Short-Term Complications and Outcomes in Pharmaco-Mechanical Thrombolysis First and Catheter-Directed Thrombolysis First in Patients with Acute Lower Limb Ischemia.

BACKGROUND: Pharmaco-mechanical thrombolysis (PMT) has emerged as a treatment option in patients with acute lower limb ischemia (ALI), especially Rutherford IIb (motor deficit) for rapid revascularization, but supportive data is scarce. The aim of the present study was to compare the effects of thrombolysis, complications, and outcomes of PMT first versus catheter-directed thrombolysis (CDT) first in a large cohort of patients with ALI. METHODS: All endovascular thrombolytic/thrombectomy events in patients with ALI performed between January 1st, 2009, and December 31st, 2018 (n = 347) were included. Successful thrombolysis/thrombectomy was defined as complete or partial lysis. Reasons for using PMT were described. Complications such as major bleeding, distal embolization, and new onset of renal impairment, and major amputation and mortality at 30 days were compared between PMT (AngioJet) first and CDT first groups in a multivariable logistic regression model with adjustment for age, gender, atrial fibrillation, and Rutherford IIb. RESULTS: The most common reason for initial use of PMT was the need for rapid revascularization, and the most common reason for use of PMT after CDT was the insufficient effect of CDT. Presentation of Rutherford IIb ALI was more common in the PMT first group (36.2% vs. 22.5%, respectively, P = 0.027). Among the 58 patients receiving PMT first, 36 (62.1%) were terminated within a single session of therapy without need of CDT. The median duration of thrombolysis was shorter (P < 0.001) for the PMT first group (n = 58) compared to the CDT first group (n = 289) (4.0 hr vs. 23.0 hr, respectively). There was no significant difference in amount of tissue plasminogen activator given, successful thrombolysis/thrombectomy (86.2% and 84.8%), major bleeding (15.5% and 18.7%), distal embolization (25.9% and 16.6%), major amputation or mortality at 30-days (13.8% and 7.7%) in the PMT first compared to the CDT first group, respectively. The proportion of new onset of renal impairment was higher in the PMT first compared to the CDT first group (10.3% vs. 3.8%, respectively), and the increased odds (odds ratio 3.57, 95% confidence interval 1.22-10.41) were maintained in the adjusted model. In Rutherford IIb ALI, no difference in rate of successful thrombolysis/thrombectomy (76.2% and 73.8%), complications or 30-day outcomes was found between PMT first (n = 21) and CDT (n = 65) first group. CONCLUSIONS: PMT first appears to be a good treatment alternative to CDT in patients with ALI, including Rutherford IIb. The found renal function deterioration in the PMT first group needs to be evaluated in a prospective, preferably randomized trial.

Iliac Endovascular Intervention Without Procedural Anticoagulation.

BACKGROUND: Adequate antithrombotic therapy is essential to prevent thrombus formation during percutaneous endovascular interventions (PVI). We hypothesize that interventions for non-complex lesions of iliac arteries do not need procedural anticoagulation if patients are under dual antiplatelet therapy (DAPT). METHODS: Iliac PVIs performed without procedural anticoagulation were retrospectively screened between 2017 and 2021. Baseline characteristics of patients, in-hospital events and 30-day follow-ups were obtained from hospital records. Each PVI was reviewed for procedural details. Primary safety outcome was thromboembolic events during intervention. Secondary safety outcome was adverse vascular events at 30-day follow-up. Procedure times of iliac interventions were compared to peripheral angiography procedures of patients with similar demographic characteristics. RESULTS: We identified 108 iliac interventions without procedural anticoagulation, median age of 62 (interquartile range 56-68) years, 9 (8.3%) females. Median lesion length was 30 (19-50) mm. We observed a thrombotic finding in 4 (3.7%) procedures. Visible luminal thrombus was observed in 2 (1.9%) and introducer sheath thrombosis in 2 procedures (1.9%), all of which were in patients with in-stent lesions. No distal embolization was observed in final angiography of these procedures. At 30-day follow-up, acute limb ischemia was not observed and clinically driven target vessel revascularization was not required in any of the patients. Procedure time of iliac interventions was similar to that of lower extremity diagnostic procedures [18 (11-24) vs 18 (14-24) min, respectively, P = .364]. No major bleeding event was observed after iliac interventions. CONCLUSION: Non-complex lesions of iliac arteries can be managed within a time frame similar to that of lower extremity diagnostic procedures. These interventions can be performed safely without procedural anticoagulation, provided patient receives DAPT. Intervention of in-stent lesions should ideally be avoided without procedural anticoagulation.

The Intervention of Nano-targeted Drugs & Angioplastryin Treatment and Prevention of Vascular Restenosis and its Influence on Monocyte Chemotactic Protein-1 in Lower Extremity Angiopathy.

It was to make use of the nano-targeted drugs and angioplastry to treat and prevent the vascular restenosis and analyze its influence on monocyte chemotactic protein 1 (MCP-1) of lower extremity angiopathy (LEA) patients since the patients with diabetic lower extremity angiopathy may be easily infected with vascular restenosis. In this article, the dexamethasone nano drugs were firstly prepared. After that, its related physical and chemical properties were tested, then, dexamethasone nano drugs were applied in treating patients with diabetic lower extremity angiopathy. The results showed that the prepared dexamethasone nanoparticles' encapsulation rate attained 99.2%. The laser light scattering experiment manifested that the particle size of the nanoparticles ranged from 200 to 300nm, and the average particle size was 258nm. The MCP-1 of the control group, conventional group, and observation group were 33.28±1.93 µg/mL, 78.27±9.73 µg/mL, and 75.29±8.99 µg/mL, respectively. The MCP-1 values of the conventional and observation groups were higher than that of the control group, and there was a notable difference (P<0.05). After interventional treatment, the MCP-1 level of the conventional group was 57.82±5.82 µg/mL, and that of the observation group was 41.93±6.92 µg/mL. The MCP-1 level of the group which received the treatment of nano-targeted drugs and angioplastry was superior to that of the conventional group which received the traditional operation, and there was a notable difference (P<0.05). In conclusion, MCP-1 is one of the major causes of lower extremity angiopathy. The nano-targeted drugs and angioplastry can raise the expression level of MCP-1 in patients with lower extremity angiopathy. The experimental results had a high application value and the nano-targeted drugs & angioplastry can be promoted clinically.

Spinal cord stimulation in the treatment of peripheral vascular disease: a systematic review - revival of a promising therapeutic option?

INTRODUCTION: Peripheral vascular disease (PVD) is caused by a blood circulation disorder of the arteries and Critical Limb Ischemia (CLI) is the advanced state of PVD. For patients with surgically non-reconstructable CLI, Spinal Cord Stimulation (SCS) appears to be an alternative therapeutic option. OBJECTIVE: The aim of our study was to investigate the efficacy of SCS in non-reconstructable CLI compared with the conservative treatment and re-appraise the existing literature in light of the recent advances in neuromodulation. METHODS: We conducted a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using electronic databases and reference lists for article retrieval. RESULTS: A total of 404 records were identified and finally 6 randomised controlled trials (RCTs), a Cochrane review and a meta-analysis were included in our systematic review. The studies assessed the efficacy of tonic SCS in the treatment of patients with non-reconstructable CLI compared with the conservative treatment. There is moderate to high quality evidence suggesting, that tonic SCS has beneficial effects for patients suffering from non-reconstructable CLI in terms of limb salvage, pain relief, clinical improvement and quality of life. The contradictory conclusions of the two meta-analyses regarding the efficacy of SCS for limb salvage at 12 months refer rather to the magnitude of the beneficial effect than to the effect itself. So far, the current literature provides evidence about the traditional tonic SCS but there is a lack of studies investigating the efficacy of new waveforms in the treatment of non-reconstructable CLI. CONCLUSION: SCS represents an alternative for PVD patients with non-reconstructable CLI and the existing literature provides encouraging clinical results, that should not be neglected. Instead, they should be re-appraised in light of the recent advances in neuromodulation with the emergence of novel waveform technologies and neuromodulation targets.

Modern approaches and innovations in the diagnosis and treatment of peripheral vascular diseases.

Amongst the three major vascular beds (coronary, cerebrovascular, and peripheral), peripheral vascular disease (PVD) has traditionally received the least attention, despite its growing global burden. The aging population has led to the increased prevalence of PVD, thereby increasing visibility to its various diagnostic and treatment modalities. In the past decade, research and development of innovations in the management of PVD has exploded. Modern advances in imaging, molecular technology, medical devices, and surgical techniques have reduced the morbidity and mortality of PVD. However, many challenges still remain due to the debilitating and progressive nature of this disease. In this article, we will introduce some common vascular diseases, the state of art in diagnosis and treatment, the limitations of modern technology, and our vision for this field over the next decade.

Pilot study to investigate differences in middle molecules, oxidative stress and markers of peripheral vascular disease in patients treated by high flux haemodialysis and haemodiafiltration.

BACKGROUND: Dialysis patients have an increased risk of mortality. Recently treatment with haemodiafiltration (HDF) has been reported to reduce mortality, particularly cardiovascular mortality, compared to standard high-flux haemodialysis (HD). However, why HDF may offer a survival advantage remains to be determined. So, we conducted a pilot study to explore differences in middle-molecules, inflammation and markers of vascular disease in patients treated by HD and HDF. METHODS: Observational cross-sectional study measuring serum ß2-microglobulin (ß2M), Advanced Glycosylation End Products (AGEs) by skin autofluorescence (SAF), oxidative stress with ischaemia modified albumin ratio (IMAR) and peripheral vascular disease assessment using Ankle-Brachial Index (ABI), and arterial stiffness using Cardio-Ankle Vascular Index (CAVI). RESULTS: We studied 196 patients, mean age 69.1 ± 12.4 years, 172 (87.8%) treated by HD and 24 (12.2%) by HDF. Age, body mass index, co-morbidity and dialysis vintage were not different between HD and HDF groups. Middle molecules; ß2M (31±9.9 vs 31.2±10 ug/mL) and SAF (2.99±0.72 vs 3.0±0.84 AU), ABI (1.06±0.05 vs 1.07±0.10) and CAVI (9.34±1.55 vs 9.35±1.23) were not different, but IMAR was higher in the HD patients (38.4±14.8 vs 31.3 ± 17.4, P = 0.035). CONCLUSIONS: In this pilot observational study, we found patients treated by HDF had lower oxidative stress as measured by IMAR, with no differences in middle molecules. Lower oxidative stress would be expected to have diverse protective effects on the cardiovascular system Although we found no differences in ABI and CAVI, future studies are required to determine whether reduced oxidative stress translates into clinically relevant differences over time.

Current status of patient-reported outcome measures in vascular surgery.

A previously published review focused on generic and disease-specific patient-reported outcome measures (PROMs) relevant to vascular surgery but limited to arterial conditions. The objective of this project was to identify all available PROMs relevant to diseases treated by vascular surgeons and to evaluate vascular surgeon perceptions, barriers to widespread implementation, and concerns regarding PROMs. We provide an overview of what a PROM is and how they are developed, and summarize currently available PROMs specific to vascular surgeons. We also report results from a survey of 78 Society for Vascular Surgery members serving on committees within the Policy and Advocacy Council addressing the barriers and facilitators to using PROMs in clinical practice. Finally, we report the qualitative results of two focus groups conducted to assess granular perceptions of PROMS and preparedness of vascular surgeons for widespread implementation of PROMs. These focus groups identified a lack of awareness of existing PROMs, knowledge of how PROMs are developed and validated, and clarity around how PROMs should be used by the clinician as main subthemes for barriers to PROM implementation in clinical practice.

Lower limb wounds in diabetes: the challenges of wound healing.

Managing ulceration in the lower limb for a patient with diabetes can be complex and challenging, requiring a multiprofessional, patient-centred, holistic approach with early referral for specialist review as key. Any delay in referral and intervention can be catastrophic, as time is tissue. Peripheral arterial disease and neuropathy both contribute significantly to the delays in wound healing, and it is important to rapidly recognise the problems with an informed assessment and understand the possible reasons for delayed wound healing, so that management is appropriate, rapid referrals are made and patient outcomes are optimised. This article discusses some of the reasons why wound healing is complicated in those with diabetes as a comorbidity.

Pre-operative Neutrophil to Lymphocyte Ratio is Associated With 30 Day Death or Amputation After Revascularisation for Acute Limb Ischaemia.

OBJECTIVE: Inflammation is an early feature of acute limb ischaemia (ALI), hence the potential prognostic significance of inflammatory biomarkers. This study aimed to assess the value of pre-operative inflammatory biomarkers, specifically the neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR), for predicting an adverse outcome after revascularisation for ALI. METHODS: All patients submitted to lower limb revascularisation for Rutherford IIa or IIb ALI at the authors' institution between 2009 and 2019 were screened retrospectively. Pre-operative NLR and PLR were analysed, along with other known prognostic factors. Primary outcome was the composite endpoint of 30 day death or amputation. RESULTS: A total of 345 patients were included, 84 of whom suffered the primary outcome (24.3%). The median follow up was 23.1 months (3.1 - 52.2). Higher age (OR 1.05 per year increase, 95% CI 1.01 - 1.09), diabetes (OR 2.63, 95% CI 1.14 - 6.06), Rutherford grade IIb vs. IIa (OR 5.51, 95% CI 2.11 - 14.42), higher NLR (OR 1.28 per unit increase, 95% CI 1.12 - 1.47), and fasciotomy need (OR 3.44, 95% CI 1.14 - 10.34) were independently associated with 30 day death or amputation, whereas pre-operative statin or anticoagulant medication were associated with a risk reduction (OR 0.23, 95% CI 0.53 - 0.96 and OR 0.20, 95% CI 0.05 - 0.84, respectively). PLR did not show an independent effect on this population. Pre-operative NLR presented a good discriminative ability (AUC 0.86, 95% CI 0.82 - 0.90). A cut off NLR level ≥ 5.4 demonstrated a 90.5% sensitivity and 73.6% specificity for 30 day death or amputation. Kaplan-Meier analysis showed that patients with pre-operative NLR ≥ 5.4 had significantly lower 30 day, six month and one year amputation free survival when compared with those with NLR < 5.4 (64.8 ± 4.0%, 44.1 ± 4.1%, and 37.5 ± 4.1% vs. 98.5 ± 0.9%, 91.9 ± 2.0%, and 85.9 ± 2.5%, log rank p < .001). CONCLUSION: In this study, higher pre-operative NLR was associated with 30 day death or amputation following intervention for Rutherford grade IIa or IIb ALI. NLR potentially stands as a simple, widely available and inexpensive biomarker that can refine decision making and possibly contribute to ALI morbidity and mortality reduction.

Case Report: Novel SAVI-Causing Variants in STING1 Expand the Clinical Disease Spectrum and Suggest a Refined Model of STING Activation.

Gain-of-function mutations in STING1 cause the monogenic interferonopathy, SAVI, which presents with early-onset systemic inflammation, cold-induced vasculopathy and/or interstitial lung disease. We identified 5 patients (3 kindreds) with predominantly peripheral vascular disease who harbor 3 novel STING1 variants, p.H72N, p.F153V, and p.G158A. The latter two were predicted by a previous cryo-EM structure model to cause STING autoactivation. The p.H72N variant in exon 3, however, is the first SAVI-causing variant in the transmembrane linker region. Mutations of p.H72 into either charged residues or hydrophobic residues all led to dramatic loss of cGAMP response, while amino acid changes to residues with polar side chains were able to maintain the wild type status. Structural modeling of these novel mutations suggests a reconciled model of STING activation, which indicates that STING dimers can oligomerize in both open and closed states which would obliviate a high-energy 180° rotation of the ligand-binding head for STING activation, thus refining existing models of STING activation. Quantitative comparison showed that an overall lower autoactivating potential of the disease-causing mutations was associated with less severe lung disease, more severe peripheral vascular disease and the absence of a robust interferon signature in whole blood. Our findings are important in understanding genotype-phenotype correlation, designing targeted STING inhibitors and in dissecting differentially activated pathways downstream of different STING mutations.

Ambulatory Patients with Cardiometabolic Disease and Without Evidence of COVID-19 During the Pandemic. The CorCOVID LATAM Study.

Background: SARS-CoV-2 pandemic has modified the cardiovascular care of ambulatory patients. The aim of this survey was to study changes in lifestyle habits, treatment adherence, and mental health status in patients with cardiometabolic disease, but no clinical evidence of COVID-19. Methods: A cross-sectional survey was conducted in ambulatory patients with cardiometabolic disease using paper/digital surveys. Variables investigated included socioeconomic status, physical activity, diet, tobacco use, alcohol intake, treatment discontinuation, and psychological symptoms. Results: A total of 4,216 patients (50.9% males, mean age 60.3 ± 15.3 years old) from 13 Spanish-speaking Latin American countries were enrolled. Among the study population, 46.4% of patients did not have contact with a healthcare provider, 31.5% reported access barriers to treatments and 17% discontinued some medication. Multivariate analysis showed that non-adherence to treatment was more prevalent in the secondary prevention group: peripheral vascular disease (OR 1.55, CI 1.08-2.24; p = 0.018), heart failure (OR 1.36, CI 1.05-1.75; p = 0.017), and coronary artery disease (OR 1.29 CI 1.04-1.60; p = 0.018). No physical activity was reported by 38% of patients. Only 15% of patients met minimum recommendations of physical activity (more than 150 minutes/week) and vegetable and fruit intake. Low/very low income (45.5%) was associated with a lower level of physical activity (p < 0.0001), less fruit and vegetables intake (p < 0.0001), more tobacco use (p < 0.001) and perception of depression (p < 0.001). Low educational level was also associated with the perception of depression (OR 1.46, CI 1.26-1.70; p < 0.01). Conclusions: Patients with cardiometabolic disease but without clinical evidence of COVID-19 showed significant medication non-adherence, especially in secondary prevention patients. Deterioration in lifestyle habits and appearance of depressive symptoms during the pandemic were frequent and related to socioeconomic status.

Clinical Outcomes of Stenting Extending Below the Inguinal Ligament for Treatment of Chronic Iliofemoral Venous Obstruction.

BACKGROUND: Patients with chronic iliofemoral venous obstructive lesions that often require stenting extending below the inguinal ligament. However, the issue of stents crossing the inguinal ligament is currently controversial. Some guidelines suggest that it should be avoided, and some guidelines suggest that in order to ensure adequate flow, the inguinal ligament can be crossed if necessary. The aim of this study was to evaluate the technical aspects and examine patency rates of stent placement across the inguinal ligament for managing iliofemoral venous obstruction. METHODS: A retrospective analysis of 127 patients with chronic iliofemoral venous obstruction were treated with interventional surgery in a single institution from January 2012 to January 2018 was conducted. All patients underwent balloon dilatation and placement of at least 2 stents extending below inguinal ligament. Inflow condition, technical success, operation duration, stent patency rates, anticoagulant selection and duration, and complications were recorded after the interventions. RESULTS: The technical success rate was 100%. No major perioperative complications occurred. The mean number of stents was 2.14 ± 0.37. Follow up periods ranged from 12 to 60 months (28.79 ± 10.90 months). Overall cumulative primary, assisted primary, and secondary stent patency rates were 81.9%, 90.5%, and 92.9% at 12 months and 70.4%, 80.9%, and 86.0% at 24 months, and 64.2%, 72.3%, and 74.3% at 36months, respectively. Cumulative patency rates at 12 months, 24 months and 36 months were significantly greater in the patients with "good" inflow as compared to "fair" inflow. The symptoms of all patients improved. None of the stents were compressed, fractured or migrated. CONCLUSIONS: Stenting across the inguinal ligament for treatment of the patients with chronic iliofemoral venous obstruction was a feasible and safe treatment with good patency and clinical results in short and midterm follow up, and stents with good inflow have better patency.

Progress in aorta and peripheral cardiovascular disease research.

Although coronavirus disease 2019 seems to be the leading topic in research number of outstanding studies have been published in the field of aorta and peripheral vascular diseases likely affecting our clinical practice in the near future. This review article highlights key research on vascular diseases published in 2020. Some studies have shed light in the pathophysiology of aortic aneurysm and dissection suggesting a potential role for kinase inhibitors as new therapeutic options. A first proteogenomic study on fibromuscular dysplasia (FMD) revealed a promising novel disease gene and provided proof-of-concept for a protein/lipid-based FMD blood test. The role of NADPH oxidases in vascular physiology, and particularly endothelial cell differentiation, is highlighted with potential for cell therapy development. Imaging of vulnerable plaque has been an intense field of research. Features of plaque vulnerability on magnetic resonance imaging as an under-recognized cause of stroke are discussed. Major clinical trials on lower extremity peripheral artery disease have shown added benefit of dual antithrombotic (aspirin plus rivaroxaban) treatment.

Six-month pivotal results of tack optimized balloon angioplasty using the Tack Endovascular System in below-the-knee arteries.

OBJECTIVE: No vascular implant is commercially available in the United States to treat post-angioplasty dissections in below-the-knee (BTK) arteries. The Tack Endovascular System (Intact Vascular, Wayne, Pa) is purpose-built to repair postpercutaneous transluminal angioplasty (PTA) BTK dissections. A trial was conducted to investigate the safety and efficacy of the first-of-a-kind implantable BTK device to treat post-PTA dissections in the setting of critical limb ischemia. METHODS: The present prospective, single-arm, multicenter study evaluated the Tack Endovascular System for treating post-PTA dissections in the mid/distal popliteal, tibial, and peroneal arteries. The primary safety endpoint was major adverse limb events (MALE) plus perioperative death (POD), assessed at 30 days after the index procedure. The primary efficacy endpoint was a composite of MALE at 6 months and POD. The unpowered secondary endpoint was primary patency at 6 months. With no available on-label comparator, the primary endpoints of the present trial were determined using objective performance goals from a systematic literature search. The secondary endpoints included Tacked segment patency and target limb salvage at 6 months. The 6-month results are reported. RESULTS: Of the 233 patients enrolled, 117 (50.2%) had Rutherford class 5 and 78 (33.5%) had Rutherford class 4. A total of 341 post-PTA dissections were treated. Each patient received at least one Tack implant, and 100% of the dissections resolved according to the angiographic core laboratory findings. The primary safety and efficacy endpoints were both met. The rate of MALE plus POD at 30 days was 1.3% (3 of 228) and freedom from MALE at 6 months plus POD at 30 days was 95.6% (196 of 205). The 6-month Tacked segment patency was 82.1% (247 of 301) and target limb salvage was 98.5% (202 of 205). The Kaplan-Meier freedom from clinically driven target lesion revascularization and amputation-free survival at 6 months was 92.0% and 95.7%, respectively. Rutherford improvement was reported in 79.4% (158 of 199). Most (90 of 122; 73.8%) preexisting wounds had healed or were improving. CONCLUSIONS: The Tack Endovascular System is safe and effective for treating post-PTA BTK dissections through 6 months, with favorable rates of MALE plus POD, patency, clinically driven target lesion revascularization, limb salvage, and wound healing.

Peripheral Vascular Disease and Kidney Transplant Outcomes: Rethinking an Important Ongoing Complication.

Peripheral vascular disease (PVD) is highly prevalent in patients on the waiting list for kidney transplantation (KT) and after transplantation and is associated with impaired transplant outcomes. Multiple traditional and nontraditional risk factors, as well as uremia- and transplant-related factors, affect 2 processes that can coexist, atherosclerosis and arteriosclerosis, leading to PVD. Some pathogenic mechanisms, such as inflammation-related endothelial dysfunction, mineral metabolism disorders, lipid alterations, or diabetic status, may contribute to the development and progression of PVD. Early detection of PVD before and after KT, better understanding of the mechanisms of vascular damage, and application of suitable therapeutic approaches could all minimize the impact of PVD on transplant outcomes. This review focuses on the following issues: (1) definition, epidemiological data, diagnosis, risk factors, and pathogenic mechanisms in KT candidates and recipients; (2) adverse clinical consequences and outcomes; and (3) classical and new therapeutic approaches.

Peripheral Vascular Disease.

Peripheral vascular disease (PVD) is a leading health concern in the United States, with an estimated prevalence of 8.5 million. The incidence of PVD is growing due to increasing rates of obesity and diabetes, as well as an aging population. Peripheral vascular disease is categorized as either venous, arterial, or mixed. A differential assessment is essential to identify the type of PVD and to plan management strategies to prevent further vascular dysfunction. This article describes assessment of patients with PVD, risk factors, treatments, and patient education.