Treatment Of Peripheral Arterial Disease Research Articles

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 <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<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<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.

Intravascular Ultrasound Use is Associated with Improved Patency in Lower Extremity Peripheral Arterial Interventions

ObjectivesIntravascular ultrasound (IVUS) facilitates detailed visualization of endoluminal anatomy not adequately appreciated on conventional angiography. However, it is unclear if IVUS use improves clinical outcomes of peripheral vascular interventions (PVI) for peripheral arterial disease (PAD). This study aimed to evaluate the impact of IVUS on 1-year outcomes of PVI in the vascular quality initiative (VQI). MethodsThe VQI-PVI modules were reviewed (2016-2020). All patients with available one-year follow up after lower extremity PVI were included and grouped as IVUS-PVI or non-IVUS PVI based on use of IVUS. Propensity matching (1:1) was performed using demographics and comorbidities. One-year major amputation and patency rates were compared. A generalized estimating equation (GEE) model was used to identify predictors of 1-year outcomes. Subgroup analysis based on Trans-Atlantic Inter-Society Consensus (TASC) classification, treatment length and treatment modalities were performed using same modeling approaches. ResultsThere were 56,633 procedures (non-IVUS PVI=55,302 vs IVUS-PVI=1,331) in 44,042 patients. Propensity matching yielded a total cohort of 1,854 patients matched (1:1), with no baseline differences. LER for claudication was performed in 60.4%, while one-third (33.9%) had chronic limb threatening ischemia (CLTI). IVUS was more commonly used for lesions >15cm in length (46.6% vs 43.3%) and for aortoiliac disease (31.8% vs 27.2%). Rates of atherectomy and stenting were significantly higher with IVUS-PVI (21.1% vs 16.8%), while balloon angioplasty was less common (13.5% vs 24.4%). One-year patency was better with IVUS-PVI (97.7% vs 95.2%, p=0.004). On subgroup analysis, IVUS (OR 2.20, 95% CI 1.29- 3.75) was associated with improved patency in CLTI patients, TASC C or D lesions, and treatment length >15cm. Adjunctive IVUS use during PVI did not significantly impact 1-year amputation (OR 1.7, 95%CI 0.78-3.91). On multivariable regression, adjunctive use of IVUS (OR 2.46 95%CI 1.43-4.25) and aortoiliac interventions (OR 2.91, 95%CI 1.09-7.75) were independent predictors of patency. Treatment modalities such as atherectomy, stenting or balloon angioplasty did not significantly impact patency at 1-year. ConclusionIVUS during lower extremity PVI is associated with improved 1-year patency, when compared to angiography alone. Certain subgroups, such as CLTI patients, lesions>15cm, and TASC C or D lesions might benefit from adjunctive use of IVUS.

Management and Pharmacological Treatment of Peripheral Arterial Disease.

Background: Peripheral arterial disease (PAD) is a complex, heterogeneous condition that has become a leading health concern globally. Peripheral arterial disease often co-exists with other vascular disease states, including cerebrovascular and cardiovascular disease. Optimal therapy for managing symptoms and progression of disease employs non-pharmacological, pharmacological, and contemporary revascularisation techniques to improve clinical outcomes and quality of life. However, large well-designed randomised control trials (RCT) and corresponding evidence-based guidelines for management of PAD are lacking, with current practice standards often extrapolated from evidence in coronary artery disease.Purpose: This review article aims to discuss currently accepted best pharmacological practice for PAD.Method: Relevant articles were searched between May 2023 and January 2024 through PubMed, Cochrane Library, Google Scholar and international guidelines, focusing on pharmacological management for PAD.Results: This narrative review discusses holistic pharmacological treatments for PAD.

Designing a platform/adaptive randomised controlled trial for peripheral arterial disease (PAD) - The PAEDIS international platform trial development project.

Peripheral artery disease (PAD) is a common health problem. There are several technologies, medications, and interventions that aim to improve or treat PAD in people with symptomatic disease. Most of these technologies, however, have been untested in high-quality randomised studies assessing effectiveness and their interactions remain unknown. We developed a proposed design for an international randomised controlled trial assessing multiple PAD treatments. Over the course of 11 months (2023) several workshops and reviews of the literature took place. More specific, the proposed platform trial was designed with 44 people with PAD and 112 experts from across the world, in five work packages. The most relevant PAD treatment with unproven effectiveness were identified and key trial components as well as success criteria were defined. With input from five clinical trials units, the final format of a potential platform PAD trial in primary and secondary care was then proposed for funding. The proposed platform PAD randomised trial involved two major multi-arm multi-stage randomised studies, assessing PAD treatments in the community setting (1 st package) and then secondary care (2 nd package). The 1 st package involved people with claudication and the 2 nd package involves people with chronic limb threatening ischaemia (CLTI). A platform PAD trial involves many challenges in terms of both design and delivery. The proposed design involving both people with claudication and CLTI will hopefully act as a blueprint for future work in this area.

Evaluation of Computerized Tomography Utilization in Comparison to Digital Subtraction Angiography in Patients with Peripheral Arterial Disease

ObjectivesPerform literature review to analyze current practices in imaging patient with peripheral arterial disease (PAD) and examine patterns in our practice in order to assess whether a lower extremity computed tomography angiography (CTA) in addition to digital subtraction angiography (DSA) enhanced the assessment of vessel calcification, percentage of stenosis; and affected outcomes in patients with peripheral arterial disease. Methods and MaterialsThe study included patients who underwent lower extremity imaging and were followed up to 12 months. This population was divided into cases who had both an angiogram and CTA performed within 30 days (n=20), and controls who underwent angiography only (n=19). Baseline characteristics, imaging results, and clinical outcomes were analyzed. ResultsThirty-nine patients met study criteria (mean age was 58.4 years, 69.2% were males, and 33.3% had diabetes). Patients mostly presented with tissue loss/rest pain (10.3%), claudication (15.4%), acute limb (10.3%), and trauma (15.4%). We have not observed any statistically significant differences in various examined blood vessels when their features (e.g. vessel diameter, stenosis, calcifications) were assessed by CTA combined with angiography versus angiography alone. The exceptions were external iliac artery, superficial femoral artery and dorsalis pedis vessels. In external iliac artery percentage of stenosis was 1.11% as determined by CT scan versus 30% by angiography (P=.009). For superficial femoral artery stenosis the percentage determined by CT was 48.68% versus 81.41% by angiography, and observed difference between two modalities was statistically significant (P=.025). For dorsalis pedis percentage of stenosis detected by CT scan was 60.63% versus 22.73% by angiography, and the differences in findings by these modalities were statistically significant (P=.039). The most frequent perioperative complication was cardiac-related (35.5%). Nineteen patients were readmitted and 8 had re-interventions within 12 months. ConclusionBoth imaging modalities yielded similar results for assessing vessel calcification and percentage of stenosis regardless of anatomic vessel location. Overall, utilization of CTA in addition to angiography for large vessels above the knee (e.g. iliac artery, superficial femoral artery) and below the knee for dorsalis pedis provided more detailed information on the properties of these vessels. Therefore, during pre-operative assessments, CTA may be helpful in addition to angiography for planning surgical and endovascular interventions for symptomatic PAD treatment in larger vessels.

MagicTouch PTA Sirolimus-Coated Balloon for Femoropopliteal and Below-the-Knee Disease: 3-Year Outcomes of the XTOSI Trial

ObjectivesSirolimus coated balloon (SCB) is a potential treatment option for peripheral arterial disease (PAD). There is currently no long term clinical data for this novel treatment for PAD. We present the 3 year results of the first-in-human study of MagicTouch PTA SCB for treatment of PAD for both femoropopliteal and below the knee arteries (BTK). MethodsXTOSI pilot study is a prospective, single-arm, open-label, single centre trial evaluating MagicTouch PTA SCB for symptomatic PAD. Assessments through 3 years included freedom from clinically driven target lesion revascularization (CD-TLR), freedom from major amputation, amputation free survival (AFS), overall survival and ulcer free status. ResultsAt 3 years, the overall freedom from CD-TLR was 84.4%, freedom from major amputation was 86.1%, AFS was 63.3%, overall survival was 63.3% and ulcer free status in remaining survivors with intact limbs was 100%.For femoropoliteal lesions, at 3 years, the freedom from CD-TLR was 92.9%, freedom from major amputation was 93.3%, AFS was 70% and overall survival was 70%. For BTK lesions, at 3 years, the freedom from CD-TLR was 77.8%, freedom from major amputation was 81.0%, AFS was 58.6% and overall survival was 58.6%. ConclusionsSCB in the XTOSI pilot study showed promising clinical results sustained to 3 years and no long term safety concerns were raised. Randomized trials are currently ongoing to investigate the safety and efficacy of SCB for treatment of PAD.

20 Characteristics of Medicare patients receiving peripheral vascular interventions for peripheral artery disease differ by outpatient site of service

OBJECTIVES/GOALS: Endovascular peripheral vascular interventions (PVIs) are increasingly utilized for the treatment of peripheral artery disease (PAD). We aimed to assess characteristics of patients receiving PVI at ambulatory surgical centers and office-based labs (ASC/OBL) versus the outpatient hospital (hospital) site of service. METHODS/STUDY POPULATION: We performed a retrospective analysis using 100% Medicare fee-for-service claims data between January 1, 2017 and December 31, 2022. We used Current Procedural Terminology (CPT) codes to identify patients undergoing angioplasty, stenting, or atherectomy. Patient demographics were collected from the Medicare Master Beneficiary Summary File and associated comorbidities and PVI indications were identified using International Classification of Disease (ICD)-10 codes. We used patient ZIP codes to determine patients’ residence densities and regions. We used site of service codes to determine whether PVI were performed in the ASC/OBL versus hospital. Results were analyzed with descriptive statistics. RESULTS/ANTICIPATED RESULTS: Of 817,241 patients undergoing PVI for PAD, 461,068 (56.4%) were treated in an ASC/OBL. Compared to patients treated in the hospital, patients receiving PVI at ASC/OBLs were more likely to be older, female, non-white race, with fewer comorbidities (end stage renal disease, diabetes, hypertension, and any history of tobacco use) (all, P<0.001). Patients treated in ASC/OBLs more frequently resided in urban (vs. rural) locations, and in the South and West (both, P<0.001). Indication for PVI was predominately chronic limb-threatening ischemia, and clinically similar between groups (77.1% vs. 76.2%). There was a significant change in site of service over time: a minority (47.6%) of PVIs were performed in the ASC/OBL in 2017, whereas the majority (64.7%) of PVIs were performed in the ASC/OBL in 2022 (P<0.001). DISCUSSION/SIGNIFICANCE: Patients treated in ASC/OBLs were less medically complex compared to those treated in the outpatient hospital setting. Further study is needed to examine whether differences in patient characteristics versus other factors (e.g. reimbursement) are driving the increase in PVIs performed in the ASC/OBL over time.

Six-month combined aerobic and resistance exercise program enhances 6-minute walk test and physical fitness in people with peripheral arterial disease: A pilot study

BackgroundExercise therapy is a recognized non-pharmacological intervention for peripheral arterial disease (PAD); however, the effects of combined exercise remain under investigation. This study aimed to compare the effects of a 6-month combined supervised exercise program (SUP) with a usual care (UC) approach on walking ability, physical fitness, and peripheral blood flow in people with PAD and claudication. MethodsTwenty-three male participants (Age=64.1 ± 6.2years and ABI=0.58±0.07) with PAD and claudication were assigned to either the SUP group (n = 10), engaging in structured supervised treadmill walking combined with three resistance exercises, three times a week, or the UC group (n = 13), receiving advice to walk. The primary outcome measure was walking ability, with assessments conducted at baseline (M0), after 3 months (M3), and 6 months (M6). ResultsAfter the 6-month intervention, the SUP group exhibited significant improvements in absolute claudication time (ACT, p = 0.045), maximal walking time (MWT, p = 0.045), maximal walking distance (MWD, p = 0.027), and pause duration (p = 0.045) during the 6-minute walk test (6MWT), when compared to the UC group. Over time, a significant increase in walking speed during the 6MWT (Speed6MWT, p = 0.001) and walking speed without claudication (SpeedNoC, p < 0.001) was found, although no significant differences were found between the groups. The SUP group increased by 0.8 km/h in both Speed6MWT and SpeedNoC, while the UC group increased by 0.3 km/h and 0.6 km/h, respectively. Despite claudication consistently occurring at the same time, the SUP group demonstrated an improved tolerance to pain or a better understanding of pain, enabling them to walk longer distances at higher speeds. A positive effect of SUP was found for chair sit-and-reach test (p = 0.023), percentage of fat mass (p = 0.048), fat-free mass (p = 0.040), and total body water (p = 0.026), suggesting potential benefits attributed to the resistance strength exercises. ConclusionA 6-month combined treadmill and resistance exercise program improved walking ability, walking speed, lower body and lower back flexibility, and body composition in people with PAD and claudication.

Artificial Intelligence to Predict Quality-of-Life Outcomes for Vascular Intervention of the Leg.

Artificial intelligence (AI) tools created to enhance decision-making may have a significant impact on treatment algorithms for peripheral arterial disease (PAD). A Markov-based AI model was developed to predict optimal therapy based on maximization of calculated quality of life (cQoL), a patient-centered system of assessment designed to report outcomes directly linked to health-related quality of life. The AI model was prospectively interrogated immediately after individual interventions for PAD over a 12-year period to test predictive performance. Patient cQoL was determined at each patient follow-up visit. A total of 1,143 consecutive patients were evaluated, with a median follow-up of 18 months. Observed mean annualized cQoL was higher than predicted by the model (0.85 ± 0.38 vs 0.79 ± 0.18, p < 0.0001). Of 5 potential clinical outcomes, the AI model correctly predicted final status in 71.3% of patients, with insignificant model performance deterioration over time (-0.15% per month, r = -0.49, p = 0.063). The chance of having the condition predicted by the model was 0.57 ± 0.32, compared with a theoretical maximum of 0.70 ± 0.19 (p < 0.0001, mean ratio 0.79). The AI model performed better in patients with claudication than limb-threatening ischemia (75.5% vs 63.6%, p = 0.014) but equally well for open or endovascular intervention (69.8% vs 70.5%, p = 0.70). Graft or artery patency and amputation-free survival were better for patients with claudication and those treated with endovascular techniques. AI can successfully predict treatment for PAD that maximizes patient quality of life in most cases. Future application of AI incorporating better estimates of patient anatomic and physiological risk factors and refinement of model structure should further enhance performance.

Machine Learning to Predict Outcomes of Endovascular Intervention for Patients With PAD

Endovascular intervention for peripheral artery disease (PAD) carries nonnegligible perioperative risks; however, outcome prediction tools are limited. To develop machine learning (ML) algorithms that can predict outcomes following endovascular intervention for PAD. This prognostic study included patients who underwent endovascular intervention for PAD between January 1, 2004, and July 5, 2023, with 1 year of follow-up. Data were obtained from the Vascular Quality Initiative (VQI), a multicenter registry containing data from vascular surgeons and interventionalists at more than 1000 academic and community hospitals. From an initial cohort of 262 242 patients, 26 565 were excluded due to treatment for acute limb ischemia (n = 14 642) or aneurysmal disease (n = 3456), unreported symptom status (n = 4401) or procedure type (n = 2319), or concurrent bypass (n = 1747). Data were split into training (70%) and test (30%) sets. A total of 112 predictive features (75 preoperative [demographic and clinical], 24 intraoperative [procedural], and 13 postoperative [in-hospital course and complications]) from the index hospitalization were identified. Using 10-fold cross-validation, 6 ML models were trained using preoperative features to predict 1-year major adverse limb event (MALE; composite of thrombectomy or thrombolysis, surgical reintervention, or major amputation) or death. The primary model evaluation metric was area under the receiver operating characteristic curve (AUROC). After selecting the best performing algorithm, additional models were built using intraoperative and postoperative data. Overall, 235 677 patients who underwent endovascular intervention for PAD were included (mean [SD] age, 68.4 [11.1] years; 94 979 [40.3%] female) and 71 683 (30.4%) developed 1-year MALE or death. The best preoperative prediction model was extreme gradient boosting (XGBoost), achieving the following performance metrics: AUROC, 0.94 (95% CI, 0.93-0.95); accuracy, 0.86 (95% CI, 0.85-0.87); sensitivity, 0.87; specificity, 0.85; positive predictive value, 0.85; and negative predictive value, 0.87. In comparison, logistic regression had an AUROC of 0.67 (95% CI, 0.65-0.69). The XGBoost model maintained excellent performance at the intraoperative and postoperative stages, with AUROCs of 0.94 (95% CI, 0.93-0.95) and 0.98 (95% CI, 0.97-0.99), respectively. In this prognostic study, ML models were developed that accurately predicted outcomes following endovascular intervention for PAD, which performed better than logistic regression. These algorithms have potential for important utility in guiding perioperative risk-mitigation strategies to prevent adverse outcomes following endovascular intervention for PAD.

Illness beliefs relation to physical activity and quality of life in patients with peripheral arterial disease

ABSTRACT Intermittent claudication is the most common symptom of Peripheral Arterial Disease (PAD) and is associated with decreased quality of life (QoL) due to walking impairment. The level of threat attributed to the disease affects QoL and physical activity. This study explores beliefs and illness drawings, and their relationship with quality of life and physical activity in patients undergoing conservative treatment for PAD. A cross-sectional study was carried out including 119 patients with PAD and Intermittent Claudication, in which patients were asked to freely draw their disease and 33 agreed to participate. The profile of beliefs about PAD is characterized by a low level of threat. Belief in the emotional impact of the disease, representations about the consequences and concern about the disease were associated with worse quality of life; the belief of having a high personal control over the disease was associated with more physical activity. The analysis of the disease drawings revealed three categories: extension of the disease (category 1), location and representations of the disease (category 2), and level of detail and complexity of the drawings (category 3). Greater disease extent was associated with more disease symptoms (IPQ 6) (r s = 0.399, p = .021). It is necessary to address beliefs and representations about the disease in consultations with patients with PAD. Patient drawings are a useful, practical, and free tool that does not require a lot of time and can facilitate the approach of health professionals to patient training and education.

Prescriber decision-making on antithrombotic therapy after endovascular intervention for peripheral artery disease: a protocol for a discrete choice experiment

IntroductionPeripheral artery disease (PAD) is a major risk factor for cardiovascular morbidity and mortality, despite surgical and endovascular treatments. Emerging evidence supports the use of immediate antithrombotic medications after endovascular...

Short-term outcomes of endovascular management of acute limb ischemia using aspiration mechanical thrombectomy.

Management of acute limb ischemia (ALI) has seen greater utilization of catheter-based interventions over the last two decades. Data on their efficacy is largely based on comparisons of catheter-directed thrombolysis (CDT) and open thrombectomy. During this time, many adjuncts to CDT have emerged with different mechanisms of action, including pharmacomechanical thrombolysis (PMT) and aspiration mechanical thrombectomy (AMT). However, the safety and efficacy of newer adjuncts like AMT have not been well established. This study is a retrospective analysis of the contemporary management of ALI comparing patients treated with aspiration mechanical thrombectomy to patients treated with the more established CDT adjunct, pharmacomechanical thrombolysis. Patients undergoing peripheral endovascular intervention for ALI using an adjunctive device were identified through query of the Vascular Quality Initiative (VQI) Peripheral Vascular Intervention (PVI) module from 2014 to 2019. Patients with a nonviable extremity (Rutherford ALI Stage 3), prior history of ipsilateral major amputation, popliteal aneurysm, procedures that were deemed elective (>72h from admission), procedures that did not utilize an endovascular adjunctive device, and patients without short-term follow-up were all excluded from analysis. The primary outcome was a composite outcome of freedom from major amputation and/or death in the perioperative time period. We identified 528 patients with Rutherford ALI Stage 1 or 2 who were treated with an endovascular adjunct. 433 patients did not undergo aspiration mechanical thrombectomy (no AMT group) and 95 patients did undergo aspiration mechanical thrombectomy (AMT group). The amputation-free survival across all patients was 93.4%. There were significant differences in demographic, comorbidity, and treatment variables between groups (e.g., gender, prior percutaneous coronary intervention (PCI), history of prior peripheral artery disease intervention, and history of prior infra-inguinal PVI), so a propensity score matched analysis was included to account for these group differences. In the propensity score matched analysis, there was no significant difference in major amputation (AMT 7.4% vs no AMT 3.2%, p = 0.13) or death (AMT 95.8% survival vs no AMT 98.4% survival, p = 0.23) with the use of aspiration mechanical thrombectomy. However, there was significantly worse amputation-free survival with the use of aspiration mechanical thrombectomy (AMT 88.4% vs no AMT 95.3%, p = 0.03). On multivariate analysis, prior supra-inguinal bypass (OR 4.85, 1.70-13.84, p = 0.003), Rutherford ALI Stage 2B (OR 3.13, 1.47-6.67, p = 0.003), and aspiration mechanical thrombectomy (OR 2.71, 1.03-7.17, p = 0.05) were associated with the composite outcome. Short-term amputation-free survival rates of endovascular management of acute limb ischemia are adequate across all modalities. However, aspiration mechanical thrombectomy was associated with significantly worse amputation-free survival compared to other endovascular adjuncts alone (i.e., pharmacomechanical thrombolysis). Severe limb ischemia (Rutherford ALI Stage 2B) and prior supra-inguinal bypass were associated with worse amputation-free survival regardless of the choice of endovascular intervention.

The impact of sex on platelet responses to aspirin in patients with peripheral artery disease.

Women with peripheral artery disease (PAD) have poorer limb salvage outcomes in spite of having lower risk factors for vascular disease than their male counterparts. Mono antiplatelet therapy with aspirin is the cornerstone of medical treatment for PAD to reduce the risk of arterial thrombosis, but platelets in women may have a variable response to this standard of care compared to men. Viscoelastic assays, such as thromboelastography with platelet mapping (TEG-PM), have been utilized to identify prothrombotic states and may provide insight into a patient's real-time coagulation profile and their response to specific antiplatelet medications. The aim of this prospective, observational study was to delineate the sex differences in platelet function using TEG-PM in patients with PAD on aspirin post-revascularization for PAD. All patients with PAD undergoing revascularization on aspirin monotherapy were prospectively enrolled between December 2020 and September 2023. The cohort was divided by sex, demographics, medications, procedure type, and outcomes were documented. Serial perioperative TEG-PM assays (1, 3, and 6 months) were performed up to 6 months postoperatively and platelet function was evaluated in both groups. Statistical analysis between women and men was performed to identify sex-specific differences in platelet function. Over the study period, a total of 303 patients were enrolled. Of this cohort, 149 patients met the study criteria and 266 samples were analyzed; 52 (34.89%) were women and 97 (65.11%) were men. In the platelet mapping assay, women showed significantly greater MAActF and MAAA, than men (16.66 vs. 14.94, p < .03 and 37.26 vs. 32.38, p < .01, respectively) indicating stronger thrombotic propensity. Additionally, platelet inhibition was significantly lower in women compared to men (52.95% vs. 61.65%, p < .05). In clinical outcomes reported as thrombotic events, women showed significantly higher occlusion in the area of intervention than men (4 vs. 1, p < .05). There is a growing awareness of the variations in the natural course, underlying mechanisms, and resulting outcomes of cardiovascular conditions, including PAD, in relation to sex. In this study, women did not achieve the same levels of platelet inhibition and displayed a procoagulant tendency in comparison to men when administered aspirin. Overall, aspirin monotherapy may be potentially sufficient for men, but women may require increased doses and/or additional antiplatelet medications to achieve an equivalent therapeutic effect.

Reconsidering the Impact of Endovascular Repair on Short-Term and Mid-Term Outcomes in Peripheral Arterial Disease: A Retrospective Analysis

ObjectiveThe aim of the study is to compare the short and medium-term outcomes in patients who underwent open repair (OR) or endovascular repair (ER) for peripheral arterial disease (PAD) also including stratifications based on severity and year of the first intervention. DesignObservational retrospective single-center cohort study. MethodsWe evaluated patients with PAD that primarily underwent ER, OR, minor and major amputations in a single center from 2005 to 2020. The patients were then subdivided according to the type of intervention (OR vs ER), and stratified according to the ICD-9 code reported in the operating documents and to the year intervention. Mortality, minor and major amputation rates occurring at 30 days, 2 and 5 years after the first intervention were evaluated as primary outcomes and compared between patient groups in both stratifications. Moreover, Kaplan-Maier (KM) curves were analyzed for these outcomes. Results1492 patients (67.0% males) with PAD were evaluated. Their clinical presentations were intermittent claudication in 51.4% of cases, rest pain in 16.8%, ulcers in 10.3%, and gangrene in 21.5%. 997 (66.8%) underwent OR and 495 (33.2%) ER as first intervention for PAD. No statistical differences were observed in terms of mortality in the two groups (OR vs ER, p=1.000, p=0.357, p=0.688 at 30 days, 2 and 5 years respectively). The rate of minor amputations was significantly higher (p<.012, p<.002, p<.007 at 30 days, 2 and 5 years respectively) for ER group in any of the observed follow-up periods. Also, we have observed that OR and ER do not have any significant short- and medium-term major amputation rate differences. ConclusionIn our experience, the impact of ER does not significantly change short- and mid-term major outcomes in patients with PAD.

Invasiveness of previous treatment for peripheral arterial disease and risk of adverse cardiac events after coronary stenting

Patients with peripheral arterial disease (PADs), undergoing percutaneous coronary intervention (PCI), have higher adverse event risks. The effect of invasiveness of PADs treatment on PCI outcome is unknown. This study assessed the impact of the invasiveness of previous PADs treatment (invasive or non-invasive) on event risks after PCI with contemporary drug-eluting stents. This post-hoc analysis pooled 3-year patient-level data of PCI all-comer patients living in the eastern Netherlands, previously treated for PADs. PADs included symptomatic atherosclerotic lesion in the lower or upper extremities; carotid or vertebral arteries; mesenteric arteries or aorta. Invasive PADs treatment comprised endarterectomy, bypass surgery, percutaneous transluminal angioplasty, stenting or amputation; non-invasive treatment consisted of medication and participation in exercise programs. Primary endpoint was (coronary) target vessel failure: composite of cardiac mortality, target vessel-related myocardial infarction, or clinically indicated target vessel revascularization. Of 461 PCI patients with PADs, information on PADs treatment was available in 357 (77.4%) patients; 249 (69.7%) were treated invasively and 108 (30.3%) non-invasively. Baseline and PCI procedural characteristics showed no between-group difference. Invasiveness of PADs treatment was not associated with adverse event risks, including target vessel failure (20.5% vs. 16.0%; HR: 1.30, 95%-CI 0.75–2.26, p = 0.35), major adverse cardiac events (23.3% vs. 20.4%; HR: 1.16, 95%-CI 0.71–1.90, p = 0.55), and all-cause mortality (12.1% vs. 8.3%; HR: 1.48, 95%-CI 0.70–3.13, p = 0.30). In PADs patients participating in PCI trials, we found no significant relation between the invasiveness of previous PADs treatment and 3-year outcome after PCI. Consequently, high-risk PCI patients can be identified by consulting medical records, searching for PADs, irrespective of the invasiveness of PADs treatment.Graphical abstractComparison of patients with non-invasive and invasive PADs treatment. PADs peripheral arterial disease, PCI percutaneous coronary intervention.

Comparison effect of high-intensity interval training and moderate intensity continuous training on vascular function in a mouse model of lower extremity peripheral artery disease

Introduction&#x0D; Lower extremity peripheral artery disease (PAD), due to narrowing of the arteries supplying the legs, represents a major cause of physical disability. Exercise training is an important part of PAD treatment, improving functional capacity. Recent research suggests that exercise training-induced endothelial function improvement is involved in the benefits of exercise in PAD (Lee et al., 2023); however, the underlying molecular mechanisms remain unknown. In addition, the potential vascular benefits of high intensity training in PAD remain unexplored. Therefore, the aim of the study was to compare the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on endurance capacity, vascular endothelial function and expression of genes related to nitric oxide (NO) bioavailability in a mouse model of PAD.&#x0D; Methods&#x0D; PAD disease model was generated in male C57BL/6 mice by ligation of the right iliac artery. Mice with PAD were divided into 3 groups: sedentary control group (SED), MICT (40 min running at 70% of maximal aerobic speed) and HIIT (8 intervals of 2.5 minutes running at 90% of maximal aerobic speed combined with 2.5 minutes of running at 50% of maximal aerobic speed). Mice were exercised three times per week for 8 weeks. Maximal running time was determined by an incremental test until exhaustion. Vascular reactivity was assessed by measuring vasoconstrictor responses to phenylephrine as well as endothelium-dependent and -independent vasodilator responses to acetylcholine and DEA-NONOate, respectively, in isolated aortic rings. Gene expression of antioxidant enzymes (catalase and superoxide dismutase isoforms), prooxidant NADPH oxidase subunits (p22phox and p47phox), enzyme involved in NO production (endothelial NO synthase), vascular smooth muscle cell relaxation (soluble guanylate cyclase) and receptors involved in vascular tone regulation (a1 and b2 adrenergic receptors) was determined in aortic tissue by qPCR.&#x0D; Results&#x0D; Maximal running time was improved in both MICT and HIIT as compared to SED at the end of the study, but with no significant difference between the two exercise groups. Phenylephrine-induced vasoconstriction as well as vasodilator responses to acetylcholine and DEA-NONOate were significantly improved in MICT compared to SED while no significant differences were reported between HIIT and SED. There was no significant difference in gene expression among the three groups.&#x0D; Discussion/Conclusion&#x0D; MICT and HIIT were equally effective at improving endurance capacity in mice with PAD. However, only MICT improved vascular reactivity.&#x0D; References&#x0D; Lee, J., Zarezadehmehrizi, A., LaVoy, E., Markofski, M., &amp; Park, Y. (2023). Exercise training improves brachial artery endothelial function, but does not alter inflammatory biomarkers in patients with peripheral artery disease: A systematic review and meta-analysis. Journal of Cardiovascular Translational Research. Advance online publication. https://doi.org/10.1007/s12265-023-10451-0

Conservative Treatment and Secondary Prevention of PAD (Peripheral Artery Disease)

The immediate and long-term success of endovascular and surgical revascularization crucially depends on the conservative treatment of the PAD. The "gentle, preserving" treatment should be understood as he absolutely basic therapy for every PAD patient, because conservative treatment adresses the "big five" of atherosclerotic risk factors. This article presents both the full spectrum of pharmacological and non-pharmacological strategies.