Management of Central Venous Stenoses and Occlusions.

Symptomatic central venous stenosis and occlusion remains the gordian knot of vascular access. Advances in techniques, like sharp recanalization, allowed for improved success rates in crossing these difficult lesions. There is also increasing evidence of new devices in treating central venous stenosis and, at the same time, improving the time needed between interventions. High-pressure balloons, paclitaxel-coated balloons, bare metal stents and covered stents have been tested with an aim to offer additional treatment options, although obstacles still exist. In the current review, authors describe relevant techniques and options, provide the evidence and evaluate the actual implementation of these devices in this demanding field.

Polymer-coated paclitaxel-eluting stents for the treatment of stenosed native arteriovenous fistulas: Long-term results from the ELUDIA study.

BACKGROUND: Percutaneous transluminal angioplasty is the preferred treatment of stenosed failing arteriovenous fistulas (AVF) but is hampered by increasing rates of vascular restenosis because of development of myointimal hyperplasia. METHODS: This multicenter observational study of polymer-coated low-dose paclitaxel-eluting stents (ELUvia stents by Boston Scientific) in stenosed AVF undergoing hemoDIAlysis (ELUDIA) was jointly conducted in three tertiary hospitals from Greece and Singapore. Failure of AVF was defined according to K-DOQI criteria and significant fistula stenosis (>50%DS by visual estimate) was determined with subtraction angiography. Patients were considered for ELUVIA stent insertion based on significant elastic recoil following balloon angioplasty for the treatment of a single vascular stenosis within a native AVF. The primary outcome measure was sustained long-term patency of the treated lesion/fistula circuit defined as successful stent placement with resumption of uninterrupted hemodialysis and without significant vascular restenosis (50%DS threshold) or other secondary interventions during follow-up. RESULTS: Some 23 patients received the ELUVIA paclitaxel-eluting stent (eight radiocephalic, 12 brachiocephalic, and three transposed brachiobasilic native AVFs). Mean AVF age at the time of failure was 33.9 ± 20.4 months. Treated lesions included 12 stenoses at the juxta-anastomotic segment, nine at the outflow veins, and two cephalic arch lesions with a mean diameter stenosis of 86 ± 8%. Median stent diameter and length used were 7 mm and 40 mm, respectively. After a median follow-up period of 20 months, some 18 stents out of 23 cases remained patent (cumulative rate 78.3%) without any clinical or imaging evidence of recurrent stenosis. Estimated primary patency of the ELUVIA stents was 80.6% and of the corresponding fistula circuit 65.1% at 2 years by Kaplan-Meier methods. CONCLUSIONS: This observational study has shown promising long-term results of polymer-coated paclitaxel-eluting stents for the treatment of failing arteriovenous fistulas. Large-scale controlled studies are necessary.

Evaluation of a new paclitaxel-coated balloon catheter in an in vivo porcine peripheral venous model: Feasibility, safety, and drug deliverability.

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.

Ultrasound-guided femoral approach for coronary angiography and interventions in the porcine model.

Coronary angiography and percutaneous coronary intervention (PCI) procedural details in swine are similar to those performed to humans, since their heart and coronary anatomy closely resembles. However, only a few detailed descriptions of the procedure are available, containing notable differences. We present a feasible and reproducible protocol for percutaneous coronary interventions in porcine experimental models, utilizing ultrasound-guided femoral approach. Nine female pigs were studied to explore the feasibility of superficial femoral arterial (SFA) access for coronary angiography and provisional PCI, as well as the most suitable guiding coronary catheters and angiographic projections for the above interventions. Experiments were performed under general anesthesia, using ultrasound-guided puncture of the SFA to gain arterial access. The Amplatzer AR1® catheter, and the Right Coronary Bypass® catheter were used for the selective engagement of the right and the left coronary artery, respectively. Successful arterial access and subsequent cardiac catheterization were performed in all pigs. Only one animal required a second puncture for femoral artery access. None of the 9 animals presented any significant tachycardia or hypotensive episode. One animal developed an access site-related complication following the first catheterization procedure. During follow-up, 100% success of SFA catheterization was achieved using the same ultrasound-guided technique. The ultrasound-guided superficial femoral artery access for coronary angiography and provisional interventions in porcine models is a quick and safe alternative to the carotid artery approach. The RCB and AR1 catheters may be the best choice for the quick and easy selective coronary engagement of the right and left ostia, respectively.

Long-term outcomes of paclitaxel-coated balloons for non-malignant ureteral strictures.

PURPOSE: To evaluate the clinical efficacy and safety of drug-coated balloon (DCB) ureteroplasty for the management of non-malignant ureteral strictures. MATERIAL AND METHODS: A prospective "off-label" monocentric single-arm pilot study investigating the safety and efficacy of drug-coated balloon (DCB) (Lutonix®; BD, USA) was performed. Twenty-five patients with benign ureteral strictures related to uretero-enteric anastomosis (n = 13); lithiasis (n = 5), post-surgical complications (iatrogenic n = 5), transplanted kidney (n = 1) and post-radiotherapy (n = 1) were included. Following lesion crossing, predilatation was performed using 4-7 mm high-pressure balloon catheter (5-6Fr) with a balloon pressure of 6-7 atm based on the manufacturer's recommendation. In the absence of rupture of the ureteral wall, the DCB was dilated for 4 min. across the lesion. The process was repeated if deemed necessary to a maximum of three stricture dilatations. We analysed both clinical and radiological primary patency (no signs of ipsilateral hydronephrosis or improvement of the existing residual dilatation at the follow-up examinations) and secondarily safety endpoints. RESULTS: Mean lesion length was 40 ± 28.5 mm. Mean time follow up was 36 months ± 10.46 months. Strictures were located at upper ureteric (12%), lower ureteric (32%), ureterovesical anastomosis (4%) and uretero-enteric anastomosis (52%) levels. The overall radiological success at 1-year follow-up was 88% (22/25 patients). In 56% patients (14/25 patients with primary patency) the nephrostomy catheter was removed 21 days following a single DCB procedure. In 32% (8/25 patients) an additional dilatation sessions were required for maintaining the ureteral patency. The overall failure rate at 1-year follow-up was 12% (3/25 patients). Only one case of febrile urinary tract infection in a female patient (acute pyelonephritis) was encountered after the first dilatation. CONCLUSIONS: Paclitaxel-coated balloon ureteroplasty proved to be safe and effective for the treatment of non-malignant ureteral strictures. Larger studies are warranted to validate these promising initial results.

Drug-Coated Balloons for the Dysfunctional Vascular Access: An Evidence-Based Road Map to Treatment and the Existing Obstacles.

An underlying stenosis within the venous limb of a hemodialysis access circuit is the main etiology for graft and fistula dysfunction as well as other symptoms such as arm, breast, and neck swelling. Treatment options for both peripheral and central venous stenoses include plain old balloon angioplasty, angioplasty with drug-coated balloons, and stenting. This article discusses the current evidence for the use of drug-coated balloon angioplasty in this patient population.

Percutaneous Arteriovenous Fistula Creation with the WavelinQ 4-French EndoAVF System: A Single-Center Retrospective Analysis of 30 Patients.

PURPOSE: To retrospectively assess the safety and efficacy of percutaneous arteriovenous fistula (pAVF) creation with the WavelinQ 4-F EndoAVF System. MATERIALS AND METHODS: From February 2018 to June 2020, 30 pAVFs were created in 30 consecutive patients (men; age, 55.3 years ± 13.6). Of the 30 patients, 21 (70%) were already on hemodialysis using a central venous catheter. The primary outcome measures were technical success, complications, and cannulation rate. The secondary outcome measures included the number of secondary procedures needed for cannulation, maintenance time to cannulation, and pAVF survival. RESULTS: Technical success was 100%. The adverse event rate was 6.7% (2/30), including a pseudoaneurysm of the brachial artery that developed immediately after sheath removal and an aneurysm of the anastomosis 17 days after the procedure, which was treated with a covered stent placed in the arterial side. The mean follow-up was 547 days ± 315.7 (range, 14-1,071 days). The cannulation rate was 86.7% (26/30). The mean time to cannulation was 61.3 days ± 32.5 (range, 15-135 days). The mean follow-up after cannulation was 566.2 days ± 252.7 (range, 35-1,041 days). Four pAVFs were thrombosed after cannulation, with 2 of them successfully declotted. Sixteen interventions were needed to achieve cannulation after the index procedure in 15 patients (overall, 0.53 procedures/patient). Seven maintenance endovascular interventions (following cannulation) were performed during the follow-up period in 6 patients (overall, 0.27 procedures/patient, 0.17 procedures/patient-years). For the pAVFs that were cannulated, patency was 96% at 1 year, and 82% at 2 and 3 years, according to the Kaplan-Meier survival analysis. CONCLUSIONS: This initial experience suggests that pAVF creation is safe and can be successfully performed with high maturation and long-term patency rates. Larger-scale prospective studies are needed to validate the results.

Editor's Choice - Risk of Major Amputation Following Application of Paclitaxel Coated Balloons in the Lower Limb Arteries: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

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 (I2 = 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.

Computed tomography angiography scoring systems and the role of skull defects in the confirmation of brain death.

To assess and compare all current computed tomography angiography (CTA) scoring systems for the diagnostic workup of brain death (BD) to digital subtraction angiography (DSA) and clinical tests. Fifty-two patients with a clinical suspicion of BD underwent CTA and subsequently DSA. The diagnostic performance of all current CTA scoring systems was compared to that of DSA, in all patients with a suspicion of BD. A comparison to clinical tests was made only in DSA-positive for BD patients (n = 49), since in DSA-negative BD patients (n = 3) clinical tests were not performed. Further subgroup analysis was performed in relation to skull defects (SDs) stratification. Statistical analysis was conducted by applying statistics-contingency tables, Cochran's-Q test and McNemar's test. The CTA -10, and -7- and all 4-point scoring systems, showed overall sensitivities of 81,6%, 87.8% and 95.9% respectively and 100% specificity, when compared to DSA. In patients with a clinical verification of BD, the CTA -10 and -7-point scoring systems were significantly inferior to clinical tests (p = 0.004 and p = 0.031), while the 4-point scoring systems showed no such difference (p = 0.5). All 4-point scoring systems showed 100% sensitivity in patients with a minor SD or no SD. In patients with a major SD, all CTA scoring systems (- 10, - 7- and all 4-point) were less sensitive (62.5%, 62.5% and 75% respectively). The presence of a major SD was associated with an 8 × relative risk for false negative results in all 4-point scoring systems. CTA showed excellent diagnostic performance in patients with a suspicion of BD. The 4-point CTA scoring systems are the most sensitive for the diagnosis of BD, although in patients with a major SD patient, the role of CTA is ambiguous.

Paclitaxel-Coated Balloons for the Treatment of Symptomatic Central Venous Stenosis in Vascular Access: Results From a European, Multicenter, Single-Arm Retrospective Analysis.

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.

A Multicenter Global Registry of Paclitaxel Drug-Coated Balloon in Dysfunctional Arteriovenous Fistulae and Grafts: 6-Month Results.

PURPOSE: To assess the safety and clinical benefit of the Lutonix drug-coated balloon (DCB) catheter for the treatment of dysfunctional arteriovenous fistulae (AVF) and grafts (AVG) in a heterogenous real-world population. MATERIALS AND METHODS: This multicenter, prospective study enrolled 320 subjects from 12 countries in 25 sites across Europe and Asia. A total of 392 lesions were treated with the Lutonix 035 DCB catheter. Lesions were de novo and restenotic, located in every part of the circuit from the cannulation zone to central venous outflow. In-stent restenotic lesions also were treated. The primary safety endpoint was freedom from serious adverse events involving the access circuit through 30 days. The primary effectiveness endpoint was target lesion primary patency (TLPP) through 6 months. Secondary endpoints included access circuit primary patency (ACPP) at 6 months and the investigation of factors that would independently influence the primary endpoints. RESULTS: The primary safety endpoint was 95.5%, while TLPP was 73.9% at 6 months, per Kaplan-Meier survival analysis. ACPP was 71% at 6 months. TLPP for stenosis of AVFs was 78.1%. Subgroup analysis showed significantly improved TLPP when DCB was dilated for ≥120 seconds (P = .007). TLPP was significantly better when predilation occurred compared with cases where only DCB angioplasty was performed (77% vs 48.6%, P = .0005). CONCLUSIONS: The Lutonix AV Global Registry confirms that the Lutonix DCB is a safe and effective treatment option in real-world patients with dysfunctional AVF or AVG. Procedural details had a significant role in TLPP. No significant difference in TLPP was observed among different treatment areas.

Multicenter retrospective study of transcatheter arterial embolisation for life-threatening haemorrhage in patients with uncorrected bleeding diathesis.

BACKGROUND: We retrospectively investigated outcomes of emergency TAE for the management of life-threatening haemorrhage in patients with uncorrected bleeding diathesis. MATERIALS AND METHODS: This multicenter, retrospective, study, was designed to investigate the safety and efficacy of percutaneous TAE for the management of life-threatening haemorrhage in patients with uncorrected bleeding disorder at the time of embolization. All consecutive patients with uncorrected coagulation who underwent TAE for the treatment of haemorrhage, between January 1st and December 31th 2019 in three European centers were included. Inclusion criteria were thrombocytopenia (platelet count < 50,000/mL) and/or International Normalized Ratio (INR) ≥2.0, and/or activated partial thromboplastin time (aPTT) > 45 s, and/or a pre-existing underlying blood-clotting disorder such as factor VIII, Von Willebrand disease, hepatic cirrhosis with abnormal liver function tests. Primary outcome measures were technical success, rebleeding rate and clinical success. Secondary outcome measures included patients' 30-day survival rate, and procedure-related complications. RESULTS: In total, 134 patients underwent TAE for bleeding control. A subgroup of 17 patients with 18 procedures [11 female, mean age 70.5 ± 15 years] which represent 12.7% of the total number of patients, presented with pathological coagulation parameters at the time of TAE (haemophilia n = 3, thrombocytopenia n = 1, cirrhosis n = 5, anticoagulants n = 7, secondary to bleeding n = 1) and were analyzed. Technical success was 100%, as in all procedures the bleeding site was detected and successfully embolised. Clinical success was 100%, as none of the patients died of bleeding during hospitalization, nor was surgically treated for bleeding relapse. Only one rebleeding case was noted (5.9%) that was successfully treated with a second TAE. No procedure-related complications were noted. According to Kaplan-Meier analysis the estimated 30-day survival rate was 84.2%. CONCLUSION: TAE in selected patients with uncorrected bleeding diathesis should be considered as a suitable individualized management approach. Emergency TAE for life threatening haemorrhage in patients with coagulation cascade disorders should be used as an aid in realistic clinical decision making.

Use of the Covera Stent Graft for the Treatment of Dysfunctional or Thrombosed Arteriovenous Grafts: A Retrospective Analysis of 64 Patients.

PURPOSE: To retrospectively evaluate the safety and effectiveness of the Covera stent graft (SG) for the treatment of dysfunctional or thrombosed arteriovenous grafts (AVGs). MATERIALS AND METHODS: Within 29 months (February 2016-August 2018), 79 patients underwent Covera SG placement in the authors' department for the treatment of dysfunctional AVGs. Data were available for 64 patients who underwent 64 procedures, using 64 devices. Minimum follow-up was 6 months, unless reintervention occurred. Mean follow-up was 277 days (6-923 days). Treatment characteristics were 51 cases with venous-graft anastomosis (VGA) stenosis (79.7%), 13 cases of puncture zone stenosis (20.3%), 14 cases of in SG stenosis (21.9%), 8 cases of pseudoaneurysm treatment (12.5%) (1 treatment area might have had more than 1 characteristic). Thirty-six patients presented with thrombosis (56.2%), and 31 of 64 case were de novo treatment areas (48.4%). Primary outcome measurements were technical success and post-intervention primary patency (PIPP) at 6 months, whereas secondary outcome measurements included factors influencing primary outcome. RESULTS: Technical success was 100%. Median PIPP was 336 days, and 73.6% of treatment areas were patent at 6 months. There were no significant differences in terms of PIPP when de novo treatment areas were compared with restenotic areas (519 vs. 320 days, respectively; P = .1); patients who presented with versus those who presented without thrombosis (320 vs. 583 days, respectively; P = .07); puncture zone stenosis or elsewhere (329 vs. 686 days, respectively; P = .52); and VGA stenosis or elsewhere (336 vs. 335 days, respectively; P = .9). CONCLUSIONS: Use of the Covera SG for AVG treatment was safe and effective in every type of treatment area presented in this retrospective analysis.