cardiovascular-agents and Ischemia

To report the risk of all-cause mortality after treatment with paclitaxel-coated devices vs uncoated controls in patients with chronic limb-threatening ischemia (CLTI).. A search of the PubMed, Embase, Cochrane, CINAHL, DARE, and PROSPERO databases was made on 5 November 2019 to identify randomized controlled trials (RCT) using intention-to-treat analysis to compare a paclitaxel-coated device to an uncoated device in PAD patients having clinical follow-up of at least 6 months. Half of the study population had to have CLTI or extractable data on the CLTI subgroup if <50%. The search identified 11 trials having 1450 patients randomized to a paclitaxel-coated device (n=866) or an uncoated control (n=584). There were 1367 (94.3%) patients with CLTI (range 10-429). The single endpoint was all-cause mortality, which was analyzed by pooling the mortality data in a DerSimonian and Laird random effects model. Summary statistics are expressed as relative risk ratios (RR) with a 95% confidence interval (CI).. The mean follow-up was 25.6 months (range 6-60); 10 of 11 studies reported a minimum 12-month follow-up. There were 161 (18.6%) deaths among 866 subjects in the paclitaxel device group and 116 deaths among 584 (19.9%) subjects in the non-coated control group (RR 0.93, 95% CI 0.78 to 1.12, p=0.45).. There was no observed difference in short- to midterm mortality among a pooled patient population of predominately CLTI patients treated with paclitaxel-coated balloons or stents compared with uncoated controls.

Topics: Aged; Angioplasty, Balloon; Cardiovascular Agents; Cause of Death; Chronic Disease; Coated Materials, Biocompatible; Drug-Eluting Stents; Female; Humans; Ischemia; Male; Paclitaxel; Peripheral Arterial Disease; Prosthesis Design; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vascular Access Devices

The aim of this article is to systematically review the literature on medical adjunctive therapy for patients with chronic limb-threatening ischemia (CLTI).. MEDLINE, Embase, and Cochrane Database of Systematic Reviews were searched for studies published between January 1st, 2009, and June 1st, 2019. Articles that studied medical treatment of CLTI patients and reported clinical outcomes were eligible. Main exclusion criteria were case reports <20 patients, incorrect publication type, and CLTI caused by Buerger disease. The primary end point was major amputation (above the ankle) in studies with a follow-up of ≥6 months. Secondary end points were other clinical end points such as death and wound healing. Study quality was assessed according to the Downs and Black checklist.. Included were 42 articles: four focused on antiplatelet therapy, five on antihypertensive medication, 6 on lipid-lowering therapy, 16 on stem cell therapy, three on growth factors, five on prostanoids, and one study each on cilostazol, glucose-lowering therapy, spinal cord stimulation, sulodexide, and hemodilution. Calcium channel blockers, iloprost, cilostazol, and hemodilution showed significant improvement of limb salvage, but data are limited. Stem cell therapy showed no significant improvement of limb salvage but could potentially improve wound healing. Antiplatelets, antihypertensives, and statins showed significantly lower cardiovascular events rates but not evident lower major amputation rates. The quality of the studies was fair to good.. Certain medical therapies serve to improve limb salvage next to revascularization in CLTI patients, whereas others are important in secondary prevention. Because high quality evidence is limited, further research is needed.

Topics: Amputation, Surgical; Cardiovascular Agents; Critical Illness; Humans; Ischemia; Peripheral Arterial Disease; Risk Factors; Treatment Outcome

Critical limb ischemia (CLI) is a highly morbid disease with many patients considered poor surgical candidates. The lack of treatment options for CLI has driven interest in developing molecular therapies within recent years. Through these translational medicine studies in CLI, much has been learned about the pathophysiology of the disease. Here, we present an overview of the macrovascular and microvascular changes that lead to the development of CLI, including impairment of angiogenesis, vasculogenesis, and arteriogenesis. We summarize the randomized clinical controlled trials that have used molecular therapies in CLI, and discuss the novel imaging modalities being developed to assess the efficacy of these therapies.

Topics: Angiogenesis Inducing Agents; Cardiovascular Agents; Critical Illness; Genetic Therapy; Humans; Ischemia; Microcirculation; Neovascularization, Physiologic; Peripheral Arterial Disease; Regional Blood Flow; Treatment Outcome

The prevalence of peripheral artery disease (PAD) is increasing worldwide and is strongly age-related, affecting about 20 % of Germans over 70 years of age. Recent advances in endovascular and surgical techniques as well as clinical study results on comparative treatment methods strengthened the need for a comprehensive review of the published evidence for diagnosis, management, and prevention of PAD. The interdisciplinary guideline exclusively covers distal aorta and atherosclerotic lower extremity artery disease. A systematic literature review and formal consensus finding process, including delegated members of 22 medical societies and two patient self-support organisations were conducted and supervised by the Association of Scientific Medical Societies in Germany, AWMF. Three levels of recommendation were defined, A = "is recommended/indicated", B = "should be considered", C = "may be considered", means agreement of expert opinions due to lack of evidence. Altogether 294 articles, including 34 systematic reviews and 98 RCTs have been analysed. The key diagnostic tools and treatment basics have been defined. In patients with intermittent claudication endovascular and/or surgical techniques are treatment options depending on appropriate individual morphology and patient preference. In critical limb ischaemia, revascularisation without delay by means of the most appropriate technique is key. If possible and reasonable, endovascular procedures should be applied first. The TASC classification is no longer recommended as the base of therapeutic decision process due to advances in endovascular techniques and new crural therapeutic options. Limited new data on rehabilitation and follow-up therapies have been integrated. The article summarises major new aspects of PAD treatment from the updated German Guidelines for Diagnosis and Treatment of PAD. Limited scientific evidence still calls for randomised clinical trials to close the present gap of evidence.

Topics: Aged; Cardiovascular Agents; Consensus; Critical Illness; Endovascular Procedures; Evidence-Based Medicine; Female; Germany; Humans; Intermittent Claudication; Ischemia; Male; Peripheral Arterial Disease; Risk Reduction Behavior; Vascular Surgical Procedures

Topics: Cardiovascular Agents; Critical Illness; Diffusion of Innovation; Endovascular Procedures; Forecasting; Humans; Ischemia; Limb Salvage; Peripheral Arterial Disease; Secondary Prevention; Time Factors; Treatment Outcome; Vascular Surgical Procedures

Peripheral arterial disease, particularly critical limb ischemia, is an area with urgent need for optimized therapies because, to date, vascular interventions often have limited life spans. In spite of initial encouraging technical success after femoropopliteal percutaneous transluminal angioplasty or stenting, postprocedural restenosis remains the major problem. The challenging idea behind the drug-coated balloon (DCB) concept is the biological modification of the injury response after balloon dilatation. Antiproliferative drugs administered via DCBs or drug-eluting stents are able to suppress neointimal hyperplasia, the main cause of restenosis. This article reviews the results of DCB treatments of femoropopliteal and infrapopliteal lesions in comparison to standard angioplasty with uncoated balloons. A systematic literature search was performed in 1) medical journals (ie, MEDLINE), 2) international registers for clinical studies (ie, www.clinicaltrials.gov), and 3) abstracts of scientific sessions. Several controlled randomized trials with follow-up periods of up to 5 years demonstrated the efficacy of paclitaxel -DCB technology. However, calcified lesions seem to affect the efficacy of DCB. Combinations of preconditioning methods with DCBs showed promising results. Although the mechanical abrasion of calcium via atherectomy or laser ablation showed favorable periprocedural results, the long-term impact on restenosis and clinical outcome has to be demonstrated. Major advantages of the DCBs are the rapid delivery of drug at uniform concentrations with a single dose, their efficacy in areas wherein stents have been contraindicated until now (ie, bifurcation, ostial lesions), and in leaving no stent scaffold behind. Reinterventions are easier to perform because DCBs leave no metal behind. Various combinations of DCBs with other treatment modalities may prove to be viable options in future. The follow-up results of clinical studies will evaluate the long-term impact of DCBs.

Topics: Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Constriction, Pathologic; Critical Illness; Equipment Design; Femoral Artery; Humans; Ischemia; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Treatment Outcome; Vascular Access Devices; Vascular Patency

Raynaud phenomenon may be a primary disorder or associated with a variety of other autoimmune processes. Raynaud phenomenon produces digital vasospasm, which can lead to ischemia and ulceration. The treatment of Raynaud phenomenon has been difficult because multiple medical treatments have not provided uniform resolution of symptoms. Many patients have turned to surgery and sympathectomies for the treatment of unrelenting vasospasm. Botulinum toxin has been shown to be an effective alternative to surgery, with a single treatment being capable of resolving pain and healing ulcer. This article reviews the use of botulinum toxin for the treatment of Raynaud phenomenon.

Topics: Botulinum Toxins, Type A; Cardiovascular Agents; Hand; Humans; Ischemia; Neuromuscular Agents; Raynaud Disease; Vasoconstriction

Critical limb ischemia (CLI) encompasses the most extreme end of the peripheral artery disease (PAD) spectrum leading to significant morbidity and mortality. CLI is defined as greater than 2 weeks of extremity rest pain, ulcers or extremity gangrene, secondary to objectively proven peripheral artery disease. Corresponding to Fontaine Stages III/IV and Rutherford category IV through VI, CLI is a complex disease comprising of both macrovascular and microvascular systems with inconsistent historical data on optimal treatment. CLI is distinct from intermittent claudication with different goals of treatment, however in both groups risk factor modification is of the utmost importance involving tobacco cessation, and treatment of underlying conditions like diabetes mellitus, hyperlipidemia and hypertension. In CLI, medical therapy involves wound care and also consists of antiplatelet therapy, anti-inflammatory therapy including statin use or ACE inhibitors. Surgical therapies include distal bypass surgery, thromboendartectomy and amputation. Endovascular techniques include percutaneous transluminal angioplasty, bare metal stents, atherectomy, drug-coated balloon and drug-eluting stents. CLI is considered the end-stage of PAD, requiring a thoughtful and multidisciplinary approach, risk-benefit analysis and treatment of comorbid conditions. Conservative and surgical treatments, along with endovascular techniques, have allowed excellent opportunities for treating complicated patients for wound healing and limb salvage.

Topics: Amputation, Surgical; Cardiovascular Agents; Critical Illness; Endovascular Procedures; Humans; Ischemia; Limb Salvage; Peripheral Arterial Disease; Risk Factors; Risk Reduction Behavior; Treatment Outcome; Vascular Surgical Procedures; Wound Healing

This paper is the review of the Consensus Document on Intermittent Claudication of the Central European Vascular Forum (CEVF), published in 2008, and and shared with the North Africa and Middle East Chapter of International Union of Angiology and the Mediterranean League of Angiology and Vascular Surgery. The Document presents suggestions for general practitioners and vascular specialists for more precise and appropriate management of PAD, particularly of intermittent claudication, and underlines the investigations that should be required by GPs and what the GP should expect from the vascular specialist (angiologist, vascular surgeon). The idea of the Faculty is to produce a short document, which is an easy reference in daily clinical practice, both for the GPs and vascular specialists.

Topics: Asymptomatic Diseases; Cardiovascular Agents; Consensus; Critical Illness; General Practice; Humans; Intermittent Claudication; Ischemia; Peripheral Arterial Disease; Referral and Consultation; Risk Factors; Risk Reduction Behavior; Severity of Illness Index; Treatment Outcome; Vascular Surgical Procedures

Peripheral arterial occlusive disease is becoming a major health problem in Western societies as the population continues to age. In addition to risk of limb loss, the complexity of the disease is magnified by its intimate association with medical comorbidity, especially cardiovascular and cerebrovascular disease. Risk factor modification and antiplatelet therapy are essential to improve long-term survival. Surgical intervention is indicated for intermittent claudication when a patient's quality of life remains unacceptable after a trial of conservative therapy. Open reconstruction and endovascular revascularization are cornerstone for limb salvage in patients with critical limb ischemia. Recent advances in catheter-based technology have made endovascular intervention the preferred treatment approach for infrainguinal disease in many cases. Nevertheless, lower extremity bypass remains an important treatment strategy, especially for reasonable risk patients with a suitable bypass conduit. In this review, we present a summary of current knowledge about peripheral arterial disease followed by a review of current, evidence-based medical and surgical therapy for infrainguinal arterial occlusive disease.

Topics: Amputation, Surgical; Cardiovascular Agents; Critical Illness; Endovascular Procedures; Evidence-Based Medicine; Humans; Intermittent Claudication; Ischemia; Limb Salvage; Lower Extremity; Peripheral Arterial Disease; Risk Factors; Treatment Outcome; Vascular Surgical Procedures

Ischemia-reperfusion injury forms the basis of tissue damage and cellular apoptosis in many pathologic and traumatic processes. The tissue damage follows a natural progression of cellular and metabolic events initiated by an ischemic episode. Ischemia causes intracellular/extracellular changes principally resulting in increased intracellular calcium, pH changes, and adenosine triphosphate depletion that end in cell death if the process is not interrupted. This interruption takes the form of reperfusion, characterized by a "flushing" of tissues with toxic metabolites, principally reactive oxygen species. The immediate effect is mitochondrial pore permeability, complement activation, cytochrome release, cytokine activation, inflammation, edema, neutrophil platelet adhesion, capillary plugging, and thrombosis. This sets the stage for the long recognized "no-reflow" phenomenon and progressive tissue death. Current recognition of cellular "cross-talk" and molecular events have introduced new logical strategies to sequentially combat the events occurring in relation to ischemia-reperfusion injury. These include mechanical preconditioning and pharmacological preconditioning and postconditioning strategies. It is likely that success in reversing or limiting tissue damage will be found in a sequential multitargeted approach using a combination of these strategies-clinical trials in this regard are sorely needed.

Topics: Cardiovascular Agents; Cell Adhesion Molecules; Endothelium-Dependent Relaxing Factors; Free Radical Scavengers; Humans; Hydrogen Sulfide; Hypothermia, Induced; Ischemia; Ischemic Postconditioning; Ischemic Preconditioning; Microcirculation; Nitric Oxide; Reperfusion Injury

Critical limb ischemia (CLI) results from inadequate blood flow to supply and sustain the metabolic needs of resting muscle and tissue. Infragenicular atherosclerosis is the most common cause of CLI, and it is more likely to develop when multilevel or diffuse arterial disease coincides with compromised run-off to the foot. Reports of good technical and clinical outcomes have advanced the endovascular treatment options, which have gained a growing acceptance as the primary therapeutic strategy for CLI, especially in patients with significant risk factors for open surgical bypass. In fact, endovascular recanalization of below-the-knee arteries has proven to be feasible and safe, reduce the need for amputation, and improve wound healing. The distribution of various vascular territories or angiosomes in the foot has been recognized, and it appears advantageous to revascularize the artery supplying the territory directly associated with tissue loss. In addition, the targeted application and local delivery of drugs using drug-coated balloons (DCB) during angioplasty has the potential to improve patency rates compared to balloon angioplasty alone.

Topics: Angioplasty, Balloon; Cardiovascular Agents; Critical Illness; Drug Carriers; Equipment Design; Humans; Ischemia; Lower Extremity; Popliteal Artery; Radiography; Treatment Outcome; Vascular Access Devices; Vascular Patency

Chronic lower limb ischemia diminishes the quality of life and is associated with a higher risk of limb amputation and cardiovascular mortality. Coexisting chronic renal disease can modulate the response to pharmacotherapy and revascularization, and thus influence prognosis. This paper reviews current literary evidence regarding therapeutic problems observed in patients with obliterative atherosclerosis and renal failure. We reviewed articles from peer-reviewed medical journals which were published between 2000 and 2011. The poorer clinical response in the discussed patients is not only connected with the direct failure of surgical and endovascular procedures, but first of all with the high mortality of the patients. There is still a lack of sufficient evidence on the effectiveness of currently used anti-atherosclerotic agents in patients with end-stage renal failure. A certain priority is the search for an effective therapeutic strategy that would reduce mortality associated with cardiovascular conditions in this particular group of patients. Identifying patients who can benefit most from costly endovascular procedures is another vital issue.

Topics: Cardiovascular Agents; Disease Progression; Humans; Ischemia; Kidney Failure, Chronic; Lower Extremity; Prognosis; Renal Dialysis; Risk Factors; Vascular Surgical Procedures

Critical limb ischemia refers to the clinical state of advanced arterial occlusive disease, placing an extremity at risk for gangrene and limb loss. Critical limb ischemia has 2 broad clinical subcategories that are vital to differentiate: acute limb ischemia and chronic arterial occlusive disease. This article reviews the etiologies, diagnosis, and treatment of critical limb ischemia.

Topics: Acute Disease; Arterial Occlusive Diseases; Cardiovascular Agents; Chronic Disease; Compartment Syndromes; Endarterectomy; Equipment Design; Humans; Ischemia; Lower Extremity; Magnetic Resonance Angiography; Reperfusion; Rhabdomyolysis; Thrombectomy; Thrombolytic Therapy; Tomography, X-Ray Computed; Upper Extremity

Critical limb ischemia (CLI) is a severe form of peripheral artery disease associated with high morbidity and mortality. The primary therapeutic goals in treating CLI are to reduce the risk of adverse cardiovascular events, relieve ischemic pain, heal ulcers, prevent major amputation, and improve quality of life (QoL) and survival. These goals may be achieved by medical therapy, endovascular intervention, open surgery, or amputation and require a multidisciplinary approach including pain management, wound care, risk factors reduction, and treatment of comorbidities. No-option patients are potential candidates for the novel angiogenic therapies. The application of genetic, molecular, and cellular-based modalities, the so-called therapeutic angiogenesis, in the treatment of arterial obstructive diseases has not shown consistent efficacy. This article summarizes the current status related to the management of patients with CLI and discusses the current findings of the emerging modalities for therapeutic angiogenesis.

Topics: Angiogenic Proteins; Animals; Bone Marrow Transplantation; Cardiovascular Agents; Critical Illness; Endovascular Procedures; Genetic Therapy; Humans; Ischemia; Lower Extremity; Neovascularization, Physiologic; Stem Cell Transplantation; Treatment Outcome; Vascular Surgical Procedures; Wound Healing

Critical limb ischemia (CLI) is the terminal stage of peripheral artery disease. Research in recent years has been largely focussed on treatment options such as bypass surgery / endovascular treatment, surgery / primary amputation and additional benefits of supportive pharmacotherapy. Despite this plethora of treatment options, however, patients continue to have a reduced health related quality of life (HRQoL). Aim of the present work was to review the available evidence of improvement of HRQoL with regard to different treatment options. We found that a number of clinical studies have been conducted using HRQoL measures mostly as secondary outcomes in patients with CLI and other less severe forms of peripheral arterial disease. The studies demonstrate a consistent improvement of HRQoL over baseline within the first few months after the intervention. Prostaglandins, but no other pharmacotherapies, appear to be effective in patients without an option for revascularization. Due to a largely differing patient population under investigation and the different degrees of disease progression it appears difficult however to compare different treatment options with respect to their impact on HRQoL. HRQoL improvement as a predefined endpoint of novel therapeutic approach studies should be considered more consequently.

Topics: Angioplasty, Balloon; Cardiovascular Agents; Critical Illness; Disease Progression; Evidence-Based Medicine; Humans; Ischemia; Predictive Value of Tests; Prostaglandins; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Treatment Outcome; Vascular Surgical Procedures

Despite obvious progress in management of diabetes mellitus, the DM-related complications rate remains inadmissibly high. Macroangiopathy is known to rank first amongst complications of diabetes mellitus, and coronary artery disease remains to be the major cause of death. Analysed herein are peculiarities of the clinical course in diabetic patients presenting with coronary artery disease and lower limb critical ischaemia, followed by discussing the issues concerning drug therapy, preoperative examination, and methods of diagnosis in this cohort of patients prior to vascular operations, assessment of the preoperative risk, indications for coronarography and myocardial revascularization. Also presented are the results of the main clinical trials dedicated to preoperative myocardial revascularization, including those in diabetic patients with limb critical ischaemia, and finally highlighting current importance of optimizing approaches to managing and working out algorithms of treatment policy for diabetic patients with a combination of coronary artery disease, diabetes mellitus, and critical limb ischaemia.

Topics: Algorithms; Cardiovascular Agents; Clinical Protocols; Clinical Trials as Topic; Combined Modality Therapy; Coronary Angiography; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Foot; Disease Management; Humans; Ischemia; Limb Salvage; Myocardial Revascularization; Preoperative Care; Risk Assessment; Severity of Illness Index; Survival Analysis

Cardiovascular diseases are among the leading causes of death in the developed world. Developing novel therapies for diseases like heart failure is crucial, but this is hampered by the high attrition rate in drug development. The withdrawal of drugs at the final hurdle of approval is mostly because of their unpredictable effects on normal cardiac rhythm. The advent of cardiac computational modeling in the last 5 decades has aided the understanding of heart function significantly. Recently, these models increasingly have been applied toward designing and understanding therapies for cardiac disease. This article will discuss how cellular models of electrophysiology, cell signaling, and metabolism have been used to investigate pharmacologic therapies for cardiac diseases including arrhythmia, ischemia, and heart failure.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Computer Simulation; Drug Discovery; Electrophysiological Phenomena; Heart; Heart Failure; Humans; Ion Channels; Ischemia; Models, Cardiovascular; Signal Transduction

Critical limb ischemia (CLI) continues to be a significantly morbid disease process for the aging population. Rigid guidelines for the management of patients with CLI are inappropriate due to the complexities that are involved in optimally treating these patients. A thin line exists in the decision process between medical management vs surgical management by revascularization or amputation, and the perception of "success" in this patient population is evolving. This review explores these issues and examines the challenges the treating physician will face when managing the care of patients with CLI. The epidemiology and natural history of CLI is discussed, along with the pathophysiology of the disease process. A review of the literature in regards to the different treatment modalities is presented to help the physician optimize therapy for patients with CLI. New scoring systems to help predict outcomes in patients with CLI undergoing revascularization or amputation are discussed, and an overview of the current status of patient-oriented outcomes is provided. Finally, we briefly examine emerging therapies for the treatment of CLI and provide an algorithm to help guide the practicing physician on how to approach the critically ischemic limb with regard to the complicated issues surrounding these patients.

Topics: Algorithms; Amputation, Surgical; Cardiovascular Agents; Clinical Protocols; Critical Illness; Disease Progression; Humans; Ischemia; Limb Salvage; Lower Extremity; Patient Selection; Practice Guidelines as Topic; Predictive Value of Tests; Reoperation; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome; Vascular Patency; Vascular Surgical Procedures

Many patients with severe intermittent claudication (IC) or critical limb ischemia (CLI) have chronic total occlusions (CTO) in their lower extremity vascular bed. The successful treatment of these lesions is becoming increasingly more important as the population ages and the prevalence of diseases such as diabetes mellitus and its consequences increases. Many of these patients have significant comorbidities and may benefit from less invasive treatment options. Several endovascular techniques have now become well established in the treatment of these lesions. Additionally, several new adjunctive tools have been developed to enhance the technical success of CTO revascularization. These tools and techniques offer a minimally invasive alternative for limb salvage in this compromised patient population and have become an established practice in many centers. Although some concerns about procedure durability and lower rates of primary patency exist, particularly when compared to surgical bypass, the limb salvage and amputation-free survival rates are much more encouraging. Advantages of these techniques compared to surgical bypass are reduced morbidity and mortality, reduced anesthesia requirements, and potential reductions in length of hospital stay and cost. In addition, bypass options are typically preserved after endovascular treatment. The more conventional and some newer endovascular treatment approaches, some of the adjunctive tools and techniques used in CTO revascularization as well as their clinical results will be discussed in this review.

Topics: Adult; Aged; Amputation, Surgical; Angioplasty, Balloon; Arterial Occlusive Diseases; Cardiovascular Agents; Chronic Disease; Constriction, Pathologic; Disease Progression; Equipment Design; Female; Humans; Intermittent Claudication; Ischemia; Limb Salvage; Male; Middle Aged; Radiography, Interventional; Stents; Treatment Outcome; Ultrasonography, Interventional; Vascular Surgical Procedures

Cancer treatment has improved extraordinarily in recent years. The development of targeted therapies has widened the cardiotoxic spectrum of antineoplastic drugs. Optimum management of cardiovascular disease before and during antineoplastic treatment is essential to reduce morbidity and mortality in cancer patients. This article reviews the incidence and characteristics of cardiotoxic effects of antineoplastic drugs with special focus on the pathophysiological mechanisms. It also emphasizes the importance of early detection and correction of cardiovascular risk factors and the relevance of close cardiac monitoring during antineoplastic treatment in order to reduce cardiotoxicity.

Topics: Antineoplastic Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Heart Diseases; Humans; Incidence; Ischemia; Molecular Targeted Therapy; Neoplasms; Ventricular Dysfunction, Left

Many randomized controlled trials (RCTs) were conducted to evaluate the efficacy of DanShen (Salvia miltiorrhizae, an herbal medicine) on ischemic vascular diseases (IVD). However, there has been no systematic evaluation of the quality of DanShen RCTs so far. The aims of this study were (1) to assess the quality of DanShen RCTs on IVD published in mainland China from 1998 to 2007 and (2) to explore the factors correlating with the quality.. A number of Chinese databases were searched, and most of DanShen RCTs on IVD were collected. According to CONSORT for TCM (Consolidated Standards for Reporting of Trials for Traditional Chinese Medicine) and the Jadad scale, the quality assessment and data abstraction were performed independently by two reviewers. One-way analysis of variance and Pearson correlation analysis were applied to explore the association between basic characteristic and the quality of the RCTs.. One hundred and fifty (150) DanShen RCTs were identified finally. The mean (standard deviation) score of 150 DanShen RCTs assessed by CONSORT for TCM was 23.87 (3.68), and 1.94 (0.82) by the Jadad scale, respectively. Only 6.7% (10/150) of RCTs were identified with high quality (Jadad score > or =4). Authors' affiliation, publication journal, sample size, and follow-up time were correlated with the quality of DanShen RCTs.. The quality of DanShen RCTs in mainland China has not been improved significantly over recent years, and the overall quality of DanShen RCTs is still poor.

Topics: Analysis of Variance; Cardiovascular Agents; Drugs, Chinese Herbal; Humans; Ischemia; Phenanthrolines; Randomized Controlled Trials as Topic; Salvia miltiorrhiza; Vascular Diseases

Critical limb ischemia (CLI) is the term used to designate the condition in which peripheral artery disease has resulted in resting leg or foot pain or in a breakdown of the skin of the leg or foot, causing ulcers or tissue loss. If not revascularized, CLI patients are at risk for limb loss and for potentially fatal complications from the progression of gangrene and the development of sepsis. The management of CLI requires a multidisciplinary team of experts in different areas of vascular disease, from atherosclerotic risk factor management to imaging, from intervention to wound care and physical therapy. In the past decade, the most significant change in the treatment of CLI has been the increasing tendency to shift from bypass surgery to less invasive endovascular procedures as first-choice revascularization techniques, with bypass surgery then reserved as backup if appropriate. The goals of intervention for CLI include the restoration of pulsatile, inline flow to the foot to assist wound healing, the relief of rest pain, the avoidance of major amputation, preservation of mobility, and improvement of patient function and quality of life. The evaluating physician should be fully aware of all revascularization options in order to select the most appropriate intervention or combination of interventions, while taking into consideration the goals of therapy, risk-benefit ratios, patient comorbidities, and life expectancy. We discuss the incidence, risk factors, and prognosis of CLI and the clinical presentation, diagnosis, available imaging modalities, and medical management (including pain and ulcer care, pharmaceutical options, and molecular therapies targeting angiogenesis). The endovascular approaches that we review include percutaneous transluminal angioplasty (with or without adjunctive stenting); subintimal angioplasty; primary femoropopliteal and infrapopliteal deployment of bare nitinol, covered, drug-eluting, or bioabsorbable stents; cryoplasty; excimer laser-assisted angioplasty; excisional atherectomy; and cutting balloon angioplasty.

Topics: Amputation, Surgical; Cardiovascular Agents; Combined Modality Therapy; Critical Illness; Extremities; Humans; Incidence; Intermittent Claudication; Ischemia; Limb Salvage; Minimally Invasive Surgical Procedures; Patient Care Team; Peripheral Vascular Diseases; Practice Guidelines as Topic; Risk Factors; Time Factors; Treatment Outcome; Vascular Surgical Procedures

Chronic critical limb ischemia still poses a substantial threat to both limb and life of the affected patients since these patients suffer typically also from associated cardiac and cerebrovascular disease and other severe comorbidities. Due to improved secondary prevention strategies and dedicated technical innovation, however, clinical outcomes have improved in the recent years. Purpose of this article is to provide a balanced discussion of contemporary treatment concepts for patients with critical limb ischemia with a focus on arterial revascularization.

Topics: Angioplasty, Balloon; Cardiovascular Agents; Chronic Disease; Critical Illness; Europe; Genetic Therapy; Humans; Ischemia; Lower Extremity; Prosthesis Design; Radiography; Secondary Prevention; Stents; Treatment Outcome; Vascular Surgical Procedures; Wound Healing

Trimetazidine (TMZ) is an effective and well-tolerated antianginal drug that possesses protective properties against ischemia-induced heart injury. Growing interest in metabolic modulation in recent years urged an up-to-date review of the literature on TMZ. This review consists of two major sections: (1) comprehensive and critical information about the pharmacological effects, mechanism of action, pharmacokinetics, side effects, and current usage of TMZ, and (2) developments in analytical techniques for the determination of the drug in raw material, pharmaceutical dosage forms, and biological samples.

Topics: Animals; Antioxidants; Cardiovascular Agents; Chemistry Techniques, Analytical; Chromatography; Coronary Circulation; Coronary Vessels; Electrochemistry; Energy Metabolism; Flow Injection Analysis; Heart Diseases; Humans; Ischemia; Luminescent Measurements; Myocardial Contraction; Myocardium; Reactive Oxygen Species; Spectrophotometry; Trimetazidine

Resistance to anticancer drugs is often related to deficient cell death execution pathways in cancer cells. Apoptosis, which denotes a form of cell death executed by caspases, was traditionally considered as the only physiological and programmed form of cell death. However, recent evidence indicates that programmed cell death (PCD) can occur in complete absence of caspase activation. Indeed, a large number of caspase-independent models are now defined and a key protein implicated in this type of PCD, apoptosis-inducing factor (AIF), has been identified. AIF is a mitochondrial protein with two faces looking in opposite life/death directions. Recently, the identification of five different isoforms allowed a better characterization of AIFs life/mitochondrial versus death/nuclear functions, as well as definition of its pro-apoptotic region and some of its nuclear partners. Importantly, much work on caspase-independent PCD has revealed that AIF participates in more PCD systems than initially thought. A wider molecular knowledge of AIF, and of the caspase-independent PCDs in which it is involved, are key to provide new insights into the role of PCD. There is no doubt that these insights will lead to the development of more selective and efficient drugs against cancer, degenerative diseases, and other pathological disorders implicating AIF.

Topics: Amino Acid Sequence; Animals; Antineoplastic Agents; Apoptosis; Apoptosis Inducing Factor; Cardiovascular Agents; Caspases; Cell Nucleus; Drug Resistance, Neoplasm; Enzyme Activation; Humans; Ischemia; Mitochondria; Models, Molecular; Molecular Sequence Data; Neoplasms; Neurodegenerative Diseases; Neuroprotective Agents; Protein Conformation; Protein Isoforms

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Algorithms; Aneurysm; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Aortic Rupture; Atherosclerosis; Cardiovascular Agents; Combined Modality Therapy; Comorbidity; Diagnostic Imaging; Evidence-Based Medicine; Female; Femoral Artery; Humans; Iliac Artery; Intestines; Ischemia; Leg; Male; Mesenteric Arteries; Middle Aged; Peripheral Vascular Diseases; Popliteal Artery; Prevalence; Randomized Controlled Trials as Topic; Renal Artery; Risk Factors; Risk Reduction Behavior; Treatment Outcome; Vascular Surgical Procedures

Mildronate (3-(2,2,2-trimethylhydrazinium)propionate; MET-88; meldonium, quaterine) is an antiischemic drug developed at the Latvian Institute of Organic Synthesis. Mildronate was designed to inhibit carnitine biosynthesis in order to prevent accumulation of cytotoxic intermediate products of fatty acid beta-oxidation in ischemic tissues and to block this highly oxygen-consuming process. Mildronate is efficient in the treatment of heart ischemia and its consequences. Extensive evaluation of pharmacological activities of mildronate revealed its beneficial effect on cerebral circulation disorders and central nervous system (CNS) functions. The drug is used in neurological clinics for the treatment of brain circulation disorders. It appears to improve patients' mood; they become more active, their motor dysfunction decreases, and asthenia, dizziness and nausea become less pronounced. Since the brain does not utilize fatty acids as fuel other mechanisms of action of mildronate in CNS should be considered. Several reports indicate the possible existence of an alternative, non-carnitine dependent mechanism of action of mildronate. Our recent findings suggest that CNS effects of mildronate could be mediated by stimulation of the nitric oxide production in the vascular endothelium by modification of the gamma-butyrobetaine and its esters pools. It is hypothesized that mildronate may increase the formation of the gamma-butyrobetaine esters. The latter are potent cholinomimetics and may activate eNOS via acetylcholine receptors or specific gamma-butyrobetaine ester receptors. This article summarizes known pharmacological effects of mildronate, its pharmacokinetics, toxicology, as well as the proposed mechanisms of action.

Topics: Animals; Cardiovascular Agents; Drug Evaluation; Humans; Ischemia; Ketone Bodies; Methylhydrazines; Models, Biological; Neuropharmacology; Nitric Oxide; Toxicology

United Therapeutics Corp (UTC) is developing treprostinil sodium (Remodulin, UT-15), a stable structural analog of prostacyclin, for the potential treatment of primary pulmonary (arterial) hypertension (PAH), peripheral vascular disease (PVD) and other cardiovascular conditions [327593], including critical limb ischemia (CLI) [412483]. In August 2000, UTC submitted the initial, non-clinical sections of an NDA for the treatment of pulmonary hypertension [378906]. Treprostinil, which had previously been designated as an Orphan Drug, was also awarded Priority Review status by the US FDA in October 2000 [385864], [386271]. In December 2000, UTC agreed with the FDA that the NDA for treprostinil did not need to be presented to the Cardiovascular and Renal Drugs Advisory Committee, which was expected to allow UTC and the FDA to work towards the 6-month Priority Review timeline [393888]. On August 9, 2001, the advisory committee recommended approval of treprostinil and UTC refiled the NDA on the same day [418682]. In February 2002, the FDA issued an approvable letter for treprostinil injection for the treatment of PAH. The FDA proposed drug labeling for PAH consistent with the treatment of both primary and secondary pulmonary hypertension in patients with New York Heart Association (NYHA) Class II-IV symptoms. The approvable letter also stated that the FDA intended to approve treprostinil with a requirement that UTC subsequently conduct a post-marketing controlled clinical trial to verify and further describe the drug's clinical benefit [439278]. In February 2001, UTC submitted a marketing authorization application (MAA) in France for approval of treprostinil for the treatment of PAH. Upon approval of the MAA, UTC planned to file for Mutual Recognition in other European countries and was also preparing similar submissions to non-European countries [391986], [397958]. By early 2001, phase II trials of treprostinil for the treatment of CLI were underway [412483]. In March 2001, the company was planning a phase III pivotal study in late-stage PVD by the end of 2001 [424180]. In April 2000, UTC was issued US-06054486 for the method of treating PVD with treprostinil [364130]. In February 2000, UTC entered into an agreement with Paladin Labs for the exclusive Canadian distribution of treprostinil for the remainder of clinical trials and after regulatory approvals [357302]. In November 2000, UTC and Antigen Pharmaceuticals entered into a strategic alliance for the distr

Topics: Cardiovascular Agents; Clinical Trials as Topic; Epoprostenol; Extremities; Humans; Hypertension, Pulmonary; Ischemia; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors

Although our understanding of the pathophysiology of atherosclerosis and peripheral vascular disease continues to grow, we have yet to discover a medication that can safely and efficaciously be given to most claudicants that will alleviate their symptoms to prevent disease progression. Many patients with intermittent claudication improve or remain stable without therapy if they attempt to alter their risk factors (e.g., control of diabetes, smoking cessation, lowering of cholesterol levels). However, many require concomitant drug therapy to alleviate symptoms of PVD, and some require surgical intervention. Even with the recent advances in therapeutic development and the promise of agents currently in clinical trials, the questions of who to treat, when treatment should begin, and which agent to use remain uncertain.

Topics: Angiotensin-Converting Enzyme Inhibitors; Arterial Occlusive Diseases; Cardiovascular Agents; Cyclooxygenase Inhibitors; Humans; Ischemia; Leg; Pentoxifylline; Platelet Aggregation Inhibitors; Prostaglandins, Synthetic; Vasodilator Agents

In toxicity studies, the examination of tissue sections for pathological changes is the principle method for the identification of organ toxicity and characterisation of the hazard of novel drugs for humans. Study of the patterns of pathological alterations also represents an important means of developing an understanding of the mechanism of toxicity. However as pathological change frequently represents a final common expression of diverse processes, additional functional information is often required for a clear understanding of the mechanisms of toxicity. This is exemplified in the evaluation of the effects of drugs on the beagle dog cardiovascular system where an understanding of mechanisms is crucial in the assessment of human risk. Particular patterns of drug-induced structural change in the myocardium or blood vessels are frequently linked to specific mechanisms of toxicity. However, assessment based on the interpretation of patterns of cardiovascular pathology alone may be misleading. Quite different changes in cardiac and vascular function or direct cellular toxicity may also be manifest by pathological features in common. Therefore, a clear understanding of mechanism frequently requires additional in vivo or in vitro physiological, pharmacological, biochemical or other mechanistic information. The beagle dog remains an important model for the study of cardiovascular toxicity because in this species, haemodynamic changes and pathological alterations can be related in a way that provides the basis for the safe study in humans of novel drugs with cardiovascular activity.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular System; Coronary Vessels; Disease Models, Animal; Dogs; Heart Atria; Heart Valves; Heart Ventricles; Humans; Ischemia; Myocardium; Species Specificity

Three consecutive periods in the natural history of atherosclerosis are amenable to medical treatment. Plaque development is the main target of prevention, which also aims at slowing the progression of already existing plaques. The control of several established risk factors (high blood cholesterol, high blood pressure, diabetes mellitus, tobacco smoking) has already yielded encouraging benefits, especially in the field of secondary prevention. More efficient prophylaxis is to be expected, either from the further improved control of these classic risk factors with earlier, stronger, and longer interventions or from the correction of newly established causal determinants of atherosclerosis. A plaque manifests itself clinically through progressive or abrupt obstruction of the arterial lumen, which can be avoided or retarded by interventions aimed at reducing thrombosis, at controlling plaque instability (the major cause of thrombosis), and at enhancing arterial remodeling (which allows compensatory enlargement of the arterial lumen). When ischemia has occurred, a third wave of palliative treatments aims at improving energy supply to the organ with compromised vascularization. Classic treatments reduce oxygen consumption or improve oxygen extraction by ischemic tissues. In addition, the design of drugs to enhance the development of collateral channels appears to be promising therapeutic approach.

Topics: Animals; Arterial Occlusive Diseases; Arteriosclerosis; Cardiovascular Agents; Humans; Ischemia

Luminor is a new drug-coated angioplasty balloon, which is approved by the European Conformity market. The aim of the present study is to analyze the 1-year results, in terms of effectiveness and safety, of the Luminor® 14/14M and 35 drug-coated balloons (iVascular, Sant Vicenç dels Horts, Barcelona, Spain) in a special cohort of critical limb ischemia (CLI) of the Luminor registry.. Luminor is phase IV, nonrandomized, prospective, observational, and multicenter clinical study. The present study includes patients with CLI to analyze the effectiveness, in terms of primary patency, and the safety defined by the major adverse effects: any cause mortality, major amputation, and/or clinically driven target lesion revascularization (TLR). Both femoropopliteal and below-the-knee infrapopliteal lesions were treated. All the end points were assessed after the procedure, at 30 days, 6 and 12 months thereafter.. About 148 patients (101 males; mean age, 73.2 ± 11.4 years) with CLI were included. About 83.3% were classified as Rutherford's class 5. Diabetes mellitus was diagnosed in 71.6%; hypertension, hyperlipidemia, renal insufficiency, and coronary disease were present in 87.2%, 57.4%, 29.7%, and 39.2% of the sample, respectively. The average follow-up was 11.2 ± 3.27 months. The primary patency and the freedom of clinically driven TLR, at 1 year, were 87.7% and 92.1%, respectively. Survival and freedom from major amputations were 85.1% and 84.7%, respectively.. Even with a very sick population, the results at 12 months are highly satisfactory with reference to survival, freedom from amputation, patency, and the absence of reintervention.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Critical Illness; Equipment Design; Female; Femoral Artery; Humans; Ischemia; Limb Salvage; Male; Middle Aged; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Progression-Free Survival; Prospective Studies; Risk Factors; Spain; Time Factors; Vascular Access Devices; Vascular Patency

The "leave nothing behind" strategies have been becoming a popular treatment for femoropopliteal arteriosclerosis obliterans. Atherectomy before drug-coated balloon (DCB) angioplasty may have an advantage in improving the efficiency of drug delivery into the blood vessel wall. This study aimed to compare the therapeutic effects of directional atherectomy combined with DCB angioplasty with DCB angioplasty alone in the treatment of femoropopliteal arteriosclerosis obliterans.. Patients with femoropopliteal arteriosclerosis obliterans who received endovascular therapy from June 2016 to June 2018 in our hospital and presented with life-limiting claudication or severe chronic limb ischemia comprised the study cohort. The patients were randomized to receive directional atherectomy combined with DCB angioplasty (n = 45) or DCB alone (n = 49). Ninety-four patients were enrolled in our study with 72 males, and the mean age was 67 ± 10 years. The mean lesion length was 112 ± 64 mm.. There were no significant differences in the baseline characteristics of patients and lesions between the 2 randomized groups (P > 0.05). Flow-limiting dissections occurred more frequently in the DCB group (n = 12; 24.5%) than in the DA-DCB group (n = 2; 4.4%; P = 0.006). The technical success rate in the DA-DCB group was superior to that in the DCB group (95.6% vs. 75.5%, P = 0.006). The mean follow-up duration was 16.7 ± 6.1 months in the DCB group and 15.3 ± 5.8 months in the DA-DCB group. No amputations were performed. The overall mortality in the DCB group was 4.1% (2/49), while all patients survived in the DA-DCB group. The 12-month and 24-month primary patencies in the DA-DCB group were greater than those in the DCB group (80.5% vs. 75.7% and 67.1% vs. 55.1%, respectively); however, using all available patency data, no significant differences over time were observed (P = 0.377).. In this study, directional atherectomy combined with DCB angioplasty can decrease the flow-limiting dissection rate in the treatment of femoropopliteal arteriosclerosis obliterans compared with DCB angioplasty alone. There was no significant difference between the 2 groups in terms of primary patency rate which was needed to be further clarified.

Topics: Aged; Angioplasty, Balloon; Arteriosclerosis Obliterans; Atherectomy; Beijing; Cardiovascular Agents; Chronic Disease; Coated Materials, Biocompatible; Female; Femoral Artery; Humans; Intermittent Claudication; Ischemia; Male; Middle Aged; Popliteal Artery; Prospective Studies; Time Factors; Treatment Outcome; Vascular Access Devices; Vascular Patency

The goal of this study was to evaluate the 5-year follow-up data of the IN.PACT DEEP (Randomized IN.PACT Amphirion Drug-Coated Balloon [DCB] vs. Standard Percutaneous Transluminal Angioplasty [PTA] for the Treatment of Below-the-Knee Critical Limb Ischemia [CLI]) trial.. Initial studies from randomized controlled trials have shown comparable short-term outcomes of DCB angioplasty versus PTA in patients with CLI with infrapopliteal disease. However, the long-term safety and effectiveness of DCB angioplasty remain unknown in this patient population.. IN.PACT DEEP was an independently adjudicated prospective, multicenter, randomized controlled trial that enrolled 358 subjects with CLI. Subjects were randomized 2:1 to DCB angioplasty or PTA. Assessments through 5 years included freedom from clinically driven target lesion revascularization, amputation, and all-cause death. Additional assessments were conducted to identify risk factors for death and major amputation, including paclitaxel dose tercile.. Freedom from clinically driven target lesion revascularization through 5 years was 70.9% and 76.0% (log-rank p = 0.406), and the incidence of the safety composite endpoint was 59.8% and 57.5% (log-rank p = 0.309) in the DCB angioplasty and PTA groups, respectively. The rate of major amputation was 15.4% for DCB angioplasty compared with 10.6% for PTA (log-rank p = 0.108). Given the recent concern regarding a late mortality signal in patients treated with paclitaxel-coated devices, additional analyses from this study showed no increase in all-cause mortality with DCB angioplasty (39.4%) compared with PTA (44.9%) (log-rank p = 0.727). Predictors of mortality included age, Rutherford category >4, and previous revascularization but not paclitaxel by dose tercile.. Tibial artery revascularization in patients with CLI using DCB angioplasty resulted in comparable long-term safety and effectiveness as PTA. Paclitaxel exposure was not related to increased risk for amputation or all-cause mortality at 5-year follow-up. (Study of IN.PACT Amphirion™ Drug Eluting Balloon vs. Standard PTA for the Treatment of Below the Knee Critical Limb Ischemia [INPACT-DEEP]; NCT00941733).

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Critical Illness; Equipment Design; Europe; Female; Humans; Ischemia; Limb Salvage; Male; Middle Aged; Paclitaxel; Peripheral Arterial Disease; Prospective Studies; Recurrence; Risk Factors; Time Factors; Treatment Outcome; Vascular Patency

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Constriction, Pathologic; Delayed-Action Preparations; Female; Femoral Artery; Germany; Humans; Ischemia; Limb Salvage; Male; Middle Aged; Peripheral Arterial Disease; Popliteal Artery; Prospective Studies; Recovery of Function; Severity of Illness Index; Sirolimus; Time Factors; Treatment Outcome; Vascular Patency

To investigate the efficacy of the paclitaxel-coated, self-expanding, nitinol Stentys Stent System in tibioperoneal lesions ≤50 mm long.. The prospective, single-arm, multicenter PES-BTK-70 trial ( ClinicalTrials.gov identifier NCT01630070) evaluated the safety and efficacy of the coronary Stentys Stent System in the treatment of a stenotic or occlusive lesion ≤50 mm long in the tibioperoneal arteries of patients with critical limb ischemia (CLI). Between January 2012 and May 2013, 70 patients (mean age 74.6±9.4 years; 45 men) with CLI [Rutherford category 4 (37, 52.9%) or 5 (33, 47.1%)] received a Stentys drug-eluting stent for the treatment of infrapopliteal stenosis (60, 85.7%) or occlusion (10, 14.3%). The mean lesion length was 17.2 mm (4.0-58.5). The primary outcome measures were primary patency at 6 months (duplex ultrasound) and 12 months (angiography). Secondary outcomes included limb salvage and freedom from target lesion revascularization (TLR). Kaplan-Meier estimates of the outcomes are given with the 95% confidence intervals (CI).. Technical and procedure success (<30% residual stenosis without major complications) was achieved in 68 (97.1%) of 70 cases. Primary patency was 87.6% (95% CI 83.5% to 91.7%) at 6 months and 72.6% (95% CI 66.9% to 78.3%) at 1 year. Freedom from TLR was 79.1% at 1 year (95% CI 73.9% to 84.3) and limb salvage was 98.5% (95% CI 97.0 to 100.0). No stent fractures were found by core laboratory review of all follow-up imaging data available up to 12 months.. In this study, the self-expanding, nitinol, paclitaxel-eluting, coronary Stentys stent was found to be safe and effective in the below-the-knee region, with results similar to the most recent limus-eluting stent trials.

Topics: Aged; Aged, 80 and over; Alloys; Angiography; Belgium; Cardiovascular Agents; Constriction, Pathologic; Critical Illness; Drug-Eluting Stents; Endovascular Procedures; Female; Humans; Ischemia; Kaplan-Meier Estimate; Limb Salvage; Male; Middle Aged; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Prospective Studies; Prosthesis Design; Risk Factors; Self Expandable Metallic Stents; Time Factors; Treatment Outcome; Vascular Patency

Clinical outcomes reported after treatment of infrapopliteal lesions with drug-eluting stents (DESs) have been more favorable compared with percutaneous transluminal angioplasty with a bailout bare metal stent (PTA-BMS) through midterm follow-up in patients with critical limb ischemia. In the present study, long-term results of treatment of infrapopliteal lesions with DESs are presented.. Adults with critical limb ischemia (Rutherford category ≥4) and infrapopliteal lesions were randomized to receive PTA-BMS or DESs with paclitaxel. Long-term follow-up consisted of annual assessments up to 5 years after treatment or until a clinical end point was reached. Clinical end points were major amputation (above ankle level), infrapopliteal surgical or endovascular reintervention, and death. Preserved primary patency (≤50% restenosis) of treated lesions was an additional morphological end point, assessed by duplex sonography. In total, 74 limbs (73 patients) were treated with DESs and 66 limbs (64 patients) were treated with PTA-BMS. The estimated 5-year major amputation rate was lower in the DES arm (19.3% versus 34.0% for PTA-BMS;. Both clinical and morphological long-term results after treatment of infrapopliteal lesions in patients with critical limb ischemia are improved with DES compared with PTA-BMS.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00471289.

Topics: Amputation, Surgical; Angioplasty, Balloon; Cardiovascular Agents; Critical Illness; Disease-Free Survival; Drug-Eluting Stents; Humans; Ischemia; Kaplan-Meier Estimate; Limb Salvage; Lower Extremity; Netherlands; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Prosthesis Design; Recurrence; Risk Factors; Time Factors; Treatment Outcome; Vascular Patency

Severe limb ischaemia (SLI) is defined as the presence of rest pain and/or tissue loss secondary to lower extremity atherosclerotic peripheral arterial disease. The superficial femoral and popliteal arteries are the most commonly diseased vessels in such patients and are being increasingly treated using endovascular revascularisation techniques. However, it is currently unknown whether drug-eluting stents and drug-coated balloons confer additional clinical benefits over more established techniques using plain balloons and bare metal stents, or whether they represent a cost-effective use of NHS resources.. The BASIL-3 trial is a UK National Institute for Health Research, Health Technology Assessment Programme-funded, multicentre, randomised controlled trial (RCT) comparing the clinical and cost-effectiveness of plain balloon angioplasty with or without bail-out bare metal stenting, drug-coated balloon angioplasty with or without bail-out bare metal stenting, and primary stenting with drug-eluting stents for SLI secondary to femoro-popliteal disease. Patients with 'multilevel' disease may receive aorto-iliac and/or infrapopliteal treatments concurrently with their randomised femoro-popliteal intervention. The primary clinical outcome is amputation-free survival defined as the time to major (above the ankle) amputation of the index limb or death from any cause. The primary outcome for the economic analysis is cost per quality-adjusted life year. Secondary outcome measures include overall survival, major adverse limb events, major adverse cardiac events, relief of ischaemic pain, healing of tissue loss, and quality of life. The required sample size has been calculated at 861 participants (287 on each arm). These patients will be recruited over 3 years and followed-up for between 2 and 5 years.. BASIL-3 is a pragmatic RCT designed to reflect current UK clinical practice. The results will inform decision-making regarding the appropriateness of funding the use of drug-coated balloons and drug-eluting stents, by the NHS, for the management of SLI due to femoro-popliteal disease.. ISRCTN Registry, identifier: ISRCTN14469736 . Registered on 22 October 2015.

Topics: Amputation, Surgical; Angioplasty, Balloon; Cardiovascular Agents; Clinical Protocols; Coated Materials, Biocompatible; Cost-Benefit Analysis; Disease-Free Survival; Drug-Eluting Stents; Health Care Costs; Humans; Ischemia; Limb Salvage; Lower Extremity; Metals; Peripheral Arterial Disease; Prosthesis Design; Quality-Adjusted Life Years; Regional Blood Flow; Sample Size; Severity of Illness Index; State Medicine; Stents; Time Factors; Treatment Outcome; United Kingdom; Vascular Access Devices; Vascular Patency

Optimal medical therapy after endovascular therapy in patients with critical limb ischemia (CLI) remains unclear. Therefore, we investigated whether cilostazol reduce restenosis after balloon angioplasty for infrapopliteal lesions in CLI patients.. This study was performed as a multicenter, prospective, randomized, open-label, blinded-end point study with independent angiographic core laboratory adjudication. Sixty patients were eligible and 53 patients were enrolled and allocated. The primary end point was 3-month angiographic restenosis. The main secondary end points included major adverse limb event (MALE defined as requirement of any reintervention or major amputation), perioperative complications, major amputation, all-cause death, and hemorrhagic events.. A total of 53 patients were randomized and all received their allocated intervention. Two patients in the cilostazol plus aspirin group and 1 in the aspirin group did not undergo any angioplasty for infrapopliteal stenotic lesions, and therefore were excluded from analysis. Finally, 38 vessels in 25 patients in the cilostazol plus aspirin group and as many cases in the aspirin group were included in the analysis. There were no significant differences in baseline characteristics between the 2 groups. The 3-month restenosis rate was 82% in the cilostazol + aspirin group and 81% in the aspirin group, with no significant difference (P = 0.91). The MALE rate was 11% in the cilostazol plus aspirin group and 8% in the aspirin group (P = 0.73). In addition, no significant difference was observed in any secondary points.. Cilostazol did not reduce 3-month angiographic restenosis after balloon angioplasty for below-the-knee lesion in CLI patients.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Angiography; Angioplasty, Balloon; Cardiovascular Agents; Cilostazol; Female; Humans; Ischemia; Japan; Leg; Limb Salvage; Male; Middle Aged; Peripheral Arterial Disease; Prospective Studies; Recurrence; Severity of Illness Index; Tetrazoles; Time Factors; Treatment Outcome

The superiority of drug eluting stents versus bare metal stents or balloon angioplasty in the treatment of patients with critical limb ischemia and infrapopliteal lesions has been established. However, only shorter lesions were evaluated. This study was designed to evaluate the immediate and long-term (up to 12 months) outcome of the Xience Prime™ Everolimus-Eluting Coronary Stent System (Abbott Vascular) in a controlled, prospective, multi-center investigation for long lesions up to 10 cm.. All patients with critical limb ischemia and long infrapopliteal lesions between 30 and 100 mm, who met the inclusion criteria, were included in this study. The primary endpoint was primary patency at 12 months, defined as absence of restenosis (≥50% stenosis) or occlusion based on quantitative analysis of contrast angiography.. Between August 2011 and October 2013, 60 patients were enrolled in this study with a mean lesion length of 47.40±25.06 mm (range 2-100 mm). The primary patency rate at 12 months was 75.4%. Freedom from target lesion revascularization was 84.9%. The amputation rate was rare (94.4% freedom from amputation). At the 12-month follow-up time point, a total of 36 out of 42 (85.7%) patients improved in their Rutherford classification by at least 1 class.. The use of everolimus-eluting stents in longer infrapopliteal lesions in the treatment of critical limb ischemia is safe and effective with a comparable primary patency, freedom from target lesion revascularization and amputation free survival as in short lesions.

Topics: Adult; Aged; Aged, 80 and over; Amputation, Surgical; Angioplasty; Australia; Belgium; Cardiovascular Agents; Disease-Free Survival; Drug-Eluting Stents; Everolimus; Germany; Humans; Ischemia; Kaplan-Meier Estimate; Leg; Limb Salvage; Male; Middle Aged; Peripheral Arterial Disease; Prospective Studies; Prosthesis Design; Risk Factors; Time Factors; Treatment Outcome; Vascular Patency; Young Adult

To report the 12-month results of the MAJESTIC clinical study of the self-expanding Eluvia paclitaxel-eluting stent in the treatment of femoropopliteal lesions.. The prospective, single-arm, multicenter trial (clinicaltrials.gov identifier NCT01820637) enrolled 57 patients (mean age 69±9 years; 47 men) with chronic lower limb ischemia referable to de novo or restenotic lesions in the native superficial femoral and/or proximal popliteal arteries. A third of the patients had diabetes. Mean lesion length was 70.8±28.1 mm, and diameter stenosis was 86.3%±16.2%; 26 (46%) lesions were occluded. Primary patency was defined as duplex ultrasound peak systolic velocity ratio ≤2.5 and the absence of target lesion revascularization (TLR) or bypass. Major adverse events (MAEs) included all-cause death through 1 month and target limb major amputation and TLR through 12 months.. All 57 patients had a single Eluvia stent implanted, employing pre- and postdilation in 93% (53/57) and 95% (54/57) of cases, respectively. Technical success was 97% (55/57; 2 failures due to residual stenosis >30%). At 12 months, primary patency was 96% (49/51) and the MAE rate was 4% (2/53); both MAEs were TLRs. No stent fractures were identified. There were no major amputations. One death occurred 368 days postprocedure, unrelated to the device or procedure. Improvements in the Rutherford category were sustained through 1 year, with 81% (43/53) exhibiting no symptoms (category 0) and 13% (7/53) presenting with mild claudication (category 1). Mean ABI improved from 0.73±0.22 at baseline to 1.02±0.20 at 12 months.. MAJESTIC results showed that patients whose femoropopliteal arteries were treated with the Eluvia drug-eluting stent sustained high patency and low MAE rates through 12 months.

Topics: Aged; Alloys; Ankle Brachial Index; Australia; Blood Flow Velocity; Cardiovascular Agents; Chronic Disease; Constriction, Pathologic; Drug-Eluting Stents; Endovascular Procedures; Europe; Female; Femoral Artery; Humans; Ischemia; Kaplan-Meier Estimate; Limb Salvage; Male; Middle Aged; New Zealand; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Prospective Studies; Prosthesis Design; Regional Blood Flow; Self Expandable Metallic Stents; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Duplex; Vascular Patency

The aim of this study was to evaluate the safety and efficacy of percutaneous catheter-delivered ultrasound energy to improve local paclitaxel delivery effects in patients with critical limb ischemia (CLI) treated for femoral-popliteal arterial disease.. Treatment of patients with CLI continues to be the greatest challenge in peripheral artery disease; in particular, treatment of femoral-popliteal chronic total occlusion is characterized by poor primary patency.. This single-center, single-blind, randomized trial included 56 patients with CLI randomly assigned to treatment in 2 groups: 28 patients (the control group) were treated with drug-eluting balloons, and 28 patients (the study group) were treated with intravascular ultrasound using the CardioProlific Genesis System followed by local administration of a liquid mixture of iopromide 370 and paclitaxel 1.0 μg/mm. No adverse procedural events were observed; all 56 patients tolerated the procedure well. At 6-month follow-up, no myocardial infarction, deaths, or amputations were observed in either group. In the study group, the rate of restenosis at 6 months was 3.6% (1 of 28), and the rate of target lesion revascularization (TLR) was 0% (0 of 28); at 12 months, the rate of TLR was 3.8% (1 of 26), and the rate of amputation was 0% (0 of 26). In the control group, the rate of restenosis at 6 months was 21.4% (6 of 28), and the rate of TLR was 10.7% (3 of 28); at 12 months, the rate of TLR was 36% (9 of 25), and the rate of amputation was 16% (4 of 25).. This study demonstrates encouraging results at 6- and 12-month follow-up in patients treated with ultrasound and paclitaxel compared with drug-eluting balloons. Larger multicenter studies are required to validate this approach.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon; Cardiovascular Agents; Catheterization, Peripheral; Coated Materials, Biocompatible; Constriction, Pathologic; Critical Illness; Equipment Design; Female; Femoral Artery; Humans; Ischemia; Male; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Single-Blind Method; Time Factors; Treatment Outcome; Ultrasonic Therapy; Ultrasonography, Interventional; Vascular Access Devices; Vascular Patency

The aim of BIOLUX P-II (BIOTRONIK'S-First in Man study of the Passeo-18 LUX drug releasing PTA Balloon Catheter vs. the uncoated Passeo-18 PTA balloon catheter in subjects requiring revascularization of infrapopliteal arteries) trial was to compare the safety and efficacy of a novel paclitaxel-coated drug-eluting balloon (DEB) versus an uncoated balloon (percutaneous transluminal angioplasty [PTA]) in de novo or native restenotic lesions of the infrapopliteal arteries in patients with claudication and critical limb ischemia.. DEB have shown promising results in femoropopliteal lesions, but data for infrapopliteal lesions are scarce.. In this prospective, multicenter, randomized first-in-man study, 72 patients were randomized 1:1 to either a Passeo-18 Lux DEB (Biotronik AG, Buelach, Switzerland) (n = 36) or Passeo-18 PTA (n = 36). Follow-up assessments were scheduled at 1, 6, and 12 months, with angiographic assessment at 6 months. Adverse events were adjudicated by an independent clinical events committee, and angiographic parameters were assessed by an independent core laboratory.. The primary safety endpoint (a composite of all-cause mortality, target extremity major amputation, target lesion thrombosis, and target vessel revascularization at 30 days) was 0% in the DEB group versus 8.3% in the PTA group (p = 0.239). The primary performance endpoint (patency loss at 6 months) was 17.1% in the DEB group versus 26.1% in the PTA group (p = 0.298), and major amputations of the target extremity occurred in 3.3% versus 5.6% of the patients at 12 months, respectively.. The Passeo-18 Lux DEB has been proven to be safe and effective in infrapopliteal lesions with comparable outcomes to PTA.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amputation, Surgical; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Critical Illness; Equipment Design; Female; Humans; Intermittent Claudication; Ischemia; Limb Salvage; Male; Middle Aged; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Prospective Studies; Radiography; Recurrence; Time Factors; Treatment Outcome; Vascular Access Devices; Vascular Patency; Young Adult

The effectiveness and durability of endovascular revascularization therapies for chronic critical limb ischemia (CLI) are challenged by the extensive burden of infrapopliteal arterial disease and lesion-related characteristics (e.g., severe calcification, chronic total occlusions), which frequently result in poor clinical outcomes. While infrapopliteal vessel patency directly affects pain relief and wound healing, sustained patency and extravascular care both contribute to the ultimate "patient-centric" outcomes of functional limb preservation, mobility and quality of life (QoL).. IN.PACT DEEP is a 2:1 randomized controlled trial designed to assess the efficacy and safety of infrapopliteal arterial revascularization between the IN.PACT Amphirion™ paclitaxel drug-eluting balloon (IA-DEB) and standard balloon angioplasty (PTA) in patients with Rutherford Class 4-5-6 CLI.. This multicenter trial has enrolled 358 patients at 13 European centers with independent angiographic core lab adjudication of the primary efficacy endpoint of target lesion late luminal loss (LLL) and clinically driven target lesion revascularization (TLR) in major amputation-free surviving patients through 12-months. An independent wound core lab will evaluate all ischemic wounds to assess the extent of healing and time to healing at 1, 6, and 12 months. A QoL questionnaire including a pain scale will assess changes from baseline scores through 12 months. A Clinical Events Committee and Data Safety Monitoring Board will adjudicate the composite primary safety endpoints of all-cause death, major amputation, and clinically driven TLR at 6 months and other trial endpoints and supervise patient safety throughout the study. All patients will be followed for 5 years. A literature review is presented of the current status of endovascular treatment of CLI with drug-eluting balloon and standard PTA. The rationale and design of the IN.PACT DEEP Trial are discussed. IN.PACT DEEP is a milestone, prospective, randomized, robust, independent core lab-adjudicated CLI trial that will evaluate the role of a new infrapopliteal revascularization technology, the IA-DEB, compared to PTA. It will assess the overall impact on infrapopliteal artery patency, limb salvage, wound healing, pain control, QoL, and patient mobility. The 1-year results of the adjudicated co-primary and secondary endpoints will be available in 2014.. NCT00941733.

Topics: Amputation, Surgical; Angioplasty, Balloon; Cardiovascular Agents; Clinical Protocols; Coated Materials, Biocompatible; Critical Illness; Disability Evaluation; Equipment Design; Europe; Humans; Ischemia; Limb Salvage; Lower Extremity; Paclitaxel; Pain Management; Pain Measurement; Popliteal Artery; Prospective Studies; Quality of Life; Research Design; Severity of Illness Index; Time Factors; Treatment Outcome; Vascular Access Devices; Vascular Patency; Wound Healing

The aim of the present paper was to make a report of the 12-month clinical outcomes of the DEBELLUM (Drug-Eluting-Balloon-Evaluation-for-Lower-Limb- mUltilevel-treatMent) randomized trial.. From September 2010 to March 2011, 50 patients were randomized between drug eluting balloon (DEB, N.=25) and conventional angioplasty balloon (PTA, N.=25). Patients were symptomatic for claudication and critical limb ischemia, with de novo stenosis or occlusion in the femoropopliteal (SFA) and infrapopliteal (BTK) region. Only in the SFA primary stenting was allowed and postdilatation performed with DEB or PTA depending on the assigned group.. One hundred and twenty-two lesions were treated: 92 (75.4%) SFA, 30 (24.6%) BTK. Twenty (40%) patients presented multilevel concomitant femoropopliteal and infra-popliteal lesions. Late lumen loss (LLL) was 0.64±0.9 mm in DEB group vs. 1.81±0.1 mm in the control group (P=0.01). In non-stented segment LLL was 0.63±0.9 mm (DEB) vs. 1.70±0.6 mm (PTA), P<0.01. In the stent subgroup was LLL 0.65±0.2 mm (DEB) vs. 1.91±0.3 mm (PTA), P<0.01. In the femoropopliteal region the overall LLL was 0.61±0.8 mm for DEB vs. 1.84±0.3 mm for PTA (P=0.02). BTK the overall LLL was 0.66±0.9 mm (DEB) vs. 1.69±0.5 mm (PTA) (P=0.03). The overall TLR was 12.2% for DEB and 35.3% for PTA (P<0.05). Amputation rate was 4% (DEB) vs. 12% (PTA), P=0.36. Thrombosis was 4% (DEB) vs. 8% (PTA), P≥0.05. Major adverse events 24% (DEB) vs. 60% (PTA), P<0.05. ABI improved more in the DEB group: 0.81±0.3 vs. 0.68±0.13 (P=0.02). Fontaine stage increased (from II b to I) 80% DEB vs. 56% PTA (P<0.05).. Results confirm and reinforce initial 6-month outcomes. In.Pact DEB balloons can be considered efficient to reduce restenosis rate.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Angioplasty, Balloon; Ankle Brachial Index; Cardiovascular Agents; Critical Illness; Drug Carriers; Equipment Design; Female; Femoral Artery; Hemodynamics; Humans; Intermittent Claudication; Ischemia; Kaplan-Meier Estimate; Limb Salvage; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Popliteal Artery; Risk Factors; Rome; Thrombosis; Time Factors; Treatment Outcome; Vascular Access Devices; Vascular Patency

Ischaemia in different arterial territories before acute myocardial infarction (AMI) may influence post-AMI outcomes. No studies have evaluated prospectively collected information on ischaemia and its effect on short- and long-term coronary mortality. The objective of this study was to compare patients with and without prospectively measured ischaemic presentations before AMI in terms of infarct characteristics and coronary mortality.. As part of the CALIBER programme, we linked data from primary care, hospital admissions, the national acute coronary syndrome registry and cause-specific mortality to identify patients with first AMI (n = 16,439). We analysed time from AMI to coronary mortality (n = 5283 deaths) using Cox regression (median 2.6 years follow-up), comparing patients with and without recent ischaemic presentations. Patients with ischaemic presentations in the 90 days before AMI experienced lower coronary mortality in the first 7 days after AMI compared with those with no prior ischaemic presentations, after adjusting for age, sex, smoking, diabetes, blood pressure and cardiovascular medications [HR: 0.64 (95% CI: 0.57-0.73) P < 0.001], but subsequent mortality was higher [HR: 1.42 (1.13-1.77) P = 0.001]. Patients with ischaemic presentations closer in time to AMI had the lowest seven day mortality (P-trend = 0.001).. In the first large prospective study of ischaemic presentations prior to AMI, we have shown that those occurring closest to AMI are associated with lower short-term coronary mortality following AMI, which could represent a natural ischaemic preconditioning effect, observed in a clinical setting.. Clinicaltrials.gov identifier NCT01604486.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Atherosclerosis; Cardiovascular Agents; Cerebrovascular Disorders; Electronic Health Records; Female; Follow-Up Studies; Humans; Ischemia; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Peripheral Arterial Disease; Prognosis; Prospective Studies; Risk Factors

Critical limb ischemia, the most severe form of peripheral arterial disease, results in extremity amputation if left untreated. Endovascular recanalization of stenotic or occluded infrapopliteal arteries has recently emerged as an effective form of therapy, although the duration of patency is typically limited by restenosis. Recently, it has been suggested that drug-eluting stents originally developed for the coronary arteries might also be effective in preventing restenosis in the infrapopliteal arteries. This prospective, randomized, controlled clinical trial tested the hypothesis that treatment of infrapopliteal arterial occlusive lesions with an everolimus-eluting stent (Xience V) would provide superior patency to treatment with a bare-metal stent (Multi-Link Vision).. A sample size of 140 patients was planned to be enrolled at five European investigative sites. The primary end point was arterial patency at 12 months, defined as the absence of ≥50% restenosis based on quantitative analysis of contrast angiography.. Between March of 2008 and September of 2009, 74 patients were treated with Xience V and 66 patients were treated with Vision. After 12 months, the primary patency rate after treatment with Xience V was 85% compared with 54% after treatment with Vision (P = .0001). Treatment with Xience V significantly reduced mean in-stent diameter stenosis (21% ± 21% vs 47% ± 27%; P < .0001) and mean in-stent late lumen loss (0.78 ± 0.63 vs 1.41 ± 0.89 mm; P = .001). There were no differences in the percentage of patients receiving a designation of Rutherford class 0 or 1 at the 12-month follow-up visit (56% for Vision, vs 60% for Xience V; P = .68). Major extremity amputations were rare in both groups (two for Vision and one for Xience V). The use of the Xience V stent significantly reduced the need for repeat intervention: freedom from target lesion revascularization was 91% for Xience V vs 66% for Vision (P = .001).. Treatment of the infrapopliteal occlusive lesions of critical limb ischemia with everolimus-eluting stents reduces restenosis and the need for reintervention compared with bare metal stents.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Angioplasty; Arterial Occlusive Diseases; Cardiovascular Agents; Constriction, Pathologic; Critical Illness; Drug-Eluting Stents; Europe; Everolimus; Female; Humans; Ischemia; Kaplan-Meier Estimate; Limb Salvage; Male; Metals; Middle Aged; Popliteal Artery; Prospective Studies; Prosthesis Design; Radiography; Recurrence; Risk Assessment; Risk Factors; Sirolimus; Stents; Time Factors; Treatment Outcome; Vascular Patency

Atherosclerotic peripheral arterial disease is a major health problem in the western world, often manifested as intermittent claudication, affecting 10-20% males above 60 years. Ischemic complications can lead to rest pain, ulceration and gangrene. The treatment of choice for critical limb ischemia (CLI) is vascular reconstruction or endovascular interventions. Medical management with vasodilator antiplatelet prostaglandins, could be considered in patients unsuitable for surgery. Long term follow-up on previous prostaglandin studies has been insufficient to evaluate amputation rates. Hence this study evaluated safety and longer term efficacy of taprostene sodium, a prostacyclin (PGI2) analogue in CLI. The aim of this study was to determine whether Taprostene sodium, a PGI2 analogue, was a safe and effective treatment for CLI.. This paper reports the data from the Scottish-Finnish-Swedish PARTNER Study Group which consisted of a double-blind placebo controlled multi-centre study evaluating Taprostene compared to placebo. The primary endpoints were pain relief and early ulcer healing response at the end of the four week infusion phase and amputation at six months follow-up. The patients were randomly allocated to receive taprostene or placebo in a two to one randomization of active versus placebo. A total of 111 patients with CLI were recruited. Taprostene was given twice a day over two 2 hour periods for four weeks. The early response was evaluated at the end of the four week infusion phase. In patients with rest pain without ulceration, a positive response was complete pain relief without any requirement for analgesic therapy. However in patients with ulceration, a positive response was defined as a decrease in the ulcer size by >30%. Amputation scores were compared at the end of the 6 months follow-up period for all participants.. Seventy-four patients received taprostene and 37 placebo. Overall, 61 male patients were enrolled in the study along with 50 females with 11% more women in the taprostene (active) group. For both patients with and without ulcers there was no statistically significant difference noted in the early response between those receiving taprostene and those receiving placebo infusion. The percentage of patients without any amputations was 43% in the taprostene group compared to 38% in the control group at the end of six months; however, these results were not statistically significant.. Although a reasonable number of patients enrolled in the study it has not been possible to demonstrate any statistically significant benefit of taprostene over placebo. This may be due to more patients with risk factors for peripheral artery disease (PAD) such as hypertension, diabetes mellitus and cigarette smoking in the actively treated group and also due the increased number of women in the active group who are known to generally respond less favourably to antiplatelet agents.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Analgesics; Cardiovascular Agents; Chi-Square Distribution; Critical Illness; Double-Blind Method; Drug Administration Schedule; Epoprostenol; Europe; Female; Humans; Infusions, Parenteral; Ischemia; Limb Salvage; Lower Extremity; Male; Pain; Pain Measurement; Placebo Effect; Time Factors; Treatment Outcome; Wound Healing

In a (negative) multicenter randomized trial on management for inoperable critical lower limb ischemia, comparing spinal cord stimulation and best medical treatment, a number of pre-defined factors were analyzed for prognostic value. We included a radiological arterial disease score, modified from the SVS/ISCVS runoff score. The purpose of this analysis was to evaluate clinical factors and commonly used circulatory measurements for prognostic modeling in patients with critical lower limb ischemia. We determined the incidence of amputation and its relation to various pre-defined risk factors. A total of 120 patients with critical limb ischemia were included in the study. The integrity of circulation in the affected limb was evaluated on five levels: suprainguinal, infrainguinal, popliteal, infrapopliteal and pedal. A total radiological arterial disease score was calculated from 1 (full integrity of circulation) to 20 (maximally compromised state). We used Cox regression analysis to quantify prognostic effects and differential treatment (predictive) effects. Major amputation occurred in 33% of the patients at 6 months and in 51% at 2 years. The presence of ischemic skin lesions and the radiological arterial disease score were independent prognostic factors for amputation. Patients with ulcerations or gangrene had a higher amputation risk (hazard ratio 2.38, p = 0.018 and 2.30, p = 0.036 respectively) as well as patients with a higher radiological arterial disease score (hazard ratio 1.17 per increment, p = 0.003). We did not observe significant interactions between prognostic factors and the effect of spinal cord stimulation. In conclusion, in patients with critical lower limb ischemia, the presence of ischemic skin lesions and the described radiological arterial disease score can be used to estimate amputation risk.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Arterial Occlusive Diseases; Cardiovascular Agents; Constriction, Pathologic; Critical Illness; Electric Stimulation Therapy; Female; Humans; Ischemia; Kaplan-Meier Estimate; Leg Ulcer; Lower Extremity; Male; Middle Aged; Netherlands; Proportional Hazards Models; Radiography; Risk Assessment; Risk Factors; Severity of Illness Index; Spinal Nerves; Time Factors; Treatment Failure

The Percutaneous transluminal Angioplasty and Drug eluting stents for Infrapopliteal lesions in critical limb ischemia (PADI) trial is a prospective, multicenter, randomized, controlled, double-arm study investigating the safety and efficacy of primary paclitaxel-eluting stent implantation vs primary percutaneous transluminal angioplasty (PTA) in infrapopliteal lesions in critical limb ischemia (CLI). PTA with provisional "bailout" stent implantation is currently an accepted treatment for arterial obstructions in CLI, including those in below-the-knee arteries. A drawback compared to open bypass surgery is the relatively high restenosis rate. One proposed method to reduce restenosis is the use of drug-eluting stents (DES), as these have shown good results in the coronary bed. Primary DES implantation for focal obstructions in infrapopliteal arteries in CLI potentially reduces restenosis compared to PTA alone and may subsequently prolong effect of treatment, allowing for better wound healing, and preventing recurrence of symptoms. In this article, we report on rationale, design, and progress of the PADI trial, which investigates the safety and efficacy of a paclitaxel-eluting stent system compared to PTA with provisional bare metal stent implantation.

Topics: Angioplasty, Balloon; Arterial Occlusive Diseases; Cardiovascular Agents; Constriction, Pathologic; Critical Illness; Drug-Eluting Stents; Humans; Ischemia; Lower Extremity; Metals; Netherlands; Paclitaxel; Popliteal Artery; Prospective Studies; Prosthesis Design; Research Design; Secondary Prevention; Stents; Treatment Outcome

To evaluate the effects of iloprost, in addition to surgery, on the outcome of acute lower limb ischemia (ALLI).. Post-hoc analysis of a randomized, double-blind, placebo-controlled study.. In the context of the ILAILL (ILoprost in Acute Ischemia of Lower Limbs) study, 192 elderly patients (>70 years old) undergoing surgery for ALLI were assigned to receive perioperative iloprost (intra-arterial, intra-operative bolus of 3000 ng, plus intravenous infusion of 0.5-2.0 ng/kg/min for six hours/day for 4-7 days following surgery), or placebo (iloprost: n=100; placebo: n=92). Patients were followed-up for three-months following surgical revascularization.. The combined incidence of death and amputation (primary study end-point) was significantly reduced in patients treated with iloprost (16.0% vs 27.2% in the placebo group; hazard ratio 1.99, 95% confidence interval 1.05-3.75, p=0.03). A statistically significant lower mortality (6.0%) was reported in patients receiving iloprost, compared to controls (15.2%) (hazard ratio 2.93, 1.11-7.71, p=0.03). The overall incidence of death and major cardiovascular events was lower in patients receiving iloprost compared to those assigned placebo (24.0% and 35.9%, respectively), at the limits of statistical significance (relative risk 1.64, 0.97-2.79, p=0.06).. These results confirm the poor outcome in elderly patients with ALLI. Based on a subgroup analysis iloprost, as an adjuvant to surgery, appears to reduce the combined end-point of death and amputation.

Topics: Acute Disease; Aged; Aged, 80 and over; Amputation, Surgical; Cardiovascular Agents; Chemotherapy, Adjuvant; Double-Blind Method; Extremities; Female; Humans; Iloprost; Incidence; Ischemia; Kaplan-Meier Estimate; Male; Proportional Hazards Models; Risk Factors; Time Factors; Treatment Outcome; Vascular Surgical Procedures

To report the 1-year angiographic and clinical outcome from a prospective single-center study investigating the infrapopliteal application of sirolimus-eluting versus bare metal stents in patients with critical limb ischemia (CLI) who underwent below-the-knee endovascular revascularization.. Stenting was performed as a bailout procedure for suboptimal angioplasty results (flow-limiting dissection, elastic recoil, or postangioplasty residual stenosis >30%). In the first 29 patients, infrapopliteal stenting was performed with bare metal stents (group B) and with sirolimus-eluting stents in the other 29 patients (group S).. Below-the-knee angioplasty and stenting involved 65 lesions in 40 infrapopliteal arteries of 29 limbs in group B and 66 lesions in 41 infrapopliteal arteries of 29 limbs in group S. Baseline comorbidities (hyperlipidemia and symptomatic cardiac and carotid disease) were more pronounced in group S (p<0.05). At 6 months, sirolimus-eluting stents demonstrated significantly higher primary patency (OR 5.625, 95% CI 1.711 to 18.493, p = 0.004) and decreased in-stent binary restenosis (OR 0.067, 95% CI 0.021 to 0.017, p<0.001) and in-segment binary restenosis (OR 0.229, 95% CI 0.099 to 0.533, p = 0.001). After 1 year, sirolimus-eluting stents were steadily associated with increased primary patency (OR 10.401, 95% CI 3.425 to 31.589, p<0.001) and significantly less in-stent (OR 0.156, 95% CI 0.060 to 0.407, p<0.001) and in-segment (OR 0.089, 95% CI 0.023 to 0.349, p = 0.001) binary restenosis. In addition, sirolimus-eluting stents were associated with significantly fewer cumulative target lesion reinterventions at 6 months (OR 0.057, 95% CI 0.008 to 0.426, p = 0.005) and 1 year (OR 0.238, 95% CI 0.067 to 0.841, p = 0.026). No significant differences between groups B and S were noted at 1 year with respect to mortality (10.3% versus 13.8%, respectively), minor amputation (17.2% versus 10.3%), or limb salvage (100% versus 96%).. The application of sirolimus-eluting stents reduces the restenosis rate in the infrapopliteal arteries and the rate of repeat endovascular procedures the first year after treatment.

Topics: Aged; Angiography, Digital Subtraction; Angioplasty, Balloon; Cardiovascular Agents; Constriction, Pathologic; Female; Follow-Up Studies; Humans; Ischemia; Leg; Male; Metals; Odds Ratio; Popliteal Artery; Prospective Studies; Prosthesis Design; Research Design; Secondary Prevention; Sirolimus; Stents; Time Factors; Treatment Outcome; Vascular Patency

Data supporting the utility of percutaneous treatment to maintain vein graft patency have been limited to a collection of single-institution, retrospective analyses. Using the prospective, multi-institutional PREVENT III database, we sought to define the outcomes for endovascular vs surgical vein bypass graft revision and to define predictors for the success or failure of these interventions.. A nested cohort study of 1404 patients in the PREVENT III trial who underwent infrainguinal vein bypass grafting for critical limb ischemia was performed to identify those patients who underwent either open surgical or endovascular graft revision. All patients in PREVENT III were followed up for 1 year from the initial bypass operation. The following were modeled as end points from the time of the initial open surgical or endovascular revision: freedom from graft reintervention, occlusion, amputation, and death.. A total of 156 open surgical and 134 endovascular reinterventions were performed, with a mean follow-up after revision of 193 and 151 days, respectively. Although the demographics for each group were similar, the choice of repair was influenced by the interval between the index graft placement and the initial revision, with a high percentage of the early graft revisions treated with an open surgical procedure (0-1 months: 84% open surgical vs 16% endovascular; P < .001). The primary end point (ie, failure resulting in repeat graft revision, graft occlusion, or major amputation) was reached in 30.2% of the endovascular and 26.2% of the open surgical individuals, with significant improvements in the durability of graft revisions noted in the open surgical group (12-month amputation-/revision-free survival of 75% for the open surgical and 56% for the endovascular group; hazard ratio, 2.2; 95% confidence interval, 0.92-5.26; P = .043). Furthermore, subgroup analysis revealed this benefit to be most profound within the subset of thrombosed grafts undergoing salvage (P = .006). For revisions performed to treat graft stenosis, early outcomes were similar, with a trend favoring the open surgical group developing beyond 6 months. Although 80% of open surgical and 64% of endovascular-revised grafts required no further intervention, endovascular revisions necessitated significantly more reinterventions to maintain patency. The mean hospital lengths of stay (open surgical, 2.1 days; endovascular, 1.7 days) and quality of life at completion of the study (VascuQoL: open surgical, 4.72; endovascular, 4.76) were similar between the groups.. Open surgical revision of infrainguinal vein grafts provides an increased freedom from further reinterventions or major amputation, but early success rates for endovascular procedures were similar, particularly for nonoccluded grafts. With time, endovascular revisions necessitate an increasing number of reinterventions and manifest higher rates of failure.

Topics: Aged; Amputation, Surgical; Angioplasty; Cardiovascular Agents; Critical Illness; Double-Blind Method; Extremities; Female; Graft Occlusion, Vascular; Humans; Ischemia; Length of Stay; Male; North America; Oligonucleotides; Patient Selection; Prospective Studies; Quality of Life; Reoperation; Risk Assessment; Risk Factors; Secondary Prevention; Time Factors; Treatment Failure; Ultrasonography, Doppler, Duplex; Vascular Patency; Vascular Surgical Procedures; Veins

The influence of operator-dependent variables on the outcomes of lower extremity bypass (LEB) surgery have primarily been reported in single-institution, retrospective studies. We utilized data from a prospective, multicenter trial to identify technical variables that were significantly associated with early and midterm results of autogenous LEB for limb salvage.. The PREVENT III trial database includes 1404 North American patients with critical limb ischemia (CLI) who underwent LEB using excised autogenous vein. The study protocol excluded claudicants and in situ reconstructions. Technical factors analyzed included vein diameter, conduit type, graft length, vein orientation, location of proximal and distal anastomoses, and performance of completion imaging. Univariate analysis was used to determine the effect of these factors on 30 day and 1-year outcomes. Multivariate Cox regression models evaluated the influence of these factors while adjusting for age, sex, race, tobacco, diabetes, dialysis-dependency, previous index limb bypass, and study drug (edifoligide) administration. The primary outcomes were primary patency (PP), primary assisted patency (PAP), and secondary patency (SP) assessed by Kaplan-Meier method.. Univariate analysis revealed that vein diameter <3.5 mm and composite graft type were significantly associated with early (30 day) graft failure. At 1 year, multivariate analysis revealed that patency rates were negatively associated with diameter <3.5 mm (PP, PAP, SP), non-great saphenous vein (GSV) type (PP, SP), and graft lengths >50 cm (PP only). Limb salvage and survival at 1 year were not significantly impacted by technical variables. Employing a prespecified trial definition of high-risk conduits (diameter <3mm or nonsingle segment GSV; 24% of entire cohort) revealed that use of such conduits was associated with a 2.1-fold increased risk of 30 day graft failure (P < .05), as well as reduced PP, PAP, and SP at 1 year. Use of a high-risk conduit was also associated with an increased index length of stay (mean 9.37 vs 8.71 days, P = .03) and a greater number of reinterventions (mean 0.67 vs 0.42, P < .0001) over the ensuing year.. In this large, multicenter cohort of patients undergoing LEB for CLI, vein diameter and conduit type were the dominant technical determinants of early and late graft failure. High-risk conduits and longer grafts may benefit from aggressive postoperative graft surveillance.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Double-Blind Method; Extremities; Female; Graft Occlusion, Vascular; Humans; Ischemia; Length of Stay; Limb Salvage; Male; Middle Aged; North America; Oligonucleotides; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Transplantation, Autologous; Treatment Failure; Ultrasonography; Vascular Patency; Vascular Surgical Procedures; Veins

The white blood cell count (WCC) is known to be predictive of cardiac and cerebral vascular events. No one has yet investigated this in critical limb ischaemia (CLI).. Baseline WCC was examined in relation to lower limb amputation 6 months after a 4 week treatment period with i.v. placebo or i.v. taprostene in 366 patients with CLI.. The WCC was related to a significant increase in amputation, relative risk 1.6 (p=0.001, 95% CI: 1.2-2.0) in CLI patients with WCC > or =9x10(9)/l vs patients with WCC <9x10(9)/l. Its association with disabling amputation persisted on logistic regression analyses which included cigarette smoking as a variable and also treatment group (p<0.001). The WCC is therefore an easily measurable prognostic variable in CLI.. The white blood cell may promote intractable tissue ischaemia by capillary plugging and/or release of toxic chemicals and may have distinct effects on tissue viability.

Topics: Amputation, Surgical; Cardiovascular Agents; Double-Blind Method; Epoprostenol; Female; Humans; Ischemia; Leg; Leukocyte Count; Logistic Models; Male; Neutrophils; Placebos; Single-Blind Method; Smoking

Several animal studies show antinociceptive effects of intrathecally administered adenosine and its analogs. However, there is no clinical experience regarding the effects of intrathecal adenosine in humans.. The side effects and analgesic effects of intrathecal adenosine (500-2,000 microg) on experimental pain were studied in 12 healthy volunteers. Before and after adenosine was given, the authors evaluated the cold pain rating of the foot (submersion in ice water for 1 min), the forearm ischemic pain rating during a 30-min tourniquet test, and the thermal and tactile pain thresholds on healthy and inflamed skin after application of mustard oil (4 min) to the calf. The areas of secondary allodynia surrounding the inflammation were also determined. The cerebrospinal fluid level of adenosine was determined before and after injection.. Intrathecal adenosine caused a 1,000- to 2,000-fold elevation of the cerebrospinal fluid concentration. One volunteer experienced transient (30 min) lumbar pain after injection at a dose of 2,000 microg. There were no other complications in any other volunteers. Adenosine reduced, in a non-dose-dependent manner, the areas of secondary allodynia after skin inflammation (brush, P < 0.06; and von Frey hair, P < 0.03) and reduced the forearm tourniquet ischemic pain rating (P = 0.01). Tactile pain thresholds were significantly reduced by mustard oil inflammation during control, whereas adenosine treatment prevented this reduction. The ice water-induced cold pain rating was not influenced by adenosine.. An intrathecal adenosine injection of 1,000 microg lacked side effects in healthy volunteers. The compound attenuated different types of experimental pain.

Topics: Adenosine; Adolescent; Adult; Blood Pressure; Cardiovascular Agents; Dermatitis; Female; Half-Life; Heart Rate; Humans; Immersion; Injections, Spinal; Ischemia; Male; Middle Aged; Pain Measurement; Sensory Thresholds

Critical limb ischaemia (CLI) is a serious clinical condition that often immediately precedes limb loss. The Consensus Documents of 1989 and 1991 attempted to define CLI and give direction to its investigation and management. Whilst the need for such a consensus was clear and should be supported we believe the definition of CLI as documented in the Consensus Documents I and II recommendation number I is wrong. We present evidence from 140 patients with severe limb ischaemia taken from the PARTNER Group studies to support our request for an amendment to the ankle pressure recommendation from < or = 50 mmHg to >50 mmHg and big toe pressure from < or = 30 mmHg to >30 mmHg for the purpose of conducting clinical trials and to include Doppler index and tcPO2 as additional parameters. We also believe that the current document may be actually excluding the only group of patients likely to benefit from drug treatment or other interventions and that the above amendment should be prioritized.

Topics: Amputation, Surgical; Blood Pressure; Cardiovascular Agents; Combined Modality Therapy; Consensus Development Conferences as Topic; Epoprostenol; Europe; Follow-Up Studies; Humans; Ischemia; Leg; Peripheral Vascular Diseases; Prostaglandins, Synthetic; Retrospective Studies; Survival Rate; Treatment Outcome; Vascular Surgical Procedures

Cardiovascular disease guidelines recommend that patients with established peripheral artery disease (PAD) are prescribed antihypertensive, lipid-lowering, and antiplatelet medication to reduce cardiovascular ischaemic events. However, the prescribing of these medications for patients with PAD within New Zealand (NZ) remains undefined.. This was a retrospective observational cohort study of patients in the Midland region of NZ, that underwent PAD-related percutaneous and surgical intervention between 1st January 2010 and 31st December 2021. Patient level data was collected. The primary outcome was prescribing of cardioprotective medications either before or within 1 year of incident procedure. Secondary outcome was overall survival.. There were 2547 patients included. Antihypertensive prescription occurred in 80.7%, lipid-lowering in 77.4% and antithrombotic in 89.9%. Concomitant ischaemic heart disease increased prescription of cardioprotective medications. Women were prescribed less lipid-lowering medication compared to men. Māori men were prescribed less antiplatelet medication compared to non-Māori men. On univariate analysis lipid-lowering and antiplatelet medication showed survival advantage, while antihypertensive and anticoagulation did not. After adjustment for age, sex, end stage renal failure and presence of chronic limb-threatening ischaemia, best medical therapy was associated with better survival (HR 0.88, 95% CI 0.79-0.98, P = 0.02).. This study highlights areas of deficiency in prescribing of cardioprotective medication in this high-risk group. These could be targets for national quality improvement initiatives.

Topics: Antihypertensive Agents; Australasian People; Cardiovascular Agents; Cardiovascular Diseases; Cohort Studies; Female; Humans; Hypolipidemic Agents; Ischemia; Lipids; Male; Maori People; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Protective Agents; Retrospective Studies; Risk Factors; Treatment Outcome

Topics: Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Diabetes Mellitus; Femoral Artery; Humans; Ischemia; Limb Salvage; Peripheral Arterial Disease; Popliteal Artery; Retrospective Studies; Time Factors; Treatment Outcome; Vascular Patency

Topics: Aged; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Femoral Artery; Humans; Ischemia; Peripheral Arterial Disease; Sirolimus; Treatment Outcome; Vascular Access Devices

We evaluated the outcomes of revascularization in patients with chronic limb-threatening ischemia (CLTI) treated in real-world settings. This is a prospective multicenter cohort study with 12-month follow-up enrolling patients (n = 287) with CLTI undergoing open, endovascular, or hybrid lower extremity revascularization. The primary end point was amputation-free survival (AFS) at 12 months. Cox proportional analysis was used to determine independent predictors of amputation and restenosis. At 30 days, major adverse cardiovascular and major adverse limb events (MALE) rates were 3.1% and 2.1%, respectively. At 1 year, the overall survival rate was 88.8%, the AFS was 86.6%, and the primary patency was 70.5%. Freedom from MALE was 62.5%. After multivariate analysis, smoking (hazard ratio [HR] = 2.2,

Topics: Aged; Amputation, Surgical; Cardiovascular Agents; Chronic Disease; Endovascular Procedures; Female; Humans; Ischemia; Italy; Limb Salvage; Male; Peripheral Arterial Disease; Prospective Studies; Recurrence; Registries; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vascular Surgical Procedures

Inflammation is a component in the pathogenesis of critical limb ischemia. We aimed to assess how inflammation affects response to treatment in patients treated for critical limb ischemia using neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocytes ratios (PLR) as markers of inflammation.. Patients in a single tertiary cardiovascular center with critical limb ischemia unsuitable for surgical or interventional revascularization were retrospectively identified. Data were collected on medical history for risk factors, previous surgical or endovascular revascularization, and outcome. A standard regimen of low molecular weight heparin, aspirin, statins, iloprost infusions, and a standard pain medication protocol were applied to each patient per hospital protocol. Patients with improvement in ischemic pain and healed ulcers made up the responders group and cases with no worsening pain or ulcer size or progression to minor or major amputations made up the non-responders group. Responders and Non-responders were compared for risk factors including pretreatment NLR and PLR.. 268 included patients who were not candidates for surgical or endovascular revascularization were identified. Responders had significantly lower pretreatment NLR (4.48 vs 8.47, p < 0.001) and PLR (162.19 vs 225.43, p = 0.001) values. After controlling for associated risk factors NLR ≥ 4.63 (p < 0.001) and PLR ≥ 151.24 (p = 0.016) were independently associated with no response to treatment.. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocytes ratio are markers of inflammation that are reduced in patients improving with medical treatment suggesting a decreased state of inflammation before treatment in responding patients.

Topics: Aged; Cardiovascular Agents; Critical Illness; Female; Humans; Iloprost; Ischemia; Lymphocyte Count; Lymphocytes; Male; Middle Aged; Neutrophils; Peripheral Arterial Disease; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Wound Healing

Topics: Aged; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Drug-Eluting Stents; Female; Humans; Ischemia; Lower Extremity; Male; Paclitaxel; Patient Safety; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Treatment Outcome

Reporting outcomes with a new generation paclitaxel eluting balloon (Luminor®; iVascular, Vascular, S.L.U., Barcelona, Spain) in the popliteal district. Endovascular treatment of popliteal artery atherosclerotic disease is still debated without definitive evidences.. From January to June 2019, patients' data presenting popliteal artery atherosclerotic diseases and treated with the Luminor® (iVascular) drug eluting balloon (DEB) were prospectively collected. Critical limb ischemia (CLI) or severe claudication associated with popliteal artery stenosis >50% were the inclusion criteria. Measured outcomes were technical success, early and late results; including mortality, morbidity, symptoms recurrence, amputation, ankle-brachial index (ABI), survival, primary patency, secondary patency, freedom from restenosis. Median follow-up was 22.43 ± 4 (mean:21.58; IQR:20-24) months.. Of the 33 included patients, 28 (85%) were diagnosed with CLI, with a mean preoperative run-off score of 5.39 (r:0-10; SD:3) and a chronic popliteal occlusion in 21 (64%). Technical success was achieved in all cases. Perioperative mortality was observed in 1 (3%) patient and perioperative complications in 2 (6%). During the follow-up were reported 2 symptoms recurrence; a significant ABI increase (0.57; IQR:0.41-0.47 vs. 0.69; IQR:0.50-0.67; P < 0.01); 1 (3%) major and 2 (6%) minor amputations. Estimated 24 months survival, primary patency, secondary patency, and freedom from restenosis were 97%, 96.9%, 100%, and 93.8% respectively.. In this prospective study, the use of the Luminor® (iVascular) was safe and effective in addressing atherosclerotic popliteal artery lesions. Larger studies with longer term-outcomes are required to assess the durability of this device in the popliteal artery.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Constriction, Pathologic; Critical Illness; Equipment Design; Female; Humans; Intermittent Claudication; Ischemia; Limb Salvage; Male; Paclitaxel; Peripheral Arterial Disease; Plaque, Atherosclerotic; Popliteal Artery; Prospective Studies; Recurrence; Severity of Illness Index; Time Factors; Treatment Outcome; Vascular Access Devices; Vascular Patency

Paclitaxel (PTX)-coated peripheral arterial devices have been shown to decrease femoropopliteal artery restenosis and the need for reintervention compared with non-PTX-coated devices. The data regarding PTX efficacy and safety come from randomized controlled trials that almost exclusively enrolled patients with claudication. The outcomes of PTX treatment in patients who present with chronic limb-threatening ischemia (CLTI) are unknown. This study compares long-term outcomes in patients with CLTI treated with and without PTX.. We retrospectively reviewed 983 patients with CLTI treated with femoropopliteal artery angioplasty, atherectomy, stent, or combination between 2011 and 2019. Procedures were performed with additional proximal or distal tibial interventions as needed. Kaplan-Meier survival analysis and multivariable Cox-regression analysis compared overall survival (OS), amputation-free survival (AFS), freedom from major amputation (ff-MA), and freedom from target vessel revascularization (ff-TVR) between patients treated with and without PTX.. Demographics, comorbidities, and Rutherford class were similar between 574 PTX (58.5%) and 409 non-PTX (41.6%) patients except that non-PTX patients were more likely to be male (56.2% vs 49.7%), dialysis dependent (19.6% vs 14.3%), and have higher average creatinine (2.3 vs 1.8 mg/dL). Through 4-year follow-up, the PTX group demonstrated a significant increase in OS (56.2% vs 43.9%, P = .013), AFS (52.6% vs 36.1%, P < .0001), ff-MA (87.4% vs 78.7%, P = .0007), and ff-TVR (77.6% vs 70.6%, P = .012). Multivariable Cox-regression analysis demonstrated that PTX treatment was associated with improved OS, AFS, ff-MA, and ff-TVR.. In patients with CLTI, treatment with a PTX-coated device is associated with improved OS, AFS, ff-MA, and ff-TVR through 4-year follow-up. PTX-coated devices may be especially beneficial in patients who present with CLTI.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Angioplasty, Balloon; Cardiovascular Agents; Chronic Disease; Coated Materials, Biocompatible; Equipment Design; Female; Humans; Ischemia; Limb Salvage; Male; Middle Aged; Paclitaxel; Peripheral Arterial Disease; Progression-Free Survival; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors

Atherosclerotic disease of the common femoral artery (CFA), commonly associated with multilevel disease affecting the femoropopliteal segment, can cause claudication or contribute to critical limb ischemia. Although endovascular therapy for the management of peripheral arterial disease (PAD) has been increasingly utilized, its role in CFA lesions remains controversial. The aim of this study was to investigate the safety and efficacy of drug (DCB) vs non drug coated balloon angioplasty (BA) at the CFA segment.. In this two-center study, we identified 154 patients treated either with DCB (n = 47) or BA (n = 107) for CFA lesions. Hazard ratios (HR) and the respective 95% confidence interval (CI) were synthesized to examine the association between the two groups in terms of target lesion revascularization (TLR), limb loss, and major adverse limb event (MALE) at 12 and 24 months of follow up.. This real-world population included a high percentage of patients with critical limb ischemia (43%) and moderate to severe lesion calcification (75%). Adjunctive atherectomy was performed in 97.9% of DCB cases (N = 46/47) and 44.7% of BA cases (N = 51/114). The overall procedural success rate was 95% without any differences between the two groups. Post-angioplasty dissections were observed in 15 cases [DCB: 8.5% (N = 4/47) vs BA: 9.7% (N = 11/113); p = .81], while distal embolization occurred in one patient in the DCB group and one in the BA group (p = .52). Provisional stenting was more commonly necessary in BA vs. DCB cases (12.3% vs 2.13%, p = .044). Physiologic assessment during follow up demonstrated a better mean 2-year ABI for the DCB group (mean: 0.9; SD: 0.2) vs BA group (mean: 0.6; SD: 0.4), although statistical significance was not reached (p = .06). No difference between the two groups was detected in terms of freedom from TLR (DCB: 75.5% vs BA: 86.8%; HR: 1.31; 95% CI: 0.46-3.67; p = .61), freedom from limb loss (DCB: 83.8% vs BA: 83.6%; HR: 1.04; 95% CI: 0.36-2.99; p = .94) or freedom from MALE (DCB: 83.5% vs BA: 78%; HR: 0.73; 95% CI: 0.26-1.99; p = .53) at 24 m of follow up. However, at the end of follow up more deaths were observed in patients treated with BA than DCB (DCB: 14.9% vs BA: 31.7%; p = .03). Patients who required provisional stenting were at higher risk for limb loss 2 years after the initial procedure (multivariate: HR: 4.54; 95% CI: 1.09-18.85; p = .04).. Both DCB and non-DCB strategies are effective modalities for revascularization of patients with CFA lesions. Larger prospective studies are necessary to determine the relative benefit, if any, of drug-eluting technologies for the treatment of common femoral artery disease.

Topics: Aged; Amputation, Surgical; Angioplasty, Balloon; Atherectomy; California; Cardiovascular Agents; Coated Materials, Biocompatible; Colorado; Comparative Effectiveness Research; Critical Illness; Female; Femoral Artery; Humans; Ischemia; Limb Salvage; Male; Middle Aged; Peripheral Arterial Disease; Retrospective Studies; Risk Assessment; Risk Factors; Stents; Time Factors; Treatment Outcome; Vascular Access Devices; Vascular Calcification; Vascular Patency

The aim of this study is to evaluate the performance and predictors of failure of paclitaxel drug-eluting stents and paclitaxel-coated balloons in the treatment of long-segment femoropopliteal disease. We report a retrospective cohort analysis of patients treated with paclitaxel-eluting stents and paclitaxel-coated balloons in lesions >100 mm, which were not included in any of the pivotal trials.. Ninety-seven patients with peripheral vascular disease (Rutherford III-VI) underwent long-segment (≥100 mm) femoropopliteal drug-eluting stent (DES) implantation or angioplasty with drug-coated balloons (DCB). Patients were followed after their initial procedure for target lesion restenosis, defined as a reduction in lumen diameter by greater than 50% as measured by duplex ultrasonography (ratio >2).. The median length of the affected arterial segments was 110 mm (interquartile range [IQR] 100-150, absolute range 100-260) using up to 4 overlapping stents. During the median 13-month follow-up (IQR 7-16), no early thrombotic occlusions occurred within 30 days, but 28 (29%) patients developed a target lesion restenosis after 1 year. Cumulative primary patency at 6 and 12 months was 87% and 71% overall, respectively. The cumulative patency during the same follow-up periods varied between patients treated with different paclitaxel modalities with 88% and 80% primary patency in patients treated with DES (n = 63) versus 81% and 49% in patients treated with DCB (n = 21) (adjusted hazard ratio 2.46, P = 0.03). Lesion length, concurrent tibial intervention, and recurrent target lesions were not associated with restenosis.. Short-term outcomes in patients treated with paclitaxel-eluting stents and paclitaxel-coated balloons in long lesions, mirror results from the clinical trials. The primary patency observed in patients treated with DES was significantly higher than in patients treated with DCB.

Topics: Aged; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Critical Illness; Databases, Factual; Drug-Eluting Stents; Female; Femoral Artery; Humans; Ischemia; Male; Middle Aged; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Prosthesis Design; Recurrence; Retrospective Studies; Time Factors; Treatment Outcome; Vascular Patency

The aim of this study was to determine the survival of patients after use of paclitaxel coated devices (PCX), as a recent meta-analysis of randomised trials reported higher mortality in patients treated with PCX balloons and stents METHODS: A retrospective health insurance claims analysis of patients covered by the second largest insurance fund in Germany, BARMER, was used to identify index femoropopliteal arterial interventions between 1 January 2010 and 31 December 2018. To ensure first PCX exposure, patients with prior deployment of PCX were excluded. The study cohort was stratified into patients with chronic limb threatening ischaemia (CLTI) and intermittent claudication (IC), then into balloons vs. stents cohorts. Within each stratum PCX were compared with uncoated devices. Propensity score matching was used to balance the study groups. Survival was evaluated using the Kaplan-Meier method and Cox regression.. There were 37 914 patients (mean age 73.3 years; 48.8% female) included in the study. The annual proportion of PCX use increased from 3% to 39% during the study period for CLTI and from 4% to 48% for IC (both p < .001). Paclitaxel coated balloons and stents were associated with improved overall survival (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.77-0.90), amputation free survival (HR 0.85, 95% CI 0.78-0.91), and freedom from major cardiovascular events (HR 0.82, 95% CI 0.77-0.89) vs. uncoated devices at five years for CLTI. In IC cohort, mortality was significantly lower after using drug coated balloons (DCB) (HR 0.87, 95% CI 0.76-0.99) or combined DCB and drug eluting stents (HR 0.88, 95% CI 0.80-0.98).. In this large health insurance claims analysis, rapid adoption of PCX, higher long term survival, better amputation free survival, and lower rates of major cardiovascular events were seen after their use for the treatment of CLTI.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Constriction, Pathologic; Female; Femoral Artery; Humans; Intermittent Claudication; Ischemia; Male; Middle Aged; Paclitaxel; Peripheral Arterial Disease; Retrospective Studies; Vascular Access Devices

Endovascular therapy is often the preferred first treatment option for chronic limb threatening ischemia (CLTI) patients. Drug coated balloons (DCB) reduce restenosis rates compared to percutaneous transluminal angioplasty (PTA), however DCB use has not been studied systematically in patients with CLTI. Thus, the optimal treatment option for these complex lesions remains controversial.. We report on 327 patients with CLTI treated either with DCB (n = 105) or non-DCB (n = 222) for femoropopliteal disease. Data were retrieved from the Excellence in Peripheral Artery Disease (XLPAD) registry (NCT01904851). Two DCB types were used at the discretion of the operator: Lutonix® (BARD Peripheral Vascular, Inc., Tempe, AZ, USA) and IN.PACT AdmiralTM (Medtronic, Santa Rosa, CA, USA). Odds ratios and the respective 95% confidence interval were synthesized to examine the association between the two groups in terms of all-cause mortality, target limb repeat endovascular or surgical revascularization, target vessel revascularization (TVR), major and minor amputation at 12 months of follow up.. The mean lesion length was 150.0 mm (SD:123.2) and 151.2 mm (SD:108.3) for the DCB and non-DCB group respectively. No difference between the two groups was detected in terms of all-cause mortality (2.86%vs2.7%,p = .94), target limb repeat endovascular or surgical revascularization (16.19%vs12.61%,p = .25), TVR (16.19%vs.11.71%,p = .26) or minor amputation (15.24%vs10.81%,p = .25) at 12 months of follow up. Although a higher incidence of 12 months major amputation was observed in the DCB group (11%vs.4%,p = .01), after adjusting for several risk factors the odds of major amputation were not statistically different between the DCB and non-DCB groups (OR:1.54;95%CI:0.53-4.51;p = .43).. Both DCB and non-DCB strategies are effective modalities for revascularization of patients with CLTI. No differences were identified between the DCB and non-DCB group in terms of late outcomes during 12 months of follow up.

Topics: Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Femoral Artery; Humans; Ischemia; Limb Salvage; Peripheral Arterial Disease; Pharmaceutical Preparations; Popliteal Artery; Registries; Time Factors; Treatment Outcome; Vascular Access Devices; Vascular Patency

Topics: Aged; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Constriction, Pathologic; Female; Femoral Artery; Humans; Intermittent Claudication; Ischemia; Limb Salvage; Male; Middle Aged; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Prospective Studies; Recovery of Function; Registries; Severity of Illness Index; Time Factors; Treatment Outcome; Vascular Patency

Endovascular revascularisation has become a standard approach for below knee lesions and paclitaxel coated devices have been widely used in patients with chronic limb threatening ischaemia. A recent meta-analysis reported higher mortality in paclitaxel coated devices compared with uncoated devices in femoropopliteal lesions. This study aimed to determine long term outcomes in below the knee interventions using paclitaxel coated devices in routine vascular care using a large and contemporary cohort.. A large cohort was created using all inclusive health insurance claims data of patients covered by the second largest insurance fund in Germany. The cohort included patients with index revascularisation of arteries below the knee performed from 1 January 2010, to 31 December 2018. Only patients with first paclitaxel coated device exposure were included. The study cohort was stratified into balloon vs. stent treatment and patients with paclitaxel coated devices were matched with uncoated devices using propensity score. Outcomes were evaluated using the Kaplan-Meier method and Cox regression.. There were 14 738 patients (mean age 77.6 years, 43.6% female) and 6 568 matched patients included in the study. Increasing use of paclitaxel coated devices was observed during the study period (6% in 2010 vs. 31% in 2018, p < .001), and a total of 2 611 (39.8%) deaths occurred within five years of follow up. In the propensity score matched Cox model, a paclitaxel related reduction of five year mortality (hazards ratio, HR 0.84, 95% confidence interval, CI 0.78-0.91), amputation or death (HR 0.87, 95% CI 0.81-0.94), and cardiovascular event or death (HR 0.86, 95% CI 0.80-0.92) were observed.. In this propensity score matched cohort, reduced long term all cause mortality, reduced rates of amputation or death and cardiovascular event or death were observed at five years after the use of paclitaxel coated devices when compared with uncoated devices for the treatment of chronic limb threatening ischaemia.

Topics: Administrative Claims, Healthcare; Aged; Aged, 80 and over; Amputation, Surgical; Cardiovascular Agents; Chronic Disease; Coated Materials, Biocompatible; Databases, Factual; Drug-Eluting Stents; Endovascular Procedures; Female; Germany; Humans; Ischemia; Leg; Limb Salvage; Male; Paclitaxel; Peripheral Arterial Disease; Propensity Score; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

The aim of the BIOLUX P-III (A Prospective, International, Multi-Centre, Post-Market All-Comers Registry to Assess the Clinical Performance of the Passeo-18 Lux Paclitaxel Releasing Balloon Catheter in Infrainguinal Arteries - III) registry was to collect real-world data on the Passeo-18 Lux paclitaxel-coated balloon.. Critical limb ischemia (CLI) is a severe condition associated with high morbidity and mortality. Prospective data are needed to provide further insights on drug-eluting devices.. BIOLUX P-III is a prospective, post-market, all-comers registry assessing the safety and performance of the Passeo-18 Lux. Clinical information was collected at 6, 12, and 24 months. The authors report 24-month outcomes of the CLI subgroup with patients in Rutherford classes 4 to 6.. The CLI subgroup included 328 patients with 422 lesions. Patients were 71.1 ± 10.5 years of age, and 61.0% had diabetes. Femoropopliteal lesions were present in 53.8% (n = 227), below-the-knee lesions were present in 27.0% (n = 114), and lesions were moderate or heavily calcified in 45.0% (n = 190). Major adverse events, defined as 30-day device- or procedure-related mortality, major target limb amputation, and clinically driven target lesion revascularization, occurred in 9.8% of patients through 6 months, in 14.9% through 12 months, and in 19.4% through 24 months. Clinically driven target lesion revascularization occurred in 4.4%, 8.5%, and 12.1%, major amputation in 4.9%, 5.2%, and 6.1%, and mortality in 8.1%, 11.1%, and 20.1%, respectively. Predictors of mortality were age ≥75 years and higher Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease class, and higher Rutherford class was associated with increased mortality and amputation rates.. In a large, multimorbid patient population with complex lesions and CLI, the safety and performance of the Passeo-18 Lux paclitaxel-coated balloon has been confirmed, with low rates of major amputation and target lesion revascularization.

Topics: Aged; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Humans; Ischemia; Limb Salvage; Middle Aged; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Prospective Studies; Time Factors; Treatment Outcome; Vascular Patency

Evidence about sex differences in management and outcomes of critical limb ischemia (CLI) is conflicting.. We identified Fee-For-Service Medicare patients within the 5% enhanced sample file who were diagnosed with new incident CLI between 2015 and 2017. For each beneficiary, we identified all hospital admissions, outpatient encounters and procedures, and pharmacy prescriptions. Outcomes included 90-day mortality and major amputation.. Incidence of CLI declined from 2.80 (95% CI, 2.72-2.88) to 2.47 (95% CI, 2.40-2.54) per 1000 person from 2015 to 2017,. Women with new incident CLI are less likely to receive statin or undergo revascularization at 90 days compared with men. However, the differences were small. There was no difference in risk of 90-day mortality between both sexes. Graphic Abstract: A graphic abstract is available for this article.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Cardiovascular Agents; Critical Illness; Fee-for-Service Plans; Female; Health Status Disparities; Healthcare Disparities; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Incidence; Ischemia; Limb Salvage; Male; Medicare; Peripheral Arterial Disease; Risk Assessment; Risk Factors; Sex Distribution; Sex Factors; Time Factors; Treatment Outcome; United States; Vascular Surgical Procedures

The aim of this study was to evaluate the performance of paclitaxel-eluting stents (PESs) and paclitaxel-coated balloons (PCBs) on amputation-free survival in patients with critical limb ischemia (CLI).. A retrospective review of all patients with Rutherford stage 5 and 6 limb ischemia undergoing endovascular revascularization with paclitaxel-related technology, both PES and PCB, was carried out over a 4-year period. Clinical grading was determined by Rutherford classification and the Society for Vascular Surgery's Wound, Ischemia, and foot Infection (WIfI) scoring system. Clinical and angiographic follow-up was reviewed based on intention-to-treat analysis. The primary endpoint of this study was amputation-free survival at 12 months. Secondary endpoints included wound healing, freedom from target lesion revascularization, and patency of target vessels at 12 months. Follow-up occurred at 3, 6, and 12 months postoperatively. Target lesion patency was defined as <50% stenosis, based on a duplex velocity ratio of less than or equal to 2. Postoperative ankle-brachial index (ABI) and duplex ultrasound were performed to verify successful treatment. Outcomes were evaluated using Kaplan-Meier and Cox proportional-hazards models.. A total of 88 limbs were revascularized in 88 patients. Drug-eluting stent (DES) was used as the sole drug technology in 56 patients (60.7% men, median age 70.5 years) and drug-coated balloon (DCB) was used as the sole drug technology in 32 patients (46.9% men, median age 66 years). Baseline demographics were well matched except for a higher prevalence of occluded target lesions in the DES group (41.1% vs. 12.5%; P = 0.004). Limbs were treated for Rutherford stage 5 CLI in 71.6% and stage 6 CLI in 28.4%. Univariate analysis identified no dependent factors affecting limb salvage, except for the use of DCBs. After 12 months of follow-up, amputation-free survival was significantly higher in the DES group than in the DCB group (88.5% vs. 71.1%; P = 0.0443). Wound healing rates after 1 year were also higher in the DES group (83.9% vs. 59.4%; P = 0.0198). Freedom from target lesion revascularization was no different between patients treated with DESs and patients treated with DCBs (90.6% vs. 85.7%; P = 0.518). Primary patency at 12 months in patients treated with DESs was significantly higher than in patients treated with PCBs (80.4% vs. 58.1%; P = 0.0255).. Overall, drug technology represents a viable option for patients with CLI; a cohort not represented in major randomized trials. In our experience, femoropopliteal lesions treated with DESs have higher primary patency rates than those treated with DCBs. This was found to support higher amputation-free survival rates in patients treated with paclitaxel DESs than those treated with paclitaxel DCB. The use of paclitaxel DESs for CLI was also associated with significantly improved wound healing compared with DCBs. Our data suggest improved outcomes with DESs compared with DCBs; however, these patients represent a nonrandomized, heterogenous group that were treated with the operator's best judgment.

Topics: Aged; Amputation, Surgical; Angioplasty, Balloon; Cardiovascular Agents; Clinical Decision-Making; Coated Materials, Biocompatible; Critical Illness; Drug-Eluting Stents; Female; Humans; Ischemia; Limb Salvage; Male; Middle Aged; Paclitaxel; Patient Selection; Peripheral Arterial Disease; Progression-Free Survival; Prosthesis Design; Retrospective Studies; Risk Factors; Time Factors; Vascular Access Devices; Vascular Patency

Topics: Administration, Intravenous; Aged; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Critical Illness; Drug Administration Schedule; Female; Humans; Iloprost; Ischemia; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Retrospective Studies; Time Factors; Treatment Outcome; Vascular Access Devices; Wound Healing

Surgical endarterectomy with or without patch angioplasty has been considered the gold standard for treatment of symptomatic common femoral artery (CFA) disease. Surgical risks include wound infection, hematoma and lymph leak in approximately 17% of patients. Endovascular therapy has less procedure-related morbidity and mortality. Endovascular approaches achieve patency rates of 60% to 90% at 1 and 2 years utilizing atherectomy and balloon angioplasty. CFA stenting has been limited due to concerns of stent kinking, thrombosis and restenosis. Combined directional atherectomy with drug-coated balloon to treat CFA disease in patients with Rutherford II/III patients has been studied recently. We sought to study the safety and outcomes of adjunct drug-coated balloon (DCB) therapy in symptomatic CFA disease patients, including critical limb ischemia (Rutherford IV), after achieving procedural success.. To evaluate the additive efficacy of drug coated balloon in treating CFA disease.. Using retrospective single center data, we analyzed the outcomes of patients who underwent CFA interventions. In this non-randomized study, all patients from December 2010 to December 2014 with CFA disease underwent atherectomy (orbital, plaque excision or both) with adjunctive scoring balloon angioplasty (Ath/PTA). After December 2014, patients treated with combination atherectomy and DCB, (Ath/DCB), underwent final drug delivery to the vessel wall with drug-coated balloon. Distal embolic protection devices were used in the majority of patients. Primary efficacy endpoint was 1-year primary patency and freedom from clinically driven target lesion revascularization (CD-TLR). Patency of vessels was assessed at 12-month interval using duplex ultrasound.. Seventy de novo common femoral artery stenotic lesions were treated in both groups. Mean age was 69 in (Ath/PTA) group and 72 in Ath/DCB group. Patients in each group had similar risk factor profiles including diabetes mellitus, hypertension, smoking, coronary artery disease, myocardial infarction, prior coronary revascularization, congestive heart failure, cerebrovascular accidents and chronic kidney disease. The Ath/DCB group had more advanced disease presentation by Rutherford classification (intermittent claudication in 61% and critical limb ischemia in 39% versus intermittent claudication in 76% and chronic limb ischemia in 24%) when compared with the Ath/PTA group. Primary efficacy endpoint was met in 85% and 94% (p = 0.26) in the Ath/PTA and Ath/DCB groups respectively. All patients had run-off angiography at the end of procedure to ensure patency.. Adjunctive drug-coated balloon therapy does not increase the primary patency rate when compared with atherectomy and scoring balloon angioplasty alone at 1-year in common femoral artery disease treatment.

Topics: Aged; Angioplasty, Balloon; Atherectomy; Cardiovascular Agents; Coated Materials, Biocompatible; Critical Illness; Embolic Protection Devices; Equipment Design; Female; Femoral Artery; Humans; Intermittent Claudication; Ischemia; Male; Middle Aged; Peripheral Arterial Disease; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vascular Patency

Currently, there exist limited data on patient outcomes following the use of drug-coated balloons (DCBs) to treat complex femoropopliteal arterial occlusive lesions. The aim of the this study is to investigate the outcomes of patient treated with DCBs and to identify the predictors of restenosis.. We retrospectively investigated medical records from 120 patients (137 limbs) treated with DCBs for femoropopliteal lesions at a single center between 2013 and 2016. Primary patency, target lesion revascularization (TLR), and risk factors of restenosis were analyzed.. There were 80 de novo and 57 in-stent restenosis lesions. Mean lesion length was 22.2 ± 11.6 cm. The clinical primary patency was 85.2% at 1 year and 65.3% after 2 years. The TLR-free survival rate was 93.0% at 1 year and 87.1% after 2 years. Critical limb ischemia (CLI; hazard ratio [HR] 5.80, 95% confidence interval [CI] 1.26-26.68, P = 0.024) and hypercholesterolemia (HR 4.66, 95% CI 1.30-16.76, P = 0.018) were identified as independent predictors of restenosis. In addition, nonuse of cilostazol and popliteal artery involvement showed trends toward an increased risk of restenosis.. Treatment with DCBs showed excellent primary patency and TLR-free survival at 1 year after the procedure. However, the primary patency continuously deteriorated beyond 1 year, suggesting a late catch-up phenomenon. The risk of restenosis after treatment with DCBs was significantly associated with CLI and hypercholesterolemia.

Topics: Aged; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Critical Illness; Equipment Design; Female; Femoral Artery; Humans; Ischemia; Male; Medical Records; Middle Aged; Peripheral Arterial Disease; Popliteal Artery; Progression-Free Survival; Recurrence; Registries; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vascular Access Devices; Vascular Patency

Topics: Aged; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Equipment Design; Female; Femoral Artery; Humans; Intermittent Claudication; Ischemia; Male; Middle Aged; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vascular Access Devices; Vascular Patency

To report the 1-year outcomes of the prospective Legflow drug-coated balloon (DCB) registry, which evaluated the safety and 12-month efficacy of the Legflow balloon in the treatment of femoropopliteal disease.. The Legflow is a new generation of DCB that has a homogenous, stable surface coating incorporating 0.1-µm paclitaxel particles. From January 2014 to June 2016, 139 patients (mean age 67.1±10.8 years; 109 men) were enrolled at 4 European institutions. Seventy-nine (56.8%) patients had claudication, while 60 (43.2%) had critical limb ischemia (CLI). Mean lesion length (MLL) was 90.0±41.2 mm. Eighty (57.6%) patients were treated for de novo lesions (MLL 83.2±41.2 mm), 29 (20.9%) for postangioplasty restenosis (MLL 81.2±30.9 mm), and 30 (21.6%) for in-stent restenosis (MLL 117.0±39.5 mm). The primary outcome measure was freedom from binary restenosis as determined by a peak systolic velocity ratio ≥2.4 on duplex or >50% stenosis on digital subtraction angiography at 12 months. The secondary outcome was freedom from clinically-driven target lesion revascularization (CD-TLR) at 12 months.. Technical success was achieved in all the 139 treated patients. During the hospital stay, 3 CLI patients died of wound-related complications and 3 CLI patients underwent urgent TLR due to early occlusion in 2 and stent thrombosis in 1. At 12 months, 4 additional patients died of cardiac disease unrelated to the procedure. Of the 132 patients available for 1-year follow-up, the primary outcome (freedom from restenosis) was obtained in 107 (81.1%) patients. Freedom from CD-TLR was obtained in 110 (83.3%). Of the 25 late restenoses >50%, only 3 asymptomatic patients did not require TLR. Freedom from CD-TLR was higher in claudicants (87.0%) than in CLI patients (78.2%, p=0.20). In patients treated for in-stent restenosis, freedom from TLR at 1 year was 89.2%.. These data suggest that the use of a new generation paclitaxel-coated balloon represents a safe and effective therapeutic strategy for femoropopliteal obstructions in different clinical and anatomical settings. These data will need to be confirmed with longer-term follow-up and in randomized controlled trials.

Topics: Aged; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Constriction, Pathologic; Critical Illness; Equipment Design; Europe; Female; Femoral Artery; Humans; Intermittent Claudication; Ischemia; Male; Middle Aged; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Prospective Studies; Recurrence; Registries; Time Factors; Treatment Outcome; Vascular Access Devices; Vascular Patency

Peripheral artery disease (PAD) causes narrowing of arteries in the limbs, leading to tissue ischemia, gangrene, and eventually limb amputation. The presence of diabetes greatly exacerbates the course of PAD, accounting for the majority of lower limb amputations. Therapeutic strategies focussing on macrovascular repair are less effective in diabetic patients where smaller vessels are affected, and proangiogenic therapies offer a viable adjunct to improve vascularisation in these at risk individuals. The purpose of the current study was to assess the proangiogenic effects of drugs routinely used to treat cardiovascular disease in a diabetic murine model of hind limb ischemia longitudinally using multimodal imaging.. Diabetic mice underwent surgical intervention to induce hind limb ischemia and were treated with simvastatin, metformin, or a combination orally for 28 days and compared to diabetic and nondiabetic mice. Neovascularisation was assessed using [. Combined use of simvastatin and metformin significantly increased neovascularisation above levels measured with either treatment alone. Early angiogenic events were accurately assessed using PET [. Combined treatment with simvastatin and metformin led to a significant improvement in limb angiogenesis, vascular volume, and sustained functional recovery in a diabetic murine model of HLI. PET imaging with [

Topics: Animals; Cardiovascular Agents; Diabetes Mellitus, Experimental; Hindlimb; Immunohistochemistry; Ischemia; Magnetic Resonance Imaging; Male; Metformin; Mice; Mice, Inbred BALB C; Muscle, Skeletal; Oligopeptides; Simvastatin

To report a post hoc analysis performed to evaluate 1-year safety and efficacy of the IN.PACT Admiral drug-coated balloon (DCB) for the treatment of femoropopliteal lesions in subjects with critical limb ischemia (CLI) enrolled in the IN.PACT Global study ( ClinicalTrials.gov identifier NCT01609296).. Of 1535 subjects enrolled in the study, 156 participants (mean age 71.8±10.4; 87 men) with CLI (Rutherford categories 4,5) were treated with DCB angioplasty in 194 femoropopliteal lesions. This cohort was compared to the 1246 subjects (mean age 68.2±10.0 years; 864 men) with intermittent claudication (IC) treated for 1573 lesions. The CLI cohort had longer lesions (13.9±10.6 vs 11.9±9.4 cm, p=0.009) and a higher calcification rate (76.8% vs 67.7%, p=0.011). Major adverse events [MAE; composite of all-cause mortality, clinically-driven target lesion revascularization (CD-TLR), major (above-ankle) target limb amputation, and thrombosis at the target lesion site], lesion and vessel revascularization rates, and EuroQol-5D were assessed through 1 year. The Kaplan-Meier method was used to estimate survival, CD-TLR, and amputation events; estimates are presented with the 95% confidence intervals (CI).. Estimates of 12-month freedom from major target limb amputation were 98.6% (95% CI 96.7% to 100.0%) in subjects with CLI and 99.9% (95% CI 99.8% to 100.0%) in subjects with IC (p=0.002). Freedom from CD-TLR through 12 months was 86.3% (95% CI 80.6% to 91.9%) in CLI subjects and 93.4% (95% CI 91.9% to 94.8%) in IC subjects (p<0.001). The MAE rate through 12 months was higher in CLI subjects (22.5% vs 10.7%, p<0.001), and CLI patients had poorer overall survival (93.0%, 95% CI 88.9% to 97.2%) than IC subjects (97.0%, 95% CI 96.0% to 97.9%, p=0.011). Health status significantly improved in all domains at 6 and 12 months in both groups.. Treatment of femoropopliteal disease with DCB in CLI patients is safe through 12-month follow-up, with a low major amputation rate of 1.4%. The rates of MAE and CD-TLR were higher in CLI subjects and reinterventions were required sooner. Additional research is needed to evaluate long-term outcomes of DCB treatment for femoropopliteal lesions in CLI patients.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Angioplasty, Balloon; Cardiovascular Agents; Clinical Trials as Topic; Coated Materials, Biocompatible; Critical Illness; Equipment Design; Female; Femoral Artery; Humans; Intermittent Claudication; Ischemia; Limb Salvage; Male; Middle Aged; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Progression-Free Survival; Risk Factors; Time Factors; Vascular Access Devices; Vascular Patency

This study intended to assess effectiveness and safety of the drug-coated balloon (DCB) angioplasty of infrapopliteal atherosclerotic lesions in patients with critical limb ischaemia (CLI) in a real-world setting.. Consecutive patients with critical limb ischaemia who underwent infrapopliteal drug-coated balloon angioplasty with the ELUTAX SV DCB were enrolled into the prospective, multicentre, single-arm observational registry. Primary outcome was clinical improvement at 6 and 12 months. Secondary outcomes were change in quality of life, primary patency, freedom from repeat revascularisation, and amputation-free survival at 6 and 12 months.. A total of 164 patients (74.7 ± 9.2 years) with CLI were included at nine German sites between November 2015 and September 2017. The majority (79.9%) of patients had diabetes mellitus, 57.3% had renal insufficiency, and 35.3% had coronary artery disease. Mean lesion length was 71.2 ± 76.5 mm. The Rutherford category improved by 3.0 ± 2.0 (p < 0.0001) within 12 months, resulting in a clinical improvement by at least one Rutherford category in 80.2% of the patients. Walking impairment questionnaire score, European Quality of Life index, and patient-reported pain improved significantly from baseline to 6 and 12 months. Primary patency was 68.5%, freedom from target lesion revascularisation 90.6%, and amputation-free survival 83.5% at 12 months.. Infrapopliteal drug-coated balloon angioplasty with the ELUTAX SV DCB in patients with critical limb ischaemia was efficacious and safe over the medium term. The study is registered with Clinical.Trials.gov (Identifier: NCT02539940).

Topics: Aged; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Female; Germany; Humans; Ischemia; Kaplan-Meier Estimate; Male; Peripheral Arterial Disease; Popliteal Artery; Prospective Studies; Time Factors; Treatment Outcome; Vascular Patency

The IN.PACT Global Study is the largest prospective, multicenter, independently adjudicated trial to evaluate a paclitaxel drug-coated balloon in patients with lifestyle-limiting claudication and/or ischemic rest pain due to atherosclerotic disease of the femoropopliteal artery and includes complex lesions beyond what are typically included in randomized controlled trials.. Randomized controlled trials have demonstrated the safety and efficacy of drug-coated balloons for the treatment of Trans-Atlantic Inter-Society Consensus Document II A and B lesions, but there is a need for large-scale prospective studies to evaluate a broader range of lesions.. The IN.PACT Global Study enrolled 1,535 subjects, and 1,406 (1,773 lesions) were included in the pre-defined clinical cohort analysis. Freedom from clinically driven target lesion revascularization was evaluated at 24 months. The safety composite endpoint was freedom from device- and procedure-related death through 30 days and freedom from target limb major amputation and clinically driven target vessel revascularization within 24 months.. Mean lesion length was 12.1 cm, 35.5% were total occlusions, and 18.0% had in-stent restenosis. Freedom from clinically driven target lesion revascularization at 24 months was 83.3%, the composite safety endpoint was met in 81.7%, the 2-year all-cause mortality rate was 7.0%, and the major target limb amputation rate was 0.7%. Increased lesion length and the presence of de novo in-stent restenosis or coronary artery disease were associated with increased risk for clinically driven target lesion revascularization by 24 months.. This real-world study of femoropopliteal artery disease treatment with drug-coated balloons confirmed positive findings reported from more strictly designed randomized controlled trials and showed that outcomes are durable in this population up to 2 years after treatment. (IN.PACT Global Clinical Study; NCT01609296).

Topics: Aged; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Constriction, Pathologic; Female; Femoral Artery; Humans; Intermittent Claudication; Ischemia; Male; Middle Aged; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Prospective Studies; Recurrence; Time Factors; Treatment Outcome; Vascular Access Devices; Vascular Patency

Objective This study was performed to determine the healing effects of pentoxifylline on molecular responses and protection against severe ischemic damage in the small intestine. Methods Thirty-six Wistar albino rats were divided into six groups. The superior mesenteric artery was clamped for 120 minutes, and reperfusion was performed for 60 minutes. Saline (0.4 mL), pentoxifylline (1 mg/kg), and pentoxifylline (10 mg/kg) were intraperitoneally administered to the rats in the C

Topics: Animals; Cardiovascular Agents; Disease Models, Animal; Hematologic Agents; Infusions, Parenteral; Intestine, Small; Ischemia; Male; Pentoxifylline; Protective Agents; Rats; Rats, Wistar; Reperfusion Injury; Wound Healing

Skin flap procedures are widely used to reconstruct skin and soft tissue defects. Skin flap necrosis is a serious postoperative complication. Many researchers have introduced pharmacological agents to improve flap ischemia in experimental studies. However, outcomes of these studies remain controversial. We previously demonstrated that transcutaneous CO. Six-week-old male Sprague-Dawley rats were divided into two equal groups: the control group (n = 6) and CO. A statistically significant difference was found in the percentage of the flap survival area between the two groups on postoperative days 3 and 5 (p < 0.05). Furthermore, the expression of VEGF and bFGF was significantly higher and that of HIF-1α was significantly lower in the CO. Transcutaneous CO

Topics: Administration, Cutaneous; Animals; Carbon Dioxide; Cardiovascular Agents; Graft Survival; Hypoxia; Ischemia; Male; Necrosis; Plastic Surgery Procedures; Postoperative Complications; Rats; Rats, Sprague-Dawley; Skin; Surgical Flaps; Treatment Outcome

Despite current progress, the prognosis of critical limb ischemia (CLI) remains poor. The ageing of the population, the increasing prevalence of diabetes mellitus, and the stability of tobacco use will increase the prevalence of CLI. CLI patients have risk factors for malnutrition, and the impact of malnutrition on morbidity and mortality has been demonstrated in the general population. However, we have little information on the consequences of undernutrition in the CLI population. The aim of this study is to assess the impact of malnutrition on the early outcomes in CLI patients.. This is a double-center prospective study that included all consecutive hospitalized patients with CLI. All patients were screened for malnutrition and divided into 2 groups: severe malnourished patients (group A) and moderate malnourished and well-nourished (group B). This distribution was based on age-indexed clinical and biological data and the patient's general condition: the Nutritional Risk Index for patients younger than 75 years, the Mini Nutritional Assessment, or the Geriatric Nutritional Risk Index for those older than 75 years. The primary end point was defined as the rate of 30-day death. Outcomes were compared in a univariate analysis. Stepwise logistic regression was used for the multivariate analysis. Variables with a P value <0.2 in the univariate analysis were introduced in the multivariate model.. We included 106 patients. The prevalence of malnutrition was 75.5%, divided into moderate malnutrition (51.9%) and severe malnutrition (23.6%). Six patients (24%) died in group A compared with 8 in group B (4.9%) (P = 0.01). By univariate analysis, severe malnutrition was the only factor associated with death at 30 days. By stepwise logistic regression, severe malnutrition (odds ratio 6.1, 95% confidence interval 1.6-23.7, P = 0.006) was found to be the significant risk factors for death at 30 days.. This study is the first to demonstrate prospectively the major importance of malnutrition in the early prognosis of CLI patients.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Cardiovascular Agents; Chi-Square Distribution; Critical Illness; Endovascular Procedures; Female; France; Geriatric Assessment; Humans; Ischemia; Length of Stay; Limb Salvage; Logistic Models; Male; Malnutrition; Multivariate Analysis; Nutrition Assessment; Nutritional Status; Odds Ratio; Peripheral Arterial Disease; Prevalence; Prospective Studies; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome; Vascular Grafting

We present a case series of upper extremity fibromuscular dysplasia (UE FMD) consisting of 22 patients from two tertiary referral centers focusing on clinical presentation, diagnostic findings, and interventional outcomes. FMD is a noninflammatory, nonatherosclerotic arteriopathy that has a predisposition for middle-aged women. Involvement of the UE is thought to be rare. Patients with UE FMD can present with claudication or ischemia, or they can be incidentally diagnosed. The treatment approach is dictated by clinical presentation.. Data were collected of patients with UE FMD evaluated at two centers. Demographic data, presenting UE symptoms, UE arteries involved, FMD type, diagnostic method, physical examination findings, management, and outcomes were included.. Twenty-two patients (29 limbs) were diagnosed with UE FMD. The brachial artery was most commonly involved (89.7% of affected limbs). More than half of limbs (n = 15 of 29 limbs [51.7%]) were asymptomatic, and of those who presented with symptoms, the most common symptoms were ischemic fingers or hand (31% of all affected limbs) and hand or arm claudication (27.6% of all affected limbs). UE FMD was noted on catheter angiography in 58.6% (n = 17 of 29 limbs), duplex ultrasound in 41.4% (n = 12 of 29 limbs), and computed tomography angiography in 27.6% (n = 8 of 29 limbs). Of the symptomatic limbs (n = 14), the majority were treated solely with medical therapy as the first intervention (57.1%). For symptomatic limbs treated with vascular intervention (n = 5), angioplasty was most commonly performed. Only 4 of the 14 limbs (28.6%) had complete symptomatic relief after the initial first intervention, in which 2 limbs were treated with medical therapy, 1 limb underwent angioplasty, and 1 limb had resolution of symptoms despite deferment of any therapy. Of the 10 limbs with residual symptoms after the first intervention, 6 limbs underwent a second intervention: angioplasty in 2 limbs initially treated medically (33.3%), surgical bypass in 2 limbs initially treated with angioplasty, surgical bypass in 1 limb initially treated with medical therapy, and sympathectomy in 1 limb (16.7%) initially treated with angioplasty. Both surgical bypass and angioplasty as secondary interventions resulted in complete symptom relief.. Presenting symptoms for patients with UE FMD vary in severity from asymptomatic disease to digital ischemia. More than half of symptomatic limbs eventually require at least one invasive intervention for complete relief of symptoms.

Topics: Adolescent; Adult; Aged; Angioplasty; Asymptomatic Diseases; Cardiovascular Agents; Child; Child, Preschool; Computed Tomography Angiography; Fibromuscular Dysplasia; Humans; Ischemia; Middle Aged; Ohio; Physical Examination; Predictive Value of Tests; Retrospective Studies; Severity of Illness Index; Tertiary Care Centers; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Duplex; Upper Extremity; Vascular Grafting; Virginia; Young Adult

Critical limb ischemia (CLI) is a feared complication of peripheral vascular disease that often requires surgical management and may require amputation of the affected limb. We developed a decision model to inform clinical management for a 63-year-old woman with CLI and multiple medical comorbidities, including advanced heart failure and diabetes.. We developed a Markov decision model to evaluate 4 strategies: amputation, surgical bypass, endovascular therapy (e.g. stent or revascularization), and medical management. We measured the impact of parameter uncertainty using 1-way, 2-way, and multiway sensitivity analyses.. In the base case, endovascular therapy yielded similar discounted quality-adjusted life months (26.50 QALMs) compared with surgical bypass (26.34 QALMs). Both endovascular and surgical therapies were superior to amputation (18.83 QALMs) and medical management (11.08 QALMs). This finding was robust to a wide range of periprocedural mortality weights and was most sensitive to long-term mortality associated with endovascular and surgical therapies. Utility weights were not stratified by patient comorbidities; nonetheless, our conclusion was robust to a range of utility weight values.. For a patient with CLI, endovascular therapy and surgical bypass provided comparable clinical outcomes. However, this finding was sensitive to long-term mortality rates associated with each procedure. Both endovascular and surgical therapies were superior to amputation or medical management in a range of scenarios.

Topics: Amputation, Surgical; Cardiovascular Agents; Clinical Decision-Making; Comorbidity; Computer Simulation; Critical Illness; Decision Support Techniques; Decision Trees; Endovascular Procedures; Female; Humans; Ischemia; Markov Chains; Middle Aged; Peripheral Arterial Disease; Predictive Value of Tests; Quality-Adjusted Life Years; Retreatment; Risk Assessment; Risk Factors; Stents; Time Factors; Treatment Outcome; Vascular Grafting

Proper management of patients with thromboangiitis obliterans (TAO) or cannabis-associated arteritis (CAA), presenting with critical lower limb ischaemia (CLI) remains controversial, and data are limited.. Patients with TAO or CAA presenting with CLI between 2011 and 2016 were retrospectively evaluated. Patients requiring primary intervention were excluded. Conservative treatment included: (a) weight-adjusted bemiparin plus six hours/day intravenous iloprost for 28 days, (b) aspirin (100 mg/day) plus cilostazol (100 mg twice/day) after discharge, and (c) strict recommendations/monitoring for smoking cessation. Main outcomes included symptom recession, ankle-brachial index (ABI) improvement, and healing of lesions at the time of discharge as well as amputation, revascularization, and abstinence rate during follow-up.. Overall, 23 patients (TAO: 15; CAA: 8) were included within six years, none of the patients reported any other factor than smoking. All patients presented with rest pain and 12 patients with ulcer or necrotic lesions. Mean ABI measurement at presentation was 0.46 ± 0.2, after 28 days of treatment, all patients showed improvement regarding clinical picture and ABI measurement (0.54 ± 0.1; p < 0.05). During follow-up, only three patients underwent bypass surgery and two patients underwent major amputation, although the smoking abstinence rate was very low (13 %).. Intravenous iloprost plus bemiparin for 28 days together with per os aspirin plus cilostazol seem to produce promising results in patients with TAO/CAA, treated for CLI, even with a low smoking abstinence rate. However, larger series are needed to further evaluate inter-group differences and potential prognostic factors.

Topics: Adult; Amputation, Surgical; Ankle Brachial Index; Anticoagulants; Arteritis; Aspirin; Cardiovascular Agents; Cilostazol; Critical Illness; Drug Therapy, Combination; Female; Heparin, Low-Molecular-Weight; Humans; Iloprost; Infusions, Intravenous; Ischemia; Limb Salvage; Lower Extremity; Male; Marijuana Abuse; Marijuana Smoking; Middle Aged; Platelet Aggregation Inhibitors; Recurrence; Remission Induction; Retrospective Studies; Risk Factors; Smoking; Smoking Cessation; Tetrazoles; Thromboangiitis Obliterans; Time Factors; Treatment Outcome; Vasodilator Agents

The aim of this study was to evaluate the performance and predictors of stent failure of paclitaxel drug-eluting stents for the treatment of femoropopliteal disease.. A retrospective review of clinical and angiographic data was performed for patients treated for femoropopliteal disease with the Zilver PTX (Cook Medical, Bloomington, IN) stent by a single operator between 2012 and 2015 at a tertiary referral center. Clinical grading was determined by both Rutherford classification and the Society for Vascular Surgery's Wound, Ischemia, and Foot Infection (WIFi) scoring system, and lesions were classified anatomically by the TransAtlantic Intersociety Consensus (TASC) II criteria. Treated lesions included those with prior in-stent restenosis and long-segment disease. Primary clinical end points were stent failure, need for reintervention, and major adverse limb events (MALE). Kaplan-Meier methods and Cox proportional hazard models were used to evaluate factors affecting outcomes.. Zilver PTX stents were placed in 52 limbs among 46 patients (71.1% male, mean age 72.6 years) with a median follow-up of 11.1 (range 1-26) months. Limbs were treated for life-disabling claudication in 76.9% and critical limb ischemia in 23.1%. Disease severity was highly variable, with 21 (40.4%) limbs with TASC C or D lesions and 16 (30.7%) treated for restenosis after prior endovascular treatment. During follow-up, 6 (12.7%) limbs experienced loss of stent patency (5 occlusions, one >50% restenosis). Four limbs underwent target lesion revascularization, 2 required open bypass, 2 underwent thrombolysis, and no patients required major amputation. Primary patency was 88.9%, 81.6%, and 81.6% at 6, 12, and 18 months, respectively. Treated lesion length (hazard ratio [HR] 4.99, 95% confidence interval [CI] 1.14-21.75) was the only independent predictor of patency loss. Freedom from target lesion revascularization at 6, 12, and 18 months was 94.2%, 87.8%, and 87.8%, respectively. Freedom from MALE (composite of thrombolysis, major amputation, and bypass operation) was 97.5%, 90.9%, and 79.6% at 6, 12, and 18 months, respectively. Chronic renal insufficiency was the only factor that trended toward increased risk of MALE (HR 9.92, 95% CI 0.86-113.35) within a multivariate model.. Our real-world experience supports the continued use of the Zilver PTX for the treatment of both de novo lesions and lesions with prior endovascular revascularization in the femoropopliteal segment. Routine follow-up between 6 and 12 months postoperatively is essential for detecting early restenosis and guiding reintervention. Careful attention when treating complex lesions and long-segment disease remains important for selecting the optimal revascularization strategy for individual patients and optimizing stent patency.

Topics: Adult; Aged; Aged, 80 and over; Arterial Occlusive Diseases; Cardiovascular Agents; Constriction, Pathologic; Critical Illness; Disease-Free Survival; Drug-Eluting Stents; Endovascular Procedures; Female; Femoral Artery; Humans; Intermittent Claudication; Ischemia; Kaplan-Meier Estimate; Limb Salvage; Male; Metals; Middle Aged; Multivariate Analysis; Paclitaxel; Popliteal Artery; Proportional Hazards Models; Prosthesis Design; Prosthesis Failure; Recurrence; Retreatment; Retrospective Studies; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome; Vascular Patency

Critical limb ischemia (CLI), despite revascularization, may result in minor or major amputations with devastating psychological effects and a negative impact on patient survival. Randomized clinical trials demonstrated that drug-eluting stents improve 1-year primary patency and decrease target lesion revascularization, compared to standard angioplasty and bare-metal stents, in patients with short occlusive below-the-knee lesions.. This prospective clinical study was designed to evaluate if one straight-line flow revascularization to the foot, using Xience-Prime Everolimus-Eluting Stent (EES), is an effective treatment of patients in Rutherford-Becker category 4 to 5 with distal popliteal and proximal tibial arteries long occlusive lesions up to 10 cm.. All patients with angiographic documented segment P3 of popliteal artery and proximal tibial arteries stenosis >70%, and lesion length between 20 mm and 100 mm, meeting the inclusion criteria, were included in the Etna Registry. The end points assessed were 1- and 3-year primary patency, major amputation-free survival, target lesion revascularization, and wound healing rates.. Between June 2011 and April 2014, 122 patients were included in the study, with mean lesion length of 52.7 mm (range: 20-100 mm). The 1- and 3-year primary patency rates were 88.9% and 80.1%, respectively. The survival, major amputation-free survival, and target lesion revascularization rates were 88.1%, 93%, and 91.5% at 1-year and 70.4%, 89.3%, and 85.1% at 3-year follow-up, respectively. Primary patency influenced major amputation rate, which was 60% in patients with no target artery patency versus 5.4% in patients with patency ( P = .022). At 1-year follow-up, 78 (88.6%) of 88 patients improved 1 or more of their Rutherford-Becker category, and 48 (80%) of 69 patients had wound healing.. The results of our study suggest that a conservative approach, with EES, seems feasible in selected patients with CLI and infrapopliteal artery occlusive disease.

Topics: Adult; Aged; Aged, 80 and over; Amputation, Surgical; Angiography; Angioplasty, Balloon; Cardiovascular Agents; Constriction, Pathologic; Critical Illness; Disease-Free Survival; Drug-Eluting Stents; Everolimus; Female; Humans; Ischemia; Italy; Kaplan-Meier Estimate; Limb Salvage; Male; Middle Aged; Peripheral Arterial Disease; Popliteal Artery; Prospective Studies; Prosthesis Design; Recurrence; Registries; Risk Factors; Tibial Arteries; Time Factors; Treatment Outcome; Vascular Patency; Wound Healing

Drag-reducing polymers are long-chain, blood soluble macromolecules that can improve microcirculation in vivo. This study aimed to examine the effects of drag-reducing polymers on exercise tolerance in a rat model of hind-limb ischemia.. After adaptive running training, bilateral femoral artery ligation models were established in 64 Wistar rats. During an exhaustive exercise, polyethylene oxide or normal saline was intravenously injected to each group (n = 32) at 4 mL/h for 10 min. The exhaustive exercise time was recorded, and lactic acid levels in gastrocnemius muscle and serum were measured. Serum levels of nitric oxide, creatine kinase and lactate dehydrogenase were measured as biomarkers of physical fatigue.. Compared with saline-treated control group, rats in polyethylene oxide-treated group had longer exhaustive exercise time (774.7 ± 171.5 s vs. 687.6 ± 166.1 s, p = 0.043), and lower lactic acid level in gastrocnemius muscle (p < 0.01) but no significant difference in serum lactic acid level between two groups was observed (p > 0.05). Nitric oxide level was higher in polyethylene oxide group than in controls (p < 0.05), but no significant differences in serum creatine kinase and lactate dehydrogenase levels between two groups were observed (p > 0.05).. Drag-reducing polymers contribute to the enhancement of exercise endurance and exert anti-fatigue effect.

Topics: Animals; Biomarkers; Cardiovascular Agents; Creatine Kinase; Disease Models, Animal; Exercise Tolerance; Hindlimb; Injections, Intravenous; Ischemia; L-Lactate Dehydrogenase; Lactic Acid; Male; Microcirculation; Muscle, Skeletal; Nitric Oxide; Polyethylene Glycols; Rats, Wistar; Regional Blood Flow; Running; Time Factors

The aim of this study was to assess the long-term, all-cause mortality among PAD patients hospitalized for invasive diagnostics and/or endovascular revascularization (ER) and the applied secondary prevention management.. From 2005 to 2009, at our center 582 consecutive patients underwent invasive peripheral angiography in part in combination with coronary angiography and/or ER. Patients were classified according to their Fontaine stage into 3 subgroups: Fontaine I/IIa, Fontaine IIb, and Fontaine stages III and IV (which were classified as critical limb ischemia, CLI). Demographic and clinical data were retrospectively obtained and patients followed up.. Mean age increased with higher Fontaine stages (P=0.009). The proportion of patients with diabetes and anemia was lowest in Fontaine stage IIb and highest in CLI (each p<0.001). The cumulative all-cause mortality during follow-up was 17% in Fontaine stage I/IIa, 22% in Fontaine stage IIb and 34% in CLI, respectively (P<0.001). In multivariate cox regression models including diabetes mellitus, gender, age, creatinine and baseline hemoglobin, patients with Fontaine stage IIb had a 1.4-fold (95%CI 0.60-3.16) and those with CLI a 2.3-fold (95%CI 1.03-5.08) increased mortality compared to Fontaine stage I/IIa. At baseline, patients with CLI received significantly less beta blocker, statins, ACE or AT1 inhibitors and less anticoagulants; at follow-up only statins were significantly less often prescribed to CLI patients (all p<0.05). Univariate analyses showed that a therapy with statins (HR 0.64; CI 0.43-0.96; P=0.03) and antiplatelet/anticoagulant agents (HR 0.5; CI 0.27-0.94; P=0.03) significantly reduced mortality.. Long-term mortality in CLI patients doubles the rate in patients with Fontaine stage I/IIa. Non-adherence to evidence-based recommendations and guidelines such as inadequate use of cardioprotective drugs might contribute to the observed high mortality rates in patients with CLI.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Critical Illness; Diabetic Angiopathies; Endovascular Procedures; Female; Germany; Guideline Adherence; Humans; Ischemia; Male; Multivariate Analysis; Peripheral Arterial Disease; Practice Guidelines as Topic; Predictive Value of Tests; Proportional Hazards Models; Retrospective Studies; Risk Factors; Secondary Prevention; Time Factors; Treatment Outcome

To report the 3-year safety and effectiveness outcomes from the prospective all-comers DEBATE-ISR study (ClinicalTrials.gov identifier NCT01558531) of symptomatic diabetic patients with femoropopliteal in-stent restenosis (ISR) undergoing treatment with paclitaxel-eluting balloons compared with historical diabetic controls.. From January 2010 to December 2011, 44 consecutive diabetic patients (mean age 74±11 years; 32 men) were treated with drug-eluting balloons (DEBs) and enrolled in the study. The control group comprised 42 consecutive diabetic patients (age 76±7 years; 23 men) treated with conventional balloon angioplasty (BA) from 2008 to 2009.. No significant differences in terms of clinical, angiographic, or procedural characteristics were observed between the study groups. Critical limb ischemia was present in the majority of patients. Tosaka class III ISR was observed in more than half of the patients. Mean lesion length was 132±86 and 137±82 mm in the DEB and BA groups, respectively (p=0.7). At 3-year follow-up, the rate of target lesion revascularization (TLR) was 40% in the DEB group vs 43% in the BA group (p=0.8); Kaplan-Meier analysis showed no significant differences in terms of freedom from TLR. The presence of a Tosaka class III occlusion was associated with a worse outcome in both study groups (odds ratio 3.96, 95% confidence interval 1.55 to 10.1, p=0.004).. Using DEBs for femoropopliteal ISR yielded similar results to BA in terms of TLR at 3-year follow-up. The treatment of more complex ISR lesions was associated with an increased rate of TLR, irrespective of the technology used.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon; Cardiovascular Agents; Chi-Square Distribution; Constriction, Pathologic; Critical Illness; Diabetic Angiopathies; Drug-Eluting Stents; Female; Femoral Artery; Historically Controlled Study; Humans; Ischemia; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Prospective Studies; Prosthesis Design; Recurrence; Registries; Retreatment; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vascular Patency

Restenosis remains the primary failure mode after stent placement in the superficial femoral artery (SFA). Drug-eluting technology aims to reduce intimal hyperplasia and subsequent stent failure, improving durability for endovascular management of SFA occlusive disease. We present our early experience with the Cook Zilver PTX stent.. We retrospectively reviewed a prospectively collected database of patients undergoing placement of the Cook Zilver PTX stent for SFA or popliteal disease since its availability to our institution in October 2013. Patients treated with additional non-PTX stents were excluded. Patient demographics, comorbidities, concomitant procedures, TASC classification, procedural details, and follow-up were reviewed.. Thirty-one limbs in 30 patients were treated with Zilver PTX stents, 5 limbs were excluded for concomitant use of non-PTX stents, leaving 26 limbs in 26 patients for analysis. Indications for intervention were claudication in 17 (65.4%), rest pain in 1 (3.8%), and tissue loss in 8 (30.8%). A median of 2 PTX stents per limb was used to treat a mean length of 14.2 ± 11 cm with technical success of 100%. Concomitant inflow (N = 4) or atherectomy (N = 2) interventions were performed in 23%. Sixty-nine percent of lesions were TASC C (N = 7) or D (N = 11) and 42% were total occlusions. Over a mean 20-week follow-up, 2 occlusions were noted (mean 27 weeks), one was treated with surgical bypass and the other with endovascular salvage. Limb salvage in the series was 92.3% with 2 patients requiring major amputations for infected, non-healing wounds, despite patent stents.. On mean 20-week follow-up, we have seen 92.3% primary patency and 96.2% secondary patency. A larger number of patients and longer follow-up will be required to determine the true real-world efficacy of this drug-eluting device, but early experience is encouraging and warrants continued trial.

Topics: Aged; Amputation, Surgical; Cardiovascular Agents; Drug-Eluting Stents; Endovascular Procedures; Female; Femoral Artery; Humans; Intermittent Claudication; Ischemia; Limb Salvage; Male; Middle Aged; Paclitaxel; Peripheral Arterial Disease; Prosthesis Design; Recurrence; Registries; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Vascular Patency

To examine patient outcomes following the use of the Lutonix drug-coated balloon (DCB) in patients undergoing endovascular intervention in below-the-knee (BTK) arteries.. A retrospective chart review identified 248 patients who were treated for symptomatic peripheral artery disease with the Lutonix DCB between May 2013 and October 2014. Forty patients were lost to follow-up, leaving 208 patients (mean age 74.1±9.7 years; 138 men) with evaluable data for outcome analysis. The patient cohort suffered from either severe claudication (38.6%) or critical limb ischemia (CLI; 61.4%) in 220 limbs. Almost two-thirds (140, 63.6%) of the 220 target lesions were total occlusions, and 37 (17.8%) of all patients had occlusion of all 3 BTK vessels before intervention.. Over a median 9-month follow-up, target lesion revascularization occurred in 15.9% of patients with an average time to first reintervention of 8 months. In total, 39 amputations were performed in 31 limbs. However, 17 of these amputations were preplanned minor amputations below the ankle; only 9 (4.1%) major amputations occurred corresponding to 6.6% of the CLI cohort. Freedom from the composite of death or major amputation was estimated as 92% and 85% at 6 and 12 months, respectively, by Kaplan-Meier analysis. In the full cohort, improvement of at least 1 Rutherford category was seen in 130 (59.1%) limbs after 1 year or at the last follow-up, with 104 (80.0%) of those limbs showing an improvement of ≥2 categories.. From this single-center experience, the Lutonix DCB shows therapeutic promise in a disease state where new treatment options are needed.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Constriction, Pathologic; Female; Germany; Humans; Intermittent Claudication; Ischemia; Kaplan-Meier Estimate; Limb Salvage; Male; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Recurrence; Retrospective Studies; Time Factors; Treatment Outcome; Vascular Access Devices; Vascular Patency

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

Peripheral artery disease (PAD) is common worldwide, and PAD patients are increasingly offered lower limb revascularization procedures. The aim of this population-based study was to describe the current risk for cardiovascular (CV) events and mortality and also to elucidate the current pharmacologic treatment patterns in revascularized lower limb PAD patients.. This observational, retrospective cohort study analyzed prospectively collected linked data retrieved from mandatory Swedish national health care registries. The Swedish National Registry for Vascular Surgery database was used to identify revascularized PAD patients. Current risk for CV events and death was analyzed, as were prescribed drugs aimed for secondary prevention. A Cox proportional hazard regression model was used to explore risk factors for suffering a CV event.. Between May 2008 and December 2013, there were 18,742 revascularized PAD patients identified. Mean age was 70.0 years among patients with intermittent claudication (IC; n = 6959) and 76.8 years among patients with critical limb ischemia (CLI; n = 11,783). Antiplatelet therapy, statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and beta-blockers were used by 73%, 60%, 57%, and 49% at admission for revascularization. CV event rate (a composite of myocardial infarction, ischemic stroke, or CV death) at 12, 24, and 36 months was 5.1% (95% confidence interval [CI], 4.5-5.6), 9.5% (95% CI, 8.7-10.3), and 13.8% (95% CI, 12.8-14.8) in patients with IC and 16.8% (95% CI, 16.1-17.6), 25.9% (95% CI, 25.0-26.8), and 34.3% (95% CI, 33.2-35.4) in patients with CLI. Best medical treatment, defined as any antiplatelet or anticoagulant therapy along with statin treatment, was offered to 65% of IC patients and 45% of CLI patients with little change during the study period. Statin therapy was associated with reduced CV events (hazard ratio, 0.76; 95% CI, 0.71-0.81; P < .001), whereas treatment with low-dose aspirin was not.. Revascularized PAD patients are still at a high risk for CV events without a declining time trend. A large proportion of both IC and CLI patients were not offered best medical treatment. The most commonly used agent was aspirin, which was not associated with CV event reduction. This study calls for improved medical management and highlights an important and partly unmet medical need among revascularized PAD patients.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Agents; Cardiovascular Diseases; Critical Illness; Disease-Free Survival; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intermittent Claudication; Ischemia; Kaplan-Meier Estimate; Lower Extremity; Male; Middle Aged; Multivariate Analysis; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Proportional Hazards Models; Recurrence; Registries; Retrospective Studies; Risk Factors; Secondary Prevention; Sweden; Time Factors; Treatment Outcome

Topics: Cardiovascular Agents; Critical Illness; Endovascular Procedures; Humans; Ischemia; Lower Extremity; Peripheral Arterial Disease; Treatment Outcome; Vascular Surgical Procedures

Thromboxane A synthase (TXAS) is the enzyme that converts the arachidonic acid derivative prostaglandin H2 to thromboxane A2 (TXA2). TXA2 induces platelet aggregation, vasoconstriction, and proliferation. TXAS and TXA2 receptors or thromboxane prostanoid (TP) receptors are elevated in numerous cardiovascular and inflammatory diseases. Platelets contain numerous angiogenesis stimulating factors. However, the involvement of TXAS on recovery from an ischemic condition is not well understood. We hypothesized that the TXAS-TXA2-TP receptor axis would induce blood flow recovery by platelet activation.. The model of hindlimb ischemia was made by the right femoral artery ligation. The blood flow was estimated by laser Doppler images. Angiogenesis was estimated by the plasma level of the vascular endothelial growth factor and the stromal cell-derived factor-1 and by immunofluorescence analysis against CD31 and P-selectin glycoprotein ligand-1 (PSGL-1).. In wild-type mice, blood flow recovery was enhanced by treatment with murine TXAS-overexpressing fibroblasts (C57-mTXAS) compared with empty vector- (EV) treated fibroblasts (C57-EV). Compared with C57-EV-treated mice, activated platelets (P-selectin(+) platelets) and plasma levels of vascular endothelial growth factor and stromal cell-derived factor-1 were increased in C57-mTXAS-treated mice. The enhanced-blood flow recovery by C57-mTXAS treatment was suppressed in the TP knockout mice (TP(-/-)). The expression of PSGL-1 in endothelial cells around the ischemic area was enhanced by C57-mTXAS treatment in wild-type but not in TP(-/-).. These results indicated that local administration of C57-mTXAS-induced angiogenesis by activated platelets that bind to PSGL-1 on ischemic endothelial cells.

Topics: Animals; Biomarkers; Cardiovascular Agents; Cell Line; Femoral Artery; Fibroblasts; Hindlimb; Ischemia; Laser-Doppler Flowmetry; Ligation; Male; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Neovascularization, Physiologic; Platelet Activation; Regional Blood Flow; Thromboxane A2; Thromboxane-A Synthase; Vascular Endothelial Growth Factor A

The aim of this study was to investigate the midterm performance of an everolimus-eluting, bioresorbable vascular scaffold (Absorb, Abbott Vascular, Santa Clara, California) for the treatment of focal tibial and distal popliteal lesions.. Drug-eluting stents are used below the knee to improve technical success and durability, but the ongoing presence of a permanent metal scaffold may have deleterious effects on the local vessel.. Tibial and distal popliteal angioplasty with scaffold placement was performed using an everolimus-eluting, bioresorbable scaffold (Absorb). Clinical and ultrasound follow-up was performed at 1, 3, 6, 12, and 24 months to detect binary restenosis and evaluate safety, restenosis, and clinical improvement.. Thirty-eight limbs in 33 patients were treated for critical limb ischemia (68.4%) or severe claudication (31.6%). Fifty scaffolds were used to treat a total of 43 lesions, with a mean length of 19.2 ± 11.6 mm. During a mean follow-up period of 12.0 ± 3.9 months, 5 patients died, and all others were available for follow-up. Among the 38 treated limbs, clinical improvement was present in 30 (79%). Binary restenosis was detected in 3 of 50 scaffolds (6%). Using the Kaplan-Meier method, rates of primary patency were 96% and 84.6% at 12 and 24 months, respectively, and rates of freedom from clinically driven target lesion revascularization were 96% and 96% at 12 and 24 months, respectively. Complete wound healing occurred in 64% of those treated for tissue loss, with no major amputation and a limb-salvage rate of 100%.. Twelve-month follow-up demonstrated excellent safety, patency, and freedom from target lesion revascularization using the Absorb bioresorbable vascular scaffold below the knee.

Topics: Absorbable Implants; Aged; Aged, 80 and over; Angiography; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Constriction, Pathologic; Critical Illness; Everolimus; Female; Humans; Intermittent Claudication; Ischemia; Kaplan-Meier Estimate; Leg; Limb Salvage; Male; Peripheral Arterial Disease; Popliteal Artery; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Recurrence; Risk Factors; Tibial Arteries; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Color; Vascular Patency

Although clinical trials demonstrated the superiority of the Zilver (Cook Medical, Bloomington, Ind) paclitaxel-eluting stent (PTX), a recently developed drug-eluting stent (DES), to conventional therapy for femoropopliteal (FP) lesions, the incidence and risk factors of the repetition of reintervention after DES implantation in clinical practice remained unrevealed.. This was a subanalysis of the ZEPHYR (ZilvEr PTX for tHe Femoral ArterY and Proximal Popliteal ArteRy) study, enrolling FP lesions undergoing endovascular therapy (EVT) with DES implantation. The current study analyzed the 2-year database including 583 FP lesions in 495 patients undergoing preoperative intravascular ultrasound imaging before DES implantation. The primary outcome measure was re-re-EVT, defined as undergoing additional EVT more than once during the 2-year follow-up after DES implantation. The secondary outcome measure was re-EVT, defined as undergoing at least one additional EVT during the follow-up.. Critical limb ischemia (CLI) was present in 28% of the study population, 23% had a history of EVT, and 43% had chronic total occlusion. Mean lesion length was 16 ± 10 cm, and intravascular ultrasound imaging-evaluated external elastic membrane area was 28 ± 10 mm. The incidence and risk factors of the repetition of reintervention after DES implantation for FP lesions were revealed. The current findings suggest that DES implantation might be a careful indication in CLI cases especially with a small vessel.

Topics: Aged; Aged, 80 and over; Angiography; Cardiovascular Agents; Critical Illness; Databases, Factual; Disease-Free Survival; Drug-Eluting Stents; Endovascular Procedures; Female; Femoral Artery; Humans; Incidence; Ischemia; Japan; Kaplan-Meier Estimate; Male; Multivariate Analysis; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Proportional Hazards Models; Prosthesis Design; Recurrence; Retreatment; Risk Factors; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Although drug-eluting balloons (DEBs) have shown promising results treating de novo (DN) atherosclerotic lesions and appear to have been widely adopted in Europe, their long-term efficacy in the broad spectrum of femoropopliteal restenosis (RE) remains to be proven. The purpose of the study was to assess the efficacy of paclitaxel-DEBs in restenotic (stented and nonstented) vs DN stenotic femoropopliteal arteries.. The study prospectively enrolled 100 patients undergoing femoropopliteal endovascular intervention by DEB for RE or DN stenosis. Patients who received additive atherectomy were excluded. The primary end point was the primary patency (PP) rate at 12 months. Secondary end points were sustained clinical improvement and clinically driven target lesion revascularization.. DEBs were used to treat 105 limbs for intermittent claudication (82 [78%]) or critical limb ischemia (23 [22%]) in 100 patients. Of these, 111 lesions were DN stenosis (46 [41%]) or RE (65 [59%]). The overall PP was 86% at 6 months and 74% at 12 months. PP of DN stenosis was higher at 6 months (93% vs 81%) and was significantly (P = .021) better than RE at 12 months (85% vs 68%). Sustained clinical improvement based on Rutherford classification was significant in both groups (P < .001). Target lesion revascularization was significantly lower in DN stenosis compared with RE at 12 months (15% vs 32%; P = .021).. DEB angioplasty is an effective therapy for DN femoropopliteal lesions. The results of DEB angioplasty for RE are inferior compared with DN stenosis after 12 months. Nevertheless, results of DEB angioplasty for RE seem comparable with technically more demanding literature-derived strategies.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Constriction, Pathologic; Critical Illness; Equipment Design; Female; Femoral Artery; Humans; Intermittent Claudication; Ischemia; Kaplan-Meier Estimate; Male; Middle Aged; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Prospective Studies; Recurrence; Stents; Time Factors; Treatment Outcome; Vascular Access Devices; Vascular Patency

To investigate the relationship between postprocedure intravascular ultrasound (IVUS) findings and restenosis after placement of drug-eluting stents (DES) for femoropopliteal lesions.. Between July 2012 and May 2013, DES were placed in 64 patients with 88 de novo femoropopliteal lesions. In 40 patients (mean age 74.2±9.4 years; 27 men), DES were placed in 50 lesions under IVUS guidance, and restenosis was monitored for 1 year. All patients were symptomatic (Rutherford 2-6), and 17 patients (43%) suffered from critical limb ischemia. IVUS findings after stenting were compared for patients with vs without restenosis, which was defined as a peak systolic velocity ratio >2.4 on duplex ultrasonography or >50% diameter stenosis on angiography.. Ten patients (14 lesions) developed restenosis, while 30 patients (36 lesions) did not. There were no significant differences in the frequency of diabetes or dialysis between the 2 groups. Female patients were predominant in the restenosis group (p<0.003). There were no significant differences of the percentage of TransAtlantic Inter-Society Consensus C/D lesions or stent edge dissection. Multivariate analysis indicated that cilostazol use [odds ratio (OR) 0.13; p=0.046], distal lumen cross-sectional area (CSA) (OR 0.86; p=0.035), and axial symmetry index (OR 0.60; p=0.045) were independent predictors of restenosis. Using receiver operator characteristic analysis, the best cutoff values of the distal lumen CSA and axial symmetry index for predicting restenosis were 17.1 cm(2) and 0.6, respectively.. IVUS guidance of DES placement in femoropopliteal lesions can offer useful predictors of restenosis at 1 year. The utility of distal lumen CSA and the axial symmetry index in the prediction of restenosis after femoropopliteal DES placement should be confirmed in a larger cohort.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon; Area Under Curve; Blood Flow Velocity; Cardiovascular Agents; Constriction, Pathologic; Critical Illness; Drug-Eluting Stents; Female; Femoral Artery; Humans; Ischemia; Japan; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Predictive Value of Tests; Prosthesis Design; Radiography; Recurrence; Regional Blood Flow; Retrospective Studies; Risk Factors; ROC Curve; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Duplex; Ultrasonography, Interventional

Topics: Angioplasty, Balloon; Cardiovascular Agents; Drug-Eluting Stents; Female; Femoral Artery; Humans; Ischemia; Male; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Ultrasonography, Interventional

We compared one-year amputation and survival rates in patients fulfilling 1991 European consensus critical limb ischaemia (CLI) definition to those clas, sified as CLI by TASC II but not European consensus (EC) definition.. Patients were selected from the COPART cohort of hospitalized patients with peripheral occlusive arterial disease suffering from lower extremity rest pain or ulcer and who completed one-year follow-up. Ankle and toe systolic pressures and transcutaneous oxygen pressure were measured. The patients were classified into two groups: those who could benefit from revascularization and those who could not (medical group). Within these groups, patients were separated into those who had CLI according to the European consensus definition (EC + TASC II: group A if revascularization, group C if medical treatment) and those who had no CLI by the European definition but who had CLI according to the TASC II definition (TASC: group B if revascularization and D if medical treatment).. 471 patients were included in the study (236 in the surgical group, 235 in the medical group). There was no difference according to the CLI definition for survival or cardiovascular event-free survival. However, major amputations were more frequent in group A than in group B (25 vs 12 %, p = 0.046) and in group C than in group D (38 vs 20 %, p = 0.004).. Major amputation is twice as frequent in patients with CLI according to the historical European consensus definition than in those classified to the TASC II definition but not the EC. Caution is required when comparing results of recent series to historical controls. The TASC II definition of CLI is too wide to compare patients from clinical trials so we suggest separating these patients into two different stages: permanent (TASC II but not EC definition) and critical ischaemia (TASC II and EC definition).

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Cardiovascular Agents; Consensus; Critical Illness; Disease-Free Survival; Female; France; Humans; Ischemia; Limb Salvage; Lower Extremity; Male; Middle Aged; Predictive Value of Tests; Reoperation; Terminology as Topic; Time Factors; Treatment Outcome; Vascular Surgical Procedures

Critical limb ischemia (CLI), a frequently encountered disorder, is associated with a high rate of limb amputation and mortality. To identify patients at high risk for CLI, we developed a simple risk score for peripheral arterial occlusive disease (PAOD).In our cross-sectional study, we first evaluated 1000 consecutive PAOD patients treated at our institution from 2005 to 2007, documenting clinical symptoms, comorbidities, and concomitant medication. We calculated odds ratios (OR) in a binary logistic regression model to find possible risk factors for CLI. We then verified the score in a second step that included the 1124 PAOD patients we treated between 2007 and 2011.In the first patient group, the greatest risk factors for CLI were age ≥75 years (OR 2.0), type 2 diabetes (OR 3.1), prior myocardial infarction (OR 2.5), and therapy with low molecular weight heparins (2.8). We scored 1 point for each of those conditions. One point was given for age between 65 and 75 years (OR 1.6) as well as for therapy with cardiac glycosides (OR 1.9) or loop diuretic therapy (OR 1.5). As statin therapy was protective for CLI with an OR of 0.5, we subtracted 1 point for those patients.In the second group, we could prove that frequency of CLI was significantly higher in patients with a high CLI score. The score correlated well with inflammatory parameters (c-reactive protein and fibrinogen). We were also able to define 3 different risk groups for low (score -1 to 1), intermediate (score 2-4), and high CLI risk (score >4).We developed a simple risk stratification scheme that is based on conditions that can be easily assessed from the medical history, without any laboratory parameters. This score should help to identify PAOD patients at high risk for CLI.

Topics: Age Factors; Aged; Aged, 80 and over; Arterial Occlusive Diseases; Cardiovascular Agents; Comorbidity; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Extremities; Female; Humans; Hypoglycemic Agents; Ischemia; Male; Microcirculation; Middle Aged; Myocardial Infarction; Odds Ratio; Peripheral Arterial Disease; Risk Assessment; Risk Factors

Topics: Angioplasty, Balloon; Cardiovascular Agents; Coated Materials, Biocompatible; Female; Humans; Intermittent Claudication; Ischemia; Male; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Vascular Access Devices

Determine the proportion of patients with chronic critical limb ischemia (CLI) who failed to adhere to Trans-Atlantic Inter-Society Consensus II guidelines of medical therapy and to quantify the effect of baseline suboptimal medical management on amputation-free survival (AFS).. The patients were identified from a prospectively maintained database of consecutive patients presenting with CLI to the Vascular Surgery service at a single hospital. The primary outcome variable was AFS. The effects of baseline demographics, comorbid medical conditions, ambulatory status, optimal medical management, and Rutherford classification were assessed. Significant univariate predictors (P < .10) of AFS were entered into a multivariate Cox proportional hazards model.. From August 1, 2010 through January 1, 2012, 98 patients (median age, 59.0; interquartile range, 53, 64 years; 58 men) were evaluated with rest pain (n = 40) or tissue loss (n = 58). Optimal medical management was identified in 31 (32%) patients at initial presentation. Compliance rates for the entire cohort were 61% for statin use, 69% for antiplatelet therapy, 56% for angiotensin-converting enzyme inhibitor use, and 53% for beta-blocker use. Significant univariate predictors of major amputation or death included: Rutherford classification (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.01-2.41; P = .04); nonambulatory status (HR, 2.17; 95% CI, 1.68-2.81; P < .01); unrevascularized patients (HR, 2.77; 95% CI, 1.32-5.85; P < .01); a history of tobacco abuse (HR, 1.49; 95% CI, 0.57-3.86; P = .09); a history of end-stage-renal disease (HR, 7.97; 95% CI, 3.10-20.52; P < .01); suboptimal medical management (HR, 4.25; 95% CI, 1.28-14.07; P = .02); and an absence of antiplatelet agents (HR, 1.94; 95% CI, 0.92-4.11; P = .08). Independent predictors of major amputation or death included: initial nonambulatory status (HR, 2.43; 95% CI, 1.03-2.05; P < .01); unrevascularized status (HR, 2.43; 95% CI, 1.76-3.34; P = .01); and suboptimal medical management at presentation (HR, 8.54; 95% CI, 2.05-35.65; P < .01).. Despite guidelines advocating the optimization of atherosclerotic risk factors, less than one-third of patients with CLI present with their risk factors optimally managed. Patients who are medically undertreated have an eight-fold risk of major amputation and/or death. The magnitude of the effect suggests that future trials and quality assessments should stratify outcomes by the quality of baseline medical management. Of the risk factors affecting AFS medical therapy optimization is the variable that can be most significantly improved by vascular surgeons and the medical community.

Topics: Amputation, Surgical; Cardiovascular Agents; Chronic Disease; Critical Illness; Disease-Free Survival; Female; Guideline Adherence; Humans; Ischemia; Kaplan-Meier Estimate; Limb Salvage; Male; Middle Aged; Multivariate Analysis; Practice Guidelines as Topic; Practice Patterns, Physicians'; Proportional Hazards Models; Risk Assessment; Risk Factors; Smoking Cessation; Texas; Time Factors; Treatment Outcome

Topics: Angiography; Anti-Inflammatory Agents; Arterial Occlusive Diseases; Cardiovascular Agents; Cryoglobulinemia; Cryoglobulins; Diabetes Mellitus, Type 2; Diagnostic Imaging; Drug Therapy, Combination; Female; Fibrinogens, Abnormal; Fingers; Humans; Hypertension; Ischemia; Ischemic Attack, Transient; Middle Aged

In United States alone there are more than 12 million people with peripheral artery disease (PAD). Long-term outcomes of plaque excision in high-risk population (patients with diabetes and patients with end stage renal disease on dialysis) are scarce.. Since November 2003, we treated 225 consecutive patients (138 male, mean age: 66.3 ± 12.4, range: 29-93) with SilverHawk(TM) plaque excision for critical limb ischemia or disabling claudication. A total of 367 procedures were performed treating 832 lesions (157 restenotic, 675 de novo). One hundred fifty-five patients (68.9%) were diabetics, 74 (32.9%) were on dialysis. All patients were treated with statins, clopidogrel, aspirin, and aggressive glycemic control. The primary endpoint for our study was target lesion revascularization (TLR), and the secondary endpoint was an assessment of major adverse events (all cause death, amputation, TLR).. The average time of observation was 2.2 ± 1.2 years. Procedural success rate was 99.4% with <30% residual stenosis achieved in 818 (98.9%) lesions. SilverHawk was used alone in 86.7%. No acute limb loss or major perforation occurred. Sixty (26.6%) patients had TLR. Long-term mortality was 16.4%. Seven (3.1%) patients had to undergo major amputations and 7 (3.1%) minor amputations. Seventy (31.1%) patients had a major adverse event. Atorvastatin 80 mg was found to be independent predictor of survival, and major amputation was found to be independent predictor of mortality.. SilverHawk Plaque Excision combined with aggressive pharmacotherapy in this presented high-risk population is associated with promising long-term outcomes that compare favorably with accepted standards of care.

Topics: Adult; Aged; Aged, 80 and over; Amputation, Surgical; Aspirin; Atherectomy; Atorvastatin; Cardiovascular Agents; Clopidogrel; Combined Modality Therapy; Critical Illness; Drug Therapy, Combination; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Intermittent Claudication; Ischemia; Kaplan-Meier Estimate; Limb Salvage; Male; Middle Aged; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Pyrroles; Recurrence; Registries; Retrospective Studies; Risk Factors; Severity of Illness Index; Ticlopidine; Time Factors; Treatment Outcome

Topics: Angioplasty; Arterial Occlusive Diseases; Cardiovascular Agents; Drug-Eluting Stents; Everolimus; Female; Humans; Ischemia; Male; Metals; Popliteal Artery; Sirolimus; Stents

To present the 5-year angiographic and clinical results of a retrospective registry assessing the performance of sirolimus-eluting stents (SES) in the treatment of infrapopliteal atherosclerotic disease.. From 2004 to 2009, 158 patients (95 men; mean age 71.9 years) with chronic lower limb ischemia (Rutherford categories 3-6) underwent primary SES placement in focal infrapopliteal lesions. The angiographic endpoint was patency, defined as freedom from in-stent stenosis (ISS) >50%. Clinical endpoints were death, amputation, and bypass surgery. Results were correlated with patient and lesion characteristics and cumulative outcomes were assessed with Kaplan-Meier analysis.. Technical success was achieved in all cases. The primary patency rates were 97.0% after 6 months, 87.0% after 12 months, and 83.8% at 60 months. In-stent stenosis was predominantly observed in the first year after stent placement. Female gender was associated with a higher rate of ISS. During clinical follow-up of 144 (91%) patients over a mean 31.1±20.3 months, there were 27 (18.8%) deaths, 4 (2.8%) amputations, and no bypass surgery. Clinical status improved in 92% of the patients with critical limb ischemia (CLI) and 77% of the patients suffering from claudication (p=0.022).. Treatment of focal infrapopliteal lesions with SES showed encouraging long-term angiographic results in this registry. Clinical improvement was evident, but more pronounced in CLI patients than in patients suffering from claudication. Further studies are needed to evaluate the potential clinical benefit of SES as compared to balloon angioplasty or bare metal stents in the treatment of infrapopliteal lesions.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Angioplasty, Balloon; Atherosclerosis; Cardiovascular Agents; Chi-Square Distribution; Chronic Disease; Constriction, Pathologic; Drug-Eluting Stents; Female; Germany; Humans; Ischemia; Kaplan-Meier Estimate; Lower Extremity; Male; Middle Aged; Popliteal Artery; Proportional Hazards Models; Prosthesis Design; Radiography; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Vascular Patency; Vascular Surgical Procedures

Topics: Angioplasty, Balloon; Atherosclerosis; Cardiovascular Agents; Drug-Eluting Stents; Female; Humans; Ischemia; Lower Extremity; Male; Popliteal Artery; Sirolimus

Topics: Aftercare; Anticoagulants; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Combined Modality Therapy; Endovascular Procedures; Extremities; Humans; Ischemia; Meta-Analysis as Topic; Minimally Invasive Surgical Procedures; Multicenter Studies as Topic; Peripheral Arterial Disease; Postoperative Complications; Radiography, Interventional; Randomized Controlled Trials as Topic; Risk; Thrombophilia; Vascular Surgical Procedures

To investigate whether cilostazol reduces restenosis and revascularization after infrapopliteal angioplasty.. This study was a retrospective analysis of a multicenter prospective registry.. Between February and April 2011, 63 patients (68 limbs, 101 lesions) with critical limb ischemia (CLI) were enrolled. Of these, 32 were cilostazol treated and 31 were the non-cilostazol-treated group. Outcome measures were binary restenosis by angiogram, reocclusion, target lesion revascularization (TLR), limb salvage rate and complete wound healing at 3 months.. Procedural success was obtained in all patients. The backgrounds and lesion characteristics of patients with isolated tibial artery disease and CLI did not differ significantly between the two groups. In a lesion-based analysis, binary restenosis and reocclusion were significantly lower in the cilostazol group than in the non-cilostazol group (56.8% vs. 86.0%; p = 0.015, 20.5% vs. 43.6%; p = 0.015, respectively). The TLR was also significantly lower in the cilostazol group (27.5% vs. 52.8%, p = 0.014). After adjustment for covariables, cilostazol was found to be associated with reduced angiographic restenosis, reocclusion and TLR rates in CLI patients at 3 months after infrapopliteal angioplasty. However, it remained unclear whether cilostazol was also associated with improved clinical outcomes.. Cilostazol may be associated with reduced restenosis, reocclusion and clinically driven TLR at 3 months after infrapopliteal angioplasty.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon; Cardiovascular Agents; Chi-Square Distribution; Cilostazol; Constriction, Pathologic; Female; Humans; Ischemia; Japan; Limb Salvage; Logistic Models; Male; Peripheral Arterial Disease; Popliteal Artery; Radiography; Registries; Retrospective Studies; Secondary Prevention; Tetrazoles; Time Factors; Treatment Outcome; Wound Healing

Cerebrovascular pathology has long moved from the category of a single medical problem in the social problem. Progression of vascular lesions of the brain results in significant disability, and in the later stages interfere with the ability to self-service and significantly reduces the quality of life. The key link is ischemic brain damage, or glutamate cascade, which many researchers believe trigger excitotoxic damage and a major cause of neuronal death. One important component of effective control of the effects of ischemic disorders is complex neuro-cytoprotective therapy. To correct for the effects of both acute and chronic ischemia of the brain need to effectively act in several directions simultaneously, normalizing metabolic changes, eliminating the cytokine imbalance transcription violations, reducing the severity of oxidative stress and excitotoxicity.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Cerebrovascular Circulation; Cerebrovascular Disorders; Energy Metabolism; Humans; Hypoxia; Ischemia; Methylhydrazines; Randomized Controlled Trials as Topic

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Biomarkers; Blood Chemical Analysis; Blood Coagulation; Blood Coagulation Tests; Cardiovascular Agents; Catastrophic Illness; Diagnosis, Differential; Electrocardiography; Humans; Immunosuppressive Agents; Ischemia; Lupus Erythematosus, Systemic; Male; Predictive Value of Tests; Severity of Illness Index; Thrombosis; Tomography, X-Ray Computed; Treatment Outcome; Vasculitis

To report the long-term outcomes of a single-center prospective study investigating primary placement of everolimus-eluting metal stents for recanalization of long infrapopliteal lesions compared to a matched historical control group treated with plain balloon angioplasty and provisional placement of bare metal stents in a bailout manner.. The study included 81 patients (63 men; mean age 71 years, range 45-85) suffering from critical limb ischemia (CLI) and angiographically proven long-segment (at least 1 lesion >4.5 cm) de novo infrapopliteal artery disease who underwent below-the-knee revascularization with either primary placement of everolimus-eluting stents (n = 47, 51 limbs, 102 lesions) or angioplasty and bailout bare metal stenting (n = 34, 36 limbs, 72 lesions). Clinical and angiographic follow-up was collected at regular time intervals. Primary clinical and angiographic endpoints included patient survival, major amputation-free survival, angiographic primary patency, angiographic binary restenosis (>50%), and overall event-free survival. Results were stratified according to endovascular treatment received. Multivariable Cox proportional hazards regression analysis was applied to adjust for confounding factors of heterogeneity.. Baseline demographics were well matched. No significant differences were identified between the 2 groups with regard to overall 3-year patient survival (82.2% versus 65.7%; p = 0.90) and amputation-free survival (77.1% versus 86.9%; p = 0.20). Up to 3 years, lesions fully covered with everolimus-eluting stents were associated with significantly higher primary patency [hazard ratio (HR) 7.98, 95% CI 3.69 to 17.25, p < 0.0001], reduced binary restenosis (HR 2.94, 95% CI 1.74 to 4.99, p < 0.0001), and improved overall event-free survival (HR 2.19, 95% CI 1.16 to 4.13, p = 0.015) versus the matched historical control group.. Primary infrapopliteal everolimus-eluting stenting for CLI treatment significantly inhibits restenosis and improves long-term angiographic patency and overall patient event-free survival compared to balloon angioplasty and bailout bare metal stenting.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Angioplasty, Balloon; Arterial Occlusive Diseases; Cardiovascular Agents; Constriction, Pathologic; Critical Illness; Disease-Free Survival; Drug-Eluting Stents; Everolimus; Female; Greece; Humans; Ischemia; Kaplan-Meier Estimate; Lower Extremity; Male; Metals; Middle Aged; Popliteal Artery; Proportional Hazards Models; Prospective Studies; Radiography; Risk Assessment; Risk Factors; Sirolimus; Stents; Time Factors; Treatment Outcome; Vascular Patency

Management of acute mesenteric ischemia is still a matter of concern for physicians. This disorder has been associated to an increased mortality mainly because of a late diagnosis and controversial treatment options.. We describe the case of a multidisciplinary approach to a cardiogenic thrombotic occlusion of superior mesenteric artery resulting in acute mesenteric ischemia. After rapid diagnosis with Duplex scan, we brought the patient to our catheterization laboratory and managed it with the common tools used for primary percutaneous coronary intervention. Among the specific issues of this case report, we observed some of the common complications of the acute myocardial infarction managed in the catheterization laboratory and treated them with the same tools used in the "myocardial area.". We showed how an "interventional cardiologist's" approach to acute mesenteric ischemia was effective in restoring superior mesenteric artery patency and in aborting a mesenteric infarction.

Topics: Acute Disease; Atrial Fibrillation; Cardiovascular Agents; Combined Modality Therapy; Female; Humans; Ischemia; Mesenteric Artery, Superior; Mesenteric Vascular Occlusion; Middle Aged; Patient Care Team; Radiography; Stents; Thrombolytic Therapy; Thrombosis; Treatment Outcome; Ultrasonography, Doppler, Duplex; Vascular Patency

Topics: Acute Disease; Aged; Angiography; Cardiovascular Agents; Humans; Iloprost; Ischemia; Male; Thrombolytic Therapy; Thumb; Tissue Plasminogen Activator

To assess the current 'real-world' management of hospitalised patients with lower-extremity peripheral artery disease (LE-PAD) and to assess the 1-year outcome.. The prospective and multicentre registry COhorte des Patients ARTériopathes (COPART) recruited consecutive patients from the departments of vascular medicine of three academic hospitals in Southwestern France.. Among the 940 patients, 27.4% had intermittent claudication (IC), 9.3% ischaemic rest pain, 54.3% ulceration or gangrene and 9.3% acute limb ischaemia (ALI). Patients with IC were younger and more likely to be men, with a history of smoking (89.5%) and chronic obstructive pulmonary disease (17%). Among those with IC, 8.9% had bypass surgery and 41.5% were treated with percutaneous angioplasty. Those with tissue loss had higher rates of cardiovascular disease (CVD) risk factors and co-morbidities. At entry to the study, the level of control of the CVD risk factors was poor. The 1-year mortality rate was of 5.7% in patients with IC, 23.1% in patients with ischaemic rest pain, 28.7% in patients with tissue loss and 23% in those with ALI. Compliance with evidence-based medicine and pharmacological treatment was sub-optimal.. This registry underscores the differences in patient profiles in the daily clinical setting, compared to those enrolled in several trials.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Angioplasty, Balloon; Cardiovascular Agents; Cardiovascular Diseases; Chi-Square Distribution; Evidence-Based Medicine; Female; France; Gangrene; Guideline Adherence; Hospital Mortality; Hospitalization; Hospitals, University; Humans; Intermittent Claudication; Ischemia; Kaplan-Meier Estimate; Leg Ulcer; Length of Stay; Lower Extremity; Male; Middle Aged; Outcome and Process Assessment, Health Care; Peripheral Vascular Diseases; Practice Guidelines as Topic; Proportional Hazards Models; Prospective Studies; Registries; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vascular Surgical Procedures

Midterm technical and clinical evaluation of stent angioplasty with drug-eluting stents in infrapopliteal lesions in patients with critical limb ischemia (CLI).. Percutaneous stent angioplasty was performed in 128 limbs in 114 patients presenting with 320 vascular lesions. Lesions with up to 6 cm in length and at least one patent vessel below the obstruction were treated; 341 drug-eluting Cypher(R) stents (diameter of 2.5-3.5 mm; length of 18-33 mm) were implanted. Follow-up examinations were performed up to 18 months postinterventionally using clinical examination, ankle-brachial index (ABI) calculation, and color coded Duplex sonography. Patency rates were calculated on the basis of the Kaplan-Meier life-table analysis.. Technical success was achieved in 99.06%. Minor complications (hematoma, distal emboli, and vessel dissection) were documented in 8.77% of the patients. The 6, 12, and 18 months primary patency rate as controlled by Duplex sonography was 89.8, 84.2 and 83.3%, respectively; 77.6% of the lesions healed postinterventionally. The cumulative limb salvage rate was 95.6%.. Drug-eluting stent (DES) angioplasty in infrapopliteal arteries is a safe and effective technique for the treatment of patients with CLI. The use of a DES results in favorable technical and clinical outcome in the midterm follow-up.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon; Ankle Brachial Index; Arterial Occlusive Diseases; Cardiovascular Agents; Critical Illness; Drug-Eluting Stents; Female; Germany; Humans; Ischemia; Kaplan-Meier Estimate; Limb Salvage; Lower Extremity; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Color; Vascular Patency

To report 12-month outcomes following application of sirolimus-eluting stents (SES) in infrapopliteal arteries in patients with chronic limb ischemia.. A prospective single-center study was conducted involving 146 consecutive patients (102 men; mean age 73+/-9 years) with Rutherford-Becker categories 2 to 5 lower limb ischemia who underwent SES placement. The average degree of stenosis at baseline was 86%+/-5%; there were 44 (30%) occlusions. The main study endpoint was the 1-year primary patency rate, defined as freedom from in-stent restenosis (luminal narrowing > or =70%) detected with angiography or, if appropriate, with duplex ultrasound. Secondary endpoints included the 6-month primary patency rate, secondary patency rate, ankle-brachial index (ABI), and changes in the Rutherford-Becker classification.. Fifteen (10%) patients were lost to follow-up, and 27 (18%) patients died during the follow-up period, leaving 104 patients undergoing the 6- and 12-month follow-up examinations. After 6 months and 1 year, the primary patency rates were 88.5% and 83.7%, respectively. The mean ABI increased from 0.6+/-0.4 at baseline to 0.8+/-0.2 after 6 months and remained significantly improved during 1-year follow-up (p<0.0001). The mean Rutherford-Becker classification decreased from 3.3+/-0.8 at baseline to 0.9+/-1.1 (p<0.0001) after 1 year.. Treatment of infrapopliteal arteries with SES yields encouraging long-term results that compare favorably with previously published data on bare metal stents or plain balloon angioplasty.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon; Ankle Brachial Index; Arterial Occlusive Diseases; Cardiovascular Agents; Chronic Disease; Constriction, Pathologic; Disease-Free Survival; Drug-Eluting Stents; Female; Germany; Humans; Ischemia; Kaplan-Meier Estimate; Logistic Models; Lower Extremity; Male; Middle Aged; Odds Ratio; Popliteal Artery; Prospective Studies; Prosthesis Design; Radiography; Recurrence; Registries; Risk Assessment; Risk Factors; Severity of Illness Index; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Duplex; Vascular Patency

Topics: Angioplasty, Balloon; Arterial Occlusive Diseases; Cardiovascular Agents; Chronic Disease; Constriction, Pathologic; Drug-Eluting Stents; Humans; Ischemia; Limb Salvage; Lower Extremity; Popliteal Artery; Prosthesis Design; Recurrence; Risk Assessment; Risk Factors; Severity of Illness Index; Sirolimus; Time Factors; Treatment Outcome; Vascular Patency

Endovascular management of limb-threatening ischemia often requires treatment of tibial occlusive disease. This study was preformed to examine the patency of drug-eluting tibial stents.. The medical records of all patients undergoing drug-eluting tibial stent placement for limb-threatening ischemia from June 2004 to June 2008 were retrospectively reviewed. Postprocedural antiplatelet therapy included clopidogrel and aspirin. Patients were followed with serial arterial duplex ultrasonography and had selective subsequent angiographic evaluation based on noninvasive findings. Primary patency of the target lesion, limb salvage, and survival rates were reported.. A total of 240 patients underwent 283 tibial angioplasty procedures to treat limb-threatening ischemia during the 4-year period. Fifty-two patients (22%) had a suboptimal balloon result and were treated with a drug-eluting tibial stent. Balloon-expandable paclitaxel-eluting stents were used in all patients (1.2 stents per patient; range, 1-3; median diameter, 2.75 mm; range, 2.5-3.5 mm; median length, 24 mm; range, 20-32 mm). Forty-eight of those 52 patients (92%) had simultaneous endovascular treatment of proximal lesions. Mean follow-up was 14.3 months (range, 1-48 months). Target lesion patency of the drug-eluting tibial stent was 73% at 24 months (SE < 10%). Limb salvage rate in patients treated with drug-eluting tibial stents was 86% at 26 months (SE < 10%), and the survival rate was 65% at 24 months (SE < 10%).. Drug-eluting tibial stents are a viable option for the endovascular management of limb-threatening ischemia and have acceptable patency rates. The majority of patients require multilevel endovascular treatment, and close surveillance is required for limb salvage.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Angioplasty, Balloon; Arterial Occlusive Diseases; Cardiovascular Agents; Constriction, Pathologic; Drug-Eluting Stents; Female; Humans; Ischemia; Life Tables; Limb Salvage; Male; Middle Aged; Minnesota; Paclitaxel; Platelet Aggregation Inhibitors; Prosthesis Design; Radiography; Recurrence; Reoperation; Retrospective Studies; Severity of Illness Index; Tibial Arteries; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Duplex; Vascular Patency

Topics: Acute Disease; Aortic Aneurysm; Aortic Dissection; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Endovascular Procedures; Hemodynamics; Humans; Ischemia; Time Factors; Treatment Outcome

This study sought to examine the impact of an aggressive approach to anatomic screening and endovascular revascularization in a veterans administration population with critical limb ischemia (CLI) on the primary treatments received and overall clinical outcomes.. The baseline clinical and angiographic characteristics and clinical outcomes of the first consecutive fifty veterans who were referred for the evaluation and treatment of CLI using the strategy outlined were assessed by retrospective review of the computerized medical record and angiographic data.. Among the entire cohort, the primary treatments received were as follows--revascularization n = 44 (88%), primary amputation n = 1 (2%), medical treatment n = 3 (6%), and primary minor amputation n = 2 (4%). Endovascular revascularization was the dominant mode of revascularization (94%), with a procedural success rate of 91%. Repeat revascularization was required in 19% of patients who had an initially successful endovascular procedure. A total of eight deaths and four major amputations occurred in the entire cohort over a mean follow-up of 397 +/- 190 days. The 1-year Kaplan-Meier estimates for survival and amputation-free survival for the entire cohort were 90 and 81%, respectively. Resolution of rest pain or complete wound healing was achieved in 85% of patients at a mean of 157 +/-126 days.. An aggressive approach to anatomic screening and contemporary endovascular treatment of CLI resulted in a higher rate of revascularization as the primary treatment for CLI than previously reported, and was associated with high rates of overall and amputation-free survival.

Topics: Aged; Amputation, Surgical; Cardiovascular Agents; Critical Illness; Female; Hemodynamics; Humans; Ischemia; Kaplan-Meier Estimate; Lower Extremity; Magnetic Resonance Angiography; Male; Mass Screening; Middle Aged; Pain; Pain Measurement; Reoperation; Retrospective Studies; Risk Assessment; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; United States; United States Department of Veterans Affairs; Vascular Surgical Procedures; Wound Healing

Topics: Amputation, Surgical; Cardiovascular Agents; Critical Illness; Hemodynamics; Humans; Ischemia; Lower Extremity; Magnetic Resonance Angiography; Mass Screening; Pain; Pain Measurement; Reoperation; Risk Assessment; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Vascular Surgical Procedures; Wound Healing

Topics: Angioplasty, Balloon; Arterial Occlusive Diseases; Cardiovascular Agents; Constriction, Pathologic; Critical Illness; Drug-Eluting Stents; Humans; Ischemia; Lower Extremity; Metals; Paclitaxel; Popliteal Artery; Prospective Studies; Prosthesis Design; Secondary Prevention; Stents; Treatment Outcome

No data are currently available on the role of oral sirolimus in the prevention of recurrent stenosis in the periphery. We report the effects of oral sirolimus in the prevention of recurrent infrainguinal obstructions in patients with complex peripheral arterial disease. Three patients with ischemic rest pain of the lower limbs and repeated short-term need for surgical and/or endovascular revascularization: 9 times within 12 months, 7 times within 15 months, 11 times within 26 months, respectively. Oral sirolimus on a case by case basis, resulted in less frequent restenosis and longer intervention-free intervals: three re-interventions within 37 months in the first patient, one balloon angioplasty within 17 months in the second, and three re-interventions within 21 months in the third patient, respectively. Side effects, in particular dyspepsia and diarrhoea, were mild and tolerable. To our knowledge, this is the first report to show that oral sirolimus was successfully administered in patients with recurrent excessive neointimal proliferation after revascularization of peripheral arterial lesions lowering the necessity of re-intervention and hence prolonging intervention-free intervals.

Topics: Administration, Oral; Aged; Angioplasty, Balloon; Cardiovascular Agents; Constriction, Pathologic; Female; Humans; Ischemia; Lower Extremity; Male; Middle Aged; Peripheral Vascular Diseases; Reoperation; Saphenous Vein; Secondary Prevention; Sirolimus; Thrombectomy; Treatment Failure; Vascular Surgical Procedures

Although Bell's palsy is the most common acute facial paralysis, the cause of it is still unknown. This made the treatment for it remain very limited. Many methods are simply symptomatic treatment. Up to now we have known that Bell's palsy is related to viral infection and the pathomechanism of Bell's palsy involves inflammatory oedema and entrapment neuropathy in the narrow bony facial canal. So treatment plans for Bell's palsy mainly focus on antiviral therapy, relieving inflammatory oedema and accelerating facial nerve recovery. Sodium beta-aescin is derived from horse chestnut and its major constituent is aescigenin which has been approved by China national drug standard. The pharmacologic action of sodium beta-aescin is to relieve tissue oedema, recover vasopermeability and eliminate pressure caused by oedema. Nowadays sodium beta-aescin has been widely used clinically for encephaledema or tumefaction caused by trauma or operation. It also can be used for treating disease of digestive system and increasing intravenous tension and improving microcirculation. Although many papers had been published on the anti-edema effects of sodium beta-aescin, little was known about the effects in treating oedema complicated by Bell's palsy.

Topics: Bell Palsy; Cardiovascular Agents; Chemistry, Pharmaceutical; Drug Design; Edema; Escin; Facial Paralysis; Humans; Inflammation; Ischemia; Models, Biological; Models, Theoretical; Pharmaceutical Preparations; Sodium

This study investigated whether polydeoxyribonucleotide (PDRN) may be efficacious in the treatment of peripheral artery occlusive diseases, which are a major cause of morbidity in Western countries and still lack standardized treatment.. We investigated the effects of PDRN, a mixture of deoxyribonucleotides, in an experimental model of hind limb ischemia (HLI) in rats to stimulate vascular endothelial growth factor (VEGF)-A production and to avoid critical ischemia. The femoral artery was excised to induce HLI. Sham-operated on rats (sham HLI) were used as controls. Animals were treated daily with intraperitoneal PDRN (8 mg/kg) or its vehicle. Animals were euthanized at day 7, 14, and 21 after the evaluation of blood flow by laser Doppler. Dissected muscles were used to measure VEGF-A messenger RNA (mRNA) and protein expression, to evaluate edema, and to assess histologic damage.. Administration of PDRN dramatically increased VEGF mRNA throughout the study (day 14: HLI, 7 +/- 2.2 n-fold/beta-actin; HLI + PDRN, 13.3 +/- 3.8 n-fold/beta-actin; P < .0001) and protein expression (HLI, 11 +/- 3.4 integrated intensity; HLI + PDRN, 16 +/- 3.8 integrated intensity; P < .0001). The compound stimulated revascularization, as confirmed by blood flow restoration (P < .005 vs HLI + vehicle), and blunted the histologic damage and the degree of edema. PDRN did not modify VEGF-A expression and blood flow in sham HLI animals. Furthermore, the concomitant administration of 3,7-dimethyl-1-propargilxanthine (DMPX), a selective adenosine A(2A) receptor antagonist, abolished the positive effects of PDRN, confirming that PDRN acts through this receptor.. These results led us to hypothesize a role for PDRN in treating peripheral artery occlusive diseases.

Topics: Adenosine A2 Receptor Agonists; Angiogenesis Inducing Agents; Animals; Arterial Occlusive Diseases; Cardiovascular Agents; Disease Models, Animal; Edema; Hindlimb; Ischemia; Laser-Doppler Flowmetry; Male; Muscle, Skeletal; Neovascularization, Physiologic; Oxidative Stress; Peripheral Vascular Diseases; Polydeoxyribonucleotides; Rats; Rats, Sprague-Dawley; Receptors, Adenosine A2; Regional Blood Flow; RNA, Messenger; Time Factors; Up-Regulation; Vascular Endothelial Growth Factor A

Stent implantation is an alternative, safe, and reliable strategy for the treatment of chronic mesenteric ischemia, especially for patients at high surgical risk. However, in-stent restenosis (the Achille's hill of bare metal stent) may occur in up to 20% of cases at 6 months and 53% at 1 year. We describe a case of celiac trunk stenosis treated by bare metal stent complicated by recalcitrant in-stent restenosis and treated by paclitaxel-eluting stent implantation.

Topics: Aged; Angioplasty, Balloon; Arterial Occlusive Diseases; Cardiovascular Agents; Celiac Artery; Chronic Disease; Constriction, Pathologic; Drug-Eluting Stents; Female; Humans; Ischemia; Magnetic Resonance Angiography; Mesenteric Vascular Occlusion; Metals; Paclitaxel; Prosthesis Design; Recurrence; Stents; Tomography, X-Ray Computed; Treatment Outcome

Every cell needs energy, i.e., adenosine triphosphate (ATP), to carry out its function. Decreased oxygen levels, decreased blood flow, and other stressful conditions can drastically effect the intracellular concentrations of these energy compounds. Skeletal muscle, unlike the heart, can address this drop in ATP by employing the myokinase reaction, ultimately producing ATP with a subsequent elevation in adenosine monophosphate (AMP). Ribose, a naturally occurring 5-carbon monosaccharide, is a key component of RNA, DNA (which has deoxyribose), acetyl coenzyme A, and ATP. Each cell produces its own ribose, involved in the pentose phosphate pathway (PPP), to aid in ATP production. States of ischemia and/or hypoxia can severely lower levels of cellular energy compounds in the heart, with an associated compromise in cellular processes, ultimately reflected in altered function. Ribose appears to provide a solution to the problem in replenishing the depressed ATP levels and improving functional status of patients afflicted with cardiovascular diseases.

Topics: Adenosine Triphosphate; Cardiovascular Agents; Cardiovascular Diseases; Dietary Supplements; Energy Metabolism; Heart; Humans; Hypoxia; Ischemia; Myocardium; Ribose

Acetazolamide (AZD) produces cerebral vasodilation. The underlying mechanism is unclear, but it is assumed to be largely due to CO2 retention and acidosis. We tested if cerebrovascular effects of AZD were similar to hypercapnia in the newborn pig.. We used the closed cranial window/intravital microscopy technique to determine pial arteriolar diameters simultaneously with laser-Doppler flowmetry (LDF) to monitor cortical blood perfusion. Anaesthetized (Na-thiopenthal +alpha-chloralose), ventilated, 1-day-old instrumented piglets (n=38) were divided into five experimental groups: time control (n=11), indomethacin, ibuprofen, Nomega-nitro-L-arginine methyl ester (L-NAME) treatments (1, 30, 15 mg/kg, i.v., n=6, 6, 4, respectively), and global ischaemia/reperfusion (I/R, 10 min induced by elevated intracranial pressure, n=11). Responses to 5-10% inhaled CO2 were recorded before and after the treatments, and then in a similar manner to AZD (10-20 mg/kg, i.v.).. Hypercapnia and AZD produced pial arteriolar vasodilation and increases in cortical perfusion. Consistent with previous data, hypercapnia-induced changes were abolished by indomethacin, unaltered by ibuprofen and L-NAME and were significantly attenuated after I/R. AZD-induced vasodilation was also sensitive to indomethacin and I/R and was unaltered by ibuprofen or L-NAME.. The mechanism of AZD-induced vasodilation appears to be similar/identical to hypercapnia, and pial arteriolar diameter changes reflect changes in cortical perfusion.

Topics: Acetazolamide; Animals; Animals, Newborn; Arterioles; Carbonic Anhydrase Inhibitors; Cardiovascular Agents; Female; Indomethacin; Ischemia; Laser-Doppler Flowmetry; Male; Pia Mater; Swine; Vasodilation

Topics: Arterial Occlusive Diseases; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Catheterization; Coated Materials, Biocompatible; Femoral Artery; Humans; Ischemia; Leg; Popliteal Artery; Radiography; Stents; Tibial Arteries; Treatment Outcome

Infrainguinal bypass (IB) surgery is an effective means of improving arterial circulation to the lower extremity for patients with critical limb ischemia (CLI). However, wound complications (WC) of the surgical incision following IB can impart significant morbidity.. A retrospective analysis of WC from the 1404 patients enrolled in a multicenter clinical trial of vein bypass grafting for CLI was performed. Univariate and multivariable regression models were used to determine WC predictors and associated outcomes, including graft patency, limb salvage, quality of life (QoL), resource utilization (RU), and mortality.. A total of 543 (39%) patients developed a reported WC within 30 days of surgery, with infections (284, 52%) and hematoma/hemorrhage (121, 22%) being the most common type. Postoperative anticoagulation (odds ratio [OR], 1.554; 95% confidence interval [CI] 1.202 to 2.009; P = .0008) and female gender (OR, 1.376; 95% CI, 1.076 to 1.757; P = .0108) were independent factors associated with WC. Primary, primary-assisted, and secondary graft patency rates were not influenced by the presence of WC; though, patients with WC were at increased risk for limb loss (hazard ratio [HR], 1.511; 95% CI 1.096 to 2.079; P = .0116) and higher mortality (HR, 1.449; 95% CI 1.098 to 1.912; P = .0089). WC was not significantly associated with lower QoL at 3 months (4.67 vs 4.79, P = .1947) and 12 months (5.02 vs 5.13, P = .2806). However, the subset of patients with serious WC (SWC) demonstrated significantly lower QoL at 3 months compared with patients without WC, (4.43 vs 4.79, respectively, P = .0166), though this difference was not seen at 12 months (4.94 vs 5.13, P = .2411). Patients with WC had higher RU than patients who did not have WC. Mean index length of hospital stay (LOS) was 2.3 days longer, mean cumulative 1-year LOS was 8.1 days longer, and mean number of hospitalizations was 0.5 occurrences greater for patients with WC compared with patients without WC (all P < .0001).. WC is a frequent complication of IB for CLI, associated with increased risk for major amputation, mortality, and greater RU. Further detailed investigation into the link between female gender and oral anticoagulation use with WC may help identify causes of WC and perhaps prevent or lessen their occurrence.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Agents; Extremities; Female; Graft Occlusion, Vascular; Health Care Costs; Health Resources; Hematoma; Humans; Incidence; Ischemia; Limb Salvage; Male; Middle Aged; North America; Odds Ratio; Oligonucleotides; Postoperative Hemorrhage; Quality of Life; Retrospective Studies; Risk Assessment; Risk Factors; Sex Factors; Surgical Wound Infection; Transplantation, Autologous; Treatment Outcome; Vascular Patency; Vascular Surgical Procedures; Veins

Topics: Arterial Occlusive Diseases; Cardiovascular Agents; Catheterization; Exercise; Humans; Ischemia; Leg; Stents; Treatment Outcome

To assess the safety and efficacy of sirolimus-eluting stents (SESs) in the treatment of severe intermittent claudication and critical limb ischaemia with "below-the-knee" lesions, unsuitable for surgery.. Limited published evidence suggests that drug-eluting stents may offer significant improvements in the treatment of infrapopliteal lesions.. Thirty consecutive patients with either severe intermittent claudication or critical limb ischemia (CLI), category 3-6 of Rutherford classification, and multivessel disease of infrapopliteal arteries (> or = 2 vessels) were treated with SES. Sixty-two arteries were treated with 106 SES. Mean age was 73.9 years, 77% of patients were male and 36% diabetic. The primary endpoint was clinical improvement and healing of ulcers at short term (1 month) and mid term (7.7 months). The secondary endpoint was primary vessel patency rate (angiographic or duplex assessment). All patients received clopidogrel (75 mg daily) or ticlopidine (150 mg daily) for 2 months or longer.. Angiographic and procedural success was achieved in all patients. At 7 months (7.7 +/- 5.8), it was necessary to amputate 1 toe in one patient and 1 mid-foot in another. Limb salvage was obtained in 100% of patients. Other events were: two cardiac deaths unrelated to CLI, one stroke with hemiparesia, one initial reperfusion syndrome, one contralateral CLI, and three recurrent homolateral claudication cases. All surviving patients had a mid-term clinical improvement with 97% of primary patency (56 patent arteries on 58 arteries).. Treatment of "below-the-knee" lesions with SES may provide an alternative treatment for patients with CLI.

Topics: Adult; Aged; Aged, 80 and over; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Coated Materials, Biocompatible; Equipment Safety; Female; Follow-Up Studies; Humans; Intermittent Claudication; Ischemia; Kaplan-Meier Estimate; Leg; Male; Middle Aged; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Popliteal Artery; Prospective Studies; Research Design; Severity of Illness Index; Sirolimus; Stents; Time Factors; Treatment Outcome; Vascular Patency

Fructose 1, 6 diphosphate (FDP), a metabolic intermediate, provides an alternative mechanism to circumvent the rate-limiting step in the Kreb's cycle. This agent has been observed to prevent the effects of ischemia on heart tissue and kidney function and the effects of endotoxic shock. It has been shown conclusively to minimize the adverse effects of ischemia-reperfusion injury in experimental pedicled skin flaps in animals. The present study was done to evaluate the effect of intra-arterial administration of FDP on salvage of ischemic microvascular transfer of gracilis muscle flaps in rats, with the premise that it might prolong the ischemia time of muscle flaps at room temperature, thus increasing chances of flap survival. Irrigation with FDP did not change the quantitative survival of the flaps, but there was qualitative improvement on histologic evaluation and DNA analysis. Decreased inflammatory damage and DNA fragmentation were seen at the 2.5-hr period. Histologic staining for mitochondrial oxygenation in gracilis muscle also showed increased uptake in the FDP-treated group vs. control at the 2.5-hr ischemia period. Further experiments with different modes of FDP administration should be carried out to identify more effective means of amelioration of flap ischemia.

Topics: Animals; Cardiovascular Agents; Fructosediphosphates; Graft Survival; Ischemia; Male; Models, Animal; Muscle, Skeletal; Rats; Rats, Sprague-Dawley; Surgical Flaps

Perfusion of the abdomen is determined by cardiac function and circulation. Intestinal ischemia can be caused by Non occlusive bowel ischemia (NOD) that is important in internal as well as surgical intensive care medicine. Cardiac medication can influence perfusion of the bowel: 1) digitalis increases muscular tonus and decreases perfusion regulation b) diuretics lead to hypovolemia, hypotonia and malperfusion, c) antihypertensive medication can cause intraoperative hypotension that demands catecholamines, d) catecholamines can reduce perfusion by pathologic vasoconstriction in the splanchnicus area. Preoperative medication should respect 1) preoperatively taken ACE-inhibitors should be given postoperatively, as they have protective influence on the microcirculation of the bowel, 2) beta-blockers stabilize the myogenic tonus of the abdominal vessels, reduce an overshot of the parasympatheticus and diminish the risk of neurogenic abdominal shock, 3) catecholamines should be used with respect to ischemia of the bowel. Therapy of NOD should be focused on the primary vascular and hemodynamic causes and also take care for bacterial translocation and consecutive sepsis.

Topics: Aged; Cardiovascular Agents; Coronary Circulation; Hemodynamics; Humans; Intestines; Ischemia; Male; Mesenteric Vascular Occlusion; Risk Factors; Shock, Cardiogenic; Splanchnic Circulation; Systemic Inflammatory Response Syndrome; Thrombosis

A possible mechanism for D-cis-diltiazem (diltiazem)-mediated improvement of the contractile function of ischemic/reperfused hearts was examined. Thirty-five-min ischemia/60-min reperfusion recovered little the left ventricular developed pressure (LVDP) and decreased myocardial high-energy phosphates (HEPs). Ischemia induced an accumulation of tissue Na+ content, an increase in cytochrome c in the cytosolic fraction, and a decrease in the oxygen consumption rate (OCR) in perfused hearts. Treatment of the heart with 1 microM diltiazem for the last 3-min of pre-ischemia did not affect the decrease in HEPs during ischemia, whereas that with 3 microM partially attenuated the decrease in ATP, suggesting that 3 microM diltiazem exerted energy-sparing effect. Treatment with 1 microM diltiazem enhanced the post-ischemic recovery of LVDP associated with attenuation of the ischemia-induced accumulation of tissue Na+, increase in cytochrome c in the cytosolic fraction, and decrease in myocardial OCR, and restoration of the myocardial HEPs during reperfusion. Combined treatment with diltiazem and a Na+/H+ exchange inhibitor, but not a Na+ channel blocker, facilitated the attenuation of Na+ accumulation in the ischemic heart and the enhancement of the post-ischemic recovery of LVDP. Sodium lactate, a possible metabolite in ischemic hearts, and sodium chloride increased the Na+ concentration in mitochondria, released cytochrome c into incubation medium, and reduced the mitochondrial respiration. Treatment of isolated mitochondria with diltiazem failed to attenuate the sodium lactate- and sodium chloride-induced alterations. These results suggest that the cardioprotection of diltiazem may be exerted via attenuating cytosolic Na+ overload through Na+ channels in the ischemic heart, leading to preservation of mitochondrial functional ability during ischemia, followed by improvement of post-ischemic energy production and contractile recovery.

Topics: Animals; Calcium; Cardiotonic Agents; Cardiovascular Agents; Cytochromes c; Diltiazem; Drug Interactions; Ischemia; Male; Mitochondria; Myocardial Contraction; Myocardial Reperfusion Injury; Myocardium; Oxygen Consumption; Phosphates; Rats; Rats, Wistar; Reperfusion Injury; Respiration; Sodium; Sodium Channel Blockers; Sodium-Hydrogen Exchangers

Vascular diseases like thrombosis, myocardial infarction, cerebral ischemia or chronic venous insufficiency affect a high proportion of the population. They are all associated with more or less pronounced ischemic conditions. We have previously shown that some venotropic drugs display an anti-ischemic activity, i.e. they prevent the hypoxia-induced decrease in ATP content in cultured cells. The effect is due to the fact that these molecules maintain mitochondrial respiratory activity during hypoxia. Among them is bilobalide. Starting from the 3D structure of bilobalide, we designed new molecules presenting the same chemical features. They were synthesized and tested for their biological activity. As the parent compound, two of them, malonic acid dicyclopent-2-enyl ester (MRC2P119) and 2-oxo-3-oxa-bicyclo[3.1.0]hexane-1-carboxylic acid allyl ester (MRC2P57), were able to markedly increase the respiratory control ratio of isolated mitochondria. They are able to prevent the inhibition of complex I by amytal and of complex III by myxothiazol, but not the uncoupling of the respiration by carbonylcyanide m-chlorophenyl hydrazone (m-CCP). Moreover, MRC2P119 and MRCP2P57 inhibit, in a dose-dependent way, the hypoxia-induced decrease in ATP content in endothelial cells as well as the subsequent activation of these cells as evidenced by an inhibition of the increase in neutrophil adherence to the endothelial cells induced by hypoxia. Finally, MRC2P119 prevent the hypoxia- and the hypoxia-reoxygenation-induced decrease in viability of SH-SY5Y neuroblastoma cells. In conclusion, we identified two new molecules, which display anti-ischemic properties when tested in vitro on endothelial and neuronal cell types. This anti-ischemic activity is probably due to a protection of complexes I and III of the mitochondrial respiratory chain.

Topics: Adenosine Triphosphate; Animals; Bridged Bicyclo Compounds; Cardiovascular Agents; Cell Adhesion; Cell Hypoxia; Cell Survival; Cells, Cultured; Cyclopentanes; Diterpenes; Dose-Response Relationship, Drug; Electron Transport; Esters; Female; Furans; Ginkgolides; Humans; Ischemia; Malonates; Mitochondria, Liver; Neutrophils; Oxygen Consumption; Rats; Rats, Wistar; Structure-Activity Relationship; Tumor Cells, Cultured

A 68 year old woman developed a sudden decrease in her visual acuity in both eyes with several central scotomas. Funduscopy demonstrated a motted alteration of the retinal pigment epithelium in both maculae. The fluorescein angiography showed a choroidal ischemia at the macular level in both eyes.. The patient was diagnosed of acute macular neuroretinopathy. This entity is included among the so-called <>. However, it is important to determine which of these diseases each patient suffers in order to determine if treatment is necessary, the visual prognosis and the possibility of recurrences.

Topics: Acute Disease; Aged; Cardiovascular Agents; Choroid; Female; Humans; Ischemia; Macula Lutea; Pigment Epithelium of Eye; Retinal Diseases; Scotoma; Syndrome; Visual Acuity

The aim of this work was to compare in the rat the cardioprotective efficacy and the total plasma antioxidant activity of a standardised Ginkgo biloba L. extract (GB) as such (300 mg/kg/day) or complexed with phosphatidylcholine (GB-PC; 1:2 w/w), after a 5 days oral administration. At the end of the treatment, the total plasma antioxidant defence was determined by the TRAP and FRAP assays, and the hearts from all groups of animals subjected to moderate ischemia (flow reduction to 1 ml/min for 20 min) and reperfusion (15 ml/min for 30 min). The recovery of left ventricular developed pressure (LVDP) at the end of reperfusion was 35-40% of the preischemic values in both control and vehicle rats, 50.2% in the GB group and 72.5% in the GB-PC pre-treated animals. Creatine kinase (CK) outflow in the perfusate from the hearts of GB and GB-PC treated animals were restrained to a different extent vs. controls (by 71% GB-PC; by 22% GB); the rate of prostacyclin (6-keto-PGF1 alpha) release was far greater in GB-PC than in GB hearts. In parallel, the GB extract significantly increased the total antioxidant plasma capacity (by 24.5% TRAP; 27.9% FRAP) only when complexed with phospholipids. This indicates an increased bioavailability of phenolic antioxidants when suitably embedded within a lipophilic carrier. The results of this study demonstrate that complexation of Ginkgo biloba with phospholipids induces in the rat, even after a short treatment a greater resistance of the heart to ischemia/reperfusion damage in respect to the native extract, due to an increased plasma antioxidant activity.

Topics: Animals; Antioxidants; Cardiovascular Agents; Drug Combinations; Ginkgo biloba; Heart; In Vitro Techniques; Ischemia; Male; Medicine, Chinese Traditional; Myocardial Reperfusion Injury; Phosphatidylcholines; Phytotherapy; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar

To evaluate in a group of seriously diseased patients with nonreconstructable chronic critical leg ischemia (CLI), treated by a combination of i.v. hydroxyethylrutosides (HR)* and oral anticoagulation (AC) by warfarin, the short-term effects on the cutaneous microvascular blood perfusion of the soles of feet and especially the long-term clinical outcome in terms of amputation and death.. A retrospective comparison between two groups of patients, HR + AC and a comparable reference group, fulfilling the same inclusion and exclusion criteria corresponding to the definition of CLI according to the Second European Consensus Document (1991). Clinical follow-up in both groups was made after 1, 3, 6, 12, and 24 months.. Patients were examined at university departments of clinical physiology with special interest in peripheral vascular disease, in cooperation with colleagues at university departments of surgery, internal medicine and dermatology of Karolinska Hospital, Södersjukhuset and Huddinge Hospital.. A total of seventy patients with CLI according to the definition of the Second European Consensus Document, 1991, ie, besides severe rest pain or ischemic lesions also a toe blood pressure < 30 mg Hg. Group with HR + anticoagulation (AC): 42 patients (19 diabetics, 23 nondiabetics). Reference group: 28 patients (18 diabetics, 10 nondiabetics). For distribution of age and toe blood pressure at baseline, see Table I.. Therapy group: besides ordinary standard therapy, daily HR infusions for a mean period of 3.6 weeks + oral anticoagulation continued to the end of the study at 24 months. A comparable reference group on the same basic therapy but without the combination HR + AC. PARAMETERS IN EVALUATION: Short-term parameters: clinical data, skin temperature, and fluorescein imaging. Long-term outcome: amputation or death.. Short-term and long-term results with HR + AC indicated that patients with severe CLI and very poor prognosis benefited in terms of survival and limb salvage from initial therapy with HR infusion combined with long-term oral anticoagulation. Results of this combined treatment seem at least comparable with those with i.v. prostacyclin analogies.

Topics: Administration, Oral; Aged; Amputation, Surgical; Anticoagulants; Arteriosclerosis; Blood Pressure; Cardiovascular Agents; Contrast Media; Diabetic Angiopathies; Drug Therapy, Combination; Fluorescein; Follow-Up Studies; Foot; Humans; Hydroxyethylrutoside; Infusions, Intravenous; Ischemia; Leg; Longitudinal Studies; Microcirculation; Prognosis; Retrospective Studies; Skin Temperature; Survival Rate; Treatment Outcome; Warfarin

Prostaglandin concentrations are elevated in intestinal lymph during brief abdominal visceral ischemia, and exogenously applied prostaglandins can directly stimulate or sensitize ischemically sensitive visceral sympathetic nerve fibers. However, it is not known if prostaglandin production during abdominal ischemia is sufficient to contribute to the reflex cardiovascular response (e.g., hypertension). Accordingly, in anesthetized cats, the femoral artery was cannulated for measurement of arterial blood pressure, and the superior mesenteric and celiac arteries were isolated and fitted with snare occluders. After dual occlusion of these arteries ( 0.05). In group 2, acetylsalicylic acid significantly (P < 0.05) reduced the reflex rise in blood pressure by 46% (28 +/- 3 to 15 +/- 4 mmHg). A second, more invasive preparation (group 3) was utilized to 1) minimize the confounding, transient, nonreflex rise in blood pressure associated with arterial ligation, and 2) further assess the inhibitory effect of indomethacin. In group 3, the ischemia-induced blood pressure rise of 28 +/- 6 mmHg was reduced by 43% to 16 +/- 4 mmHg after indomethacin (n = 4, P < 0.05). Thus blockade of the cyclooxygenase pathway by two structurally dissimilar inhibitors attenuated the visceral-cardiovascular reflex response to brief ischemia, suggesting that prostaglandins released during visceral ischemia contribute significantly to the activation of the reflex cardiovascular response.

Topics: Abdomen; Animals; Aspirin; Blood Pressure; Cardiovascular Agents; Cardiovascular System; Cats; Cyclooxygenase Inhibitors; Female; Indomethacin; Ischemia; Male; Prostaglandins; Reflex; Viscera

Topics: Aged; Cardiovascular Agents; Cardiovascular Diseases; Glaucoma; Humans; Ischemia; Male; Ocular Hypertension; Optic Atrophy; Optic Disk; Sclerostomy; Trabeculectomy; Visual Fields

Topics: Animals; Cardiovascular Agents; Ear; Epoprostenol; Iloprost; Ischemia; Mice; Mice, Hairless; Necrosis; Perfusion; Vascular Diseases

Topics: Cardiovascular Agents; Epoprostenol; Extremities; Humans; Iloprost; Ischemia; Raynaud Disease

The protective effect of E-2001 (2-(4-(p-fluorobenzoyl)-piperidin-1-yl)-2'-acetonaphthone hydrochloride) was examined in various ischemic models, and the mechanisms of its action were investigated in vitro and in vivo. 1. Pretreatment with E-2001 ameliorated the degeneration of pyramidal neurons in the hippocampal CA1 sector following transient ischemia in Mongolian gerbils. 2. E-2001 improved stroke symptoms induced by permanent unilateral carotid artery ligation in gerbils. 3. E-2001 prolonged the survival time following permanent bilateral carotid artery ligation in gerbils and mice. E-2001 also prolonged the survival time following intravenous injection of KCN into mice. 4. E-2001 suppressed the high potassium-evoked release of glutamate from rat hippocampal slices. Furthermore, E-2001 prevented the excessive accumulation of extracellular glutamate induced by a brief ischemia in gerbils. 5. E-2001 exerted calcium antagonistic action, i.e., a relaxing effect on high potassium-induced contraction of rat aorta. 6. E-2001 exerted inhibitory action on the lipoperoxide production in vitro and in vivo, and exhibited a radical scavenging effect against O- and N-radicals. These results suggest that E-2001 might be effective as a novel anti-ischemic agent.

Topics: Animals; Brain Ischemia; Cardiovascular Agents; Female; Free Radicals; Gerbillinae; Glutamates; Hippocampus; Ischemia; Lipid Peroxides; Male; Mice; Muscle Contraction; Muscle, Smooth, Vascular; Naphthalenes; Neurons; Piperidines; Potassium; Potassium Cyanide; Rats

Kidneys of five pigs were preoperatively perfused with iloprost in situ (infusion of 0.5 microgram X kg-1 for 15 minutes) and exposed to a warm ischemic period of 45 minutes. The behaviour of these kidneys during initial perfusion by gravity and hypothermic mechanical perfusion for 24 hours was comparable to that of kidneys having had a warm ischemic period of less than 5 minutes. After retransplantation all kidneys showed a sufficient blood flow and immediate production of urine during the test period of 3 hours.

Topics: Animals; Blood Pressure; Cardiovascular Agents; Epoprostenol; Iloprost; Ischemia; Kidney; Kidney Transplantation; Kinetics; Renal Artery; Renal Circulation; Swine; Tissue Preservation; Vascular Resistance

Topics: Adenosine Diphosphate; Arterial Occlusive Diseases; Blood Platelets; Cardiovascular Agents; Collagen; Epoprostenol; Fingers; Humans; Iloprost; Ischemia; Male; Middle Aged; Platelet Aggregation; Scleroderma, Systemic; Time Factors

Topics: Adult; Cardiovascular Agents; Diabetic Angiopathies; Epoprostenol; Humans; Iloprost; Ischemia; Leg; Male

Topics: Alprostadil; Cardiovascular Agents; Ductus Arteriosus, Patent; Epoprostenol; Extracorporeal Circulation; Humans; Infant, Newborn; Ischemia; Prostaglandins E

Topics: Adolescent; Cardiovascular Agents; Ergot Alkaloids; Ischemia; Leg; Lower Extremity; Methysergide; Migraine Disorders; Toxicology; Vascular Diseases

Topics: Cardiovascular Agents; Cerebrovascular Disorders; Ischemia; Isoxsuprine; Muscle Relaxants, Central; Phenethylamines; Vasodilator Agents