Optical Coherence Tomography in Arteriovenous Fistula Management: a proof of principle study

The life expectancy of patients with established kidney failure is considerably
shortened with worsening quality of life. With renal replacement therapy, such
as hemodialysis and peritoneal dialysis, the quality of life and survival of
advanced renal disease patients can be markedly improved. The efficiency of
hemodialysis treatment relies on the functional status of vascular access.
There are three main methods of providing vascular access, which include an
arteriovenous fistula (AVF), central venous catheter (CVC) or an arteriovenous
graft (AVG). CVCs are used temporarily to ensure vascular access for
hemodialysis patients awaiting the creation or maturation of an AVF or AVG.
CVCs can also be used permanently if there are no other vascular access options
[1].

An AVF is created by connecting a native artery and vein while an AVG is
created by using a synthetic graft to make the connection between the artery
and vein. An AVF is considered to provide the best long-term functional
vascular access with the lowest mortality rate and lowest rate of
re-intervention as well as being the most cost-effective. An AVF also has the
longest secondary patency rates, defined as the time interval between AVF
creation and abandonment with or without surgical or endovascular intervention
[2, 3]. The most common site for AVF creation is the forearm using the radial
artery and cephalic vein. The AVF could also be placed on the upper arm using
the brachial artery and cephalic vein or using the brachial artery and basilic
vein [4].
AVF primary failure or failure to mature can occur early due to thrombosis,
which can be triggered by a hematoma, low flow rates resulting from low blood
pressure or by a hypercoagulable state [5]. Progressive intimal hyperplasia in
the venous outflow system can lead to stenosis, resulting in a reduction in the
flow rate which can cause late thrombosis of an AVF [5, 6].

The development of a stenosis is the primary cause of fistula failure. The
formation of stenosis is initiated by endothelial cell injury, leading to
smooth muscle proliferation and neointimal hyperplasia [1, 7]. The endothelium
is the largest organ in the body consisting of endothelial cells lining every
blood vessel [1, 8]. In healthy subjects, the vascular endothelium has many
functions, including identifying hormonal stimuli such as vasoactive
substances, as well as mechanical stimuli such as pressure and shear stress.
They regulate inflammation, cell proliferation, vascular tone and coagulation
due to their output of compounded substances [1, 9]. Endothelial dysfunction
occurs when there is an imbalance between vasoconstricting and vasodilating
products [1, 10]. Endothelial dysfunction is exhibited by patients with chronic
kidney failure, resulting in a higher risk of fistula failure. Fistula failure
can occur in the early phase, mainly due to thrombosis which is triggered by
hematoma, low flow rates resulting from low blood pressure or by a
hypercoagulable state [1, 11]. Furthermore, late fistula failure can be caused
by progressive neointimal hyperplasia in the venous outflow system or at the
anastomosis causing a stenosis [1]. The most common site of stenosis is
juxta-anastomotic, followed by the body of the fistula, the peripheral draining
veins and lastly the feeding artery [12]. The occurrence of late fistula
failure can be caused by turbulent flow, high intraluminal pressure and regular
needle insertion during hemodialysis. These factors can cause endothelial
damage leading to hemostatic activation in the AVF resulting in occlusion.
These mechanical stimuli can additionally result in thrombosis and consequently
dysfunction of the AVF [13]. However, the exact pathophysiological mechanism
remains a point of discussion [14].

Treatment of dysfunctional AVF consists primarily of percutaneous transluminal
angioplasty (PTA), which is preferred over open surgery due to its associated
short and long term benefits [15]. There is a variety of balloons that can be
used to perform PTA of an AVF, including plain old balloons, high-pressure
balloons, cutting balloons, scoring balloons and drug-eluting balloons. The
choice of balloon depends on the expertise of the surgeon and characteristics
of the stenosis, however the most commonly used balloon is a noncompliant
high-pressure balloon [15, 16]. Although efficacious on short-term, PTA
frequently requires reintervention after the initial procedure, either due to
regrowing of occlusive intimal hyperplasia and/or fibrotic scarring of the AVF
wall. This is due to the fact that PTA does cause significant injury to the
vessel due to stretching of the vein and compression of the intima causing
shear mechanical stress, which is additionally one of the triggers for intimal
overgrowth [1, 14].

Currently, Digital Subtraction Angiography (DSA) is used during PTA to assess
the stenosis in the AVF. However, DSA has its limitations. Firstly, DSA does
not allow objective measurement of the vessel diameter. This means that the
surgeon must estimate the vessel diameter causing interobserver variability and
difficulties in selecting the correct balloon size. Secondly, DSA does not give
the surgeon sufficient information on the morphology and shape of the stenosis
in the vessel [17]. This information could change intraoperative
decision-making as it might influence the size and type of the balloon that is
to be used, as well as decision to carry on the procedure after PTA. Past
studies have investigated the use of intravascular ultrasound (IVUS),
indicating that its use could be beneficial in PTA of AVF. However, IVUS has
its limitations as it poorly differentiates between the different vascular
layers and has a low resolution resulting in poorer image quality [18].

Optical Coherence Tomography (OCT) is an intravascular imaging modality that is
able to provide objective information regarding the morphology of the vessel
wall and quality of the vessel. It visualizes the morphology of the stenosis
and diameter of the vessel [17]. Using a catheter that is positioned within the
affected blood vessel, OCT visualizes the vessel wall by emitting near-infrared
light to provide a high definition, cross-sectional and three dimensional image
of the vessel microstructure. The tip of the catheter is placed distal to the
stenosis and, while administering a bolus of iodine contrast agent, the tip of
the catheter is pulled back while making images to capture the structures of
the vessel wall and stenosis. While this is performed, a simultaneous image is
made using DSA [19]. Compared to IVUS, OCT has a 10-fold greater spatial
resolution. This allows for better visualization of the morphology and shape of
the stenosis, preferring OCT over IVUS [20]. OCT is often used within the field
of Cardiology and its advantages have improved patient outcomes in percutaneous
coronary intervention (PCI) procedures, where it is part of the standard
practice in both acute and chronic myocardial ischemia [21]. PTA has comparable
limitations to PCI using merely DSA. However, this has not been studied outside
of the coronary arteries thus far. This proof of principle study aims to prove
the first insight of the usability and safety of OCT in AVF using a small
population of patients undergoing PTA due to AVF stenosis.

This proof of principle study aims to provide the safety and feasibility of OCT
in patients with primary shunt failure requiring re-intervention. Safety is
defined as conducting the OCT measurement without complications caused by the
OCT measurement. Feasibility is defined as successfully completing the OCT
measurement before and after PTA.

This study will be a proof of principle study. It will be a one-armed trial
where patients are their own control, thus the measurements as described do not
necessitate a control group to provide the information required to achieve the
stated objectives. The study will be conducted between April 1, 2023, and April
1, 2024, in the Zuyderland Medical Center. 10 patients who will undergo a PTA
of their AVF will be included. Images using OCT will be made before and after
PTA. After the procedure, the surgeon will be asked to assess the OCT-images
and discuss whether the intraoperative decision-making would have been altered
knowing the information supplied by OCT. As per the standard protocol of the
Zuyderland MC, there is no follow-up after the PTA. As this is the first
prospective study using OCT in AVF, a validation in a small group is necessary
as a step-up to larger studies.

There are no additional risks for participating subjects. Subjects undergo a
PTA, which they undergo regardless of participation in the study. During this
procedure, a catheter is inserted intra-arterially as standard. The OCT
measurement is done with the help of this catheter. This means that only an
extra measurement is done through this catheter, which does not entail any
additional risks for the test subject. No radiation is used. Contrast fluid is
used, but the main risk associated with its use is renal insufficiency. This
patient population already has end stage renal insufficiency and the amount of
contrast medium used is so minimal that it does not entail any additional risk.
The OCT system uses iodinated contrast agent during measurements, the same
substance that is already used during PTA to create DSA images. OCT uses
4ml/sec during measurement. The total volume of contrast depends on the length
of the stenosis, the maximum amount of contrast administered is equal to what
is used with a regular PTA. The contrast is injected into the blood vessel at
the site of the stenosis at the level of the arteriovenous fistula. Although it
is known that there is a risk of acute renal failure with the use of iodinated
contrast media, there is no additional risk in this patient population as they
already have end-stage renal disease. Also, the amount used for the OCT
measurement is minimal compared to the amount used for DSA. Its use is
therefore justified.