European Heart Journal (2017) 0, 1–15 CLINICAL REVIEW

doi:10.1093/eurheartj/ehx319

Acute aortic syndromes: diagnosis and

management, an update
Eduardo Bossone1*, Troy M. LaBounty2, and Kim A. Eagle2*
1
Heart Department, University Hospital, Salerno, Italy; and 2University of Michigan Cardiovascular Center, 24 Frank Lloyd Wright Dr, Ann Arbor, MI 48105, USA

Received 17 March 2016; revised 1 April 2017; editorial decision 10 May 2017; accepted 13 June 2017

Acute aortic syndromes (AAS) encompass a constellation of life-threatening medical conditions including classic acute aortic dissection
(AAD), intramural haematoma, and penetrating atherosclerotic aortic ulcer. Given the non-specific symptoms and physical signs, a high
clinical index of suspicion is necessary to detect the disease before irreversible lethal complications occur. In order to reduce the diagnos-
tic time delay, a comprehensive flowchart for decision-making based on pre-test sensitivity of AAS has been designed by the European
Society of Cardiology guidelines on aortic diseases and should be thus applied in the emergency scenario. When the definitive diagnosis is
made, prompt and appropriate therapeutic interventions should be undertaken if indicated by a highly specialized aortic team. Urgent sur-
gery for AAD involving the ascending aorta (Type A) and medical therapy alone for AAD not involving the ascending aorta (Type B) are
typically recommended. In complicated Type B AAD, thoracic endovascular aortic repair (TEVAR) is generally indicated. On the other
hand, in uncomplicated Type B AAD, pre-emptive TEVAR rather than medical therapy alone to prevent late complications, while intuitive,
requires further study in randomized cohorts. Finally, it should be highlighted that there is an urgent need to increase awareness of AAS
worldwide, including dedicated education/prevention programmes, and to improve diagnostic and therapeutic strategies, outcomes, and
lifelong surveillance.
...................................................................................................................................................................................................
Keywords Acute aortic syndromes • Aortic dissection • Intramural haematoma • Penetrating aortic ulcer

..
Introduction .. Acute aortic syndromes
..
The aorta, called ‘the greatest artery’ by the ancients, is the ulti-
.. Acute aortic syndromes are a constellation of life-threatening medical
..
mate conductance vessel carrying roughly 200 million litres of .. conditions, including classic acute aortic dissection (AAD), intramural
blood to the body in an average lifetime. Anatomically, it is divided
.. haematoma (IMH), penetrating atherosclerotic aortic ulcer (PAU)
..
into thoracic and abdominal components that are located above .. (even thoracic aortic rupture), which share common pathophysiolog-
and below the diaphragm, respectively. The thoracic aorta is div-
.. ical pathways (breakdown of the intima and media), clinical character-
..
ided into the aortic root and the ascending, arch, and descending .. istics, and diagnostic and therapeutic challenges.2,9
..
segments; and the abdominal aorta into the suprarenal and ..
infrarenal segments.1,2 ..
..
As a ‘whole organ’, the aorta may be affected by several congenital ..
or acquired diseases, either acute or chronic, involving the thoracic .. Classification
.. Anatomically, there are two commonly used classification schemes
and/or abdominal components (holistic approach).2,3 In this review, ..
we focus on recent advances in the diagnostic and therapeutic path- .. for aortic dissection. The DeBakey system categorizes dissections
.. based on the origin of the intimal tear and the extent of the dissec-
ways of acute aortic syndromes (AAS) derived in large measures ..
from multiple registries/population-based studies and recent consen- .. tion, and the Stanford system divides dissections according
.. to whether the ascending aorta is involved (Type A) or not
sus statements/guidelines developed by American and European ..
Specialty Societies.2–8 .. involved (Type B), regardless of the site of origin (Table 1, Figures 1
.. and 2).2,9–11

* Corresponding authors. Email: keagle@med.umich.edu; Tel: þ39 081 824 0067, þ39 328 541 5438, Fax: þ39 081 824 0067, Email: ebossone@hotmail.com
Published on behalf of the European Society of Cardiology. All rights reserved. V
C The Author 2017. For permissions, please email: journals.permissions@oup.com.
2 E. Bossone et al.

..
.. Historically, acute dissection has been defined as occurring within
Table 1 Classification schemes of aortic dissection .. 2 weeks of symptom onset, with chronic dissection occurring beyond
..
DeBakey (Figure 1) .. the second week. This cut-off of 14 days is based on survival esti-
.. mates derived in part from the work of Hirst et al.12 in the late 1950s.
Category I Dissection tear in the ascending aorta propagat- ..
ing distally to include at least the aortic arch .. As a result of substantial advances in diagnostic modalities, treatment
.. strategies, and their relative impact on early and late outcomes, the
and typically the descending aorta ..
Category II Dissection tear only in the ascending aorta
.. European Society of Cardiology (ESC) guidelines have recently sug-
.. gested to further divide the time course of aortic dissection into
Category III Dissection tear in the descending aorta propa- ..
gating most often distally
.. acute (<14 days), subacute (15–90 days), and chronic (>90 days)
.. phases.2 Booher et al.,13 using data from the International Registry of
Category IIIa Dissection tear only in the descending thoracic ..
aorta
.. Aortic Dissection (IRAD), developed Kaplan–Meier survival curves
.. distinct for dissection and treatment type (surgical þ medical or med-
Category IIIb Tear extending below the diaphragm ..
Stanford (Figure 1)
.. ical alone for Type A; medical, medical þ endovascular, and medical-
..
þ open surgical intervention for Type B) and identified four time
Type A All dissections involving the ascending aorta ...
irrespective of the site of tear .. domains: hyperacute (<24 h), acute (2–7 days), subacute (8–30 days),
.. and chronic (>30 days). Interestingly, overall survival was progres-
Type B All dissections that do not involve the ascending ..
aorta; note that involvement of the aortic .. sively lower through the four time periods, regardless of treatment
.. strategy (see Supplementary material online, Figures S1 and S2).
arch without involvement of the ascending ..
aorta in the Stanford classification is labelled ..
..
as Type B ..
Svensson (Figure 2) .. Classic acute aortic dissection
..
Class I Classical dissection with true and false lumen ..
Class II Intramural haematoma or haemorrhage .. Classic aortic dissection (85–95% of all AAS) is characterized by the
.. presence of an intimal flap separating the true lumen and the false
Class III Subtle dissection without haematoma ..
Class IV Penetrating atherosclerotic aortic ulcer .. lumen.2,14 Although the true incidence of AAD is difficult to define
.. (pre-hospital mortality and sudden death cases may be missed unless
Class V Iatrogenic or traumatic dissection ..
.. autopsy is carried out), population-based studies suggest that it may
Modified from Nienaber and Clough.9 .. range between 2.6 and 3.5 cases per 100 000 person-years, and nec-
..
.. ropsy series have reported a prevalence ranging from 0.2% to
.. 0.8%.2,3,15 Notably, many studies support the presence of an evident

Figure 1 Classification of aortic dissection localization (see Table 1). Modified from Erbel et al.,2 with copyright permission.
Acute aortic syndromes 3

Figure 2 Classification of acute aortic syndromes by Svensson et al.11 (see Table 1). Modified from Erbel et al.,2 with copyright permission.

chronobiologic rhythmic pattern in the incidence of acute aortic

.. Physicians should also be aware of the possibility of iatrogenic aortic
..
events, characterized by significant higher risk in winter (December),
on Monday, and in morning hours (between 6 a.m. and 12 a.m.).16,17
Risk factors
Risk factors for development of thoracic aortic dissection mainly
reflect conditions associated with increased wall stress (hypertension
and physical trauma) and/or aortic media abnormalities (syndromic
and non-syndromic genetic diseases) (Table 2).3,5–7 Based on the
IRAD data, the majority of patients have a history of systemic hyper-
tension (77%), which is more prevalent in Type B than in Type A
AAD (81% vs. 74%).5 Specifically, hypertension, either historically or
at presentation, is less common in the young (<40 years) when com-
pared with the older AAD patients. Furthermore, patients aged
<40 years (68 of 951, 7%) are more likely to have Marfan syndrome,
bicuspid aortic valve, prior aortic surgery, and larger aortic dimen-
sions. Mortality risk is similar in the two age groups, irrespective of
the site of dissection.18 If race-related differences are considered in
AAD, African patients (14%), when compared with Caucasian
patients, are more likely to be younger and to be affected by Type B
AAD (52.4%).19 Hypertension and cocaine abuse are identified pre-
dominantly as a cause of AAD in Blacks.19,20 Yet, overall similar in-
hospital and long-term survival have been reported between Blacks
and Whites.19 However, up-to-date data on racial and ethnic groups
remain scarce, underlying the need for further investigations.
.. dissection after invasive vascular procedures or cardiac surgery.21
.. In the Registry on Aortic Iatrogenic Dissection (RAID), among
..
.. >100 000 cardiac catheterizations, the incidence of iatrogenic
.. ascending aorta dissection was very low (74 cases; 0.06%), with a
..
.. good short-term (only 2 patients died of cardiogenic shock) and
.. long-term prognosis (no subsequent death and/or major complica-
..
.. tions after a median follow-up of 51.2 months) with the adoption of a
..
.. conservative, non-surgical approach.22
.. Finally, during clinical evaluation of patients involved in high-energy
..
.. deceleration trauma (motor vehicle crash or falls), clinicians must
.. consider the possibility of acute transection of the aortic wall as a
..
.. direct consequence of an instantaneous peak increase in wall stress.
.. In fact, it is notable that 15–20% of deaths secondary to high-speed
..
.. accidents are related to aortic trauma (95% at the level of aortic isth-
.. mus and 5% at the ascending aorta) and are frequently associated
..
.. with myocardial contusion (cardiac failure, myocardial infarction, and
.. tamponade).2
..
..
..
..
.. Clinical profile
.. The most common presentation of a patient with AAD, as reported
..
.. in the IRAD registry, is a male (two-thirds of the study population) in
.. his seventh decade (32% were >70 years of age, while 7% were
..
.. <40 years) with a history of hypertension, who present with abrupt
.. onset of severe chest pain. However, clinical manifestations are
4 E. Bossone et al.
..
Table 2 Risk factors for development of thoracic
.. disease before irreversible lethal complications occur,24 which can
.. sometimes be challenging, given the potential for overlapping symp-
aortic dissection ..
.. toms between AAD and the more common acute coronary syn-
Conditions associated with increased aortic wall stress .. dromes and/or stroke.14,24
..
Hypertension, particularly if uncontrolled
Pheochromocytoma
Cocaine or other stimulant use
Weightlifting or other Valsalva manoeuvre
Trauma
Deceleration or torsion injury (e.g. motor vehicle crash, fall)
Coarctation of the aorta
Conditions associated with aortic media abnormalities
Genetic
Marfan syndrome
Ehlers–Danlos syndrome, vascular form
Bicuspid aortic valve (including prior aortic valve replacement)
Turner syndrome
Loeys–Diez syndrome
Familial thoracic aortic aneurysm and dissection syndrome
Other mutations in genes (e.g. fibrillin, tumour growth factor-
beta receptor, SMAD3)
Inflammatory vasculitis
Takayasu arteritis
Giant cell arteritis
Behçet arteritis
Other
Atherosclerosis
Pregnancy
Polycystic kidney disease
Chronic corticosteroid or immunosuppression agent
administration
Infection involving the aortic wall either from bacteremia or
extension of adjacent infection
Modified from Hiratzka et al.3
diverse and overlapping. For a small fraction of patients (<5%), classi-
cal symptoms and signs may be absent. Neither the electrocadiogra-
phy (ECG) nor the chest X-ray is particularly helpful for diagnosing
aortic dissection. The 12-lead ECG most frequently shows non-spe-
cific abnormalities or evidence of ischaemia and is within the normal
limits in only one-third of patients. Also mediastinal widening on
chest X-ray may be absent in half of cases (Table 3).4,5 Gender-
focused systematic data analysis among 1078 IRAD patients highlights
that women are significantly less frequently affected by AAD (32.1%
of the population), but when they are affected, they are significantly
older than men, with AAD occurring on average 6 or 7 years later
(50% of cases >_70 years of age). Interestingly, the diagnosis of AAD is
more often delayed in women than in men. This may be explained
in part by less typical pain or less severe perception of pain at
presentation along with more frequently observed alterations of con-
sciousness. Multivariate logistic regression analysis indicates higher
in-hospital death rates in women than men, primarily due to a differ-
ence in outcomes of surgically treated Type A AAD (21.9% mortality
in men vs. 31.9% in women, P = 0.013).23 For both women and men,
a high index of clinical suspicion is necessary, in order to detect the
..
..
..
.. Laboratory testing
..
..
.. Laboratory testing complements the clinical assessment of
.. patients with suspect or overt AAD and may be useful for differ-
..
.. ential diagnosis and/or detection of life-threatening complications
.. (Table 4).2,25,26
..
.. In this regard, D-dimer is the most widely available diagnostic bio-
.. marker for AAD diagnostic test (point-of-care test) and is the most
..
.. promising in achieving the ‘gold standard status’.2,25 Several investiga-
.. tors have demonstrated that a cut-off level of 500 ng/mL (currently
..
.. used for pulmonary embolism) is highly sensitive to rule out classical
.. AAD within the first 6 h of symptom onset.25,27–29 It should be noted
..
.. that D-dimer levels <500 ng/mL may be found in patients with IMH,
.. PAU, and/or AAD with thrombosis of the false lumen.14,30 However,
..
.. D-dimer is not a specific biomarker for AAD, as it may be elevated in
.. many other disorders, including acute myocardial infarction compli-
..
.. cated by mural thrombus and acute pulmonary embolism.2,25 In sum-
.. mary, there is good evidence to consider D-dimer as an AAD rule
..
.. out marker. Further studies are needed to confirm preliminary data,
.. suggesting that AAD could also be ruled out using a D-dimer cut-off
..
.. level of 1600 ng/mL in the first 6 h of symptom onset.27
..
..
..
..
.. Imaging
..
.. Computed tomography (CT), transoesophageal echocardiography
..
.. (TOE), and magnetic resonance imaging (MRI) all have excellent
.. accuracy to diagnose AAD.31,32 The choice depends on the availabil-
..
.. ity and expertise of the particular hospital as well as the patient’s pre-
.. senting clinical status. (Table 5).33 In the IRAD registry, CT is most
..
.. frequently selected worldwide as the initial test, followed by
.. TOE.5,34,35 More than two-thirds of patients require not less than
..
.. two imaging tests, stressing the concept that in high-risk patients with
..
.. an initial negative imaging result, it is wise to perform a second test to
.. exclude the disease and/or to detail distinct aortic segment involve-
..
.. ment, enabling subsequent treatment planning.2,3,34–36
..
..
.. Echocardiography
..
.. Transthoracic echocardiography (TTE) is widely used in the emer-
.. gency setting as part of a multidisciplinary approach to rapid diag-
..
.. nosis.37 A focused TTE on aortic valve complex and distinct aorta
.. segments (suprasternal, subcostal, and abdominal views) along
..
.. with a glimpse to left heart structure and function may provide
.. essential information needed in critical scenarios for time-
..
.. sensitive clinical decision-making.38,39 However, while TTE is an
.. excellent tool to quickly detect potentially lethal complications of
..
.. AAD, such as aortic regurgitation, pericardial effusion, cardiac
.. tamponade, and wall motion abnormalities, its accuracy for AAD
..
.. remains relatively low (sensitivity of 78–100% for Type A AAD
.. but only 31–55% for Type B AAD). Therefore, a negative TTE
..
. does not rule out AAD.36
Acute aortic syndromes 5

Table 3 Presenting symptoms, signs, chest X-ray, and electrocardiographic features from the International Registry
of Aortic Dissection registry

Category Overall (n 5 5638) Type A AAD (n 5 3747) Type B AAD (n 5 1891) P-value
....................................................................................................................................................................................................................
Symptoms and signs
Chest or back pain 4692 (87.9%) 3113 (87.5%) 1579 (88.7%) 0.191
Severe or worst ever pain 4692 (87.9%) 3113 (87.5%) 1579 (88.7%) 0.191
Abrupt onset of pain 4220 (84.0%) 2789 (83.3%) 1431 (85.4%) 0.052
Migrating pain 664 (14.8%) 400 (13.7%) 264 (16.8%) 0.005
Pain presenting within 6 h of symptom onset 2950 (75.8%) 1700 (77.0%) 790 (73.1%) 0.015
Any focal neurological deficit 695 (13.7%) 575 (17.2%) 120 (7.0%) <0.001
Hypotension, shock, or tamponade 1136 (23.4%) 1054 (32.6%) 82 (5.0%) <0.001
Hypertension at presentation 1943 (40.0%) 893 (27.6%) 1050 (64.6%) <0.001
Any pulse deficit 1170 (32.3%) 811 (35.9%) 359 (26.3%) <0.001
Aortic regurgitation 1440 (38.7%) 1266 (51.8%) 174 (13.6%) <0.001
Abdominal pain 1442 (30.5%) 766 (24.9%) 676 (41.1%) <0.001
Chest radiography
Normal 999 (28.1%) 588 (26.9%) 411 (30.2%) 0.031
Widened mediastinum 1509 (49.5%) 1016 (53.7%) 493 (42.6%) <0.001
Abnormal aortic contour 1289 (43.7%) 760 (41.8%) 529 (46.6%) 0.011
Electrocardiography
Normal 1763 (39.1%) 1147 (38.3%) 616 (40.7%) 0.120
Left ventricular hypertrophy 817 (23.1%) 490 (20.9%) 327 (27.3%) <0.001
Myocardial ischemia or infarction 647 (18.0%) 526 (21.9%) 121 (10.1%) <0.001

AAD, acute aortic dissection.

Table 4 Laboratory tests required for patients with

.. Table 5 Relative strengths of imaging modalities for
.. acute aortic syndromes
acute aortic dissection ..
..
Laboratory tests To detect signs of .. TTE TOE MRI CT
................................................................................................. .. .................................................................................................
..
Red blood cell count Blood loss, bleeding, anaemia .. Imaging factors
White blood cell count Infection, inflammation (SIRS) .. Comprehensive aortic þ þþ þþþ þþþ
..
C-reactive protein Inflammatory response .. assessment
Procalcitonin Differential diagnosis between SIRS
.. Tomographic (3D - - þþþ þþþ
..
and sepsis .. reconstruction)
Creatine kinase Reperfusion injury, rhabdomyolysis
.. Functional data þþþ þþþ þþ þ
..
Troponin I or T Myocardial ischaemia, myocardial infarction .. Tissue characterization - - þþþ þþþ
D-dimer Aortic dissection, pulmonary embolism,
.. Clinical factors
..
thrombosis .. Portability þþþ þþþ - -
Creatinine Renal failure (existing or developing)
.. Patient access/monitoring þþþ þþþ þ þþ
..
AST/ALT Liver ischaemia, liver disease .. Rapidity þþþ þþ þþ þþþ
.. Need for contrast - - þþ þþþ
Lactate Bowel ischaemia, metabolic disorder ..
Glucose Diabetes mellitus .. Need for sedation - þþþ - -
.. Lack of radiation exposure þþþ þþþ þþþ -
Blood gases Metabolic disorder, oxygenation ..
..
ALT, alanine aminotransferase; AST, aspartate transaminase; SIRS, systemic .. 3D, three-dimensional; CT, computed tomography; MRI, magnetic resonance
inflammatory response syndrome. .. imaging; TOE, transoesophageal echocardiography; TTE, transthoracic
Reproduced from Erbel et al.2 ... echocardiography.
.. Modified from Bossone et al.33
..
..
Provided prompt availability and local expertise, TOE remains a .. room without the need of radio contrast agents. On the other hand,
..
valid ultrasound option to accurately evaluate patients with known .. it is less suited than CT and MRI for long-term imaging surveillance, in
or suspected Type A AAD (sensitivity and specificity up to 99% and
.. which a comprehensive assessment of the entire aorta and its branch
..
89%, respectively).40,41 Advantages of TOE over CT and MRI consist .. vessels as well as serial measurements at easily identifiable landmarks
of the possibility to be performed at bedside and/or in the operative
.. are necessary.2,36
6 E. Bossone et al.

A B

Figure 3 Imaging pitfalls in acute aortic dissection. (A) A 62-year-old male who presented with chest pain and a known thoracic aortic aneurysm.
The initial ungated computed tomography of the thoracic aorta has significant motion artefact, which can be confused with a possible dissection flap
(arrows). (B) Repeat computed tomography of the thoracic aorta with electrocardiographic gating, demonstrating the absence of any dissection flap.
(C) A 51-year-old male with a transthoracic echocardiographic examination ordered for a systolic ejection murmur, which showed a linear echoden-
sity (arrows) in the ascending aorta that could represent a dissection flap. (D) Subsequent computed tomography displayed a normal ascending aorta,
suggesting that this echodensity represented an artefact.

.. department for the differential diagnosis of acute chest pain (high

Computed tomography and magnetic ..
resonance imaging ..
..
Tomographic imaging—whether by CT or MRI—enables a complete ..
..
and detailed map of the entire aorta and its branches. Both modalities ..
..
are characterized by high spatial/contrast resolution without limits for
..
imaging window, giving an excellent accuracy to detect AAS and related ..
complications such as pericardial and/or pleural effusion. Compared ..
..
with echocardiography, tomographic imaging modalities do not allow ..
bedside use and this may limit their feasibility in unstable patients.36,42,43 ..
..
Non-enhanced CT followed by contrast-enhanced CT angiogra- ..
..
phy should generally be preferred (16 detector systems or high-end
..
devices) to assess patients with suspected AAS, considering its excel-
lent diagnostic accuracy (pooled sensitivity 100% and pooled specific-
ity 98%), widespread availability, easier patient access and tolerance,
and short-time image acquisition/processing, enabling rapid collection
of key information for clinical decision-making.2,32 Emergency CT
angiography is also considered the first-line technique (followed by
TOE) in case of clinically suspected traumatic thoracic aortic injury
(sensitivity and specificity close to 100%).2 Recently, ECG-gated 64-
detector CT has been more often implemented in the emergency
negative predictive value) among AAS, pulmonary embolism, and
coronary artery disease (‘triple rule out’ strategy).44,45 Computed
tomography also permits assessment of aortic calcification patterns
and can be helpful in follow-up imaging of patients with aortic stents.
The quick pulsatile movement of the aortic wall during the cardiac
cycle may produce fake linear intraluminal structures on CT images
of the ascending aorta, mimicking an intimal flap (pulsation artefacts),
particularly in non-ECG-gated studies (Figure 3). When considering
CT angiography, it should be remembered that the use of iodinated
contrast agents leads to a non-negligible risk for allergic reaction and
renal insufficiency. In the case of serial imaging, over a period of years,
..
.. substantial concern remains over the use of ionizing radiation and the
.. related cancer risk, which is considerably higher in women and in
..
.. young individuals.2,46
.. Magnetic resonance imaging also provides high levels of diagnostic
..
.. accuracy in the evaluation of patients with suspected AAS (pooled
.. sensitivity 98% and pooled specificity 98%).32
..
.. In addition to detailed anatomical information on the aortic vessel
.. wall, MRI can also provide a reliable characterization of aortic
.
Acute aortic syndromes 7

..
insufficiency typically associated with Type A aortic dissection, by ..
including phase-contrast velocity mapping for flow quantification. ..
..
Furthermore, the time-resolved angiographic techniques as well as ..
the most common cine bright blood images may add dynamic infor- ..
..
mation by visualizing flow patterns within the true lumen and the false ..
lumen. Newer approaches with 4D flow MRI have shown promise in ..
..
defining the flow characteristics and associated parameters of aortic ..
dissection but need to be further refined.9,47–49 Owing to the long ..
..
scan time duration (20–30 min for the aortic evaluation protocol), ..
MRI is certainly less suited in emergent or unstable scenarios than ..
..
CT. Additional drawbacks of MRI include potential contraindications ..
such as ferromagnetic and/or magnetically activated implants and ..
..
claustrophobia. Gadolinium-based contrast agents used for contrast- ..
enhanced angiography with MRI are definitely less nephrotoxic than ..
..
iodinated agents, while a severe adverse reaction such as nephro- ..
genic systemic fibrosis is extremely rare and occurs only in patients
..
..
with advanced renal failure. When compared with CT, however, MRI ..
remains an excellent option for surveillance imaging of at-risk and/or
..
..
known aortic diseases, without the burden of ionizing radiation and ..
the need for intravenous administration of iodinated contrast
..
..
agent.2,36 In the post-operative setting, the potential with MRI for ..
..
severe artefacts from structures such as aortic stents and/or prosthe- ..
ses obscuring the visualization of aortic lumen should also be ..
..
considered. ..
..
..
Other techniques
Intravascular ultrasound
Intravascular ultrasound provides real-time imaging of aortic pathol-
ogy and is a reliable and safe tool to guide stent graft positioning.
Along with TOE, it may be useful for identifying the landing zones,
origins of vessels, entry tears, presence of PAU, and/or saccular
aneurysm. The possibility of off-centre measurements and the lack of
Doppler capabilities remain major limitations.2,36,50,51 Intraluminal
phased-array imaging (also known as intra-cardiac echocardiography)
is an alternative approach that may be implemented to identify com-
munications between the true and false lumens and to guide fenestra-
tion procedures.52
Positron emission tomography
18
F-fluorodeoxyglucose (18F-FDG) positron emission tomography
(PET) is playing an increasing role in assessing inflammatory and/or
infectious processes of the aortic wall.2,53–55 Nowadays, dual-
modality PET/CT angiography or magnetic resonance angiography
image acquisition has substantially improved PET limited spatial reso-
lution, providing more precise anatomical localization with better
definition of mural or luminal abnormalities.2
PET signal of enhanced 18F-FDG uptake in the wall of an acute dis-
sected aorta as well as increased levels of serological markers of
inflammation (D-dimer and C-reactive protein) and/or thrombus
renewal/lysis (P-selectin, thrombin–antithrombin III complexes,
plasmin–alpha2–antiplasmin complexes, and D-dimer) may have a
potential risk prediction added value during follow-up.54,56,57
Aortography and coronary angiography
Retrograde aortography (sensitivity up to 90% vs. specificity >95%)
was the historic diagnostic gold standard to assess patients with
suspected AAS. Owing to its invasive nature, time and cost, it is now
rarely performed (except in the case of coronary angiography or
endovascular interventions), having been replaced by non-invasive
imaging techniques.2 Coronary artery involvement may be present in
approximately 20% of Type A AAD patients as a direct consequence
of flow obstruction by the dissection flap occluding the orifice and/or
propagating down the coronary artery with or without pre-existing
atherosclerotic disease. However, routine coronary angiography is
not recommended before surgery. Major concerns include additional
time delay to emergency surgery and technical difficulties along with
an increased risk of aorta injury. In an IRAD review of 1343 Type A
AAD, only 156 patients (11.6%) underwent pre-operative coronary
angiography. As a note, they were more likely to have a history of
atherosclerosis and present with ECG signs of myocardial ischaemia/
infarction. However, when performed pre-operatively, coronary
angiography was not associated with any significant changes in in-
hospital and long-term mortality.58 Thus, the decision to perform
pre-operative coronary angiography should probably be limited to
the occasional highly selected patient (history of coronary artery dis-
ease, prior coronary artery bypass surgery, showing acute ischaemic
ECG changes) in whom a more precise definition of the coronary
anatomy is required by the surgical team.
Integrated diagnostic algorithm
..
.. In the emergency scenario, a rapid comprehensive diagnostic workup
..
.. is mandatory, including clinical assessment (pre-test probability of dis-
.. ease), laboratory data (mainly D-dimer and troponin), chest X-ray,
..
.. and ECG, in order to expedite aortic imaging (TTE þ CT and/or
.. TOE) in the appropriate subset of these patients as defined by the
..
.. ESC guidelines2 (Figure 4). In 2010, the American Heart Association/
.. American College of Cardiology (and other professional societies)
..
.. guidelines for the management of thoracic aortic disease offered a
.. specific diagnostic algorithm, in order to provide each patient’s treat-
..
.. ing physician with an easy and rapid risk assessment tool in case of
.. clinical suspicion of AAD.3 Briefly, the ‘aortic dissection detection’
..
.. (ADD) risk stratifies patients into low- (score = 0), intermediate-
.. (score = 1), and high- (score = 2–3) risk groups essentially based on
..
.. predisposing conditions, presenting pain features, and clinical exami-
..
.. nation findings. When tested in the IRAD registry, the ADD scoring
.. tool yielded a diagnostic sensitivity of 95.7% for AAD. Among 4.3% of
..
.. patients without clinical markers for AAD (ADD score = 0), nearly
.. half (48.6%) who underwent chest X-ray had evidence of widened
..
.. mediastinum.59 However, prospective validation studies are needed
.. to determine the accuracy and, in particular, to assess the specificity
..
.. of the ADD risk score in the real-world emergency department set-
.. ting. Furthermore, it is important to investigate the incremental diag-
..
.. nostic value of D-dimer testing on top of historical, prior conditions,
.. and exam features included in the AAD score.2,60 This may help to
..
.. further stratify patients identified as low–intermediate risk by the
.. ADD risk score, especially in community hospitals or clinics (usually
..
.. not equipped with advanced imaging technology), where the initial
.. diagnostic decision is made, in order to define the appropriate and
..
.. available imaging test (TTE þ CT or TOE), alert the aorta team and,
.. then, transfer the patient to a tertiary centre with availability and
..
. expertise for imaging and management of aortic disease.5
8 E. Bossone et al.

B
A

FL
TL

C D E

Figure 4 Multimodality imaging of acute aortic dissection. A common approach to suspected acute aortic dissection includes the combination of
computed tomography and echocardiography. This patient was a 75-year-old male presenting with acute abdominal pain, who was imaged by a non-
gated computed tomography at another hospital, which identified a Type A AAD, with a flap originating just above the right coronary artery (arrow),
which came off the true lumen (A) and extended to the abdominal aorta [thoracic aorta dissection flap indicated by arrows on the 3D image from
non-gated computed tomography (B)]. A transthoracic echocardiogram was obtained, which also visualized the dissection flap in the aortic root
[arrow, (C)], with a communication between the true and false lumen on color Doppler [arrow, (D)]. There was only mild aortic regurgitation
[arrow, (E)], and left ventricular function and wall motion were normal, suggesting normal flow into the coronary arteries. The patient underwent
emergent surgery for aortic repair, with transoesophageal echocardiography performed during the operation and survived with no significant post-
operative complications.

..
In-hospital management and ..
..
outcome ..
..
..
In all patients presenting with AAS, regardless of definitive therapeu- ..
tic interventions, initial medical therapy should aim to decrease wall ..
..
stress in order to limit extension of the dissection and reduce the risk ..
of developing end-organ damage and rupture.61 It is important to ..
..
obtain adequate control of pain (intravenous opiate analgesia), heart
rate (<60 b.p.m.), and blood pressure (systolic blood pressure
between 100 and 120 mmHg).2 In this regard, patient-tailored intra-
venous beta-blockers (propranolol, metoprolol, labetalol, or esmo-
lol) represent first-line drugs.2 Non-dihydropyridine calcium channel
antagonists (verapamil and diltiazem) are reasonable alternatives in
patients truly intolerant to beta-blockers. In some cases, vasodilators
(intravenous sodium nitroprusside) in addition to beta-blockers may
be needed, in order to rapidly achieve optimal blood pressure levels,
with beta-blockers initiated first to counteract reflex tachycardia and
increased inotropy that may accompany vasodilator therapy.2
Consistent with the ESC guidelines, IRAD has observed over the past
17 years that patients with both Type A and Type B AAD experi-
enced significantly greater use of beta-blockers (most recently 88%
and 91% for Type A and Type B AAD, respectively) and decreased
use of vasodilators (most recently 7% and 24% for Type A and
Type B AAD, respectively).2,5
..
.. Definitive management includes emergency surgery for Type A
.. AAD, and medical therapy alone for uncomplicated Type B AAD.2
..
.. Notably, the net benefit of endovascular (TEVAR) treatment for
.. ‘stable’ Type B AAD remains a matter of debate.8,14,28,62,63 There is a
..
.. need for more and larger randomized trials with long-term follow-up,
.. in order to define optimal indications for TEVAR.8,62,64 Recent data
..
.. from the Investigation of Stent Grafts in Aortic Dissection (INSTEAD-
.. XL) trial demonstrated that TEVAR, in addition to optimal medical
.
Acute aortic syndromes 9

..
treatment, was associated with improved 5-year aorta-specific survival, ..
..
Long-term follow-up
delayed disease progression, and positive remodelling. However, no
.. The 10-year actuarial survival rate among patients with aortic
difference regarding total mortality was observed, and the trial was rel- ..
atively small in size.8 .. dissection who survive initial hospitalization ranges from 30% to
.. 60%.2,9,74–80 AAS should be considered a lifelong problem involving
Currently, TEVAR is recommended by ESC guidelines for compli- ..
cated Type B dissection defined by persistent or recurrent pain, .. the entire aorta and its branches that remain at high risk for redissec-
..
uncontrolled hypertension, despite full medication, early aortic .. tion, aneurysm formation, and rupture even after successful treat-
expansion, malperfusion, and signs of rupture (haemothorax, increas- .. ment of the acute index event.81 Thus, patients with AAS, regardless
..
ing periaortic and mediastinal haematoma).2,65–67 .. of the initial therapeutic strategy (medical, interventional, or surgical),
A small cohort of Type B AAD patients may require surgery .. require lifelong clinical and imaging monitoring, patient education,
..
usually when TEVAR is contraindicated and/or not feasible.2,65–67 .. and, if appropriate, screening of family members for aortic disease.
It should be underlined that open surgery carries high in-hospital .. Given that the risk of aortic complications (especially false lumen
..
mortality (from 25% to 50%) and major complications rates (spi- .. expansion) is substantial in the first few months after the acute event,
nal cord ischaemia, stroke, mesenteric ischaemia infarction, and .. current guidelines recommend CT or MRI surveillance (both enable
..
acute renal failure).2,14,65–67 Interestingly, in a retrospective series .. comprehensive assessment of the aorta and its branch vessels)
of 133 patients with AAS undergoing TEVAR, Gorla et al.68 have
.. before discharge and at 1, 3, 6, and 12 months and annually thereafter,
..
highlighted the occurrence of post-implantation syndrome in .. depending on clinical conditions, aortic size, and related increase in
15.8% of cases, defined as fever >38  C, white blood cell count
.. dimension over time. Although more expensive and less widely avail-
..
>12.0 nL, and C-reactive protein >10 mg/dL within 72 h after .. able, as previously discussed, MRI should be preferred to CT particu-
TEVAR, despite negative blood culture. Although the presence of
.. larly in younger patients at increased cancer risk from ionizing
..
post-implantation syndrome did not appear to affect in-hospital .. radiation.2 It is important to perform surveillance imaging using simi-
.. lar techniques, preferably at the same institution, to aid direct com-
outcome, at a mean follow-up of 4 years, it was associated with an ..
increased rate of major adverse events (aortic rupture and/or .. parison of serial studies along with standardized reports and
.. measurements at given landmarks.2
need for reintervention) but not mortality.68 Further prospective ..
studies are needed to validate the above results and to investigate .. In addition, matrix metalloproteinases and transforming growth
.. factor-b circulating levels may be useful in therapeutic monitoring of
the pathophysiologic background and relative role of corticoste- ..
roids as therapeutic agents.68–70 .. aortic remodeling.25,82,83 However, the exact role of these bio-
.. markers in daily practice is yet to be defined.
Unique in-hospital AAD outcome data are provided by a trend ..
analysis of 4428 AAD patients enrolled in the IRAD registry over a .. Meticulous blood pressure (<120/80 mmHg) and heart rate control
..
17-year period.5 In particular, surgical management was increas- .. (<60 b.p.m.) remain the key target for medical therapy,2 beta-blockers
ingly employed to treat Type A AAD (79% to 90%, P < 0.001).5 As .. being the first-line treatment.84–89 In this regard, long-acting beta-block-
..
a possible consequence, there were significant decreases in over- .. ers should be preferred to short-acting beta-blockers to reduce side
all in-hospital mortality (31% to 22%, P < 0.001), owing in part to a .. effects and increase compliance. Patients with AAS often require the
..
decline in surgical mortality (25% to 18%, P = 0.003) along with the .. combination of at least two drugs to achieve optimal blood pressure
increasing willingness of IRAD centres to operate on older or .. and heart rate control. Additional (not optimal blood pressure and
..
more complex patients with Type A AAD. The in-hospital mortal- .. heart rate control) or alternative (‘true’ beta-blocker intolerance)
ity rate among those Type A AAD patients managed medically
.. agents are angiotensin receptor blockers and angiotensin-converting
..
remained unchanged and prohibitively high over time (up to 57%). .. enzyme inhibitors (second-line treatment).89–92 The administration of
Reported reasons not to perform surgery were advanced age, co-
.. long-acting calcium channel blockers may also be considered in addi-
..
morbidity, patient refusal, and death prior to planned surgery.5 .. tion to adequate beta-blockade to reach optimal blood pressure con-
These findings suggest the need for an earlier and aggressive surgi-
.. trol (third-line treatment).88
..
cal treatment, in order to provide a reasonable chance of survival .. Patients with atherosclerotic thoracic aortic disease, with or with-
to these patients with an otherwise dismal prognosis. In this
.. out dissection, should be considered a coronary risk equivalent and
..
regard, the possibility of surgical/hybrid treatment (fenestration/ .. treated with statins as appropriate. In addition to lowering choles-
.. terol level, statins may reduce thoracic aortic aneurysm growth rate
stenting) in highly selected cases with dynamic/static obstructive ..
malperfusion syndrome should be carefully considered based on .. and the proportion of thoracic aortic aneurysms progressing to dis-
.. section, rupture or death.93,94
an individual patient’s comprehensive evaluation.2,71 ..
In the case of Type B AAD, the majority of patients enrolled in the .. Finally, patient education about this condition and smoking
.. cessation and risk factor modification for atherosclerotic disease
IRAD registry over a 17-year period were treated medically (63%), ..
but a steady increase in endovascular treatment was observed over 3 .. need to be reinforced in all patients (Table 6).2,95–99
..
tertiles of time (7–31%, P < 0.001). However, no significant decrease ..
in overall in-hospital mortality was documented (12–14%) (see ..
..
Supplementary material online, Figures S3).5 .. Aortic dissection variants
Finally, it should be underlined that in all patients with AAS, close ..
..
clinical, laboratory testing, and imaging surveillance (preferably with .. In addition to AAD, IMH and PAU constitute variants of the aortic
CT or MRI) are essential during hospitalization in order to detect .. syndrome spectrum sharing similar clinical characteristics but also
..
early signs of disease progression and/or malperfusion.2,72,73 . demonstrating distinct diagnostic–prognostic features and specific
10
..
Table 6 Long-term follow-up
.. consists of a circular or crescentic thickening of >5 mm of the aortic
.. wall, without evidence of blood flow on imaging examination; CT and
..
Ten-year survival rate from 30% to 60%
Late complications
Progressive aortic insufficiency
Progressive diameter increase, aneurysm formation, and rupture
Recurrent dissection or progression of dissection
Leakages/haemorrhage at surgical anastomoses/stent-grafted sites
Malperfusion
Patients at particularly high risk
Those with Marfan syndrome—very high risk of recurrent
dissection or aneurysm formation with rupture
Those with a patent false lumen—increased incidence of late
complications and death
Medical treatment
A. Optimal blood pressure (<120/80 mmHg) and heart rate
(<60 b.p.m.) control
First line: beta-blockers
Second line: ACE-inhibitors or ARBs
Third line: calcium channel blockers (long-acting
dihydropyridine)
B. Lipid-lowering therapy: target of LDL-cholesterol <70 mg/dL
Imaging surveillance
CT or MRI of chest and abdomen þ TTE before discharge and at
1, 3, 6, and 12 months and annually thereafter.a
Patient education and lifestyle goals
Adherence to medical treatment
Genetic counselling.
Smoking cessation and risk factor modification for atherosclerotic
disease
Avoid cocaine or other stimulating drugs such as
methamphetamine, strenuous physical activities (isometric
exercise, pushing, or straining that would require a Valsalva
manoeuvre), and contact sports (e.g. competitive football, ice
hockey, or soccer, etc.).
Mild aerobic exercise and daily activities are not restricted.
ACE, angiotensin-converting enzyme; ARBs, angiotensin II receptor blockers; CT,
computed tomography; LDL, low-density lipoprotein; MRI, magnetic resonance
imaging; TTE, transthoracic echocardiography.
a
Similar surveillance strategy for intramural haematoma and penetrating aortic
ulcer is recommended.2
Modified from Booher et al.96
management strategies. From a pathologic standpoint, aortic dissec-
tion and IMH may be considered diseases that affect primarily the
media, whereas PAU the intima.100 It should be highlighted that the
late fate of PAU and IMH is highly variable and may be lethal in a sub-
stantial number of patients (aortic dissection/aneurysm and/or rup-
ture), underscoring the importance of appropriate longitudinal
clinical and imaging follow-up similar to that for patients with classic
aortic dissection.2,3
Intramural haematoma
Aortic IMH (5–25% of AAS) is a clinical entity characterized by hae-
morrhage within the aortic wall in the absence of an intimal flap or
false lumen and a primary intimal tear.2,101 The diagnostic hallmark
E. Bossone et al.
.. MRI are the techniques of choice. In particular, the combination of an
.. unenhanced acquisition. followed by a contrast-enhanced CT acquisi-
..
.. tion yields a sensitivity of up to 96% for the detection of IMH.2 IMH is
.. more frequently observed in the descending thoracic aorta (Type B
..
.. IMH, 60–70%) and less commonly in the ascending aorta and aortic
.. arch (Type A IMH; 30% and 10%, respectively). Compared with clas-
..
.. sic aortic dissection, patients with IMH have quite similar symptoms
.. and risk factors, with acute chest pain/back pain predominating.
..
.. However, they tend to be older and less frequently show aortic valve
.. insufficiency, pulse deficits, acute myocardial infarction, and aneurys-
..
.. mal dilation of the aorta.102,103
.. Intramural haematoma is characterized by a dynamic evolution
..
.. and may lead to classic aortic dissection (28% to 47%) and/or aortic
.. rupture (20% to 45%). Regression is seen in just 10% of patients.
..
.. Involvement of the ascending aorta (Type A IMH) carries a high in-
.. hospital mortality (up to 40%), directly related to its proximity to the
..
.. aortic valve. Thus, urgent or emergent surgery is generally indicated.2
.. A ‘wait-and-watch’ strategy (optimal blood pressure and pain control
..
.. with serial imaging) may be an option to be considered on an individual
..
.. patient basis, particularly in the case of substantial surgery risk
.. (advanced age and severe co-morbidities), smaller aortic dimensions
..
.. (<50 mm), and decreased IMH thickness (<11 mm).2,101,104
.. Interestingly, according to several investigators, type A IMH may be sig-
..
.. nificantly more common in Japan and Korea than in Western regions
.. of the world, with higher rates of early medical treatment and lower
..
.. overall mortality.105,106 On the other hand, Type B IMH is less likely to
.. be associated with an adverse outcome, with an in-hospital mortality
..
.. risk of <10%. In uncomplicated Type B IMH, initial medical therapy
.. along with careful imaging surveillance (MRI or CT) is recommended.2
..
.. In complicated Type B IMH, endovascular treatment should be pre-
.. ferred over surgery if favourable anatomy and appropriate vascular
..
.. access are present.2 Signs of a complicated course consist of persistent
.. chest pain despite medical treatment, haemodynamic instability, signs
..
.. of aortic rupture (periaortic haemorrhage), presence of a large ulcer-
.. like projection (depth >10 mm), maximum aortic diameter (>55 mm),
..
.. and/or rapid aortic diameter growth during hospital stay.2,72,73,101
..
..
.. Penetrating aortic ulcer
..
.. Penetrating aortic ulcer is defined as an ulceration of an aortic athero-
.. sclerotic plaque penetrating the internal elastic lamina into the media,
..
.. often associated with a variable degree of IMH formation.1,2,101
.. Aortic ulcers are often multiple and may vary greatly in size (ranging
..
.. from 5 mm in diameter and 4–30 mm in depth). They can occur at
.. any point throughout the aorta, most commonly in the middle and
..
.. lower descending aorta, less frequently in the aortic arch and
.. abdominal aorta, and rarely in the ascending aorta. Although the true
..
.. prevalence of PAU is unknown, it may account for 2–7% of all AAS.
.. Typically, patients with PAU are older (>70 years) than those with
..
.. aortic dissection and present more often with extensive and diffuse
.. atherosclerotic disease involving both the aorta and coronary
..
.. arteries. Additional common comorbidities include hypertension,
.. tobacco use, chronic obstructive pulmonary disease, and renal insuffi-
..
.. ciency. The clinical presentation overlaps with classical AAD.
.. However, owing to the localized nature of the lesion, most patients
..
. do not have aortic regurgitation, pulse deficits, or visceral ischaemia.
Acute aortic syndromes 11

..
An asymptomatic lesion may also be identified as an incidental finding .. It remains, thus, essential to design and implement regionalized sys-
during axial imaging screening performed for other indications. In .. tems of care for cardiovascular emergencies along with multidiscipli-
..
addition, incidental aortic findings are not uncommon on cardiovas- .. nary aortic centres equipped with advanced imaging techniques that
cular imaging, and future research may be helpful to determine which .. include structural and functional assessment of the entire aorta in a
..
findings should prompt further testing and/or management changes. .. comprehensive concept of personalized treatment for every
Among imaging modalities, contrast-enhanced CT, including axial .. patient.118,119 In this regard, more evidence is needed on the
..
and multiplanar reformations, is considered the diagnostic technique of .. volume–outcome relationship in the field of aortic diseases.
choice.2 The natural course of PAU continues to be debated and may .. In the near future, we may see an increasing number of uncompli-
..
include the formation of medial haematoma, classical dissection, and/or .. cated Type B dissection patients receiving pre-emptive TEVAR
adventitial false aneurysm, and transmural rupture. In this regard, com- .. instead of medical therapy alone to prevent late complica-
..
pared with aortic dissection, the risk of rupture (7% for Type A and 4% .. tions.9,64,120–123 This strategy, while intuitive, requires further study in
for Type B AAD) is considerably higher (up to 40% for PAU).107 Thus, .. randomized cohorts.
..
the management strategy should be tailored to each individual patient, .. Finally, stent grafting as therapeutic option for Type A AAD
taking into account clinical presentation and coexistence of co-morbid- .. patients with prohibitive surgical risk constitutes ‘the last frontier’ of
..
ities. At present, the general consensus is to consider surgery for Type .. the emerging device technology challenging the complex anatomo-
A PAU and medical therapy with careful clinical follow-up and imaging
.. physiopathology of the dissected ascending aorta segment.124–126
..
surveillance for Type B PAU.2 In complicated Type B PAU (signs of ..
aortic rupture), endovascular stent grafting (TEVAR/EVAR) is usually
..
..
preferred to surgical repair considering the lesions’ segmental nature .. Supplementary material
(anatomical landmarks) and the patients’ increased risk profile.2,108,109
..
..
However, randomized controlled trials comparing TEVAR with open .. Supplementary material is available at European Heart Journal online.
..
surgery and medical therapy will be needed to further delineate the ..
optimal management of these patients. .. Funding
..
.. W.L. Gore & Associates, Inc., Medtronic, the Varbedian Aortic Research
.. Fund, the Hewlett Foundation, the Mardigian Foundation, UM Faculty
..
Future perspectives .. Group Practice, Terumo, and Ann and Bob Aikens.
..
.. Conflict of interest: none declared.
Despite remarkable diagnostic and therapeutic progress over the ..
past several decades, mortality and morbidity of AAS remain high.2,5 ..
..
Reduction in disease burden will require allocation of resources to .. References
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