demonstrated that TRI independently predicted improved MACE (hazard ratio 0.64, 95% CI 0.43 to 0.91, p = 0.024). In conclusion, TRI is associated with reduced bleeding rates and better clinical outcomes than TFI in all patients undergoing PCI. [ABSTRACT FROM AUTHOR]

Aims Restenosis- an adverse consequence following angioplasty, and atherosclerosis are characterized by abnormal vascular smooth muscle cell (VSMC) proliferation and migration leading to neo-intima formation. In the present study, we investigated the inhibitory effects of alkaloid rich fraction (ARF) from Nelumbo nucifera and isolated compound neferine on platelet-derived growth factor (PDGF-BB) induced VSMC proliferation and migration in vitro and neo-intima formation in a rat carotid artery injury model. Methods PDGF-BB induced VSMC proliferation and migration was assessed using colorimetric assay and modified Boyden chamber method respectively. Gene expression of cell cycle associated molecules was determined by reverse transcription-polymerase chain reaction (RT-PCR). The signaling molecules such as PDGF-Rβ, extracellular regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK), P38, metalloproteinase (MMP)-9 and nuclear factor-kappa B (NF-κB) were determined by western blot analysis. Stress fiber formation was evaluated using immunofluorescence microscopy. The rat carotid artery balloon injury model was performed to assess the effect of ARF on neo-intima formation. Results ARF possessed the strongest anti-oxidant activities. The anti-proliferative activity of both ARF and neferine was due to suppression of cyclin D1, cyclin E and cyclin-dependent kinase (Cdk) gene expression. Moreover, ARF and neferine inhibited PDGF-Rβ, ERK1/2, JNK and P38 activations and NF-κB translocation. Also, ARF and neferine inhibited VSMC migration by inhibiting MMP-9 activity without affecting cytoskeleton remodeling. In a rat carotid artery injury model, ARF inhibited neo-intima formation. Conclusion Our results indicate that ARF targets VSMC proliferation and migration to attenuate neo-intima formation by inhibition of PDGF-Rβ mediated signaling. [ABSTRACT FROM AUTHOR]