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Accepted Manuscript
Canadian Cardiovascular Society Position Statement on the Management of Thoracic
Aortic Disease
Munir Boodhwani, MD, MMSc Gregor Andelfinger, MD, PhD Jonathan Leipsic, MD
Thomas Lindsay, MD, MSc M. Sean McMurtry, MD, PhD Judith Therrien, MD Samuel
C. Siu, MD
PII:
S0828-282X(14)00112-3
DOI:
10.1016/j.cjca.2014.02.018
Reference:
CJCA 1128
To appear in:
Canadian Journal of Cardiology
Received Date: 8 November 2013
Revised Date:
1 February 2014
Accepted Date: 1 February 2014
Please cite this article as: Boodhwani M, Andelfinger G, Leipsic J, Lindsay T, McMurtry MS, Therrien
J, Siu SC, Canadian Cardiovascular Society Position Statement on the Management of Thoracic Aortic
Disease, Canadian Journal of Cardiology (2014), doi: 10.1016/j.cjca.2014.02.018.
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Canadian Cardiovascular Society Position Statement
on the Management of Thoracic Aortic Disease
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Primary Panel: Munir Boodhwani1 MD, MMSc (Co-chair), Gregor Andelfinger2, MD, PhD,
Jonathan Leipsic3, MD, Thomas Lindsay4,MD, MSc, M. Sean McMurtry5, MD, PhD, Judith
Therrien6, MD, Samuel C. Siu7 MD (Co-chair)
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Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario
Department of Pediatrics, University of Montreal, Montreal, Quebec
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Department of Radiology, University of British Colombia, Vancouver British Colombia
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Division of Vascular Surgery, University Health Network, Toronto, Ontario
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Division of Cardiology, University of Alberta, Edmonton, Alberta
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Division of Cardiology, McGill University, Montreal, Quebec
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Division of Cardiology, Western University, London, Ontario
Corresponding Author:
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Munir Boodhwani, MD, MMSc
H3405, 40 Ruskin Street,
Ottawa, Ontario K1Y 4W7
Phone: (613) 761-4313
Fax: (613) 761-5107
Email: [email protected]
Word Count: 6,381 words
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Abstract:
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This Canadian Cardiovascular Society position statement aims to provide succinct
perspectives on key issues in the management of thoracic aortic disease (TAD). This
document is not a comprehensive overview of thoracic aortic disease and important
elements of the epidemiology, presentation, diagnosis, and management of acute aortic
syndromes are deliberately not discussed; readers are referred to the 2010 guidelines
published by the American Heart Association, American College of Cardiology, American
Association of Thoracic surgery and other stakeholders1. Rather, this document is a
practical guide for clinicians managing adult patients with TAD. Topics covered include
size thresholds for surgical intervention, emerging therapies, imaging modalities,
medical and lifestyle management, and genetics of TAD. The primary panel consisted of
experts from a variety of disciplines that are essential for comprehensive management
of TAD patients. The methodology involved a focused literature review with an
emphasis on updates since 2010 and the use of GRADE methodology to arrive at specific
recommendations. The final document then underwent review by a secondary panel.
This document aims to provide recommendations for most patients and situations.
However, the ultimate judgement regarding the management of any individual patients
should be made by their health care team.
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Brief Summary:
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This is the first Canadian Cardiovascular Society position statement on the management
of thoracic aortic disease. Developed by a nationally representative, multi-disciplinary
group, this document provides a succinct review of contemporary literature and
practical recommendations on key aspects of management of patients with thoracic
aortic disease including size thresholds for intervention, imaging modalities, medical and
lifestyle management, and genetics. Brief perspectives on emerging therapies and
models of care are also provided.
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Section 1. Size Thresholds for Elective Thoracic Aortic Intervention
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Thoracic Aortic aneurysms are largely asymptomatic until a sudden and catastrophic
event, including aortic rupture or dissection, occurs, and is rapidly fatal in a large
proportion of patients2, 3. Elective intervention on the thoracic aorta carries a much
lower risk of mortality and morbidity, and prophylactic aortic surgery can be life-saving.
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The decision to perform aortic intervention is a balance between risks of natural history
of the disease versus the risk of the surgical intervention itself and any additional longterms risks of treatment. The risk of aortic complications is influenced by a number of
patient-related factors e.g. family history of aortic disease, history of smoking, etc. and
disease-related factors e.g. true vs. false aneurysm, bicuspid valve aortopathy,
connective tissue disorders, etc. (Table 1). Similarly, the risk of surgical intervention
may be significantly influenced by comorbidities (e.g. COPD, coronary or valve disease,
etc.) and anatomy (presence of dissection, aortic arch involvement).
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The risk related to intervention is an instantaneous risk whereas the risk of aortic
complications accrues over time (e.g. 5-year risk of rupture is greater than 1-year risk of
rupture). Therefore, it may be acceptable for patients to accept a one-time risk of
intervention (e.g. 5%) to prevent the long-term consequences of aortopathy (e.g. 2 -3
%/year). Maximum aortic diameter is the most important predictor of aortic
complications. However, since many factors influence the relationship between size and
aortic complications, absolute size should not be used in isolation. There are
occasionally long-term consequences that deserve consideration, such as minimizing the
risk of valve-related complications in patients eligible for aortic valve sparing or repair
surgery. Lastly, estimates of risk of aortic complications based on natural history studies
are not well established in all subsets of TAD.
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The size threshold for considering aortic intervention has decreased successively over
recent years, due to substantial reduction in morbidity and mortality for elective
procedures. In experienced centers, elective repair of ascending aorta and aortic root
aneurysms carries a mortality of 1%. Aneurysms involving the aortic arch and
descending thoracic aorta typically carry a higher risk of mortality and neurologic
morbidity.
The International Registry of Aortic Dissection (IRAD) registry and other data have
questioned the current threshold of aortic diameter of 5.5 cm for ascending aortic
aneurysm, as the median diameter of patients presenting with type A and B aortic
dissections was significantly less than 5.5 cm4, 5. With an intervention threshold of 5.5
cm, over half of type A aortic dissections would not be prevented. However, the number
of patients in the general population with aortic diameters between 5.0 – 5.5 cm (and
4.5 – 5.0 cm) is large and their annual risk of aortic complications is not well
characterized. Even with the low risk of elective aortic replacement, at some level, this
number needed to treat (NNT) would be prohibitively high.
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Recommendation: “We recommend that the decision to perform prophylactic aortic
intervention should be tailored to the individual patient and incorporate patientrelated and disease-related factors.” (Strong Recommendation, Moderate Quality of
Evidence)
Values and Preferences: The important factors influencing the risk of aortic
complications and risk of operative intervention are listed in Table 1. Where there is
uncertainty regarding decision making, patients should be referred to specialists in the
management of thoracic aortic disease for consideration of operative intervention.
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Intervention Thresholds for Thoracic Aortic Aneurysms:
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Recommendation: “We recommend that surgical intervention be considered for
thoracic aortic aneurysms according to the disease etiology and anatomic region
affected as indicated in table 2.” (Strong Recommendation, Moderate Quality of
Evidence)
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Certain factors confer increased risk and include (in increasing order of significance):
bicuspid aortic valve aortopathy, Marfan syndrome, Familial Thoracic Aortic Disease,
Ehlers Danlos (vascular type), Turner Syndrome and in particular, Loeys-Dietz syndrome
. The size threshold for intervention is lower for these conditions. Patient body size is an
important variable; a lower threshold may be used in females and patients of shorter
stature.
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1. Degenerative Aneurysms: Patients with degenerative aortic aneurysms do not have
connective tissue disorders, familial aortopathy, or bicuspid aortic valve aortopathy.
They are typically older and have atherosclerotic risk factors, particularly
hypertension and smoking. Increased aortic size has been linked to increased risk of
dissection, rupture, and death, particularly when the size of the aneurysm exceeds
6.0 cm (7% annual risk of rupture or dissection and 12% annual risk of death)6.
Surgical intervention is recommended at a diameter of 5.5 cm for the ascending
aorta. For the descending thoracic aorta, surgical intervention is recommended at a
diameter of 6.5 cm7.
2. Bicuspid Aortic Valve Aortopathy: Patients with bicuspid aortic valves have an
increased risk of aortic dilation and molecular and histological changes suggesting an
aortopathy independent of valve function8, 9. The risk of aortic dissection in BAV
patients is higher than the general population but is lower than that for patients
with Marfan syndrome or other genetic aortopathies10. Surgical intervention in this
population should be considered when the size of the ascending aorta is between
5.0 – 5.5 cm, accounting for patient size, particularly in the presence of other risk
factors.
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3. Marfan Syndrome: Marfan syndrome individuals are susceptible to thoracic aortic
aneurysms with a higher incidence of aortic dissection11, 12. However, a low risk of
aortic complications is noted in patients with an aortic size below 5.0 cm11. For the
aortic root and ascending aorta, a size threshold of 5.0 cm is appropriate. For the
descending thoracic aorta, a size threshold of 5.5 – 6.0 cm is recommended. Patients
with a family history of premature aortic dissection warrant consideration of surgical
intervention at smaller diameters.
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4. Familial Thoracic Aortic Aneurysm: These individuals have one or more relatives with
thoracic aortic aneurysms with or without a previous history of aortic dissection.
Aortic dilation progresses more rapidly in patients with familial aortopathy with e a
higher risk of aortic complications13, 14. The threshold for surgical intervention may
be guided by the aortic size at which other family members have had aortic
complications, if known. If not known, then a size threshold of 4.5 – 5.0 for the
ascending aorta and 5.5 – 6.0 for the descending thoracic aorta is reasonable.
Other Considerations:
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5. Non-Marfan Genetic Aortopathy: A number of genetic disorders including LoeysDietz, Turner and Ehlers Danlos (vascular type) are linked to thoracic aortic
aneurysm and dissection. Because of the low prevalence of these syndromes, there
is a paucity of data on the risk of aortic complications, it is significantly higher
compared to degenerative aneurysms and Marfan syndrome. Patients with LoeysDietz syndrome have a high risk of aortic dissection at small diameters leading to
limited life expectancy15. The threshold for surgical intervention is therefore lower
than that for Marfan syndrome. Patients with vEDS can have a high risk of surgical
complication due to poor quality of vascular tissue.
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In addition to size thresholds, the following factors deserve careful consideration:
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1. Presence of Symptoms: A small subset of patients will present with compressive
symptoms, malperfusion, or pain, all of which are associated with poor outcome16
and surgical intervention should be considered in all symptomatic thoracic aortic
aneurysms, regardless of absolute size.
2. Pseudoaneurysms: False aneurysms of the thoracic aorta may occur secondary to
blunt trauma, prior aortic surgery, catheter based manipulation, or in association
with penetrating atherosclerotic ulcers. Rates of aortic rupture for
pseudoaneurysms are not well-characterized. Surgical intervention may be
considered when the total diameter of the aorta (including the native aorta and the
false aneurysm) meets the criteria in Table 2 or if the pseudoaneurysm is greater
than 2 cm in maximum diameter.
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3. Rate of Growth: Typical growth rate of thoracic aortic aneurysms is 0.1 cm/year.
Rapidly growing aneurysms (> 0.5 cm/year increase in diameter) are uncommon but
are associated with increased aortic complications17. Surgical intervention should be
considered in rapidly growing aneurysms regardless of absolute diameter.
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4. Concomitant Cardiac Surgical Procedures: Surgical intervention on the moderately
dilated ascending aorta (> 4.5 cm) should be considered in patients undergoing open
cardiac surgical procedures as it minimizes the long-term risk of dissection and
rupture and avoids a future higher risk reoperation18-20. However, other factors
including patient age, body size, co-morbidities, additional risk of procedure, and life
expectancy must be considered in the decision making process. In some patients,
aortic dilation below the thresholds recommended for surgical intervention may
lead to aortic valve insufficiency due to cusp malcoaptation and a lower threshold
for aortic resection is reasonable to facilitate aortic valve repair.
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5. Indexing for patient size: The normal thoracic aorta is smaller in females and in
shorter individuals. In these individuals, aortic size index (maximum aortic diameter
/ body surface area) > 2.75 cm/m2 is a better predictor of aortic complications 21.
Other investigators have suggested that the ratio between the cross-sectional area
of the aorta (at its maximum diameter) divided by the patient’s height (m) is another
useful method to adjust for differences in body size22. Indexed measurements are
most useful for females, patients with short stature and certain genetic syndromes
(e.g. Turner syndrome).
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Section 2. Emerging Interventions for Thoracic Aortic Disease
A. Thoracic Endovascular Aneurysm Repair
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In contrast to open surgical repair, Thoracic Endovascular Aneurysm Repair (TEVAR)
involves exclusion of the aneurysm sac with a covered stent. Compared to open surgical
repair, TEVAR is associated with a lower procedural mortality and morbidity 23, 24, but a
greater need for re-interventions and concerns remain regarding long-term outcome
and late aneurysm-related mortality25.
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While TEVAR is used primarily for the descending thoracic aorta, alternate approaches
to aortic arch disease in high-risk candidates include a combination of open and
endovascular techniques, depending on anatomic suitability. Open surgical treatment is
the standard of care for the ascending aorta26, 27.
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Type B dissections without complications are treated medically28, with surgery reserved
for complications including malperfusion syndromes (visceral, renal or limb perfusion),
rupture and rapid expansion. In the IRAD registry, TEVAR therapy for complicated, acute
type B aortic dissections was associated with lower mortality and complications than
open surgical intervention. The STABLE trial suggests this therapy is associated with
increased true lumen size, and favorable clinical and anatomic results29. TEVAR may
therefore offer better outcomes compared to open surgical approaches in complicated
cases. For non-complicated type B dissections, the INSTEAD trial did not demonstrate
any advantage for TEVAR in the short-term30, 31. However, longer-term follow-up
suggests reduced aorta-specific mortality following TEVAR32.
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TEVAR may be associated with a number of complications including paralysis and
paraperesis. Spinal CSF drains that allow drainage of CSF and improve spinal cord
perfusion, 33, 34 intra operative monitoring of motor and sensory evoked potentials to
monitor spinal cord function, and improved preoperative imaging to identify critical
intercostals arteries are some techniques employed to minimize this complication 35.
Stroke, renal failure and retrograde Type A dissection are other potential complications.
B. Aortic Valve Preservation and Repair
Patients with aortic root aneurysms, with or without associated aortic valve disease
have traditionally been treated with composite aortic valve and root replacement with
reimplantation of the coronary arteries (Bentall procedure). While this procedure is
effective at treating the aortopathy, patients are left with the long-term risks associated
with prosthetic heart valves which include thromboembolism, structural and nonstructural valve dysfunction, endocarditis, and anti-coagulant related hemorrhage for
those with mechanical prostheses36. Since many of these patients have morphologically
normal aortic valve leaflets, there has been increasing interest in valve sparing aortic
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root operations. Long-term observational cohort studies have demonstrated excellent
outcome at over 15 years of follow-up37.
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The concepts, innovations38 and techniques39 in valve preserving operations have also
been applied in patients with aortic insufficiency and bicuspid aortic valves and
associated aortopathy with promising results40, 41, including a low risk of valve related
complications42, 43. These benefits are most significant for young patients who are likely
to accrue valve-related events over time. The likelihood of valve repair may be a
consideration in determining the threshold for aortic replacement in these patients.
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Recommendation: “We recommend that patients with complex TAD that stand to
benefit from the above emerging techniques and technologies be referred to teams
experienced in these approaches.” (Conditional Recommendation, Low Quality of
Evidence)
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Section 3: The Role of Imaging in Diagnosis and Surveillance
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Imaging is fundamental for diagnosis and surveillance of TAD. The test chosen should be
determined by the presentation, location and patient age, with renal dysfunction, local
expertise and access to imaging modalities as additional considerations. Height and
weight should be recorded for calculation of body surface area. Strengths and
weaknesses of the various imaging modalities are summarized in Table 3. Details on
technical aspects of imaging are provided in Appendix 1.
Overview of Imaging Modalities
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A. Multi-detector Computerized Tomography (CT)
ECG gated scans are useful for imaging the ascending aorta enabling assessment of the
aortic valve and at least the proximal coronary arteries (see Appendix 1). After aortic
intervention, CT is also preferred to detect post procedural leaks or pseudoaneurysms
as echocardiography (echo) is often limited by the presence of metallic devices and clips
and transesophageal echocardiography is semi-invasive and thus not optimal for
surveillance.
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Currently, external aortic diameters are reported for CT or magnetic resonance (MR)
derived measurements. Echo-derived measurements are typically reported as luminal
size; this difference is important in the descending thoracic aorta where mural thrombus
is more prevalent. Pronounced arterial wall calcifications can lead to underestimation
of the lumen.
While the potential stochastic risk of radiation exposure drops significantly when
patients reach the 5th decade of life, CT must be used with caution in neonates, children,
and young adults in whom the risk of radiation-induced malignancy is the highest44-48.
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B. Magnetic Resonance Imaging (MRI)
The avoidance of radiation or iodinated contrast exposure with MRI is a particularly
valuable feature in younger patients and for serial follow up imaging. Disadvantages
include longer scan times which is a particular issue in the setting of acute chest pain
and claustrophobic patients, as well as issues related to the use of Gadolinium contrast
agents in renal failure owing to concerns regarding nephrogenic systemic fibrosis and
implanted cardiac devices. MRI may be particularly helpful in distinguishing mural
thrombus from intramural blood in the setting of acute aortic syndromes with early
potential being shown by new dual energy CT techniques 49, 50 .
C. Transthoracic (TTE) and Transesophageal (TEE) Echocardiography
Imaging of the aortic root and proximal ascending aorta is part of the standard TTE with
images obtained at end diastole 51, 52. Three-dimensional echocardiography, particularly
combined with TEE, has the potential of enhancing diagnostic utility53, but its aortic
application has been focused on the proximal ascending aorta. TEE is superior to TTE for
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visualization of the thoracic aorta and has an important role in settings where CT or MR
may not be available or feasible, such as the intensive care unit or the operating room.
Criteria for TTE/TEE diagnosis of acute aortic dissection are: 1) Intimal or dissection flap
seen on multiple views, 2) Independent motion of the intimal flap, 3) Differential colour
flow in true and false lumens1. Echo is operator dependent, therefore serial
examinations should be performed with standardized protocols and by experienced
individuals in laboratories with quality assurance processes in place52.
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D. Cardiac catheterization and angiography
The main use of angiography is in the evaluation of a suspected aortic syndrome while
the patient is undergoing a cardiac catheterization procedure, but it has otherwise been
replaced by CT, MR, and TEE.
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Recommendation: “For Acute Aortic Syndromes :
A. We recommend CT as the preferred initial imaging test (Strong
Recommendation, Moderate quality evidence)
B. We suggest TEE as an appropriate alternative in the following situations
(Conditional Recommendation, Moderate quality evidence) :
a. An indeterminate CT examination
b. When transport to CT is not feasible due to hemodynamic instability
c. Intraoperative TEE when a dissection flap is seen on the initial TTE
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C. We suggest MR for characterizing acute intramural hematomas when CT is
equivocal” (Conditional Recommendation, Low quality evidence)
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Values and Preferences: These recommendations are based on cohort studies,
overviews, and expert opinion, as there are no contemporary studies comparing
diagnostic accuracy of the imaging modalities. A systematic review concluded that TEE,
helical CT, and MRI, yield clinically equally reliable diagnostic value for confirming or
ruling out aortic dissection 54. There are no standards for the appropriate phase of the
cardiac cycle to evaluate aortic size by CT or MR, therefore the phase (diastolic vs.
systolic) used should be reported to allow for consistent serial measurements to assess
interval changes.
Recommendation: “For ongoing aortic surveillance in patients who are candidates for
intervention, we suggest:
A. For preoperative planning, the entire thoracic aorta should be imaged by CT or
MR (Conditional Recommendation, Moderate quality evidence)
B. For post repair surveillance in those without residual aortopathy, the entire
aorta should be imaged by CT or MR at least once every 3-5 years after repair
(Conditional Recommendation, Low quality evidence)
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C. MR should be considered the first line test of choice if serial repeat
examinations are being considered in an adolescent or in the adult population
below the age of 50 years (Conditional Recommendation, Low quality
evidence)
D. If dilation is established to only involve the root or proximal ascending aorta
then TTE serves as a reasonable alternative, with TEE reserved for those with
non-diagnostic TTE images (Conditional Recommendation, Low quality
evidence)
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Values and Preferences: To reduce variability, serial aortic imaging should be performed
using the same imaging protocols and modality, in the same laboratory. Follow up
studies should be scheduled at 6-12 months following diagnosis, and then every 6 or 12
months thereafter depending on aortic size and the rate of change. In patients with
stable dimensions between serial examinations, imaging intervals may be increased.
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Section 4: Medical Therapy and Lifestyle Considerations for Patients with Thoracic
Aortic Disease
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A. Antihypertensive Therapy:
The rationale for antihypertensive therapy is based on mechanistic and animal studies55,
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, as well as observational reports linking aortic dissection with hypertension57, 58.
Randomized controlled trials of antihypertensive therapies have not included patients
with TAD per se or reported consistently on aortic endpoints.59, 60 While summaries of
antihypertensive trials support treatment of hypertension when present, they do not
offer specific guidance on the management of patients with thoracic aortic aneurysm,
dissection, or aortopathy, either for choice of drug therapy or for blood pressure
targets61-69.
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For Marfan syndrome, the available studies report surrogate outcomes, and are limited
by small sample size, lack of blinding, and choice of comparator. Small randomized trials
of beta blockers or losartan in addition to beta-blockers showed lower rates of aortic
root dilation, with no difference in other clinical outcomes (Appendix 1, Table 2). No
published trials compare beta-blocker monotherapy with ACE-inhibitor monotherapy,
and in a recent trial of losartan only a subset were on losartan monotherapy70. In other
subsets of TAD including BAV, Loeys-Dietz, Ehlers Danlos, and other genetic
aortopathies, there are no randomized trials or observational studies.
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In patients with chronic aortic dissection, observational reports suggest lower risk for
operative repair with beta-blocker therapy71. In a series of 722 and 579 patients with
type A and type B aortic dissections respectively, beta-blockers were associated with
improved survival in both groups, while ACE inhibitors were not associated with
improved survival72. Use of calcium-channel blockers was associated with improved
survival in type B aortic dissections72, as well as decreased aortic expansion in a smaller
cohort of 191 type B aortic dissections73. A cohort of 78 consecutive type B aortic
dissection cases identified an association between ACE inhibitor and better survival74.
Poor blood pressure control (≥140/90 mmHg) has been linked with late mortality74, 75.
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Recommendation: “We recommend antihypertensive drug therapy for hypertensive
patients with thoracic aortic disease to achieve a goal blood pressure of < 140/90
mmHg, or < 130/80 mmHg in those with diabetes, to reduce the risk of myocardial
infarction, stroke, heart failure, and cardiovascular death76.” (Strong
recommendation, moderate quality evidence)
“We recommend beta-blocker or angiotensin receptor blocker therapy for patients
with Marfan syndrome to reduce the rate of aortic dilation. If tolerated, we
recommend consideration of additional therapy (ACE-inhibitor, angiotensin receptor
blocker, or beta-blocker) for patients with Marfan syndrome to reduce the rate of
aortic dilation.” (Strong recommendation, low quality of evidence)
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Values and Preferences: Though there are no randomized trials that support lower
blood pressure targets (e.g. < 120/80 mmHg), aggressive therapy may be reasonable
based on the physiologic rationale and patient-specific factors including type of
aortopathy, prior patient or family history of acute aortic syndrome or sudden death,
aortic aneurysm growth despite medical therapy, or patient preference. To date, there
are no randomized trials supporting that monotherapy with a specific agent is superior
to others for any form of TAD.
B. Preventing hypertension and atherosclerosis:
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Diet and Smoking Cessation: Standard dietary advice for prevention of hypertension
and atherosclerosis as well as smoking cessation are appropriate for most patients with
thoracic aortic disease (Appendix 1).
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Lipid Lowering Therapy: Some observational studies suggest benefit and many patients
with thoracic aortic disease have multiple atherosclerotic risk factors (Appendix 1). Lipid
lowering, generally with statin drugs, should be offered according to general
guidelines77.
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Exercise: Aortic dissection has been linked with severe physical exertion due to weight
lifting78. The mean aortic diameter of these cases was 4.6 cm, therefore strenuous
strength training may be dangerous for patients with TAD. The proposed mechanism is
transiently elevated blood pressure associated with isometric exercise or valsalva
maneuver79. Exercise-based cardiac rehabilitation for patients with coronary artery
disease has been shown to reduce mortality in randomized controlled trials80, and
exercise cardiac rehabilitation was found to be safe in a small series of survivors of type I
aortic dissection81.
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Recommendation: “We recommend that patients with thoracic aortic disease be
evaluated for risk for atherosclerotic vascular disease, and that recommendations for
ameliorating this risk, whether by endurance exercise, dietary changes, smoking
cessation, or medical therapy, be made in accordance with current general
guidelines.” (Strong recommendation, low quality of evidence)
Values and Preferences: Both patients and clinicians commonly require guidance with
respect to these issues, and basing clinical decisions on the minimal observational data
available, or extrapolating results from other populations, is a sensible compromise.
Recommendation: “We suggest patients with thoracic aortic disease avoid strenuous
resistance and isometric exercise.” Strong recommendation, very low quality of
evidence.
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Values and Preferences: Though the data are minimal, the risks associated with
strenuous isometric exercise 78 appear great enough to strongly recommend avoiding
this exposure.
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Driving: Neither the Canadian Cardiovascular Society Conference nor the Canadian
Medical Association (CMA) have made recommendations about fitness for driving in the
context of thoracic aortic disease82. However, the CMA has recommended that patients
with abdominal aortic aneurysm be precluded from driving when the rupture risk
exceeds 10% per year. Based the best observational data available, these thresholds of
risk occur for thoracic aortic aneurysms greater than 6.0 cm in the ascending aorta or
arch, and greater than 6.5 cm in the descending aorta. A lower threshold for rupture risk
is reasonable for commercial driving.82
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“We suggest that patients with thoracic aortic disease be precluded from private
driving if the ascending aorta diameter is greater than 6.0 cm or the descending aorta
diameter is greater than 6.5 cm, and restricted from commercial driving if the
ascending thoracic aorta diameter is greater than 5.5 cm or the descending thoracic
aorta is greater than 6.0 cm83. (Conditional recommendation, very low quality
evidence).
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Values and preferences: These thresholds are based on the methodology of the CMA
and Canadian Cardiovascular Society Consensus Conference on the assessment of the
cardiac patient for fitness to drive and fly82 and the best available observational
evidence. Risk thresholds may be reached at different aortic diameters for different
aortopathies. Further studies are required to provide reliable estimates of rupture risk.
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“We suggest that patients return to private driving six weeks following and
commercial driving three months following open aortic repair.” (Conditional
recommendation, low quality evidence)
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Values and preferences: This practice is in accordance with current recommendations
for patients after cardiac valve surgery. Patients undergoing endovascular aortic
procedures may resume driving sooner based on assessment by their treating physician.
Pregnancy: Information related to pregnancy in patients with TAD is provided in
Appendix 1, Table 3.
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Section 5: Screening for family members of patients with genetic aortopathy
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A. Marfan syndrome
Marfan Syndrome is an autosomal dominant disorder with high penetrance and varying
phenotypic expression, which is associated with progressive aortopathy including
dilation of the ascending aorta (sinuses of Valsalva) and can lead to dissection (usually
type A) or rupture if not operated11. Clinical screening of patients suspected to have
Marfan syndrome should be done using the revised Ghent criteria84. Routine CT or MRI
for definite Marfan syndrome should be initiated in early adulthood or at surgery,
whichever comes first.
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Screening of the first degree family members is indicated as the transmission rate is
50%. Genetic screening may help to clarify 1) the nature of the disease, 2) the risk to the
patient when the clinical diagnosis is uncertain, 3) to ascertain sporadic cases or 4)
prenatal diagnosis85. Imaging in family members suspected to have the disease should
include at least a transthoracic echocardiogram to assess the ascending aorta and a
baseline CT scan or MRI to assess the entire aorta. When dilation of the ascending aorta
is found, a repeat transthoracic echo at 6 months should be performed to ascertain the
rate of progression. If stable, a yearly echo should be done thereafter86. Any family
member who has Marfan syndrome (clinically or genetically determined) with a normal
size ascending aorta, should undergo yearly echocardiography 86.
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Recommendations for Marfan syndrome:
“We recommend clinical and genetic screening for suspected Marfan syndrome to
clarify the nature of the disease and provide a basis for individual counselling”. (Strong
recommendation, high quality of evidence)
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“We recommend echocardiographic screening be performed at diagnosis to measure
aortic root and ascending aorta diameters, and repeated 6 months thereafter to
determine rate of progression. If aortic diameters remain stable, annual imaging is
recommended. If the aortic diameter exceeds 45 mm or if significant deviation from
baseline studies occurs, more frequent imaging should be considered.” (Strong
recommendation, high quality of evidence)
“We recommend that women with Marfan syndrome who want to become pregnant
be considered for aortic root and ascending aorta replacement if the diameter reaches
41 to 45 mm). These women should undergo surgery at centres with expertise in
aortic valve sparing surgery (see recommendation from section 2B)”. (Conditional
recommendation, low quality of evidence)
B. Loeys-Dietz syndrome
Loeys-Dietz syndrome (LDS) associated with arterial tortuosity and aggressive,
progressive dilation of the ascending aorta; although the aorta at any level can be
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affected. Cerebral aneurysms are common in LDS. Accompanying craniofacial
involvement can include bifid uvula, cleft palate, craniosynostosis and hypertelorism. It
is autosomal dominant with a 50% transmission rate. First degree family members
should undergo clinical as well as genetic screening. In affected family members, an
initial transthoracic echocardiogram is recommended with a repeat at 6 months if aortic
dilation is present or at 1 year if aorta is not dilated86. Prophylactic aortic root surgery is
recommended in these patients when the ascending aorta reaches 42mm87. A MRI from
the base of the neck to the pelvis is also recommended every 18-24 months to assess
the degree of arterial tortuosity and presence of arterial aneurysms, or more frequently
if specific pathology is followed 88
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C. Bicuspid aortic valve
Bicuspid Aortic Valve (BAV) is the most common cardiac malformation with a prevalence
of 1-2% in the general population. BAV is a heritable disorder with a significantly
increased recurrence risk in first-degree relatives (5-30%) 89-93. Although autosomal
dominant transmission with reduced penetrance and variable expression has been
reported, it is likely a complex genetic trait influenced by several loci. Fifty percent of
patients with BAV have an associated aortopathy that can involve the proximal aorta,
usually the mid ascending aorta. Some affected family members may not have BAV but
may have aortopathy 89, 94, 95. Because of its high risk of recurrence, clinical screening of
first degree relatives is suggested with a transthoracic echo to ascertain the presence of
BAV and/or ascending aorta dilation. CT scan or MRI may be indicated to completely
visualize the ascending aorta and arch 96. Echocardiographic screening of first degree
relatives in the pediatric age range may be useful.
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D. Familial thoracic aortic aneurysm
Familial Thoracic Aortic Aneurysm (FTAA) is a genetic disease that occurs in “non
syndromic” patients with aortopathy and a family history of aortic aneurysm. The
majority of FTAA demonstrate an autosomal dominant inheritance with decreased
penetrance and variable expression. A positive family history for TAA should prompt a
search for signs of syndromic disease. To date, a number of genetic mutations have
been identified which explain 20% of the FTAA.. Imaging of the aorta of first degree
relatives to identify asymptomatic aneurysm is critical. Transthoracic echocardiogram is
recommended, with additional CT scan or MRI if the entire aorta needs imaging.
E. Aneurysm-Osteoarthritis Syndrome
Aneurysm-osteoarthritis syndrome is an autosomal dominant trait with aneurysms of
the arterial tree, skeletal and cutaneous anomalies97, 98. Phenotypic overlap with LDS
encompasses hypertelorism and abnormal palate/uvula, and velvety skin. Early-onset
osteoarthritis and intervertebral disc degeneration are present. Arterial disease mostly
presents as aneurysm of the aortic root, but can also affect the thoracic aorta and the
remainder of the arterial tree with an aggressive course99. Imaging of the entire vascular
tree and genetic testing should be performed in such patients. First-degree relatives of
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patients with AOS should be screened for arterial disease and genetic testing be offered
when a causal mutation is identified in the index case.
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F. Vascular Ehlers-Danlos syndrome (vEDS)
vEDS is an autosomal dominant disorder caused by a mutation in the COL3A1 gene 100.
The ensuing deficiency in collagen III formation results in connective tissue fragility
including aneurysms, arteriovenous fistulae, spontaneous vascular dissections and
ruptures, as well as bowel and uterus ruptures. Patients present with easy bruising,
translucent skin and spontaneous arterial bleeding. Typically, aneurysms involve any
medium-to-large sized muscular artery including branch vessels in the head, neck,
thorax, abdomen and extremities. Dilation of the ascending aorta may occur. Surgical
complications are common, with high procedural mortality101. Surgery should be
avoided unless a lesion is considered to be imminently life-threatening. Clinical and
genetic screening is recommended for first degree relatives. Widespread imaging
modalities should be performed to document anatomy of the entire vascular tree 100.
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G. Turner syndrome
Turner syndrome is a chromosomal anomaly in which one sex chromosome is lacking in
a female, most commonly in the form of monosomy X (45, X). Salient features are short
stature, ovarian failure, and cardiovascular disease. Between 10% - 25% of females with
Turner syndrome have bicuspid aortic valve, and approximately 8% have coarctation.
The risk of aortic dissection is increased in women with Turner syndrome 102, and occurs
in young individuals at smaller aortic diameters than in the general population or other
forms of genetically triggered aortopathy. The absence of aortic valve or other cardiac
malformations reduces the risk of aortic dissection. Data from the international Turner
syndrome aortic dissection registry suggest that individuals with Turner syndrome who
are >18 years of age with an ascending aortic size index >2.5 cm/m2 should be
considered for an aortic operation to prevent aortic dissection103.
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Recommendations for Non-Marfan, Genetic forms of aortic disease:
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“We recommend aortic imaging for first-degree relatives of patients with genetic
forms of TAD to identify asymptomatic carriers.” (Strong recommendation, moderate
quality of evidence)
“We recommend cardiac imaging in adult first-degree relatives of patients with BAV to
identify asymptomatic carriers.” (Strong recommendation, moderate quality of
evidence)
“We recommend screening for TAD-associated genes in non-BAV aortopathy index
cases to clarify the origin of disease and improve clinical and genetic counselling”.
(Strong recommendation, moderate quality evidence)
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“We recommend that genetic counselling and testing be offered to first-degree
relatives of patients in whom a causal mutation of a TAD-associated gene is identified.
We recommend that aortic imaging be offered only to mutation carriers”. (Strong
recommendation, Low quality evidence)
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“We recommend complete aortic imaging at initial diagnosis and at 6 months for
patients with Loeys-Dietz syndrome or a confirmed genetic aortopathy (e.g. TGFBR1/2,
TGFB, SMAD3, ACTA2, or MYH11) to establish if enlargement is occurring.” (Strong
recommendation, moderate quality evidence)
SC
“We recommend that patients with Loeys-Dietz syndrome have whole body magnetic
resonance imaging every 18-24 months to assess progression of vascular disease, or
more frequently if specific pathology is followed”. (Strong recommendation, moderate
quality of evidence)
Section 6: Knowledge Gaps
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“We recommend that patients with Turner syndrome should have a complete
assessment of cardiac and aortic structures. If normal, repeat imaging should be
performed every 5 years. If abnormalities are detected, annual imaging should be
performed. In children, annual imaging may be recommended.” (Strong
recommendation, moderate quality of evidence)
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Most of the epidemiology and natural history of TAD is based on: 1) Surgical series from
selected populations, 2) Retrospective cohorts of acute aortic syndromes, 3) Single
center studies of patients with inherited or degenerative forms of TAD, and 4)
Extrapolation from non TAD patients, leaving important knowledge gaps in this patient
population.
Future research should be focused on these key knowledge gaps in the
pathophysiology, natural history, and treatment of patients with TAD, including but not
limited to:
1. Contemporary natural history data on the risks of aortic complications.
2. Predictors of aortic complications (other than size) in patients with moderate aortic
dilation.
3. Genetic, epigenetic, and imaging determinants of the development and progression
of the various forms of TAD and predictors of acute aortic syndromes.
4. Prevalence of TAD in susceptible populations and the role of age in development of
disease
5. The efficacy of screening strategies and the psychological, social and legal
consequences of such screening
6. The efficacy of risk factor modification on preventing TAD or attenuating its
progression.
7. The outcomes and impact of emerging therapies in the management of TAD
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Section 7: Multi-disciplinary Care and Quality Indicators
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Comprehensive management of thoracic aortic disease spans multiple disciplines
including but not limited to cardiac surgery, vascular surgery, cardiology, genetics,
imaging, and adult congenital heart disease. Therefore, care for these patients is best
provided in such a multi-disciplinary environment and clinics are currently emerging
across major cardiac centers in Canada. These may also be an important source of
critical natural history data on thoracic aortic pathologies, and facilitate prospective
clinical trials and mechanistic studies to help advance care for these patients.
SC
Assessment of quality of care indicators for TAD may include 1) timely referral for
surgery (as per propsed size thresholds), 2) appropriate imaging surveillance, and 3) risk
factor management (anti-hypertensives, smoking cessation, etc.).
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Acknowledgements:
The authors would like to thank the members of the secondary panel listed below for
their thorough review of the manuscript draft and insightful comment that helped
shape the final document
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Secondary Panel: Hal Dietz1 MD, Francois Dagenais2 MD, Christopher Fiendel3 MD,
Raymond Kwong4 MD, PhD, Erwin Oechslin5 MD
1
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McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore,
MD, USA
2
Division of Cardiac Surgery, Laval University, Quebec City, Quebec
3
Division of Cardiac Surgery, University Health Network, Toronto, Ontario
4
Division of Cardiology, Brigham and Women’s Hospital, Harvard University, Boston,
MA, USA
5
Division of Cardiology, University of Toronto, Toronto, Ontario
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Tables
Table 1: Factors* determining increased risk of aortic complications and of increased
risk of surgical intervention.
Factors Associated with Increased Risk of
Surgical Intervention
Aortic Arch Pathology
Descending Thoracic Aortic Pathology
Chronic Obstructive Pulmonary Disease
Renal Dysfunction
Previous Cardiac Surgery
Advanced Age
Left Ventricular Dysfunction
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Factors Associated with Increased Risk of
Aortic Complications
Aortic size
Connective Tissue Disorder
Family History of Aortopathy
Bicuspid Aortic Valve
Smoking History
Aneurysm related symptoms
Rapid Growth (> 0.5 cm/year)
Concomitant Aortic Valve Disease
Uncontrolled Hypertension
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* Additional factors may be relevant for risk stratification in some patients
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Table 2: Recommended Size thresholds for Intervention for Asymptomatic Thoracic
Aortic Aneurysms*
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Aortic Root
Ascending
Arch
Descending
Degenerative
5.5 cm
5.5 cm
6.0 cm
6.5 cm
Bicuspid Aortic Valve
5.0 – 5.5 cm
5.0 – 5.5 cm
5.5 cm
6.5 cm
Marfan Syndrome
5.0 cm***
5.0 cm
5.5 – 6.0 cm 5.5 – 6.0 cm
Familial Aortopathy
4.5 – 5.0 cm
4.5 – 5.0 cm
5.5 – 6.0 cm 5.5 – 6.0 cm
Other Genetic Syndromes**
4.0 – 5.0 cm
4.2 – 5.0 cm
5.5 – 6.0 cm 5.5 – 6.0 cm
Undergoing Cardiac Surgery
4.5 cm
* Size thresholds for intervention should take into consideration patient body size either
empirically or using proposed formulas for adjustment
** Loeys-Dietz, Turner, Ehlers-Danlos
*** For women anticipating pregnancy, the threshold is 4.1-4.5 cm.
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Table 3: Advantages and disadvantages of various modalities for thoracic aortic Imaging
CT
•
•
•
•
•
•
Availability
Imaging of aorta, neck
vessels, and thorax
Short image acquisition time
Able to define coronary
anatomy
Tissue characterization
No radiation
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Portable
Readily Available
Excellent visualization
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Transesophageal •
echocardiography •
•
Disadvantages
• Limited acoustical access,
particularly in obese or
postoperative patients
• Best for visualization of proximal
portion of ascending aorta
• Operator Dependent
• Limited visualization of distal
ascending aorta
• Reduced diagnostic accuracy for
intramural hematoma
• Operator dependent
• Radiation exposure
• Renal insufficiency may require
restriction in contrast
administration *
SC
Modality
Advantages
Transthoracic
• Portable
echocardiography • Readily available
• Established role in evaluation
of structural cardiac disease
•
•
Long acquisition time
Cannot be performed in unstable
patients or patients with renal
dysfunction*, pacemakers/AICD
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CT – Computed Tomography, MR – Magnetic Resonance Imaging
*See online supplement for options in patients with mild to moderate renal dysfunction
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Table 4: Screening for patients and family members with genetic aortopathy
Gene(s)
involved
Transmission Part of
Screening of
Imaging
mode
aorta
family
modality
affected
members
Marfan
FBN1
Autosomal
Asc: ++
Clinical: Ghent Echo +
syndrome
Dominant
Arch: +
criteria
CT vs.
with
Desc: +
Genetic: in
MRI
different
some cases
phenotypic
Imaging: yes
expression
Loeys-Dietz
TGFBR1
Autosomal
Asc: ++
Clinical: yes
Echo +
syndrome
TGFBR2
Dominant
Arch: +
Genetic: yes
CT vs.
SMAD3
with variable Desc: +
Imaging: yes
MRI
TGFB2
expression
$
AneurysmAutosomal
Asc:++
Clinical: yes
Echo +
osteoarthritis SMAD3
dominant
Desc: +
Genetic: yes
CT vs.
syndrome
$
Imaging: yes
MRI
Ehlers-Danlos
Autosomal
Asc:+
Clinical: yes
Echo +
Type IV
COL3A1
dominant
Desc: +
Genetic: yes
CT vs.
$
Imaging: yes
MRI
Bicuspid aortic Likely
Complex
Asc: ++
Clinical: yes
Echo +
valve
multiple
trait
Arch: +
Genetic: no
CT vs.
genes
Familial
Desc: Imaging: yes
MRI
clustering
Familial
TGFB2
Autosomal
Asc: ++
Clinical: yes
Echo +
thoracic aortic TGFBR1
Dominant
Arch: +
Genetic: yes
CT vs.
aneurysm
TGFBR2
with reduced Desc: +
Imaging: yes
MRI
MYH11
penetrance
SMAD3
and variable
ACTA2
expression
CT – Computed Tomography, Echo – echocardiogram, MRI – Magnetic Resonance
Imaging, Asc – Ascending Aorta, Desc – Descending Thoracic Aorta
$: See text for imaging of other vessels.
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Aortopathy
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Appendix 1: Supplementary Materials
1. Supplementary Information for endovascular treatment of thoracic aortic disease
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Thoracic Endovascular Aneurysm Repair (TEVAR) requires normal caliber aorta (~ 2 cm)
proximal and distal to the aneurysm to achieve a seal and complete aneurysm exclusion.
Seal zones have been expanded by proximal subclavian coverage and revascularization
of the left subclavian artery (LSA) is recommended1. Treatment strategy for TEVAR is
largely determined based on the location of the pathology and the suitability of adjacent
aortic segments where the stents can be placed (Figure 1). The greatest experience with
TEVAR has been accrued for descending thoracic aortic pathology.
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To facilitate TEVAR with zone 1 and zone 2 proximal landing zones, debranching of arch
vessels can be performed either via sternotomy or in an extra-anatomic fashion
(carotid-carotid and carotid-subclavian bypass) followed by stent implantation. Chimney
grafts have also been described for the aortic arch2. This technique involves the
placement of stents (covered or uncovered) parallel to a TEVAR graft to perfuse the arch
vessels to avoid surgical debranching or bypassing these arch vessels. This technique
adds sealing zone length while maintaining perfusion to the artery of interest.
Some very short endografts have been produced for therapy of type A aortic dissections
in poor operative candidates and a few published series exist3, 4.
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Placement of any endovascular device requires a sufficiently large femoral/external iliac
artery for delivery or a surgically-created iliac conduit may be required. Tortuous arterial
anatomy may complicate device delivery to the site of desired deployment. Accurate
placement of proximal thoracic grafts has been facilitated with either the use of
intraoperative hypotension induced by pharmacologic means (adenosine, esmolol) or
rapid ventricular pacing using a right ventricular pacing wire. The ventricular pacing
technique allows rapid onset and reversal of hypotension for accurate graft deployment.
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While the results of endovascular treatment of selected thoracic aortic pathologies are
promising, these results are achieved by those with advanced experience, skills and
access to the multiple additional technologies (e.g. Intravascular ultrasound) that aid in
therapy of these complex patients.
The use of TEVAR for genetic conditions associated with a generalized impairment of
vessel wall integrity remains highly controversial and requires further study. The
concern relates to maintenance of vessel wall and stent integrity at the loading zones. In
addition, initiation and propagation of dissection can still occur within or immediately
adjacent to the vascular region isolated by the stent. Currently TEVAR should be
considered a temporizing measure that can be used (largely in the descending aorta) in
specialized emergent situations or to bridge vascular segments that have already been
replaced by Dacron grafts.
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2. Supplementary information for imaging in thoracic aortic disease
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The following suggestions are provided so that practitioners can utilize imaging
modalities to achieve the most diagnostic value and to facilitate communication
between providers and centres.
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Thoracic Aortic Assessment with CT
• CT examinations should be performed with iodinated contrast
• Multiplanar reformation or centerline reconstruction should be used to achieve
cross-sectional visualization.
o From these reconstructed images, the minimal luminal diameter along
the course of the vascular access should be determined
o Aortic Dimensions should be measured orthogonal to the direction of
blood flow in systole and reflect the external aortic diameter (Figure)
• CT with the implementation of modern dose reduction strategies may be a
reasonable imaging option particularly in those over the age of 50
• ECG Gating should be considered for all cases when heart rate and scanner
technology available will permit it.
o If serial surveillance is performed with CT this should be optimally
performed with ECG gating to ensure optimal image quality so changes in
aortic dimension can be adequately identified
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Thoracic Aorta Assessment in the setting of Abnormal renal function
• Echocardiographic assessment of aortic size is the first line test where the
concerns lie in the ascending aorta
• MR alternatives include:
o Non-Gadolinium enhanced MRI with bright blood or black blood
sequences
o non-contrast based MR angiography
o reduced dose of gadolinium in patients with mild to moderate renal
insufficiency (GFR> 30)
• Depending on the severity of renal impairment, CT with the use of contrast
reduction strategies such as dual energy CT and high pitch helical acquisitions
are also alternatives
Standard Report Elements for Thoracic Aortic Disease Evaluation
• Anatomical location(s) and extent where the aorta is dilated
• Maximum diameter of the dilated segment from the outer vessel margin in
addition to the length of the dilated segment. Measurements must be
performed in the short axis of the vessel
• The presence of either calcified or non-calcified aortic atherosclerosis
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•
•
SC
•
Atherosclerosis must be distinguished from intramural hematoma
Measurements of the aortic root, annulus, sinuses, and tubular aorta in patients
with suspected or confirmed genetic conditions
Involvement of aortic branch vessels including dissection or dilatation as well as
any secondary evidence of end-organ injury (e.g., renal or bowel hypoperfusion)
When a prior examination is available, direct comparison should be performed
to allow for the image measurements to be performed by the same interpreting
physician to determine if there has been interval change
Evidence of aortic rupture, including periaortic and mediastinal hematoma,
pericardial and pleural fluid, and contrast extravasation from the aortic lumen
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3. Supplementary Information for Medical Therapy and Lifestyle Considerations
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Anti-Hypertensive Therapy: Table 2 summarizes the clinical trials of anti-hypertensive
therapy in patients with Marfan Syndrome. These trials show lower rates of aortic root
dilation with treatment, and no difference in other clinical outcomes
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Diet: There are no studies of dietary interventions in patients with thoracic aortic
disease. However, a diet rich in fruits and vegetables with reduced saturated and total
fat (DASH diet) reduces blood pressure in a randomized controlled trial5. The
combination of sodium reduction with the DASH diet has been shown to be more
effective in lowering blood pressure than either dietary intervention alone6. Nationwide
programs to reduce dietary sodium have been associated with improvements in blood
pressure and decreases in deaths from strokes and coronary artery disease.7, 8 In
addition, a Mediterranean diet, rich in fruits, vegetables, and supplemented with extra
virgin olive oil or nuts, was associated with lower risk for cardiovascular events
(myocardial infarction, stroke, or death from a cardiovascular cause) in a randomized
controlled trial9.
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Smoking Cessation: Tobacco smoking has been associated with increased rate of growth
of thoracic aortic aneurysm in an observational study10. Moreover, tobacco smoking is
associated with increased mortality from cancer, chronic obstructive pulmonary disease,
coronary artery disease, and stroke, and smoking cessation at any age is linked with
reduced death rates11-13.
Lipid Lowering Therapy: Trials of lipid lowering therapies have generally not included
patients with thoracic aortic disease nor have they reported on thoracic aortic aneurysm
or acute aortic syndromes.14, 15 Moreover, many forms of thoracic aortic aneurysm
appear unrelated to dyslipidemia. A small, underpowered, observational study of
patients with thoracic aortic aneurysm (n = 59) did not show a mortality benefit for
statin therapy16. An intriguing observational report of 147 patients with bicuspid aortic
valve reported smaller ascending aortic sizes in those taking statins17. Another series of
649 patients with thoracic aortic aneurysm, of whom 147 were taking statins, found that
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statin use was associated with better survival and lower risk for aneurysm repair18.
Though there are no good data which support that statins alter the course of thoracic
aortic disease, statin drugs are safe and effective for reducing all cause mortality, major
vascular events (myocardial infarction, stroke), and revascularizations in patients
without prior cardiovascular disease and at relatively low (< 1% per year) cardiovascular
risk, and many patients with thoracic aortic aneurysms have risk factors for
atherosclerosis.19, 20
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Driving: The Canadian Medical Association has not addressed driving recommendations
for patients with thoracic aortic disease, but did recommend patients with infrarenal
abdominal aortic aneurysms with annual rupture risk greater than 10% be precluded
from driving21. The Canadian Cardiovascular Society Consensus Conference on the
assessment of the cardiac patient for fitness to drive and fly also did not address
patients with thoracic aortic disease22, but did suggest a return to driving after valve
surgery, assuming no thromboembolic complications, normal functional capacity, and
absence of severe left ventricular dysfunction (left ventricular ejection fraction ≥ 35%),
at six weeks for private driving and three months for commercial driving. Rates of
rupture or acute dissection for ascending aortic aneurysms ≥ 6.0 cm are 36.2% (95% CI
5.1-85.6%) and 6.6% (95% CI 1.3-27%) for ascending thoracic aortic aneurysms between
5.0 and 5.9 cm23. Similarly, for descending thoracic aneurysms ≥ 7.0 cm the incidence of
rupture or aortic dissection was 47.1% (95% CI 12.6-84.8%) and 12.2% (95% 1.2-59.8%)
%) for descending thoracic aortic aneurysms between 6.0 and 6.9 cm. The rupture risk
for a given aortic size may be higher for some forms of aortic disease, including
aortopathies associated with bicuspid aortic valve, connective tissue disorders, or
familial aortic aneurysm syndromes.23, 24
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Pregnancy: Information related to pregnancy in various subsets of patients with TAD is
outlined in Table 3.
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Table 1: Possible Approaches to Endovascular management of thoracic aortic aneurysms
Zone 2
a) Thoracic EVAR with or without
LSA reconstruction using insitu
fenestration of graft
b) Thoracic EVAR with LSA branch
c) Chimney graft for LSA and TEVAR
Thoracic EVAR
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Zone 3/4
Sternotomy with debranching
for innominate, LCC and LSA
(several configurations)
followed by TEVAR placed ante
or retrograde
Carotid-Carotid bypass with or
without LSA reconstruction
and TEVAR to edge of
innominate artery (possible
use of custom graft with
scallop for innominate for
extra fixation)
Thoracic EVAR with bypass to
re-attach LSA by extra
anatomic technique
SC
Zone 1
a) Aortic Arch graft (branches for
innominate and LCC) with or
without LSA reconstruction
b) Chimney graft(s) and TEVAR
graft
Chimney graft for LCC and/or LSA
with TEVAR graft (or without LSA
reconstruction)
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Proximal Aortic
Landing zone
Zone 0
Possible Approaches to Repair
TEVAR alone
Hybrid (Open and TEVAR)
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TEVAR – Thoracic Endovascular Aneurysm Repair, LSA – Left Subclavian Artery, LCC –
Left Common Carotid
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Table 2: Summary of trials of anti-hypertensive therapy in Marfan Syndrome
Propranolol
vs. no therapy
Groenink et
26
al
233
Ahimastos et
al27
29
Ladouceur
30
Investigator
Blinding
Outcome
Main Finding
Yes
No
Rate of
increase in
aortic ratio
Slower increase in
aortic ratio in
propranolol group
(0.023 vs. 0.084 per
year, P < 0.001)
Losartan plus
usual care vs.
usual care
(73% on βblockers)
3.1
years
Yes
No
Aortic root
dilatation
root
Lower aortic root
dilatation in losartan
group (0.77 ± 1.36
vs. 1.35 ± 1.55 mm, P
< 0.014)
17
Perindopril
plus betablocker vs.
beta-blocker
24
weeks
Yes
Yes
Mean
change in
aortic root
diameter
Lower aortic root
diameter change
with perindopril (2.3
± 0.5 mm vs. 0.4 ±
0.1, p < 0.001)
28
Losartan plus
beta-blocker
vs. betablocker
35
month
s
Yes
No
Annual aortic
root
dilatation
rate
Lower annual aortic
root dilatation rate
in losartan treated
subjects (0.10 mm/yr
vs 0.89 mm/yr;
P=.02)
155
Beta-blockers
vs. no betablockers
1.3
years
No
No
Annual aortic
root
dilatation
rate
Lower annual aortic
root dilatation rate
in beta-blocker
treated subjects
(1.05 mm/yr vs 1.15
mm/yr; P < 0.001)
ARB (no
control group;
historical
control only)
12 to
47
month
s
No
No
Annual aortic
root
dilatation
rate before
and after
ARB
Annual aortic root
dilatation rate 3.54
±2.87 mm/yr before
and 0.46 ± 0.62
mm/yr after
angiotensin receptor
blocker
Losartan (no
control group;
historical
control only)
33.2
month
s
No
No
Mean
normalized
aortic root
diameter
change
Mean normalized
aortic root diameter
change
-3.0 ± 2.8 mm/m2,
p <0.001
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28
Random
ized
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Shores et
25
al
Chiu et al
Follow
-up
Durati
on
10.7
years
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Intervention
&
Comparator
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Table 3. Pregnancy in patients with TAD
Bicuspid Aortic
Valve
Familial Thoracic
Aortic Aneurysm
•
•
•
•
•
•
•
•
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Ehlers-Danlos IV
•
•
•
•
•
•
•
•
•
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Loeys-Dietz
•
•
•
•
•
•
•
Pregnancy
CID if ascending aorta > 45 mm 32, 33
Relative CID if aorta > 40 mm 32, 33
Increased rate of aortic growth during pregnancy 32
BB during pregnancy
BP control
TTE every 4-6 weeks
Assisted delivery (outlet forcep or vacuum) if aorta <
40mm
Consider Cesarian delivery if aorta > 40mm 34
50% transmission rate to offspring
CID if any aortic dilatation 35
BP control*
TTE q4-6 weeks
Consider elective Cesarian delivery at 34-36 weeks 36
50% transmission rate to offspring
CID for risk arterial and uterine rupture 35
Consider elective Cesarian delivery at 34-36 weeks 37 +
DDAVP to diminish perioperative bleed 34
50% transmission rate to offspring
CID if ascending aorta > 50 mm
Relative CID if aorta > 45mm 38
BP control*
TTE q4-6 weeks
Consider elective Cesarian delivery at 34-36 weeks if
aorta dilated
CID if ascending aorta > 50 mm
CID if family history of aortic dissection at normal
aortic size
BP control*
TTE q4-6 weeks
Consider elective Cesarian delivery at 34-36 weeks if
aorta dilated
CID if ascending aorta > 55 mm
BP control*
TTE q 4-6 weeks if ascending aneurysm
TEE or MRI if descending aortic aneurysm
Consider elective Cesarian delivery at 34-36 weeks if
aorta dilated
CID
EP
Aortopathy
Marfan
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•
•
•
Acquired
•
•
•
•
•
Chronic
dissection
•
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BB- Beta adrenergic blockade CID – Contraindicated; BP – Blood pressure; TTE –
transthoracic echocardiogram; TEE – transesophageal echocardiogram; MRI – magnetic
resonance imaging
*lowering the upper limit of acceptable systolic blood pressure to <120 mmHg has been
empirically proposed, to reduce the shear stress on the aorta during pregnancy
Figure Legends (insert figure)
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Figure 1 – This anatomic landing zone map describes the area of the aorta where the
proximal end of the endograft will be located3.
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Figure 2- The use of multiplanar reconstruction and centre line techniques enable the
accurate measurement of the aorta in its true short axis along the plane of blood flow
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