Description
Chronic kidney disease (CKD) can often lead to end stage renal disease (ESRD). Once an individual reaches ESRD, dialysis will likely be required. Vascular access to the bloodstream is often preferred in order to administer dialysis treatment. An arteriovenous fistula (AVF) creates a direct connection between a vein and an artery in an individual’s arm. This results in a closed circuit that provides adequate blood flow for dialysis. Surgery is the traditional method of creating this AVF.

While these procedures are typically straightforward, overall maturation-to-use rates remain low, with nearly 25% failing to mature despite high utilization of subsequent procedures to aid in maturation. Over 50% of patients may ultimately require reintervention to maintain patency of the AV access once maturation has occurred. Other complications of traditional AV hemodialysis access include infection, steal syndrome, aneurysm formation, and pulmonary and venous hypertension. As a result of complications or AV access failure, patients often require several different access procedures performed in multiple extremities.

The available percutaneous hemodialysis AV fistula systems create a connection between a forearm artery (ulnar or radial artery) and a perforating vein or the named vein that corresponds to the artery (ulnar or radial vein). Once the connection is created, blood is shunted from the arterial system to the deep venous system and subsequently to the superficial venous system via the perforating vein. Once matured, the arterialized superficial veins can then be accessed for hemodialysis in a manner like surgically created AV fistulas using these superficial veins. See Table 1.

Ellipsys^® Vascular Access System
The Ellipsys^® Vascular Access System (Medtronic, Minneapolis, MN) is a percutaneous catheter system intended to create an AVF for hemodialysis access in patients with chronic kidney disease. The system is indicated for use in patients with a minimum vessel diameter of 2 mm and less than 1.5 mm of separation between the artery and vein at the fistula creation site. The anastomosis is created in the proximal radial artery and adjacent vein using direct current thermal heating. Using ultrasound guidance, the system uses an outer access cannula, guidewire and vessel capture construct that creates a connection of the vein to the artery using an intravascular approach. A low power thermal energy source is used to cut the walls of the vessels and fuse the tissue, creating an anastomosis without leaving any foreign material, including sutures, in the resulting AV fistula.^1,2

WavelinQ™ Endovascular Arteriovenous Fistula (EndoAVF) System
The WavelinQ™ EndoAVF System (Becton, Dickinson and Company [BD], Franklin Lakes, NJ) (originally marketed at EverlinQ) is a minimally invasive electrosurgical tool intended to create AVFs for patients with minimum artery and vein diameters of 2 mm at the fistula creation site with catheters that are each inserted into an artery (brachial) and a vein (brachial, ulnar or radial) in the arm through a small puncture or incision. Using fluoroscopy, the catheters are both advanced to the appropriate location for endovascular AVF creation. The magnets in the catheters allow them to be precisely aligned while pulling the two adjacent vessels closer together. The venous catheter, which contains the electrode, delivers a burst of radiofrequency energy to create a connection between the artery and the vein.^3,4

Table 1. Comparison of the Two Percutaneous Arteriovenous Fistula Devices (5)

EndoAVF: endovascular arteriovenous fistula; Fr: French; ESU: electrosurgical unit; mm: millimeters.

Regulatory Status
The U.S. Food and Drug Administration (FDA) granted 510k(k) marketing clearance for the Ellipsys System (K191114) in August 2019 based on its substantial equivalence to a previous device model, which initially received 510(k) clearance in October 2018 (K181725). The FDA first cleared Ellipsys through the De Novo pathway in January 2017 (DEN170004).^2,6

The WavelinQ Plus EndoAVF System was granted 510(k0 marketing clearance by the FDA in October 2019 (K192239) and the WavelinQ 4F EndoAVF System in February 2019 (K182796). Prior to the 510(k) clearance, the FDA granted De Novo clearance to the EverlinQ EndoAVF System in June 2018 (DEN160006).^4,7

Policy
The use of an endovascular percutaneous device (e.g., Ellipsys^® System; WavelinQ™ System) for the creation of an arteriovenous fistula (AVF) for hemodialysis access is considered experimental, investigational and/or unproven therefore NOT MEDICALLY NECESSARY.

Rationale
In a systematic review of literature published in 2020, Choinski et al. compared the available studies for the Ellipsys® Vascular Access System and the WavelinQ™ EndoAVF System.⁵ They found that in all trials with percutaneous arteriovenous fistulas (pAVFs), patients were only considered for the procedure if they were not candidates for a surgically created distal radiocephalic AVF at the wrist. Patients were typically CKD IV/CKD V (chronic kidney disease), planning for future dialysis, or already in end-stage renal disease (ESRD), receiving dialysis via a tunneled venous catheter. Patients with a previously failed surgical AVF were eligible for pAVF creation. Both devices had a high technical success rate in pAVF creation ranging from 94 – 100% for the WavelinQ™ and 88 – 100% for the Ellipsys^®. Patency had been more extensively studied for the Ellipsys pAVF than for the WavelinQ and appear to have a higher patency. Analysis for two-year patency has only been conducted for the Ellipsys pAVF, displaying a cumulative patency of 92.7%. Both endovascular and open secondary interventions were required for the maturation and maintenance of pAVFs, with balloon angioplasty used most frequently for the Ellipsys pAVF. The authors noted the creation of a pAVF does not prohibit future conversion to a surgical AVF if pAVF failure occurs. Current trials offer the pAVF as a possible alternative to surgical AVF when the creation of a distal, wrist radiocephalic fistula is not possible. They also noted none of the trials reviewed had direct comparison of pAVF to surgical AVF outcomes; and given that, the evidence does not support pAVF as a first-line approach in comparison to surgical AVF. Surgical AVFs, if selected properly, have high maturation rates, with a distal radiocephalic maturation rate up to 75 – 85%. Surgical maturation rates are further improved with proximal AVF creations, with approximately 80% for brachial-cephalic fistulas and up to 90% for brachial-basilic fistulas. The authors concluded further studies are warranted to investigate the maturation rates, long-term patencies, and dialysis capabilities of pAVF in comparison to surgical AVF to better understand its utility in dialysis access creation.

Ellipsys^® Vascular System Access
Hull et al. in 2017 reported on a pivotal trial to evaluate the safety and efficacy of arteriovenous fistula (AVF) created with a thermal resistance anastomosis device.⁸ A prospective single-arm trial at 5 sites enrolled 107 patients between February 2015 and June 2016. Patients underwent ultrasound (US)-guided anastomosis creation between the proximal radial artery and perforating vein with the Ellipsys Vascular Access System (Avenu Medical, Inc, San Juan Capistrano, California — now Medtronic) followed by separate maturation procedures in an office-based laboratory. Primary endpoints were brachial artery flow volume ≥ 500 mL/min and target vein diameter ≥ 4 mm in > 49% of patients and absence of device-related complications at 90 days. AVFs with fused anastomoses were created in 95% (102/107) of patients. Maturation procedures included anastomotic balloon dilation in 72% (77/107), brachial vein embolization in 32% (34/107), cubital vein ligation in 31% (33/107), and surgical transposition in 26% (28/107) of patients. Primary flow and diameter endpoints were achieved in 86.0% (92/107) of patients, exceeding performance goal of 49% (P < .0001). No major adverse events were attributed to the device. Cumulative patency was 91.6%, 89.3%, and 86.7% at 90 days, 180 days, and 360 days. Target dialysis veins were cephalic, basilic, and brachial veins in 74% (73/99), 24% (24/ 99), and 2% (2/99) of patients. Two-needle dialysis was achieved in 88% (71/81) of patients on hemodialysis at a mean 114.3 days ± 66.2. Functional patency was 98.4%, 98.4%, and 92.3% at 90 days, 180 days, and 360 days. While the authors note the primary safety and efficacy endpoint goals in this trial were met, the following limitations should be noted. The study was a single-arm design without direct comparison of thermal resistance anastomosis devices (TRAD) with surgical fistulas. There was no defined protocol for maturation and there was a tendency to underdilate the anastomosis during maturation and not achieve brachial artery flow volume > 500 mL/min. The patient population was 73% male, which is higher than the approximately 57.8% of patients with end-stage renal disease in the United States. The higher number of male patients was attributed to a higher screen failure rate among female patients failing to have a vein diameter ≥ 2 mm in diameter.

In a retrospective review of data between May 2017 and July 2019, Mallios et al. reported on the midterm results of percutaneous arteriovenous fistula (pAVF) of their single-center database of patients who had a pAVF creation using the Ellipsys device.⁹ Between May 2017 and July 2019, there were 234 patients (mean age, 64 years; 148 male [63%]) who had a pAVF created. Technical success was achieved in 232 individuals (99%), and average duration of the procedure was 15 minutes (7 – 35 minutes). Average follow-up was 252 days (range, 83 – 696 days). The 1-year primary, primary assisted, and secondary patency rates were 54%, 85%, and 96%, respectively. Average pAVF flow was 923 mL/min (range, 425 – 1440 mL/min). There were no significant adverse events related to the procedure. Only three patients (1%) required a later conversion of the pAVF anastomosis to a surgical fistula. Twenty-four (10%) patients required superficialization of deep outflow veins because of difficult cannulation. Average maturation time was 4 weeks (range, 1 – 12 weeks). Fourteen patients (6%) had early (< 2 weeks after creation) cannulation of the pAVF. The authors concluded the Ellipsys AVF Vascular Access System allows for rapid and safe creation of a reliable autogenous access, with rates of technical success, patency and maturation being excellent. Despite the larger numbers and longer follow-up of pAVF patients, large scale randomized studies are needed to confirm their findings.

A retrospective review by Hebibi et al. in 2019 looked at records of 34 patients between May 2017 and November 2018 who had a pAVF created using the Ellipsys system.¹⁰ Technical success was achieved in 33 patients (97%). Twenty?eight out of 34 (82%) patients had successful two-needle cannulation within 10 days to 6 weeks after pAVF creation. The mean dialysis adequacy (Kt/v) was 1.6 (1.2?2) and the average recirculation was 10%. Fifteen patients (44%) needed no further access intervention. Twelve patients (35%) required an additional procedure to assist maturation of the pAVF in order to facilitate puncture. The average blood flow measured at the brachial artery, before the first cannulation, was 850 ml/min. From causes unrelated to the procedure, four patients died during the follow?up study. Two patients required revision to a surgical AVF. None of the pAVFs developed aneurysmal degeneration steal syndrome, or high access flow related issues. Limitations include the retrospective single arm observational nature of the study, the relatively small number of patients and short follow-up. Larger and longer prospective studies are needed to confirm the authors findings.

In 2020, Beathard et al. published results of a retrospective analysis of data generated by five vascular access programs in the United States.¹¹ An endovascular arteriovenous fistula was created in 105 patients using either local or regional anesthesia and conscious sedation. Patient data were obtained from each program’s electronic health record system. Data collection was truncated at 2 years post-procedure and used to calculate cumulative patency. Post-access creation patient satisfaction was assessed. A physiologically mature arteriovenous fistula (blood flow ≥ 500 mL/min and a target vein internal diameter ≥ 4 mm) was obtained in 98%. A clinically functional arteriovenous fistula (supporting two-needle dialysis according to the patient’s dialysis prescription) was demonstrated in 95%. Access failure resulting in the loss of access occurred in eight cases during the study period. The cumulative patency rate at 6, 12, 18, and 24 months was 97.1%, 93.9%, 93.9%, and 92.7%, respectively. The post-procedure patient evaluation emphasized a high level of patient satisfaction. The proximal radial artery arteriovenous fistula created using an endovascular approach for the anastomosis is associated with excellent 2-year cumulative patency and is associated with a high level of patient satisfaction.

WavelinQ™ Endovascular Arteriovenous Fistula (EndoAVF) System
Zemela et al. in 2021 published the results of a review of 35 patients undergoing placement of the WavelinQ AVF.¹² All consecutive patients undergoing placement of a WavelinQ AVF from October 2018 to July 2019 were included. Preoperative/intraoperative variables including demographics, preoperative/postoperative duplex ultrasonography, success rate of procedure, and subsequent endovascular/surgical procedures were obtained. Descriptive statistics and comparison of groups requiring subsequent intervention were performed. Thirty-five patients underwent placement of the WavelinQ AVF, with 32 (91%) patients having at least one documented follow-up. These patients were predominantly male (23/32, 72%) with an average age of 60.2 and 23 of 32 (72%) patients were on dialysis. Initial fistula creation success rate was 100%. Average procedural length was 120 min, fluoroscopy time 9.6 min, and contrast usage 52.2mL. Eight of 32 (25%) patients had perioperative complications (3 hematomas, 3 contrast extravasations, 1 resolved vessel spasm all resolving spontaneously, and 1 pseudoaneurysm requiring surgical repair). Thirteen of 32 (41%) patients underwent subsequent endovascular interventions to assist with maturation [9/32 (28%) branch coiling, 5/32 (16%) angioplasty/stenting, and 3/32 (9%) access thrombectomy] and 4 of 32 (13%) patients required subsequent surgical interventions (1pseudoaneurysm repair, 1 revision of fistula, and 2 definitive AVF creation in thrombosed grafts). The majority of accesses (30/32, 94%) were ulnar-ulnar fistulas and overall patency at average follow-up of 73 days was 88% (28/32) with average brachial artery inflow volume of 1,078 cc/min and average cephalic vein (18/32) outflow volume of 447 cc/min. Eleven of 23 (48%) patients on dialysis were successfully using the EndoAVF at follow-up. The WavelinQ AVF system has a high initial procedural success rate, although a significant portion of patients require subsequent endovascular procedures to aid in maturation. Further work on determining factors predictive of need for reintervention is necessary.

Berland et al. published results of pooled data from three prospective, multicenter, single-arm trials conducted outside of the United States in 2021.¹³ The use of the 4F WavelinQ system in three studies, EASE (32 patients), EASE-2 (24 patients), and the European Union (EU) post-market clinical follow-up study (64 patients) was aggregated and analyzed. Patients were followed with duplex ultrasound at discharge and follow-up visits at 1, 3, and 6 months. Primary, assisted primary, and secondary patency rates were evaluated as Kaplan-Meier estimates and standard errors. Time to maturity and time to successful cannulation were defined as the mean 6 standard deviation days from the procedure in patients enrolled on dialysis. Procedural success was achieved in 116 patients (96.7%). Primary, assisted-primary, and secondary 6-month patency rates were 71.9% ± 4.5%, 80.7% ± 4.1%, and 87.8% ± 3.3%, respectively. Time to maturity averaged 41 ± 17 days. Time to successful cannulation averaged 68 ± 51 days. Device related serious adverse events were reported in 3 of 120 patients (2.5%) and procedure-related serious adverse events occurred in 7 of 120 patients (5.8%). Arterial or venous access complications were not reported in any of the patients. Access circuit reinterventions were performed in 23 patients (19.2%), split between those performed for EndoAVF maturation (13/120 [10.8%]) and maintenance (11/120 [9.2%]). Percutaneous creation of native dialysis fistulae with the 4F WavelinQ EndoAVF System is safe and effective, with favorable durability and a low rate of serious complications and reinterventions through 6-month follow-up. Use of the 4F device allows for percutaneous fistula creation between the radial artery and radial vein or the ulnar artery and ulnar vein. These findings suggest that the 4F device is a useful percutaneous alternative to open surgical AVF or endovascular AVF with larger bore devices. The authors note this study has all the limitations of a single-arm study. It is difficult to compare the outcomes from the current study with those of other studies because there can be no assurances that the study populations are similar. There can be no assurance that the current study population is analogous to the real-world experience outside of a clinical trial. Indeed, this study population included patients who were undergoing fistula creation before and after the initiation of dialysis. Also, the end point definitions used in this study differ in some cases from those used in other studies, limiting the comparability of outcome data between series. The current study was not powered to detect differences between fistula locations, ulnar vs radial.

A retrospective analysis by Kitrou et al. published in 2022 assessed the safety and efficacy of pAVF creation with the WavelinQ 4-F EndoAVF System.¹⁴ 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. 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. 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.

Summary of Evidence
The evidence reviewed for percutaneous arteriovenous fistula creation using the Ellipsys^® Vascular Access System or the WavelinQ™ Endovascular Arteriovenous Fistula (EndoAVF) System includes a pivotal trial as well as retrospective reviews of literature. There were no identified head-to-head comparative studies found comparing either system to surgical arteriovenous fistula creation. The literature to date is inconclusive; and therefore, the use of an endovascular percutaneous device (e.g., Ellipsys™ System; WavelinQ™ System) for the creation of an arteriovenous fistula (AVF) for hemodialysis access is considered experimental, investigational and/or unproven.

Ongoing and Unpublished Clinical Trials
Some currently ongoing or unpublished clinical trials that might influence this policy are listed in Table 2.

Table 2. Summary of Key Trials

NCT: national clinical trial.

References

1. Medtronic. Ellipsys® Vascular Access System Brochure. Available at <http://www.medtronic.com> (Accessed November 16, 2022).
2. ECRI Institute. Ellipsys Vascular System Access (Avenu Medical, Inc.) for Creating Hemodialysis Arteriovenous Fistulas. Plymouth Meeting (PA): ECRI Institute; August 2021. Clinical Evidence Assessment.
3. Becton, Dickinson and Company (BD). WavelinQ™ EndoAVF Screening and Procedure Frequently Asked Questions. Available at <http://www.wavelinq.bd.com> (Accessed November 16, 2022).
4. ECRI Institute. WavelinQ EndoAVF System (BD) for Creating Hemodialysis Arteriovenous Fistulas. Plymouth Meeting (PA): ECRI Institute; April 2022. Clinical Evidence Assessment.
5. Choinski KN, Sundick SA, Roa, AG, et al. The Current Role of the Percutaneous Arteriovenous Fistula for Hemodialysis Access. Surg Technol Int. 2020 Nov 28; 37:217-224. PMID 32681730
6. FDA. Ellipsys Vascular Access System 510(k) Premarket Notification. U.S. Food and Drug Administration. 2019. Available at <http://www.fda.gov> (Accessed November 16, 2022).
7. FDA.WavelinQ EndoAVF System. 510(k) Premarket Notification. U.S. Food and Drug Administration. 2019. Available at <http://www.fda.gov> (Accessed November 16, 2022).
8. Hull JE, Jennings WC, Cooper RI, et al. The Pivotal Multicenter Trial of Ultrasound-Guided Percutaneous Arteriovenous Fistula Creation for Hemodialysis Access. J Vasc Interv Radiol. 2018; 29:149-158. PMID 29275056
9. Mallios A, Bourquelot P, Franco G et al. Midterm Results of Percutaneous Arteriovenous Fistula Creation with the Ellipsys Vascular Access System, Technical Recommendations, and an Algorithm for Maintenance. J Vasc Surg. Dec 2020; 72(6):2097-2106. PMID 32276012
10. Hebibi H, Achiche J, Franco G, et al. Clinical Hemodialysis with Percutaneous Arteriovenous Fistulas Created with the Ellipsys® Vascular Access System. Hemodial Int. 2019 Apr; 23(2):167-172. PMID 30821894
11. Beathard GA, Litchfield T, Jennings WC. Two-year Cumulative Patency of Endovascular Arteriovenous Fistula. J Vasc Access. 2020 May; 21(3): 350-356. PMID 31566061
12. Zemela MS, Minami HR, Alvarez AC, et al. Real-World Usage of the WavelinQ EndoAVF System. Ann Vasc Surg. 2021 Jan; 70:116-122. PMID 32417285
13. Berland T, Clement J, Inston N, et al. Percutaneous Arteriovenous Fistula Creation with the 4F WavelinQ EndoAVF System.J Vasc Surg. 2022 Mar; 73(3):1038-1046. PMID 34601046
14. Kitrou PM, Balta L, Papachristou E, et al. Percutaneous Arteriovenous Fistula Creation with the WavelinQ 4-French EndoAVF System: A Single-Center Retrospective Analysis of 30 Patients. J Vasc Interv Radiol. 2022 Jan; 33(1):33-40. PMID 34610421

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each Policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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