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Purpose: To evaluate in vivo the feasibility, safety, and paclitaxel (PTX) deliverability of a newly developed non-commercially available Paclitaxel-Coated Balloon (PCB) catheter in the swine healthy peripheral vein model., Materials and Methods: In total 12 PCBs were deployed in 12 venous segments. Primary feasibility endpoint was the successful application of the devices to the veins of the animals. Primary efficacy endpoint was the determination of the drug content in the venous tissue at 24 h and 7 days after balloon expansion, as assessed by analysis of the vein tissue with High Performance Liquid Chromatography (HPLC) coupled with tandem mass spectrometry. Primary safety endpoint was freedom from any major adverse event. Secondary endpoint was the investigation of any independent factor affecting the primary endpoints., Results: Paclitaxel was detected in five out of six tissue samples 24 h post-intervention and five out of six tissues at 7 days following the procedure (10 tissue samples out of 12). The mean weight of tissue that was examined was 0.20604 ± 0.29822 g (range: 1.02823-0.03377 g) and the mean PTX concentration detected was 8.4 ± 13.1 μg/g (range: 0-36.1 μg/g). The average drug content detected at 24 h (17.1 ± 17.1 μg/g) was numerically superior, but non-statistically significant, compared to 7 days (3.1 ± 3.6 μg/g). An average of 33.8% of the drug remained on the balloon after retrieval. According to the multiple linear regression analysis, there was no significant correlation between transition time, PTX remaining on the balloon, time of analysis (24 h/7 days) and PTX tissue concentration. No abnormalities were noted during autopsy., Conclusion: The newly developed PCB successfully delivered within the healthy venous wall a dose of Paclitaxel that inhibits neointimal hyperplasia. No safety issues were raised at short-term follow-up., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: There have been concerns about the long term safety of paclitaxel coated devices in the lower limbs. A formal systematic review and meta-analysis of randomised controlled trials (RCTs) was performed to examine the long term risk of major amputation using paclitaxel coated balloons in peripheral arterial disease (PAD)., Method: This systematic review was registered with PROSPERO (ID 227761). A broad bibliographic search was performed for RCTs investigating paclitaxel coated balloons in the peripheral arteries (femoropopliteal and infrapopliteal) for treatment of intermittent claudication or critical limb ischaemia (CLI). The literature search was last updated on 20 February 2021 without any restrictions on publication language, date, or status. Major amputations were analysed with time to event methods employing one and two stage models. Sensitivity and subgroup analyses, combinatorial meta-analysis, and a multivariable dose response meta-analysis to examine presence of a biological gradient were also performed., Results: In all, 21 RCTs with 3 760 lower limbs were analysed (52% intermittent claudication and 48% CLI; median follow up two years). There were 87 major amputations of 2 216 limbs in the paclitaxel arms (4.0% crude risk) compared with 41 major amputations in 1 544 limbs in the control arms (2.7% crude risk). The risk of major amputation was significantly higher for paclitaxel coated balloons with a hazard ratio (HR) of 1.66 (95% CI 1.14 - 2.42; p = .008, one stage stratified Cox model). The prediction interval was 95% CI 1.10 - 2.46 (two stage model). The observed amputation risk was consistent for both femoropopliteal (p = .055) and infrapopliteal (p = .055) vessels. Number needed to harm was 35 for CLI. There was good evidence of a significant non-linear dose response relationship with accelerated risk per cumulative paclitaxel dose (chi square model p = .007). There was no evidence of publication bias (p = .80) and no significant statistical heterogeneity between studies (I 2  = 0%, p = .77). Results were stable across sensitivity analyses (different models and subgroups based on anatomy and clinical indication and excluding unpublished trials). There were no influential single trials. Level of certainty in evidence was downrated from high to moderate because of sparse events in some studies., Conclusion: There appears to be heightened risk of major amputation after use of paclitaxel coated balloons in the peripheral arteries. Further investigations are warranted urgently., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: This was a European, multicenter, investigator-initiated and run, single-arm retrospective analysis to assess the safety and the clinical benefit of the use of paclitaxel-coated balloon (PCB) for the treatment of symptomatic central venous stenosis (CVS)., Materials and Methods: Eleven centers from 7 countries across Europe, submitted 86 cases performed during the period between October 2015 and June 2018. Minimum follow-up was 6 months. Patient baseline demographics and procedural details were collected. Mean age was 62.6 years (SD 15.2 years). Median vascular access age was 3.0 years (IQR 1.2-4.8 years). A total of 55 were arteriovenous fistulas (64%) the rest arteriovenous grafts (31/86, 36%). Vessels treated were 43 subclavian veins, 42 brachiocephalic veins and 1 superior vena cava. Median drug-coated balloon diameter was 10 mm (IQR 8-12 mm). Primary outcome measures were clinically assessed intervention-free period (IFP) of the treated segment at 6 months and procedure-related minor and major complications. Secondary outcome measures included access circuit survival, patient survival, and the investigation of independent factors that influence the IFP., Results: IFP was 62.7% at 6 months. Median patient follow-up time was 1.0 year (IQR 0.5-2.2 years). There was 1 minor complication (1/86; 1.2%) and no major complications. Access circuit survival was 87.7% at 6 months. Patient survival was 79.7% at 2 years according to Kaplan-Meier survival analysis. Higher balloon diameters significantly favored IFP [HR 0.71 (0.55-0.92), p=0.006; 5-7 mm group vs 8-12 mm group, p=0.025]., Conclusion: In this analysis, use of PCBs for the treatment of symptomatic CVS was safe. Efficacy was comparable to previous trials. Increased balloon size had a significant effect on patency rates.

There have been concerns about the long-term risk of all-cause death with the use of paclitaxel-coated devices in the lower limbs. Results from a 2018 meta-analysis were corroborated by the US Food and Drug Administration and later confirmed by an individual patient data meta-analysis. However, population-based observational studies have produced contradictory results and often claimed a survival benefit with the use of paclitaxel. The recently published Swedish drug-elution trial in peripheral arterial disease did not confirm a significant mortality risk. In this review, the authors discuss the key elements of the identified mortality signal and stress important facts and figures that remain underrecognized and elusive. They also highlight the important types of epidemiological bias that pertain to the ongoing debate on paclitaxel., (Copyright © 2021 SIR. Published by Elsevier Inc. All rights reserved.)

A formal systematic review and study-level meta-analysis of randomized controlled trials investigating treatment of the infrapopliteal arteries with paclitaxel-coated balloons compared with conventional balloon angioplasty for critical limb ischemia (CLI) was conducted. Medical databases and online content were last screened in September 2019. The primary safety and efficacy endpoint was amputation-free survival defined as freedom from all-cause death and major amputation. Target lesion revascularization (TLR) constituted a secondary efficacy endpoint. Summary effects were synthesized with a random-effects model. Some 8 randomized controlled trials with 1,420 patients (97% CLI) were analyzed up to 1 year follow-up. Amputation-free survival was significantly worse in case of paclitaxel (13.7% crude risk of death or limb loss compared to 9.4% in case of uncoated balloon angioplasty; hazard ratio 1.52; 95% confidence interval: 1.12-2.07, p = .008). TLR was significantly reduced in case of paclitaxel (11.8% crude risk of TLR versus 25.6% in control; risk ratio 0.53; 95% confidence interval: 0.35-0.81, p = .004). The harm signal was evident when examining the high-dose (3.0-3.5 μg/mm 2 ) devices, but attenuated below significance in case of a low-dose (2.0 μg/mm 2 ) device. Actual causes remain largely unknown, but non-target paclitaxel embolization is a plausible mechanism., (Copyright © 2019 SIR. All rights reserved.)

Introduction: Percutaneous transluminal angioplasty (PTA) currently remains the endovascular treatment of choice in a large percentage of patients suffering from peripheral artery disease (PAD). However, the mechanism of angioplasty itself can cause some extent of arterial dissection leading to early vessel restenosis/reocclusion. Current endovascular imaging studies have reported a higher rate of arterial dissection than previously reported in literature and advocated the correlation of dissection with poor patency. Thus, there is the need of developing devices to minimize dissection and bailout stenting., Areas Covered: The present review focuses on newly-developed balloon angioplasty technologies designed to minimize arterial wall distress and consequently the rate of dissections. Available literature regarding three new specialty balloons is being reviewed, highlighting their value and limitations. Authors' future perspective about the benefits of utilizing specialty balloons towards a metal free and dissection free future is also provided., Expert Opinion: By understanding the mechanism of angioplasty and thus developing devices which cause minimal or no arterial wall distress, the rate of dissections and bailout stenting can be minimized and long-term clinical outcomes of endovascular therapy can be optimized.

Background Several randomized controlled trials ( RCT s) have already shown that paclitaxel-coated balloons and stents significantly reduce the rates of vessel restenosis and target lesion revascularization after lower extremity interventions. Methods and Results A systematic review and meta-analysis of RCT s investigating paclitaxel-coated devices in the femoral and/or popliteal arteries was performed. The primary safety measure was all-cause patient death. Risk ratios and risk differences were pooled with a random effects model. In all, 28 RCT s with 4663 patients (89% intermittent claudication) were analyzed. All-cause patient death at 1 year (28 RCT s with 4432 cases) was similar between paclitaxel-coated devices and control arms (2.3% versus 2.3% crude risk of death; risk ratio, 1.08; 95% CI, 0.72-1.61). All-cause death at 2 years (12 RCT s with 2316 cases) was significantly increased in the case of paclitaxel versus control (7.2% versus 3.8% crude risk of death; risk ratio, 1.68; 95% CI, 1.15-2.47; -number-needed-to-harm, 29 patients [95% CI , 19-59]). All-cause death up to 5 years (3 RCT s with 863 cases) increased further in the case of paclitaxel (14.7% versus 8.1% crude risk of death; risk ratio, 1.93; 95% CI , 1.27-2.93; -number-needed-to-harm, 14 patients [95% CI , 9-32]). Meta-regression showed a significant relationship between exposure to paclitaxel (dose-time product) and absolute risk of death (0.4±0.1% excess risk of death per paclitaxel mg-year; P<0.001). Trial sequential analysis excluded false-positive findings with 99% certainty (2-sided α, 1.0%). Conclusions There is increased risk of death following application of paclitaxel-coated balloons and stents in the femoropopliteal artery of the lower limbs. Further investigations are urgently warranted. Clinical Trial Registration URL : www.crd.york.ac.uk/PROSPERO . Unique identifier: CRD 42018099447.

Background: This is a retrospective single-center analysis investigating the results of a percutaneous lysis-assisted balloon (LAB) thrombectomy procedure for the treatment of thrombosed arteriovenous dialysis grafts (AVGs)., Materials and Methods: Within 5 years (January 2012-December 2016), 291 declotting procedures were performed for the treatment of thrombosed dialysis arteriovenous fistulas or grafts. Data were available for 129 patients (75 men, 58.1%) with an AVG, undergoing 241 procedures [1.87 procedures/patient (1-10)]. Procedure includes initial lysis with 5 mg recombinant tissue plasminogen activator followed by thrombectomy with a high-pressure balloon for thrombus maceration using "facing sheaths" technique. 61 patients had ≥ 2 declotting procedures. In 80 cases (80/241; 33.2%), a stent graft (SG) was used for treatment of persistent stenosis. Main primary outcome measures were clinical success and postintervention assisted primary patency (PAPP). Secondary outcome measures included procedural complications and investigation of independent factors that could influence circuit survival., Results: Median PAPP was 434 days according to Kaplan-Meier survival analysis. Clinical success was 96.26%. In six cases (6/241, 2.49%) declotting failed and a catheter was placed. There were 16 minor (16/241, 6.64%) and no major complications. There was no significant difference in circuit survival regardless of SG use (No SG 406 days vs. SG 349 days; p = 0.24). There was a significant difference in favor of the second declotting compared to the first in 61 patients (first: 162 days vs. second: 447 days; p < 0.0001)., Conclusion: LAB thrombectomy resulted in high-circuit survival rates with increased technical success and minimum complications without the use of thrombectomy devices.

Purpose: To compare the clinically-assessed intervention-free period (IFP) of paclitaxel-coated balloon (PCB) vs conventional balloon angioplasty (CBA) for the treatment of symptomatic central venous stenosis (CVS) in dialysis access., Materials and Methods: Within 20 months, 40 dialysis patients (19/40 arteriovenous fistulae [AVFs] and 21/40 arteriovenous grafts [AVGs]) were randomized to undergo angioplasty either with a PCB (PCB group, n = 20; 14/20 male; age: 56.7) or CBA (CBA group, n = 20; 15/20 male; age: 57). There were 15/20 restenotic lesions in PCB group and 12/20 in CBA group. In 25/40 cases, patients had an ipslateral catheter insertion in the past. Primary endpoint was clinically-assessed intervention-free period (IFP) of the treated segment at 6 months, while secondary endpoints included complication rates during follow-up period and identification of factors influencing IFP., Results: Median IFP was significantly better in PCB group (PCB group: 179 days, vs CBA group: 124.5 days, P = .026). Mean follow-up period was 180 days (range, 5-479). There was no significant difference between AVGs and AVFs (P = .17), treatment of de novo vs restenotic lesions (P = .33), or prior presence of catheter insertion (P = .21). No complications were observed. In restenotic lesions in PCB group, longitudinal comparison between treatments also showed a significant difference in favor of PCB treatment (median IFP in PCB* group 177 vs 91 days in CBA* group; P = .01)., Conclusions: In this prospective study, PCB had significantly better results compared with CBA for the treatment of symptomatic central venous stenosis in dialysis access. Retrospective longitudinal comparison of treatments in the same patients also showed a significant difference in favor of PCBs., (Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the safety and effectiveness of lutonix paclitaxel-coated balloon (PCB) for the treatment of dysfunctional dialysis access., Materials and Methods: This was a single-center, single-arm, retrospective analysis of 39 patients (23 male, 59 %) undergoing 61 interventions using 69 PCBs in a 20-month period. There was a balance between arteriovenous fistulae (AVF) and grafts (AVG) (20 AVFs, 19AVGs), and the majority of lesions were restenotic (25/39, 64.1 %). Mean balloon diameter used was 6.6 mm and length 73.4 mm. Primary outcome measure was target lesion primary patency (TLPP) at 6 months, while secondary outcome measures included factors affecting TLPP and major complications. As there were lesions treated more than once with PCB, authors also compared patency results after first and second PCB angioplasty., Results: TLPP was 72.2 % at 6 months with a median patency of 260 days according to the Kaplan-Meier survival analysis. No major complications occurred. TLPP between AVFs and AVGs (311 vs. 237 days, respectively; p = 0.29) and de novo and restenotic lesions was similar (270.5 vs. 267.5 days, respectively; p = 0.50). In 14 cases, in which lesions were treated with two PCB angioplasties, a statistically significant difference in TLPP after the second treatment was noted (first intervention 179.5 days vs. second intervention 273.5 days; p = 0.032)., Conclusion: In this retrospective analysis, Lutonix PCB proved to be safe and effective in treating restenosis in dysfunctional dialysis access with results comparable to the literature available. Larger studies are needed to prove abovementioned results.

Introduction: Percutaneous transcatheter balloon angioplasty has evolved to the current mainstay treatment for salvage of dysfunctional dialysis access. Nonetheless, it is frequently associated with recurrent vessel restenosis and the need for multiple repeat treatments in order to maintain hemodynamic patency. Cutting-balloons, covered stents or stent-grafts, and paclitaxel-coated balloons have been extensively tested and investigated with the aim to improve immediate anatomical and long-term clinical results. Areas covered: In the present overview, we discuss the background and appraise relevant medical literature on the aforementioned technologies and provide a more in-depth synthesis of the results of different clinical studies for each device category. We will also discuss the limitations in the mode of action of each group of devices and envision what the future holds for the challenging field of dialysis access interventions. Expert commentary: We propose a good practice algorithm for the treatment of thrombosed or dysfunctional dialysis access.

Purpose: To report a Bayesian network meta-analysis of randomized controlled trials (RCTs) comparing bare metal stents (BMS), paclitaxel-coated balloons (PCBs), and drug-eluting stents (DES) with balloon angioplasty (BA) or with each other in the infrapopliteal arteries., Methods: Sixteen RCTs comprising 1805 patients with 1-year median follow-up were analyzed. Bayesian random effects binomial models were employed (WinBUGS). Relative treatment effects were expressed as odds ratios (ORs) with 95% credible intervals (CrI), and the cumulative rank probabilities were calculated to provide hierarchies of competing treatments. Quality of evidence (QoE) was assessed with the GRADE (grading of recommendations assessment, development, and evaluation) system. Sensitivity, heterogeneity, and consistency analyses were performed., Results: There was high QoE that infrapopliteal DES significantly reduced restenosis compared with BMS (OR 0.26, 95% CrI 0.12 to 0.51) and BA (OR 0.22, 95% CrI 0.11 to 0.45). Likewise, DES significantly reduced target lesion revascularization (TLR) compared with BA (OR 0.41, 95% CrI 0.22 to 0.75) and BMS (OR 0.26, 95% CrI 0.15 to 0.45). Paclitaxel-coated balloons also reduced TLR compared with BA (OR 0.55, 95% CrI 0.34 to 0.90) and BMS (OR 0.35, 95% CrI 0.18 to 0.67), but QoE was low to moderate. BA had lower TLR than BMS (OR 0.63, 95% CrI 0.40 to 0.99) with high QoE. DES was the only treatment that significantly reduced limb amputations compared with BA (OR 0.58, 95% CrI 0.35 to 0.96), PCB (OR 0.51, 95% CrI 0.26 to 0.98), or BMS (OR 0.38, 95% CrI 0.19 to 0.72) with moderate to high QoE. DES also significantly improved wound healing compared with BA (OR 2.02, 95% CrI 1.01 to 4.07) or BMS (OR 3.45, 95% CrI 1.41 to 8.73) with high QoE. Results were stable on sensitivity and meta-regression analyses without any significant publication bias or inconsistency., Conclusion: Infrapopliteal DES were associated with significantly lower rates of restenosis, TLR, and amputations and improved wound healing compared to BA and BMS. DES also significantly reduced amputations compared with PCB., (© The Author(s) 2016.)

Purpose: To provide a qualitative analysis and quantitative synthesis of randomized controlled trials (RCTs) investigating paclitaxel-coated balloons (PCBs) in the femoropopliteal artery., Methods: PubMed, EMBASE, AMED, Scopus, CENTRAL, online content, and abstracts from international meetings were last screened in April 2015 for eligible RCTs using the PRISMA selection process. Risk of bias was assessed using the Cochrane Collaboration's tool, and quality of evidence was evaluated with the GRADE system. Outcome measures included late lumen loss (LLL) at 6 months and event rates of major limb amputations, binary lesion restenosis, and target lesion revascularization (TLR). Pooled treatment effects were analyzed in a random effects model to account for clinical heterogeneity; the outcomes are presented as the rate ratios (RRs) and their 95% confidence intervals (CIs). Extensive meta-regression was performed to analyze potential confounders. The review was registered in the PROSPERO database (CRD42015023938; www.crd.york.ac.uk/PROSPERO)., Results: Eleven RCTs with 1609 subjects (1403 claudicants and 206 patients with critical limb ischemia) with medium-length femoropopliteal lesions (mean range 5.1-11.9 cm) were included. There was consistently high-quality evidence supporting the clear superiority of PCBs in terms of reduced LLL (mean difference -0.89 mm, 95% CI -1.14 to -0.64, p<0.001), less binary restenosis (RR 0.47, 95% CI 0.37 to 0.61, p<0.001), and fewer TLR events (RR 0.33, 95% CI 0.22 to 0.49, p<0.001). Major amputations were rare in both active and control arms (pooled event rate: 0.7%, 95% CI 0.3% to 1.2%). Results were stable across all potential risk modifiers and in the presence of stents as well. There was high-quality evidence that the dose of paclitaxel was related to the magnitude of the treatment effect; standard dose (3.0-μg and 3.5-μg) PCBs were significantly more effective compared with low-dose 2-μg PCB in reducing both restenosis (RR 2.1, 95% CI 1.2 to 3.4, p<0.001) and TLR (RR 2.5, 95% CI 1.9 to 3.8, p<0.001)., Conclusion: PCBs reduce by more than half the rates of restenosis and TLR in the femoropopliteal artery regardless of stent placement. Biologic effect size may vary according to paclitaxel bioavailability., (© The Author(s) 2016.)

Objectives: The authors sought to report the wound healing outcomes, health-related quality-of-life changes and quality-adjusted life-years (QALYs) gain in the 2 treatment arms of the ACHILLES (Comparing Angioplasty and DES in the Treatment of Subjects With Ischemic Infrapopliteal Arterial Disease) multicenter randomized trial., Background: The ACHILLES randomized trial has previously shown that sirolimus-eluting stents (SES) may achieve lower vessel restenosis and higher event-free survival rates compared with plain balloon angioplasty (PTA) for infrapopliteal lesions., Methods: A total of 200 patients were randomly assigned between SES and PTA for the treatment of infrapopliteal arterial occlusive lesions. Progression of wound healing was serially assessed by digital photography. Health-related quality-of-life scores were assessed with the self-administered EQ-5D questionnaire up to 1 year from randomization. QALYs gained were calculated with a standard multiplicative model using distribution-free Bayesian modeling., Results: In total, 109 open wounds (n = 54 in SES; n = 55 in PTA) were documented at baseline. At 6 months, wound volume reduction (%) was significantly higher in the SES group (95% healing [95% confidence interval (CI): 80% to 99%] compared with 60% healing [95% CI: 13% to 90%] in the PTA group; p = 0.048). At 1 year, rates of complete wound closure were higher in the case of SES (72.9% vs. 55.6% closed wounds in PTA; p = 0.088). The recorded weighted EQ-5D score improved significantly up to 1 year in case of SES (p < 0.0001), but not in case of PTA. There was a trend of more QALYs gained with SES compared with PTA up to 1 year after randomization. Relative QALY gain was 0.10 (95% CI: -0.01 to 0.21; p = 0.08) in the whole study and 0.17 (95% CI: -0.03 to 0.35; p = 0.09) in the wound subgroups comparison., Conclusions: Infrapopliteal SES accelerates wound healing and may improve quality of life compared with PTA. (Comparing Angioplasty and DES in the Treatment of Subjects With Ischemic Infrapopliteal Arterial Disease [ACHILLES]; NCT00640770)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: To report 1-year results of a single-center randomized controlled trial comparing paclitaxel-coated balloon (PCB) versus high-pressure plain balloon angioplasty for the treatment of failing arteriovenous fistulae (AVFs)., Materials and Methods: Forty patients (26 men; mean age, 61 y ± 14.63) were randomized at 1:1 to undergo PCB (n = 20) or high-pressure balloon (HPB; n = 20) angioplasty of dysfunctional AVFs. There were no significant differences in baseline demographics between groups. Enrollment required a clinical diagnosis of a dysfunctional AVF attributed to a single stenotic lesion verified with digital subtraction angiography. Primary endpoints included device success, anatomic success, clinical success, and target lesion revascularization (TLR)-free survival. Secondary endpoints included dialysis circuit primary patency and procedure-related complication rates., Results: Device success rates were 100% in the HPB group and 35% in the PCB group (P < 0001): further dilation with an HPB was needed to achieve anatomic success in 13 of 20 cases in the PCB group (65%). Anatomic and clinical success rates were 100% in both groups. TLR-free survival (PCB, 308 d; HPB, 161 d; hazard ratio [HR], 0.478; 95% confidence interval [CI], 0.236-0.966; P = .03) and access circuit primary patency (PCB, 270 d; HPB, 161 d; HR, 0.479; 95% CI, 0.237-0.968; P = .04) were significantly in favor of PCB angioplasty. No minor or major procedure-related complications occurred., Conclusions: In this single-center study, the use of PCBs resulted in superior TLR-free survival and dialysis access circuit primary patency of dysfunctional AVFs. However, additional HPB postdilation was required in the majority of cases., (Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.)

Objective: To report the final results and cost-effectiveness analysis of a prospective randomized controlled trial investigating drug-eluting balloon (DEB) versus plain balloon angioplasty (BA) for the treatment of failing dialysis access (NCT01174472)., Methods: 40 patients were randomized to angioplasty with either DEB (n=20) or BA (n=20) for treatment of significant venous stenosis causing a failing dialysis access. Both arteriovenous fistulas (AVF) and synthetic arteriovenous grafts (AVG) were included. Angiographic follow up was scheduled every two months. Primary endpoints were technical success and target lesion primary patency at 1 year. Cumulative and survival analysis was performed. Incremental net benefit (INB) and incremental cost effectiveness ratio (ICER) were calculated and the cost-effectiveness acceptability curve (CEAC) was drawn., Results: Baseline variables were equally distributed between the two groups. At 1 year, cumulative target lesion primary patency was significantly higher after DEB application (35% vs. 5% after BA, p<0.001). Overall, median primary patency was 0.64 years in case of DEB vs. 0.36 years in case of BA (p=0.0007; unadjusted HR=0.27 [95%CI: 0.13-0.58]; Cox adjusted HR=0.23 [95%CI: 0.10-0.50]). ICER was 2198 Euros (€) per primary patency year of dialysis access gained. INB was 1068€ (95%CI: 31-2105€) for a willingness-to-pay (WTP) threshold of 5000€ (corresponding acceptability probability >97%)., Conclusion: DEB angioplasty may be a cost-effective option that significantly improves patency after angioplasty of venous stenoses of failing vascular dialysis access. Further large-scale randomized trials are warranted., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Introduction: This protocol was designed to evaluate the safety and feasibility of implanting drug-eluting stents (DES), as well as to compare their long-term results versus bare-metal stents (BMS), in a rabbit venous model, using frequency-domain optical coherence tomography (FD-OCT)., Methods: Thirteen New Zealand white rabbits underwent implantation of a zotarolimus-eluting stent in the iliac vein (DES Group) and a BMS in the contralateral iliac vein (BMS Group). The study's primary endpoints included technical success and the comparison of in-stent neointimal hyperplasia in the two study groups, using ex vivo FD-OCT, at 3 months., Results: Thirteen DES and 13 BMS were successfully implanted. The technical success rate was 100% (26/26 stents). Three animals (3/13, 23.0%) died within the first 45 days. The remaining 10/13 animals (77%) were euthanized on the 90th day following stent implantation. The 20 stents were successfully removed. Successful ex vivo FD-OCT was performed in all stent-implanted iliac vein segments, 10 in the DES Group and 10 in the BMS Group. There was no statistically significant difference in the mean neointimal thickness between the two groups (3.02 ± 1.19 mm2 in DES Group vs. 2.76 ± 1.17 mm2 in BMS Group; p=0.0501)., Conclusions: In this experimental protocol, DES implantation in the venous system was safe and feasible. Hyperplasia thickness was similar in both groups after 3 months' follow up.

Objectives: This study sought to report the results of a prospective randomized controlled trial comparing paclitaxel-coated balloons (PCB) versus drug-eluting stents (DES) in long infrapopliteal lesions., Background: DES have an established role in the treatment of short infrapopliteal lesions, whereas there is increasing evidence for the use of PCB in longer below-the-knee lesions., Methods: Inclusion criteria were patients with Rutherford classes 3 to 6 and angiographically documented infrapopliteal disease with a minimum lesion length of 70 mm. The primary endpoint was target lesion restenosis >50% assessed by digital angiography at 6 months. Secondary endpoints included immediate post-procedure stenosis and target lesion revascularization., Results: Fifty patients were randomized to undergo infrapopliteal PCB angioplasty (25 arteries in 25 limbs; PCB group) or primary DES placement (30 arteries in 27 limbs; DES group). Immediate residual post-procedure stenosis was significantly lower in DES (9.6 ± 2.2% vs. 24.8 ± 3.5% in PCB; p < 0.0001). At 6 months, 5 patients died (2 in PCB vs. 3 in DES; p = 1.00) and 3 suffered a major amputation (1 in PCB vs. 2 in DES; p = 1.00). In total, 44 angiograms were evaluable with quantitative vessel analysis. Binary (>50%) angiographic restenosis rate was significantly lower in DES (7 of 25 [28%] vs. 11 of 19 [57.9%] in PCB; p = 0.0457). There were no significant differences with regard to target lesion revascularization (2 of 26 [7.7%] in DES vs. 3 of 22 [13.6%] in PCB; p = 0.65). Positive vessel wall remodeling was observed in 3 cases in the PCB arm (3 of 19 [(15.8%)] vs. 0 of 19 [0%] in DES; p = 0.07)., Conclusions: Compared with PCB in long infrapopliteal lesions, DES are related with significantly lower residual immediate post-procedure stenosis and have shown significantly reduced vessel restenosis at 6 months. PCB may produce positive vessel remodeling. (Infrapopliteal Drug-Eluting Angioplasty Versus Stenting [IDEAS-I]; NCT01517997)., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the phenomenon of distal embolization during subintimal angioplasty with or without stenting of femoropopliteal chronic total occlusions (CTOs)., Methods: This prospective study included 40 consecutive patients (35 men; mean age 65.4±9.3 years) who underwent subintimal angioplasty alone (n=14) or with stenting (n=26) of CTOs in the femoropopliteal segment. A Spider protection filter was used to capture any possible macro- or microemboli generated during balloon inflation/stenting. Arterial outflow was angiographically checked during each consecutive procedural step. All filters were examined on site for macroscopic material, while the first 20 filters underwent further histopathological qualitative and semiquantitative analysis using a 0+ to 3+ score., Results: There was no angiographically or clinically evident distal embolization. Macroscopic particulate debris was not detected in any filter. Histopathology confirmed the absence of macroemboli but revealed microembolic material (diameter <100 μm) in all filters (20/20). The mean number of particles detected was 9.4±4.5 (range 5-17). Histopathological findings included fibrin conglomerates (20/20), trapped erythrocytes (19/20), inflammatory cells (16/20), calcification minerals (6/20), extracellular matrix (6/20), cholesterol clefts (6/20), and endothelial cells (6/20). Captured material was classified as fresh and old thrombus in 7/20 and 4/20 cases, respectively. Semiquantitative analysis demonstrated that the collected microparticles consisted primarily of fibrin conglomerates (median score 2+), trapped erythrocytes (median score 1+), and inflammatory cells (median score 1+)., Conclusion: Macroscopically evident emboli were not detected following subintimal angioplasty or stenting of femoropopliteal CTOs. Microscopic debris was present in all filters. The clinical significance of the phenomenon remains to be determined.

Purpose: To investigate the safety and feasibility of percutaneous endovascular recanalization of late total occlusions of infrapopliteal drug-eluting stents (DES)., Methods: A retrospective study investigated all 408 infrapopliteal stent procedures performed in 367 patients between January 2007 and October 2013 to identify those who underwent percutaneous reintervention for symptomatic infrapopliteal balloon-expandable DES occlusion. The search identified 49 patients with at least one infrapopliteal DES occlusion in 61 (14.9%) of 408 limbs. Seven (14.3%) patients were excluded from the analysis owing to asymptomatic status (n=6) and acute thrombotic occlusion (n=1), leaving 42 patients who underwent endovascular revascularization of occluded stents in 54 limbs. The study's primary outcomes were technical success and complication rates of endovascular recanalization, while secondary outcomes included limb salvage and the identification of factors influencing primary results., Results: Technical success was 90.7% (49/54 procedures). Technical failure was seen only in cases of stent collapse and overlapping native popliteal artery-infrapopliteal stent occlusion. According to Kaplan-Meier analysis, survival was 89.6%, 81.1%, and 73.5% at 1, 2, and 3 years, respectively, while limb salvage rates were 86.1%, 79.3%, and 72.7% at the same time points. There was 1 (1.8%) case of distal embolization. No factors influencing outcomes could be identified., Conclusion: Percutaneous recanalization of infrapopliteal stent total occlusions is safe and feasible. Technical failure was noted in cases of stent deformation occurring at the pedal artery and in overlapping native popliteal artery-infrapopliteal stent occlusion.

Objective: Several randomized controlled trials (RCTs) have shown the superiority of some of these technologies over balloon angioplasty, but direct comparisons between these treatment options are lacking. The authors conducted a network meta-analysis of RCTs comparing bare nitinol stents, covered nitinol stents, paclitaxel- or sirolimus-eluting stents (PES or SES), and paclitaxel-coated balloons (PCB) with plain balloon angioplasty or with each other in the femoropopliteal artery (PROSPERO registry: CRD42013004845)., Methods: Sixteen RCTs comprising 2532 patients with 4227 person-years of follow-up were analyzed on an intention-to-treat basis. Bayesian random effects Poisson and binomial models were used for mixed treatment comparisons (WinBUGS). Clinical heterogeneity was accounted for by incorporating a meta-regression model on trial-specific baseline risk. End points included technical success, vascular restenosis, target lesion revascularization, and major amputations. Pairwise odds ratios and rate ratios (ORs and RRs) of absolute treatment effects were calculated, and the probabilities of each treatment being best are reported. Summary estimates are reported as the posterior median and associated credible intervals (CrIs) that serve the same purpose as confidence intervals in the context of the Bayesian framework. Extensive sensitivity, meta-regression, and network consistency analyses were performed to evaluate heterogeneity., Results: Technical success was highest with covered stents (pooled OR, 13.6; 95% CrI, 3.3-31.1, probability best 82%) followed by uncovered stents (pooled OR, 7.0; 95% CrI, 2.6-129, probability best 18%) when compared with balloon angioplasty (reference treatment). Vascular restenosis was lowest with PES (RR, 0.43; 95% CrI, 0.16-1.18, probability best 45%) followed by PCB (RR, 0.43; 95% CrI, 0.26-0.67, probability best 42%). Target lesion revascularization was lowest with PCB (RR, 0.36; 95% CrI, 0.23-0.55, probability best 56%) followed by PES (RR, 0.42; 95% CrI, 0.16-1.06, probability best 33%). Major amputations were rare in all treatment and control groups (pooled amputation rate of 0.7 events per 100 person-years)., Conclusions: Immediate technical success is better with the use of covered stents, whereas paclitaxel-eluting stents and paclitaxel-coated balloons offer the best long-term results in the femoropopliteal artery., (Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Purpose: To report the long-term angiographic and clinical results in a series of below-the-ankle (BTA) angioplasty procedures and to present some biomechanical issues related to the unique anatomical geometry of the ankle., Methods: We performed a retrospective analysis of BTA angioplasty procedures. Clinical end points included technical success, patient mortality, salvage of the treated foot, and repeat target lesion revascularization. Imaging end points included primary patency, binary restenosis of the target lesion at the 50% threshold, and stent integrity (stent fracture, deformation, or collapse). Univariate subgroup analysis was performed., Results: In total, 40 limbs in 37 patients (age 73.5 ± 8.2 years) with critical limb ischemia were included and 42 inframalleolar lesions (4.2 ± 1.4 cm) were analyzed. Technical success was achieved in 95.2% (40 of 42). Provisional stent placement was performed in 45.2% (19 of 42). Two patients died, and two major amputations occurred up to 3 years. At 1 year, overall primary vessel patency was 50.4 ± 9.1%, lesion binary restenosis rate was 64.1 ± 8.3%, and repeat intervention-free survival was 93.6 ± 4.3% according to life table analysis of all treated lesions. Pairwise subgroup analysis showed that BTA self-expanding stents were associated with significantly higher restenosis and poorer primary patency compared to plain balloon angioplasty or sirolimus-eluting balloon-expandable stents. Significant deformation and/or fracture of balloon-expandable stents placed BTA were identified in five of 11. Dynamic imaging showed that the dorsalis pedis artery is kinked during foot dorsiflexion, whereas the distal posterior tibial artery is kinked during plantar flexion of the foot., Conclusion: BTA angioplasty for critical limb ischemia treatment is safe and feasible with satisfactory long-term results. BTA stent placement must be reserved for bailout indications.

Purpose: Application of metal stents is complicated by neointimal hyperplasia leading to vessel restenosis and reocclusion. Treatment options in cases presenting with complete occlusion of the stented segment and recurrent critical limb ischemia (CLI) are limited. We present the option of the subintimal/substent technique in dealing with occluded stents., Methods: The study included patients presenting with recurrent CLI due to impaired blood flow as a result of complete occlusion of previously inserted metal stents and unsuccessful intraluminal crossing of the lesion via either the antegrade or retrograde approach. In these cases, crossing the occlusion through the subintimal/substent plane was attempted. Primary end points included technical success, safety of the procedure, clinical improvement, and limb salvage, while secondary end points were patient survival, primary patency, and vessel restenosis rates at 1-year follow-up. Study end points were calculated by Kaplan-Meier survival analysis., Results: Between July 2006 and October 2011, a total of 14 patients (mean age 69.14 ± 12.59 years, 12 men) were treated with the substent technique and included in the analysis. Technical success rate was 85.71% (12 of 14), with a total lesion length of 193.57 ± 90.78 mm. The mean occluded stented segment length was 90.21 ± 44.34 mm. In 10 (83.33%) of 12 cases, a new stent had to be placed by the side of the old occluded one, while the remaining two cases (16.67%) were treated only with balloon angioplasty. No serious adverse events were noted during the immediate postprocedural period. All successfully treated patients improved clinically. Estimated limb salvage was 90.9%, and patient survival rate was 90.0% at 1 year's follow-up. Primary patency was 45.50% and vessel restenosis 77.30%., Conclusion: Subintimal recanalization of occluded metal stents through the substent plane is a valuable alternative treatment option, especially in patients with recurrent CLI with few alternatives.

Drug-coated balloon (DCB) technologies represent the latest and hottest development in the field of endovascular treatment of peripheral arterial disease. Initial experience with paclitaxel-coated balloon use in the femoral artery has demonstrated lower mid-term restenosis and superior mid-term clinical outcomes in terms of improved wound healing and reduced repeat angioplasty rates compared with standard balloon angioplasty. Many companies are presently developing and/or improving DCB catheters and therefore ongoing, technical improvements of the already existing platforms, new drugs, and innovative carriers are expected. The ongoing basic research studies and various multicenter randomized, controlled trials that are currently in progress will offer valuable scientific insights regarding the long-term effectiveness and other crucial issues, such as efficacy in various vascular beds, optimal balloon dosage, and post angioplasty antiplatelet therapy. Future applications of these devices also could include in-stent restenosis, anastomotic stenosis of surgical bypass, and benign stenoses of the central venous system. The authors envision that DCB angioplasty will evolve to a major paradigm shift in the endovascular treatment of occlusive vascular diseases.

Background: A well-established method to preserve failing synthetic arteriovenous grafts (AVGs) dialysis accesses is percutaneous transluminal angioplasty (PTA). Nevertheless, the one-year primary patency rate following PTA is approximately 25%. This study was designed to compare the angiographic and clinical outcomes following stent-graft insertion versus angioplasty and/or bare metal stenting (BMS) of recurrently failing AVGs, because of anastomotic and/or venous outflow stenoses., Methods: Self-expanding stent-grafts were deployed for the treatment of failing AVGs in case of recurrent stenosis after treatment with conventional angioplasty or bail-out BMS. Regular angiographic follow-up was scheduled every two months the first six months and every three months thereafter. Data from previous procedures on the same treatment site were retrieved from our database. Primary patency was defined as a functioning graft with a patent treatment site without angiographic restenosis >50% and without any subsequent repeat procedures. Outcome data were analyzed by Kaplan-Meier analysis., Results: In total, 35 patients previously treated with angioplasty and/or BMS for the treatment of recurrent significant AVG stenosis (group PTA), underwent stent-graft placement of the same treatment site (group SG). Of those, 20 patients had undergone angioplasty and 15 bail-out BMS. Mean lesion length was 4.8±1.7cm. Primary patency was significantly improved in the SG group (Hazard Ratio [HR] = 0.2 [95% CI= 0.11-0.36], P=.0001) by log-rank test. The estimated six and 12-month patency rates were 76.9% vs. 25.7%, and 61.4% vs. 8.6% for groups SG and PTA respectively, (P<.0001)., Conclusions: Stent-graft placement significantly improves primary patency of anastomotic and venous outflow stenoses in recurrently failing prosthetic arteriovenous grafts.

Introduction: There are no cost-utility data about below-the-knee placement of drug-eluting stents. The authors determined the cost-effectiveness of infrapopliteal drug-eluting stents for critical limb ischemia (CLI) treatment., Methods: The event-free individual survival outcomes defined by the absence of any major events, including death, major amputation, and target limb repeat procedures, were reconstructed on the basis of two published infrapopliteal series. The first included spot Bail-out use of Sirolimus-eluting stents versus bare metal stents after suboptimal balloon angioplasty (Bail-out SES).The second was full-lesion Primary Everolimus-eluting stenting versus plain balloon angioplasty and bail-out bare metal stenting as necessary (primary EES). The number-needed-to-treat (NNT) to avoid one major event and incremental cost-effectiveness ratios (ICERs) were calculated for a 3-year postprocedural period for both strategies., Results: Overall event-free survival was significantly improved in both strategies (hazard ratio (HR) [confidence interval (CI)]: 0.68 [0.41-1.12] in Bail-out SES and HR [CI]: 0.53 [0.29-0.99] in Primary EES). Event-free survival gain per patient was 0.89 (range, 0.11-3.0) years in Bail-out SES with an NNT of 4.6 (CI: 2.5-25.6) and a corresponding ICER of 6,518 (range 1,685-10,112). Survival gain was 0.91 (range 0.25-3.0) years in Primary EES with an NNT of 2.7 (CI: 1.7-5.8) and an ICER of 11,581 (range, 4,945-21,428) per event-free life-year gained. Two-way sensitivity analysis showed that stented lesion length >10 cm and/or DES list price >1000 were associated with the least economically favorable scenario in both strategies., Conclusions: Both strategies of bail-out SES and primary EES placement in the infrapopliteal arteries for CLI treatment exhibit single-digit NNT and relatively low corresponding ICERs.

Purpose: To investigate the outcomes following primary deployment of drug-eluting stents (DES) for the treatment of infrapopliteal bifurcation lesions in patients suffering from critical limb ischemia (CLI)., Methods: This was a retrospective study of a registry enrolling all patients suffering from chronic infrapopliteal artery disease and undergoing treatment of tibial bifurcation lesions with DES using 3 techniques: balloon and stent (single stent), T-shape double-stent, and culotte double-stent. The analysis included 39 CLI patients (32 men; mean age 69 ± 10 years) who underwent primary stenting of 41 infrapopliteal bifurcations. Most patients (29, 70.7%) were classified as Rutherford category 4. The mean lesion length was 31.3 ± 13.1 mm. The primary endpoints were amputation-free survival, target lesion revascularization (TLR)-free survival, angiographic 2-vessel primary patency (2VPP), and 1-vessel primary patency (1VPP). Secondary endpoints included survival and angiographic binary restenosis. A Cox regression analysis was performed to identify independent predictors influencing outcomes, Results: Technical success was achieved in all cases. The mean clinical and angiographic follow-up intervals were 47.5 ± 14.8 and 17.5 ± 12.5 months, respectively. According to the Kaplan-Meier analysis, overall survival, amputation-free survival, and TLR-free survival estimates were 79.5%, 84.3%, and 58.0%, respectively, at 5 years. At 12, 24, and 36 months, the 2VPP rates were 77.2%, 47.5%, and 33.9%, and the 1VPP rates were 84.0%, 65.5%, and 54.5%, respectively. Binary restenosis rates were 26.4%, 57.3%, and 82.2% at 12, 24, and 36 months; restenotic lesions were mainly detected at the origin of the bifurcations. The regression model did not identify any independent predictors influencing outcome., Conclusion: DES application for below-the-knee bifurcation lesions was safe and resulted in satisfactory long-term angiographic and clinical outcomes comparable to those reported following infrapopliteal endovascular treatment.

Purpose: This study was designed to investigate the long-term angiographic and clinical outcomes of percutaneous transluminal angioplasty (PTA) of the arteria profunda femoralis (PFA), in a series of patients suffering from critical limb ischemia (CLI) or severe intermittent claudication (IC)., Methods: Our department's database was searched to identify patients who underwent PTA or bail-out stenting of the PFA. Among the study's inclusion criteria were Rutherford categories 3-6 and ≥70% stenosis of the PFA. Only de novo stenotic lesions were assessed. Primary endpoints were technical success, angiographic lesion primary patency, angiographic binary in-lesion restenosis, and target lesion recanalization (TLR) rates. Secondary endpoints included patient survival, limb salvage, and complication rates. Patient's baseline demographics, lesion, and procedural details were analyzed., Results: Between 2001 and 2011, 20 consecutive patients (17 males) with a mean age of 73 ± 9 (range 53-87) years underwent PTA or bail-out stenting in 23 PFA lesions. Critical limb ischemia was the indication in eight of 20 patients (40%). The mean lesion length was 31 ± 9.5 mm. The procedural technical success was 100% (23/23), whereas mean time angiographic and clinical follow-up was 26.8 ± 24.6 months. According to the Kaplan-Meier analysis, primary patency and binary restenosis rate were 95 and 86.1% respectively up to 8 years follow-up. No TLR procedures were performed. The 8-year patient survival and limb salvage rates were 87.5 and 84.7% respectively., Conclusions: PTA or stenting of focal, stenotic, PFA lesions, in patients suffering from CLI or IC, exhibit high long-term primary patency rates, as well as low binary restenosis and TLR rates. Large, multicenter studies are required to validate these results.

Purpose: To report the 6-month results of a prospective randomized trial investigating angioplasty with paclitaxel-coated balloons (PCB) vs. plain balloon angioplasty (BA) for the treatment of failing native arteriovenous fistulae (AVF) or prosthetic arteriovenous grafts (AVG)., Methods: The enrollment criteria for this non-inferiority hypothesis trial included clinical signs of failing dialysis access with angiographic documentation of a significant venous stenotic lesion in patients with AVF or AVG circuits. From March to December 2010, 40 patients (29 men; mean age 64.1 ± 14.3 years) were randomized to undergo either PCB dilation (n = 20) or standard BA (n = 20) of a stenosed venous outflow lesion. Regular angiographic follow-up was scheduled bimonthly. Study outcome measures included device success (<30% residual stenosis without postdilation), procedural success (<30% residual stenosis), and primary patency of the treated lesion (<50% angiographic restenosis and no need for any interim repeat procedures)., Results: Baseline and procedural variables were comparably distributed between both groups. Device success was 9/20 (45%) for the PCB device vs. 20/20 (100%) for standard control BA (p<0.001). Procedural success was 100% in both groups after further high-pressure post-dilation as necessary. There were no major or minor complications in either group. At 6 months, cumulative target lesion primary patency was significantly higher after PCB application (70% in PCB group vs. 25% in BA group, p<0.001; HR 0.30, 95% CI 0.12 to 0.71, p<0.006)., Conclusion: PCB angioplasty improves patency after angioplasty of venous stenoses of failing vascular access used for dialysis.

Modern critical limb ischemia management algorithms endorse an "endovascular first" strategy of treatment. The advent of stents coated with anti-restenotic agents that are gradually eluted to the vessel wall has revolutionized modern endovascular therapies. Several single-center, non-randomized cohort series have provided compelling data about the short- to mid-term safety and effectiveness of drug-eluting stents in below-the-knee lesions and have fuelled further large-scale research. Three multicenter randomized trials (the YUKON-BTX, the DESTINY and the ACHILLES trials) are now available and have paved the way for level I-A evidence about infrapopliteal use of drug-eluting stents. Amassed evidence strongly supports the use of olimus-eluting metal stents for focal obstructive infrapopliteal lesions in order to inhibit restenosis, prolong vessel patency and thereby achieve sustained patient improvement, as reflected by the significantly improved Rutherford-Becker classification, reduced number of repeat procedures and a trend towards improved wound healing. The present overview outlines current evidence about clinical outcomes after below-the-knee drug-eluting stent placement compared to more traditional endovascular treatments like conventional old balloon angioplasty and bare metal stents. Available evidence is appraised in the context of clinically meaningful results and relevant unresolved issues are highlighted.

Endovascular procedures have evolved to the mainstream treatment of choice for revascularization of infrapopliteal obstructive disease, especially in patients suffering from critical limb ischemia and multiple comorbidities. However, standard balloon angioplasty is limited by the potential of a suboptimal acute outcome due to elastic recoil and/or flow-limiting dissection, followed by neointimal hyperplasia and progressive vascular restenosis even in the case of bare-metal stent use. Drug-eluting stents and drug-coated balloons are emerging endovascular technologies with the promise of significant inhibition of vessel restenosis and improved clinical outcomes. The current review outlines the drug-eluting properties of those instruments and summarizes the currently available clinical data. The authors critically appraise the current status and also provide a glimpse of the near future of endovascular below-the-knee treatments.

Purpose: To in vivo investigate the histological response after single and double cryoplasty therapy in a rabbit iliac artery model., Materials and Methods: In total, 40 New Zealand White rabbits underwent percutaneous transluminal angioplasty of the iliac artery using either PolarCath balloon or a conventional angioplasty balloon of equal diameter. Arterial injury, inflammatory response and smooth muscle cells (SMC) apoptosis with the TUNEL (Terminal deoxynucleotidyl transferase dUTP Nick End Labeling) immunohistochemical assay were analyzed. Rabbits were divided between single or double balloon inflation and histological results were compared between cryoplasty and control angioplasty both at 30 min and 72 h., Results: Arterial injury and wall inflammation scores were low and similar between cryoplasty and control groups after single and double balloon inflation. Compared to conventional balloon angioplasty, Polarcath cryoplasty demonstrated superior SMC apoptosis after single inflation at 30 min [12.0±1.2 cells/(0.025 mm)2 vs 7.0±1.5 cells/(0.025 mm)(2), p=0.002], single inflation at 72 h [9.0±1.0 cells/(0.025 mm)(2) vs 5.4±1.4 cells/(0.025 mm)(2), p=0.001], double inflation at 30 min [11.6±1.5 cells/(0.025 mm)(2) vs 6.8±1.4 cells/(0.025 mm)(2), p=0.001] and double inflation at 72h [9.2±0.8 cells/(0.025 mm)(2) vs 5.0±0.7 cells/(0.025 mm)(2), p=0.001]. There were no significant differences in apoptosis between single and double cryoplasty application at 30 min and 72 h., Conclusion: Cryoplasty demonstrated superior rates of SMC apoptosis at 30 min and 72 h and was associated to relatively low arterial injury and inflammation scores. An immediate second PolarCath inflation did not achieve superior apoptosis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To report the long-term outcomes of a single-center prospective study investigating primary placement of everolimus-eluting metal stents for recanalization of long infrapopliteal lesions compared to a matched historical control group treated with plain balloon angioplasty and provisional placement of bare metal stents in a bailout manner., Methods: The study included 81 patients (63 men; mean age 71 years, range 45-85) suffering from critical limb ischemia (CLI) and angiographically proven long-segment (at least 1 lesion >4.5 cm) de novo infrapopliteal artery disease who underwent below-the-knee revascularization with either primary placement of everolimus-eluting stents (n = 47, 51 limbs, 102 lesions) or angioplasty and bailout bare metal stenting (n = 34, 36 limbs, 72 lesions). Clinical and angiographic follow-up was collected at regular time intervals. Primary clinical and angiographic endpoints included patient survival, major amputation-free survival, angiographic primary patency, angiographic binary restenosis (>50%), and overall event-free survival. Results were stratified according to endovascular treatment received. Multivariable Cox proportional hazards regression analysis was applied to adjust for confounding factors of heterogeneity., Results: Baseline demographics were well matched. No significant differences were identified between the 2 groups with regard to overall 3-year patient survival (82.2% versus 65.7%; p = 0.90) and amputation-free survival (77.1% versus 86.9%; p = 0.20). Up to 3 years, lesions fully covered with everolimus-eluting stents were associated with significantly higher primary patency [hazard ratio (HR) 7.98, 95% CI 3.69 to 17.25, p < 0.0001], reduced binary restenosis (HR 2.94, 95% CI 1.74 to 4.99, p < 0.0001), and improved overall event-free survival (HR 2.19, 95% CI 1.16 to 4.13, p = 0.015) versus the matched historical control group., Conclusion: Primary infrapopliteal everolimus-eluting stenting for CLI treatment significantly inhibits restenosis and improves long-term angiographic patency and overall patient event-free survival compared to balloon angioplasty and bailout bare metal stenting.

The purpose of this study was to investigate the immediate and long-term results of cryoplasty versus conventional balloon angioplasty in the femoropopliteal artery of diabetic patients. Fifty diabetic patients (41 men, mean age 68 years) were randomized to cryoplasty (group CRYO; 24 patients with 31 lesions) or conventional balloon angioplasty (group COBA; 26 patients with 34 lesions) of the femoropopliteal artery. Technical success was defined as <30% residual stenosis without any adjunctive stenting. Primary end points included technical success, primary patency, binary in-lesion restenosis (>50%), and freedom from target lesion recanalization. Cox proportional hazards regression analysis was performed to adjust for confounding factors of heterogeneity. In total, 61.3% (19 of 31) in group CRYO and 52.9% (18 of 34) in group COBA were de novo lesions. More than 70% of the lesions were Transatlantic Inter-Society Consensus (TASC) B and C in both groups, and 41.4% of the patients in group CRYO and 38.7% in group COBA suffered from critical limb ischemia. Immediate technical success rate was 58.0% in group CRYO versus 64.0% in group COBA (p = 0.29). According to 3-year Kaplan-Meier estimates, there were no significant differences with regard to patient survival (86.8% in group CRYO vs. 87.0% in group COBA, p = 0.54) and limb salvage (95.8 vs. 92.1% in groups CRYO and COBA, respectively, p = 0.60). There was a nonsignificant trend of increased binary restenosis in group CRYO (hazard ratio [HR] 1.3; 95% CI 0.6-2.6, p = 0.45). Primary patency was significantly lower in group CRYO compared with group COBA (HR 2.2; 95% CI 1.1-4.3, p = 0.02). Significantly more repeat intervention events because of recurrent symptoms were required in group CRYO (HR 2.5; 95% CI 1.2-5.3, p = 0.01). Cryoplasty was associated with lower primary patency and more clinically driven repeat procedures after long-term follow-up compared with conventional balloon angioplasty.

Purpose: To investigate the incidence, anatomical location, and clinical impact of fractures and/or compression of infrapopliteal balloon-expandable metal stents implanted for critical limb ischemia (CLI) treatment., Methods: This prospective study included 63 CLI patients (45 men; mean age 71.3+/-9.5 years) who had been treated with infrapopliteal angioplasty and stent placement for 191 lesions in 84 limbs. In all, 369 stents (296 stainless steel and 73 cobalt-chromium alloy) were implanted; 239 were placed overlapping in tandem lesions. Mean length of the overall stented segment was 4.4+/-6.3 cm (range 1.6-14.0). Stents were located in the tibioperoneal (n = 34), anterior tibial (n = 195), posterior tibial (n = 63), and peroneal (n = 77) arteries. Follow-up consisted of digital subtraction angiography and infrapopliteal radiography imaging at 2 different angles. Evaluation of stents for the presence of fracture and/or compression was done after digital processing at the highest possible magnification. Stent fractures were defined according to published standards, whereas compression was classified as severe shape alteration and/or collapse of the stent mesh. Angiographic restenosis was based on a 50% threshold., Results: Mean follow-up was 15+/-11 months (range 6-60). Image analysis detected 1 (0.3%) severe stent fracture (complete separation and misalignment of stent struts) and 11 (3.0%) stent compressions. Infrapopliteal stent fracture and compressions were associated with increased artery restenosis [100% (12/12) versus 47.3% (169/357), p<0.001] and an increased rate of clinical deterioration and clinically-driven reinterventions [41.7% (5/12 limbs) versus 19.4% (14/72 limbs), p = 0.04]. The single fracture and most of the compressions were located in the distal third of the anterior tibial artery., Conclusion: Stent fractures and compressions of infrapopliteal balloon-expandable metal stents are infrequent. However, they may be related to increased restenosis.