Clinical results with the Resolute zotarolimus-eluting stent in total coronary occlusions.

Aims: We conducted a pooled post hoc analysis (RESOLUTE All Comers and RESOLUTE International) of patients who had the Resolute® zotarolimus-eluting stent (R-ZES) implanted in revascularised total occlusions (TO) compared with patients treated with R-ZES for non-occluded lesions. Methods and results: Patients were divided into three groups: chronic TO (CTO; n=256), non-chronic TO (n=292), and no occlusion (n=2,941). Clinical and safety outcomes assessed through two years included target lesion failure (TLF: cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularisation) and Academic Research Consortium definite or probable stent thrombosis. The rate of TLF at two years was not significantly different among patients in the CTO (9.1%), TO (9.8%), and no occlusion (10.4%) groups (log-rank p=0.800); neither were the components of TLF. Definite or probable stent thrombosis occurred more frequently in the TO group (2.8% vs. 1.2% in the CTO and 1.1% in the group with no occlusion, p=0.027). There were 10 late and six very late stent thrombosis events. Conclusions: Apart from a higher rate of stent thrombosis in patients with TO, patients with totally occluded coronary arteries who receive revascularisation with an R-ZES have clinical outcomes comparable to those who receive a similar stent in non-occluded lesions.

Drug-eluting balloon versus standard balloon angioplasty for infrapopliteal arterial revascularization in critical limb ischemia: 12-month results from the IN.PACT DEEP randomized trial.

BACKGROUND Drug-eluting balloons (DEB) may reduce infrapopliteal restenosis and reintervention rates versus percutaneous transluminal angioplasty (PTA) and improve wound healing/limb preservation. OBJECTIVES The goal of this clinical trial was to assess the efficacy and safety of IN.PACT Amphirion drug-eluting balloons (IA-DEB) compared to PTA for infrapopliteal arterial revascularization in patients with critical limb ischemia (CLI). METHODS Within a prospective, multicenter, randomized, controlled trial with independent clinical event adjudication and angiographic and wound core laboratories 358 CLI patients were randomized 2:1 to IA-DEB or PTA. The 2 coprimary efficacy endpoints through 12 months were clinically driven target lesion revascularization (CD-TLR) and late lumen loss (LLL). The primary safety endpoint through 6 months was a composite of all-cause mortality, major amputation, and CD-TLR. RESULTS Clinical characteristics were similar between the 2 groups. Significant baseline differences between the IA-DEB and PTA arms included mean lesion length (10.2 cm vs. 12.9 cm; p = 0.002), impaired inflow (40.7% vs. 28.8%; p = 0.035), and previous target limb revascularization (32.2% vs. 21.8%; p = 0.047). Primary efficacy results of IA-DEB versus PTA were CD-TLR of 9.2% versus 13.1% (p = 0.291) and LLL of 0.61 ± 0.78 mm versus 0.62 ± 0.78 mm (p = 0.950). Primary safety endpoints were 17.7% versus 15.8% (p = 0.021) and met the noninferiority hypothesis. A safety signal driven by major amputations through 12 months was observed in the IA-DEB arm versus the PTA arm (8.8% vs. 3.6%; p = 0.080). CONCLUSIONS In patients with CLI, IA-DEB had comparable efficacy to PTA. While primary safety was met, there was a trend towards an increased major amputation rate through 12 months compared to PTA. (Study of IN.PACT Amphirion™ Drug Eluting Balloon vs. Standard PTA for the Treatment of Below the Knee Critical Limb Ischemia [INPACT-DEEP]; NCT00941733).

Everolimus-eluting bioresorbable stent vs. durable polymer everolimus-eluting metallic stent in patients with ST-segment elevation myocardial infarction: results of the randomized ABSORB ST-segment elevation myocardial infarction-TROFI II trial.

AIMS Patients with ST-segment elevation myocardial infarction (STEMI) feature thrombus-rich lesions with large necrotic core, which are usually associated with delayed arterial healing and impaired stent-related outcomes. The use of bioresorbable vascular scaffolds (Absorb) has the potential to overcome these limitations owing to restoration of native vessel lumen and physiology at long term. The purpose of this randomized trial was to compare the arterial healing response at short term, as a surrogate for safety and efficacy, between the Absorb and the metallic everolimus-eluting stent (EES) in patients with STEMI. METHODS AND RESULTS ABSORB-STEMI TROFI II was a multicentre, single-blind, non-inferiority, randomized controlled trial. Patients with STEMI who underwent primary percutaneous coronary intervention were randomly allocated 1:1 to treatment with the Absorb or EES. The primary endpoint was the 6-month optical frequency domain imaging healing score (HS) based on the presence of uncovered and/or malapposed stent struts and intraluminal filling defects. Main secondary endpoint included the device-oriented composite endpoint (DOCE) according to the Academic Research Consortium definition. Between 06 January 2014 and 21 September 2014, 191 patients (Absorb [n = 95] or EES [n = 96]; mean age 58.6 years old; 17.8% females) were enrolled at eight centres. At 6 months, HS was lower in the Absorb arm when compared with EES arm [1.74 (2.39) vs. 2.80 (4.44); difference (90% CI) -1.06 (-1.96, -0.16); Pnon-inferiority <0.001]. Device-oriented composite endpoint was also comparably low between groups (1.1% Absorb vs. 0% EES). One case of definite subacute stent thrombosis occurred in the Absorb arm (1.1% vs. 0% EES; P = ns). CONCLUSION Stenting of culprit lesions with Absorb in the setting of STEMI resulted in a nearly complete arterial healing which was comparable with that of metallic EES at 6 months. These findings provide the basis for further exploration in clinically oriented outcome trials.

Arterial healing following primary PCI using the Absorb everolimus-eluting bioresorbable vascular scaffold (Absorb BVS) versus the durable polymer everolimus-eluting metallic stent (XIENCE) in patients with acute ST-elevation myocardial infarction: rationale and design of the randomised TROFI II study

AIMS The Absorb bioresorbable vascular scaffold (Absorb BVS) provides similar clinical outcomes compared with a durable polymer-based everolimus-eluting metallic stent (EES) in stable coronary artery disease patients. ST-elevation myocardial infarction (STEMI) lesions have been associated with delayed arterial healing and impaired stent-related outcomes. The purpose of the present study is to compare directly the arterial healing response, angiographic efficacy and clinical outcomes between the Absorb BVS and metallic EES. METHODS AND RESULTS A total of 191 patients with acute STEMI were randomly allocated to treatment with the Absorb BVS or a metallic EES 1:1. The primary endpoint is the neointimal healing (NIH) score, which is calculated based on a score taking into consideration the presence of uncovered and malapposed stent struts, intraluminal filling defects and excessive neointimal proliferation, as detected by optical frequency domain imaging (OFDI) six months after the index procedure. The study will provide 90% power to show non-inferiority of the Absorb BVS compared with the EES. CONCLUSIONS This will be the first randomised study investigating the arterial healing response following implantation of the Absorb BVS compared with the EES. The healing response assessed by a novel NIH score in conjunction with results on angiographic efficacy parameters and device-oriented events will elucidate disease-specific applications of bioresorbable scaffolds.

Prevention of Rebleeding From Esophageal Varices in Patients With Cirrhosis Receiving Small-Diameter Stents Versus Hemodynamically Controlled Medical Therapy

BACKGROUND & AIMS Patients with cirrhosis and variceal hemorrhage have a high risk of rebleeding. We performed a prospective randomized trial to compare the prevention of rebleeding in patients given a small-diameter covered stent vs those given hepatic venous pressure gradient (HVPG)-based medical therapy prophylaxis. METHODS We performed an open-label study of patients with cirrhosis (92% Child class A or B, 70% alcoholic) treated at 10 medical centers in Germany. Patients were assigned randomly more than 5 days after variceal hemorrhage to groups given a small covered transjugular intrahepatic portosystemic stent-shunt (TIPS) (8 mm; n = 90), or medical reduction of portal pressure (propranolol and isosorbide-5-mononitrate; n = 95). HVPG was determined at the time patients were assigned to groups (baseline) and 2 weeks later. In the medical group, patients with an adequate reduction in HVPG (responders) remained on the drugs whereas nonresponders underwent only variceal band ligation. The study was closed 10 months after the last patient was assigned to a group. The primary end point was variceal rebleeding. Survival, safety (adverse events), and quality of life (based on the Short Form-36 health survey) were secondary outcome measures. RESULTS A significantly smaller proportion of patients in the TIPS group had rebleeding within 2 years (7%) than in the medical group (26%) (P = .002). A slightly higher proportion of patients in the TIPS group experienced adverse events, including encephalopathy (18% vs 8% for medical treatment; P = .05). Rebleeding occurred in 6 of 23 patients (26%) receiving medical treatment before hemodynamic control was possible. Per-protocol analysis showed that rebleeding occurred in a smaller proportion of the 32 responders (18%) than in nonresponders who received variceal band ligation (31%) (P = .06). Fifteen patients from the medical group (16%) underwent TIPS placement during follow-up evaluation, mainly for refractory ascites. Survival time and quality of life did not differ between both randomized groups. CONCLUSIONS Placement of a small-diameter, covered TIPS was straightforward and prevented variceal rebleeding in patients with Child A or B cirrhosis more effectively than drugs, which often required step-by-step therapy. However, TIPS did not increase survival time or quality of life and produced slightly more adverse events. Clinical Trial no: ISRCTN 16334693.

Everolimus-Eluting Bioresorbable Vascular Scaffold System in the Treatment of Cardiac Allograft Vasculopathy: the CART (Cardiac Allograft Reparative Therapy) Prospective Multicenter Pilot Study.

Cardiac allograft vasculopathy (CAV) is a form of accelerated atherosclerosis, which represents the leading cause of late morbidity and mortality after heart transplantation. The recent bioresorbable vascular scaffold (BVS) technology represents a potential novel therapeutic tool, in the context of CAV, by allowing transient scaffolding and concomitant vessel healing. Eligible subjects will be treated by using the Absorb Everolimus-Eluting BVS (Abbott Vascular, Santa Clara, CA, USA), and evaluated at pre-determined time points, up to 3 years since the index procedure. Both clinical and imaging data will be collected in dedicated case report forms (CRF). All imaging data will be analyzed in an independent core laboratory. The primary aim of the study is to evaluate the angiographic performance at 1 year of second-generation Absorb BVS, in heart transplant recipients affected by CAV.

Simulation of a mechanical thrombectomy device based in the use of self-expandable stents for the blood clots extraction

Recently, we have presented some studies concerning the analysis, design and optimization of one experimental device developed in the UK - GPTAD - which has been designed to remove blood clots without the need to make contact with the clot itself, thereby potentially reducing the risk of problems such as downstream embolisation. Based on the idea of a modification of the previous device, in this work, we present a model based in the use of stents like the SolitaireTM FR, which is in contact with the clot itself. In the case of such devices, the stent is self-expandable and the extraction of the blood clot is faciliatated by the stent, which must be inside the clot. Such stents are generally inserted in position by using the guidewire inserted into the catheter. This type of modeling could potentially be useful in showing how the blood clot is moved by the various different forces involved. The modelling has been undertaken by analyzing the resistances, compliances and inertances effects. We model an artery and blood clot for range of forces for the guidewire. In each case we determine the interaction between blood clot, stent and artery.

Estudio del flujo sanguíneo para diferentes técnicas de implantación de stents en bifurcaciones coronarias

Las enfermedades arteriales vienen presididas por la aterosclerosis, que es un proceso crónico de degeneración, que evoluciona hacia la obstrucción de la luz arterial. La pared de la arteria se engrosa debido al depósito de elementos grasos tales como el colesterol. Los stents intraluminales son diminutas estructuras tubulares autoexpandibles de malla de metal, que se colocan dentro de la arteria coronaria después de una angioplastia con balón para prevenir el cierre de dicha arteria. A pesar de estar diseñados para ser compatibles con el tejido humano, a menudo se da una reacción en cadena de consecuencias indeseables. La reestenosis intra-stent es un problema creciente debido al importante incremento que se ha producido en la utilización del stent intracoronario como forma de revascularización percutánea. Se habla de una incidencia global del 28%, siendo la causa principal de su aparición la proliferación neointimal a través de una compleja cascada de sucesos que pueden tardar meses en desarrollarse. Una de las reacciones más importantes es la trombosis o la formación de una fina capa de coágulo como respuesta a la presencia de un material extraño. Este proceso es multifactorial, y en él intervienen la regresión de la pared como consecuencia del estiramiento previo, la denudación endotelial, lo que permite la agregación plaquetaria, la proliferación neointimal, lo que facilita a los receptores de membrana desencadenar un proceso de agregación posterior y, por último, el remodelado negativo inadecuado de la pared, lo que produce pérdida de luz arterial. Se ha observado frecuentemente que el depósito de ateroma en la pared arterial está relacionado con el valor de los esfuerzos cortantes en la misma. Hay mayores probabilidades de engrosamiento de la pared en las zonas donde son bajos los esfuerzos cortantes, quizá por el mayor tiempo de residencia de las partículas circulantes por el torrente sanguíneo. Si nos centramos en la afirmación anterior, el siguiente paso sería buscar las zonas susceptibles de presentar un valor bajo de dichos esfuerzos. Las zonas potencialmente peligrosas son los codos y bifurcaciones, entre otras. Nos hemos centrado en una bifurcación coronaria, ya que los patrones de flujo que se suelen presentar, tales como recirculación y desprendimiento de vórtices están íntimamente relacionados con las técnicas de implantación de stents en esta zona. Proyectamos nuestros esfuerzos en el estudio de dos técnicas de implante, utilizando un único stent y una tercera a través de una configuración de culotte con el uso de dos stents. El primer caso trata de una bifurcación con un único stent en la rama principal cuyos struts cierran el orificio lateral que da salida a la rama secundaria de la bifurcación, es decir sería un stent sin orificio. El segundo consiste en un único stent también, pero con la diferencia de que éste presenta un orificio de comunicación con la rama lateral. Todas estas técnicas se aplicaron a bifurcaciones de 45º y de 90º. Introdujimos las geometrías -una vez confeccionadas con el código comercial Gambit- en el programa Ansys-Fluent contemplando régimen estacionario. Los resultados obtenidos fueron cotejados con los experimentales, que se realizaron paralelamente, con el fin de corroborarlos. Una vez validados, el estudio computacional ya contó con la fiabilidad suficiente como para abordar el régimen no estacionario, tanto en la versión de reposo como en la de ejercicio –hiperemia- El comportamiento reológico de la sangre para régimen no estacionario en estado de reposo es otra de las tareas abordadas, realizando una comparativa de los modelos Newtoniano, Carreau y Ley de Potencias. Finalmente, en una última etapa, debido a la reciente incursión de los stents diseñados específicamente frente a los convencionales, se aborda el comportamiento hemodinámico de los mismos. Concretamente, se comparó el patrón de flujo en un modelo de bifurcación coronaria con los nuevos stents (Stentys) y los convencionales. Se estudiaron cuatro modelos, a saber, stent simple en la rama principal, stent simple en la rama secundaria, culotte desplegando el primer stent en la rama principal y culotte desplegando el primer stent en la rama secundaria. La bifurcación estudiada presenta un ángulo de apertura de 45º y la relación de diámetros de las ramas hija se ajustaron de acuerdo a la ley de Finet. Se recogieron resultados experimentales en el laboratorio y se corrieron simulaciones numéricas con Ansys Fluent paralelamente. Las magnitudes que se tuvieron en cuenta con el fin de ubicar las regiones potencialmente ateroscleróticas fueron los esfuerzos cortantes, vorticidad y caída de presión. ABSTRACT Nowadays, restenosis after percutaneous dilation is the major drawback of coronary angioplasty. It represents a special form of atherosclerosis due to the healing process secondary to extensive vessel trauma induced after intracoronary balloon inflation. The use of coronary stents may decrease the incidence of this phenomenon. Unfortunately, intra-stent restenosis still occurs in 20-30% of the cases following the stent implantation. Most experiments suggest a correlation between low wall shear stress and wall thickness. The preferential locations for the atherosclerotic plaque are bifurcations. The objective of this work is to analyze the local hemodynamic changes caused in a coronary bifurcation by three different stenting techniques: simple stenting of the main vessel, simple stenting of the main vessel with kissing balloon in the side branch and culotte. To carry out this study an idealized geometry of a coronary bifurcation is used, and two bifurcation angles, 45º and 90º, are chosen as representative of the wide variety of real configurations. Both numerical simulations and experimental measurements are performed. First, steady simulations are carried out with the commercial code Ansys-Fluent, then, experimental measurements with PIV (Particle Image Velocimetry), obtained in the laboratory, are used to validate the numerical simulations. The steady computational simulations show a good overall agreement with the experimental data. Then, pulsatile flow is considered to take into account the transient effects. The time averaged wall shear stress, oscillatory shear index and pressure drop obtained numerically are used to compare the behavior of the stenting techniques. In a second step, the rheologic behavior of blood was considered comparing Newtonian, Carreau and Power Law models. Finally, as a result of previous investigations with conventional stents and after the recent emergence of several devices specifically designed for coronary bifurcations angioplasty, the hemodynamic performance of these new devices (Stentys) was compared to conventional ones and techniques in a coronary bifurcation model. Four different stenting techniques: simple stenting of the main vessel, simple stenting of the side vessel, culotte deploying the first stent in the main vessel and culotte deploying the first stent in the side vessel have been considered. To carry out this study an idealized geometry of a coronary bifurcation is used. A 45 degrees bifurcation angle is considered and the daughter branches diameters are obtained according to the Finet law. Both experiments in the laboratory and numerical simulations were used , focusing on important factors for the atherosclerosis development, like the wall shear stress, the oscillation shear index, the pressure loss and the vorticity.

Novel bioactive scaffolds incorporating nanogels as potential drug eluting devices

Big advances are being achieved in the design of new implantable devices with enhanced properties. For example, synthetic porous three-dimensional structures can mimic the architecture of the tissues, and serve as templates for cell seeding. In addition, polymeric nanoparticles are able to provide a programmable and sustained local delivery of different types of biomolecules. In this study novel alternative scaffolds with controlled bioactive properties and architectures are presented. Two complementary approaches are described. Firstly, scaffolds with nanogels as active controlled release devices incorporated inside the three-dimensional structure are obtained using the thermally induced phase separation (TIPS) method. Secondly, a novel coating method using the spraying technique to load these nanometric crosslinked hydrogels on the surface of two-dimensional (2D) and three-dimensional (3D) biodegradable scaffolds is described. The scanning electron microscopy (SEM) images show the distribution of the nanogels on the surface of different substrates and also inside the porous structure of poly-a-hydroxy ester derivative foams. Both of them are compared in terms of manufacturability, dispersion and other processing variables.