Endovascular Treatment of Critical Limb Ischemia in Buerger
Disease (Thromboangiitis Obliterans) With Midterm Follow-Up:
A Viable Option When Bypass Surgery Is Not Feasible
Sadık Ahmet Uyanık, MD1, Umut Öğüşlü, MD1, Ibrahim Sani Aminu, MD2, Bırnur Yılmaz, MD1, Halime Çevik, MD1,
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Eray Atlı, MD1, Burçak Gümüş, MD1
Inter ventional Radiology · Original Research
Keywords
Buerger disease, endovascular treatment,
thromboangiitis obliterans
Submitted: Feb 25, 2020
Revision requested: Apr 4, 2020
Revision received: Apr 23, 2020
Accepted: May 8, 2020
The authors declare that they have no
disclosures relevant to the subject matter of
this article.
Uyanik et al.
Endovascular Treatment of Critical Limb Ischemia
Interventional Radiology
Original Research
Uyanik SA, Öğüşlü U, Aminu IS, et al.
doi.org/10.2214/AJR.20.23023
AJR 2021; 216:1–7
ISSN-L 0361–803X/21/2162–1
© American Roentgen Ray Society
AJR:216, February 2021 www.ajronline.org | 1
OBJECTIVE. Thromboangiitis obliterans (TAO) is an occlusive inflammatory disease
affecting small- and medium-sized vessels that causes decrease in life quality and even-
tually limb loss. The only proven treatment method is smoking cessation, but it may be
insufficient for limb salvage in patients with critical limb ischemia. In this single-cen-
ter retrospective study, the feasibility and efficiency of endovascular treatment in TAO
were evaluated.
MATERIALS AND METHODS. After approval of the local institutional review
board, 41 patients who underwent endovascular treatment of TAO between Janu-
ary 2014 and June 2019 were evaluated retrospectively. Technical success and proce-
dure-related complications were recorded. Decrease in Rutherford classification score,
relief of pain, and wound healing were evaluated to determine clinical success. Primary
patency, limb salvage rate, and amputation-free survival were also evaluated.
RESULTS. A total of 45 limbs were treated during the study period. Technical suc-
cess was achieved in 82.2% of procedures. Mean follow-up was 29.8 months. Clinical
improvement was achieved in 35 limbs. Three patients underwent major amputation
and 12 patients underwent minor amputation. Amputation-free survival and limb sal-
vage were both 93.3% at both 1 and 2 years. Reintervention was performed in 14 pa-
tients because of occlusion and clinical relapsing of the symptoms.
CONCLUSION. Endovascular treatment of TAO is feasible, has a potential to prevent
limb amputation in patients with critical limb ischemia, and has acceptable technical
success and limb salvage rates. Because there is no consensus in treatment of TAO, pro-
spective comparative studies are needed to determine the effectiveness of an endo-
vascular approach.
Thromboangiitis obliterans (TAO), or Buerger disease, is an occlusive inflammatory
vascular disease that affects predominantly small- and medium-sized vessels in the ex-
tremities, leading to loss of perfusion in the affected area and eventually resulting in am-
putation [1]. TAO is more prevalent in the younger male population, and its incidence cor-
responds with tobacco exposure. TAO is also more prevalent in Asian and Middle Eastern
countries compared with Western Europe [2].
The pathophysiologic mechanisms of TAO are still unclear; however, the disease con-
sists of an acute inflammatory phase followed by a chronic fibrotic phase. The prognosis
of the disease is dependent on the progression to the latter phase [3]. As the disease pro-
gresses, ischemic signs ranging from intermittent claudication, cyanosis, and Raynaud
phenomenon to paresthesia, rest pain, and phlebitis migrans begin to manifest [2, 4, 5].
It may eventually lead to life-limiting claudication and limb-threatening ischemia, which
are two main indications for treatment of TAO. Infrapopliteal vessels are predominantly
affected in TAO. Although femoropopliteal vessels may be included, distal crural arteries
are the most commonly affected vessels [6].
There is still no consensus over the treatment of TAO, and the only accepted effective
treatment is the cessation of smoking [1, 5, 7]. Nevertheless, for patients with critical limb
ischemia, revascularization should be considered in addition to cessation of smoking be-
cause critical limb ischemia results in decreases in productivity and quality of life [8]. Al-
though methods such as surgical bypass, lumbar sympathectomy, spinal cord stimulation,
and prostaglandin analogs have been reported in the literature, endovascular treatment
of TAO is gaining focus paralleling the advancements in endovascular ­techniques [9–13].
1
Department of Radiology, Okan University Hospital, Aydınlı Cad No 2, Okan Universitesi Hastanesi İçmeler, Tuzla,
­Istanbul, Turkey 34947. Address correspondence to S. A. Uyanik (drsadikahmetuyanik@gmail.com).
School of Medicine, Okan University, Istanbul, Turkey.
2
 Uyanik et al.

­ revious studies have reported surgical bypass as an effective

P lar treatment were included in this study. Inclusion criteria were
method for limb salvage. Unfortunately, severe multisegmental a diagnosis of TAO according to the Shionoya criteria (Appen-
below-the-knee involvement of the disease results in the lack of a dix 1) and angiographic findings compatible with TAO, Ruther-
suitable artery for anastomosis, and coexisting phlebitis may less- ford classification 4 or higher (rest pain, minor ulceration, major
en the chance for autogenous graft usage. In addition, patency of ulceration, or gangrene), and not being eligible for surgical re-
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the bypass grafts in TAO is lower than for atherosclerotic occlusive vascularization because of a lack of suitable venous conduit or
disease, which may be attributed to on-going inflammation be- distal nondiseased artery for anastomosis [23]. Exclusion crite-
cause of the nature of TAO [14–17]. Previously, endovascular treat- ria were patients with a history of allergic reaction precluding
ment of TAO has been shown to be feasible, but the data are still angiography, patients with a main presentation of claudication
being accumulated [4, 18–22]. The primary aim of this single-cen- (Rutherford class 3 or less), and patients who were candidates
ter study is to evaluate the technical and clinical outcomes of endo- for bypass surgery.
vascular treatment in TAO and contribute to the growing literature Demographic features of the patients included in the study are
supporting endovascular treatment in patients with TAO who are presented in Table 1.
not candidates for bypass surgery.
Interventional Procedure
Materials and Methods The procedures were performed under local anesthesia and
Patient Population mild to moderate sedation. An antegrade 5-French sheath was
This study was approved by the ethics committee of Okan placed in the ipsilateral common femoral artery and angiography
University Hospital, and informed consent was waived. A to- of the lower extremity was performed. After depiction of the le-
tal of 41 consecutive patients between January 2016 and June sions with angiography, IV 5000 IU heparin was administered and
2019 who had a TAO diagnosis and who underwent endovascu- 100 µg nitroglycerin was injected from the sheath if there was
no contraindication. All inflow lesions (superficial femoral artery
and popliteal artery) were targeted for recanalization as a rou-
TABLE 1: Demographic Characteristics of the tine protocol. The decision on how many tibial vessels were tar-
Patients geted for treatment was made on a case basis according to the
main clinical presentation and condition of the wound if present.
Characteristic Value The main objective was to achieve at least one additional patent
Sex runoff artery to the foot. For patients with tissue loss, the prima-
Male 39 (95.1) ry target for revascularization was the artery of the related angio-
some. If direct revascularization of the target angiosome failed,
Female 2 (4.9)
indirect vascularization was attempted by treating other runoff
Age (y) arteries. Lesions were crossed with a 4-French support catheter
Mean 41.9 (NaviCross, Terumo Medical) and 0.035-inch hydrophilic guide-
Range 28–55 wire combination. Lesions were first attempted to be crossed
with an endoluminal approach. If this approach failed, a subinti-
Diabetes 0 (0)
mal technique was used. Retrograde pedal access was also used
Coronary artery disease 4 (9.8) when both techniques from the antegrade route failed.
Chronic renal disease 0 (0) After crossing of the lesion was successful, balloon dilatation was
applied for a specific length of time (mean, 3 minutes) and under
Hypertension 5 (12.2)
high pressure (18–24 atm). Primary stenting was avoided because
Hyperlipidemia 0 (0) of the underlying inflammatory nature of the disease and was re-
Smoking history (y) served for bail-out procedures. After angioplasty, if the control an-
Mean 20.9 giography showed straight inflow of the target arteries without
more than 50% residual stenosis or flow-limiting dissection, the
Range 10–31
procedure was terminated. A sample case is presented in Figure 1.
Current smoker 12 (29.3)
Previous endovascular intervention 7 (17.0) Follow-Up
Previous amputation After the procedure, patients received daily dual antiplatelet
therapy (acetylsalicylic acid and clopidogrel) during follow-up for 6
Major 0 (0)
months. Lifelong single antiplatelet therapy with acetylsalicylic acid
Minor 4 (9.7) was continued daily after 6 months. Control follow-up visits were
Rutherford classification scheduled at the first week, first month, and every 6-month inter-
vals after the procedure. At their follow-up visits, patients were eval-
4 21 (46.7)
uated with Doppler ultrasound, and clinical symptoms and condi-
5 13 (28.9) tion of the wound (if present) were also assessed. Wound care was
6 11 (24.4) performed by a wound care specialist. Aggressive antibiotic thera-
Note—Unless otherwise indicated, values are reported as number (%). Total py administered in infected wounds and extensive débridement of
number of patients was 41; total number of limbs was 45. necrotic tissues were done after endovascular therapy.

2 AJR:216, February 2021

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A B C

D E F

G H I
Fig. 1—35-year-old man with ischemic rest pain.
A–C, Diagnostic angiography shows long segmental occlusions of superficial femoral artery (A) and crural arteries (B and C).
D–F, After crossing lesions, balloon angioplasty was performed on superficial femoral artery (D), peroneal artery (E), and posterior tibial artery (F).
G–I, Control angiography shows recanalization of superficial femoral artery (G), peroneal artery (H), and posterior tibial artery (I).

Outcomes defined as wound healing, relief of pain, and decrease in Ruther-

Primary outcomes of this study were technical success, clini- ford classification of at least 1 point. Limb salvage was defined as
cal success, limb salvage, and amputation-free survival. Technical the time from the procedure to time of major amputation. Ampu-
success was defined as achieving direct inflow in the target vessel tation-free survival was defined as the time from the procedure
without residual stenosis greater than 30%. Clinical success was to the time of death or major amputation. Major amputation was

AJR:216, February 2021 3

 Uyanik et al.

glycerin injection. Another three patients did not respond to in-

TABLE 2: Procedural Details
traarterial vasodilators, which resulted in failure of the procedure.
Procedure Detail No. of Procedures One patient with vessel perforation and one patient with arte-
riovenous fistulation were treated with prolonged balloon dila-
Treated artery
tion and were relieved without any further therapy. There were
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SFA 10 no thrombosis or embolic complications. Procedural details are

Popliteal artery 17
ATA 30
PTA 32
Peroneal artery 11
Plantar artery 21
Total 121
Technical success 37/45 (82.2)
Transpedal access 9/45 (20.0)
Complication
Vasospasm 6 (13.3)
Perforation 1 (2.2)
Arteriovenous fistula 1 (2.2)
Note—Total number of patients was 41; total number of limbs involved was 45.
SFA = superficial femoral artery, ATA = anterior tibial artery, PTA = posterior
tibial artery.
defined as amputation above the ankle level, and minor amputa-
tion was defined as amputation below the ankle level.
Complications are classified according to descriptions of the So-
ciety of Interventional Radiology Clinical Practice Guidelines [24].
Statistical Analysis
Descriptive statistics were evaluated as mean, SD, median, fre-
quency, percentage, minimum, and maximum. The difference of
Rutherford scores before and after the procedure were evaluated
with Wilcoxon test. A p value less than 0.05 was considered sta-
tistically significant. Limb salvage, amputation-free survival, and
patency rates were evaluated with Kaplan-Meier analysis.
Results
A total of 45 limbs were treated in 41 patients. Target vessels
for angioplasty were superficial femoral artery in 10 limbs, popli-
teal artery in 17, anterior tibial artery in 30, posterior tibial artery
in 32, peroneal artery in 11, and plantar artery in 21. For each pa-
tient, the mean number of treated runoff arteries was 1.6 ± 0.49
(SD) (range, 1–2 arteries). Retrograde pedal access was used in
nine cases because of failure of lesion crossing via the antegrade
path. Technical success was achieved in 37 of 45 procedures
(82.2%). The reasons for technical failure were inability of reentry
to true lumen in five cases and insufficient response to balloon
angioplasty in three cases, which were assumed to be because of
vasospasm. Before treatment, 13 limbs had no runoff artery and
32 limbs had one runoff artery. After treatment, one limb ended
with no runoff artery, 10 limbs ended with one runoff artery, 29
limbs ended with two runoff arteries, and five limbs ended with
three runoff arteries.
There were no major procedural complications. Eight minor
complications were reported. In six of the procedures there was
vasospasm, three of which were treated with intraarterial nitro-
summarized in Table 2.
Mean follow-up of the patients was 29.8 months (range, 8–61
months). The median Rutherford score before treatment was 5
(range, 4–6) and 3 after treatment (range, 2–6). Changes in Ruth-
erford scores were statistically significant (p < 0.001). Clinical im-
provement was reported in 35 limbs. Wound healing was report-
ed in 19 limbs and pain relief was reported in 33 limbs. There was
no change in rest pain in two patients although endovascular
treatment was successful.
Primary patency was 64.2% at 1 year and 60.0% at 2 years. Four-
teen patients underwent reintervention during the follow-up pe-
riod because of relapsing of the symptoms and occlusion of the
treated vessels. After reintervention, patency was achieved in all
of the patients and secondary patency was 88.6% at 1 year and
80.9% at 2 years.
During the follow-up, three patients with technical failure un-
derwent major amputation. Twelve of the patients underwent
minor amputation because of established necrosis of the toes.
There were no mortalities. Amputation-free survival and limb sal-
vage rates were 93.3% at 1 year and 2 years. Kaplan-Meier curves
of amputation-free survival, limb salvage, primary patency, and
secondary patency are presented in Figure 2.
Discussion
TAO is a disabling peripheral artery disease with poor progno-
sis and high risk of amputation [25]. The underlying pathologic
mechanism is still not understood, and thus there is no consensus
on the most effective treatment method. The only proven effec-
tive treatment is cessation of tobacco use [1, 5, 7]. Nevertheless, in
patients with critical limb ischemia, cessation of smoking only is
not enough to avoid limb loss, and further intervention is needed
for better outcomes [8].
Treatment of TAO is challenging. Various additional treatment
methods have been used. Pharmacologic treatment with prosta-
cyclin and prostaglandin analogs has been reported to improve
pain and ulcer healing in previous studies, but these studies did
not report long-term outcomes such as limb salvage and ampu-
tation-free survival, and data are still lacking to support their rou-
tine usage [9, 10, 13]. Lumbar sympathectomy and spinal cord
stimulation have been used to decrease high sympathetic activ-
ity causing vasospasm in TAO. Sympathectomy improves blood
flow by decreasing peripheral resistance of the regional blood
vessels; however, this method of treatment is beneficial only in
the short term (approximately 6 months) before symptoms re-
turn and sexual and autonomic dysfunction are reported [26, 27].
Although spinal cord stimulation has promising results, it has not
been not studied in randomized controlled studies [11, 12]. A re-
cent study of endovascular sympathectomy with radiofrequency
ablation showed clinical improvement in TAO without sexual and
autonomic dysfunction [28].
In this study, we presented our single-center experience of en-
dovascular treatment in TAO. Our midterm results showed that

4 AJR:216, February 2021

 E n d o v a s c u l a r Tr e a t m e n t o f C r i t i c a l L i m b I s c h e m i a

1.0 1.0
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0.8 0.8
Amputation-Free Survival

0.6 0.6

Limb Salvage
0.4 0.4

0.2 0.2

Survival function Survival function

0 Censored 0 Censored

0 500 1000 1500 2000 0 500 1000 1500 2000

Time Since Treatment (d) Time Since Treatment (d)

A B

1.0 1.0

0.8 0.8
Secondary Patency
Primary Patency

0.6 0.6

0.4 0.4

0.2 0.2

Survival function Survival function

0 Censored 0 Censored

0 500 1000 1500 2000 0 500 1000 1500 2000

Time Since Treatment (d) Time Since Treatment (d)

C D
Fig. 2—Kaplan-Meier curves for patients with thromboangiitis obliterans.
A–D, Graphs show Kaplan-Meier curves demonstrating amputation-free survival (A), limb salvage (B), primary patency (C), and secondary patency (D).

endovascular treatment of TAO is feasible, and in patients with
critical limb ischemia it has a potential to lower amputation rates
when used in addition to smoking cessation. Smoking cessation
is key to the long-term treatment of TAO. In our clinic, patients are
instructed to quit smoking or any form of tobacco use at least 1
month before any endovascular procedure. We believe that this
adequately prevents inflammatory reactions in the blood vessels.
Endovascular treatment of TAO presents several challenges.
First, there is an increased tendency of vasospasm during catheter
and guidewire manipulation. For that reason, if there were no con-
traindications, we administered nitroglycerin before starting the
procedure and used hydrophilic 0.035-inch guidewires initially in
lesion crossing if possible, and then 0.018-inch guidewires in the
distal crural segment. Dedicated total occlusion guidewires cause
severe vasospasm in this group of patients and should be avoid-
ed during the crossing of the lesions. Second, because of the ad-
vanced involvement of distal runoff arteries, lesion crossing and
reentry into the true lumen at the distal level (which is crucial for a
successful procedure) is difficult. Although technically successful
lesion crossing and reentry may be achieved, response to balloon

AJR:216, February 2021 5

 Uyanik et al.
angioplasty may be inadequate. Prolonged balloon inflation and
incremental increase in pressure and balloon size may overcome
this adversity, but in some cases all efforts may be fruitless. Last,
depending on the pathologic mechanism of TAO, there may be
an increased risk of acute thrombosis and embolic events during
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endovascular therapy and thrombolytic treatment, which may in-
crease morbidity, mortality, and hospital stay.
Few studies have investigated the efficiency of endovascular
treatment of TAO. Graziani et al. [19] first reported a case series
of 17 patients in 2012, and they achieved a technical success of
95% and a limb salvage rate of 100% with no complications. The
authors proposed that endovascular treatment is a feasible, safe,
and effective treatment method in TAO. Another study by Moda-
ghegh and Hafezi [22] reported a technical success rate and limb
salvage rate of 92% in 13 patients. Kawarada et al. [21] treated 20
lower limbs and five upper limbs endovascularly in 20 patients
with TAO. They also investigated intravascular ultrasound find-
ings in these patients and found some typical findings correlat-
ing the underlying pathologic changes in the vessel wall. Similar
to other studies, they achieved a limb salvage rate of 100% with
high technical success (96%). They reported an acute thrombosis
in one patient that was treated endovascularly with administra-
tion of thrombolytics. There were 12 reocclusions in their series
and seven required reintervention. In the largest case series of 44
patients by Kim et al. [3], technical success was reported in 80%,
and the limb salvage rate was reported to be 86.7% at 5 years.
Fifteen patients needed reintervention during follow-up, and re-
intervention and amputation-free survival was 62.7% at 5 years.
In the present study, we achieved an 82.2% technical success
rate, which is lower than most of the previous reports. In three
cases there was evident vasospasm that did not respond to va-
sodilators, and in five cases an inability to reenter true lumen at
the plantar artery was the cause of technical failure. We believe
our lower technical success rate may be a result of extensive in-
volvement of the plantar artery in the patient population. The
limb salvage rate in our study was 93.3% and compatible with the
mentioned reports. Firat and Igus [18] reported a case series of 28
patients who underwent 40 procedures, and they achieved a limb
salvage rate of 96.8% at 2 years. They also reported primary pa-
tency rates of 84%, 78%, and 75% at 1, 2, and 3 years, respectively.
In eight patients in whom antegrade lesion crossing failed, retro-
grade transpedal access was used and they showed that a com-
bined antegrade and retrograde approach is feasible in techni-
cally challenging cases of TAO. Similarly, Kaçmaz et al. [20] used a
retrograde crossing technique in two cases in their study. We used
retrograde access in nine patients in whom antegrade crossing of
the occlusion failed, and we achieved success in all of them. Retro-
grade access is promising in suitable patients, but it is not always
possible because of occlusion of the classic pedal access sites at
ankle level. Puncture of the occluded vessels may be an option in
TAO, and we used the technique in one of our patients. Previous
studies reported reintervention rates between 25–35% because
of reocclusion [3, 18, 19, 21, 22]. There was a need for reinterven-
tion in 14 patients in the present study and they were all treated
successfully with an endovascular approach similar to the previ-
ous reports. Repeatability of endovascular treatment may be ac-
cepted as superior to surgery because surgery has a potential to
6 AJR:216, February 2021
compromise future endovascular treatment of the effected vessel,
and revision of the surgery has higher morbidity.
The only prospective study that has reported on endovascular
treatment of TAO was by Ghoneim et al. [28]. In that study, the au-
thors reported the outcomes of 39 patients; 15 were managed en-
dovascularly, 15 were treated medically, five were treated surgical-
ly, and four were treated by sympathectomy. They reported lower
technical success and patency rates than previous studies and
comparable limb salvage rates. There was no comparison between
the treatment groups, and the study was lacking randomization.
Surgical revascularization has reported acceptable limb sal-
vage rates between 91.4% and 95% [14–16, 29–31]. The most lim-
iting issues with surgical revascularization are the absence of a
suitable venous conduit and a patent distal runoff artery for anas-
tomosis. Unfortunately, most patients with TAO lack these two
conditions because of extensive runoff artery disease and coex-
isting phlebitis migrans [16]. In addition, the patency of bypass
conduits is lower in TAO than atherosclerotic disease, resulting
in a need for early reintervention and morbidity. Although the
reported patency rates were longer than for endovascular ther-
apy, surgical revascularization carries more complication rates
than endovascular therapy and requires surgical reintervention
because early failure increases the morbidity of patients. For this
reason, in addition to the feasibility of surgical intervention in pa-
tients, it is still debatable whether endovascular treatment or sur-
gical treatment is the most suitable option for revascularization
in patients with TAO. Two studies compare results of endovascu-
lar treatment and surgery in the literature. Lee et al. [4] compared
33 consecutive cases with critical limb ischemia (22 endovascular
procedures vs 11 inframalleolar bypass surgeries). Limb salvage
rates and patency rates were both similar between the groups.
The other study by Ye et al. [32] again compared endovascu-
lar treatment and bypass surgery results and showed that both
limb-salvage rate and major reintervention rates were similar in
both groups. In both studies, primary patency was significantly
longer and ulcer healing was faster in the surgery group than en-
dovascular treatment group. However, these results must be in-
terpreted carefully because patients in the surgery group were
also candidates for endovascular treatment, but patients in the
endovascular group were not candidates for surgery. This reflects
that the baseline involvement of the endovascular group was
more advanced so the comparison is of two unmatched groups.
There are some limitations in this study. First is the retrospective
design of the study with a limited number of patients. This case se-
ries study lacks a control group so there is no comparison of endo-
vascular treatment with medical therapy or other interventions. In
addition, an approach with the combination of other therapies to
endovascular recanalization may achieve better outcomes.
Conclusion
Endovascular treatment of TAO is a feasible and viable option
for patients with critical limb ischemia who are not candidates
for bypass surgery with acceptable limb salvage rates and clinical
improvement of symptoms. There is still a lack of data comparing
endovascular therapy with other treatment methods, and pro-
spective randomized studies are needed to determine the clin-
ical benefits of endovascular therapy.
 E n d o v a s c u l a r Tr e a t m e n t o f C r i t i c a l L i m b I s c h e m i a
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APPENDIX 1: Shionoya Criteria
• Smoking history
• Onset before the age of 50 years
• Infrapopliteal occlusions
• Upper extremity involvement or phlebitis migrans
• Absence of atherosclerotic risk factors other than smoking
AJR:216, February 2021 7
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