Purpose. The primary objective was to compare primary and secondary patency, number of percutaneous transluminal angioplasty (PTA) interventions and cost-effectiveness among PTA, deployment of a stent, or a stent graft in the treatment of failing arteriovenous dialysis grafts. The secondary objective was to compare the residual diameter at the site of dialysis shunt stenosis using sonography and digital subtraction angiography (DSA). Methods. Sixty patients were randomly assigned to either PTA, placement of a stent or stent graft. Follow-up angiography was scheduled at 3, 6, and 12 months or when requested by the physician. Residual diameter of a dialysis shunt stenosis was measured in 20 patients with significant stenosis by ultrasonography and on an angiogram from DSA. Results. During a median follow-up of 22.4 months patients with PTA, stent, or stent graft required 3.1±1.7, 2.5±1.7, or 1.7±2.1 (P=0.031) secondary PTA interventions. The primary patency rates were 0%, 18%, and 65% at 12 months and 0%, 18%, and 37% at 24 months in the PTA, stent, and stent graft group respectively (P<0.0001). The cost of the procedures was €7,900±€3,300 in PTA group, €8,500±€4,500 in stent group, and €7,500±€6,200 in stent graft group (P=0.45). The mean residual diameter measured by ultrasonography and DSA was...

Introduction: Bivalirudin and heparin are the two most commonly used anticoagulants used during Percutaneous Coronary Intervention (PCI). The results of Randomized Controlled Trials (RCTs) comparing bivalirudin versus heparin monotherapy in the era of radial access are controversial, questioning the positive impact of bivalirudin on bleeding. The purpose of this systematic review is to summarize the results of RCTs comparing the efficacy and safety of bivalirudin versus heparin with or without Glycoprotein IIb/IIIa Inhibitors (GPI). Methods: This systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA statements for reporting systematic reviews. We searched the National Library of Medicine PubMed, Clinicaltrial.gov and the Cochrane Central Register of Controlled Trials to include clinical studies comparing bivalirudin with heparin in patients undergoing PCI. Sixteen studies met inclusion criteria and were reviewed for the summary. Findings: Several RCTs and meta-analyses have demonstrated the superiority of bivalirudin over heparin plus routine GPI use in terms of preventing bleeding complications but at the expense of increased risk of ischemic complications such as stent thrombosis. The hypothesis of post-PCI bivalirudin infusion to mitigate the risk of acute stent thrombosis has been tested in various RCTs with conflicting results. In comparison, heparin offers the advantage of having a reversible agent, of lower cost and reduced incidence of ischemic complications. Conclusion: Bivalirudin demonstrates its superiority over heparin plus GPI with better clinical outcomes in terms of less bleeding complications, thus making it as anticoagulation of choice particularly in patients at high risk of bleeding. Further studies are warranted for head to head comparison of bivalirudin to heparin monotherapy to establish an optimal heparin dosing regimen and post-PCI bivalirudin infusion to affirm its beneficial effect in reducing acute stent thrombosis.

The purpose of this research is to explore the potential of using carbon-infiltrated carbon nanotubes (CI-CNT) as a material for coronary artery stents. Stents are commonly fabricated from metal, which may not perform as well as many polymers and ceramics in biomedical applications. Pyrolytic carbon, a ceramic, is currently used in medical implant devices due to its preferrable biocompatibility properties. Micro-patterned pyrolytic carbon devices can be created by growing carbon nanotubes, and then filling the space between with amorphous carbon via chemical vapor deposition. We prepared multiple samples of two different planar stent-like flexible geometries and smaller cubic structures out of carbon infiltrated carbon nanotubes. These samples were tested in tension to failure. The cubic structures were used for separate compression tests. We also examined existing auxetic patterns for possible application in the stent designs and a second iteration of design and fabrication was performed using data and understanding obtained from the work in the first iteration. Slight changes were made to the mask design and fabrication processes based on the new geometries and testing considerations. The auxetic planar designs were tested in compression to demonstrate flexibility and collect material data. The testing results show that CI-CNTs can be designed and fabricated into flexible geometries capable of stent-like compression. The samples in this work were found to have moduli ranging from 5 to 27 GPa, with the majority being between 10 and 20 GPa. We also found fracture strength greater than 100 MPa, with it sometimes getting as high as 200 MPa. Lastly, fracture strain values were measured, with the maximum reaching 1.4% and the average between 0.75-1%. We also found that the CI-CNTs material lends itself to fracture at weak locations (if present) before the anticipated fracture strength has been reached and concluded that a tightly controlled process (including fabrication machines) environment is necessary to ensure consistent results and a CI-CNT material whose imperfections have been minimized.

The purpose of this research was to design, develop, and test coronary stent designs composed of carbon-infiltrated carbon nanotubes (CI-CNTs). Coronary stents currently have two major complications: restenosis and thrombosis. CI-CNT stents have potential to address both of these issues, and therefore may provide improved clinical outcomes. CI-CNT stent geometry is patterned using high-resolution photolithography that provide advantages in design possibilities.To develop a coronary stent, a standard design process was followed including: background, design specifications, concept generation, development, analysis, and testing. Background research was first completed and general design specifications for coronary stent performance were compiled. Multiple design concepts were generated, evaluated, and finally a design was selected. This stent design was further developed and optimized using analytical tools along with finite element analysis. This stent design used tapered struts in repeating segments to reduce stress and improve radial force. The design was modeled and analyzed as both a flat geometry as well as in a cylindrical configuration. Mechanics of materials equations and geometry specific finite element analysis were used to guide the final coronary stent design. The stent design was tested mechanically, and additional tests were performed to verify the blood compatibility of the CI-CNT material. The flat version of the stent design was manufactured and mechanically tested to verify performance. The performance of the cylindrical stent configuration was analyzed using an FE model of an atherosclerotic artery. This arterial FE model was created and validated by analyzing balloon angioplasty of a common stainless steel stent. The biocompatibility of CI-CNTs was explored and studied. Blood compatibility testing of CI-CNT samples was performed with results comparable in performance to stainless steel. A method of stent deployment was planned, and several other stent design concepts were analyzed. This research demonstrates that a functioning coronary stent can be manufactured from CI-CNTs. The optimized design has potential to address problems currently associated with stents. However, a major challenge for CI-CNT stent designs is meeting the design requirement of sufficient radial force. CI-CNT stents also need to have excellent blood compatibility to justify being used in stent applications.

Conventionally manufactured stents are available in uniform sizes and straight forms. These standard products are not suitable for all patients and research indicates that this is the reason for migration of stents in the vessel, and tubular structure in general, after deployment. The occurrence of migration makes readmission into hospital and the removal of the deployed stent necessary. This thesis develops a method which results in patient-customized stents which can be manufactured through additive manufacturing. These individualized stents intent to offer the same advantages of conventional stents while mitigating the disadvantages. The work’s core part is thedesign of a stent based on the geometric information through a medical scan. It converts the relevant areas from the medical scan data which is in the DICOM format to the STL file format. After cleaning and further processing, the shape will be the base for the design process of a stent using CAD software. Additionally, it also gives insight into the subjacent technologies such as medical scanning, additive manufacturing, choice of material and necessary further processing steps. A process chain from scanning, data transformation, 3D printing and post processing is described.The developed method delivers a reliable model and results in a fully individualized stent. In the current stage, it involves manual work since the representation of data in the steps is different. Further suggestions for steps to automate the process and an estimation of economic efficiency is given. / Det finns konventionellt tillverkade stenter i likformiga storlekar och raka former. Dem här standardprodukter är inte lämpliga för alla patienter och forskning tyder på att detta är orsaken till migrationen av stenter i blodkärl efter placering. Förekomsten av migration skapa återtagande på sjukhus och avlägsnande av den placerade stenten är nödvändig. Den här avhandlingen utvecklar en metod som resulterar i patient anpassade stenter som kan varatillverkad genom additiv tillverkning. Dessa individualiserade stenter avser att erbjuda samma fördelar som konventionella stenter och mildra nackdelarna. Arbetets kärna är designen av en stent baserad på den geometriska informationen baserande på en medicinsk bildteknik. Det omvandlar relevanta kroppsdelar från det medicinska bildteknik som finns i DICOM-formatet till STLfilformatet. Efter rengöring och vidare bearbetning kommer formen att vara basen för stentens designprocess med CAD-mjukvara. Dessutom ger den också inblick i de underliggande teknikerna som medicinsk bildteknik, tillsatsframställning, materialval och nödvändig vidarebehandling steg. En processkedja från skanning, datatransformation, 3D-utskrift och efterbehandling är beskrivits.Den utvecklade metoden ger en tillförlitlig modell och resulterar i en helt individualiserad stent. I det aktuellt stadium, innebär det manuellt arbete eftersom representationen av data i stegen är annorlunda. Ytterligare förslag till åtgärder för att automatisera processen och en uppskattning av ekonomisk effektivitet är given.

Coronary artery disease affects millions of people and the ability to detect and treat the disease is advancing at a rapid rate. As a result, the development of intravascular technologies is the focus of many medical device manufacturers. Specifically, coronary stent implantation is being performed in an increasing number of patients and a number of new stent designs have been introduced to the market, resulting in the need for improved preclinical testing methods. An in vitro tissue engineered “blood vessel mimic” (BVM) system has previously been established and its feasibility for the initial testing of newly emerging intravascular technology has been demonstrated. There are limitations that exist with this original design, however, and the focus of this thesis was to both improve and expand upon the original model. Therefore, research was conducted based on two specific aims. The first aim was to develop a more ideal BVM system to accommodate a wider range of stent lengths and diameters, while allowing for easy graft insertion and seal-ability. The second aim was to develop next generation BVM systems,focused on future needs and technology, such as long, angulated and bifurcated geometries. The work described in this thesis demonstrates that a BVM chamber can be created which has the advantages of easy graft insertion and seal-ability, as well as the ability to accommodate varying sizes of vessel scaffolds, all while maintaining the needs of a tissue engineering bioreactor system. The next generation BVM systems presented demonstrate that the BVM concept can be expanded to meet the needs of long, angulated and bifurcated geometries. Overall, the work in this thesis describes the design and optimization of an in vitro blood vessel mimic bioreactor system for the evaluation of intravascular devices, specifically coronary stents, in simple and complex vessel geometries.

Despite advancements in percutaneous coronary intervention, stents are still limited by a 2% annual rate of in-stent restenosis (ISR) related to neointimal (NI) tissue proliferation. Efforts to prevent ISR formation remain the focus of ongoing work. Adenosine (ADO) is a purine nucleoside with integral roles in vascular homeostasis, though it has limited clinical application. ADO signals primarily via four receptors with ADO receptor-A2B (ADOR-A2B) considered to play an integral role in vascular healing. Dipyridamole (DP) is a commercially approved therapy known to improve vascular events and modulate adenosine biology. Our objectives with this study included (i) assessing whether ADO could serve as a biomarker of cardiac events; (ii) determine if DP could mitigate NI formation in a pre-clinical stent model; and, (iii) quantify the mechanisms of DP-related vasculoprotection, specifically related to ADOR-A2B. We assessed the analytic and biologic variability of circulating ADO levels in humans and demonstrated that circulating ADO was not predictive of cardiac events at one year following invasive coronary angiography. We then assessed whether modulation of adenosine biology with DP had therapeutic efficacy in a pre-clinical model. Utilizing meta-analysis, we confirmed the sustained effects of DP on vascular patency rates in both pre-clinical and clinical studies. We refined a pre-clinical rabbit model of stent implantation with assessment of stent healing by intravascular optical coherence tomography – with excellent translation to clinical observations. We then assessed DP in a pre-clinical model, demonstrating reduction in ISR and improved stent healing with DP compared to control. Last, we sought to elucidate the mechanisms behind the observed DP effects, specifically related to ADOR-A2B. In vivo, DP therapy demonstrated reduced NI smooth muscle cell (SMC) content. In vitro assessment of DP demonstrated dose-dependent inhibition of SMC proliferation and migration with alteration of SMC phenotypic switching, while selective modulation of ADOR-A2B and ADOR-A2B knockdown support an ADOR-A2B-mediated component to the observed DP effects. Adenosine biology is integral to vascular homeostasis. In humans, circulating adenosine levels in humans are not predictive of one year cardiovascular events. However, DP may improve vascular healing post stent implantation and warrants clinical evaluation for stent healing. The observed DP benefits may, in part, stem from ADOR-A2B modulation. ADOR-A2B is a viable target for assessment of small molecule modulation as a novel therapeutic target to improve vascular outcomes.

No description available.

La réparation endovasculaire (EVAR) est une technique minimalement invasive permettant de traiter l’anévrisme de l’aorte abdominale (AAA) par l’entremise d’un stent- graft (SG). L’utilisation d’EVAR est actuellement limitée par de fréquentes complications liées à une guérison inadéquate autour de l’implant. Ce manque de guérison est principalement dû au type de recouvrement polymérique des SG, au milieu pro-apoptotique des AAA et à l’accès réduit aux nutriments et à l’oxygène après EVAR. L’objectif de cette thèse consistait à concevoir un revêtement bioactif permettant d’inhiber l’apoptose et stimuler la croissance des cellules musculaires lisses vasculaires (CMLV), pour ainsi favoriser la guérison des tissus vasculaires autour des SG. La chondroïtine-4-sulfate (CS) a d’abord été choisie, car elle a été identifiée comme un médiateur important de la réparation vasculaire. Il a été démontré que la CS en solution influence directement la résistance à l’apoptose des CMLV, en plus de favoriser la différenciation myofibroblastique chez les fibroblastes. Dans le cadre de ce projet, un premier revêtement à base de CS et de collagène a été créé. Bien que le revêtement permettait d’induire une résistance à l’apoptose chez les CMLV, il se désintégrait trop rapidement dans des conditions aqueuses. Une nouvelle méthodologie a donc été adaptée afin de greffer la CS directement sur des surfaces aminées, à l’aide d’un système utilisant un carbodiimide. Dans le but d’accroître la croissance des CMLV à la surface des revêtements, le facteur de croissance de l’épiderme (EGF) a ensuite été sélectionné. En plus de ses propriétés mitogéniques et chimiotactiques, l’EGF stimule la production d’éléments de la matrice extracellulaire, comme le collagène et la fibronectine. De plus, l’activation du récepteur de l’EGF inhibe également l’apoptose des CMLV. L’EGF a donc été greffé sur la CS. Le revêtement de CS+EGF a démontré une bonne uniformité et bioactivité sur des surfaces de verre aminé. iii iv Dans une 3ème étape, afin de permettre de transposer ce revêtement bioactif sur des implants, plusieurs méthodes permettant de créer des groupements d’amines primaires sur les biomatériaux polymériques comme le PET ou le ePTFE ont été étudiées. La polymérisation par plasma a été choisie pour créer le revêtement CS+EGF à la surface de PET. Une fois de plus, celui-ci a permis d’inhiber l’apoptose des CMLV, dans des conditions pro-apoptotiques, et de favoriser la croissance des cellules. Le revêtement de CS et d’EGF, déposé sur des surfaces aminées, possède des caractéristiques biologiques intéressantes et semble donc prometteur pour favoriser une meilleure guérison autour des SG. / Endovascular aneurysm repair (EVAR) is a minimally invasive technique performed to treat abdominal aortic aneurysm (AAA) through the use of a stent-graft (SG). The usage of EVAR is presently limited by postoperative complications related to an incomplete healing of the surrounding tissues. The materials currently used in SG, the pro- apoptotic phathophysiology of AAA and the limited access to nutrients and oxygen, all limit the wound healing process and proper tissue ingrowth around the implant. The main objective of this thesis was to create of a bioactive coating inhibiting cell apoptosis and increasing vascular smooth muscle cells (VSMC) growth, to promote healing of the vascular tissues surrounding SG. Chondroitin sulfate (CS) was chosen since recent findings have shown that this polysaccharide triggers key mechanisms involved in vascular repair. CS in solution was shown to inhibit apoptosis of VSMC, as well as stimulate myofibroblast differentiation. A coating of CS and collagen was first created for the purpose of this work. Although the coating was shown to increase cell resistance to apoptosis with VSMC, it was not stable enough, since it rapidly disintegrated in aqueous solutions. A new methodology was thus proposed, where CS was grafted right on aminated surfaces, through carbodiimide chemistry. Epidermal growth factor (EGF) was then chosen to increase VSMC growth on the coatings. EGF is a known mitogenic and chemotactif growth factor for VSMC. It also stimulates the production of extracellular matrix elements, such as collagen and fibronectin. The activation of EGF receptor (EGFR) also triggers various cell signalling pathways modulating VSMC resistance to apoptosis. EGF was thus grafted on CS. CS+EGF coating on aminated glassed slides was shown to be uniform and bioactive. Finally, several methodologies to produce primary amines on polymeric biomaterials, such as PET and ePTFE, were studied in order to eventually transfer the v vi coating on implants. Plasma polymerization was chosen to create the CS+EGF coating. Once again the coating was shown to decrease VSMC apoptosis, in apoptotic conditions, and favour cell growth. Overall, the CS and EGF coating on aminated surfaces possesses interesting biological features and is a promising avenue to stimulate vascular healing around SG.

OBJECTIVES The aim of this analysis was to assess the 7-year long-term safety and effectiveness of a randomized comparison of percutaneous coronary intervention (PCI) with sirolimus-eluting stents (SES) versus minimally invasive direct coronary artery bypass (MIDCAB) surgery for the treatment of isolated proximal left anterior descending lesions. BACKGROUND Long-term follow-up data comparing PCI by SES and MIDCAB surgery for isolated proximal left anterior descending lesions are sparse. METHODS Patients were randomized either to PCI with SES (n ¼ 65) or MIDCAB (n ¼ 65). Follow-up data were obtained after 7 years with respect to the primary composite endpoint of death, myocardial infarction, and target vessel revas- cularization. Angina was assessed by the Canadian Cardiovascular Society classification and quality of life with Short Form 36 and MacNew quality of life questionnaires. RESULTS Follow-up was conducted in 129 patients at a median time of 7.3 years (interquartile range: 5.7, 8.3). There were no significant differences in the incidence of the primary composite endpoint between groups (22% PCI vs. 12% MIDCAB; p ¼ 0.17) or the endpoints death (14% vs. 17%; p ¼ 0.81) and myocardial infarction (6% vs. 9%, p ¼ 0.74). However, the target vessel revascularization rate was higher in the PCI group (20% vs. 1.5%; p < 0.001). Clinical symptoms and quality of life improved significantly from baseline with both interventions and were similar in magnitude between groups. CONCLUSIONS At 7-year follow-up, PCI by SES and MIDCAB in isolated proximal left anterior descending lesions yielded similar long-term outcomes regarding the primary composite clinical endpoint and quality of life. Target vessel revascularization was more frequent in the PCI group. (Randomied Comparison of Minimally Invasive Direct Coronary Artery Bypass Grafting and Percutaneous Coronary Intervention With Drug-Eluting Stents in Patients With Proximal Stenosis of the Left Anterior Descending Coronary Artery; NCT00299429) (J Am Coll Cardiol Intv 2014;-:-–-) © 2014 by the American College of Cardiology Foundation.