Therapy For Peripheral Arterial Disease Research Articles

Advances in Cell-based therapies for peripheral arterial disease.

Advances in Cell-based therapies for peripheral arterial disease.

Multicomponent interventions designed to support adherence to guideline-recommended therapy in patients with peripheral artery disease: A scoping review.

Adherence to guideline-recommended therapies for peripheral artery disease (PAD), including pharmacotherapy (antiplatelet, lipid-lowering, and antihypertensive agents) and lifestyle modifications (smoking cessation, diet, weight management, and physical activity) remains low. Though single-component interventions targeting smoking cessation, exercise, or medication adherence show some efficacy, comprehensive multicomponent interventions are vital for addressing the complexity of PAD management. This review systematically synthesized multicomponent interventions for patients with PAD. A systematic search was conducted in Embase, MEDLINE, Cochrane Library, APA PsycINFO, CINAHL, Web of Science Core Collection, ProQuest, and Google Scholar to identify primary research describing multicomponent interventions supporting PAD treatment adherence, published between 2007 and 2024. A narrative synthesis was reported using the Template for Intervention Description and Replication (TIDieR) checklist and the behavioral change techniques (BCT) taxonomy. Out of 15 studies (2462 patients, 60.4% men) included in this review, only two addressed all guideline-recommended treatment aspects. Key intervention components included structured exercise (12/15) and education programs (10/15). Most interventions were delivered by multidisciplinary teams in hospital settings over 3 months. Only one study employed behavioral theory in its development, and most interventions (13/15) focused on the BCT 'instructions on how to perform a behavior' rather than diverse BCTs. No interventions significantly increased adherence to all PAD therapies. Few studies measured the intervention's impact on adherence, making it difficult to determine effective intervention characteristics. Most interventions lacked behavioral science approaches and were not designed to address specific adherence determinants. Future interventions should incorporate these elements to effectively address patients' needs. Open Science Framework Registry ID: osf.io/7xqzj.

Sauna use as a novel management approach for cardiovascular health and peripheral arterial disease.

Heat therapy (HT), particularly in the form of whole-body sauna bathing, has emerged as a promising intervention for the management of cardiovascular disease (CVD). Passive HT can induce both local and systemic physiological responses, primarily through repeated thermal stress consisting of short-term passive exposure to high temperatures. Such responses closely parallel the physiological adaptations observed during aerobic exercise. Peripheral arterial disease (PAD) poses significant health challenges, impacting millions of individuals worldwide. Supervised exercise is considered a cornerstone therapy for PAD, yet many patients face significant health-related barriers that complicate its broad implementation. We conducted a comprehensive review of the literature to explore the therapeutic implications of various HT practices beyond sauna. The review aimed to evaluate the potential use of these practices as adjunctive management strategies for cardiovascular diseases, particularly in patients with PAD. Recent studies have demonstrated the potential role of HT in alleviating PAD symptoms, improving functional capacity, and reducing cardiovascular and limb events. HT practices might be beneficial as adjunctive management strategies, in addition to or as alternatives to exercise, for management of cardiovascular diseases. This review highlights the potential benefits, underlying mechanisms of action, challenges, and safety considerations associated with HT. We emphasize the importance of exploring HT as a viable option for patients with cardiovascular conditions, particularly those with PAD, who face barriers to traditional exercise regimens.

Cilostazol following endovascular therapy in peripheral arterial disease: Patient adherence (to yet another medication) could prove to be a bridge too far.

Cilostazol following endovascular therapy in peripheral arterial disease: Patient adherence (to yet another medication) could prove to be a bridge too far.

Unmet Needs and Opportunities for Australian Innovation and Clinical Research to Improve Quality of Life and Outcomes in Patients With Peripheral Artery Disease.

Peripheral arterial disease (PAD) is characterised by atherosclerotic stenosis or occlusion of arteries that leads to reduced blood flow to the limbs. PAD is associated with a very high rate of cardiovascular morbidity and mortality making the health and economic burden of PAD substantial. Despite high-quality evidence and international guidelines recommending conservative medical management of risk factors, and exercise and lifestyle interventions, surgical revascularisation (open or endovascular) remains the main treatment for PAD. Alarmingly, up to one-third of patients do not receive best medical therapy after revascularisation surgery despite evidence supporting this treatment reduces cardiovascular events. Due to the considerable health burden that PAD presents, this manuscript aims to identify gaps in care and clinical research in PAD across Australia and proposes potential collaborative solutions. In Australia, there is significant disparity in care between rural/regional and metropolitan communities. These gaps are exacerbated by inequitable access to services across Australia, particularly for First Nation Australians, culturally and linguistically diverse groups and those living in regional and remote areas. This review identifies unmet needs for patients with PAD that are multifaceted, spanning from improved understanding of disease mechanisms, diagnostic tools for risk stratification and personalised therapy, to a paucity of medical and rehabilitation therapies for symptoms or prevention of cardiovascular complications. Furthermore, there are opportunities for national and international registries to optimise clinical trial quality and outcomes. Strategies should be applied to improve implementation of optimal medical therapy in PAD which will improve quality of life, reduce health care costs, and prevent secondary complications, limb loss, and mortality across Australia's diverse population.

Prescriber implementation of guideline-directed medical therapy remains poor in the peripheral artery disease population.

Prescriber implementation of guideline-directed medical therapy remains poor in the peripheral artery disease population.

Limb Preservation Program and Peripheral Arterial Disease

Limb – derived from the old English ‘Lim’. A paired parts (Arm, Leg and Wing) of human that stick out/extends from the trunk of a body. Limb preservation refers to the crucial steps taken in order to save a damaged limb from amputation. Amputation of a limb may be needed when there is serious infection a wound that won’t heal or poor circulation that causes tissue to die. Patients with vascular disease are at high risk for foot and leg wounds that do not heal and may ultimately require amputation to save their lives. Severe cases of Peripheral Artery Disease (PAD) can cause irreversible tissue damage and increase the risk for amputation if not treated. The Limb Preservative Program focuses on saving limbs and also on the overall health and well being of the patient. Limb-Preservation Program (LPP) requires coordinated effort by clinicians, nurses, allied health professionals and administrators dedicated to the cause of saving and maintaining functional limbs. This is a significant consideration because over 1.5 million people live after the loss of a limb; this number is expected to increase due to the aging of the population and the worldwide exponential rise in diabetes mellitus. Peripheral Arterial Disease (PAD) is one the important cause of limb amputation. The prevalence of PAD continues to increase worldwide. It is important to identify patients with PAD because of the increased risk of myocardial infarction, stroke and cardiovascular death and impaired quality of life because of a profound limitation in exercise performance. Lower extremity PAD affects approximately 10% of population, with 30% to 40% of these patients presenting with claudication symptoms. Peripheral arterial disease is common, but the diagnosis frequently is overlooked because of subtle physical findings and lack of classic symptoms. Screening based on the ankle brachial index using doppler ultrasonography may be more useful than physical examination alone. Noninvasive modalities to locate lesions include duplex scanning, computed tomography angiogram, magnetic resonance angiography and invasive modalities peripheral angiogram is the gold standard. Major risk factors for peripheral arterial disease are cigarette smoking, diabetes mellitus, older age (Older than 40 years) hypertension, hyperlipidemia and hyperhomocystinemia. Intermittent claudication may be improved by risk-factor modification, exercise and pharmacologic therapy. Based on available evidence, a supervised exercise program is the most effective treatment. Effective drug therapies for peripheral arterial disease include aspirin (With or without dipyridamole) clopidogrel, cilostazol, and pentoxifylline. By contrast, Critical Limb Ischemia (CLI) is considered the most severe pattern of peripheral artery disease. It is defined by the presence of chronic ischemic rest pain, ulceration or gangrene attributable to the occlusion of peripheral arterial vessels. It is associated with a high risk of major amputation, cardiovascular events and death. The management of CLI should include an exercise program, guideline-based medical therapy to lower the cardiovascular risk. Most of the cases, revascularization is indicated to save limbs, an “Endovascular First” approach and lastly surgical approach if all measures were failed. The choice of the intervention is dependent on the anatomy of the stenotic or occlusive lesion, percutaneous interventions are appropriate when the lesion is focal and short but longer lesions must be treated with surgical revascularization to achieve acceptable long-term outcome. A LPP should include a patient support group as there is a significant mental component to loss of limb or living with a foot ulcer. A patient support group can be very important both preoperatively and postoperatively in helping patients deal with the clinical situation in maintaining functionality and mentaloutlook. Education can be incorporated into the program in the form of seminars for patients and referring physicians. Education is critical to achieve the goal of limb preservation through the reduction of amputation and enhancement of the patient’s quality of life. The LPP also provides a format for research that is increasingly important to the healthcare system. Chatt Maa Shi Hosp Med Coll J; Vol.22 (2); July 2023; Page 1-2

Abstract 4140889: Preclinical study of human induced pluripotent stem cell-derived endothelial cells for peripheral artery disease

Background: Peripheral artery disease (PAD) affects approximately 230 million people globally and chronic limb-threatening ischemia (CLTI) can lead to limb amputation. Human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) offer a promising source for PAD treatment. However, to date, regulatory criteria for the clinical application of hiPSC-ECs have not been established yet, and there have been no reports on preclinical studies involving hiPSC-ECs. This study aims to address this gap by investigating the feasibility, safety, and efficacy of clinical-grade hiPSC-ECs through a preclinical proof-of-concept analysis. Methods and Results: Clinical-grade hiPSC lines were established from the blood of three PAD patients using episomal plasmids. Their pluripotency was confirmed by assessing their expression of pluripotency markers through qRT-PCR and immunostaining, as well as their pluripotency in a teratoma assay. Furthermore, PAD-hiPSCs exhibited normal karyotypes. Subsequently, we differentiated PAD-hiPSCs into ECs, all of which displayed a cobble-stone EC morphology and expressed EC markers as confirmed by qRT-PCR and immunostaining. PAD-hiPSC-derived ECs also expressed CDH5 at a minimum of 98.4 ± 0.2% and VWF at 94.4 ± 1.3% by flow cytometry. PAD-hiPSC-ECs maintained their normal karyotypes and copy number variation across the genome, as determined by CGH array. Additionally, they exhibited endothelial characteristics such as tube formation in Matrigel and intracellular nitric oxide production. Administration of PAD-hiPSC-ECs into ischemic hindlimbs of both female and male mice led to improved blood flow recovery (~3.3 fold), reduced risk of limb loss (~8.8 ± 0.6%), and increased vascular density (~2.7 fold) compared to control groups. These engrafted hiPSC-ECs exhibited vessel-forming capacities, thereby contributing to neovascularization. More importantly, we evaluated the toxicity, biodistribution, and tumorigenic potential of these cells in immunodeficient nude mice over one year. The results demonstrated non-detection of tumorigenic cells in twelve organs and adverse events. With all the data, the use of hiPSC-ECs was approved for a clinical trial to treat PAD. Conclusions: Our preclinical proof-of-concept findings demonstrate, for the first time, the clinical compatibility of hiPSC-ECs derived from patients for autologous cell therapy for PAD. Our study further suggests regulatory guidance for the clinical development of hiPSC-ECs.

Supervised Exercise Therapy for Peripheral Artery Disease

This Teachable Moment discusses a woman in her 60s with hypertension, hyperlipidemia, coronary artery disease, and smoking history who presented with bilateral, aching leg pain triggered by walking and relieved by rest.

Safety and Efficacy of Home-Based Walking Exercise for Peripheral Artery Disease

Safety and Efficacy of Home-Based Walking Exercise for Peripheral Artery Disease

Benefits and Challenges of Drug-Coated Balloons in Peripheral Artery Disease: From Molecular Mechanisms to Clinical Practice.

Multiple clinical trials have reported favorable outcomes after drug-coated balloon therapy for peripheral artery disease in above-the-knee and below-the-knee lesions and in both de novo and in-stent restenosis. However, there are still insufficient data to identify and tackle the risk factors associated with a higher risk of restenosis, which is the primary concern for patients who are treated with an endovascular approach. A modern armamentarium, which includes improved lesion preparation techniques such as plaque modification balloons, mechanical atherectomy, intravascular lithotripsy, and imaging, is crucial for obtaining better long-term clinical outcomes. Moreover, a better understanding of the molecular properties of drug-coated balloons has led to improved devices that could tackle the shortcomings of previous generations. This comprehensive review focuses on drug-coated balloon technology as a tool to treat peripheral artery disease and the effects of the molecular mechanisms involved in preventing vascular restenosis.

Correlation between timed-up-and-go test and 6-minute walk test in patients with peripheral artery disease.

Peripheral artery disease (PAD) is a widespread condition affecting over 200 million people worldwide. PAD leads to a restricted blood flow to the extremities, causing painful limitations and the risk of amputation in advanced stages. Among medical and surgical interventions, the therapy of PAD involves walking training. Two commonly used standardized tests to measure walking performance and general mobility are the 6-minute walk test (6MWT) and the timed-up-and-go (TUG) test. Since a 6MWT takes more time and effort to complete than a TUG test, assessing the correlation between these two tests is crucial to determine the viability of the TUG test as a practical alternative to the 6MWT. The comparison of 36 TUG tests and 6MWTs revealed a significant inverse correlation across all parameters of both tests, with Pearson's correlation coefficients up to R = -0.69 between the total TUG time and the total 6MWT distance. Future work should explore the potential substitution of the 6MWT with the TUG test and assess the impact of incorporating routine TUG tests in clinical practice.

MT39 Reporting Characteristics of Randomized Controlled Trials of Endovascular Therapy for Peripheral Artery Disease: A Systematic Review

MT39 Reporting Characteristics of Randomized Controlled Trials of Endovascular Therapy for Peripheral Artery Disease: A Systematic Review

Medical Therapy for Peripheral Artery Disease.

Patients with lower extremity peripheral artery disease (PAD) are at high risk for major adverse cardiovascular events (MACE) and major adverse limb events (MALE). This manuscript will review the current evidence for medical therapy in patients with PAD according to different clinical features and the overall cardiovascular (CV) risk. The management of PAD encompasses non-pharmacologic strategies, including lifestyle modification such as smoking cessation, supervised exercise, Mediterranean diet and weight loss as well as pharmacologic interventions, particularly for high risk patients. Benefits for reduction of CV and limb outcomes have been demonstrated for new therapies, including antithrombotic therapy (i.e., low-dose rivaroxaban plus aspirin), lipid lowering therapy (i.e., proprotein convertase subtilisin/kexin type 9inhibitors), and glucose lowering therapy (i.e., sodium-glucose cotransporter-2inhibitors and glucagon-like peptide-1receptor agonists). However, the adoption of these therapies in PAD remains suboptimal in practice. Implementation science studies have recently shown promising results in PAD patients. Comprehensive medical and non-medical management of PAD patients is crucial to improving patient outcomes, mitigating symptoms, and reducing the risk of MACE and MALE. A personalized approach, considering the patient's overall risk profile and preference, is essential for optimizing medical management of PAD.

AB077. SOH24AB_072. Is it reasonable to recommend best medical therapy for peripheral arterial disease based on general practitioner (GP) referral alone?—A correlation of vascular clinic outcomes to GP referrals for peripheral arterial disease

AB077. SOH24AB_072. Is it reasonable to recommend best medical therapy for peripheral arterial disease based on general practitioner (GP) referral alone?—A correlation of vascular clinic outcomes to GP referrals for peripheral arterial disease

Exercise Therapy for Peripheral Artery Disease.

To summarize evidence regarding exercise treatments for lower extremity peripheral artery disease (PAD). Supervised walking exercise is recommended by practice guidelines for PAD. Supervised treadmill exercise improves treadmill walking distance by approximately 180m and 6-min walk distance by 30-35m, compared to control. The Centers for Medicaid and Medicare Services covers 12weeks of supervised exercise, but most people with PAD do not participate. Home-based walking exercise may be more convenient and accessible than supervised exercise. In randomized clinical trials, home-based walking exercise interventions incorporating behavioral methods, such as accountability to a coach, goal-setting, and self-monitoring, improved 6-min walk distance by 40-54m, compared to control. Arm and leg ergometry also improved walking endurance for people with PAD, but efficacy compared to walking exercise remains unclear. Walking exercise is first-line therapy for PAD-related walking impairment and can be effective in either a supervised or a structured home-based setting.

Enabling Non-invasive Tracking of Vascular Endothelial Cells Derived from Induced Pluripotent Stem Cells Using Nuclear Imaging.

The absence of clinically applicable imaging techniques for continuous monitoring of transplanted cells poses a significant obstacle to the clinical translation of stem cell-based therapies for vascular regeneration. This study aims to optimize a clinically applicable, non-invasive imaging technique to longitudinally monitor vascular endothelial cells (ECs) for vascular regeneration in peripheral artery disease (PAD). Human induced pluripotent stem cells (HiPSCs) were employed to generate ECs (HiPSC-ECs). Lentiviral vectors encoding human sodium iodide symporter (hNIS) and enhanced green fluorescent protein (eGFP) genes were introduced to HiPSCs and HiPSC-ECs at varying multiplicities of infection (MOI). Through a combination of fluorescence microscopy and flow cytometry, an optimized transduction technique for introducing hNIS-eGFP into HiPSC-ECs was established. Subsequently, single-photon emission computed tomography (SPECT) was utilized for imaging of the transduced cells in vitro and in vivo after transplantation into the gastrocnemius muscle of nude mice. Lentiviral transduction resulted in sustained co-expression of hNIS and eGFP in HiPSC-ECs when transduced post-endothelial differentiation. An optimal MOI of five yielded over 90% hNIS-eGFP expression efficiency without compromising cell viability. hNIS-eGFP+ HiPSC-ECs exhibited 99mTc uptake and were detectable through SPECT in vitro. Additionally, intramuscular injection of hNIS-eGFP+ HiPSC-ECs with MatrigelTM into the hindlimbs of nude mice enabled real-time SPECT/CT tracking, from which a reduction in signal exceeding 80% was observed within 7days. This study establishes an optimized cell modification and imaging protocol for tracking transplanted cells. Future efforts will focus on enhancing cell survival and integration via improved delivery systems, thereby advancing the potential of cell-based therapies for PAD.

Gene therapy for peripheral arterial disease

Gene therapy for peripheral arterial disease

Medical Therapy for Peripheral Arterial Disease: A Small Step Before a Giant Leap

Medical Therapy for Peripheral Arterial Disease: A Small Step Before a Giant Leap

Open Surgical Therapy for Peripheral Artery Disease.

The surgical management of symptomatic peripheral artery disease (PAD) has changed in the last few decades. Improvement in endovascular technology has resulted in more complex lesion once reserved for open surgery being addressed in an endovascular fashion. Even with these advances, there are lesions and patients that are better managed with an open surgical procedure. The aim of this review is to describe the most commonly performed open surgical procedures for PAD. The recently published Best Endovascular versus Best Surgical Therapy (BEST-CLI) trial was an international, prospective, randomized controlled trial that aimed to investigate which revascularization (endovascular vs. surgical bypass) approach was superior for limb salvage. The evidence supports an open surgical bypass as an initial approach. The advancements made in the surgical management of PAD have provided options for patients who were once deemed poor surgical candidates. The goal continues to be utilization of the best available tools to address patient disease. In this current era, it is important to be familiar with the open surgical therapies.