Symptomatic Peripheral Artery Disease Patients Research Articles

DETOUR2 trial outcomes demonstrate clinical utility of percutaneous transmural bypass for the treatment of long segment, complex femoropopliteal disease

ObjectivePercutaneous transmural arterial bypass (PTAB) using the DETOUR system aims to create a percutaneous, endovascular femoropopliteal bypass for the treatment of long segment, complex superficial femoral and proximal popliteal artery disease. The goal of the DETOUR2 study is to investigate the safety and effectiveness of the therapy in comparison with pre-established performance goals. MethodsThe DETOUR2 investigational device exemption study is a prospective, single-arm, multicenter, international trial of symptomatic peripheral arterial disease patients (Rutherford classes 3-5) undergoing the DETOUR procedure for long segment (>20 cm) superficial femoral artery disease. Prespecified end points included primary safety (composite of major adverse events) at 30 days, and effectiveness (primary patency defined as freedom from restenosis or clinically driven target lesion revascularization) at 1 year. ResultsWe enrolled 202 patients at 32 sites with 200 treated with the DETOUR system. The mean lesion length was 32.7 cm, of which 96% were chronic total occlusions (CTO) and 70% were severely calcified. Technical success was achieved in 100% of treated patients. The primary safety end point was met with a 30-day freedom from major adverse event rate of 93.0%. The 1-year primary effectiveness end point was met with 72.1% primary patency at 12 months. Primary-assisted and secondary patency were 77.7% and 89.0%, respectively, at 12 months. The 12 month deep venous thrombosis incidence was 4.1% with no pulmonary emboli reported. Venous quality-of-life scores showed no significant changes from baseline. There was a Rutherford improvement of at least one class through 12 months in 97.2% of patients. The mean ankle-brachial index also improved from 0.61 to 0.95 during this period. There were marked improvements in quality-of-life and functional status measures. ConclusionsThe DETOUR2 study met both the primary safety and effectiveness end points, demonstrating clinical usefulness of this novel therapeutic strategy in long femoropopliteal lesions.

Intermittent Sargramostim Administration Expands Proliferating Naïve T Cells, Tregs, HLA-DR+ PD-L1+ Monocytes and Myeloid-Derived Suppressor Cells: Results from a Randomized Placebo-Controlled Clinical Trial of GM-CSF in Patients with Peripheral Artery Disease

Introduction: Sargramostim (rhuGM-CSF; Leukine ®) is an FDA-approved drug known for mobilizing hematopoietic progenitor cells and expediting hematopoietic reconstitution in patients with acute myeloid leukemia (AML) as well as after autologous and allogeneic bone marrow transplantation. While GM-CSF has been explored as an adjuvant for cancer vaccines due to its ability to promote dendritic cell differentiation and maturation, continuous daily administration of sargramostim has been associated with leukocytosis and adverse side effects. To validate and expand upon our previously published findings that thrice-weekly sargramostim administration in patients with severe peripheral artery disease (PAD) is both well-tolerated and beneficial for claudication symptoms, we conducted a placebo-controlled randomized clinical trial to assess the efficacy of an extended dosing regimen of sargramostim in PAD patients. Data regarding progenitor mobilization kinetics and claudication symptoms will be presented elsewhere. In this analysis, we investigated the impact of intermittent sargramostim dosing on immune cell subsets in the bloodstream, aiming to support the use of this dosing schedule for enhancing adaptive immunity. Methods: Symptomatic atherosclerotic PAD patients were enrolled and randomly assigned to receive either 500 μg/day of sargramostim or placebo via self-administered subcutaneous injections thrice weekly for 3 weeks, for two separate courses 3 months apart. The study was IRB-approved with adverse events and safety signals monitored by an independent Data Safety Monitoring Board. A total of 61 patients (40 receiving sargramostim and 21 receiving placebo) participated in the immune-monitoring sub-study. Blood mononuclear cells were collected at various time points and cryopreserved. Thawed peripheral blood mononuclear cells (PBMCs) were stained using immune cell-specific antibody cocktails, and analyzed by flow cytometry. Statistical significance was determined using the Student's t-test. Results: No dose-limiting leukocytosis or drug-related side effects were observed. As expected, the numbers of white blood cells (WBCs) increased by an average of 68% in the blood of sargramostim-treated patients compared to placebo-treated patients, with peak values reached after 3 weeks of intermittent study drug administration, followed by return to baseline before the next treatment course. Absolute counts of CD3+, CD4+, and CD8+ T cells, B cells, and CD14+ monocytes significantly increased one and two weeks after starting intermittent sargramostim treatment compared to the control group. Notably, sargramostim-treated patients exhibited higher levels of proliferating naïve, Ki-67+ CD4+ T cells (106.83/uL ± 70.28) compared to placebo-treated patients (44.94/uL ± 33.84, p=0.001), as well as increased numbers of naïve Ki-67+ CD8+ T cells (33.05/uL ± 25.43 after sargramostim versus 15.77/uL ± 15.73 for placebo, p=0.01) (Fig. 1, A). However, sargramostim treatment did not influence the quantities of central memory CD4+ and CD8+ T cells. Besides the heightened proliferation of naïve T cells, sargramostim treatment also resulted in a significant increase in the numbers of CD3+CD4+CD25+FoxP3+ Tregs (Fig. 1, A), as well as PD-1-expressing CD4+ and CD8+ T cells, compared to the control group. Moreover, sargramostim treatment led to elevated levels of CD14+HLA-DR+ and CD14+PDL-1+ monocytes, as well as myeloid-derived suppressor cells, 2 and 3 weeks after initiation of treatment, when compared to the control group (Fig. 1, B). Conversely, sargramostim treatment had no impact on the levels of gamma-delta T cells, natural killer (NK) cells, plasmacytoid dendritic cells, or classical dendritic cells. Conclusions: Our findings demonstrate that intermittent dosing with sargramostim is well-tolerated and induces significant but transient increases in the numbers and activation status of T cells in the bloodstream. Sargramostim treatment also increased numbers of proliferating naïve T cells, Tregs, and certain subsets of myelo-monocytic cells with immunosuppressive phenotypes. These results support the use of intermittent sargramostim dosing to avoid excessive leukocytosis and associated adverse effects. Further investigation is warranted to elucidate the clinical implications of these findings in the context of immune modulation.

Clinical impact of the infrapatellar location in symptomatic peripheral arterial disease patients.

Peripheral artery disease (PAD) frequently affects multiple segments of the limbs. Contradictory data have reported worse prognosis in aortoiliac lesions, nevertheless, diabetes and chronic limb ischemia frequently affects the infrapatellar territory. Our aim was to assess the impact of infrapatellar disease in cardiovascular outcomes. We performed a retrospective, observational cohort study at a university hospital in Argentina. Electronic health records were retrospectively reviewed including symptomatic PAD patients requiring revascularization. A multivariable regression model was performed to account for confounders. The primary endpoint was a composite of hospitalizations due to chronic limb threatening ischemia (CLTI) and major amputation events between infrapatellar and suprapatellar patients. Minor amputation events, all-cause death, myocardial infarction (MI), stroke, and major cardiovascular events (MACE) were secondary endpoints. From January 2014 through July 2020, a total of 309 patients were included in the analysis. 151 patients had suprapatellar disease, and 158 had infrapatellar disease. The primary composite endpoint occurred in 35 patients (22.2%) in the infrapatellar patients and 18 patients (11.9%) in the suprapatellar patients (HR = 2.16; 95% confidence interval [CI]= [1.22-3.82]; p = 0.008). Both components of the primary outcomes occurred more frequently in infrapatellar patients.Minor amputation events were more prevalent in infrapatellar patients (HR = 5.09; 95% CI = [1.47-17.6]; p = 0.010). Death,MI, stroke, and MACE events were not different among groups (all p > 0.05). Infrapatellar disease was anindependent factor for increased hospitalization of CLTI, major and minor amputations events, compared to suprapatellardisease in symptomatic revascularized PAD patients.

NT-proBNP as a surrogate for unknown heart failure and its predictive power for peripheral artery disease outcome and phenotype

Patients with peripheral artery disease (PAD) are at high risk of excess mortality despite major improvements in multimodal pharmacotherapy for cardiovascular disease. However, little is known about co-prevalences and implications for the combination of heart failure (HF) and PAD. Thus, NT-proBNP as a suggested surrogate for HF was evaluated in symptomatic PAD regarding long-term mortality. After approval by the institutional ethics committee a total of 1028 patients with PAD, both with intermittent claudication or critical limb ischemia were included after admission for endovascular repair and were followed up for a median of 4.6 years. Survival information was obtained from central death database queries. During the observation period a total of 336 patients died (calculated annual death rate of 7.1%). NT-proBNP (per one standard deviation increase) was highly associated with outcome in the general cohort in crude (HR 1.86, 95%CI 1.73–2.01) and multivariable-adjusted Cox-regression analyses with all-cause mortality (HR 1.71, 95%CI 1.56–1.89) and CV mortality (HR 1.86, 95% CI 1.55–2.15). Similar HR’s were found in patients with previously documented HF (HR 1.90, 95% CI 1.54–2.38) and without (HR 1.88, 95%CI 1.72–2.05). NT-proBNP levels were independently associated with below-the-knee lesions or multisite target lesions (OR 1.14, 95% CI 1.01–1.30). Our data indicate that increasing NT-proBNP levels are independently associated with long-term mortality in symptomatic PAD patients irrespective of a previously documented HF diagnosis. HF might thus be highly underreported in PAD, especially in patients with the need for below-the-knee revascularization.

Prognostic Role of Polyvascular Involvement in Patients with Symptomatic Peripheral Artery Disease.

Background: Statin therapy is recommended for patients with peripheral artery disease (PAD). However, PAD patients with polyvascular (PV) extent remain threatened by an increased residual cardiovascular (CV) risk. Purpose: To investigate the association of prescribed statin therapy and mortality in PAD patients with or without PV extent. Methods: A single-center retrospective longitudinal observational study originating from a consecutive registry with 1380 symptomatic PAD patients over a mean observational time of 60 ± 32 months. The association of atherosclerotic extent and statin use (PAD, plus one additional region (CAD or CeVD, [+1 V]), +2 vascular regions (+CAD and CeVD [+2 V]) with the risk of all-cause mortality was evaluated using Cox proportional hazard models adjusted for potential confounding factors. Results: The mean age of the study's participants was 72.0 ± 11.7 years, with 36% being female. PAD patients with PV extent [+1 V] and [+2 V] were older and suffered from diabetes, hypertension, or dyslipidemia more often; they, too, had more severely impaired kidney function (all p < 0.0001) compared to patients with PAD only. PAD patients with PV [+1 V] and [+2 V] received better statin medication and reached the recommended LDL-C target compared to PAD-only patients (p < 0.001). Despite better statin treatment, the rate of all-cause mortality was higher in PV patients than in PAD-only patients (PAD only: 13%; [+1 V]: 22%; [+2 V]: 35%; p < 0.0001). Conclusion: PV patients receive better statin therapy than PAD-only patients but nevertheless still have higher mortality rates. Future studies are needed to explore whether more aggressive LDL-lowering treatment for PAD patients may be translated into better prognosis.

Obesity prevalence and variability in management practices for patients with symptomatic peripheral artery disease

Obesity has been associated with poor disease outcomes in patients with lower extremity peripheral arterial disease (PAD). Given evolving treatments for obesity, evaluating its prevalence and treatment practices are key to develop a holistic management of PAD. We aimed to examine prevalence of obesity and variability of management strategies in symptomatic PAD patients enrolled in the international multicenter PORTRAIT registry from 2011 to 2015. Obesity management strategies studied included weight and/or dietary counseling and prescription of weight loss medications (orlistat, lorcaserin, phentermine-topiramate, naltrexone-buproprion, and liraglutide). Use frequency of obesity management strategies were calculated by country and compared across centers using adjusted median odds ratios (MOR). Of 1002 patients included, 36 % had obesity. No patients received weight loss medications. Weight and/or dietary counseling was prescribed in only 20 % of patients with obesity with significant variability in practices between centers (range 0.0–39.7 %; MOR 3.6, 95 % CI 2.04–9.95, p = < 0.001). In conclusion, obesity is a prevalent modifiable comorbidity in PAD that is hardly addressed during PAD management, with significant variability across practices. As obesity prevalence rates are growing, along with treatment modalities to treat it, especially in those with PAD, building systems to integrate systematic evidence-based weight and dietary management strategies in PAD are essential to close this gap in care.

Mono or Dual Antiplatelet Therapy for Treating Patients with Peripheral Artery Disease after Lower Extremity Revascularization: A Systematic Review and Meta-Analysis.

The efficacy of dual antiplatelet therapy (DAPT) for patients with peripheral artery disease (PAD) after lower-limb intervention remains controversial. Currently, the prescription of DAPT after an intervention is not fully recommended in guidelines due to limited evidence. This study compares and analyzes the prognosis for symptomatic PAD patients receiving DAPT versus monotherapy after lower-limb revascularization. Up to November 2021, PubMed/MEDLINE, Embase, and Cochrane databases were searched to identify studies reporting the efficacy, duration, and bleeding complications when either DAPT or monotherapy were used to treat PAD patients after revascularization. Three randomized controlled trials and seven nonrandomized controlled trials were included in our study. In total, 74,651 patients made up these ten studies. DAPT in PAD patients after intervention was associated with lower rates of all-cause mortality (HR = 0.86; 95% CI, 0.79–0.94; p < 0.01), major adverse limb events (HR = 0.60; 95% CI, 0.47–0.78; p < 0.01), and major amputation (HR = 0.78; 95% CI, 0.64–0.96) when follow-up was for more than 1-year. DAPT was not associated with major bleeding events when compared with monotherapy (OR = 1.22; 95% CI, 0.69–2.18; p = 0.50) but was associated with a higher rate of minor bleeding as a complication (OR = 2.54; 95% CI, 1.59–4.08; p < 0.01). More prospective randomized studies are needed to provide further solid evidence regarding the important issue of prescribing DAPT.

Prevention of arterial and venous thrombotic events in symptomatic peripheral arterial disease patients after lower extremity revascularization in the VOYAGER PAD trial: Dual anticoagulant/antiplatelet regimen vs antiplatelet therapy alone

BackgroundVascular disease burden after lower extremity revascularization (LER) comprises more than the first event, more vascular beds than the local arteries, and more than one clinical event type. ObjectivesAssess total arterial and venous thrombotic burden after LER for symptomatic peripheral artery disease (PAD) and effect of low‐dose anticoagulation added to low‐dose antiplatelet therapy. Patients/MethodsVOYAGER PAD randomized 6564 symptomatic PAD patients undergoing LER to rivaroxaban 2.5 mg twice‐daily or placebo on aspirin background. Marginal proportional‐hazards models used to generate treatment hazard ratios and associated 95% CIs for first and total events; non‐thrombotic deaths treated as competing terminal events. Incidence rates calculated as number of events per 100 patient‐years follow‐up. ResultsOver 2.5 years (median), first and total thrombotic event rates: 7.1 and 10.3 events/100 patient‐years, respectively, in placebo group. Two‐thirds (925/1372) of total thrombotic events (arterial 95%, venous 5%) were nonfatal first events. Nearly one‐third of patients with first event had a second arterial or venous thrombotic event. Rivaroxaban plus aspirin reduced first and total arterial and venous thrombotic events to 5.4 and 7.9 events/100 patient‐years, respectively, a reduction in total thrombotic events over aspirin of 23% (HR: 0.77, 95%CI: 0.67–0.89, p = .0005), preventing 6.1 total arterial and venous thrombotic events at 3 years. ConclusionsAssessing total arterial and venous thrombotic events, not just first events, provides more complete information about disease burden and absolute on‐treatment impact. Following LER, judicious modulation of more than one coagulation pathway can provide broader benefit than intensifying inhibition of one hemostatic system component.

Abstract P121: Measuring The Impact Of Inaction On Health Disparities In Limb Amputation

Objective: Peripheral artery disease (PAD) is a common atherosclerotic disorder that reduces blood flow to the lower extremities. There are significant racial disparities in the outcomes of patients with PAD. Ideally, understanding the result of inadequate implementation of proven interventions on health disparities might provoke a policy and culture shift in the provision of care for minoritized persons. We demonstrate a method that leverages knowledge of interventions that we know should be implemented to optimize care for people with PAD, to identify the extent to which disparities might be mitigated by more universal uptake of those interventions. Methods: We compare racial disparities as they exist currently with disparities that would exist under complete uptake of interventions to improve PAD and vascular care. This counterfactual world is modeled by upweighting people who received the proposed interventions to represent the study population at the start of follow-up. It relies on the assumption that we have measured (and adjusted for) all confounders of the intervention (a hypothesized mediator of the observed health disparities) and the outcome. A unique feature of the application of this method to this problem is our ability to demonstrate how, even when guideline-based care appears evenly distributed by race/ethnicity, increasing access to such care may still decrease health disparities. This method was previously proposed for estimating potential reductions in racial disparities for people with HIV. Results: Across 100,579 infrainguinal revascularizations among Black (n=15,442), Hispanic (n=5,506) and White (n=67,651) patients treated for symptomatic PAD, Black (56.5%) and Hispanic patients (57.6%) were slightly less likely than White patients (59.8%) to receive Class I recommended aspirin and statin therapy prior to their procedures. One-year risk of amputation was 2.7% (95% CI: 2.6%,2.8%) in White patients, 5.8% (5.4%,6.2%) in Black patients and 5.6% (5.0%,6.2%) in Hispanic patients. Had all patients received the appropriate anti-ischemic medications, amputation risk would have been lower across all three race-ethnicity groups. However, specifically, the risk difference (RD) for Black vs White patients would have reduced by 8% (-3%,20%) and the RD for Hispanic vs White patients would have reduced by 18% (-1%,36%). Conclusions: Not only is provision of aspirin and statin for infrainguinal revascularization good for all PAD patients, it is also a social justice imperative.

Antithrombotic Treatment in Lower Extremity Peripheral Arterial Disease.

Lower extremity arteries might be affected by atherosclerotic peripheral arterial disease (PAD), or by embolization causing ischaemic symptoms. Patients with PAD often have widespread atherosclerosis, and progression of PAD is associated with increased risk for both other cardiovascular events and cardiovascular mortality. Peripheral arterial disease patients should therefore be offered both non-pharmacological and pharmacological secondary prevention to reduce the risk for future ischemic arterial complications. This review is focussed on the rationale for recommendations on antiplatelet and anticoagulant treatment in PAD. Asymptomatic PAD does not warrant either anticoagulant or antiplatelet treatment, whereas patients with ischaemic lower extremity symptoms such as intermittent claudication or critical limb ischemia caused by atherosclerosis should be offered platelet antiaggregation with either low dose aspirin or clopidogrel. Combined treatment with aspirin and low-dose of the direct oral anticoagulant (DOAC) rivaroxaban should be considered and weighed against bleeding risk in symptomatic PAD patients considered at high risk for recurrent ischaemic events and in patients having undergone endovascular or open surgical intervention for PAD. Patiens with cardiogenic embolization to lower extremity arteries should be recommended anticoagulant treatment with either one of the DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) or warfarin.

Effect of nitrate administration on plasma nitric oxide levels in patients with peripheral arterial disease at Dr. Sardjito General Hospital, Yogyakarta

Peripheral arterial disease (PAD) is a disease involving reduction of blood flow to the inferior extremity associated with atherosclerotic lesions. In 2010, more than 200 million people with PAD were reported globally, including 54.8 million in Southeast Asia. The high prevalence of PAD causes its management become challenging for clinicians. Nitric oxide (NO) has a role in endothelial function that is associated with the appearance of symptoms in PAD patients. Exogenous nitrate is usually used as a primary vasodilator in the treatment of angina pectoris and Prinzmetal angina. However, information concerning the role of nitrate administration to improve symptomatic PAD patients is limited. This study aimed to evaluate the effectiveness of exogenous nitrates in increasing plasma NO levels and improving PAD patients. A prospective pre-post clinical trial involving PAD patients who were registered in the vascular registry at Dr. Sardjito General Hospital, Yogyakarta was conducted. Primary endpoint was the change in plasma NO levels after short term administration of nitroglycerin oral 2.5 mg once daily (4 h) and long term (7 d). Analysis of variance test with Bonferroni posttest was used for statistical hypothesis testing. Among 33 subjects who completed this study, no negative side effects, and only one hypotensive patient was reported at the first follow-up after 4 h of the nitroglycerin administration. Plasma NO levels increased in the post 4 h and in the post 7 d administration. However, no statistically significant was observed (p &gt; 0.05). Administration of exogenous nitrates in patients with PAD increases the plasma NO levels, even though it is not statistically significant.

Symptomatic and Asymptomatic Peripheral Artery Disease and the Risk of Abdominal Aortic Aneurysm: The Atherosclerosis Risk in Communities (ARIC) Study

A prospective cohort study was performed at visit 1 (1987-1989) and a cross-sectional cohort study was performed at visit 5 (2011-2013) from four U.S. communities (Washington County, Md; suburban Minneapolis, Minn; Jackson, Miss; Forsyth County, NC) in the Atherosclerosis Risk in Communities (ARIC) study. Of 14,148 participants (55% female, 26% black, 1% with symptomatic peripheral arterial disease), after a median follow-up of 23 years, 3.7% had developed incident abdominal aortic aneurysms (AAAs). The presence of symptomatic peripheral artery disease (PAD) resulted in a higher hazard ratio (HR) of incident AAA (HR, 4.9), as did asymptomatic PAD with an ankle brachial index (ABI) of ≤0.9 (HR, 2.33) compared with the reference ABI of >1.1. The crude 15-year cumulative incidence of AAAs was 12% in the symptomatic PAD group, 4% in the asymptomatic PAD group with an ABI of <0.9, and 2% in the asymptomatic PAD group with an ABI of >1.1. The cross-sectional analysis demonstrated similar patterns for ultrasound-based AAAs, with odds ratio for AAAs of 2.5 for symptomatic PAD and 4.0 for asymptomatic PAD in a demographically adjusted model. These prospective and cross-sectional data showed an elevated risk of AAAs in patients with symptomatic and asymptomatic PAD. These data support the current recommendation of AAA screening for symptomatic PAD patients and suggest the potential extension to asymptomatic PAD patients as well.

Abstract 9758: Estimating Cardiovascular and Limb Benefits of Combined Contemporary Risk Reduction Therapies in Patients with Symptomatic Peripheral Artery Disease: An Analysis of Randomized Controlled Trials

Introduction: Individual randomized controlled trials (RCTs) have shown beneficial effects of low dose rivaroxaban and PCSK9 inhibition (PCSK9i) in addition to background aspirin and statin in patients with peripheral artery disease (PAD). However, the combined effect of these pharmacotherapies is not known. In this analysis of RCT data, we sought to estimate the combined effect of contemporary risk reduction therapies in patients with PAD. Methods: We used data from the COMPASS (n=4,129) and FOURIER (n=3,642) trials to estimate the combined effect of contemporary (aspirin, statin, low dose rivaroxaban and PCSK9i) versus standard therapy (aspirin and statin) in symptomatic PAD patients. The primary outcome was a composite of major adverse cardiovascular (MACE) or limb (MALE) events. Using the hazard rates for low dose rivaroxaban versus control and PCSK9i versus control from the two trials, we estimated the hazard rate for combined therapy by assuming that the treatment effects are approximately additive on the log hazard rate (no interaction between the two treatments). We then used an exponential model to simulate event-free survival and cumulative incidence functions, and hazard ratios (HRs) for the combined versus the standard therapy group. Results: Compared with standard therapy, combined contemporary pharmacotherapy estimated a 50% reduction in MACE or MALE (HR, 0.50; 95% confidence interval [CI], 0.36-0.70; P&lt;0.001). The 3-year cumulative incidence probability of MACE or MALE was 9.1% in the combined group and 15.4% in the standard therapy group ( Figure ). The hazards for MACE (HR, 0.52; 95% CI, 0.36-0.75; P=0.001) and MALE (HR, 0.35; 95% CI, 0.18-0.68; P=0.002) also favored combined contemporary therapy. Conclusions: Thoughtful incorporation of contemporary pharmacotherapies that include low dose rivaroxaban and PCSK9i in addition to aspirin and statin has the potential to substantially reduce cardiovascular and limb events in patients with PAD.

Abstract 11751: Long Term Quality of Life Improvement After Peripheral Vascular Intervention- Insights From the Liberty 360 Study

Background: Improving patients’ quality of life (QoL) is a primary indication for peripheral endovascular intervention (PVI) for peripheral arterial disease (PAD). Little is known about the long-term improvement in QoL following PVI or predictors of those who may experience the greatest benefit. Methods: We studied 1204 patients enrolled in LIBERTY 360 Study, a prospective, multicenter study that evaluated clinical outcomes in symptomatic PAD patients undergoing lower extremity PVI. Patient reported QoL measures were assessed at 30 days, 12 months and 36 months using EuroQol and VascuQol-25. Multivariable regression was used to identify significant predictors of improved quality of life at 12 months. Results: For claudication patients (Rutherford 2-3), the baseline VascuQol total score was 4.3±1.3 and EuroQol composite score indicated that 21.5% had no/slight functional problems (NSFP). Health status significantly improved by 30 days, with VascuQol score 5.4±1.3 and 48.2% with NSFP), and persisted through 3 years (1 year: VascuQol score 5.3±1.3, 46.3% with NSFP; 3 years: VascuQol score 5.3±1.4, 46.9% with NSFP). For patients with critical limb ischemia (CLI; Rutherford 4-6), baseline VascuQol total score was 3.8±1.4 and 16.6% had NSFP. Health status significantly improved by 30 days, with VascuQol score 4.7±1.4 and 29.9% with NSFP, and persisted through 3 years (1 year: VascuQol score 5.0±1.4, 35.0% with NSFP; 3 years: VascuQol score 5.0±1.4, 38.0% with NSFP). In multivariable regression, baseline symptom severity, disease severity, BMI, gender, history of PVI, target lesion residual stenosis and renal disease were significant predictors of QoL improvement post-intervention (Figure 1). Conclusions: Endovascular intervention is associated with significant, long-term improvement in QoL measures across different disease severity. Baseline symptom severity and comorbidities were strong predictors of QoL improvement 1 year after intervention.

The prognostic role of RBP-4 and adiponectin in patients with peripheral arterial disease undergoing lower limb endovascular revascularization

BackgroundRBP4 is an adipokine with an established role in atherosclerosis, while adiponectin has unique anti-inflammatory properties. We investigated the association of RBP4 and adiponectin with the presence of symptomatic peripheral artery disease (PAD) and their possible prognostic role in major adverse cardiovascular events (MACE).MethodsWe enrolled 168 consecutive patients with symptomatic, established PAD, requiring revascularization by endovascular means of any or both of their lower limbs. 88 age- and sex-matched subjects with less than 2 classical cardiovascular risk factors served as controls. Clinical parameters, glycemic and lipid profile, RBP4 and adiponectin levels were assayed. The occurrence of MACE was recorded during the 6-month follow-up and patients were assigned to MACE and non-MACE subgroups.ResultsThe presence of symptomatic PAD was significantly correlated with age, diabetes, hsCRP, RBP4 and low adiponectin levels (p < 0.05). After adjustment for age, RBP4 (β = 0.498, p < 0.001), and adiponectin (β = –0.288, p < 0.001) levels remained as independent predictors of PAD presence in the whole study cohort. At baseline, MACE subgroup appeared with higher RBP-4 and hsCRP serum levels than non-MACE subgroup (p < 0.001), but no differences were detected for adiponectin (p = 0.758). Serum RBP4 levels remained independent predictor of MACE (β = 0.455, p < 0.001) after adjustment for traditional cardiovascular risk factors.ConclusionsHigh RBP4 and low adiponectin serum levels are independently associated with PAD presence. In addition, RBP4 is an independent predictor of MACE incidence in symptomatic PAD patients.

Infrared Thermography as a Diagnostic Tool for the Assessment of Patients with Symptomatic Peripheral Arterial Disease Undergoing Infrafemoral Endovascular Revascularisations

Aim: The aim of this study was to evaluate the utility and reliability of temperature foot changes measured by infrared thermography (IRT) for the evaluation of patients with atherosclerotic peripheral arterial disease (PAD) before and after endovascular revascularisation. Methods: This is an observational prospective study carried out on symptomatic PAD patients. Evaluations consisted of a clinical examination, duplex scan with ankle–brachial index calculation (ABI) and IRT measurements with infrared camera FLIR-ONE connected to a smartphone with android technology. Locations on the foot sampled with IRT were the anterior tibial, pedal, posterior and arcuate arteries. Results obtained with IRT on the symptomatic foot were compared to the contralateral foot and with the ABI values obtained bilaterally before and 24 h after revascularisation. Results: Within one year, 40 patients were enrolled, among whom 87,5% suffered from critical limb ischaemia. In three patients, it was impossible to obtain ABI measurements because of ulcerations on the limb. Skin temperature changes obtained by IRT between the symptomatic limb and the contralateral limb had a mean difference of 1.7 °C (range: 1.1–2.2 °C), p < 0.001. There was a positive correlation between ABI and temperature values of the limb needed for treatment before revascularisation (p = 0.025; r = 0.36) and after revascularisation (p = 0.024, r = 0.31). The technical success rate was 100% in all cases, achieving a significant increase in temperature at all points of the foot analysed, with a median change of 2 °C (p < 0.001). Conclusion: IRT is a safe, reliable and simple application. It could be a valuable tool for the assessment of the clinical presentation and severity of foot blood perfusion in symptomatic PAD patients and the evaluation of the technical success of endovascular revascularisation. IRT might have a role in follow-up of revascularisation procedures.

Are Vascular Parameters Associated with Walking Impairment in Patients with Claudication?

The mechanisms underlying functional impairments in symptomatic PAD patients are controversial and poorly understood. Endothelial dysfunction and arterial stiffness have been proposed as potential mechanisms related to functional impairment in symptomatic PAD patients, however, more studies are needed to confirm these associations. To analyze the association between vascular function and walking impairment in patients with peripheral arterial disease (PAD) and symptoms of claudication. This was a cross-sectional study that included 68 patients with symptomatic PAD. All patients underwent an objective (Six-minute walk test [6MWT], 4-meter walk test) and a subjective (Walking Impairment Questionnaire [WIQ]) measurement of walking impairment. Vascular parameters measured were pulse-wave velocity (PWV) and flow-mediated dilation (FMD). Multiple linear regression was performed to investigate the association among walking impairment variables with vascular function parameters. No significant associations between the claudication onset distance (PWV: b=.060, P=0.842; FMD: b=-.192, P=0.456), 6MWT (PWV: b=.007, P=0..975; FMD: b=.090, P=0.725), WIQ distance (PWV: b=.337, P=0.117; FMD: b=-.025, P=0.895) WIQ speed (PWV: b=.320, P=0.181; FMD: b=-.028, P=0.497), WIQ stairs (PWV: b=.256, P=0.204; FMD: b=-.228, P=0.230), 4-meter usual walk (PWV: b=-.421, P=0.107; FMD: b=-.338, P=0.112), 4-meter fast walk (PWV: b=-.496, P=0.063; FMD: b=-.371, P=0.086) and vascular function were found. In symptomatic PAD patients, vascular function is not associated to walking impairment, even when adjusting for comorbid conditions and diabetes.

Symptomatic and asymptomatic peripheral artery disease and the risk of abdominal aortic aneurysm: The Atherosclerosis Risk in Communities (ARIC) study

Background and aimsSymptomatic peripheral artery disease (PAD) is a risk factor for abdominal aortic aneurysm (AAA). However, data on the association of asymptomatic PAD with AAA are limited. We explored the association of symptomatic and asymptomatic PAD with AAA. MethodsWe primarily assessed a prospective association of symptomatic (based on clinical history) and asymptomatic (ankle-brachial index ≤0.9) PAD at baseline (1987–89 [ages 45–64 years]) with incident AAA in a biracial community-based cohort, the Atherosclerosis Risk in Communities Study. We secondarily investigated a cross-sectional association of PAD with ultrasound-based AAA (diameter≥3.0 cm) (2011–13 [ages 67–91 years]). ResultsOf 14,148 participants (55.1% female, 25.5% black, 0.9% with symptomatic PAD) in our prospective analysis (median follow-up 22.5 years), 530 (3.7%) developed incident AAA. Symptomatic PAD had a higher hazard ratio (HR) of incident AAA [4.91 (95%CI 2.88–8.37)], as did asymptomatic PAD with ABI≤0.9 [2.33 (1.55–3.51)], compared to the reference ABI>1.1–1.2 in demographically-adjusted models. Crude 15-year cumulative incidence of AAA in these three groups were 12.3%, 3.9%, and 1.5%, respectively. The associations remained significant after accounting for other potential confounders [corresponding HR 2.96 (95%CI 1.73–5.07) and 1.52 (95%CI 1.00–2.30), respectively]. The cross-sectional analysis demonstrated similar patterns with ultrasound-based AAA [odds ratio 2.46 (95%CI 1.26–4.81) for symptomatic PAD and 3.98 (1.96–8.08) for asymptomatic PAD in a demographically-adjusted model]. ConclusionsOur prospective and cross-sectional data show elevated risk of AAA in both symptomatic and asymptomatic PAD. Our data support the current recommendation of AAA screening in symptomatic PAD patients and suggest the potential extension to asymptomatic PAD patients as well.

Effect of frailty on physical activity levels and walking capacity in patients with peripheral artery disease: A cross-sectional study

BackgroundThis study aimed to analyze the effect of frailty on walking capacity and physical activity levels of patients with peripheral artery disease (PAD). MethodsA cross-sectional study including 216 symptomatic PAD patients (e.g. claudication) was conducted. Moreover, the frailty profile was established, for which six-minute walk test, Walking Impairment Questionnaire (WIQ), and physical activity level were evaluated. ResultsFrailty was prevalent in 13.4%, 72.2%, and 14.4% of frail, pre-frail, and not-frail patients, respectively. Walking capacity was lower in frail patients than in not-frail patients (p < 0.024). The domains of distance and speed of WIQ were lower in frail patients than in not-frail patients, and these domains were also lower in pre-frail than in not-frail patients (p < 0.050 for all). The domain of stairs was lower in frail patients than in not-frail and pre-frail patients (p = 0.016). Physical activity levels were similar among groups (p > 0.050). ConclusionFrailty is associated with further walking impairment in patients with PAD.

Additive prognosis of clinical presentation in revascularized peripheral arterial disease patients.

Peripheral artery disease (PAD) is a frequent cause of morbidity and mortality. It may present with diverse clinical presentations. The aim of this study was to evaluate the prognosis of these clinical presentations. We performed a retrospective cohort study, in which symptomatic PAD patients were included from 2014 to 2020 at a university hospital in Argentina. We classified symptomatic PAD in intermittent claudication (IC), chronic limb-threatening ischemia (CLTI) and acute ischemia (AI). Our primary endpoint was to compare the composite of all-cause mortality and major amputation events between the three groups. We included 309 patients, with a median follow up of 1.87 years (IQR 0.72-3.67). The primary endpoint was more prevalent in CLTI and AI patients (33% and 33.3%) compared to IC patients (8.1%), P<0.001. CLTI and AI were independently associated with the primary endpoint after adjusting for clinical variables of interest (OR 4.04 95%CI [1.86-9.07], P<0.001 and OR 5.40 95%CI [2.18-13.7], P<0.001, respectively). Mortality incidence rate (per 100 patients/year) was similar between AI and CLTI patients (14.2 95% CI [8.0-24.1] and 13.1 95%CI [8.8-19.7], respectively, P=0.67) but higher compared to IC (2.9 95%CI [1.6-5.1], P<0.01). Major amputation events were more prevalent in CLTI (16.5%) compared to AI (8.9%) and IC patients (1.2%), P<0.01. Those with CLTI and AI have a particular increased risk of all-cause death and major amputation events. Although mortality incidence was similar between AI and CLTI patients, the latter have an increased risk of major amputation events compared to AI and IC patients.