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Contemporary Reviews in Cardiovascular Medicine
Thoracic and Abdominal Aortic Aneurysms
Eric M. Isselbacher, MD
A
neurysms of the aorta are at times evaluated and treated
by physicians from a number of specialties. Indeed,
whereas cardiac surgeons operate on the ascending aorta and
arch and vascular surgeons manage abdominal aortic aneurysms, at present the responsibility often falls to cardiologists
to oversee the medical care of patients with aortic disease of
all types. However, although formally trained in “cardiovascular medicine,” most cardiologists devote their attention to
the heart and its coronary arteries, and relatively few have
experience in the management of diseases of the aorta. It is
therefore important that cardiologists acquire a sufficient
knowledge base so that they can confidently evaluate and
manage patients with aortic disease and know when it is
appropriate to refer them for surgery. Toward this end, the
purpose of this review is to summarize the current understanding of thoracic and abdominal aortic aneurysms.
the genes for fibrillin-1, which is a structural protein that is
the major component of microfibrils of elastin. The mutations
result in both a decrease in the amount of elastin in the aortic
wall and a loss of elastin’s normally highly organized
structure. As a consequence, the aorta exhibits markedly
abnormal elastic properties that lead to progressive increases
in stiffness and dilatation.2
Familial Thoracic Aortic Aneurysm Syndrome
Cystic medial degeneration is also seen in patients with
ascending thoracic aortic aneurysms who do not have overt
connective-tissue disorders. Moreover, it is now recognized
that although cases of thoracic aortic aneurysms in the
absence of overt connective-tissue disorders may be sporadic,
they are often familial and are now referred to as the familial
thoracic aortic aneurysm syndrome. In an analysis of their
large database of thoracic aortic aneurysm patients, Coady
and colleagues3 found that at least 19% of patients had a
family history of a thoracic aortic aneurysm, and they
presented at significantly younger ages than did those with
sporadic aneurysms.
Most pedigrees suggest an autosomal-dominant mode of
inheritance, but there is marked variability in the expression
and penetrance of the disorder, such that some inherit and
pass on the gene but show no manifestation of the disease.
Several mutations have been identified. A mutation on
3p24.2–25 can cause both isolated and familial thoracic aortic
aneurysms, with histological evidence of cystic medial degeneration.4,5 Mutations have also been mapped to 2 other
chromosomal loci (5q13–14 and 11q23.2-q24).1,6 The extent
of genetic heterogeneity is likely to become more evident as
more families with thoracic aortic aneurysms are studied. It is
also possible that this is actually a polygenic condition, thus
explaining the variable expression and penetrance. Consequently, at present, it is not possible to perform routine
genetic screening for this syndrome.
Thoracic Aortic Aneurysms
Thoracic aneurysms may involve one or more aortic segments (aortic root, ascending aorta, arch, or descending aorta)
and are classified accordingly (Figure 1). Sixty percent of
thoracic aortic aneurysms involve the aortic root and/or
ascending aorta, 40% involve the descending aorta, 10%
involve the arch, and 10% involve the thoracoabdominal
aorta (with some involving ⬎1 segment). The etiology,
natural history, and treatment of thoracic aneurysms differ for
each of these segments.
Etiology and Pathogenesis
Aneurysms of the ascending thoracic aorta most often result
from cystic medial degeneration, which appears histologically as smooth muscle cell dropout and elastic fiber degeneration. Medial degeneration leads to weakening of the aortic
wall, which in turn results in aortic dilatation and aneurysm
formation. When such aneurysms involve the aortic root, the
anatomy is often referred to as annuloaortic ectasia. Cystic
medial degeneration occurs normally to some extent with
aging, but the process is accelerated by hypertension.1
Bicuspid Aortic Valve
Many cases of ascending thoracic aortic aneurysms are
associated with an underlying bicuspid aortic valve. It was
once thought that such aneurysms were due to “poststenotic
dilatation” of the ascending aorta, but the data suggest
otherwise. Nistri et al7 used echocardiography to evaluate
young people with normally functioning bicuspid aortic
valves and found that 52% had aortic dilatation (44% at the
Marfan Syndrome
The occurrence of cystic medial degeneration in young
patients is classically associated with Marfan syndrome (or
with other less-common connective-tissue disorders, such as
Ehlers-Danlos syndrome). Marfan syndrome is a heritable
autosomal-dominant disorder caused by mutations in one of
From the Thoracic Aortic Center and Cardiology Division, Massachusetts General Hospital, Boston, Mass.
Correspondence to Eric M. Isselbacher, MD, Thoracic Aortic Center and Cardiology Division, Massachusetts General Hospital, 55 Fruit St,
YAW-5A-5800, Boston, MA 02114. E-mail [email protected]
(Circulation. 2005;111:816-828.)
© 2005 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
DOI: 10.1161/01.CIR.0000154569.08857.7A
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Isselbacher
Aortic Aneurysms
817
valve having undergone the Ross procedure develop late
dilatation of the pulmonary autograft (see later sections).
Additionally, in a recent study of patients with ascending
thoracic aortic aneurysms, Schmid et al12 found that compared with tricuspid aortic valve controls, the aortic aneurysm
tissue of those with a bicuspid aortic valve demonstrated
more lymphocyte infiltration and smooth muscle cell apoptosis. This suggests that the walls of aneurysms associated with
bicuspid aortic valves may be weaker than more “typical”
aneurysms.
Because half of those with a bicuspid valve have aortic
dilatation, cardiologists should routinely image the ascending
aorta in all bicuspid aortic valve patients. In many cases, this
can be accomplished with echocardiography. However,
whereas the aortic root is easily visualized in most transthoracic echocardiograms, in many cases the midportion of the
ascending aorta is not. Consequently, if an ascending aortic
diameter is not reported on an echocardiogram, one cannot
safely assume that it was visualized and found to be normal
in diameter. One might review the images to specifically
examine the ascending aorta, but if it was not adequately
visualized, one should instead obtain a computed tomography
(CT) scan or magnetic resonance imaging (MRI) study to
determine aortic diameter.
Figure 1. Anatomy of thoracic and proximal abdominal aorta.
(©Massachusetts General Hospital Thoracic Aortic Center. Used
with permission.)
level of the tubular portion of the ascending aorta and 20% at
the level of the sinuses [ie, root]). Indeed, other studies have
demonstrated that a bicuspid aortic valve is associated with a
dilated aorta, regardless of the presence or absence of
hemodynamically significant valve dysfunction.8
Cystic medial degeneration has been found to be the
underlying cause of the aortic dilatation associated with a
bicuspid aortic valve. In one study, 75% of those with a
bicuspid aortic valve undergoing aortic valve replacement
surgery had biopsy-proven cystic medial necrosis of the
ascending aorta, compared with only 14% of those with
tricuspid aortic valves undergoing similar surgery.9 Inadequate production of fibrillin-1 during embryogenesis may
result in both the bicuspid aortic valve and a weakened aortic
wall.10 Fedak et al11 examined ascending aortic specimens
from those with bicuspid aortic valves and tricuspid aortic
valves undergoing cardiac surgery. They found that patients
with bicuspid aortic valves had significantly less fibrillin-1
than did patients with tricuspid aortic valves, and the reduction in fibrillin-1 was independent of patient age or aortic
valve function. Interestingly, samples of the pulmonary arteries of the same subjects showed a similar reduction in
fibrillin-1 content among those with bicuspid aortic valves.
This might account for why some patients with a bicuspid
Atherosclerosis
Atherosclerosis is an infrequent cause of ascending thoracic
aortic aneurysms. Conversely, atherosclerosis is the predominant etiology of aneurysms of the descending thoracic aorta.
These aneurysms typically originate just distal to the origin of
the left subclavian artery. The pathogenesis of atherosclerotic
aneurysms in the thoracic aorta may resemble that of abdominal aneurysms (see later sections), but this has not been
extensively investigated.
Syphilis
Syphilis was once perhaps the most common cause of
ascending thoracic aortic aneurysms, but in the era of aggressive antibiotic treatment, such luetic aneurysms are rarely
seen in modern medical centers. The latent period from initial
spirochetal infection to aortic complications is typically 10 to
30 years, although it may range anywhere from 5 to 40 years.
During the secondary phase of the disease, spirochetes
directly infect the aortic media, causing an obliterative
endarteritis of the vasa vasorum, particularly the proximal
ascending thoracic aorta. Destruction of collagen and elastic
tissues leads to dilatation of the aorta, fibrosis, and calcification. Longitudinal wrinkling of the aortic wall produces a
radiographic pattern of “tree barking.” Weakening of the
aortic wall leads to progressive aortic dilatation, resulting in
aneurysms that may be fusiform but are often saccular. The
ascending aorta is most often affected, but aneurysms can
involve the arch or root. The ascending aortic involvement
often produces secondary aortic regurgitation, and inflammation within the aortic root may result in ostial coronary artery
stenoses.
Turner Syndrome
Turner syndrome is associated with a number of cardiovascular anomalies, including a bicuspid aortic valve (present in
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February 15, 2005
one third of subjects) and coarctation of the aorta. Thoracic
aortic aneurysms are also found and typically involve the
ascending aorta. In a recent systematic study of adults with
Turner syndrome, Elsheikh et al13 screened 38 asymptomatic
women and found that 42% had aortic root dilatation. Of
these, 4 of 38 (11%) had a bicuspid aortic valve and 11 of 38
(29%) had hypertension. This population is at increased risk
for aortic dissection and rupture. Indeed, those with both a
bicuspid aortic valve and aortic dilatation may be at particularly high risk, given that both the bicuspid aortic valve and
Turner syndrome are potent risk factors for aortic dissection.
Consequently, it has been recommended that all women with
Turner syndrome undergo a complete cardiac evaluation and
echocardiographic or MRI examination at least every 5 years
to detect potential aortic dilatation.14
Aortic Arteritis
Takayasu’s arteritis—the most striking of arteritides that
affect the aorta—is a chronic inflammatory disease of unknown etiology. The disease affects women far more often
than men, and the mean age at the time of diagnosis is 29
years.15 It typically causes obliterative luminal changes in the
aorta and other involved arteries. However, in 15% of cases,
aortic dilatation may occur and result in aneurysms. These
may arise either in the acute inflammatory (early) stage of the
disease or in the sclerotic (late) stage of the disease. Therefore, the finding of a thoracic aortic aneurysm in a young
woman with symptoms of a systemic inflammatory process
should raise consideration of the disease.
Giant-cell arteritis typically affects the temporal or cranial
arteries but can also affect the aorta and produce aneurysms.
In a longitudinal cohort of 169 patients in Olmstead County
with giant-cell arteritis, 30 (18%) developed aortic aneurysms
(18 thoracic and 16 abdominal).16 Overall, 9 patients suffered
aortic dissection, and in 2 cases there was no evidence of
aortic dilatation as a predisposing factor. Unfortunately, there
were no clinically useful predictors of aortic involvement.
Ankylosing spondylitis is associated with inflammation of
fibrocartilage, and it is hypothesized that the inflammation is
directed at tissues rich in fibrillin-1.17 Thus, this may be the
cause of aneurysms of the ascending aorta.18
Aortic Dissection
Chronic aortic dissections tend to dilate over time. The
affected aortic walls were weakened at baseline (leading to
dissection), and after dissection, the outer wall of the false
lumen is weakened further because its inner half (the intimal
flap) has been dissected away. Consequently, those with
chronic aortic dissection are at high risk for aneurysm
formation and need to be followed up vigilantly with surveillance imaging studies.
Trauma
Nonpenetrating traumatic aortic injuries typically occur as the
result of deceleration injuries. Most often, the trauma results
in a partial or complete transection of the descending thoracic
aorta at the level adjacent to the left subclavian artery. The
majority of those with aortic transection die within the hour,
and others undergo aortic repair during their initial hospitalization. However, in 1% to 2% of such patients, the traumatic
aortic transection is not diagnosed initially, and patients may
go on to develop chronic pseudoaneurysms at that site. These
aneurysms are distinct in that they are typically saccular
(rather than the more common fusiform shape), relatively
discrete, and located immediately distal to the left subclavian
artery.19 Over time they tend to calcify.
Clinical Manifestations
Most patients with thoracic aortic aneurysms are asymptomatic at the time of diagnosis, because the aneurysms are
typically discovered incidentally on imaging studies (chest
x-ray, CT scan, or echocardiogram) ordered for other indications. Aneurysms of the root or ascending aorta may produce
secondary aortic regurgitation, so a diastolic murmur may be
detected on physical examination or, less often, patients may
present with congestive heart failure. When thoracic aortic
aneurysms are large, patients may suffer a local mass effect,
such as compression of the trachea or mainstem bronchus
(causing cough, dyspnea, wheezing, or recurrent pneumonitis), compression of the esophagus (causing dysphagia), or
compression of the recurrent laryngeal nerve (causing hoarseness). Rarely, chest or back pain may occur with nondissecting aneurysms as a result of direct compression of other
intrathoracic structures or erosion into adjacent bone.
The feared consequence of thoracic aneurysms is aortic
dissection or rupture (often referred to as an acute aortic
syndrome), which is potentially lethal. Typical symptoms of
acute aortic syndrome include the abrupt onset of severe pain
in the chest, neck, back, and/or abdomen.
Diagnosis and Sizing
Often, thoracic aortic aneurysms are evident on chest x-ray
films and are characterized by widening of the mediastinal
silhouette, enlargement of the aortic knob, or tracheal deviation. However, smaller aneurysms and even some large ones
may not produce any abnormalities on chest x-ray films. One
should be cautious in interpreting a radiology report that
describes an abnormal aortic silhouette as an “ectatic aorta.”
“Ectasia” is formally defined as dilatation of a vessel, but
commonly radiologists use the term to describe a tortuosity of
the thoracic aorta that often occurs with later age (see
discussion). In fact, on the basis of the chest x-ray film alone,
one cannot typically distinguish whether an enlarged aortic
silhouette represents a tortuous aorta or the presence of an
aneurysm. Consequently, if a chest x-ray film shows an
enlarged aortic silhouette, one should have a low threshold
for ordering a tomographic imaging study (eg, CT scan) to
define the aortic anatomy.
Contrast-enhanced CT scanning and MR angiography are
the preferred modalities to define aortic (and branch vessel)
anatomy, and both accurately detect and size thoracic aortic
aneurysms (Figure 2). However, the specific aortic anatomy
may dictate which imaging study is optimal. For example,
when aneurysms involve the aortic root, MR is preferable to
CT scanning, because CT images the root less well and is less
accurate in sizing its diameter.
When imaging a tortuous thoracic aorta, which is common
among the elderly, one must use caution in measuring the
aortic diameter on axial images; such images may slice
Isselbacher
Aortic Aneurysms
819
Figure 2. Contrast-enhanced CT scan demonstrating a
7.5⫻8.3-cm ascending thoracic aortic aneurysm. A indicates
ascending; D, descending.
through the aorta off-axis, resulting in a falsely large diameter
(Figure 3A). One option is to reconstruct the axial data into
3-dimensional images (ie, CT angiography), with which one
can then measure the tortuous aorta in true cross section to
obtain an accurate diameter (Figure 3B). An alternative is MR
angiography (Figure 4), which images the thoracic aorta in
multiple planes and therefore readily permits on-axis
measurements.
Transthoracic echocardiography is effective for imaging
the aortic root (Figure 5) and is thus often used to evaluate
patients with Marfan syndrome. However, it does not consistently visualize the mid or distal ascending aorta well, nor
does it well visualize the descending aorta. Therefore, other
than for those with Marfan syndrome, transthoracic echocardiography should generally not be used for diagnosing and
sizing thoracic aortic aneurysms. Although transesophageal
echocardiography can visualize the entire thoracic aorta well,
given its semi-invasive nature it is not favored for the routine
imaging of those with stable (nondissecting) thoracic
aneurysms.
Natural History
The natural history of thoracic aortic aneurysms has not been
well defined. One reason for this is that both the etiology and
location of an aneurysm may affect its rate of growth and
propensity for dissection or rupture. A second reason is that it
is rare, in the era of modern imaging and aneurysm sizing, to
actually allow known aneurysms to grow until they rupture,
because surgery is usually performed when aneurysms are
just large enough to be considered at significant risk for
rupture. Although some patients with large aneurysms do not
undergo surgery, they are usually elderly or have important
comorbidities, thus increasing their mortality, irrespective of
the aneurysm.
On the basis of longitudinal data from the Yale group,
Davies et al20 found that the mean rate of growth for all
thoracic aneurysms was 0.1 cm/y. The rate of growth,
however, was greater for aneurysms of the descending aorta
Figure 3. A, Standard axial image from a contrast-enhanced CT
scan showing what appears to be an oval-shaped descending
thoracic aortic aneurysm, appearing to measure as much as
8.0⫻5.2 cm in diameter (arrows). B, Three-dimensional reconstruction in a left anterior oblique view of same CT scan demonstrating that the descending aorta is tortuous and was consequently cut off-axis (dotted arrow) on axial CT image. The true
maximal diameter of this aortic segment was only 5.6 cm (solid
arrow).
versus ascending aorta, was greater for dissected aneurysms
versus nondissected ones, and was greater for those with
Marfan syndrome versus those without. Initial size is an
important predictor of the rate of thoracic aneurysm growth.
However, even controlling for initial aneurysm size, there is
still substantial variation in individual aneurysm growth
rates,21 thus making it difficult to prospectively predict
growth for a given aneurysm. Therefore, all aneurysms need
to be followed up with regular surveillance imaging to
monitor growth. With regard to aneurysm size and the risk of
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February 15, 2005
Figure 6. Composite aortic graft repair of aneurysm involving
the aortic root and ascending thoracic aorta. The coronary arteries are excised as buttons, and the aneurysm is resected to the
level of the aortic annulus, with sacrifice of the native aortic
valve. A prosthetic valve is attached directly to a Dacron graft,
and this composite graft is sewn directly to the annulus. The
native coronary buttons are then reimplanted into the graft.
(©Massachusetts General Hospital Thoracic Aortic Center. Used
with permission.)
Management
Figure 4. MR angiogram demonstrating a 4.7-cm ascending
thoracic aortic aneurysm.
rupture or dissection, in their series Davies et al20 found an
annual rate of 2% for aneurysms ⬍5 cm, 3% for aneurysms
5 to 5.9 cm, and 7% for aneurysms ⱖ6 cm in diameter.
Therefore, the risk appears to rise abruptly as thoracic
aneurysms reach a size of 6 cm.
Figure 5. A transthoracic echocardiogram, in a parasternal long-axis
view, demonstrating a dilated aortic root (4.4 cm) and ascending aorta
(4.2 cm). Whereas the aortic root is well visualized, the ascending
aorta is less so, as is often the case with transthoracic imaging. RV
indicates right ventricle; LV, left ventricle; and LA, left atrium.
Surgical Treatment
The optimal timing of surgical repair of thoracic aortic
aneurysms remains somewhat uncertain, given the limited
data on their natural history. For most ascending thoracic
aortic aneurysms, surgery is indicated at a diameter of ⱖ5.5
cm. Among those with an increased operative risk (eg, the
elderly or those with comorbidities), we will typically raise
the threshold to 6 cm or more before recommending surgery.
Conversely, among patients who are at increased risk of
aortic dissection or rupture (eg, Marfan syndrome or bicuspid
aortic valve), we often recommend ascending aortic repair
when aneurysms reach only 5 cm and in selected cases (those
at especially high risk), at even smaller diameters.22 Moreover, when patients with a bicuspid valve require aortic valve
replacement surgery, we recommend prophylactic replacement of the ascending aorta if its diameter is 4 cm or greater,
given that we now recognize that such patients would
otherwise remain at high risk for subsequent aortic dissection.
For most descending thoracic aortic aneurysms, we recommend surgery at an aortic diameter of 6 cm or greater.
Ascending Thoracic Aortic Aneurysms
The mortality of elective surgical repair of ascending aortic
aneurysms in large centers is 3% to 5%. Thoracic aortic repair
requires cardiopulmonary bypass (there is no “off-the-pump”
option), and the aneurysm is generally resected and replaced
with a prosthetic Dacron tube graft of appropriate size. When
the aneurysm involves the aortic root and is associated with
significant aortic regurgitation, one usually performs a composite aortic repair (Bentall procedure) by using a tube graft
with a prosthetic aortic valve sewn into one end. The valve
and graft are sewn directly into the aortic annulus, and the
coronary arteries are then reimplanted into the Dacron aortic
graft (Figure 6).
Isselbacher
Figure 7. Valve-sparing procedure to repair an aneurysm involving the aortic root and ascending thoracic aorta. The aortic
sinuses are excised, but the valve leaflets are not. The leaflets
are then placed within the lumen of a Dacron graft that is then
sewn directly to the aortic annulus. The valve leaflets are then
reimplanted within the base of the graft to restore competency.
(©Massachusetts General Hospital Thoracic Aortic Center. Used
with permission.)
Alternatively, when the aortic valve leaflets are structurally
normal and the aortic regurgitation is secondary to dilatation
of the root, a valve-sparing root replacement may be performed (Figure 7). This technique, advanced by Dr Tirone
David, involves excising the sinuses of Valsalva while
sparing the aortic leaflets, sewing a Dacron graft to the base
of the aortic annulus, and reimplanting the aortic valve
leaflets within the graft to restore their normal anatomic
configuration.23 When successful, this procedure avoids the
need for prosthetic valve replacement and the associated
long-term risks and reduces the risk for repeated valve
surgery. In a series of 151 patients with aortic root aneurysms
who underwent valve-sparing surgery, David et al23 found
that at 8 years of follow-up, 67% had mild or no aortic
regurgitation, whereas only 2% developed severe aortic
regurgitation.
Some younger patients have a dilated aortic root, but
because of intrinsic valve dysfunction, the aortic valve cannot
be spared. For those wishing to avoid the prosthetic valve
required with the composite aortic graft, one option has been
a pulmonary autograft, also known as the Ross procedure. In
this procedure, the patient’s aortic valve and root are excised.
The patient’s own pulmonary root is then excised and
transplanted into the aortic position. The pulmonary root is, in
turn, replaced with a cryopreserved pulmonary (or aortic)
homograft. Though conceptually attractive, the procedure has
not been free of complications. One of its major limitations is
the development of late autograft root dilatation, which is
particularly problematic among those who had aortic root
dilatation preoperatively. In one series of 91 patients, the
incidence of pulmonary autograft root dilatation was 61% at
5 years among those with a prior aortic aneurysm, compared
with 27% among those with no prior aortic aneurysm (ie,
those who had surgery for aortic valve disease only).24
When full aortic root/valve replacement is necessary,
another alternative to a composite graft is the use of cryopre-
Aortic Aneurysms
821
Figure 8. Repair of an aneurysm involving ascending thoracic
aorta and arch by using a multilimbed prosthetic graft. (©Massachusetts General Hospital Thoracic Aortic Center. Used with
permission.)
served aortic allografts (cadaveric aortic root and proximal
ascending aorta). However, after the procedure, late structural
valvular deterioration does occur and may lead to subsequent
reoperation. Moreover, the aortic valve deterioration appears
to progress more rapidly in younger patients than in older
ones, making the homograft less likely to serve as a durable,
lifelong prosthesis.25
Arch Aneurysms
Surgical replacement of aortic arch aneurysms is particularly
challenging and carries a significant risk of neurological
damage from embolization of atherosclerotic debris or from
global ischemic injury during circulatory arrest. To replace
the dilated arch with a prosthetic tube graft, the brachiocephalic vessels must be removed from the arch before its
resection and then reimplanted into the tube graft arch after its
interposition. Traditionally, this involved removing and then
reimplanting the brachiocephalic vessels en bloc during
hypothermic circulatory arrest. However, many surgeons
have now adopted a newer surgical technique by using a
multilimbed prosthetic arch graft, to which each arch vessel is
in turn anastomosed individually (Figure 8), which reduces
the duration of hypothermic circulatory arrest and the frequency of embolic events.
Three methods of cerebral protection have been used for
aortic arch surgery. The traditional method had been the use
of profound hypothermic circulatory arrest with arrest of
cerebral perfusion. Subsequently, retrograde cerebral perfusion via a superior vena cava cannula was introduced as an
adjunct for cerebral protection during hypothermic arrest. It
was believed that this technique would improve outcomes by
providing nutrients and oxygen to the brain and flushing out
particulate matter from the cerebral and carotid arteries that
would otherwise embolize. However, systematic studies of
retrograde cerebral perfusion have shown no improvement in
outcomes.26,27 More recently, the technique of selective
antegrade cerebral perfusion was introduced. With this
method, perfusion cannulas are inserted directly into the
cerebral vessels to perfuse the brain during all but brief
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Circulation
February 15, 2005
Figure 9. Repair of a descending thoracic aortic aneurysm. (© Massachusetts
General Hospital Thoracic Aortic Center.
Used with permission.)
periods of surgery. In fact, the use of the multilimbed,
prosthetic aortic graft has made such selective antegrade
cerebral perfusion easier and more effective. The data available thus far suggest that selective antegrade cerebral perfusion significantly reduces the incidence of temporary neurological dysfunction, although its impact on stroke risk
remains unclear.27
Descending Thoracic Aortic Aneurysms
The most feared nonfatal complication of resection of descending thoracic and thoracoabdominal aneurysms is postoperative paraplegia secondary to interruption of the blood
supply to the spinal cord (Figure 9). Fortunately, a number of
methods have been introduced to reduce the likelihood of
paraplegia; these include regional hypothermic protection of
the spinal cord by epidural cooling during surgery, cerebrospinal fluid drainage, reimplantation of patent critical intercostal arteries, the use of intraoperative somatosensory
evoked-potential monitoring, and maintenance of distal aortic
perfusion during surgery with the use of atriofemoral (left
heart) bypass to the distal aorta. With the use of these
adjuncts, the incidence of paraplegia has fallen from a
historical rate of 13% to 17% to a rate of 5% to 6% in most
modern series. Elective surgical repair of descending thoracic
aortic aneurysms is also associated with a mortality rate
ranging from 5% to 14%. Importantly, a recent study of
surgical repair of thoracoabdominal aortic aneurysms found
that surgical mortality was substantially higher in low-
volume hospitals and for low-volume surgeons compared
with high-volume hospitals and high-volume surgeons.28
An alternative approach for the repair of descending
thoracic aneurysms is the use of a transluminally placed
endovascular stent-graft (Figure 10). This technique has the
advantage of being far less invasive than surgery, with
potentially fewer postoperative complications and lower morbidity. Ellozy et al29 recently reported a series of 84 patients
receiving endovascular stent-grafts to treat descending thoracic aortic aneurysms. Primary technical success was
achieved in 90%, and successful exclusion of the aneurysm
was achieved in 82%. However, major procedure-related or
device-related complications occurred in 38%, including
proximal attachment failure (8%), distal attachment failure
(6%), mechanical device failure (3%), periprocedural death
(6%), and late aneurysm rupture (6%). More encouraging was
the fact that only 3% suffered persistent neurological complications. Compared with open surgical repair, endovascular
stent-grafting does appear to have an acceptable perioperative
morbidity and mortality, but clearly, technical refinements
need to be made before it can become a routine treatment for
such aneurysms. At present, it is best reserved for those with
ideal aortic anatomy or those who are otherwise poor surgical
candidates.
Staged Repair
Some patients requiring surgical repair have aneurysms that
involve multiple aortic segments (the ascending, arch, and/or
descending thoracic aorta). Trying to repair both the ascend-
Figure 10. Minimally invasive repair of a
descending thoracic aortic aneurysm
using a transluminally placed endovascular stent-graft. The unexpanded stent is
advanced and positioned across the aneurysm. The proximal portion is
expanded and anchored, and then the
distal portion is expanded and anchored.
The covered stent then serves as a conduit for blood flow while excluding the
aneurysmal aorta from the circulation.
The aneurysm sac then thromboses.
(©Massachusetts General Hospital Thoracic Aortic Center. Used with
permission.)
Isselbacher
ing and descending segments in one operation is both
challenging and risky. Therefore, most centers will address
these complicated situations by performing staged procedures, with repair of one aortic segment (ascending or
descending) first, to be followed at a later date by a second
surgery. The order of surgical repair is dictated by the
individual’s specific aortic anatomy—for example, depending on which aortic segment is at greatest risk of rupture and
where the surgeon can expect to place the aortic cross-clamp.
However, in some cases, the lack of an adequate neck (a
relatively nondilated segment of the proximal descending
aorta) makes it difficult to perform such a staged procedure.
In such cases, an alternative staged surgical approach known
as the “elephant trunk” technique is used.30 The first part of
the surgery is, for the most part, similar to the standard
ascending aneurysm and total arch repair. However, the distal
end of the arch aortic graft is several centimeters longer than
the native arch, so that after the anastomosis is made to the
proximal descending aorta (just distal to the left subclavian
artery), the excess length of the graft is left protruding distally
within the lumen of the descending thoracic aortic aneurysm.
In the second stage of this procedure, the descending or
thoracoabdominal aortic aneurysm is repaired via a standard
left thoracotomy. However, the surgeon cross-clamps the
distal end of the existing elephant trunk (rather than clamping
the dilated native aorta), and the proximal end of the new
descending aortic graft is now anastomosed to the free distal
end of the elephant trunk.
Medical Management
The medical therapies available to slow the growth of
thoracic aortic aneurysms and reduce their risk of dissection
or rupture are quite limited. In a randomized study of adults
with Marfan syndrome, Shores et al31 found that treatment
with propranolol (versus no ␤-blocker therapy) over 10 years
resulted in a significantly slower rate of aortic dilatation,
fewer aortic events, and lower mortality. Unfortunately,
whether these benefits can truly be extrapolated to the
non-Marfan population with thoracic aneurysms remains
unknown. Nevertheless, it is mechanistically logical that
medical therapy to reduce dP/dt and to control blood pressure
would be beneficial for the treatment of all patients with
thoracic aortic aneurysms. Moreover, given the safety of
␤-blockers, there is no downside to presumptive therapy,
provided it is well tolerated. There is some early experimental
evidence to suggest that oxidative stress may play a role in the
pathogenesis of atherosclerotic thoracic aortic aneurysms and
that perhaps statin therapy and angiotensin II receptor blocker
therapy may potentially have a protective effect.32,33 However, much further research is needed before any therapeutic
implications can be drawn.
Once ␤-blocker therapy is maximized (or in the event that
␤-blockers are contraindicated or not tolerated), any persistent hypertension should be treated with other antihypertensive agents to bring the blood pressure down to a low-normal
range, eg, a systolic pressure of 105 to 120 mm Hg. “Whitecoat hypertension” is not uncommon among patients undergoing evaluation for aneurysms, and it may therefore be
challenging for a physician to determine whether or not the
Aortic Aneurysms
823
in-office blood pressure is truly representative. Consequently,
it is often helpful to have a patient use an automatic arm blood
pressure cuff to regularly monitor his or her response to
therapy and thereby confirm that the blood pressure is within
the prescribed range.
Although the majority of aortic dissections appear to occur
spontaneously, a minority are known to occur in the setting of
strenuous isometric exertion.34 Patients should therefore be
counseled to avoid heavy lifting or straining, because these
activities may abruptly increase intrathoracic pressure and
blood pressure. Aerobic exercise is generally safe, provided
the patient does not have a hypertensive response to exercise.
Consequently, should a patient wish to engage in vigorous
aerobic exercise (eg, running or biking), it is prudent to obtain
an exercise treadmill test— on ␤-blockers and/or other baseline antihypertensive medications—to assess the physiological response to exercise and ensure that the systolic blood
pressure does not rise above 180 mm Hg.
Patients should be informed of the typical symptoms of
acute aortic dissection. Moreover, patients should be instructed that should they ever experience the abrupt onset of
significant chest, neck, back, or abdominal pain, they should
present immediately to an emergency department for evaluation. They should be warned of the risks, should they choose
to wait hours or days to see whether the symptoms resolve
spontaneously. In addition, patients should be instructed to
inform the emergency physician of the existence of a thoracic
aortic aneurysm and explain explicitly that their physician
recommends an urgent CT scan of the chest (or transesophageal echocardiography or MRI if a CT is contraindicated) to
rule out acute aortic dissection or rupture. This may prompt
an emergency department physician who might not otherwise
consider aortic dissection in the differential diagnosis to
image the aorta promptly.
As detailed earlier, several etiologies of thoracic aortic
aneurysms, including a bicuspid aortic valve,10 may be
familial. Because thoracic aneurysms are typically asymptomatic, the only way to detect their presence among other
potentially affected family members is with formal screening.
For relatives of those with Marfan syndrome or a bicuspid
aortic valve, a screening echocardiogram may be appropriate.
For all other etiologies (including idiopathic aneurysms), a
CT scan or MRI is preferred, because imaging of the
ascending aorta is crucial.
It should be recognized that the presence of an aortic
aneurysm may be a marker of more diffuse aortic disease, as
up to one quarter of those with thoracic aortic aneurysms have
concomitant abdominal aortic aneurysms. Therefore, to exclude the presence of other aneurysms, it is essential that all
patients diagnosed with a thoracic aneurysm undergo at least
one baseline imaging study that includes the abdominal aorta.
This can be accomplished easily by CT scanning or MRI.
Serial Imaging
Patients should be followed up with serial imaging studies for
surveillance. When a thoracic aortic aneurysm is first detected, it is typically not possible to determine the rate of
growth. It is therefore appropriate to obtain a repeated
imaging study 6 months after the initial study. If the aneu-
824
Circulation
February 15, 2005
rysm is unchanged in size, it is then reasonable to obtain an
imaging study on an annual basis in most cases. In those
without Marfan syndrome or acute aortitis, thoracic aortic
aneurysms tend to grow quite slowly, so annual imaging is
sufficient for surveillance. However, should there be a significant increase in aortic size from one study to the next, the
interval between studies should be decreased to 3 or 6 months
(according to the aortic diameter).
To be useful for surveillance, imaging reports must include
the diameters of affected aortic segments; general descriptions, such as “there is an ascending aortic aneurysm” or “the
descending thoracic aorta is dilated,” are inadequate. To
quantify aneurysm growth over time, maximal aortic diameters must be compared. In addition, one must be cautious in
relying entirely on the conclusions reported by the reader.
Some readers may state, “There is a 5-cm ascending thoracic
aortic aneurysm, which is unchanged compared with the prior
examination.” However, if, for example, the previous aortic
diameter was 4.8 cm and before that it was only 4.6 cm, the
conclusion that the aneurysm is “unchanged” is misleading,
because it fails to illuminate the true pattern of progressive
aneurysm growth. Moreover, it is ideal to have serial imaging
studies performed in the same center with the same technique,
so that direct comparisons can be made between comparable
images.
Finally, individual readers may measure aortic diameters
differently, so even when the report states that the aortic
diameter has changed, it does not necessarily mean that the
aorta has truly grown in size from one study to the next. In
fact, in a recent systematic evaluation of interobserver variability, 8 experienced readers interpreted CT scans of aortic
aneurysms, and among them, there was a mean difference of
4 mm in the measurement of maximal aortic diameter.35
Consequently, the only way to be absolutely certain as to
whether or not the aortic diameter has changed is for a given
reader to compare similar images from sequential studies and
then to make each set of measurements personally.
Abdominal Aortic Aneurysms
Abdominal aortic aneurysms are much more common than
thoracic aortic aneurysms. Age is an important risk factor,
and the incidence of abdominal aortic aneurysm rises rapidly
after the age of 55 years in men and 70 in women. The
prevalence of abdominal aortic aneurysms is ⬇5% among
men ⱖ65 years of age screened by ultrasound.36
Etiology and Pathogenesis
Smoking is the risk factor most strongly associated with
abdominal aortic aneurysms, followed by age, hypertension,
hyperlipidemia, and atherosclerosis.37 Sex and genetics also
influence aneurysm formation. Men are 10 times more likely
than women to have an abdominal aortic aneurysm of 4 cm or
greater.38 Those with a family history of abdominal aortic
aneurysm have an increased risk of 30%,39 and their aneurysms tend to occur at a younger age and carry a greater risk
of rupture than do sporadic aneurysms. Unfortunately, no
gene defects have yet been identified.
The strength of the aortic wall lies in the elastin and
collagen of its extracellular matrix. Consequently, degrada-
tion of these structural proteins weakens the aortic wall and
allows aneurysms to develop. Classically, atherosclerosis has
been considered the underlying cause of abdominal aortic
aneurysms: The infrarenal abdominal aorta is most affected
by the atherosclerotic process and is similarly the most
common site of abdominal aneurysm formation. However,
current research suggests that genetic, environmental, hemodynamic, and immunologic factors all contribute to the
development of aneurysms.
There is histological evidence of inflammatory infiltrates
within the wall of aortic aneurysms, and such inflammation
has been implicated in the degradation of the extracellular
matrix. Matrix metalloproteinases are enzymes that are produced by smooth muscle and inflammatory cells, and several
of these proteinases may participate in abdominal aortic
aneurysm formation. Indeed, certain of the matrix metalloproteinases can degrade elastin and collagen. The levels of
some matrix metalloproteinases are significantly elevated in
the walls of aneurysms compared with controls. In addition,
several other proteinases, including plasminogen activators,
serine elastases, and cathepsins, may also contribute to the
formation of aneurysms.
Clinical Manifestations
Most abdominal aortic aneurysms are asymptomatic and are
discovered incidentally on routine physical examination or on
imaging studies ordered for other indications. When symptoms do arise, pain is the typical complaint. The pain is
usually located in the hypogastrium or lower back and is
typically steady and gnawing, lasting hours to days. Actual
rupture is associated with an abrupt onset of back pain along
with abdominal pain and tenderness. Most patients have a
palpable, pulsatile abdominal mass, and many are hypotensive and appear critically ill.
Physical Examination
Many aneurysms can be detected on physical examination as
a pulsatile mass extending from the xiphoid to the umbilicus.
However, the sensitivity of the physical examination is
limited, and even large aneurysms may be difficult or
impossible to detect in overweight or obese individuals.40 The
size of an aneurysm tends to be overestimated on physical
examination, so even normal aortas may sometimes feel
enlarged.
Diagnosis and Sizing
Several diagnostic imaging modalities are available for detecting and serially monitoring abdominal aortic aneurysms.
Abdominal ultrasonography is perhaps the most practical way
to screen for aneurysms. Its major advantages are that it is
relatively inexpensive and noninvasive and does not require
the use of a contrast agent.
Compared with ultrasonography, CT scanning has the
advantage that it can better define the shape and extent of
the aneurysm, as well as the local anatomic relationships
of the visceral and renal vessels. It is also superior to
ultrasonography in imaging suprarenal aortic aneurysms.
Disadvantages include its cost and its use of ionizing
radiation and intravenous contrast media. Nevertheless,
although CT is less practical than ultrasonography as a
Isselbacher
Aortic Aneurysms
825
Figure 12. Growth rates of small abdominal aortic aneurysms vs
aneurysm size. Solid lines indicate growth rates adapted from 5
longitudinal series (a⫽Brown PM et al45; b⫽Lindholt JS et al54;
c⫽Stonebridge PA et al57; d⫽Vardulaki KA et al58; and
e⫽Santilli SM et al59). Dashed line represents approximation of
mean expected growth rate vs size, based on these series.
(©Massachusetts General Hospital Thoracic Aortic Center. Used
with permission.)
Figure 11. Contrast-enhanced CT scan with 3-dimensional
reconstruction demonstrating a 5.6-cm infrarenal abdominal
aortic aneurysm. The image has been rotated in space so that
one is viewing the posterior aspect of the aneurysm. The kidneys, spleen, and liver are also visualized.
screening tool, its high accuracy in sizing aneurysms
makes it an excellent modality for serially monitoring
changes in aneurysm size. It is important to note that CT
measurements of aneurysm size tend to be larger than
ultrasound measurements by a mean of 3 to 9 mm,
according to the aneurysm size.41,42 CT angiography (3dimensional display of the aorta and its branches) is
particularly useful, in that it provides more comprehensive
evaluation of the anatomy of both the abdominal aortic
aneurysm and the renal, mesenteric, and iliac arteries
(Figure 11).
In those in whom contrast-enhanced CT scanning is contraindicated (eg, renal insufficiency or allergy), MR angiography is an alternative for the comprehensive evaluation of
aortic aneurysms. Given the image quality that both CT and
MR angiography provide, traditional catheter-based contrast
aortography is now infrequently used in the evaluation of
abdominal aneurysms.
Screening
In the past decade, much attention has been paid to the
potential utility of routine screening of asymptomatic adults
for the presence of abdominal aneurysms. The largest and the
most definitive controlled trial to date is from the Multicenter
Aneurysm Screening Study Group,36 in which a populationbased sample of 67 800 men (aged 65 to 74 years) were
randomized to an invitation to ultrasound screening or to a
control group not offered screening. Those with aneurysms
were followed up with serial ultrasound scans for a mean of
4 years, and surgery was considered when the diameter
reached ⱖ5.5 cm. There were 65 aneurysm-related deaths in
the screening group versus 113 in the control group, yielding
an estimated risk reduction of 42%.
Calculating the cost per life-year gained requires factoring
in numerous financial variables, and differences in assumptions about costs (eg, screening, surgery, and hospitalizations)
and cost savings (eg, avoiding emergency surgery for aortic
rupture) significantly impact conclusions about cost efficacy.
Consequently, estimates of cost per life-year gained vary
from as low as $110743 to as high as $57 000,36 with
screening of 700 to 1000 subjects required to prevent 1 death.
Although the exact cost for life-year gained remains uncertain, it nevertheless does appear that screening is grossly
cost-effective. Indeed, in a recent “consensus statement,” a
number of US vascular specialists have recommended screening of all men 60 to 85 years of age, all women 60 to 85 years
of age with cardiovascular risk factors, and both men and
women ⬎50 years of age with a family history of abdominal
aortic aneurysm.44
Natural History
The major risk posed by an abdominal aortic aneurysm is
rupture and its high associated mortality. In one large trial of
those with ruptured aneurysms, 25% died before reaching a
hospital, another 51% percent died at the hospital without
undergoing surgery, and of the those who had surgery, the
operative mortality was 46%, yielding an overall 30-day
survival of just 11%.45 The goal then is to have patients
undergo elective aortic repair—with a mortality of only 4% to
6%—when aneurysms are considered to be at significant risk
of rupture.
The risk of rupture increases with aneurysm size. The UK
Small Aneurysm Trial found that for aneurysms ⬍4 cm, 4 to
4.9 cm, and 5 to 5.9 cm, the annual risk of rupture was 0.3%,
1.5%, and 6.5%, respectively.45 For aneurysms 6 cm or
greater, the risk of rupture rises sharply, although an exact
risk cannot be estimated. Although abdominal aneurysms are
less prevalent among women than men, when present they
rupture 3 times more frequently and at a smaller aortic
diameter (mean of 5 versus 6 cm). Rupture is also more
826
Circulation
February 15, 2005
common among current smokers and those with hypertension.45 A rapid rate of expansion predicts aneurysm rupture.
Although the mean rate of abdominal aortic aneurysm
expansion is thought to approximate 0.4 cm/y, the rates of
expansion within a population are extremely variable. Baseline aneurysm size is the best predictor of aneurysm growth
rate, with larger aneurysms expanding more rapidly than
small ones. Figure 12 summarizes graphically the aneurysm
growth rates as determined in a number of longitudinal series.
A promising new technique for predicting the fate of abdominal aortic aneurysms is the analysis of wall stress. A
3-dimensional reconstruction of the aortic aneurysm is performed with the use of CT angiography, and wall stress is
then determined by finite-element analysis and blood pressure. In a recent analysis of 103 patients, Fillinger et al46
found that the sensitivity and specificity of peak wall stress
were superior to maximum aortic diameter for predicting risk
of aortic rupture. Although this technique still needs to be
refined and better studied, it holds promise to become an
important tool in determining the timing of aortic repair.
Management
Surgical Treatment
Aneurysm size is the primary indicator for repair of asymptomatic aneurysms, and in the wake of 2 recent large-scale
trials, there is now a reasonable consensus as to the appropriate aneurysm diameter that necessitates surgery. The UK
Small Aneurysm Trial47 and the Aneurysm Detection and
Management (ADAM) Veterans Affairs Cooperative Study48
randomized patients with small aortic aneurysms (diameter of
4 to 5.5 cm) to either early elective surgery or regular
surveillance imaging, and both found no difference in survival between the 2 groups. The outcomes of the trials
suggest that surgery is not indicated, in most instances, for
asymptomatic aneurysms ⬍5.5 cm. However, one important
limitation is that these 2 study populations consisted almost
entirely of men, and because the risk of aneurysm rupture is
greater and occurs at smaller diameters in women than in
men, it is believed that these results are not generalizable to
women.33 Indeed, in a recently published set of guidelines,
the Joint Council of the American Association for Vascular
Surgery and Society for Vascular Surgery concurred with the
5.5-cm threshold for the “average” male patient but recommended that women should undergo elective repair at a
smaller aortic diameter of 4.5 to 5 cm.49
Elective repair carries an average operative mortality of
4% to 6% and of only 2% in low-risk patients. A number of
studies have shown that mortality is inversely related to a
surgeon’s volume. In fact, in a recent analysis, both a high
surgeon volume and a high hospital volume were both
associated with lower mortality than low-volume providers
and that surgeons specializing in vascular surgery had a lower
mortality than did nonspecialized surgeons with the same
aortic repair volume.50
A less-invasive alternative to open surgery for repair of
abdominal aortic aneurysms is the use of percutaneously
implanted, expanding endovascular stent-grafts. Once deployed, the stent-graft serves to bridge the region of the
aneurysm, thereby excluding it from the circulation while
Suggested Intervals for Surveillance Imaging of Abdominal
Aortic Aneurysms vs Baseline Aortic Diameter
Present Aneurysm
Diameter, cm
Reimage
Aorta in
2.5–2.9
5y
3.0–3.4
3y
3.5–3.9
2y
4.0–4.4
1y
4.5–4.9
6 mo
5.0–5.5
3–6 mo*
*In addition to planning repeated surveillance imaging, one should also
consider referral to a vascular surgeon. Note that for abdominal aortic
diameters of ⬍2.5 cm, rescreening is generally thought to be unnecessary.
Data derived from References 53–56.
allowing aortic blood flow to continue distally through the
prosthetic stent-graft lumen. To begin with, only 30% to 60%
of abdominal aortic aneurysms are anatomically suitable for
endovascular repair. When undertaken, the rate of successful
stent-graft implantation has ranged from 78% to 94%. One of
the major technical difficulties associated with the stent-graft
technique that has yet to be overcome is the frequent
occurrence of endoleaks, which occur in 10% to 20% of
cases49 and are seen angiographically as persistent contrast
flow into the aneurysm sac because of failure to completely
exclude the aneurysm from the aortic circulation. If left
untreated, these endoleaks may potentially leave the patient at
continued risk for aneurysm expansion or rupture. Indeed, in
a follow-up study of outcomes at 12 months or longer among
⬎1000 stent-graft recipients, the EUROSTAR investigators
reported that almost 10% of patients per year required
secondary interventions, suggesting that there should be
caution in the broad application of endovascular aneurysm
repair.51 Moreover, at present, the long-term outcome of
endovascular repair versus conventional surgical repair remains unknown. Therefore, the use of stent-grafts for endovascular repair of abdominal aortic aneurysms has generally
been limited to older patients and those at high operative risk.
Medical Management
As with thoracic aortic aneurysms, ␤-blocker therapy is
considered important for reducing the risk of abdominal
aortic aneurysm expansion52 and rupture. Risk factor modification is fundamental: Hypercholesterolemia and hypertension should be controlled and cigarette smoking discontinued.
Aneurysms too small to merit surgery should be followed up
with periodic surveillance imaging to monitor their size. On
the basis of an aneurysm’s current size and its anticipated rate
of growth (as in Figure 12), one can estimate how quickly an
aneurysm might grow to a size large enough to merit repair
and thus recommend appropriate intervals for reimaging. A
sample schedule of surveillance imaging is summarized in the
Table.53–56 In a recent analysis of aneurysm growth, Brady et
al53 have estimated that following such a rescreening algorithm would limit the possibility of an aneurysm reaching
⬎5.5 cm between screenings to ⬍1%. When monitoring
growth of aneurysms with a diameter ⱖ4 cm, CT scanning
Isselbacher
may be preferable to ultrasound because CT sizing is more
accurate.
Conclusions
Whereas aortic aneurysms are less common that many other
cardiovascular conditions, the fact that they can be life
threatening and that even large aneurysms may not produce
symptoms makes it all the more important for clinicians to be
vigilant in their evaluation of patients at risk. Because
aneurysms are often first detected on an imaging study
ordered for other indications, any suggestion of an enlarged
aorta should prompt follow-up with an appropriate dedicated
imaging study. Fortunately, modern imaging techniques—
especially CT and MRI— have now made the sizing and
surveillance of aneurysms relatively easy. In the future,
genetic screening may also play a role in the screening of
those with a family history of thoracic aortic aneurysms.
Ideally, a broadening clinical awareness of aortic aneurysms and the methods of diagnosis will help reduce the
morbidity and mortality associated with this condition. Indeed, clinicians who understand the principles of medical and
surgical management of aortic aneurysms can comfortably
determine when they should manage patients with medication
and serial imaging studies (to follow aneurysm size and rate
of growth) and when to refer to a cardiothoracic or vascular
surgeon. Finally, whereas open surgical repair remains the
standard approach to treating most large aortic aneurysms, it
is likely that endovascular stent-grafting will assume an
increasingly important role as the technique is further refined.
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KEY WORDS: aneurysm
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aorta
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diagnosis
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imaging
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surgery