Treatment Of Peripheral Arterial Disease Research Articles

Systematic review of clinical guidelines and consensus statements concerning heparin and protamine dosing and monitoring of anticoagulation levels for non-cardiac arterial procedures.

This systematic review was performed to examine all published practice Guidelines and Consensus Statements (together: GCS) on heparin dosing and monitoring during non-cardiac arterial procedures (NCAP). The objective was to scrutinize the recommendations and advice outlined within these GCS documents and to evaluate the supporting evidence for these recommendations. Additionally, the use of the activated clotting time (ACT) and target ACT values were explored. This systematic review was performed in accordance with the PRISMA Guidelines. Medline and Embase databases were searched to identify all GCSs in the English language on NCAP. The final literature search was performed in January 2023. This search was supplemented by searching websites of relevant professional vascular surgical organizations for GCSs. Titles and abstracts were assessed by two independent reviewers. Of 9716 titles identified, 27 GCSs met the predefined inclusion criteria: six GCSs regarding carotid intervention, seven regarding procedures for aneurysmal disease of the abdominal aorta and iliac arteries, 12 regarding interventions for acute and chronic peripheral arterial occlusive disease and two regarding open and endovascular interventions of thoraco-abdominal aortic aneurysms. Administration of heparin is advised for al NCAP. There was high variability concerning heparin dose: both standard dose as weight based dosing (30-150 IU/kg) was advised. Recommendations on repeated doses, ACT monitoring and heparin reversal using protamine also varied widely. In none of the GCSs, the type of the ACT measuring device or used cartridges were specified. Large variability was found between the included GCSs with regard to the recommendations on heparin dose and target ACT values during NCAP. Advice and recommendations in GCSs were based on low-quality studies or without providing any reference at all. The described variability in recommendations emphasizes the need for large prospective (randomized) studies or the incorporation of data on heparin and the use of ACT monitoring into verified vascular surgery registries, to develop evidence-based, practical and uniform applicable recommendations.

Factors effecting the success of retrograde tibiopedal access and recanalization in infrapopliteal artery occlusions.

Peripheral arterial disease (PAD) is increasingly prevalent, particularly among the aging population. Retrograde tibiopedal access (RTPA) has emerged as a useful endovascular treatment for PAD. However, there is limited research examining factors that influence the efficacy of RTPA. To investigate factors affecting the access, crossing, and recanalization success rates of RTPA for infrapopliteal PAD treatment. A retrospective study was conducted on 720 patients who underwent endovascular treatment for PAD. Of these, 104 patients (mean age: 65.5 ± 16.2; 89 men) with 131 RTPA trials were included in the final evaluation. The disease and its duration, Rutherford score, smoking status, access site, and its occlusion status, access, crossing, and recanalization success were noted. Data were analyzed using Pearson's chi-square and Mann-Whitney U tests and multivariate logistic regression to evaluate the impact of various factors on success rates. The access success rate was 82.6%, the crossing success rate was 95.4%, and the recanalization success rate was 74%. Access success was significantly higher when the dorsal pedal artery (DPA) was the access artery compared with the posterior tibial artery (91.3% vs. 74.2%, P = 0.009). Access success was notably lower in patients with thromboangiitis obliterans compared with patients with diabetes mellitus (DM) and non-DM atherosclerosis (68.6% vs. 90.3% and 80.3%, P = 0.019). Recanalization success was higher when the puncture site was non-occluded (76.7% vs. 53.5%, P = 0.023). The study suggests that RTPA is a generally effective and safe technique for infrapopliteal PAD treatment. The most favorable outcomes are observed in individuals with DM who have a non-occluded DPA at the puncture site. Recanalization success is only affected by the patency of the artery at the puncture site. These findings offer targeted guidance for clinicians and highlight areas requiring further investigation.

One-Year Analysis of Autologous Peripheral Blood Mononuclear Cells as Adjuvant Therapy in Treatment of Diabetic Revascularizable Patients Affected by Chronic Limb-Threatening Ischemia: Real-World Data from Italian Registry ROTARI.

Wounds in diabetic patients with peripheral arterial disease (PAD) may be poorly responsive to revascularization and conventional therapies. Background/Objective: This study's objective is to analyze the results of regenerative cell therapy with peripheral blood mononuclear cells (PBMNCs) as an adjuvant to revascularization. Methods: This study is based on 168 patients treated with endovascular revascularization below the knee plus three PBMNC implants. The follow-up included clinical outcomes at 1-2-3-6 and 12 months based on amputations, wound healing, pain, and TcPO2. Results: The results at 1 year for 122 cases showed a limb rescue rate of 94.26%, a complete wound healing in 65.59% of patients, and an improvement in the wound area, significant pain relief, and increased peripheral oxygenation. In total, 64.51% of patients completely healed at 6 months, compared to the longer wound healing time reported in the literature in the same cohort of patients, suggesting that PBMNCs have an adjuvant effect in wound healing after revascularization. Conclusions: PBMNC regenerative therapy is a safe and promising treatment for diabetic PAD. In line with previous experiences, this registry shows improved healing in diabetic patients with below-the-knee arteriopathy. The findings support the use of this cell therapy and advocate for further research.

Effects of L-Ornithine-L-Aspartate on Angiogenesis and Perfusion in Subacute Hind Limb Ischemia: Preliminary Study.

The current treatment options for peripheral arterial disease (PAD) are limited due to a lack of significant high-level evidence to inform clinical decisions and unfavorable outcomes in terms of cost-effectiveness and amputation rates. In order to suggest the use of the commercially available L-Ornithine-L-Aspartate (LOLA) for treating PAD, we induced hind limb ischemia (HLI) by unilaterally ligating the femoral artery in a rat model. The rats were randomly divided into three groups, with seven rats assigned to each group: group 1 (control), group 2 (sorbitol), and group 3 (LOLA). Intraperitoneal injections were administered five times on post-operative days (PODs) 3, 5, 7, 10, and 12. Perfusion imaging was conducted on PODs 7 and 14 and compared to pre-operative perfusion imaging. Immunohistochemistry staining and Western blotting were performed after the final perfusion imaging. Group 3 showed a significant increase in perfusion, high CD31-positive capillary lumen density, and substantial overexpression of VEGF in the ischemic limb during the subacute phase of HLI. In conclusion, this study provides the first documented evidence of angiogenesis and perfusion recovery in the subacute phase of the HLI model following the administration of LOLA. With LOLA readily available on the commercial market, the implementation of LOLA treatment for PAD in humans can be expedited compared to other therapies still in the developmental stage.

Clinical Outcomes of Non–Stent-Based Interventions for Symptomatic Below-the-Knee Peripheral Artery Disease in the Excellence in Peripheral Artery Disease (XLPAD) Registry

BackgroundFor endovascular treatment of below-the-knee (BTK) peripheral artery disease (PAD), independently adjudicated real-world outcomes comparing non-stent (balloon angioplasty or PTA and adjunctive treatment) with or without a concomitant ipsilateral femoropopliteal (FP) artery intervention are scarce. Methods1060 patients from the multicenter XLPAD Registry between 2006-2021 with non-stent based BTK PAD intervention are included. Primary outcome: 1-year incidence of major adverse limb events (MALE), a composite of all-cause death, any amputation, or clinically driven repeat revascularization. Results566 patients underwent BTK and 494 BTK + FP interventions; 72% men, with mean age 68.4 ± 10.9 years. Diabetes mellitus is more prevalent in BTK only group (76.5% vs. 69%, p=0.006). Mean Rutherford class 4.2 ± 1.18; chronic limb threatening ischemia is more frequent in the BTK group (55.3% vs. 49%, p=0.040). Moderate to severe calcification is higher in BTK + FP (21.2% vs. 27.1%, p=0.024), so is lesion length (110.6 ± 77.3 vs. 135.4 ± 86.3 mm; p<0.001). Nearly, 81% lesions are treated with PTA. DCB (1.6% vs 14%, p<0.001) and atherectomy (38% vs. 58.5%; p<0.001) use is greater in BTK + FP. Procedural success is higher in BTK + FP group (86% vs. 91%, p=0.009), with amputation being the most common complication at 3.3% ≤30 days. One-year MALE (21.2% vs. 22.3%, p=0.675) and mortality (4.6% vs. 3.4%; p=0.3) are similar across BTK and BTK + FP groups. ConclusionNon-stent treatment for BTK PAD with concomitant FP intervention leads to high procedural success and similar rates of 1-year MALE compared with isolated BTK intervention. Condensed abstractThe vast majority of below-the-knee (BTK) peripheral artery disease (PAD) interventions are performed with balloon angioplasty. Presence of inflow femoropopliteal (FP) PAD in patients undergoing BTK interventions can affect the outcome of the procedure. This report explores the immediate procedural success and major adverse limb events at 1 year following balloon angioplasty treatment for isolated BTK and in those undergoing an additional FP PAD intervention.

Current Applications and Future Perspectives of Artificial and Biomimetic Intelligence in Vascular Surgery and Peripheral Artery Disease.

Artificial Intelligence (AI) made its first appearance in 1956, and since then it has progressively introduced itself in healthcare systems and patients' information and care. AI functions can be grouped under the following headings: Machine Learning (ML), Deep Learning (DL), Artificial Neural Network (ANN), Convolutional Neural Network (CNN), Computer Vision (CV). Biomimetic intelligence (BI) applies the principles of systems of nature to create biological algorithms, such as genetic and neural network, to be used in different scenarios. Chronic limb-threatening ischemia (CLTI) represents the last stage of peripheral artery disease (PAD) and has increased over recent years, together with the rise in prevalence of diabetes and population ageing. Nowadays, AI and BI grant the possibility of developing new diagnostic and treatment solutions in the vascular field, given the possibility of accessing clinical, biological, and imaging data. By assessing the vascular anatomy in every patient, as well as the burden of atherosclerosis, and classifying the level and degree of disease, sizing and planning the best endovascular treatment, defining the perioperative complications risk, integrating experiences and resources between different specialties, identifying latent PAD, thus offering evidence-based solutions and guiding surgeons in the choice of the best surgical technique, AI and BI challenge the role of the physician's experience in PAD treatment.

Effects of Rheopheresis in dialysis patients with peripheral artery disease and diabetic foot ulcers: A multicentric Italian study.

Peripheral artery disease (PAD) in hemodialysis (HD) patients has a significant social impact due to its prevalence, poor response to standard therapy and dismal prognosis. Rheopheresis is indicated by guidelines for PAD treatment. Twenty-five HD patients affected by PAD stage IV Lerichè-Fontaine and ischemic ulcer 1C or 2C according to the University of Texas Wound Classification System (UTWCS), without amelioration after traditional medical therapy and/or revascularization, were selected and underwent 12 Rheopheresis sessions in 10 weeks. Improvements in pain symptoms using Numerical Rating Scale (NRS), healing ulcers and laboratory hemorheological parameters have been evaluated. A clinically and statistically significant mean value reduction and of relative percentage differences between estimated marginal means (Δ), calculated at each visits, of NRS was observed, with a maximum value (-48.5%) between the first and last visit. At the end of the treatment period 14.3% of ulcers were completely healed, 46.4% downgraded, 53.6% were stable. Overall, no ulcers upgraded. A statistically significant reduction of the Δ, between the first and last visit, for fibrinogen (-16%) was also observed. Rheopheresis reduced overall painful symptoms; data suggest that it could heal or improve ulcers and hemorheological laboratory parameters in HD patients with PAD and ischemic ulcers resistant to standard therapies.

Single Access and X-Over Reversed Iliac Extension Technique in a PAD Patient Needing Complex Endovascular Aortic Aneurysm Repair.

To describe the X-over reversed iliac extension technique in a patient with severe peripheral arterial disease (PAD) scheduled for inner branched endovascular aortic repair (iBEVAR). A multimorbid 62-year-old male patient was planned for iBEVAR due to a 58 mm suprarenal aortic aneurysm. The patient had a previous right femoropopliteal bypass and stenting of the left iliac axis. At admission, he presented with recent onset severe left limb claudication, which was attributed to left iliac stent occlusion. To avoid the postoperative compression of the right common femoral artery (CFA) and preserve the patency of the bypass, a single left CFA access, followed by left iliac artery recanalization, was decided. The right iliac axis was catheterized with a Lunderquist wire using X-over access from the left CFA. An iliac extension (ZISL, 24-59, Cook Medical, Bloomington, USA) was reversed and resheathed on back-table and implanted in the right common iliac artery using the X-over technique. The left CFA access was used to complete the remaining steps of the procedure. The predischarge computed tomography angiography confirmed bilateral iliac artery and femoropopliteal bypass patency. The X-over reversed iliac extension technique may be applied in selected PAD patients, when undergoing complex endovascular aortic repair. As the number of patients with peripheral arterial disease (PAD) is expected to increase the upcoming decades, out of the box solutions may be needed to assist complex endovascular aortic management. The X over technique, which consist of the contralateral advancement of an on-table reversed iliac limb, was successfully applied in a patient with severe PAD and numerous previous peripheral interventions, who was managed with branched endovascular aortic repair . The X Over technique may provide an additional alternative in well-selected patients with demanding vascular access undergoing complex endovascular aortic procedures.

Peripheral arterial disease in women.

Peripheral arterial disease (PAD) represents one of the most frequent manifestations of atherosclerosis in men and women. In both sexes, PAD is related to classical risk factors of atherosclerosis, which are similarly distributed, but some additional factors determine differences between men and women. More frequent asymptomatic disease in women than in men and less frequent screening in women may result in a false underestimation of the prevalence of PAD in women. All these factors may cause delayed diagnosis and treatment of PAD in women. Estrogen hormones have vasoprotective properties that lower the prevalence of atherosclerosis in women of younger age. However, estrogen probably does not have a protective role against the development of cardiovascular disease in women of an older age. Hormone replacement therapy (HRT) of less than one year does not appear to reduce the odds of developing PAD in postmenopausal women. It may even increase the risk of morbidity from vascular interventions. However, some studies indicated that HRT for more than one year significantly decreases the risk of PAD if administered early after the last menstruation. Also, treatment of PAD in women differs to some extent from men.

Stellarex Drug-Coated Balloon for the Treatment of Peripheral Artery Disease: Five-Year Results from the ILLUMENATE Pivotal Randomized Controlled Trial

This study aimed to report the 5-year outcomes from the ILLUMENATE Pivotal randomized controlled trial of the lower dose (2 µg/mm2) Stellarex drug-coated balloon (DCB) (Philips, formerly Spectranetics Corp, Colorado Springs, Colorado) compared with percutaneous transluminal angioplasty (PTA) for the treatment of symptomatic peripheral arterial disease. Long-term safety and effectiveness data for DCBs remains limited. The ILLUMENATE Pivotal was a prospective, randomized, multi-center, single-blinded study. Patients (Rutherford Clinical Category 2 to 4) were randomized 2:1 to Stellarex DCB or PTA. Follow-up was through 60 months. In total, 300 patients were enrolled. The mean age was 68.8 ± 10.2 years. At 60 months, freedom from a primary safety event was 69.2% in the Stellarex DCB arm and 68.2% in the PTA arm (log-rank, p = 0.623). The cumulative rate of major adverse events was 41.0% compared with 44.6% (p = 0.597), respectively. Freedom from clinically-driven target lesion revascularization (CD-TLR) was 70.3% in the Stellarex DCB arm compared with 68.2% in the PTA arm (p = 0.505). Time to first CD-TLR was 768.3 ± 478.9 days compared with 613.5 ± 453.4 days, respectively (p = 0.161). Kaplan-Meier estimates of freedom from all-cause mortality were 80.1% in the Stellarex DCB arm and 80.2% in the PTA arm (log-rank, p = 0.980). In conclusion, the 5-year results of the ILLUMENATE Pivotal randomized controlled trial add to the consistent safety data from the broader ILLUMENATE clinical program. These are the first data to report the 5-year safety and efficacy of a lower dose (2 µg/mm2) DCB for the treatment of symptomatic peripheral arterial disease. Clinicaltrials.gov Registration:NCT01858428.

Gene therapy by virus-like self-spooling toroidal DNA condensates for revascularization of hindlimb ischemia

Peripheral arterial diseases (PAD) have been reported to be the leading cause for limb amputations, and the current therapeutic strategies including antiplatelet medication or intervene surgery are reported to not clinically benefit the patients with high-grade PAD. To this respect, revascularization based on angiogenetic vascular endothelial growth factor (VEGF) gene therapy was attempted for the potential treatment of critical PAD. Aiming for transcellular delivery of VEGF-encoding plasmid DNA (pDNA), we proposed to elaborate intriguing virus-like DNA condensates, wherein the supercoiled rigid micrometer-scaled plasmid DNA (pDNA) could be regulated in an orderly fashion into well-defined nano-toroids by following a self-spooling process with the aid of cationic block copolymer poly(ethylene glycol)-polylysine at an extraordinary ionic strength (NaCl: 600 mM). Moreover, reversible disulfide crosslinking was proposed between the polylysine segments with the aim of stabilizing these intriguing toroidal condensates. Pertaining to the critical hindlimb ischemia, our proposed toroidal VEGF-encoding pDNA condensates demonstrated high levels of VEGF expression at the dosage sites, which consequently contributed to the neo-vasculature (the particularly abundant formation of micro-vessels in the injected hindlimb), preventing the hindlimb ischemia from causing necrosis at the extremities. Moreover, excellent safety profiles have been demonstrated by our proposed toroidal condensates, as opposed to the apparent immunogenicity of the naked pDNA. Hence, our proposed virus-like DNA condensates herald potentials as gene therapy platform in persistent expressions of the therapeutic proteins, and might consequently be highlighted in the management of a variety of intractable diseases.

Applications of SPECT and PET Imaging for the Physiological Evaluation of Lower Extremity Peripheral Artery Disease.

Peripheral artery disease (PAD) is classified as the narrowing or complete occlusion of the lower extremity arteries due to atherosclerosis. The risk of developing PAD increases with increased age and risk factors such as smoking, diabetes, hypertension, and hypercholesterolemia. Current treatment for PAD involves lifestyle and symptom management, statin and antiplatelet therapy, and/or surgical interventions to improve quality of life with varying efficacy. PAD affects approximately 5 to 6 percent of the global population, with this global burden continuing to increase. Despite the increase in disease prevalence, no gold standard functional diagnostic tool has been established for enabling early detection of the disease, appropriate medical management, and prediction of adverse outcomes for PAD patients. The visualization and quantification of the physiological consequences of PAD are possible by way of nuclear imaging: specifically, via scintigraphy, single-photon emission computed tomography (SPECT), and positron emission tomography (PET) imaging. These non-invasive modalities, when combined with targeted radionuclides, possess utility for detecting functional perfusion deficits and provide unique insight into muscle tissue- and vascular-level characteristics of PAD patients. This review discusses the past, present, and emerging applications of hybrid nuclear imaging modalities in the evaluation and monitoring of patients with PAD.

Intravascular Ultrasound during Endovascular Intervention for Peripheral Artery Disease, by Severity, Location, Device, and Procedure

There is limited evidence for the role of Intravascular Ultrasound (IVUS) in patients undergoing peripheral vascular intervention (PVI). We conducted retrospective cohort study utilizing the HCUP-AHRQ National Readmission database(NRD) to delineate outcomes in IVUS guided PVI versus non-IVUS guided PVI. The current study utilized NRD between January 1, 2016, and December 31, 2019. We identified patients undergoing endovascular intervention for peripheral artery disease using relevant ICD-10-PCS. The cohort was divided based on the use of IVUS during the procedure. The primary outcome was major amputation at 6 months after index hospitalization. Measured confounders were matched using propensity score inverse probability of treatment weighing method. We further performed a subgroup analysis based on disease severity, location of intervention, device, and procedure.A total of 434901 hospitalizations were included in the present analysis. PVI with IVUS compared with no IVUS had similar risk of amputation at 6 months (195 of 8939[2.17%] versus 10404 of 384003 [2.71%]);Hazard Ratio,0.98;CI, 0.77–1.25. Further, there was no difference in the rates of secondary outcomes. On subgroup analysis, amputation rates were significantly lower among patients with rest pain, in iliac intervention, or patients undergoing drug eluting stent implantation with the use of IVUS compared with no IVUS. This nationwide observational study showed that there was no difference in major amputation rates with the use of IVUS in patients undergoing PVI. However, in subgroup of patients with rest pain, iliac intervention or drug-eluting stent implantation IVUS use was associated with significantly lower major amputation rates.

Medicine's Glass Slipper: The PAVAEX Boot and 20th Century Negative Pressure Therapy.

Before the 20th century, peripheral artery disease (PAD) manifested as extreme pain, chronic wounds, and, eventually, gangrene requiring amputation. Despite this, it was rarely diagnosed. However, at the turn of the century, Western medicine shifted focus from infectious to chronic illnesses, and with this change, physicians' engagement with PAD transformed. Aiming to mitigate long-term injury, physicians now worked to identify and treat vessel disease to restore meaningful blood circulation. This article explores the development and deployment of a new device resulting from this refocus, the PAssive VAscular EXerciser (PAVAEX) Boot, and its role as a creative response to a previously intractable clinical problem. The PAVAEX Boot, designed in 1933 by vascular surgeons Louis G. Herrmann and Mont R. Reid, was one of the few interventions for PAD at the time. Based on the observation that continuous negative pressure results in vasoconstriction, while short bursts transiently increase blood flow, the PAVAEX Boot utilized intermittent negative pressure to enhance peripheral vascular perfusion. Well-marketed and praised throughout the 1930s, it vanished from public writing and academic literature just 20years later. However, negative pressure wound therapy resurged in the late 20th century, and though its inventors failed to recognize the precedent of the PAVAEX Boot, many of these devices and therapies are rooted in identical theories. We examine why the PAVAEX Boot faded from use and argue that the device remains a crucial advancement in negative pressure therapy.

Practice patterns of peripheral vascular interventions for peripheral artery disease in the office-based laboratory setting versus outpatient hospital

ObjectiveControversy exists regarding the value and limitations of different sites of service for peripheral artery disease treatment. We aimed to examine practice patterns associated with peripheral vascular interventions (PVIs) performed in the office-based laboratory (OBL) vs outpatient hospital site of service using a nationally representative database. MethodsUsing 100% Medicare fee-for-service claims data, we identified all patients undergoing PVI for claudication or chronic limb-threatening ischemia (CLTI) between January 2017 and December 2022. We evaluated the associations of patient and procedure characteristics with site of service using multivariable hierarchical logistic regression. We used multinomial regression models to estimate the relative risk ratios (RRRs) of site of service and intervention type (angioplasty, stent, or atherectomy) and intervention anatomic level (iliac, femoropopliteal, or tibial) after adjusting for baseline patient characteristics and clustering by physician. ResultsOf 848,526 PVI, 485,942 (57.3%) were performed in an OBL. OBL use increased significantly over time from 48.3% in 2017 to 65.5% in 2022 (P < .001). Patients treated in OBLs were more likely to be Black (adjusted odds ratio [aOR], 1.14; 95% confidence interval [CI], 1.11-1.18) or other non-White race (aOR, 1.13; 95% CI, 1.08-1.18), have fewer comorbidities, and undergo treatment for claudication vs CLTI (aOR, 1.30; 95% CI, 1.26-1.33) compared with patients treated in outpatient hospital settings. Physicians with majority practice (>50% procedures) in an OBL were more likely to practice in urban settings (aOR, 21.58; 95% CI, 9.31-50.02), specialize in radiology (aOR, 18.15; 95% CI, 8.92- 36.92), and have high-volume PVI practices (aOR, 2.15; 95% CI, 2.10-2.29). The median time from diagnosis to treatment was shorter in OBLs, particularly for patients with CLTI (29 vs 39 days; P < .001). The OBL setting was the strongest predictor of patients receiving an atherectomy alone (adjusted RRR [aRRR] 6.67; 95% CI, 6.59-6.76) or atherectomy + stent (aRRR, 10.84; 95% CI, 10.64-11.05), and these findings were consistent in subgroup analyses stratified by PVI indication. The OBL setting was also associated with higher risk of tibial interventions for both claudication (aRRR, 3.18; 95% CI, 3.11-3.25) and CLTI (aRRR, 1.89; 95% CI, 1.86-1.92). The average reimbursement (including professional and facility fees) was slightly higher for OBLs compared with the hospital ($8742/case vs $8459/case; P < .001). However, in a simulated cohort resetting the OBL's intervention type distribution to that of the hospital, OBLs were associated with a hypothetical cost savings of $221,219,803 overall and $2602 per case. ConclusionsThe OBL site of service was associated with greater access to care for non-White patients and a shorter time from diagnosis to treatment, but more frequently performed high-cost interventions compared with the outpatient hospital setting. The benefit to patients from improved access to peripheral artery disease care in OBL settings must be balanced with the potential limitations of receiving differential care.

Diabetic peripheral arterial disease in COVID-19 pandemic.

Both diabetes and peripheral arterial disease (PAD) have complex interactions with COVID-19. PAD is one of the most important underlying factors in the development of diabetic foot. The COVID-19 pandemic has also caused an increase in cardiovascular complications in those with chronic diseases, including diabetics, due to both the thrombophilic course of the viral disease and the lockdown measures applied for prevention. Since both COVID-19 and diabetes mellitus predispose to thrombosis, PAD is likely to have a more severe course in diabetic patients with COVID-19. The aim of our study is to discuss the complications, prophylaxis, and treatment of PAD, which is a serious complication of diabetes, during the pandemic period.

Patient Factors Influencing Prescription of Antithrombotic Medication After Lower Limb Endovascular Intervention

There is significant practice variation in the use of antithrombotic therapy after endovascular intervention for lower limb peripheral arterial disease, with differences in medication choice and duration. Prescriber decision making is complex, and patient factors have been shown to substantially contribute to prescribing variation. To determine the influence of patient factors on antithrombotic prescribing, a discrete choice experiment was distributed to vascular surgeons and trainees across Australia and Aotearoa New Zealand. After pilot testing, the discrete choice experiment questionnaire was distributed to 300 vascular surgeons and trainee members of the Australian and New Zealand Society for Vascular Surgery. Multinomial logistic regression models were used to analyse patient factors that had the most influence on decisions to prescribe a second antithrombotic agent, and the preferred choice of antithrombotic (clopidogrel 75 mg daily or rivaroxaban 2.5 mg twice daily) in addition to aspirin 100 mg daily. The odds ratio (OR) with 95% confidence interval (CI) reported preference strength. A total of 44 questionnaires were completed between September and October 2023, reaching the 15% targeted response rate. Prescribing a second antithrombotic was more likely after femoropopliteal stenting compared withangioplasty (OR 1.89, 95% CI 1.20 - 2.13), and in chronic limb threatening ischaemia compared with intermittent claudication (OR 1.58, 95% CI 1.20 - 2.13). Most respondents preferred clopidogrel over rivaroxaban (62%), with overa third of respondents exclusively prescribing clopidogrel. Patients with stents (OR 1.77, 95% CI 1.32 - 2.37) ormoderate bleeding risk (OR 1.38, 95% CI 0.97 - 1.84) were more likely to receive clopidogrel than rivaroxaban. This study demonstrates that vascular surgeons primarily prioritise antithrombotic prescribing decisionsbyprocedure type. Clopidogrel is more likely to be prescribed than rivaroxaban as a second agent in combination with aspirin, especially after stenting. Knowing these clinician preferences can target implementation strategies towards supporting decision making in subgroups of patients according to individual risk profiles.

Association of Sex and Trends in Guideline-directed Medical Therapy Use Among Patients Undergoing Intervention for Infrainguinal Peripheral Artery Disease in the Vascular Quality Initiative, 2010-2023

Association of Sex and Trends in Guideline-directed Medical Therapy Use Among Patients Undergoing Intervention for Infrainguinal Peripheral Artery Disease in the Vascular Quality Initiative, 2010-2023

UFM1 inhibits hypoxia-induced angiogenesis via promoting proteasome degradation of HIF-1α.

Angiogenesis is crucial for blood flow recovery and ischemic tissue repair of peripheral artery disease (PAD). Exploration of new mechanisms underlying angiogenesis will shed light on the treatment of PAD. Ubiquitin-fold modifier 1 (UFM1), a newly identified ubiquitin-like molecule, has been discovered to be involved in various pathophysiological processes. However, the role of UFM1 in the pathogenesis of PAD, especially in endothelial angiogenesis remains obscure, and we aimed to clarify this issue in this study. We initially found UFM1 was significantly upregulated in gastrocnemius muscles of PAD patients and hind limb ischemia mice. And UFM1 was mainly colocalized with endothelial cells in ischemic muscle tissues. Further, elevated expression of UFM1 was observed in hypoxic endothelial cells. Subsequent genetic inhibition of UFM1 dramatically enhanced migration, invasion, adhesion, and tube formation of endothelial cells under hypoxia. Mechanistically, UFM1 reduced the stability of hypoxia-inducible factor-1α (HIF-1α) and promoted the von Hippel-Lindau-mediated K48-linked ubiquitin-proteasome degradation of HIF-1α, which in turn decreased angiogenic factor VEGFA expression and suppressed VEGFA related signaling pathway. Consistently, overexpression of UFM1 inhibited the angiogenesis of endothelial cells under hypoxic conditions, whereas overexpression of HIF-1α reversed this effect. Collectively, our data reveal that UFM1 inhibits the angiogenesis of endothelial cells under hypoxia through promoting ubiquitin-proteasome degradation of HIF-1α, suggesting UFM1 might serve as a potential therapeutic target for PAD.

Abstract 2038: Statin Targeted Treatment Against Intimal Hyperplasia Using Unique Chitosan-PLGA Nanoparticles

Introduction: Statins have beneficial pleiotropic effects, including reducing intimal hyperplasia (IH) after intervention for peripheral arterial disease. Using a unique nanoparticle (NP) to locally maximize statin’s pleiotropic benefits, we hypothesized chitosan-functionalized polylactic-co-glycolic nanoparticles loaded with simvastatin (SL-cNPs) would: 1) be taken up by endothelial cells (ECs) and vascular smooth muscle cells (VSMCs); 2) affect EC and VSMC function; and 3) reduce IH compared to systemic simvastatin. Methods: cNPs were loaded with simvastatin (2% w/w ) and encapsulated with lipophilic tracer, DiD. In vitro , human aortic ECs and VSMCs (passage 3-5) were cultured with 0.2mg SL-cNPs or basal media (30 min). After 24 hours, uptake of SL-cNPs was assessed by immunostaining and flow cytometry. Functional effect of SL-cNPs was determined using qPCR for mRNA expression of RhoA, RhoB and Ras. In vivo, male Sprague-Dawley rats (n=6-9/group) underwent carotid artery balloon injury in the following groups: 1) intraluminal therapy using normal saline control, empty cNPs or SL-cNPs; and 2) oral simvastatin (10mg/kg/day, 7 days pre-operative until sacrifice) plus intraluminal saline or SL-cNPs. Rats were sacrificed (day 14), perfusion fixed, arteries harvested, and IH quantified with morphometric analysis. Student’s t-test and one-way ANOVA was performed (p &lt;0.05 for significance). Results: In vitro , SL-cNPs were readily taken up by ECs (79.6%, 38,606/48,501) and VSMCs (46.4%, 25,774/55,549). SL-cNPs induced a compensatory increase in expression of EC RhoA (1.3-fold) and VSMC RhoA (1.7-fold) and RhoB (5.4-fold) (p&lt;0.05). In vivo, oral simvastatin plus intraluminal SL-cNPs reduced IH compared to controls (0.44 ± 0.04 vs 0.34 ± 0.03, p&lt;0.05). Although oral simvastatin and SL-cNPs alone trended toward IH reduction, the effect was not significant (0.35 ± 0.03 and 0.377 ± 0.03, respectively). No difference existed between oral simvastatin and SL-cNP therapy. Conclusion: cNPs can be used as a novel vehicle to locally deliver statins to vascular cells. Although only the combination of oral simvastatin and SL-cNPs effectively reduced IH, different routes and/or concentration of SL-cNPs may allow for a more robust effect on IH prevention.