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\begin{document}

\title{Complicated Type B Aortic Dissection in Late Pregnancy: Management
Strategy and Outcomes}



\author[1]{Zhen Wang}%
\author[1]{Xuechen Yu}%
\author[2]{Shuai Ding}%
\author[2]{Chuan Liang}%
\author[1]{Huijun Chen}%
\affil[1]{Zhongnan Hospital of Wuhan University Department of Obstetrics}%
\affil[2]{Zhongnan Hospital of Wuhan University Department of Cardiovascular Surgery}%


\vspace{-1em}



  
  \date{May 19, 2024}


\begingroup
\let\center\flushleft
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\endgroup





\selectlanguage{english}
\begin{abstract}
\textbf{Objective:} Pregnancy with complicated type B aortic dissection
is a rare but devastating scenario. And there are no definitive
guidelines for management and therapy. We report our exploration and
experiences of managing five pregnant with complicated TBAD in the
second or third trimesters, aiming to propose an appropriate management
strategy. \textbf{Design:} Retrospective study. \textbf{Setting:}
Zhongnan Hospital of Wuhan University. \textbf{Population:} Pregnant
women with TBAD \textbf{Methods:} The clinical data of 5 pregnant women
with TBAD who were admitted to the Zhongnan Hospital of Wuhan University
from January 2022 to June 2023 were collected. The clinical features,
diagnostic procedures, treatment strategies and corresponding maternal
and infant outcomes were retrospectively analyzed. \textbf{Main Outcome
Measures:} The survival of mother and fetus. \textbf{Result:} All five
pregnant women with TBAD were diagnosed with complicated TBAD. The
average age of the patients was (34.8\selectlanguage{ngerman}±8.13) years, and the range of
gestational weeks at admission was 27 weeks plus 3 days to 36 weeks plus
6 days. The first patient intending to receive a cesarean section and
subsequent TEVAR died of rupture of aortic dissection during cesarean
section. Her neonate was successfully rescued. The remaining four
patients who underwent TEVAR first survived. Three underwent
single-stage aortic repair and delivery, and one patient underwent
cesarean section 27 days after TEVAR. Three preterm live births of these
four patients were recorded. During late follow-up, no maternal and
fetal deaths occurred. Neither device-related nor systemic complications
post TEVAR were observed in the mother. Routine physical examinations of
four live births showed no abnormalities. \textbf{Conclusion:} When a
pregnant woman in the second or third trimester has thoracic back pain
and highly suspected aortic dissection, CTA should be performed to avoid
missed diagnosis, misdiagnosis and diagnostic delay. Once diagnosed,
maternal survival should be prioritized over fetal concerns. TEVAR is
safe and feasible for such patients. For complicated TBAD in the third
trimester single-stage delivery and TEVAR are preferred, and TEVAR
followed by cesarean section performed in one operative session is the
treatment of choice.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{Introduction}

Aortic dissection (AD) in pregnancy is a rare and life-threatening
complication. Data from the International Registry of Acute Aortic
Dissection showed that aortic dissection in pregnancy accounts for
0.0004\% of all pregnancies, and 0.1\% to 0.4\% of all aortic
dissection\textsuperscript{1}. Although, it was reported that pregnancy
with type B aortic dissection (TBAD) accounts for 11\% to 21\% of this
disease\textsuperscript{2}. The incidence of TBAD during pregnancy and
puerperium rose from 2002 to 2017 based on the data from the National
Inpatient Sample (NIS) database of the United States\textsuperscript{3}.
Moreover, it was surprising that the hospital mortality of TBAD group
was higher than that of type A AD (TAAD) group. In addition, it was
reported that fetal outcomes were worse in TBAD group due to possible
involvement of the iliac arteries\textsuperscript{4}. Despite the
elevated incidence and serious hazard of pregnant with TBAD, the optimal
management strategy for this disease remains controversial and
undetermined.

For TBAD in pregnancy, current treatment experience is still
insufficient and primarily based on case reports and small case series.
TBAD can be divided into complicated and uncomplicated according to
clinical features and disease severity. Uncomplicated TBAD in is usually
recommended to be treated medically, while complicated TBAD is
preferably treated with thoracic endovascular aortic repair (TEVAR). The
success rate of TEVAR for TBAD in unpregnant people was reported as high
as 97.66\% to 99.20\%\textsuperscript{5}. However, its effectiveness and
safety in TBAD in pregnancy remains uncertain especially taken fetus
life into consideration in late gestation. Therefore, it is necessary to
explore the optimal treatment strategy for patients with TBAD in late
pregnancy. This article summarized the data of five cases with
complicated TBAD in late pregnancy at our center and analyzed the
corresponding maternal and fetal outcomes. The aim of this study is to
investigate an optimal management strategy of pregnant with complicated
type B aortic dissection during the late second or third trimesters.

\textbf{Methods}

\textbf{Study design}

We retrospectively reviewed medical records from five pregnant women
with complicated TBAD admitted to Zhongnan Hospital of Wuhan University
from Jan 2022 to Jun 2023. Stanford classification was adopted in the
study, and TBAD refers to the absence of involvement of the ascending
aorta. Complicated TBAD is defined as the presence of malperfusion
syndrome or rupture. Diagnosis of complicated TBAD was based on clinical
features and CT angiography (CTA) according to the Society of Thoracic
Surgeons/American Association for thoracic surgery clinical practice
guidelines on the management of TBAD\textsuperscript{6}. This study was
reviewed and approved by the Medical Ethical Committee of Zhongnan
Hospital of Wuhan University (approval number 2023216K). Obtaining
patient consent was not required according to the committee's
procedures.

\textbf{Treatment}

Patients were admitted to the hospital through emergency or referral.
After admission, multiple departments, including obstetrics,
anesthesiology, cardiovascular surgery, pediatrics and intensive care
unit (ICU), jointed to formulate combined treatment schemes. The safety
of both mother and fetus was considered, which mother's safety was given
priority. According to the patient's condition, low flow oxygen
inhalation and drugs for pain relief and sedation were given.
Medications were used to maintain systolic blood pressure between 100
and 120 mmHg\textsuperscript{7}, to limit the extension of the
dissection and reduce the risk of developing end-organ damage and
rupture\textsuperscript{8}. The status of the fetus was monitored by
ultrasound and fetal heart electronic monitoring.

All five patients were planned to perform TEVAR and terminate pregnancy
through cesarean section. The timing and method of surgery were
determined by the patient's condition, gestational age and
comorbidities. Cesarean section might be conducted before, immediately
after, or for a period after TEVAR. For patients planning to experience
TEVAR first, the times of arterial imaging should be minimized as much
as possible, and the surgery should be finished within a short time to
reduce the impact of radiation exposure and general anesthesia on the
fetus. For patients undergoing cesarean section, abdominal pressure and
uterotonics should be avoided to minimize the impact on the
cardiovascular system and fluctuations of the hemodynamic. Uterine
artery ligation should be used to prevent postpartum hemorrhage. Infants
were resuscitated by neonatologists according to the Neonatal
Resuscitation Program guidelines. For patients who have not terminated
pregnancy yet, the status of the fetus should be monitored intensively.

\textbf{Follow up}

The patients were followed up for at least three months after discharge.
For mothers, blood routine, coagulation, and other tests were examined
every week after discharge for one month and then detected every month.
CTA testing was performed at one month, six months, 12 months, and then
yearly after discharge to monitor the condition of the affected arteries
and detect any postoperative complications\textsuperscript{7}. For
newborns, the growth and development of infants were monitored by
pediatricians.

\textbf{Data collection}

Socio-demographic variables of patients were collected, including age,
gestation weeks, clinical manifestation, comorbidities, gravidity
history and medical history. Laboratory and imaging examination results
were obtained from medical record. The treatment process was recorded in
detail. Primary outcomes are the survival of mother and fetus. Secondary
outcomes are the completion of coated stent-graft implantation, the
changes in the size of true and false lumens of aortic dissection, and
the occurrence of postoperative complications, including endoleaks,
endograft migration, graft infection, end-organ ischemia,
cerebrovascular and cardiovascular events and post-implantation
syndrome.

\textbf{Results}

\textbf{Clinical and laboratory characteristics}

The clinical and laboratory characteristics of patients are summarized
in Table 1. All patients had complicated TBAD. The age range of the
patients was 27 to 44 years, and the range of gestational weeks at
admission was 27 weeks plus three days to 36 weeks plus six days. Among
these patients, none of them had diabetes, chronic hypertension,
connective tissue disorder, or cardiovascular disease before pregnancy.
However, three patients developed pre-eclampsia during pregnancy. In
addition, all patients were multipara and had a history of cesarean
section. All five patients presented with severe chest pain and/or back
pain. Since the occurrence of thoracic back pain, three patients showed
elevated blood pressure, and two of them had refractory hypertension.
All patient has asymmetric blood pressure. Only one patient had a
cardiac function rating of III, while the other three patients had a
cardiac function rating of II. Additionally, one patient had signs of
threatened premature delivery, including uterine contraction and
cervical shortening.

All five patients had a CTA test after admission and showed typical
signs of complicated TBAD (Figure 1). Three patients' lesions were
evaluated from the aortic arch. In contrast, the lesion formation of
another two patients started distal to the left subclavian artery. Three
patients had imaging evidence of malperfusion, mainly manifested as
extensive arterial involvement, including the renal artery, celiac
trunk, and superior mesenteric artery. The range of aortic width was
18.57-31.35mm. One patient's cardiac ultrasound showed aortic
regurgitation and aneurysmal dilatation of the aortic sinus. Data from
laboratory tests showed that four of the five patients had elevated
level of D-Dimer, with an average of (719 \selectlanguage{ngerman}± 243.79) ng/L. Four patients
had increased lymphocyte ratio (mean value: 86.74\selectlanguage{english} \% +- 7.22\%), three of
which had elevated white blood-cell counts (mean value 13.54 +-
4.54x109/L). Pro-BNP and myocardial enzymes were in the normal range in
all patients.

\textbf{Treatment process}

All five patients received \selectlanguage{greek}β-\selectlanguage{english}blockers to control blood pressure ([?]120/80
mm Hg) and heart rate (\textless{}70 beats/min). Drugs for pain relief
and sedation were also given. Other supporting treatments were applied
according to the patients' condition. All the patients received aortic
repair and cesarean section following the above essential medicine
treatment. The operative data for the five patients is shown in Table 2.

Based on the recommendation of Chinese experts' consensus of
standardized diagnosis and treatment for aortic
dissection\textsuperscript{9}, the first patient with a gestational age
of over 32 weeks, suffering from preeclampsia, underwent a cesarean
section under combined spinal and epidural anesthesia first. However,
she experienced a rapid elevation of blood pressure within minutes after
delivery of the fetus, leading to rupture of dissection. Although a
thoracotomy was performed, the patient died due to hemorrhagic shock.
The newborn of this patient had no asphyxia. Based on the lessons
learned from case one, the subsequent four cases underwent TEVAR first,
followed by a cesarean section under general anesthesia for better
control of blood pressure. Case two completed the TEVAR and cesarean
section without any adverse effects on the mother or fetal outcomes. The
third case chose to continue the pregnancy after TEVAR since her
gestational age was only 27 weeks plus three days. The status of the
mother and fetus was closely monitored by obstetricians and surgeons.
However, she presented with back pain at 30 gestational weeks, and her
CTA showed strip-like leakage of contrast agent into the false lumen. A
cesarean section was performed at 31 weeks plus five gestational weeks
following fetal lung maturation-promoting therapy. Her newborn infant
had mild asphyxia (Apgar score of 7 at 1 min) but recovered well after
primary resuscitation initiated immediately after delivery. The fourth
case had severe preeclampsia and fetal distress before surgery. The
mother experienced a rupture of the right iliac artery during the
pushing stent-graft delivery system, and the bleeding was stopped by
compressing temporarily. She underwent a cesarean section and femoral
iliac artery artificial vascular replacement. The newborn of case four
had a 1-min Apgar score of 5 and a 5-min Apgar score of 2, and the
rescue was given up eventually. With the same procedure as that of the
above patient case, the fifth case also underwent TEVAR and subsequent
cesarean section. The 1-min Apgar score was 5 and the 5-min Apgar score
was 7 for her newborn. Unfortunately, she developed TAAD three days
later. Then, she received total aortic arch artificial vascular
replacement and stent elephant trunk surgery (Sun's Surgery) plus aortic
valve and ascending aortic replacement and coronary transplantation
(Bentall Surgery).

Four preterm live births were recorded. Neonatal death occurred in case
four at a gestational age of 29 weeks plus five days, and the pregnancy
was complicated by fetal distress before surgery. Neonate one and two
had a gestational age exceeding 36 weeks, and Apgar scores at birth were
8 at 1 min and 9 at 5 min. Neonate three and five had a gestational age
of 31 weeks and a birthweight of around 1700g. These two neonates
experienced transient mild asphyxia but were discharged without any
complications. During the follow-up period, routine physical
examinations of four live births showed no abnormalities. Their thyroid
function was within normal range on the 14th day after delivery.

\textbf{Discussion}

Due to the increasing incidence rate and high mortality of TBAD in
pregnancy, the effective rescue procedures and surgical methods of this
disease deserves more concern. To date,there is no specific guideline,
and its treatment experiences are mainly based on case series or a
synthesis of current published opinions\textsuperscript{10}. While TEVAR
has been widely used in complicated TBAD in unpregnant patients and is
increasingly being utilized in pregnant patients for aortic repair, the
literature lacks consensus regarding whether to conducting TEVAR first
or cesarean section. The available literature exhibits divergent
treatment options across different medical centers, with some authors
advocating for aortic repair surgery first and others approving the
priority of caesarean section to avoid the influences of radiation
caused by TEVAR on the neonates\textsuperscript{11-14}.Due to the
different levels of treatment and the severity of the patient's
condition, it is difficult to evaluate the treatment strategies. Here,
we reported clinical data from five patients with complicated TBAD in
late second and third trimester. By exploring the optimal strategy for
complicated TBD in late pregnancy in clinical practice, we found that
TEVAR is safe and feasible. In addition, the strategy of TEVAR first can
avoid rupture of aortic dissection caused by delivery, thus improving
both maternal and fetal outcomes.

\textbf{Clinical implication}

As is known to all, pregnancy is a risk factor for
AD\textsuperscript{15}. Previous studies have reported a higher
incidence rate of TAAD in pregnancy than TBAD\textsuperscript{4, 12}.
However, recent data indicates an increasing trend in the occurrence of
TBAD, especially in women with pregnancy\textsuperscript{3}. Consistent
with this, all five pregnant patients with AD admitted to our hospital
were Stanford type B in the past two years. In our study, advanced in
maternal age, preeclampsia and cesarean delivery may be contributing
risk factors of TBAD, which is consistent with literature
reports\textsuperscript{16, 17}. It is recommended that patients with
high risks for aortic dissection should receive transthoracic ultrasound
every 4-6 weeks of pregnancy as part of routine prenatal
examination\textsuperscript{18}, and should be given more attention to
the occurrence of AD.

Early identification and diagnosis of AD are crucial for treatment.
However, the diagnosis of AD in pregnancy is challenging. The symptoms
vary among patients, especially in those with TBAD, and are easily
confused with physiological discomfort and other diseases during
pregnancy\textsuperscript{19}. Given the rarity of AD, it is easily
misdiagnosed. CTA has high sensitivity and specificity in the detection
of dissection\textsuperscript{20}. However, patients may refuse to
undergo CTA due to concerns about the impact of radiation on the fetus.
In fact, fetal radiation doses delivered by CT examinations are
generally below the consensus levels for negligible risk (\textless{} 50
mGy)\textsuperscript{21}. In addition, although iodinated contrast
agents typically traverse the placenta, the use of contrast agents in
pregnancy is considered relatively safe\textsuperscript{22}.
Transthoracic echocardiography (TTE) is recommended as a preliminary
screening method for pregnant women complicated with AD because of its
high safety and technical popularity\textsuperscript{12, 23}. However,
only lesions near the aortic root can be detected by transthoracic
echocardiography, and missed diagnosis may occur in the diagnosis of
TBAD\textsuperscript{24}. In our study, all five patients were diagnosed
TBAD timely through CTA. Notably, not all the patients had no signs of
TBAD in transthoracic echocardiography. Since cardiac Magnetic Resonance
imaging (MRI) is time-consuming, we did not choose MRI before treatment.
Based on our experience, CTA is the optimal examination for pregnant
patients with suspected TBAD. It can not only quickly detect the
existence of dissection, but also clarify the type and extent of the
lesion. Moreover, CTA can show the iliac artery tortuosity and
pathological changes, which is essential for selecting safest surgical
approaches\textsuperscript{25}.

Complicated TBAD with malperfusion or rupture is considered a medical
emergency and requires surgery management\textsuperscript{26}. In the
endovascular era, new technologies are constantly emerging. TEVAR has
been shown to have lower mortality and morbidity compared with open
aortic repair in patients with TBAD \textsuperscript{27, 28}. Currently,
there are limited reports on the application of TEVAR in pregnant
patients with TBAD. The timing of TEVAR and cesarean section is also
controversial. Considering the negative impact of cardiac surgery on
fetus, a cesarean section was recommended before any surgical
intervention with the mother\textsuperscript{19, 29}. Shu et al.,
reported two cases of TBAD in late pregnancy, who were successfully
treated through TEVAR\textsuperscript{11}. They suggested that for the
late third trimester of pregnancy (beyond 37 weeks gestational age),
emergency intervention on the aorta should be before delivery if
accompanied by the complication\textsuperscript{11}. In our study, the
first case experienced dissection rupture during cesarean section and
died unexpectedly. On the contrary, the following four patients who
underwent TEVAR before cesarean section survived following successful
treatment. Thus, we think that for patients with complicated TBAD in the
third trimester, there is a risk of dissection rupture during delivery.
This may be because of the cessation of placental circulation and an
increase in cardiac blood volume after fetal delivery. Given this,
performing TEVAR first may be a wise choice. Even though, this treatment
method is still challenging as TEVAR may become complex in patients with
late pregnancy. Due to the compression of the uterus, the stent-graft
delivery system is difficult to pass through the iliac artery. One
patient in our study experienced rupture of right iliac artery because
of above reason. Moreover, the amount of radiation was limited for the
safety of the fetus. Thus, TEVAR during pregnancy requires experienced
and skilled cardiac surgeons to ensure the safety and short duration of
the surgery.

Due to the small numbers reported globally, there is a lack of recorded
long-term outcomes for pregnant patients with TBAD who were treated by
TEVAR. The outcomes are satisfying in our series. Despite complications,
such as internal leakage, iliac artery rupture, and progression to TAAD,
which occurred during the treatment process, patients successfully
completed TEVAR and survived. Moreover, no major late complication was
detected, and a recovery of cardiac function was observed at last
follow-up. Another concern for applying TEVAR in pregnancy is the safety
of the fetus. It was reported that the total radiation dose during
endovascular therapy and one year after surgery is lower than 50
mGy\textsuperscript{30}, which is within the safe range for the fetus.
In addition, except for the death of one neonate with preoperative fetal
distress died, three neonates survived TEVAR without any complications.
It is undeniable that brief neonatal asphyxia has occurred and may
worsen if the surgical time is extended. Besides trying to control the
duration of surgery, other methods to ensure the safety of newborns
should be explored.

\textbf{Strengths and limitation}

The primary strength of the study is that it has the highest number of
pregnant individuals with complicated TBAD, although there are five
cases. Of note, this study also has limitations. Due to the low
incidence rate of TBAD, the number of cases in the study is small and
comes from a single center. In addition, this study did not set up a
control group. Finally, the long-term effects of TEVAR were absent. To
further elucidate the role of TEVAR in complicated TBAD during
pregnancy, more cases with long follow-ups are needed.

\textbf{Conclusion}

Complicated TBAD in late pregnancy is a rapid onset and severe disease
that endangers the lives of both mother and fetus. Pregnant women with
increased blood pressure during pregnancy should be on the alert for AD.
Once obvious chest pain occurs, CTA should be performed to avoid missed
diagnosis and time consumption. The management of these patients
requires a multidisciplinary team, but the best course of action remains
debatable. Patients treated with TEVAR in this series revealed
satisfying short-term and midterm outcomes, providing a promising
treatment option for complicated TBAD in late pregnancy. Considering the
priority of maternal safety and the relative safety of TEVAR for the
fetus, we recommend that TEVAR can be performed before the delivery of
newborns. Specifically, for patients in the third trimester, a
single-stage delivery combined with thoracic endovascular aortic repair
is the preferred approach, and TEVAR should be conducted prior to
cesarean section. As for patients in the second trimester, pregnancy can
be continued if conditions of the mother and the fetus are
comprehensively evaluated and intensely monitored.

\textbf{Acknowledgement:} We would like to Jiafu Li, Jingpin Liu, for
their insight discussion and constructive comments on the manuscript.

\textbf{Author contributions:} SD: Investigation, Data collection,
Methodology. ZW, XCY: Visualization, Writing- Original draft
preparation. HJC, CL: Conceptualization, Writing-Reviewing and Editing,
Supervision. All authors critically reviewed and approved the final
version of the manuscript.

\textbf{Funding:} The authors received no financial support for the
research, authorship, and/or publication of this article.

\textbf{Conflict of interests:} None declared.

\textbf{Ethics approval:} This study was reviewed and approved by the
Medical Ethical Committee of Zhongnan Hospital of Wuhan University
(approval number 2023216K). Obtaining patient consent was not required
according to the committee's procedures.

\textbf{Data availability statement:} Research data are not share.

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