Natural History and Survival in Operated Thoracic Aortic Aneurysm Patients-Juniper Publishers
JUNIPER PUBLISHERS-OPEN ACCESS JOURNAL OF CARDIOLOGY & CARDIOVASCULAR THERAPY
Introduction
This paper forms the second of a two part series on
the natural history and survival of Thoracic aortic aneurysms (TAA), in
which this part focuses on patients following surgical operation [1].
Surgical intervention on the thoracic aorta has historically been thwart
with such high rates of morbidity and mortality that in the past
surgeons have previously given all hope of being able to successfully
operate on patients suffering from TAAs. It has required innovation,
persistence and pioneering surgeons to achieve the reduced morbidity and
mortality of today’s acceptable rates.
The natural history of thoracic aortic aneurysms
(TAA) is still highly debated within the world of aortic surgery.
Particular considerations are made to the aetiology of aortic disease.
Certain genetic conditions, particularly those affecting connective
tissue, predispose patients to development of thoracic aortic aneurysms,
infamously Marfan syndrome. Pertaining to Marfan, it is well documented
that these patients are not only susceptible to the development of
thoracic aortic disease but are at a significantly higher risk of
reoperation following surgery that is not seen in patients suffering
from aneurysms of the degenerative type [2]. There is a vast array of
genetic diseases that have be attributed to the development of TAAs
other than Marfan syndrome.
However, existing research into the natural history
of this patient is limited and this is reflective of the rarity of these
diseases including; marfans, familial nonsyndromic thoracic aortic
aneurysm syndromes, vascular ehlers-danlos syndrome, Loeys-Dietz
syndrome, bicuspid aortic valves as well as others. The extent of
aneurysm can be considered to increase the risk of morbidity and
mortality following surgery. The thoraco-abdominal aneurysm carries the
highest risk of mortality and morbidity rates on both operated and
non-operated patients [3].
This paper outlines a brief surgical history and key
developments in TAA surgery setting the stage of how TAA
surgery has developed with time. It describes the geneticdiseases
associated with thoracic aortic aneurysm and how aetiology is linked to
mortality and morbidity. Furthermore, this paper explores how
post-operative survival following open surgical repair has improved over
time, current morbidity and mortality and how this relates to
aetiology. We focus on patients that have undergone elective surgical
repair opposed to those in an emergent situation and those undergoing
open repair.
An extensive literature search was performed, to
assess the scope of literature currently available. A search of major
medical databases was carried out including PubMed and the Cochrane
Central Register of Controlled Trials (CENTRAL). Limits were placed on
all articles to those published between 1990 and 2013, and to those
written in English only, except when assessing literature in regards to
historical developments when these limits were removed. Search terms
were charted to subject headings and combined using Boolean operations.
Search terms included; natural history, thoracic aortic aneurysms,
aneurysm size, risk factors, survival rates, Marfan syndrome, medical
therapy, aneurysm growth, aortic arch. Abstracts of papers found in the
literature search were read to assess suitability for inclusion in this
review. Reference lists of papers found in the literature search were
manually searched to assess suitability for inclusion in this review.
The word aneurysm has its roots derived from the
ancient Greek words aneurusma and eurunein, meaning to dilate and to
widen. Development for treatments of aortic aneurysms throughout history
has focused on abdominal aortic aneurysms (AAA). This is in part due
toits larger prevalence and easier detection clinically, particularly
before the advent of radiological imaging. Many principles underpinning
surgical correction of thoracic aortic aneurysms (TAA) have foundations
in treatments developed for AAA. The first documented evidence of
aorticaneurysm repair dates back to Egyptian times on the ancient
medical papyrus scrolls found in the “Book of Hearts” where it
describes that tumor of the arteries can only be cured by magic
[4].
The initial treatments developed for aortic aneurysms were
that of simple ligation proximal to the aneurysm. A technique
that had been first described for peripheral aneurysms by the
Greek surgeon Antyllus, in the first half of the second century AD
[4,5]. Notably, this technique was used by Astley Cooper, a pupil
of the infamous John Hunter, who ligated an AAA, understandably
this technique was used with limited success and mortality and
detrimental morbidity remained high. Despite the poor survival
rates this practice continued. Marin-Theodore Tuffier is credited
as the first surgeon to attempt this technique in TAAs. He used
catgut to ligate both proximal and distal to an ascending aortic
aneurysm [6]. His endeavor in 1901 was unsuccessful, as were
attempts on a subsequent three patients.
Renewed attempts to consolidate aneurysms through the
promotion of coagulation, by means of the introduction of
foreign material was tried in AAA, again with limited success.
Moore et al. [7] was the first surgeon to attempt this procedure
on a TAA protruding from the right side of the sternum in the
second intercostal space in 1864. Moore placed 26 yards of iron
wire within the aneurysm. Initially, the patient did well but did
not survive past day 4. Surgeons attempted this technique with
other foreign materials including different metals and even one
case describing watch springs. However, all were met without
success. A small review of these practices in the 1900s revealed a
100% mortality in TAAs treated with the method of placing wire
into the aneurysm described by Moore (n=8). The same review
describes a modified method by Corradi, which involved passing
a galvanic current through a wire inserted into the aneurysm,
later named the Moore-Corradi method. This method produced
more favorable results, and of the 17 patients described in the
review undergoing this procedure, there was a 24% recovery rate
[8]. The most successful development in the coagulation method
was described in 1938 by Blackmore and King. In a case series
of 63 syphilitic aneurysms, their electrothermic coagulation
method gave a 27% survival rate 2-11 years post operatively,
and the majority of surviving patient’s symptom free.
The first report of cellophane wrapping as a method to induce
periarterial fibrosis in a subclavian aneurysm was described in
1943 by Harrison & Chandy [9]. This method produced reduction
of the aneurysm in a long and gradual process requiring an
average of 19 months. This method was tried in TAAs, however
limited success was achieved with unpredictable results as
reported by Poppe in 1948 [10]. Interestingly, Albert Einstein,
who suffered from an AAA was treated with this method, and
survived a further 5 years before rupture.
It was not until 1951 that direct treatments for aneurysms
evolved, rather than the indirect methods of ligation, wiring and
cellophane wrapping. Charles Dubost, of France, resected an AAA,and replaced the diseased segment with an allograft obtained
from a young girl 3 weeks previous [5,10]. In the same year Lam
& Aram [11] followed Dubost and resected a descending TAA
with allograft replacement. Lam’s patient survived the operation
but developed a mediastinal abscess ultimately leading to his
death. Despite this the operation was replicated with success
by other notable surgeons including DeBakey & Cooley [12].
It led to the development of numerous allograft aortic banks
worldwide in anticipation of a growing number of surgeries to
the aorta. However, these methods were introduced before the
introduction of cardiopulmonary bypass (CPB) and although
operative and post-operative survival was increasing it gave rise
to a significant risk of paraplegia due to aortic ischaemia. It is at
this critical time, before the dawn of CPB, important research
to prevent operative morbidity evolved including; induced
hypothermia and shunts. Furthermore, development of artificial
aortic substitutes were researched during this time, and DACRON
was deemed to be the most suitable for graft implantation, first
used by DeBakey in the 1950s, and still widely used in vascular
surgery today.
At this time repair of ascending and aortic arch aneurysms
still remained an unachievable goal by resection due to the
unpreventable risk of cerebral ischaemia. This changed with
the advent of CPB when Cooley and DeBakey were the first to
successfully resect an ascending thoracic aortic aneurysm and
replace it with anallograft [12]. Repair of an aortic arch aneurysm
came in 1957 with successful resection and replacement with a
homograft, again by DeBakey et al. [13]. These operations led
to the widespread uptake in TAA resection with either artificial
DACRON or allograft replacement.
Recently, endovascular repair has excited the vascular
world, particularly when Dake et al. [14] successfully repaired a
thoracic aortic aneurysm in 1994 with this technique. However,
with the first endovascular grafts being FDA approved in 2005
little long term data is available. Currently, it is AAAs that
commonly are treated via an endovascular approach. With
regards to TAA, endovascular repair remains a source of great
debate, in terms of long term survival, long term durability of the
grafts, and operative morbidity of paraplegia and stroke. Hybrid
endovascular approaches to thoracic aortic aneurysm repair will
undoubtedly remain at the forefront of modern research in these
cases, however at present open repairs remain the standard
treatment with more substantial data, and practice qualifying its
use.
There exists conflict surrounding the aetiology of TAAs
in the literature. The prevailing consensus, reflected in the
most recent guidelines for thoracic aortic disease, cites medial
degeneration as the primary causative factor for the majority of
TAAs [15]. Historically, atherosclerosis was credited as the main
cause for aortic aneurysms, which was based upon findings
from post mortems [16,17]. Although atherosclerotic lesionsare commonly associated with thoracic aneurysms, typically
they are preceded by medial degeneration [16,18,19]. This
key point is still not conclusive proven. Patel et al. [19] wrote
a detailed review discussing the pathogenesis of ascending
and aortic arch aneurysms. They describe three separate
pathological aetiologies namely; degenerative, Marfan and other
inherited connective tissue diseases, and syphilitic aneurysms.
Degenerative aneurysms undergo a classical and specific
pathological process. Post mortem examinations reveal greatly
reduced elastin content within the ascending aorta, the media
of the aneurysms displays a lack of smooth muscle cells [16].
Cystic medial degeneration can be observed in the media, which
is described microscopically as fragmentation of elastin fibers.
Although this process is widely regarded to be associated
with aging, the recent analysis of the large Yale TAA database
reveals a strong familial component [20]. Matrix metalloprotease
(MMPs) are recognized to play a critical role in aneurysm
formation [21,22]. MMPs are still being studied in vitro and in
vivo, however it is known that MMPs significantly contribute to
proteolysis of the aorta causing the aneurysm to expand. It is this
observation that has developed a lot of interest lately in medical
treatment of TAAs. In the past the majority of cases could be
attributed to syphilitic infection, however with the modern era
of screening and antibiotics it is now a rarity and is not discussed
here.
In the absence of connective tissue disease, current
evidence points toward a strong inherited genetic phenotype
of accelerated medial degeneration as the primary culprit for
TAAs. However, there are many risk factors that contribute to
formation of a TAA, which are discussed below. Therefore, the
likelihood that this is a multi-factorial disease, of genetics and
lifestyle factors, is the consensus of most papers [15].
Classically, Marfan syndrome has been the most
extensively
studied connective tissue disorder in relation to thoracic aortic
disease. Marfan syndrome is an autosomal dominant genetic
disorder of the FBN1 gene encoding for fibrillin-1 [23]. Usually
fibrillin-1 is found in microfibrils located in the extracellular
matrix. Microfibrils play a crucial role in maintaining the elastic
fibers of connective tissues, and it is this that predisposes Marfan
patients to TAAs [24,25]. It is a rare disease with an incidence
of approximately 1 in 5000, displaying a high penetrance and
variable phenotype. Diagnosis is made using the 2010 revised
Ghent nosology, superseding a diagnostic criteria primarily
based on clinical features alone [26]. The revised criteria
critically emphasize the presence of aortic root dilation or ectopic
lentis (displacement or malposition of the eyes crystalline lens)
in new patients without a family history, as a cardinal feature
for a definitive diagnosis. A family history of Marfan syndrome,
present in approximately 50% of patients, is more indicative of
a diagnosis and thus requiring only one other factor of; an aorticroot
aneurysm, ectopic lentis, a pathogenic fibrillin-1 (FBN-1)
mutation, or systemic features defined in the Ghent Nosology, to
formulate a diagnosis.
It is well documented that approximately 50-90% of these
patients will develop aortic root dilation. Because of this
predictable progression, Marfan syndrome has previously been
used to extrapolate clinical findings, practice and research,
to TAAs of different aetiologies [27-29]. Currently, TAA
guidelines segregate Marfan patients into a distinct subset of
patients, preferentially indicating earlier surgical intervention
for TAA. The evidence for this stems from numerous studies
demonstrating a high association with an accelerated growth
rate of the aortic root (0.2-0.3cm/year) [27,30,29].
The trend of using Marfan patients for research and
extrapolating this to all aetiologies of TAAs has long discontinued.
In part, this is due to the obvious differences in pathogenesis
and varied clinical findings, and it is now realized substantial
variation exists.
Familial Non-syndromic Thoracic Aortic Aneurysm
Syndromes are defined as patients who have a first degree
relative that suffered an aortic aneurysm but are without a
known associated genetic syndrome. Elefteriades et al. [22]
have an extensive database of approximately 1200 patients who
were diagnosed with TAA in Connecticut [20,22,31,32]. Their
analysis of this database identified 21% of this cohort who had
a first degree relative with known or likely aortic aneurysm, in
the absence of a connective tissue disorder. Within this subset
of patients an autosomal dominant pattern with incomplete
penetrance pattern was displayed. This observation has
been made before, but due to the rarity and absence of large
databases in previous years has not be studied extensively [20].
Elefteriades et al. [22] note that this percentage is likely to be
higher as these results were based upon family interview and
are subject to bias.
Because this observation is only recently been brought
to light within the research world genetic identification of
associated genes is still in its infancy. Currently, ACTA 2, MYH11
and TGFBR2 are implicated as the primary gene candidates
associated with this syndrome. As genetic testing becomes more
widely available and readily understood in the general public,
ACTA 2 detection is recommended in suspected familial TAAs.
In the future more genes may be tested but this requires further
research and time.
A bicuspid aortic valve (BAV) is well recognized as an
independent risk factor for aortic aneurysm [33-35]. This
congenital cardiac malformation is reported to exist in the
general population at a prevalence of 1-2%. In this subset of
patients, one study found thoracic aortic dilation at a prevalenceof 88% in those over the age of 80. It is known that BAVs can
show an autosomal dominant inheritance in families, which is
seen in approximately 9% of TAA cases [36].
Davies et al. [37] were the first to show that bicuspid aortic
valves are associated with a increased aortic aneurysm growth
rate. Because the risk of TAA formation is so significant in these
patients the latest TAA guidelines recommend intervening
surgically earlier, when their aneurysms reach a size of 5.0cm
[15]. The pathogenesis remains a mystery. However, an aortic
aneurysm associated with a BAV is histologically similar to
that of Marfan patients chiefly; medial degeneration, increased
metalloproteinase activity and decreased FBN-1 in the aortic
wall. Combined this leads to increased aortic aneurysm growth
rates with a propensity for rupture earlier than TAAs not
associated with an inherited genetic condition [34].
Of note, co-arctation of the aorta is highly suggestive of BAV
(up to 50% of patients). Originally, the pathogenesis was linked
to the common embryological development of the aortic valve
and the ascending aorta [35]. This observation suggests that
pathological changes are not isolated to the proximal aorta and
may well involve the arch and the descending aorta.
Also, referred to as Ehlers-Danlos (ED) syndrome type
IV, is another rare autosomal dominant disorder affecting the
COL3A1 gene [24]. Typically, these patients have a distinctive
facial appearance with an accompanying body habitus and a
propensity to develop ecchymoses. It is described as a more
serious form of ED syndrome in that blood vessels, particularly
arterial vasculature, are prone to rupture. The syndrome causes
a deficiency in the synthesis of type III collagen, the main
component of connective tissue, the loss of which increases
vessel fragility making surgical repair more difficult. These
patients have a severely reduced life span approximated at 48
years.
Loeys-Dietz (LD) syndrome is described as an autosomal
dominant aortic aneurysm disorder with involvement of other
systems [24,27]. The classical triad of features is arterial
tortousity and aneurysms, hypertelorism and bifid uvula or
cleft palate, or a uvula with a wide base and prominent ridge.
Diagnosis is made on mutational analysis in TGFBR1 or TGFBR2,
which are genes recently discovered as the primary defect in
LD syndrome [38]. Unlike VD syndrome surgical intervention
is not complicated by vessel fragility, thus these patients can
be managed aggressively in respects to aneurysm treatment.
The majority of these patients have aneurysms of the aortic
root (98%), rupture of which is reported to occur at smaller
diameters than other genetic syndromes, thus the bar is further
lowered to a diameter of 4.4-4.6cm in TAA as an indication for
surgical repair [12].
Operative mortality has drastically improved over the
last century when thoracic aortic aneurysm repair was not
survivable. Significant advances have been seen in Mortality
following thoracic aortic aneurysm repair is dependent on many
variables, the main ones being; extent and size of aneurysm,
patient co-morbidities present, operation underdone on an
elective or emergent basis, and recent evidence from the US
showing better outcomes in centers who undergo higher volume
of cases.
The current 2010 guidelines for thoracic aortic disease
describe death following composite valve graft as unusual and
the risk is between 1 and 5% [15]. This risk is however center
dependent.
Many centers have reported learning curves in all aspects
of thoracic aortic surgery which improvements over time in
terms of mortality, which adds to the argument that volume is
an important factor in operative mortality. In 2007, Kalkat et
al. [39] from Birmingham, UK, interrogated the UK heart valve
registry which contained data on 1962 patients undergoing
first time composite valve graft replacement and report 30 day
mortality as 10.7%. These results include patients operated on
an emergency basis as with those with genetic conditions, which
may explain the reported higher incidence of mortality compared
to that of the 2010 guidelines. In consideration of patients with
genetic conditions, Karck et al. [40] from Germany, describe
postoperative mortality in Marfan patients as high as 6.8% in
those undergoing composite valve grafts in a retrospective
group of 119 patients. A further paper in 2010 by Bernhradt
et al describes 30 day mortality in Marfan patients undergoing
composite graft replacement as 0%, however this rose to 10%
at follow up. Patel et al also describe a 10% mortality following
Bentall procedure in Marfan patients at 8 year follow up [41].
Other papers describing other genetic syndromes, such as
Loeys-Dietz, and composite graft replacement report series too
small to draw any relevant conclusions [42]. BAV and ascending
aorta repair is now a commonly recognized procedure. El Khoury
et al. [43] report no hospital mortality following repair of a
regurgitant bicuspid aortic valve with aortic root replacement.
A BAV does not significantly increase the risk of mortality
following operation compared to those with a tricuspid valve.
Aortic arch operations carry a pre-requisite of cerebral
protection due to the nature of the procedure. This opens
patients to higher risk of mortality, relating to reduced cerebral
perfusion, time of operation, cardiopulmonary bypass time, aortic
cross clamp times and periods of deep hypothermic circulatory
arrest. The 2010 thoracic aortic guidelines quote a 2 to 6% risk
of death in patients undergoing these types of operations [15].
Leshnower et al. [44] report their center experience between
2004 and 2009 encompassing 412 patients and report andoperative mortality of 7.0%, this included patients undergoing
emergency operations. The Mayo clinic reports 9 years of results
from 2001 to 2010 of 209 patients and report a procedure
specific mortality of 5.5% and 1.0% in total arch and hemiarch
procedures respectively [45]. Furthermore, the same paper
describes how even over 9 years they have seen decreases in rates
of mortality from the first half of their study period compared
to their second half (7.9% vs 4.5% respectively). Other centers
have reported similar decreases in mortality over short spans
of time including Mount Sinai [46,47]. Gega et al. [48] from Yale
published results in 2007 using deep hypothermic circulatory
arrest as the sole means of cerebral protection. In their study
of 394 patients over 10 years they report a mortality rate of
3.6% in elective cases. Such rapid advancements in aortic arch
surgery have led to different techniques being used by different
centers worldwide. This adds a further variable that should be
considered when studying mortality rates. Although mortality
rates vary worldwide, in general mortality rates reported are in
the single digits, particularly so in elective repair and modern
day aortic arch surgery is performed with low risk of mortality.
Thoraco-abdominal aortic aneurysm surgery represents the
most challenging operation that can be undertaken on the aorta.
The 2010 guidelines describe an approximate mortality of 10%
in patients undergoing type II thoraco-abdominal repair, again
this is center dependent and furthermore this is recognized in
the guidelines [15]. Wong et al, describe 305 patients undergoing
TAAA repair of which operative survival following elective repair
is 6.2% [49]. In 2007, Coseli et al. [50] report their entire open
thoraco-abdominal aneurysm repair encompassing a total of
2286 patients and report 30 day survival rate of 95.0%. Coseli et
al have also reported their experience of TAAA surgery in patients
with Marfans syndrome, which totally 50 patients between 1986
and 1996. 30 day survival in these patients was 96%. Cambria et
al. [51] from Havard, performed 337 operations on the thoracoabdominal
aorta, and reported operative mortality of 8.3%. This
mortality rate included patients undergoing operations in a
non-elective setting and all types of TAAA repair. Endovasular
interventions are becoming ever popular in TAAA repair,
particularly as hybrid techniques are being developed. However,
these are still very much in their infancy. Although there is some
published literature on long term data it still represents an area
that is currently under close investigation.
The rapid and evolving nature of thoracic aortic surgery
means long term survival is hard to assess. Many centers have
reported “learning curves” that show even over a ten year period
their mortality rates can be reduced by half. Such advancements
are not limited to the surgery itself but also to anaesthetic, pre
and post-operative management of these patients.
Higgins et al. [52] analyzed a database containing data on
all adult patients who had undergone thoracic aortic aneurysmrepair in British Columbia which totaled 1960 patients. Longterm
survival was 77.7%, 59.6%, and 44.7% at 5, 10 and 15
years, respectively. Survival in the first half of the study was
significantly less compared to the second half of the study
74.3% (95% CI, 70.6-77.7) versus 60.4% (95% CI, 56.6-63.9)
respectively. Crawford et al report a similar experience of 605
patients in 1986 and report a 5 year survival of 60% [53].
Mount Sinai published long term data in 2010 after aortic
arch replacement in 206 patients between 1999 and 2009.
Bischoff et al. [54] describe at 6 years, 75% of patients were still
alive, compared with 92% in a matched New York State control
population (P <.001). In Japan, Minakawa et al analyzed data
from 122 patients who underwent total aortic arch replacement.
Overall long-term survival was 80.4% at 5 years and 58.9% at 10
years. Estrera et al. [55] have published results in 2002 relating
to long term survival in aortic arch patients, with long term
survival rates 72% at 5 years and 71% at 10 years after surgery.
Cambria et al. [51] from Havard Medical School reported
their 15-year experience of 337 TAAA repairs survival rates at
2 and 5 years were 81.2+/-3% and 67.2+/-5%, which in their
study is comparable to routine aortic abdominal repair.
Fehrenbacher et al. [3] reviewed 343 patients in their
center undergoing TAAA repair or descending aortic aneurysm
repair and report the 1, 5, and 10-year survival rates were 90%,
69%, and 54%, respectively [2]. Kouchokos et al. [56] looked at
survival following TAAA using hypothermic circulatory arrest in
243 patients between 1986 and 2012. They reported a 5 year
survival rate of 55%.
Long term survival is hard to assess particularly considering
many centers report significant reductions in mortality in as
short a time as ten years. This can be attributed to major advances
made in this subspecialty, as well as improved anaesthetic, pre
and post-operative management. The wealth of techniques and
devices available for use also add to variables that can potentially
affect long term survival. However, the amount of data available
to assess best practice is still in its infancy. It is because of this,
thoracic aortic surgery is a rapidly advancing subspecialty which
is exciting to see what developments are made in the near future.
All operations carried out on the thoracic aorta carry a risk
of reoperation. It is thought that this risk is reduced with the use
of beta blockers. Theoretically, with reduction of the heart rate
the blood pressure is subsequently reduced and in turn relieves
the pressure that the repair is subjected to from the heart.
Beta blockers are also thought to reduce the expansion rate of
thoracic aortic aneurysms before operation; however, the use of
beta blockers before and after operation is highly debated [1]. To
date though, the 2010 guidelines still recommend the use of beta
blockers lifelong following diagnosis of aneurysm [15].
It is well described that reoperation is significantly increased
in patients with Marfan syndrome. Geisbuesch et al. [57] describe
that almost half of the Marfan patients who undergo surgical
repair will require reoperation. This is well described in centers
that deal with high volumes of patients and come across a higher
number of Marfan patients [58]. In comparison, Osslen et al. [59]
report analysis of the Swedish national healthcare register of
patients with thoracic aortic disease, incorporating over 14000
patients. In this paper, Osslen describes a reoperation rate of
7.8%.
However, survival following reoperation in all aetiologies
can be described as low. The 2010 guidelines describe the risk
of death following reoperation as between 2 and 6%. This is also
described in a similar report on Marfan patients by Geisbuesch
who describe re-operative hospital mortality between 0 to 1.6%
[14]. Although more common in Marfan patients reoperation is
considered a procedure that when undertaken electively can be
done with a low mortality rate.
Modern day thoracic aortic aneurysm surgery is a relatively
new specialty, but has roots deeply embedded in history.
Mortality rates have remained high until the advent of specialty
has progressed at a rapid rate. In general, mortality is higher in
patients with a larger extent of aneurysm and those associated
with a genetic syndrome. However, TAA surgery can be carried
out on an elective basis with excellent results, in terms of postoperative
mortality and reoperation. It is of vital importance
to understand how operation affects TAAs so we can confer
this knowledge to the patient and to be able to improve on our
current results. Genetic syndromes represent a rare subset of
patients who suffer from aortic aneurysms and they represent
an area of medicine for which there remains many unanswered
questions. Undoubtedly, considering the pace of discoveries
and developments within this specialty in such a short amount
of time, we will see research become more focused towards a
personalized approach.
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