Arteriovenous fistula construction with the VasQ™ external support device: a pilot study

Introduction

One of the principal problems following the creation of an arteriovenous fistula (AVF) for haemodialysis is non-maturation, resulting in an inability for the fistula to dilate adequately in response to local blood flow increments (1). Although native AVFs are the preferred type of vascular access for dialysis, a high early failure rate necessitates frequent revision, which carries a high economic burden (2). Large series have shown that although native AVFs have a low rate of complications and improved longevity of use when functional, they suffer from relatively poor early patency rates with more than half being unsuitable for dialysis use by one year (3). The precise reasons for these early failures remain to be fully elucidated, although it is clear that inability to increase inflow often results from perianastomotic stenosis (4) and venous neointimal hyperplasia (5). It has been postulated that these effects are related to endothelial and smooth muscle cell activation in the area of the anastomosis, which then triggers adhesion molecules and inflammatory mediators capable of inducing AVF stenosis (6, 7).

Turbulent flow has been identified as a driver for neointimal hyperplasia and as a cause of stenosis (8). A laminar flow has been postulated to be protective and as a predictor for successful maturation in a newly formed AVF (9). Various approaches have attempted to create a more protective flow pattern. Various vascular access devices incorporate features which attempt to regulate shunt haemodynamics. One design features external support elements as well as a unique geometrical configuration, which aims to improve flow patterns. Others target anastomotic haemodynamics using a siliconised polyurethane implant providing a more controlled geometry between the artery and the vein.

The VasQ™ (Laminate Medical Technologies, Israel) is a novel device which attempts to address the root causes of AVF failure by minimising flow disturbances around the area of anastomosis. This external support device targets the two main fistula failure mechanisms; namely, turbulent flow around the area of connection and increased venous wall tension resultant from arterial circulation conditions. It is a Nitinol implant, externally surrounding and supporting the vein and “hugging” the artery near the junction site without being in contact with the blood flow. Figure 1 shows the VasQ™ device.

Fig. 1 -

This paper represents the preliminary data of a prospective single-centre study designed to evaluate the safety and efficacy of the VasQ™ external support device for brachiocephalic arteriovenous fistula in patients requiring vascular access.

Study population and methods

Patients

The conduct of the study was approved by the NHS Research Ethics Committee (Reference number 14/EE/0062) in accordance with the Helsinki Declaration for the performance of such research on human subjects. The trial was conducted as a prospective, single-arm study design so as to determine device safety and initial efficacy (NCT02112669). All patients provided signed informed consent for participation in the trial. The study was conducted at St. George’s Vascular Institute, St. George’s University Hospitals Foundation Trust, London, UK, in accordance with the Helsinki Declaration.

Patients were considered for inclusion if they were suitable for a new brachiocephalic arteriovenous fistula for long-term haemodialysis and were able to be followed for a minimum period of 6 months after the procedure. Women were recruited if they were aged >50 years. Patients were excluded if they had target vessel diameters of <3 mm, an outflow stenosis or obstruction, and/or a known coagulation disorder. Further exclusions were made in cases where the depth of the vein exceeded 8 mm, patients with prior steal syndrome, or those with an active AVF site infection or poor life expectancy.

Surgical procedure

The VasQ™ implantation procedure is seamlessly integrated into a standard end-to-side fistula procedure, not affecting current surgical practice. Once the vessels were exposed through a 6 cm incision, the diameter of the artery was assessed for size selection of the most suitably fitting VasQ™ model out of the three available sizes. The device was threaded along the vein, which was cut in preparation for an end-to-side anastomosis. An arteriotomy was made and the vein was anastomosed in a routine manner using a 6/0 prolene running suture. The fistula was then perfused and examined for adequate flow and haemostasis. The device was slid distally along the vein and onto the anastomosis and the brace eyelets were knotted with a suture around the artery. The venous outflow was intraoperatively measured by Transit Time Flow Measurement (TTFM, VeriQ by Medistim, Norway) and the surgical incision was then closed. An intraoperative image is shown in Figure 2.

Fig. 2 -

Patients were assessed for the purposes of the study at 1, 3 and 6 months. Unassisted maturation at 3 months was our primary end-point and was confirmed by colour duplex spectral analysis of venous outflow and measurement of the vein diameter. Patency of the AVF was determined as a secondary end-point by clinical examination where there was an audible continuous bruit at least 8 cm proximal to the anastomotic site. Maturation was considered successful if the vein diameter was ≥5 mm and flow exceeded 500 mL/min. These assessments were supplemented by contrast angiography (where appropriate) performed at 3 months. All adverse events and serious adverse events (SAEs) were recorded.

Results

In total, 24 patients consented between June 19^th 2014 and January 8^th 2015. There were four exclusions after recruitment, including one explantation because the fistula was felt to be compressed by the device and two cases where the access procedure was cancelled for logistical reasons. In a further case, the anatomy was deemed inappropriate for a brachiocephalic fistula and the surgeon decided to pursue a different surgical approach.

Overall, 20 patients were implanted with the VasQ™ for analysis (15 males, overall mean age 65.2 years, range 44-85 years). Table I shows the patient demographics with a range of end-stage renal disorders including diabetes, glomerulonephritis and polycystic disease. Table II provides the baseline access and dialysis status. Preoperative ultrasonography confirmed that there was no stenosis in all cases with a normal inflow pulse in 19/20 and a slightly diminished arterial inflow in one case. The mean total operative time (from incision to skin closure) was 42 minutes (range 11 minutes to 1 hour and 10 minutes).

TABLE I -

Laminate device.

Intraoperative image of the VasQ™ device placed over an arteriovenous fistula.

Patient demographics VasQ™ external support device for AVF construction in haemodialysis (n = 20)

Demographic of implanted patients	n = 20
BMI = body mass index; CHD = coronary heart disease; CAD = coronary artery disease; NIDDM = non-insulin-dependent diabetes mellitus; IDDM = insulin-dependent diabetes mellitus.
Mean age (yr)	65.2 (range 44-85, median 64)
Male (%)	75
Ethnic origin (%)
Caucasian	60 (12)
Asian	20 (4)
African	5 (1)
Hispanic	0
Caribbean	15 (3)
Height (m)	1.70 (range 1.47-1.95, median 1.70)
Weight (kg)	82 (range 50-132, median 78)
BMI	28
Blood pressure systolic/diastolic (mmHg)	141/74
Aetiology of renal disease (% [n])
Diabetes mellitus	35 (7)
Focal segmental glomerulosclerosis	10 (2)
Polycystic disease	10 (2)
Interstitial nephritis	15 (3)
Unknown	10 (2)
Other	20 (4)
Smoking status (% [n])
Never	20 (4)
Ex	10 (2)
Current	15 (3)
Unknown	55 (11)
Diabetes (% [n])
No history	50 (10)
Adult onset NIDDM	20 (4)
Adult onset IDDM	25 (5)
Juvenile onset	5 (1)
Demographic of implanted patientsHypertension (% [n])
None	15 (3)
Controlled with single drug	15 (3)
Controlled with 2 drugs	30 (6)
Controlled with ≥3 drugs	40 (8)
Coronary/cardiac disease (% [n])
None	85 (17)
CHD or CAD	5 (1)
Coronary angioplasty	5 (1)
Angina	5 (1)

TABLE II -

Dialysis history and access information

Dialysis and access baseline	n = 20
Years on dialysis (% [n])
0-1	90 (18)
2-3	0 (0)
4-5	5 (1)
6+	5 (1)
Total prior access procedures (all limbs and types) (% [n])
0	80 (16)
1	20 (4)
2	0 (0)
≥3	0 (0)
Prior access procedures in study limb (% [n])
0	90 (18)
1	10 (2)
2	0 (0)
≥3	0 (0)
Temporary access catheter (% [n])
Currently used	30 (6)
Previously used	0 (0)
Never used	70 (14)
Indication for index access procedure (% [n])
First time access	80 (16)
Failed autogenous access	20 (4)

Table III shows the intraoperative measured data. The cephalic vein was deemed fair for use in six cases and excellent in the remaining 14 patients with a median diameter of 4.5 mm (range 3-7 mm) and a median brachial artery diameter of 5 mm (range 3-8 mm). Outflow was assessed using TTFM in 18/20 cases before and after device deployment (median flow before = 300 mL min^-1; range 180-870; median flow after = 270 mL/min^-1; range 145-870, respectively).

TABLE III -

Procedural data

Procedure	N = 20
TTFM = transit time flow measurement.
Access limb (% [n])
Right	60 (12)
Dominant	40 (8)
Skin incision to skin closure time (h)	0:43 (range 0:11-1:26, median 0:44)
Cephalic vein diameter (mm)	4.5 (range 3-7, median 4)
Brachial artery diameter (mm)	4.9 (range 3-8, median 5)
Cephalic vein quality (% [n])
Excellent	70 (14)
Fair	30 (6)
Poor	0 (0)
TTFM flow before device deployment (mL/min) (n = 18)	354 (range 180-870, median 300)
TTFM flow after device deployment (mL/min) (n = 18)	366 (range 145-870, median 280)
Device model
5B	100 (20)

No patient was lost to follow-up and there were no recorded device-related SAEs. The complications in the study were typical to our patient population. There was one death due to multiple organ failure and toxic epidermal necrolysis in a patient with prior cardiac comorbidities (prosthetic aortic valve). During follow-up at 1, 3 and 6 months, the mean venous outflow was 1130, 1426 and 1304 mL/min^-1, respectively, with unassisted maturation rates of 80%, 79% and 74%, respectively. These correlated with primary patency rates of 95%, 79% and 79%, respectively (Tab. IV). One patient underwent successful salvage surgery with the fistula reconstructed and the VasQ™ explanted. At the time of the 6-month follow-up, 14/19 patients were dialysing through the AVF with one patient using a venous access catheter and four not yet requiring haemodialysis. Overall, at 6 months three patients (one on dialysis and two still pre-emptive) had AVFs thrombosed and unsuitable for dialysis use.

TABLE IV -

Clinical and ultrasound (US) assessments

	1 Month	3 Months	6 Months
a Maturation ≥5 mm, ≥500 mL/min-1.
Venous outflow of patent fistulas (mL/min) by US	1130 (n = 20)	1426 (n = 15)	1304 (n = 15)
Vein diameter of patent fistulas (mm) by US	6.6 (n = 20)	8.4 (n = 15)	10.0 (n = 14)
Fistula primary unassisted patency	95 (19/20)	79 (15/19)	79 (15/19)
Fistula patency (% [n])	95 (19/20)	79 (15/19)	84 (16/19)
Matured rate of patent fistulasa	80 (16/20)	100 (15/15)	93 (14/15)
Thrill palpation (% [n])
Strong	95 (19)	79 (15)	84 (16)
Weak	0 (0)	0 (0)	0 (0)
None	5 (1)	21 (4)	16 (3)
Bruit (% [n])
Continuously audible	95 (19)	79 (15)	84 (16)
Not continuously audible	5 (1)	21 (4)	16 (3)
Subjects on dialysis (% [n])	35 (7/20)	58 (11/19)	79 (15/19)
On dialysis via study access	14 (1/7)	72 (8/11)	93 (14/15)
On dialysis via catheter	86 (6/7)	18 (2/11)	7 (1)
On other dialysis access	0 (0)	10 (1/11)	0 (0)
Access site complications
Steal syndrome	10 (2)	11 (2)	5 (1)
Aneurysm	0 (0)	0 (0)	0 (0)
Infection	5 (1)	0 (0)	0 (0)
Bleeding	0 (0)	0 (0)	0 (0)

Discussion

The ideal access for haemodialysis will deliver a sustained flow rate sufficient for use with long-term utilisation along with a low rate of significant complications and minimal requirement for assistance designed to maintain maturation and patency. Overall, autogenous AVFs are the preferred options for dialysis access with lower complication rates, more established longevity and lower overall costs than prosthetic AV grafts or central venous catheters (10). The “Fistula First” initiative in the USA has resulted in a significant increase in AVF prevalence from 24%-60% over the decade between 2003 and 2013 (11), although it has uncovered a high early fistula failure rate largely as a result of non-maturation. This is most likely influenced by the concept of “a native AVF at any cost” which encouraged many surgeons to consider veins that they would not normally have selected as potentially acceptable outflow for native access. The prevalence of first-up AVF use in Europe generally exceeds that observed in the USA, reflecting differences in facility practice and culture as well as shorter European times between referral and access placement (12). In this regard, there are more European dedicated vascular access teams performing more cases with a larger experience.

In our study, the VasQ™ was shown to be safe without any documented device-related adverse events or SAEs. The overall prevalence of procedure-related complications is markedly lower than that reported by Dember et al (3) as a reference standard for complications inherently associated with the construction of an AVF.

This preliminary study shows very good unassisted maturation rates for AVFs using the VasQ™ external support device at 1, 3 and 6 months of follow-up (80%, 79% and 74%, respectively) with high primary patency rates (95%, 79% and 79%, respectively) and high mean access flow rates (1130, 1426 and 1304 mL/min^-1, respectively). These early results from a limited size study show promise with good sustained performance characteristics of the VasQ™ implant where the venous flow rates exceed those reported by Robbin et al as necessary for efficient dialysis in more than 95% of AVFs (13). Our results (ranging from 50%-70%) exceed those of the available literature for primary patency rates reported at between 40% and 60% (3) and where between 15%-40% of AVFs require assistance revision (14-15-16). Comparison with implant-enhanced fistulas (the Optiflow Patency and the Maturation [OPEN] study) (17-18-19-20-21) show significantly improved maturation and flow rates with comparable patency rates.

Although the factors involved in maturation are currently unclear, it would appear that the greatest increase in patent access flow occurs early following AVF construction. There is a requirement for some remodelling capable of accommodating a markedly increased flow resulting from the arteriovenous anastomosis. An increase in shear wall stress and radial forces with cyclic stretching of the media and endothelium are most likely involved (22) where it is anticipated that an enhanced geometric configuration will significantly reduce local turbulence. In this respect, the aim of the VasQ™ is to target those perianastomotic areas prone to the development of neointimal hyperplasia. The use of external supports is expected to positively influence early failure rates which are often due to juxta-anastomotic stenosis in brachiocephalic fistulas. In the perianastomotic area it has been shown that even with an increased blood flow, local flow disturbances are predictive of future stenosis, particularly when there is excessive angulation of the anastomosis (23). Consequently, although reasons for the early high AVF failure rates are multifactorial, geometric construction and mechanical factors are significant predictors for a successful outcome. Maturation therefore depends upon optimal haemodynamics, which may be achieved in the perianastomotic area with the help of some external support. In this respect, VasQ™ has proven efficacy in this initial small study with promising results that have shown early failure and maturation rates comparable with the literature including the DAC study and the OPEN study featuring an anastomotic implant, which influences local haemodynamics and geometry of the anastomosis in brachiocephalic AVFs (3, 17, 19).

The purpose of VasQ™ is to address root causes leading to failure by providing a smoother geometry around the AVF anastomosis usually prone to stenosis and neointimal hyperplasia. Standardisation of ultrasound assessment (measurement of access flow, vein size, vein depth and stenosis) will better define the likely need for pre-emptive revision and define those factors beyond AVF patency (such as depth, potential cannula site locations, outflow capacity and steal syndromes), which are important outcome predictors for AVF lifespan and usage (24).

There are several limitations of this study. First, the data are preliminary with small patient numbers and limited follow-up. Furthermore, differences in the ‘culture’ of AVF use may affect the early unassisted maturation rates, particularly where patient exclusions (most commonly for suboptimal target vessels) are less rigid.

In summary, the VasQ™ used in autogenous brachiocephalic AVFs is associated with higher short- and medium-term maturation and patency rates for externally supported AVFs than previously reported. Larger, longer-term prospective studies are required in order to confirm these promising results. VasQ™ may obviate some of the problems implicated in early AVF failure providing a fixed outflow diameter and shielding the anastomosis from adhesions and inflammatory reaction.

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