Early Results with the Use of Heparin-bonded Stent Graft to Rescue Failed Angioplasty of Chronic Femoropopliteal Occlusive Lesions: TASC D Lesions Have a Poor Outcome

Abstract

To evaluate early patency rate of the heparin-bonded stent grafts in atherosclerotic long femoropopliteal occlusive disease, and to identify factors that affect outcome.
Heparin-bonded Viabahn stent grafts were placed in 33 limbs in 33 patients during 2009-2010. The stents were deployed to rescue failed conventional balloon angioplasty. Mean age was 69 (range 44-88) years, and 67 % (22 of 33) were men. Most procedures (21 of 33, 64 %) were performed for critical limb ischemia (33 % for rest pain, 30 % tissue loss). Kaplan-Meier plots and Cox regression analysis were used to identify significant risk factors.
The average length of lesions treated was 25 ± 10 cm, and they were predominantly TASC (Transatlantic Intersociety Consensus) D (n = 13) and C (n = 17) lesions. The median primary patency was 5.0 months (95 % confidence interval 1.22-8.77). The mean secondary patency was 8.6 months (95 % confidence interval 6.82-10.42). Subsequently, 4 patients underwent bypass surgery and 5 patients underwent major amputation. One patient died. There were 5 in-stent or edge-stent stenoses. Cox multivariate regression analysis identified TASC D lesions to be a significant risk factor for early occlusion (p = 0.035).
TASC D lesions of femoropopliteal occlusions have poor patency rates with the use of heparin-bonded stent grafts after failed conventional angioplasty. Alternative options should be considered for these patients.

Full text

CLINICAL INVESTIGATION ARTERIAL INTERVENTIONS
Early Results with the Use of Heparin-bonded Stent Graft
to Rescue Failed Angioplasty of Chronic Femoropopliteal
Occlusive Lesions: TASC D Lesions Have a Poor Outcome
Ganesh Kuhan •Said Abisi •Bruce D. Braithwaite •
Shane T. R. MacSweeney •Simon C. Whitaker •
Said B. Habib
Received: 5 October 2011 / Accepted: 8 April 2012 / Published online: 14 June 2012
ÓSpringer Science+Business Media, LLC and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2012
Abstract
Purpose To evaluate early patency rate of the heparin-
bonded stent grafts in atherosclerotic long femoropopliteal
occlusive disease, and to identify factors that affect
outcome.
Methods Heparin-bonded Viabahn stent grafts were
placed in 33 limbs in 33 patients during 2009–2010. The
stents were deployed to rescue failed conventional balloon
angioplasty. Mean age was 69 (range 44–88) years, and
67 % (22 of 33) were men. Most procedures (21 of 33,
64 %) were performed for critical limb ischemia (33 % for
rest pain, 30 % tissue loss). Kaplan–Meier plots and Cox
regression analysis were used to identify significant risk
factors.
Results The average length of lesions treated was
25 ±10 cm, and they were predominantly TASC (Trans-
atlantic Intersociety Consensus) D (n=13) and C
(n=17) lesions. The median primary patency was
5.0 months (95 % confidence interval 1.22–8.77). The
mean secondary patency was 8.6 months (95 % confidence
interval 6.82–10.42). Subsequently, 4 patients underwent
bypass surgery and 5 patients underwent major amputation.
One patient died. There were 5 in-stent or edge-stent ste-
noses. Cox multivariate regression analysis identified
TASC D lesions to be a significant risk factor for early
occlusion (p=0.035).
Conclusion TASC D lesions of femoropopliteal occlu-
sions have poor patency rates with the use of heparin-
bonded stent grafts after failed conventional angioplasty.
Alternative options should be considered for these patients.
Keywords Occlusion Patency Peripheral arterial
disease Stent graft
Introduction
Peripheral arterial disease affects 12–14 % of the general
population, and its prevalence increases with age, affecting
up to 20 % of patients over the age of 75 years [1]. En-
dovascular therapy is an attractive option for patients
because of low morbidity and mortality compared with
open surgery. Endovascular options for the treatment of
femoropopliteal disease include balloon angioplasty, stents,
and stent grafts.
Improved patency rates with bare metal stents compared
with balloon angioplasty have been hampered by intimal
hyperplasia and stent fractures [2]. Drug-eluting stents to
halt intimal hyperplasia have been successfully used in the
coronary system [3]. A previous randomized, controlled
trial failed to find a benefit for drug-eluting stents in the
femoropopliteal artery compared with bare metal stents [4].
A recently published randomized, controlled trial indicated
better early patency rates with drug-eluting stents for short
superficial femoral artery occlusions [5]. Stent grafts
appear to have properties that are resistant to neointimal
hyperplasia and stent fractures [6]. Heparin has an anti-
coagulation and antiproliferative effect on smooth muscle
cells [7]. Addition of heparin as a bioactive surface can
provide sustained thromboresistance. The outcome of
heparin-bonded stent grafts on an unselected group of
G. Kuhan (&)S. Abisi B. D. Braithwaite 
S. T. R. MacSweeney
Vascular and Endovascular Unit, Queens Medical Centre,
Nottingham University Hospitals, Nottingham NG7 2UH, UK
e-mail: gkuhan@nhs.net
S. C. Whitaker S. B. Habib
Department of Radiology, Queen’s Medical Centre, Nottingham
University Hospitals, Nottingham NG7 2UH, UK
123
Cardiovasc Intervent Radiol (2012) 35:1023–1028
DOI 10.1007/s00270-012-0400-6

patients with long femoropopliteal arterial occlusions is not
known.
The aim of this study was to determine the early patency
rate of the heparin-bonded covered stents in challenging
atherosclerotic femoropopliteal occlusions and to identify
factors that affected outcome.
Methods
Heparin-bonded Viabahn stent grafts (W. L. Gore Asso-
ciates, Flagstaff, AZ) were placed in 33 limbs in 33 patients
during 2009 and 2010. Most procedures (21 of 33, 64 %)
were performed to treat critical limb ischemia (33 % for
rest pain, 30 % tissue loss), and the rest were for lifestyle-
limiting claudication (12 of 33, 36 %). All patients
underwent duplex scans of the arterial system before the
procedure to determine inflow to the femoral artery, the
anatomical extent of the occluded segment, and the calf
vessel runoff.
All patients with femoropopliteal occlusive disease were
considered for the study. The use of stents to correct failed
angioplasty using bare nitinol stents and non-heparin-
bonded stent grafts is a well-established practice at our
study center. Separate ethics approval for the study was not
considered necessary by the ethics committee. Failure of
conventional balloon angioplasty was the main indication
to consider stent graft deployment. Stents were deployed
when the vascular radiologist thought that leaving the
patient with a failed or poor angioplasty result would result
in reocclusion of the treated section. These included lesions
with significant recoil, residual ([30 %) stenosis, and flow-
limiting dissection flaps. End points were primary and
secondary patency rates. Primary patency was defined as
no evidence of significant restenosis (peak systolic velocity
ratio of [2) or occlusion based on velocity criteria on
duplex ultrasound at follow-up. Secondary patency was
defined by reintervention after occlusion or significant
stenosis of the treated segment of the artery. Immediate
technical success of the procedure was defined by \30 %
residual stenosis at the end of the procedure in the treated
segment with no flow impedance. Data were collected
prospectively and entered into a database. Lesions were
categorized according to the TASC (Transatlantic Interso-
ciety Consensus) working group definitions [8]. Demo-
graphic data and data on length of the lesion, presence of
calcification, inflow disease, and outflow disease were
obtained. Outflow scores were calculated from the angio-
graphic findings as described by Rutherford et al. [9]. The
scoring system was based on the degree of stenosis and the
degree of contribution to outflow of each runoff vessel.
The stent grafts were placed percutaneously either via a
retrograde (over the aortic bifurcation) or an antegrade
approach to the common femoral artery with 10–15 %
oversizing for the diameter of the superficial femoral
artery. Only lesions with poor technical success after sub-
intimal balloon angioplasty were considered for stent
grafting. These included lesions with significant recoil,
residual stenosis, and multiple dissection flaps compro-
mising flow. Inflow and outflow were assessed during
angiography, and if necessary, additional procedures were
performed to improve flow. At least a single runoff vessel
was considered adequate for stent graft placement.
Most patients stayed overnight and were discharged
with dual antiplatelet agents (aspirin 75 mg and clopido-
grel 75 mg) or warfarin for life. Patients were brought back
for clinical assessment and duplex scan of the treated
artery, as well as for assessment of compliance for anti-
platelet agents and statins at 1, 3, and 6 months after the
procedure. Clinical status was assessed at the follow-up
visit on the basis of criteria set by Rutherford et al. [9], to
learn whether patients were better, the same, or worse.
Kaplan–Meier survival analysis was performed to plot
primary and secondary patency. Statistical analysis was
performed by SPSS software, version 16 (SPSS, Chicago,
IL). Median or mean patency (in months) was compared
for primary and secondary patency plots. The log rank test
was performed to identify significant factors that might
affect patency rates. Cox regression analysis was per-
formed to identify multiple factors influence on the
patency.
Results
Mean age was 69 (range 44–88) years, and 67 % (22 of 33)
were men; patients had a high prevalence of hypertension
and hypercholesterolemia (Table 1). Smokers and patients
with diabetes comprised a third of the study group (11
patients). Patients receiving statins and antiplatelet or
anticoagulants were 73 and 81 %, respectively.
Mean ±standard deviation length of occlusion treated
was 25.3 ±10.5 cm, with 70 % requiring [2 stent grafts
(15 cm long and 5 or 6 mm in diameter each). An overlap
of 1 cm was considered adequate when [1 stent graft was
used. TASC C and D lesions were prevalent in 91 % of the
population, and 43 % of the procedures were for recurrent
disease after previous failed angioplasty. Severe calcifica-
tion was present in 24 %, and 49 % had flush occlusion of
the entire length of the superficial femoral artery. A sub-
intimal route was used to recanalize the artery in 67 % of
the patients. Severe outflow disease (score of [10) was
present in 21 %, while inflow disease was present in 15 %.
A stent graft was deployed extending into the popliteal
artery without crossing the knee in 12 patients. Flush
occlusions were recanalized subintimally, and stent grafts
1024 G. Kuhan et al.: Stent Graft for Femoropopliteal Occlusions
123

were placed at the bifurcation without compromising flow
to the profunda femoris artery.
Good technical success was initially achieved in all
procedures. Dual antiplatelet agents or warfarin was pro-
vided in 96 % of the patients after the procedure. One
patient did not receive dual antiplatelet agent to minimize
bleeding. The median primary patency was 5.0 months
(95 % confidence interval 1.22–8.77) (Fig. 1). The mean
secondary patency was 8.6 months (95 % confidence
interval 6.82–10.42) (Fig. 2). Of the 12 patients with life-
style-limiting claudication, the symptoms of 10 improved.
The remaining 2 patients with claudication went on to
undergo successful bypass surgery. The first patient had
stent graft occlusion at 5 months, and despite thrombolysis,
it reoccluded. The second patient had in-stent stenosis and
residual inflow stenosis.
Of the 21 patients with critical limb ischemia, 12 had
improved symptoms. One patient had successful bypass
surgery, and 5 had major amputations. There was 1 death,
unrelated to the procedure, in a patient with critical
ischemia. There were 2 in-stent or edge-stent stenoses
requiring further intervention. There were no stent graft
fractures.
Analysis by log rank test identified TASC D lesions and
flush occlusions to be significant risk factors (p\0.05)
(Table 2). The significant risk factors were entered into a
risk model to identify their combined effect on secondary
patency. Cox multivariate regression analysis identified
Table 1 Patient characteristics Characteristic Value pvalue
Log rank test for
primary patency
Log rank test for
secondary patency
Age [70 y 52 % (17/33) 0.78 0.36
Male gender 67 % (22/33) 0.30 0.46
Critical limb ischemia 63 % (21/33) 0.59 0.20
Smoker 33 % (11/33) 0.25 0.73
Diabetes 36 % (12/33) 0.75 0.80
Heart disease 33 % (11/33) 0.49 0.23
Hypercholesterolemia 72 % (24/33) 0.40 0.38
Renal failure 0 % (0/33) NA NA
Hypertension 68 % (24/33) 0.75 0.60
Statin use 73 % (24/33) 0.21 0.50
Antiplatelet or warfarin use 81 % (26/33) 0.57 0.27
Fig. 1 Primary patency. Kaplan–Meier survival analysis was per-
formed; primary patency (y-axis) is plotted against months after
procedure (x-axis). ?indicates censored data. Censored data indicate
that the period of observation was cut off before the event of interest
has occurred—in this case, significant stenosis or occlusion
Fig. 2 Kaplan–Meier survival analysis was performed; secondary
patency (y-axis) is plotted against months after procedure (x-axis). ?
indicates censored data
G. Kuhan et al.: Stent Graft for Femoropopliteal Occlusions 1025
123

TASC D lesions to be the only significant risk factor
(p=0.035) (Fig. 3), with an odds ratio of 0.23 (range
0.059–0.899).
Discussion
This study identified TASC D lesions to have a poor outcome
when treated with heparin-bonded stent grafts. The presence
of TASC D lesions in claudicants and critically ischemic
limbs were 25 % (3 of 12) and 47 % (10 of 21), respectively.
The median primary patency was 5 months, and the mean
secondary patency time was 8.6 months (Fig. 2). Previous
studies have revealed patency rates of[80 % at 1 year with
the non-heparin-bonded stent graft [10–14]. These studies
used strict inclusion and exclusion criteria, and there were
fewer TASC D category patients. The study we present here
included acute admissions, calcified arteries, flush occlu-
sions, recurrent disease, inflow disease, and outflow disease.
Stent grafts were used only if a poor result was obtained with
conventional angioplasty. This study reflects real-life clini-
cal practice in an unselected group of patients, which may
explain the poor patency rate.
Previous studies have identified length of lesion, renal
failure, diabetes, runoff scores, and occlusion, as opposed
to stenosis, to be significant factors affecting treatment
outcome [10,15–20]. None was significant in our study
group. A poor patency rate for TASC D lesions has been
reported previously with non-heparin-bonded stent graft
with primary patency rates of 39 % at 3 years [21,22].
Table 2 Angiographic
characteristics Characteristic Value pvalue
Log rank test for
primary patency
Log rank test for
secondary patency
TASC
A0
B 9 % (3/33)
C 52 % (17/33)
D 39 % (13/33) 0.62 0.05
Repeated procedure 43 % (14/33) 0.80 0.37
Subintimal percutaneous
transluminal angioplasty
67 % (22/33) 0.57 0.86
Flush occlusions 49 % (16/33) 0.40 0.05
Severe calcified plaque 24 % (8/33) 0.56 0.39
Inflow disease 15 % (5/33) 0.72 0.56
Outflow score
[10 27 % (9/33) 0.55 0.48
1–10 36 % (12/33)
0 36 % (12/33)
Length of lesion (cm), mean ±SD 25 ±11 0.54 0.42
No. of stents
1 24 % (8/33) 0.71 0.91
2 45 % (15/33)
3 30 % (10/33)
Technical success 100 % (33/33) 0.25 0.51
Postprocedure antiplatelet/warfarin use 96 % (32/33) 0.41 0.54
Fig. 3 Secondary patency for TASC D vs. B and C. Secondary
patency for TASC category B, C is compared with D by Cox
multivariate regression analysis. Three significant risk factors (flush
occlusions, no statin use, TASC D lesions) were entered into
the analysis. TASC D lesions were the only significant risk factor.
?indicates censored data
1026 G. Kuhan et al.: Stent Graft for Femoropopliteal Occlusions
123

This study further supports those findings. Despite the
addition of a heparin bioactive surface for stent grafts, the
endovascular therapy results for TASC D lesions remain
poor, particularly in unselected cases.
There were 5 major amputations after stent graft inser-
tion. All 5 patients had critical limb ischemia. The ampu-
tation rate of 23 % (5 of 21) at 6 months in this study is
similar to the BASIL (Bypass versus Angioplasty in Severe
Ischaemia of the Leg) trial data (46 of 224, 20 %) [23]. The
BASIL trial did not find a difference in amputation-free
survival between angioplasty and surgery before 2 years.
Irrespective of the intervention, a fifth of the patients had
lost limbs at 6 months.
The ideal lesions for stent graft insertion are shorter
lesions, lesions not involving the popliteal artery or trifur-
cation, nonflush occlusions of the superficial femoral artery,
and noncalcified arteries with no significant inflow or out-
flow disease. A good 1-cm normal artery above and below
the lesion is necessary for stent graft placement. Only a small
proportion of patients matched these criteria in our study
population. Our study had predominantly longer lesions
([20 cm) and flush occlusions. When an angioplasty fails to
improve flow or it appears that the site will occlude in these
lesions, it is tempting to use a stent graft to improve the
patient’s chance of a successful outcome. If bypass surgery is
not an option, endovascular therapy can be attempted. Cur-
rently the use of a longer-length single stent graft is preferred
to multiple shorter stent grafts at our study center. The use of
short drug-eluting stents at the edges of the stent graft to
prevent edge stenosis is also currently evaluated. Surveil-
lance by duplex scanning is needed for TASC D lesions with
stent grafts. Patients and primary care clinicians should be
informed of the importance of the patients’ receiving anti-
platelet agents and statins, and compliance should be
assessed regularly. In the study group, 33 % of the patients
were smokers; needless to say, this needs to be addressed in
the primary care setting.
This study demonstrates that the placement of a stent graft
can be done without additional complications, but the cli-
nician and the patient should be realistic about the outcome
when a TASC D lesion is treated. Surgical bypass remains
the treatment of choice for TASC D lesions. However, in the
presence of multiple comorbidities or no suitable conduit,
endovascular therapy is an option, provided that the clinician
and the patient can accept a poor outcome.
Acknowledgments W. Tennant, S. Chandresekar, and A. Oluwole
contributed patients to the study. G. Ramjas and R. Oneil performed
some of the procedures. Vascular technologists performed all the
duplex scans.
Conflict of interest The authors declare that they have no conflict
of interest.
References
1. Hiatt WR, Hoag S, Hamman RF (1995) Effect of diagnostic
criteria on the prevalence of peripheral arterial disease. The San
Luis Valley Diabetes Study. Circulation 91:1472–1479
2. Schlager O, Dick P, Sabeti S et al (2005) Long-segment SFA
stenting—the dark sides: in-stent restenosis, clinical deteriora-
tion, and stent fractures. J Endovasc Ther 12:676–684
3. Greenhalgh J, Hockenhull J, Rao N et al (2010) Drug-eluting
stents versus bare metal stents for angina or acute coronary
syndromes. Cochrane Database Syst Rev (5):CD004587
4. Duda SH, Bosiers M, Lammer J et al (2005) Sirolimus-eluting
versus bare nitinol stent for obstructive superficial femoral artery
disease: the SIROCCO II trial. J Vasc Interv Radiol 16:331–338
5. Dake MD, Ansel GM, Jaff MR et al (2011) Paclitaxel-eluting
stents show superiority to balloon angioplasty and bare metal
stents in femoropopliteal disease: twelve-month Zilver PTX
randomized study results. Circ Cardiovasc Interv 4:495–504
6. Wong G, Li JM, Hendricks G et al (2008) Inhibition of experi-
mental neointimal hyperplasia by recombinant human thrombo-
modulin coated ePTFE stent grafts. J Vasc Surg 47:608–615
7. Clowes AW, Karnowsky MJ (1977) Suppression by heparin of
smooth muscle cell proliferation in injured arteries. Nature
265(5595):625–626
8. Norgren L, Hiatt WR, Dormandy JA et al (2007) Inter-society
consensus for the management of peripheral arterial disease
(TASC II). Eur J Vasc Endovasc Surg 33(suppl 1):S1–S75
9. Rutherford RB, Baker JD, Ernst C et al (1997) Recommended
standards for reports dealing with lower extremity ischemia:
revised version. J Vasc Surg 26:517–538
10. Kougias P, Chen A, Cagiannos C et al (2009) Subintimal
placement of covered stent versus subintimal balloon angioplasty
in the treatment of long-segment superficial femoral artery
occlusion. Am J Surg 198:645–649
11. Lammer J, Dake MD, Bleyn J et al (2000) Peripheral arterial
obstruction: prospective study of treatment with a transluminally
placed self-expanding stent-graft. International Trial Study
Group. Radiology 217:95–104
12. Kedora J, Hohmann S, Garrett W et al (2007) Randomized
comparison of percutaneous Viabahn stent grafts vs prosthetic
femoral-popliteal bypass in the treatment of superficial femoral
arterial occlusive disease. J Vasc Surg 45:10–16
13. Saxon RR, Dake MD, Volgelzang RL et al (2008) Randomized,
multicenter study comparing expanded polytetrafluoroethylene-
covered endoprosthesis placement with percutaneous translumi-
nal angioplasty in the treatment of superficial femoral artery
occlusive disease. J Vasc Interv Radiol 19:823–832
14. Lammer J (2001) Femoropopliteal artery obstructions: from the
balloon to the stent-graft. Cardiovasc Intervent Radiol 24:73–83
15. Davies MG, Saad WE, Peden EK et al (2008) Impact of runoff on
superficial femoral artery endoluminal interventions for rest pain
and tissue loss. J Vasc Surg 48:619–625
16. DeRubertis BG, Pierce M, Chaer RA et al (2007) Lesion severity
and treatment complexity are associated with outcome after
percutaneous infra-inguinal intervention. J Vasc Surg 46:709–716
17. Clark TW, Groffsky JL, Soulen MC (2001) Predictors of long-
term patency after femoropopliteal angioplasty: results from the
STAR registry. J Vasc Interv Radiol 12:923–933
18. Capek P, McLean GK, Berkowitz HD (1991) Femoropopliteal
angioplasty. Factors influencing long-term success. Circulation
83(2 suppl):I70–I80
19. Gray BH, Olin JW (1997) Limitations of percutaneous translu-
minal angioplasty with stenting for femoropopliteal arterial
occlusive disease. Semin Vasc Surg 10:8–16
G. Kuhan et al.: Stent Graft for Femoropopliteal Occlusions 1027
123

20. Johnston KW (1992) Femoral and popliteal arteries: reanalysis of
results of balloon angioplasty. Radiology 183:767–771
21. Alimi YS, Hakam Z, Hartung O et al (2008) Efficacy of Viabahn
in the treatment of severe superficial femoral artery lesions:
which factors influence long-term patency? Eur J Vasc Endovasc
Surg 35:346–352
22. Hartung O, Otero A, Dubuc M et al (2005) Efficacy of Hemobahn
in the treatment of superficial femoral artery lesions in patients
with acute or critical ischemia: a comparative study with clau-
dicants. Eur J Vasc Endovasc Surg 30:300–306
23. Adam DJ, Beard JD, Cleveland T et al (2005) Bypass versus
angioplasty in severe ischaemia of the leg (BASIL): multicentre,
randomised controlled trial. Lancet 366(9501):1925–1934
1028 G. Kuhan et al.: Stent Graft for Femoropopliteal Occlusions
123

Reproducedwithpermissionofthecopyrightowner.Furtherreproductionprohibitedwithoutpermission.