8 diseases of the aorta

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8: Diseases of the Aorta

Overview

Aortic diseas e is discussed in this chapter's 2 modules on aneurysm disease and the acute syndromes of dissection,

intramural hematoma, and penetrating ulcer, respectively. Patient assessment, management, and surveillance are emphasized,

as highlighted in recent guidelines.

Authors

Patrick T. O'Gara, MD, FACC

Editor-in-Chief

Thomas M. Bashore, MD, FACC

Associate Editor

James C. Fang, MD, FACC

Associate Editor

Glenn A. Hirsch, MD, MHS, FACC

Associate Editor

Julia H. Indik, MD, PhD, FACC

Associate Editor

Donna M. Polk, MD, MPH, FACC

Associate Editor

Sunil V. Rao, MD, FACC

Associate Editor


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8.1: Aneurysm Disease

Author(s):

Eric M. Isselbacher, MD

Learner Objectives

Upon completion of this module, the reader will be able to:

1. Screen first-degree relatives of the affected individual in order to detect unrecognized aneurysms, because aortic root and

ascending thoracic aortic aneurysms (TAAs) may be familial.

2. Recognize the association between bicuspid aortic valve (BAV) and ascending TAAs, and make certain that the aorta hasbeen imaged in patients with a BAV.

3. Monitor aneurysm growth with surveillance imaging in order to make timely referrals for aortic repair.

4. Compare the risk of aortic dissection or rupture against the risk of aortic repair for the individual patient when deciding on

the timing of the aortic repair.


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Abdominal Aortic Aneurysms

Aortic aneurysms may involve either the abdominal aorta, the thoracic aorta, or,

rarely, both segments (thoracoabdominal aortic aneurysms). Abdominal aortic

aneurysms (AAAs) are much more common than TAAs. Importantly, among those

with an aneurysm in one segment of the aorta, there is a 25% chance of having a

concomitant aneurysm involving another aortic segment. It is therefore important to

image the entire aorta of affected patients to look for the presence of aneurysms

elsewhere.

The true prevalence of AAAs is not well defined, due to variation in both diagnostic

criteria and the baseline risk of the populations screened. However, screening a

population 65 years of age has revealed a prevalence of 5-7% among men and

approximately 1% among women. The rate of aneurysm diagnosis has been

increasing over the past several decades. The majority of AAAs arise below the renal

arteries (infrarenal abdominal aneurysms), whereas a minority arise above the level

of the renal arteries (suprarenal aneurysms). Stagnation of blood may result in

thrombus formation along the aneurysm wall the thrombus may embolize distally,

and its presence also appears to increase the risk for aneurysm growth and rupture.

There are a number of important risk factors for AAA, as summarized in Table 1.

Atherosclerosis, which had long been considered the cause of AAAs, clearly

contributes to the process of aneurysm formation, but there is also evidence that

genetic, environmental, hemodynamic, and immunological factors contribute as

well. There is histological evidence of inflammatory infiltrates within the walls of

aneurysms. Moreover, certain matrix metalloproteinases (MMPs), enzymes

produced by smooth muscle and inflammatory cells, can degrade elastin and

collagen, the primary components of the aortic extracellular matrix that give the aortic

wall its tensile strength. The levels of some MMPs are significantly higher in the

walls of aneurysms compared with controls. Conversely, in animal models of AAA,

treatment with doxycycline, which inhibits MMPs through a mechanism unrelated to

its antibiotic activity, leads to lower levels of MMP-9 in the aortic wall, reduced

degradation of medial elastin, and reduced expansion of aneurysms.

Early data from human trials have shown promising results, but randomized clinical

trials have not yet been performed, so the use of such therapies is not currently

recommended. Statin therapy has also been shown to reduce MMP-9 expressionand to protect against aneurysm growth in a mouse model, regardless of the

cholesterol level. Additionally, in humans undergoing elective AAA repair,

preoperative statin therapy is associated with a decrease in MMP-9 levels in the

aortic wall. One meta-analysis of five observational studies found significantly

slower aneurysm growth among patients treated with statins, but another study

showed no benefit1 unfortunately, there are no completed randomized controlled

trials. Beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor

blockers, and aspirin may also have potential benefits in treating AAAs, but these

therapies have yet to be studied in prospective controlled clinical trials.

Most patients with AAAs are asymptomatic, and their aneurysms are discovered

incidentally on physical examination or via imaging ordered for another indication.

Patients who have symptoms usually present with gnawing pain located in the

hypogastrium or lower back. Aneurysm rupture is associated with abrupt onset ofpain, along with abdominal tenderness and a pulsatile abdominal mass.

Several imaging techniques can identify and size AAAs. Abdominal ultrasonography

is accepted as the most practical way to screen for AAAs. This technique is

inexpensive and without risk, but it is limited in the accuracy of its measurements

and its ability to image the suprarenal aorta and the mesenteric and renal arteries

well. Computed tomography angiography (CTA), on the other hand, is extremely

accurate in imaging and sizing all segments of the aorta, as well as in defining

branch vessel anatomy. However, CTA is more expensive, and requires the use of

iodinated contrast and ionizing radiation.

There has been much debate historically about the value of screening for AAAs.

However, data from multiple large prospective trials have convincingly demonstrated

Table 1

Table 2

Figure 1

Figure 2


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that screening at-risk populations is effective and, more importantly, cost effective.

The US Preventive Services Task Force has concluded that the evidence supports

one-time ultrasonography screening for AAAs among men 65-75 years old who are

current or former smokers.2 Many experts also recommend screening those who

have a first-degree relative with an AAA. At present, however, there is no evidence to

support the routine screening of women.

The major risk associated with AAAs is that of rupture. Among the participants in

the United Kingdom Small Aneurysm Trial who suffered a ruptured AAA, 25% died

before reaching the hospital, another 50% died at the hospital prior to aortic repair,

and the overall 30-day survival was just 11%.3 It is therefore critical to repair AAAs

when they are first recognized by size criteria to be at significant risk of rupture. Therisk of rupture increases with aneurysm diameter, as shown in Table 2.

Although AAAs are less prevalent among women, they are more prone to rupture

and tend to rupture at smaller aortic diameters compared with men. In order to

prevent aneurysm rupture, elective repair of asymptomatic AAAs is recommended

when the diameter reaches 5.5 cm. In good surgical candidates and women, many

experts lower the threshold to 5.0 cm, especially among patients of a smaller body

size or with a family history of rupture.4

Open surgical repair requires opening the aneurysm and inserting an artificial tube

graft if the aneurysm extends distally, then the repair may be carried into the

common iliac arteries with a branched graft. Alternatively, AAAs can often be repaired

via a minimally invasive approach called "endovascular aortic repair" (EVAR), with

the use of a percutaneously implanted, endovascular, covered stent-graft that serves

to bridge the aneurysm sac and to exclude it from the circulation (Figure 1). The

stent-graft may be a straight tube or bifurcated, with branches extending into the

common iliac arteries.

When attempted, stent-grafts are successfully deployed 98% of the time. However,

one limitation of EVAR is that only about one-half of patients with AAAs have anatomy

that is suitable for the procedure. A second limitation of the procedure is the frequent

occurrence of endoleaks, in which there is persistence of blood flow into the

excluded aneurysm sac. Such endoleaks may occur because of failure to

adequately seal the proximal or distal end of the stent-graft (type I endoleak) or,

more often, due to retrograde flow from small branch arteries (such as the inferior

mesenteric or lumbar arteries) back into aneurysm sac (type II endoleak). Often,

additional percutaneous procedures are needed to treat the endoleak left untreated,they may leave the patient at risk for continued aneurysm expansion and rupture.

Patients with endoleaks, therefore, require monitoring with surveillance imaging.

Multiple prospective randomized trials have shown significant lower early mortality

among those treated with EVAR compared with open repair. However, both

the EVAR 1 (Endovascular Aneurysm Repair 1) trial5 and the DREAM (Dutch

Randomized Endovascular Aneurysm Repair) trial6 demonstrated that, in the long

term, there were no significant differences in total mortality or aneurysm-related

mortality (Figure 2). Moreover, in the long term, EVAR was associated with increased

complication rates and the need for more re-interventions (even as far as 8 years out

from the index procedure). Thus, EVAR offers no clear late advantage over open

repair among those who are good candidates for either procedure. Consequently,

the choice of which approach to take for aortic repair should be individualized for

each patient and based on age, comorbidities, patient preference, and aortic

anatomy.


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Risk Factors for Abdominal Aortic Aneurysms

Table 1


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Annual Risk of Abdominal Aortic Aneurysm Rupture vs. Aneurysm Diameter in the United Kingdom Small Aneurysm Trial

Table 2

Adapted with permission from Brown LC, Powell JT. Risk factors for aneurysm rupture in patients kept under ultrasound surveillance. Ann Surg

1999230:289-96.


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Endovascular Abdominal Aortic Aneurysm Repair (EVAR)

Figure 1

The image in the upper left demonstrates the typical appearance of an infrarenal abdominal aortic aneurysm. Panel A: An endograft has been

introduced retrograde from the access site and deployed across the aneurysm sac, with one limb extending into the ipsilateral common iliac

artery. The proximal end of the graft needs a landing zone that is of relatively normal diameter. Panel B: Barbs or hooks at the proximal end

prevent distal migration. A guidewire is then advanced into the graft retrograde from the contralateral side. Panel C: The contralateral iliac artery

limb of the graft is introduced over the guidewire and expanded. Panel D: The ipsilateral limb is fully deployed and an endovascular balloon is

inflated along the stentgraft to secure fixation of the anastomotic sites. The blue arrows indicate movement of the guidewire.

Reproduced with permission from Greenhalgh RM, Powell JT. Endovascular repair of abdominal aortic aneurysm. N Engl J Med 2008358:494-

501.


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KaplanMeier Estimates for Total Survival and Aneurysm-Related Survival During 8 Years of Follow-Up

Figure 2

Among patients randomly assigned to either endovascular repair or open repair of an abdominal aortic aneurysm, an early benefit with respect to

aneurysm-related mortality in the endovascular-repair group was lost by the end of the study, at least partially because of fatal endograft

ruptures (adjusted hazard ratio with endovascular repair, 0.92 95% confidence interval [CI], 0.57-1.49 p = 0.73). By the end of 8 years of

follow-up, there was no significant difference between the two groups in the risk of death from any cause (adjusted hazard ratio, 1.03 95% CI,

0.86-1.23 p = 0.72).

Reproduced with permission from The United Kingdom EVAR Trial Investigators. Endovascular versus open repair of abdominal aortic aneurysm.

N Engl J Med 2010362:1863-71.


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Thoracic Aortic Aneurysms

TAAs are less common than AAAs. TAAs may involve the aortic root, ascending

aorta, aortic arch, or descending aorta when they extend below the diaphragm, they

are referred to as "thoracoabdominal aortic aneurysms." Aneurysms of the aortic

root and ascending aorta are most common, and usually occur as a consequence

of underlying medial degeneration (previously termed, cystic medial necrosis).

Medial degeneration is notable for the loss of smooth muscle cells and elastic fiber

degeneration, resulting in weakening of the aortic wall. Aneurysms of the

descending aorta are more often associated with atherosclerosis. The known

etiologies of TAAs are listed in Table 3.

Medial degeneration is well recognized in association with Marfan syndrome, which

is a connective tissue disorder associated with a decreased amount of elastin in the

aortic media and abnormal elastic properties of the aortic wall. Marfan syndrome is

an autosomal dominant heritable disorder due to mutations in the gene FBN-1,

which encodes for fibrillin-1, a component of the microfibrils of elastin.

Dietz and colleagues have demonstrated that fibrillin-1 not only is of structural

importance, but also plays a role in regulating transforming growth factor (TGF)- in

Marfan syndrome, the abnormal elastin leads to excessive TGF- signaling, which in

turn leads to elastic fiber fragmentation and progressive aortic root enlargement. In

a mouse model of Marfan syndrome (with fibrillin-1 mutations and aortic root

enlargement), treatment with a TGF- neutralizing antibody resulted in reduced TGF-

signaling in the aortic media and arrested aortic growth. Losartan is also a TGF-

inhibitor, and similarly prevents aortic aneurysms in the mouse model of Marfan

syndrome.7

BAV disease is an important risk factor for aortic root and ascending TAA. BAV

disease is the most common congenital valve disorder, occurring in 1.4% of the

general population. Men are affected four times as commonly as women. It was

once thought that the aortic enlargement seen in patients with BAV disease was a

consequence of associated bicuspid aortic stenosis, and it was therefore referred to

as "poststenotic dilatation." However, current evidence argues otherwise.

Approximately 50% of patients with BAVs have enlargement of the proximal aorta,

and the prevalence is independent of the function of the valve, meaning that aorticdilatation is seen as often among patients with regurgitant or normally functioning

BAVs as patients with stenotic valves. Moreover, among patients undergoing aortic

valve replacement surgery for aortic stenosis, 75% of those with a native BAV are

found to have medial degeneration compared with only 14% of those with a native

tricuspid aortic valve.

BAV disease may be heritable, as 20% will have an affected first-degree relative,

but no single responsible gene has yet been identified. Because aortic enlargement

is so common, all patients with a BAV should be formally evaluated for evidence of

aortic root or ascending aortic dilatation. The aortopathy associated with BAV

disease can extend to the level of the ligamentum arteriosum and includes

coarctation.

Ascending aortic aneurysms may be idiopathic, and in many such cases, aortichistology reveals medial degeneration similar to what is seen in Marfan syndrome

and BAV disease. Such aneurysms may be sporadic, but in 20% of cases, other

family members may be affected, suggesting a heritable condition that is referred to

as "familial TAA syndrome." Most pedigrees suggest an autosomal dominant mode

of inheritance, but there is marked variability in expression and penetrance.

Mutations have been identified in approximately 20% of affected families, including

the genesACTA2, TGFBR2, and MYH11. The role of genetic testing in patients with

TAAs remains to be clarified. Nevertheless, given the fact that Marfan syndrome,

BAVs, and idiopathic TAAs can be heritable, first-degree relatives of affected

individuals should be screened for thoracic aortic disease with diagnostic imaging.

Most TAAs are asymptomatic and are not detectable on a routine physical

examination the large majority are discovered incidentally on an imaging study

ordered for another reason. When TAAs present clinically, it is usually due to

Table 3

Table 4

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8


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enlargement of the root or ascending aorta that leads to tethering of the aortic valve

leaflets, resulting in incomplete valve closure and aortic insufficiency the aortic

insufficiency may present early, as a diastolic heart murmur, or late, as heart failure.

Less often, TAAs present with symptoms caused by a mass effect, such as cough,

dysphagia, or hoarseness due to tracheal, esophageal, or recurrent laryngeal nerve

compression, respectively. Large or rapidly expanding TAAs may also present with

symptoms of chest or back pain.

TAAs can be detected by CTA, magnetic resonance angiography (MRA),

echocardiography, and aortography. CTA is used most often for evaluation of the

thoracic aorta, as it provides outstanding anatomic detail and accurate sizing of the

aorta. MRA also images the aorta well, although it is less convenient and cannot beused in patients with pacemakers or implantable cardioverter defibrillators.

Transthoracic echocardiography is very good at imaging the aortic root, but is less

reliable in imaging the ascending aorta. Transesophageal echocardiography

images the thoracic aorta well, but is minimally invasive. Invasive aortography can

identify dilated aortic segments, but it cannot be used to size the aorta accurately.

Most TAAs grow over time. The rates of growth are greater for large versus small

aneurysms, for patients with Marfan syndrome or with a chronic aortic dissection,

and for aneurysms involving the descending, rather than the ascending, aorta.

Similiar to AAAs, the risk of TAA dissection or rupture increases with aortic diameter

and, although dissection can occur at any diameter, the risk rises abruptly for aortic

diameters of 6 cm. The mortality associated with aortic dissection or rupture is

high, whereas the mortality of elective repair is reasonable, so the goal is to repair

the aorta prior to any aortic catastrophe. The indications for repair of asymptomaticTAAs, based on the 2010 American College of Cardiology Foundation/American

Heart Association (ACCF/AHA) guidelines,8 are listed in Table 4. However, the

timing of elective aortic repair must be individualized for each patient, weighing the

risk of surgery against the risk of aortic dissection or rupture.

Open repair is required for proximal TAAs. If the ascending aorta alone is enlarged,

a simple interposition tube graft should suffice (Figure 3). If the aortic root is

enlarged, traditional surgery required sacrificing the aortic valve, with resection of the

root and replacement of the root and valve collectively with a "composite aortic graft,"

also called the Bentall procedure (Figure 4). However, in the modern era, if the aortic

valve leaflets are healthy, the native valve can be preserved and resuspended within

the prosthetic tube graft, in what is known as valve-sparing aortic root repair, also

called the David procedure (Figure 5).

When the aortic arch is dilated, a total arch replacement is usually required. Most

often, this is performed using a multilimbed prosthetic arch graft, to which each arch

vessel is anastomosed individually (Figure 6). The major risk of arch repair is brain

injury, either from anoxia or embolization of debris. Methods of cerebral protection

include deep hypothermic circulatory arrest, retrograde cerebral perfusion, or

antegrade cerebral perfusion. Most surgeons now use antegrade cerebral perfusion

via cannulation of the right axillary artery,9 which has been associated with

significantly improved outcomes. More recently, for very high-risk patients with arch

aneurysms, a hybrid procedure has been introduced in which the arch is

debranched by bypassing the brachiocephalic arteries using a trifurcated trunk from

the proximal ascending aorta, and then an endovascular stent-graft is deployed

across the arch aneurysm.10

Aneurysms of the descending thoracic aorta have traditionally been repaired with

open surgery via a left thoracotomy (Figure 7). However, the procedure is associated

with significant morbidity and a mortality rate of approximately 10%. The most feared

complication is postoperative paraplegia secondary to impairment of the arterial

blood supply to the spinal cord, with an incidence of approximately 5% in high-

volume centers.

A number of techniques have been introduced to reduce the risk of ischemic spinal

cord injury, including cerebrospinal fluid drainage, epidural cooling, the

reimplantation of patent critical intercostal arteries, the use of intraoperative

somatosensory- or motor-evoked potential monitoring, atriofemoral (i.e., left atrial to

femoral) bypass to maintain distal aortic perfusion during surgery, and the

maintenance of sufficiently high systemic arterial pressure during the first several


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days after surgery.

In recent years, thoracic endovascular aortic repair (TEVAR) with stent-grafting has

emerged as a promising alternative to open surgical repair for aneurysms of the

descending thoracic aorta (Figure 8). The TEVAR procedure is far less invasive and

is associated with a lower postoperative morbidity than open repair. At present, there

are no randomized prospective trials comparing TEVAR to open repair.

In a multicenter prospective nonrandomized phase II study of the Gore TAG graft,

TEVAR implantation was successful in 98% of patients, and the 30-day event rates

were 3% for paraplegia and 2% for death, which were significantly better than the

respective event rates in an open surgical control population.11

At 5 years,aneurysm-related mortality was lower for the TEVAR patients than for open controls,

at 3% versus 12%, respectively.12 Yet, despite this advantage, there was no

difference in all-cause mortality at 5 years, likely reflecting the fact that the TEVAR

patient populations tend to be older and have numerous comorbidities.

Candidacy for TEVAR requires suitable aortic anatomy, including favorable proximal

and distal landing zones. As is the case with stent-grafting of the abdominal aorta,

even after successful deployment of endovascular stent-grafts in the thoracic aorta,

patients may be left with endoleaks. The average prevalence of endoleaks at 30

days is 10%, with type I endoleaks occurring most commonly with TEVAR, reflecting

the challenges of achieving an optimal seal at the proximal attachment site.13

TEVAR patients require annual surveillance imaging with CTA to monitor for

endoleaks, to confirm that the aneurysm sac is not expanding, and to assess both

stent-graft integrity and residual thoracic aortic anatomy.

Beta-blockers have long been the mainstay of medical therapy for TAAs. Beta-

blockers have been shown to significantly reduce the rate of aortic growth in patients

with Marfan syndrome, although their benefit in treating aneurysms of other

etiologies has not been proven. As noted previously, losartan has been shown to

reduce the rate of aneurysm growth in a murine model of Marfan syndrome. There is

an ongoing multicenter randomized prospective clinical trial comparing the use of

beta-blockers versus losartan in young patients with Marfan syndrome. There also

exist limited trial data to suggest that angiotensin-converting enzyme inhibitors may

also slow the rate of aortic growth in patients with Marfan syndrome. Whichever

agent is prescribed, the goal of medical therapy is a systolic blood pressure in the

low-normal range (e.g., 110-120 mm Hg).

Another element of medical therapy is surveillance imaging to monitor for aortic

growth. In most cases, the imaging should be repeated annually, and when the

aortic diameter nears the threshold for intervention, patients should be referred to an

appropriate aortic specialist for evaluation.


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Etiology of Thoracic Aortic Aneurysms

Table 3


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Recommended Size Thresholds for Elective Thoracic Aortic Repair in Asymptomatic Patients

Table 4

Adapted with permission from Hiratzka LF, Bakris GL, Beckman JA, et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelinesfor the diagnosis and management of patients with thoracic aortic disease. A Report of the American College of Cardiology Foundation/American

Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American

Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of

Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. J Am Coll Cardiol 201055:e27-e129.


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Interposition Graft to Repair an Aneurysm of the Ascending Thoracic Aorta

Figure 3

Massachusetts General Hospital Thoracic Aortic Center, used with permission.


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Composite Aortic Graft to Repair an Aneurysm of the Aortic Root

Figure 4



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Valve-Sparing Aortic Root Repair for a Root Aneurysm

Figure 5



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Total Arch Replacement for Aortic Arch Aneurysm

Figure 6



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Open Surgical Repair of a Descending Thoracic Aortic Aneurysm

Figure 7



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Endovascular Stent-Grafting of a Descending Thoracic Aortic Aneurysm (TEVAR)

Figure 8



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Key Points

Multiple large prospective trials have demonstrated that screening at-risk populations for AAAs is cost effective,

and the US Preventive Services Task Force supports screening by ultrasonography for AAAs among men 65-75

years old who are current or former smokers.

Elective repair of asymptomatic AAAs is recommended at a diameter of 5.5 cm, although in good surgical

candidates and women, many experts lower that threshold to 5.0 cm.

Multiple prospective randomized trials have shown significant lower early mortality among those treated with

EVAR compared with open surgery repair, yet such trials have found no significant difference in longer term total

mortality.

In patients with Marfan syndrome, the abnormal elastin leads to excessive TGF- signaling that, in turn, leads to

elastic fiber fragmentation and progressive aortic root enlargement.

BAV is an important risk factor for aortic root and ascending aortic aneurysms.

Marfan syndrome, BAV, and idiopathic thoracic aortic aneurysms can be heritable thus, first-degree relatives of

affected individuals should be screened for thoracic aortic disease using diagnostic imaging studies.

Traditional surgery for replacing a dilated aortic root required sacrificing the aortic valve, with resection of the root

and replacing the root and valve collectively with a "composite aortic graft," which is also known as the Bentall

procedure.

In the modern era of aortic root surgery, if the aortic valve leaflets are healthy, the valve is preserved and

resuspended within a prosthetic tube graft in what is known as a "valve-sparing aortic root repair," or the David

procedure.


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Suggested Reading

1. Greenhalgh RM, Brown LC, Powell JT, and the United Kingdom EVAR Trial Investigators. Endovascular versus

open repair of abdominal aortic aneurysm. N Engl J Med 2010362:1863-71.

2. Chaikof EL, Brewster DC, Dalman RL, et al. The care of patients with an abdominal aortic aneurysm: the Society

for Vascular Surgery practice guidelines. J Vasc Surg 200950(4Suppl):S2-S49.

3. Hiratzka LF, Bakris GL, Beckman JA, et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for

the diagnosis and management of patients with thoracic aortic disease. A Report of the American College of

Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for

Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular

Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology,

Society of Thoracic Surgeons, and Society for Vascular Medicine. J Am Coll Cardiol 201055:e27-e129.

4. Coady MA, Ikonomidis JS, Cheung AT, et al. Surgical management of descending thoracic aortic disease: open

and endovascular approaches: a scientific statement from the American Heart Association. Circulation

2010121:2780-804.

5. Habashi JP, Judge DP, Holm TM, et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model

of Marfan syndrome. Science 2006312:117-21.


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References

1. Twine CP, Williams IM. Systematic review and meta-analysis of the effects of statin therapy on abdominal aortic

aneurysms. Br J Surg 201198:346-53.

2. US Preventive Services Task Force. Screening for abdominal aortic aneurysm: recommendation statement. Ann

Intern Med 2005142:198-202.

3. Brown LC, Powell JT. Risk factors for aneurysm rupture in patients kept under ultrasound surveillance. Ann Surg

1999230:289-96.

4. Brewster DC, Cronenwett JL, Hallett JW Jr, et al. Guidelines for the treatment of abdominal aortic aneurysms.

Report of a subcommittee of the Joint Council of the American Association for Vascular Surgery and Society for

Vascular Surgery. J Vasc Surg 200337:1106-17.

5. Greenhalgh RM, Brown LC, Kwong GP, et al. Comparison of endovascular aneurysm repair with open repair in

patients with abdominal aortic aneurysm (EVAR trial 1), 30-day operative mortality results: randomised controlled

trial. Lancet 2004364:843-8.

6. Prinssen M, Verhoeven EL, Buth J, et al., on behalf of the Dutch Randomized Endovascular Aneurysm

Management (DREAM) Trial Group. A randomized trial comparing conventional and endovascular repair of

abdominal aortic aneurysms. N Engl J Med 2004351:1607-18.

7. Habashi JP, Judge DP, Holm TM, et al. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model

of Marfan syndrome. Science 2006312:117-21.




Thoracic Surgery, American College of Radiology, American Stroke Association, Society of CardiovascularAnesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology,


9. Kulik A, Castner CF, Kouchoukos NT. Outcomes after total aortic arch replacement with right axillary artery

cannulation and a presewn multibranched graft. Ann Thorac Surg 201192:889-97.

10. Milewski RK, Szeto WY, Pochettino A, Moser GW, Moeller P, Bavaria JE. Have hybrid procedures replaced open

aortic arch reconstruction in high-risk patients? A comparative study of elective open arch debranching with

endovascular stent graft placement and conventional elective open total and distal aortic arch reconstruction. J

Thorac Cardiovasc Surg 2010140:590-7.

11. Makaroun MS, Dillavou ED, Kee ST, et al. Endovascular treatment of thoracic aortic aneurysms: results of the

phase II multicenter trial of the GORE TAG thoracic endoprosthesis. J Vasc Surg 200541:1-9.

12. Makaroun MS, Dillavou ED, Wheatley GH, Cambria RP, and the Gore TAG Investigators. Five-year results of

endovascular treatment with the Gore TAG device compared with open repair of thoracic aortic aneurysms. J Vasc

Surg 200847:912-8.

13. Ricotta JJ II. Endoleak management and postoperative surveillance following endovascular repair of thoracicaortic aneurysms. J Vasc Surg 201052:91S-9S.


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8.2: Acute Aortic Syndromes

Author(s):

Bradley A. Maron, MD

Patrick T. OGara, MD, FACC

Learner Objectives

Upon completion of this module, the reader will be able to:

1. Define each of the acute aortic syndromes.

2. Identify risk factors associated with the development of acute aortic dissection and aortic rupture.3. Recognize strengths of and limitations to contemporary imaging modalities available for diagnosing acute aortic

syndromes.

4. Recommend appropriate medical, endovascular, or surgical treatment for patients with acute aortic syndromes.

5. Recommend appropriate post-hospital discharge care for acute aortic syndrome patients.


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Introduction

The acute aortic syndromes encompass a constellation of anatomic and pathophysiological changes to the normal

structure and function of the aortic wall, which threaten central aortic pressure, vital organ perfusion, and survival. These

include aortic dissection, intramural hematoma (IMH), penetrating aortic ulcer (PAU), rapid aneurysm expansion, and

trauma-induced aortic rupture.1

Recently described genetic, epidemiological, and clinical advances provide clinicians with a greater range of tools with

which to identify at-risk patients and diagnose acute aortic syndromes earlier in the natural history of these diseases.

Prompt delivery of appropriate medical, endovascular, and/or surgical therapy is a critical determinate of outcome in this

patient population.


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Classification

The acute aortic syndromes are defined according to their anatomical location

(Table 1). Acute aortic dissection is most commonly described according to the

DeBakey2 or Stanford3 classification schemes (Figure 1). In the DeBakey system, a

type I dissection originates within the ascending aorta and extends beyond the origin

of the innominate artery. This is in contrast to a type II dissection, which is confined

to the ascending aorta, or a type III dissection that initiates distal to the origin of the

left subclavian artery.

The Stanford classification model, which will be referenced in the remainder of this

module, divides dissections into two types: involvement of the ascending aorta

constitutes a type A dissection, whereas a dissection that does not involve the

ascending aorta is a type B dissection. In this schema, arch dissections are not

strictly defined, but are most often aggregated with the most affected portion of

contiguous aorta.

Table 1

Figure 1

The Acute Aortic Syndromes

Table 1


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Aortic Dissection Type According to the De Bakey and Stanford Classification Systems

Figure 1

Reproduced with permission from Nienaber CA, Eagle KA. Aortic dissection: new frontiers in diagnosis and management: Part I: from etiology todiagnostic strategies. Circulation 2003108:628-35.


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Epidemiology

Declining autopsy rates, misdiagnosis, and an unknown contribution of acute aortic syndromes to prehospital sudden

death are factors that obscure the true incidence of these events.1, 4 Data derived from large international registries

estimate that the incidence of aortic aneurysm and dissection in the general population is 16.3 and 9.1 per 100,000 men

and women, respectively, with a mean age of 63 years.5, 6

Importantly, disease rates vary (greatly) in accordance to the sample population. For example, patients with Marfan

syndrome (MFS), which afflicts 1 in 5,000 individuals, are significantly more likely to develop an aortic dissection

compared to the general population (see the next section on Predisposing Risk Factors). IMH is believed to account for

up to 13% of acute aortic syndromes.5, 6 Aortic rupture may occur as a complication of type A dissection, but is rare

outside the setting of trauma. By some estimates, aortic rupture accounts for 20% of motor vehicle collision-related

fatalities.


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Predisposing Risk Factors

The likelihood of developing an acute aortic syndrome is influenced by genetic

and/or acquired risk factors that weaken the medial layer of the aortic wall (Table 2).

"Cystic medial degeneration" describes the noninflammatory loss of elastic fibers in

the aortic media due to the accumulation of mucopolysaccharide and vascular

smooth muscle cell degeneration. Cystic changes are in fact not commonly present.

These maladaptive changes to the cellular architecture of the aorta are observed in

acute aortic dissection due to a wide variety of etiologies thus, the presence of

medial degeneration is notpathognomonic for any single cause of aortic dissection.

Genetic Risk Factors

Marfan Syndrome

Numerous genetic etiologies are implicated in the pathophysiology of acute aortic

syndromes. Marfan Syndrome is the most common genetic cause of acute aortic

dissection and occurs owing to mutations in the gene encoding for fibrillin-1 ( FBN-

1), which is a major component of microfibrils that form a structure-supporting

sheath around elastin. Dysfunctional microfibrils result in the loss of intercellular

adhesions and, ultimately, in a cardiovascular syndrome that includes aneurysm of

the aorta (most often affecting the root and sinuses of Valsalva), dilation of the

proximal main pulmonary artery, myxomatous thickening of the atrioventricular

valves, mitral valve prolapse, and mitral annular calcification.7

The diagnosis of MFS is established primarily on clinical grounds. In the setting of a

family history of MFS, the presence of ectopia lentis or aortic dilatation ( zscore 2 for

those older than 20 years of age) is sufficient to secure the diagnosis.8 Since up to

one-third of cases present in patients without an affected parent, 7 strategies to

diagnose MFS exist that rely on clinical examination findings, imaging, and

molecular testing (Table 3).

Furthermore, MFS variants that affect primarily the cardiovascular system (i.e., forme

frustes) have been described, and are important to recognize clinically due to their

association with aortic aneurysm and/or dissection. These include the MASS

phenotype (myopia, mitral valve prolapse, nonprogressive aortic root dilation,

skeletal abnormalities, and striae) and familial thoracic aortic aneurysm disease(FTAAD). FTAAD has also been mapped to mutations in MYH11 andACTA2.9-11

Ehlers-Danlos Syndrome

Vascular Ehlers-Danlos Syndrome (EDS) (i.e., EDS type IV) is a rare autosomal

dominant disorder that occurs due to a mutation in the COL3A1 gene encoding for

type III procollagen synthesis. Notably, up to one-half of cases are not inherited and

are believed to be sporadic.12 In vascular EDS, aortic aneurysm, dissection, and

rupture have been reported, and mortality rates are elevated significantly compared

to the normal population, with cumulative survival of approximately 50% at age 40. 13

Bicuspid Aortic Valve Disease and Other Genetic Risk Factors

Bicuspid aortic valve (BAV) disease is the most common congenital heart defectaffecting 1-2% of the general population, and is present in a male to female ratio of

3:1.14 Compared to the general population, affected individuals demonstrate a

relative risk for aortic dissection and aortic aneurysm of 8.5 and 86.2, respectively.15

Although the mechanism by which to account for the aortopathy of BAV is

unresolved, disrupted laminar flow within the post-valvular segment of the proximal

aorta is associated with medial degeneration, smooth muscle cell disarray, and

fragmentation of elastin.14 Other genetic syndromes associated with an increased

rate of aortic aneurysm/dissection include aortic coarctation, Noonan syndrome,

Turner syndrome, and polycystic kidney disease.

Acquired Risk Factors

Table 2

Table 3


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Systemic hypertension and tobacco use are the most common acquired (i.e.,

modifiable) risk factors for aortic dissection. Recreational use of cocaine and

methamphetamine are recognized increasingly as stimulators of aortic vascular

injury. Other acquired risk factors for aortic dissection include inflammatory

diseases of the large arteries such as Takayasu disease, giant cell aortitis, Behhet

disease, relapsing polychondritis, systemic lupus erythematosus, and, rarely,

inflammatory bowel disease-associated vasculitis.16 However, vasculopathies

characterized by significant replacement fibrosis and subsequent scarring of the

blood vessel wall, as occurs in response to Treponema pallidum infection (i.e.,

syphilis), are notassociated with increased risk for aortic dissection.

Changes in circulating blood volume, increased levels of the vascular effectorsrelaxin and estrogen, Valsalva maneuver-mediated increases in intrathoracic

pressure during labor, and undiagnosed MFS or other connective tissue diseases

are proposing factors for aortic dissection during pregnancy (which also includes

the early postpartum phase). Although these events are rare and most commonly

occur in the context of a previously unrecognized connective tissue abnormality, up to

50% of all dissections in women younger than 40 years of age occur in the

peripartum period.17

Iatrogenic causes of aortic dissection account for up to 5% of all events, and occur

most commonly during cardiac surgery or catheterization. Peripheral vascular

disease, tobacco use, a history of systemic hypertension, and the preprocedural

presence of an atherosclerotic plaque or PAU are associated with increased risk of

iatrogenic dissection.

18

Genetic and Acquired Risk Factors for Acute Aortic Syndromes

Table 2


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Selected Criteria for the Diagnosis of Marfan Syndrome

Table 3

Adapted with permission from Loeys BL, Dietz HC, Braverman AC, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet201047:476-85.


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Pathophysiology

Aortic Dissection

There is a positive, sigmoid relationship between thoracic aortic diameter and

probability of aortic dissection/rupture with a steep upward inflection point at 6 cm

(Figure 2).19 Nevertheless, dissection will often occur at much smaller aortic

diameters.20

In 80-90% of cases of acute syndromes, an intimal tear is identified at autopsy or

through advanced imaging of the aorta, and is most likely to occur at points of high

shear or mechanical stress, such as within a few centimeters of the aortic valve for

type A dissections and just distal to the insertion of the ligamentum arteriosum for

type B dissections.16 Propagation of the dissecting hematoma may occur

anterograde or retrograde, resulting in involvement of both the ascending and

descending aorta. Re-entry sites may be multiple.

The coagulation status of blood contained within the false lumen of a dissection

influences the natural history of the disease. Generally, complete thrombosis of the

false lumen is a favorable finding, as it is indicative of a "sealed off" dissection. In

contrast, partial thrombosis of the false lumen predicts future dissection-associated

complications, possibly due to increased compression of the true lumen by the false

lumen, or owing to sustained inflammation-mediated injury to the aortic wall.

Tsai and colleagues showed that partial false lumen thrombosis was associated

with reduced long-term survival among patients with type B aortic dissection and

proposed that hemodynamic forces within the false lumen lead ultimately to

progressive aneurysm formation and/or rupture.21 Blood within the false lumen that

is free flowing indicates communication between the false and true lumen. Patency

of the false lumen is common among patients with MFS and aortic dissection, and

could be a risk factor for late complications.

Clinical manifestations of aortic dissection are intimately related to the site of entry,

course of the propagating hematoma, and branch vessel compromise. The

dissection plane of a type A dissection may propagate retrograde across the origin

of the coronary arteries, particularly the right coronary artery, causing myocardial

ischemia, or involve the aortic annulus with resultant valvular regurgitation. Ruptureinto the pericardial space can result in tamponade and early death. End-organ

malperfusion syndromes due to aortic branch vessel compromise equate with

increased morbidity and mortality.16

Aortic Intramural Hematoma

"Aortic intramural hematoma" is defined as a collection of blood within the media of

the aorta in the absence of dissection flap or a detectable entry tear ( Figure 3).16 It is

thought to occur as a result of spontaneous bleeding within the wall of the aorta from

damaged vasa vasorum. Diagnosis of IMH is most often accomplished using

transesophageal echocardiography (TEE), computed tomographic angiography

(CTA), or magnetic resonance angiography (MRA), with demonstration of partial or

circumferential wall thickening or the presence of a fresh hematoma in the vessel

wall. CTA outperforms TEE as a diagnostic imaging modality, and acquisition of an

initial noncontrast image is most informative.

The natural history of IMH is variable: spontaneous resorption may occur in up to

one-third of cases, although if present in the ascending aorta, a diameter of >11 mm

is predictive of dissection complications, death, and the need for surgical

repair.16,22,23 The incidence rates of aortic regurgitation and pulse deficits are lower

with IMH compared with dissection. Over time, approximately 10% of patients with

IMH will develop a classic dissection and 50-60% will develop true or false aortic

aneurysms.24

Penetrating Atherosclerotic Aortic Ulcer

The perturbation of stable aortic atherosclerotic plaques from inflammation or shear

Figure 2

Figure 3

Figure 4


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stress may result in subsequent erosion across the internal elastic membrane of

the aorta, allowing for the formation of a blood-filled false space within the wall of the

aorta (Figure 4). PAU depth >1.0 cm, diameter >2.0 cm, and location in the proximal

aspect of the descending aorta are associated with worse outcomes. For

uncomplicated lesions, serial imaging and a conservative medical strategy are

recommended (see section on Clinical Management of Aortic Dissection).

Acute Aneurysm Expansion

Acute aneurysm expansion is an under-recognized cause of severe chest pain and

portends impending aortic rupture. Acute aneurysm expansion has been described

as a complication of most aortopathies, including aortitis, aortic dilation due to MFS,and atherosclerotic aortic disease. For these patients, prompt surgical evaluation is

indicated.

Influence of Aortic Size on Cumulative, Lifetime Incidence of Natural Complications of Aortic AneurysmFigure 2

An inflection point in the risk of aneurysm complications (i.e., dissection, rupture) is observed in non-Marfan syndrome patients at an aortic

diameter >6 cm (blue arrow).

Reproduced with permission from Elefteriades JA. Natural history of thoracic aortic aneurysms: indications for surgery, and surgical versus

nonsurgical risks. Ann Thorac Surg 200274:S1877-80.


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Aortic Intramural Hematoma Captured on Computed Tomographic Angiogram

Figure 3

Contrast nonenhancing circumferential region (arrows) of the aorta represents an aortic intramural hematoma.

Reproduced with permission from Takahashi K, Stanford W. Multidetector CT of the thoracic aorta. Int J Cardiovasc Imaging 200521:141-53.


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Penetrating Atherosclerotic Ulcer Captured on Transesophageal Echocardiography

Figure 4

*penetrating atherosclerotic ulcer

Reproduced with permission from Firschke C, Orban M, Andrssy P, Lange R, Schmig A. Images in cardiovascular medicine. Penetrating

atherosclerotic ulcer of the aortic arch. Circulation 2003108:e14-5.


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Clinical Presentation

History

A low clinical index of suspicion for aortic dissection is necessary to avoid

misdiagnosis. Point of care clinical prediction scales have been recently validated to

provide a simple and uniform strategy for determining the likelihood of dissection at

the patient's bedside (Table 4).25

Chest pain is the most common presenting symptom among patients with acuteaortic dissection (Table 5). The quality of chest pain tends to be described by

patients as severe, ripping, or tearing. Radiation of discomfort anteriorly is

suggestive of type A aortic dissection, whereas radiation of discomfort to the lower

back or abdominal region is suggestive of type B dissection.

Syncope is a particularly concerning symptom of aortic dissection, and should raise

immediate concern for cerebral malperfusion or cardiac tamponade. Other major

symptoms that are associated with worse outcome in aortic dissection include

abdominal pain and paraplegia, which may occur in the presence of impaired blood

flow to the spinal cord.

Physical Examination

Patients with acute aortic dissection often present acutely ill. Hypertension may beobserved in either type A or type B aortic dissection. If present, an aortic regurgitation

murmur is often faint, short in duration, and low in pitch. Identifying pulse deficits is

critical, as this predicts mortality in acute aortic dissection. 26 Patients should also

be evaluated for clinical signs of cardiac tamponade such as pulsus paradoxus and

elevation of the jugular venous pressure. Transudative pleural effusions (left > right)

are reported in acute type B aortic dissection, and should be considered in patients

for whom dullness to percussion or decreased breath sounds are observed on

clinical examination.

Table 4

Table 5


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The Average Sensitivity of Various Clinical Features Reported in Patients With Acute Thoracic Aortic Dissection

Table 5

Data are derived from a meta-analysis involving 16 different studies and 1,553 patients.

Adapted with permission from Klompas M. Does this patient have an acute thoracic aortic dissection? JAMA 2002287:2262-72.


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Biomarkers

A low D-dimer (2.5 g/L) raises clinical index of suspicion for acute

type A aortic dissection. The role of these and other biomarkers, such as C-reactive

protein and soluble elastin fragment for aortic dissection diagnosis or patient risk

stratification, continues to evolve (Figure 5).

Figure 5

Circulating Level of Aortic Biomarkers After Acute Dissection

Figure 5

Reproduced with permission from Trimarchi S, Sangiorgi G, Sang X, et al. In search of blood tests for thoracic aortic diseases. Ann Thorac Surg

201090:1735-42.


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Diagnostic Imaging

The chest roentgenograph is abnormal in the majority of aortic dissection patients,

but alone is not sufficient for establishing an accurate diagnosis. Common findings

include widening of the mediastinum and angulation of the aortic border. Similarly,

the electrocardiogram (ECG) is often abnormal, but nondiagnostic. Importantly,

although present in


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Transesophageal Echocardiographic Capture of Aortic Dissection

Figure 6

An ascending aortic dissection visualized by transesophageal echocardiography demonstrates a communication (arrow) through the dissectionflap that joins the true lumen (TL) and false lumen (FL). *, aortic valve leaflets.

Reproduced with permission from Meredith EL, et al: Echocardiography in the emergency assessment of acute aortic syndromes. Eur J Echo

10:i31, 2009


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Planar Computed Tomographic Angiogram and Three Dimensional Reconstructed Images of Stanford Type A Aortic Dissection

Figure 7

In (A), coronal CTA image delineates the dissection plane that separates the true lumen (TL) from false lumen (FL). In (B) three-dimensional

reconstruction imaging in the same patient provides enhanced spatial resolution post-surgical repair of the aortic dissection and the surrounding

anatomic structures. In this case, the aortic dissection extends from the aortic root to the innominate and left subclavian arteries, continues

through the aortic arch and into the descending aorta, with termination near the bifurcation of the left common iliac artery.

Reproduced with permission from Maron BA and OGara PT. Pathophysiology, Clinical Evaluation, and Medical Management of Aortic Dissection.

In Vascular Medicine: A Companion to Braunwald's Heart Disease (Creager, Beckman, Loscalzo) 2nd Ed. In press.


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Clinical Management of Aortic Dissection

The clinical management of acute aortic dissection is performed methodically and

expeditiously, often combining medical and surgical therapies. The clinical

indication(s) for the use of endovascular aortic stent grafts for type B dissection

continues to evolve. One proposed pathway algorithm for the management of

patients with acute aortic dissection is provided in Figure 8.

Medical Therapy

Medical therapy with intravenous (IV) agents to control heart rate and blood pressure

is the cornerstone of the initial therapeutic strategy for patients with type A or type B

aortic dissection. Exceptions to this include patients with cardiogenic shock and

profound systemic hypotension, typically due to type A aortic dissection complicated

by aortic rupture or cardiac tamponade. In this case, volume resuscitation is

indicated, but functions as a temporizing measure. Emergent surgery withoutdelay

for bedside pericardiocentesis is advised.

Short-acting -adrenergic receptor antagonists are preferred first-line

pharmacotherapeutic agents, as these drugs reduce the rate of pressure

development (i.e., change in pressure divided by change in time [dP/dT]) by

decreasing both left ventricular contractility and heart rate (Table 6). The target heart

rate in the acute phase of management is 60 bpm.

In patients requiring additional therapy to achieve a target blood pressure of 110 mm

Hg, the IV administration of short-acting direct vasodilators is recommended, such

as nitroprusside, labetalol, enalaprilat, hydralazine, or nicardipine.29 Other

supportive measures may be necessary to alleviate hypoxemia, patient discomfort,

and anxiety, which collectively may exacerbate dissection pathophysiology.

Surgery

The indications for surgical repair of acute and chronic aortic dissection are outlined

in Table 7.

Emergency surgery is recommended for all patients with acute type A aortic

dissection, as well as for patients with type A IMH. The potential for aortic arch

reconstruction, coronary artery re-implantation, aortic valve repair or replacement,and branch vessel repair is dependent on aortic dissection anatomy and assessed

in each patient. Surgical repair of chronic stable type A aortic dissection is

recommended in the presence of significant aortic valve dysfunction (regurgitation),

left ventricular cavity dilation, or left ventricular systolic dysfunction. Likewise, surgery

to treat type A aortic aneurysm is indicated for a maximal dimension 5.5 cm or 4.5

cm in MFS patients, or accelerated dilation at a rate of 1 cm/y.1

Surgery typically consists of resection and replacement of the dissected ascending

aorta using a Gelweave interposition graft, although aortic valve resuspension or

use of a composite valve-graft conduit with re-implantation of the coronary arteries

may be required, depending on the extent of root involvement and the mechanism of

any associated aortic regurgitation. Techniques for managing complex arch

dissections and branch vessel involvement with bifurcated grafts are beyond the

scope of this module. Cannulation for cardiopulmonary bypass is usually performed

via the right axillary artery, and a period of hypothermic circulatory arrest may be

necessary for completion of the distal anastomosis.

Surgery is also indicated for complicated type B aortic dissection defined by

refractory pain or hypertension, rapid aneurysmal expansion, rupture, or

malperfusion syndrome (i.e., end-organ ischemia). Dissection location within a

previously aneurysmal aortic segment is an anatomical indication for surgical repair.

Consideration of aggressive surgical repair might also be given to patients with

MFS. Surgery to treat chronic descending thoracic aortic aneurysm is indicated for a

maximal dimension 5.5 cm. Lower size thresholds may be appropriate for patients

with connective tissue disorders and in the presence of accelerated growth at a rate

of 1 cm/y.

Figure 8

Table 6

Table 7

Figure 9

Figure 10


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Endovascular Repair

Thoracic endovascular stent grafting (thoracic endovascular aortic repair [TEVAR]),

percutaneous fenestration, and branch vessel stenting have been evaluated in

patients with acute (or chronic) aortic syndromes (Figure 9). TEVAR has gained

increasing acceptance as the treatment of choice for complicated type B dissection,

as well as for anatomically appropriate aneurysm disease, although randomized

prospective trial data are lacking.

In observational series, morbidity and mortality rates are lower for TEVAR compared

with open surgery, and similar to those reported for medical therapy in patients with

uncomplicated type B dissection (International Registry of Acute Aortic Dissection[IRAD]). A comprehensive long-term assessment of device-related complications,

such as rates of endoleak and stent migration, is needed. It seems unlikely that a

randomized trial of TEVAR compared with surgery for complicated acute type B

dissection will be performed.

The INSTEAD (Ivestigation of Stent Grafts in Aortic Dissection) trial enrolled patients

with uncomplicated, chronic type B dissection, and showed no difference in clinical

or aortic endpoints out to 2 years for patients treated with TEVAR versus those

managed medically (Figure 10).30 Anatomical considerations for TEVAR are

reviewed elsewhere.

The Society of Thoracic Surgeons has assigned a Class IA recommendation to the

use of thoracic stent grafts for repair of acute complicated type B aortic dissection,

and a Class IC recommendation for acute traumatic transsection.31 TEVAR is alsorecommended for management of complicated PAU disease not responsive to

medical therapy or with signs of threatened rupture.


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One Proposed Management Pathway for Acute Aortic Dissection

Figure 8

In step 1, a low index of clinical suspicion for acute aortic dissection should prompt early diagnostic testing while medical therapy is initiated. Step

2 involves the determination of ascending aortic involvement, which influences significantly the importance of emergent surgical consultation. In

step 3, patients with type A aortic dissection are referred for surgery and patients with complicated type B aortic dissection are referred for

endovascular therapy or surgery. Patients with uncomplicated type B aortic dissection are continued on medical therapy and monitored for

changes in clinical status. In step 4, a care plan is established that emphasizes the importance of long-term medical therapy, radiologic

surveillance, and lifestyle modifications to decrease the risk of post-dissection complications. Long-term medical therapy should include -

receptor antagonists and angiotensin-receptor blockers or angiotensin-converting enzyme inhibitors to achieve a resting heart rate (HR) of 60

bpm and blood pressure (BP) of 120/80 mm Hg, respectively.

CTA = computed tomography angiography ECG = electrocardiogram TEE = transesophageal echocardiography TEVAR = thoracic endovascular

aortic repair.

Legend adapted with permission from Maron BA, OGara PT. Pathophysiology, clinical evaluation, and medical management of aortic dissection.

In: Creager MA, Beckman JA, Loscalzo J. Vascular Medicine: A Companion to Braunwalds Heart Disease. 2nd ed. Philadelphia: Saunders 2012.

Image adapted with permission from Hiratzka LF, Bakris GL, Beckman JA, et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM

Guidelines for the diagnosis and management of patients with thoracic aortic disease. A Report of the American College of Cardiology

Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of

Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and

Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. J Am Coll Cardiol

201055:e27-e129.

Intravenous Beta-Adrenergic Receptor Antagonists for the Management of Acute Aortic Dissection

Table 6

Reproduced with permission from Maron BA, OGara PT. Pathophysiology, clinical evaluation, and medical management of aortic dissection. In:

Creager MA, Beckman JA, Loscalzo J. Vascular Medicine: A Companion to Braunwalds Heart Disease. 2nd ed. Philadelphia: Saunders 2012.


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Surgical Indications for Acute and Chronic Aortic Dissection

Table 7

Adapted with permission from Hiratzka LF, Bakris GL, Beckman JA, et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines

for the diagnosis and management of patients with thoracic aortic disease. A Report of the American College of Cardiology Foundation/American

Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American

Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of

Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. J Am Coll Cardiol 201055:e27-e129.


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Endovascular Stent Graft in Type B Dissection

Figure 9

Cartoon demonstrating the typical features of type B dissection with flow in both the true and the expanded false lumen, resulting from a major

proximal entry tear (left) planes A to D were followed up longitudinally in every patient. A stent graft was placed to scaffold the dissected aorta

and to seal the entry to the false lumen, resulting in reconstruction of the true lumen with subsequent false-lumen thrombosis (right). Levels were

defined as (A) at the sinotubular junction, (B) at the center of the arch between truncus brachiocephalicus and left common carotid artery, (C) at

the level of the maximum aortic diameter, and (D) at the hiatus.

Reproduced with permission from Nienaber CA, Rousseau H, Eggebrecht H, et al. Randomized comparison or strategies for type B aortic

dissection: the INvestigation of STEnt Grafts in Aortic Dissection (INSTEAD) trial. Circulation 2009120:2519-28.


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Randomized Comparison of Strategies for Type B Aortic Dissection

Figure 10

Panel A: KaplanMeier estimates of 2-year overall cumulative survival rate in optimal medical therapy (OMT) versus thoracic endovascular aortic

repair (TEVAR) p = 0.15 by log-rank test. Panel B: KaplanMeier estimates of 2-year aorta-related survival rate in both groups p = 0.44 by log-

rank test. Panel C: KaplanMeier estimates of 2-year cumulative freedom from combined endpoint of progression and adverse events. The

combined endpoint consisted of related death, conversion, and ancillary interventions (including a second stent-graft procedure, access

revision, and peripheral interventions). Endovascular interventions (conversion to TEVAR in the control group or additional TEVAR in the stent-

graft group) are an integral part of the combined endpoint of progressive aortic pathology. There was no difference between groups (log-rank

test p = 0.65). Pat. at risk indicates patients at risk.

Reproduced with permission from Nienaber CA, Rousseau H, Eggebrecht H, et al. Randomized comparison or strategies for type B aortic



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Prognosis and Recommendations for Aortic Dissection Aftercare

The estimated 1-year survival rate for type A aortic dissection is 60%, although this is contingent upon prompt surgical

repair. Hospital mortality rates still approach 25% in many series. The 1-month survival rate for uncomplicated type B

aortic dissection is 90%.27 Many of these patients are self-selected.

Factors associated with worse prognosis in acute type B aortic dissection include advanced age, malperfusion

syndrome, false lumen partial thrombosis, and surgical treatment. Surgical outcomes are worse because of unavoidable

adverse selection bias. Historically, patients with type B dissection referred for surgery have had a greater burden of

dissection-related complications and antecedent comorbidities. Patients with a maximal thoracic aortic diameter of 4.0

cm and a patent false lumen have an increased likelihood of developing a subsequent aortic aneurysmal disease.16,30

Re-operation for late, long-term aortic complications is required in up to one-third of survivors.

Routine clinical evaluation at short time intervals and aggressive medical therapy to maintain a target blood pressure of

130/80 mm Hg and heart rate of 60 bpm are central to the management of acute aortic syndrome patients following

hospital discharge. Beta-receptor antagonists are the mainstay of long-term therapy other antihypertensive agents are

commonly required. Observational data suggest a salutary survival benefit of beta-receptor blockers in survivors of type A

dissection and for calcium channel blockers for survivors of type B dissection. 32 In the absence of a contraindication,

statin therapy is typically initiated, owing to the contribution of atherosclerosis to aortic dissection in some patients.

To assess for pathological changes in aortic anatomy, patients should undergo serial imaging of the entire aorta at 1, 3,

6, and 12 months following hospital discharge.33 Patients should be advised against engaging in strenuous exercise,

particularly those that involve straining or lifting of heavy weights. These activities are associated with increased aorticwall strain and/or torsion stress.


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Key Points

Mutations in the FBN-1 and COL3A genes cause MFS and vascular EDS, respectively, which are two key genetic

risk factors for aortic aneurysm and/or dissection.

Acquired risk factors for aortic dissection include systemic hypertension, tobacco use, and the development of

various autoimmune diseases. Aortic rupture most commonly occurs following a motor vehicle collision.

Severe and abrupt onset of chest pain is the most common symptom in acute aortic dissection.

Rapid diagnosis of aortic dissection is critical to a favorable outcome.

TEE, CTA, and MRA are effective imaging modalities for diagnosis of acute aortic dissection. CTA has become the

most widely used initial test to diagnose suspected aortic dissection.

An initial treatment strategy that aims to decrease aortic wall strain by controlling heart rate and left ventricular

contractility (dP/dT) with an IV short-acting -adrenergic receptor antagonist is advised in acute aortic dissection.

Acute type A aortic dissection is a surgical emergency.

Medical therapy is the preferred first-line treatment strategy for patients with uncomplicated type B aortic

dissection.

Surgery or TEVAR may be required in the management of unstable or complicated acute type B aortic dissection,

such as in those with malperfusion syndrome or early expansion. In most centers, TEVAR has replaced surgery

for this indication.

Partial thrombosis of the false lumen, false lumen patency, increased age, and malperfusion syndrome are poor

prognostic signs in acute aortic dissection.

Serial imaging of the entire aorta is indicated in follow-up for aortic dissection patients surviving to hospital

discharge.


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13. Pepin M, Schwarze U, Superti-Furga A, Byers PH. Clinical and genetic features of Ehlers-Danlos syndrome type IV,

the vascular type. N Engl J Med 2000342:673-80.

14. Sorrell VL, Panczyk E, Alpert JS. A new disease: bicuspid aortic valve aortopathy syndrome. Am J Med

2012125:322-3.

15. Michelena HI, Khanna AD, Mahoney D, et al. Incidence of aortic complications in patients with bicuspid aortic

valves. JAMA 2011306:1104-12.

16. Maron BA, O'Gara PT. Pathophysiology, clinical evaluation, and medical management of aortic dissection. In:Creager MA, Beckman JA, Loscalzo J. Vascular Medicine: A Companion to Braunwald's Heart Disease. 2nd ed.

Philadelphia: Saunders 2012.

17. Braverman AC. Acute aortic dissection: clinician update. Circulation 2010122:184-8.

18. Ketenci B, Enc Y, Ozay B, et al. Perioperative type I aortic dissection during conventional coronary artery bypass

surgery: risk factors and management. Heart Surg Forum 200811:E231-6.

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observations from the International Registry of Acute Aortic Dissection (IRAD). Circulation 2007116:1120-7.

21. Tsai TT, Evangelista A, Nienaber CA, et al. Partial thrombosis of the false lumen in patients with acute type B

aortic dissection. N Engl J Med 2007357:349-59.

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compared with acute aortic dissection. Am J Cardiol 199881:202-6.23. Nienaber CA, von Kodolitsch Y, Petersen B, et al. Intramural hemorrhage of the thoracic aorta. Diagnostic and

therapeutic implications. Circulation 199592:1465-72.

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outcome. Circulation 2003108:583-89.

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guideline-based tool for identification of acute aortic dissection at initial presentation: results from the

international registry of acute aortic dissection. Circulation 2011123:2213-8.

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mortality in patients with acute type A aortic dissection. Am J Cardiol 200289:851-5.

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Cardiology. Diagnosis and management of aortic dissection. Eur Heart J 200122:1642-81.

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Additional Reading

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2012125:226-32.

2. Bosner RS, Ranasinghe AM, Loubani M, et al. Evidence, lack of evidence, controversy, and debate in the provision

and performance of the surgery of acute type A aortic dissection. J Am Coll Cardiol 201158:2455-74.

3. Harris KM, Strauss CE, Eagle KA, et al. Correlates of delayed recognition and treatment of acute type A aortic

dissection: the International Registry of Acute Aortic Dissection (IRAD). Circulation 2011124:1911-8.

4. Milewicz DM. Stopping a killer: improving the diagnosis, treatment, and prevention of acute ascending aortic

dissections. Circulation 2011124:1902-4.


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1.

You diagnosed a 78-year-old female patient with a descending TAA that was 6.5 cm

in diameter. She underwent successful thoracic endovascular stent-graft repair of

the aneurysm. In addition to treating her risk factors, which of the following imaging

techniques should be used to image her aorta?

A. A chest radiograph (chest X-ray) every 6 months.

B. A CTA annually.

C. An echocardiogram annually.

D. An abdominal ultrasound every 6 months.

E. No follow-up imaging is necessary.

2.

You care for a 67-year-old man with hypertension and hyperlipidemia, who was

recently diagnosed with a 5.7 cm AAA. You have recommended aortic repair, and he

tells you he prefers to have it repaired with an endovascular stent-graft because he

has read that it is both less invasive and safer than an open repair. You would like to

help him to make an informed decision about how his aneurysm should be

repaired. Which of the following would you tell him regarding EVAR compared with

open repair for the treatment of AAAs?

A. EVAR is associated with lower short-term mortality, but equivalent long-term

mortality.

B. EVAR is associated with fewer endoleaks.

C. EVAR is associated with both lower short-term and long-term mortality.

D. EVAR is associated with lower short-term mortality and fewer long-term

repeat interventions.

E. EVAR is associated with an equivalent short-term mortality, but a lower long-

term mortality.

3. A 65-year-old man presents to the emergency department with abdominaldiscomfort that began 2 days prior, but resolved over the previous 4 hours. His blood

pressure is 125/82 mm Hg and heart rate is 72 bpm and regular. Physical

examination reveals mild abdominal tenderness on palpation and strong,

symmetric femoral, popliteal, and dorsalis pedis pulses. Magnetic resonance

imaging of the abdomen reveals a two-channel 4 cm in length descending aortic

dissection that terminates within 1 cm proximal to the origin of the splenic artery.

There is complete thrombosis of the false lumen without evidence of

communication between the true and false lumen.

Which of the following statements most appropriately characterizes the patients

clinical condition?

A. This is a high-risk Stanford type A dissection due to complete thrombosis

Chapter 8 Exam

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within the false lumen.

B. This is a high-risk Stanford type B dissection due to complete thrombosis


C. This is a low-risk Stanford type A dissection due to complete thrombosis


D. This is a low-risk Stanford type B dissection complete thrombosis within the

false lumen.

4. A 31-year-old woman is 6 days postpartum and evaluated in the emergency

department for a complaint of severe anterior chest pain. She appears anxious and

complains of chest discomfort that began the previous hour, which is associated

with nausea. She denies shortness of breath. Her right upper extremity and left

upper extremity blood pressure is 150/65 and 161/67 mm Hg, respectively. The

patients ECG reveals 2 mm ST-segment elevation in leads II, III, and aVF and is

otherwise significant for sinus tachycardia at a rate of 115 bpm. Plain

roentgenogram reveals mild cardiomegaly without evidence of mediastinal widening

or pulmonary edema.

Which of the following is the next most appropriate step in the patients

management?

A. Initiate therapy with IV esmolol titrated to a heart rate of 60 bpm and request

an emergency contrast CT scan of the chest and abdomen.

B. Initiate therapy with IV unfractionated heparin, including a loading bolus, and

perform an emergency transthoracic echocardiogram to assess right ventricular

function.

C. Initiate therapy with IV unfractionated heparin, including a loading bolus,

aspirin 325 mg by mouth, 0.5 mg nitroglycerin tablet sublingual, and activate the

cardiac catheterization laboratory.

D. Prepare for emergency pericardiocentesis.

Please visit the online version to engage in this Exam.

1. The correct answer is B. Even after successful deployment of an endograft, endoleaks occur

in approximately 10% of patients at 30 days. Also, even if not present early post-procedure, they

may also appear late and pressurize the aneurysm sac, leaving it at risk for rupture. Therefore,

the aneurysm sac needs to be followed with annual surveillance CTAs to identify the presence of

endoleaks, as well as to assess stabilization of the aneurysm sac and to exclude the

appearance of aneurysms elsewhere.

Chest radiography is too crude to permit detection of aneurysm growth or changes in the status

of the aneurysms sac. Echocardiography is very useful to examine the aortic root, ascending

thoracic aorta, and aortic arch, but typically images the descending thoracic aorta poorly, so it

would not be helpful in this setting. An abdominal ultrasound images the abdominal aorta well,

but not the thoracic aorta.

2. The correct answer is A. In randomized prospective trials, EVAR is associated with lower

short-term mortality than open repair, but by 2 years following aortic repair, the mortality is

equivalent. EVAR is associated with more long-term complications that, in turn, result in the need

for more repeat interventions. Endoleaks are a complication that may arise after EVAR when

there is persistent blood flow into the aneurysm sac endoleaks do not occur with open aortic

repair.


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3. The correct answer is D. Option D is the correct answer for two reasons. First, compared to

partial thrombosis or free flowing blood in the false lumen of a dissection, complete thrombosis

is associated with a more favorable outcome. Therefore, in the absence of other clinical features

suggestive of hemodynamic compromise, this patients risk profile is relatively low. Second, the

aortic dissection is 4 cm in length and terminates near the origin of the splenic artery thus,

ascending aortic arch involvement is not present. The correct Stanford aortic dissection

classification for dissections that do not involve the ascending aorta is type B.

Options A, B, and C are incorrect because these choices do not accurately characterize either the

appropriate Stanford aortic dissection type or clinical risk profile.

References

1. Tsai TT, Evangelista A, Nienaber CA, et al. Partial thrombosis of the false lumen in patients with acute

type B aortic dissection. N Eng

8 diseases of the aorta

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