Angleitner et al Adult: Aorta

ADULT
Bilateral or unilateral antegrade cerebral perfusion during
surgery for acute type A dissection
Philipp Angleitner, MD,a Marie-Elisabeth Stelzmueller, MD,a Stephane Mahr, MD,a
Alexandra Kaider, MSc,b Guenther Laufer, MD,a and Marek Ehrlich, MDa

ABSTRACT Bilateral ACP versus Unilateral ACP

Objective: The study objective was to investigate outcomes associated with the
application of bilateral or unilateral antegrade cerebral perfusion during surgery
for acute type A dissection. 100

80
100

80

Survival (%)

Survival (%)
60 60

40 40

Methods: Patients who underwent surgery for type A dissection with the applica- 20

0 Logrank P = .02
20

0 Logrank P = .91

0 1 2 3 4 5 6 7 8 0 1 2 3 4 5 6 7 8

tion of antegrade cerebral perfusion between 2009 and 2017 at the Division of 1
2
27
16
22
6
18
5
Survival time (years)

15
5
13
5
10
4
9
3
6
2
3
1
1
2
64
77
44
60
33
52
Survival time (years)

24
45
21
37
16
29
14
23
9
8
5
1

Cardiac Surgery, Medical University of Vienna were analyzed retrospectively 1: Bilateral ACP 2: Unilateral ACP 1: Bilateral ACP 2: Unilateral ACP

(bilateral antegrade cerebral perfusion: n ¼ 91, 49.5%; unilateral antegrade cere- ACP durations ≥ 50 min ACP durations < 50 min

bral perfusion: n ¼ 93, 50.5%). The primary outcome variable was overall sur- b-ACP and superior overall survival in patients with
vival. Subgroup analyses were performed in patients requiring antegrade ACP durations of 50 minutes or more.
cerebral perfusion durations of 50 minutes or more and less than 50 minutes. Sec-
ondary outcome variables were 30-day mortality, adverse outcome, permanent Central Message
and temporary neurologic deficits, renal replacement therapy, prolonged ventila- b-ACP and u-ACP are associated with compa-
tion, intensive care unit stay, and hospital stay. rable outcomes after surgery for acute TAD.
b-ACP might be preferentially applied in pa-
Results: Multivariable Cox proportional hazards analysis demonstrated no signif- tients with longer ACP durations.
icant association of bilateral antegrade cerebral perfusion with overall survival
(hazard ratio, 0.63; 95% confidence interval, 0.34-1.14, P ¼ .126). Propensity Perspective
score modeling using the method of inverse probability of treatment weighting In the present analysis, b-ACP and u-ACP are
confirmed this result (hazard ratio, 0.73; 95% confidence interval, 0.33-1.60, associated with similar outcomes after surgery
P ¼ .428). Bilateral antegrade cerebral perfusion was associated with significantly for acute TAD. Subgroup analyses suggest
improved overall survival in patients requiring antegrade cerebral perfusion dura- that b-ACP is associated with superior overall
survival in patients requiring ACP durations
tions of 50 minutes or more (P ¼ .017). The bilateral antegrade cerebral perfusion of 50 minutes or more. An adequately powered
and unilateral antegrade cerebral perfusion groups showed comparable rates of randomized controlled trial is required to vali-
secondary outcome variables. date these results.

Conclusions: In the present study, bilateral antegrade cerebral perfusion and uni-
lateral antegrade cerebral perfusion are associated with comparable outcomes af- See Commentaries on pages 2168,
ter surgery for type A dissection. Subgroup analyses suggest that bilateral 2170, and 2171.
antegrade cerebral perfusion is associated with superior overall survival in pa-
tients requiring antegrade cerebral perfusion durations of 50 minutes or more.
An adequately powered prospective randomized controlled trial is required to
validate these results. (J Thorac Cardiovasc Surg 2020;159:2159-67)

Surgery for acute type A dissection (TAD) is still associated

with considerable rates of early mortality (11.6%-18.4%)
From the aDivision of Cardiac Surgery, Department of Surgery, Medical University of
Vienna, Vienna, Austria; and bCenter for Medical Statistics, Informatics, and Intel-
and permanent neurologic deficit (PND) (6.3%-14.8%).1-4
ligent Systems, Medical University of Vienna, Vienna, Austria. Over the last decades, various intraoperative cerebral
Institutional review board approval: Ethical review board of the Medical University of protection strategies have been studied with the aim of
Vienna, Vote Number 076/2005, granted on April 18, 2005.
Angleitner and Stelzmueller contributed equally.
Received for publication Dec 26, 2018; revisions received May 17, 2019; accepted for
publication June 4, 2019; available ahead of print Aug 1, 2019. Scanning this QR code will
Address for reprints: Philipp Angleitner, MD, Division of Cardiac Surgery, Depart- take you to the article title
ment of Surgery, Medical University of Vienna, Spitalgasse 23, 1090 Vienna,
page to access supplementary
Austria (E-mail: philipp.angleitner@meduniwien.ac.at).
0022-5223/$36.00 information.
Copyright Ó 2019 by The American Association for Thoracic Surgery
https://doi.org/10.1016/j.jtcvs.2019.06.057

The Journal of Thoracic and Cardiovascular Surgery c Volume 159, Number 6 2159
 Adult: Aorta
ADULT
Abbreviations and Acronyms
ACP ¼ antegrade cerebral perfusion
b-ACP ¼ bilateral antegrade cerebral perfusion
CI ¼ confidence interval
CPB ¼ cardiopulmonary bypass
DHCA ¼ deep hypothermic circulatory arrest
HCA ¼ hypothermic circulatory arrest
HR ¼ hazard ratio
ICU ¼ intensive care unit
MHCA ¼ moderate hypothermic circulatory arrest
NIRS ¼ near-infrared spectroscopy
PND ¼ permanent neurologic deficit
RRT ¼ renal replacement therapy
TAD ¼ type A dissection
TND ¼ temporary neurologic deficit
u-ACP ¼ unilateral antegrade cerebral perfusion
improving survival and neurologic outcomes. These
techniques include moderate hypothermic circulatory
arrest (MHCA) and deep hypothermic circulatory arrest
(DHCA) with the addition of antegrade cerebral perfusion
(ACP) or retrograde cerebral perfusion.5 Also, some groups
advocate the use of straight DHCA without cerebral
perfusion.6 Considerable differences exist between centers
and individual surgeons regarding the preferred use of these
strategies.7,8 In Europe, the most commonly applied
strategy is MHCA with the application of ACP.9 However,
it is still a matter of debate whether bilateral ACP (b-ACP)
should preferentially be applied or whether it is
sufficient to use unilateral ACP (u-ACP).9-11 The aim of
this study was to analyze outcomes associated with the
application of b-ACP or u-ACP during surgery for TAD at
the Division of Cardiac Surgery, Medical University of
Vienna.
MATERIALS AND METHODS
Study approval was granted by the ethical review board of the Medical
University of Vienna (Vote Number 076/2005). We performed a retrospec-
tive chart review of all patients who underwent surgery for TAD between
January 2009 and December 2017 at our center. Inclusion criteria were
acute TAD (surgery within 14 days after first medical contact) and intrao-
perative application of either b-ACP or u-ACP in addition to MHCA or
DHCA. Patients with a diagnosis of chronic TAD and patients operated
with the application of retrograde cerebral perfusion were excluded from
this analysis.
Preoperative and intraoperative baseline characteristics of the study
cohort are shown in Tables 1 and 2. The variable ‘‘history of stroke’’ de-
lineates patients with a history of ischemic or hemorrhagic stroke. Pre-
operative presence of ‘‘malperfusion’’ (coronary, cerebral, spinal,
mesenteric, renal, peripheral) was assessed using computed tomography
reports and clinical records. Criteria defining ‘‘hemodynamic insta-
bility’’ were the presence of significant hypotension (systolic arterial
blood pressure <90 mm Hg) despite pharmacologic support or mechan-
ical resuscitation within 1 hour before skin incision. Iatrogenic
dissection occurred as a complication of cardiac surgery, coronary
2160 The Journal of Thoracic and Cardiovascular Surgery c June 2020
Angleitner et al
angiography, or thoracic endovascular aortic repair of type B dissection.
The variables ‘‘surgery within 6 hours’’ and ‘‘surgery within 48 hours’’
refer to the period between first documented medical contact after symp-
tom onset and skin incision (Table 1). The variable ‘‘DHCA’’ indicates a
nasopharyngeal temperature between 14.1 C and 20 C during HCA,
whereas MHCA indicates temperatures between 20.1 C and 28 C
(Table 2).12
Surgical Strategy
At our department, an aortic team of 2 specially trained and experienced
surgeons has been established to optimize outcomes after surgery for TAD
(Table 2).13,14 These surgeons are frequently involved in the most complex
TAD cases. Moreover, they perform the majority of elective ascending and
aortic arch aneurysm repairs. During surgery for TAD, a surgical standard
operating procedure is followed. Preoperatively, hemodynamic monitoring
is installed using bilateral radial arterial lines. Near-infrared spectroscopy
(NIRS) (INVOS 5100C, Medtronic, Dublin, Ireland) is used to continu-
ously monitor oxygen saturation over both cerebral hemispheres. Addition-
ally, temperature probes are inserted into the esophagus and urinary
bladder. The right axillary artery is preferentially cannulated in hemody-
namically stable patients (85.3%) (Table 2). Alternatively, the femoral ar-
tery is used for arterial perfusion. After median sternotomy and venous
cannulation, cardiopulmonary bypass (CPB) is initiated and the patient is
cooled to moderate (20.1 C-28 C) or deep hypothermia (14.1 C-20 C)
as assessed via a nasopharyngeal probe. When the target core temperature
is reached, hypothermic circulatory arrest (HCA) is initiated and cold car-
dioplegic solution is administered via a coronary sinus catheter. The bra-
chiocephalic trunk, left common carotid artery, and left subclavian artery
are clamped and u-ACP is started via the right axillary arterial cannula
(flow rate: 10-15 mL/kg/min; pressure: 50-60 mm Hg) (Figure 1). In the
presence of a severely incompetent aortic valve, the ascending aorta is
clamped during the cooling phase and proximal aortic repair is performed
first.
After initiation of HCA, the ascending aorta is incised and the aortic
arch is examined to assess the involvement of supra-aortic vessels. Depend-
ing on the extent of aortic arch involvement, 1 of the following 4 surgical
techniques is applied: replacement of the ascending aorta; hemiarch repair
including the inner curvature of the aortic arch; partial arch repair including
more than 1 supra-aortic vessel; or total arch replacement including all
supra-aortic vessels (Table 2).
At this stage, the surgeon decides whether an additional perfusion can-
nula is inserted into the left common carotid artery to initiate b-ACP during
performance of the open distal anastomosis. This decision is dependent on
the operating surgeon’s preference and experience, as well as his/her esti-
mation of the required ACP duration. During the period of ACP, cerebral
oxygen saturation is monitored bilaterally using NIRS. If an oxygen satu-
ration decrease of 15% to 20% develops unilaterally during u-ACP, the left
common carotid artery is also cannulated to proceed with b-ACP.15,16 After
completion of the distal anastomosis or reimplantation of supra-aortic ves-
sels, ACP is stopped, the aortic arch graft is cannulated, de-aired, and
clamped, and CPB is reinitiated. During the rewarming phase, the aortic
root is examined and repaired if necessary.
Statistical Analysis
Continuous variables are described by mean values  standard devia-
tions or by medians and interquartile ranges in case of non-normal distribu-
tions. Absolute frequencies and percentages are used for categoric
variables. Continuous variables with skewed distributions were log2-
transformed before statistical analysis. The Student t test was used to
compare continuous variables. Chi-square tests and Fisher exact tests
were used for the comparison of categoric variables.
The primary outcome variable was overall survival during the follow-up
period. Patients were censored on May 31, 2018. The resultant median
Angleitner et al Adult: Aorta

ADULT
TABLE 1. Preoperative baseline characteristics
All patients Bilateral ACP Unilateral ACP
Variables n ¼ 184 (100%) n ¼ 91 (49.5%) n ¼ 93 (50.5%) P value
Age (y) 61.0  14 61.0  13.8 60.9  14.3 .961*
Female (%) 55 (29.9) 24 (26.4) 31 (33.3) .303y
BMI (kg/m2) 26.8  4.8 26.8  4.5 26.7  5.1 .831*
Hypertension (%) 155 (84.2) 78 (85.7) 77 (82.8) .587y
Diabetes mellitus (%) 10 (5.4) 6 (6.6) 4 (4.3) .534z
Atrial fibrillation (%) 26 (14.1) 16 (17.6) 10 (10.8) .184y
COPD (%) 15 (8.2) 3 (3.3) 12 (12.9) .017y
CAD (%) 36 (19.6) 15 (16.5) 21 (22.6) .297y
PAD (%) 18 (9.8) 9 (9.9) 9 (9.7) .961y
CVD (%) 12 (6.5) 8 (8.8) 4 (4.3) .218y
History of stroke (%) 15 (8.2) 8 (8.8) 7 (7.5) .754y
Creatinine (mg/dL) 1.1 (0.8-1.3) 1.1 (0.9-1.4) 1.1 (0.8-1.3) .239*
Marfan syndrome (%) 4 (2.2) 0 (0) 4 (4.3) .121z
Previous sternotomy (%) 7 (3.8) 4 (4.4) 3 (3.2) .719z
DeBakey type I (%) 129 (70.1) 65 (71.4) 64 (68.8) .699y
Malperfusion (%)
Coronary 33 (17.9) 15 (16.5) 18 (19.4) .612y
Cerebral 36 (19.6) 15 (16.5) 21 (22.6) .297y
Spinal 1 (0.5) 1 (1.1) 0 (0) NT
Mesenteric 12 (6.5) 5 (5.5) 7 (7.5) .577y
Renal 52 (28.3) 26 (28.6) 26 (28.0) .926y
Peripheral 35 (19.0) 17 (18.7) 18 (19.4) .907y
Hemodynamic instability (%) 45 (24.5) 20 (22) 25 (26.9) .439y
Lactate (mmol/L) 1.5 (1.1-2.6) 1.7 (1.1-2.7) 1.5 (1-2.4) .925*
Iatrogenic dissection (%) 18 (9.8) 8 (8.8) 10 (10.8) .654y
Complication of cardiac surgery 9 (4.9) 4 (4.4) 5 (5.4) NT
Complication of coronary angiography 6 (3.3) 2 (2.2) 4 (4.3) NT
Complication of TEVAR 3 (1.6) 2 (2.2) 1 (1.1) NT
Surgery within 6 h (%) 111 (60.3) 48 (52.8) 63 (67.7) .038y
Surgery within 48 h (%) 172 (93.5) 85 (93.4) 87 (93.6) .969y
Bold indicates statistical significance (P<.05). ACP, Antegrade cerebral perfusion; BMI, body mass index; COPD, chronic obstructive pulmonary disease; CAD, coronary artery
disease; PAD, peripheral arterial disease; CVD, cerebrovascular disease; NT, not tested; TEVAR, thoracic endovascular aortic repair. *t test. yChi-square test. zFisher exact test.

follow-up was 51.9 months. Survival probabilities were estimated by the
Kaplan–Meier method, and the log-rank test was used to compare survival
curves. Univariate and multivariable Cox proportional hazards models
were applied to analyze the effect of b-ACP on overall survival during
the follow-up period. Covariates for the multivariable model were chosen
with regard to clinical experience and published evidence.17 To confirm the
findings of the multivariable Cox proportional hazards analysis, propensity
score modeling was performed using the method of inverse probability of
treatment weighting. Baseline characteristics assumed to influence the de-
cision for applying b-ACP or the patient’s outcome were included in the
propensity score model, namely, aortic team, surgical year, surgery within
6 hours, mesenteric malperfusion, hemodynamic instability, age, female
sex, chronic obstructive pulmonary disease, and creatinine (log2-
transformed).
Univariate and multivariable subgroup analyses were performed to
analyze the impact of b-ACP on overall survival in patients requiring
ACP durations of 50 minutes or more or less than 50 minutes, respectively.
These subgroup analyses were motivated by a statistically significant inter-
action between the effects of b-ACP and ACP duration on overall survival
(P ¼ .039) as evaluated in the multivariable Cox proportional hazards
model. The cutoff of ‘‘50 minutes’’ was chosen in accordance with the re-
sults of 2 meta-analyses showing improved outcomes after the application
of b-ACP in patients requiring ACP durations ‘‘longer than 40 to 50 mi-
nutes’’ and ‘‘longer ACP durations.’’18,19
Secondary outcome variables were defined as 30-day mortality, adverse
outcome (in-hospital mortality or PND), PND (ischemic or hemorrhagic
lesion documented by cranial computed tomography, or irreversible
coma), temporary neurologic deficit (TND) (full recovery before hospital
discharge), renal replacement therapy (RRT) during the postoperative hos-
pital stay, prolonged ventilation (ventilation >48 hours or death during
48 hours after surgery), prolonged intensive care unit (ICU) stay
(>7 days), and prolonged hospital stay (>30 days). Chi-square tests were
used to compare the rates of secondary outcome variables between the b-
ACP and u-ACP groups.

The Journal of Thoracic and Cardiovascular Surgery c Volume 159, Number 6 2161
 Adult: Aorta Angleitner et al
ADULT

TABLE 2. Intraoperative baseline characteristics

All patients Bilateral ACP Unilateral ACP
Variables n ¼ 184 (100%) n ¼ 91 (49.5%) n ¼ 93 (50.5%) P value
Aortic team (%) 58 (31.5) 34 (37.4) 24 (25.8) .092*
Surgical year 2013 (2011-2016) 2015 (2011-2016) 2013 (2011-2014) .045y
Extent of replacement .272*
Ascending aorta (%) 88 (47.8) 42 (46.2) 46 (49.5)
Hemiarch (%) 62 (33.7) 29 (31.9) 33 (35.5)
Partial arch (%) 14 (7.6) 6 (6.6) 8 (8.6)
Total arch (%) 20 (10.9) 14 (15.4) 6 (6.5)
Duration of surgery (min) 407.5 (340-497.5) 415 (342-515) 400 (335-480) .370y
Duration of CPB (min) 216 (169.5-283.5) 227 (185-303) 209 (159-265) .040y
Duration of CC (min) 116 (85.5-167.5) 126 (91-172) 107 (79-152) .036y
Duration of HCA (min) 34 (27-49) 38 (30-57) 30 (25-45) .008y
Duration of ACP (min) 34 (26-49) 36 (29-56) 30 (25-42) .012y
DHCA (%) 38 (20.7) 26 (28.6) 12 (12.9) .009*
Axillary cannulation (%) 157 (85.3) 75 (82.4) 82 (88.2) .270*
Bentall (%) 37 (20.1) 18 (19.8) 19 (20.4) .912*
David (%) 4 (2.2) 2 (2.2) 2 (2.2) 1.000z
Concomitant CABG (%) 29 (15.8) 14 (15.4) 15 (16.1) .890*
Peak lactate (mmol/L) 7.0 (5.1-9.6) 6.8 (5.2-9) 7.1 (5-10.6) .434y
Bold indicates statistical significance (P <.05). ACP, Antegrade cerebral perfusion; CPB, cardiopulmonary bypass; CC, crossclamping; HCA, hypothermic circulatory arrest;
DHCA, deep hypothermic circulatory arrest; CABG, coronary artery bypass grafting. *Chi-square test. yt test. zFisher exact test.

In addition, characteristics of cerebral lesions in patients with PND were
analyzed descriptively. Moreover, causes of death were descriptively
analyzed in patients with ACP durations of 50 minutes or more. All ana-
lyses were performed using SAS software version 9.4 (SAS Institute Inc,
Cary, NC).
RESULTS
During the study period, 184 patients underwent surgery
for TAD with the use of ACP. b-ACP was applied in 91 pa-
tients (49.5%), and u-ACP was applied in 93 patients
(50.5%). Fourteen patients (7.6%) were initially perfused
using u-ACP but immediately switched to b-ACP after a
unilateral decrease in oxygen saturation occurred. These pa-
tients were assigned to the b-ACP group for all statistical
analyses.
Preoperative baseline characteristics of the b-ACP and
u-ACP groups are shown in Table 1. The mean age of the
study cohort was 61.0  14 years. The majority of patients
had a DeBakey type I dissection (n ¼ 129, 70.1%). In pa-
tients undergoing surgery within 6 hours after first medical
contact, u-ACP was more commonly applied (Table 1).
Intraoperative baseline characteristics are shown in Table
2. The aortic team was operating on 31.5% of patients.
b-ACP was more frequently applied by these surgeons,
although the difference did not reach statistical significance.
However, a significant trend toward generally increased use
of b-ACP was evident in more recent years. No differences
were found between the b-ACP and u-ACP groups with
regard to the extent of replacement, although the rate of to-
tal arch replacement was numerically higher in the b-ACP
group (Table 2). As expected, the b-ACP group was charac-
terized by significantly longer median durations of CPB,
crossclamping, HCA, and ACP. Also, DHCA was more
frequently used in the b-ACP group (28.6% vs 12.9%)
(Table 2).
Primary Outcome: Overall Survival
Kaplan–Meier survival curves of the b-ACP and u-ACP
groups are visualized in Figure 2 (log-rank test, P ¼ .40).
The univariate hazard ratio (HR) for b-ACP was 0.79
(95% confidence interval [CI], 0.45-1.38, P ¼ .40). The
multivariable Cox proportional hazards model demon-
strated that the application of b-ACP was not associated
with overall survival (HR, 0.63; 95% CI, 0.34-1.14;
P ¼ .126) (Table 3). Covariates used in this model were
age, mesenteric malperfusion, duration of CPB, duration
of ACP, and use of DHCA.
To confirm these results, propensity score modeling was
performed, showing an HR for b-ACP of 0.73 (95% CI,
0.33-1.60; P ¼ .428) adjusted for the same covariates as
in the multivariable Cox proportional hazards model.
Subgroup Analyses
Subgroup analyses were performed because of a statisti-
cally significant interaction between the effects of b-ACP

2162 The Journal of Thoracic and Cardiovascular Surgery c June 2020

Angleitner et al Adult: Aorta

ADULT
Bilateral ACP versus Unilateral ACP

100 100

80 80
Survival (%)

Survival (%)
60 60

40 40

20 20

0 Logrank P = .02 0 Logrank P = .91

0 1 2 3 4 5 6 7 8 0 1 2 3 4 5 6 7 8
Survival time (years) Survival time (years)

1 27 22 18 15 13 10 9 6 3 1 64 44 33 24 21 16 14 9 5
2 16 6 5 5 5 4 3 2 1 2 77 60 52 45 37 29 23 8 1

1: Bilateral ACP 2: Unilateral ACP 1: Bilateral ACP 2: Unilateral ACP

ACP durations ≥ 50 min ACP durations < 50 min

FIGURE 1. b-ACP and superior overall survival in patients with ACP durations of 50 minutes or more. ACP, Antegrade cerebral perfusion.

and ACP duration on overall survival (P ¼ .039) as evalu-
ated in the multivariable Cox proportional hazards model.
The subgroup of patients requiring ACP durations of 50 mi-
nutes or more consisted of 43 patients (b-ACP: n ¼ 27,
62.8%; u-ACP: n ¼ 16, 37.2%). Kaplan–Meier survival
curves in Figure 3, A show the significantly improved over-
all survival of patients receiving b-ACP in comparison with
u-ACP in this subgroup (log-rank test, P ¼ .02). Multivari-
able Cox proportional hazards analysis confirmed that
b-ACP was associated with significantly improved overall
survival in patients requiring ACP durations of 50 minutes
or more (HR, 0.26; 95% CI, 0.09-0.79; P ¼ .017) (Table
4). Duration of CPB was used as a covariate for this
analysis.
The subgroup of patients with ACP durations less than
50 minutes consisted of 141 patients (b-ACP: n ¼ 64,
45.4%; u-ACP: n ¼ 77, 54.6%). Figure 2, B shows similar
survival curves of patients receiving b-ACP and u-ACP
(log-rank test, P ¼ .91). Multivariable Cox proportional
hazards analysis demonstrated no association of b-ACP
with overall survival in this subgroup (HR, 0.84; 95% CI,
0.43-1.66; P ¼ .620) (Table 4).
Secondary Outcome Variables
Comparison of the b-ACP and u-ACP groups demon-
strated similar rates of 30-day mortality (b-ACP: 12.1%,
u-ACP: 16.1%, P ¼ .431), adverse outcome (26.4% vs
30.1%, P ¼ .574), PND (18.7% vs 19.4%, P ¼ .753),

The Journal of Thoracic and Cardiovascular Surgery c Volume 159, Number 6 2163
 Adult: Aorta Angleitner et al
ADULT

100 Causes of Death in Patients With Antegrade Cerebral

Logrank P = .40
Perfusion Durations 50 Minutes or More
80 Comparative analysis of causes of death suggested that in
the b-ACP group, death was less frequently caused by major
neurologic events (ischemic stroke, hemorrhagic stroke, or
Survival (%)

60
hypoxic brain injury) than in the u-ACP group (33.3% vs
75%) (Table E3).
40

20 DISCUSSION
In the present study, the application of b-ACP was not
0 associated with overall survival after surgery for TAD.
Moreover, the b-ACP and u-ACP groups showed similar
0 1 2 3 4 5 6 7 8
rates of 30-day mortality, adverse outcome, PND, TND,
Survival Time (Years)
RRT, prolonged ventilation, ICU stay, and hospital stay.
Numbers at risk:
Several retrospective studies have yielded comparable re-
1 91 66 51 39 34 26 23 15 8
sults.3,20-23
2 93 66 57 50 42 33 26 10 2
Subgroup analyses demonstrated that b-ACP was associ-
1: Bilateral ACP 2: Unilateral ACP ated with significantly improved overall survival in patients
FIGURE 2. Primary outcome: overall survival (Kaplan–Meier survival requiring ACP durations of 50 minutes or more (Table 4,
curves, log-rank test). Kaplan–Meier survival curves show that overall sur- Figure 3, A). Comparative analysis of causes of death in
vival is similar (log-rank P ¼ .40) in patients receiving b-ACP (n ¼ 91) or this subgroup suggested that in patients receiving b-ACP,
u-ACP (n ¼ 93) during surgery for acute TAD. ACP, Antegrade cerebral death was less frequently caused by major neurologic
perfusion. events than in the u-ACP group (Table E3). These findings
are in line with the results of 2 meta-analyses showing that
TND (7.7% vs 9.7%, P ¼ .226), RRT (23.1% vs 22.6%, the application of b-ACP is associated with improved out-
P ¼ .996), prolonged ventilation (47.3% vs 52.7%, comes in patients with prolonged ACP durations during
P ¼ .461), prolonged ICU stay (57.1% vs 61.3%, aortic arch surgery. Malvindi and colleagues18 analyzed
P ¼ .567), and prolonged hospital stay (40.7% vs 44.1%, 17 studies including a total of 2949 patients receiving
P ¼ .638) (Table E1). b-ACP and 599 patients receiving u-ACP. The authors
concluded that b-ACP was associated with improved sur-
Characteristics of Cerebral Lesions in Patients With vival and lower rates of cerebrovascular events in patients
Permanent Neurologic Deficit with ACP durations over 40 to 50 minutes.18 Angeloni
Ischemic stroke was the most common type of lesion and colleagues19 reviewed 32 studies including 3723 pa-
characterized as PND (Table E2). Some patients had com- tients receiving b-ACP and 3065 patients receiving
bined lesions (eg, ischemic stroke and hypoxic brain u-ACP. Meta-regression analysis demonstrated that pro-
injury). The rate of right-sided lesions was higher in patients longed HCA times were associated with increased mortality
receiving b-ACP, whereas the rate of left-sided lesions was in patients receiving u-ACP, but not in patients receiving
higher in patients receiving u-ACP. Overall, most lesions b-ACP.19
occurred bilaterally (Table E2). The pathophysiologic basis for this association remains
to be elucidated. In the majority of patients operated with
TABLE 3. Primary outcome: Overall survival (multivariable Cox
the application of u-ACP via the right axillary artery, bi-
proportional hazards model)
hemispheric cerebral blood supply is provided by the circle
Hazard ratio of Willis.24 Clinical data even suggest that bi-hemispheric
Variables (95% CI) P value perfusion is preserved independently of an anatomically
Bilateral ACP 0.63 (0.34-1.14) .126 complete circle of Willis, likely via collateral vessels.25
Age (y) 1.02 (1.00-1.04) .085 The adequacy of cerebral perfusion and metabolism during
Mesenteric malperfusion 6.24 (2.89-13.47) <.001 ACP is influenced by flow rate, pH, hematocrit, and temper-
Duration of CPB (min, log2-transformed) 3.69 (2.15-6.33) <.001 ature.26 The cerebroprotective effects of hypothermia have
Duration of ACP (min, log2-transformed) 0.77 (0.52-1.14) .189
long been used during aortic surgery.27 On the one hand, hy-
pothermic ACP decreases cerebral oxygen extraction as a
DHCA 1.07 (0.55-2.08) .854
measure of metabolism.28 On the other hand, hypothermia
Bold indicates statistical significance (P <.05). CI, Confidence interval; ACP, ante-
grade cerebral perfusion; CPB, cardiopulmonary bypass; DHCA, deep hypothermic significantly reduces cerebral blood flow during ACP, as
circulatory arrest. shown in animal studies by Strauch and colleagues.29 The

2164 The Journal of Thoracic and Cardiovascular Surgery c June 2020

Angleitner et al Adult: Aorta

ADULT
100 100

80 80
Survival (%)

60 60

Survival (%)
40 40

20 20

Logrank P = .02 0 Logrank P = .91

0
0 1 2 3 4 5 6 7 8 0 1 2 3 4 5 6 7 8
Survival Time (Years) Survival Time (Years)
Numbers at risk: Numbers at risk:
1 27 22 18 15 13 10 9 6 3 1 64 44 33 24 21 16 14 9 5
2 16 6 5 5 5 4 3 2 1 2 77 60 52 45 37 29 23 8 1
1: Bilateral ACP 2: Unilateral ACP 1: Bilateral ACP 2: Unilateral ACP
A B
FIGURE 3. A, Subgroup analysis: overall survival in patients requiring ACP for 50 minutes or more (Kaplan–Meier survival curves, log-rank test). In
patients requiring durations of ACP for 50 minutes or more during surgery for acute TAD, b-ACP is associated with significantly improved overall survival
(log-rank P ¼ .02) in comparison with u-ACP. B, Subgroup analysis: overall survival in patients requiring ACP for less than 50 minutes (Kaplan–Meier
survival curves, log-rank test). In patients requiring ACP for less than 50 minutes during surgery for acute TAD, b-ACP, and u-ACP are associated with
similar overall survival (log-rank P ¼ .91). ACP, Antegrade cerebral perfusion.

same authors have also demonstrated that cerebral blood
flow remains relatively constant for limited durations of
ACP but is significantly decreased after 60 minutes of
ACP.30 Against this background, our clinical findings sug-
gest that b-ACP might enable more physiologic bi-
hemispheric perfusion than u-ACP during prolonged
periods of HCA.
Surgery for TAD is characterized by considerable intrao-
perative risk of technical complications related to the aortic
arch (eg, intractable bleeding or progressive dissection in
the area of the distal anastomosis). Thus, the surgeon needs
to be prepared for scenarios necessitating unexpected total
arch replacement with substantial prolongation of HCA.
In situations like these, b-ACP seems to provide a ‘‘safety
TABLE 4. Subgroup analyses: Overall survival (multivariable Cox
proportional hazards models)
Hazard ratio
Variables (95% CI)
ACP durations 50 min
Bilateral ACP 0.26 (0.09-0.79)
Duration of CPB (min, log2-transformed) 4.55 (1.78-11.64)
ACP durations <50 min
Bilateral ACP 0.84 (0.43-1.66)
Duration of CPB (min, log2-transformed) 2.65 (1.42-4.94)
Bold indicates statistical significance (P <.05). CI, Confidence interval; ACP, ante-
grade cerebral perfusion; CPB, cardiopulmonary bypass.
net’’ by ensuring acceptable postoperative outcomes even
if ACP durations of 50 minutes or more are required. This
notion is supported by one study that exclusively focused
on patients receiving total arch replacement and showed a
trend toward lower rates of 30-day mortality and PND in
the group receiving b-ACP.3 Although u-ACP might be
applied safely when bi-hemispheric cerebral perfusion is
continuously monitored via NIRS, it needs to be remem-
bered that further investigations into this technology are
necessary to determine its sensitivity to detect cerebral
ischemia.16,31 On the basis of these considerations, we
share the opinion of Bachet,10 Takayama and Borger,11
and Spielvogel and colleagues26 that b-ACP should prefer-
entially be applied during surgery for TAD (Video 1).
Critics of the use of b-ACP have raised concerns
regarding unnecessary manipulation of supra-aortic vessels
with potentially devastating consequences, including ca-
rotid dissection or embolization of particulate matter from
P
the aortic arch. In fact, a trend toward a higher stroke rate
value was shown in recipients of b-ACP in one retrospective anal-
ysis of 246 propensity score–matched patients undergoing
.017
elective aortic arch surgery (b-ACP: 6%, u-ACP: 2%,
.002 P ¼ .06).32 In the present analysis, however, the rates of
bilateral cerebral lesions and unilateral left-sided lesions
.620 were higher in patients receiving u-ACP, whereas the rates
.002 of unilateral right-sided lesions were higher in patients
receiving b-ACP (Table E2). These findings imply that the
insertion of a perfusion cannula into the left common

The Journal of Thoracic and Cardiovascular Surgery c Volume 159, Number 6 2165
 Adult: Aorta
ADULT
VIDEO 1. Philipp Angleitner and Marek Ehrlich present the results and
implications of this study. Video available at: https://www.jtcvs.org/
article/S0022-5223(19)31353-4/fulltext.
carotid artery does not increase the risk of left-sided embo-
lization and subsequent stroke. Clinical data have shown
that the presence of preoperative cerebral malperfusion is
significantly associated with postoperative rates of PND.33
Moreover, substantial postoperative neurologic improve-
ment has been shown in patients presenting with preopera-
tive neurologic deficits.34,35 These findings suggest that
timely resolution of cerebral malperfusion by surgery
might play a more important role in the prevention of
PND than the choice of ACP. In the present study, the b-
ACP and u-ACP groups had similar rates of preoperative
cerebral malperfusion (corresponding to
hemodynamically significant dissection of supra-aortic ves-
sels), suggesting that surgeons did not consider the presence
or absence of dissection in supra-aortic vessels when
deciding between the use of b-ACP or u-ACP (Table 1).
Notably, the b-ACP and u-ACP groups showed differ-
ences regarding several aspects of the surgical procedure.
b-ACP was more frequently applied by the aortic team,
although the difference did not reach statistical significance
(Table 2). However, a significant trend toward increased use
of b-ACP during more recent years of the study period was
demonstrated (Table 2). In the early 2000s, surgeons at our
department used b-ACP almost exclusively in patients
showing a unilateral decrease in cerebral oxygen saturation
as assessed by NIRS. Currently, our departmental policy
recommends the universal application of b-ACP in patients
operated for TAD in response to recent publications
showing improved outcomes in patients receiving
b-ACP.18,19 The lower rate of b-ACP in patients operated
within 6 hours after first medical contact possibly
indicates that u-ACP was preferentially applied in more
urgent cases to decrease procedural complexity, although
this difference was not evident in the rates of
hemodynamic instability or axillary cannulation (Tables 1
and 2). The b-ACP and u-ACP groups were similar
regarding the extent of aortic replacement, although a
numerically higher rate of patients receiving total arch
2166 The Journal of Thoracic and Cardiovascular Surgery c June 2020
Angleitner et al
replacement was operated with the use of b-ACP (Table
2). The fact that median durations of CPB, crossclamping,
HCA, and ACP, as well as the rate of DHCA, were signifi-
cantly higher in the b-ACP group also suggests that b-ACP
was preferentially used in longer and more complex cases
(Table 2).
Study Limitations
Several limitations need to be considered when interpret-
ing these findings. First, this study is likely subject to selec-
tion bias. Also, the increased use of b-ACP in more recent
years might have biased the results. To adjust for these in-
fluences, a propensity score model was generated, including
the variables ‘‘aortic team,’’ ‘‘surgery within 6 hours,’’ and
‘‘surgical year,’’ among others. This analysis confirmed the
results of the multivariable Cox proportional hazards anal-
ysis. Furthermore, this single-center analysis is limited by
the relatively small sample size. As a consequence, this
study might be underpowered to detect a potentially signif-
icant influence of b-ACP on postoperative outcomes. Unfor-
tunately, the small number of patients requiring ACP
durations of 50 minutes or more precluded more detailed
subgroup analyses of secondary outcome variables, most
importantly PND and TND. Moreover, continuous NIRS
monitoring data were not documented for the entire study
cohort and thus could not be included for statistical
analysis.
CONCLUSIONS
The present study demonstrates comparable overall sur-
vival and similar rates of secondary outcome variables in
patients receiving b-ACP or u-ACP during surgery for
TAD. Subgroup analyses suggest that b-ACP is associated
with significantly improved overall survival in patients
requiring ACP durations of 50 minutes or more. On the ba-
sis of these findings, we believe that b-ACP should prefer-
entially be applied during surgery for TAD. Nevertheless,
an adequately powered prospective randomized controlled
trial is required to validate these results.
Conflict of Interest Statement
Laufer: Consultant and Proctor activity for Edwards/Intuity
Valve. All other authors have nothing to disclose with re-
gard to commercial support.
The authors thank Marina Manduric for assistance with the sur-
gical database of the Division of Cardiac Surgery, Medical Univer-
sity of Vienna.
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Key Words: acute type A dissection, antegrade cerebral
perfusion, aortic dissection
2167
 Adult: Aorta Angleitner et al
ADULT

TABLE E1. Secondary outcome variables (chi-square tests)

All patients Bilateral ACP Unilateral ACP
Outcome variables N ¼ 184 (100%) n ¼ 91 (49.5%) n ¼ 93 (50.5%) P value
30-d mortality (%) 26 (14.1) 11 (12.1) 15 (16.1) .431
Adverse outcome (%) 52 (28.3) 24 (26.4) 28 (30.1) .574
PND (%) 35 (19.0) 17 (18.7) 18 (19.4) .753
Alive without PND 132 (71.7) 67 (73.6) 65 (69.9)
Dead without PND 17 (9.2) 7 (7.7) 10 (10.8)
TND (%) 16 (8.7) 7 (7.7) 9 (9.7) .226
Alive without TND 140 (76.1) 74 (81.3) 66 (71)
Dead without TND 28 (15.2) 10 (11) 18 (19.4)
RRT (%) 42 (22.8) 21 (23.1) 21 (22.6) .996
Alive without RRT 132 (71.7) 65 (71.4) 67 (72)
Dead without RRT 10 (5.4) 5 (5.5) 5 (5.4)
Prolonged ventilation (%) 92 (50) 43 (47.3) 49 (52.7) .461
Prolonged ICU stay (%) 109 (59.2) 52 (57.1) 57 (61.3) .567
Prolonged hospital stay (%) 78 (42.4) 37 (40.7) 41 (44.1) .638
ACP, Antegrade cerebral perfusion; PND, permanent neurologic deficit; TND, temporary neurologic deficit; RRT, renal replacement therapy; ICU, intensive care unit.

TABLE E2. Characteristics of cerebral lesions in patients with permanent neurologic deficit
All patients Bilateral ACP Unilateral ACP
Cerebral lesions N ¼ 35 (100%) n ¼ 17 (48.6%) n ¼ 18 (51.4%)
Lesion type
Ischemic stroke 30 (85.7) 16 (94.1) 14 (77.8)
Hemorrhagic stroke 3 (8.6) 2 (11.8) 1 (5.6)
Hypoxic brain injury 10 (28.6) 5 (29.4) 5 (27.8)
Lesion laterality
Unilateral right-sided lesions 11 (31.4) 10 (58.8) 1 (5.6)
Unilateral left-sided lesions 5 (14.3) 1 (5.9) 4 (22.2)
Bilateral lesions 16 (45.7) 6 (35.3) 10 (55.6)
ACP, Antegrade cerebral perfusion.

2167.e1 The Journal of Thoracic and Cardiovascular Surgery c June 2020

Angleitner et al Adult: Aorta

ADULT
TABLE E3. Causes of death in patients with antegrade cerebral perfusion durations 50 minutes or more
All patients Bilateral ACP Unilateral ACP
Patients n ¼ 14 (100%) n ¼ 6 (42.9%) n ¼ 8 (57.1%)
Ischemic stroke/hemorrhagic stroke/hypoxic brain injury 8 (57.1) 2 (33.3) 6 (75)
Multiorgan failure 4 (28.6) 2 (33.3) 2 (25)
Cardiogenic shock 2 (14.3) 2 (33.3) 0 (0)
ACP, Antegrade cerebral perfusion.

The Journal of Thoracic and Cardiovascular Surgery c Volume 159, Number 6 2167.e2