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\begin{document}

\title{Clinical outcomes of the Frozen Elephant Trunk procedure in 70 emergent
and elective patients undergoing aortic arch surgery: the Salerno
experience with Thoraflex Hybrid}



\author[1]{Paolo Masiello}%
\author[1]{Generoso Mastrogiovanni}%
\author[1]{Oreste Presutto}%
\author[2]{Pierpaolo Chivasso}%
\author[3]{Vito Bruno}%
\author[1]{Mario Colombino}%
\author[1]{Mario Miele}%
\author[1]{Francesco Cafarelli}%
\author[1]{Rocco Leone}%
\author[1]{Donato Triggiani}%
\author[1]{Severino Iesu}%
\affil[1]{University Hospital 'San Giovanni di Dio e Ruggi d’Aragona'}%
\affil[2]{Azienda Ospedaliera Universitaria 'San Giovanni di Dio e Ruggi d'Aragona'}%
\affil[3]{University of Bristol Medical School}%


\vspace{-1em}



  
  \date{May 26, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background and aim of the study. To report early clinical outcomes of
the frozen elephant trunk technique (FET) for the treatment of complex
aortic diseases after transition from conventional elephant trunk.
Methods. A single-center, retrospective study of patients who underwent
hybrid aortic arch and FET repair for aortic arch and/or proximal
descending aortic aneurysms, acute and chronic Stanford type A aortic
dissection with arch and/or proximal descending involvement, Stanford
type B acute and chronic aortic dissections with retrograde aortic arch
involvement. Results. Between December 2017 and May 2020, 70 consecutive
patients (62.7\selectlanguage{ngerman}±10.6 years, 59 male) were treated: 41 (58.6\%) for acute
conditions and 29 (41.4\%) for chronic. Technical success was 100\%.
In-hospital mortality was 14.2\% (n=12, 17.1\% emergency vs. 10.3\%
chronic, P=NS); 2 (2.9\%) major strokes; 1 (1.4\%) spinal cord injury.
Follow-up was 12.5 months (IQR 3.7---22.3. Overall survival at 3, 6, 12
and 24 months was 90\% (95\% CI, 83.2---97.3), 85.6\% (95\% CI,
77.7---94.3), 79.1\% (95\% CI, 69.9---89.5), 75.6\% (95\% CI,
65.8---86.9) and 73.5 (95\% CI, 63.3---85.3). There were no aortic
re-interventions and no dSINE; 5 patients with residual type B
dissection underwent TEVAR completion. Conclusions. In a real-world
setting, FET demonstrated a rapid learning curve and good clinical
outcomes, even in acute type A aortic dissections. Techniques to perfect
the procedure and to reduce remaining risks, and consensus on
considerations such as standardized cerebral protection need to be
reported.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{INTRODUCTION}

The Frozen Elephant Trunk (FET) procedure has become established as a
proven and attractive option to treat aortic disease when the arch and
the thoracic aorta are involved to facilitate the conventional two-stage
access.\textsuperscript{1} In acute and chronic aortic dissection, the
use of FET can help to expand and stabilize the true lumen and cover
eventual supplementary tears but the perceived technical complexity of
the operation may be restricting its adoption, especially in the acute
setting.\textsuperscript{2--4} Undoubtedly, the constant development of
new branched prostheses, which increases the surgeons' armamentarium in
the treatment of complex aortic arch pathology, plays an important role
in reducing the risk of procedural failure.\textsuperscript{5} At
present, there is little evidence weighing the burden of replacing the
aortic arch as an additional procedure during elective or emergency
proximal aortic repair, thus making comparison with patients undergoing
secondary total arch replacement difficult.\textsuperscript{6} The aim
of this study was to evaluate safety and short term outcomes after FET
with the Thoraflex\textsuperscript{TM} Hybrid (Terumo Aortic, Inchinnan,
Scotland, UK) prosthesis in aortic arch reconstruction both in emergency
and elective setting.

\textbf{METHODS}

This is a single center, retrospective, observational study based on
prospectively collected data obtained from institutional cardiac surgery
dataset at University Hospital San Giovanni di Dio and Ruggi d'Aragona
in Salerno, Italy. The study was conducted in accordance with the
principles of the Declaration of Helsinki. Institutional board approval
was obtained for the study, and patient consent was waived.

All patients who underwent FET for acute and chronic arch and thoracic
aorta pathologies between December 2017 and May 2020 were included. The
dates were chosen to capture all routine use of the Thoraflex Hybrid FET
device which consists of a proximal unstented tubular gelatin-coated
Dacron graft and a distal stent-graft polyester made with a
self-expandable nitinol skeleton, deployable antegrade during
circulatory arrest over a guidewire. The unstented proximal graft
diameters vary from 22---32 mm, the distal stent-graft from 24---40 mm.
We use exclusively the Plexus configuration with four integrated lateral
branches: three for the reconstruction of supra-aortic vessels and one
for systemic perfusion. A sewing collar between the two portions
facilitates the distal anastomosis and improves hemostasis. Two
different distal lengths are available (100 and 150 mm). The combination
of the different sizes and lengths allow to tailor the graft to each
patient's anatomy.

We size the stent-graft portion according to the aortic diameter of the
distal landing zone as evaluated by preoperative CT angiogram: 0\%
oversizing in acute and chronic aortic dissections; 10---15\% oversizing
in ascending aorta and/or arch aneurysms, particularly when a second
stage was anticipated. In order to minimize the risk of spinal cord
ischemia, we only implant the 100 mm length.

\textbf{Surgical Technique}

All cases are operated under general anesthesia after invasive arterial
pressure monitoring of bilateral radial arteries and a femoral artery.
We cannulate the right jugular vein after oro-tracheal intubation and
position a Swan-Ganz catheter. All patients are monitored with a
continuous transesophageal echocardiography (TEE) and bilateral cerebral
oxymetry (INVOS\textsuperscript{TM} system). Median sternotomy is
performed in all cases: the usual incision is extended in a small right
or bilateral supra-clavicular cervicotomy to improve access and
harvesting of supra-aortic vessels. Central cannulation is routinely via
the right intrathoracic subclavian artery via side graft . Our approach
is ``branch-first'' and beating heart arch vessel reconstruction. During
the initial cooling phase, on a beating heart, the left carotid artery
(LCA) and the left subclavian artery (LSA) are isolated and prepared for
selective cannulation with the interposition of a 8---10 mm Dacron graft
(respectively for LCA and LSA) to avoid direct cannulation of the artery
(Figure 1). The vessel perfusion is sequentially started to achieve
complete antegrade cerebral perfusion. Bladder and esophageal
temperature are monitored. Right atrium and right superior pulmonary
vein are cannulated for venous return and venting.

After debranching completion at 30\selectlanguage{ngerman}°C core temperature, the aorta is
cross-clamped and opened and a single dose of Custodiol® cardioplegia is
administered for cardiac protection. Proximal aortic reconstruction
varies according to underlying pathology. Patients are cooled to 26°C
for hypothermic circulatory arrest and the brachiocephalic artery
clamped and selective antegrade perfusion begun at 10---12 mL/kg/min,
consequently stopping systemic circulation. INVOS is monitored and
radial pressure maintained at 60---80 mmHg. The aortic arch is then
opened and inspected.

The landing zone (usually zone 2) is reinforced with Teflon strip and,
eventually, bioglue. At this stage, the distal stent-graft of the FET
device is released into the descending thoracic aorta. The reinforced
collar of the prosthesis is sutured to the aortic isthmus and, after
cannulation of the fourth lateral branch and careful de-airing, systemic
perfusion resumed, starting to rewarm the body. The anastomosis between
the surgical graft and sinotubular junction (either native or
prosthetic, depending on the proximal repair) is completed and
cross-clamp released. The prosthesis-elongated supra-aortic vessels are
then end-to-end sequentially re-anastomosed to the corresponding
branches of the graft, starting with the LSA to LCA and finally
brachiocephalic artery. The correct deployment and fully expansion of
the prosthesis is assessed by TEE.

\textbf{Cerebral and Systemic Perfusion}

Extracorporeal circulation and cerebral antegrade perfusion are
performed using a homemade, 4-branched perfusion circuit (Figure 2). It
consists of four branches of the same diameter driven by a single pump
LSA, LCA, brachiocephalic artery and prosthetic branch for systemic
perfusion. Perfusion is kept at full flow for CPB and it redistributes
depending on physiological systemic resistance. When the brachiocephalic
artery is clamped, the flow is lowered to 10---12 mL/Kg/min for isolated
cerebral perfusion. After the circulatory arrest time the full flow was
restarted via prosthetic side branch and single cerebral vessels.

\textbf{Endpoints}

The primary endpoints of the study were 30-day and in-hospital
mortality, defined as death due to any cause during postoperative course
at 30 days and until discharge, usually to a rehabilitation unit,
respectively. Secondary endpoints included post-operative major stroke
(defined as clinical and radiological evidence of a new postoperative
cerebrovascular event {[}CVA{]} with a mRS \selectlanguage{english}[?] 4), spinal cord injury
(SCI) temporary or permanent, return to operating room for cardiac
causes, renal failure requiring replacement therapy, respiratory
insufficiency requiring prolonged ventilation and/or tracheostomy, deep
sternal wound infection involving sternal bone and/or mediastinal
structures, recurrent laryngeal nerve palsy and in-hospital length of
stay.

\textbf{Statistical Analysis}

Data are presented as mean and standard deviation (SD) if numerical and
as count and percentages if categorical. Normality was assessed using
Shapiro-Wilk test. Continuous numerical variables have been compared
using the Student t-test, while categorical variables have been compared
with chi-square test or Fisher exact test as appropriate. Time to event
analysis has been conducted using Log-rank test and displayed with
Kaplan-Meier curves. Univariable and Multiple Cox proportional Hazard
models were run to identify potential factors affecting mid-term
survival with hazard ratios (HR) and confidence intervals (CI). The
final multivariable model was obtained using those variables that had a
significant p-value at the univariable analysis with backward/forward
selection based on AIC. Alpha error was set at 0.05 for significance and
all tests are two-sided. The statistical analysis was conducted with R
version 3.6.0 (2019-04-26; R Core Team (2019). R: A language and
environment for statistical computing. R Foundation for Statistical
Computing, Vienna, Austria. URL\emph{https://www.R-project.org/}.)

\textbf{RESULTS}

Between December 2017 and May 2020, 70 consecutive patients (mean age
62.7+-10.6 years, 84\% male) underwent FET for arch and thoracic aorta
pathologies, 41 (58.6\%) acute aortic dissections (AAD) and 29 (41.6\%)
chronic pathologies: ascending aorta/aortic arch aneurysm (An) in 19
(24.3\%) and chronic type I dissection (CAD) in 10 (14.2\%). The
distributions of baseline characteristics for the overall population are
presented in Table 1. Twelve (17.1\%) patients had already undergone
cardiac surgery. Fifteen AAD patients (36.5\%) presented with peripheral
malperfusion. There were no significant differences in terms of age,
gender and other preoperative comorbidities between the groups. The only
significant difference was previous cardiac surgery (redo) (4.9\% in
emergency group vs. 34.5\% in elective group, P\textless{}0.01) Patients
presenting in emergency setting had a higher incidence of malperfusion
but this difference did not reach statistical significance.

No intraoperative deaths were recorded. Operative characteristics and
their distributions among the two groups are showed in Table 2.
Concomitant procedures were required in 36 (51.4\%) patients: 12
(17.1\%) coronary artery bypass grafting, 10 (14.3\%) aortic valve
replacement, 14 aortic root surgery such as 9 (12.9\%) Florida sleeve
procedures and 5 (7.1\%) modified Bentall. There was a statistically
significant difference between the two groups in terms of
cardiopulmonary bypass time (212.9+-42.7 minutes in the emergency group
vs. 175.5+-51.1 minutes in the elective group, P\textless{}0.01) and
aortic cross clamp time (123.8+-38.9 minutes in the emergency group vs.
87.1+-31.9 in the elective group, P\textless{} 0.01). The mean deep
hypothermic circulatory arrest time was 30.6+-6 minutes and did not
differ among the two groups.

Postoperative outcomes are summarized in Table 3. Thirty-day mortality
was 10.0\% (n=7) for the entire cohort of patients (12.1\% in emergency
vs. 6.8\% in chronic settings, P=0.421). Cumulative in-hospital
mortality was 14.2\% (n=12, 17.1\% in emergency vs. 10.3\% in chronic
settings, P=0.312). No differences were found in terms of postoperative
CVA (mRS 5/6, 2.4\% in the emergency group vs. 0\% in the elective
group, P=1), SCI with paraplegia (2.4\% in the emergency group vs. 0\%
in the elective group, P=1) and AKI requiring hemodialysis (31.7\% in
the emergency group vs. 20.7\% in the elective group, P=0.454). The
incidence of respiratory failure requiring tracheostomy did not differ
between the two groups (31.7\% vs 24.1\%, P=0.673).

The final multivariable Cox proportional hazard model showed that higher
LVEF (HR, 0.93; 95\% CI 0.88---0.99; P=0.03) was a protective factor for
mid-term survival, while cerebral malperfusion at presentation (HR,
4.42; 95\% CI, 1.19---16.33; P=0.03) and aortic cross-clamp time (HR,
1.01; 95\% CI, 1---1.02; P=0.05) were found to be independent predictor
factors affecting mid-term survival. Emergency surgery did not
significantly impact on long-term survival (elective HR, 0.60; 95\% CI,
0.21--1.7; P=0.33).

There were no aortic re-interventions in either group. Five patients
with residual type B dissection underwent TEVAR successful completion of
repair which was performed at least 6 weeks after the primary operation
in order to reduce the spinal cord ischemia risk. There was no dSINE and
no intraluminal thrombosis.

Median follow-up was 12.5 months (IQR 3.9---22.3). Overall survival for
the entire cohort at 3 months, 6 months, 12 months and 24 months was
90\% (95\% CI, 83.2---97.3), 85.6\% (95\% CI, 77.7---94.3), 79.1\% (95\%
CI, 69.9---89.5), 75.6\% (95\% CI, 65.8---86.9) and 73.5 (95\% CI,
63.3---85.3), respectively (Figure 3). Survival rate by group were
85.2\% vs. 86.1\% at 3 months, 77.3\% vs. 82.2\% at 6 months, 71.7\% vs.
82.2\% at 12 months and 68.6\% vs. 82.2\% at 24 months, all emergency
vs. elective, respectively (Figure 4).

\textbf{DISCUSSION}

Surgical repair of aneurysms and aortic dissections involving the aortic
arch is still challenging, carrying high mortality and morbidity. Our
experience with the first 70 consecutive patients treated with FET using
Thoraflex Hybrid has been overall satisfactory; technical success was
achieved in all patients even in the first part of our experience,
started after performing only conventional elephant trunk (ET) or
conventional surgery in acute dissection (ascending aorta or hemiarch
replacement). Our results show that the implantation technique for
Thoraflex Hybrid graft is doable and reproducible, also in acute
setting.

Correct cerebral perfusion during hypothermic circulatory arrest is one
of the main factors determining neurological
outcomes.\textsuperscript{7--9} Our strategy allows a uniform cerebral
perfusion throughout the operation, except for the short time needed for
LCA and LSA anastomosis, thus minimizing cerebral ischemia time. We
believe that this technical aspect is important to explain our
particularly good results in terms of neurological complications, with a
significantly lower overall incidence of permanent stroke (1.4\%)
compared to data from similar studies.\textsuperscript{7} Shresta et al.
reported 8\% of major CVA in their first experience in performing a FET
with the Thoraflex with a different brain protection strategy, while Chu
et al. reported a 5\% stroke incidence.\textsuperscript{10,11} In
addition to our cerebral perfusion strategy, we believe that our
technique, avoiding direct cannulation and manipulation of cerebral
vessels, could reduce the embolism rate thus helping to minimize CVA
complications.

Another interesting finding from our study is the very low rate of
spinal cord injury which occurred in only one patient (1.4\%) operated
for acute aortic dissection. We believe that our good results are due to
the use of a combination of 100 mm stented length (less intercostal
arteries coverage), Thoraflex Hybrid deployment in zone 2, short
circulatory arrest time and correct sizing of the stented
graft.\textsuperscript{12} Fiorentino et al reported a low overall
incidence of SCI (two cases of temporary isolated papaparesis) but only
in 150 mm distal stented grafts.\textsuperscript{13} Flores et al
reported a very high incidence of SCI in FET when the stented was
deployed at the lower level of the thoracic aorta.\textsuperscript{14}

It has been reported that in Thoraflex implant the LSA anastomosis
remains the Achilles heel being too close to the collar
device.\textsuperscript{11} We overcome this problem by extending the
surgical incision with a small left supra-clavicular cervicotomy and
``elongating'' the LSA with a tubular prosthesis, thus making the
anastomosis technically easier and achieving success in all cases. In
one case, not included in this series, we successfully used a
custom-made Thoraflex Hybrid, in which the plexus is separated from the
main part of the prosthesis, in order to make anastomosis easier,
improve operating times and correctly position the intra-thoracic
vessels.\textsuperscript{15}

Overall survival for the entire cohort at 30 days was 90\% (95\% CI,
83.2---97.3), without statistically significant differences between
emergency and elective surgery (87.9\% vs. in emergency vs. 93.2\% in
chronic settings, P=0.312).

We believe that our results should contribute to encourage employing
this surgical strategy, especially in emergency setting where the FET
may be helpful particularly in patients with malperfusion and could
result in a definitive treatment. The idea of specialized centers with a
high volume of aortic surgery to treat both chronic and acute aortic
syndrome is now becoming paramount. There is a large consensus that
patients affected by acute aortic syndromes may benefit from treatment
at dedicated specialized aortic centers with significantly improved
outcomes and decreased mortality. Patients undergoing emergency repair
of acute aortic dissection by lower-volume surgeons and centers have
approximately double the risk-adjusted mortality of patients undergoing
repair by the highest volume care providers.\textsuperscript{16} We
think that the future treatment of acute type A aortic dissection is
going toward a total arch approach with standardized cerebral protection
that should more and more be delivered by specialist aortic centers with
expertise in this technique. In this case the Thoraflex Hybrid proved to
be an easy-to-implant prosthesis, making the brain protection strategy
easier and reporting a low complication rate.

Finally, an important aspect of our study is the relatively large number
of cases done in a short period of time in a single institution, thus
allowing for a significant reduction of multicenter studies bias. Other
series available in literature report results of a similar cohort of
patients but operated in different centers: the Canadian experience
enrolled 40 consecutive cases in 9 different centers, in about 3 years
of activity while the English experience counts 66 cases in 4 years from
9 centers throughout UK.\textsuperscript{17}

\textbf{STUDY LIMITATIONS}

Due to the relatively low complication rate and limited follow-up, it
was not possible to detect differences between the groups or
pathologies. At present, the follow-up has a shorter duration compared
to other series.

\textbf{CONCLUSIONS}

Surgical techniques involving stenting of the descending thoracic aorta
during primary surgery for both acute and chronic complex aortic disease
involving the arch are associated with promising early and midterm
results. Result of this study and growing evidence in the literature
suggest that FET in acute aortic dissection should also be routine when
performed by experienced operators in dedicated aortic centers.

\emph{}

Figure legends

\begin{enumerate}
\tightlist
\item
  \textbf{Figure 1:} \emph{selective cannulation of left carotid artery
  (LCA) and the left subclavian artery (LSA) with interposition of a
  Dacron graft}
\item
  \textbf{Figure 2} . \emph{Homemade perfusion system driven by a single
  pump: 1, right intrathoracic subclavian artery perfusion (systemic
  perfusion); 2, left subclavian artery perfusion; 3, left carotid
  artery perfusion; 4, side branch systemic perfusion}
\item
  \textbf{Figure 3:} \emph{Kaplan--Meier survival curve for the overall
  surgical population.}
\item
  \textbf{Figure 4:} \emph{Kaplan--Meier survival curves between the 2
  groups (raw data). AAD, acute aortic disease treated in emergency
  setting; CAD, chronic aortic disease treated in elective setting.}
\end{enumerate}

\textbf{Author contributions:}

Concept/Design: Masiello, Mastrogiovanni

Data analysis: Bruno, Presutto

Drafting article: Masiello, Chivasso, Cafarelli

Critical revision: Masiello, Mastrogiovanni, Iesu

Approval of article: Iesu

Statistical: Bruno

Data collection: Presutto, Leone, Triggiani, Colombino, Miele

\textbf{Glossary of abbreviations}\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
FET & Frozen elephant trunk\tabularnewline
\midrule
\endhead
SCI & Spinal cord ischemia\tabularnewline
CVA & Cerebrovascular accident\tabularnewline
CSF & Cerebrospinal fluid\tabularnewline
mRS & Modified Rankin scale\tabularnewline
TEE & Transesophageal echocardiography\tabularnewline
LCA & Left carotid artery\tabularnewline
LSA & Left subclavian arterty\tabularnewline
CT & Computed tomography\tabularnewline
CPB & Cardiopulmonary bypass\tabularnewline
CVVH & Continuous veno-venous hemofiltartion\tabularnewline
AKI & Acute kidney injury\tabularnewline
AAD CAD CO & Acute aortic disease Chronic aortic disease Cardiac
output\tabularnewline
\bottomrule
\end{longtable}



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17. Mariscalco G, Bilal H, Catarino P, et al. Reflection From UK Aortic
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Acute Aortic Dissection. \emph{Semin Thorac Cardiovasc Surg} . Published
online April 10, 2019. doi:10.1053/j.semtcvs.2019.03.010\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\textbf{Characteristics} & \textbf{Overall} & \textbf{Emergency} &
\textbf{Elective} & \textbf{p value}\tabularnewline
\midrule
\endhead
& \textbf{N=70} & \textbf{n=41} & \textbf{n=29} &\tabularnewline
Age (years) & 62.76 (10.6) & 61.80 (9.7) & 64.10 (11.9) &
0.38\tabularnewline
Male gender & 59 (84.3) & 35 (85.4) & 24 (82.8) & 1\tabularnewline
COPD & 17 (24.3) & 9 (22.0) & 8 (27.6) & 0.796\tabularnewline
History of hypertension & 65 (92.9) & 38 (92.7) & 27 (93.1) &
1\tabularnewline
CKD & 5 (7.1) & 3 (7.3) & 2 (6.9) & 1\tabularnewline
History of cancer & 6 (8.6) & 2 (4.9) & 4 (13.8) & 0.379\tabularnewline
Peripheral vascular disease & 11 (15.7) & 5 (12.2) & 6 (20.7) &
0.53\tabularnewline
Previous cardiac surgery & 12 (17.1) & 2 (4.9) & 10 (34.5) &
0.004\tabularnewline
Left Ventricle Ejection Fraction (\%) & 58.11 (6.18) & 57.44 (7.26) &
59.07 (4.16) & 0.28\tabularnewline
Cerebral malperfusion at presentation & 4 (5.7) & 4 (9.8) & 0 (0) &
na\tabularnewline
Abdominal malperfusion at presentation & 5 (7.1) & 5 (12.2) & 0 (0) &
na\tabularnewline
Lower limb ischemia at presentation & 6 (8.6) & 6 (14.6) & 0 (0) &
na\tabularnewline
Ascending aorta/arch aneurysm & 19 (24.3) & 0 (0) & 19 (65.5) &
\textless{}0.001\tabularnewline
Chronic aortic dissection & 10 (14.2) & 0 (0) & 10 (31) &
0.001\tabularnewline
De Bakey dissection classification & & & &
\textless{}0.001\tabularnewline
I & 44 (62.8) & 38 (92.7) & 6 (20.6) &\tabularnewline
III B & 7 (10.0) & 3 (7.3) & 4 (13.7) &\tabularnewline
Stanford dissection classification & & & &
\textless{}0.001\tabularnewline
A & 42 (61.8) & 38 (92.7) & 4 (14.8) &\tabularnewline
B & 9 (12.8) & 3 (7.31) & 6 (20.6) &\tabularnewline
\textbf{Table 1. Preoperative Characteristics:} \emph{COPD, Chronic
Obstructive Pulmonary Disease; CKD, Chronic Kidney Disease. Data are
reported as mean (SD) for numerical variables and as count (\%) for
categorical variables.} & \textbf{Table 1. Preoperative
Characteristics:} \emph{COPD, Chronic Obstructive Pulmonary Disease;
CKD, Chronic Kidney Disease. Data are reported as mean (SD) for
numerical variables and as count (\%) for categorical variables.} &
\textbf{Table 1. Preoperative Characteristics:} \emph{COPD, Chronic
Obstructive Pulmonary Disease; CKD, Chronic Kidney Disease. Data are
reported as mean (SD) for numerical variables and as count (\%) for
categorical variables.} & \textbf{Table 1. Preoperative
Characteristics:} \emph{COPD, Chronic Obstructive Pulmonary Disease;
CKD, Chronic Kidney Disease. Data are reported as mean (SD) for
numerical variables and as count (\%) for categorical variables.} &
\textbf{Table 1. Preoperative Characteristics:} \emph{COPD, Chronic
Obstructive Pulmonary Disease; CKD, Chronic Kidney Disease. Data are
reported as mean (SD) for numerical variables and as count (\%) for
categorical variables.}\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
& \textbf{Overall} & \textbf{Emergency} & \textbf{Elective} & \textbf{p
value}\tabularnewline
\midrule
\endhead
& \textbf{N=70} & \textbf{n=41} & \textbf{n=29} &\tabularnewline
CPB time (min) & 197.46 (49.49) & 212.95 (42.47) & 175.55 (51.08) &
0.001\tabularnewline
Aortic cross-clamp time (min) & 108.64 (40.29) & 123.85 (38.89) & 87.14
(31.97) & \textless{}0.001\tabularnewline
HCA time (min) & 30.61 (6.80) & 29.63 (6.06) & 32.00 (7.63) &
0.153\tabularnewline
Concomitant procedures & & & &\tabularnewline
CABG & 12 (17.1) & 8 (19.5) & 4 (13.8) & 0.762\tabularnewline
AV Replacement & 10 (14.3) & 4 (9.8) & 6 (20.7) & 0.347\tabularnewline
Aortic root surgery & & & &\tabularnewline
Florida Sleeve & 9 (12.9) & 8 (19.5) & 1 (3.4) & 0.106\tabularnewline
Modified Bentall & 5 (7.1) & 5 (12.2) & 0 (0.0) & 0.139\tabularnewline
\textbf{Table 2. Operative carachteristics\emph{:}} \emph{CPB, Cardio
Pulmonary Bypass; HCA, Hypotermic Circulatory Arrest (including
selective antegrade cerebral and visceral perfusioin); CABG, Coronary
Artery Bypass Graft; AV, Aortic Valve. Data are reported as mean (SD)
for numerical variables and as count (\%) for categorical variables.} &
\textbf{Table 2. Operative carachteristics\emph{:}} \emph{CPB, Cardio
Pulmonary Bypass; HCA, Hypotermic Circulatory Arrest (including
selective antegrade cerebral and visceral perfusioin); CABG, Coronary
Artery Bypass Graft; AV, Aortic Valve. Data are reported as mean (SD)
for numerical variables and as count (\%) for categorical variables.} &
\textbf{Table 2. Operative carachteristics\emph{:}} \emph{CPB, Cardio
Pulmonary Bypass; HCA, Hypotermic Circulatory Arrest (including
selective antegrade cerebral and visceral perfusioin); CABG, Coronary
Artery Bypass Graft; AV, Aortic Valve. Data are reported as mean (SD)
for numerical variables and as count (\%) for categorical variables.} &
\textbf{Table 2. Operative carachteristics\emph{:}} \emph{CPB, Cardio
Pulmonary Bypass; HCA, Hypotermic Circulatory Arrest (including
selective antegrade cerebral and visceral perfusioin); CABG, Coronary
Artery Bypass Graft; AV, Aortic Valve. Data are reported as mean (SD)
for numerical variables and as count (\%) for categorical variables.} &
\textbf{Table 2. Operative carachteristics\emph{:}} \emph{CPB, Cardio
Pulmonary Bypass; HCA, Hypotermic Circulatory Arrest (including
selective antegrade cerebral and visceral perfusioin); CABG, Coronary
Artery Bypass Graft; AV, Aortic Valve. Data are reported as mean (SD)
for numerical variables and as count (\%) for categorical
variables.}\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
& \textbf{Overall} & \textbf{Emergency} & \textbf{Elective} & \textbf{p
value}\tabularnewline
\midrule
\endhead
& \textbf{N=70} & \textbf{n=41} & \textbf{n=29} &\tabularnewline
30-day mortality & 7 (10.0) & 5 (12.1) & 2(6.8) & 0.421\tabularnewline
In-hospital mortality & 10 (14.3) & 7 (17.1) & 3 (10.3) &
0.312\tabularnewline
Prolonged ventilation & 23 (32.9) & 15 (36.6) & 8 (27.6) &
0.595\tabularnewline
ICU duration (days) & 15.77 (16.6) & 16.95 (17.9) & 14.10 (14.7) &
0.485\tabularnewline
Hospitalization (days) & 32.11 (21.6) & 31.56 (23.7) & 32.90 (18.5) &
0.801\tabularnewline
Return to operating room & 8 (11.4) & 6 (14.6) & 2 (6.9) &
0.535\tabularnewline
Low CO syndrome & 32 (45.7) & 21 (51.2) & 11 (37.9) &
0.392\tabularnewline
Respiratory failure & 42 (60.0) & 25 (61.0) & 17 (58.6) &
1\tabularnewline
Tracheostomy & 20 (28.6) & 13 (31.7) & 7 (24.1) & 0.673\tabularnewline
Anaemia & 55 (78.6) & 32 (78.0) & 23 (79.3) & 1\tabularnewline
Pericardial effusion requiring drainage & 16 (22.9) & 12 (29.3) & 4
(13.8) & 0.219\tabularnewline
Pleural effusion requiring drainage & 15 (21.4) & 12 (29.3) & 3 (10.3) &
0.108\tabularnewline
Deep sternal wound infection & 7 (10.0) & 6 (14.6) & 1 (3.4) &
0.258\tabularnewline
Recurrent laryngeal nerve palsy & 8 (11.4) & 6 (14.6) & 2 (6.9) &
0.535\tabularnewline
AKI requiring CVVH & 19 (27.1) & 13 (31.7) & 6 (20.7) &
0.454\tabularnewline
Spinal cord injury/paraplegia & 1 (1.4) & 1 (2.4) & 0 (0.0) &
na\tabularnewline
Permanent CVA & 1 (1.4) & 1 (2.4) & 0 (0.0) & na\tabularnewline
Lower limb ischemia & 1 (1.4) & 1 (2.4) & 0 (0.0) & na\tabularnewline
\textbf{Table 3. Postoperative Outcomes\emph{: ICU, Intensive Care Unit;
CO, Cardiac Output; AKI, Acute Kidney Injury; CVVH, Continuous
Veno-Venous Haemofiltartion; CVA, Cerebrovascural accident. Data are
reported as mean (SD) for numerical variables and as count (\%) for
categorical variables.}} & \textbf{Table 3. Postoperative
Outcomes\emph{: ICU, Intensive Care Unit; CO, Cardiac Output; AKI, Acute
Kidney Injury; CVVH, Continuous Veno-Venous Haemofiltartion; CVA,
Cerebrovascural accident. Data are reported as mean (SD) for numerical
variables and as count (\%) for categorical variables.}} & \textbf{Table
3. Postoperative Outcomes\emph{: ICU, Intensive Care Unit; CO, Cardiac
Output; AKI, Acute Kidney Injury; CVVH, Continuous Veno-Venous
Haemofiltartion; CVA, Cerebrovascural accident. Data are reported as
mean (SD) for numerical variables and as count (\%) for categorical
variables.}} & \textbf{Table 3. Postoperative Outcomes\emph{: ICU,
Intensive Care Unit; CO, Cardiac Output; AKI, Acute Kidney Injury; CVVH,
Continuous Veno-Venous Haemofiltartion; CVA, Cerebrovascural accident.
Data are reported as mean (SD) for numerical variables and as count (\%)
for categorical variables.}} & \textbf{Table 3. Postoperative
Outcomes\emph{: ICU, Intensive Care Unit; CO, Cardiac Output; AKI, Acute
Kidney Injury; CVVH, Continuous Veno-Venous Haemofiltartion; CVA,
Cerebrovascural accident. Data are reported as mean (SD) for numerical
variables and as count (\%) for categorical variables.}}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 4. Univariable and Multivariable Cox Proportional Hazard
Model}\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
Variables & HR\tabularnewline
Age, years & 1.05\tabularnewline
Gender, Male & 0.38\tabularnewline
LVEF (perc.) & 0.94\tabularnewline
COPD & 0.97\tabularnewline
PVD & 2.40\tabularnewline
History of CAD & 1.40\tabularnewline
Previous cardiac surgery & 0.62\tabularnewline
Cerebral malperfusion & 3.74\tabularnewline
Abdominal malperfusion & 2.75\tabularnewline
Peripheral malperfusion & 2.43\tabularnewline
CPB time (min) & 1.01\tabularnewline
Cross clamp time (min) & 1.01\tabularnewline
Cerebral perfusion time (min) & 0.98\tabularnewline
Elective surgery & 0.60\tabularnewline
\textbf{Table 4. Univariable and Multivariable Cox Proportional Hazard
Model:} \emph{CI=Confidence Intervals, AMI= acute myocardial infarction,
LVEF= left ventricular ejection fraction, eGFR= effective glomerular
filtration rate, CPB=Cardio-pulmonary bypass. Data are reported as mean
(SD) for numerical variables and as count (\%) for categorical
variables.} & \textbf{Table 4. Univariable and Multivariable Cox
Proportional Hazard Model:} \emph{CI=Confidence Intervals, AMI= acute
myocardial infarction, LVEF= left ventricular ejection fraction, eGFR=
effective glomerular filtration rate, CPB=Cardio-pulmonary bypass. Data
are reported as mean (SD) for numerical variables and as count (\%) for
categorical variables.}\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

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\end{figure}\selectlanguage{english}
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\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

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\end{figure}\selectlanguage{english}
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\includegraphics[width=0.70\columnwidth]{figures/Figure-3/Figure-3}

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\end{figure}\selectlanguage{english}
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\includegraphics[width=0.70\columnwidth]{figures/Figure-4/Figure-4}

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\textbf{Hosted file}

\verb`Table 1.docx`  available at \url{https://authorea.com/users/316415/articles/530680-clinical-outcomes-of-the-frozen-elephant-trunk-procedure-in-70-emergent-and-elective-patients-undergoing-aortic-arch-surgery-the-salerno-experience-with-thoraflex-hybrid}

\textbf{Hosted file}

\verb`Table 2.docx`  available at \url{https://authorea.com/users/316415/articles/530680-clinical-outcomes-of-the-frozen-elephant-trunk-procedure-in-70-emergent-and-elective-patients-undergoing-aortic-arch-surgery-the-salerno-experience-with-thoraflex-hybrid}

\textbf{Hosted file}

\verb`Table 3.docx`  available at \url{https://authorea.com/users/316415/articles/530680-clinical-outcomes-of-the-frozen-elephant-trunk-procedure-in-70-emergent-and-elective-patients-undergoing-aortic-arch-surgery-the-salerno-experience-with-thoraflex-hybrid}

\textbf{Hosted file}

\verb`Table 4.docx`  available at \url{https://authorea.com/users/316415/articles/530680-clinical-outcomes-of-the-frozen-elephant-trunk-procedure-in-70-emergent-and-elective-patients-undergoing-aortic-arch-surgery-the-salerno-experience-with-thoraflex-hybrid}

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