Advanced Peripheral Arterial Disease Research Articles

Smoking and diabetes attenuate number of CD34+ haematopoietic stem cells in peripheral blood of patients with advanced peripheral artery disease: A cross sectional study

Smoking and diabetes attenuate number of CD34+ haematopoietic stem cells in peripheral blood of patients with advanced peripheral artery disease: A cross sectional study

Current Opinion on Diagnosis of Peripheral Artery Disease in Diabetic Patients.

Peripheral arterial disease (PAD) prevalence and diabetes mellitus (DM) prevalence are continuously increasing worldwide. The strong relationship between DM and PAD is highlighted by recent evidence. PAD diagnosis in diabetic patients is very important, particularly in patients with diabetic foot disease (DFD); however, it is often made difficult by the characteristics of such diseases. Diagnosing PAD makes it possible to identify patients at a very high cardiovascular risk who require intensive treatment in terms of risk factor modification and medical therapy. The purpose of this review is to discuss the diagnostic methods that allow for a diagnosis of PAD in diabetic patients. Non-invasive tests that address PAD diagnosis will be discussed, such as the ankle-brachial index (ABI), toe pressure (TP), and transcutaneous oxygen pressure (TcPO2). Furthermore, imaging methods, such as duplex ultrasound (DUS), computed tomography angiography (CTA), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA), are described because they allow for diagnosing the anatomical localization and severity of artery stenosis or occlusion in PAD. Non-invasive tests will also be discussed in terms of their ability to assess foot perfusion. Foot perfusion assessment is crucial in the diagnosis of critical limb ischemia (CLI), the most advanced PAD stage, particularly in DFD patients. The impacts of PAD diagnosis and CLI identification in diabetic patients are clinically relevant to prevent amputation and mortality.

Comparative outcomes of arterial bypass using the human acellular vessel and great saphenous vein in patients with chronic limb ischemia

ObjectiveThe Human Acellular Vessel (HAV) is a novel, off-the-shelf biologic conduit being evaluated for arterial reconstructions. Regulatory studies in peripheral arterial disease (PAD) to date have consisted of single-arm cohorts with no comparator groups to contrast performance against established standards. This study aimed to compare outcomes of the HAV with autologous great saphenous vein (GSV) in patients with advanced PAD undergoing infrageniculate bypass. MethodsPatients with advanced PAD and no autologous conduit who underwent bypass with the 6-mm diameter HAV (Group 1; n = 34) (March 2021-February 2024) were compared with a multicenter historical cohort who had bypass with single-segment GSV (group 2; n = 88) (January 2017-December 2022). The HAV was used under an Investigational New Drug protocol issued by the Food and Drug Administration (FDA) under the agency's Expanded Access Program. ResultsDemographics were comparable between groups (mean age 69 ± 10 years; 71% male). Group 1 had higher rates of tobacco use (37 pack-years vs 28 pack-years; P = .059), coronary artery disease (71% vs 43%; P = .007), and prior coronary artery bypass grafting (38% vs 14%; P = .003). Group 1 had more patients classified as wound, ischemia, and foot infection clinical stage 4 (56% vs 33%; P = .018) and with previous index leg revascularizations (97% vs 53%; P < .001). Both groups had a similar number of patients with chronic limb-threatening ischemia (Rutherford class 4-6) (88% vs 86%; P = .693) and Global Anatomic Staging System stage III (91% vs 96%; P = .346). Group 1 required a composite conduit (two HAV sewn together) in 85% of bypasses. The tibial vessels were the target in 79% of group 1 and 100% of group 2 (P < .001). Group 1 had a lower mean operative time (364 minutes vs 464 minutes; P < .001). At a median of 12 months, major amputation-free survival (73% vs 81%; P = .55) and overall survival (84% vs 88%; P = .20) were comparable. Group 1 had lower rates of primary patency (36% vs 50%; P = .044), primary-assisted patency (45% vs 72%; P = .002), and secondary patency (64% vs 72%; P = .003) compared with group 2. ConclusionsImplanted under Food and Drug Administration Expanded Access provisions, the HAV was more likely to be used in redo operations and cases with more advanced limb ischemia than GSV. Despite modest primary patency, the HAV demonstrated resilience in a complex cohort with no autologous conduit options, achieving good secondary patency and providing major amputation-free survival comparable with GSV at 12 months.

The Incidence and Significance of Bleeding in Patients With Advanced Peripheral Arterial Disease

The Incidence and Significance of Bleeding in Patients With Advanced Peripheral Arterial Disease

Preoperative Chronic Steroid Use is Associated with Increased Incidence of Postoperative Mortality and Limb Loss following Peripheral Arterial Bypass Surgery for Chronic Limb Threatening Ischemia

Steroids are a commonly prescribed medication in the United States and have been associated with poor surgical and treatment outcomes. The objective of this study is to assess the relationship between chronic steroid use and surgical outcomes of femoropopliteal and femoral-distal bypasses in patients suffering from chronic limb threatening ischemia (CLTI). All adult patients undergoing femoropopliteal and femoral-distal bypasses with single segment autologous vein with an indication of CLTI in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) between 2012 and 2021 were stratified between chronic preoperative steroid use (Group I) and no preoperative use (Group II). Primary outcomes of the study included 30-day mortality, amputation, and combined outcome of mortality and/or limb loss. Secondary outcomes included specific bypass related, cardiovascular, respiratory and renal outcomes. A total of 8,324 patients (66.8% Male, 33.2% Females) underwent peripheral arterial bypass operations for the indication of chronic limb threatening ischemia. The median age was 68 years. Group I included 408 patients (4.9%) and Group II included 7,916 patients (95.1%). As compared to patients in Group II, those in Group I were more likely to be females (Group I: 42.2% vs. Group II: 32.8%), more likely to have co-existing COPD (Group I: 20.6% vs. Group II: 11.8%), less likely to be diabetic (Group I: 45.9% vs. Group II: 48%), less likely to be smokers (Group I: 30.6% vs. Group II: 45.4%) and more likely to be in ASA III or IV Classes (Group I: 98% vs. Group II: 96.5%) (all p<0.05). Primary outcomes were as follows: 30-day mortality (Group I: 3.3% vs. Group II: 1.7%), amputation (Group I: 5.9% vs. Group II: 2.8%), 30-day mortality and/or amputation (Group I: 9.1% vs. Group II: 4.5%) (all p<0.05). Among secondary outcomes, the following were found to be statistically significant: untreated loss of patency (Group I: 4.2% vs. Group II: 1.7%), significant bleeding (Group I: 26.2% Vs. Group II: 16.5%), wound infection/complication (Group I: 18.6% vs. Group II: 15%), and return to OR (Group I: 21.8% vs. Group II: 16.7%) (all p<0.05). As compared to patients with an indication of tissue loss (Rutherford's class V and VI), patients in Group I with an indication of rest pain (Rutherford's class IV) were more likely to experience 30-day mortality, major amputation and a composite of mortality and amputation. Risk adjusted analysis showed that chronic steroid use has a statistically significant effect on 30-day mortality (AOR 1.7, p=0.05), amputation (AOR 2.05, p<0.001), composite outcomes of mortality and amputation (AOR 1.959, p<0.001), untreated loss of patency (AOR 2.31, p=0.002), bleeding (AOR 1.33, p<0.011) and unplanned return to the OR (AOR 1.36, p=0.014). Chronic steroid use in patients undergoing femoropopliteal or femoral-distal bypass is associated with a higher risk of 30-day mortality, major amputation, readmission, bleeding, return to operating room, and untreated loss of patency. No significant difference in outcomes were appreciated in patients with chronic steroid use and with Rutherford class V or VI disease (tissue loss), suggesting that the effects of steroids may be less prominent in those with the most advanced peripheral arterial disease. These findings may aid physicians with risk stratification and preoperative discussions regarding open revascularization in patients receiving chronic steroid therapy. More studies including randomized trials are needed to guide perioperative management of steroids in this cohort.

Abstract 15167: The Use of Echocardiography in Patients With Advanced Peripheral Arterial Disease

Introduction: Patients with peripheral arterial disease (PAD) are at high risk of concomitant cardiac diseases. Transthoracic echocardiography (TTE) is a common imaging modality to assess cardiac function and is used as a screening tool, especially for patients with advanced PAD undergoing lower extremity revascularization (LER). The current study evaluates the incidental use of TTE in patients undergoing LER. Hypothesis: Patients with a perioperative TTE have improved outcomes compared to patients who do not undergo TTE. Methods: The electronic records of patients undergoing LER between 2013-2020 were reviewed. All TTE within 6 months of initial LER were captured. Patient characteristics and outcomes were compared between patients who underwent TTE and those who did not. Results: A total of 1,988 patients underwent LER, and 69.3% (N=1,377) had TTE. Patients in the TTE group were more likely to be African American and have diabetes mellitus, chronic kidney disease, and coronary artery disease. Patients with TTE were more likely to be on aspirin and undergo open/hybrid revascularization. There was no significant difference between the 2 groups in perioperative MI, major amputation, or mortality. Furthermore, patients with TTE had higher MALEs. (Table) However, there were no differences in MALE-free survival between the two groups (Figure 1) Conclusion: TTE was obtained in 69.3% of patients with advanced PAD undergoing LER but did not seem to be associated with outcomes in this institutional series. Further research is warranted to identify PAD patients that would benefit from TTE prior to LER.

Peripheral Artery Disease: Underappreciated Impact and Residual Cardiovascular Risk Despite Revascularization

This Commentary highlights the under-recognized prevalence and heavy burden of peripheral artery disease (PAD) and its important role as a harbinger of complications of atherosclerotic cardiovascular disease. Although increasing in prevalence globally, PAD is being further accelerated with diabetes, and patients with advanced PAD are at high risk for chronic limb-threatening ischemia. The need for (repeated) revascularization and amputation places a heavy social burden on patients and family, and a heavy financial burden on the health care system, exceeding the cost of coronary artery and cerebrovascular diseases. Clinical trial research in PAD will be enhanced by widely agreed-upon definitions of major adverse cardiovascular events and major adverse limb events. Antithrombotic and lipid-lowering therapies are recommended but underutilized, while the optimal peri-interventional antithrombotic regimen is still under debate. Additional antiinflammatory treatment is currently an unaddressed strategy in the management of patients with PAD, and there is a strong case for the evaluation of widely available antiinflammatory agents such as colchicine.

Smoking and Diabetes Attenuate Number of CD34+ Haematopoietic Stem Cells in Peripheral Blood of Patients with Advanced Peripheral Artery Disease.

Peripheral artery disease (PAD) is a globally prevalent problem with limited treatment options, leaving up to a fifth of patients remediless. The emergence of new studies on cell therapy in recent years offers a new promising option for their treatment. Our aim was to explore how the number of CD34+ hematopoietic cells in the peripheral blood of PAD patients is associated with patients' functional as well as atherogenic factors. We selected 30 patients with advanced PAD, recorded their performance in a walking test in standard conditions and sampled their blood for further analysis with an emphasis on CD34+ cell selection and counting. No correlation of the CD34+ cell number was confirmed with any of the observed laboratory parameters. There was an association between the claudication distance and the number of CD34+ cells (r = -0.403, p = 0.046). The number of CD34+ cells differed between patients with and without type II diabetes (p = 0.071) and between active smokers, past smokers, and non-smokers (p = 0.035; p = 0.068, p = 0.051, respectively), with both smoking and presence of diabetes type II having a negative effect on the number of CD34+ cells. Our study demonstrated a dependence of the CD34+ cell number on the patient's characteristics.

The impact of class I compression stockings on the peripheral microperfusion of the lower limb: A prospective pilot study

ObjectiveThe use of medical compression stockings (MCS) in patients with peripheral arterial disease (PAD) and diabetes is the subject of an ongoing critical debate. While reducing leg edema of various origins by improving venous back flow, there is a concern about additional arterial flow obstruction when compression therapy is applied in pre-existing PAD. The aim of this study is to obtain further information on the use of class I MCS in patients with advanced PAD and to evaluate the framework conditions for a safe application. MethodsThe total collective (n = 55) of this prospective, clinical cohort study consisted of 24 patients with PAD Fontaine stage IIb and higher studied before revascularization, of whom 16 patients were examined again after revascularization, and 15 healthy participants included for reference. The microperfusion of the lower extremity of all participants was examined in a supine, elevated, and sitting position using the oxygen to see (O2C) method. ResultsThe results indicate that leg positioning had the strongest influence on microcirculation (SO2 and flow: p = 0.0001), whereas MCS had no significant effect on the perfusion parameters (SO2: p = 0.9936; flow: p = 0.4967) and did not lead to a deterioration of values into critical ranges. ConclusionMild medical compression therapy appears to be feasible even in patients with advanced PAD. Larger studies are warranted to observe any long-term effects, in particular for the treatment of reperfusion edema after revascularization.

Compression therapy in dermatology.

Compression therapy is a conservative therapy that can be used in many patients with dermatological conditions, especially those associated with edema. In addition to its well-established use in venous and lymphatic disorders, there is increasing evidence that compression therapy supports the healing of inflammatory dermatoses. The presence of edema, regardless of its etiology, is an indication for the use of compression therapy. Nowadays, a variety of materials and treatment options are available for compression therapy, each with their own advantages and disadvantages. Often, compression therapy with low resting pressures is sufficient for effective therapy and is better tolerated by patients. The main contraindications to compression therapy are advanced peripheral arterial disease and decompensated heart failure. Individual factors and economic considerations should be taken into account when deciding on compression therapy with the patient. Patient self-management should be encouraged whenever possible. This requires education and support tools.

Involvement of APOE in Incidence of Revascularization in Patients Affected by Peripheral Arterial Disease: A Prospective Study from Southern Italy.

Atherosclerosis is a complex multifactorial disease and apolipoprotein E (APOE) polymorphism has been associated with cardiovascular events. The APOE gene, located on chromosome 19q13.2, has an important role in lipid metabolism, in particular on circulating cholesterol levels, implying further pleiotropic effects; from its polymorphism are derived three alleles (ε2, ε3 and ε4), which induce different phenotypes, while its impact on carotid and femoral atherosclerosis is still controversial. The aim of the study is to investigate the relationship between APOE genotypes and peripheral revascularization in a cohort of patients affected by advanced peripheral arterial disease (PAD) at a prolonged follow-up. Some 332 patients (259 males and 73 females; mean age 70.86 ± 7.95 years) with severe PAD were enrolled in a longitudinal study, with a 90.75 ± 32.25 month follow-up, assessing major adverse cardiovascular events (MACE). As compared with ε3/ε3, in ε4 patients we observed a significant higher incidence of carotid (13.2% vs. 5.6%; HR = 2.485, 95% CI 1.062-5.814; p = 0.036) and lower limb (11.8% vs. 4.3%; HR = 2.765, 95% CI 1.091-7.008; p = 0.032) revascularizations and, accordingly, a higher incidence of total peripheral revascularizations (13.5% vs. 9.5%; HR = 2.705, 95% CI 1.420-5.151; p = 0.002). HR remained statistically significant even when adjusted for classic cardiovascular risk factors. In our observational study, we confirm that the ε4 allele is associated with higher total peripheral revascularization in patients with advanced atherosclerotic vascular disease at prolonged follow-up.

Prospective Comparison of Wound Complication Rates after Elective Open Peripheral Vascular Surgery - Endovascular Versus Open Vascular Surgeons

Skill and experience of surgeons are likely to influence the incidence of surgical wound complications (SWC) after open lower limb revascularization. Differences in SWC between surgeons with predominantly endovascular or open vascular surgical profiles could be expected. The aim of this study was to compare SWC rates after elective open vascular surgery between primarily endovascular and primarily open vascular surgeons. Prospective data from patients undergoing elective surgery for peripheral artery disease (PAD) was collected between 2013 and 2019. Senior surgeons were assigned to the open-surgeon or the endo-surgeon group based on the percentage of their open surgical case load during the 6year study period. SWC was measured by their clinical impact scale (grade 1-outpatient treatment to grade 6-death). Surgical site infection was defined by Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of deep tissues, Isolation of bacteria, and Stay (ASEPSIS) criteria. Propensity score adjusted analysis (PSAA) was used to account for differences in baseline and perioperative characteristics and expressed as odds ratios (ORs) with 95% confidence intervals (CIs). The proportion of chronic limb-threatening ischemia (P=0.001), ipsilateral foot wound (P=0.012) and femoro-popliteal bypass procedures (P<0.001) were higher in the open-surgeon group. A lower incidence of SWC according to ASEPSIS criteria (25.6% vs. 38.6%, respectively, P=0.042) and SWC grade ≥1 (33.7% vs. 51.0%, respectively, P=0.010) was found in the endo-surgeon group (n=86) compared to the open-surgeon group (n=153). These differences disappeared after PSAA (OR 0.63, 95% CI 0.27-1.44, and OR 0.60, 95% CI 0.27-1.33, respectively). Patients operated by endo-surgeons had less advanced PAD and lower incidence of SWC compared to those treated by open-surgeons. No difference in SWC remained after PSAA.

Abstract 300: Physiologic Oxygen Conditions Preserve Ipsc-ec Progenitor Identity

Background: Advanced peripheral artery disease (PAD) is characterized by disabling lower extremity pain at rest and non-healing wounds. Many patients are limited to palliation with major amputation. There remains a great need for improved therapeutic modalities to treat advanced PAD and prevent limb loss. Induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) have improved limb perfusion without surgery in pre-clinical mouse models. iPSC-ECs lose angiogenic capacity under standard culture conditions, currently limiting scalability for larger animals and humans. Our prior work demonstrated that this is driven by accumulation of dysfunctional mitochondria. The current study evaluates the effect of oxygen metabolism on driving angiogenic capacity of iPSC-ECs in culture. Methods and Results: Purified ECs, differentiated from the Y6 iPSC line (Yale Stem Cell Core), were sub-cultured under standard (21% oxygen) or physiologic (4% oxygen) conditions. In the early phase, after 24 hours, Y6-ECs under physiologic conditions had significantly lower NO synthase activity (DAF-FM assay, Invitrogen) (p&lt;0.05). There were no significant differences in the remaining EC function metrics: tubule formation on Matrigel to assess angiogenesis, beta galactosidase for senescence, or Edu-labeling for proliferation. All early phase cells expressed EC progenitor marker CD34. In the late phase, after 2 weeks, the physiologic conditions retained progenitor marker CD34 and EC marker CD31 while the normoxic conditions did not. Despite this, physiologic conditions demonstrated decreased tubule formation by some but not all measures but did not differ from normoxic conditions in the other EC function metrics. Additionally, late phase cells had a significant increase in senescence compared to early phase cells (p&lt;0.05). Conclusion: In summary, physiologic culture conditions promoted retention of EC progenitor marker CD34 over serial passages in culture. However, some but not all in vitro metrics of angiogenic capacity appeared reduced in physiologic conditions. Future studies will be necessary to investigate the in vivo angiogenic capacity of iPSC-ECs grown under physiologic conditions.

Coronary Artery Disease in Patients Hospitalized for Peripheral Artery Disease: A Nationwide Analysis of 1.8 Million Patients.

Coronary artery disease (CAD) and peripheral artery disease (PAD) are highly prevalent in society. This nationwide analysis aimed to evaluate the trends of in-hospital treatment of patients admitted due to PAD with and without concomitant CAD, to determine the prevalence and risk factors of concomitant CAD in patients with PAD. Using data from the German Federal Statistical Office, we included all admissions for PAD (with and without concomitant CAD) in Germany between 2009 and 2018. Baseline patient characteristics, outcomes and comorbidities were analyzed. Elixhauser comorbidity groups and the linear van Walraven comorbidity score (vWs) were calculated to assess the comorbidity burden. Of all 1,793,517 patients hospitalized for PAD, a total of 21.8% (390,259) had concomitant CAD, increasing from 18.6% in 2009 to 24.4% in 2018. Patients with accompanying CAD showed higher in-hospital mortality (3.7 vs. 2.6%), more major amputations (9.0 vs. 7.7%) and more comorbidities (Elixhauser score: 4.2 vs. 3.2 and vWs: 9.1 vs. 6.1), resulting in higher costs (median: EUR 4541 vs. EUR 4268 per case). More advanced stages of PAD were associated with multi-vessel CAD (10% of all patients with PAD Fontaine IV showed 3-vessel CAD) and the prevalence of multi-vessel CAD increased predominantly in patients with advanced PAD. One in four patients hospitalized for PAD had concomitant CAD, showing an increase over time with an additional medical and economic burden for hospitals compared with patients without CAD.

The term mixed leg ulcer should no longer be used today

Awound on the lower legs of patients with chronic venous insufficiency (CVI) and peripheral arterial disease (PAD) is today usually referred to as amixed leg ulcer. This does not take into account the different stages of the diseases and, thus, their pathophysiological relevance. In everyday clinical practice, this often leads, among other things, to these patients not receiving compression therapy. The multidisciplinary professional association Initiative Chronische Wunden (ICW) e. V., therefore, recommends that this undifferentiated and misleading term should no longer be used. Instead, aleg ulcer with advanced CVI and concomitant PAD in stageI-IIb according to Fontaine or Rutherford category0-3 should be classified as avenous leg ulcer, while aleg ulcer with advanced PAD in stageIII orIV according to Fontaine or Rutherford category4-6 and advanced CVI is termed an arteriovenous leg ulcer. Aleg ulcer in advanced PAD stageIV according to Fontaine or Rutherford category5 or6 without advanced CVI is called an arterial leg ulcer. Other relevant comorbidities with an influence on wound healing should also be described separately.

Asian race is associated with peripheral arterial disease severity and postoperative outcomes

ObjectiveThe nature of peripheral arterial disease and postoperative outcomes are understudied in Asian patients. We aimed to determine if there are disparities in disease severity at the time of presentation and postoperative outcomes with regard to Asian race. MethodsWe analyzed the Society for Vascular Surgery Vascular Quality Initiative Peripheral Vascular Intervention dataset from 2017 to 2021, which includes endovascular lower extremity interventions. Propensity scores were used to match White and Asian patients based on age, sex, comorbidities, ambulatory/functional status, and intervention level. Differences were examined with regard to Asian race across all patients in the United States, Canada, and Singapore, and separately in the United States and Canada only. The primary outcome was emergent intervention. We also examined differences in severity of disease and postoperative outcomes. ResultsA total of 80,312 White and 1689 Asian patients underwent peripheral vascular intervention. After propensity score matching, we identified 1669 matched pairs of patients across all centers including Singapore and 1072 matched pairs in the United States and Canada only. Among the matched cohort consisting of all centers, Asian patients had a higher rate of emergent intervention to prevent limb loss (5.6% vs 1.7%, P < .001). The majority of Asian patients presented with chronic limb threatening ischemia at a higher rate than White patients within the cohort including Singapore (71% vs 66%, P = .005). Within both propensity-matched cohorts, the rate of in-hospital death was higher in Asian patients (all centers: 3.1% vs 1.2%, P < .001; United States and Canada only: 2.1% vs 0.8%, P = .010). Logistic regression demonstrated greater odds of emergent intervention in Asian patients from all centers including Singapore (odds ratio [OR], 3.3; 95% confidence interval [CI], 2.2-5.1, P < .001) but not in the United States and Canada only (OR, 1.4; 95% CI, 0.8-2.8, P = .261). In addition, Asian patients had greater odds of in-hospital death in both matched cohorts (all centers: OR, 2.6; 95% CI, 1.5-4.4, P < .001; United States and Canada: OR, 2.5; 95% CI, 1.1-5.8, P = .026). Asian race was associated with a greater risk of loss of primary patency at 18 months (all centers: hazard ratio, 1.5; CI, 1.2-1.8, P = .001; United States and Canada only: hazard ratio, 1.5; CI, 1.2-1.9, P = .002). ConclusionsAsian patients are more likely to present with advanced peripheral arterial disease and undergo emergent intervention to prevent limb loss, in addition to having worse postoperative outcomes and long-term patency. These results highlight the need for improved screening and postoperative follow-up in this understudied population.

Disease-Specific Quality of Life among Patients with Peripheral Artery Disease in Hungary.

Peripheral artery disease (PAD) is a progressive atherosclerotic disease significantly impacting functional status and health-related quality of life (HRQoL). This study aimed to investigate HRQoL among PAD patients in Hungary using the validated Hungarian version of the PADQoL questionnaire. Patients with symptomatic PAD were consecutively recruited from the Department of Angiology, Clinical Center, University of Pécs, Hungary. Demographics, risk factors, and comorbidities were registered. Disease severity was measured by Fontaine and WIFI stages. Descriptive statistical analysis, Chi-square test, and non-parametric tests were performed (p < 0.05). Overall, 129 patients (mean age 67.6 ± 11.9 years, men 51.9%) participated in our study. The Hungarian PADQoL demonstrated good internal consistency (α range: 0.745-0.910). Factors on intimate and social relationships gave the best (89.15 ± 20.91; 63.17 ± 26.05) and sexual function (28.64 ± 27.42), and limitations in physical functioning (24.68 ± 11.40) the worst scores. PAD had a significant negative impact on the social relationships of patients aged 21-54 years (51.6 ± 25.4). Fontaine stage IV patients experienced significantly lower HRQoL due to fear and uncertainty (46.3 ± 20.9) and limited physical functioning (33.2 ± 24.8). The Hungarian PADQoL identified central aspects of HRQoL. Advanced PAD was found to impact several areas of HRQoL, primarily physical functioning and psycho-social well-being, drawing attention to the importance of early diagnosis and management.

Iliofemoral artery predilation prior to transfemoral transcatheter aortic valve implantation in patients with aortic valve stenosis and advanced peripheral artery disease

To investigate the feasibility and safety of percutaneous transluminal angioplasty (PTA) of the iliofemoral arteries (IFA) before transfemoral transcatheter aortic valve implantation (Tf-TAVI) in patients with advanced peripheral artery disease (PAD). Although Tf-TAVI represents the access of choice, alternative vascular access routes are preferred for patients displaying advanced PAD. PTA of the IFA represents a less invasive option, broadening the spectrum of patients eligible for Tf-TAVI. All patients requiring PTA of the IFA before Tf-TAVI, between 2012 and 2021, were included. Primary efficacy endpoint was the rate of successful transcatheter heart valve (THV) delivery and implantation. Primary safety endpoint was the rate of PTA and access-site-related vascular complications, procedural- and in-hospital complications. Among 2726 Tf-TAVI procedures, 59 patients required IFA predilation. Successful THV delivery and implantation was achieved in 57 (96.6%) patients, respectively. Sheath placement was achieved in 59 (100%) patients with only one minor dissection and no major vascular complications following iliofemoral PTA. Regarding access site complications, two (3.4%) vessel perforations and one (1.7%) vessel rupture were observed, with eight (13.5%) patients requiring unplanned endovascular interventions. There was one intraprocedural death due to THV-induced vessel laceration, while in-hospital all-cause mortality was 8.5% in the present high-risk patient cohort. Predilation of IFA is safe and effective in patients with advanced PAD. Careful preprocedural planning is paramount in improving procedural safety and efficacy. This strategy has the potential to broaden the spectrum of patients eligible for Tf-TAVI.

Ceramides in peripheral arterial plaque lead to endothelial cell dysfunction

BackgroundPeripheral arterial atheroprogression is increasingly prevalent, and is a risk factor for major limb amputations in individuals with risk factors such as diabetes. We previously demonstrated that bioactive lipids are significantly altered in arterial tissue of individuals with diabetes and advanced peripheral arterial disease. MethodsHere we evaluated whether sphingolipid ceramide 18:1/16:0 (C16) is a cellular regulator in endothelial cells and peripheral tibial arterial tissue in individuals with diabetes. ResultsWe observed that C16 is the single most elevated ceramide in peripheral arterial tissue from below the knee in individuals with diabetes (11% increase, P < .05). C16 content in tibial arterial tissue positively correlates with sphingomyelin (SPM) content in patients with and without diabetes (r2 = 0.5, P < .005; r2 = 0.17, P < .05; respectively). Tibial arteries of individuals with diabetes demonstrated no difference in CERS6 expression (encoding ceramide synthase 6; the predominate ceramide synthesis enzyme), but higher SMPD expression (encoding sphingomyelin phosphodiesterase that catalyzes ceramide synthesis from sphingomyelins; P < .05). SMPD4, but not SMPD2, was particularly elevated in maximally diseased (Max) tibial arterial segments (P < .05). In vitro, exogenous C16 caused endothelial cells (HUVECs) to have decreased proliferation (P < .03), increased apoptosis (P < .003), and decreased autophagy (P < .008). Selective knockdown of SMPD2 and SMPD4 decreased native production of C16 (P < .01 and P < .001, respectively), but only knockdown of SMPD4 rescued cellular proliferation (P < .005) following exogenous supplementation with C16. ConclusionsOur findings suggest that C16 is a tissue biomarker for peripheral arterial disease severity in the setting of diabetes, and can impact endothelial cell viability and function. Clinical relevancePeripheral arterial disease and its end-stage manifestation known as chronic limb-threatening ischemia (CLTI) represent ongoing prevalent and intricate medical challenges. Individuals with diabetes have a heightened risk of developing CLTI and experiencing its complications, including wounds, ulcers, and major amputations. In the present study, we conducted a comprehensive examination of the molecular lipid composition within arterial segments from individuals with CLTI, and with and without diabetes. Our investigations unveiled a striking revelation: the sphingolipid ceramide 18:1/16:0 emerged as the predominant ceramide species that was significantly elevated in the peripheral arterial intima below the knee in patients with diabetes. Moreover, this heightened ceramide presence is associated with a marked impairment of endothelial cell function and viability. Additionally, our study revealed a concurrent elevation in the expression of sphingomyelin phosphodiesterases, enzymes responsible for catalyzing ceramide synthesis from sphingomyelins, within maximally diseased arterial segments. These findings underscore the pivotal role of ceramides and their biosynthesis enzymes in the context of CLTI, offering new insights into potential therapeutic avenues for managing this challenging disease process.

Comparação das alterações angiográficas entre pacientes diabéticos e não diabéticos com doença arterial periférica

Abstract Background Diabetics are at 5-15 times greater risk of developing peripheral arterial disease (PAD) and few studies have compared risk factors and distribution and severity of arterial changes in diabetics compared with non-diabetics. Objectives To compare angiographic changes between diabetic and non-diabetic patients with advanced PAD and correlate them with risk factors. Methods A retrospective cross-sectional study was conducted of consecutive patients undergoing lower limb arteriography for PAD (Rutherford 3-6) using TASC II and Bollinger et al. angiographic scores. Exclusion criteria were upper limb angiographies, unclear images, incomplete laboratory test results, and previous arterial surgeries. Statistical analyses included chi-square tests, Fisher's test for discrete data, and Student’s t test for continuous data (significance level: p &lt; 0.05). Results We studied 153 patients with a mean age of 67 years, 50.9% female and 58.2% diabetics. A total of 91 patients (59%) had trophic lesions (Rutherford 5 or 6) and 62 (41%) had resting pain or limiting claudication (Rutherford 3 and 4). Among diabetics, 81.7% were hypertensive, 29.4% had never smoked, and 14% had a history of acute myocardial infarction. According to the Bollinger et al. score, infra-popliteal arteries were more affected in diabetics, especially the anterior tibial artery (p = 0.005), while the superficial femoral artery was more affected in non-diabetics (p = 0.008). According to TASC II, the most severe angiographic changes in the femoral-popliteal segment occurred in non-diabetic patients (p = 0.019). Conclusions The most frequently affected sectors were the infra-popliteal sectors in diabetics and the femoral sector in non-diabetics.