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Objective: To investigate the mid-term efficacy and patency rate of TurboHawk peripheral plaque excision system in the treatment of femoral popliteal artery lesions with different Global Limb Anatomic Staging System (GLASS) grades., Methods: The clinical data of 141 patients with femoral popliteal arteriosclerosis obliterans who were treated with TurboHawk from January 2018 to July 2022 in our institution were retrospectively analyzed. There were 109 male patients and 32 female patients. Recordings were made of the patient's symptoms of limb ischemia, technical success rate, primary patency rate of target vessels, ankle brachial index (ABI), GLASS grades, postoperative complications, and a statistical analysis with the patient's preoperative treatment was conducted., Results: All patients had improved limb ischemia symptoms to varying degrees after surgery, with a technical success rate of 100% (femoral artery puncture and superficial femoral artery recanalization) without bleeding, hematoma, pseudoaneurysm, arteriovenous fistula or other complications. The follow-up period was 1-24 months, during which the severity of claudication, resting pain, and toe ulcers significantly improved. The primary patency rate of the target vessel was 98.58% (139/141), and the ABI significantly increased on the second day, three months, and six months after surgery compared to before surgery. No major adverse events were found during follow-up. The patency rates at 1, 6, 12 and 24 months after intervention were 100%, 80%, 75% and 60% respectively., Conclusion: The mid-term efficacy and patency rate of TurboHawk in the treatment of femoral popliteal artery lesions with GLASS I patients have the best mid-term prognosis, the highest mid-term survival rate, and the highest vascular patency. The plaque removal system has proven to be an effective treatment for individual localized chronic total occlusion lesions. Additionally, the TurboHawk system provides a safe and minimally invasive treatment alternative for superficial femoral artery conditions, achieving significant therapeutic results within a brief period., Competing Interests: The authors declare there are no competing interests., (©2024 Yue et al.)

Background: Cardiovascular disease is a major cause of morbidity in an aging HIV population. However, risk estimation with the most frequent equations usually classifies HIV patients as having a low or moderate risk. Several studies have described a very high prevalence of subclinical atherosclerosis in a middle-aged, non-HIV population. There is insufficient body of knowledge to understand if this is the case in people living with HIV (PLWH). We aim to calculate the proportion of patients with subclinical atherosclerosis in a single site cohort of HIV-infected subjects., Methods: We have analyzed chronically HIV infected adults (≥ 18 years) who were on active follow-up in an HIV unit specialized in the care of cardiovascular health. The most recent clinical visit and vascular ultrasonography were used to assess the objectives of our research. Our primary objective was to describe the proportion of participants with subclinical atherosclerosis (focal protrusion into the lumen > 0.5 mm or > 50% of the surrounding IMT or a diffuse thickness > 1.5 mm) in a single site cohort of PLWH. Carotid and iliofemoral territories were evaluated. As a secondary objective we have run a multivariate analysis to determine which HIV and non-HIV factors might be related with the presence of atherosclerotic plaques. Findings We included a total of 463 participants between November 2017 to October 2019. Subjects were predominantly male (84.2%) with a mean age of 48.8 years (SD 10.7). Hypercholesterolemia (36%) was the most prevalent comorbidity followed by Hypertension (18%) and Hypertriglyceridemia (16%). Mean duration of HIV infection is 12.3 years. Overall, participants had been receiving cART for a median of 9.5 years. Subclinical atherosclerosis was found in 197 subjects (42.5%; CI 95% [38.0-47.2]). The disease was found more frequently in the femoral arteries (37.8%) than in the carotid vascular bed (18.6%). Despite some HIV factors correlated with the presence of plaques in a univariate analysis (e.g., time with HIV-1 RNA > 50 copies/mL or time from HIV diagnosis), the only two explanatory factors that remained associated with the presence of atherosclerotic plaques in the multivariate analysis were smoking (OR 5.47, 95% CI 3.36 - 8.90) and age (OR 1.13, 95%CI 1.10 - 1.16). Interpretation We have found a very high prevalence of subclinical atherosclerosis among our cohort of PLWH. Despite having analyzed several HIV factors, age and smoking have been found to be the only factors associated with the development of atherosclerotic plaques., (© 2024. The Author(s).)

Background: A recent meta-analysis of randomized control trials demonstrated a significantly higher risk of major amputation in patients treated with drug-coated balloons (DCBs) compared with standard treatment, especially in high-dose paclitaxel-coated DCBs. Distal particulate embolization after DCB use was considered a potential cause of the higher incidence of major amputation. The current study aimed to histologically and biologically compare biologic drug effect and distal particulate embolization in 3 DCBs (a high-dose paclitaxel-coated DCB [IN.PACT Admiral] and 2 low-dose paclitaxel-coated DCBs [Ranger and Lutonix])., Methods and Results: The DCBs were inflated in the healthy descending aortas of 18 rabbits, followed by euthanasia 28 days after the procedure. The treated descending aorta and distal skeletal muscles were histopathologically evaluated, and paclitaxel concentrations were measured. The paclitaxel concentration of the treated lesion was highest for Ranger, followed by IN.PACT and Lutonix (Ranger vs IN.PACT vs Lutonix: 1089 [745-2170] pmol/mg vs 638 [160-2075] pmol/mg vs 25 [10-304] pmol/mg, respectively; p<0.0001). In the histopathological evaluation, the angle of severe medial smooth muscle cell loss was largest for Ranger followed by IN.PACT and Lutonix (12.8 [8.0-20.4] degree vs 1.4 [1.2-5.2] degree vs 0.8 [0.5-2.5] degree, respectively), with significant differences for Ranger vs IN.PACT (p=0.007) and Ranger vs Lutonix (p=0.002). However, paclitaxel concentrations of distal skeletal muscles were lowest for Lutonix, followed by Ranger and IN.PACT (12 [1-58] pmol/mg vs 15 [13-21] pmol/mg vs 42 [19-108] pmol/mg, respectively, p<0.0001). The numbers of arteries with downstream DCB effects were highest for IN.PACT, followed by Ranger and Lutonix (Ranger vs IN.PACT vs Lutonix, 3 [3-4] vs 4 [3-7] vs 2 [1-2], respectively), which was consistent with the measured tissue paclitaxel concentrations., Conclusion: These findings suggest that Ranger demonstrates the strongest paclitaxel effect, as well as the second-best effect regarding distal particulate embolization, making it a good treatment option for patients with peripheral artery disease among the 3 DCBs evaluated in the current study. Further clinical head-to-head comparisons with larger numbers of patients are needed to explore which DCB is the most effective and safe treatment option.Clinical Impact:The findings of the current preclinical study suggests that Ranger demonstrates the strongest paclitaxel effect, as well as the second-best effect regarding distal particulate embolization making it a good treatment for patients with intermittent claudication and chronic limb-threatening ischemia., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: This study was sponsored by Boston Scientific Japan (Tokyo, Japan). S.T. received research grants from Abbot Vascular Japan, Boston Scientific Japan, Medtronic, and received honoraria from Boston Scientific Japan. G.N. is a consultant for Boston Scientific, Abbott Vascular, Terumo Corp., and Japan Medical Device Technology Co., Ltd, and received research grants from Boston Scientific, Abbott Vascular, Terumo Corp., and Japan Medical Device Technology Co., Ltd.

Arteriogenesis is an inflammatory driven mechanism, describing the growth of a natural bypass from pre-existing collateral arteries to compensate for an occluded artery. The complement system component C3 is a potent natural inflammatory activator. Here, we investigated its impact on the process of collateral artery growth using C3-deficient (C3 -/-) and wildtype control mice in a murine hindlimb model of arteriogenesis. Induction of arteriogenesis by unilateral femoral artery ligation resulted in decreased perfusion recovery in C3 -/- mice on day 7 as shown by Laser Doppler imaging. Immunofluorescence staining revealed a reduced vascular cell proliferation in C3 -/- mice. Gene expression analysis displayed a significant reduction in monocyte chemoattractant protein-1 (MCP-1) expression in C3 -/- mice. Interestingly, 3 days after induction of arteriogenesis, the number of macrophages (CD68 + ) recruited to growing collaterals was not affected by C3 deficiency. However, a significant reduction in inflammatory M1-like polarized macrophages (CD68 + /MRC1 - ) was noted. Forced mast cell activation by Compound 48/80 as well as exogenous MCP-1 application rescued the number of M1-like polarized macrophages along with perfusion recovery in C3 -/- mice. In summary, this study demonstrates that complement C3 influences arteriogenesis by mediating MCP-1 expression, which is essential for the induction and enhancement of sterile inflammation.

Purpose: To describe our experience in performing transfemoral-transcaval liver biopsy (TFTC) and transjugular liver biopsy (TJLB) in patients with Fontan-associated liver disease (FALD)., Methods: A single-center, retrospective review of 23 TFTC and seven TJLB performed between August 2011 and May 2023 on patients who previously underwent the Fontan procedure (median age 23.1 years, ranging 11-43 years, 48% female). Patient demographics, laboratory values, pathology, radiology, and cardiology reports were reviewed. Liver explants were correlated with histopathological evaluation to determine sampling accuracy when available., Results: All biopsies achieved technical success (accurate targeting and safe tissue sample extraction) and histopathological success (yielding sufficient tissue for accurate diagnosis). Liver biopsies were performed during simultaneous cardiac catheterization in 28 of 30 (93%) procedures. There was no statistically significant change in hemoglobin, hematocrit, platelet count post-procedure, and fluoroscopy times. There was one major complication within the TJLB group and one minor complication within the TFTC group., Conclusion: Transvenous liver biopsies, whether via transfemoral or transjugular route, may be safely performed in FALD patients while yielding samples with technical and histopathological success. The transfemoral approach, which is our preferred method; its compatibility with simultaneous cardiac catheterization and its potentially increased safety profile stemming from the avoidance of transversing the Fontan shunt-makes it a particular advantageous option in the management of FALD., (© 2024. The Author(s).)

Background: Plaque erosion, a type of coronary atherothrombosis, involves superficial injury to smooth muscle cell (SMC)-rich plaques. Elevated levels of coagulation factor VIII (FVIII) correlate with an increased ischemic heart disease risk. FVIII may contribute to thrombus formation on eroded plaques., Aims: We aimed to elucidate the role of elevated FVIII in arterial thrombus formation within SMC-rich neointima in rabbits., Methods and Results: We assessed the effect of recombinant human FVIII (rFVIII) on blood coagulation in vitro and platelet aggregation ex vivo. An SMC-rich neointima was induced through balloon injury to the unilateral femoral artery. Three weeks after the first balloon injury, superficial erosive injury and thrombus formation were initiated with a second balloon injury of the bilateral femoral arteries 45 min after the administration of rFVIII (100 IU/kg) or saline. The thrombus area and contents were histologically measured 15 min after the second balloon injury. rFVIII administration reduced the activated partial thromboplastin time and augmented botrocetin-induced, but not collagen- or adenosine 5'-diphosphate-induced, platelet aggregation. While rFVIII did not influence platelet-thrombus formation in normal intima, it increased thrombus formation on SMC-rich neointima post-superficial erosive injury. Enhanced immunopositivity for glycoprotein IIb/IIIa and fibrin was observed in rFVIII-administered SMC-rich neointima. Neutrophil count in the arterial thrombus on the SMC-rich neointima correlated positively with thrombus size in the control group, unlike the rFVIII group., Conclusions: Increased FVIII contributes to thrombus propagation within erosive SMC-rich neointima, highlighting FVIII's potential role in plaque erosion-related atherothrombosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Excessive blood vessel wall thickening, known as intimal hyperplasia, can result from injury or inflammation and increase the risk of vascular diseases. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays key roles in tumor surveillance, autoimmune diseases, and apoptosis; however, its role in vascular stenosis remains controversial. Treatment with recombinant isoleucine zipper hexamerization domain soluble TRAIL (ILz(6):TRAIL) significantly inhibited the progression of neointimal hyperplasia (NH) induced by anastomosis of the carotid artery and jugular vein dose dependently, and adenovirus expressing secretable ILz(6):TRAIL also inhibited NH induced by balloon injury in the femoral artery of rats. This study demonstrated the preventive and partial regressive effects of ILz(6):TRAIL on anastomosis of the carotid artery and jugular vein- or balloon-induced NH., Competing Interests: Declaration of Competing Interests All authors report no conflicts of interest related to this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The femoropopliteal artery (FPA) is the main artery in the lower limb. It supplies blood to the leg muscles and undergoes complex deformations during limb flexion. Atherosclerotic disease of the FPA (peripheral arterial disease, PAD) is a major public health burden, and despite advances in surgical and interventional therapies, the clinical outcomes of PAD repairs continue to be suboptimal, particularly in challenging calcified lesions and biomechanically active locations. A better understanding of human FPA mechanical and structural characteristics in relation to age, risk factors, and the severity of vascular disease can help develop more effective and longer-lasting treatments through computational modeling and device optimization. This review aims to summarize recent research on the main biomechanical and structural properties of human superficial femoral and popliteal arteries that comprise the FPA and describe their anatomy, composition, and mechanical behavior under different conditions., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

The objective of this study was to establish an animal model of arteriosclerosis for assessing vasospasm and to investigate the relationship between arteriosclerosis and vasospasm. Twelve-week-old male Sprague-Dawley rats were fed a diet supplemented with adenine and vitamin D (adenine/vitD). Body weight, blood, and femoral artery histopathology were assessed at 2, 4, and 6 weeks. Change in the femoral artery was examined by transmission electron microscope (TEM). Vasospasm was induced by administering epinephrine extravascularly into the femoral artery and released by the treatment with lidocaine as a vasodilator. During this period, the extravascular diameter and blood flow were measured. The rats in the adenine/vitD group developed renal dysfunction, uremia, hyperphosphatemia, and elevated serum alkaline phosphatase. Histological and TEM analyses of the femoral arteries in the treated rats revealed the degeneration of elastic fibers and extensive calcification of the tunica media and intima. Vascular smooth muscles were degenerated and osteoblasts were developed, resulting in calcified arteriosclerosis. Vasospasm in arteriosclerotic arteries was detected; however, vasodilation as well as an increase in the blood flow was not observed. This study revealed the development of vasospasm in the femoral arteries of the arteriosclerotic rats and, a conventional vasodilator did not release the vasospasm., (© 2023. The Author(s) under exclusive licence to The Japanese Society for Clinical Molecular Morphology.)

Objective: There is a lack of consensus regarding the optimal strategy for evaluating the efficiency and safety of dual-pathway inhibition (DPI) in preventing femoropopliteal restenosis in patients undergoing repeated endovascular interventions. Despite several therapeutic interventions available for preventing femoropopliteal restenosis post repeated endovascular interventions, the ideal strategy, particularly evaluating the efficacy and safety of DPI, remains a matter of debate., Methods: From January 2015 to September 2021, patients who underwent repeated endovascular interventions for femoropopliteal restenosis were compared with those who underwent DPI or dual antiplatelet therapy (DAPT) after surgery using a propensity score-matched analysis. The primary outcome was clinically driven target lesion revascularization (CD-TLR). The principal safety outcome was a composite of major bleeding and clinically relevant non-major (CRNM) bleeding. To further enhance the rigor, Kaplan-Meier plots, Cox proportional hazards modeling, and sensitivity analyses, as well as subgroup analyses were employed, reducing potential confounders., Results: A total of 441 patients were included in our study, of whom 294 (66.7%) received DAPT and 147 (33.1%) received DPI, with 114 matched pairs (mean age, 72.21 years; 84.2% male). Cumulative probability of CD-TLR at 36 months in the DPI group (17%) trended lower than that in the DAPT group (32%) (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.26-0.78; P =.004). The cumulative probability of freedom from CD-TLR at 36 months in the DPI group was 83%. No significant difference was observed in the composite outcome of major or CRNM bleeding between the DPI and DAPT groups (HR, 1.26; 95% CI, 0.34 to 4.69; P = .730). The DPI group was associated with significantly lower rates of CD-TLR in the main subgroup analyses of diabetes (P = .001), previous smoking history (P = .008), longer lesion length (>10 cm) (P = .003), and treatment with debulking strategy (P = .003)., Conclusions: In our investigation focused on CD-TLR, we found that DPI exhibited a significant reduction in the risk of reintervention compared with other treatment modalities. This underscores the potential of DPI as a viable therapeutic strategy in preventing reinterventions. Moreover, our assessment of safety outcomes revealed that the bleeding risks associated with DPI were on par with DAPT, thereby not compromising patient safety. These findings pave the way for potential broader clinical implications, emphasizing the effectiveness and safety of DPI in the context of reducing reintervention risks., Competing Interests: Disclosures None., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: To report the outcomes of the IN-DEPT trial assessing the feasibility, preliminary safety data, and 12-month outcomes of a new drug-coated balloon (DCB) product for peripheral artery disease (PAD) in Chinese patients., Materials and Methods: This is a prospective, multicenter, single-arm clinical trial. A total of 160 patients with superficial femoral artery (SFA) and/or proximal popliteal artery lesions were treated with a new paclitaxel-coated DCB. The preliminary effectiveness end point was 12-month primary patency. The primary safety end point was freedom from device- and procedure-related mortality over 30 days and freedom from major target limb amputation and clinically driven target lesion revascularization (CD-TLR) within 12 months after the index procedure., Results: In total, 160 patients presented with 162 target lesions. A total of 139 lesions (85.8%) were treated with 1 DCB, whereas the other 23 lesions (14.2%) were treated with 2 devices. The device success rate was 100%. A total of 135 subjects reached the preliminary effectiveness end point, with a 12-month primary patency rate of 84.4%. There was no 30-day device- or procedure-related death or unplanned major target limb amputation at 12 months. Five CD-TLRs (3.1%) occurred during the 12-month follow-up period., Conclusions: Results from the IN-DEPT SFA trial showed satisfactory feasibility and safety of the new DCB over 12 months in Chinese patients with PAD and femoropopliteal de novo lesions, including both stenoses and total occlusions., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the long-term results of the Eluvia drug-eluting stent (DES) implantation for femoropopliteal arterial disease, including the 'halo' phenomenon. Long-term data of DES is scarce. A focal reaction ('halo') following Eluvia DES deployment has been described. However, the long-term clinical impact of this phenomenon remains unclear., Methods: This prospective, non-randomized, single-arm study included 130 consecutive patients treated with an Eluvia DES for symptomatic femoropopliteal disease between March 2016 and December 2018. Clinical outcomes and imaging were assessed after 6 months and annually thereafter for up to 5 years. The primary outcome measure was primary patency. Secondary outcomes were freedom from clinically driven target lesion revascularization (CD-TLR), freedom from major amputation, overall survival and amputation-free survival rates., Results: The primary patency was 65% at 5 years. The freedom from CD-TLR and from major amputation at 5 years was 79 and 96%, respectively. The overall survival and amputation-free survival rates were 88 and 83% at 60 months, respectively. Out of the 27 patients with a halo sign, two showed an increased (7.4%) and 6 (22.2%) a decreased diameter. In 19 cases (70.4%), the diameter remained unchanged at the latest follow-up. The presence of the 'halo' sign was associated with increased primary patency (87% versus 59%, HR: 2.48, 95%CI 1.19-5.16, P = .015)., Conclusions: The presented patient cohort treated with the Eluvia DES for femoropopliteal artery lesions indicates durable efficacy and a good safety profile regardless of the halo phenomenon. The results need to be confirmed in a larger patient cohort., Level of Evidence Iii: Non-randomized controlled cohort/follow-up study., (© 2024. The Author(s).)

Background: The treatment of complex infra-inguinal disease with drug-coated balloons (DCBs) is associated with a significant number of patients undergoing provisional stenting to treat a suboptimal result. To determine the potential long-term impact of DCB treatment with provisional bare metal stenting in complex lesions in real-world patients, a post hoc analysis was performed on data from the IN.PACT Global Study (The IN.PACT Global Clinical Study for the Treatment of Comprehensive Superficial Femoral and/or Popliteal Artery Lesions Using the IN.PACT Admiral Drug-Eluting Balloon). Five-year outcomes were compared between participants who were stented after DCB treatment versus those treated with DCB alone., Methods: The IN.PACT Global Study enrolled 1535 participants with intermittent claudication and/or ischemic rest pain caused by femoropopliteal lesions; 1397 patients were included in this subgroup analysis (353 stented and 1044 nonstented). Effectiveness was assessed as freedom from clinically driven target lesion revascularization through 60 months. The primary safety composite end point was defined as freedom from device- and procedure-related death through 30 days, and freedom from major target limb amputation and clinically driven target vessel revascularization through 60 months., Results: Lesions in the stented group were longer (15.37 versus 10.98 cm; P <0.001) and had more total occlusions (54.7% versus 28.6%; P <0.001) compared with the nonstented group. The 5-year Kaplan-Meier estimated freedom from clinically driven target lesion revascularization was similar between groups (66.8% stented versus 70.0% nonstented group, log-rank P =0.22). The safety composite end point was achieved in 64.5% stented versus 68.2% nonstented participants (log-rank P =0.19) as estimated by the Kaplan-Meier method. No significant difference was observed in the cumulative incidence of major adverse events (49.1% stented versus 45.0% nonstented; log-rank P =0.17), including all-cause death (19.6% stented versus 19.3% nonstented, log-rank P =0.99)., Conclusions: In this real-world study, revascularization of complex femoropopliteal artery lesions with DCB angioplasty alone or DCB followed by provisional bare metal stenting in certain lesions achieved comparable long-term safety and clinical effectiveness., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01609296., Competing Interests: Disclosures Dr Ansel is a consultant for Boston Scientific, Medtronic, Veryan Medical, Cook Medical, Becton Dickinson, Alucent, and Surmodics. Dr Brodmann has received honoraria from Bard Peripheral Vascular, Biotronik, Medtronic, Philips-Spectranetics, and VIVA Physicians. Dr Brodmann is a consultant for Bard Peripheral Vascular, Biotronik, Medtronic, and Philips-Spectranetics. Dr Rocha-Singh is a consultant for Alucent Biomedical and Philips-Spectranetics and received research grant monies from Boston Scientific, Medtronic, and Philips. Mr Menk is a full time employee of Medtronic. Dr Zeller has received honoraria from Abbott Vascular, BIBA Medical, Biotronik, Boston Scientific, Cook Medical, Efemoral, Gore & Associates, Medtronic, Philips-Spectranetics, Shockwave, and Veryan, consulted for Bayer, Boston Scientific, CSI, Gore & Associates, Medtronic, Philips–Spectranetics, Intact Vascular, Shockwave, Veryan, and Vesper Medical Research, and received clinical trial or drug study funds from B. Braun, Bard Peripheral Vascular, Biotronik, Boston Scientific, Cardiovascular Systems, Inc, Cook Medical, Gore & Associates, Intact Vascular, Med Alliance, Medtronic, Philips-Spectranetics, Pluristem, PQ Bypass, Shockwave, Terumo, TriReme, University of Jena, and Veryan, and holds common stock in QT Medical.

Background: Restenosis (RS) poses a significant concern, leading to recurrent ischemia and the potential for amputation following intraluminal angioplasty in the treatment of Peripheral Artery Disease (PAD). Through microRNA microarray analysis, the study detected a significant downregulation of miR-199a-5p within arterial smooth muscle cells (ASMCs) associated with RS., Objective: This research aims to explore the possible function and the underlying mechanisms of miR-199a-5p in the context of RS., Methods: Primary ASMCs were extracted from the femoral arteries of both healthy individuals and patients with PAD or RS. The expression levels of miR-199a-5p were assessed using both qRT-PCR and in situ hybridization techniques. To examine the impacts of miR-199a-5p, a series of experiments were performed, including flow cytometry, TUNEL assay, EdU assay, CCK8 assay, Transwell assay, and wound closure assay. A rat carotid balloon injury model was employed to elucidate the mechanism through which miR-199a-5p mitigated neointimal hyperplasia., Results: MiR-199a-5p exhibited downregulation in RS patients and was predominantly expressed within ASMCs. Elevated the expression of miR-199a-5p resulted in an inhibitory effect of proliferation and migration in ASMCs. Immunohistochemistry and a dual-luciferase reporter assay uncovered that RS exhibited elevated expression levels of both HIF-1α and E2F3, and they were identified as target genes regulated by miR-199a-5p. The co-transfection of lentiviruses carrying HIF-1α and E2F3 alongside miR-199a-5p further elucidated their role in the cellular responses mediated by miR-199a-5p. In vivo , the delivery of miR-199a-5p via lentivirus led to the mitigation of neointimal formation following angioplasty, achieved by targeting HIF-1α and E2F3., Conclusion: MiR-199a-5p exhibits promise as a prospective therapeutic target for RS since it alleviates the condition by inhibiting the proliferation and migration of ASMCs via its regulation of HIF-1α and E2F3., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Ischemia reperfusion (IR) injury may result in rhabdomyolysis and compartment syndrome when blood supply returns after thrombectomy for patients with acute limb ischemia., Objective: We highlight the value of early diagnosis and treatment in post-thrombectomy patients with IR injuries in their lower legs., Case Description: Two patients received thrombectomy due to left superficial femoral artery occlusion. Both patients complained of left calf pain during ambulation at the 1- and 3-day follow up post-thrombectomy, as well as a heating sensation, swelling, weakness, and sensory changes in the affected leg. For early diagnosis musculoskeletal ultrasounds were performed and in both cases revealed swelling and change of echogenicity in the left calf. To further diagnosis, magnetic resonance imaging of the left leg revealed limb IR-induced muscular injury and rhabdomyolysis, respectively. In both cases, an electrodiagnostic study revealed peripheral nerve injury in the left leg. Medications were provided for neuropathic pain control and early rehabilitation was performed to improve function. In both cases, patients reported during their follow-up that their pain and muscle weakness had improved., Conclusion: When post-thrombectomy calf pain occurs early evaluation and treatment should be performed to identify any potential IR injury.

The femoropopliteal artery (FPA) is a long, flexible vessel that travels down the anteromedial compartment of the thigh as the femoral artery and then behind the kneecap as the popliteal artery. This artery undergoes various degrees of flexion, extension, and torsion during normal walking movements. The FPA is also the most susceptible peripheral artery to atherosclerosis and is where peripheral artery disease manifests in 80% of cases. The connection between peripheral artery location, its mechanical flexion, and its physiological or pathological biochemistry has been investigated for decades; however, histochemical methods remain poorly leveraged in their ability to spatially correlate normal or abnormal extracellular matrix and cells with regions of mechanical flexion. This study generates new histological image processing pipelines to quantitate tissue composition across high-resolution FPA regions-of-interest or low-resolution whole-section cross-sections in relation to their anatomical locations and flexions during normal movement. Comparing healthy ovine femoral, popliteal, and cranial-tibial artery sections as a pilot, substantial arterial contortion was observed in the distal popliteal and cranial tibial regions of the FPA which correlated with increased vascular smooth muscle cells and decreased elastin content. These methods aim to aid in the quantitative characterization of the spatial distribution of extracellular matrix and cells in large heterogeneous tissue sections such as the FPA. RESEARCH HIGHLIGHTS: Large-format histology preserves artery architecture. Elastin and smooth muscle content is correlated with distance from heart and contortion during flexion. Cell and protein analyses are sensitive to sectioning plane and image magnification., (© 2023 The Authors. Microscopy Research and Technique published by Wiley Periodicals LLC.)

Background: Longitudinal associations of noninvasive 2-dimensional phase-contrast magnetic resonance imaging (2D-PC-MRI) velocity markers of the superficial femoral artery (SFA) were analyzed along with the characteristics of peripheral artery disease (PAD). We hypothesized that the 2-year differences in MRI-based measures of SFA velocity were associated with longitudinal changes in markers of PAD., Methods: A total of 33 (11 diabetic, 22 nondiabetic) patients with PAD with baseline and 2-year follow-up MRI scans were included in this secondary analysis of the Effect of Lipid Modification on Peripheral Artery Disease after Endovascular Intervention Trial (ELIMIT). Electrocardiographically gated 2D-PC-MRI was performed at a proximal and a distal location of the distal SFA territory. SFA lumen, wall, and total vessel volumes and the normalized wall index (NWI) were analyzed., Results: Baseline characteristics did not differ between diabetic and nondiabetic PAD patients. Maximum proximal and distal SFA velocity measures did not differ between baseline and 2 years (41.98 interquartile range (IQR) (23.58-72.6) cm/s vs. 40.31 IQR (26.69-61.29) cm/s; P = 0.30). Pooled analysis (N = 33) showed that the 24-month change in the NWI was inversely associated with the 24-month change in the proximal maximal SFA velocity (beta = -168.36, R2 = 0.150, P value = 0.03). The 24-month change of the maximum velocity differences between the proximal and distal SFA locations was inversely associated with the 24-month changes in peak walking distance (beta = -0.003, R2 = 0.360, P value = 0.011)., Conclusion: The 2-year change of SFA plaque burden is inversely associated with the 2-year change of proximal peak SFA blood flow velocity. 2D-PC-MRI measured SFA velocity may be of interest in assessing PAD longitudinally., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives:  This study was conducted to assess the relationship between adventitial vasa vasorum neovascularization (VVn) in femoral artery of type 2 diabetic patients with macroangiopathy and the recruitment of macrophages and lymphocytes, and to relate the density of VVn to the occurrence of cardiovascular events., Materials:  Femoral artery samples were obtained from amputation cases. A total of 55 type 2 diabetic patients with macroangiopathy, 15 autopsy cases with type 2 diabetes without atherosclerosis., Methods:  Hematoxylin and eosin (H&E) staining to observe the histopathological features; Victoria blue staining to analyze the histological features; immunohistochemistry (CD34, CD68, CD20, and CD3) to determine the VVn density and the expression of macrophages, B lymphocytes, and T lymphocytes., Results:  Type 2 diabetic patients with macroangiopathy showed a higher mean adventitial VVn density in femoral artery (48.40 ± 9.39 no./mm 2 ) than patients with type 2 diabetes without atherosclerosis (19.75 ± 6.28 no./mm 2 ) ( p  < 0.01). In addition, the VVn density was positively associated with the expression of CD68 macrophages ( r  = 0.62, p  < 0.01) and CD20 B lymphocytes ( r  = 0.59, p  < 0.01). Type 2 diabetic patients with high VVn density showed more adverse cardiovascular events (27/35 vs. 8/20 events, p  = 0.006). In multivariable analysis adjusted for main risk factors for cardiovascular disease, VVn was still independently associated with adverse cardiovascular events ( p  = 0.01)., Conclusion:  VVn density in type 2 diabetic patients with macroangiopathy is positively correlated with the adventitial immune-inflammatory cell numbers and the development of atherosclerotic lesions. Furthermore, VVn density is associated with adverse cardiovascular events., Competing Interests: None declared., (Thieme. All rights reserved.)

Purpose: There is a little datum about the impact of paclitaxel dosage in patients undergoing drug-coated balloons (DCB) in endovascular therapy (EVT) for femoropopliteal lesions. In the current study, the authors sought to compare the clinical outcomes of low-dose (LD) and high-dose (HD) paclitaxel DCBs for patients undergoing EVT for femoropopliteal lesions in a real-world setting., Materials and Methods: The study population was derived from a multicenter registry named "Evaluation of clinical outcome after endovascular therapy for femoropopliteal artery disease in Kanagawa" (LANDMARK registry). This registry consists of patients from 5 hospitals in Kanagawa, Japan. Overall, 1,378 patients with 1,777 lesions received treatment between July 2017 and June 2020. Among these, DCB angioplasty was performed in 477 patients (516 lesions). Propensity score matching analysis was performed to compare the clinical outcomes of LD-DCB (Lutonix; Becton Dickinson and Company, Franklin Lakes, New Jersey) and HD-DCB (IN.PACT Admiral; Medtronic Vascular, Santa Clara, CA, USA)., Results: A total of 160 matched pairs of lesions were analyzed. Primary patency and freedom from target lesion revascularization at 2 years were similar between the two groups (LD-DCB vs. HD-DCB: 72% vs. 70%, p = 0.53; and 75% vs. 73%, p = 0.59, respectively)., Conclusion: No significant differences were found in the clinical outcomes between LD-DCB and HD-DCB angioplasty for femoropopliteal lesions., Level of Evidence: Level 3., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Background: Despite the increase in the number of patients with peripheral artery disease (PAD), the pathophysiology is not fully elucidated. Recently, angioscopy with a 0.48-megapixel equivalent resolution camera became available for patients with PAD. We aimed to compare the plaque component between native stenosis and occlusion in the femoropopliteal artery using this modality., Materials and Methods: Thirty-two consecutive patients who underwent endovascular treatment for native femoropopliteal artery disease with angioscopy were studied. The major angioscopic classifications of each lesion were defined as follows: atheromatous plaque (AP) was defined as luminal narrowing without any protrusion, calcified nodule (CN) was defined as a protruding bump with surface irregularity, a mainly reddish thrombus was defined as organizing thrombus (OG), and organized thrombus (OD) was defined by more than half of the thrombus showing a whitish intima-like appearance., Results: A total of 34 lesions (stenosis, n=18; occlusion, n=16) from 32 patients were included. All stenotic lesions showed AP or CN (n=8 [44%], n=10 [56%], respectively), whereas all occluded lesions showed OG or OD (n=5 [31%], n=11 [69%], respectively), which amounted to a statistically significant difference (p<0.001). In occluded lesions, stiff wires (>3 g) were required to cross all lesions classified as OD, whereas this was not always necessary for lesions classified as OG (11 [100%] of 11, 1 [25%] of 5, respectively; p=0.04). Yellow color plaques were observed to a similar degree in all angioscopic classifications. Major adverse limb events, defined as amputation and any reintervention at 12 months, were highly variable, depending on the angioscopic findings, and tended to be more frequently observed in CN and OD (13% in AP, 40% in CN, 0% in OT, and 36% in OD, p=0.25)., Conclusion: Angioscopy revealed varying components in stenosis and occlusion with different degrees of clinical impact. This may provide new information on the pathophysiology of PAD.

Background: Mechanism of femoropopliteal in-stent restenosis has been underappreciated., Aim: The aim of this animal study was to elucidate vascular response after femoropopliteal bare nitinol self-expanding stents (SESs) implantation., Methods: Misago, Smart Flex, or Innova stent was randomly implanted in 36 swine femoropopliteal arteries. At week 4, quantitative vessel analysis (QVA) was performed on 36 legs, of which 18 underwent histological evaluation after angiography. The remaining 18 legs underwent QVA and histological evaluation at week 13., Results: Fibrin deposition was excessive at week 4. Internal elastic lamina (IEL) progressively enlarged over time, and vessel injury developed from mild level at week 4 to moderate level at week 13. Vessel inflammatory reaction was mild to moderate at week 4, and was moderate to severe at week 13. Increased fibrin deposition was an early-acting, IEL enlargement and increased vessel inflammation were long-acting, and increased vessel injury and giant cells infiltration were late-acting contributors to neointimal hyperplasia (NIH). Stent type altered time-dependent process of vessel injury, vessel inflammation, eosinophils and giant cells infiltration. Misago had less fibrin deposition and vessel enlargement, and less progressive vessel injury, vessel inflammation, and eosinophils and giant cells infiltration. Net lumen as assessed by percent diameter stenosis or minimum lumen diameter was preserved with Misago, but was not preserved with the other stents., Conclusions: In the context of bare nitinol SES platform with less progressive mechanical stress and inflammatory reaction, the advantage of less NIH outweighed the disadvantage of less vessel enlargement, leading to net lumen preservation., (© 2022. The Author(s).)

Lipoprotein(a) [Lp(a)] is a risk factor for peripheral artery disease (PAD). However, the relationship between Lp(a) levels and clinical events after endovascular therapy (EVT) for the femoropopliteal artery in PAD patients remains unclear. Thus, this study aimed to assess the impact of Lp(a) levels on primary patency after EVT for de novo femoropopliteal lesions in PAD patients. A retrospective analysis was conducted on 109 patients who underwent EVT for de novo femoropopliteal lesions, and Lp(a) levels were measured before EVT between June 2016 and December 2019. Patients were divided into low Lp(a) [Lp(a) < 30 mg/dL; 78 patients] and high Lp(a) [Lp(a) ≥ 30 mg/dL; 31 patients] groups. The main outcome was primary patency following EVT. Loss of primary patency was defined as a peak systolic velocity ratio > 2.4 on a duplex scan or > 50% stenosis on angiography. Cox proportional hazards analysis was performed to determine whether high Lp(a) levels were independently associated with loss of primary patency. The mean follow-up duration was 28 months. The rates of primary patency were 83 and 76% at 1 year and 75 and 58% at 2 years in the low and high Lp(a) groups, respectively (P = 0.02). After multivariate analysis, High Lp(a)[Lp(a) ≥ 30 mg/dL] (hazard ratio 2.44; 95% CI 1.10-5.44; P = 0.03) and female sex (hazard ratio 2.65; 95% CI 1.27-5.51; P < 0.01) were independent predictors of loss of primary patency. Lp(a) levels might be associated with primary patency after EVT for de novo femoropopliteal lesions., (© 2022. Springer Japan KK, part of Springer Nature.)

For advanced hepatocellular carcinoma, an 80's woman underwent right inguinal reservoir port implantation and hepatic arterial infusion chemotherapy. The patient developed sepsis caused by methicillin-resistant Staphylococcus aureus 40 days after starting treatment. After the reservoir port was removed, an infected pseudoaneurysm developed. Interventional radiology treatment could not be completed because of the shape of the aneurysm, and deep femoral artery suture closure was conducted surgically. Unfortunately, the pseudoaneurysm recurred two months after surgery, and treatment for hepatocellular carcinoma was discontinued. It is important to remember that the formation of pseudoaneurysms is a complication after reservoir port placement.

Purpose: Although effectiveness and safety of many different paclitaxel coated balloons in the treatment of peripheral arterial disease (PAD) are extensively studied, there is a lack of direct head-to-head comparison studies. To meet this need and to avoid potential "class-effects", the BIOPACT was set up. The purpose is to demonstrate the safety and efficacy of the Passeo-18 Lux DCB (Biotronik) for treatment of patients with symptomatic PAD due to femoropopliteal lesions., Methods: 302 patients are randomized in a 1:1 manner to treatment with either the Passeo-18 Lux DCB or the IN.PACT Admiral DCB (Medtronic) for testing of a formal non-inferiority hypothesis. The participants will be followed for 5 years. The primary efficacy endpoint is freedom from clinically-driven target lesion revascularization (CD-TLR) at 12 months, defined as any re-intervention at the target lesion due to symptoms, drop of ankle brachial index (ABI) > 20% or > 0.15 compared to post-procedural ABI. Primary safety endpoint is a composite of freedom from device/procedure-related death through 30 days post-index procedure, freedom from major target limb amputation and clinically-driven target vessel revascularization (CD-TVR) through 12 months post-index procedure. Secondary endpoints can be found at clinicaltrials.gov, ID NCT03884257., Discussion: As full enrolment was reached by the beginning of September, the investigators expect complete analysis of the primary endpoints by the end of 2022; Meanwhile preliminary results will be disclosed during 2022. As in terms of randomized head-to-head efficacy and safety analysis, this study on paclitaxel coated balloons may provide additional information to clinicians and healthcare providers. Trial registration ClinicalTrials.gov ID: NCT03884257 LEVEL OF EVIDENCE: Level 2, Randomized trial., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Background: Paclitaxel-coated balloons have shown safety and efficacy in the short- to intermediate-term; however, long-term data remain limited., Objectives: To report late safety and efficacy outcomes for a low-dose paclitaxel drug-coated balloon (DCB) compared with percutaneous transluminal angioplasty (PTA) in femoropopliteal lesions from a large randomized controlled trial (RCT)., Methods: ILLUMENATE Pivotal is a multicenter, single-blind RCT conducted across 43 US and EU centers to examine the safety and efficacy of the Stellarex DCB for the treatment of femoropopliteal disease. Assessments were recorded for all active patients at 36 and 48 months. Vital status of patients formally exited from the study was also collected., Results: Primary patency through 36 months for patients treated with DCB was significantly higher compared with PTA (p=0.016). The primary safety endpoint through 36 months was 77.4% and 72.4%, respectively (p=0.377). Kaplan-Meier analysis indicated that a higher proportion of DCB subjects were event-free compared with PTA at all study visits. The rate of major adverse event (MAE) through 48 months was 32.9% in the DCB group and 37.9% in the PTA group (p=0.428). No differences in the rate of mortality were evident through 48 months of follow-up with 15.6% in the DCB group and 15.2% in the PTA group (p=0.929)., Conclusions: Stellarex DCB was associated with significantly higher patency compared with PTA through 3 years with no mortality difference detected through 4 years. The data from the ILLUMENATE Pivotal RCT support the long-term safety and efficacy of the low-dose Stellarex DCB.

Background: A clear patency benefit of a drug-eluting stent (DES) over bare metal stents (BMSs) for treating peripheral artery disease of the femoropopliteal segment has not been definitively demonstrated. The EMINENT study (Trial Comparing Eluvia Versus Bare Metal Stent in Treatment of Superficial Femoral and/or Proximal Popliteal Artery) was designed to evaluate the patency of the Eluvia DES (Boston Scientific, Marlborough, MA), a polymer-coated paclitaxel-eluting stent, compared with BMSs for the treatment of femoropopliteal artery lesions., Methods: EMINENT is a prospective, randomized, controlled, multicenter European study with blinded participants and outcome assessment. Patients with symptomatic peripheral artery disease (Rutherford category 2, 3, or 4) of the native superficial femoral artery or proximal popliteal artery with stenosis ≥70%, vessel diameter of 4 to 6 mm, and total lesion length of 30 to 210 mm were randomly assigned 2:1 to treatment with DES or BMS. The primary effectiveness outcome was primary patency at 12 months, defined as independent core laboratory-assessed duplex ultrasound peak systolic velocity ratio ≤2.4 in the absence of clinically driven target lesion revascularization or surgical bypass of the target lesion. Primary sustained clinical improvement was a secondary outcome defined as a decrease in Rutherford classification of ≥1 categories compared with baseline without a repeat target lesion revascularization. Health-related quality of life and walking function were assessed., Results: A total of 775 patients were randomly assigned to treatment with DES (n=508) or commercially available BMSs (n=267). Baseline clinical, demographic, and lesion characteristics were similar between the study groups. Mean lesion length was 75.6±50.3 and 72.2±47.0 mm in the DES and BMS groups, respectively. The 12-month incidence of primary patency for DES treatment (83.2% [337 of 405]) was significantly greater than for BMS (74.3% [165 of 222]; P <0.01). Incidence of primary sustained clinical improvement was greater among patients treated with the DES than among those who received a BMS (83.0% versus 76.6%; P =0.045). The health-related quality of life dimensions of mobility and pain/discomfort improved for the majority of patients in both groups (for 66.4% and 53.6% of DES-treated and for 64.2% and 58.1% of BMS-treated patients, respectively) but did not differ significantly. At 12 months, no statistical difference was observed in all-cause mortality between patients treated with the DES or BMS (2.7% [13 of 474] versus 1.1% [3 of 263]; relative risk, 2.4 [95% CI, 0.69-8.36]; P =0.15)., Conclusions: By demonstrating superior 1-year primary patency, the results of the EMINENT randomized study support the benefit of using a polymer-based paclitaxel-eluting stent as a first-line stent-based intervention for patients with symptomatic peripheral artery disease attributable to femoropopliteal lesions., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02921230.

Background: The objective of the RANGER II SFA long lesion cohort analysis was to evaluate the safety and effectiveness of the Ranger drug-coated balloon (DCB) in patients with lesion lengths greater than 100 mm., Methods: Patients from the RANGER II SFA randomized controlled trial and long balloon sub-study were included in the long lesion cohort if their baseline lesion measurement was > 100 mm and if they had been treated with a RANGER DCB. Patients had symptomatic lower limb peripheral artery disease and Rutherford classification 2-4 symptomatology. The endpoints of interest included the 12-month target lesion primary patency and freedom from major adverse events (MAEs).Additional patient outcomes including changes in Rutherford classification were also evaluated., Results: A total of 129 patients met the inclusion criteria and were included in the long lesion cohort. Mean lesion length was 144.5 ± 31.7 mm. Seventy-five lesions had Peripheral Arterial Calcium Scoring System (PACSS) grades 3 (33.3%, 43/129) and 4 (24.8%, 32/129). The Kaplan-Meier estimate of the primary patency rate at 12 months was 88.0%. The rate of freedom from MAEs at 12 months was 95.1% (117/123; 95% CI: 89.7%, 98.2%); all MAEs were clinically driven target lesion revascularization (4.9%, 6/123). The 12-month mortality rate was 2.4% (3/125)., Conclusions: Patients with lesions > 100 mm treated with Ranger DCBs demonstrated excellent 1-year safety and efficacy results, comparable to those of the overall RANGER II SFA randomized clinical trial. This suggests that the Ranger DCB can provide consistent results regardless of lesion length. (ClinicalTrials.gov Identifier: NCT03064126) .

Purpose: Sex-based differences in peripheral arterial disease are well-known. Aim of this study was to evaluate sex-related disparities in patients undergoing endovascular treatment of isolated popliteal artery lesions., Material and Methods: Between 1th January 2004 and 1th January 2021 304 patients underwent endovascular treatment of an isolated popliteal artery lesion at three vascular centers. A retrospective analysis was performed comparing the outcomes in female versus male patients., Results: The majority of the patients were female (51.3%). Male patients were younger (70.4 vs. 76.8 years, p < 0.01). Hyperlipidemia (62.2% vs. 45.5%, p < 0.01) and diabetes (62% vs. 40%, p < 0.01) were more common in male group. There were more current and former smokers in the male group (p = 0.04 and p = 0.01). There were no differences regarding lesion length (mean 94.5 mm) nor location of the lesion. Technical success was comparable in both groups 94.6% vs. 97.4%), no differences in terms of in-hospital complications (9.5% vs. 7.7%) were found. At 3 years estimates did not demonstrate any difference in terms of clinically driven target lesion revascularization (23% vs. 34%), secondary patency (86% vs. 96%), and all-cause mortality (77% vs. 67%) between the two groups., Conclusion: In our experience the female sex showed clinical signs of popliteal artery lesion at higher age with less aggressive atherosclerotic risk factors. However, during the follow-up no sex-related significant differences were found in terms of morphological and clinical outcomes after endovascular revascularization., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Background: First-generation drug-coated balloons (DCBs) have significantly reduced the rate of restenosis compared with balloon angioplasty alone; however, high rates of bailout stenting and dissections persist. The Chocolate Touch DCB is a nitinol constrained balloon designed to reduce acute vessel trauma and inhibit neointima formation and restenosis., Methods: Patients with claudication or ischemic rest pain (Rutherford class 2-4) and superficial femoral or popliteal disease (≥70% stenosis) were randomized 1:1 to Chocolate Touch or Lutonix DCB at 34 sites in the United States, Europe, and New Zealand. The primary efficacy end point was DCB success, defined as primary patency at 12 months (peak systolic velocity ratio <2.4 by duplex ultrasound without clinically driven target lesion revascularization in the absence of clinically driven bailout stenting). The primary safety end point was freedom from major adverse events at 12 months, a composite of target limb-related death, major amputation, or reintervention. Both primary end points were tested for noninferiority, and if met, sequential superiority testing for efficacy followed by safety was prespecified. An independent clinical events committee, and angiographic and duplex ultrasound core laboratories blinded to treatment allocation reviewed all end points., Results: A total of 313 patients were randomized to Chocolate Touch (n=152) versus Lutonix DCB (n=161). Follow-up at 1 year was available in 94% of patients. The mean age was 69.4±9.5 years, the average lesion length was 78.1±46.9 mm, and 46.2% had moderate-to-severe calcification. The primary efficacy rates of DCB success at 12 months was 78.8% (108/137) with Chocolate Touch and 67.7% (88/130) with Lutonix DCB (difference, 11.1% [95% CI, 0.6-21.7]), meeting noninferiority ( P noninferiority <0.0001) and sequential superiority ( P superiority =0.04). The primary safety event rate was 88.9% (128/144) with Chocolate Touch and 84.6% (126/149) with Lutonix DCB ( P noninferiority <0.001; P superiority =0.27)., Conclusions: In this prospective, multicenter, randomized trial, the second-generation Chocolate Touch DCB met both noninferiority end points for efficacy and safety and was more effective than Lutonix DCB at 12 months for the treatment of femoropopliteal disease., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02924857.

Objective: Restenosis is a common complication after endovascular treatment of peripheral artery disease. Drug-coated balloon (DCB) treatment has been proven safe and effective in reducing the rate of restenosis for simple and short lesions. However, the clinical results of DCBs for long lesions are still very limited. This study aimed to evaluate the efficacy and safety of DCBs in the treatment of long femoropopliteal artery disease. And the results of this study will also complement the existing evidence of DCB treatment of long lesions., Methods: Patients with lesion length ≥ 15cm according to computed tomography angiography (CTA) or angiography in the AcoArt I Study were included into this study. Based on the balloon catheter used in treatment, patients were divided into the DCB group and the percutaneous transluminal angioplasty (PTA) group. The demographic, lesion, and procedural characteristics and 24-month follow-up results were compared between the 2 groups. The primary efficacy endpoints were angiographic late lumen loss (LLL) at 6 months or at the time of clinically driven target lesion revascularization (CD-TLR), primary patency (PP), freedom from CD-TLR, and changes in the ankle-brachial index (ABI) and Rutherford class during 24 months of follow-up. The safety endpoint was the occurrence of major adverse events., Results: The total number of patients was 87, including 42 in the DCB group and 45 in the PTA group. There were no significant differences between the 2 groups in demographic, lesion,and procedural characteristics. The 6-month follow-up angiography showed that the LLL was significantly smaller in the DCB group than the PTA group (0.27 ± 0.90 mm vs 1.32 ± 0.91 mm; P < 0.001). At 24 months, compared with the PTA group, the DCB group had a significantly higher rate of freedom from CD-TLR (81.58% vs 43.18%; P < 0.001) and a significantly higher PP rate (46.88% vs 15.00%; P = 0.003). The DCB group had a significantly higher ABI than the PTA group at 6, 12, and 24 months (P < 0.001, P = 0.004 and P = 0.018, respectively). The DCB group had a better Rutherford class than the PTA group at 6 and 12 months (P = 0.033 and P = 0.012, respectively); the Rutherford class did not significantly differ between the 2 groups at 24 months (P = 0.127). The incidence of major adverse events did not significantly differ between the 2 groups., Conclusion: The effectiveness of the DCB is superior to a standard uncoated balloon in treating long lesions during 24 months of follow-up. Furthermore, the safety of the DCB is equivalent to that of PTA., (Copyright © 2021. Published by Elsevier Inc.)

Background: Data are mixed concerning the safety and effectiveness of drug-coated balloons (DCBs) for treating below-the-knee (BTK) lesions., Aims: The aim of this study was to assess the safety and effectiveness of the IN.PACT 014 paclitaxel-coated balloon catheter versus conventional percutaneous transluminal angioplasty (PTA) for infrapopliteal chronic total occlusions (CTOs) in patients with chronic limb-threatening ischaemia (CLTI)., Methods: The IN.PACT BTK randomised study is a prospective, multicentre, randomised pilot study. Fifty CLTI participants (Rutherford clinical category 4-5) with BTK CTOs were randomised 1:1 to DCB (N=23) or PTA (N=27). The primary effectiveness endpoint was late lumen loss (LLL) at 9 months post procedure. Safety outcomes up to 9 months included all-cause mortality, major target limb amputation, and clinically driven target lesion revascularisation (CD-TLR)., Results: Mean lesion length was 215.41±83.81 mm in the DCB group and 218.19±80.43 mm for PTA (p=0.806). The 9-month angiographic LLL was 0.892±0.774 mm for the DCB group and 1.312±0.720 mm for the PTA group (p=0.070) in a classic analysis, and 0.592±0.944 mm for DCB and 1.260±0.810 mm for PTA (p=0.017) in a subsegmental analysis. The Kaplan-Meier estimated freedom from CD-TLR up to 9 months was 91.1% for DCB and 91.8% for PTA (log-rank p=0.942). At 9 months, 1 patient died in the DCB group and 2 in the PTA group (p=1.000); there were no major target limb amputations in either arm., Conclusions: The 9-month subsegmental LLL was lower after treatment with the IN.PACT 014 DCB compared with PTA with no differences in safety or revascularisation events in a small complex population of patients with BTK CTOs., Clinicaltrials: gov: NCT02963649.

Purpose: An indwelling arterial access system via the brachial artery, System-i, has been previously reported. We have modified the technique for the femoral artery approach. This study aimed to evaluate the feasibility and safety of the modified System-i for patients with malignant liver tumors., Materials and Methods: The modified System-i is an indwelling catheter that provides vascular access for inserting a microcatheter without repeated punctures to the femoral artery. Between 2018 and 2020, the system was implanted for 50 patients with malignant liver tumors. We used the system for patients with difficulty in inserting the conventional indwelling catheter system. To place the system, a side-holed catheter was implanted in the femoral artery, and the tip of the catheter was placed in the superficial femoral artery through the contralateral iliac artery. Using this system, transcatheter arterial chemoembolization or hepatic arterial infusion chemotherapy was performed. A shaped high-flow microcatheter and a non-tapered microcatheter were used with the system. The technical aspects and outcomes of the system were also assessed., Results: Implantation of the system was successful in all patients. The median implantation time was 40 min. The main reason for implantation was obstruction or stenosis of the hepatic artery. Among the 50 patients, 11 (22%) showed complications, of which four had major complications/class C based on the SIR criteria., Conclusion: The modified System-i is a safe system that can be a feasible repeated interventional radiological treatment via the femoral approach. We need to evaluate the efficacy of this system in the treatment of advanced cancers in the future. The modified System-i is a novel indwelling catheter system that allows vascular access to perform intermittent transarterial therapy, such as transcatheter arterial chemoembolization and hepatic arterial infusion chemotherapy via the femoral approach. In this study, we report the technical details and safety of the system., (© 2021. Japan Radiological Society.)

Mesenchymal stem cells (MSCs) can promote osteogenesis and are a promising therapy for postmenopausal osteoporosis. However, the relationship between improved intraosseous microcirculation and increased bone mass induced by MSCs in postmenopausal osteoporosis remains unclear. After the primary MSCs were characterized, they were transplanted into ovariectomized mice. MSCs transplantation enhanced the trabecular number, trabecular bone volume/total volume, and trabecular bone mineral density in ovariectomized mice. To determine the role of MSCs in vascular repair, mice were subjected to femoral artery ligation. Through laser speckle flowmetry, vascular perfusion and femoral trabecular bone and cortical bone analyses, we determined the effects of MSCs in promoting intraosseous angiogenesis and preventing osteoporosis in mice. MSCs effectively prevented postmenopausal osteoporosis development, which is associated with the involvement of MSCs in reestablishment of microcirculation within the skeleton., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Limited data are available regarding the vascular response after fluoropolymer paclitaxel-eluting stent (FP-PES) implantation. This study sought to assess the vascular response at 6 and 12 months after FP-PES implantation for femoropopliteal artery lesions using serial optical coherence tomography (OCT) examination., Methods and results: From the IMPERIAL trial, this study evaluated 10 de novo femoropopliteal lesions treated with FP-PES. The primary study endpoint was neointimal tissue coverage at a 6- and 12-month follow up, as assessed by serial OCT examination. The incidence of peri-strut low-intensity area (PLIA) and extra-stent lumen (ESL) was also assessed. A total of 203 matched cross-sectional images were evaluated at 6 and 12 months (5,615 and 5,763 struts, respectively). From 6 to 12 months, the mean neointimal thickness tended to increase from 198 µm to 233 µm, with a significant reduction in the incidence of malapposed struts (0.59% vs. 0.28%, P=0.039). Conversely, uncovered struts and PLIA were more frequently observed at 12 months (4.4% vs. 7.8%, P=0.01; 12.7% vs. 21.0%, P<0.001, respectively). The ESL area significantly increased over time without any difference in its incidence (0.24±0.32 mm 2 vs. 0.38±0.36 mm 2 , P=0.009)., Conclusions: Neointimal proliferation was markedly inhibited from 6 to 12 months after FP-PES implantation, whereas the incidence of uncovered struts and PLIA significantly increased over time with the enlargement of ESL.

Aim: Originally developed for predicting the risk of stroke in patients with atrial fibrillation (AF), the CHA 2 DS 2 -VASc score also has the potential to predict the risk of other cardiovascular disease. This study aimed to investigate the prognostic value of the CHA 2 DS 2 -VASc score in patients with peripheral artery disease (PAD) requiring Femoral popliteal (FP) endovascular therapy (EVT)., Methods: This multicenter, retrospective study analyzed the clinical database of 2190 patients who underwent FP EVT for symptomatic PAD (Rutherford categories 2-4) between January 2010 and December 2018. We calculated the CHA 2 DS 2 -VASc score and then investigated the association between the score, as well as AF, and their prognosis. Outcome measures were major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs)., Results: During a median follow-up of 3.0 years (interquartile range, 1.5-5.0 years), 532 MACEs and 562 MALEs occurred. The CHA 2 DS 2 -VASc score and AF were independently associated with an increased risk of MACEs; their adjusted hazard ratios [95% confidence intervals] were 1.28 [1.20-1.36] (P＜0.001) per 1-point increase and 1.49 [1.06-2.09] (P=0.022), respectively. The CHA 2 DS 2 -VASc score was almost linearly associated with MACEs, without any clear threshold point. On the other hand, these variables were not associated with MALEs risk (P=0.32 and 0.48)., Conclusion: The CHA 2 DS 2 -VASc score and AF were independently associated with the increased risk of MACEs but not of MALEs in patients with symptomatic PAD who underwent FP EVT. The score might be useful in stratifying the MACEs risk in this type of patients.

Background The subintimal approach (SA) is widely used in endovascular therapy for femoropopliteal chronic total occlusion lesions. However, when compared with the intraluminal approach (IA), the safety and efficacy of SA in real-world practice are not well characterized. Furthermore, there is a paucity of data on the clinical impact of subintimal and intraluminal wire passage (SWP and IWP, respectively) assessed by intravascular ultrasound. Methods and Results From the IVORY (Intravascular Ultrasound-Supported Endovascular Therapy in Superficial Femoral Artery) registry, this study included 500 patients undergoing endovascular therapy for femoropopliteal chronic total occlusion lesions (SA, n=67; IA, n=433; and SWP, n=186; IWP, n=314). The primary end point was the cumulative 1-year incidence of restenosis. The rate of perioperative complications was also assessed. Propensity score matching analysis was performed to adjust for the intergroup differences. After propensity score matching, the final study population consisted of 59 pairs (SA, n=59; IA, n=348) and 170 pairs (SWP, n=170; IWP, n=293), respectively. Cumulative 1-year incidence of restenosis was comparable between the SA and IA groups (41.0% versus 43.4%, P =0.40). No significant difference in 1-year restenosis rate between the SWP and IWP groups was observed (48.2% versus 40.8%, P =0.40), although the SWP group tended to be a higher rate of perioperative complications than the IWP group (8.2% versus 4.1%, P =0.07). Conclusions At 1 year, both SA and IA showed acceptable results for femoropopliteal chronic total occlusion lesions. Cumulative 1-year incidence of restenosis was not significantly different between SWP and IWP, whereas perioperative complications occurred more frequently in SWP than in IWP. Registration URL: https://www.umin.ac.jp; Unique identifier: UMIN000020472.

Objective: Vascular leiomyomas are rare begin tumor comprising mature vascular smooth muscles that originate in the tunica media of the blood vessels. Most of the tumors arise from the veins. Only a dozen cases of artery-arising vascular leiomyoma have been reported, most of which are presented as small nodules in the hand., Methods: Here we report an interesting case of a large artery-arising vascular leiomyoma and perform a systematic review., Results: A 55-year-old man complained a 6 × 3 cm firm, mobile, tender and pulseless mass in the medial region of his left thigh. The computed tomography showed a well-demarcated fusiform tumor encircling the superficial femoral artery and was enhanced significantly with contrast. The patency of the superficial femoral artery was intact. The magnetic resonance image exhibited slightly hypointense relative to skeletal muscle on T1-weighted images and a heterogeneous appearance on T2-weighted images. We performed the en bloc resection of the tumor and used a vascular graft to revascularize the artery through end-to-end anastomosis. After histopathological assessments, the tumor was diagnosed as an artery-arising vascular leiomyoma. We also performed a systematic review on artery-arising leiomyomas, discovering 21 cases. Most of the artery-arising vascular leiomyomas were small nodules (mean length: 2.4cm) and most of them were superficial solitary mass located in the hand (13 cases, 62%). Excision of the tumor was an effective treatment. The histological subtype of the artery-arising vascular leiomyoma in all cases was solid type. During the follow-up of each patient, there was no recurrence., Conclusions: Artery-arising vascular leiomyomas are extremely rare. Most of them are painless and locate in the hand. Their pathological subtype is solid type in all patients. Due to their begin nature, excision is a cure with little chance of recurrence., (Copyright © 2021. Published by Elsevier Inc.)

In-stent restenosis (ISR) represents a major drawback of stented superficial femoral arteries (SFAs). Motivated by the high incidence and limited knowledge of ISR onset and development in human SFAs, this study aims to (i) analyze the lumen remodeling trajectory over 1-year follow-up period in human stented SFAs and (ii) investigate the impact of altered hemodynamics on ISR initiation and progression. Ten SFA lesions were reconstructed at four follow-ups from computed tomography to quantify the lumen area change occurring within 1-year post-intervention. Patient-specific computational fluid dynamics simulations were performed at each follow-up to relate wall shear stress (WSS) based descriptors with lumen remodeling. The largest lumen remodeling was found in the first post-operative month, with slight regional-specific differences (larger inward remodeling in the fringe segments, p < 0.05). Focal re-narrowing frequently occurred after 6 months. Slight differences in the lumen area change emerged between long and short stents, and between segments upstream and downstream from stent overlapping portions, at specific time intervals. Abnormal patterns of multidirectional WSS were associated with lumen remodeling within 1-year post-intervention. This longitudinal study gave important insights into the dynamics of ISR and the impact of hemodynamics on ISR progression in human SFAs., (© 2021. The Author(s).)

Objective: Arterial restenosis is the pathological narrowing of arteries after endovascular procedures, and it is an adverse event that causes patients to experience recurrent occlusive symptoms. Following angioplasty, vascular smooth muscle cells (SMCs) change their phenotype, migrate, and proliferate, resulting in neointima formation, a hallmark of arterial restenosis. SIKs (salt-inducible kinases) are a subfamily of the AMP-activated protein kinase family that play a critical role in metabolic diseases including hepatic lipogenesis and glucose metabolism. Their role in vascular pathological remodeling, however, has not been explored. In this study, we aimed to understand the role and regulation of SIK3 in vascular SMC migration, proliferation, and neointima formation., Approach and Results: We observed that SIK3 expression was low in contractile aortic SMCs but high in proliferating SMCs. It was also highly induced by growth medium in vitro and in neointimal lesions in vivo. Inactivation of SIKs significantly attenuated vascular SMC proliferation and up-regulated p21CIP1 and p27KIP1. SIK inhibition also suppressed SMC migration and modulated actin polymerization. Importantly, we found that inhibition of SIKs reduced neointima formation and vascular inflammation in a femoral artery wire injury model. In mechanistic studies, we demonstrated that inactivation of SIKs mainly suppressed SMC proliferation by down-regulating AKT (protein kinase B) and PKA (protein kinase A)-CREB (cAMP response element-binding protein) signaling. CRTC3 (CREB-regulated transcriptional coactivator 3) signaling likely contributed to SIK inactivation-mediated antiproliferative effects., Conclusions: These findings suggest that SIK3 may play a critical role in regulating SMC proliferation, migration, and arterial restenosis. This study provides insights into SIK inhibition as a potential therapeutic strategy for treating restenosis in patients with peripheral arterial disease.

Atherosclerosis may starts early in life and each artery has peculiar characteristics likely affecting atherogenesis. The primary objective of the work was to underpin the microRNA (miR)-profiling differences in human normal femoral, abdominal aortic, and carotid arteries. The secondary aim was to investigate if those identified miRs, differently expressed in normal conditions, may also have a role in atherosclerotic arteries at adult ages. MiR-profiles were performed on normal tissues, revealing that aorta and carotid arteries are more similar than femoral arteries. MiRs emerging from profiling comparisons, i.e., miR-155-5p, -27a-5p, and -139-5p, were subjected to validation by RT-qPCR in normal arteries and also in pathological/atheroma counterparts, considering all the available 20 artery specimens. The three miRs were confirmed to be differentially expressed in normal femoral vs aorta/carotid arteries. Differential expression of those miRs was also observed in atherosclerotic arteries, together with some miR-target proteins, such as vimentin, CD44, E-cadherin and an additional marker SLUG. The different expression of miRs and targets/markers suggests that aorta/carotid and femoral arteries differently activate molecular drivers of pathological condition, thus conditioning the morphology of atheroma in adult life and likely suggesting the future use of artery-specific treatment to counteract atherosclerosis., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Previous studies reported that single vascular atherosclerosis was an effective indicator for white matter lesions (WMLs)., Purpose: To investigate the added value of femoral atherosclerosis for determining severity of WMLs by carotid atherosclerosis using three-dimensional vessel wall magnetic resonance imaging (MRI)., Material and Methods: Elderly individuals without cardiovascular symptoms within the previous six months were recruited. The plaque features of carotid and femoral arteries were evaluated and compared between individuals with WML score ≤ 3 and those with WML score > 3. Logistic regression and receiver operating characteristic (ROC) analyses were used to determine the value of plaque features in discriminating WMLs with score > 3., Results: In total, 112 individuals (49 men, mean age 72.0±5.6 years) were included. Participants with a WML score > 3 showed a significantly greater carotid wall area and femoral artery stenosis and higher incidence of carotid calcification and femoral artery calcification and lipid-rich necrotic cores (LRNC) compared to those with a WML score ≤ 3 (all P  < 0.05). Carotid artery calcification and femoral artery calcification, LRNC, and stenosis were found to be significantly associated with severe WMLs before and after adjustment for clinical factors (odds ratio 1.51-3.79, all P  < 0.05). ROC analysis showed, in discriminating severe WMLs, the area under the curve increased from 0.615 to 0.754 after combining femoral artery LRNC and stenosis with carotid calcification compared to the carotid calcification alone., Conclusion: Characteristics of femoral artery atherosclerosis determined by vessel wall MRI have added value for carotid atherosclerosis in determining the severity of WMLs.

The aim of the study is to examine the mechanism of Aralia armata (Wall.) Seem (AAS) in improving intimal hyperplasia after vascular injury in rats. Rats with femoral artery injury were randomly divided into three groups: the model group, AAS low-dose group (40 mg/kg), and AAS high-dose group (80 mg/kg). The sham operation group was used as a control group. HE staining was used to observe the changes in femoral artery vessels. Immunohistochemistry was adopted to detect α -SMA, PCNA, GSK-3 β , and β -catenin proteins in femoral artery tissue. The CCK-8 test and wound healing assay were employed to analyze the effect of AAS on proliferation and migration of vascular smooth muscle cells (VSMCs) cultured in vitro . Western blotting (WB) and polymerase chain reaction (PCR) assays were used to evaluate the molecular mechanism. AAS reduced the stenosis of blood vessels and the protein expressions of α -SMA, PCNA, GSK-3 β , and β -catenin compared to the model group. In addition, AAS (0-15  μ g/mL) effectively inhibited the proliferation and migration of VSMCs. Moreover, the results of WB and PCR showed that AAS could inhibit the activation of β -catenin induced by 15% FBS and significantly decrease the expression levels of Wnt3 α , Dvl-1, GSK-3 β , β -catenin, and cyclin D1 in the upstream and downstream of the pathway. AAS could effectively inhibit the proliferation and migration of neointima after vascular injury in rats by regulating the Wnt/ β -catenin signaling pathway., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Xiangpei Zhao et al.)

Background: Self-expanding nitinol stent (SENS) implantation is commonly oversized in the superficial femoral artery (SFA), and leads to chronic outward force (COF) and in-stent restenosis (ISR). This study aimed to investigate the impact of COF of oversizing SENS on ISR of SFA., Methods: In patients with implanted SENS in SFA, intimal hyperplasia especially between proximal segment and distal segment was evaluated by quantitative angiography, and the impact of COF on mid-term angiographic outcomes was investigated. In addition, porcine model with implanted SENS was used to evaluate the impact of COF on angiographic and histopathologic outcomes at 1 month. Excised stented arteries were evaluated by histopathologic analysis., Results: We analyzed 65 SENS in 61 patients with follow-up angiography at 6 months to 1 year. The baseline diameter was 6.8 ± 0.71 mm and length were 97.0 ± 33.8 mm for the SENS. The ratio of the diameter of the stent to the reference vessel was 1.3 ± 0.24 at the proximal portion and 1.53 ± 0.27 at the distal portion (P < 0.001). In the long SFA stent, stent-to-vessel ratio was significantly higher in the distal stent than in the proximal stent (1.3 ± 0.2 vs. 1.55 ± 0.25, P = 0.001). ISR incidence was higher at the distal stent (37.3% vs 52.6%, P = 0.029). All 11 pigs survived for 4 weeks after SENS implantation. The vessel diameter was 4.04 ± 0.40 mm (control group) vs 4.45 ± 0.63 mm (oversized group), and the implanted stent diameter was 5.27 ± 0.46 mm vs. 7.18 ± 0.4 mm (P = 0.001). The stent-to-vessel diameter ratio was 1.31 ± 0.12 versus 1.63 ± 0.20 (P < 0.001). After 4 weeks, restenosis % was 29.5 ± 12.9% versus 46.8 ± 21.5% (P = 0.016). The neointimal area was 5.37 ± 1.15 mm 2 vs. 8.53 ± 5.18 mm 2 (P = 0.05). The restenosis % was 39.34 ± 8.53% versus 63.97 ± 17.1% (P = 0.001)., Conclusions: COF is an important cause of restenosis in the distal portion of the SFA stent. Optimal sizing of the SFA stent is important to reduce the incidence of restenosis. Therefore, COF was an important factor of restenosis following distal SFA stenting.

Recently, coronary angiography (CAG) and percutaneous coronary intervention (PCI) via the distal radial access (DRA), are gaining attention owing to fewer complications. Despite the advantages of the DRA, there is difficulty to initiate this new vascular approach. The data from 1000 patients who underwent CAG and PCI via the DRA by a single experienced radial operator were retrospectively analyzed. The primary outcome was the success rate of the DRA per 100 cases. Moreover, the predictors of the failed DRA were analyzed. Overall, 952 (95.2%) of the total 1,000 patients underwent a successful DRA. After experiencing 200 cases, the DRA success rate was well maintained at > 94%, and there was no difference in success rate per 100 cases (P trend  = 0.216). The predictors of failure were female sex [odds ratio (OR) 1.84, 95% confidence interval (CI) 1.01-3.39, P = 0.049] and systolic blood pressure (SBP) of < 120 mmHg (OR 1.87, 95% CI 1.04-3.36, P = 0.036). For achieving a stable DRA with the success rate of > 94%, 200 procedures would be needed. Moreover, this new approach could fail in women and patients with low SBP.Trial registration: https://cris.nih.go.kr/cris/index/index.do (Unique identifier: KCT0005349).

Objective: To compare the safety and efficacy between the SpiderFX EPD and Emboshield NAV6 filter in the collection of embolic debris created from lower limb atherectomy procedures in patients with PAD., Materials and Methods: Between January 2014 and October 2015, 507 patients with symptomatic peripheral artery disease were treated with directional atherectomy (SilverHawk), rotational atherectomy (JetStream), or laser atherectomy (Turbo Elite) based on operator discretion. Emboshield NAV6 ( n  = 161) and SpiderFX ( n  = 346) embolic protection devices were used with each of the 3 atherectomy devices. The primary study endpoint was 30-day freedom from major adverse events (MAEs). An MAE was defined as death, MI, TVR, thrombosis, dissection, distal embolization, perforation at the level of the filter, and unplanned amputation. A descriptive comparison of the MAE rates between Emboshield NAV6 and SpiderFX embolic protection devices was conducted., Results: The freedom from major adverse event (MAE) rate was 92.0% (CI: 86.7%, 95.7%) in patients who received an Emboshield NAV6 filter compared to 91.6% (CI: 88.2%, 94.3%) in patients who received the SpiderFX filter ( p =0.434). The lower limit of 86.7% freedom from major adverse event rate in the Emboshield NAV6 group was above the performance goal of 83% ( p < 0.0008)., Conclusions: There were no significant clinical outcome differences between Emboshield NAV6 and SpiderFX EPD filters in the treatment of lower extremities. This evaluation indicates the safety and efficacy to use either filter device to treat PAD patients with lower extremity lesions., Competing Interests: There are no conflicts of interest., (Copyright © 2021 Prakash Krishnan et al.)

Adventitial abnormalities including enhanced vasa vasorum malformation are associated with development and vulnerability of atherosclerotic plaque. However, the mechanisms of vasa vasorum malformation and its role in vascular remodeling have not been fully clarified. We recently reported that ninjurin-1 (Ninj1) is a crucial adhesion molecule for pericytes to form matured neovessels. The purpose is to examine if Ninj1 regulates adventitial angiogenesis and affects the vascular remodeling of injured vessels using pericyte-specific Ninj1 deletion mouse model. Mouse femoral arteries were injured by insertion of coiled wire. Four weeks after vascular injury, fixed arteries were decolorized. Vascular remodeling, including intimal hyperplasia and adventitial microvessel formation were estimated in a three-dimensional view. Vascular fragility, including blood leakiness was estimated by extravasation of fluorescein isothiocyanate (FITC)-lectin or FITC-dextran from microvessels. Ninj1 expression was increased in pericytes in response to vascular injury. NG2-CreER/ Ninj1 loxp mice were treated with tamoxifen (Tam) to induce deletion of Ninj1 in pericyte ( Ninj1 KO). Tam-treated NG2-CreER or Tam-nontreated NG2-CreER/ Ninj1 loxp mice were used as controls. Intimal hyperplasia was significantly enhanced in Ninj1 KO compared with controls. Vascular leakiness was significantly enhanced in Ninj1 KO. In Ninj1 KO, the number of infiltrated macrophages in adventitia was increased, along with the expression of inflammatory cytokines. In conclusion, deletion of Ninj1 in pericytes induces the immature vasa vasorum formation of injured vasculature and exacerbates adventitial inflammation and intimal hyperplasia. Thus, Ninj1 contributes to the vasa vasorum maturation in response to vascular injury and to reduction of vascular remodeling. NEW & NOTEWORTHY Although abnormalities of adventitial vasa vasorum are associated with vascular remodeling such as atherosclerosis, the mechanisms of vasa vasorum malformation and its role in vascular remodeling have not been fully clarified. The present study provides a line of novel evidence that ninjurin-1 contributes to adventitial microvascular maturation during vascular injury and regulates vascular remodeling.