Eur J Vasc Endovasc Surg (2017) 54, 464e471

Long-term Outcome of Endovascular Treatment for Mycotic Aortic

Aneurysm
C.-M. Luo a, C.-Y. Chan b, Y.-S. Chen b, S.-S. Wang b,c,d
, N.-H. Chi b,c
, I.-H. Wu b,c,*

a
Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan
b
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
c
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
d
Department of Surgery, Fu Jen Catholic University Hospital, and Fu Jen Catholic University College of Medicine, New Taipei City, Taiwan

WHAT THIS PAPER ADDS

Endovascular repair (EVAR) has been described a safe and viable alternative for high risk patients presenting
with mycotic aortic aneurysm (MAA). The present analysis of 40 consecutive cases not only demonstrates the
feasibility of EVAR for MAA, but also shows a considerable proportion of persistent infection despite prolonged
antibiotic treatment. Both positive blood cultures before and persistent infection after EVAR seemed closely
associated with a poor prognosis as a result of fatal infectious complications when further surgical treatment
was not performed. This suggests that infections should be treated with antibiotics as comprehensively as
possible before endovascular repair.

Objective/Background: Endovascular repair (EVAR) of mycotic aortic aneurysm (MAA) has become an alternative
treatment for high risk patients. The aim of this study was to evaluate long-term survival and outcomes.
Methods: Retrospective analysis of 40 consecutive patients with MAAs undergoing EVAR and subsequent
intravenous antibiotic treatment between September 2009 and April 2015. Follow-up was truncated on 30 April
2015. Uni- and multivariate logistic regression were used to assess risk factors of adverse outcomes. Cumulative
survival was calculated using the KaplaneMeier method.
Results: Median age at repair was 73 years (range 48e88 years) and 31 (77%) were men. Eleven (27%) patients
were infected with Salmonella, 12 (30%) with non-Salmonella species, and 17 (42%) had negative cultures.
Anatomical locations included the aortic arch/thoracic area in 10 (25%), the paravisceral area in seven (17%), and
the infrarenal area in 23 (57%). Ten (25%) patients presented with aneurysm rupture and underwent emergency
repair. Median follow-up was 25 months (range 1e69 months). Cumulative 1 and 5 year survival rates were 71%
and 53%, respectively. Persistent or recurrent infection occurred in 20% (n ¼ 8). Patients with persistent infection
were treated with long-term medical therapy, but all died (75%; n ¼ 6) within 6 months of repair. No survival
difference was found between patients with or without Salmonella infections. However, there was a trend
toward better survival in culture negative patients.
Conclusion: EVAR of MAA is an acceptable alternative treatment of MAA. However, persistent infection after
endovascular treatment does occur and is often fatal without surgical treatment.
Ó 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
Article history: Received 6 March 2017, Accepted 9 July 2017, Available online 18 August 2017
Keywords: Abdominal aortic aneurysm, Chimney graft/technique, Emergency procedure, Endovascular aneurysm
repair, Mycotic aneurysm, Thoracic aortic aneurysm

INTRODUCTION persistent infection and subsequent aneurysm rupture.4

Mycotic aortic aneurysm (MAA) is an uncommon but
potentially lethal disease. The incidence is estimated to be
0.65e2% of all aortic aneurysms and is reportedly higher in
East Asia.1e5 With medical treatment only, the reported
hospital mortality ranges from 36% to 82% because of
* Corresponding author. Department of Surgery, Cardiovascular Division,
National Taiwan University Hospital, No. 7, Chung-Shan S. Road, Taipei,
Taiwan.
E-mail address: aaronihuiwu@gmail.com (I.-H. Wu).
1078-5884/Ó 2017 European Society for Vascular Surgery. Published by
Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ejvs.2017.07.004
Early diagnosis, appropriate surgical intervention, and
potent antibiotic therapy are essential for survival.6e8
Over the last decade, endovascular repair (EVAR) of
thoracic and abdominal aortic aneurysms has become
widely accepted. However, reports on MAA repair have
been controversial.8e10 Compared with open repair, the
unresected infected aneurysm sac and surrounding tissue,
which may cause persistent sepsis and late prosthetic graft
infection, are the major concerns after EVAR. However,
EVAR rapidly stops aneurysm expansion and prevents the
rupture without a large incision and significant
Long-term Outcome of Endovascular Treatment
haemodynamic instability, which is the primary risk factor
for mortality in open repair.5,11
In the last several years, EVAR has been the preferred
treatment at the authors’ institution for high risk patients
with MAA. In this study, its efficacy and durability was
assessed by evaluating the long-term outcome, the inci-
dence of and risk factors for persistent infection, the
causative microorganism related mortality, and anatomical
location related mortality after endovascular treatment of
MAA.
MATERIALS AND METHODS
Patients with MAA who underwent EVAR at the authors’
institution from September 2009 to April 2015 were
retrospectively reviewed. Clinical details, including age, sex,
clinical presentations, aneurysm location, culture results,
treatment, surgical complications, persistent infection, and
mortality were collected for analysis. Patients were fol-
lowed until 30 April 2015. Completeness of follow-up was
measured and follow-up information was truncated on 30
April 2015. High risk patients were defined as American
Society of Anesthesiologists grade > III. The diagnosis of
MAA was established based on a combination of factors: (i)
clinical evidence of infection (fever, elevated C-reactive
protein, leukocytosis, or positive cultures); (ii) radiological
and aneurysm findings [rapid aneurysm expansion, saccular,
multi-lobular or eccentric aneurysms shape, peri-aortic gas,
Figure 1. (A) Saccular proximal thoracic aortic aneurysms (arrow) with haematoma were noted on both axial and coronal computed
tomography (CT). (B) A perigraft air-fluid abscess in the axial CT (solid arrow) and positive gallium scan (dotted arrow) after previous
endovascular repair.
465
and peri-aortic soft tissue mass on computed tomography
(CT)] (Fig. 1A). Late endograft infection (LEGI) was defined
as either peri-graft fluid or abscess associated with positive
blood cultures (Fig. 1B). Persistent infection was defined as
a recurrent bloodstream infection, LEGI, or an aorto-enteric
fistula (AEF).2,8,12,13
Ethical statement
The study was approved by the institutional review board of
National Taiwan University Hospital. Medical records and
patient information were anonymised and de-identified
prior to analysis.
Pre-operative management
Intravenous (IV) broad spectrum antibiotics were adminis-
tered empirically, and the infectious disease specialist was
consulted after the diagnosis of MAA was confirmed. A
specific antibiotic was determined after blood culture and
sensitivity reports were available. Salmonella species
infection was treated with IV ceftriaxone, 1000e2000 g
every 12 h. Non-Salmonella infection was treated with
antibiotic therapy based on the culture results and sensi-
tivity testing. If the patients had a good response to anti-
biotic treatment with declining leukocytosis and fever, the
endovascular intervention was postponed until the
completion of antibiotic treatment with infection control
466 C.-M. Luo et al.

for four weeks. If the patients had an uncontrolled infection Table 1. Demographic, clinical, laboratory, and treatment
with persistent fever, positive blood culture, septic shock, or characteristics.
evidence of impending aortic rupture such as haemody- Demographic and clinical N (%) Missing (%)
namic instability, persistent pain, or any progression of characteristics
rupture signs on an imaging study, urgent EVAR was per- Mean (range) age (y) 73 (48e88) 0 (0)
formed before the 4 week antibiotic treatment was Sex (M/F) 31/9 0 (0)
completed. Hypertension 17 (42) 2 (5)
Diabetes mellitus 14 (35) 1 (2)
CKD (creatinine: 12 (30) 0 (0)
Surgical technique > 2.0 mg/dL)
In patients with thoracic MAAs, thoracic endovascular aortic Cancer 6 (15) 0 (0)
repair (TEVAR) was performed to cover the MAA with or Ischaemic heart disease 5 (12) 0 (0)
without adjunctive procedures such as chimney or Cerebrovascular disease 5 (12) 0 (0)
Smoking 5 (12) 2 (5)
debranching techniques for an inadequate proximal landing
COPD 3 (7) 1 (2)
zone. The left subclavian artery was preserved in all patients Dyslipidaemia 2 (5) 1 (2)
undergoing TEVAR. Cerebrospinal fluid (CSF) drainage was CHF 2 (5) 1 (2)
suggested in patients with anticipated long thoracic Arrhythmia 1 (2) 3 (7)
segment coverage. In patients with an abdominal MAA, PAD 1 (2) 2 (5)
abdominal EVAR was performed to cover the MAA. If the Pre-operative manifestations
MAA was located near the visceral segment of the Elevated CRP (> 1 mg/dL) 31 (77) 0 (0)
abdominal aorta, hybrid or chimney repairs were per- or WBC (> 10,000 k/mL)
formed. Surgical complications were recorded according to Abdominal or chest pain 25 (62) 0 (0)
the Reporting Standards of Endovascular Aortic Repair.14 Fever 23 (57) 0 (0)
Antibiotics treatment 23 (57) 0 (0)
> 4 weeks
Post-operative management Ischaemic bowel 5 (12) 0 (0)
In hospital intravenous antibiotics were administered for 6 Haemodynamic shock 5 (12) 0 (0)
weeks after EVAR for all patients. The specific antibiotic Haemoptysis 4 (10) 1 (2)
was determined according to the available culture and Consciousness disturbance 3 (7) 0(0)
GI bleeding 1 (2) 0 (0)
sensitivity reports. In patients with negative culture, an
CVA 1 (2) 0 (0)
empirical broad spectrum IV antibiotic was chosen. Anti-
Surgical complications 9 (22)
biotic therapy was then shifted to the oral form after CVA 3 (8) 0 (0)
discharge, and the surgeon determined the duration of Acute renal insufficiency 3 (8) 0 (0)
antibiotic treatment. Follow-up CT imaging studies were Access site haematoma 1 (2) 0 (0)
performed at 1, 6, and 12 months, and yearly thereafter. Lower limb ischaemia 1 (2) 0 (0)
Patients with peri-aortic abscess also underwent CT guided Bowel ischaemia 1 (2) 0 (0)
drainage if indicated. Spinal cord ischaemia 1 (2) 0 (0)
Acute endograft thrombosis 1 (2) 0 (0)
Causative pathogens
Statistical analysis
Salmonella species 11 (27) 0 (0)
For risk factor analysis, the microbiological cultures were Non-Salmonella species 12 (30) 0 (0)
categorized into three groups: culture negative, Salmonella Culture negative 17 (42) 0 (0)
positive, and non-Salmonella positive cultures. Uni- and Aneurysm characteristics
multivariate Cox regression risk factor analyses were per- Aneurysm location
formed to identify the risk factors for all-cause mortality. A Aortic arch 1 (2) 0 (0)
p value < .05 was considered significant. Cumulative sur- Descending 9 (22) 0 (0)
Para-visceral 7 (17) 0 (0)
vival was calculated using the KaplaneMeier method.
Infrarenal 23 (57) 0 (0)
Follow-up was truncated on 30 April 2015 and patients at Ruptured aneurysm 10 (25) 0 (0)
risk were censored on that date. Completeness of follow-up Operative characteristics
was measured using the follow-up index (FUI). All missing Simple EVAR 21 (52) 0 (0)
data were excluded from the analyses. Only risk factors that Simple TEVAR 9 (22) 0 (0)
tested significantly (p < .05) by the univariate analysis were EVAR with adjunctive 3 (7) 0 (0)
included in the multivariate model. All statistical analyses procedure
were performed using SAS System Version 9.2 (SAS Institute TEVAR with adjunctive 7 (17) 0 (0)
Inc., Cary, NC, USA). 2procedure
Persistent infection 8 (20)
Bloodstream infection 4 (10) 0 (0)
RESULTS
Late endograft infection 4 (10) 0 (0)
Between September 2009 and April 2015, 56 patients un-
derwent MAA repair: four were conservatively treated, 12
Long-term Outcome of Endovascular Treatment
Table 1-continued
Demographic and clinical N (%) Missing (%)
characteristics
Post-operative endoleak 3 (7)
Type Ib 1 (2) 0 (0)
Type II 2 (5) 0 (0)
Note. Data are n (%) unless otherwise indicated. M ¼ male;
F ¼ female; CKD ¼ chronic kidney disease; COPD ¼ chronic
obstructive pulmonary disease; CHF ¼ congestive heart failure;
PAD ¼ peripheral arterial disease; CRP ¼ C-reactive protein;
WBC ¼ white blood cells; GI ¼ gastrointestinal;
CVA ¼ cerebrovascular accident; EVAR ¼ endovascular aortic
repair; TEVAR ¼ thoracic endovascular aortic repair.
were treated by open repair, and 40 by EVAR. Table 1 lists
the demographic, clinical, laboratory, and treatment char-
acteristics of all patients. The median age was 73 years
(range 48e88 years). Thirty-one (77%) patients were men.
Salmonella and non-Salmonella species were found in 11
(27%) and 12 patients (30%), respectively. The locations of
the MAAs were: 10 (25%) in the thoracic aorta, seven (17%)
in the para-visceral aorta, and 23 (57%) in the infrarenal
aorta. Ten patients (25%) underwent emergency surgery for
ruptured MAA. Fever and pain were among the most
frequent presenting symptoms. All patients started IV an-
tibiotics before surgery.
Simple EVAR and TEVAR were performed in 21 (52%)
patients and nine (22%) patients, respectively. Associated
procedures to preserve branch vessels for inadequate
proximal landing zones were required in the remaining ten
patients. Only one patient required CSF drainage, and no
CSF infectious complication occurred. Nine patients (22%)
developed surgical complications. Endoleaks were noted in
three (7%) patients. Type II endoleaks resolved without
Figure 2. Actuarial KaplaneMeier overall long-term survival curve. Note. CI ¼ confidence interval.
467
treatment by the 1 month follow-up CT scan in two pa-
tients. The other patient with a type Ib endoleak was
treated conservatively owing to multiple comorbidities and
died as a result of severe sepsis 1 month after the
procedure.
By 30 April 2015, follow-up regarding survival status was
complete (FUI 1.0  0). The minimum follow-up was 1
month (MarcheApril 2015) and maximum 69 months
(September 2009eApril 2015) with a median of 25 months.
The 1 month, 6 month, 1 year, and 5 year freedom from all-
cause mortality was 90%, 82%, 71% and 53%, respectively
(Fig. 2). Eight patients (20%) developed persistent infections
during the follow-up. Pre-operative Salmonella and non-
Salmonella infections were noted in three and two patients,
respectively, and the remaining three patients were culture
negative. Fulminating bloodstream infections were diag-
nosed in four patients (10%) at a mean of 1 month post-
operatively. The other four patients (10%) developed LEGI,
and one of them (2%) experienced aortic rupture with an
AEF after 57 months follow-up. All patients but one were on
oral antibiotics after EVAR. They were treated with intra-
venous antibiotics only, without endograft explantation,
owing to multiple comorbidities, and all died of multiple
organ failure related to severe sepsis. Compared with pa-
tients with persistent infection, patients without persistent
infection had significantly better survival at the 4 year
follow-up evaluation (84%) (Fig. 3).
In the univariate analysis, all-cause mortality was signif-
icantly associated with chronic kidney disease (CKD), cancer,
ischaemic bowel, peri-operative surgical complications,
persistent infection, bloodstream infection, and LEGI.
Elevation of inflammatory markers, fever, locations of
MAAs, complete pre-operative antibiotic treatment for 4
468
Figure 3. Actuarial KaplaneMeier long-term survival curve in patients with or without persistent infection.
weeks, causative bacteria, and emergency repair were not
significantly related to long-term outcome (Table 2). How-
ever, in the multivariate Cox regression analysis, only CKD
(hazard ratio [HR] 3.561, 95% confidence interval [CI]
1.175e10.792; p ¼ .025) and surgical complications (HR
4.127, 95% CI 1.362e12.501; p ¼ .012) (Table 3) were
associated with all-cause mortality. In patients with persis-
tent infection or LEGI, only surgical complications were
found to be significantly associated with mortality in the
univariate analysis (Table 2). In the subgroup analysis, there
was a trend towards better 4 year survival of patients with
negative blood culture (81%), followed by patients with
non-Salmonella (72%) and with Salmonella (63%) infection
(Fig. 4).
DISCUSSION
MAAs are rare, and management remains challenging.2
Open surgical repair has been the widely accepted gold
standard treatment. This approach carries a significant in
hospital mortality risk of up to 20e40% and a 5 year sur-
vival rate of 35e50%.1,2,5,15e23 The goal of EVAR of MAAs is
to prevent haemodynamic compromise by sealing the aortic
leakage first, and then to eradicate the infection with spe-
cific antibiotics and CT guided percutaneous drainage or
minimal surgical debridement. In the last few years, EVAR
has been the authors’ preferred choice of treatment in high
risk patients with MAAs. Compared with open surgical
repair, EVAR has comparable outcomes with 30 day and 5
year survival rates of 90% and 53%, respectively, at the
authors’ institution.
In this study, CKD and peri-operative complications were
significant in the multivariate regression analysis. It is
C.-M. Luo et al.
believed that the relatively immunocompromised status of
the patients with CKD and the negative haemodynamic
effects of surgical complications were critically associated
with the long-term outcome. The avoidance of a large
incision, aortic cross-clamping, cardiopulmonary bypass,
and massive blood transfusion in endovascular treatment
might protect these patients from further definitive
treatment by simplifying the procedure and quickly
restoring haemodynamic stability, especially in patients
presenting with suprarenal locations or aneurysm
rupture.3,5,22e24
Persistent infection has always been the primary concern
in endovascular treatment.1,2 Whether infection can be
controlled with IV antibiotics alone when the endopros-
thesis is implanted in infected tissue is controversial. In the
present study, the incidence of persistent infection was 20%
(n ¼ 8/40), which was similar to that of open repair.1,13 LEGI
occurred in half of these patients (n ¼ 4). An increased risk
of persistent infection in patients undergoing emergency
endograft implantation with signs of active infection or in
those without prolonged pre-operative antibiotic usage was
not observed. Preventing persistent infection and aneurysm
rupture is the key to successful endovascular treatment of
MAAs.24 It was also hypothesized that the early exclusion of
an infected aneurysm sac from the bloodstream followed by
prolonged post-operative antibiotic therapy could prevent
complications such as massive bleeding and persistent in-
flammatory processes. Once the endoprosthesis seals the
blood leakage from the aorta and prevents the turbulent
flow in the aneurysm sac, the antibiotic can slowly
permeate through the graft into the surrounding tissue,
eradicating the infection.6
Long-term Outcome of Endovascular Treatment 469

Table 2. Univariate Cox-regression analysis of long-term mortality and persistent infection.

Long-term mortality Persistent infection
HR (95% CI) p HR (95% CI) p
Demographic and clinical characteristics
Age 1.013 (0.951e1.080) .6829 0.983 (0.906e1.066) .6823
Sex (male vs. female) 1.050 (0.287e3.842) .9416 0.840 (0.138e5.115) .85
Hypertension 1.764 (0.590e5.275) .3095 1.462 (0.309e6.921) .6324
Diabetes mellitus 0.505 (0.139e1.839) .3005 0.556 (0.096e3.207) .5111
Ischaemic heart disease 0.404 (0.052e3.137) .3865 NA NA
Dyslipidaemia 1.871 (0.239e14.675) .551 NA NA
CKD (creatinine > 2.0 mg/dL) 3.405 (1.132e10.246) .0293 1.534 (0.302e7.792) .6062
Smoking 3.478 (0.918e13.184) .0667 NA
Arrhythmia NA NA NA NA
CHF NA NA NA NA
COPD NA NA NA NA
Cancer 3.734 (1.085e12.849) .0366 0.771 (0.077e7.713) .8252
Pre-operative manifestations
Fever 1.791 (0.551e5.821) .3326 2.647 (0.463e15.148) .2741
Elevated CRP (> 1 mg/dL) or 1.017 (0.279e3.706) .9799 2.333 (0.248e21.980) .4591
WBC (> 10,000 k/mL)
Haemodynamic shock 1.842 (0.398e8.530) .4349 3.222 (0.439e23.654) .25
Consciousness disturbance NA NA 2.143 (0.169e27.103) .5561
GI bleeding NA NA NA NA
Haemoptysis NA NA 1.381 (0.124e15.361) .7927
CVA NA NA NA NA
Ischaemic bowel 18.997 (1.722e209.514) .0162 NA .9798
Emergency repair 1.600 (0.490e5.233) .4365 4.333 (0.836e22.469) .0808
Aneurysm location 1. 699 (0. 520e5.555) . 3806 NA NA
(abdominal vs. thoracic)
Antibiotic treatment 0.535 (0.118e2.413) .4156 NA NA
(> 4 wk vs.  4 wk)
Surgical complications 3.931 (1.309e11.808) .0147 11.664 (1.979e68.733) .0066
Persistent infection 9.220 (1.764e48.188) .0085 NA NA
Bloodstream infection 12.176 (3.869e38.321) < .0001 NA NA
Late endograft infection 3.991 (1.201e13.257) .0239 NA NA
Causative pathogens
Non-Salmonella vs. Salmonella species 0.737 (0.146e3.727) .7117 0.533 (0.071e4.006) .5412
Culture negative vs. Salmonella species 1.521 (0.392e5.900) .5445 0.571 (0.093e3.530) .5469
Note. HR ¼ hazard ratio; CI ¼ confidence interval; NA ¼ not available; CKD ¼ chronic kidney disease; CHF ¼ congestive heart failure;
COPD ¼ chronic obstructive pulmonary disease; CRP ¼ C-reactive protein; WBC ¼ white blood cells; GI ¼ gastrointestinal;
CVA ¼ cerebrovascular accident.
In this study, it was noted that without further definitive first year,2,6 or the first 6 months, as in the present study.
surgical intervention, all patients with persistent infection However, once re-infection occurred, endoprosthesis
died and 75% died within 6 months of EVAR. Similar to a explantation was essential for the best chance of survival.9
report from a European multicentre study,2 most fatal late Most investigators report that non-Salmonella infection is
complications occurred during the first post-operative year, a significant risk factor for operative mortality,2,12,24
and this poor outcome was primarily found in patients that whereas culture negative infection is associated with bet-
did not have further definitive surgical intervention. Pro- ter survival. Although the 1 year survival rate did not differ
longed post-operative parenteral antibiotics for 4e6 weeks, between the groups in this study, patients in the culture
followed by 6e12 months, or possibly lifelong, oral antibi- negative group had the best long-term survival in the cur-
otics was mandatory to prevent persistent infection since rent study. The main cause of poorer survival in the other
most infection related complications occurred within the two groups was probably due to the development of
persistent infection. This observation might also indicate the
Table 3. Multivariate logistic regression analysis of long-term necessity for lifelong oral antibiotics in patients with posi-
mortality. tive blood cultures.
HR (95% CI) p
CKD (creatinine 3.561 (1.175e10.792) .0248
Study limitations
> 2.0 mg/dL)
Surgical complications 4.127 (1.362e12.501) .0122 The major limitations of the present study are its retro-
Note. HR ¼ hazard ratio; CI ¼ confidence interval; CKD ¼ chronic spective nature and the limited number of patients. Owing
kidney disease. to the small sample size, no significant risk factors were
470
Figure 4. Actuarial KaplaneMeier long-term survival curve in patients with negative culture, Salmonella and non-Salmonella species
infection.
found for long-term mortality and persistent infection after
Bonferroni-adjustment. Some of the significant variables
related to long-term open repair outcomes could not be
evaluated because of differences in patient populations.
Patients with persistent infection all declined further
treatment owing to the underlying disease, which could
have influenced the study results. A multi-institutional
prospective study of optimal treatment strategies and
prognostic factors is needed to improve understanding of
MAA treatment.
CONCLUSION
This study summarizes a single-centre experience of endo-
vascular treatment of MAA. In patients presenting with
rupture, EVAR should probably be considered, regardless of
fever, to prevent further haemodynamic compromise.
However, stable patients should be treated with antibiotics
first, because those with pre-operative positive blood cul-
tures and those with persistent infection after EVAR were at
higher risk of premature death due to fatal infectious
complications. This might also indicate the necessity of
lifelong oral antibiotic treatment after EVAR of MAA.
CONFLICT OF INTEREST
None.
FUNDING
None.
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