Drug-Eluting Stent for the Treatment of Early Fistula Failure

doi:10.4236/ijcm.2011.23032

Paper Menu >>

Journal Menu >>

International Journal of Clinical Medicine, 2011, 2, 196-200

doi:10.4236/ijcm.2011.23032 Published Online July 2011 (http://www.SciRP.org/journal/ijcm)

Drug-Eluting Stent for the Treatment of Early

Fistula Failure

Luigi di Serafino, Laura Scudiero, Mario de Laurentis, Federica Ilardi, Fabio Magliulo, Giuseppe

Carotenuto, Cinzia Perrino, Giovanni Esposito

Division of Cardiology, Federico II University, Naples, Italy.

Email: [email protected]

Received November 26th, 2010; revised February 1st, 2011; accepted February 10th, 2011.

ABSTRACT

Introduction: Morbidity and mortality in chronic haemodialysis patients is related to dialysis efficiency. Several com-

plications may occur with vascular access usually associated with a stenosis. This is known to occur frequently in the

venous outflow. Stenosis of the arterial side is not as frequently discussed, but it is also likely to compromise fistula

function. Traditionally, surgical and percutaneous interventions have been used to treat failing fistulas, but the em-

ployment of drug-eluting stents for the treatmen t of failing fistulas due to the arterial sten osis ha s been described rarely.

Methods: A 65-year-old male patient referred to our ambulatory because of hand ischemia during haemodialysis

treatments only few days after radial-cep halic fistula creation. After physical and echo-color-doppler examination, an-

giography was performed and percutaneous intervention was proposed. After the positioning of a guiding catheter, the

lesion was crossed with a 0.014” guide wire followed by direct drug-eluting stent implantation. Results: Final an-

giogram sho wed a good result and a preserved flow through the fistula. Six months later the patien t was asymptomatic

and the fistula was still working. Conclusions: Although further prospective studies are necessary, percutaneous trans-

luminal angioplasty (PTA) with drug-eluting stents implantatio n could be considered a safe and effective technique for

the treatment of arteriovenous fistulas stenosis.

Keywords: Arteriovenous Fistula, Percutaneous Transluminal Angioplasty, Haemodialysis, Drug-Eluting Stents

1. Introduction

Autogenous fistula is a very common strategy for pa-

tients with end-stage renal disease who receive haemo-

dialysis. Primary placement of autogenous haemodialy-

sis fistulas is preferred to other types of haemodialysis

access due to benefits including longer patency, fewer

infection, lower mortality and higher quality of life [1].

However, autogenous haemodialysis fistulas are also

susceptible to dysfunction and failure [2]. Fistula failure

can be classified as early and late. Early fistula failure

refers to those cases in which the arteriovenous fistula

(AVF) never develops, or it fails within the first 3

months of usage. Late failure refers to those cases that

fail after 3 months of successful usage [3]. The clinical

manifestations of early fistula failure are: 1) inadequate

development to permit repetitive cannulation for dialysis;

2) inadequate flow limiting dialysis and 3) thrombosis.

However, generally, those clinical manifestations are

related to some anatomical problems [3,4], and a lesion

is usually found to be the cause of the dysfunction. Al-

though it has been common practice to abandon these

early spoilt fistulas, aggressive evaluation and treatment

of early fistula failures has been shown to result in the

salvage of a large percentage of patients [4].

Several studies reported that non-maturing AVFs

might be salvaged by various surgical and interventional

approaches. Surgical ligation of tributaries, superficiali-

zation procedures, or revision of anastomoses may sal-

vage a significant number of fistulas that fail to mature

adequately. Although autogenous AVFs fail to mature

for several reasons, a commonly encountered angio-

graphic finding is the presence of an anastomotic steno-

sis [5]. Thrombosis is the most frequent AVF complica-

tion resulting in the loss of access for haemodialysis.

Most events of thrombosis (more than 85% of cases)

coincide with the development of vascular stenosis,

generally located in the venous segment proximal to the

arteriovenous anastomosis. Stenosis in the arterial seg-

ment has been less studied, but also compromises the

patency of the vascular access, and also results in limb

Drug-Eluting Stent for the Treatment of Early Fistula Failure197

ischemia. Thus, it should be identified in the dialytic

population, generally composed of elderly patients with

comorbidities, many of whom with generalized arterial

disease.

Percutaneous transluminal angioplasty (PTA), per-

formed only using the plain old balloon angioplasty

(POBA) technique, has proved to be efficacious in the

treatment of stenoses located across the AVF [6]. Only

few reports are currently available regarding the use of

stents, which have been used predominantly in the case

of failed or complicated angioplasty (venous rupture,

elastic recoil, rapidly recurrent stenosis after PTA or

residual stenosis >30%) or as adjunctive therapy [7]. To

our knowledge, this is the first clinical case reporting

percutaneous correction of arterial stenosis responsible

for early fistula dysfunction using a drug-eluting stent.

2. Case Report

A 65-year-old male patient with history of hypertension,

smoking habit and suffering from autosomal dominant

polycystic kidney disease (ADPKD) referred to our am-

bulatory because of hand ischemia during hemodialysis

treatments.

In the 1998, he had undergone nephrectomy and, two

years later, kidney transplantation had been suggested

and performed. Ten years later (April 2010), the patient

needed haemodialysis, due to the failure of the trans-

planted kidney. Central venous catheters (CVCs) had

been used for one month until a left radial-cephalic fis-

tula (RCF) had been created. Unfortunately, few days

later, the patient reported a decrease in AVF thrill and he

suffered from hand ischemia during haemodialysis

treatments. These symptoms typically occurred within 1

hour after dialysis initiation and they were temporally

related to the gradual drop in blood pressure during the

treatment, limiting the patient ability to attain optimal

post-dialysis weight. Moreover, nephrologists referred a

decreased hemodialysis flow rate (<500 ml/min).

After physical examination, power- and color-doppler

were used to explore the left arm vessels, and a critical

stenosis (PSV > 3.5 m/s) of the left radial artery was eas-

ily evidenced, above the fistula (Figure 1). No other

critical stenosis was found through the venous segment

and across the fistula. Due to symptoms intensification,

the patient was admitted to our Cath-Lab and a left arm

angiography was performed using the right arterial fem-

oral access with a 6 Fr. Sheath introducer. The angio-

graphy showed a critical stenosis of the left radial artery

(Figure 2), and it showed also a competitive flow be-

yond the RCF because of the higher perfusion pressure

coming from the ulnar artery. In order to evaluate if the

lesion was due to the artery tortuosity or to a spam, the

operator injected nitrates (NTG), through the diagnostic

Figure 1. Pw- and color-doppler showed a critical stenosis

(PSV > 3.5 m/s) of the left radial artery, above the AVF.

catheter, and he asked the patient to perform prono-su-

pination movements of the left arm. Since the stenosis

did not change after NTG infusion and after forearm

prono-supination movements, the interventional proce-

dure was performed using the same right arterial femoral

access used for the angiography. Heparin (5000 UI) was

administered and a 6 Fr. Multiporpouse guiding catheter

(Medtronic Launcher® Coronary Guide Catheter) was

advanced into the left brachial artery using a 0,035” stiff

guide wire (Terumo, Radifocus® Guide Wire M stiff

type) as support. The catheter was stopped after the ori-

gin of the brachial artery before the bifurcation. The le-

sion was then crossed with a 0.014” guide wire (BHW,

190 cm, from Guidant Corp.) and direct stenting (En-

deavor® Resolute Drug-Eluting Stent, 4 × 15 mm Med-

tronic) was performed inflating the balloon up to 14 atm

(Figure 3). No post-dilation was considered necessary.

The last angiogram showed a good final result without

any residual stenosis (Figure 4) and a preserved flow

through the AV fistula and through the hand also fur-

nished from the ulnar artery. At the end of the procedure,

doppler examination demonstrated a normal flow through

Figure 2. (a) Angiography showed a critical stenosis of the

left radial artery. Stenosis did not change after NTG infu-

sion and after forearm prono-supination. (b) Widen wiew of

the lesion.

Drug-Eluting Stent for the Treatment of Early Fistula Failure

198

Figure 3. (a) The lesion was crossed with a 0.014” guide

wire (BHW, 190cm, from Guidant Corp). (b) Direct stent-

ing (Endeavor® Resolute Drug-Eluting Stent, 4 × 15 mm

Medtronic) was performed inflating the balloon up to

14atm. (c) The final angiogram, without contrast, showed

good stent strut apposition.

Figure 4. The final angiogram showed a good result without

any residual stenosis.

the radial artery and the optimal apposition of the stent

struts. After 6 months, color-doppler showed a normal

flow through the radial and ulnar arteries, and also a

normal stent patency with normal doppler velocities

(Figure 5). Presered function of the AV fistula has been

also clinically demonstrated through increased thrill, in-

creased haemodialysis flow rate (>500 ml/min) and no

upper left limb ischemia during haemodialysis. Follow

Figure 5. At 6 months echo-color-doppler showed patent

stent with normal flow through the vessel.

up is still on-going.

3. Discussion

Several international professional societies [8] recom-

mend an autogenous fistula as the access of choice for

haemodialysis. Insertion of vascular access has become

one of the most common operations performed by vas-

cular surgeons [9], but only 42% - 80% of AVFs mature

adequately for haemodialysis [10-13].

Reduction in haemodialysis access blood flow rates

can compromise the delivery of adequate dialysis and

may cause acute ischemia and thrombosis. Chronic is-

chemia related to the presence of a dialysis access is a

relatively infrequent, but potentially catastrophic com-

plication. It can be due to three main mechanisms: 1)

venous hypertension (diagnosis that can be easily made

by clinical observation of a significant limb swelling and

sometimes visible collateral venous circulation), 2) steal

syndrome (flow reversal in the portion of the artery distal

to the fistula due to a lower pressure system on the out-

flow side of the anastomosis) and 3) arterial lesions.

In the past, fistula ligation was the preferred treatment

strategy for patients with hand ischemia after access sur-

gery. However, this approach required the abandonment

of potentially valuable vascular access sites. Several oth-

er surgical approaches have been proposed to treat steal

syndrome and to preserve the access, most of them re-

ducing fistula flow [14-16], thus increasing the risk of

thrombosis. In contrast, the treatment of ischemia by

arterial PTA increases flow to the access.

Few reports have been published regarding diagnosis

and treatment of lesions of the radial artery. The largest

series reported 11 cases of dilation of the radial artery

because of low fistula flow, hand ischemia or access

thrombosis [17]. The results were combined with those

achieved after dilation of brachial and ulnar arteries,

yielding a primary patenc y rate of 50% at 1 year. Propor-

tions of 6% - 7% of stenosis located in the radial artery

Drug-Eluting Stent for the Treatment of Early Fistula Failure199

were reported by Turmel and Manninen [5,18]. Stent-

graft placement has been also proposed as solution to the

complication of restenosis caused by neo-intimal hyper-

plasia only along the venous outflow.

Although arterial restenosis appears to be significantly

less common compared to the situation that currently

occurs in the venous system, larger studies showed a

40% primary patency rate at 12 months after arterial PTA

(performed with POBA) [17]. This means that about 60%

of patients could have been submitted to a new interven-

tion at 12 months. Moreover, flow-limiting restenosis

could be considered the primum movens to the AVF

thrombosis followed by its failure. For these reasons,

restenosis should be avoided, in particular for older pa-

tients to who could be difficult to find a new access and

who do not tolerate the onset of a new su b-optimal dialy-

sis session. The use of drug-eluting stents could be pro-

posed to ensure a better primary patency rate. Indeed,

although arterial restenosis appears to be different in

each arterial district, the experience coming from the

percutaneous treatments of the coronary artery disease

can be useful also for the treatment of the arterial vessels

disease in the upper limbs. This suggests that the use of

drug-eluting stents might reduce neointimal proliferation

also in this district, ensuring a better primary AVF patency

for these patients.

Endeavor® Resolute drug-eluting stent, which we used

in our case, has a proprietary new biocompatible polymer

called BioLinx. The BioLinx polymer is designed to

confer the same biocompatibility as the Endeavor stent’s

phosphorylcholine (PC) polymer while extending the

duration of drug exposure (Zotarolimus) in the vessel.

Developed by Medtronic scientists, BioLinx is the first

polymer specifically created for use on a drug-eluting

stent. The BioLinx polymer features a unique blend of

hydrophilic and hydrophobic elements for optimal per-

formance. Extensive preclinical studies have established

the biocompatibility and drug delivery capabilities of the

BioLinx polymer. Patients treated with the Endeavor

Resolute stent in the RESOLUTE clinical trial required

no repeat procedures through 9 months and had experi-

enced no protocol-defined stent thrombosis through 12

months of follow-up. Instent late lumen loss at 9 months,

the study’s primary endpoint, was met at 0.22  0.27 mm,

providing assurance of vessel healing in the targeted

range while preventing repeat procedures. Among the

trial’s 130 patients, only one required clinically-driven

Target Lesion Revascularition (TLR) or Target Vessel

Revascularization (TVR) through 12 months. The inci-

dence of major adverse cardiac events was 8.5 through

12 months [19].

We report the case of a patient who was suffering from

left hand ischemia during sub-optimal haemodialysis

treatments. The interventional procedure was performed

without any complication and after direct stent implanta-

tion no further dilatation was necessary. Peri-procedural

Color-doppler examination showed a good final result

with complete stent struts apposition to the arterial wall.

The patient, after successful angioplasty of the pre-an-

astomotic inflow stenosis, had a significant increase in

fistula pressure. Adaptive remodelling and enhanced

blood flow in the fistula permitted hemodialysis to be

successfully performed. 6 months later, the patient was

asymptomatic and the AV access was still working.

Moreover, echo-color-doppler examination showed the

patent stent without any image of in-stent restenosis ref-

erable to the neointimal pro liferation. To our knowledge,

this is the first case report of PTA using a drug-eluting

stent in a case of radial artery stenosis responsible for

early fistula failure.

4. Conclusions

Traditionally, surgical and percutaneous interventions

have been employed to treat failing fistulas and included

surgical revision, PTA with or without stent placement.

PTA could be considered as the treatment of choice in

cases of malfunctioning AVFs and it should always be

attempted before making a new surgical access in order

to preserve the vascular tree. The employment of drug-

eluting stents for the treatment of failing fistulas due to

the arterial stenosis has not been already described. Fur-

ther prospective studies are necessary to confirm that

PTA with drug-eluting stents implantation is a safe and

effective technique to correct such lesions.

REFERENCES

[1] K. R. Polkinghorne, S. P. McDonald, R. C. Atkins and P.

G. Kerr, “Vascular Access and All-Cause Mortality: A

Propensity Score Analysis,” Journal of American Society

of Nephrology, Vol. 15, No. 2, 2004, pp. 477-486.

doi:10.1097/01.ASN.0000109668.05157.05

[2] C. L. Bent, D. K. Rajan, K. Tan, et al., “Effectiveness of

Stent-Graft Placement for Salvage of Dysfunctional Arte-

riovenous Hemodialysis Fistulas,” Journal of Vascular

Interventional Radiology, Vol. 21, No. 4, 2010, pp. 496-

502. doi:10.1016/j.jvir.2009.12.395

[3] G. A. Beathard, “Angioplasty for Arteriovenous Grafts

and Fistulae,” Seminars Nephrology, Vol. 22, No. 3, 2002,

pp. 202-210. doi:10.1053/snep.2002.31739

[4] G. A. Beathard, S. M. Settle and M. W. Shields, “Salvage

of the Nonfunctioning Arteriovenous Fistula,” American

Journal of Kidney Diseases, Vol. 33, No. 5, 1999, pp.

910-916. doi:10.1016/S0272-6386(99)70425-7

[5] L. Turmel-Rodrigues, A. Mouton, B. Birmele, et al.,

“Salvage of Immature Forearm Fistulas for Haemodialy-

sis by Interventional Radiology,” Nephrology Dialysis

Transplantation, Vol. 16, No. 12, 2001, pp. 2365-2371.

Drug-Eluting Stent for the Treatment of Early Fistula Failure

200

doi:10.1093/ndt/16.12.2365

[6] D. G. Miquelin, L. F. Reis, A. A. da Silva and J. M. de

Godoy, “Percutaneous Transluminal Angioplasty in the

Treatment of Stenosis of Arteriovenous Fistulae for He-

modialysis,” International Archives Medicine, Vol. 1, No.

1, 2008, p. 16. doi:10.1186/1755-7682-1-16

[7] M. R. Chan, S. Bedi, R. J. Sanchez, et al., “Stent Place-

ment versus Angioplasty Improves Patency of Arterio-

venous Grafts and Blood Flow of Arteriovenous Fistu-

lae,” Clinical Journal of the American Society Nephrol-

ogy, Vol. 3, No. 3, 2008, pp. 699-705.

doi:10.2215/CJN.04831107

[8] S. Ohira, H. Naito, I. Amano, et al., “2005 Japanese So-

ciety for Dialysis Therapy Guidelines for Vascular Ac-

cess Construction and Repair for Chronic Hemodialysis,”

Therapeutic Apheresis Dialysis, Vol. 10, No. 5, 2006, pp.

449-462. doi:10.1111/j.1744-9987.2006.00410.x

[9] J. M. Weiswasser, D. Kellicu t, S. Arora and A. N. Sidawy,

“Strategies of Arteriovenous Dialysis Access,” Seminars

Vascular Surgery, Vol. 17, No. 1, 2004, pp. 10-18.

doi:10.1053/j.semvascsurg.2003.11.008

[10] A. Asif, P. Roy-Chaudhury and G. A. Beathard, “Early

Arteriovenous Fistula Failure: A Logical Proposal for

When and How to Intervene,” Clinical Journal of Ameri-

can Society Nephrology, Vol. 1, No. 2, 2006, pp. 332-339.

doi:10.2215/CJN.00850805

[11] S. T. Patel, J. Hughes and J. L. Mills Sr, “Failure of Arte-

riovenous Fistula Maturation: An Unintended Conse-

quence of Exceeding Dialysis Outcome Quality Initiative

Guidelines for Hemodialysis Access,” Journal of Vascu-

lar Surgery, Vol. 38, No. 3, 2003, pp. 439-445.

doi:10.1016/S0741-5214(03)00732-8

[12] S. S. Berman and A. T. Gentile, “Impact of Secondary

Procedures in Autogenous Arteriovenous Fistula Matura-

tion and Maintenance,” Journal of Vascular Surgery, Vol.

34, No. 5, 2001, pp. 866-871.

[13] L. M. Dember, G. J. Beck, M. Allon, et al., “Effect of

Clopidogrel on Early Failure of Arteriovenous Fistulas

for Hemodialysis: A Randomized Controlled Trial,” The

Journal of American Medical Association, Vol. 299, No.

18, 2008, pp. 2164-2171.

[14] M. Haimov, H. Schanzer and M. Skladani, “Pathogenesis

and Management of Upper-Extremity Ischemia Following

Angioaccess Surgery,” Blood Purification, Vol. 14, No. 5,

1996, pp. 350-354. doi:10.1159/000170286

[15] J. C. West, D. J. Bertsch, S. L. Peterson, et al., “Arterial

Insufficiency in Hemodialysis Access Procedures: Cor-

rection by ‘Banding’ Technique,” Transplantation Pro-

ceedings, Vol. 23, No. 2, 1991, pp. 1838-1840.

[16] A. B. Redfern and N. B. Zimmerman, “Neurologic and

Ischemic Complications of Upper Extremity Vascular

Access for Dialysis,” The Journal of Hand Surgery, Vol.

20, No. 2, 1995, pp. 199-204.

doi:10.1016/S0363-5023(05)80007-3

[17] A. Guerra, A. Raynaud, B. Beyssen, J. Y. Pagny, M.

Sapoval and C. Angel, “Arterial Percutaneous Angio-

plasty in Upper Limbs with Vascular Access Devices for

Haemodialysis,” Nephrology Dialysis Transplantation,

Vol. 17, No. 5, 2002, pp. 843-851.

doi:10.1093/ndt/17.5.843

[18] H. I. Manninen, E. Kaukanen, K. Makinen and P. Karha-

paa, “Endovascular Salvage of Nonmaturing Autogenous

Hemodialysis Fistulas: Comparison with Endovascular

Therapy of Failing Mature Fistulas,” Journal of Vascular

Interventional Radiology, Vol. 19, No. 6, 2008, pp. 870-

876. doi:10.1016/j.jvir.2008.02.024

[19] I. T. Meredith, S. Worthley, R. Whitbourn, et al., “Clini-

cal and Angiographic Results with the Next-Generation

Resolute Stent System: A Prospective, Multicenter, First-

in-human Trial,” JACC: Cardiovasc Interventions, Vol. 2,

No. 10, 2009, pp. 977-985.

doi:10.1016/j.jcin.2009.07.007