Thrombogenicity and early vascular healing response in metallic biodegradable polymer-based and fully bioabsorbable drug-eluting stents.

Background: Acute thrombogenicity and re-endothelialization represent clinically relevant end points pertaining to the safety of coronary stents, which have not been compared among biodegradable polymer-based drug-eluting metallic stents and fully bioabsorbable scaffolds to date.

Methods And Results: We investigated comparative outcomes with respect to acute thrombogenicity and re-endothelialization among thin-strut biodegradable polymer metallic everolimus eluting stents (EES), thick-strut fully bioabsorbable EES, thick-strut biodegradable polymer metallic biolimus-eluting stents and control bare metal stents. An ex-vivo porcine arterio-venous shunt model was used to assess platelet aggregation, whereas a healthy rabbit model of iliofemoral stent implantation was used to assess re-endothelialization and inflammation.

A pathological perspective on the natural history of cerebral atherosclerosis.

Background: The natural history of intracranial large artery atherosclerosis has been mainly described from lumen-based imaging studies, and much of what is reported to be known about atherosclerosis is derived from non-cerebral arteries.

Aims: To test the hypothesis that atherosclerosis is only partially represented by stenosis and that advanced atherosclerosis is more common that severe stenosis in noncardioembolic infarcts.

Methods: Cerebral large arteries from 196 autopsy cases were studied.

A change in inflammatory footprint precedes plaque instability: a systematic evaluation of cellular aspects of the adaptive immune response in human atherosclerosis.

Background: Experimental studies characterize adaptive immune response as a critical factor in the progression and complications of atherosclerosis. Yet, it is unclear whether these observations translate to the human situation. This study systematically evaluates cellular components of the adaptive immune response in a biobank of human aortas covering the full spectrum of atherosclerotic disease.

Optical coherence tomography surveillance following drug-eluting stent implantation.

Drug-eluting stents are currently used in the majority of percutaneous coronary interventions. Preclinical investigations and human autopsy studies have shown that the high efficacy of drug-eluting stents (DES) in preventing restenosis is achieved at the expense of a delay in healing. Optical coherence tomography (OCT) represents a novel intracoronary imaging tool to evaluate vascular healing response after stent implantation.

Vascular healing and integration of a fully bioresorbable everolimus-eluting scaffold in a rabbit iliac arterial model.

Aims: We aimed to investigate a fully bioresorbable poly-l-lactide (PLLA) scaffold to assess vascular remodelling in comparison to a permanent polymeric metal DES.

Methods And Results: Twenty-five New Zealand white rabbits received an Absorb bioresorbable vascular scaffold (BVS, 1.0 and 1.

Comparison of vascular closure devices vs manual compression after femoral artery puncture: the ISAR-CLOSURE randomized clinical trial.

Importance: The role of vascular closure devices (VCD) for the achievement of hemostasis in patients undergoing transfemoral coronary angiography remains controversial.

Objective: To compare outcomes with the use of 2 hemostasis strategies after diagnostic coronary angiography performed via transfemoral access-a VCD-based strategy with 2 types of devices, an intravascular device and an extravascular device, vs standard manual compression. The primary hypothesis to be tested was that femoral hemostasis achieved through VCD is noninferior to manual compression in terms of vascular access-site complications.

Controlled circumferential renal sympathetic denervation with preservation of the renal arterial wall using intraluminal ultrasound: a next-generation approach for treating sympathetic overactivity.

Aims: The Paradise Ultrasound Renal Denervation System is a next-generation catheter-based device which was used to investigate whether the target ablation area can be controlled by changing ultrasound energy and duration to optimise nerve injury while preventing damage to the arterial wall.

Methods And Results: Five ultrasound doses were tested in a thermal gel model. Catheter-based ultrasound denervation was performed in 15 swine (29 renal arteries) to evaluate five different doses in vivo, and animals were euthanised at seven days for histopathologic assessment.

Exploring unknowns in cardiology.

To mark the 10th anniversary of Nature Reviews Cardiology in November 2014, five of our Advisory Board members were invited to consider a topic within cardiology about which we know too little. A diverse range of subjects are highlighted in this Perspectives article, including preoperative assessment of right ventricular function, the burden of cardiomyopathies in Africa, the measurement of fractional flow reserve to guide coronary intervention, the interaction between genes and environment in cardiovascular disease, and the difficulty of predicting atherosclerotic plaque rupture. The five key opinion leaders from around the globe also suggest ways in which future research could be targeted to address the deficits in our understanding, with the aim of preventing cardiovascular disease, improving patient care, and reducing morbidity and mortality.

Mechanisms of plaque formation and rupture.

Atherosclerosis causes clinical disease through luminal narrowing or by precipitating thrombi that obstruct blood flow to the heart (coronary heart disease), brain (ischemic stroke), or lower extremities (peripheral vascular disease). The most common of these manifestations is coronary heart disease, including stable angina pectoris and the acute coronary syndromes. Atherosclerosis is a lipoprotein-driven disease that leads to plaque formation at specific sites of the arterial tree through intimal inflammation, necrosis, fibrosis, and calcification.

Has our understanding of calcification in human coronary atherosclerosis progressed?

Coronary artery calcification is a well-established predictor of future cardiac events; however, it is not a predictor of unstable plaque. The intimal calcification of the atherosclerotic plaques may begin with smooth muscle cell apoptosis and release of matrix vesicles and is almost always seen microscopically in pathological intimal thickening, which appears as microcalcification (≥0.5 μm, typically <15 μm in diameter).

Preclinical evaluation of second-generation everolimus- and zotarolimus-eluting coronary stents.

Objectives: This study was designed to evaluate the pharmacokinetic and vascular healing of a second-generation everolimus-eluting stent (EES) and slow-release zotarolimus-eluting stent (R-ZES).

Background: Second-generation DESs have alleviated the safety concerns of late stent thrombosis by addressing issues of polymer biocompatibility and stent design, and optimizing drug loads and release kinetics. No preclinical comparison study exists between these stents.

Pathologic Etiologies of Late and Very Late Stent Thrombosis following First-Generation Drug-Eluting Stent Placement.

Several randomized and observational studies have reported steady increase in cumulative incidence of late and very late ST (LST/VLST) following first-generation drug-eluting stents (DES: sirolimus-(SES) and paclitaxel-(PES)) up to 5 years. Pathologic studies have identified uncovered struts as the primary substrate responsible for LST/VLST following DES, where delayed arterial healing is associated with stent struts penetrating into the necrotic core, long/overlapping stents, and bifurcation stenting especially in flow divider region. Grade V stent fracture also induces LST/VLST and restenosis.

Pathology of drug-eluting versus bare-metal stents in saphenous vein bypass graft lesions.

Objectives: The purpose of this study was to assess the pathological responses of atherosclerotic saphenous vein bypass grafts (SVBGs) to drug-eluting stents (DES) versus bare-metal stents (BMS).

Background: Repeat bypass surgery is typically associated with a high rate of morbidity and mortality. Percutaneous coronary interventions have emerged as the preferred treatment; however, only limited data are available on SVBGs pathological responses to DES and BMS.

The importance of the endothelium in atherothrombosis and coronary stenting.

Deployment of drug-eluting stents instead of bare-metal stents has dramatically reduced restenosis rates, but rates of very late stent thrombosis (>1 year postimplantation) have increased. Vascular endothelial cells normally provide an efficient barrier against thrombosis, lipid uptake, and inflammation. However, endothelium that has regenerated after percutaneous coronary intervention is incompetent in terms of its integrity and function, with poorly formed cell junctions, reduced expression of antithrombotic molecules, and decreased nitric oxide production.

Evaluation of polymer-based comparator drug-eluting stents using a rabbit model of iliac artery atherosclerosis.

Background: Although atherosclerotic models, especially in the rabbit, have existed for a long time, a comparative study of various drug-eluting stent (DES) implantations in atherosclerotic arteries have not been systematically studied.

Methods And Results: New Zealand White rabbits (n=44) with induced atheroma received bilateral iliac artery stents: bare metal stent (BMS) (Driver) or a stent eluting zotarolimus (ZES) (Endeavor), sirolimus (SES) (Cypher), or everolimus (EES) (Xience V). After 28 days, tissues were harvested for histomorphometric analyses, en face analysis of endothelial coverage, and expression of endothelial nitric oxide synthase (eNOS).

Correlation between carotid intimal/medial thickness and atherosclerosis: a point of view from pathology.

A widely adopted surrogate for predicting rates of cardiovascular events involves measure of carotid intimal-medial thickness (CIMT) by B mode ultrasound, a technique available since the mid 1980s. The value of this modality remains in its ability to noninvasively assess cardiovascular risk beyond traditional factors identified by the Framingham risk score, and it is among the few available techniques for monitoring the effectiveness of pharmacotherapy on plaques. There are, however, existing limitations to this methodology.

The significance of preclinical evaluation of sirolimus-, paclitaxel-, and zotarolimus-eluting stents.

Comparative preclinical histologic studies remain the most effective method for assessing the healing characteristics of vascular stents. The 2 most commonly used animal models to assess vascular responses to stent implantation are the porcine coronary artery and the rabbit iliac artery. Neither model alone is comparable to the human response to the implantation of a drug-eluting stent (DES).

Cardiac inflammatory myofibroblastic tumor: a "benign" neoplasm that may result in syncope, myocardial infarction, and sudden death.

Cardiac tumors other than myxomas are rare. We report a series of 10 intracavitary polypoid myofibroblastic proliferations in children and young adults emphasizing gross, histologic, and clinical features. There were 6 females and 4 males, with a mean age of 10 years (range 5 wk to 21 y).

Pioglitazone inhibits in-stent restenosis in atherosclerotic rabbits by targeting transforming growth factor-beta and MCP-1.

Objective: Although emerging data from preclinical and clinical studies suggests a reduction of in-stent restenosis with peroxisome proliferator-activated receptor (PPAR)-gamma agonists, the reduction of neointimal growth via anti-inflammatory mechanisms has not been explored.

Methods And Results: Hypercholesterolemic New Zealand White rabbits (n=45) received bilateral balloon-expandable stents implanted into atherosclerotic iliac arteries. Animals were randomized to oral pioglitazone 3 (low dose) or 10 mg/kg per day (high dose) started on the day of stent implantation; control rabbits received placebo.