Efficiency and safety of dual pathway inhibition for the prevention of femoropopliteal artery restenosis in repeated endovascular interventions.

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.

A New Drug-Coated Balloon for the Treatment of Superficial Femoropopliteal Artery Disease: 12-Month Results from the IN-DEPT SFA Trial.

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.

Vessel Geometry Estimation for Patients with Peripheral Artery Disease.

The estimation of vessels' centerlines is a critical step in assessing the geometry of the vessel, the topological representation of the vessel tree, and vascular network visualization. In this research, we present a novel method for obtaining geometric parameters from peripheral arteries in 3D medical binary volumes. Our approach focuses on centerline extraction, which yields smooth and robust results. The procedure starts with a segmented 3D binary volume, from which a distance map is generated using the Euclidean distance transform. Subsequently, a skeleton is extracted, and seed points and endpoints are identified. A search methodology is used to derive the best path on the skeletonized 3D binary array while tracking from the goal points to the seed point. We use the distance transform to calculate the distance between voxels and the nearest vessel surface, while also addressing bifurcations when vessels divide into multiple branches. The proposed method was evaluated on 22 real cases and 10 synthetically generated vessels. We compared our method to different state-of-the-art approaches and demonstrated its better performance. The proposed method achieved an average error of 1.382 mm with real patient data and 0.571 mm with synthetic data, both of which are lower than the errors obtained by other state-of-the-art methodologies. This extraction of the centerline facilitates the estimation of multiple geometric parameters of vessels, including radius, curvature, and length.

Pathological Changes in the Gastrocnemius Muscle throughout Hind Limb Ischemia Modeling in Rats.

We present a two-stage model for the study of chronic hind limb ischemia in rats. In the area of ischemia, sclerotic changes with atrophic rhabdomyocytes and reduced vascularization were revealed. CD31 expression in the endothelium increased proportionally to the number of vessels in the ischemic zone, and at the same time, focal expression of ßIII-tubulin was detected in the newly formed nerve fibers. These histological features are equivalent to the development of peripheral arterial disease in humans, which allows using our model in the search for new therapeutic strategies.

Efficacy of a Drug-Eluting Stent Versus Bare Metal Stents for Symptomatic Femoropopliteal Peripheral Artery Disease: Primary Results of the EMINENT Randomized Trial.

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.

Randomized Trial of Chocolate Touch Compared With Lutonix Drug-Coated Balloon in Femoropopliteal Lesions (Chocolate Touch Study).

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 (Pnoninferiority<0.0001) and sequential superiority (Psuperiority=0.04). The primary safety event rate was 88.9% (128/144) with Chocolate Touch and 84.6% (126/149) with Lutonix DCB (Pnoninferiority<0.001; Psuperiority=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.

Impact of Cardiac Function on Loss of Patency in Patients With Peripheral Artery Disease Presenting the Femoropopliteal Lesions Endovascularly Treated With New-Generation Devices.

PURPOSE: The current study sought to investigate the impact of cardiac condition on loss of patency after endovascular therapy (EVT) using new-generation devices for femoropopliteal (FP) lesions. MATERIALS AND METHODS: We retrospectively studied 547 lesions (chronic limb-threatening ischemia: 44%, TASC II C/D lesion: 61%, chronic total occlusion: 37%, in-stent restenosis: 13%, involving popliteal arterial lesion: 45%) belonging to 416 patients (average age: 75±9 years, male: 69%, diabetes mellitus: 62%, hemodialysis: 33%) who underwent EVT with new-generation FP-specific devices (polymer-free paclitaxel-eluting stent, n=186; stent graft, n=119; fluoropolymer-based paclitaxel-eluting stent, n=29; interwoven stent, n=17; drug-coated balloon, n=196) from June 2012 to May 2019. Cardiac function was evaluated using echocardiography. The primary outcome measure was primary patency, which was defined as free from peak systolic velocity ratio (PSVR) >2.5 assessed by duplex ultrasound. Predictors for loss of patency were evaluated using Cox proportional hazards regression analysis. RESULTS: Overall 12 primary patency were 80.0±1.8%. After the multivariate analysis, reduced stroke volume evaluated by echocardiography (hazard ratio [HR]=0.99, 95% confidence interval [CI]=0.97-0.99, p=0.03), chronic heart failure (HR=1.76, 95% CI=1.05-2.97, p=0.03), and a smaller distal reference vessel diameter (HR=0.73, 95% CI=0.55-0.97, p=0.03) were significantly associated with loss of 12-month primary patency, whereas lesion length (HR=1.01, 95% CI=0.99-1.03, p=0.33) and presence of chronic total occlusion (CTO; HR=0.92, 95% CI=0.61-1.40, p=0.70) were not statistically significant. CONCLUSION: The current study revealed that cardiac function represented by reduced stroke volume and presence of chronic heart failure as well as a smaller distal reference vessel diameter were significantly associated with loss of 12-month primary patency in patients with peripheral artery disease (PAD) presenting FP lesions endovascularly treated with new-generation devices.

Angioscopic Findings of Stenosis Versus Occlusion in Femoropopliteal Artery Disease.

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.

Reporting Peripheral Artery Disease in Claudicants: Lessons Learned From the TASC-Ability Study.

BACKGROUND: The Trans-Atlantic Inter-Society Consensus Document (TASC II) aims to comprehensively describe the case scenarios of aortoiliac and femoropopliteal lesions to suggest an endovascular or a surgical approach. Over time, it has become a guide for describing the gravity of arterial lesions. PURPOSE: To assess the revised TASC II system for classifying arterial lesions in a large database of patients presenting with claudication. MATERIALS AND METHODS: This study was a retrospective review of the arteriograms of patients with intermittent claudication. Aortoiliac and femoropopliteal lesions were classified according to the TASC II. When no consensus was reached, the lesion was rated as unTASCable. RESULTS: In total, 1454 patients were included (male: 62.1%, 66.8±9.3 years). There were 39% aortoiliac lesions (n=960/2462) and 61% femoropopliteal lesions (n=1502/2462); 33.6% of the patients (n=489/1454) were associated with aortoiliac and femoropopliteal lesions. In addition, 20% of the lesions (n=493/2462) were unTASCable, and 26.7% of the patients (n=388/1454) had at least 1 unTASCable lesion. There were 4 categories of unTASCable lesions: (1) association with a common femoral artery lesion in 53.1% (n=262/493); (2) iliac artery lesions in 23.1% (n=114/493); (3) femoropopliteal lesions whose lengths did not fit into any category in 16.6% (n=82/493); and (4) association with an aortic lesion in 7.1% (n=35/493). The interobserver agreement was 0.97 for anatomically describing the infrarenal arterial tree and 0.85 for TASCing, with the lesions lowering to 0.69 for aortoiliac lesions. CONCLUSION: Using the revised TASC II case scenario, 26.7% of the patients had at least 1 unTASCable lesion. Reporting peripheral artery disease using a comprehensive anatomical description of the infrarenal arterial tree showed better interobserver reproducibility.

Medial Arterial Calcification: A Significant and Independent Contributor of Peripheral Artery Disease.

Over 200 million individuals worldwide are estimated to have peripheral artery disease (PAD). Although the term peripheral can refer to any outer branch of the vasculature, the focus of this review is on lower-extremity arteries. The initial sequelae of PAD often include movement-induced cramping pain in the hips and legs or loss of hair and thinning of the skin on the lower limbs. PAD progresses, sometimes rapidly, to cause nonhealing ulcers and critical limb ischemia which adversely affects mobility and muscle tone; acute limb ischemia is a medical emergency. PAD causes great pain and a high risk of amputation and ultimately puts patients at significant risk for major adverse cardiovascular events. The negative impact on patients' quality of life, as well as the medical costs incurred, are huge. Atherosclerotic plaques are one cause of PAD; however, emerging clinical data now shows that nonatherosclerotic medial arterial calcification (MAC) is an equal and distinct contributor. This ATVB In Focus article will present the recent clinical findings on the prevalence and impact of MAC in PAD, discuss the known pathways that contribute specifically to MAC in the lower extremity, and highlight gaps in knowledge and tools that limit our understanding of MAC pathogenesis.

Disease Specific Health Related Quality of Life in Patients With Chronic Limb Threatening Ischaemia Undergoing Revascularisation of Femoropopliteal Lesions.

OBJECTIVE: Patients with chronic limb threatening ischaemia (CLTI) suffer from pain and non-healing ulcers, which impact negatively on both their physical and mental health. While maintaining and improving quality of life is a principal aim with all treatments, little is known about the health related quality of life (HRQoL) of CLTI patients and how revascularisation procedures impact on HRQoL endpoints. The aim of this study was to investigate disease specific HRQoL before and after revascularisation in patients with CLTI undergoing femoropopliteal revascularisation. METHODS: HRQoL was prospectively analysed in 190 CLTI patients with main atherosclerotic target lesions in the femoropopliteal segment, who were planned for endovascular or open revascularisation. The choice of revascularisation method was made by the vascular team, represented by both open and endovascular expertise. The Vascular Quality of Life (VascuQoL) questionnaire was used to assess disease specific HRQoL before revascularisation and one month, one year, and two years after the procedure. Main endpoints were mean VascuQoL score changes, effect sizes of observed changes and the proportion reaching a minimally important difference (half a standard deviation change from baseline) during two years after revascularisation. RESULTS: Patient reported VascuQoL scores were low at baseline (mean 2.68, 95% CI 1.18 - 4.17). After revascularisation, the mean VascuQoL score improved statistically significantly over time, with the largest improvement observed after one year (difference from baseline 2.02, 95% CI 1.75 - 2.29; p < .001). No differences in HRQoL change over time were observed between patients treated with endovascular approaches compared with bypass surgery. Approximately half the patients reached the minimally important threshold at one year (53%), which was largely maintained also at two years (41%). CONCLUSION: While CLTI profoundly affected HRQoL, a large and clinically meaningful HRQoL increase was observed after revascularisation. This confirms the value of CLTI revascularisation on HRQoL and underlines the importance of including patient reported outcomes when evaluating revascularisation procedures in CLTI patients.

Impact of lipoprotein(a) levels on primary patency after endovascular therapy for femoropopliteal lesions.

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.

The Role of Neutrophils in Lower Limb Peripheral Artery Disease: State of the Art and Future Perspectives.

In recent years, increasing attention has been paid to the role of neutrophils in cardiovascular (CV) disease (CVD) with evidence supporting their role in the initiation, progression, and rupture of atherosclerotic plaque. Although these cells have long been considered as terminally differentiated cells with a relatively limited spectrum of action, recent research has revealed intriguing novel cellular functions, including neutrophil extracellular trap (NET) generation and inflammasome activation, which have been linked to several human diseases, including CVD. While most research to date has focused on the role of neutrophils in coronary artery and cerebrovascular diseases, much less information is available on lower limb peripheral artery disease (PAD). PAD is a widespread condition associated with great morbidity and mortality, though physician and patient awareness of the disease remains low. To date, several studies have produced some evidence on the role of certain biomarkers of neutrophil activation in this clinical setting. However, the etiopathogenetic role of neutrophils, and in particular of some of the newly discovered mechanisms, has yet to be fully elucidated. In the future, complementary assessment of neutrophil activity should improve CV risk stratification and provide personalized treatments to patients with PAD. This review aims to summarize the basic principles and recent advances in the understanding of neutrophil biology, current knowledge about the role of neutrophils in atherosclerosis, as well as available evidence on their role of PAD.

Endothelial Palmitoylation Cycling Coordinates Vessel Remodeling in Peripheral Artery Disease.

RATIONALE: Peripheral artery disease, common in metabolic syndrome and diabetes mellitus, responds poorly to medical interventions and is characterized by chronic vessel immaturity leading to lower extremity amputations. OBJECTIVE: To define the role of reversible palmitoylation at the endothelium in the maintenance of vascular maturity. METHODS AND RESULTS: Endothelial knockout of the depalmitoylation enzyme APT-1 (acyl-protein thioesterase 1) in mice impaired recovery from chronic hindlimb ischemia, a model of peripheral artery disease. Endothelial APT-1 deficiency decreased fibronectin processing, disrupted adherens junctions, and inhibited in vitro lumen formation. In an unbiased palmitoylation proteomic screen of endothelial cells from genetically modified mice, R-Ras, known to promote vessel maturation, was preferentially affected by APT-1 deficiency. R-Ras was validated as an APT-1 substrate, and click chemistry analyses demonstrated increased R-Ras palmitoylation in cells with APT-1 deficiency. APT-1 enzyme activity was decreased in endothelial cells from db/db mice. Hyperglycemia decreased APT-1 activity in human umbilical vein endothelial cells, due, in part, to altered acetylation of the APT-1 protein. Click chemistry analyses demonstrated increased R-Ras palmitoylation in the setting of hyperglycemia. Altered R-Ras trafficking, increased R-Ras palmitoylation, and fibronectin retention were found in diabetes mellitus models. Loss of R-Ras depalmitoylation caused by APT-1 deficiency constrained R-Ras membrane trafficking, as shown by total internal reflection fluorescence imaging. To rescue cellular phenotypes, we generated an R-Ras molecule with an inserted hydrophilic domain to circumvent membrane rigidity caused by defective palmitoylation turnover. This modification corrected R-Ras membrane trafficking, restored fibronectin processing, increased adherens junctions, and rescued defective lumen formation induced by APT-1 deficiency. CONCLUSIONS: These results suggest that endothelial depalmitoylation is regulated by the metabolic milieu and controls plasma membrane partitioning to maintain vascular homeostasis.

Twelve-Month Outcomes From the Japanese Post-Market Surveillance Study of the Viabahn Endoprosthesis as Treatment for Symptomatic Peripheral Arterial Disease in the Superficial Femoral Arteries.

PURPOSE: To assess the midterm safety and effectiveness of the Gore® Viabahn® Endoprosthesis as treatment for symptomatic peripheral arterial disease (PAD) in the superficial femoral arteries (SFA). MATERIALS AND METHODS: A prospective, multicenter, post-market surveillance study was conducted in Japan. Patients with symptomatic SFA lesions ≥ 10 cm and reference vessel diameters ranging from 4.0 to 7.5 mm were eligible for enrollment; patients with traumatic or iatrogenic vessel injury in the thoracic, abdominal, or pelvic arteries were excluded. Outcomes evaluated at 12 months were primary patency (PP), primary-assisted patency (PAP), secondary patency (SP), freedom from target lesion revascularization (fTLR), occurrence of device- or procedure-related serious adverse events (SAEs), and stent fractures. RESULTS: From August 2016 to May 2017, 321 patients were enrolled at 64 Japanese sites (mean age, 73.9±8.7 years; 77.3% male). Hypertension, diabetes, and end stage renal disease were present in 84.4%, 54.8%, and 23.1% of patients, respectively. Mean lesion length was 23.6 cm±6.6 cm, with lesions ≥ 15 cm in 271 patients (84.4%). TASC C/D lesions accounted for 86.6% (39.1% TASC C, 47.5% TASC D); 26.5% had critical limb ischemia. Baseline ABI was 0.60±0.16. A total of 562 devices were implanted in 324 limbs, with a majority of patients (68.8%) receiving 2 stents. Through 12 months, 92.1% of patients were evaluable. Kaplan-Meier-estimated PP, PAP, and SP at 12 months was 85.6%, 91.7%, and 94.8%, respectively. Twelve-month fTLR was 92.3%. Mean change in ABI at 12 months was 0.343±0.21; mean improvement in Rutherford class was 2.5. Device- or procedure-related SAEs occurred in 3.1% through 30 days, with a majority of early SAEs consisting of access complications. Through 12 months, a cumulative 10.6% had device- or procedure-related SAEs, with the most common being device occlusions in 4.0%. Lower limb amputation occurred in 0.9% and was related to pre-existing ulceration or gangrene in all 3 cases. No stent fractures were observed at 12-month x-ray evaluation. CONCLUSION: In a real-world Japanese patient population characterized by long SFA lesions and complex PAD, the Viabahn endoprosthesis was associated with excellent patency rates through 12 months and an acceptable safety profile.

IN.PACT AV Access Randomized Trial: 12-Month Clinical Results Demonstrating the Sustained Treatment Effect of Drug-Coated Balloons.

PURPOSE: To present the 12-month outcomes of the IN.PACT AV Access Study, a prospective, single-blind trial enrolling participants with obstructive de novo or restenotic native upper extremity arteriovenous dialysis fistula lesions treated with a drug-coated balloon (DCB) or percutaneous transluminal angioplasty (PTA). MATERIALS AND METHODS: After successful high-pressure PTA, participants at 29 international sites were randomized 1:1 to treatment with an IN.PACT AV DCB (n = 170) or standard uncoated PTA (n = 160). Outcomes at 12 months include target lesion primary patency (TLPP), defined as freedom from clinically driven target lesion revascularization or access circuit thrombosis; access circuit primary patency; number of reinterventions; and adverse events involving the access circuit. RESULTS: At 12 months, TLPP was 63.8% (90/141) in the DCB group compared with 43.6% (61/140) in the PTA group (P < .001). The total number of reinterventions required to maintain TLPP through 360 days was 93 in the DCB group and 144 in the PTA group, with a 35.4% reduction in reinterventions when DCB was used. Access circuit thrombosis occurred in 2.9% (4/138) of the participants in the DCB group and in 6.2% (8/129) of those in the PTA group (P = .19). Time to TLPP was assessed using a multivariable analysis to identify the factors associated with loss of patency. The treatment device was the independent predictor with the largest effect, with a hazard ratio of 0.42 (95% confidence interval, 0.29-0.60; P < .001). CONCLUSIONS: TLPP was statistically significantly higher with DCBs than with standard PTA at 12 months, demonstrating the sustained and superior effectiveness of this device for the treatment of dysfunctional arteriovenous dialysis fistulae.

High relative amount of nodular calcification in femoral plaques is associated with milder lower extremity arterial disease.

BACKGROUND: Clinical implications of different types of vascular calcification are poorly understood. The two most abundant forms of calcification, nodular and sheet calcification, have not been quantitatively analyzed in relation to the clinical presentation of lower extremity arterial disease (LEAD). METHODS: The study analyzed 51 femoral artery plaques collected during femoral endarterectomy, characterized by the presence of > 90% stenosis. Comprehensive clinical data was obtained from patient records, including magnetic resonance angiography (MRA) images, toe pressure and ankle brachial index measurements and laboratory values. The plaques were longitudinally sectioned, stained with Hematoxylin and Eosin and digitized in a deep learning platform for quantification of the relative area of nodular and sheet calcification to the plaque section area. A deep learning artificial intelligence algorithm was designed and independently validated to reliably quantify nodular calcification and sheet calcification. Vessel measurements and quantity of each calcification category was compared to the risk factors and clinical presentation. RESULTS: On average, > 90% stenosed vessels contained 22.4 ± 12.3% of nodular and 14.5 ± 11.8% of sheet calcification. Nodular calcification area proportion in lesions with > 90% stenosis is associated with reduced risk of critically low toe pressure (< 30 mmHg) (OR = 0.910, 95% CI = 0.835-0.992, p < 0.05), severely lowered ankle brachial index (< 0.4) (OR = 0.912, 95% CI = 0.84-0.986, p < 0.05), and semi-urgent operation (OR = 0.882, 95% CI = 0.797-0.976, p < 0.05). Sheet calcification did not show any significant association. CONCLUSIONS: Large amount of nodular calcification is associated with less severe LEAD. Patients with nodular calcification may have better flow reserves despite local obstruction.

Drug-Coated Balloon Angioplasty Versus Standard Uncoated Balloon Angioplasty for Long Femoropopliteal Lesions: Post Hoc Analysis of the 24-Month Results of the AcoArt I Study.

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.

Orchid drug-coated balloon versus standard percutaneous transluminal angioplasty for the treatment of femoropopliteal artery disease: 12-month result of the randomized controlled trial.

PURPOSE: To assess the efficacy and safety of the Orchid drug-coated balloon (coated with paclitaxel) for the treatment of femoropopliteal artery disease versus percutaneous transluminal angioplasty in Chinese population. METHODS: This is a prospective, single center, single-blinded, randomized controlled trial that randomized (1:1) 60 patients (38 men; mean age 68.7 ± 8.8) to drug-coated balloon group (n = 30) or percutaneous transluminal angioplasty group (n = 30). The primary efficacy endpoint was primary patency of the target lesion and clinically driven target lesion revascularization (CD-TLR) at 12 months. The primary safety end point was freedom from perioperative death at 30 days and freedom from limb-related death and major amputation at 12 months. RESULTS: Baseline characteristics were similar between the two groups. Drug-coated balloon group resulted in higher primary patency (82.8% vs. 48.3%, p = 0.005) and lower CD-TLR rates (3.5% vs. 27.6%; p = 0.001) versus percutaneous transluminal angioplasty group at 12 months. The ABI was significantly higher in drug-coated balloon group than percutaneous transluminal angioplasty group (0.86 ± 0.13 vs. 0.72 ± 0.18, p = 0.025). There were no perioperative death at 30 days, no limb-related death and no major amputation at 12 months in either group. CONCLUSIONS: The randomized controlled trial showed superior treatment effect with drug-coated balloon versus percutaneous transluminal angioplasty, with remarkably higher patency and lower CD-TLR rates. The result is consistent with other study and demonstrates the safety and efficacy of the Orchid drug-coated balloon for the treatment of femoropopliteal artery disease.

The antithetic role of ceramide and sphingosine-1-phosphate in cardiac dysfunction.

Cardiovascular diseases (CVDs) are the leading cause of death globally and the number of cardiovascular patients, which is estimated to be over 30 million in 2018, represent a challenging issue for the healthcare systems worldwide. Therefore, the identification of novel molecular targets to develop new treatments is an ongoing challenge for the scientific community. In this context, sphingolipids (SLs) have been progressively recognized as potent bioactive compounds that play crucial roles in the modulation of several key biological processes, such as proliferation, differentiation, and apoptosis. Furthermore, SLs involvement in cardiac physiology and pathophysiology attracted much attention, since these molecules could be crucial in the development of CVDs. Among SLs, ceramide and sphingosine-1-phosphate (S1P) represent the most studied bioactive lipid mediators, which are characterized by opposing activities in the regulation of the fate of cardiac cells. In particular, maintaining the balance of the so-called ceramide/S1P rheostat emerged as an important novel therapeutical target to counteract CVDs. Thus, this review aims at critically summarizing the current knowledge about the antithetic roles of ceramide and S1P in cardiomyocytes dysfunctions, highlighting how the modulation of their metabolism through specific molecules, such as myriocin and FTY720, could represent a novel and interesting therapeutic approach to improve the management of CVDs.