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\begin{document}

\title{The impact of age in acute type A aortic dissection}



\author[1]{Junxia Wang}%
\author[1]{Yunxing Xue}%
\author[2]{Xiyu Zhu}%
\author[1]{Zhong Chen}%
\author[3]{Qing Zhou}%
\author[3]{Hoshun Chong}%
\author[4]{Jason Qu}%
\author[3]{Dongjin Wang}%
\affil[1]{Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital}%
\affil[2]{Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University}%
\affil[3]{Affiliation not available}%
\affil[4]{Massachusetts General Hospital, Harvard Medical School}%


\vspace{-1em}



  
  \date{May 29, 2024}


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\selectlanguage{english}
\begin{abstract}
Background: Acute type A aortic dissection (aTAAD) is a lethal disease
and age is an important risk factor for outcomes. This retrospective
study was to analyze the impact of age stratification in aTAAD. Methods:
From January 2011 to December 2019, 1092 aTAAD patients from Nanjing
Drum Tower Hospital received surgical therapy. Patients were divided
into seven groups according to every ten-year interval (20s-80s). The
differences between the groups were analyzed in terms of the baseline
preoperative conditions, surgical methods, and postoperative outcomes of
patients of different age groups. During a median follow-up term of 17
months, the survival rates were compared among seven groups through
Kaplan-Meier analysis. Results: The median age was 52.0 years old in the
whole cohort. The multiple comorbidities were more common in old age
groups (60s, 70s, 80s), while the 20s group patients had the highest
proportion of Marfan syndrome (28.1\%). Preoperative hypotension was
highest in 80s (16.7\%, P=0.038). Young age groups (20s-60s) had a
higher rate of root replacement and total arch replacement, which led to
a longer duration of operation and hypothermic circulation arrest. The
overall mortality was 14.1\%, the tendency of mortality was increased
with age except 20s group (33.3\% in 80s, P=0.016). The postoperative
morbidity of gastrointestinal bleeding and bowel ischemia were 16.7\%
and 11.1\% in 80s group. Conclusion: Age is a major impact factor for
aTAAD surgery. Old patients presented more comorbidities before surgery,
the mortality and complications rate were significantly higher even with
less invasive and conservative surgical therapy.%
\end{abstract}%



\sloppy


\textbf{1. Introduction}

Age has shown to be a strong independent impact factor of outcomes in
acute type A aortic dissection (aTAAD), while treatment strategies and
surgical methods differentiate according to age stratification. Old age
has long been thought to increase the risk of surgery, which likely
explains the higher rate of medical therapy especially in patients older
than 70 years old \textsuperscript{1}. As the population ages and
surgical techniques continue to improve, advanced age is no longer a
major deterrent of surgical repair of aTAAD albeit conservative therapy
is chosen by patients and physicians \textsuperscript{2,3}. Studies have
shown that the average age of patients with aTAAD is 55 years old in
China, a decade younger than that in the western
countries\textsuperscript{4,5}. With the recent improvement in surgical
techniques and perioperative management, an extensive one-stage surgery,
total arch replacement and frozen elephant trunk, has become the
preferred the surgical strategy in China\textsuperscript{6,7}. There are
more reports on one-stage total aortic arch replacement in other
counties.

As the number of patients with aTAAD increases in age groups in China,
especially in the groups of 60-80 years of age, the long-term survival
of this extensive surgery is largely unknown. Should age be factored in
the consideration before such an extensive surgery be planed? The
age-stratified clinical characteristics, treatment strategies, and
outcomes in Chinese patients are not yet known. The aim of this
retrospective study is to investigate the clinical characteristics,
treatment strategy and surgical outcomes of aTAAD in different age
stratification groups in our center.

\textbf{2. Methods}

\textbf{2.1 Patients}

Between January 2011 and December 2019, a total of 1174 patients with
aTAAD were admitted to Nanjing Drum Tower Hospital (NDTH). Patients were
divided into seven groups according to every ten-year interval
(20s-80s). Diagnosis of aTAAD was confirmed by computed tomographic
angiography (CTA) scanning within two weeks after the onset of symptoms.

All clinical data were collected prospectively by admission and during
the in-hospital stay. We retrieved the data retrospectively by review of
hospital records. The study was conducted in accordance with the
Declaration of Helsinki (as revised in 2013). The current study was
approved by the institutional review board of Nanjing Drum Tower
Hospital (2020-185-01).

\textbf{2.2 Treatment}

All patients diagnosed with aTAAD were transferred to cardiac surgery
intensive care unit and optimal medical therapy was initiated. Open
surgery was recommended for all patients, but for patients with advanced
age, dissection associated organ malperfusion or family refusal, medical
therapy was the treatment of choice. The patients received open surgery
underwent general anesthesia via a standard median sternotomy after
signing the informed consents. Cardiopulmonary bypass (CPB) was
initiated with femoral artery or axillary artery arterial cannulation
and right atrium or superior/inferior venous cannulation. Deep or mild
hypothermic circulatory arrest (HCA) was used in all patients. Selective
antegrade or retrograde cerebral perfusion was applied for brain
protection during the period of HCA at operating surgeon's choice. The
distal aortic arch surgical strategy included partial arch replacement,
total arch replacement with or without frozen elephant trunk (Microport
Corp.Ltd, Shanghai, China) and arch stent (Yuhengjia Sci Tech Corp.Ltd,
Beijing, China) based on the pathological involvement of the aortic
arch\textsuperscript{7-9}. After finishing the distal repair, the
re-warming stage begun as the proximal part of aorta or root was being
reconstructed and the patients were weaned off CPB. Bentall procedure or
root reinforcement reconstruction was applied based on the anatomic
indications \textsuperscript{10,11}. The patients were transferred to
the floor after recovering in cardiac surgery ICU, and discharged from
the hospital per institution protocol.

\textbf{2.3 Statistical analysis}

Statistical analysis was performed with SPSS 26.0 (IBM Corp. Released
2019. IBM SPSS Statistics for Macintosh, Version 26.0. Armonk, NY: IBM
Corp.). Descriptive statistics were used to describe patient
characteristics throughout the study. Means and standard deviations were
presented for normally distributed continuous variables whereas median
and the interquartile ranges were computed to describe non-normally
distributed continuous data. Categorical data are presented as frequency
distributions and simple percentages. Between group differences were
analyzed using a Student's t-test,Kruskal-Wallis H test or Mann-Whitney
U-test for continuous variables and a Chi-square or Fisher's exact test
for categorical variables. The survival curve was draw using
Kaplan-Meier method and compared using the log-rank test. The median
follow-up time was calculated with reverse Kaplan-Meier method.
Statistical significance was considered when P \textless{} 0.05.

\textbf{Results}

\textbf{Demographics and Preoperative characteristics}

Eighty-two of the 1174 aTAAD patients chose medical management that was
chosen by 30.8\% of patients in 80 years group due to rupture of the
dissection (Figure 1a/b). The patients aged 40-60 years constituted the
largest proportion of patients (71.2\%) and the youngest 20s (2.9\%) and
oldest 80s (1.6\%) groups accounted for minimum percentage of patients.
There was higher proportion of female patients as age increases.

Further analysis showed that the 20s group patients had the highest
proportion of connective tissue diseases (Marfan's syndrome) (28.1\%).
History of hypertension was present in 63 \% patients ages between 40-70
years old and hypotension on admission was highest in 80s group (16.7\%,
P=0.038). (Table 1). The average BMI was 25.6 with the highest 33.1 in
30s group and lowest 19.5 in 80s group. There is significantly increased
history of stroke(9.6\% vs 1.9\%, OR=5.5, 95\% CI 2.6-11.5) , coronary
artery disease (CAD)(5.9\% vs 2.0\%, OR=3.1, 95\% CI 1.3-7.2)in
patients over 70 years old.

Pain was the main presenting symptom, while chest pain presented as
similar among groups. Preoperative malperfusion were present in 34\% of
patients with no significant difference among age groups.

\textbf{3.2 Operative characteristics}

The duration of surgery, CPB, X-clamp and HCA decreased with advanced
age starting from age group of 50 years old. Cannulating both femoral
and axillary artery were preferred arterial cannulation approach
compared to single femoral or axillary artery. Bentall procedure
accounted for a large part of root methods in young age group (43.8\% in
20s) and total arch replacement with FET had a higher rate in age group
of 50s(45.8\%), 60s(41.7\%) than the 70s(26.3\%) and 80s (16.7\%)(P
\textless{} 0.001)(Table 2).

\textbf{3.3 Immediate postoperative outcomes}

One hundred and fifty-four patients (14.1\%) died within 30 days after
surgery, 93 (60.4\%) from circulatory failure, 21 (13.6\%) neurological
complications, 15 (9.7\%) aortic rupture, 13 (8.4\%) respiratory failure
or other reasons, 12 (7.8\%) gastrointestinal bleeding or ischemia,
(Table 3). Group 80s had significantly higher mortality than group 70s
(33.3\% vs 18.6\%, p=0.016) (Figure 2a). A decreasing trend of mortality
rate in 70s and 80s group was shown with year (Figure 2b). Age was
related to postoperative complications. The stroke rates (died and not
died) were 8.5\%, 5.1\% and 5.6\% in 60s, 70s and 80s group
respectively. Among patients succumbed in the 80 year group, there were
significant high rate of GI bleeding and ischemia (16.7\% and 11.1\%,
respectively) compared with other groups of 50s, 60s and 70s (1.4\%,
0\%, 0.8\%, respectively ). The 70s group had higher duration of ICU
stay when compared with other groups ( 20s group: p=0.048, 30s group:
p=0.047, 50s group: p=0.011); however, the duration of hospital stay
showed no significant difference in all age groups. There was no
significant difference in mechanical ventilation, reintubation,
tracheotomy, neurological complications, renal complications and
re-exploration. The 20s group showed lowest postoperative neurological
and gastrointestinal complications as they presented at admission.
(Table 3).

\textbf{3.4 Follow-up}

927 (84.9\%) patients completed followed up and the median follow-up was
17 months (1-102months). The 17-month survival rate was 82\%. Thirty-
eight discharged patients died during follow-up, 1(3.1\%) in 20s group,
4(12.5\%) in 30s group, 8(25\%) in 40s group, 7(21.9\%) in 50s group,
9(28.1\%) in 60s group, 8(25\%) in 70s group, and 1(3.1\%) in 80s group.
Figure 3a shows the mortality associated with age, the general tendency
is that mortality increases with increasing age, 15.6\% in 20s group,
7.5\% in 30s group, 11.7\% in 40s group, 14.3\% in 50s group, 17.1\% in
60s group, 18.6\% in 70s group, and 33.3\% in 80s group; however, the
mortality of patients over 70 years old decreased over these years while
the ratio of these patients remains relatively stable. Among the
patients who died, 10 (26.3\%) from aortic rupture, 5(13.2\%) from
neurological complications, and 2(5.3\%) patients died for stent
leakage. 137 patients had readmissions, of whom 34 (24.8\%) patients had
thoracoabdominal aortic dissection/aneurysm which is the leading cause
of readmission. Figure 3b/3c shows the ratio of patients readmission for
recurrence of aortic dissection, the tendency of readmission for
abdominal aortic dissection decreased with age.

\textbf{Discussion}

The average age of aTAAD patients was significantly younger in China,
the results from Sino-RAD was 50.5 years\textsuperscript{12} and 52
years in our center's previous
reports\textsuperscript{5}.\textsuperscript{13}. In this study, we found
the median age of patients of aTAAD is 52. Furthemore, there was a
significant increasing number of patients underwent aTAAD in the older
patients at their 70s and 80s. There was also significant increase of
aTAAD repair in patients aging 70 years and older. The underlining
reasons maybe multi-factorial. One of the main reasons is the increasing
awareness of aTAAD among the public and emergency room physicians
particularly since the introduction of our aTAAD refereral program (6hr
life circle); the second is attributed to the improvement of surgical
successful rate of aTAAD surgery; and 3\textsuperscript{rd} maybe
related to the recent increase of national and regional healthcare
coverage\textsuperscript{14} and especially in the second half the study
period(2016-2019). For older patients with aTAAD, the optimal
treatment strategy is in debate depending on the risk and benefit ratio
and the upper age limit is unknown. A study by Trimarchi et al using
IRAD data showed that patients older than 70 years old received higher
rates of medical therapy than those of surgical repair (28.6\% vs
10.9\%; p<0.0001), and there was no difference in survival between the
two treatment strategies (55.8\% vs 53.8\%; p=0.32)\textsuperscript{1}.
Our results are consistent with the above findings. The increasing risks
and lower predictable late survival rate contributed to the lower
proportion of open surgery. Many studies have shown that advanced age is
related to poor postoperative survival, the long-term survival and the
quality of daily life\textsuperscript{15-17}. The poor outcome in
patients of advanced age may have deterred the Septuagenarian and
Octogenarian from undergoing extensive total arch surgery because there
is no better alternative treatment such as endovascular repair.

Our present study also demonstrated that the proportion of patients who
received surgical treatment over 70 years old remained relatively stable
in last decade in our center. The higher 30 mortality in this group of
patients suggested the negative impact of surgery on the postoperative
recovery of patients with advanced age. In addition, the favorable long
term survival indicated that the simple or less extensive arch repair is
the preferred surgery for patients over 70 years old. This finding is
also corroborated by other studies \textsuperscript{2,18}.

Chest pain is the common clinical presentations of aTAAD for younger
patients; however, the main etiology of aTAAD for patients in their 20s
is connective tissue disorders, such as Marfan syndrome while history of
hypertension is more common in patients of aging 30, 40 and 50s.
Compared to the patients older than 70 years, the surgical strategies
are totally different. More extensive surgical methods are applied for
younger patients in order to avoid re-intervention because of aortic
events\textsuperscript{19-23} . Our study demonstrated that the
recurrence rate of aTAAD was significantly lower in younger patients
between 30 to 50 years old. The patients of 20s group had the highest
recurrent AD, consistant with the findings in Marfan's syndrome paitents
reported by Isselbacher et al. from the IRAD data\textsuperscript{24}.
The ratio of readmission for aortic dissection is also decreased with
age. Because older patients had more complications than younger
patients. These complications not only affect the time and strategies of
surgery, but also affect the outcomes of the patients. And they had to
have readmission to deal with the complications after surgery. On the
contrary, the 20s group had readmission most likely to deal with the
recurrent aortic dissection. Therefore, extensive surgery strategy with
higher surgical risk could not lower late recurrence and
re-intervention.

The mode of the age was in the 40s group, these patients were at the
middle age of their life. It was necessary to pay more attention to
their long term follow up and the quality of life. In the next years, we
would focus on their changes and show what would happen to these
post-operative aortic dissection patients. For the increasing number of
hypertension patients in China, it was meaningful to know whether the
40s group patients could totally recovery from the emergency surgery and
go back to the society.

\textbf{Limitations}

First, the retrospective study has its design limitation. Data were
collected retrospectively so there are defects like incomplete, missing
or inaccurate to report the event. The long-term survival rate would be
underestimate as the follow-up interval is large and the follow-up time
of some patients is shorter than one year. Second, The data obtained are
of a single center and therefore could not represent the whole
population. Third, as the number of patients in 20s and 80s group being
limited, there is a need for further studies.

\textbf{Conclusions}

Age is a major impact factor for aTAAD surgery. Old patients presented
more comorbidities before surgery, the mortality and complications rate
were significantly higher even with less invasive and conservative
surgical therapy.

\textbf{References:}

1. Trimarchi S, Eagle KA, Nienaber CA, et al. Role of age in acute type
A aortic dissection outcome: report from the International Registry of
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2. Kondoh H, Satoh H, Daimon T, et al. Outcomes of limited proximal
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3. Suenaga E, Sato M, Fumoto H. Ascending aortic replacement for acute
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4. Rylski B, Suedkamp M, Beyersdorf F, et al. Outcome after surgery for
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\textbf{Figure legends:}

Figure1. a. Number and sex ratio of patients in different age groups of
our center; b. The reason for non-surgery after admission. The main
reason was a rupture.

Figure2. a. Ratio of mortality in different age groups. b. Ratio and
mortality of [?]70 years old patients each year, and the overall mortality
fluctuation from 2011-2019.

Figure3. a. Survival functions of different age groups. b. The
reintervention rate of different age groups. c. The ratio of readmission
for aortic dissection.

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