Drug-coated balloon therapy for in-stent restenosis in patients with iliofemoral deep vein thrombosis: A single-arm observational study.

BACKGROUND: Iliofemoral deep vein thrombosis (IFDVT) causes severe symptoms and affect the quality of life to a great extent. Endovascular thrombectomy and stent implantation have been a feasible strategie to alleviate the signs and symptoms of IFDVT. However, venous in-stent restenosis (ISR) has become an emerging non-negligible problem. METHODS: To evaluate the histological characteristics of venous ISR, neointima of arterial and venous ISR patients were collected and examed. To explore the effect of drug-coated balloon (DCB) on venous ISR lesions, we conducted a single-center retrospective case series study involving IFDVT patients with ISR after venous stenting who were treated with paclitaxel-coated balloon dilatation. RESULTS: We found a collagen-rich matrix but not elastin, as well as fewer cells and less neovascularization in venous intimal hyperplasia compared with neointima in arteries. Thirteen IFDVT patients were involved in the study, with average preoperative stenosis degree of 87.69% ± 13.48%. After intervention, the stenosis degree was significantly reduced to 14.6% ± 14.36% immediately (p < 0.0001) and to 16.54% ± 15.73% during follow-up (p < 0.0001). During follow-up, the VEINES-QOL scores (p < 0.0001), VEINES-Sym scores (p < 0.0001), and Villalta scores (p = 0.04) of patients was improved significantly compared with those before intervention. No major adverse events were observed. CONCLUSIONS: The use of DCB may have a positive effect in the treatment of venous ISR by targeting intimal hyperplasia. Moreover, the application of DCB dilatation in IFDVT stenting patients with ISR is deemed safe and effective.

Safety and Efficacy of the Passeo-18 Lux Drug-Coated Balloon Catheter in Atherosclerotic Femoropopliteal Lesions: The Multicenter BIOLUX P-IV China Study.

BACKGROUND: The purpose of this trial was to assess the safety and effectiveness of a paclitaxel-coated balloon catheter in Chinese patients with de novo or nonstented restenotic femoropopliteal atherosclerotic lesions. METHODS: BIOLUX P-IV China is a prospective, independently adjudicated, multicenter, single-arm trial conducted in China. Patients with Rutherford class 2-4 were eligible, excluded were patients in which predilation resulted in severe (≥ grade D) flow-limiting dissection or residual stenosis > 70%. Follow-up assessments were conducted at 1, 6, and 12 months. The primary safety end point was 30-day major adverse event rate and the primary effectiveness end point was primary patency at 12 months. RESULTS: We enrolled 158 patients with 158 lesions. Mean age was 67.6 ± 9.6 years, diabetes was present in 53.8% (n = 85), and previous peripheral intervention/surgeries in 17.1% (n = 27). Lesions were 4.1 ± 0.9 mm in diameter and 74 ± 50 mm long with a mean diameter stenosis of 91 ± 13%; 58.2% (n = 92) were occluded (core laboratory analysis). Device success was achieved in all patients. The rate of major adverse events was 0.6% (95% confidence interval: 0.0; 3.5) at 30 days, consisting of 1 target lesion revascularization. At 12 months, binary restenosis was present in 18.7% (n = 26) and target lesion revascularization was performed in 1.4% (n = 2, all clinically driven), resulting in a primary patency of 80.0% (95% confidence interval: 72.4, 85.8); no major target limb amputation occurred. Clinical improvement at 12 months, defined as improvement of at least 1 Rutherford class, was 95.3% (n = 130). The median walking distance per 6-minute walk test was 279 m at baseline and improved by 50 m at 30 days and by 60 m at 12 months; the visual analogue scale changed from 76.6 ± 15.6 at baseline to 80.0 ± 15.0 at 30 days and 78.6 ± 14.6 at 12 months. CONCLUSIONS: Our results confirmed the clinical effectiveness and safety of a paclitaxel-coated peripheral balloon dilatation catheter for the treatment of de novo and nonstented restenotic lesion of the superficial femoral and proximal popliteal artery in Chinese patients (NCT02912715).

Drug-Coated Balloon Angioplasty Compared With Uncoated Balloons in the Treatment of Infrapopliteal Artery Lesions (AcoArt II-BTK).

PURPOSE: To compare the safety and efficacy of drug-coated balloon (DCB) vs uncoated balloon angioplasty in the treatment of de novo and restenotic infrapopliteal lesions in patients with chronic limb-threatening ischemia (CLTI). MATERIALS AND METHODS: The prospective, multicenter, randomized study AcoArt II-BTK study (ClinicalTrials.gov identifier NCT02137577) enrolled 120 patients who were randomly assigned to angioplasty with either a DCB (n=61; mean age 70.7±7.4 years; 36 men) or a conventional balloon catheter (n=59; mean age 70.8±9.0 years; 36 men). There were no significant differences observed in baseline clinical or target lesion characteristics between the groups. The target lesion length was 169.95±86.35 mm in the DCB group vs 179.93±80.16 mm in the control group, and approximately three-quarters of the lesions were chronic occlusions. Primary patency was assessed by angiography at 6 months, and mortality and clinically-driven target lesion revascularization (CD-TLR) were evaluated at 12 months. RESULTS: Primary patency at 6 months was 75.0% in the DCB group and 28.3% in the control group (p<0.001), while late lumen loss was 0.43±0.62 mm for DCBs vs 0.99±0.55 mm for controls (p<0.001). Freedom from CD-TLR at 12 months was 91.5% in the DCB group vs 76.8% in the controls (p=0.03); there was no significant difference in mortality (1.7% DCB vs 3.6% controls; p=0.53). CONCLUSION: This study demonstrated that the Litos/Tulip DCBs are safe and effective in treating infrapopliteal lesions, with improved angiographic and clinical outcomes vs plain balloon angioplasty. The DCBs demonstrated significantly higher primary patency with fewer CD-TLRs than conventional angioplasty. The safety of the DCBs was noninferior to that of the uncoated balloons after 1 year of follow-up.

Outcomes of Drug-Coated Balloon Angioplasty for Isolated Chronic Occlusion of the Popliteal Artery: A Retrospective Single-Institution Study.

PURPOSE: To assess the 12-month safety and effectiveness of paclitaxel drug-coated balloon (DCB) for the treatment of patients with isolated chronic occlusions in popliteal arteries and evaluate the risk factors of lesion reocclusion. MATERIALS AND METHODS: From January 2018 to December 2019, DCB angioplasty was performed in 54 limbs with isolated chronic popliteal artery occlusion of 48 patients (32 men) with a mean age of 71.5 ± 12.1 (range, 50-97) years, mean occlusive length of 6.3 ± 3.0 (range, 1-15) cm, and mean preoperative ankle-brachial index (ABI) of 0.42 ± 0.12 (range, 0.19-0.58). A total of 18.5% (10/54) of lesions were long-segment occlusions involving the entire popliteal artery from P1 to P3. Twenty seven of 54 limbs presented with critical limb ischemia (CLI) with a mean ABI of 0.33 ± 0.10 (range, 0.19-0.51). The primary endpoint was primary patency rate at 12 months. The secondary endpoints included technical success rate, 1-year secondary patency rate, limb salvage rate, and improvement in clinical symptoms. Univariate Cox regression analysis was used to determine the predictors of lesion reocclusion. RESULTS: The technical success rate was 85.2% (46/54), and bailout stenting was performed in 14.8% (8/54) of lesions. The 12-month primary and secondary patency rates by the Kaplan-Meier estimate were 72.6% and 88.3%, respectively. Two thirds of the reocclusions occurred within 6 months after intervention. No 30-day mortality was observed. The limb salvage rate was 100% during a mean follow-up period of 13 months, and all minor amputations occurred in the limbs presented with CLI. The mean ABI increased from 0.42 before the procedure to 0.73 after the procedure. Patients younger than 60 years and the lesions exhibiting long-segment occlusions present as trending risk factors for lesion reocclusion. CONCLUSIONS: Paclitaxel DCB angioplasty is safe and effective in managing isolated chronic occlusion of popliteal arteries. Younger patients and long-segment occlusions of the popliteal artery are associated with a relatively higher reocclusion rate after the procedure.

Endovascular treatment of atherosclerotic popliteal artery disease based on dynamic angiography findings.

OBJECTIVE: To evaluate efficacy, safety, and midterm patency of endovascular treatment of obstructive popliteal artery (PA) disease. METHODS: A retrospective evaluation of patients with atherosclerotic PA disease who underwent percutaneous transluminal balloon angioplasty and provisional stent, based on both conventional and dynamic angiographies, was conducted from June 2011 to June 2014. Forty-three patients were included in the study, and most patients had limited surgical revascularization options. Demographic characteristics, angiographic findings, interventional data, complications, vessel patency, limb salvage rates, and survival rates were analyzed. RESULTS: The median lesion length was 5 cm with 72.1% having total occlusions. The second popliteal segment (P2) was involved most frequently (60.5%, n = 26). Critical limb ischemia was present in 69.8%. The technical success rate was 92.9% (42/43 limbs), with 29 cases requiring adjunctive nitinol stents after balloon angioplasty (47.6% based on conventional angiography, 21.4% based on dynamic angiography, and 4.8% additional stents based on dynamic angiography). Complications included thromboembolism (2.3%), perforation (2.3%), pseudoaneurysm (2.3%), and myocardial infarction (2.3%). Stent fracture was present in three cases (7.1%) during the mean follow-up period of 18.3 months. The baseline ankle-brachial index significantly improved after the intervention, from 0.49 ± 0.11 to 0.92 ± 0.14 (P < .01). The Rutherford-Becker class decreased from 3.95 ± 0.76 to 1.76 ± 0.95 (P < .01) at 12 months. The 1-year primary, primary-assisted, and secondary patency rates were 75.2% ± 6.8%, 82.4% ± 6.0%, and 89.9% ± 4.8%, respectively. The limb salvage and amputation-free survival rates at 12 months were 91.6% and 87.0%, respectively. CONCLUSIONS: Balloon angioplasty with a provisional stent based on dynamic angiography is a feasible, safe, and effective therapy for patients with obstructive PA disease. Although the occurrence of stent fracture is still inevitable, patients with critical limb ischemia who have limited surgical options may get more benefits from the endovascular treatment of PA obstructive diseases.

Physicochemical Properties and In Vitro Biocompatibility of Three Bacterial Nanocellulose Conduits for Blood Vessel Applications.

A novel design of bioreactor G-BNC, in combination with two previously reported designs of bioreactor were used to fabricate three small caliber bacterial nanocellulose (BNC) conduits (G-BNC, S-BNC and D-BNC). They were compared systematically with a clinically-used ePTFE graft. S-BNC possessed a laminated structure, the lowest BNC content, roughest luminal surface and weakest mechanical properties, and so might not be sufficiently strong for use as an artificial blood vessel alone. The D-BNC conduit possessed an unstratified structure with a fiber network that was more dense and the greatest BNC content, providing the strongest mechanical properties. G-BNC possessed a looser network with the smoothest luminal surface and greater hemocompatibility. Following comprehensive evaluation of mechanical properties and performance, we judge that D-BNC and G-BNC should possess greater potential in application as small caliber vascular grafts, however the patency of the three BNC conduits need be further verified in animal studies in vivo.

Highly aligned core-shell structured nanofibers for promoting phenotypic expression of vSMCs for vascular regeneration.

This study was designed to assess the efficacy of hyaluronan (HA) functionalized well-aligned nanofibers of poly-l-lactic acid (PLLA) in modulating the phenotypic expression of vascular smooth muscle cells (vSMCs) for blood vessel regeneration. Highly aligned HA/PLLA nanofibers in core-shell structure were prepared using a novel stable jet electrospinning approach. Formation of a thin HA-coating layer atop each PLLA nanofiber surface endowed the uni-directionally oriented fibrous mats with increased anisotropic wettability and mechanical compliance. The HA/PLLA nanofibers significantly promoted vSMC to elongation, orientation, and proliferation, and also up-regulated the expression of contractile genes/proteins (e.g., α-SMA, SM-MHC) as well as the synthesis of elastin. Six weeks of in vivo scaffold replacement of rabbit carotid arteries showed that vascular conduits made of circumferentially aligned HA/PLLA nanofibers could maintain patency and promoted oriented vSMC regeneration, lumen endothelialization, and capillary formation. This study demonstrated the synergistic effects of nanotopographical and biochemical cues in one biomimetic scaffold design for efficacious vascular regeneration.

An effective approach to reduce inflammation and stenosis in carotid artery: polypyrrole nanoparticle-based photothermal therapy.

Photothermal therapy (PTT), as a promising treatment for tumours, has rarely been reported for application in artery restenosis, which is a common complication of endovascular management due to enduring chronic inflammation and abnormal cell proliferation. In our study, biodegradable polypyrrole nanoparticles (PPy-NPs) were synthesized and characterized, including their size distribution, UV-vis-NIR absorbance, molar extinction coefficients, and photothermal properties. We then verified that PPy-NP incubation followed by 915 nm near-infrared (NIR) laser irradiation could effectively ablate inflammatory macrophages in vitro, leading to significant cell apoptosis and cell death. Further, it was found that a combination of local PPy-NP injection with 915 nm NIR laser irradiation could significantly alleviate arterial inflammation by eliminating infiltrating macrophages and further ameliorating artery stenosis in an ApoE(-/-) mouse model, without showing any obvious toxic side effects. Thus, we propose that PTT based on PPy-NPs as photothermal agents and a 915 nm NIR laser as a power source can serve as a new effective treatment for reducing inflammation and stenosis formation in inflamed arteries after endovascular management.

Noninvasive detection of macrophages in atherosclerotic lesions by computed tomography enhanced with PEGylated gold nanoparticles.

Macrophages are becoming increasingly significant in the progression of atherosclerosis (AS). Molecular imaging of macrophages may improve the detection and characterization of AS. In this study, dendrimer-entrapped gold nanoparticles (Au DENPs) with polyethylene glycol (PEG) and fluorescein isothiocyanate (FI) coatings were designed, tested, and applied as contrast agents for the enhanced computed tomography (CT) imaging of macrophages in atherosclerotic lesions. Cell counting kit-8 assay, fluorescence microscopy, silver staining, and transmission electron microscopy revealed that the FI-functionalized Au DENPs are noncytotoxic at high concentrations (3.0 µM) and can be efficiently taken up by murine macrophages in vitro. These nanoparticles were administered to apolipoprotein E knockout mice as AS models, which demonstrated that the macrophage burden in atherosclerotic areas can be tracked noninvasively and dynamically three-dimensionally in live animals using micro-CT. Our findings suggest that the designed PEGylated gold nanoparticles are promising biocompatible nanoprobes for the CT imaging of macrophages in atherosclerotic lesions and will provide new insights into the pathophysiology of AS and other concerned inflammatory diseases.