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Chapter 14
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Pathophysiology, Classication
andPrinciples ofManagement ofAcute
Aortic Syndromes
MarkHamilton
Key Learning Points
Be able to describe the underlying anatomical and pathological processes that
•
occur in AAS and the risk factors for development of AAS.
• Be able to clearly describe the various classication systems for AAS, and dem-
onstrate an understanding of the utility of the various systems.
•
Describe the diagnostic modalities available for AAS, and their relative strengths
and weaknesses
• Demonstrate an understanding of the medical management of AAS
14.1 Introduction
Acute aortic syndrome describes a number of discrete but related pathological processes in the thoracic aorta [2]. These include thoracic aortic dissection [3], penetrating aortic ulcer [4] and intra-mural haematoma (IMH) as the main interlinked
variants of thoracic aortic pathology. AAS is a relatively uncommon condition overall, with incidence ranging from 2.6 to 3.5/100,000 perannum [5]. The diagnosis
carries a signicant morbidity and mortality risk, both in the acute and chronic
phases of disease.
This chapter will outline the pathophysiology of AAS, describe the current classication systems for AAS, the role of imaging in diagnosis, and some of the current
controversies in management of AAS (see Chap. 13 for further information on the
genetics of AAS).
M. Hamilton (*)
Vascular Surgery, Royal Darwin Hospital, Darwin, NT, Australia
e-mail: mark.hamilton@nt.gov.au
R. Fitridge (ed.), Mechanisms of Vascular Disease,
https://doi.org/10.1007/978-3-030-43683-4_14
317© Springer Nature Switzerland AG 2020
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M. Hamilton
14.2 Anatomical andMolecular Considerations
intheThoracic Aorta
There are differences at both ultrastructural and molecular levels between the thoracic and abdominal aorta. Embryologically the thoracic aorta is more complex in
its development than the abdominal aorta, and vascular smooth muscle cells
(VSMCs) in the thoracic aorta are predominantly derived from neuroectoderm,
compared to mesoderm in the abdominal aorta [6]. This is important because of the
pivotal role that VSMCs play in aortic wall strength and extracellular matrix metabolism, particularly the interaction of VSMCs, elastin and collagen molecules. There
is also evidence that VSMCs undergo some degree of de-differentiation and phenotype switching in aortas that develop AAS. Our understanding of the molecular
inuences of these changes is evolving, with numerous cytokines being implicated
in the development of aortic dissection. These include platelet derived growth factor
[7], MMP2 [8], the complement cascade—particularly C3-C3a [9] and
osteopontin [10].
There are also differential proportions of elastin and collagen in the two segments. In the normal course of events, elastin is a robust bre and once produced has
a half-life of 74years [5]. Thus further production of elastin is minimal after completion of maturation/growth. Degradation of elastin in the thoracic aorta and
increased levels of collagen deposition, under the inuence of VSMCs, is one of the
hallmark pathologic processes in AAS.
The differing embryologic origin of VSMC has implications for the way in
which signaling pathways inuence the activity of VSMC and their response to a
number of mediators such as Transforming Growth Factor Beta 1 (TGFβ1), an
important modulator of the extracellular matrix (ECM) in the thoracic aorta.
Neuroectodermal VSMC growth is potentiated by TGFβ1, as is Collagen I production, leading to increasing arterial stiffness. Phenotypically, thoracic VSMCs enter
a secretory phenotype under the inuence of TGFβ, which also occurs with osteopontin [
mesodermal VSMC’s where TGFβ1 inhibits growth and has no inuence on collagen deposition. Because VSMC’s are inuential in aortic strength, varying the concentration of VSMC’s and subsequent differential alterations in ECM composition
inuence the sites of dissection or aneurysm development.
the aorta, combining elastin lamellae and VSMC’s) throughout the aorta, with
higher levels of elastic lamella and VSMC’s in the thoracic aorta than in the abdominal segment. Similarly, there is a decrease in the elastin:collagen ratio in the abdominal aorta compared to the thoracic aorta [6]. There is also an inuence of
haemodynamic cyclical strain on the secretion of mediators such as TGFβ1 and
hence arterial wall architecture. This may relate to the inuence of high blood
pressure, wall tension and shear stress on the secretion of cytokines.
10] and platelet-derived growth factor (PDGF) [5]. This is in comparison to
There is a variable pattern of elastic lamellar units (the functional elastic unit in
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14.3 Haemodynamics ofThoracic Compared
toAbdominal Aorta
Dissection aps occur in the regions of the aorta subject to the greatest uctuations
in pressure over time. Due to the torsional manner in which the heart contracts and
the physical effects of cardiac motion on the arch of the aorta, the areas subject to
the greatest changes in pressure are the ascending aorta and the proximal descending aorta, particularly in association with increased angulation as is seen in the Type
III aortic arch [11] or increased tortuosity. This was demonstrated in a model created by Qiao etal. based on a thoracic aortic aneurysm patient [12]. This model
demonstrated differential shear and ow at varying points in the thoracic aorta,
particularly the outer curves of the ascending and proximal descending aorta. There
has been further work in computational biomechanics and uid dynamics in aortic
dissection with the aim of predicting which individual patients will develop further
dissection in the future [13].
The alterations in elastic recoil ability, collagen concentrations and function in
the aorta that are present in a number of genetic or inammatory aortic pathologies, combined with the magnitude of the force involved in blood ow (related to
absolute blood pressure, pulse pressure and dP/dT) results in the most likely sites
of dissection being where the physical forces on the aorta are greatest and the
diminution in aortic strength is maximal. VSMC apoptosis (see Glossary), which
is inuenced by TGFβ1 is greatest at the convexities of the ascending and descending aorta, particularly in patients with bicuspid aortic valves. This may alter aortic
strength and stiffness at these sites, predisposing to dissection or aneurysm at
these sites. It is likely that a combination of underlying connective tissue or
genetic abnormalities, plus particular anatomical conformations of the aortic arch
(e.g. the Type III arch conguration) [14] predispose to increased rates of
AAS [11].
Arterial tortuosity is strongly associated with a number of aortopathies and congenital connective tissue disorders and is becoming more recognized as a risk factor
for AAS.Arterial tortuosity is felt to be a marker for increased risk of developing
aortic complications in both syndromic and non-syndromic aortic diseases [
Loeys-Deitz syndrome (LDS), Marfan Syndrome (MFS) (although less commonly
reported than LDS), Cutis Laxa related to abnormality of the Fibrillin-4 gene
(FBLN4/EFEMP2), arterial tortuosity syndrome, and a number of rarer syndromes
all have increased rates of AAS and tortuosity [15]. A study by Shirali etal. [16]
demonstrated some increased AAS risk from tortuosity, increased aortic length and
volume in non-syndromal aortas. The increase in risk is less than in syndromal aortic tortuousity, where there was a strong correlation between increased aortic tortuosity index and type B dissection (although not with aortic root dilatation) [17]. In
Marfan syndrome and LDS, there are efforts to classify tortuosity for risk stratication purposes.
15].
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M. Hamilton
14.4 Risk Factors fortheDevelopment ofAAS
Well-recognised risk factors for non-traumatic AAS include:
1. Poorly controlled hypertension—present in >70% of cases of AAS.Surges in
blood pressure such as are seen in strenuous Valsalva, or cocaine use (~1.5% of
AAS) [18], are also correlated. Similarly, amphetamine use may also be impli-
cated. There are also reports of marijuana-associated AAS, possibly from hyper-
tension [19].
2. Genetic syndromes associated with connective tissue abnormality such as MFS,
LDS, Turner Syndrome, and Ehlers-Danlos Syndrome (EDS). The incidence of
genetic syndromes is approximately 5% of total cases, predominantly occurring
in the younger cohort.
3. Pre-existing aortic aneurysms and atherosclerosis of the aorta with approxi-
mately 30% of patients with AAS demonstrating atherosclerosis in the aorta.
4. Vasculitides or inammatory aortopathies such as giant cell arteritis or Takayasu
arteritis.
5. Family history—the presence of non-syndromal genetic predisposition such as
Familial Thoracic Aortic Aneurysm Dissection (FTAAD)—a set of genetic poly-
morphisms associated with increased risk of aneurysm and dissection [20] (see
Chap. 13).
6. Pregnancy and childbirth in patients with underlying genetic predisposition. A
Dutch study reported a cardiovascular-related maternal mortality during preg-
nancy or post-partum of 3/100,000 and nearly half were related to aortic dissec-
tion [21]. Maternal mortality is as high as 30% in AAS in pregnancy, with an
associated 50% foetal mortality rate. Management of pregnancy in aortic syn-
dromal patients is complex and an algorithm has been outlined by Wanga
etal. [22].
7. Instrumentation or catheterization of the aorta.
14.5 Epidemiology
Based on large cohorts of data available through registries such as IRAD [23],
epidemiological data around AAS demonstrates a male predilection (66%), a generally older population with a mean age of all patients of 63years (women were
on average 4years older than males) and a peak in the range of 40–70years. The
most common underlying comorbidity is hypertension at 72%, with atherosclerosis the second most common association (40%). MFS is present in 5% of patients,
predominantly in the younger age cohort (<40years), along with other connective
tissue disorders such as LDS, EDS and Turner Syndrome. Although aortic dilatation (>5.5cm root) has been felt to be a predictor of dissection, the vast majority
of dissections occur in patients with aortic diameters smaller than this [24].
Current AHA/ACS guidelines suggest repair of the ascending aorta at diameters
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>5.5 cm. Diabetes on the other hand appears to be negatively associated with
AAS, presumably in similar ways to its negative correlation with infrarenal aortic
aneurysm [25].
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14.6 Pathophysiology ofAcute Aortic Syndrome
The modern understanding of AAS is based on signicant advances in imaging and
genetic and molecular biology that have occurred in the last two decades. While our
understanding of the underlying pathology of AAS has altered, the pathognomic
lesion remains the same. There is haemorrhagic incursion into the media from either
a linear, partly circumferential intimal tear, intramural de-novo haemorrhage in the
setting of an intramural haematoma (IMH), or a focal ulcerated lesion leading to
haemorrhage through the intima (and occasionally the medial and adventitia) in
penetrating aortic ulcer [4]. There is a continuum between these pathological processes, and there may be underlying molecular and genetic factors in common.
Certainly, PAU and IMH often occur together.
In the setting of true thoracic aortic dissection [3], a dynamic pulsatile ow of
blood into an anatomical cleavage plane leads to an extending false lumen which
can be either blind or communicating with the true lumen via fenestrations. This
lumen may in turn be patent, partially thrombosed or completely thrombosed. The
pressure differential between lumens (and therefore ow volume through each
lumen) will vary depending on a combination of these factors.
14.7 Classication Systems forAAS
Acute aortic syndromes can be classied in a number of ways, including chronicity,
anatomy and on the basis of the underlying pathology and complications.
14.7.1 Temporal Classication (Acute/Chronic)
In the traditional reporting literature, acute dissections are those present for less
than 14days and chronic are those present for longer. In 2013 it was suggested
by the IRAD investigators that a more useful temporal classication was to separate the disease process into four groups—hyperacute (0–24h), acute (2–7days),
subacute (8–30 days) and chronic (>30 days). This was on the basis of an
observed difference in mortality between these phases, presumably due to alterations in the plasticity of the aorta and the dissection septum during the subacute
phase [26]. The implication is that this more nuanced approach to assessing chronicity may guide therapy more appropriately in various stages of the disease
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process. The analysis demonstrated an ongoing decline in survival after the
beginning of the traditional chronic stage, suggesting that vigilance in the subacute phase is necessary to improve long term survival [23]. There has also been
some evidence suggesting that there are improved early outcomes with endovascular management when the dissection ap is still relatively acute and mobile,
with enhanced remodelling [27].
M. Hamilton
14.7.2 Complicated Versus Uncomplicated Dissection
In the modern era of medical, surgical and endovascular management of AAS, it is
necessary to risk stratify patients on the basis of the presence or absence of complications in the early phases of AAS, given the emerging evidence from multiple trials
reporting that early management of complicated, or high risk, uncomplicated
dissections may be benecial in the long term.
Complications of AAS include rupture, periaortic haematoma, haemorrhagic
pleural effusion, end-organ malperfusion, refractory pain, malignant hypertension
despite medical therapy, or shock. Approximately 30% of patients with AAS will
present with complications [28]. The presence of these clinical complications is
correlated with a mortality of 17% compared to 4% for uncomplicated acute dissection. Mortality in one series was strongly correlated to the presence of a pleural
haematoma. As many as 24% of patients with Type B dissection will develop a
complication requiring crossover to surgical treatment within the rst 14days of
presentation—the so-called sub-acute phase [29]. It is pragmatic to stratify patients
based on presence of complications, and also on perceived high-risk clinical presentation, appearances and behavior of the dissection. Some of the predictors of
aneurysmal degeneration included age <60 years, Caucasian race, Marfan syndrome, and high levels of brin degradation products (FDPs) (>20mg/mL) on
admission.
14.7.3 Penn Classication
In 2012, Augoustides etal. proposed the Penn classication system for type B
dissections on the basis of the presence or absence of complications (branch vessel
malperfusion and/or rupture). Uncomplicated dissections were further divided into
low or high risk on the basis of adequacy of hypertension control, aortic diameter
>40mm, false lumen size and patency, intimal tear location and the presence of
what was termed ulcer-like projections (presumable penetrating aortic ulceration).
These features were felt to increase risk of development of aortic complications [30].
Stanf
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14.7.4 DeBakey Anatomical Classication
The DeBakey classication system separates classical TAD into three types, with
two subtypes of Type 3 (Fig.14.1 and Table14.1). Initially described by De Bakey
and colleagues in 1965 [31], this classication is based on both the anatomy of the
entry tear and the extent of the dissection. It is an anatomical classication and has
been simplied on the basis of outcome measures and prognosis into the Stanford
Classication.
De Bakey
ord
Fig. 14.1 Diagrammatic representation of aortic dissection class 1, divided into De Bakey and
Stanford classications. Based on Figure4 from Erbel etal. 2014 [5]
Table 14.1 Relationship between Stanford and DeBakey classication of class I dissection
Stanford type
A Type I and II Ascending aorta +/− Arch
B Type III Descending thoracic aorta distal to left subclavian artery
Subtype a Conned to aorta above diaphragm
Subtype b Extends through diaphragm into visceral or abdominal
I
A
DeBakey
equivalent Site of involvement
aorta
II
A
III
B
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M. Hamilton
14.7.5 Stanford Classication
The Stanford classication arose from the recognition that prognosis was largely
dependent on the involvement of the ascending aorta and was published by Daily
and colleagues in 1970 [32]. The De Bakey Classication was thus simplied into
two subclasses, Type A and B depending on involvement of the ascending aorta and
arch (Table 14.1 and Fig. 14.1). Although the Stanford classication has allowed
stratication into immediate surgical treatment or potentially conservative management groups, it fails to take into account the variations of thoracic aortic pathology
that comprise AAS.In 1999 the European Task Force on aortic dissection undertook
to address this with an extensive literature review, and formulation of a more complex but inclusive classication [33]. Approximately 60% of AAS are classied as
Stanford Type A, independent of whether they are true TAD, or IMH/PAU.There
are variations between the different pathologic processes (e.g. IMH is predominantly Type B, classical dissection is more commonly Type A).
14.7.6 European Society ofCardiology Task Force
onDiagnosis andTreatment ofAortic Diseases
In 1999, Svensson etal. [34] published a new classication of thoracic aortic pathology that included not only classical TAD but also a number of recognised subtype
pathologies. This classication had become possible due to advances in imaging
technology which allowed visualization of intramural lesions of the aorta that were
not previously possible. These lesions make up part of the continuum of aortic dissection, and may progress from one presentation to formal classical TAD.This system should be considered an adjunct to the Stanford classication. The 2001 ESC
guidelines for treatment of aortic pathology were updated in 2014 to include other
non-thoracic pathology such as infrarenal aortic aneurysm [5]. These guidelines are
comprehensive and wide ranging. This classication is outlined below (Table14.2
and Fig.14.2).
14.7.7 “DISSECT” Classication
A single mnemonic based system has been introduced by Dake etal. [35] in 2013,
intended to guide therapy in the context of emerging evidence for endovascular
management of AAS.Although more complex than previous systems, it provides a
complete framework for consideration of aspects of dissection. It includes;
1. Duration of dissection
2. Intimal tear position
3. Size of aorta
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Table 14.2 Summary of aortic dissection classication systems
Stanford classication
Type A Dissection of the ascending with or without involvement of the descending aorta
Type B Dissection of the descending aorta
DeBakey classication
Type 1 Dissection of the entire aorta
Type 2 Dissection of the ascending aorta
Type 3 Dissection of the descending aorta
New classication
Class 1 Classical aortic dissection with an intimal ap between true and false lumen
Class 2 Medial disruption with formation of intramural haematoma/haemorrhage
Class 3 Discrete/subtle dissection without haematoma, eccentric bulge at tear site
Class 4 Plaque rupture leading to aortic ulceration, penetrating aortic atherosclerotic ulcer [4]
with surrounding haematoma, usually subadventitial
Class 5 Iatrogenic and traumatic dissection
Classes 1–5 represent a subdivision of the Stanford or DeBakey classication
4. Segmental Extent of the dissection
5. Clinical complications of the dissection
6. Thrombosis of the false lumen
By codifying these characteristics, the mnemonic attempts to ensure consider-
ation of all aspects of possible therapy.
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14.7.7.1 Anatomical Descriptors oftheThoracic Aorta
The Society for Vascular Surgery reporting standards for TEVAR have outlined a
segmental approach to describing aortic anatomy in the context of the site and extent
of disease, as well as landing zones for endograft repair in the thoracic aorta
(Fig. 14.3) [36]. These are useful in conjunction with the traditional anatomical
descriptors of the aorta. Similarly, the STORAGE guidelines [4] have proposed
standardised reporting and nomenclature for thoracic aortic interventions.
14.8 Individual Types ofPathology
14.8.1 Classical TAAD (Class 1 Dissection)
The pathognomonic lesion in aortic dissection is a tear in the intima and media,
which allows pulsatile surging of blood into the intimo-medial plane of the aorta.
Typically, the entry site is transverse but not involving the whole circumference of
the aorta. The dissection plane usually extends down the left posterolateral plane of
the aorta, in a spiral fashion [37]. These dissections may have communication
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M. Hamilton
Class 1 Class 2
Class 5Class 4Class 3
Fig. 14.2 Classes of aortic dissection. Class 1—Classical Aortic Dissection (intimal ap between
true and false lumen); Class 2—Intramural haematoma (Medial disruption with formation of
IMH); Class 3—Discrete/subtle dissection without haematoma and eccentric bulge at tear site;
Class 4—Penetrating aortic ulcer (plaque rupture leading to aortic ulceration or a classical penetrating aortic ulcer with surrounding haematoma (usually sub-adventitial); Class 5—iatrogenic and
traumatic dissection. Based on Figure5 from Erbel at al 2014 [5] and Svensson etal. 1999 [34]
between the false and true lumen, with intimal ap tears being present in >70% of
cases at autopsies [33]. The presence of fenestrations in sudden death patients, however, was seen in only 33%. This suggests an increased rate of false lumen pressurization and rupture in patients without fenestrations. Flow in the false lumen is
usually antegrade but occurs retrograde in a small proportion of cases, which may
lead to involvement of the ascending aorta or arch from an initial Stanford Type B
dissection. Differences in the elasticity of the dissection ap and the aortic adventitia, and the increase in pressure in the false lumen (particularly in the blind ending
or unfenestrated false lumen) predispose to collapse of the true lumen, with a higher
frequency of true lumen compression in non-fenestrated aortic dissection.
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