John R. Ross

Objective: We report the 6-month outcomes of the Ark Cannulation Trial (ACT) I early feasibility study. This investigation examined the Ark as a potential innovative access tool for overcoming cannulation-related challenges and improving arteriovenous fistula (AVF) dependent hemodialysis through targeted cannulation. Methods: During this first-in-human, interventional, prospective, single arm, single site investigation, 13 patients were treated. Cohort 1 included patients with existing fistulas meeting the criteria for Ark implantation at planned sites, including depth (4–15 mm), diameter (⩾4 mm), flow (⩾500 mL/min) and a poorly accessible cannulation zone. Cohort 2 included patients who underwent AVF creation and implantation of Arks at time of initial surgery. For both Cohorts, clinical need determined if one or two Arks were implanted. The primary endpoint was effective initial cannulation of the access site after Ark implantation. The secondary endpoint was continued access of the Ark cannulation zone for hemodialysis and evaluation of device or procedure-related adverse events collected for 6 months post-implantation. The exploratory endpoint evaluated the Ark implantation procedure. Results: Of 13 patients, 2 were withdrawn prior to initial cannulation through the Ark—1 patient due to an exacerbated baseline condition and the other patient due to loss of follow-up. In the efficacy analysis, 11 of 13 treated patients demonstrated successful primary and secondary outcomes. Of the 11 treated patients who initiated cannulation through the Arks, 100% experienced successful primary and secondary outcomes. None of the patients experienced adverse events related to the Ark and surgeons had the necessary skills to implant Arks. Conclusion: The results demonstrated the Ark could be used successfully in End-Stage Renal Disease (ESRD) patients undergoing hemodialysis three times a week. These results suggest preliminary safety and efficacy of the Ark as a promising cannulation tool for dialysis vascular access and warrant further exploration of long-term safety and effectiveness through a pivotal clinical study involving a larger population and extended follow-up.

Objective: The Ark is a 3-D printed titanium device designed to be implanted around the draining vein of an arteriovenous fistula (AVF) to facilitate vascular access. The purpose of this study was to assess AVF maturation after Ark implantation in a large animal model. Methodology: End-to-side AVFs were created between the carotid artery and jugular vein in nine pygmy goats that included three control (AVF only) and six experimental (AVF and Ark device) animals. For experimental animals, an Ark device was implanted approximately 10 cm downstream of the anastomosis at the time of AVF creation. Postoperative ultrasounds and cannulations of the jugular vein fistula were performed over 12 months. At the conclusion of the study, the AVF was ligated and Ark devices along with a segment of the arterialized vein and surrounding tissues were explanted for gross and histological assessment. Results: The control and experimental Ark groups exhibited increased dilation and flow as well as diminished depth underscoring the parallel developments in vascular attributes and AVF maturation between the two groups. Gross pathology, histology, and micro-CT imaging revealed intact endothelium, mature tissue integration throughout the porous Ark device, and no underlying stenosis. No adverse events such as foreign body reaction, skin or vessel erosion were identified. Conclusion: The study showed maturation without stenosis of the fistula in all animals. This study confirmed that the Ark device functions as a scaffold around the access vein, allows fistula maturation, and can be consistently cannulated without infiltrations over a 12-month period in a large animal model.

A more accurate descriptive and clinically useful diagnosis based upon pathophysiology for what is commonly referred to as venous outflow stenosis is inflow-outflow imbalance. In these cases, the total outflow capacity of the AV access is inadequate to handle the inflow volume (Qa) without an increase in pressure. The relative inadequacy of the access outflow capacity in comparison to Qa results in increased outflow resistance and a proportional increase in intraluminal pressure. The clinical indicators associated with venous stenosis are the resulting manifestations of this imbalance. The point at which this occurs is dependent upon variations in these two parameters—Qa and outflow resistance. The variations in these two parameters are considerable and reciprocal. Excessive Qa results in or can lead to an entire list of serious problems that adversely affect patient morbidity and mortality. Most studies dealing with AV access Qa reduction have been for the treatment of an existing condition rather than its prevention; however, prevention of disease rather than waiting for its development is an important tenet of medical practice. The resulting clinical picture of inflow-outflow imbalance is taken as an indication for corrective treatment. In the past, in most cases this has meant angioplasty to open the outflow if it is reduced; however, this clinical picture may be associated with an excessive Qa and angioplasty in these cases creates the risk for a further increase in Qa. It is the authors’ opinion that access flow measurements should be a part of the evaluation of these cases prior to planning treatment. Using this information, a bimodal approach to primary treatment should be adopted involving either angioplasty for cases with a low or normal Qa or flow reduction in cases with an elevated Qa.

Background: Preventative strategies that minimize hemodialysis access complications remain limited. Objective: This study aimed to address this gap by developing a Caprine cannulation model to investigate the impact of repeated cannulations on vascular access patency rates. Research design and measures: In this pilot study, a meta-analysis was conducted using experimental control data from four trials to explore the impact of Caprine breed (independent variable) on the dependent variables that affect hemodialysis cannulation, including AVF growth, AVF depth, and flow rate. Subjects: Arteriovenous Fistulas (AVFs) were created using the carotid artery and jugular vein in the necks of seven goats from the French alpine, dwarf, and pygmy breeds. All seven AVFs exhibited vessel remodeling patterns similar to that observed in humans and remained patent, enabling hemodialysis access over the 6 month study. Results: Over the course of 18 weeks, a total of 291 cannulations were completed using standard 15 g dialysis needles without complications demonstrating the feasibility of using the Caprine species as a cannulation model. The ease of access coupled with the animals’ cooperative behavior further contributes to the suitability of the Caprine species for hemodialysis investigations. Notably, no infections or clinically significant incidents were observed throughout the study. Conclusions: The stability of AVF patency and flow underscores the viability and potential of the Caprine species animal model as a valuable research platform for exploring interventions aimed at improving vascular access survival in hemodialysis patients.

Introduction: The traditional sutured venous anastomosis used during arteriovenous graft implantation is associated with a high incidence of subsequent stenosis that is attributed to neointimal hyperplasia. Hyperplasia results from multiple factors, including hemodynamic abnormalities and vessel trauma during implantation. A novel anastomotic connector device was designed to provide an alternative, less traumatic, endovascular venous anastomosis that may ameliorate the clinical challenges associated with a sutured anastomosis. A prospective single-arm multicenter study was performed to evaluate safety and effectiveness of graft implantation using the study device. Methods: Patients requiring graft creation and who met the study criteria were enrolled between February 2018 and July 2021 and observed for 6 months. Collected data included baseline characteristics, graft patency and use for hemodialysis, graft interventions, and adverse events. The primary study endpoint was cumulative graft patency, compared to a pre-specified Performance Goal of 75%. Secondary endpoints included primary unassisted patency and serious adverse events, defined as the occurrence of death, graft infection, emergent surgery, significant bleeding, and pseudoaneurysm. Results: A total of 158 patients were enrolled from 10 study sites, among which 144 subjects were evaluable at 6 months and 14 were censored with partial follow-up observation. Three patients died and the graft was abandoned in 12. The primary endpoint was met ( p-value < 0.001). By Kaplan Meier survival analysis, cumulative patency was 92.08% with a lower 95% Confidence Bound of 86.98%. Primary unassisted patency was 60.21% with a lower 95% Confidence Bound of 50.84%. Graft infections occurred in six patients, all unrelated to the study device. There were no reports of emergent surgery, significant bleeding or pseudoaneurysm. Conclusion: These results demonstrate that the study device can be used for successful endovascular anastomosis of a vein to a graft for hemodialysis, with acceptable cumulative patency and safety profile at 6 months. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02532621

Background: Arteriovenous fistulae (AVF) are considered the preferred hemodialysis access but up to 50% of all AVF created in the United States never mature. Doppler ultrasound (DUS) is useful for predicting fistula maturity and impending fistula failure. DUS is resource-intensive and is associated with poor compliance rates in dialysis patients, ranging from 12% to 33%. Methods: EchoSure is an FDA-cleared 3D Doppler ultrasound device that automatically delivers quantitative blood flow and anatomic vascular information. The technology can be used at the bedside by personnel without formal sonographic training, nullifying limitations of traditional Duplex ultrasound imaging. This study compared the EchoSure system in the hands of inexpert personnel to a traditional expert-operated DUS for rapid assessment of a benchtop model vascular system with flow, diameter, and depth expected in a human AVF. Results: Both Duplex and EchoSure performed within the expected tolerance of ultrasound readings (35%) for volume flow, with the average error (AE) between the observed measurement and the ground truth being 8% for Duplex and 8% for EchoSure. However, the average coefficient of variation (CV) for Duplex pooled over all flow rate measurements was 17% versus 4% for EchoSure. Regarding diameter, Duplex measurements had AE of 15% with an average CV of 6% across all measurements versus EchoSure AE of 4% and average CV of 2%. Duplex and EchoSure measurements over all depths had the same AE of 2%. The two modalities were not statistically different for depth measurement ( p = 0.05) but EchoSure measured closer to the ground truth for flow rate and vessel diameter (flow: p = 0.028, ρ = −0.07; diameter: p < 0.001, ρ = 0.69). The inexpert personnel using EchoSure acquired data 62% faster than the expert sonographers using the Duplex ultrasound (141 min for Duplex vs 87 min for EchoSure). Conclusions: EchoSure may offer an accurate and convenient alternative for imaging fistulas in the clinic.

Brachiocephalic arteriovenous fistulas (AVF) makeup approximately one third of prevalent dialysis vascular accesses. The most common cause of malfunction with this access is cephalic arch stenosis (CAS). The accepted requirement for treatment of a venous stenosis lesion is ⩾50% stenosis associated with hemodynamically abnormalities. However, the correlation between percentage stenosis and a clinically significant decrease in access blood flow (Qa) is low. The critical parameter is the absolute minimal luminal diameter (MLD) of the lesion. This is the parameter that exerts the key restrictive effect on Qa and results in hemodynamic and functional implications for the access. CAS is the result of low wall shear stress (WSS) resulting from the effects of increased blood flow and the unique anatomical configuration of the CAS. Decrease in WSS has a linear relationship to increased blood flow velocity and neointimal hyperplasia exhibits an inverse relationship with WSS. The result is a stenotic lesion. The presence of downstream venous stenosis causes an inflow-outflow mismatch resulting in increased pressure within the access. Qa in this situation may be decreased, increased, or within a normal range. Over time, the increased intraluminal pressure can result in marked aneurysmal changes within the AVF, difficulties with cannulation and the dialysis treatment, and ultimately, increasing risk of access thrombosis. Complete characterization of the lesion both hemodynamically and anatomically should be the first step in developing a strategy for management. This requires both access flow measurement and angiographic imaging. Patients with CAS present a relatively broad spectrum as relates to both of these parameters. These data should be used to determine whether primary treatment of CAS should be directed toward the anatomical lesion (small MLD and low Qa) or the pathophysiology (large MLD and high Qa).

Thrombectomy is a common procedure for maintenance of arteriovenous (AV) access and is critical to prolong access life. Techniques for performing thrombectomy are incredibly diverse, ranging from open surgical procedures to percutaneous interventions. Percutaneous interventions include a combination of thrombectomy devices to clear the thrombus and balloon angioplasty to treat the underlying lesion. In this case report we describe a novel technique using a single device, the Chameleon™ PTA balloon catheter (Medtronic, Minneapolis, MN) balloon catheter, to safely and efficiently perform a percutaneous intervention.

Introduction: Transposed brachiobasilic AV fistulas (BVT) have increasingly been performed in two stages. Published reports give conflicting results, perhaps in part as many reports of staged procedures eliminate those patients who “fail” the first stage (i.e. are lost to follow-up in addition to anatomic failure). Methods: A prospectively maintained database was reviewed to identify all patients at two institutions who underwent the first stage of planned two-stage BVT by the senior author. Success in this context was defined as patients who eventually underwent second stage fistula creation, leaving the operating room after the second stage with a patent, transposed fistula. Results: From October 2012 to June 2020, 218 patients underwent first-stage procedures. At the first visit, 185 (85%) of fistulas were patent, 23 (11%) were occluded, 8 (4%) of patients were lost to follow-up, and 2 (1%) died. In the interval before the second operation, another eight (4%) patients were lost to follow-up, two were cancelled for medical reasons, and two declined surgery, leaving a total of 173 patients who made it to the second stage (80%). At operation, four patients were found to have unusable veins, leaving a total of 169 patients who completed both stages. If all patients who underwent first stage are included, 77% of patients entering this pathway left the OR after their second stage with patent access. If those lost to follow-up are excluded, this number increases to 84%, while if all those lost to follow-up are assumed to mature, success increases to 85%. Conclusions: Depending on results in patients lost to follow-up, between 77% and 85% of patients undergoing first stage brachiobasilic fistulae undergo successful second stage transposition. These numbers are equivalent or slightly lower than published maturation rates for single-stage BVT, so there is little margin for failure at the second stage.

Hemodialysis Reliable Outflow (HeRO) grafts are used when venous outflow is inadequate to support conventional access. These have been perceived as complex to implant and being associated with high risk. We have evolved a defined protocol for insertion that minimizes morbidity and maximizes efficiency. Our protocol includes staged intravenous access versus HeRO graft placement, reverse Trendelenburg positioning, subcutaneous access of the deep portion of the existing catheter, use of a stiff wire placed within the inferior vena cava, dilation of the tract to 8 mm, device lubrication, all insertion procedures directly visualized, and use of immediate access conduits with SuperHeRO connector. From 7/1/18 to 8/13/19, 55 HeRO grafts were placed at our institution following this protocol, average age 58 ± 15 (26–86) years (mean ± SD, range). 53 (96%) had had prior ipsilateral central access (13 by means of “inside out” 2 weeks prior) the other two had on-table access. Mean procedure time was 70 ± 26 (38–148) min. Excluding seven “complex” cases, procedure time for our first 20 cases using this protocol was 72 ± 29 min, while that of the last 28 was 62 ± 18 min (p < 0.05). One patient suffered acute CHF after unclamping; despite reclamping and ligation he died on POD 3 (mortality rate 2%). 71% were done as outpatients, and 47 of 53 evaluable patients (89%) had their grafts used within 36 h for dialysis. Only one patient (2%) has had an infection within 30 days (cellulitis). At a mean followup of 95 ± 105 (maximum 383) days, three additional patients have had graft infections requiring excision, for a total infection rate of 5/53 (9%). Our results suggest that HeRO graft placement can be performed with minimal morbidity and mortality on an outpatient basis. Short-term infection rates are low and 89% of patients have their grafts immediately accessed and are discharged without a catheter.