CVPath Institute Inc.

Gaithersburg, MD, United States

CVPath Institute Inc.

Gaithersburg, MD, United States
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Lutter C.,CVPath Institute Inc.
Clinical Journal of Sport Medicine | Year: 2017

OBJECTIVE:: Sport climbers strain passive and active anatomical structures of their hands and fingers to the maximum during training or competition. This study was designed to investigate bone marrow edema (BME) in rock climbing athletes. DESIGN:: Systematic detection, treatment, and follow-up investigation of rock climbing athletes with BME of the hand. SETTING:: Primary-level orthopedic surgery and sports medicine division of a large academic medical center. PATIENTS:: Thirty-one high-level climbers with diffuse pain in the hand and wrist joint caused by rock climbing were included in this study. INTERVENTIONS:: The therapy consisted of consequent stress reduction and a break from sports. MAIN OUTCOME MEASURES:: Reduction of BME shown through magnetic resonance imaging (MRI) and regaining of preinjury climbing levels (Union Internationale des Associations dʼ Alpinisme metric scale). RESULTS:: In 28 patients, MRI revealed osseous edema because of overload at the respective area of interest, mainly in the distal radius, the distal ulna, or the carpal bones, which could not be otherwise diagnosed as inflammations, tumors, or injuries. We classified these edemas and fractures of the hamate because of overload. The edema was a stress reaction to highly intensive training and climbing with presumably high traction to the wrist area. The control MRIs demonstrated that even with a consequent stress reduction, the edemas required 3 to 4 months to disappear completely. CONCLUSIONS:: Climbers with nonspecific, diffuse pain in the wrist and/or the fingers should be examined with MRI to detect or exclude the diagnosis of a BME. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

Juni R.P.,Maastricht University | Duckers H.J.,Erasmus Medical Center | Virmani R.,CVPath Institute Inc. | Moens A.L.,Maastricht University
Journal of the American College of Cardiology | Year: 2013

Oxidative stress greatly influences the pathogenesis of various cardiovascular disorders. Coronary interventions, including balloon angioplasty and coronary stent implantation, are associated with increased vascular levels of reactive oxygen species in conjunction with altered endothelial cell and smooth muscle cell function. These alterations potentially lead to restenosis, thrombosis, or endothelial dysfunction in the treated artery. Therefore, the understanding of the pathophysiological role of reactive oxygen species (ROS) generated during or after coronary interventions, or both, is essential to improve the success rate of these procedures. Superoxide O2 ·- anions, whether derived from uncoupled endothelial nitric oxide synthase, nicotinamide adenine dinucleotide phosphate oxidase, xanthine oxidase, or mitochondria, are among the most harmful ROS. O2 ·- can scavenge nitric oxide, modify proteins and nucleotides, and induce proinflammatory signaling, which may lead to greater ROS production. Current innovations in stent technologies, including biodegradable stents, nitric oxide donor-coated stents, and a new generation of drug-eluting stents, therefore address persistent oxidative stress and reduced nitric oxide bioavailability after percutaneous coronary interventions. This review discusses the molecular mechanisms of ROS generation after coronary interventions, the related pathological events - including restenosis, endothelial dysfunction, and stent thrombosis - and possible therapeutic ways forward. © 2013 American College of Cardiology Foundation.

Park S.-J.,University of Ulsan | Kang S.-J.,University of Ulsan | Virmani R.,CVPath Institute Inc. | Nakano M.,CVPath Institute Inc. | Ueda Y.,Osaka Police Hospital
Journal of the American College of Cardiology | Year: 2012

Percutaneous coronary intervention with stenting is the most widely performed procedure for the treatment of symptomatic coronary disease, and drug-eluting stents (DES) have minimized the limitations of bare-metal stents (BMS). Nevertheless, there remain serious concerns about late complications such as in-stent restenosis and late stent thrombosis. Although in-stent restenosis of BMS was considered as a stable condition with an early peak of intimal hyperplasia, followed by a regression period beyond 1 year, recent studies have reported that one-third of patients with in-stent restenosis of BMS presented with acute coronary syndrome that is not regarded as clinically benign. Furthermore, both clinical and histologic studies of DES have demonstrated evidence of continuous neointimal growth during long-term follow-up, which is designated as "late catch-up" phenomenon. Here, we present emerging evidence of de novo neoatherosclerosis based on histology, angioscopy, and intravascular images that provide a new insight for the mechanism of late stent failure. In-stent neoatherosclerosis is an important substrate for late stent failure for both BMS and DES, especially in the extended phase. In light of the rapid progression in DES, early detection of neoatherosclerosis may be beneficial to improving long-term outcome of patients with DES implants. © 2012 American College of Cardiology Foundation.

Yahagi K.,CVPath Institute Inc. | Davis H.R.,CVPath Institute Inc. | Arbustini E.,Center for Inherited Cardiovascular Diseases | Virmani R.,CVPath Institute Inc.
Atherosclerosis | Year: 2015

Cardiovascular disease (CVD) remains the most frequent cause of death in both men and women. Many studies on CVD have included mostly men, and the knowledge about coronary artery disease (CAD) in women has largely been extrapolated from studies primarily focused on men. The influence of various risk factors is different between men and women; untoward effects of smoking of CAD are greater in women than men. Furthermore, the effect of the menopause is important in women, with higher incidence of plaque erosion in young women versus greater incidence of plaque rupture in older women. This review focuses on differences in plaque morphology in men and women presenting with sudden coronary death and acute myocardial infarction. © 2015 Elsevier Ireland Ltd.

Chaabane C.,University of Geneva | Otsuka F.,CVPath Institute Inc. | Virmani R.,CVPath Institute Inc. | Bochaton-Piallat M.-L.,University of Geneva
Cardiovascular Research | Year: 2013

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. © The Author 2013.

Bekkers S.C.A.M.,Maastricht University | Yazdani S.K.,CVPath Institute Inc. | Virmani R.,CVPath Institute Inc. | Waltenberger J.,Maastricht University
Journal of the American College of Cardiology | Year: 2010

Successful restoration of epicardial coronary artery patency after prolonged occlusion might result in microvascular obstruction (MVO) and is observed both experimentally as well as clinically. In reperfused myocardium, myocytes appear edematous and swollen from osmotic overload. Endothelial cell changes usually accompany the alterations seen in myocytes but lag behind myocardial cell injury. Endothelial cells become voluminous, with large intraluminal endothelial protrusions into the vascular lumen, and together with swollen surrounding myocytes occlude capillaries. The infiltration and activation of neutrophils and platelets and the deposition of fibrin also play an important role in reperfusion-induced microvascular damage and obstruction. In addition to these ischemia-reperfusion-related events, coronary microembolization of atherosclerotic debris after percutaneous coronary intervention is responsible for a substantial part of clinically observed MVO. Microvascular flow after reperfusion is spatially and temporally complex. Regions of hyperemia, impaired vasodilatory flow reserve and very low flow coexist and these perfusion patterns vary over time as a result of reperfusion injury. The MVO first appears centrally in the infarct core extending toward the epicardium over time. Accurate detection of MVO is crucial, because it is independently associated with adverse ventricular remodeling and patient prognosis. Several techniques (coronary angiography, myocardial contrast echocardiography, cardiovascular magnetic resonance imaging, electrocardiography) measuring slightly different biological and functional parameters are used clinically and experimentally. Currently there is no consensus as to how and when MVO should be evaluated after acute myocardial infarction. © 2010 American College of Cardiology Foundation.

Yazdani S.K.,CVPath Institute Inc.
JACC. Cardiovascular interventions | Year: 2012

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). 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. Formalin-fixed SVBG of >2 years duration (n = 31) were collected to histologically characterize advanced atherosclerotic lesions in native SVBG. In a separate group, SVBGs treated with DES (n = 9) and BMS (n = 9) for >30 days duration were assessed for morphological and morphometric changes. Necrotic core lesions were identified in 25% of SVBG sections, and plaque rupture with luminal thrombosis was observed in 6.3% of histological sections (32% [10 of 31] vein grafts examined). Morphometry of DES demonstrated reduction in neointimal thickening versus BMS (0.13 mm [interquartile range: 0.06 to 0.16 mm] vs. 0.30 mm [interquartile range: 0.20 to 0.48 mm], p = 0.004). DES lesions also showed greater delayed healing characterized by increased peristrut fibrin deposition, higher percentage of uncovered struts, and less endothelialization compared with BMS. Stent fractures (DES 56% vs. BMS 11%, p = 0.045) and late stent thrombosis (DES 44% vs. BMS 0%, p = 0.023) were more common in DES versus BMS. Advanced SVBG atherosclerotic lesions are characterized by large hemorrhagic necrotic cores. Stenting of such lesions is associated with delayed vascular healing and late thrombosis particularly following DES implantation, which may help explain the higher rates of cardiovascular events observed in SVBG stenting as compared with native coronary arteries. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Nakazawa G.,CVPath Institute Inc. | Finn A.V.,Emory University | Vorpahl M.,CVPath Institute Inc. | Ladich E.R.,CVPath Institute Inc. | And 2 more authors.
Journal of the American College of Cardiology | Year: 2011

Objectives The purpose of this study was to assess the mechanism(s) of late stent thrombosis (LST) and vascular healing responses in first-generation polymeric drug-eluting stents (DES). Background Recent clinical trials have reported variations in late lumen loss between first-generation sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). Little is known, however, about the vascular responses, time course of healing, and underlying mechanism(s) of complications of LST between platforms in human coronary implants. Methods The overall analysis included 174 cases (230 DES lesions) from the CVPath Institute's stent registry. Histomorphometry was performed on coronary stents from 127 patients (171 lesions) who died <30 days after receiving stent implants in which fibrin deposition, endothelial strut coverage, inflammatory response, and mechanism(s) of in-stent thrombosis were assessed. Results Both platforms demonstrated increased neointimal thickness over time where values were greater in PES (mean 0.13 mm; range 0.03 to 0.20 mm) than SES (mean 0.10 mm; range 0.04 to 0.15 mm; p = 0.04). The percentage of uncovered struts was similar between SES and PES including stents with LST (SES = 21% vs. PES = 27%; p = 0.47). The underlying mechanism(s) of LST, however, was strikingly different between platforms; localized strut hypersensitivity was exclusive to SES, whereas malapposition secondary to excessive fibrin deposition was the underlying cause in PES. Moreover, although both PES and SES showed nearly complete strut coverage after 12 months for on-label use, the majority of stents placed for off-label indications remained unhealed after 12 months in both types of DES. Conclusions Differential mechanisms of LST involving either hypersensitivity or excessive fibrin were identified between first-generation DES in which overall stent healing was further delayed in DES placed for off-label indications. © 2011 American College of Cardiology Foundation.

Michel J.-B.,French Institute of Health and Medical Research | Virmani R.,CVPath Institute Inc. | Arbustini E.,Centro Malattie Genetiche Cardiovascolari | Pasterkamp G.,Experimental Cardiology Laboratory
European Heart Journal | Year: 2011

Atherothrombosis remains one of the main causes of morbidity and mortality in the western countries. Human atherothrombotic disease begins early in life in relation to circulating lipid retention in the inner vascular wall. Risk factors enhance the progression towards clinical expression: dyslipidaemia, diabetes, smoking, hypertension, ageing, etc. The evolution from the initial lipid retention in the arterial wall to clinical events is a continuum of increasingly complex biological processes. Current strategies to fight the consequences of atherothrombosis are orientated either towards the promotion of a healthy life style 1 and preventive treatment of risk factors, or towards late interventional strategies. 2 Despite this therapeutic arsenal, the incidence of clinical events remains dramatically high, 3 dependent, at least in part, on the increasing frequency of type 2 diabetes and ageing. But some medical treatments, focusing only on prevention of the metabolic risk, have failed to reduce cardiovascular mortality, thus illustrating that our understanding of the pathophysiology of human atherothrombosis leading to clinical events remain incomplete. New paradigms are now emerging which may give rise to novel experimental strategies to improve therapeutic efficacy and prediction of disease progression. Recent studies strengthen the concept that the intraplaque neovascularization and bleeding (Figure 1, upper panel) are events that could play a major role in plaque progression and leucocyte infiltration, and may also serve as a measure of risk for the development of future events. The recent advances in our understanding of IntraPlaque Hemorrhage as a critical event in triggering acute clinical events have important implications for clinical research and possibly future clinical practice. Figure 1Macroscopic view and schematic representation of the detrimental consequences of intraplaque haemorrhages on plaque biology and stability. © 2009 The Author.

Agency: National Science Foundation | Branch: | Program: STTR | Phase: Phase I | Award Amount: 224.56K | Year: 2014

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project addresses the estimated 8 million people in the US with peripheral artery disease (PAD). The population of PAD is increasing due to the aging population, high prevalence of obesity and diabetes, and improved diagnosis of the disease. Patients with PAD suffer from pain, ischemia, and infection in their lower limbs, and cost the healthcare system an estimated $6000 in direct spending per patient annually. The current and emerging technologies to treat PAD are ineffective in patients with long, diffuse lesions, calcified plaques, or patients with kidney disease. Further, the standard practice of using cytostatic agents and antiplatelet drugs adds additional risk to the patient and cost to the healthcare system. There is therefore great need to develop new, effective, and safe therapies for use in vascular interventions, including balloon angioplasty, stenting, or atherectomy. New therapies should be robust enough to be effective in a wide range of interventions and patient populations and address the specific injury that is caused to the vessel during the intervention. The proposed project examines the therapeutic use of a new material in vascular interventions with robust application and that specifically targets the initiating injury. This new material is delivered to the vessel wall at the site of injury, where it binds and prevents the cascading inflammatory response that leads to scarring of the vessel. Additionally, the new therapeutic is expected to promote re-endothelialization of the vessel wall, so that the injury site is rapidly healed. This proposal will examine how the therapeutic is delivered to the vessel wall following injury, how long it remains on the vessel wall, and if it can promote the vessel healing so that the neo-intimal hyperplasia does not form. A rabbit animal will be used, and balloon angioplasty will be performed, followed by delivery of the new therapeutic. Visualization of the therapeutic, platelets, and endothelial cells will take place from 2 hours to 7 days to determine the interaction of the components during the healing process. It is expected that the therapeutic will remain at the site of injury and prevent undesirable platelet binding until healing of the vessel occurs through re-endothelialization. By protecting the injured site, it can be demonstrated that vessel scarring is prevented.

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