Treatment Of Peripheral Arterial Disease Research Articles

Improving peripheral artery disease screening and treatment: a screening, diagnosis, and treatment tool for use across multiple care settings.

Peripheral artery disease (PAD) is an atherosclerotic disease that contributes to significant morbidity and mortality, including loss of limb, myocardial infarction (MI), stroke, and death. Treatment options are often underutilized. A major limiting factor in PAD care is the ability to efficiently identify and screen at-risk patients. A PAD patient screening and clinician decision support tool was created to improve access to high-quality, evidence-based care to drive improved clinical outcomes. The tool identifies known PAD risk factors and presenting symptoms, in combination with objective data obtained via the ankle-brachial index (ABI). The tool utilizes this data to drive PAD diagnosis, risk assessment, and treatment, and it is adaptable across multiple care settings, by varied health professions. The implementation of a PAD screening and treatment toolkit enhances anticoagulation and PAD stewardship, and it has been integrated into use across various care settings.

Intravascular Lithotripsy for Peripheral Artery Calcification: 30-Day Outcomes From the Disrupt PAD III Observational Study.

Intravascular lithotripsy (IVL) has shown promising safety and effectiveness in calcified peripheral artery disease (PAD) in large trials and small real-world experiences. Real-world evidence from a larger cohort is lacking, so we aimed to evaluate the real-world acute performance of IVL in the treatment of calcified PAD. The Disrupt PAD III Observational Study (OS) is a prospective, multicenter, single-arm study. Patients with claudication or critical limb-threatening ischemia (CLTI) and at least moderate calcification were eligible. Independent predictors of procedural outcomes were assessed by multivariable analysis. Between November 2017 and June 2021 across 30 global sites, 1373 patients with 1677 lesions (1531, 91.3% core lab evaluable) were enrolled. Diameter stenosis and lesion length was 80.6±17.6% and 93.5±74.3 mm, respectively. Target vessels included femoropopliteal (61%), iliac (15.8%), common femoral (10.7%), and infrapopliteal arteries (12.8%). Lesion characteristics included 31.1% chronic total occlusions (CTOs) and 19.3% long lesions (≥15 cm). At final assessment, residual stenosis was 23.8±11.3%, with 0.9% serious angiographic complications, no abrupt closures, distal embolization, no flow, or thrombotic events. Independent predictors of ≤30% residual stenosis were lesion length ≥15 cm (odds ratio [OR]=0.384), female sex (OR=1.850), age ≤75 years (OR=1.625), IVL balloon to artery ratio ≥1.0 (OR=1.538), and CTO lesions (OR=0.638). Lesion length ≥15 cm (OR=16.076) was an independent predictor of procedural complications. The Disrupt PAD III OS represents the largest assessment of IVL periprocedural outcomes in calcified PAD. It confirmed excellent procedural safety and effectiveness in complex lesions across multiple peripheral vascular beds. This final analysis of the PAD III OS represents the largest report of peripheral IVL utilization in daily clinical practice. The outcomes of this study indicate that previously reported procedural results in clinical trial settings can be translated to a broader patient population. Treatment with peripheral IVL in severely calcified stenotic lower limb lesions demonstrated consistent acute safety and stenosis reduction, even in complex patients across multiple vessel beds. In addition, the importance of proper IVL balloon sizing to achieve excellent acute stenosis reduction was confirmed by multivariate analysis.

Graduating Vascular Surgery Trainee Proficiency in Endovascular and Open Peripheral Revascularization Procedures

Endovascular interventions for peripheral artery disease have increased in prevalence over time given the inherent benefits of minimally invasive approaches. While it is essential that vascular surgery graduates are facile with endovascular techniques, the results of the BEST-CLI trial highlight the equivalent importance of ensuring trainee competence in open skills. Recent studies demonstrate increasing case volume of both endovascular and open procedures during vascular surgery training. Case volume is merely a surrogate marker for competence, however, and the objective competence attained by trainees at the time of graduation is unknown. We sought to investigate operative autonomy and competence of graduating vascular surgery trainees performing endovascular as compared to open peripheral vascular revascularization procedures. Operative performance and autonomy ratings for infrainguinal endovascular and open revascularizations from the Society for Improving Professional Learning Operative (SIMPL OR) application database were collected for all vascular surgery participating institutions from 2018-23. The distribution for autonomy and performance ratings were determined by training level for endovascular and open procedures, respectively. Mixed effects logistic regressions were conducted to estimate the predictive association between procedure type and autonomy and performance assessment, adjusting for training level and case complexity. Subsequently, the estimated model was applied to predict the probability of a graduating trainee being rated as meaningfully autonomous or competent while performing endovascular and open procedures across various case complexities. Sixty-nine residents from 23 programs (12 fellowship, 11 residency) were assessed on 706 revascularization procedures (n=383 endovascular, 323 open). When controlling for training level and case complexity, there were no differences in autonomy (OR 1.11 [95% CI: 0.62-1.99]) or competency assessment (OR 0.86 [95% CI: 0.46-1.59]) for endovascular, as compared to open, peripheral revascularization procedures. For average complexity procedures, the predicted probability of a trainee being assessed as competent and autonomous at the time of graduation was high (competent: 88% endovascular, 86% open; autonomous: 96% endovascular, 97% open). Predicted probability of competence and autonomy for complex procedures was lower but remained similar between groups (competent:73% endovascular, 70% open; autonomous: 92% endovascular, 92% open). There is no difference in the graduating level of autonomy and competence of endovascular as compared to open peripheral revascularization procedures for vascular surgery trainees. These findings suggest vascular surgery trainees enter independent practice with adequate proficiency to utilize the full scope of techniques to care for patients requiring peripheral revascularization procedures.

TCT-395 Differences in Outcomes Between Rutherford 4 and Rutherford 5/6 Patients Undergoing Endovascular Intervention for Lower Extremity Peripheral Artery Disease

TCT-395 Differences in Outcomes Between Rutherford 4 and Rutherford 5/6 Patients Undergoing Endovascular Intervention for Lower Extremity Peripheral Artery Disease

PERCUTANEOUS AXILLARY ACCESS IN THE ENDOVASCULAR ERA: A VIABLE ALTERNATIVE?

The common femoral artery is the most commonly used vascular access due to its low complication rate and high technical success rate. However, this approach may be less suitable in patients with certain factors such as obesity, the need to treat both lower limbs, and the inability to access the lesion via crossover. In this context, endovascular approaches using percutaneous puncture or upper arm access have emerged. Therefore, we evaluated the feasibility of percutaneous access to the axillary artery in routine endovascular procedures. This single-center observational study included consecutive patients requiring percutaneous access to the axillary artery for endovascular procedures from January 2020 to December 2023. Demographic and procedural characteristics were collected. The primary endpoint was efficacy (technical success rate) and safety (complications rate) at 30 days. Secondary endpoints were minor complications and risk factors of complications. 85 patients were included. Axillary approach was used to treat peripheral artery disease (PAD) in 77.6% (n=66), complex aortic aneurysm in 17.7% (n=15), and acute type B aortic dissection in 4.7% (n=4) of patients. This approach was used due to bilateral PAD treatment (n=20), obesity (n=18), prior EVAR (n=12), prior common femoral artery stenting (n=9), major iliac tortuosity (n=9), prior kissing stent (n=8), favorable angulation (n=5) and true lumen positioning in type B aortic dissection (n=4). The left axillary approach was used in 97.6% (n=83) of cases. The efficacy was 100%. At 30 days, safety was 85.6% with a major complication rate of 14.2% (n=12), including 10.6% (n=9) surgical conversion for hemostasis, 2.4% (n=2) covered stenting, and 1.2% (n=1) stroke. Body mass index was associated with a higher rate of complications (25.2 ± 6.17 vs. 29.0 ± 6.04, OR: 1.2 [1.05; 1.37] p=0.006). Axillary arteries are an effective alternative access route for patients with unsuitable iliofemoral arteries. Randomized clinical trials are needed to confirm our findings and to assess the best approach for the upper arm.

12. Vascular pain: Ischemic pain in the extremities and Raynaud's syndrome

Peripheral artery diseases (PAD) and Raynaud's syndrome are associated with substantial morbidity. PAD, through the restriction of blood flow to the extremities, may lead to critical limb ischemia with symptoms of pain at rest which may eventually progress to severe limb ischemia with gangrene. This serious and painful clinical condition requires extensive medical care, is limb-threatening and, in case of delayed or unsuccessful treatment, is associated with a high mortality rate. In Raynaud's syndrome, the blood supply to certain parts of the body, usually the fingers and toes and less frequently the nose or ears, is restricted because of vasculopathy of the smaller vessels at acral sites. Under certain circumstances, with cold as the most well-known provoking factor, blood flow restriction occurs, leading to demarcated color changes and symptoms such as pain, paresthesia, and numbness. In severe cases of Raynaud syndrome tissue ischemia may lead to necrosis and the need for amputation of the affected area. In this narrative review, the literature on the diagnosis and interventional pain treatment of PAD and Raynaud's syndrome was updated and summarized. This review focused on interventional pain treatment. In PAD, the effects of the intervention on limb salvage, ulcer healing, and ischemic pain were summarized. Additionally, results with respect to skin microcirculation and quality of life were reported if available. In Raynaud's syndrome, we focused on the effect of the intervention on peripheral blood flow metrics and pain intensity during attacks. In PAD, prevention and treatment of risk factors are important. Initially, conservative treatment and pharmacological therapy are preferred first-line therapies. However, when disease progression occurs, interventional management may be considered. The literature search yielded conflicting evidence for sympathectomy as a treatment for PAD. Spinal cord stimulation (SCS) as a treatment modality for advanced PAD had high-quality evidence for limb salvage in subgroups of patients but conflicting evidence for other outcome measures such as pain, wound healing, and quality of life. The literature search for interventional pain management in Raynaud's syndrome was limited to only one randomized controlled trial (RCT) studying the effect of thoracic sympathectomy. This study had several limitations and hence the level of evidence for this interventional treatment is very low. No RCTs studying SCS in patients with Raynaud's syndrome were found. In both PAD and Raynaud's syndrome, additional RCTs are needed to substantiate interventional (pain) management and bolster the evidence base for sympathectomy and SCS as treatment options.

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

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

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

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

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

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

STATINS IN DISEASES OF THE PERIPHERAL ARTERIES: ARE THE CLINICAL RECOMMENDATIONS BEING FOLLOWED?

Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis and is associated with high mortality due to cardiovascular events. Since lipid-lowering therapy has proven effective in the treatment of patients with PAD, current clinical guidelines regulate statin treatment for all patients with PAD. However, in real clinical practice, the administration of statins in this category of patients is clearly insufficient. The purpose of this study was to study compliance with current clinical recommendations on the frequency of statin prescribing in various regimens among patients with PAD who sought medical help in a specialized hospital. It has been shown that in real clinical practice, the administration of statins does not comply with current clinical recommendations, and the desired low-density lipoproteins targets are not achieved in a significant number of patients. It is necessary to raise awareness among doctors of various specialties about the need for early diagnosis and treatment of PAD in accordance with clinical recommendations, especially in the absence of coronary heart disease and other atherosclerosis-associated diseases. When diagnosed with PAD, the patient should start taking statins in the most tolerable doses with the most effective drugs

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

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

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

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

Popliteal access for iliofemoral occlusive disease in the office-based catheter laboratory

ObjectivePopliteal access as an alternative to conventional femoral access has not been reported in the office-based catheter laboratory setting (OBL) and may be perceived to have higher risks. The purpose of this study was to evaluate the safety and efficacy of popliteal access for the endovascular treatment of iliofemoral arterial occlusive disease in an OBL setting. MethodsFrom October 2018 to October 2023, a total of 1408 interventions for peripheral artery disease were performed in our OBL. A cohort of 27 popliteal access consecutive procedures for femoral and iliac artery occlusions were studied. All interventions were done using a micropuncture needle under ultrasound guidance. All patients were discharged 1 hour after completion of the procedure. Indications for popliteal access were presence of aortoiliac stent grafts, aortobifemoral or aortoiliac bypasses, difficult contralateral or antegrade femoral access, and flush superficial femoral artery occlusions. Procedures were determined to be successful upon complete resolution of the target lesions and safety was measured perioperatively and at 90 days. Patency was determined clinically, by arterial duplex examination, and by need for reintervention for ≤2 years. ResultsWe performed 27 popliteal access procedures in 25 patients (21 complete femoral artery occlusions, 6 severe stenosis). Iliac disease was present in nine. Indications for popliteal access were existing aortoiliac stent graft in 11, aortobifemiliac bypass in 4, noncrossable iliac occlusions in 3, failed antegrade femoral access in 4, flush superficial femoral artery occlusion in 3, and bilateral common femoral artery disease precluding access in 2. Trans-Atlantic Inter-Society Consensus classification preoperatively was B, 4; C, 4; and D, 19. Treatments included atherectomy/balloon angioplasty and stent in 12, balloon angioplasty and stenting in 4, atherectomy/balloon angioplasty in 5, and balloon angioplasty alone in 6. Successful opening of occlusions occurred in 25 of 27 patients (92.5%). No complications or major adverse cardiac events occurred, except one asymptomatic small popliteal arteriovenous fistula. Of the 25 successful procedures, the duplex patency at 3, 6, and 12 months was 19/20 (95%), 11/15 (69.3%), and 11/13 (61%). Rutherford Classification improved from a preoperative value of >4 in 24 of 27 (89%) to a postoperative value of <2 at 1 month in 23 of 23 (100%), at 3 months in 19 of 20 (95%), at 6 months in 11 of 15 (69.3%), and at 12 months in 11 of 13 (61%). Freedom from reintervention at 3 months occurred in 19 of 20 (95%), at 6 months in 13 of 15 (86%), and at 12 months in 12 of 13 (79%). ConclusionsPopliteal artery access for complex iliofemoral disease is safe and effective and should be considered as a valid alternative option in the OBL setting.

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

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

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

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

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

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

Peripheral arterial disease in women.

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

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

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

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

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

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

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