cardiovascular-agents and Neointima

Thrombosis initiated by abnormal platelet aggregation is a pivotal pathological event that precedes most cases of cardiovascular diseases (CVD). Recently, growing evidence indicates that platelet could be a potential target for CVD prevention. However, as the conventional antithrombotic management strategy, applications of current antiplatelet agents are somewhat limited by their various side effects, such as bleeding risk and drug resistance. Hence, efforts have been made to search for agents as complementary therapies. Ginsenoside, the principal active component extracted from Panax ginseng, has gained much attention for its regulations on multiple crucial events of platelet aggregation. From structural characteristics to clinical applications, this review anatomized the intrinsic structure-function relationship of antiplatelet potency of ginsenosides, and the involved signal pathways were specifically summarized. Additionally, the emphasis was placed on clinical studies that investigate the antithrombotic efficacy of ginsenosides in the treatment of CVD. Further, a broad overview of approaches for improving the bioavailability of ginsenosides was concluded. Limitations and prospects of current studies were also discussed. This study may provide some new insights into the systematic understanding of ginsenosides in CVD treatment and lay a foundation for future research.

Topics: Animals; Biological Availability; Blood Platelets; Cardiovascular Agents; Cardiovascular Diseases; Ginsenosides; Humans; Molecular Structure; Muscle, Smooth, Vascular; Neointima; Platelet Aggregation; Platelet Aggregation Inhibitors; Signal Transduction; Structure-Activity Relationship; Vascular Remodeling

Topics: Cardiovascular Agents; Drug-Eluting Stents; Humans; Hyperplasia; Neointima; Tunica Intima

Restenosis by myointimal hyperplasia after peripheral arterial angioplasty or stenting often limits long term patency. Drug-eluting balloons (DEBs) which inhibit the proliferation of neo-intimal growth of vascular smooth muscle cells may prevent restenosis. The aim of this paper was to examine the evidence in published literature on the use of DEBs in the treatment of peripheral arterial in-stent restenosis (ISR).. A systematic literature review was undertaken of all published literature on the treatment of peripheral ISR with drug eluting balloon using Medline and cross-referenced. All published papers on the use of DEBs in peripheral arterial disease (PAD) were used. Cochrane Central Register of Controlled Trials and electronic databases were also searched for on-going studies.. There were no level 1 or 2 evidence published on this subject. The number of high-quality publications is few, and consequently a sufficient analysis is not possible. Recently data from non-randomized cohort studies showed encouraging results with DEB as treatment modality for ISR, whether used alone or as combined strategies.. Evidence from the published literature suggests that DEBs are safe in preventing peripheral ISR. Despite strong corporate pressure for the use of DEBs, there is only circumstantial evidence that this is a useful modality for ISR. Results from on-going studies may allow further meta-analysis for efficiency and cost-effectiveness.

Topics: Angioplasty, Balloon; Animals; Cardiovascular Agents; Humans; Hyperplasia; Lower Extremity; Neointima; Peripheral Arterial Disease; Recurrence; Retreatment; Stents; Treatment Outcome; Vascular Access Devices; Vascular Patency

Bioresorbable scaffolds have emerged as a potential alternative to non-erodible metal implants to alleviate the long-term risk of permanent device vascular implant-related adverse events. Bioresorbable scaffolds provide a temporary mechanical support function until the vessel reaches complete healing, and the implant progressively disappears and vasomotion resumes. A polymer matrix with embedded drugs coated onto the scaffold surface degrades slowly, reducing the size from the exterior toward the interior, and this allows controlled drug release to a local vascular segment. Drug elution from a bioresorbable scaffold system is characterized by a rapid initial release that achieves high concentration along the intimal surface, which is designed to prevail vascular dilation-induced injury and formation of neointimal hyperplasia. This review highlights diverse types of bioresorbable biomaterials as vascular scaffolds, drug release kinetics, adaptive arterial wall remodeling, and complexities in the advancement of vascular scaffolds to treat restenosis.

Topics: Absorbable Implants; Animals; Cardiovascular Agents; Coated Materials, Biocompatible; Delayed-Action Preparations; Drug Liberation; Endovascular Procedures; Humans; Hyperplasia; Kinetics; Neointima; Prosthesis Design; Recurrence; Risk Factors; Treatment Outcome; Vascular Diseases; Vascular Remodeling

Nanoparticles promise to advance strategies to treat vascular disease. Since being harnessed by the cancer field to deliver safer and more effective chemotherapeutics, nanoparticles have been translated into applications for cardiovascular disease. Systemic exposure and drug-drug interactions remain a concern for nearly all cardiovascular therapies, including statins, antithrombotic, and thrombolytic agents. Moreover, off-target effects and poor bioavailability have limited the development of completely new approaches to treat vascular disease. Through the rational design of nanoparticles, nano-based delivery systems enable more efficient delivery of a drug to its therapeutic target or even directly to the diseased site, overcoming biological barriers and enhancing a drug's therapeutic index. In addition, advances in molecular imaging have led to the development of theranostic nanoparticles that may simultaneously act as carriers of both therapeutic and imaging payloads. The following is a summary of nanoparticle therapy for atherosclerosis, thrombosis, and restenosis and an overview of recent major advances in the targeted treatment of vascular disease.

Topics: Animals; Cardiovascular Agents; Chemotaxis, Leukocyte; Cholesterol; Drug Carriers; Drug Evaluation, Preclinical; Forecasting; Humans; Inflammation; Macrophages; Mice; Nanoparticles; Neointima; Neovascularization, Pathologic; Plaque, Atherosclerotic; RNA Interference; RNA, Small Interfering; Thrombosis; Vascular Diseases

In the era of drug-eluting stents, large-scale randomized trials and all-comer registries have shown excellent clinical results. However, even the latest-generation drug-eluting stent has not managed to address all the limitations of permanent metallic coronary stents, such as the risks of target lesion revascularization, neoatherosclerosis, preclusion of late lumen enlargement, and the lack of reactive vasomotion. Furthermore, the risk of very late stent, although substantially reduced with newer-generation drug-eluting stent, still remains. These problems were anticipated to be solved with the advent of fully biodegradable devices. Fully bioresorbable coronary scaffolds have been designed to function transiently to prevent acute recoil, but have retained the capability to inhibit neointimal proliferation by eluting immunosuppressive drugs. Nevertheless, long-term follow-up data of the leading bioresorbable scaffold (Absorb) are becoming available and have raised a concern about the relatively higher incidence of scaffold thrombosis. To reduce the rate of clinical events, improvements in the device, as well as implantation procedure, are being evaluated. This review will focus on the current CE-mark approved bioresorbable scaffolds, their basic characteristics, and clinical results. In addition, we summarize the current limitations of bioresorbable scaffold and their possible solutions.

Topics: Absorbable Implants; Cardiovascular Agents; Clinical Trials as Topic; Coated Materials, Biocompatible; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Diffusion of Innovation; Forecasting; Humans; Neointima; Percutaneous Coronary Intervention; Polymers; Risk Factors; Treatment Outcome

Currently, endovascular therapy is the standard of care for peripheral artery disease. The main issue of these techniques is restenosis which is a complex mechanism associating elastic recoil, constrictive remodelling and intimal hyperplasia. More and more evidence show that drug-coating balloon (DCB) is a promising device to prevent and to treat restenosis. Herein we have reviewed the role for DCB's in the treatment of in-stent restenosis (ISR).. Currently, few studies are available regarding DCB use for femoropopliteal (FP) ISR treatment. In different studies evaluating DCB for treatment of FP ISR the freedom from target lesion revascularization rate at one year are range from 87% to 92.1%. In comparison to other devices used for treatment of FP ISR such as atherectomy, cutting balloon, standard angioplasty, DCB seems to show better results in terms of freedom from TLR and primary patency. Other devices such as drug-eluting stent, brachytherapy, covered stent show also good results for FP ISR.. Majority of assessed data on FP ISR treated with DCB derived from uncontrolled study or historical comparisons. Only one randomized, controlled study compared DCB versus standard angioplasty. The FAIR trial showed better results in favour of DCB in terms of freedom from TLR at 12 months (90.8%).. Drug coating balloon could be the first choice of devices for the treatment of FP ISR, because of its efficacy, its ease of use in comparison with more complex and less efficient devices.

Topics: Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Constriction, Pathologic; Endovascular Procedures; Femoral Artery; Humans; Hyperplasia; Neointima; Peripheral Arterial Disease; Popliteal Artery; Recurrence; Retreatment; Risk Factors; Stents; Time Factors; Treatment Outcome; Vascular Access Devices

Since the advent of percutaneous coronary intervention, enormous advances have been made in the treatment of coronary artery disease. Angioplasty and bare metal stents were plagued by high rates of restenosis leading to repeat revascularization procedures. Examination of the underlying pathophysiology of restenosis led to the development of drug-eluting stents to reduce neointimal hyperplasia. However, as restenosis rates declined, length of dual antiplatelet therapy use and risk of long-term stent thrombosis associated with drug-eluting stents increased. Subsequent generations have improved each facet of stent design. Novel alloys maintain durability and reduce strut thickness to increase deliverability, biocompatible polymers decrease the inflammatory response and improve drug elution kinetics, and new generations of drugs predictably inhibit restenosis. Developments on the horizon include stents with bioabsorbable polymers and platforms. The purpose of this review is to assess the evolution of stent design and the evidence behind each generation and to peer into the future of stent technology.

Topics: Angioplasty, Balloon, Coronary; Animals; Cardiovascular Agents; Coronary Artery Disease; Drug-Eluting Stents; Humans; Neointima; Thrombosis

Drug-coated balloons are a new tool for the treatment of patients with coronary artery disease. The main feature of this technology is a rapid and homogenous transfer of an antiproliferative drug (paclitaxel) to the vessel wall just at the time of balloon inflation, when neointimal proliferation, in response to angioplasty, is the highest. Moreover, drug-coated balloons share adjuntive advantages over stents: the absence of permanent scaffold and polymer, the respect of the original coronary anatomy, and limited inflammatory stimuli, thereby allowing for short-term dual antiplatelet therapy. To this day, a lot of devices are available in the market, with limited scientific data for the vast majority of them. Thus, the Italian scientific society of interventional cardiologists GISE decided to coordinate the efforts of a group of reknown experts on the field, in order to obtain a Position Paper on the correct use of drug-coated balloons in all the settings of coronary artery disease, giving a class of indication to each one, based on the clinical evidence. This Position Paper represents a quick reference for operators, investigators, and manufactures to promote the understanding and the correct use of the drug-coated balloon technology in everyday clinical practice.

Topics: Angioplasty, Balloon, Coronary; Cardiac Catheters; Cardiology; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Artery Disease; Coronary Restenosis; Drug Administration Schedule; Drug Therapy, Combination; Equipment Design; Humans; Myocardial Infarction; Neointima; Platelet Aggregation Inhibitors; Treatment Outcome

The treatment of in-stent restenosis (ISR) in the femoro-popliteal artery (FPA) is one of the major challenges of endovascular therapy, occurring in up to 40% of femoro-popliteal lesions treated with bare-metal stents within 1 year of treatment. Drug-eluting technologies, involving local delivery of paclitaxel, are providing a new paradigm for the treatment of ISR. Preliminary experience shows promising results compared to other techniques such as cutting balloon angioplasty and debulking strategies. Based on available data, drug-eluting balloons (DEBs) seem sufficient as stand-alone treatment of FPA-ISR. However, larger evidence from randomized studies is warranted to identify the clinical and/or anatomical setting in which they could fail.

Topics: Angioplasty, Balloon; Animals; Cardiovascular Agents; Constriction, Pathologic; Drug-Eluting Stents; Femoral Artery; Humans; Neointima; Peripheral Arterial Disease; Plaque, Atherosclerotic; Popliteal Artery; Prosthesis Design; Radiography; Recurrence; Retreatment; Time Factors; Treatment Outcome; Vascular Access Devices; Vascular Patency

Despite significant advances in vascular biology, bioengineering, and pharmacology, restenosis remains a limitation to the overall efficacy of vascular reconstructions, both percutaneous and open. Although the pathophysiology of intimal hyperplasia is complex, a number of drugs and molecular tools have been identified that can prevent restenosis. Moreover, the focal nature of this process lends itself to treatment with local drug administration. This article provides a broad overview of current and future techniques for local drug delivery that have been developed to prevent restenosis after vascular interventions.. A systematic electronic literature search using PubMed was performed for all accessible published articles through September 2012. In an effort to remain current, additional searches were performed for abstracts presented at relevant societal meetings, filed patents, clinical trials, and funded National Institutes of Health awards.. The efficacy of local drug delivery has been demonstrated in the coronary circulation with the current clinical use of drug-eluting stents. Until recently, however, drug-eluting stents were not found to be efficacious in the peripheral circulation. Further pursuit of intraluminal devices has led to the development of balloon-based technologies, with a recent surge in trials involving drug-eluting balloons. Early data appear encouraging, particularly for treatment of superficial femoral artery lesions, and several devices have recently received the Conformité Européene mark in Europe. Investigators have also explored the periadventitial application of biomaterials containing antirestenotic drugs, an approach that could be particularly useful for surgical bypass or endarterectomy. In the past, systemic drug delivery has been unsuccessful; however, there has been recent exploration of intravenous delivery of drugs designed specifically to target injured or reconstructed arteries. Our review revealed a multitude of additional interesting strategies, including >65 new patents issued during the past 2 years for approaches to local drug delivery focused on preventing restenosis.. Restenosis after intraluminal or open vascular reconstruction remains an important clinical problem. Success in the coronary circulation has not translated into solutions for the peripheral arteries. However, our literature review reveals a number of promising approaches, including drug-eluting balloons, periadventitial drug delivery, and targeted systemic therapies. These and other innovations suggest that the future is bright and that a solution for preventing restenosis in peripheral vessels will soon be at hand.

Topics: Animals; Cardiac Catheters; Cardiovascular Agents; Coronary Restenosis; Coronary Stenosis; Drug Carriers; Drug-Eluting Stents; Endovascular Procedures; Equipment Design; Humans; Hyperplasia; Neointima; Percutaneous Coronary Intervention; Peripheral Vascular Diseases; Secondary Prevention; Treatment Outcome; Vascular Access Devices

Vascular walls change their dimension and mechanical properties in response to injury such as balloon angioplasty and endovascular stent implantation. Placement of bare metal stents induces neointimal proliferation/restenosis which progresses through different phases of repair with time involving a cascade of cellular reactions. These phases just like wound healing comprise distinct steps consisting of thrombosis, inflammation, proliferation, and migration followed by remodelling. It is noteworthy that animals show a rapid progression of healing after stent deployment compared with man. During stenting, endothelial cells are partially to completely destroyed or crushed along with medial wall injury and stretching promoting activation of platelets, and thrombus formation accompanied by inflammatory reaction. Macrophages and platelets play a central role through the release of cytokines and growth factors that induce vascular smooth muscle cell accumulation within the intima. Smooth muscle cells undergo complex phenotypic changes including migration and proliferation from the media towards the intima, and transition from a contractile to a synthetic phenotype; the molecular mechanisms responsible for this change are highlighted in this review. Since studies in animals and man show that smooth muscle cells play a dominant role in restenosis, drugs like rapamycin and paclitaxel have been coated on stent with polymers to allow local slow release of drugs, which have resulted in dramatic reduction of restenosis that was once the Achilles' heel of interventional cardiologists.

Topics: Animals; Arteries; Biomechanical Phenomena; Cardiovascular Agents; Cell Movement; Cell Proliferation; Constriction, Pathologic; Endothelial Cells; Endovascular Procedures; Hemodynamics; Humans; Mechanotransduction, Cellular; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neointima; Phenotype; Regional Blood Flow; Stents; Stress, Mechanical; Vascular System Injuries; Wound Healing

Cardiovascular diseases (CVD) are one of the leading causes of death across the globe. Pathogenesis of coronary artery disease (CAD) is lead by the progression of atherosclerotic lacerations in coronary arteries. Percutaneous coronary intervention (PCI) using balloon angioplasty was introduced in 1979 and was majorly used in the treatment of these lesions. Introduction of bare metal stents (BMS) has revolutionized stenting procedures overcoming elastic recoil and reducing restenosis commonly associated with balloon angioplasty, but follow up studies have shown 20-30% prevalence of in-stent restenosis (ISR), this led to the development of drug eluting stents (DES). But long-term follow up studies have shown increased liability of stent thrombosis. Boosting the development of safer and effective DES expounding for therapies like biodegradable polymer based DES, polymer free DES, bioresorbable DES and combination DES to collectively reduce neointimal hyperplasia and promote endothelial healing. In dual-DES development, a combination employing an anti-restenotic agent (for preventing VSMC's proliferation), which is released for the first few weeks, and then the second drug a pro-healing agent (promoting re-endothelialization) released after a month would be ideal. Growing understanding in the areas of polymer therapeutics, nanoscale surface modifications and gene therapy would assist in the delivery of multiple drugs, which would further help in the design of promising therapeutic strategies for the treatment of CAD using stent based therapies.

Topics: Angioplasty, Balloon, Coronary; Animals; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug Carriers; Drug Combinations; Drug-Eluting Stents; Humans; Hyperplasia; Neointima; Prosthesis Design; Time Factors; Treatment Outcome; Wound Healing

Exaggerated neointimal hyperplasia is considered as the primary mechanism for increased restenosis in patients with diabetes mellitus (DM) treated with bare-metal stent. However, the vessel response in DM and non-DM treated with different drug-eluting stents (DES) has not been systematically evaluated.. We investigated 3D intravascular ultrasound (postprocedure and 6 to 9 months) in 971 patients (267 with DM and 704 without DM) treated with sirolimus- (n=104), paclitaxel- (n=303), zotarolimus- (n=391), or everolimus- (n=173) eluting stents. Volumetric data were standardized by length as volume index (VI). At postprocedure, lumen VI at the stented segment was significantly smaller in DM than in non-DM, whereas vessel VI was similar between the 2 groups. At follow-up, neointimal obstruction and maximum cross-sectional narrowing (neointimal area/stent area) were not significantly different between the 2 groups with no interaction for the DES type. Consequently, lumen VI was smaller in DM than in non-DM at follow-up. In the reference segments, residual plaque burden at postprocedure was significantly greater in DM than in non-DM, although change in lumen VI was similar between the 2 groups. The arterial responses at the reference segments also showed no interaction for the DES type.. DM and non-DM lesions showed similar vessel response in both in-stent and reference segments regardless of the DES type. In the DES era, the follow-up lumen in DM patients seems to be determined primarily by the smaller lumen at postprocedure rather than exaggerated neointima within the stent or plaque proliferation at the reference segments.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Linear Models; Male; Middle Aged; Multicenter Studies as Topic; Multivariate Analysis; Neointima; Paclitaxel; Predictive Value of Tests; Prosthesis Design; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Topics: Cardiovascular Agents; Coronary Stenosis; Drug-Eluting Stents; Endovascular Procedures; Femoral Artery; Humans; Japan; Neointima; Paclitaxel; Peripheral Arterial Disease; Polymers; Popliteal Artery; Predictive Value of Tests; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome; Ultrasonography, Interventional; Vascular Patency

The pathomechanisms underlying restenosis of the bioabsorbable sirolimus-eluting metallic scaffold (Magmaris) remain unknown. Using serial optical coherence tomography, we investigated causes of restenosis, including the contribution of late scaffold recoil versus neointimal hyperplasia.. Patients enrolled in BIOSOLVE-II undergoing serial angiography and optical coherence tomography (post-intervention and follow-up: 6 months and/or 1 year) were analyzed. Patients were divided into 2 groups according to angiographic in-scaffold late lumen loss (LLL) <0.5 or ≥0.5 mm. End points were late absolute scaffold recoil and neointimal hyperplasia area as assessed by optical coherence tomography.. In addition to neointimal hyperplasia, late scaffold recoil contributed significantly to LLL of sirolimus-eluting absorbable metal scaffolds. The extent of late scaffold recoil was dependent on the underlying plaque morphology and was the highest among fibrotic lesions. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01960504.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Coronary Restenosis; Coronary Vessels; Female; Fibrosis; Humans; Male; Metals; Middle Aged; Myocardial Ischemia; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Given the characteristic differences between intravascular ultrasound (IVUS) and optical frequency domain imaging (OFDI), their approach to therapeutic guidance during percutaneous coronary interventions (PCIs) and arterial healing response after stenting may also vary.. MISTIC-1 (The Multimodality Imaging Study in Cardiology cohort 1) is a multicenter, randomized-controlled, noninferiority trial that compared imaging end points between OFDI- and IVUS-guided PCI. Patients with stable coronary artery disease were randomly assigned to either OFDI- or IVUS-guided PCI using a Biolimus A9-eluting stent according to a prespecified protocol for imaging guidance. Stent sizing was based on external elastic lamina in IVUS-guided PCI while lumen up-size in OFDI-guided PCI. Postprocedural OFDI was investigated regardless of randomization, while operators in IVUS-guided PCI arm were blinded to the images. The primary end point was in-segment minimum lumen area assessed using OFDI at 8 months, while the secondary end point was a composite of cardiovascular mortality, target-vessel myocardial infarction, or target-lesion revascularization (device-oriented composite end point). Patients were followed up to 3 years after the index procedure.. OFDI-guided PCI was not inferior to IVUS-guided PCI in terms of in-segment minimum lumen area at 8 months. Although a small sample size was acknowledged, OFDI could be an alternative to IVUS when considering intracoronary imaging-guided PCI in selected populations with coronary artery diseases. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03292081.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Japan; Male; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Durable polymers used in drug-eluting stents are considered a potential cause of hypersensitivity inflammatory response adversely affecting stent healing. Using a sequential follow-up with optical coherence tomography, we compared the differences in healing profiles of 2 drug-eluting stents with a biodegradable or durable polymer.. Sixty patients with multivessel disease were prospectively enrolled to receive both study stents, which were randomly assigned to 2 individual vessels, a Resolute Integrity zotarolimus-eluting stent with a durable BioLinx polymer and a BioMatrix NeoFlex Biolimus A9-eluting stent with a biodegradable polylactic acid polymer. Optical coherence tomography was performed at baseline, then in 5 randomly assigned monthly groups at 2 to 6 months, and at 9 months in all patients. The primary end point was the difference in optical coherence tomography strut coverage at 9 months. Key secondary end points included angiographic late lumen loss and composite major adverse cardiac events (cardiac death, myocardial infarction, target lesion revascularization, and definite or probable stent thrombosis) at 9 months. Resolute Integrity zotarolimus-eluting stent showed significantly better strut coverage than BioMatrix NeoFlex Biolimus A9-eluting stent at 2 to 6 months (. Despite having a durable polymer, Resolute Integrity zotarolimus-eluting stent exhibited better strut coverage than BioMatrix NeoFlex Biolimus A9-eluting stent having a biodegradable polymer; both showed similar antiproliferative efficacy. This novel, longitudinal, sequential optical coherence tomography protocol using each patient as own control could achieve conclusive results in small sample size.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01742507.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Hong Kong; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Balloon dilatation or debulking seems to be essential to allow successful stent implantation in calcified coronary lesions. Compared with standard balloon predilatation, debulking using high-speed rotational atherectomy (RA) is associated with higher initial procedural success albeit with higher in-stent late lumen loss at intermediate-term follow-up. Whether modified (scoring or cutting) balloons (MB) could achieve similar procedural success compared with RA is not known. In addition, whether new-generation drug-eluting stents could counterbalance the excessive neointimal proliferation triggered by RA remains to be determined.. We randomly assigned patients with documented myocardial ischemia and severely calcified native coronary lesions undergoing percutaneous coronary intervention to a strategy of lesion preparation using MB or RA followed by drug-eluting stent implantation. Stenting was performed using a third-generation sirolimus-eluting stent with a bioabsorbable polymer. The trial had 2 primary end points: strategy success (defined as successful stent delivery and expansion with attainment of <20% in-stent residual stenosis in the presence of TIMI [Thrombolysis in Myocardial Infarction] 3 flow without crossover or stent failure; powered for superiority) and in-stent late lumen loss at 9 months (powered for noninferiority). Two hundred patients were enrolled at 2 centers in Germany (n=100 in each treatment group). The mean age of the study population was 74.9±7.0 years; 76% were men, and 33.5% had diabetes mellitus. Strategy success was significantly more common in the RA group (81% versus 98%; relative risk of failure with an MB- versus RA-based strategy, 9.5; 95% CI, 2.3-39.7; P=0.0001), but mean fluoroscopy time was longer (19.6±13.4 versus 23.9±12.2 minutes; P=0.03). At 9 months, mean in-stent late lumen loss was 0.16±0.39 mm in the MB group and 0.22±0.40 mm in the RA group ( P=0.21, P=0.02 for noninferiority). Target lesion revascularization (7% versus 2%; P=0.17), definite or probable stent thrombosis (0% versus 0%; P=1.00), and target vessel failure (8% versus 6%; P=0.78) were low and not significantly different between the MB and RA groups.. Lesion preparation with upfront RA before drug-eluting stent implantation is feasible in nearly all patients with severely calcified coronary lesions, is more commonly successful as a primary strategy compared with MB, and is not associated with excessive late lumen loss. A strategy of provisional MB remains feasible, safe, and effective as long as bailout RA is readily available and may offer the advantages of compatibility with smaller sized catheters and less irradiation. Both strategies are associated with excellent clinical outcome at 9 months.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT02502851.

Topics: Absorbable Implants; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Atherectomy, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Germany; Humans; Male; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Risk Factors; Severity of Illness Index; Sirolimus; Time Factors; Treatment Outcome; Vascular Calcification

The aim of this study was to investigate the impact of attenuated-signal plaque (ASP) observed by intravascular ultrasound (IVUS) on vessel response after drug-eluting stent implantation.. Data were derived from the IVUS cohort of the J-DESsERT trial comparing paclitaxel- and sirolimus-eluting stents. Serial IVUS analysis (pre- and post-intervention, and 8-month follow-up) was performed in 136 non-AMI lesions. ASP was defined as hypoechoic plaque with ultrasound attenuation without calcification. Calcified plaque (CP) was defined as brightly echoreflective plaque with acoustic shadowing. ASP and CP scores were calculated by grading their measured angle as 0 to 4 for 0°, <90°, 90-180°, 180-270° and >270°, respectively. The entire stented segment was analyzed at 1-mm intervals.. At pre-intervention, ASP was observed in 40.4% of lesions, and this group had greater % neointimal volume (%NIV) at follow-up than the no-ASP group (p = 0.011). ASP score at pre-intervention positively correlated with %NIV (p = 0.023). During the follow-up, ASP score significantly decreased (p < 0.001), and CP score significantly increased (p < 0.001), with a negative correlation between them (p < 0.001). A decrease in the ASP score was associated with less %NIV in PES (p = 0.031), but not in SES (p = 0.229).. The greater extent of plaque with IVUS-signal attenuation at pre-intervention and its persistence during follow-up were associated with neointimal proliferation, possibly representing sustained inflammatory status, depending on the type of DES used.

Topics: Aged; Cardiovascular Agents; Cell Proliferation; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Japan; Male; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Predictive Value of Tests; Prospective Studies; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional; Vascular Calcification

The PRISON IV trial investigated the next-generation sirolimus-eluting stent (SES) with ultra-thin struts and biodegradable polymer against the second-generation everolimus-eluting stent (EES) with thin struts and durable polymer in patients with successfully recanalised chronic total occlusions (CTO). In this study, we examined the secondary optical coherence tomography endpoints.. The main PRISON IV trial randomised 330 patients to either SES or EES. At nine months, 281 (85%) patients underwent repeat angiography. Of these, 60 consecutive patients received optical coherence tomography divided over both stent groups. The mean number of struts analysed was 750±337 and 633±358 in SES and EES patients, respectively (p=0.07). The minimal lumen area, minimal stent area, maximal neointima area and neointimal thickness were comparable between the groups (4.8±2.1 and 4.4±1.5 mm2; 5.3±1.8 and 5.3±1.4 mm2; 2.5±2.0 and 2.2±1.5 mm2; 0.7±1.7 and 0.4±0.2 mm). The percentage of uncovered struts was higher with EES (6.2±7.5% and 11.9±13.4%, p=0.04), whereas the percentage of malapposed struts and mean number of coronary evaginations were significantly higher with SES (2.9±4.0% and 1.2±2.4%, p=0.02; 18.5±17.7 and 5.3±3.1, p=0.004).. The optical coherence tomography findings of this substudy demonstrated improved strut coverage with ultra-thin strut SES with bioresorbable polymer compared to thin-strut EES with durable polymer in CTO. On the other hand, SES showed a higher rate of stent strut malappositon and coronary evaginations. The clinical relevance of these findings remains to be demonstrated.

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

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.. 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.. 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).. 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.

Topics: Adolescent; Adult; Aged; Cardiovascular Agents; Cell Proliferation; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Egypt; Female; Humans; Male; Metals; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Risk Factors; Stents; Time Factors; Treatment Outcome; Young Adult

The aim of this study was to compare neointimal modification with scoring balloon pre-dilation before drug-coated balloon (DCB) versus DCB standard therapy in patients presenting with drug-eluting stent (DES) restenosis.. DCB angioplasty for the treatment of coronary drug-eluting stent restenosis has demonstrated encouraging results. The efficacy of DCB treatment relies on rapid initial drug transfer and tissue retention of the antiproliferative drug. Neointimal modification with scoring balloon pre-dilation may enhance the efficacy of DCB therapy.. In this randomized, open-label, active-controlled trial, 252 patients with clinically significant DES restenosis were enrolled at 4 centers in Germany. Patients undergoing DCB angioplasty were randomly assigned to treatment with scoring balloon pre-dilation or standard therapy. The primary endpoint of the study was in-segment percentage diameter stenosis on 6- to 8-month follow-up angiography. The secondary endpoints included binary angiographic restenosis and late lumen loss on follow-up angiography, the combined incidence of death or myocardial infarction, target lesion revascularization, and target lesion thrombosis at 1 year.. Follow-up angiographic data at 6 to 8 months were available for 203 patients (80.6%). Scoring balloon pre-dilation compared with standard therapy showed significantly lower rates with respect to the primary endpoint (35.0 ± 16.8% vs. 40.4 ± 21.4%; p = 0.047) and binary angiographic restenosis (18.5% vs. 32.0%; p = 0.026). Late lumen loss was numerically lower after scoring balloon pre-dilation compared with standard therapy (0.31 ± 59 mm vs. 0.41 ± 0.74 mm; p = 0.27). There was no difference between the groups in the incidence of death or myocardial infarction (4.0% vs. 3.4%; p = 0.73). Scoring balloon versus standard therapy showed comparable rates of target lesion revascularization (16.2% vs. 21.8%; p = 0.26). No target lesion thrombosis occurred out to 1 year.. In patients presenting with drug-eluting stent restenosis, neointimal modification with scoring balloon improves the antirestenotic efficacy of DCB therapy. (Intracoronary Stenting and Angiographic Results: Optimizing Treatment of Drug Eluting Stent In-Stent Restenosis 4 [ISAR-DESIRE 4]; NCT01632371).

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiac Catheters; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Germany; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Therapeutics; Time Factors

To assess the vessel-healing pattern of Ultimaster drug-eluting stent using optical frequency domain imaging. Our hypothesis is that biodegradable polymer-based drug-eluting technology allows complete very early strut coverage.. The DISCOVERY 1TO3 study (Evaluation With OFDI of Strut Coverage of Terumo New Drug Eluting Stent With Biodegradable Polymer at 1, 2, and 3 Months) is a prospective, single-arm, multicenter study. A total of 60 patients with multivessel disease requiring staged procedure at 1 month were treated with Ultimaster. Optical frequency domain imaging was acquired at baseline, 1, 2, and 3 months. The primary end point is optical frequency domain imaging-assessed strut coverage at 3 months. Mean age of patients was 67.2±9.9 years, and 73.3% were male, and 36.7% presented with acute coronary syndrome. A total of 132 lesions were treated, with average 1.4 lesions per patient treated at baseline and 1.1 lesions treated at 1 month. Strut coverage at 3 months of single implanted stents (n=71, primary end point) was 95.2±5.2% and of combined single and overlapped stents was 95.4±4.9%. Strut coverage of combined single and overlapped stents at 1 (n=49) and 2 months (n=38) was 85.1±12.7% and 87.9±10.8%, respectively. The median neointimal hyperplasia thickness was 0.04, 0.05, and 0.06 mm, whereas mean neointimal hyperplasia obstruction was 4.5±2.4%, 5.2±3.4%, and 6.6±3.3% at 1, 2, and 3 months, respectively.. Nearly complete strut coverage was observed in this complex population very early after implantation of Ultimaster drug-eluting stent.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01844843.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Europe; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polyesters; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

We sought to compare, by means of IVUS and OCT imaging, the performance of a novel sirolimus-eluting drug-eluting stent (DES) with biodegradable polymer (Inspiron™) to the Biomatrix™ DES. From the DESTINY trial, a total of 70 randomized patients (2:1) were enrolled in the IVUS substudy (Inspiron™, n = 46; Biomatrix™: n = 20) while 25 patients were evaluated with OCT (Inspiron™, n = 19; Biomatrix™: n = 06) at 9-month follow-up. The main endpoints were % of neointimal tissue obstruction (IVUS) and neointimal stut coverage (OCT) at 9 months. Patients treated with both DES had very little NIH formation at 9 months either by IVUS (% of NIH obstruction of 4.9 ± 4.1 % with Inspiron™ vs. 2.7 ± 2.9 % with Biomatrix™, p = 0.03) or by OCT (neointimal thickness of 144.2 ± 72.5 µm Inspiron™ vs. 115.0 ± 53.9 µm with Biomatrix™, p = 0.45). Regarding OCT strut-level assessment, again both devices showed excellent 9-month performance, with high rates of strut coverage (99.49 ± 1.01 % with Inspiron™ vs. 97.62 ± 2.21 % with Biomatrix™, p < 0.001) and very rare malapposition (0.29 ± 1.06 % with Inspiron™ vs. 0.53 ± 0.82 % with Biomatrix™, p = 0.44). Patients with any uncovered struts were more frequently identified in the Biomatrix™ group (9.78 ± 7.13 vs. 2.29 ± 3.91 %, p < 0.001). In the present study, midterm IVUS and OCT evaluations showed that both new generation DES with biodegradable polymer were effective in terms of suppressing excessive neointimal response, with very high rates of apposed and covered struts, suggesting a consistent and benign healing pattern.

Topics: Absorbable Implants; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Humans; Metals; Neointima; Percutaneous Coronary Intervention; Polymers; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

The aim of the present study was to evaluate vascular healing of the bioengineered COMBO Dual Therapy Stent compared with a cobalt-chromium (CoCr) everolimus-eluting stent (EES) as assessed by optical coherence tomography in patients with acute coronary syndromes.. CD34+ cells promote endothelial repair after vascular injury. The bioengineered COMBO Dual Therapy Stent combines CD34+ cell-capturing technology with abluminal sirolimus release, but more data from clinical studies evaluating the vascular response are needed.. In a prospective randomized multicenter clinical trial, 60 patients with acute coronary syndromes were randomized 1:1 to COMBO or CoCr EES implantation. The primary endpoint was the percentage of uncovered stent struts per stent. Stent assessment by optical coherence tomography was performed at baseline and at 60 days, followed by independent core laboratory analysis.. The percentage of uncovered struts per stent was higher with the COMBO than the CoCr EES at 60 days (median 14.7% vs. 7.7%; p = 0.04). However, no significant difference in uncovered stent struts was observed in the strut level-based analysis at 60 days, which also accounted for clustering (COMBO vs. CoCr EES; 13.6% vs. 6.9%; p = 0.09; generalized linear mixed models-adjusted analysis). Neointimal thickness at 60 days was lower with the COMBO compared with the CoCr EES (median 30.17 vs. 50.26 μm; p = 0.02; stent-level analysis). There were no significant differences in the frequency of major adverse cardiac events and each component of major adverse cardiac events within the study population between the 2 groups at 30, 60, 180, 360, and 540 days post-procedure. No target vessel stent thrombosis has been documented within 540 days.. The present multicenter, prospective clinical study for the first time compared the vascular response of the bioengineered COMBO Dual Therapy Stent with a CoCr EES in patients early after acute coronary syndrome by using intracoronary optical coherence tomographic analysis. The percentage of uncovered stent struts per stent was somewhat higher after COMBO versus CoCr EES implantation as detected by optical coherence tomography, associated with reduced neointimal thickness.

Topics: Acute Coronary Syndrome; Aged; Antibodies; Antigens, CD34; Cardiovascular Agents; Chromium Alloys; Coronary Vessels; Drug-Eluting Stents; Endothelial Cells; Europe; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; United States; Wound Healing

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

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Japan; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prospective Studies; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The efficacy of DEB in modifying the high restenosis risk associated with BMS implantation is doubtful. Optical coherence tomography (OCT) may allow precise assessment of neointimal formation after stent implantation. We performed a single-center, prospective, 1:2 randomized trial comparing BMS implantation alone (BMS group) vs. additional DEB (DEB group). DEB patients were further randomized 1:1 to DEB before stenting (pre-DEB group), or after stenting (post-DEB group). Primary endpoint was OCT-assessed neointimal hyperplasia (expressed both as mean in-stent neointimal area and as percentage obstruction of the mean stent area) at 6 months. Secondary endpoints were the percentage of uncovered and malapposed stent struts. Thirty patients were enrolled and randomized to BMS (n = 10), pre-DEB (n = 10), post-DEB (n = 10). At 6-month OCT follow-up, DEB significantly reduced neointimal area compared with BMS: mean neointimal area 2.01 ± 0.89 vs. 3.03 ± 1.07 mm(2) (p = 0.02), percentage area obstruction 24.56 ± 12.50 vs. 37.51 ± 12.26 % (p = 0.02). The percentage of uncovered and malapposed stent struts did not differ significantly between BMS and DEB. In the comparison between pre-DEB and post-DEB, no significant difference was observed for both primary and secondary endpoints. In de novo coronary lesions treated with BMS, DEB use could be associated with a mild reduction in neointimal hyperplasia at 6 months; this effect could be unrelated to the timing of DEB dilation (pre- or post-stenting).. http://www.clinicaltrials.gov . Identifier: NCT01057563.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiac Catheters; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Female; Humans; Hyperplasia; Male; Metals; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prospective Studies; Risk Factors; Rome; Stents; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Topics: Cardiovascular Agents; Drug-Eluting Stents; Endovascular Procedures; Femoral Artery; Humans; Neointima; Paclitaxel; Peripheral Arterial Disease; Prospective Studies; Prosthesis Design; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

The aim of this study was to compare the efficacy of amphilimus-eluting stents (AES) with that of everolimus-eluting stents (EES) in patients with diabetes mellitus (DM).. The AES is a polymer-free drug-eluting stent that elutes sirolimus formulated with an amphiphilic carrier from laser-dug wells. This technology could be associated with a high efficacy in patients with DM.. This was a multicenter, randomized, noninferiority trial. Patients with DM medically treated with oral glucose-lowering agents or insulin and de novo coronary lesions were randomized in a 1:1 fashion to AES or EES. The primary endpoint was the neointimal (NI) volume obstruction assessed by optical coherence tomography at 9-month follow-up.. A total of 116 lesions in 112 patients were randomized. Overall, 40% were insulin-treated patients, with a median HbA1c of 7.3% (interquartile range: 6.7% to 8.0%). The primary endpoint, NI volume obstruction, was 11.97 ± 5.94% for AES versus 16.11 ± 18.18% for EES, meeting the noninferiority criteria (p = 0.0003). Pre-specified subgroup analyses showed a significant interaction between stent type and glycemic control (p = 0.02), with a significant reduction in NI hyperplasia in the AES group in patients with the higher HbA1c (p = 0.03). By quantitative coronary angiography, in-stent late loss was 0.14 ± 0.24 for AES versus 0.24 ± 0.57 mm for EES (p = 0.27), with a larger minimal lumen diameter at follow-up for AES (p = 0.02), mainly driven by 2 cases of occlusive restenosis in the EES group.. AES are noninferior to EES for the coronary revascularization of patients with DM. These results suggest a high efficacy of the AES and may support the potential benefit of this stent in patients with DM. (A Randomized Comparison of Reservoir-Based Polymer-Free Amphilimus-Eluting Stents Versus Everolimus-Eluting Stents With Durable Polymer in Patients With Diabetes Mellitus [RESERVOIR]; NCT01710748).

Topics: Aged; Biomarkers; Blood Glucose; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Diabetes Mellitus; Drug-Eluting Stents; Everolimus; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Prospective Studies; Prosthesis Design; Risk Factors; Sirolimus; Spain; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The purpose of this study was to evaluate the efficacy and long-term outcomes of a novel polymer/carrier-free drug-coated stent (DCS) in patients with de novo coronary lesions.. The BioFreedom (BFD) DCS incorporates a low-profile, stainless-steel platform, with a surface that has been modified to create a selectively microstructured abluminal surface that allows adhesion and further release of Biolimus A9 (Biosensors Europe SA, Morges, Switzerland).. A total of 182 patients (183 lesions) were randomized into a 1:1:1 ratio for treatment with BFD "standard dose" (BFD) or BFD "low dose" (BFD-LD) versus first-generation paclitaxel-eluting stents (PES) at 4 sites in Germany.. Baseline and procedural characteristics were well matched. At 4-month angiographic follow-up (Cohort 1, n = 75), in-stent late lumen loss (LLL) was significantly lower with BFD and BFD-LD versus PES (0.08 and 0.12 mm vs. 0.37 mm, respectively; p < 0.0001 for BFD vs. PES, and p = 0.002 for BFD-LD vs. PES). At 12 months (Cohort 2, n = 107), in-stent LLL (primary endpoint) was 0.17 mm in BFD versus 0.35 mm in PES (p = 0.001 for noninferiority; p = 0.11 for superiority); however, the BFD-LD (0.22 mm) did not reach noninferiority (p = 0.21). At 5 years (175 of 182), there were no significant differences in major adverse cardiac events (23.8%, 26.4%, and 20.3%) and clinically indicated target lesion revascularization (10.8%, 13.4%, and 10.2%) for BFD, BFD-LD, and PES, respectively; also, there was no definite/probable stent thrombosis reported.. The BFD, but not the BFD-LD, demonstrated noninferiority versus PES in terms of in-stent LLL, a surrogate of neointimal hyperplasia, at 12-month follow-up. At 5 years, clinical event rates were similar, without occurrence of stent thrombosis in all groups. (BioFreedom FIM Clinical Trial; NCT01172119).

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Germany; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Risk Factors; Single-Blind Method; Sirolimus; Stainless Steel; Surface Properties; Time Factors; Treatment Outcome

This study sought to report the late multimodality imaging and clinical outcomes of the novel poly-l-lactic-acid-based DESolve novolimus-eluting bioresorbable coronary scaffold for the treatment of de novo coronary lesions.. Bioresorbable scaffolds are an alternative to drug-eluting metallic stents and provide temporary vascular scaffolding, which potentially may allow vessel restoration and reduce the risk of future adverse events.. Overall, 126 patients were enrolled at 13 international sites between November 2011 and June 2012. The primary endpoint was in-scaffold late lumen loss at 6 months. Major adverse cardiac events, the main safety endpoint, were defined as the composite of cardiac death, target vessel myocardial infarction, or clinically indicated target lesion revascularization. All patients underwent angiography at 6 months. Serial intravascular ultrasound and optical coherence tomography were performed in a subset of patients.. The scaffold device success rate was 97% (n = 122 of 126), and procedural success was 100% (n = 122 of 122). The major adverse cardiac event rate was 3.3% (n = 4 of 122) at 6 months and 7.4% (n = 9 of 122) at 24 months, including 1 probable stent thrombosis within the first month. At 6-month angiographic follow-up, in-scaffold late lumen loss was 0.20 ± 0.32 mm. Paired intravascular ultrasound analysis demonstrated a significant increase in vessel, lumen and scaffold dimensions between post-procedure and 6-month follow-up, and strut-level optical coherence tomography analysis showed full strut coverage in 99 ± 1.7%.. Our results showed favorable performance of the DESolve scaffold, effective inhibition of neointimal hyperplasia, and for the first time, early luminal and scaffold growth at 6 months with sustained efficacy and safety through 2 years. (Elixir Medical Clinical Evaluation of the DESolve Novolimus Eluting Bioresorbable Coronary Scaffold System-The DESolve Nx Trial; NCT02086045).

Topics: Absorbable Implants; Aged; Brazil; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Europe; Female; Humans; Hyperplasia; Macrolides; Male; Middle Aged; Neointima; New Zealand; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Second-generation drug-eluting stent (DES) have shown a better safety and efficacy as compared to first generation DES due to an improved vascular healing process. This process has not been so far evaluated in vivo in an overtime fashion by optical coherent tomography (OCT). We sought to evaluate the vascular healing process after everolimus-eluting stent (EES) implantation at 6, 9 and 12months, by OCT.. Consecutive 36 patients undergoing percutaneous coronary intervention with EES were randomized 1:1:1 to receive OCT imaging at 6 (group A), 9 (group B) or 12-month follow-up (group C). One patient from group C was excluded because of target lesion revascularization at 1-month, whereas 5 patients withdraw the informed consent. Finally, 30 patients were analyzed.. Neointimal thickness was not different between 3 groups (group A: 99.50 [94.06-127.79] μm, group B: 107.26 [83.48-133.59] μm, group C: 127.67 [102.51-138.49] μm; p=0.736). Although the percentage of "uncovered struts" was significantly higher in group A as compared to the other groups (8.0% vs. 4.4% vs. 2.9%, respectively; p=0.180), the ratio of uncovered to total struts per section <30% was similar between 3 groups (0.3% vs. 0.3% vs. 0%, respectively; p=1.000).. Healing process following EES implantation seems almost completed at 6-month follow-up. These data, which need to be confirmed in a larger study, may support the decision to shorten dual antiplatelet therapy.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Spain; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

This registry evaluated the safety and clinical outcomes of the Combo stent in an all-comers population in routine clinical practice. We report 1-year results.. Limitations of current generation drug-eluting stents (DES) are 3-fold: stent thrombosis, neoatherosclerosis related to impaired healing, and repeat revascularization due to (late-) in-stent restenosis. The Combo stent combines an abluminal biodegradable coating eluting sirolimus and a luminal anti-CD34(+) antibody layer to attract endothelial progenitor cells in order to promote vessel healing, thus preventing neointima formation and restenosis.. The REMEDEE (Randomized study to Evaluate the safety and effectiveness of an abluMinal sirolimus coatED bio-Engineered StEnt) post-market registry was an international, multicenter, prospective trial that evaluated clinical outcomes after deployment of the Combo stent, in an all-comers population of patients treated with a Combo stent in the setting of routine clinical care. Clinical endpoints were target lesion failure (TLF), defined as a composite of cardiac death, nonfatal myocardial infarction (MI), or target lesion revascularization (TLR).. Between June 2013 and March 2014, a total of 1,000 patients were included in the registry, 49.9% of whom presented with acute coronary syndrome. Mean age was 65 ± 11 years old (range: 34 to 94 years of age), and 74% of patients were male; 58.9% of 1,255 lesions were American Heart Association type B2 or C lesions. The primary endpoints were 5.7% TLF, 1.7% cardiac death, 0.7% target vessel MI, and 4.4% TLR. Definite stent thrombosis occurred in 0.5% of subjects; no thrombosis occurred after 9 days post-stenting.. This registry showed excellent 1-year results of novel Combo bioengineered stent technology in an all-comers patient population. (Prospective Registry to Assess the Long-term Safety and Performance of the Combo Stent [REMEDEE]; NCT01874002).

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Europe; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Neointima; Percutaneous Coronary Intervention; Product Surveillance, Postmarketing; Prospective Studies; Prosthesis Design; Registries; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Wound Healing

The aim of this study was to analyze the difference in neointima pattern assessed by intravascular ultrasound (IVUS) between two dedicated bifurcation stents, BiOSS® Expert and BiOSS® LIM at 12-month follow-up. This manuscript reports IVUS findings obtained from the analysis of patients enrolled into first-in-man registries initially assessing the BiOSS Expert® (paclitaxel) and BiOSS LIM® (sirolimus) stents. Quantitative angiographic analysis was performed pre, post-stenting, and at follow-up. IVUS examination was performed at 12 months. There were analyzed 34 cases (BiOSS Expert® 11 patients, BiOSS LIM® 23 patients). Procedural characteristics in the two groups were similar, except for rates of main vessel predilatation and FKB/POT, which were higher in BiOSS® LIM group, 54.5 % vs 73.9 % (P < 0.05) and 0 % vs 39.1 % (P < 0.05), respectively. When comparing late lumen loss (LLL) for both stents there were significantly bigger values for main vessel and main branch in the BiOSS® Expert group, but not in side branch. Intravascular ultrasound examination showed that in the BiOSS LIM® group comparing with the BiOSS Expert® group there was lower neointima burden in the whole stent (24.7 ± 7.5 % vs 19.4 ± 8.6 %, P < 0.05) as well as in main vessel (22.8 ± 5.6 % vs 16.9 ± 6.1 %, P < 0.05) and main branch (36.1 ± 6.5 % vs 27.6 ± 8.7 %, P < 0.05), but not at the level of bifurcation (15.1 ± 3.8 % vs 13.6 ± 5.4 %, P = NS). In addition, we found that final kissing balloon/proximal optimization technique (FKB/POT) was associated with significantly smaller value of LLL in main vessel (0.24 ± 0.09 mm vs 0.32 ± 0.14 mm, P < 0.05), which in IVUS analysis resulted in smaller neointima burden in main vessel (13.7 ± 3.9 % vs 18.9 ± 4.45 %, P < 0.05) as well as at the bifurcation site (12.6 ± 4.1 % vs 14.1 ± 2.4 %, P < 0.05). The obtained results suggest that neointima proliferation was the largest in main branches of both stents assessed in quantitative angiography (LLL) as well as in IVUS (neointima burden) and the neointima increase was smaller in BiOSS LIM® stents than in BiOSS Expert® stents. Moreover, the middle part of the stent seems to not to be associated with excessive neointima proliferation and more aggressive protocol of implantation with the use FKB/POT seems to decrease this process.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cell Proliferation; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Non-ST Elevated Myocardial Infarction; Paclitaxel; Predictive Value of Tests; Prosthesis Design; Registries; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Current monotherapy drug-eluting stents are associated with impaired healing, neoatherosclerosis, and late stent thrombosis. The healing profile and neointimal transformation of the first dual-therapy endothelial progenitor cell-capturing sirolimus-eluting stent are unknown.. In this prospective, single-center study, 61 patients treated with the Combo stent had optical coherence tomography at baseline, early follow-up (4 monthly groups in a 1:2:2:1 ratio from 2 to 5 months), 9 months, and 24 months. Optical coherence tomography early strut coverage increased from 77.1% to 92.5% to 92.7% to 94.9% between 2 and 5 months. At 9 months, the major adverse cardiac event rate was 1.64%, and angiographic in-stent late loss was 0.24 mm (0.08-0.40). The 36-month major adverse cardiac event rate was 3.3%. From 9 to 24 months, neointimal regression was confirmed by optical coherence tomography: neointimal thickness (median [first quartile and third quartile]), 0.14 mm (0.08 and 0.21) versus 0.12 mm (0.07 and 0.19), P<0.001; neointimal volume, 29.9 mm(3) (22.1 and 43.2) versus 26.2 mm(3) (19.6 and 35.8), P=0.003; and percent neointimal volume, 17.8% (12.2 and 21.2) versus 15.7% (11.2 and 19.4), P=0.01. No definite or probable late stent thrombosis was recorded.. With additional endothelial progenitor cell-capturing technology, the Combo stent exhibits a unique late neointimal regression (from 9 to 24 months) that has not been reported in any drug-eluting stents, translating into good 36-month clinical results with minimal restenosis and no late stent thrombosis. This is the first study testing the concept of using a longitudinal sequential optical coherence tomography protocol to continuously document early healing profile and late neointimal transformation, predicting long-term outcomes of a new novel stent platform.. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01274234, NCT01756807, and NCT02263313.

Topics: Aged; Cardiovascular Agents; Combined Modality Therapy; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Endothelial Progenitor Cells; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Patients with diabetes mellitus (DM) remain at high risk for stent restenosis and adverse cardiovascular events in the drug-eluting stent era. The amphilimus-eluting stent (AES) is a third generation reservoir-based polymer-free drug-eluting stent that has shown promising preliminary results in patients with DM. It has been suggested that the formulation of the drug with fatty acids could not only modulate the drug release in a timely manner but also achieve convenient levels of drug concentration in diabetic cardiac cells. The aim of this trial is to assess the efficacy of the AES in patients with DM compared with the cobalt chromium everolimus-eluting stent with non-erodible polymer (EES).. This is an investigator-initiated, multicenter, randomized clinical trial, performed in patients with DM. A total of 112 diabetic patients receiving glucose-lowering agents and requiring percutaneous revascularization of a de novo lesion will be randomized in a 1:1 fashion to receive AES or EES. The primary endpoint is the neointimal volume obstruction at 9 months, evaluated by optical coherence tomography. Secondary endpoints will include strut coverage, angiographic in-stent late loss and clinical endpoints such as target vessel revascularization or probable/definite stent thrombosis. This study completed the inclusion in October 2013.. The RESERVOIR trial is an investigator-initiated trial that will evaluate whether the polymer-free AES is not inferior to the EES inhibiting the neointimal hyperplasia in patients with DM. These results are also expected to improve our knowledge of the neointimal healing process in this population (Clinicaltrials.gov number NCT01710748).

Topics: Cardiovascular Agents; Chromium Alloys; Clinical Protocols; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Fatty Acids; Humans; Neointima; Percutaneous Coronary Intervention; Polymers; Prosthesis Design; Research Design; Spain; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The aim of this study was to evaluate the extent of neointimal response after the implantation of a second-generation drug-eluting stent, zotarolimus-eluting stent (ZES-ER, Endeavor Resolute) or everolimus-eluting stent (EES, Xience V), using intravascular ultrasound (IVUS) in diabetic patients.. In all, 154 diabetic patients with de-novo coronary lesions were randomized to be implanted with a ZES-ER or EES, and the angiographic follow-up at 9 months combined with a complete IVUS study was available for 96 patients with 101 lesions.. Baseline demographic and lesion parameters were similar in both groups at index percutaneous coronary intervention. On follow-up angiography, in-stent late lumen loss and minimal lumen diameter were not different between the two groups. On IVUS study, neointimal hyperplasia volume [median (interquartile range): ZES-ER vs. EES; 2.25 mm (0.57-6.25) vs. 1.59 mm (0.45-8.37), P=0.615] and in-stent percentage of volume obstruction [median (interquartile range): ZES-ER vs. EES; 1.16% (0.33-3.61) vs. 0.77% (0.29-4.01), P=0.615] showed similar results between the two groups.. In diabetic patients, the second-generation drug-eluting stents, ZES-ER and EES, were comparable in inhibiting neointimal proliferation.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Pilot Projects; Predictive Value of Tests; Prosthesis Design; Republic of Korea; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

To evaluate the preliminary safety and efficacy of the EXCEL II stent system.. Although the first biodegradable polymer drug-eluting stent (BP-DES), EXCEL, was launched nearly a decade ago, in-stent restenosis and stent thrombosis remain pertinent clinical problems in practice. A new cobalt-chromium BP-DES EXCEL II has been developed with the aim of improving stent safety and efficacy.. Forty-five patients with single de novo native coronary lesions were enrolled and randomized to two groups in a 2:1 ratio, the 4-month follow-up group (n = 30) and the 12-month follow-up group (n = 15). All patients underwent percutaneous coronary intervention (PCI) with the EXCEL II stent system. Quantitative coronary angiography (QCA) and optical coherence tomography (OCT) were used to assess coronary vasculature at the designated 4- or 12-month follow-up. The primary outcome was major adverse cardiac events (MACE) at 30 days post-PCI.. No MACE, thrombotic events, or target lesion failure was found in the 45 patients during the 12-month follow-up. There was no significant difference (P > 0.05) between the two groups in terms of in-stent and in-segment late lumen loss (LLL). No in-stent and in-segment restenosis was found in either group. At follow-up, the ratio of >10% uncovered struts per lesion was 26.67% in the 4-month group and 0% in the 12-month group (P < 0.05). Neointimal coverage in the 12-month group was significantly better than in the 4-month group (98.58% vs. 93.51%, P < 0.01).. This first-in-man study demonstrates promising feasibility, safety, and efficacy of EXCEL II stents. These stents were found to have rapid endothelialization and low LLL rates at 4 and 12 months after implantation.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; China; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Biodegradable polymers for release of antiproliferative drugs from drug-eluting stents aim to improve vascular healing. We assessed noninferiority of a novel ultrathin strut drug-eluting stent releasing sirolimus from a biodegradable polymer (Orsiro, O-SES) compared with the durable polymer Xience Prime everolimus-eluting stent (X-EES) in terms of the primary end point in-stent late lumen loss at 9 months.. A total of 452 patients were randomly assigned 2:1 to treatment with O-SES (298 patients, 332 lesions) or X-EES (154 patients, 173 lesions) in a multicenter, noninferiority trial. The primary end point was in-stent late loss at 9 months. O-SES was noninferior to X-EES for the primary end point (0.10±0.32 versus 0.11±0.29 mm; difference=0.00063 mm; 95% confidence interval, -0.06 to 0.07; Pnoninferiority<0.0001). Clinical outcome showed similar rates of target-lesion failure at 1 year (O-SES 6.5% versus X-EES 8.0%; hazard ratio=0.82; 95% confidence interval, 0.40-1.68; log-rank test: P=0.58) without cases of stent thrombosis. A subgroup of patients (n=55) underwent serial optical coherence tomography at 9 months, which demonstrated similar neointimal thickness among lesions allocated to O-SES and X-EES (0.10±0.04 mm versus 0.11±0.04 mm; -0.01 [-0.04, -0.01]; P=0.37). Another subgroup of patients (n=56) underwent serial intravascular ultrasound at baseline and 9 months indicating a potential difference in neointimal area at follow-up (O-SES, 0.16±0.33 mm(2) versus X-EES, 0.43±0.56 mm(2); P=0.04).. Compared with durable polymer X-EES, novel biodegradable polymer-based O-SES was found noninferior for the primary end point in-stent late lumen loss at 9 months. Clinical event rates were comparable without cases of stent thrombosis throughout 1 year of follow-up.. http://www.clinicaltrials.gov. Unique identifier: NCT01356888.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Europe; Everolimus; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neointima; Polymers; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

The aim of this study was to assess the safety and the efficacy of the novel sirolimus-eluting Prolim® stent with a biodegradable polymer in the all-comers population.. We prospectively enrolled all patients with stable coronary artery disease or acute coronary syndrome treated with Prolim® stent between January and December 2013 in two interventional cardiology centers in Poland. Angiographic control was planned at 12 months, in which 15 % of patients (randomly chosen) underwent optical coherence tomography imaging. The primary end-point was the cumulative rate of cardiac death, myocardial infarction, and target lesion revascularization at 12 months.. There were 204 patients enrolled, in whom 238 Prolim® stents were deployed (1.17 stent per patient). The mean age was 68 ± 10 years and 32.8 % were females. The examined stent was implanted in 5.9 % in STEMI patients, in 21.6 % - in NSTE-ACS and in 72.5 % - in patients with stable coronary artery disease. The Prolim® stent was most frequently implanted in right coronary artery (38.2 %) followed by left anterior descending artery (34.0 %). The cumulative major adverse cardiovascular events rate at 12 months was 6.9 %, and the clinically-driven target lesion revascularization rate - 5.4 %. At 12 months in quantitative coronary angiography the late lumen loss was 0.21 ± 0.18 mm, and in optical coherence tomography the mean neointima burden was 24.6 ± 8.6 %.. Sirolimus-eluting Prolim® stent with a biodegradable polymer is a feasible device with a very good safety profile and long-term clinical effectiveness.. ClinicalTrials.gov NCT02545985 .

Topics: Absorbable Implants; Acute Coronary Syndrome; Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Neointima; Percutaneous Coronary Intervention; Poland; Polymers; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Registries; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The aim of this study was to evaluate the Sparrow sirolimus-eluting stent (Sparrow-SES) against the Sparrow bare-metal stent (Sparrow-BMS) and conventional balloon-expandable bare-metal stent (BMS: Driver/Micro-Driver stent, Medtronic Vascular, Santa Rosa, CA).. The Sparrow stent (Biosensors International, Singapore) consists of a guide wire-based, self-expandable, ultra-thin nitinol stent. The performance of this device with sirolimus in a fully biodegradable polymer has not been determined.. A total of 74 patients were included in this intravascular ultrasound (IVUS) sub-study of the CARE II trial, which was a prospective, randomized, multicenter trial in the treatment of single de novo native coronary artery lesions in vessels ranging from 2.0 mm to 2.75 mm in diameter (Sparrow-SES: n = 31, Sparrow-BMS: n = 22, BMS: n = 21).. Stent volume index (VI) was significantly increased 8-month later in Sparrow-SES and Sparrow-BMS, but not in BMS (4.0 ± 1.0 to 4.6 ± 1.0 mm(3) /mm, p<0.0001, 4.0 ± 0.6 to 4.4 ± 0.8 mm(3) /mm, p<0.05, and 5.2 ± 1.0 to 5.1 ± 0.9 mm(3) /mm, p=0.421, respectively). % neointimal obstruction in Sparrow-SES was significantly smaller than those in Sparrow-BMS and BMS at follow-up (17.6 ± 9.4 vs. 36.2 ± 13.8 and 39.9 ± 11.1%, p<0.001). Sparrow-SES showed a mean 15% stent expansion and good suppression of neointimal proliferation, resulting in a significantly lower percentage of change in lumen VI during follow-up period (Sparrow-SES: -6.2 ± 16.2%, Sparrow-BMS: -30.4 ± 11.6%, BMS: -40.4 ± 10.0%, p<0.001).. The self-expanding Sparrow-SES demonstrated chronic stent expansion, good suppression of neointimal proliferation and resulted in a more preserved lumen in stented small vessels compared with the Sparrow-BMS and conventional balloon expandable BMS.

Topics: Aged; Alloys; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cell Proliferation; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Stents; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Persistence of stent polymer coating has been associated with incomplete endothelialization, expansive vessel remodeling, neoatherosclerosis, and delayed healing associated with inflammation that may contribute to late adverse events.. The BICARE (Lepu Medical, Beijing, China) stent is a novel polymer-free, nanotechnology-based stent eluting sirolimus and probucol. As a first in human feasibility study, patients with a single de novo native coronary stenosis <30 mm in length and with reference vessel diameter from 2.5 to 4.0 mm underwent revascularization with the BICARE stent. The primary endpoint of target lesion failure (TLF) was assessed at 30 days. Secondary endpoints included in-stent late lumen loss and proportion of uncovered or malapposed stent struts by optical coherence tomography at 4-month angiographic surveillance.. Among 32 consecutive patients (age, 55.7 ± 8.7 years; men, 62.5%; diabetes, 18.8%), the average baseline reference vessel diameter and lesion length were 2.85 ± 0.48 mm and 15.0 ± 5.6 mm, respectively. At 30 days there was no occurrence of TLF. At 4 months (angiographic follow-up, N=32), angiographic in-stent late loss was 0.14 ± 0.19 mm, and the in-stent binary restenosis rate was 3.1%. Complete strut coverage was 98.2% with 0.2% malapposition among 16,751 analyzed struts. At 18 months, TLF occurred in 3 (9.4%) patients related to repeat revascularization with no adverse safety events identified.. The preliminary feasibility and safety of a polymer-free, dual-drug eluting stent are demonstrated by absence of early adverse safety events and favorable angiographic suppression of neointimal hyperplasia. Stent imaging suggests favorable healing with extensive stent strut coverage and very low malapposition. These findings further inform comparison with biopermanent polymer DES.

Topics: Cardiovascular Agents; China; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug Combinations; Drug-Eluting Stents; Feasibility Studies; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Probucol; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To evaluate the effects of the everolimus-eluting Xience™/Promus™ stent (EES) and the sirolimus-eluting Cypher™ stent (SES) on intimal hyperplasia (IH) in diabetic patients.. Patients with diabetes mellitus have increased risk of in-stent restenosis after coronary stent implantation due to intimal hyperplasia (IH).. In a sub study of the Randomized Comparison of Everolimus-Eluting and Sirolimus-Eluting Stents in Patients Treated with Percutaneous Coronary Intervention (SORT OUT IV trial), serial intravascular ultrasound (IVUS) 10-month follow-up data were available in 88 patients, including 48 EES and 40 SES treated patients. IVUS endpoints included IH volume, in-stent % volume obstruction and changes in external elastic membrane (EEM) volume.. Compared with the SES group, IH volume was increased in the EES group [median (interquartile range): 2.8 mm(3) (0.0-12.6) vs. 0.0 mm(3) (0.0-1.1), P = 0.001]. In-stent % volume obstruction was increased in EES compared to SES [median (interquartile range): 1.6% (0.0-8.2) vs. 0.0% (0.0-1.0), P = 0.001]. Peri-stent external elastic membrane (EEM) volume: (post procedure vs. follow-up EES [300 mm(3) (219-491) vs. 307 mm(3) (223-482), P = 0.73] and SES [316 mm(3) (235-399) vs. 323 mm(3) (246-404), P = 0.05]) and peri-stent plaque volume: EES [163 mm(3) (103-273) vs. 184 mm(3) (115-291), P = 0.18] and SES [186 mm(3) (139-248) vs. 175 mm(3) (153-243), P = 0.26]) were unchanged in both groups. In the proximal reference segment a significant increase in plaque area was seen in the EES group only, without vascular remodeling.. In diabetic patients, EES stent implantation was associated with increased IH volume obstruction without involvement of vascular remodeling.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional; Vascular Remodeling

This study sought to perform clinical and imaging assessments of the DESolve Bioresorbable Coronary Scaffold (BCS).. BCS, which is drug eluting, may have potential advantages compared with conventional metallic drug-eluting stents. The DESolve system, designed to provide vessel support and neointimal suppression, combines a poly-l-lactic acid-based scaffold with the antiproliferative myolimus.. The DESolve First-in-Man (a non-randomized, consecutive enrollment evaluation of the DESolve myolimus eluting bioresorbable coronary stent in the treatment of patients with de novo native coronary artery lesions) trial was a prospective multicenter study enrolling 16 patients eligible for treatment. The principal safety endpoint was a composite of cardiac death, myocardial infarction, and clinically indicated target lesion revascularization. The principal imaging endpoint was in-scaffold late lumen loss (LLL) assessed by quantitative coronary angiography (QCA) at 6 months. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) imaging was performed at baseline and 6 months; multislice computed tomography (MSCT) was performed at 12 months.. Acute procedural success was achieved in 15 of 15 patients receiving a study scaffold. At 12 months, there was no scaffold thrombosis and no major adverse cardiac events directly attributable to the scaffold. At 6 months, in-scaffold LLL (by QCA) was 0.19 ± 0.19 mm; neointimal volume (by IVUS) was 7.19 ± 3.56%, with no evidence of scaffold recoil or late malapposition. Findings were confirmed with OCT and showed uniform, thin neointimal coverage (0.12 ± 0.04 mm). At 12 months, MSCT demonstrated excellent vessel patency.. This study demonstrated the feasibility and efficacy of the DESolve BCS. Results showing low in-scaffold LLL, low % neointimal volume at 6 months, no chronic recoil, and maintenance of lumen patency at 12 months prompt further study. (DESolve First-in-Man; EudraCT number 2011-000027-32).

Topics: Absorbable Implants; Aged; Aged, 80 and over; Belgium; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Humans; Lactic Acid; Male; Materials Testing; Models, Cardiovascular; Multidetector Computed Tomography; Multimodal Imaging; Myocardial Infarction; Neointima; New Zealand; Percutaneous Coronary Intervention; Polyesters; Polymers; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Time Factors; Tissue Scaffolds; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional; Vascular Patency

The Cobra-P drug-eluting stent (DES) system consists of cobalt chromium alloy with bio-absorbable siloxane sol-gel matrix coating that elutes low dose paclitaxel within 6 months. The aim of this first-in-man trial was to evaluate the safety and performance of 2 doses of the Cobra-P DES.. A total of 60 lesions (54 patients) were sequentially assigned to 2 different paclitaxel doses: group A (3.7 μg/18mm, n=30) or group B (8 μg/18mm, n=30). The primary endpoint was MACE at 4 months defined as cardiac death, myocardial infarction, and target lesion revascularization.. Patient and lesion characteristics were matched between the 2 groups except for male sex. MACE at 4 months was 3.3% and 0% respectively (P=1.000) and at 1-year follow-up remained unchanged. In-stent late loss at 4 months was similar in both groups (0.36 ± 0.30mm and 0.34 ± 0.20mm P=.773).. In this FIM study, implantation of the Cobra-P low dose paclitaxel-eluting stent with a bioabsorbable sol-gel coating was proven to be feasible and safe. Moderate neointimal proliferation was observed as well as an acceptable MACE rate up to 1 year.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Cell Proliferation; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Feasibility Studies; Female; Humans; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Time Factors; Treatment Outcome

The INSPIRON-I trial is a first-in-man evaluation of the safety and efficacy of the Inspiron drug-eluting stent, a sirolimus-eluting stent with abluminal biodegradable polymer coating and thin cobalt-chromium alloy.. This is a randomised, multicentre comparison between Inspiron and a stent with the same metallic structure but without polymer coating or drug elution (Cronus). The primary objective was to evaluate the in-segment late loss (LLL) at six months. Secondary endpoints included percent in-stent obstruction as measured by intravascular ultrasound (IVUS) at six months and major adverse cardiac events (MACE). Fifty-eight patients were enrolled (60 lesions), 39 for Inspiron and 19 for Cronus. Baseline clinical and angiographic characteristics of both groups were similar. At six months, the in-segment LLL was reduced in the Inspiron group compared to the control group (0.19±0.16 mm vs. 0.58±0.4 mm, respectively; p<0.001), as well as the percent neointimal obstruction (7.8±7.1% vs. 26.5±11.4%; p<0.001). At two-year follow-up, incidence of MACE was similar between groups (7.9 vs. 21.1%, respectively; p=0.20), with lower target lesion revascularisation for Inspiron (0 vs. 21.1%, respectively; p=0.01) and no stent thrombosis.. Sirolimus eluted from an abluminal biodegradable polymer on a cobalt-chromium alloy proved effective in reducing restenosis at six months.

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Brazil; Cardiovascular Agents; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Prospective Studies; Prosthesis Design; Single-Blind Method; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

This study sought to assess in vivo sex differences in the pathophysiology of ST-segment elevation myocardial infarction (STEMI) and vascular response to primary percutaneous coronary intervention (PCI).. There is no consensus on whether differences in the pathophysiology of STEMI and response to primary PCI between women and men reflect biological factors as opposed to differences in age.. In this prospective, multicenter study, 140 age-matched men and women with STEMI undergoing primary PCI with everolimus-eluting stent were investigated with intravascular optical coherence tomography, histopathology-immunohistochemistry of thrombus aspirates, and serum biomarkers. Primary endpoints were the percentages of culprit plaque rupture at baseline and everolimus-eluting stent strut coverage at 9-month follow-up as determined by optical coherence tomography.. Men and women had similar rates of plaque rupture (50.0% vs. 48.4%; risk ratio [RR]: 1.03; 95% confidence interval [CI]: 0.73 to 1.47; p = 0.56). Nonruptured/eroded plaques comprised 25% of all cases (p = 0.86 in men vs. women). There were no sex differences in composition of aspirated thrombus and immune and inflammatory serum biomarkers. At 9 months, women had similar strut coverage (90.9% vs. 92.5%; difference in medians: RR: 0.2%; 95% CI: -0.4% to 1.3%; p = 0.89) and amount of in-stent neointimal obstruction (10.3% vs. 10.6%; p = 0.76) as men did. There were no sex differences in clinical outcome either at 30-day or 1-year follow-up.. In patients presenting with STEMI undergoing primary PCI, no differences in culprit plaque morphology and factors associated with coronary thrombosis were observed between age-matched men and women. Women also showed similar vascular healing response to everolimus-eluting stents as men did. (Optical Coherence Tomography Assessment of Gender Diversity In Primary Angioplasty: The OCTAVIA Trial [OCTAVIA]; NCT01377207).

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Female; Health Status Disparities; Humans; Male; Middle Aged; Myocardial Infarction; Neointima; Odds Ratio; Percutaneous Coronary Intervention; Prospective Studies; Risk Factors; Rupture, Spontaneous; Sex Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

In this randomized trial, strut coverage and neointimal proliferation of a therapy of bare metal stents (BMSs) postdilated with the paclitaxel drug-eluting balloon (DEB) was compared with everolimus drug-eluting stents (DESs) at 6-month follow-up using optical coherence tomography. We hypothesized sufficient stent coverage at follow-up.. A total of 105 lesions in 90 patients were treated with either XIENCE V DES (n=51) or BMS postdilated with the SeQuent Please DEB (n=54). At follow-up, comparable results on the primary optical coherence tomography end point (percentage uncovered struts 5.64±9.65% in BMS+DEB versus 4.93±9.29% in DES; P=0.366) were found. Thus, BMS+DEB achieved the prespecified noninferiority margin of 5% uncovered struts versus DES (difference between treatment means, 0.71%; one-sided upper 95% confidence interval, 4.14%; noninferiority P=0.04). Optical coherence tomography analysis showed significantly more global neointimal proliferation in the BMS+DEB group (15.7±7.8 versus 11.0±5.2 mm(3) proliferation volume/cm stent length; P=0.002). No significant focal in-stent stenosis analyzed with angiography (percentage diameter stenosis at follow-up, 22.8±11.9 versus 16.9±10.4; P=0.014) and optical coherence tomography (peak local area stenosis, 39.5±13.8% versus 36.8±15.6%; P=0.409) was found.. Good stent strut coverage of >94% was found in both therapy groups. Despite greater suppression of global neointimal growth in DES, both DES and BMS+DEB effectively prevented clinically relevant focal restenosis at 6-month follow-up.. http://www.clinicaltrials.gov. Unique identifier: NCT01056744.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cell Proliferation; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Germany; Humans; Male; Metals; Middle Aged; Neointima; Paclitaxel; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Single-Blind Method; Sirolimus; Stents; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Vascular Access Devices

to compare the vascular healing process between the sirolimus-eluting NEVO and the everolimus-eluting Xience stent by optical coherence tomography (OCT) at 1-year follow-up.. Presence of durable polymer on a drug-eluting metallic stent may be the basis of an inflammatory reaction with abnormal healing response. The NEVO stent, having a bioresorbable polymer eluted by reservoir technology, may overcome this problem.. All consecutive patients, who received NEVO or Xience stent implantation between September 2010 and October 2010 in our institution, were included. Vascular healing was assessed at 1-year as percentage of uncovered struts, neointimal thickness (NIT), in-stent/stent area obstruction and pattern of neointima.. A total 47 patients (2:1 randomization, n = 32 NEVO, n = 15 Xience) were included. Eighteen patients underwent angiographic follow-up (eight patients with nine lesions for NEVO vs. 10 patients with 11 lesions for Xience). The angiographic late loss was numerically higher but not statistically different in NEVO compared with Xience treated lesions (0.38 ± 0.47 mm vs. 0.18 ± 0.27 mm; P = 0.171). OCT analysis of 4,912 struts demonstrated similar rates of uncovered struts (0.5 vs. 0.7%, P = 0.462), higher mean NIT (177.76 ± 87.76 µm vs. 132.22 ± 30.91 µm; P = 0.170) and in stent/stent area obstruction (23.02 ± 14.74% vs. 14.17 ± 5.94%, P = 0.120) in the NEVO as compared with Xience.. The NEVO stent with a reservoir technology seems to exhibit more neointimal proliferation as compared to Xience stent. The findings of our study, which currently represent the unique data existing on this reservoir technology, would need to be confirmed in a large population.

Topics: Aged; Cardiovascular Agents; Cell Proliferation; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Europe; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

This study was designed to compare neointimal hyperplasia and peri-stent arterial remodeling after implantation of everolimus-eluting stent (EES) versus sirolimus-eluting stent (SES) using intravascular ultrasound (IVUS). The study population was a subgroup of 278 patients from the EXCELLENT trial, a randomized study comparing EES to SES in de novo coronary artery lesions (total n = 1,443, 3:1 randomization) who underwent post-PCI and 9-month follow-up IVUS evaluation. There were 209 patients in the EES group and 69 in the SES group. Baseline clinical and angiographic characteristics were similar between the two groups except for age and target lesion locations. At 9 months, percent neointimal volume obstruction did not differ between EES and SES (2.6 ± 4.0 % vs. 2.5 ± 4.8 %, p = 0.814). However, the relative change in the vessel (4.3 ± 13.7 % vs. 8.8 ± 18.6 %, p = 0.030) and plaque volume index (4.2 ± 17.4 % vs. 10.5 ± 22.3 %, p = 0.016) of the stented segment from post-intervention to follow-up was significantly less with EES than with SES. In addition, positive peri-stent vascular remodeling defined as an increase in vessel volume index >10 % (27.8 vs. 42.0 %, p = 0.027) and late acquired stent malapposition (LASM, 1.9 vs. 15.9 %, p < 0.001) were observed less frequently with EES than SES. EES and SES were similarly effective in reducing neointimal hyperplasia. However, positive peri-stent vascular remodeling and LASM occurred less frequently with EES than SES.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Logistic Models; Male; Middle Aged; Multivariate Analysis; Neointima; Odds Ratio; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Republic of Korea; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Restenosis after percutaneous transluminal angioplasty (PTA) of the superficial femoral artery (SFA) may occur in 45% of patients at 2 years follow-up. Paclitaxel-coated balloons have been found to reduce neointimal hyperplasia, and thus reduce restenosis. Recently, the Legflow(®) paclitaxel-coated balloon (Cardionovum Sp.z.o.o., Warsaw, Poland) (LPEB) has been introduced. This balloon is covered with shellac, a Food and Drug Administration (FDA) approved natural resin, to obtain an equally distributed tissue concentration of paclitaxel. The RAPID trial is designed to assess restenosis after PTA using the Legflow balloon combined with nitinol stenting versus uncoated balloons with nitinol stenting in SFA lesions >5 cm.. A total of 176 adult patients with Rutherford class 2 to class 6 symptoms due to intermediate (5-15 cm) or long (>15 cm) atherosclerotic lesions in the SFA will be randomly allocated for treatment with LPEB with nitinol stenting or uncoated balloon angioplasty with stenting. Stenting will be performed using the Supera(®) stent in both groups (IDEV Technologies Inc., Webster, TX). The primary endpoint is the absence of binary restenosis of the treated SFA segment. Secondary outcomes are target lesion revascularization (TLR), clinical and hemodynamic outcome, amputation rate, mortality rate, adverse events, and device-specific adverse events. Follow up consists of four visits in which ankle-brachial indices (ABI), toe pressure measurements, and duplex ultrasound (DUS) will be performed. Furthermore, a peripheral artery questionnaire (PAQ) will be completed by the patients at each follow-up. In the event that DUS reveals a symptomatic >50% restenosis, or a >75% asymptomatic restenosis, additional digital subtraction angiography will be performed with any necessary re-intervention.. The RAPID trial is a multicenter randomized controlled patient blind trial that will provide evidence concerning whether the use of the Legflow paclitaxel/shellac coated balloons with nitinol stenting significantly reduces the frequency of restenosis in intermediate and long SFA lesions compared to standard PTA and stenting.. ISRCTN47846578.

Topics: Alloys; Amputation, Surgical; Angiography, Digital Subtraction; Angioplasty, Balloon; Ankle Brachial Index; Arterial Occlusive Diseases; Cardiovascular Agents; Clinical Protocols; Coated Materials, Biocompatible; Constriction, Pathologic; Equipment Design; Equipment Failure; Femoral Artery; Hemodynamics; Humans; Hyperplasia; Limb Salvage; Neointima; Netherlands; Paclitaxel; Predictive Value of Tests; Prosthesis Design; Prosthesis Failure; Recurrence; Research Design; Resins, Plant; Single-Blind Method; Stents; Surveys and Questionnaires; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Duplex; Vascular Access Devices

The ZOMAXX I trial tested the noninferiority of a zotarolimus-eluting coronary stent (ZoMaxx(™) ) when compared with a paclitaxel-eluting coronary stent (Taxus(™) Express(2™) ) in a randomized trial of percutaneous intervention for de novo coronary artery stenosis. Angiographic analysis at the primary endpoint of 9 months has been reported previously. The purpose of this follow-on analysis was to describe the clinical results of the ZoMaxx and Taxus cohorts of the ZOMAXX I trial after 5 years.. In the ZOMAXX I trial, 199 patients received a ZoMaxx stent and 197 patients received a Taxus stent at 29 investigative sites in Europe, Australia, and New Zealand. The two groups were generally well matched with respect to both clinical and lesional characteristics, including the incidence of diabetes (ZoMaxx 22% vs. Taxus 26%; P = 0.29), reference vessel diameter (ZoMaxx 2.79 ± 0.43 mm vs. Taxus 2.81 ± 0.46 mm; P = 0.65), and lesion length (ZoMaxx 14.9 ± 5.7 mm vs. Taxus 14.6 ± 5.5; P = 0.61). Through 5 years of follow-up, a total of 21 patients had died, six patients had withdrawn, nine had been lost to follow-up, and 13 missed their 5-year visit, leaving a total of 347 patients for analysis (169 ZoMaxx and 178 Taxus). At the 5-year time point, there were no significant differences in any clinical metric including ischemia-driven target lesion revascularization (TLR; ZoMaxx 10.6% vs. Taxus 7.1%; P = 0.29), Q-wave myocardial infarction (ZoMaxx 1.5% vs. Taxus 1.0%; P = 0.99), definite/probable stent thrombosis (ZoMaxx 1.5% vs. Taxus 3.0%; P = 0.34), and cardiac death (ZoMaxx 3.0% vs. Taxus 1.0%; P = 0.28).. After 5 years, the differences in clinical outcome between patients treated with ZoMaxx vs. Taxus stents did not reach statistical significance. However, the nominally higher rate of ischemia-driven TLR (10.6 vs. 7.1%) and the previously reported higher rate of restenosis after 9 months suggest that the ZoMaxx stent afforded less neointimal inhibition when compared with Taxus. © 2013 Wiley Periodicals, Inc.

Topics: Aged; Australia; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Drug-Eluting Stents; Europe; Female; Humans; Male; Middle Aged; Myocardial Infarction; Neointima; New Zealand; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Risk Factors; Severity of Illness Index; Sirolimus; Time Factors; Treatment Outcome

Everolimus-eluting stents (EES) have shown favorable clinical outcomes. However, there have been no studies evaluating early vascular response after EES implantation. We designed a prospective study to compare the neointimal response between zotarolimus-eluting stents (ZES) and EES at 3 and 12 months using serial optical coherence tomography examinations.. Sixty patients who underwent 3-month and 12-month follow-up optical coherence tomography (36 EES, 24 ZES) were included. Neointimal coverage and malapposition were evaluated using a strut-based analysis at both 3 and 12 months. Neointimal hyperplasia area and thrombus were assessed. ZES showed a higher incidence of covered struts (81.5 vs. 77.1%, P<0.0001) and lower incidence of malapposed struts (1.4 vs. 2.3%, P=0.001) than EES at 3 months. However, at 12 months, EES showed a slightly higher incidence of covered struts (96.4 vs. 93.6%, P<0.0001) and a lower incidence of malapposed struts (0.9 vs. 1.1%, P=0.03) than ZES. Neointimal hyperplasia area was greater in the ZES group than in the EES group at both 3 and 12 months (0.77 vs. 0.49 mm, P=0.03 and 1.50 vs. 0.97 mm, P=0.01, respectively). No significant difference in the incidence of thrombus was observed at both 3 and 12 months.. ZES showed rapid neointimal healing compared with EES at 3 months. However, at 12 months, EES had a slightly better vascular healing profile than ZES.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Observer Variation; Odds Ratio; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Reproducibility of Results; Republic of Korea; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Incomplete stent endothelialization is associated with late and very late stent thrombosis. In a post hoc analysis of the BASE-ACS trial, we sought to assess neointimal coverage and coronary flow reserve (CFR) 9 months after implantation of titanium-nitride-oxide-coated bioactive stents (BAS) versus everolimus-eluting stents (EES) in patients with acute coronary syndrome (ACS). In the BASE-ACS trial, 827 patients with ACS were randomized to receive either BAS or EES. In the current study, we examined neointimal growth and strut coverage by optical coherence tomography and CFR by trans-thoracic echocardiography in 28 consecutive non-diabetic patients with the culprit lesion in the left anterior descending coronary artery. The primary endpoints were binary stent strut coverage and CFR at 9-month follow-up. A total of 13 patients were included in the BAS group (2,033 struts); 15 in the EES group (2,898 struts). Binary stent strut coverage was higher and malapposed struts lower with BAS versus EES (99.4 vs 89.2, and 0.2 vs 4.6%, respectively, p < 0.001 for both). Neointimal hyperplasia thickness was greater with BAS versus EES (274.2 vs 100.1 μm, respectively, p < 0.001). CFR was lower with EES versus BAS (2.2 ± 0.8 vs. 3.0 ± 0.5, respectively, p = 0.001). Abnormal CFR (<2.5) were detected in 10 patients in the EES group versus one in the BAS group (p = 0.002). The current study demonstrated that in patients with ACS, BAS resulted in improved neointimal stent strut coverage and better coronary vasodilator function as compared with EES at 9-month follow-up.

Topics: Acute Coronary Syndrome; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Circulation; Coronary Vessels; Drug-Eluting Stents; Echocardiography, Doppler, Color; Echocardiography, Doppler, Pulsed; Everolimus; Humans; Hyperplasia; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Single-Blind Method; Sirolimus; Stents; Time Factors; Titanium; Tomography, Optical Coherence; Treatment Outcome; Vasodilation

This first-in-human multicenter study sought to examine prospectively the safety and efficacy of a new, cobalt chromium thin-strut, coronary absorbable polymer-coated, sirolimus-eluting stent.. Bioabsorbable polymers on drug-eluting stents may lower the long-term risks of inflammation, delayed healing, and adverse events.. We enrolled patients with symptomatic coronary artery disease with stable or unstable angina pectoris and >50% diameter stenosis, amenable to coverage with a ≤23-mm long stent in a vessel 2.5 to 3.5 mm in diameter. All patients received dual antiplatelet therapy after implantation. Patients, in groups of 10, underwent repeat angiography, intravascular ultrasound, and optical coherence tomography at 4, 6, or 8 months, and all patients were seen or contacted at 18 months of follow-up.. The median (range) in-stent late lumen loss (LLL) was 0.03 mm (-0.22 to 0.21 mm), 0.10 mm (-0.03 to 1.2 mm), and 0.08 mm (-0.01 to 0.28 mm), at 4, 6, and 8 months, respectively. At 18 months, the median in-stent LLL was 0.08 mm (-0.30 to 0.46 mm). On optical coherence tomography, the proportion of uncovered stent struts decreased from a median of 7.3% (range 0.4% to 46.3%) at 4 months to 0% (range: 0% to 3.4%) at 18 months. The percentage of neointimal volume obstruction by intravascular ultrasound increased from a median of 5.3% to 9.1% between 4 and 6 months and remained nearly unchanged thereafter through 18 months of follow-up. The only recorded major adverse cardiac event was a myocardial infarction.. At 18 months of follow-up, this absorbable polymer-coated, cobalt chromium sirolimus-eluting stent was associated with a low and stable in-stent LLL, complete strut coverage, and no stent thrombosis. (First-In-Human Trial of the MiStent Drug-Eluting Stent [DES] in Coronary Artery Disease [DESSOLVE-I]; NCT01247428).

Topics: Absorbable Implants; Adult; Aged; Aged, 80 and over; Angina, Stable; Angina, Unstable; Australia; Belgium; Cardiovascular Agents; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug Therapy, Combination; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Myocardial Infarction; Neointima; New Zealand; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Polymers; Prospective Studies; Prosthesis Design; Severity of Illness Index; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

To evaluate long-term patterns of luminal changes after implantation of different types of drug-eluting stents (DES), we analyzed the serial angiographic outcomes of patients implanted with zotarolimus-eluting stents (ZES), sirolimus-eluting stents (SES), or paclitaxel-eluting stents (PES).. Little is known regarding long-term luminal changes after DES implantation.. As a subgroup analysis of the ZEST trial, we performed complete angiographic evaluation immediately after the procedure and at 9 months and 2 years in 111 patients with 165 lesions (36 patients with ZES, 40 with SES, and 35 with PES).. Baseline clinical, angiographic, and procedural characteristics were similar among the three groups. Quantitative angiographic analysis revealed significant decreases in minimal luminal diameter 9 months after stent implantation in the ZES (from 2.71 ± 0.49 to 2.21 ± 0.42 mm, P < 0.001), SES (from 2.79 ± 0.49 to 2.58 ± 0.57 mm, P < 0.001), and PES (from 2.66 ± 0.45 to 2.19 ± 0.52 mm, P < 0.001) groups. However, significant late improvements with different degree in luminal diameter were observed between 9 months and 2 years in the ZES (from 2.21 ± 0.42 to 2.39 ± 0.58 mm, P = 0.001), SES (from 2.58 ± 0.57 to 2.66 ± 0.60 mm, P = 0.039), and PES (from 2.19 ± 0.52 to 2.43 ± 0.52 mm, P < 0.001) groups.. Serial angiographic follow-up study revealed a biphasic luminal response after DES implantation, characterized by an early progression phase for the first 9 months and a late regression phase from 9 months to 2 years.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Linear Models; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Republic of Korea; Single-Blind Method; Sirolimus; Time Factors; Treatment Outcome

To quantify the circumferential healing process at 6 and 12 months following scaffold implantation.. The healing process following stent implantation consists of tissue growing on the top of and in the space between each strut. With the ABSORB bioresorbable vascular scaffold (BVS), the outer circumference of the scaffold is detectable by optical coherence tomography (OCT), allowing a more accurate and complete evaluation of the intra-scaffold neointima.. A total of 58 patients (59 lesions), who received an ABSORB BVS 1.1 implantation and a subsequent OCT investigation at 6 (n=28 patients/lesions) or 12 (n=30 patients with 31 lesions) months follow-up were included in the analysis. The thickness of the neointima was calculated circumferentially in the area between the abluminal side of the scaffold and the lumen by means of an automated detection algorithm. The symmetry of the neointima thickness in each cross section was evaluated as the ratio between minimum and maximum thickness.. The neointima area was not different between 6 and 12 months follow-up (1.57±0.42 mm(2) vs. 1.64±0.77 mm(2); p=0.691). No difference was also found in the mean thickness of the neointima (median [IQR]) between the two follow-up time points (210 μm [180-260]) vs. 220 μm [150-260]; p=0.904). However, the symmetry of the neointima thickness was higher at 12 than at 6 months follow-up (0.23 [0.13-0.28] vs. 0.16 [0.08-0.21], p=0.019).. A circumferential evaluation of the healing process following ABSORB implantation is feasible, showing the formation of a neointima layer, that resembles a thick fibrous cap, known for its contribution to plaque stability.

Topics: Absorbable Implants; Algorithms; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Delayed-Action Preparations; Endovascular Procedures; Everolimus; Fibrosis; Humans; Image Processing, Computer-Assisted; Neointima; Polyesters; Predictive Value of Tests; Sirolimus; Time Factors; Tissue Scaffolds; Tomography, Optical Coherence; Treatment Outcome

Drug-eluting stents (DES) have reduced the rate of restenosis but recent studies have raised concern over the risk of late stent thrombosis (LST). Incomplete stent endothelialization and delayed vascular healing have been associated with LST. The titanium-nitride-oxide coated bio-active stent (BAS) has shown promising results in patients with acute coronary syndromes, but there is little long-term optical coherence tomography (OCT) data comparing BAS with DES. The TITAX-AMI trial is a prospective, randomized, multicenter trial comparing BAS to paclitaxel-eluting stent (PES) in 425 patients with acute myocardial infarction. A total of 18 patients (9 per group) with no major cardiac events during follow-up, were enrolled in this substudy >36 months (mean 47 months) after stent implantation. Quantitative coronary angiography was performed and stent strut endothelialization and vascular healing were assessed with OCT. The binary stent strut coverage was significantly higher in the BAS group compared with the PES group (99.6 vs. 89.2%, p < 0.001) and there were less malapposed struts in the BAS group (0.2 vs. 13.8%, respectively, p < 0.001). The neointimal hyperplasia (NIH) thickness (266 ± 166 vs. 126 μm ± 126 μm, p < 0.001) and percentage of NIH area (26.2 vs. 7.6%, p < 0.001) were greater in the BAS group than in the PES group. Late incomplete endothelialization was not uncommon after PES implantation. Stents in the BAS group were completely endothelialized. This difference may contribute to the more common LST after PES implantation in the TITAX-AMI trial.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Endothelial Cells; Female; Humans; Hyperplasia; Male; Middle Aged; Myocardial Infarction; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Stents; Time Factors; Titanium; Tomography, Optical Coherence; Treatment Outcome

Neointimal hyperplasia plays a pivotal role in the pathogenesis of in-stent restenosis in patients undergoing percutaneous coronary interventions. Drug-eluting balloons are a promising tool to prevent restenosis after coronary angioplasty. Moreover, an increased knowledge of the pathophysiology of restenosis my help improve therapeutic strategies.. We present the design of an open-label, randomized three-arm clinical trial aimed to assess whether a strategy of bare-metal stent implantation with additional use of drug-eluting balloons, either before (pre-dilation) or after stenting (post-dilation), reduces the primary endpoint of in-stent neointimal hyperplasia area as compared with a strategy of bare-metal stent implantation alone. This primary endpoint will be assessed by optical coherence tomography at follow-up. Secondary endpoints will be the percentage of uncovered struts, and the percentage of struts with incomplete apposition. An ancillary study investigating the relation between systemic levels of endothelial progenitors cells and neointimal hyperplasia, and the interaction between endothelial progenitors cell levels and drug-eluting balloons has been planned. Thirty consecutive patients undergoing percutaneous coronary intervention will be randomized with a 1:1:1 design to bare-metal stent implantation alone (n = 10); bare-metal stent implantation after pre-dilation with a drug-eluting balloon (n = 10); or bare-metal stent implantation followed by post-dilation with a drug-eluting balloon (n = 10). Six-month follow-up coronary angiography with optical coherence tomography imaging of the stented segment will be performed in all patients. Blood samples for the assessment of endothelial progenitors cell levels will be collected on admission and at 6 months.. Experimental and early clinical data showed that inhibition of neointimal hyperplasia may be obtained by local administration of antiproliferative drugs loaded on the surface of angioplasty balloons. The INtimal hyPerplasia evAluated by oCT in de novo COROnary lesions treated by drug-eluting balloon and bare-metal stent (IN-PACT CORO) trial was conceived to test the superiority of a strategy of bare-metal stent implantation with additional drug-eluting balloon use (either before or after stenting) versus a strategy of bare-metal stent implantation alone for the reduction of neointimal hyperplasia. We also planned an ancillary study to assess the role of endothelial progenitors cells in the pathophysiology of neointimal hyperplasia.. Clinicaltrials.gov NCT01057563.

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Catheters; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Endothelial Cells; Equipment Design; Humans; Hyperplasia; Italy; Metals; Neointima; Paclitaxel; Predictive Value of Tests; Prosthesis Design; Research Design; Stem Cells; Stents; Time Factors; Tomography, Optical Coherence; Treatment Outcome

This study sought to assess stent strut coverage, malapposition, protrusion, and coronary evaginations as markers of healing 5 years after implantation of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES), by optical coherence tomography (OCT).. Early-generation drug-eluting stents have been shown to delay vascular healing.. A total of 88 event-free patients with 1 randomly selected lesion were suitable for final OCT analysis 5 years after drug-eluting stent implantation. The analytical approach was based on a hierarchical Bayesian random-effects model.. OCT analysis was performed at 5 years in 41 SES lesions with 6,380 struts, and in 47 PES lesions with 6,782 struts. A total of 196 struts were uncovered in SES (1.5%) compared with 185 struts in PES lesions (1.0%, 95% credibility interval [CrI]: 0.5 to 1.6; p = 0.32). Malapposed struts were present in 1.2% of SES compared with 0.7% of PES struts (0.7%, 95% CrI: 0.03 to 1.6; p = 0.23). Protruding struts were more frequent among SES (n = 114; 0.8%) than PES lesions (n = 24; 0.1%, 95% CrI: 0.3 to 1.3; p < 0.01). Coronary evaginations were more common among SES- than PES-treated lesions (17 vs. 7 per 100 cross sections, p = 0.003). During extended clinical follow-up, 2 patients suffered from very late stent thrombosis showing a high degree of malapposition, protrusion, and coronary evaginations at the time of OCT investigation.. Early-generation drug-eluting stents show a similar degree of strut coverage and malapposition at 5 years of follow-up. Despite an overall low degree of uncovered and malapposed struts in event-free patients, some lesions show a clustering of these characteristics, indicating a heterogeneous healing response, which may be the source for very late adverse events.

Topics: Angioplasty, Balloon, Coronary; Bayes Theorem; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Paclitaxel; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Nonserial observations have shown this bioresorbable scaffold to have no signs of area reduction at 6 months and recovery of vasomotion at 1 year. Serial observations at 6 months and 2 years have to confirm the absence of late restenosis or unfavorable imaging outcomes.. The ABSORB trial is a multicenter single-arm trial assessing the safety and performance of an everolimus-eluting bioresorbable vascular scaffold. Forty-five patients underwent serial invasive imaging, such as quantitative coronary angiography, intravascular ultrasound, and optical coherence tomography at 6 and 24 months of follow-up. From 6 to 24 months, late luminal loss increased from 0.16±0.18 to 0.27±0.20 mm on quantitative coronary angiography, with an increase in neointima of 0.68±0.43 mm(2) on optical coherence tomography and 0.17±0.26 mm(2) on intravascular ultrasound. Struts still recognizable on optical coherence tomography at 2 years showed 99% of neointimal coverage with optical and ultrasonic signs of bioresorption accompanied by increase in mean scaffold area compared with baseline (0.54±1.09 mm(2) on intravascular ultrasound, P=0.003 and 0.77±1.33 m(2) on optical coherence tomography, P=0.016). Two-year major adverse cardiac event rate was 6.8% without any scaffold thrombosis.. This serial analysis of the second generation of the everolimus-eluting bioresorbable vascular scaffold confirmed, at medium term, the safety and efficacy of the new device.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00856856.

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Australia; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Diagnostic Imaging; Drug-Eluting Stents; Europe; Everolimus; Female; Humans; Male; Middle Aged; Neointima; New Zealand; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Tissue Scaffolds; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

The purpose of this study was to investigate the vascular response of the everolimus-eluting stent (EES) compared with the paclitaxel-eluting stent (PES) using serial intravascular ultrasound (IVUS).. Data were obtained from the SPIRIT III trial, a multicentre, 2:1 randomised, controlled study comparing EES and PES in de novo native coronary artery lesions. IVUS images were eligible for volumetric analysis at eight-month follow-up in 158 lesions (EES: 113, PES: 45). At eight months, EES had a smaller neointimal volume index (VI: mm3/mm) (EES: 0.4±0.4 vs. PES: 0.8±0.8 mm3/mm, p=0.002) and also a smaller % neointimal obstruction (EES: 7.1±6.7% vs. PES: 11.1±10.5%, p=0.005) compared with PES. While there was no significant change in vessel VI with EES, there was a significant increase in vessel VI in PES during eight-month follow-up (EES: 0.1±1.2 vs. PES: 1.2±0.8 mm3/mm, p=0.001). There were no statistical differences in the frequency of edge dissection or incomplete stent apposition between the two groups.. Detailed IVUS analysis confirmed significantly less neointimal hyperplasia with EES compared with PES. While there was no increase in vessel volume with EES during the eight-month follow-up period, vessel enlargement was seen at the stented segment in PES.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Japan; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Registries; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional; United States

Percutaneous recanalization of total coronary occlusion (TCO) was historically hampered by high rates of restenosis and reocclusions. The PRISON II trial demonstrated a significant restenosis reduction in patients treated with sirolimus-eluting stents compared with bare metal stents for TCO. Similar reductions in restenosis were observed with the second-generation zotarolimus-eluting stent and everolimus-eluting stent. Despite favorable anti-restenotic efficacy, safety concerns evolved after identifying an increased rate of very late stent thrombosis (VLST) with drug-eluting stents (DES) for the treatment of TCO. Late malapposition caused by hypersensitivity reactions and chronic inflammation was suggested as a probable cause of these VLST. New DES with bioresorbable polymer coatings were developed to address these safety concerns. No randomized trials have evaluated the efficacy and safety of the new-generation DES with bioresorbable polymers in patients treated for TCO.. The prospective, randomized, single-blinded, multicenter, non-inferiority PRISON IV trial was designed to evaluate the safety, efficacy, and angiographic outcome of hybrid sirolimus-eluting stents with bioresorbable polymers (Orsiro; Biotronik, Berlin, Germany) compared with everolimus-eluting stents with durable polymers (Xience Prime/Xpedition; Abbott Vascular, Santa Clara, CA, USA) in patients with successfully recanalized TCOs. In total, 330 patients have been randomly allocated to each treatment arm. Patients are eligible with estimated duration of TCO ≥4 weeks with evidence of ischemia in the supply area of the TCO. The primary endpoint is in-segment late luminal loss at 9-month follow-up angiography. Secondary angiographic endpoints include in-stent late luminal loss, minimal luminal diameter, percentage of diameter stenosis, in-stent and in-segment binary restenosis and reocclusions at 9-month follow-up. Additionally, optical coherence tomography is performed in the first 60 randomized patients at 9 months to assess neointima thickness, percentage of neointima coverage, and stent strut malapposition and coverage. Personnel blinded to the allocated treatment will review all angiographic and optical coherence assessments. Secondary clinical endpoints include major adverse cardiac events, clinically driven target vessel revascularization, target vessel failure and stent thrombosis to 5-year clinical follow-up. An independent clinical event committee blinded to the allocated treatment will review all clinical events.. Clinical Trials.gov: NCT01516723. Patient recruitment started in February 2012.

Topics: Angioplasty, Balloon, Coronary; Belgium; Cardiovascular Agents; Clinical Protocols; Coronary Angiography; Coronary Occlusion; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Humans; Neointima; Netherlands; Polymers; Prospective Studies; Prosthesis Design; Research Design; Single-Blind Method; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To compare early vascular healing following cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation between groups with or without aggressive stent expansion in patients treated by CoCr-EES for stable coronary artery disease (CAD). Seventy-one stable CAD lesions underwent CoCr-EES implantation and analysis of serial optical coherence tomography (OCT) images obtained post-procedure and at early-term (1- or 3-month) follow-up. The endpoints of this study were neointimal thickness at the time of 1- or 3-month OCT and presence and healing of stent edge dissection. Aggressive stent expansion was defined as a lesion complying with ILUMIEN III sizing protocol; that is, external elastic lamina (EEL) diameter minus maximum balloon diameter ≤ 0.25 mm.  Comparing groups with and without aggressive stent expansion, median neointimal thickness at 1 and 3 months after CoCr-EES implantation was similar (1 month: 0.031 mm vs. 0.041 mm, respectively, p = 0.27; 3 months: 0.036 mm vs. 0.040 mm, respectively, p = 0.84). Regarding stent edge findings, the presence of any stent edge dissection immediately after percutaneous coronary intervention was also similar between the groups (25% vs. 15%, respectively; p = 0.30) and most stent edge dissections resolved completely within 3 months, regardless of location or dissection severity. After 1 year, no clinically driven target lesion revascularization or stent thrombosis was observed in either cohort. Even after aggressive stent expansion, early neointimal proliferation appeared modest with CoCr-EES implantation, and most stent edge dissections had resolved by 3 months. These findings may support the feasibility of EEL-based sizing by pre-stenting OCT.

Topics: Aged; Cardiovascular Agents; Chromium Alloys; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Japan; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

To compare the long-term vascular healing responses of healthy swine iliofemoral arteries treated with a polymer-free paclitaxel-eluting stent (Z-PES, Zilver PTX) or a fluoropolymer-based paclitaxel-eluting stent (FP-PES, Eluvia).. Bilateral iliofemoral arteries in 20 swine were treated with a Z-PES (n = 16) or a FP-PES (n = 24) and were examined histologically at 1, 3, 6, and 12 months.. Morphometric analysis revealed larger external and internal elastic lamina, stent expansion, and lumen area in the FP-PES than in the Z-PES at all timepoints. Luminal narrowing was similar in the 2 groups at 1 month; however, greater stenosis was observed in the Z-PES group at 3 months, with significant regression thereafter, resulting in equivalent stenosis at 6 and 12 months. Greater drug effect and less complete vessel healing were found in the FP-PES group at all timepoints, including greater numbers of malapposed struts with excessive fibrin deposition at 1 and 3 months, than in the Z-PES group. Three of 12 FP-PESs from the 6- and 12-month cohorts also showed circumferential medial disruption with peri-strut inflammation, whereas no abnormal findings were observed in contralateral Z-PESs.. Prolonged paclitaxel release with the presence of a permanent polymer may contribute to the differential vascular responses seen for the Z-PES and FP-PES groups, including medial layer disruption and aneurysmal vessel degeneration that was sometimes observed in the FP-PES group. These distinct features should be confirmed by pathology and in vivo imaging of human superficial femoral arteries to determine their clinical significance.

Topics: Animals; Cardiovascular Agents; Drug-Eluting Stents; Endovascular Procedures; Femoral Artery; Neointima; Paclitaxel; Polymers; Prosthesis Design; Swine; Swine, Miniature; Time Factors; Vascular Remodeling; Wound Healing

Zilver PTX nitinol self-expanding drug-eluting stent with paclitaxel coating is effective for treatment of superficial femoral artery (SFA) disease. However, as with any stent, it induces a measure of vascular inflammatory response. The current clinical trial (NCT02734836) aimed to assess vascular patency, remodeling, and inflammatory markers with intravascular optical coherence tomography (OCT) in patients with SFA disease treated with Zilver PTX stents.. Serial OCT examinations were performed in 13 patients at baseline and 12-month follow-up. Variables evaluated included neointimal area, luminal narrowing, thrombus area, stent expansion as well as measures of inflammation including, peri-strut low-intensity area (PLIA), macrophage arc, neovascularization, stent strut apposition and coverage.. Percentage of malapposed struts decreased from 10.3 ± 7.9% post-intervention to 1.1 ± 2.2% at 12-month follow-up, but one patient showed late-acquired stent malapposition (LASM). The percent of uncovered struts at follow-up was 3.0 ± 4.5%. Average expansion of stent cross-sectional area from baseline to follow-up was 35 ± 19%. The average neointimal area was 7.8 ± 3.8 mm. At 12-month follow-up, OCT analysis of Zilver PTX stent shows outward remodeling and minimal neointimal growth, but evidence of inflammation including PLIA, neovessels, thrombus and macrophages.. Thirteen patients with PAD had paclitaxel-coated stents implanted in their SFAs and were then imaged with OCT at baseline and 12-month follow-up. OCT proxy metrics of inflammation were quantified.

Topics: Aged; Aged, 80 and over; Alloys; Angioplasty, Balloon; Cardiovascular Agents; Drug-Eluting Stents; Female; Femoral Artery; Humans; Inflammation; Male; Middle Aged; Neointima; Paclitaxel; Peripheral Arterial Disease; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Risk Factors; Self Expandable Metallic Stents; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Vascular Patency; Vascular Remodeling

The diameter of balloons or stents is selected according to the estimated reference vessel diameter and do not adapt to the vessel anatomy. The aim of the present preclinical studies was to investigate a novel, vessel anatomy adjusting hypercompliant drug-coated balloon catheter (HCDCB).. Hypercompliant balloon membranes were coated in a constricted state with high drug density. Drug adherence was investigated in vitro, transfer to the porcine peripheral arteries and longitudinal distribution in vivo. In young domestic swine, neointimal proliferation was induced by vessel overstretch and continuous irritation by permanent stents. Uncoated hypercompliant balloons (HCB), and standard uncoated balloons and drug-coated balloons (DCB) served as controls. Efficacy was assessed by angiography, optical coherence tomography (OCT), and histomorphometry.. HCDCB lost 18.0 ± 3.9% of dose during in vitro simulated delivery to the lesion. Drug transfer to the vessel wall was 13.9 ± 6.4% and drug concentration was 1,044 ± 529 ng/mg tissue. Four weeks after treatment, the histomorphometric neointimal area was smaller with HCDCB versus uncoated HCB (2.39 ± 0.55 mm. HCDCB were found to inhibit excessive neointimal proliferation. Balloon adaption to different vessel diameters and shapes may provide drug-delivery in irregular lumen and facilitate balloon selection.

Topics: Angiography; Angioplasty, Balloon; Animals; Cardiovascular Agents; Cell Proliferation; Coated Materials, Biocompatible; Equipment Design; Iliac Artery; Neointima; Paclitaxel; Sus scrofa; Time Factors; Tomography, Optical Coherence; Vascular Access Devices

The combination of a bioresorbable scaffold and antiproliferative drugs is a promising treatment for peripheral artery disease. The novel paclitaxel-eluting peripheral Igaki-Tamai stent (PTX-ITS) has the same backbone design as the drug-free peripheral Igaki-Tamai stent and a paclitaxel coating. Arterial responses to the PTX-ITS and ITS using optical coherence tomography (OCT) and histological analysis in a porcine iliac artery model were compared.Methods and Results:In total, 6 PTX-ITSs and 6 ITSs implanted in porcine iliac arteries were evaluated. Quantitative measurements of the scaffold, lumen, neointimal areas, and percent area stenosis were performed using OCT at 1 and 3 months. Histological evaluations (PTX-ITS [n=5], ITS [n=4]) were performed following euthanasia at 3 months. Injury, inflammation, endothelialization, and fibrin scores were measured. Baseline angiographic characteristics were similar in both groups. The ITS group showed significantly smaller scaffold areas than the PTX-ITS group at 1 month (18.50±3.62 mm. PTX-ITSs showed significantly better suppression of late scaffold shrinkage and lower in-scaffold stenosis for up to 3 months. Additionally, PTX-ITSs exhibited high biocompatibility, which is comparable to ITSs.

Topics: Angioplasty, Balloon; Animals; Cardiovascular Agents; Drug-Eluting Stents; Female; Iliac Artery; Male; Models, Animal; Neointima; Paclitaxel; Predictive Value of Tests; Prosthesis Design; Stents; Sus scrofa; Tomography, Optical Coherence

Chronic second-generation drug-eluting stent recoil in severely calcified coronary lesions has not been studied. We aimed to evaluate chronic stent recoil by optical coherence tomography (OCT) in severely calcified lesions treated with thin strut stents after rotational atherectomy. In 28 lesions (26 patients with 23% on hemodialysis) treated with everolimus-eluting stents after rotational atherectomy, baseline and 8-month follow-up OCT were compared. Stent recoil was defined as >10% decrease in stent area from baseline to follow-up. Overall, there was no change in minimal stent area (6.0 mm

Topics: Aged; Atherectomy, Coronary; Cardiovascular Agents; Chronic Disease; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Severity of Illness Index; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Vascular Calcification

The first commercially available bioresorbable scaffold (BRS) had a strut thickness of 156 microns. As such, it had the potential for delivery challenges and higher thrombogenicity. The aim herein, is to evaluate biomechanical performance, pharmacokinetics and vascular healing of a novel thin strut (100 μm) sirolimus eluting BRS (MeRes-100, Meril Life Sciences, Gujarat, India) against the once clinically used BRS (Absorb BVS, Abbott, Santa Clara, CA) in porcine coronary arteries.. Following device implantation, angiographic and optical coherence tomography (OCT) evaluation were performed at 45, 90, 180 days, 1 year and 2 years. Histological evaluation was per-formed at 30, 90 and 180 days.. At 2 years, both lumen (MeRes-100 7.07 ± 1.82 mm² vs. Absorb BVS 7.57 ± 1.39 mm2, p = NS) and scaffold areas (MeRes-100 9.73 ± 1.80 mm² vs. Absorb BVS 9.67 ± 1.25 mm², p = NS) were comparable between tested and control scaffolds. Also, the late lumen area gain at 2 years was similar in both groups tested (MeRes-100 1.03 ± 1.98 mm² vs. Absorb BVS 0.85 ± 1.56 mm², p = NS). Histologic examination up to 6 months showed comparable healing and inflammation profiles for both devices.. The novel sirolimus-eluting BRS with thinner struts and hybrid cell design showed similar biomechanical durability and equivalent inhibition of neointimal proliferation when compared to the first-ever Absorb BVS up to 2 years in normal porcine coronary arteries.

Topics: Absorbable Implants; Animals; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Vessels; Materials Testing; Models, Animal; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Swine; Swine, Miniature; Time Factors; Tomography, Optical Coherence

Early-generation drug-eluting stents (DES) have been demonstrated to delay vascular healing. Limited optical coherence tomography (OCT) data on the very long-term neointimal response after DES implantation are available. The aim of this study was a serial OCT assessment of neointimal thickness, stent strut coverage, malapposition, and protrusion as markers of neointimal response at 3 and 9 years after implantation of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). In this single-centre, longitudinal study consecutive patients undergoing elective PCI with SES or PES were included. OCT analysis was performed after 3 and 9 years by the independent core laboratory. A total of 22 subjects (8 SES and 14 PES) underwent an OCT assessment at 3 and 9 years post index procedure. The lumen, neointimal and malapposition area and the neointimal thickness (SES ∆50 µm, p = 0.195, PES ∆10 µm, p = 0.951) did not change significantly over the 6 year follow-up. No differences in the incidence of uncovered, malapposed or protruding struts were found in each type of stent. At 3 and 9 years after PCI, implantation of early-generation SES and PES may be associated with similar neointimal thickness, strut coverage, malapposition and protrusion, as assessed by serial OCT examination among patients with uneventful follow-up at 3 years post procedure. The small size of the study warrants judicious interpretation of our results and confirmation in larger multimodality imaging studies, including patients treated with contemporary stent platforms.

Topics: Aged; Cardiovascular Agents; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Longitudinal Studies; Male; Middle Aged; Neointima; Observer Variation; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Reproducibility of Results; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Drug-eluting stent (DES) strut fracture (SF) is associated with higher incidence of In-stent restenosis (ISR)-return of blockage in a diseased artery post stenting-than seen with bare metal stents (BMS). We hypothesize that concomitance of drug and SF leads to greater neointimal response.. Controlled release of therapeutic agents, such as sirolimus and its analogs, or paclitaxel from has reduced tissue based DES failure modes compared to BMS. ISR is dramatically reduced and yet the implications of mechanical device failure is magnified.. Bilateral Xience Everolimus-eluting stents (EES) were implanted in 20 New Zealand White rabbits on normal (n = 7) or high fat (HF)/high cholesterol (HC) (n = 13) diets. Implanted stents were intact or mechanically fractured. Everolimus concentration was as packaged or pre-eluted. After 21 days, stented vessels were explanted, resin embedded, MicroCT scanned, and analyzed histomorphometrically.. Fractured EES were associated with significant (P < 0.05) increases in arterial stenosis and neointimal formation and lower lumen-to-artery area ratios compared to intact EES. Hyperlipidemic animals receiving pre-eluted EES revealed no significant difference between intact and fracture groups.. SF increases intimal hyperplasia, post EES implant, and worse with more advanced disease. Pre-eluted groups, reflective of BMS, did not show significant differences, suggesting a synergistic effect of everolimus and mechanical injury, potentially explaining the lack of SF reports for BMS. Here, we report that ISR has a higher incidence with SF in EES, the clinical implication is that patients with SF after DES implantation merit careful follow-up.

Topics: Animals; Atherosclerosis; Cardiovascular Agents; Cholesterol, Dietary; Diet, High-Fat; Disease Models, Animal; Drug-Eluting Stents; Endovascular Procedures; Everolimus; Hyperplasia; Iliac Artery; Neointima; Prosthesis Design; Prosthesis Failure; Rabbits; Time Factors

Intimal hyperplasia (IH) is the most common indicator for secondary intervention in peripheral vascular disease. Matrix metalloproteinases (MMPs) play a role in IH development due to their degradation of the extracellular matrix. Doxycycline (Doxy), a member of the tetracycline family of antibiotics, is a potent MMP inhibitor. We have previously shown that Doxy inhibits MMP activity and vascular smooth muscle cell migration in vitro. We hypothesized that Doxy would decrease MMP activity in vivo and inhibit the development of IH in a rodent model of vascular injury.. Doxy (400 mg/pellet) was delivered by a slow-release pellet implanted 3 days prior to or at the time of balloon angioplasty (BA) of the common carotid artery in female rats. At 14 days post-BA, intima-to-media (I:M) ratios were 0.77 ± 0.21 and 1.04 ± 0.32 in the Doxy treated groups, respectively, compared to 1.25 ± 0.26 in the control group (P = not significant; n = 3). Additionally, the tested dose of Doxy in either group had no inhibitory effect on membrane type 1-MMP or MMP-2 tissue levels, as measured by immunohistochemistry, or on systemic levels of MMP, as measured by total MMP serum levels using enzyme-linked immunosorbent assay. At 14 days post-BA, VSMC proliferation in the injured artery was increased to Doxy treatment prior to and at the time of surgery (23.5 ± 3.4 and 27.2 ± 3.9%, respectively), compared to control (11.4 ± 0.4%; n = 3), as measured by proliferating cellular nuclear antigen immunostaining.. In our in vivo model of vascular injury, systemic Doxy administration prior to or at the time of vascular injury does not significantly hinder the progression of IH development. Additional doses and routes of administration could be examined in order to correlate therapeutic serum levels of Doxy with effective MMP inhibition in serum and arterial tissue. However, alternative drug delivery systems are needed in order to optimize therapeutic administration of targeted MMP inhibitors for the prevention of IH development.

Topics: Angioplasty, Balloon; Animals; Cardiovascular Agents; Carotid Artery Injuries; Carotid Artery, Common; Cell Proliferation; Disease Models, Animal; Doxycycline; Female; Hyperplasia; Matrix Metalloproteinase 14; Matrix Metalloproteinase 2; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neointima; Rats, Sprague-Dawley

We aimed to compare the coronary angioscopic appearance of neointimal coverage (NIC) over durable-polymer everolimus-eluting stents (XIENCE-EES) and bioresorbable-polymer everolimus-eluting stents (SYNERGY-EES) 1 year after implantation.. XIENCE-EES and SYNERGY-EES have been developed to prevent delayed arterial healing associated with first generation drug-eluting stents. However, the process of arterial healing after XIENCE-EES and SYNERGY-EES implantation has not been clarified.. Patients who underwent implantation of XIENCE-EES (n = 20) or SYNERGY-EES (n = 20) were enrolled in this study. Coronary angiography and coronary angioscopy were performed 12 ± 1 months after stent implantation. The NIC over the stent was classified into four grades: grade 0, stent struts fully exposed; grade 1, stent struts bulging into the lumen and, still visible; grade 2, stent struts embedded in neointima but still visible; and grade 3, stent struts fully embedded and invisible. Stents exhibiting more than one NIC grade was defined as heterogeneous. Moreover, presence of thrombi was investigated.. The distribution of dominant NIC grade (XIENCE-EES: grade 0, 0%; grade 1, 25%; grade 2, 50%; grade 3, 25%; SYNERGY-EES: grade 0, 0%; grade 1, 5%; grade 2, 15%; grade 3, 80%; P = 0.002) and NIC heterogeneity was significantly different (P = 0.004). Thrombi were more frequent in XIENCE-EES than in SYNERGY-EES (40 versus 10%, respectively; P = 0.03).. Compared with XIENCE-EES, SYNERGY-EES were well covered by neointima and accompanied by fewer thrombi. These findings implied arterial healing of SYNERGY-EES was better than that of XIENCE-EES.

Topics: Aged; Aged, 80 and over; Angioscopy; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Time Factors; Treatment Outcome; Wound Healing

The SYNERGY coronary stent is new-generation drug-eluting stents, which has a thin-strut platinum-chromium platform with everolimus in a biodegradable polymer applied to the abluminal surface. It would be speculated that favorable arterial healing with early strut coverage could be achieved. The present study investigated the degree of strut coverage using optical coherence tomography (OCT) 2 weeks after SYNERGY implantation and clinical factors contributing to strut coverage. A total of 29 patients who underwent staged percutaneous coronary intervention (PCI) to residual lesions 2 weeks after the index PCI with SYNERGY stent implantation were enrolled. At the time of staged PCI, OCT examinations of the SYNERGY stent were performed for conventional OCT analysis on both cross-sectional and strut level. SYNERGY stent showed a high level of strut coverage and apposition, and the percentage was 82.4 ± 12.4% and 96.2 ± 5.0%, respectively. The lesion complexity was significantly related to greater strut coverage on univariate analysis; however, it was found to be insignificant in multivariate analysis. Our findings suggest early arterial healing after SYNERGY stent implantation.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Chromium; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Japan; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Platinum; Polyesters; Prospective Studies; Prosthesis Design; Tomography, Optical Coherence

The aim of this study was to elucidate the vascular responses to paclitaxel-eluting stent (Zilver PTX stent) in superficial femoral artery lesion at different elapsed times using angioscopy. Patients who received Zilver PTX stent implantation from five centers were enrolled. We performed angioscopic examinations at 2, 6, and 12 months after implantation and evaluated neointimal coverage (NIC) grade, intra-stent thrombus (IS-Th) grade, and presence of yellow plaque. NIC grade 0 was defined as stent struts exposed; grade 1, struts transparently visible although covered; grade 2, struts embedded in the neointima, but translucent; and grade 3, struts fully embedded and invisible. IS-Th was graded as follows: grade 0 (none), 1 (focal), and 2 (diffusely spread). Angioscopic follow-up evaluation was performed at 2 months (25 patients, 42 lesions), 6 months (18 patients, 23 stents), and 12 months (14 patients, 24 stents) after stent implantation. Dominant NIC grade significantly increased over time; however, 16.3% of the cases had NIC grade 1 or 2 at 12 months. IS-Th grade decreased; however IS-Th and yellow plaque were persistently observed in 62.5% and 83.3% cases, respectively, at 12 months. An ongoing healing response was observed at 12 months after implantation; however, thrombogenic findings were noted. Prolonged dual antiplatelet therapy could potentially enhance the clinical utility of Zilver PTX.

Topics: Aged; Aged, 80 and over; Alloys; Angioscopy; Cardiovascular Agents; Cell Proliferation; Drug-Eluting Stents; Endovascular Procedures; Female; Femoral Artery; Humans; Japan; Male; Middle Aged; Neointima; Paclitaxel; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Registries; Risk Factors; Self Expandable Metallic Stents; Time Factors; Treatment Outcome; Wound Healing

Normalized optical density (NOD) measured by optical coherence tomography represents neointimal maturity after coronary stent implantation and is correlated with morphologic information provided by both light and electron microscopy. We aimed to test the hypothesis that even second generation drug-eluting stents (DESs) are problematic in terms of neointimal maturity. We implanted bare-metal stents (BMS: n = 14), everolimus-eluting stents (EESs: n = 15) or zotarolimus-eluting stents (ZESs: n = 12) at 41 sites in 32 patients with stable coronary artery disease. OCT was performed at up to 12 months of follow-up, and the average optical density of neointima covering struts was evaluated. NOD was calculated as the optical density of stent-strut covering tissue divided by the optical density of the struts. We also measured circulating CD34+ /CD133+ /CD45low cells, and serum levels of stromal cell-derived factor (SDF)-1, interleukin (IL)-8 and matrix metalloproteinase (MMP)-9 at baseline and follow-up. NOD was lower in the EES (0.70 ± 0.06) group than in the BMS (0.76 ± 0.07, P < 0.05) and ZES (0.76 ± 0.06, P < 0.05) groups. The mean neointimal area (R = 0.33, P < 0.05) and mean neointimal thickness (R = 0.37, P < 0.05) were correlated with NOD. Although NOD was not correlated with percent changes in circulating endothelial progenitor cells, and the levels of SDF-1 and IL-8, it was negatively correlated with the change in MMP-9 level (R = - 0.51, P < 0.01). Neointimal maturity might be lower at EES sites than BMS or ZES sites. This might lead to impaired neointimal tissue growth and matrix degradation. These results suggest a specific pathophysiology after DES implantation.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Chemokine CXCL12; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Endothelial Progenitor Cells; Everolimus; Female; Humans; Interleukin-8; Male; Matrix Metalloproteinase 9; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Vascular Remodeling

Topics: Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Drug Administration Schedule; Drug-Eluting Stents; Everolimus; Humans; Neointima; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prosthesis Design; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

The aim of this study was to compare neointima proliferation in three drug-eluting stents (DES) produced by the same company (Balton, Poland) which are covered with a biodegradable polymer and elute sirolimus (concentration: 1.0 and 1.2 µg/mm

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Cell Proliferation; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The aim of the study was to capture the evolution of neointima after implantation of a biodegradable polymer-coated, sirolimus-eluting, cobalt-chromium coronary stent system (BP-DES).. Optical coherence tomography (OCT) suggests that in-stent neointimal morphology influences clinical outcomes after DES implantation.. Sixty patients treated with single BP-DES implantation were examined by quantitative coronary angiography (QCA) and OCT at 3, 6, and 12-month follow-up.. Median late lumen loss by QCA (mm) was 0.04 (IQR 0, 0.08), 0.17 (IQR 0, 0.32), and 0.14 (IQR 0.07, 0.31) at 3, 6, and 12-month follow-up respectively (P = 0.03). OCT cross-section multilevel analysis showed uncovered struts in 3.90%, 1.78%, and 0.02% of struts respectively (P = 0.03). The corresponding malapposition rates were 0.12%, 0.04%, and 0%. Lipid-rich neointima was observed only at 12-month follow-up in one restenotic lesion (0.77% cross-sections) that was accountable for the only target vessel revascularization. The homogeneous pattern was prevalent at all three time points, but its incidence displayed an upward trend (3 months: 59%; 6 months: 71%; 12 months: 88%) despite no difference in neointimal volume between 6 and 12 months. Conversely, a trend could be observed of decreasing incidence of heterogeneous pattern as the follow-up length increased.. In this study of a single-type BP-DES, the majority of stent struts were covered within 3 months from implantation. While the quantitative neointimal accumulation plateaued at 6 months with no further significant increase beyond 6 months, the neointima continued to evolve qualitatively and mature along with better strut coverage between 6 and 12 months after implantation.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Poland; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Polymeric component is associated with the increased risk of delayed vessel healing and stent endothelialization. We aimed to clarify neointimal coverage within 1 month after implantation of the new-generation abluminal biodegradable polymer (BP) drug-eluting stent (DES) compared with the second-generation durable polymer (DP) everolimus-eluting stent (EES). Between November 2015 and October 2016, 32 BP-DES and 25 DP-EES were evaluated by optical frequency domain imaging (OFDI) within 1 month after the procedure. The average interval to follow-up OFDI was not significantly different between the groups (16.3 ± 7.7 days in BP-DES vs. 15.4 ± 7.4 days in DP-EES, P = 0.75). Neointimal coverage was significantly superior in BP-DES in both apposed and malapposed strut (apposed: 53.9% in BP-DES vs. 28.0% in DP-EES, P < 0.001; malapposed: 22.9% in BP-DES vs. 7.5% in DP-EES, P = 0.001). When the follow-up period was divided into < 2 and > 2 weeks, neointimal coverage was also significantly superior in BP-DES (< 2 weeks: 47.7% in BP-DES vs. 19.2% in DP-EES, P < 0.001; > 2 weeks: 60.1% in BP-DES vs. 37.4% in DP-EES, P = 0.001). The new-generation BP-DES showed excellent early neointimal coverage compared with the second-generation DP-EES in both apposed and malapposed struts.

Topics: Absorbable Implants; Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Vascular smooth muscle cell (VSMC) proliferation and migration are crucial events in the pathological course of restenosis after percutaneous coronary intervention (PCI). N-oleoylethanolamide (OEA) is a bioactive lipid amide released upon dietary fat digestion with many reported actions. However, the effect of OEA on restenosis after vascular injury remains unknown. Here, we investigated the effects of OEA on intimal hyperplasia after balloon injury in vivo, its effect on VSMC proliferation and migration induced by platelet-derived growth factor (PDGF) stimulation in vitro, and the underlying mechanism underlying these effects. The results showed that OEA-treated rats displayed a significant reduction in neointima formation after balloon injury. In cultured VSMCs, treatment with OEA decreased cell proliferation and migration induced by PDGF. OEA treatment both in vivo and in vitro led to an increase in adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and peroxisome proliferator-activated receptor alpha (PPARα), and a decrease in proliferating cell nuclear antigen (PCNA) and cyclinD1 expression. Pharmacological inhibition of AMPK and PPARα reversed the suppressive effects of OEA on VSMC proliferation and migration, suggesting that the suppressive effect of OEA on VSMC proliferation and migration is mediated through the activation of AMPK and PPARα. In conclusion, our present study demonstrated that OEA attenuated neointima formation in response to balloon injury by suppressing SMC proliferation and migration through an AMPK and PPARα-dependent mechanism. Our data suggests that OEA may be a potential therapeutic agent for restenosis after PCI.

Topics: AMP-Activated Protein Kinases; Animals; Cardiovascular Agents; Carotid Artery Injuries; Carotid Artery, Common; Cell Movement; Cell Proliferation; Cell Survival; Cyclin D1; Endocannabinoids; Endothelial Cells; Hyperplasia; Male; Muscle, Smooth, Vascular; Neointima; Oleic Acids; Phosphorylation; Platelet-Derived Growth Factor; PPAR alpha; Primary Cell Culture; Proliferating Cell Nuclear Antigen; Rats; Rats, Sprague-Dawley; Tunica Intima

Carotid artery web is considered an exceptional cause of recurrent ischemic strokes in the affected arterial territory. The underlying pathology proposed for this entity is an atypical fibromuscular dysplasia. We present the case of a 43-year-old woman with no cardiovascular risk factors who had experienced 2 cryptogenic ischemic strokes in the same arterial territory within an 11-month period. Although all diagnostic tests initially yielded normal results, detailed analysis of the computed tomography angiography images revealed a carotid web; catheter angiography subsequently confirmed the diagnosis. Carotid surgery was performed, since which time the patient has remained completely asymptomatic. The histological finding of intimal hyperplasia is consistent with previously reported cases of carotid artery web. Carotid artery web is an infrequent cause of stroke, and this diagnosis requires a high level of suspicion plus a detailed analysis of vascular imaging studies.

Topics: Adult; Aspirin; Atorvastatin; Biopsy; Brain Ischemia; Cardiovascular Agents; Carotid Artery Diseases; Carotid Artery, Internal; Computed Tomography Angiography; Female; Fibromuscular Dysplasia; Humans; Hyperplasia; Neointima; Recurrence; Risk Factors; Stroke

The objectives of this study are to assess the healing score (HS) and neointimal thickness of the Xinsorb scaffold, and explore the relationships between the implanted patterns, neointimal thickness, and HS. The Xinsorb bioresorbable sirolimus-eluting scaffold is the first domestically designed and fabricated bioresorbable scaffold in China. The 6-month follow-up found it to be safe and effective in the treatment of single de novo coronary lesions. The Xinsorb scaffolds were implanted in 30 patients with symptomatic ischemic coronary disease. A 6-month follow-up was performed in a subset of 19 patients; the HS and neointimal thickness were evaluated by optical coherence tomography. Struts were classified as ApposedCovered, ApposedUncovered, MalapposedCovered, MalapposedUncovered, jailing and presence of intraluminal masses. The implanted pressure, implanted duration, and post-expansion pressure were recorded during the operation. We evaluated the relationship between the HS or neointimal thickness and the implanted pressure, holding time, and post-expansion pressure. The device and procedure success rates were both 100%. No major adverse cardiac or scaffold-thrombus related events occurred. At 6 months, 12,295 struts were analyzed to determine the HS (6.23) and neointimal thickness (0.1021 ± 0.05718 mm) in the Xinsorb scaffolds. There was a strong negative relationship between the HS and the implantation duration (Pearson r = - 0.518, p = 0.023). A significant negative relationship also existed between the HS and post-dilatation (Pearson r = - 0.631, p = 0.004). The Xinsorb scaffold HS appears negative correlated with the implanted duration and post-dilatation. We will further evaluate the HS of randomized controlled trial of the Xissorb scaffold.

Topics: Absorbable Implants; Adult; Aged; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Coronary Angiography; Coronary Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prospective Studies; Severity of Illness Index; Sirolimus; Tissue Scaffolds; Tomography, Optical Coherence

To compare the drug effect in treated vessels and downstream effects in distal skeletal muscle of drug-coated balloons (DCBs) and drug-eluting stents (DESs) in a healthy preclinical swine model.. Four groups of treated iliofemoral arteries (percutaneous transluminal angioplasty [PTA]+DES, DCB+DES, DCB+bare metal stent [BMS], and DCB alone) of 12 healthy swine were assessed, with euthanasia at 30 days. Biological drug effect was evaluated using smooth muscle cell (SMC) loss score according to both depth and circumference as well as a neointimal fibrin and medial proteoglycan scores which were compared between the 4 groups. Vascular and skeletal muscle changes in regions downstream from the treated site were also assessed histologically for evidence of emboli.. DESs showed greater medial SMC loss in the treated arteries irrespective of preceding DCB or PTA treatment in terms of depth (DCB+DES vs PTA+DES vs DCB+BMS vs DCB alone; median, 4.0 mm vs 3.8 mm vs 3.0 mm vs 2.2 mm; P = .009) and circumference (4.0 mm vs 3.5 mm vs 2.0 mm vs 1.2 mm, respectively; P = .007). Sections of skeletal muscles downstream from the treated arteries showed arteriolar changes of fibrinoid necrosis consistent with paclitaxel effect exclusively in the DCB groups (DCB+BMS, 26.9% of sections; DCB+DES, 14.3%; DCB alone, 19.2%; PTA+DES, 0%; P = .02).. In the treated arteries, irrespective of preceding DCB treatment or PTA, DES treatment showed maximum drug effects vs DCB alone or in combination with BMS placement, and there was no detrimental toxic effect in DCB-treated iliofemoral arteries before DES treatment compared with PTA before DES treatment. Downstream vascular changes were exclusively seen in groups treated with DCBs.

Topics: Angioplasty, Balloon; Animals; Cardiovascular Agents; Coated Materials, Biocompatible; Drug-Eluting Stents; Femoral Artery; Fibrin; Models, Animal; Muscle, Skeletal; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neointima; Paclitaxel; Popliteal Artery; Proteoglycans; Sus scrofa; Time Factors; Vascular Access Devices

The aim of this study was to investigate whether the underlying plaque type affects the neointimal coverage after drug-eluting stent implantation.. A total of 1793 struts in 22 zotarolimus-eluting stents were assessed using optical coherence tomography imaging within 3 months of implantation. Neointimal coverage was evaluated within 5 mm from each stent edge on cross-sectional optical coherence tomography images at every 1-mm interval. The percentage of struts covered by neointima was compared among the normal segment group, the fibrous plaque group, and the lipid plaque group on the basis of the underlying plaque type.. The percentage of covered strut was significantly lower in the normal segment group than in the fibrous plaque group (35.9±30.2 vs. 57.1±31.0%, P<0.05) and the lipid plaque group (vs. 64.7±23.5%, P<0.01). The neointima was significantly thinner in the normal segment group than in the lipid plaque group (19.0±22.3 vs. 32.0±18.8 μm, P<0.01). The percentage of struts on the normal segment was significantly higher in cross-sections with a ratio of uncovered to total struts per section more than 0.3 than in cross-sections with a ratio up to 0.3 (32.4±31.7 vs. 19.5±33.8%, P<0.01).. Struts on the normal segment were less covered and had thinner neointima than struts on the lipid plaque at the stent edge within 3 months after zotarolimus-eluting stent implantation. Caution should be exercised when implanting longer drug-eluting stents to achieve uniform strut coverage in the early phase.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Fibrosis; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Prosthesis Design; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To compare vascular healing after drug-eluting stent (DES) implantation between plaque rupture (PR) and plaque erosion (PE).. Vascular response after stent implantation in patients with PR has been extensively studied. Little is known about vascular healing after stent implantation in PE.. Sixty-five ACS patients who received optical coherence tomography (OCT) imaging of the culprit lesions both before and after stent implantation at baseline as well as at 6 months were included in this study. Patients were divided into two groups: PR (n = 19) and PE (n = 24). Prestent thrombus burden and poststent intrastent structure (ISS) volume were analyzed during the index procedure. The ratio of uncovered to total stent struts per cross-section score (RUTTS) and neointimal thickness and area were measured at follow-up.. OCT imaging showed that compared with PR, PE showed a significantly lower prestent thrombus score (34.2 ± 19.2 vs. 68.6 ± 44.2, P = 0.009) at baseline and a smaller poststent ISS volume (0.7 ± 0.9 mm. PE was associated with less favorable healing following DES implantation when compared to PR at 6 months, indicating longer dual-antiplatelet therapy may be necessary for patients with PE. © 2017 Wiley Periodicals, Inc.

Topics: Aged; Cardiovascular Agents; Chronic Disease; Coronary Occlusion; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Predictive Value of Tests; Prosthesis Design; Rupture, Spontaneous; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

A polymer-free peripheral paclitaxel-eluting stent (PES, Zilver PTX, Cook, IN) has shown to improve vessel patency after superficial femoral angioplasty. A new-generation fluoropolymer-based PES (FP-PES; Eluvia, Boston Scientific, MA) displaying more controlled and sustained paclitaxel delivery promise to improve the clinical outcomes of first-generation PES. We sought to compare the biological effect of paclitaxel delivered by 2 different stent-coating technologies (fluoropolymer-based versus polymer-free) on neointimal proliferation and healing response in the familial hypercholesterolemic swine model of femoral restenosis.. The biological efficacy of clinically available FP-PES (n=12) and PES (n=12) was compared against a bare metal stent control (n=12; Innova, Boston Scientific, MA) after implantation in the femoral arteries of 18 familial hypercholesterolemic swine. Longitudinal quantitative vascular angiography and optical coherence tomography were performed at baseline and at 30 and 90 days. Histological evaluation was performed at 90 days. Ninety-day quantitative vascular angiography results showed a lower percent diameter stenosis for FP-PES (38.78% [31.27-47.66]) compared with PES (54.16% [42.60-61.97]) and bare metal stent (74.52% [47.23-100.00];. In the familial hypercholesterolemic swine model of femoral restenosis, the implantation of an FP-PES resulted in lower levels of neointimal proliferation and sustained biological effect ≤90 days compared with a polymer-free stent-based approach.

Topics: Angiography; Animals; Cardiovascular Agents; Cell Proliferation; Constriction, Pathologic; Disease Models, Animal; Drug-Eluting Stents; Endovascular Procedures; Femoral Artery; Hyperlipoproteinemia Type II; Methacrylates; Neointima; Paclitaxel; Peripheral Arterial Disease; Polymers; Polyvinyls; Prosthesis Design; Recurrence; Sus scrofa; Time Factors; Tomography, Optical Coherence; Vascular Patency; Wound Healing

We aimed to investigate the safety and efficacy of XINSORB bioresorbable sirolimus-eluting scaffold in porcine model. XINSORB scaffolds and metallic Firebird2™ stents were randomly implanted into minipigs' coronary arteries. Angiography, optical coherent tomography (OCT) and histopathological analyses were performed at post-procedure and 14-, 28-, 90-, 180-day follow-up. Thirty-two minipigs were enrolled. Eight XINSORB scaffolds and 8 Firebird2 stents were examined at each time point. Quantitative coronary angiography showed that in-scaffold late luminal loss (LLL) of XINSORB scaffold was 0.26 ± 0.13, 0.50 ± 0.16, 0.88 ± 0.29 and 0.43 ± 0.24 mm at 14-, 28, 90-, and 180-day follow-up respectively, and the corresponding diameter stenosis (DS) was 7.3 ± 4.7, 12.0 ± 9.5, 22.1 ± 8.0, and 16.0 ± 9.5%. Neither in-scaffold LLL nor DS of XINSORB scaffold was significantly different in comparison with Firebird2 stent. No difference of luminal area, device area, neointimal hyperplasia, and area stenosis was detected between two devices under OCT. Scaffold area of XINSORB remained steady through the observation. Histopathology revealed the similar findings. The greatest late recoil of XINSORB scaffold was about 4.12% at 90-day follow-up, which was comparable to Firebird2 stent. Both devices showed low injury or inflammation of vessel wall. XINSORB scaffold showed early neointimal coverage on struts within 28 days under scanning electron microscopy. XINSORB scaffold suppressed neointimal hyperplasia as effectively as Firebird2 did without obvious late device recoil during the 180 days follow-up. It is feasible to carry out clinical trial to investigate the safety and efficacy of XINSORB scaffold for patients with coronary artery diseases.

Topics: Animals; Cardiac Catheterization; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Vessels; Drug-Eluting Stents; Hyperplasia; Metals; Microscopy, Electron, Scanning; Models, Animal; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Prosthesis Failure; Sirolimus; Swine; Swine, Miniature; Time Factors; Tomography, Optical Coherence

This study sought to investigate endothelial coverage and barrier protein expression following stent implantation.. Biodegradable polymer drug-eluting stents (BP-DES) have been purported to have biological advantages in vessel healing versus durable polymer DES (DP-DES), although clinical trial data suggest equipoise.. Biodegradable polymer-sirolimus-eluting stents (BP-SES), durable polymer-everolimus-eluting stents (DP-EES), and bare-metal stents (BMS) were compared. In the rabbit model (28, 45, and 120 days), stented arteries underwent light microscopic analysis and immunostaining for the presence of vascular endothelium (VE)-cadherin, an endothelial barrier protein, and were subjected to confocal microscopy and scanning electron microscopy. A cell culture study in stented silicone tubes was performed to assess cell proliferation.. Light microscopic assessments were similar between BP-SES and DP-EES. BMS showed nearly complete expression of VE-cadherin at 28 days, whereas both DES showed significantly less with results favoring BP-SES versus DP-EES (39% coverage in BP-SES, 22% in DP-EES, 95% in BMS). Endothelial cell morphologic patterns differed according to stent type with BMS showing a spindle-like shape, DP-EES a cobblestone pattern, and BP-SES a shape in between. VE-cadherin-negative areas showed greater surface monocytes regardless of type of stent. Cell proliferation was suppressed in both DES with numerically less suppression in BP-SES versus DP-EES.. This is the first study to examine VE-cadherin expression after DES. All DES demonstrated deficient barrier expression relative to BMS with results favoring BP-SES versus DP-EES. These findings may have important implications for the development of neoatherosclerosis in different stent types.

Topics: Absorbable Implants; Animals; Antigens, CD; Cadherins; Cardiovascular Agents; Cell Proliferation; Cells, Cultured; Drug-Eluting Stents; Endothelial Cells; Endovascular Procedures; Everolimus; Iliac Artery; Intercellular Junctions; Male; Metals; Models, Animal; Neointima; Polymers; Prosthesis Design; Rabbits; Sirolimus; Time Factors

Lipid mediators derived from omega-3 polyunsaturated fatty acids such as resolvin D1 (RvD1) accelerate the resolution of inflammation and have potential as vascular therapeutics. The objective of this study was to evaluate local perivascular delivery of RvD1 as a means to attenuate neointimal hyperplasia in a rat model of arterial injury.. Smooth muscle cells were harvested from rat aortas to study the effects of RvD1 on rat arterial vascular smooth muscle cell responses in vitro, with focus on inflammation, proliferation, migration, cytoskeletal changes, and cytotoxicity. The safety and efficacy of perivascular delivery of RvD1 through thin biodegradable three-layered poly(lactic-co-glycolic acid) wraps or 25% Pluronic F127 gels were studied in a rat model of carotid angioplasty. A total of 200 ng of RvD1 was loaded into each construct for perivascular delivery after injury. Morphometric and histologic analyses were performed 3 and 14 days after injury.. RvD1 attenuated rat arterial vascular smooth muscle cell inflammatory pathways, proliferation, migration, and mitogen-induced cytoskeletal changes in vitro, without evidence of cytotoxicity. RvD1-loaded wraps reduced neointimal formation after carotid angioplasty by 59% vs no-wrap controls (P = .001) and by 45% vs vehicle-wrap controls (P = .002). RvD1-loaded Pluronic gels similarly reduced neointimal formation by 49% vs no-gel controls (P = .02) and by 52% vs vehicle-gel controls (P = .02). No group was associated with infection, thrombosis, or negative vessel remodeling. Wraps were found to be easier to apply than gel constructs. Ki67 proliferation index was significantly lower in RvD1-loaded wrap-treated arteries compared with both no-wrap and vehicle-wrap controls at both 3 and 14 days after injury (65% vs no-wrap group and 70% vs vehicle-wrap group at day 3, 49% vs both control groups at day 14; P < .05). Similarly, oxidative stress (30% and 29%; P < .05) and nuclear factor κB activation (42% and 45%; P < .05) were significantly lower in the RvD1-loaded wrap group compared with both no-wrap and vehicle-wrap controls at 3 days after injury.. Local perivascular delivery of RvD1 attenuates formation of neointimal hyperplasia without associated toxicity in a rat model of carotid angioplasty. This effect is likely due to attenuation of inflammatory pathways as well as decreased arterial smooth muscle cell proliferation and migration.

Topics: Angioplasty, Balloon; Animals; Aorta; Cardiovascular Agents; Carotid Artery Diseases; Cell Movement; Cell Proliferation; Cells, Cultured; Cytoskeleton; Disease Models, Animal; Docosahexaenoic Acids; Drug Carriers; Drug Compounding; Hyperplasia; Inflammation Mediators; Ki-67 Antigen; Lactic Acid; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neointima; Oxidative Stress; Poloxamer; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rats, Sprague-Dawley; Time Factors; Transcription Factor RelA

The aim of this study was to evaluate neointimal coverage in the very early phase after second-generation drug-eluting stent (DES) implantation using optical coherence tomography (OCT). Patients who underwent staged percutaneous coronary intervention within 30 days after DES implantation were enrolled. OCT was performed to observe DES previously implanted. The median time interval from implantation to OCT examination was 21.5 days. A total of 10,625 struts of 54 stents (52 everolimus-eluting stents and 2 zotarolimus-eluting stents) in 42 lesions were analyzed. Strut tissue coverage was observed in 71.1 ± 19.2 % of the struts, malapposed struts in 2.56 ± 3.37 %, strut tissue coverage at the side branch orifice in 10.6 ± 17.2 %, and struts with protrusion in 0.95 ± 3.46 %. Mean tissue thickness on the covered struts was 39.8 ± 14.2 µm. The percentage of stent coverage was significantly lower in the overlapping segments than in the non-overlapping segments (48.4 ± 17.5 % vs. 74.4 ± 20.2 %, P < 0.05). Most of the stent struts were covered by tissue within 30 days after second-generation DES implantation. However, the percentage of strut coverage was lower in the overlapping segments than in the non-overlapping segments, suggesting that very early interruption of dual antiplatelet therapy might result in increased risk of stent thrombosis, even in second-generation DES.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Japan; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Heterogeneity of neointimal thickness is observed after drug-eluting stents implantation in bifurcation lesions (BL). We evaluated the vascular response of everolimus-eluting bioresorbable scaffold (BRS) struts deployed at BL using optical coherence tomography (OCT). 50 patients (64 scaffolds) underwent follow-up OCT after BRS implantation. Cross-sectional areas of each BL with a side branch more than 1.5 mm were analyzed using OCT every 200 µm. All images were divided into three regions according to shear stress: the 1/2 circumference of the vessel opposite to the ostium (OO), the vessel wall adjacent to the ostium (AO) and the side-branch ostium (SO). The %uncovered strut and the averaged neointimal thickness (NIT) were calculated. Overall, there were significant differences in both NIT and %uncovered strut among the three regions (OO, 119.2 ± 68.5 μm vs. AO, 94.2 ± 35.7 μm vs. SO, 80.5 ± 41.4 μm, p = 0.03; OO, 0.4 %vs. AO, 1.4 %vs. SO, 4.8 %, p = 0.02). Scaffolds were divided into two groups: a large-ratio side-branch group (LRSB; n = 32) and a small-ratio side-branch group (SRSB; n = 32), based on the median value of the ratio of the diameter of side branch ostium (Ds) to that of the main branch (Dm). In the LRSB alone, there were significant differences in both NIT and %uncovered strut among the three regions (OO, 128.0 ± 61.1 μm vs. AO, 97.3 ± 34.3 μm vs. SO, 75.9 ± 39.4 μm, p < 0.01; OO, 0.3 % vs. AO, 2.3 % vs. SO, 8.7 %, p < 0.01). After BRS implantation in BL, neointimal response was pronounced at the vessel wall opposite to the side branch ostium, especially in those with large side branches.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Retrospective Studies; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Few studies have directly compared vascular responses to second-generation drug-eluting stents (DESs). We performed optical coherence tomography examinations in 56 consecutive patients with implanted single stent [19 cobalt-chromium everolimus-eluting stents (CoCr-EES), 22 platinum-chromium EES (PtCr-EES), and 15 resolute zotarolimus-eluting stents (R-ZES)] for de novo lesions, and who did not have restenosis at their 9-month follow-up. Neointimal thickness (NIT), stent apposition, and neointimal coverage were assessed in every strut. A neointimal unevenness score [(NUS), maximum NIT/average NIT in the same cross-section] was determined for every 1-mm cross-section (CS). A total of 8350 struts and 1159 CSs were analyzed. The CoCr- and PtCr-EES had significantly fewer malapposed struts compared to the R-ZES (CoCr-EES: 0.19 % vs. PtCr-EES: 0.19 % vs.. 0.61 %, p = 0.007). Furthermore, the PtCr-EES had a lower frequency of uncovered struts compared to the others (CoCr-EES: 2.0 % vs. PtCr-EES: 1.4 % vs.. 2.3 %, p = 0.047). The NUS correlated with the frequency of uncovered struts (p < 0.001, r = 0.54). The EESs demonstrated more homogenous neointimal growth, as shown in the NUS, compared to the R-ZES [CoCr-EES: 1.66 (1.38-1.97) vs. PtCr-EES: 1.67 (1.41-2.00) vs.. 1.94 (1.56-2.28), p < 0.001]. Our results demonstrate that unevenness neointimal growth may relate with strut coverage after second-generation DES implantation. The PtCr-EES had a high frequency of strut coverage with a homogeneous neointima, suggesting fewer risks for stent thrombosis.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Metals; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To develop an ameliorated sirolimus (SIR) liposome for intramural delivery, the effects of various carrier physicochemical parameters on the antirestenosis efficacy were evaluated.. Different liposomes were prepared, characterized and administered to balloon injured rats (12 animal groups). Their efficacies were investigated using morphometric, immunohistochemical and in vivo computed tomography imaging analyses.. The antirestenosis efficacy of SIR liposomes decreased in the following order: cationic 100 nm vesicles ≥ cationic 60 nm vesicles > neutral 100 nm vesicles ≥ stealth 100 nm vesicles > anionic 100 nm vesicles. The 100 µg SIR loaded in cationic liposomes showed almost no artery stenosis.. Appropriate modulation of physicochemical characteristics makes it possible to optimize the liposomes for local delivery.

Topics: Animals; Cardiovascular Agents; Carotid Arteries; Carotid Artery Injuries; Coronary Restenosis; Ki-67 Antigen; Liposomes; Male; Neointima; Plasma; Polysorbates; Rats; Rats, Sprague-Dawley; Sirolimus

Neointimal hyperplasia (NIH) remains one of the leading causes of graft failure after vascular anastomoses. Cytotoxic drugs, such as rapamycin and tacrolimus, have been shown to inhibit the development of NIH. In this study, the aim was to test the impact of a sustained releasing tacrolimus-chitosan-eluting suture on the development of NIH in a rat model.. In vitro tacrolimus release tests for a 7/0 tacrolimus-chitosan coated PVDF suture were confirmed for 1 month without an initial burst release. Endothelialisation over the aortotomy line occurred in both groups. The area of neointima was significantly reduced in group T compared with group C (ratio 0.22 ± 0.12 vs. 0.42 ± 0.11; p = .017) 1 month post-operatively. Likewise, the percentage of PCNA immunostaining significantly decreased in group C compared with group T (3.83 ± 2.85% vs. 11.17 ± 7.78%; p = .026). The cells constituting NIH were positive for ASMA immunostaining.. Tacrolimus-chitosan-eluting suture is shown to be an effective way to reduce NIH without interfering with normal endothelialisation.

Topics: Actins; Animals; Aorta; Cardiovascular Agents; Coated Materials, Biocompatible; Equipment Design; Hyperplasia; Male; Neointima; Proliferating Cell Nuclear Antigen; Rats, Wistar; Solubility; Suture Techniques; Sutures; Tacrolimus; Time Factors

To compare a new stent with an asymmetric coating, eluting the drug to the abluminal surface, to a stent with a conventional coating eluting the drug both to the luminal and the abluminal side.. Stents with asymmetric coating, eluting the drug to the vessel wall (BPSES-A), could potentially give faster reendothelialization after percutaneous coronary interventions (PCI) and decrease in in-stent thrombosis and late restenosis.. BPSES-A, conventional coated stents (BPSES-C), biodegradable polymer stents without drug (BPS, for control), and bare metal stents (BMS, for control) were implanted into the coronary arteries of 38 pigs (75 stents). Pigs were sacrificed after 4, 12, and 24 weeks. Quantitative coronary angiography was used to compare in-stent late lumen loss (LLL) and electron microscopy was used to reveal levels of reendothelialization.. The stents were all successfully implanted. LLL of BPSES-A, BPSES-C, BMS, and BPS were 0.56 ± 0.51, 0.60 ± 0.58, 0.89 ± 0.43, and 1.68 ± 0.30 mm, respectively, after 4 weeks. LLL of BPSES-A and BPSES-C were 0.63 ± 0.53 and 0.69 ± 0.24 mm, respectively, after 12 weeks. LLL of BPSES-A, BPSES-C, and BMS were 0.42 ± 0.15 m, 0.56 ± 0.28 mm, and 0.99 ± 0.13 mm, respectively, after 24 weeks. The scaling of reendothelialization was as follows: after 4 weeks BMS > = BPS > BPSES-A > BPSES-C, after 12 weeks BPSES-A > BPSES-C, and after 24 weeks BMS > BPSES-A > BPSES-C. Reendothelialization was better in BPSES-A than BPSES-C (P < 0.05). There was no correlation between LLL and reendothelialization (P = 0.42).. Asymmetric coating of coronary stents might be helpful to improve reendothelialization. © 2016 Wiley Periodicals, Inc.

Topics: Animals; Cardiovascular Agents; Cell Proliferation; Coronary Angiography; Coronary Vessels; Drug-Eluting Stents; Endothelial Cells; Lactic Acid; Models, Animal; Neointima; Percutaneous Coronary Intervention; Pilot Projects; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Prosthesis Design; Re-Epithelialization; Swine; Time Factors

Following percutaneous coronary interventions (PCI) for revascularisation of chronic total occlusions (CTO) patients are at increased risk for stent thrombosis (ST). Delayed drug-eluting stent (DES) coverage has previously been shown to be related to ST. Using optical coherence tomography (OCT), we tested the hypothesis that CTO-PCI is associated with delayed DES coverage compared to non-CTO lesions.. From 06/2010 to 11/2013, 105 patients (111 lesions) with clinically driven follow-up angiography after PCI with DES received an OCT analysis. Patients with successful CTO-PCI (19 patients/20 lesions, 6.5±2.1 months post PCI) were included in the CTO group, and patients with non-CTO lesions and total stent length >24 mm (28 patients/28 lesions, 4.9±2.2 months post PCI) were used as a control group. Struts were analysed by OCT (CTO vs. control, mean±SD): covered: 68.9±21.9% vs. 89.6±10.4%, p<0.001; uncovered apposed: 20.2±16.2% vs. 7.5±8.7%, p=0.001; uncovered malapposed: 10.9±10.3% vs. 2.9±2.6%, p<0.001. Neointimal thickness was 92.0±61.2 m vs. 109.3±39.2 m, p=0.033. No differences concerning different CTO-PCI approaches were found.. A significantly delayed DES coverage after CTO-PCI was observed. Given the known increased rate of ST following CTO-PCI and the known association between delayed DES coverage and ST, OCT may aid in determining the optimal duration of dual antiplatelet therapy after CTO-PCI.

Topics: Aged; Cardiovascular Agents; Case-Control Studies; Chronic Disease; Coronary Angiography; Coronary Occlusion; Coronary Thrombosis; Coronary Vessels; Drug Therapy, Combination; Drug-Eluting Stents; Female; Germany; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prosthesis Design; Registries; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Restenosis due to intimal hyperplasia is a major clinical problem that compromises the success of angioplasty and endovascular surgery. Resveratrol (RSV) has demonstrated a beneficial effect on restenosis from angioplasty. Unfortunately, the physicochemical characteristics of RSV reduce the practicality of its immediate clinical application. This work proposes an experimental model aiming to setup an intravessel, elutable, RSV-containing compound.. A 140 μg/mL RSV sterile injectable solution with a suitable viscosity for intravascular administration by drug-delivery catheter (RSV-c) was prepared. This solution was locally administered in the common iliac artery of adult male New Zealand White rabbits using a dedicated device (Genie; Acrostak, Geneva, Switzerland) after the induction of intimal hyperplasia by traumatic angioplasty. The RSV concentrations in the wall artery were determined, and the thickness of the harvested iliac arteries was measured over a 1-month period.. The Genie catheter was applied in rabbit vessels, and the local delivery resulted in an effective reduction in restenosis after plain angioplasty. Notably, RSV-c forced into the artery wall by balloon expansion might accumulate in the interstitial areas or within cells, avoiding the washout of solutions. Magnification micrographs showed intimal proliferation was significantly inhibited when RSV-c was applied. Moreover, no adverse events were documented in in vitro or in vivo studies.. RSV can be advantageously administered in the arterial walls by a drug-delivery catheter to reduce the risk of restenosis.

Topics: Angioplasty, Balloon; Animals; Cardiovascular Agents; Cell Proliferation; Cells, Cultured; Coated Materials, Biocompatible; Disease Models, Animal; Equipment Design; Humans; Hyperplasia; Iliac Artery; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neointima; Rabbits; Resveratrol; Stilbenes; Vascular Access Devices; Vascular System Injuries

Incomplete stent apposition and uncovered struts are associated with a higher risk of stent thrombosis. No data exist on the process of neointimal coverage and late apposition status of the bioresorbable vascular scaffold (BVS) when implanted in the highly thrombogenic setting of ST-segment elevation acute myocardial infarction (STEMI). The aim of this study was to assess the serial changes in strut apposition and early neointimal coverage of the BVS using optical coherence tomography (OCT) in selected patients enrolled in the PRAGUE-19 study. Intracoronary OCT was performed in 50 patients at the end of primary percutaneous coronary intervention for acute STEMI. Repeated OCT of the implanted BVS was performed in 10 patients. Scaffold area, scaffold mean diameter and incomplete strut apposition (ISA) were compared between baseline and control OCT. Furthermore, strut neointimal coverage was assessed during the control OCT. Mean scaffold area and diameter did not change between the baseline and control OCT (8.59 vs. 9.06 mm(2); p = 0.129 and 3.31 vs. 3.37 mm; p = 0.202, respectively). Differences were observed in ISA between the baseline and control OCT (0.63 vs. 1.47 %; p < 0.05). We observed 83.1 % covered struts in eight patients in whom the control OCT was performed 4-6 weeks after BVS implantation, and 100 % covered struts in two patients 6 months after BVS implantation. Persistent strut apposition and early neointimal coverage were observed after biodegradable vascular scaffold implantation in patients with acute ST-segment elevation myocardial infarction.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Vessels; Czech Republic; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; ST Elevation Myocardial Infarction; Time Factors; Tomography, Optical Coherence; Treatment Outcome

A 70-year-old man underwent stent implantation for right coronary artery (RCA) lesions with a bare metal stent (BMS) and two sirolimus-eluting stents (SES). However, as both the BMS and SES stented sites developed restenosis after 13 months, he underwent target lesion revascularization using directional coronary atherectomy (DCA). On histopathology, the restenosis lesion at the SES-deployed site showed greater inflammation and less re-endothelialization than that at the BMS-deployed site. Three months later, the SES-deployed site developed a second restenosis, in which paclitaxel-eluting stents (PES) were implanted (PES-in-SES), while the BMS-deployed site was restenosis free. Five years later, restenosis was absent in these RCA lesions. However, by optical coherence tomography and/or coronary angioscopy, the PES-in-SES site in the RCA showed poor neointimal coverage over the stent struts and yellowish neointima, suggesting lipid-rich neoatheroma formation, whereas at the BMS site appropriate white neointima formation was observed. Drug-eluting stents still have problems of persistent inflammation, inappropriate neointima formation, and neoatherosclerosis. Although we are now in the era of second generation DESs in which better stent performance would be promising, we should remember that we are obliged to continue to follow-up all patients in whom first generation DESs such as SES or PES have been placed.

Topics: Aged; Angioscopy; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Humans; Immunohistochemistry; Male; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Retreatment; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

A 54-year-old woman treated with cobalt-chromium everolimus eluting stents (CoCr-EES) for her left distal circumflex and diagonal branch lesions suffered from repeated in-stent restenosis in both lesions. Neointimal proliferation occurred rapidly and almost simultaneously in the two lesions. The cause was established to be metal allergy, as determined by patch tests which were strongly positive for bare metal stents and weakly positive for CoCr-EES. Following the third successive angioplasty, we initiated treatment with prednisolone (30 mg daily) and the anti-allergic and anti-proliferative drug tranilast (300 mg daily). An elective angiogram performed 3 months later showed no evidence of in-stent restenosis in any of the stented lesions. Furthermore, the patient has remained angina-free for 15 months. The unique features of this case include: (1) near-simultaneous repeated multivessel in-stent restenosis in a patient with skin test-documented metal allergy to cobalt-chromium stents; (2) adjunctive systemic medical therapy with prednisolone and tranilast appeared to terminate the malignant restenotic cycle.

Topics: Anti-Allergic Agents; Cardiovascular Agents; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug Therapy, Combination; Drug-Eluting Stents; Everolimus; Female; Glucocorticoids; Humans; Hypersensitivity; Middle Aged; Neointima; ortho-Aminobenzoates; Patch Tests; Percutaneous Coronary Intervention; Predictive Value of Tests; Prednisolone; Prosthesis Design; Recurrence; Risk Factors; Tomography, Optical Coherence; Treatment Outcome

Very late stent thrombosis (VLST) is a serious complication after percutaneous coronary intervention. However, the best therapy for VLST with late-acquired incomplete stent apposition and incomplete neointimal coverage remains unknown. In these cases, neointimal coverage was nearly complete and no late-acquired malapposition was detected at 18 months after Endeavor zotarolimus-eluting stent (ZES) implantation for the treatment of VLST with late-acquired incomplete stent apposition after sirolimus-eluting stent implantation. We presented that Endeavor ZES implantation may become an attractive therapeutic strategy for the treatment of VLST with late-acquired incomplete stent apposition and incomplete neointimal coverage.

Topics: Aged; Angioplasty, Balloon; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Thrombectomy; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

In this study we sought to evaluate coverage and apposition of Synergy™ stent at 3 and 6 months after implantation.. The Pt-Cr everolimus-eluting stent with abluminal bioabsorbable polymer (Synergy™) is a new generation drug-eluting stent with features potentially favoring an early healing process which could make safe a shorter period of dual antiplatelet-therapy treatment.. Prospective, two-centers study enrolling patients with similar lesions treated with Synergy™ stents undergoing examination with OCT at 3 and 6 months in the respective centers. Blinded analysis was done at a core lab. Co-primary endpoints were proportion of struts with coverage and with apposition at 3 and 6 months.. Finally, 22 patients (30 stents) in the 3 months group and 20 patients (30 stents) in the 6 months group were included. There were no significant differences between groups regarding clinical, angiographic measurements, and procedural data. The rate of strut coverage was 94.5% at 3 months and 96.6% at 6 months (P < 0.001), the rates of apposition were 93.8% and 96.2%, respectively, (P < 0.001), the proportion of uncovered but apposed struts was 2.5% and 1.9% (P = 0.03) and the proportion of uncovered and malapposed struts was 3% and 1.8%, respectively (P < 0.001). The maximal area of malapposition related with uncovered struts was 0.43 ± 0.4 mm(2) at 3 months and 0.14 ± 0.2 mm(2) at 6 months (P = 0.001).. The everolimus-eluting stent with absorbable polymer, Synergy™, is associated to a high degree of intimal coverage and apposition at 3 months after implantation with additional increase at 6 months. © 2015 Wiley Periodicals, Inc.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Polymers; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Spain; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

To evaluate the biological effect of a paclitaxel-coated balloon (PCB) technology on vascular drug distribution and healing in drug eluting stent restenosis (DES-ISR) swine model.. The mechanism of action and healing response via PCB technology in DES-ISR is not completely understood.. A total of 27 bare metal stents were implanted in coronary arteries and 30 days later the in-stent restenosis was treated with PCB. Treated segments were harvested at 1 hr, 14 days and 30 days post treatment for the pharmacokinetic analysis. In addition, 24 DES were implanted in coronary arteries for 30 days, then all DES-ISRs were treated with either PCB (n = 12) or uncoated balloon (n = 12). At day 60, vessels were harvested for histology following angiography and optical coherence tomography (OCT).. The paclitaxel level in neointimal tissue was about 18 times higher (P = 0.0004) at 1 hr Cmax , and retained about five times higher (P = 0.008) at day 60 than that in vessel wall. A homogenous distribution of paclitaxel in ISR was demonstrated by using fluorescently labeled paclitaxel. Notably, in DES-ISR, both termination OCT and quantitative coronary angioplasty showed a significant neointimal reduction and less late lumen loss (P = 0.05 and P = 0.03, respectively) post PCB versus post uncoated balloon. The PES-ISR + PCB group displayed higher levels of peri-strut inflammation and fibrin scores compared to the -limus DES-ISR + PCB group.. In ISR, paclitaxel is primarily deposited in neointimal tissue and effectively retained over time following PCB use. Despite the presence of metallic struts, a uniform distribution was characterized. PCB demonstrated an equivalent biological effect in DES-ISR without significantly increasing inflammation. © 2015 Wiley Periodicals, Inc.

Topics: Animals; Cardiac Catheterization; Cardiac Catheters; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Equipment and Supplies; Fibrin; Metals; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Stents; Swine; Tissue Distribution; Tomography, Optical Coherence; Wound Healing

We aimed to investigate short-term outcomes of the XINSORB bioresorbable sirolimus-eluting scaffold in human coronary artery.. Bioresorbable scaffolds are considered to be the fourth milestone in percutaneous coronary intervention.. Thirty patients with symptomatic ischemic coronary disease were enrolled and treated with the XINSORB scaffolds that were 3.0 × 12, 15, and 18 mm in size. The primary angiographic endpoint was late luminal loss (LLL), whereas the primary clinical endpoint was major adverse cardiac events (MACEs) at the 6 month follow-up. In a subset of 19 patients, intravascular ultrasound (IVUS) and optical coherence tomography (OCT) were performed at follow-up.. The success rates of the procedure and the device were both 100%. Twenty-seven patients received angiographic follow-up. All patients were clinically assessed. Neither MACEs nor stent thrombus-related events were recorded. The percentage of diameter stenosis at follow-up was similar to that at postprocedure. In-scaffold and periscaffold LLL were 0.17 ± 0.12 and 0.13 ± 0.24 mm, respectively. No in-stent restenosis was detected. IVUS showed that the mean areas of the lumen, scaffold, and neointima at follow-up were 6.27 ± 0.69, 6.48 ± 0.70, and 0.20 ± 0.09 mm(2) , while in-device stenosis was 3.1 ± 1.3%. OCT showed that 97.9% of the struts presented a preserved box, while 2.1% had an open box after 6 months. A total of 95.9% of the struts were covered by neointima.. This first-in-human study demonstrates the effectiveness and safety of the XINSORB scaffold in treating single de novo coronary lesions.

Topics: Absorbable Implants; Adult; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Coronary Vessels; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Limus-eluting stents are dominating coronary interventions, although paclitaxel is the only drug on balloon catheters with proven inhibition of restenosis. Neointimal inhibition by limus-coated balloons has been shown in few animal studies, but data from randomized clinical trials are not available. The aim of the present preclinical studies was to achieve high and persistent sirolimus levels in the vessel wall after administration by a coated balloon.. Different coating formulations and doses were studied in the porcine coronary model to investigate sirolimus tissue levels at different time points as well as efficacy at 1 month using quantitative coronary angiography and histomorphometry. Loss of the selected coating in the valve, guiding catheter, and blood was low (2±14% of dose). Acute drug transfer to the vessel wall was 14.4±4.6% with the crystalline coating, whereas the amorphous coatings were less effective in this respect. Persistence of sirolimus in the vessel wall until 1 month was 40% to 50% of the transferred drug. At 1-month follow-up, a modest but significant reduction of neointimal growth was demonstrated in a dose range from 4 μg/mm(2) to 2×7 μg/mm(2), for example, maximum neointimal thickness of 0.38±0.13 versus 0.65±0.21 mm in the uncoated control group.. Various sirolimus-coated balloons effectively reduce neointimal proliferation in the porcine coronary model but differ considerably in retention time in the vessel wall. It has to be determined if such a formulation with persistent high vessel concentration will result in a relevant clinical effect.

Topics: Animals; Cardiac Catheters; Cardiovascular Agents; Cell Proliferation; Coated Materials, Biocompatible; Coronary Angiography; Coronary Vessels; Drug-Eluting Stents; Equipment Design; Male; Models, Animal; Neointima; Percutaneous Coronary Intervention; Sirolimus; Swine; Time Factors

Restenosis due to intimal hyperplasia (IH) is a major clinical issue that affects the success of lower limb endovascular surgery. After 1 year, restenosis occurs in 40% to 60% of the treated vessels. The possibility to reduce IH using local antiproliferative drugs, such as taxols, has been the rationale for the clinical applications of drug-eluting stents and drug-eluting balloons (DEBs). The purpose of this study was to evaluate the clinical and instrumental efficacy of DEBs versus simple percutaneous transluminal angioplasty (PTA) in patients affected by chronic limb ischemia (CLI) with tibial artery "de novo" lesions.. A retrospective analysis was performed and included all consecutive patients who underwent endovascular treatment for CLI in our centers between January 2011 and March 2013. Inclusion criteria were (1) "de novo" tibial artery stenosis and (2) Rutherford class >4. Lesions were further divided by TransAtlantic Inter-Societal Consensus (TASC) classification into groups A, B, C, and D.. Between January 2010 and March 2013, a total of 138 patients underwent simple PTA or DEB for CLI, and the groups were clinically and demographically homogenous. We decided to use DEBs in 70 cases. An improvement in the Rutherford Scale in cumulative and single TASC lesions classification was better in the DEB group (74% vs 51%; P = .024) at 24 months than in the PTA group. In the DEB group, the increase in ankle-brachial index was significantly higher than in the PTA group (P = .039).. Our experience in addition to the existing literature supports the use of DEB in patients with CLI Rutherford class >3.

Topics: Aged; Amputation, Surgical; Angioplasty, Balloon; Ankle Brachial Index; Cardiovascular Agents; Coated Materials, Biocompatible; Equipment Design; Europe; Female; Humans; Hyperplasia; Ischemia; Limb Salvage; Lower Extremity; Male; Middle Aged; Neointima; Peripheral Arterial Disease; Recurrence; Retrospective Studies; Tibial Arteries; Time Factors; Treatment Outcome; Vascular Access Devices

Drug-eluting coronary stents reduce restenosis rate and late lumen loss compared with bare-metal stents; however, drug-eluting coronary stents may delay vascular healing and increase late stent thrombosis. The peroxisome proliferator-activated receptor-delta (PPARδ) exhibits actions that could favorably influence outcomes after drug-eluting coronary stents placement.. Here, we report that PPARδ ligand-coated stents strongly reduce the development of neointima and luminal narrowing in a rabbit model of experimental atherosclerosis. Inhibition of inflammatory gene expression and vascular smooth muscle cell (VSMC) proliferation and migration, prevention of thrombocyte activation and aggregation, and proproliferative effects on endothelial cells were identified as key mechanisms for the prevention of restenosis. Using normal and PPARδ-depleted VSMCs, we show that the observed effects of PPARδ ligand GW0742 on VSMCs and thrombocytes are PPARδ receptor dependent. PPARδ ligand treatment induces expression of pyruvate dehydrogenase kinase isozyme 4 and downregulates the glucose transporter 1 in VSMCs, thus impairing the ability of VSMCs to provide the increased energy demands required for growth factor-stimulated proliferation and migration.. In contrast to commonly used drugs for stent coating, PPARδ ligands not only inhibit inflammatory response and proliferation of VSMCs but also prevent thrombocyte activation and support vessel re-endothelialization. Thus, pharmacological PPARδ activation could be a promising novel strategy to improve drug-eluting coronary stents outcomes.

Topics: Angioplasty, Balloon; Animals; Aorta; Aortic Diseases; Atherosclerosis; Blood Platelets; Cardiovascular Agents; Carotid Artery Injuries; Cell Movement; Cell Proliferation; Cells, Cultured; Coronary Artery Disease; Disease Models, Animal; Dose-Response Relationship, Drug; Drug-Eluting Stents; Energy Metabolism; Glucose Transporter Type 1; Human Umbilical Vein Endothelial Cells; Humans; Mice, Knockout; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neointima; Platelet Activation; PPAR delta; Protein Serine-Threonine Kinases; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Rats; Rats, Sprague-Dawley; Re-Epithelialization; Recurrence; Signal Transduction; Steroids; Thrombosis; Time Factors; Transfection

Current commercially available drug-eluting stents (DESs) are criticized for the problem of stent thrombosis by induced impaired re-endothelialization (RE). The solving of this challenge could be boosted by endothelial progenitor cells (EPCs). The purpose of this study was to examine the effects of hepatocyte growth factor (HGF) on this process.. The abundance and functional capacity of circulating EPC was analyzed by a fluorescence-activated cell sorter and western blot. The in vivo effect of HGF on DES patency, RE, and neointimal formation was investigated in a hypercholesterolemic rabbit model.. HGF efficiently ameliorates the vascular response to stent implantation, and has an important redeeming influence on the deleterious endothelial effects of DES.

Topics: Angioplasty, Balloon; Animals; Apoptosis; Cardiovascular Agents; Carotid Arteries; Carotid Artery Diseases; Cell Movement; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Eluting Stents; Endothelial Progenitor Cells; Hepatocyte Growth Factor; Hypercholesterolemia; Injections, Subcutaneous; Male; Neointima; Paclitaxel; Rabbits; Re-Epithelialization; Time Factors

Our aim was to assess vascular response after polymer-free sirolimus-eluting stent (SES) implantation by using an optical coherence tomography (OCT)-derived vascular healing score (HS), quantifying the deficiency of healing.. In a prospective, multicentre, single-arm, open-label study, OCT examinations were performed at three months in 45 patients (47 lesions). Per protocol, 24 lesions which had not reached adequate vascular healing according to study criteria were scheduled for OCT examination at six months. The HS was calculated at two time points. Serial OCT imaging demonstrated that the proportion of covered stent struts increased from a median of 87.1% at three months to 98.6% at six months (p<0.001). The neointimal thickness increased from a median of 82.8 µm to 112.2 µm (p<0.001), whereas the median percentages of malapposed struts were 0.2% and 0.0% at the two respective time points. Neointimal volume obstruction increased from 6.3% to 12.8%, and the HS decreased from a median of 28.1 at three months to 2.4 at six months.. In patients who had inadequate vascular healing three months after polymer-free SES implantation, serial OCT showed almost complete vascular healing at six months.

Topics: Absorbable Implants; Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Artery Disease; Coronary Stenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Sirolimus; Tomography, Optical Coherence

Different carrier excipients unique to individual drug-coated balloons (DCBs) may influence embolic safety characteristics in peripheral vascular territories through embolization of released particulates. A comparator study of IN.PACT Admiral vs Lutonix 035 balloons in healthy swine was therefore performed to assess which balloon produces more downstream emboli.. Single or overlapping 80-mm IN.PACT and Lutonix 035 DCBs were assessed in the femoral arteries of 21 swine with 28- and 90-day follow-up, with standard balloon angioplasty as a control. Histologic analysis of arterial wall and downstream skeletal muscle and coronary band was performed. This analysis was supported by an analytic measurement of paclitaxel levels.. IN.PACT DCBs demonstrated a more pronounced change in medial wall composition, characterized by a paclitaxel-induced loss of medial smooth muscle cells accompanied by increased proteoglycans. The percentage of sections with arterioles exhibiting paclitaxel-associated fibrinoid necrosis in downstream tissues was higher at 90 days with overlapping IN.PACT DBCs compared with Lutonix 035 DCBs (46.2% [interquartile range, 19.2-57.7] vs 0.0% [0.0-11.5]; P = .01), with similar trends noted for 28-day single and overlapping DCBs. Drug analysis in parallel tissues further confirmed higher paclitaxel concentrations in nontarget tissues for IN.PACT than Lutonix 035 balloons for single and overlapping configurations at both time points. Rare embolic crystalline material was observed in downstream tissues, but only for IN.PACT balloons.. There was more fibrinoid necrosis in tissues treated with IN.PACT DCBs compared with Lutonix DCBs, suggesting increased emboli debris with higher paclitaxel levels.

Topics: Angioplasty, Balloon; Animals; Arterioles; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Vessels; Embolism; Equipment Design; Femoral Artery; Fibrosis; Models, Animal; Muscle, Skeletal; Necrosis; Neointima; Paclitaxel; Sus scrofa; Time Factors; Vascular Access Devices

Clinically available bioresorbable scaffolds (BRS) rely on polymer crystallinity to achieve mechanical strength resulting in limited overexpansion capabilities and structural integrity when exposed to high-loading conditions. We aimed to evaluate the biomechanical behavior and vascular healing profile of a novel, sirolimus-eluting, high-molecular-weight, amorphous poly-l-lactic acid-based BRS (Amaranth BRS).. In vitro biomechanical testing was performed under static and cyclic conditions. A total of 99 devices (65 Amaranth BRS versus 34 Absorb bioresorbable vascular scaffold [BVS]) were implanted in 99 coronary arteries of 37 swine for pharmacokinetics and healing evaluation at various time points. In the Absorb BVS, the number of fractures per scaffold seen on light microscopy was 6.0 (5.0-10.5) when overexpanded 1.0 mm above nominal values (≈34%). No fractures were observed in the Amaranth BRS group at 1.3 mm above nominal values (≈48% overexpansion). The number of fractures was higher in the Absorb BVS on accelerated cycle testing over time (at 24K cycles=5.0 [5.0-9.0] Absorb BVS versus 0.0 [0.0-0.5] Amaranth BRS). Approximately 90% of sirolimus was found to be eluted by 90 days. Optical coherence tomography analysis demonstrated lower percentages of late scaffold recoil in the Amaranth BRS at 3 months (Amaranth BRS=-10±16.1% versus Absorb BVS=10.7±13.2%; P=0.004). Histopathology analysis revealed comparable levels of vascular healing and inflammatory responses between both BRSs up to 6 months.. New-generation high-molecular-weight amorphous poly-l-lactic acid scaffolds have the potential to improve the clinical performance of BRS and provide the ideal platform for the future miniaturization of the technology.

Topics: Absorbable Implants; Animals; Biopsy; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Vessels; Materials Testing; Models, Animal; Molecular Weight; Neointima; Percutaneous Coronary Intervention; Polyesters; Prosthesis Failure; Sirolimus; Swine; Swine, Miniature; Tomography, Optical Coherence; Wound Healing

The local delivery of paclitaxel onto a graft has been reported to prevent neointimal hyperplasia. Because more than half of vascular stenoses occur within 3 cm of the venous anastomosis, this study tested the effectiveness of a paclitaxel coating restricted to both ends of the expanded polytetrafluoroethylene (ePTFE) graft to reduce the amount of drug delivered.. Both ends of ePTFE grafts were coated with paclitaxel at a dose of 0.58 μg/mm(2); the total amount of paclitaxel per graft was 0.66 mg. Paclitaxel-coated hemodialysis grafts 15 cm in length were surgically implanted between the common carotid artery and external jugular vein in female Landrace pigs. The animals were sacrificed 6 weeks after graft placement. Cross sections of the anastomosis sites were analyzed histomorphometrically to measure the ratio of neointimal hyperplasia to the graft area (H/G ratio) and the percentage of luminal stenosis. The experimental results were compared between grafts coated with paclitaxel at the ends only (n = 8), grafts coated over the entire length (n = 6), and uncoated control grafts (n = 6).. The mean ± standard error values of the H/G ratios for the arterial anastomosis were 0.82 ± 0.13 (control), 0.41 ± 0.09 (terminal coating), and 0.21 ± 0.04 (whole coating). The values for the venous anastomosis were 0.82 ± 0.12 (control), 0.39 ± 0.11 (terminal coating), and 0.12 ± 0.03 (whole coating). Compared with the uncoated grafts, neointimal hyperplasia was suppressed effectively in the vascular grafts coated terminally with paclitaxel (artery, P = 050; vein, P < .001). However, the suppressive effect was less than that of grafts coated with paclitaxel over the entire length. The percentages of luminal stenosis showed similar tendency to the H/G ratios.. Despite a reduced amount of the drug, paclitaxel coating applied to both ends of the ePTFE hemodialysis grafts effectively suppressed neointimal hyperplasia at the sites of anastomosis.

Topics: Animals; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Carotid Artery, Common; Coated Materials, Biocompatible; Constriction, Pathologic; Disease Models, Animal; Female; Graft Occlusion, Vascular; Hyperplasia; Jugular Veins; Neointima; Paclitaxel; Polytetrafluoroethylene; Prosthesis Design; Renal Dialysis; Swine; Time Factors

This study investigated p aclitaxel-induced luminal changes following drug-coated balloon (DCB) angioplasty to treat coronary de novo lesions without additional stenting. DCB-mediated local drug delivery reduces late lumen loss in de novo coronary artery lesions. We performed a retrospective clinical assessment based on a pre-specified quantitative coronary angiography (QCA) protocol.. QCA was performed for each centre to assess the primary endpoint late lumen changes, i.e. the difference between in-lesion minimal lumen diameter (MLD) at the routine angiographic follow-up as compared to post-procedural in-lesion MLDs. These MLD changes were compared to corresponding reference vessel diameter changes as an intra-patient control.. We evaluated 58 consecutive native coronary artery lesions directly after DCB angioplasty and at a routine target follow-up angiography of 4 months by QCA. Target lesion MLD increased significantly within the 4.1 ± 2.1 month observation period (1.75 ± 0.55 vs. 1.91 ± 0.55 mm, p < 0.001, diameter stenosis 33.8 ± 12.3 vs. 26.9 ± 13.8 %, p < 0.001), while there were no changes in non-target reference vessel diameters (2.33 ± 0.60 vs. 2.34 ± 0.61 mm, p = ns). A total of 69 % of patients showed luminal enlargement whereas 29 % had minor luminal loss.. Local application of paclitaxel by DCB angioplasty to native coronary arteries after pre-dilatation without major dissection and recoil leads to late lumen increase.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiac Catheters; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Paclitaxel; Retrospective Studies; Time Factors; Treatment Outcome; Vascular Remodeling

To compare the vascular response after paclitaxel-coated nitinol drug-eluting stent (Zilver PTX) implantation for superficial femoral artery lesions after 6 and 12 months using optical coherence tomography (OCT).. Serial OCT examinations were performed in 5 patients (4 men; mean age 78.4 ± 6.8 years) with 9 Zilver PTX stents at 6- and 12-month follow-up. Variables evaluated included neointimal thickness and apposition on each strut, the incidence of extrastent lumen (ESL), peristrut low-intensity area (PLIA), and neovascularization at 1-mm intervals.. A total of 249 matched cross-section images were evaluated and included 4788 and 4826 struts at 6 and 12 months, respectively. Mean neointimal thickness significantly increased from 480 to 540 µm between 6 and 12 months (p < 0.001). The percentage of uncovered struts tended to decrease at 12 months (3% vs. 2.3%, p = 0.054), whereas the percentage of malapposed struts were similar at both examinations (0.2% vs. 0.2%, p > 0.99). Although the incidence of ESL in cross sections was not different (35% vs. 31%, p = 0.29), median ESL area significantly increased from 6 to 12 months [0.12 (0.04-0.36) vs. 0.31 (0.14-0.59) mm(2), p = 0.003)]. The presence of PLIA (29% vs. 44%, p < 0.001) and neovascularization (14% vs. 27%, p < 0.001) increased from 6 to 12 months.. These findings suggest that delayed vascular healing and persistent peristent inflammation may be present even at 12 months after Zilver PTX implantation.

Topics: Aged; Aged, 80 and over; Alloys; Cardiovascular Agents; Drug-Eluting Stents; Female; Femoral Artery; Follow-Up Studies; Humans; Male; Neointima; Paclitaxel; Peripheral Arterial Disease; Predictive Value of Tests; Retrospective Studies; Risk Factors; Sensitivity and Specificity; Tomography, Optical Coherence; Treatment Outcome

Topics: Absorbable Implants; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Prosthesis Failure; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Topics: Aged, 80 and over; Autopsy; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Fatal Outcome; Female; Humans; Neointima; Percutaneous Coronary Intervention; Polycythemia Vera; Predictive Value of Tests; Prosthesis Design; Risk Factors; Tomography, Optical Coherence; Treatment Outcome

This study sought to compare the effect of paclitaxel-coated balloon (PCB) concentration on tissue levels and vascular healing using 3 different PCB technologies (In.Pact Pacific = 3 μg/mm(2), Lutonix = 2 μg/mm(2) and Ranger = 2 μg/mm(2)) in the experimental setting.. The optimal therapeutic dose for PCB use has not been determined yet.. Paclitaxel tissue levels were measured up to 60 days following PCB inflation (Ranger and In.Pact Pacific) in the superficial femoral artery of healthy swine (18 swine, 36 vessels). The familial hypercholesterolemic swine model of superficial femoral artery in-stent restenosis (6 swine, 24 vessels) was used in the efficacy study. Two weeks following bare-metal stent implantation, each in-stent restenosis site was randomly treated with a PCB or an uncoated control balloon (Sterling). Quantitative vascular analysis and histology evaluation was performed 28 days following PCB treatment.. All PCB technologies displayed comparable paclitaxel tissue levels 4 h following balloon inflation. At 28 days, all PCB had achieved therapeutic tissue levels; however, the In.Pact PCB resulted in higher tissue concentrations than did the other PCB groups at all time points. Neointimal inhibition by histology was decreased in all PCB groups compared with the control group, with a greater decrease in the In.Pact group. However, the neointima was more mature and contained less peri-strut fibrin deposits in both 2-μg/mm(2) PCB groups.. Compared with the clinically established PCB dose, lower-dose PCB technologies achieve lower long-term tissue levels but comparable degrees of neointimal inhibition and fewer fibrin deposits. The impact of these findings in restenosis reduction and clinical outcomes needs to be further investigated.

Topics: Animals; Cardiovascular Agents; Coated Materials, Biocompatible; Constriction, Pathologic; Disease Models, Animal; Endovascular Procedures; Femoral Artery; Fibrin; Hyperlipoproteinemia Type II; Metals; Neointima; Paclitaxel; Peripheral Arterial Disease; Radiography; Stents; Swine; Tissue Distribution; Vascular Access Devices; Wound Healing

Novel polymer-free drug-eluting stents have been developed to reduce polymer-related adverse events. However, neointimal coverage after polymer-free DES implantation is unclear and validation between optical coherence tomography (OCT) and histology is required. Sixteen polymer-free sirolimus-eluting stents were randomly implanted into coronary arteries of 8 normal swine. OCT and histological measurement were conducted at 3 or 6 months after stent placement. For quantitative measures, lumen area, stent area, neointimal area and neointimal thickness were validated in every single OCT and histology matched cross-section. Moreover, for qualitative analysis, OCT signal patterns of neointimal tissue were classified as homogeneous, layered and heterogeneous patterns based on optical intensity and backscatter pattern and peri-strut inflammation was also determined by histology. In total, 70 OCT and histology matched cross-sections were analyzed. At quantitative analysis, good correlations and agreements were found in the measurement of lumen area (ICC = 0.67, P<0.001), neointimal area (ICC = 0.89, P<0.001) and neointimal thickness (ICC = 0.94, P<0.001) except for stent area (ICC 0.19, P = 0.13) between OCT and histology. At qualitative analysis, lymphocyte infiltrations of peri-strut were more frequently seen in heterogeneous sections than in homogeneous sections (10/14 sections, 71.4% vs. 12/50 sections, 24%; P = 0.003). In conclusion, OCT has proper correlation and agreement with histology in assessment of neointimal formation and heterogeneous neointima assessed by OCT may also be associated with peri-strut inflammation detected in histology after polymer-free sirolimus-eluting stents implantation, supporting the use of OCT to evaluate neointimal coverage after polymer-free stent implantation in clinical practice.

Topics: Animals; Cardiovascular Agents; Coronary Vessels; Drug-Eluting Stents; Models, Animal; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Reproducibility of Results; Sirolimus; Swine; Time Factors; Tomography, Optical Coherence

New paclitaxel coated balloons (PCB) developments have been proposed to maintain therapeutic levels of drug in the tissue while decreasing particle release. In this series of studies, we evaluated the pharmacokinetic profile and biological effects after paclitaxel delivery via novel microcrystalline PCB coating (mcPCB, Pax®, Balton) in porcine iliofemoral arteries.. Ten domestic swine were enrolled yielding 24 iliofemoral segments for evaluation. In the pharmacokinetic study, nine mcPCBs were dilated for 60 sec and animals sacrificed after 1 hr, 3 and 7 days. Studied segments were harvested and tissue paclitaxel concentration was analyzed utilizing HPLC. In the biological response evaluation, self-expandable stents were implanted followed by post dilation with either mcPCB (n = 10) or POBA (n = 5). After 28 days, angiography was performed, animals were sacrificed and stented segments harvested for histopathological evaluation.. The 1-hr, 3 and 7 days vessel paclitaxel concentrations were 152.9 ± 154.5, 36.5 ± 49.5, and 0.9 ± 0.7 ng/mg respectively. In the biological response study, stents in the mcPCB group presented lower angiographic measures of neointimal hyperplasia as expressed by late loss when compared to POBA (-0.43 ± 0.9 vs. 0.23 ± 1.2; P = 0.24) at 28 days. In the histopathological evaluation, percent area of stenosis (%AS) was reduced by 42% in the mcPCB group (P < 0.05). The healing process in mcPCB group was comparable to POBA with regard to fibrin deposition (0.7 vs. 0.7; P = ns), neointimal maturity (1.97 vs. 1.93; P = ns), inflammation score (0.92 vs. 1; P = ns) and endothelialization score (1.77 vs. 1.73; P = ns). The mcPCB group did however display a greater tendency of medial cell loss and mineralization (60% vs. 0; P = 0.08).. Delivery of paclitaxel via a novel mcPCB resulted in low long-term tissue retention of paclitaxel. However, this technological approach displayed reduced neointimal proliferation and favorable healing profile.

Topics: Angioplasty, Balloon; Animals; Cardiovascular Agents; Cell Proliferation; Chromatography, High Pressure Liquid; Coated Materials, Biocompatible; Crystallization; Drug-Eluting Stents; Female; Femoral Artery; Hyperplasia; Iliac Artery; Male; Materials Testing; Models, Animal; Neointima; Paclitaxel; Prosthesis Design; Radiography; Sus scrofa; Wound Healing

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

Topics: Aged; Cardiovascular Agents; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Metals; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Stents; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Several studies have reported re-endothelialization and endothelial function after drug-eluting stent (DES) implantation; however, the relationship between re-endothelialization and endothelial function after DES implantation has not been investigated yet.. A total of 14 patients underwent evaluation of re-endothelialization by optical coherence tomography (OCT) and endothelial function by incremental Ach infusion at 9 months after DES implantation (ZES: N = 7, PES: N = 7). The neointimal thickness (NIT) inside each strut, strut coverage, and malapposition at every 1 mm cross-section were evaluated by OCT and the endothelial function was estimated by measuring the coronary vaso-reactivity in response to acetylcholine (Ach) infusion into coronary arteries.. Zotarolims eluting stent (ZES), compared with paclitaxcel eluting stent (PES), showed more homogeneous neointimal coverage of stent struts and low rate of malapposition. Vasoconstriction in response to Ach in the peri-stent region was also less pronounced in ZES than PES. In particular, vasoconstriction was more often observed in cases with inhomogeneous neointimal coverage of stent struts in the PES group.. Our findings suggest that endothelial function seems to be better preserved with ZES than PES, and homogeneous neointimal coverage of stent struts seem to be associated with the preserved endothelial function.

Topics: Acetylcholine; Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Endothelial Cells; Female; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Re-Epithelialization; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Vasoconstriction; Vasoconstrictor Agents

Topics: Angioscopy; Autopsy; Biopsy; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Fatal Outcome; Fibrosis; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Tomography, Optical Coherence

Intimal hyperplasia produces restenosis (re-narrowing) of the vessel lumen following vascular intervention. Drugs that inhibit intimal hyperplasia have been developed, however there is currently no clinical method of perivascular drug-delivery to prevent restenosis following open surgical procedures. Here we report a poly(ε-caprolactone) (PCL) sheath that is highly effective in preventing intimal hyperplasia through perivascular delivery of rapamycin. We first screened a series of bioresorbable polymers, i.e., poly(lactide-co-glycolide) (PLGA), poly(lactic acid) (PLLA), PCL, and their blends, to identify desired release kinetics and sheath physical properties. Both PLGA and PLLA sheaths produced minimal (<30%) rapamycin release within 50days in PBS buffer. In contrast, PCL sheaths exhibited more rapid and near-linear release kinetics, as well as durable integrity (>90days) as evidenced in both scanning electron microscopy and subcutaneous embedding experiments. Moreover, a PCL sheath deployed around balloon-injured rat carotid arteries was associated with a minimum rate of thrombosis compared to PLGA and PLLA. Morphometric analysis and immunohistochemistry revealed that rapamycin-loaded perivascular PCL sheaths produced pronounced (85%) inhibition of intimal hyperplasia (0.15±0.05 vs 1.01±0.16), without impairment of the luminal endothelium, the vessel's anti-thrombotic layer. Our data collectively show that a rapamycin-loaded PCL delivery system produces substantial mitigation of neointima, likely due to its favorable physical properties leading to a stable yet flexible perivascular sheath and steady and prolonged release kinetics. Thus, a PCL sheath may provide useful scaffolding for devising effective perivascular drug delivery particularly suited for preventing restenosis following open vascular surgery.

Topics: Animals; Cardiovascular Agents; Carotid Artery Injuries; Carotid Stenosis; Cell Proliferation; Chemistry, Pharmaceutical; Delayed-Action Preparations; Disease Models, Animal; Drug Carriers; Hyperplasia; Kinetics; Linear Models; Male; Neointima; Polyesters; Rats; Rats, Sprague-Dawley; Sirolimus; Solubility; Technology, Pharmaceutical

Topics: Cardiovascular Agents; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Neointima; Paclitaxel; Sirolimus

Although drug-eluting stents have significantly reduced the midterm incidence of target lesion revascularization (TLR), in vivo studies on long-term vessel healing of sirolimus-eluting stents (SESs) and paclitaxel-eluting stents (PESs) are limited. The aim of this study was to compare long-term arterial healing with SESs and PESs.. We evaluated 27 SESs (23 patients) and 21 PESs (20 patients) by serial optical coherence tomography at 6 months (midphase) and ≥ 3 years (late phase) after stenting and evaluated the change of neointimal thickness (NIT), the percentages of uncovered and malapposed struts, peristrut low-intensity area (region around stent struts with a homogeneously lower intensity appearance than surrounding tissue), thrombus, and atherogenic neointima.. At follow-up, most SESs showed a progressive increase in the average NIT, whereas PESs showed variable changes. Between midphase and late phase, NIT increased significantly in SESs (midphase, 94.1 ± 49.3; late phase, 130.2 ± 78.7; P = 0.001) but decreased significantly in PESs (midphase, 167.4 ± 122.9; late phase, 136.0 ± 77.7; P = 0.04). The percentages of uncovered struts decreased significantly in SESs; conversely, variable changes were observed in PESs. Peristrut low-intensity area and thrombus formation decreased in SESs but remained largely unchanged in PESs. The prevalence of atherogenic neointima was greater in the late phase than in the midphase in both groups but was similar for both stents.. Long-term vessel healing was different for SESs and PESs. Progressive vessel healing was consistently observed in SESs, whereas a heterogeneous process of delayed vessel healing was noted for PESs.

Topics: Aged; Cardiovascular Agents; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Sirolimus; Tomography, Optical Coherence

Topics: Algorithms; Angina, Unstable; Automation; Cardiovascular Agents; Coronary Vessels; Drug-Eluting Stents; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Topics: Autopsy; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Fatal Outcome; Hemorrhage; Humans; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Prosthesis Design; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

To evaluate the potential role, safety, and efficacy of paclitaxel-eluting balloon angioplasty for treatment of recurrent carotid in-stent restenosis (ISR).. Among 856 consecutive patients who underwent carotid artery stenting from May 2002 to January 2008, 41 patients had a significant ISR (>80% stenosis). Of these, 9 patients (7 women; mean age 78.1±5.6 years) had recurrent ISR despite multiple endovascular treatments (3.4±0.9 interventions) within a short period of time (2-5 months). These patients were treated with drug-eluting balloon (DEB) angioplasty for neointimal hyperplasia. Imaging (ultrasound or computed tomographic angiography) was performed at 1, 3, and 6 months and yearly thereafter.. Technical success was obtained in 100% of cases, with angiographic stenosis decreasing from 87%±4% to 6%±4% post treatment. Peak systolic velocity decreased significantly from 4.7±1.5 m/s to 0.6.±0.3 m/s after the procedure. Over a mean follow-up of 36.6±2.7 months, ultrasound imaging indicated recurrent ISR in only 3 patients at 18, 25, and 32 months after DEB angioplasty, respectively. The target vessel revascularization rate was 33.3% at 36 months. No neurological or myocardial events were recorded during follow-up. One patient died at 3 months.. DEB may have a potential role improving outcomes of those patients treated for early recurrent carotid ISR.

Topics: Aged; Angioplasty, Balloon; Blood Flow Velocity; Cardiovascular Agents; Carotid Stenosis; Drug-Eluting Stents; Endovascular Procedures; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Paclitaxel; Prosthesis Design; Recurrence; Regional Blood Flow; Retreatment; Risk Factors; Stents; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography, Doppler; Vascular Patency

Topics: Aged; Angioplasty, Balloon, Coronary; Angioscopy; Biopsy; Cardiovascular Agents; Coronary Aneurysm; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Myocardial Infarction; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Syndrome; Thrombectomy; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Arterial repair in the early phase following implantation of a zotarolimus-eluting stent (ZES) remains unknown.. Following implantation of 49 Endeavor ZES in 33 patients, follow-up angioscopy was performed in 13 patients (26 ZES) in the early phase (EP; 123±24 days) and in 20 patients (23 ZES) in the middle phase (MP; 247±17 days). Neointimal coverage (NIC) was graded as follows: grade 0, stent struts exposed; grade 1, struts bulging into the lumen, although covered; grade 2, struts were embedded by the neointima but were seen translucently; grade 3, struts fully embedded and invisible. NIC was defined as heterogeneous for NIC grade variation≥1. The presence of thrombus and yellow plaque was also investigated. Although NIC heterogeneity tended to be more frequent in EP than in MP (50% vs. 22%, P=0.070), and yellow plaque significantly more frequent (58% vs. 13%, P=0.0025), the majority of stents were dominant NIC grade 3 at both follow-up periods (73% in EP vs. 78% in MP, P=0.75). There was no significant difference in thrombus (23% in EP vs. 4% in MP, P=0.10) between the follow-ups.. Sufficient arterial repair may have occurred by 4 months after ZES implantation. 

Topics: Aged; Aged, 80 and over; Angioscopy; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Two patients who underwent simultaneous kissing stenting with sirolimus-eluting stents in the left main coronary artery were investigated with optical coherence tomography (OCT) at just more than 1 year postoperatively. In both cases, follow-up angiogram indicated complete coverage of the new metal carina with a membranous diaphragm, yet OCT showed varying tissue-coverage patterns transitioning from stent inflow to stent outflow. These patterns included single-strut coverage, bridge-like membrane formation between more than 1 strut, and end-to-end coverage of the carina; no uncovered stent struts were detected. OCT also demonstrated mixed patterns of tissue characteristics on the metal carina, ranging from poor endothelialization to modest neointima formation. These varying tissue characteristics suggest that the process of tissue coverage in the metal carina is different from that occurring on the vessel wall; this may indicate delayed healing in the carina.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Endothelium, Vascular; Female; Humans; Hyperplasia; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

First generation drug-eluting stents (DES) are associated with reduced in-stent restenosis but significant increased risk of very late stent thrombosis (VLST). The absence of polymer in DES systems may reduce the occurrence of VLST. Optic coherence tomography (OCT) has been used for stent analysis as a surrogate safety endpoint. This study aimed to assess the long-term follow up of strut apposition and tissue coverage of BioMatrix DES by OCT. 20 patients undergoing BioMatrix DES (n = 15) or S-Stent BMS (n = 5) implantation were followed for at least 5 years and evaluated by quantitative coronary angiography, intravascular ultrasound, and OCT. The difference between the stent types was evaluated by nonparametric Mann-Whitney U test while categorical variables were evaluated by Fisher exact test. Rates of in-stent late loss were similar between groups [0.40 (0.21;0.77) vs. 0.68 (0.66; 0.82) mm, p = 0.205, for BioMatrix and S-Stent, respectively]. The vessel, stent and lumen volumes did not differ between groups. Patients treated with BioMatrix had significantly less stent obstruction [5.6 (4.4;9.7) vs. 28.6 (24.7;29.0) %, p = 0.001]. OCT analysis of 12 stents (Biomatrix = 9 and S-Stent = 3) demonstrated 126 (8.7 %) uncovered struts in the BioMatrix group compared to 23 (4.0 %) in the S-Stent group (p = 0.297), being the majority of them well apposed (117/126 and 21/23, respectively, p = 0.292). Only 9 (0.6 %) struts in the DES and 2 (0.4 %) struts in the BMS groups were simultaneously uncovered and malapposed (p = 0.924). BioMatrix DES was associated with lower rates of in-stent obstruction, and similar percentage of neointimal coverage on struts and of complete strut apposition.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

The optimal therapy for in-stent restenosis (ISR) is controversial. We evaluated three different strategies for the treatment of in-stent restenosis: cutting balloon angioplasty (CBA), paclitaxel-eluting balloon angioplasty (PEBA) and cutting balloon followed by paclitaxel-eluting balloon angioplasty (CB+PEBA).. Forty-five coronary arteries in 45 mini-pigs underwent oversized bare-metal stent (stent-to-artery ratio, 1.2:1) implantation to induce in-stent restenosis. After 28 days, vessels with in-stent restenosis (≥50% diameter stenosis) were randomly divided into three groups: CBA, PEBA and CB+PEBA. In vivo angiography was performed before intervention, immediately after intervention and at 28-day follow-up. Stented arteries were harvested for pathological analyses. The proliferation and apoptosis of vascular smooth muscle cells were evaluated by immunohistochemical staining and the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, respectively.. Acute lumen gain was not different between the three groups. Late lumen loss and neointimal area at follow-up were lower for CB+PEBA compared with CBA but similar for CB+PEBA compared with PEBA. There were no significant differences in proliferating cell nuclear antigen-positive vascular smooth muscle cells and TUNEL-positive vascular smooth muscle cells between the CB+PEBA and PEBA groups.. PEBA with or without cutting balloon was superior to CBA alone for in-stent restenosis. The underlying mechanism was probably related to inhibition of smooth muscle cell proliferation and increased apoptosis. In this porcine coronary artery restenosis model, PEBA with or without cutting balloon was superior.

Topics: Angioplasty, Balloon, Coronary; Animals; Apoptosis; Cardiac Catheters; Cardiovascular Agents; Cell Proliferation; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Equipment Design; Immunohistochemistry; In Situ Nick-End Labeling; Metals; Muscle, Smooth, Vascular; Neointima; Paclitaxel; Prosthesis Design; Stents; Swine; Swine, Miniature; Time Factors

Epigallocatechin-3-gallate (EGCG), a catechin gallate ester, is the major component of green tea and has been demonstrated to inhibit tumor growth as well as inhibit smooth muscle cell migration. We evaluated the effect of the phytochemicals resveratrol, allicin, sulforaphane (SFN), and EGCG on intimal hyperplasia in the carotid artery injury model.. Intimal hyperplasia was induced in carotid arteries of adult Sprague-Dawley rats with a wire injury. Experimental animals received intraperitoneal injections of one of the four phytochemicals daily beginning 1 day prior to surgery and continued for up to 4 weeks. Control animals were administered saline. Carotid specimens were harvested at 2 weeks and subjected to quantitative image analysis. In addition, EGCG specimens were analyzed for cell proliferation, immunohistochemistry, and Western blot analysis.. Quantitative image analysis showed significant phytochemical suppression of intimal hyperplasia at 2 and 4 weeks postoperatively with EGCG (62% decrease in intimal area). Significant decreases were also noted at 2 weeks for SFN (56%) and resveratrol (44%), whereas the decrease with allicin (24%) was not significant. Quantification of intimal hyperplasia by intima:media ratio showed similar results. Cell proliferation assay of specimens demonstrated suppression by EGCG. Immunohistochemical staining of EGCG-treated specimens showed extracellular signal-regulated kinase (ERK) suppression but not of the c-jun N-terminal kinase or p38 pathways. Western blot analysis confirmed reduced ERK activation in arteries treated with EGCG.. Intraperitoneal injection of the phytochemicals EGCG, SFN, resveratrol, and allicin have suppressive effects on the development of intimal hyperplasia in the carotid artery injury model, with maximal effect due to EGCG. The mechanism of EGCG action may be due to inhibition of ERK activation. EGCG may affect a common pathway underlying either neoplastic cellular growth or vascular smooth muscle cellular proliferation.

Topics: Animals; Cardiovascular Agents; Carotid Artery Injuries; Carotid Artery, Common; Carotid Intima-Media Thickness; Catechin; Cell Proliferation; Disease Models, Animal; Disulfides; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Hyperplasia; Injections, Intraperitoneal; Isothiocyanates; Male; Neointima; Protein Kinase Inhibitors; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Sulfinic Acids; Sulfoxides; Time Factors

Among three versions of bioresorbable magnesium scaffolds featuring different paclitaxel-elution kinetics, we determined the best-performing scaffold and compared it with established, paclitaxel-eluting, permanent stents TAXUS Liberté and eucaTAX.. Drug-elution kinetics in magnesium scaffolds were modulated by varying the composition of their bioresorbable poly(lactide-co-glycolide) coating loaded with paclitaxel. A 50:50 ratio of lactide to glycolide, or an 85:15 ratio and either high- or low-molecular-weight polymer was applied in the "50/50", "85/15H", and "85/15L" scaffolds, respectively. Seventy-three magnesium scaffolds (25 50/50, 24 85/15H, 24 85/15L) and 36 control stents (18 TAXUS Liberté, 18 eucaTAX) were implanted in coronary arteries of 50 Yucatan mini-pigs. Angiography, histomorphometry, and histopathology data were acquired at 28, 90 and 180 days. The best-performing magnesium scaffold, 85/15H, was equivalent to TAXUS Liberté and superior to eucaTAX regarding late luminal loss, intimal area, fibrin score, and endothelialisation. Intimal inflammation score was higher in 85/15H than in the control stents at 28 days, but this effect disappeared at later time points.. By selecting suitable paclitaxel-elution kinetics, it was feasible to develop a bioresorbable magnesium scaffold whose efficacy and healing characteristics in a porcine coronary model are comparable with those of established paclitaxel-eluting permanent metallic stents.

Topics: Absorbable Implants; Alloys; Animals; Cardiovascular Agents; Coronary Angiography; Coronary Vessels; Drug-Eluting Stents; Feasibility Studies; Female; Fibrosis; Kinetics; Magnesium; Male; Materials Testing; Models, Animal; Molecular Weight; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Polyglactin 910; Prosthesis Design; Swine; Swine, Miniature

This study sought to elucidate the underlying mechanism through which drug-eluting balloons (DEB) restore coronary blood flow, by assessing the coronary vessel before, immediately after, and at 6-month follow-up with angiography, optical coherence tomography (OCT), and fractional flow reserve (FFR).. In-stent restenosis (ISR) treatment remains challenging. Drug-eluting balloons have been shown to be a valid treatment option in several studies. These studies focused on efficiency of the device, whereas the mechanisms of action of DEB in ISR treatment have not been investigated.. In this prospective, single-center observational study, patients with ISR were treated with a second-generation DEB. Serial angiographic, OCT, and FFR measurements were performed before and after the procedure, as well as at 6-month follow-up.. Twenty-five patients were assigned to DEB treatment, with an angiographic and device success of 100% and 92%, respectively. Late luminal loss was 0.01 ± 0.43 mm. Median percent changes [interquartile range] between pre-and post-procedure, and post-procedure and follow-up were, respectively: lumen volume 75.1% increase [43.7 to 115.0], and 8% increase [-14.0 to 25.8]; stent volume 23.7% increase [15.5 to 40.0], and -1.2% decrease [-6.9 to 5.9]; and neointimal volume -14.4% decrease [-29.2 to -9.5], and -15.8% decrease [-38.1 to 28.3]. The FFR gradient along the treated stent (difference in FFR between the distal and the proximal stent edge) was 0.37 ± 0.18 pre-procedure, 0.06 ± 0.04 post-procedure, and 0.05 ± 0.05 at follow-up. In all post-procedural OCT images, intrastent dissections were seen, which were sealed at follow-up OCT.. DEB restore coronary blood flow by means of a short-term mechanical effect, causing an increase in lumen and stent volumes and compression of neointimal hyperplasia (with intra-stent dissections). Due to the local drug effect, patency persists and may even improve at follow-up, with further increase in lumen volume, decrease in neointimal volume, and complete sealing of neointimal dissections.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiac Catheterization; Cardiac Catheters; Cardiovascular Agents; Chi-Square Distribution; Coronary Restenosis; Coronary Vessels; Drug Carriers; Equipment Design; Female; Fractional Flow Reserve, Myocardial; Humans; Male; Middle Aged; Neointima; Netherlands; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Stents; Time Factors; Tomography, Optical Coherence; Tomography, X-Ray Computed; Treatment Outcome; Vascular Patency

Implantation of drug eluting stents (DES) has become a standard treatment of patients undergoing percutaneous coronary intervention (PCI). Incomplete strut coverage is a potential risk factor for late stent thrombosis. Optical coherence tomography (OCT) enables in vivo identification of incomplete neointimal coverage.. Study included 62 patients after sirolimus eluting stents (SES) or paclitaxel eluting stents (PES) implantation. OCT examination was performed at least 24 months after the initial procedure (35.4± 9.4 months). In cross-sectional still frames selected from each 1 mm of analyzed stents a total number of visible struts and number of struts with or without complete neointimal coverage was assessed. Measurements of neointimal coverage, presented as a mean thickness of tissue, were performed. Patients were followed up for 3 years and the frequency ofmajor adverse cardiac events was recorded.. In the analyzed 28 SES and 37 PES 9998 struts were identified. Complete neointimalcoverage was observed in 83.5% and 79.2% of SES and PES struts respectively (p = 0.48).There was no difference in incidence of not covered or malapposed struts between SES and PES groups. Mean thickness of the tissue covering SES struts was 0.165 ± 0.095 mm, and 0.157 ± 0.121 mm for PES. The mean neointimal thickness difference (SES vs. PES) was notstatistically significant. In a 36 months follow-up 1 death was observed - potentially attributed to stent thrombosis.. A long term OCT follow-up after DES implantation shows high incidence ofuncovered struts regardless of the stent type. Clinical significance of this finding remains questionable and requires further large scale trials.

Topics: Aged; Cardiovascular Agents; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Registries; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To obtain imaging evidence by 2-week optical coherence tomography (OCT) on the completion of neointimal coverage (NIC; the percentage of stent strut coverage and thickness of the formed neointima) completion after implantation of the Endeavor zotarolimus-eluting stent (E-ZES).. Despite the fact that NIC is a cardinal process in the pathomechanism of late stent thrombosis, little imaging information is available on morphological changes thereof on a short-time interval basis.. 27 Japanese patients with stable angina pectoris and de novo native coronary artery lesions were enrolled, and 27 lesions (30 implantations) were examined. OCT was performed at weeks 2, 4, 6, 8, and 10 after E-ZES implantation. NIC was examined using cross-sectional OCT images obtained at the 1.0-mm intervals.. In total, 621 cross-sectional OCT images, which depicted 7,747 stent struts, were analyzed. The mean percentages of stent strut coverage at weeks 2, 4, 6, 8, and 10 after E-ZES implantation were 12.3, 70.4, 67.9, 86.0, and 99.2%, respectively; a marked increase was found between weeks 2 and 4. The mean thicknesses of the formed neointima were 40.2, 52.1, 48.1, 86.5, and 146.2 μm at respective weeks, with the high-signal and thick neointima (146 µm) at week 10. An intracoronary thrombus was detected in only one stent at week 4.. The full circumferential coverage of the vessel wall by the high-signal neointima was found at as early as week 10 after E-ZES implantation, imparting a surrogate index for vascular healing by NIC.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Japan; Male; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

The routine use of paclitaxel-coated balloons (PCB) in combination with bare metal stents (BMS) in de novo coronary lesions has been questioned. In this study, we aimed to compare the vascular response of BMS implanted using a second-generation PCB (BMS+PCB) with the TAXUS stent (PES) and a BMS control (BMS) in the familial hypercholesterolaemic swine (FHS) model of coronary injury.. A total of 17 stents (PES=6, BMS+PCB=6, and BMS=5) were implanted in the coronary territory of 10 FHS using a 20% overstretch injury ratio. Imaging evaluation (QCA and IVUS) was conducted in all animals at baseline and 28 days following stent implantation. Following terminal imaging all animals were euthanised and stented coronary segments harvested for histological evaluation. At 28 days, the lowest degree of percentage diameter stenosis by QCA was achieved by the PES (2.9 ± 9%) followed by the BMS+PCB (9.5 ± 16.4%) and the BMS group (25.65 ± 18.7%, p<0.05). In histology, percentage area of stenosis (BMS+PCB=29.6 ± 6.4% vs. PES=21.5 ± 3.3% vs. BMS=55.2 ± 12.9%; p<0.01) and neointimal thickness (BMS+PCB=0.26 ± 0.1 mm vs. PES=0.21 ± 0.1 mm vs. BMS=0.59 ± 0.2 mm; p<0.01) were significantly reduced in both paclitaxel groups in comparison to BMS controls. Both BMS+PCB and BMS groups had higher endothelialisation scores (PES=1.50 ± 0.9 vs. BMS+PCB=2.73 ± 0.4 vs. BMS=3.00; p<0.05) and lower peri-strut inflammatory scores (PES=0.83 ± 0.4 vs. BMS+PCB=0.20 ± 0.2 vs. BMS=0.43 ± 0.6, p<0.05) when compared to PES. Neointima maturity (PCB+BMS: 2.00 [2-2.4] vs. PES: 1.00 [0.3-1] vs. BMS: 3.00, p<0.05) and fibrin deposition (PCB+BMS: 1.40 ± 0.3 vs. PES: 2.17 ± 0.7 vs. BMS: 0.27 ± 0.3, p<0.05) scores in PCB+BMS appeared to fall between the PES and the BMS ranges.. In the FHS coronary injury model, BMS implantation using a PCB yields a degree of neointimal inhibition comparable to the PES. The BMS+PCB combination presented lower degrees of inflammation and fibrin deposition; however, signs of delayed healing were still present.

Topics: Angioplasty, Balloon, Coronary; Animals; Cardiovascular Agents; Constriction, Pathologic; Coronary Artery Disease; Coronary Vessels; Disease Models, Animal; Drug-Eluting Stents; Iohexol; Neointima; Paclitaxel; Polymers; Swine

This study sought to evaluate vascular drug uptake, distribution and response of second-generation paclitaxel coated balloon (PCB) (Cotavance, MEDRAD Interventional, Indianola, Pennsylvania) and compare it with first-generation technology, containing identical excipient and drug concentration.. Original PCB technologies displayed a heterogeneous deposition of crystalline paclitaxel-iopromide inside the balloon folds, whereas second-generation PCBs consisted of more homogeneous, circumferential coatings.. Paclitaxel tissue uptake was assessed in 20 iliofemoral arteries of a domestic swine. Vascular healing response was assessed in the familial hypercholesterolemic model of iliofemoral in-stent restenosis. Three weeks after bare-metal stent implantation, vascular segments were randomly revascularized with first-generation PCBs (n = 6), second-generation PCBs (n = 6), or plain balloon angioplasty (PBA) (n = 6). At 28 days, angiographic and histological evaluation was performed in all treated segments.. One-hour paclitaxel tissue uptake was 42% higher in the second-generation PCBs (p = 0.03) and resulted in more homogeneous segment-to-segment distribution compared with first-generation PCBs. Both angiography (percentage of diameter stenosis: second-generation 11.5 ± 11% vs. first-generation 21.9 ± 11% vs. PBA 46.5 ± 10%; p < 0.01) and histology (percentage of area stenosis: second-generation 50.5 ± 7% vs. first-generation 54.8 ± 18% vs. PBA 78.2 ± 9%; p < 0.01) showed a decrease in neointimal proliferation in both PCB groups. Histological variance of the percentage of area stenosis was lower in second-generation compared with first-generation PCBs (51.7 vs. 328.3; p = 0.05). The presence of peristrut fibrin deposits (0.5 vs. 2.4; p < 0.01) and medial smooth muscle cell loss (0 vs. 1.7; p < 0.01) were lower in the second-generation compared with first-generation PCBs.. In the experimental setting, second-generation PCB showed a comparable efficacy profile and more favorable vascular healing response when compared to first-generation PCB. The clinical implications of these findings require further investigation.

Topics: Angioplasty, Balloon; Animals; Arterial Occlusive Diseases; Cardiovascular Agents; Cell Proliferation; Coated Materials, Biocompatible; Constriction, Pathologic; Contrast Media; Disease Models, Animal; Equipment Design; Femoral Artery; Fibrosis; Hyperlipoproteinemia Type II; Iliac Artery; Iohexol; Neointima; Paclitaxel; Radiography; Sus scrofa; Tissue Distribution; Vascular Access Devices; Wound Healing

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

This study sought to assess stent-vessel interactions after drug-eluting stent (DES) implantation in unprotected left main coronary artery (ULM) by frequency-domain optical coherence tomography (FD-OCT).. Percutaneous coronary intervention using DES in ULM has been increasingly performed in routine practice. Recently, FD-OCT assessments of DES-vessel interactions have been used as surrogates for DES safety; however, there are no FD-OCT studies in ULM.. We prospectively enrolled 33 consecutive patients with ULM disease treated with sirolimus- (n = 11) and everolimus-eluting stents (n = 22). FD-OCT assessments were performed post-percutaneous coronary intervention and at 9-month follow-up. Three different segments of ULM were compared: distal (DIS), bifurcation (BIF), and ostial-body (BODY). The primary endpoints were percentages of uncovered and malapposed struts at 9-month follow-up, and the secondary endpoint was neointimal hyperplasia area.. We analyzed 25,873 stent struts. Significant differences were demonstrated for percentage of uncovered struts (3.4%, 11.7%, and 18.7%, respectively for DIS, BIF, and BODY; p < 0.05 for all the comparisons). Malapposition was also more common in BODY (5.3%) than in DIS (0.6%) and BIF (2.0%) segments (p < 0.05 for BODY vs. DIS, and BODY vs. BIF). Equivalent neointimal hyperplasia areas were demonstrated in all segments. Acute malapposition rates led to different patterns of DES-vessel interactions at 9-month follow-up.. Distinct patterns of DES-vessel interactions were demonstrated in different segments of ULM. Acute stent strut malapposition affects these findings.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

We investigate the influence of stent design on stent coverage at 6-9 months after sirolimus eluting stent (SES) implantation using optical coherence tomography (OCT).. Although some reports suggest that stent design may correlate with stent coverage of stent struts, there were few detailed data whether stent design impact on stent coverage in the same drug-eluting stent.. A total of 21 SESs (15 patients), who had implanted 2.5, 2.75, and 3.0 mm stents, underwent OCT at 6-9 months after stent implantation. SES is constructed by two different strut width-components; narrow strut width parts (59 μm) and wide strut width parts (115 μm). Thus, we divided stent struts of SESs into two groups: narrow strut width parts (narrow group) and wide ones (wide group). We compared the incidence of incomplete apposed struts, uncovered struts, and neointimal hyperplasia (NIH) thickness between the two groups.. We could detect 2,948 struts (narrow group consisted of 1,132 struts and wide group consisted of 1,816 struts). Incidence of uncovered struts in the narrow group was significantly lower than in the wide group (30.2% vs. 40.8%, P < 0.001), and NIH thickness in the narrow group was significantly greater than in the wide group (127.5 ± 93.4 μm vs. 118.6 ± 81.4 μm, P = 0.03).. Stent design, especially strut width, affects stent coverage of SES. The narrow strut may avoid the absence of stent coverage in SES, which correlates with stent thrombosis.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Chi-Square Distribution; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To test the local delivery of sirolimus nanoparticles following percutaneous transluminal coronary angioplasty (PTCA) to treat in-stent restenosis (ISR) in a swine model.. Coronary bare-metal stent (BMS) implantation reduces major adverse cardiac events when compared with PTCA; however, ISR rates remain high.. Eighteen swine underwent BMS deployment guided by intravascular ultrasound (IVUS). Of these, 16 developed ISR (1 stent/swine) and underwent angioplasty with a noncompliant balloon (PTCA-NC). The animals were then randomized into four groups for local infusion of sirolimus nanoparticles through a porous balloon catheter, as follows: (1) PTCA-NC alone (control); (2) PTCA-NC + (polylactic acid)-based nanoparticle formulation (anionic 1); (3) PTCA-NC + (polylactic-co-glycolic acid)-based nanoparticle formulation (anionic 2); and (4) PTCA-NC + Eudragit RS nanoparticle formulation (cationic). Coronary angiography and IVUS follow-up were performed 28 days after ISR treatment.. There was one episode of acute coronary occlusion with the cationic formulation. Late area loss was similar in all groups at 28 days according to IVUS. However, luminal volume loss (control = 20.7%, anionic 1 = 4.0%, anionic 2 = 6.7%, cationic = 9.6%; P = 0.01) and neointimal volume gain (control = 68.7%, anionic 1 = 17.4%, anionic 2 = 29.5%, cationic = 31.2%; P = 0.019) were significantly reduced in all treatment groups, especially in anionic 1.. PTCA-NC followed by local infusion of sirolimus nanoparticles was safe and efficacious to reduce neointima in this model, and this strategy may be a promising treatment for BMS ISR. Further studies are required to validate this method in humans.

Topics: Acrylic Resins; Animals; Cardiac Catheters; Cardiovascular Agents; Chemistry, Pharmaceutical; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Drug Carriers; Drug Delivery Systems; Equipment Design; Infusions, Parenteral; Lactic Acid; Nanoparticles; Neointima; Percutaneous Coronary Intervention; Polyesters; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Porosity; Sirolimus; Swine; Time Factors; Ultrasonography, Interventional

The aim of this study was to assess the efficacy of stent-based delivery of succinobucol alone and in combination with rapamycin in a porcine coronary model.. Current drugs and polymers used to coat coronary stents remain suboptimal in terms of long term efficacy and safety. Succinobucol is a novel derivative of probucol with improved antioxidant and anti-inflammatory properties.. Polymer-free Yukon stents were coated with 1% succinobucol (SucES), 2% rapamycin (RES), or 1% succinobucol plus 2% rapamycin solutions (SucRES) and compared with a bare metal stent (BMS).. The in vivo release profile of SucES indicated drug release up to 28 days (60% drug released at 7 days); 41 stents (BMS, n = 11; SucES, n =10; RES, n = 10; SucRES, n = 10) were implanted in the coronary arteries of 17 pigs. After 28 days, mean neointimal thickness was 0.31 ± 0.14 mm for BMS, 0.51 ± 0.14 mm for SucES, 0.19 ± 0.11 mm for RES, and 0.36 ± 0.17 mm for SucRES (P < 0.05 for SucES vs. BMS). SucES increased inflammation and fibrin deposition compared with BMS (P < 0.05), whereas RES reduced inflammation compared with BMS (P < 0.05).. In this model, stent-based delivery of 1% succinobucol using a polymer-free stent platform increased neointimal formation and inflammation following coronary stenting.

Topics: Animals; Cardiovascular Agents; Cattle; Cell Survival; Cells, Cultured; Coronary Vessels; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug-Eluting Stents; Endothelial Cells; Fibrin; Inflammation; Male; Metals; Models, Animal; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neointima; Percutaneous Coronary Intervention; Probucol; Prosthesis Design; Sirolimus; Swine

Late stent thrombosis related to delayed endothelialization is a major concern after drug-eluting stent (DES) implantation. The long-term vascular response towards DES implantation remains unclear. Optical coherence tomography (OCT) is a high-resolution imaging modality which provides new opportunities for evaluating neointimal coverage and stent strut apposition after stent implantation.. Fifty two patients who accepted 64 sirolimus-eluting stents (SESs, Cypher Select) were enrolled in the study. The OCT procedure was performed in 20 patients at 12 months (group 1), 17 patients at 24 months (group 2), and 15 patients at 48 months (group 3) after SESs implantation, respectively. The neointimal hyperplasia (NIH) thickness and stent strut apposition were assessed at 1-mm interval, and the presence of thrombus was observed in each stent.. The NIH thickness was significantly higher at 48 months than that of 12 months (0.1694 ± 0.1455 mm in G3 vs. 0.1455 ± 0.1373 mm in G1, P < 0.01) and 24 months (0.1514 ± 0.1296 mm in G2, P <0.01) after SESs implantation, but no significant difference existed between that of 12 months and 24 months (P > 0.05). Longer follow-up time was associated with significant decrease in the prevalence of uncovered struts (17.3% in group 1 vs. 8.8% in group 2 vs. 2.6% in group 3, P < 0.01) and malapposed struts (14.2% in group 1 vs. 10.3% in group 2 vs. 4.7% in group 3, P < 0.01). The incidence of intracoronary thrombus steadily decreased from 3.6% at 12 months to 2.4% at 24 months, and to 0.8% at 48 months (P < 0.01).. Neointimal growth continued for as long as 48 months after SES implantation. NIH thickness increased insignificantly from 12 to 24 months, but markedly increased at 48 months after stent implantation. Late neointimal growth was accompanied by a higher rate of covered struts and lower rate of malapposed stent struts.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Multivariate Analysis; Neointima; Odds Ratio; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To evaluate differences in strut coverage, inflammation and endothelialization between two second-generation polymer-based drug-eluting stents (DES) in an atherosclerotic rabbit double-injury iliac artery model at 28 days follow-up.. Rabbits with induced atheroma received bilateral iliac artery stents: everolimus-eluting stent (Xience V EES; Abbott Vascular), zotarolimus-eluting stent (Resolute ZES; Medtronic CardioVascular), or bare-metal stent (BMS; MultiLink Vision; Abbott Vascular). After 28 days, total neointimal coverage examined by scanning electron microscopy was >98% for all three stent types. Neointimal thickness above stent struts was decreased by 50% in Xience V EES (0.06 ± 0.01 mm; P = 0.00001) compared with BMS (0.15 ± 0.03 mm) and Resolute ZES (0.12 ± 0.04 mm). Luminal area was largest for Xience V EES (3.79 ± 0.33 mm(2) ; P = 0.0003 for Xience V EES vs. BMS), followed by Resolute ZES (3.46 ± 0.45 mm(2) ; P = 0.083 for Resolute ZES vs. BMS) and BMS (3.07 ± 0.53 mm(2) ). Percentage area stenosis was smallest for Xience V EES (17.23 ± 3.64%; P = 0.00001), while BMS (30.25 ± 7.48%) and Resolute ZES (30.79 ± 7.15%) did not differ. Endothelial monolayer regrowth was significantly lower in Resolute ZES (65 ± 13%) versus BMS (79 ± 11%; P = 0.004). There was no difference between Xience V EES (74 ± 10%) and BMS. Xience V EES was further associated with a lower number of inflammatory cells surrounding the stent struts (7 ± 2 per strut) in comparison to Resolute ZES (15 ± 6; P = 0.0001) and BMS (17 ± 9; P = 0.0005).. In this atherosclerotic rabbit model, Xience V EES suppressed neointimal thickening better, with normal endothelial regrowth as compared with BMS, and less strut-induced inflammation.

Topics: Angioplasty, Balloon; Animals; Atherosclerosis; Cardiovascular Agents; Cell Proliferation; Disease Models, Animal; Drug-Eluting Stents; Endothelial Cells; Everolimus; Iliac Artery; Inflammation; Male; Neointima; Prosthesis Design; Rabbits; Radiography; Sirolimus; Time Factors; Vascular System Injuries

The aim of this study was to evaluate neointimal coverage obtained using a new method of polytetrafluoroethylene-covered stent (PCS) implantation combined with underlying longer sirolimus-eluting stent (SES) implantation using optical coherence tomography. Nine patients were enrolled in this study, including patients with coronary artery perforations, original coronary aneurysms, and acquired coronary aneurysms after drug-eluting stent implantation. All patients were first treated with long SES implantation and then with focal PCS implantation. Postprocedural and follow-up angiographic and optical coherence tomographic examinations were performed in all patients, and intravascular ultrasound was performed in 5 patients. All patients were asymptomatic during follow-up, without recurrent angina. There was no stent-edge or stent-segment binary restenosis. Values of late loss for proximal SES segments, PCS segments, and distal SES segments were similar (0.09, 0.07, and 0.04 mm, respectively, p = 0.8113). The mean neointimal thickness of PCS was less than that of proximal and distal SES. However, no malapposed cross sections or uncovered cross sections were found in PCS segments compared with SES segments (p = 0.0011). In conclusion, the combination of PCS and underlying longer SES implantation can offer better angiographic follow-up results. High-resolution optical coherence tomography provided convincing proof of full neointimal coverage of PCS. This new method of combined PCS and SES implantation may be a better choice compared with direct PCS implantation in certain clinical settings.

Topics: Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Drug-Eluting Stents; Humans; Neointima; Polytetrafluoroethylene; Radiographic Image Interpretation, Computer-Assisted; Sirolimus; Statistics, Nonparametric; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

We aimed to uncover the protein changes of coronary artery in-stent restenosis (ISR) tissue in minipigs with and without streptozotocin-induced diabetes mellitus by quantitative 2-dimensional fluorescence in-gel electrophoresis (2D-DIGE), and to investigate the influences of crucial proteins identified, particularly adipocyte fatty acid binding protein (AFABP), in human arterial smooth muscle cells.. Sirolimus-eluting stents were implanted in the coronary arteries of 15 diabetic and 26 nondiabetic minipigs, and angiography was repeated after 6 months. The intima tissue of significant ISR and non-ISR segments in both diabetic and nondiabetic minipigs was analyzed by 2D-DIGE and MALDI-TOF/TOF mass spectrometry. AFABP level was significantly increased in ISR tissue than in non-ISR tissue in both diabetic and nondiabetic minipigs, with level being higher in diabetic ISR than in nondiabetic ISR tissue. In human arterial smooth muscle cells, overexpression of AFABP significantly altered phenotype and promoted growth and migration, with effects more prominent in high-glucose than in low-glucose medium, whereas AFABP knockdown inhibited these effects. AFABP overexpression increased reactive oxygen species production by upregulating the expression of NADPH oxidase subunits Nox1, Nox4, and P22 through multiple pathways, with elevation of downstream gene cyclin D1, matrix metalloproteinase-2, and monocyte chemoattractant protein-1. However, AFABP-induced effects were inhibited by diphenyleneiodonium, pathway inhibitors, and small interfering RNA. In addition, the supernatant from AFABP-expressing human arterial smooth muscle cells and recombinant AFABP also promoted cellular growth and migration.. This study has demonstrated that AFABP is significantly increased in coronary artery ISR segments of both diabetic and nondiabetic minipigs. Increased AFABP expression and secretory AFABP of human arterial smooth muscle cells promote growth and migration via reactive oxygen species-mediated activation.

Topics: Animals; Cardiovascular Agents; Cell Movement; Cell Proliferation; Cells, Cultured; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus, Experimental; Drug-Eluting Stents; Electrophoresis, Gel, Two-Dimensional; Enzyme Inhibitors; Fatty Acid-Binding Proteins; Fluorescence; Glucose; Humans; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; NADPH Oxidases; Neointima; NF-kappa B; Oxidative Stress; Percutaneous Coronary Intervention; Phenotype; Reactive Oxygen Species; RNA Interference; RNA, Messenger; Signal Transduction; Sirolimus; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; STAT3 Transcription Factor; Swine; Swine, Miniature; Time Factors; Transcription Factor AP-1; Transfection; Up-Regulation

This study examined whether sirolimus-eluting stent (SES) implantation exerts an antiproliferative action on a bare metal stent (BMS) placed distally in the same coronary artery.. Diffusion of sirolimus into flowing coronary blood may cause accumulation of this drug in the coronary bed beyond the distal edge of an SES.. We analyzed data from 115 consecutive patients with ischemic heart disease who were treated with two overlapping stents without a gap in the same coronary artery for a long de novo lesion. The distal stent was a 2.25 mm BMS in all patients, and the proximal stent was an SES in 73 patients (SES-BMS group) and a BMS in 42 patients (BMS-BMS group). Quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) were performed at stent implantation and 8 months later.. Clinical and procedural variables were comparable between the two groups. QCA and IVUS showed that the SES-BMS group had less luminal late loss and a lower percent of in-stent volume obstruction in the distal BMS compared with the BMS-BMS group. Furthermore, compared with the BMS-BMS group, the SES-BMS group had less in-stent restenosis (23.3 vs. 54.8%, P < 0.0005) and target lesion revascularization (21.9 vs. 50.0%, P < 0.005).. SES implantation just proximal to a BMS inhibits neointimal proliferation in the BMS, when both stents are implanted in the same coronary artery to treat a de novo lesion.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Cell Proliferation; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Metals; Neointima; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Severity of Illness Index; Sirolimus; Stents; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Recent studies reported favorable angiographic and clinical outcomes after everolimus-eluting stent (EES) implantation. However, there were no studies to assess vascular responses after EES implantation using optical coherence tomography (OCT). Therefore, the OCT findings in EES were investigated and compared with those in sirolimus-eluting stent (SES). Follow-up OCT studies were performed in 110 lesions (40 EES and 70 SES) of 104 patients at 9 months after stent implantation. The strut apposition, neointimal hyperplasia (NIH) thickness and stent coverage on each stent struts were evaluated. The mean NIH thickness was significantly greater in EES-treated lesions than in SES-treated lesions (115 ± 52 μm vs. 89 ± 58 μm, P = 0.001, respectively). The percentage of uncovered strut was significantly smaller in EES-treated lesions than in SES-treated lesions (4.4 ± 4.7% vs. 10.5 ± 12.7%, P = 0.016, respectively). There was no significant difference in the percentage of malapposed strut between the two groups (0.4 ± 0.8% in EES vs. 1.7 ± 4.5% in SES, P = 0.344). The incidence of intracoronary thrombus was significantly lower in EES-treated lesions than in SES-treated lesions (5.0% vs. 34.3%, P < 0.001, respectively). EES showed a significantly lower incidence of uncovered stent struts and intracoronary thrombus than SES in 9-month follow-up OCT examination. Compared to SES, EES might have more favorable vascular responses after stent implantation.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Predictive Value of Tests; Registries; Republic of Korea; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To quantify with in vivo OCT and histology, the device/vessel interaction after implantation of the bioresorbable vascular scaffold (BVS). We evaluated the area and thickness of the strut voids previously occupied by the polymeric struts, and the neointimal hyperplasia (NIH) area covering the endoluminal surface of the strut voids (NIH(EV)), as well as the NIH area occupying the space between the strut voids (NIH(BV)), in healthy porcine coronary arteries at 2, 3 and 4 years after implantation of the device. Twenty-two polymeric BVS were implanted in the coronary arteries of 11 healthy Yucatan minipigs that underwent OCT at 2, 3 and 4 years after implantation, immediately followed by euthanasia. The areas and thicknesses of 60 corresponding strut voids previously occupied by the polymeric struts and the size of 60 corresponding NIH(EV) and 49 NIH(BV) were evaluated with both OCT and histology by 2 independent observers, using a single quantitative analysis software for both techniques. At 3 and 4 years after implantation, the strut voids were no longer detectable by OCT or histology due to complete polymer resorption. However, analysis performed at 2 years still provided clear delineation of these structures, by both techniques. The median [ranges] areas of these strut voids were 0.04 [0.03-0.16] and 0.02 [0.01-0.07] mm(2) by histology and OCT, respectively. The mean (±SD) thickness by histology and OCT was 220 ± 40 and 120 ± 20 μm, respectively. The median [ranges] NIH(EV) by histology and OCT was 0.07 [0.04-0.20] and 0.03 [0.01-0.08] mm(2), while the mean (±SD) NIH(BV) by histology and OCT was 0.13 ± 0.07 and 0.10 ± 0.06 mm(2). Our study indicates that in vivo OCT of the BVS provides correlated measurements of the same order of magnitude as histomorphometry, and is reproducible for the evaluation of certain vascular and device-related characteristics. However, histology systematically gives larger values for all the measured structures compared to OCT, at 2 years post implantation.

Topics: Absorbable Implants; Angioplasty, Balloon, Coronary; Animals; Cardiovascular Agents; Coronary Vessels; Everolimus; Feasibility Studies; Hyperplasia; Models, Animal; Neointima; Pilot Projects; Sirolimus; Swine; Swine, Miniature; Time Factors; Tissue Scaffolds; Tomography, Optical Coherence

Previous optical coherence tomography (OCT) studies in patients with drug-eluting stents (DESs)-related very late stent thrombosis (VLST) were scarce. Therefore, we investigated OCT findings of VLST after implantation of DESs. Using OCT, we analyzed the status of stent struts and neointimal characteristics in 18 patients who developed VLST after DES implantation. These results were compared to those in 57 patients with neointimal hyperplasia causing >40% diameter stenosis. Lipid-laden neointima was defined as a region with marked signal attenuation and a diffuse border. Four (22.2%) of 18 patients with VLST had ruptured and lipid-laden neointima inside DESs without uncovered or malapposed stent struts. In the remaining 14 patients who developed VLST without neointimal rupture, uncovered and malapposed struts were observed in nine and seven patients, respectively, and lipid-laden neointima in four patients. Lipid-laden neointima was more frequently observed in four patients with neointimal rupture than in 14 patients without neointimal rupture (100% vs. 28.6%, respectively, P = 0.023). Of 57 patients with neointimal hyperplasia, eight (14.0%) had lipid-laden neointima. Time to OCT study after DES implantation was significantly longer in the eight patients with lipid-laden neointima than in 49 patients without lipid-laden neointima (45.5 ± 17.7 months vs. 11.7 ± 7.2 months, respectively, P < 0.001). Lipid-laden neointima was detected in some patients with neointimal hyperplasia > 1 year after DES implantation. In addition to uncovered or malapposed struts, rupture of lipid-laden neointima inside DESs was identified in some patients with DES-related VLST.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Lipid Metabolism; Male; Middle Aged; Neointima; Paclitaxel; Predictive Value of Tests; Prosthesis Design; Republic of Korea; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The time course of complete arterial healing after drug eluting stent implantation is unknown. We present a case of incomplete endothelialization and late stent malapposition identified by optical coherence tomography 8 years after a sirolimus-eluting stent implantation, which was not related with any adverse clinical event.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Humans; Male; Neointima; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

The Resolute zotarolimus-eluting stent (ZES-R) has a thinner stent strut with biocompatible polymer than first generation drug-eluting stents. However, minimal optical coherence tomography (OCT) data exists about vascular responses after ZES-R implantation. This study investigated OCT findings in ZES-R implantation and compared them to those in sirolimus-eluting stent (SES) implantation. A total of 123 lesions (43 ZES-R and 80 SES) in 111 patients were evaluated with OCT at 9 months after stent implantation. Strut apposition, neointimal hyperplasia (NIH) thickness, and stent coverage on each stent strut were evaluated. Mean NIH thickness was significantly greater in ZES-R-treated lesions than in SES-treated lesions (166 ± 73 μm vs. 96 ± 63 μm, respectively, P < 0.001). The percentage of uncovered strut was significantly lower in ZES-R-treated lesions than in SES-treated lesions (4.4 ± 4.8% vs. 10.3 ± 13.2%, respectively, P = 0.05). The percentage of malapposed struts was also significantly lower in ZES-R-treated than in SES-treated lesions (0.1 ± 0.4% vs. 1.5 ± 4.2%, respectively, P = 0.002). Intracoronary thrombus was less frequently detected in ZES-R-treated lesions (4.7% vs. 30.0%, respectively, P = 0.001). ZES-R showed a lower incidence of uncovered or malapposed stent struts and intracoronary thrombus than SES at 9-month follow-up OCT examination. Compared with SES, ZES-R may elicit more favorable vascular responses at the expense of an increased neointimal proliferation.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Registries; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

This study aimed to compare the neointimal coverage (NIC), subclinical thrombus, color of plaque underneath the stent at 9-month after implantation of sirolimus-eluting stent (SES) either with durable or with biodegradable polymer (BDPM).. A total of 175 patients were assigned as Cypher (n = 81, 97 stents with durable polymer) and Excel (n = 94, 112 stents with BDPM) stent at 9-month after indexed procedure. NIC was classified from grade 0-3. Color of plaque was divided into white, light-yellow, yellow, and dark yellow. Thrombus was diagnosed as white or red material with cotton-like or ragged appearance. Incomplete NIC (grade 0/1) circled by a blush was termed by "inflaming.". There were significant differences in unstable angina (90.5 vs. 52.4%, P = 0.015), previous myocardial infarction (33.3 vs. 4.0%, P = 0.045) and left ventricular eject fraction (55.2 ± 7.8 vs. 62.6 ± 6.3%, P = 0.021) between the Excel and Cypher groups. The minimal- and maximal-NIC grades in the Cypher group were 0.67 ± 0.58 and 2.29 ± 0.46, respectively, when compared with 1.45 ± 0.67 (P < 0.001) and 2.64 ± 0.49 (P = 0.023) in the Excel group. The percentage of yellow plaque, thrombus, "inflaming" and NIC grade of 0 in the Excel and Cypher groups, respectively, were as follows: 8.0 vs. 26.8% (P = 0.031), 9.8 vs. 32.9% (P = 0.024), 8.0 vs. 38.1% (P = 0.017), and 38.1 vs. 0% (P < 0.001). Of the stents with "inflaming," 63.6% had thrombus when compared with 20.1% of the non-erosion stents (P < 0.001). Overlapping segments had the lowest NIC grades and more "inflaming" demonstrating a significant difference between Cypher vs. Excel stents. NIC grade was positively correlated with thrombus.. SES with BDPM has improved NIC resulting in less yellow plaque, thrombus, and "inflaming." Overlapping segments had the lowest NIC grade and more "inflaming."

Topics: Absorbable Implants; Aged; Angioscopy; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Polymers; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Treatment Outcome

Topics: Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Neointima; Percutaneous Coronary Intervention; Sirolimus; Tomography, Optical Coherence

To evaluate the effect of a polymer-free Biolimus A9-eluting stent [BioFreedom (BF)], compared with that of a biodegradable polymer-based Biolimus A9-eluting stent [BioMatrix Flex (BMF)] and a bare metal stent (BMS) in balloon denuded and radiated hypercholesterolemic rabbit iliac arteries.. Rabbits were fed with 1% cholesterol diet (n = 14) for 14 days, both iliac arteries were balloon denuded and radiated, and then rabbits were switched to 0.15% cholesterol diet. After 4 weeks, BF (n = 8), BMF (n = 8), and BMS (n = 8) were deployed in denuded and radiated areas. Four weeks later animals were euthanized, arterial segments were processed for morphometry.. The neointimal area in vessels implanted with BF stents was significantly less than that seen in vessels implanted with BMS (0.90 mm(2) ± 0.14 vs. 1.29 mm(2) ± 0.23, P <0.01). Percent fibrin and fibrin score were higher with BMF stents compared to BMS (P <0.03 and <0.04) and giant cell number was significantly higher with both BMF and BF stents (P < 0.01 for both). Percent endothelialization was significantly higher and % uncovered struts were lower with BMS compared to either BMF or BF stents (P < 0.05 for both).. This study demonstrates that compared to BMS, BF stents significantly decreased neointimal hyperplasia.

Topics: Absorbable Implants; Angioplasty, Balloon; Animals; Atherosclerosis; Cardiovascular Agents; Constriction, Pathologic; Disease Models, Animal; Drug-Eluting Stents; Fibrin; Hypercholesterolemia; Hyperplasia; Iliac Artery; Inflammation; Male; Metals; Neointima; Plaque, Atherosclerotic; Polymers; Prosthesis Design; Rabbits; Sirolimus; Stents; Time Factors

The authors investigate whether the combination of anti-CD34 antibody with DES is win-win cooperation.. DES may reduce the risk of restenosis compared to bare-metal stents (BMS), but they were found to inhibit the healing process of intima.. Fifteen BMS, 17 DES, and 16 combined anti-CD34 antibody and DES were randomly implanted in the coronary arteries of 22 minipigs. Ten minipigs were followed up to 2 weeks. The stenting coronary segments were examined by histological examination and scanning electron microscopy after in vivo coronary angiography and intracoronary optical coherence tomography (OCT) examinations. The other 12 minipigs were followed up to 3 months. Coronary angiography and intracoronary OCT examination were performed in vivo and histological examination was performed on the stenting coronary segments.. After 2 weeks, the neointimal covering level of the DES was lower than that in BMS, but the covering level of the combined stents was even better than the BMS. After 3 months, neointimal hyperplasia was significant in the BMS, but not in the other two types of stents. The in-stent late lumen loss of the combined stents even showed a decreasing tendency when compared with the DES.. The combination of anti-CD34 antibody and DES can not only well offset the short-term inhibitory effect on re-endothelialization but also slightly enhance the long-term antiproliferative effect.

Topics: Angioplasty, Balloon, Coronary; Animals; Antibodies; Antigens, CD34; Cardiovascular Agents; Cell Proliferation; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Hyperplasia; Metals; Microscopy, Electron, Scanning; Neointima; Prosthesis Design; Sirolimus; Stents; Swine; Swine, Miniature; Time Factors; Tomography, Optical Coherence

Arterialized vein grafts often fail due to intimal hyperplasia. Hydrogen potently protects organs and cells from many insults via its anti-inflammatory and antioxidant properties. We investigated the efficacy of oral administration of hydrogen-rich water (HW) for prevention of intimal hyperplasia.. The inferior vena cava was excised, stored in cold Ringer solution for 2 h, and placed as an interposition graft in the abdominal aorta of syngeneic Lewis rats. HW was generated by immersing a magnesium stick in tap water (Mg + 2H(2)O → Mg (OH)(2) + H(2)). Beginning on the day of graft implantation, recipients were given tap water [regular water (RW)], HW or HW that had been subsequently degassed water (DW). Six weeks after grafting, the grafts in the rats given RW or DW had developed intimal hyperplasia, accompanied by increased oxidative injury. HW significantly suppressed intimal hyperplasia. One week after grafting, the grafts in HW-treated rats exhibited improved endothelial integrity with less platelet and white blood cell aggregation. Up-regulation of the mRNAs for intracellular adhesion molecules was attenuated in the vein grafts of the rats receiving HW. Activation of p38 mitogen-activated protein kinase, matrix metalloproteinase (MMP)-2, and MMP-9 was also significantly inhibited in grafts receiving HW. In rat smooth muscle cell (A7r5) cultures, hydrogen treatment for 24 h reduced smooth muscle cell migration.. Drinking HW significantly reduced neointima formation after vein grafting in rats. Drinking HW may have therapeutic value as a novel therapy for intimal hyperplasia and could easily be incorporated into daily life.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Antioxidants; Aorta, Abdominal; Cardiovascular Agents; Cell Movement; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Drinking; Endothelial Cells; Enzyme Activation; Humans; Hydrogen; Hyperplasia; Interleukin-6; Macrophages; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neointima; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Rats; Rats, Inbred Lew; Time Factors; Transplantation, Isogeneic; Tumor Necrosis Factor-alpha; Tunica Intima; Vascular Grafting; Vena Cava, Inferior

Dedifferentiation, migration, and proliferation of resident vascular smooth muscle cells (SMCs) are key components of neointima formation after vascular injury. Activation of signal transducer and activator of transcription-3 (STAT3) is suggested to be critically involved in this process, but the complex regulation of STAT3-dependent genes and the functional significance of inhibiting this pathway during the development of vascular proliferative diseases remain elusive. In this study, we demonstrate that STAT3 was activated in neointimal lesions following wire-induced injury in mice. Phosphorylation of STAT3 induced trans-activation of cyclin D1 and survivin in SMCs in vitro and in neointimal cells in vivo, thus promoting proliferation and migration of SMCs as well as reducing apoptotic cell death. WP1066, a highly potent inhibitor of STAT3 signaling, abrogated phosphorylation of STAT3 and dose-dependently inhibited the functional effects of activated STAT3 in stimulated SMCs. The local application of WP1066 via a thermosensitive pluronic F-127 gel around the dilated arteries significantly inhibited proliferation of neointimal cells and decreased the neointimal lesion size at 3 weeks after injury. Even though WP1066 application attenuated the injury-induced up-regulation of the chemokine RANTES at 6 h after injury, there was no significant effect on the accumulation of circulating cells at 1 week after injury. In conclusion, these data identify STAT3 as a key molecule for the proliferative response of SMC and neointima formation. Moreover, inhibition of STAT3 by the potent and specific compound WP1066 might represent a novel and attractive approach for the local treatment of vascular proliferative diseases.

Topics: Animals; Apoptosis; Binding Sites; Cardiovascular Agents; Cell Movement; Cell Proliferation; Cells, Cultured; Chemokine CCL5; Cyclin D1; Disease Models, Animal; Humans; Inhibitor of Apoptosis Proteins; Male; Mice; Mice, Inbred C57BL; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neointima; Phosphorylation; Promoter Regions, Genetic; Pyridines; Repressor Proteins; STAT3 Transcription Factor; Survivin; Time Factors; Tyrphostins

The neointimal tissue characteristics inside sirolimus-eluting stent (SES) were evaluated by optical coherence tomography (OCT) according to follow-up duration. One hundred and thirty-three Optical coherence tomography was performed in 96 patients with 143 SES which were retrospectively included and divided into 2 groups according to follow-up duration: Group 1, <24 months (98 stents in 71 patients); Group 2, >24 months (35 stents in 25 patients). The neointimal tissue coverage pattern and characteristics were studied using a new OCT analysis system which can quantitatively analyze tissue property by measuring attenuation, backscatter and signal intensity in the region of interest. Using these parameters, a multivariable logistic regression model was constructed to divide neointima into homogenous or heterogeneous type. We defined homogeneous nointima as neointimal tissue having uniform optical properties and does not showing focal variations in backscattering pattern and heterogeneous neointima as neointimal tissue with focally changing optical properties and showing various backscattering patterns. The average time between stent implantation and follow-up OCT imaging was 1.2 years in Group 1 and 3.2 years in Group 2. The number of neointima covered cross-sections, neointimal thickness, and neointimal area increased significantly with the length of follow-up duration after SES implantation (P < 0.01). The incidence of heterogeneous neointima was higher in Group 2 than in Group 1 (P < 0.01). Heterogeneous neointima was associated with higher incidence of microvessels (P = 0.0023) and lipid rich plaque (P = 0.0015) compared with homogeneous neointima. The neointimal tissue characteristics may change over time after SES implantation. The incidence of heterogeneous pattern was higher in the SES group with longer follow-up duration. Microvessels and lipid rich plaques were more frequently observed in neointima with heterogeneous pattern. Neointimal heterogeneity could be an important factor for the late stability of SES.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Image Interpretation, Computer-Assisted; Logistic Models; Male; Microvessels; Middle Aged; Multivariate Analysis; Neointima; Odds Ratio; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Predictive Value of Tests; Prosthesis Design; Retrospective Studies; Sirolimus; Software; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Clinical trials have consistently demonstrated benefits of paclitaxel-coated balloons (PCB) in particular clinical situations such as in-stent restenosis and peripheral vascular interventions. However, the long-term vascular effects of bare metal stents (BMS) delivered via PCB (PCB+BMS) are still unknown. The aim of this study was to assess the long-term effects of PCB+BMS on vascular healing and neointimal formation (NF).. A total of 208 stents: 56 BMS crimped on PCB, 50 BMS crimped on uncoated balloons (UCB+BMS), 52 Taxus and 50 Cypher stents were implanted in normal coronary arteries of 104 pigs using 1.2:1.0 stent-to-artery ratio. Follow-up occurred at 3, 7, 28, 90, and 180 days. Vascular effects were assessed based on angiographic and histological analysis. Endothelialization was evaluated using an anti von-Willebrand Factor stain.. At 28 days, delivery of a BMS using a PCB led to a significant reduction in NF compared to the UCB+BMS and the Taxus stent (P < 0.01). Between 28 and 180 days, the progression of NF tended to be lower in the PCB+BMS compared to all DES groups. At 90 days, the PCB+BMS (2.56 ± 0.43) and the Taxus stents (2.60 ± 0.59) had a trend toward higher inflammatory scores compared to the UCB+BMS group (1.85 ± 1.13, P = 0.09). By 180 days, inflammation and NF had completely normalized between the groups. Expression of peristrut vWF was comparable among all tested groups at 28 days.. The long-term pattern of vascular healing occurring following PCB+BMS deployment appears to be comparable to what has been reported with DES technologies.

Topics: Angioplasty, Balloon, Coronary; Animals; Cardiac Catheters; Cardiovascular Agents; Cell Proliferation; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Drug-Eluting Stents; Endothelial Cells; Equipment Design; Metals; Neointima; Paclitaxel; Prosthesis Design; Stents; Swine; Swine, Miniature; Time Factors; von Willebrand Factor

The goal of this study was to describe the neointimal healing on the abluminal side (ABL) of malapposed (ISA) struts and nonapposed side-branch (NASB) struts in terms of coverage by optical coherence tomography (OCT) and in comparison with the adluminal side (ADL).. The neointimal healing on the ABL of ISA and NASB struts has never to our knowledge been explored in vivo and could be involved in the correction of acute malapposition. The bioresorbable vascular scaffold (BVS) is made of a translucent polymer that enables imaging of the ABL with OCT.. Patients enrolled in the ABSORB B (ABSORB Clinical Investigation Cohort B) study were treated with implantation of a BVS and imaged with OCT at 6 months. Thickness of coverage on the ADL and ABL of ISA and NASB struts was measured by OCT.. Twenty-eight patients were analyzed; 114 (2.4%) struts were malapposed or at side branches. In 76 ISA struts (89.4%) and 29 NASB struts (100%), the thickness of ABL coverage was >30 μm. Coverage was thicker on the ABL than on the ADL side (101 vs. 71 μm; 95% confidence interval [CI] of the difference: 20 to 40 μm). In 70 struts (60.7%, 95% CI: 50.6% to 70.0%), the neointimal coverage was thicker on the ABL, versus only 20 struts (18.5%, 95% CI: 11.6% to 28.1%) with thicker neointimal coverage on the ADL side (odds ratio: 3.35, 95% CI: 2.22 to 5.07).. Most of the malapposed and side-branch struts are covered on the ABL side 6 months after BVS implantation, with thicker neointimal coverage than on the ADL side. The physiological correction of acute malapposition involves neointimal growth from the strut to the vessel wall or bidirectional. (ABSORB Clinical Investigation, Cohort B [ABSORB B]; NCT00856856).

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Australia; Cardiovascular Agents; Cell Proliferation; Coated Materials, Biocompatible; Coronary Artery Disease; Coronary Vessels; Europe; Everolimus; Female; Humans; Lactic Acid; Male; Middle Aged; Neointima; New Zealand; Polyesters; Polymers; Predictive Value of Tests; Prosthesis Design; Registries; Sirolimus; Time Factors; Tissue Scaffolds; Tomography, Optical Coherence; Treatment Outcome

Biodegradable stent coatings were recently introduced as a potential solution to overcome sustained inflammatory responses observed with permanent polymer-based drug-eluting stents. In a preliminary study, selected biodegradable or permanent polymer-based sirolimus-eluting stent (SES) formulations were screened for effectiveness in comparison to bare metal stents (BMS) at 28 days. Subsequently, the most favourable SES formulation was compared to commercially available SES (Cypher™) at 28, 90 and 180 days to investigate the histopathologic response as well as tissue, blood and organ pharmacokinetics. Overlapping SES implantation was conducted to evaluate vascular healing at 28 days in this particular setting. SES with biodegradable poly (L-lactide) polymer (PLLA) or poly(lactide-co-glycolide) showed the most favourable outcome with regards to reductions in neointimal area in comparison to BMS at 28 days. The PLLA SES showed a similar reduction in neointimal area compared to Cypher™ at 28 days, with significant greater reductions at 90 and 180 days (1.7 ± 0.7 mm² vs. 3.1 ± 1.5 mm², p=0.03 and 1.8 ± 1.2 mm² vs. 3.0 ± 1.5 mm², p=0.01, respectively). Sirolimus vascular tissue concentrations were detectable up to 90 days following implantation. Overlapping stented segments showed favourable histopathologic results with respect to fibrin deposition and endothelialisation at 28 days. In conclusion, the use of PLLA as drug-eluting matrix resulted in mild inflammatory responses in the presence of effective sirolimus tissue concentrations. The greater efficacy observed at long-term follow-up in PLLA SES compared to Cypher™ may be a multifactorial result of stent design, polymer biocompatibility and improved release kinetics.

Topics: Absorbable Implants; Angioplasty, Balloon, Coronary; Animals; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Lactic Acid; Models, Animal; Neointima; Polyesters; Polyglactin 910; Polymers; Prosthesis Design; Sirolimus; Sus scrofa; Time Factors; Tissue Distribution

Revascularization procedures used for treatment of atherosclerosis often result in restenosis. Resveratrol (RSV), an antioxidant with cardiovascular benefits, decreases neointimal formation after arterial injury by a mechanism that is still not fully clarified. Our main objective was to address the role of nitric oxide synthases (NOSes) and more specifically the endothelial-NOS (eNOS) isoform as a mediator of this effect. RSV (4 mg/kg/day, s.c.) alone or in combination with the NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME) (2 mg/kg/day, s.c.) was given to Sprague-Dawley rats beginning at 3 days before arterial (carotid or aortic) injury. RSV reduced neointimal formation by 50% (P<0.01), decreased intimal cell proliferation by 37% (P<0.01) and reduced inflammatory markers such as PECAM and MMP-9 mRNA. These effects of RSV were all abolished by coadministration of l-NAME. Oral RSV (beginning at 5 days before arterial injury) reduced neointimal thickness after femoral wire injury in mice, however this effect was not observed in eNOS knockout mice. This is the first report of RSV decreasing neointimal cell proliferation and neointimal growth through an eNOS-dependent mechanism.

Topics: Administration, Oral; Animals; Aorta; Cardiovascular Agents; Carotid Arteries; Carotid Artery Injuries; Cell Proliferation; Disease Models, Animal; Enzyme Inhibitors; Femoral Artery; Gene Expression Regulation; Male; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Mice, Knockout; Neointima; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase Type III; Platelet Endothelial Cell Adhesion Molecule-1; Rats; Rats, Sprague-Dawley; Resveratrol; RNA, Messenger; Stilbenes; Time Factors; Vascular System Injuries

The purpose of this study was to investigate the elimination of paclitaxel from the arterial wall after a single short administration with a coated balloon.. Slightly oversized paclitaxel-coated balloons (dose 3 or 9 μg/mm(2)) without or with premounted stents were inflated in nonatherosclerotic coronary arteries of either young domestic pigs or adult Goettingen minipigs. The paclitaxel content of plasma, arterial segments, and residual hearts (without treated arteries) was measured for up to 180 days using high-performance liquid chromatography/ultraviolet detection or mass spectrometry. Angiograms were evaluated for lumen narrowing. The paclitaxel concentration in plasma remained <10 ng/mL. In arteries of domestic pigs and minipigs treated with paclitaxel-coated balloons with premounted stents, 10%±5% or 21%±8% of dose, respectively, was initially detected and decreased to 3.5%±3.1% of dose (domestic pig) by Day 7. Within 6 months it fell with a half-life of 1.9 months to 0.40%±0.35%. After 3 months the concentration in the arterial wall was 17±11 μmol/L. Without a stent, drug transfer to the vessel wall was somewhat reduced and elimination faster. Immediately after treatment up to 26%±4% of dose was detected in the residual whole hearts. It dropped with a half-life of 45 days to 1.5%±0.6% of dose (0.3 μmol/L) within 6 months.. After a single local administration with coated balloons, paclitaxel stays in the vessel wall of pigs long enough to explain persistent inhibition of neointimal proliferation. The pharmacokinetics of paclitaxel does, however, not exclude other reasons for sustained efficacy such as early blocking of processes initiating excessive and prolonged neointimal proliferation.

Topics: Angioplasty, Balloon, Coronary; Animals; Cardiovascular Agents; Catheters; Chromatography, High Pressure Liquid; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Half-Life; Mass Spectrometry; Myocardium; Neointima; Paclitaxel; Spectrophotometry, Ultraviolet; Stents; Sus scrofa; Swine; Swine, Miniature; Tissue Distribution

Delayed endothelialization contributes to stent thrombosis of current drug-eluting stents. The asymmetrical coating technique provides an anti-proliferative effect abluminally without affecting luminal endothelialization. Layer-by-layer self-assembled chitosan/heparin (C/H LBL) has been proved to promote re-endothelialization. A novel stent system, C/H LBL coated luminally and sirolimus released abluminally (C/H LBL-SES), was fabricated.. Bare metal stents (BMS), traditionally circumferential sirolimus-eluting stents (SES), and C/H LBL-SES were implanted into porcine coronary arteries. At the 7, 14 and 28 days follow-up (FU), angiography, intravascular ultrasound (IVUS), vasomotor function induced by acetylcholine (Ach), scanning-electron microscopy and histopathology were performed. Remodeling index (RI) was based on IVUS and defined as cross-sectional area (CSA) of vessel at in-stent segment divided by CSA of reference vessel and expressed as a percentage with a normal range from 0.95 to 1.05.. Thirty-eight mini pigs were enrolled and 74 stents (BMS = 23, C/H LBL = 28, SES = 23) were implanted in this study. At 28 days after implantation, the diameter stenosis of C/H LBL-SES by quantitative coronary angiography was 18.8 ± 2.5 %, the area stenosis by histomorphometry was 24.2 ± 2.9 %, which were comparable to that of SES and superior to BMS. At 14 days, re-endothelialization of C/H LBL-SES was almost completed, while only about 50 % of surface of SES was covered by endothelium. At 7, 14 and 28 days FU, although C/H LBL-SES suffered a greater vasoconstriction induced by Ach infusion than BMS (P < 0.05), it behaved better than SES (P < 0.01). No sign of stent malapposition was detected, while RI was within the normal range by IVUS. No acute or subacute thrombotic events occurred in all three groups.. The asymmetrically designed C/H LBL-SES successfully inhibited neointima hyperplasia, while diminishing vasoconstriction after Ach-stress. Endothelialization of C/H LBL-SES was less affected compared with traditionally circumferentially coated SES.

Topics: Acetylcholine; Animals; Cardiovascular Agents; Chitosan; Coated Materials, Biocompatible; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Drug-Eluting Stents; Endothelial Cells; Heparin; Hyperplasia; Metals; Microscopy, Electron, Scanning; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Swine; Swine, Miniature; Time Factors; Ultrasonography, Interventional; Vasoconstriction

Diabetes remains a significant risk factor for restenosis/thrombosis following stenting. Although vascular healing responses following drug-eluting stent (DES) treatment have been characterized previously in healthy animals, comparative assessments of different DES in a large animal model with isolated features of diabetes remains limited. We aimed to comparatively assess the vascular response to paclitaxel-eluting (PES) and everolimus-eluting (EES) stents in a porcine coronary model of streptozotocin (STZ)-induced type I diabetes.. Twelve Yucatan swine were induced hyperglycemic with a single STZ dose intravenously to ablate pancreatic β-cells. After two months, each animal received one XIENCE V® (EES) and one Taxus Liberte (PES) stent, respectively, in each coronary artery. After three months, vascular healing was assessed by angiography and histomorphometry. Comparative in vitro effects of everolimus and paclitaxel (10-5 M-10-12 M) after 24 hours on carotid endothelial (EC) and smooth muscle (SMC) cell viability under hyperglycemic (42 mM) conditions were assayed by ELISA. Caspase-3 fluorescent assay was used to quantify caspase-3 activity of EC treated with everolimus or paclitaxel (10-5 M, 10-7 M) for 24 hours.. After 3 months, EES reduced neointimal area (1.60 ± 0.41 mm, p < 0.001) with trends toward reduced % diameter stenosis (11.2 ± 9.8%, p = 0.12) and angiographic late-loss (0.28 ± 0.30 mm, p = 0.058) compared to PES (neointimal area: 2.74 ± 0.58 mm, % diameter stenosis: 19.3 ± 14.7%, late loss: 0.55 ± 0.53 mm). Histopathology revealed increased inflammation scores (0.54 ± 0.21 vs. 0.08 ± 0.05), greater medial necrosis grade (0.52 ± 0.26 vs. 0.0 ± 0.0), and persistently elevated fibrin scores (1.60 ± 0.60 vs. 0.63 ± 0.41) with PES compared to EES (p < 0.05). In vitro, paclitaxel significantly increased (p < 0.05) EC/SMC apoptosis/necrosis at high concentrations (≥ 10-7 M), while everolimus did not affect EC/SMC apoptosis/necrosis within the dose range tested. In ECs, paclitaxel (10-5 M) significantly increased caspase-3 activity (p < 0.05) while everolimus had no effect.. After 3 months, both DES exhibited signs of delayed healing in a STZ-induced diabetic swine model. PES exhibited greater neointimal area, increased inflammation, greater medial necrosis, and persistent fibrin compared to EES. Differential effects of everolimus and paclitaxel on vascular cell viability may potentially be a factor in regulating delayed healing observed with PES. Further investigation of molecular mechanisms may aid future development of stent-based therapies in treating coronary artery disease in diabetic patients.

Topics: Animals; Apoptosis; Cardiovascular Agents; Cells, Cultured; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Disease Models, Animal; Dose-Response Relationship, Drug; Drug-Eluting Stents; Endothelial Cells; Everolimus; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Necrosis; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Swine; Time Factors; Wound Healing

The A(2B) adenosine receptor (A(2B)R) is highly expressed in macrophages and vascular smooth muscle cells and has been established as an important regulator of inflammation and vascular adhesion. Recently, it has been demonstrated that A(2B)R deficiency enhances neointimal lesion formation after vascular injury. Therefore, we hypothesize that A(2B)R agonism protects against injury-induced intimal hyperplasia.. Apolipoprotein E-deficient mice were fed a Western-type diet for 1 week, after which the left common carotid artery was denuded. Mice were treated with the A(2B) receptor agonist BAY60-6583 or vehicle control for 18 days. Interestingly, lumen stenosis as defined by the neointima/lumen ratio was inhibited by treatment with the A(2B) receptor agonist, caused by reduced smooth muscle cell proliferation. Collagen content was significantly increased in the BAY60-6583-treated mice, whereas macrophage content remained unchanged. In vitro, vascular smooth muscle cell proliferation decreased dose dependently whereas collagen content of cultured smooth muscle cells was increased by BAY60-6583.. Our data show that activation of the adenosine A(2B) receptor protects against vascular injury, while it also enhances plaque stability as indicated by increased collagen content. These outcomes thus point to A(2B) receptor agonism as a new therapeutic approach in the prevention of restenosis.

Topics: Adenosine A2 Receptor Agonists; Aminopyridines; Animals; Apolipoproteins E; Cardiovascular Agents; Carotid Artery Injuries; Carotid Artery, Common; Carotid Stenosis; Cell Adhesion; Cell Proliferation; CHO Cells; Collagen; Cricetinae; Cricetulus; Dietary Fats; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; HEK293 Cells; Humans; Mice; Mice, Knockout; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neointima; Neutrophil Activation; Neutrophils; Platelet Activation; Receptor, Adenosine A2B; Time Factors; Transfection

High mobility group box 1 protein (HMGB1) is expressed in atherosclerotic lesions. However, its role in vascular system is unknown. In this study, we explore whether the inhibition of HMGB1 attenuates neointimal formation in animal models.. Experiments were performed with VSMCs from thoracic aorta of SD rats in vitro, and a rat carotid artery balloon injury model in vivo. HMGB1 levels were increased after stimulation of angiotensin II (Ang II) and 10% serum in cultured VSMCs. HMGB1 inhibitor (glycyrrhizin) significantly inhibited the proliferation and migration of Ang II-treated VSMCs, which was accompanied with decreased oxidative stress and inflammation. The underlying mechanisms were related with the promotion of antioxidant systems activity and deactivation of p38 MAPK/NF-κB signaling pathway, respectively. Furthermore, inhibition of HMGB1 blunted Notch signaling pathway during VSMCs phenotypic transition, and correspondingly restored VSMCs differentiated phenotype under 10% serum stimulation. In vivo study, HMGB1 expression was elevated after artery injury. Meanwhile, glycyrrhizin treatment suppressed HMGB1 expression, which was accompanied with blunted inflammation and oxidative stress after 7 days of balloon injury. Moreover, the area of neointimal to media area ratio was significantly decreased in glycyrrhizin group compared with injury group at 14 days after balloon injury.. Inhibition of HMGB1 activity attenuated VSMCs activation and neointimal formation after carotid injury. Therefore, blockage of HMGB1 might represent a novel therapeutic strategy for vascular injury.

Topics: Angiotensin II; Animals; Anti-Inflammatory Agents; Antioxidants; Cardiovascular Agents; Carotid Arteries; Carotid Artery Injuries; Cell Differentiation; Cell Movement; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Glycyrrhizic Acid; HMGB1 Protein; Hyperplasia; Inflammation Mediators; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neointima; NF-kappa B; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Phenotype; Rats; Rats, Sprague-Dawley; Receptors, Notch; Signal Transduction; Time Factors

Topics: Angina, Unstable; Cardiovascular Agents; Coronary Angiography; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Humans; Hyperplasia; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Thrombectomy; Time Factors; Tomography, Optical Coherence; Treatment Outcome

We aimed to assess the influence of different sirolimus analogues released from a uniform stent platform on re-endothelialisation and vascular healing responses.. Bare metal stents (BMS) were coated with a fluoropolymer containing everolimus (EES), sirolimus (SES) or zotarolimus (ZES) to generate drug-eluting stents (DES) with identical stent backbones, drug loads and release kinetics. DES constructs and control BMS were implanted into the iliac arteries of rabbits and were analysed at 14 days by scanning electron microscopy (SEM) and confocal microscopy for en face evaluation of endothelialisation (n=6 for each stent), or at 28 days to determine histomorphometric characteristics (n=11 for each stent). SEM analysis revealed low degrees of strut re-endothelialisation within the DES without differences among groups, while the BMS control showed almost complete endothelialisation. Percent stenosis was significantly reduced in all DES compared to BMS. Strut-based fibrin analysis revealed significantly greater deposition in the DES compared to BMS, with EES showing maximum fibrin deposition among the DES groups.. Sirolimus and its derivatives have similar effects on endothelial regrowth and neointimal thickening. The observation of greatest fibrin deposition in the experimental EES group indicates that everolimus may affect vascular healing differently.

Topics: Angioplasty, Balloon; Animals; Biomarkers; Cardiovascular Agents; Drug-Eluting Stents; Endothelial Cells; Everolimus; Fibrin; Iliac Artery; Immunohistochemistry; Male; Metals; Microscopy, Confocal; Microscopy, Electron, Scanning; Models, Animal; Neointima; Platelet Endothelial Cell Adhesion Molecule-1; Prosthesis Design; Rabbits; Sirolimus; Time Factors; Wound Healing

The study evaluated serial quantitative and qualitative changes in vascular responses to drug-eluting stents (DES) using optical coherence tomography (OCT).. Serial changes in stent strut coverage and neointima characteristics in DES-treated lesions have not been sufficiently investigated using OCT.. Serial OCT was performed in 72 patients with 76 DES-treated lesions at 9 months and 2 years after DES implantation (sirolimus-eluting stent, n = 23; paclitaxel-eluting stent, n = 20; zotarolimus-eluting stent, n = 25; everolimus-eluting stent, n = 8). Serial changes in quantitative parameters (neointimal thickness, stent strut coverage, and apposition at each strut) and qualitative characteristics of the neointima were evaluated.. Mean neointimal thickness significantly increased from 164 μm to 214 μm between 9 months and 2 years (p < 0.001), and the percentage of uncovered stent struts significantly decreased (from 4.4% to 2.3%, p < 0.001). Completely covered lesions were more frequently observed at 2 years (44.7% vs. 59.2%, p = 0.07). However, the percentage of malapposed struts (0.6% vs. 0.9%, p = 0.24) and incidence of intracoronary thrombi (10.5% vs. 9.2%, p > 0.99) were similar. On qualitative evaluation of neointimal morphology, lipid-laden neointima (27.6% vs. 14.5%, p = 0.009) and thin-cap neoatheroma (13.2% vs. 3.9%, p = 0.07) were more frequently detected at 2-year follow-up compared with 9 months. In matched cross-sectional evaluation, the change of neointimal morphology from homogeneous to heterogeneous or lipid-laden pattern was observed in 23 (30.3%) of 76 lesions. There was a significant increase in percent neointimal hyperplasia cross-sectional area in those lesions.. This OCT study suggested that neointimal coverage improved from 9 months to 2 years without significant changes in the incidence of malapposed struts and intracoronary thrombus. Additionally, in-stent neoatherosclerosis including transformation to lipid-laden neointima might progress during extended follow-up periods after DES implantation.

Topics: Aged; Cardiovascular Agents; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Registries; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome