Arteriovenous Access Stenosis Research Articles

Choosing the right treatment for the right lesion, Part II: a narrative review of drug-coated balloon angioplasty and its evolving role in dialysis access maintenance.

Drug-coated balloons (DCBs) seek to inhibit restenosis in treated hemodialysis access lesions by delivering an anti-proliferative agent (paclitaxel) into the vessel wall. While DCBs have proven effective in the coronary and peripheral arterial vasculature, the evidence for their use in arteriovenous (AV) access has been less robust. In part two of this review, a comprehensive overview of DCB mechanisms, implementation, and design is provided, followed by an examination of the evidence basis for their use in AV access stenosis. An electronic search was performed on PubMed and EMBASE to identify relevant randomized controlled trials (RCTs) comparing DCBs and plain balloon angioplasty from January 1, 2010 to June 30, 2022 published in English. As part of this narrative review, a review of DCB mechanisms of action, implementation, and design is provided, followed by a review of available RCTs and other studies. Numerous DCBs have been developed, each with unique properties, although the degree to which these differences impact clinical outcomes is unclear. Target lesion preparation, achieved by pre-dilation, and balloon inflation time have proven important factors in achieving optimal DCB treatment. Numerous RCTs have been performed, but have suffered from significant heterogeneity, and have often reported contrasting clinical results, making it difficult to draw conclusions on how to implement DCBs in daily practice. On the whole, it is likely there is a population of patients who benefit from DCB use, but it is unclear which patients benefit most and what device, technical, and procedural factors lead to optimal outcomes. Importantly, DCBs use appears safe in the end-stage renal disease (ESRD) population. DCB implementation has been tempered by the lack of clear signal regarding the benefits of DCB use. As further evidence is obtained, it is possible that a precision-based approach to DCBs may shed light onto which patients will truly benefit from DCBs. Until that time, the evidence reviewed herein may serve to guide interventionalists in their decision making, knowing that DCBs appear safe when used in AV access and may provide some benefit in certain patients.

Paclitaxel Coated Balloon Angioplasty vs. Plain Balloon Angioplasty for Haemodialysis Arteriovenous Access Stenosis: A Systematic Review and a Time to Event Meta-Analysis of Randomised Controlled Trials

A systematic review and meta-analysis of randomised controlled trials (RCTs) was performed to determine the effectiveness and safety of drug coated balloon (DCB) angioplasty compared with uncoated plain balloon (PB) angioplasty in treating arteriovenous access stenosis. MEDLINE, Embase, Scopus, and the Cochrane Central Register of Controlled Trials were searched for RCTs comparing paclitaxel coated DCB and PB angioplasty for arteriovenous access stenosis. The last date of the literature search was 31 December 2020. Risk of bias of the retrieved studies was assessed with the Cochrane Collaboration tool for assessing risk of bias (RoB 2.0). The random effects model was used to estimate the risk of loss of target lesion patency (six and 12 months) and circuit patency (six and 12 months). Procedure related adverse events and mortality rate were also compared. Patency results were pooled using the time to event meta-analytical method and the quality of evidence was assessed according to the GRADE approach. Sixteen eligible trials, including 1 682 lesions, were included in the quantitative analysis for the efficacy and safety of paclitaxel coated DCBs. DCBs were associated with a lower risk of loss of target lesion patency at six months (HR 0.53, 95% CI 0.42 – 0.66) and 12 months (HR 0.60, 95% CI 0.47 – 0.76), and were also associated with improved six and 12 month circuit patency. Overall quality of evidence was moderate to low. Procedural complications were rare, and the risk of death up to 12 months was similar between the two groups (OR 1.03, 95% CI 0.68 – 1.56). Paclitaxel coated DCBs reduced the risk of loss of target lesion patency and circuit patency in arteriovenous access stenosis compared with PBs. Considering the heterogeneity of the included trials, there is a need to investigate optimal treatment regimens regarding drug dose and agent of the DCB and the treatment procedure.

Drug-Coated Balloon for Arteriovenous Access Stenosis in Hemodialysis Patients

Hemodialysis access stenosis is a pervasive problem that occurs due to the physiology of the high-flow circuit. Stenosis occurs due to endothelial and smooth muscle injuries that result in neointimal hyperplasia. Percutaneous transluminal angioplasty is the standard treatment for dialysis access-induced stenosis. Unfortunately, it is also associated with vessel wall trauma, which causes further intimal hyperplasia and restenosis. Data from randomized controlled trials (RCTs) and systematic reviews of the use of drug-coated balloons (DCBs) for dialysis access stenosis have been controversial. While several single-center trials or RCTs have reported safe and effective use of DCBs, conflicting results still exist. Furthermore, paclitaxel is known to be associated with an increased mortality risk. Herein, we review the current evidence on the role of DCBs in the treatment of dialysis access stenosis.

Con: Vascular access surveillance in mature fistulas: is it worthwhile?

The risks and benefits of hemodialysis arteriovenous (AV) access surveillance have been debated since the introduction of AV access surveillance techniques. The debate is fuelled by the lack of robust, high-quality evidence with consistent and comparable patient-important outcomes. Additionally, there is a lack of clarity regarding the diagnostic cut points for AV access stenosis using the various surveillance techniques, questions about the appropriateness of the 'knee-jerk' response to intervention on a stenosis >50% regardless of the presence of clinical indicators and whether the intervention results in desired patient-important outcomes. The physiology of the AV access is complex considering the different hemodynamics within an AV fistula, which vary by time of dialysis, location, size of vessels and location of the stenosis. The current evidence suggests that the use of AV access surveillance in an AV fistula does detect more stenosis compared with clinical monitoring alone and leads to an increased number of procedures. It remains uncertain if that leads to improved patient-important outcomes such as prolonged AV fistula patency. Vascular access is an essential component of hemodialysis and further study is needed to clarify this long-standing debate. There needs to be better distinction between the strategies of vascular access surveillance, clinical monitoring with clinical indictors and preemptive intervention and their respective impacts on patient-important outcomes. Randomized controlled studies must be conducted with defined indications for intervention, reproducible methods of intervention and clinically important AV fistula and patient outcomes. The current guidelines need to be challenged and revised to permit these necessary studies to be done.

Clinical Evaluation of the Cook Advance Enforcer 35 Focal-Force PTA Balloon Catheter for Treatment of Hemodialysis Fistula Stenoses: A Feasibility Study

PurposeA prospective, single-center, single-arm feasibility study evaluated procedural and short-term performance of the Advance Enforcer 35 focal-force percutaneous transluminal angioplasty (PTA) balloon catheter in treating stenoses of mature native arteriovenous (AV) hemodialysis access circuits. Materials and MethodsTwenty-eight patients undergoing treatment for stenosis of a mature native AV hemodialysis access circuit were enrolled at a single institution. Angiographic assessments of the study lesion were required at baseline and after the procedure. Adjunctive procedures for significant residual stenosis were permitted, and patients had clinical and imaging follow-up for as long as 6 months. ResultsTreatment with the study balloon was effective in reducing the average percent diameter stenosis of the treated lesion from 66.3% (range, 43.8%–93.3%) before the procedure to 23.7% (range, −6.7% to 51.4%) after the procedure. The average inflation pressure required was 12.3 atm. Only 1 patient required an adjunctive procedure, and all patients could resume normal dialysis following the study procedure. At 3 months, 62.0% of study lesions remained patent, and the 6-month patency rate was 25.1%. Two adverse events associated with the study procedure were reported: access-site hematoma and forearm pain (3.6% each). ConclusionsThe results demonstrate safety of the study balloon in treating AV access stenosis. Nominal-diameter angioplasty was achieved at relatively low pressure in most study patients without the use of adjunctive procedures, and resumption of normal dialysis was achieved for all patients.

AVA 1. Salvage of Failing Native Arteriovenous Fistula by Interwoven Nitinol Stenting: A Review of Early Experience

Percutaneous angioplasty remains the most commonly employed method for treatment of native arteriovenous access stenosis. There is growing evidence that demonstrates benefit with covered stenting of recalcitrant stenosis in patients with an arteriovenous graft. Currently, the use of either bare-metal stents or covered stents in patients with native arteriovenous fistulas (AVFs) is not considered a first-line intervention. This case series aimed to examine the clinical effectiveness and feasibility of interwoven nitinol stenting in the salvage of failing AVFs. A prospective analysis was conducted of five patients who underwent interwoven nitinol stenting as a final salvage intervention for their failing AVFs. Clinical surveillance was performed with dialysis flow sheets; radiology surveillance was performed with duplex ultrasound at 6 weeks and 6 months. All patients were male, with a mean age of 67 years. The average AVF age was 17.6 months (range, 7-35 months); the average number of prior interventions was 1.4 fistuloplasties per patient. Fistuloplasty and stenting were performed as a final salvage procedure. Technical success rate was 100% with no complications. All patients were observed in the outpatient clinic 6 weeks after stenting. There was an average positive improvement in access flow rate of 209 mL/min, with average access flow rates of 154 mL/min before stenting and 359.1 mL/min after stenting (P = .059). Primary patency at 6 months and 12 months was 100%. Dialysis nurses were able to cannulate through the stents, and there was no occurrence of stent ulceration. Based on our initial experience, treatment of recurrent stenotic AVF with interwoven nitinol stenting is a safe and effective method of salvaging failing AVFs.

The association of genotype polymorphisms with vascular access patency in hemodialysis patients.

Some hemodialysis patients suffer from repeat dysfunction of dialysis vascular access and need procedures of angioplasty, thrombectomy, and even temporary catheter use. Why these patients are vulnerable to vascular access dysfunction and how to improve its patency are imperative to be discovered. Traditional risk factors for vascular access function had been widely investigated but could not fully explain this question. Several genotype polymorphisms were demonstrated to increase the incidence of cardiovascular disease and might also be linked to higher risk of vascular access dysfunction. As the major causes of arteriovenous access thrombosis are hypercoagulable status and arteriovenous access stenosis, the investigated genes mainly focus on the mediators of the coagulation cascade, inflammatory process, and endothelial dysfunction. The reported polymorphisms of genes significantly associated with arteriovenous access dysfunction included genes encoding methylene tetrahydrofolate reductase, coagulation factors, heme oxygenase-1, matrix metalloproteinase, transforming growth factor-β1, tumor necrosis factor-α, vascular endothelial growth factor-A, renin-angiotensin-aldosterone system, and protein methyl transferase. However, further prospective study is indispensable to elucidate the association between the genotype polymorphisms and the outcome of vascular access. More and more therapeutic options that focus on genotype polymorphisms may generate a great benefit to the patency of vascular access of uremic patients.

Meta‐analysis and commentary: Preemptive correction of arteriovenous access stenosis

Background: A recent meta-analysis by Ravani and colleagues (Ravani, P., et al., Am J Kidney Dis, 2016. 67(3): p. 446-60.) studied the effect of pre-emptive correction of arterio-venous dialysis vascular access versus deferred care, based on data from 11 trials. The authors reported a non-significant protective treatment effect of pre-emptive correction on access loss, while showing a significant protective effect on thrombosis rates conferred by pre-emptive correction. We revisit this analysis, including data extraction and effects of a heterogenous study population. Methods: We repeated data extraction from all referenced publications in the meta-analysis by Ravani et al. and corrected event counts where applicable. We repeated the meta-analyses with access loss as the outcome for studies that recruited patients with arterio-venous fistulae (AVF) and grafts (AVG), respectively, using a random effects model with relative risk (RR) and risk difference (RD) of access loss as the outcomes of interest. We repeated data extraction from all referenced publications, and corrected event counts where applicable. Results: Our conclusions differ from the original findings in two ways. First, after some amendment of the event counts extracted from Mayer et al. (Vascular and Endovascular Surgery 1993), we find a significant overall positive effect of pre-emptive correction on arterio-venous access loss in the overall study population [RR 0.80 (95% CI 0.64 to 0.99), RD -0.07 (95% CI -0.12 to -0.02); Figure 1]. Secondly, we highlight the impact of heterogeneous study populations on the meta-analysis. Whereas the data do not conclusively show a benefit of pre-emptive correction for arteriovenous grafts (AVG; RR = 0.87, 95% CI: 0.69 - 1.11), they show a strong protective effect for arteriovenous fistulae (AVF; RR = 0.5, 95% CI: 0.29 to 0.86). Discussion and Conclusion: These findings corroborate clinical arguments such as superior long-term patency of AVF and the nature of AVG failure that often involve infectious causes. The available data indicate mild or no benefit of pre-emptive correction for AVG, but strongly support tight monitoring of dialysis accesses and preemptive intervention and correction upon the slightest suspicion of access stenosis for AVF.

Pre-emptive correction for haemodialysis arteriovenous access stenosis.

Guidelines recommend routine arteriovenous (AV) graft and fistula surveillance (technology-based screening) in addition to clinical monitoring (physical examination) for early identification and pre-emptive correction of a stenosis before the access becomes dysfunctional. However, consequences on patient-relevant outcomes of pre-emptive correction of a stenosis in a functioning access as opposed to deferred correction, i.e. correction postponed to when the access becomes dysfunctional, are uncertain. We aimed to evaluate 1) whether pre-emptive correction of an AV access stenosis improves clinically relevant outcomes; 2) whether the effects of pre-emptive correction of an AV access stenosis differ by access type (fistula versus graft), aim (primary and secondary prophylaxis), and surveillance method for primary prophylaxis (Doppler ultrasound for the screening of functional and anatomical changes versus measurement of the flow in the access); and 3) whether other factors (dialysis duration, access location, configuration or materials, algorithm for referral for intervention, intervention strategies (surgical versus radiological or other), or study design) explain the heterogeneity that might exist in the effect estimates. We searched the Cochrane Kidney and Transplant Specialised Register to 30 November 2015 using search terms relevant to this review. We included all studies of any access surveillance method for early identification and pre-emptive treatment of an AV access stenosis. We extracted data on potentially remediable and irremediable failure of the access (i.e. thrombosis and access loss respectively); infection and mortality; and resource use (hospitalisation, diagnostic and intervention procedures). Analysis was by a random effects model and results expressed as risk ratio (RR), hazard ratio (HR) or incidence rate ratio (IRR) with 95% confidence intervals (CI). We identified 14 studies (1390 participants), nine enrolled adults without a known access stenosis (primary prophylaxis; three studies including people using fistulas) and five enrolled adults with a documented stenosis in a non-dysfunctional access (secondary prophylaxis; three studies in people using fistulas). Study follow-up ranged from 6 to 38 months, and study size ranged from 58 to 189 participants. In low- to moderate-quality evidence (based on GRADE criteria) in adults treated with haemodialysis, relative to no surveillance and deferred correction, surveillance with pre-emptive correction of an AV stenosis reduced the risk of thrombosis (RR 0.79, 95% CI 0.65 to 0.97; I² = 30%; 18 study comparisons, 1212 participants), but had imprecise effect on the risk of access loss (RR 0.81, 95% CI 0.65 to 1.02; I² = 0%; 11 study comparisons, 972 participants). In analyses subgrouped by access type, pre-emptive stenosis correction did not reduce the risk of thrombosis (RR 0.95, 95% CI 0.8 to 1.12; I² = 0%; 11 study comparisons, 697 participants) or access loss in grafts (RR 0.9, 95% CI 0.71 to 1.15; I² = 0%; 7 study comparisons; 662 participants), but did reduce the risk of thrombosis (RR 0.5, 95% CI 0.35 to 0.71; I² = 0%; 7 study comparisons, 515 participants) and the risk of access loss in fistulas (RR 0.5, 95% CI 0.29 to 0.86; I² = 0%; 4 studies; 310 participants). Three of the four studies reporting access loss data in fistulas (199 participants) were conducted in the same centre. Insufficient data were available to assess whether benefits vary by prophylaxis aim in fistulas (i.e. primary and secondary prophylaxis). Although the magnitude of the effects of pre-emptive stenosis correction was considerable for patient-centred outcomes, results were either heterogeneous or imprecise. While pre-emptive stenosis correction may reduce the rates of hospitalisation (IRR 0.54, 95% CI 0.31 to 0.93; I² = 67%; 4 study comparisons, 219 participants) and use of catheters (IRR 0.58, 95% CI 0.35 to 0.98; I² = 53%; 6 study comparisons, 394 participants), it may also increase the rates of diagnostic procedures (IRR 1.78, 95% CI 1.18 to 2.67; I² = 62%; 7 study comparisons, 539 participants), infection (IRR 1.74, 95% CI 0.78 to 3.91; I² = 0%; 3 studies, 248 participants) and mortality (RR 1.38, 95% CI 0.91 to 2.11; I² = 0%; 5 studies, 386 participants).In general, risk of bias was high or unclear in most studies for many domains we assessed. Four studies were published after 2005 and only one had evidence of registration within a trial registry. No study reported information on authorship and/or involvement of the study sponsor in data collection, analysis, and interpretation. Pre-emptive correction of a newly identified or known stenosis in a functional AV access does not improve access longevity. Although pre-emptive stenosis correction may be promising in fistulas existing evidence is insufficient to guide clinical practice and health policy. While pre-emptive stenosis correction may reduce the risk of hospitalisation, this benefit is uncertain whereas there may be a substantial increase (i.e. 80%) in the use of access-related procedures and procedure-related adverse events (e.g. infection, mortality). The net effects of pre-emptive correction on harms and resource use are thus unclear.

Preemptive Correction of Arteriovenous Access Stenosis: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Preemptive correction of a stenosis in an arteriovenous (AV) access (fistula or graft) that is adequately providing hemodialysis (functional AV access) may prolong access survival as compared to waiting for signs of access dysfunction to intervene (deferred salvage). However, the evidence in support of preemptive intervention is controversial. We evaluated benefits and harms of preemptive versus deferred correction of AV access stenosis. Systematic review and meta-analysis of randomized controlled trials. Adults receiving hemodialysis by a functional AV access. We searched the Cochrane Kidney and Transplant Specialised Register and EMBASE to October 15, 2015. Active access surveillance (flow measurement and Doppler or venous pressure) and preemptive correction of a newly identified stenosis versus routine clinical monitoring and deferred salvage, or preemptive correction of a known stenosis versus deferred salvage. Access loss (primary outcome) and thrombosis (overall and by access type), infection, mortality, hospitalization, and access-related procedures. We included 14 trials (1,390 participants; follow-up, 6-38 months). Relative to deferred salvage, preemptive correction of AV access stenosis had a nonsignificant effect on risk for access loss (risk ratio [RR], 0.81; 95% CI, 0.65-1.02; I(2)=0%) and a significant effect on risk for thrombosis (RR, 0.79; 95% CI, 0.65-0.97; I(2)=30%). Treatment effects were larger in fistulas than in grafts for both risk for access loss (subgroup difference, P=0.05) and risk for thrombosis (subgroup difference, P=0.002). Results were heterogeneous or imprecise for mortality, rates of access-related infections or procedures, and hospitalization. Small number and size of primary studies limited analysis power. Preemptive stenosis correction in a functional AV access does not improve access longevity. Although preemptive stenosis correction may be promising in fistulas, existing evidence is insufficient to guide clinical practice and health policy.

Endovascular Stent Placement for Hemodialysis Arteriovenous Access Stenosis.

This study aims to report the outcomes of nitinol and polytetrafluoroethylene covered stent placement to treat hemodialysis arteriovenous access stenosis at a single center over a five-year period. Clinical and radiological information was reviewed retrospectively. Poststent primary and secondary patency rates were determined using Kaplan-Meier analysis. Ten clinical variables were subjected to multivariate Cox regression analysis to determine predictors of patency after stent placement. During the study period 60 stents were deployed in 45 patients, with a mean follow-up of 24.5 months. The clinical and anatomical success rate was 98.3% (59/60). Poststent primary patency rates at 6, 12, and 24 months were 64%, 46%, and 35%, respectively. Poststent secondary patency rates at 6, 12, and 24 months were 95%, 89%, and 85%, respectively. Stent placement for upper arm lesions and in access less than 12 months of age was associated with reduced primary patency (adjusted hazards ratio [HR] 5.1, p = 0.0084, and HR 3.5, p = 0.0029, resp.). Resistant or recurrent stenosis can be successfully treated by endovascular stent placement with durable long-term patency, although multiple procedures are often required. Stent placement for upper arm lesions and in arteriovenous access less than 12 months of age was associated with increased risk of patency loss.

Phonographic signal with a fractional-order chaotic system: a novel and simple algorithm for analyzing residual arteriovenous access stenosis

To detect the early developmental stages of arteriovenous access (AVA) stenosis in hemodialysis patients, this study explored a stenosis detector based on the Burg method and the fractional-order chaos system (FOCS). The bruit developed by the blood flowing through AVA can be a viable noninvasive strategy for monitoring AVA functions. We used the Burg method of the autoregressive model to estimate the frequency spectra of phonographic signals recorded by an electronic stethoscope in patients' AVAs and to identify the spectral peaks in the region of 25-800 Hz. The frequency spectra differed significantly between normal and stenosis statuses in AVA. We found that the frequency and amplitude in power spectra analysis varied in accordance with the severity of AVA stenosis. However, the correlation of these parameters for classifying the degree of stenosis is limited when only using the Burg method. Therefore, we used an FOCS to monitor the differing frequency spectra between the normal condition and AVA stenosis. The variances of these two conditions were dynamic errors that were the coupling variables that tracked the responses between the master system and the slave system. A total of 42 patients who had received percutaneous transluminal angioplasty (PTA) for their failing AVAs was recruited for this study. In this study, the dynamic error, Index Ψ, was used to calculate the frequency spectrum redistribution in patients undergoing PTA. In addition, ΔImp was the index used to evaluate improvements in the luminal diameter between pre- and post-PTA. Therefore, we used linear regression to model the relationship between ΔImp and Index Ψ. The findings indicate that the proposed method has enhanced efficiency, especially in the venous anastomosis (V-site). The FOCS is a novel and simple algorithm for analyzing the residual AVA stenosis of PTA treatment.