Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3711_Библиотеки_им_академика_М_И_Перельмана
.pdf
31 Acute Aortic Thrombosis
https://t.me/med1917
425
11. Gologorsky E, Andrews DM, Gologorsky A, Sampathi V,
Sundararaman L, Govindaswamy R, Ravch Y, Izakis AG, Pretto
EA Jr. Devastating intracardiac and aortic thrombosis: a case report
of apparent catastrophic antiphospholipid syndrome during liver
transplantation. J Clin Anesth. 2011;23:398–402.
12. Akil MA, Kaya H, Ertas F, Bilik MZ.Mineeld in the aorta: a rare
case of thrombus. Turk Kardiyol Din Ars. 2013;41(3):266.
13. Kaschwich M, Behrendt CA, Tsilimparis N, Kölbel T, Wipper SH,
Debus ES.Management of acute aortic thrombosis. J Cardiovasc
Surg. 2017;58(2):313–20.
14. Ha SJ, Oh JH, Kim SJ.Unexpected development of acute abdominal aortic thrombosis during percutaneous coronary intervention.
Korean J Intern Med. 2014;29(5):664–6.
15. Verma H, Meda N, Vora S, George RK, Tripathi RK.Contemporary
management of symptomatic primary aortic mural thrombus. J Vasc
Surg. 2014;60(6):1524–34.
16. Metsemakers WJ, Duchateau J, Vanhoenacker F, Tulemans
Y, DeLursnyder J. Floating aortic thrombus: the endovascular
approach. Acta Chir Belg. 2013;113(1):47–50.
Management ofAortic Atherothrombi
https://t.me/med1917
RuojiaDebbieLi, LuisFelipeGomez, SashiK.Inkollu,
MarkG.Rabbat, andCarlosF.Bechara
32
Atherosclerotic Lesions: Types ofPlaque
The formation of plaque starts with the development of atherosclerosis, a slow process that takes years to reach a critical point but can become catastrophic within minutes [1].
Some plaque will remain stable, but others will be prone to
rupture and cause complications [2]. The plaques that tend to
rupture more are characterized by having a large lipid core
and a thin brous cap. Originally thought differently, atherosclerosis is now considered a dynamic process and plaques
can progress or regress, and this is believed to be inuenced
by modication of risk factors.
Plaques that develop in the aortic arch are among the
main causes of stroke and peripheral emboli. Pujadas
Capmany et al. found that there is a high risk of embolic
events when complex aortic arch plaques are present; this
was dened as a plaque thicker than 4mm or with mobile
components. They found that the risk is elevated in ulcerated
plaques or hypoechoic plaques which likely represent the
presence of high lipid content [3].
The American Heart Association provided a denition
of the advanced types of atherosclerotic lesions and a histological classication of atherosclerosis [4] (Table 32.1).
The main growth mechanism of lesion types I–IV is due to
R. D. Li
Rush Medical College, Chicago, IL, USA
L. F. Gomez
Vascular Surgery Department, Houston Methodist Hospital,
DeBakey Heart and Vascular Center, Houston, TX, USA
S. K. Inkollu
Vascular Surgery, West Virginia University School of Medicine,
Morgantown, WV, USA
M. G. Rabbat
Medicine and Radiology, Division of Cardiology,
Loyola University Chicago, Maywood, IL, USA
C. F. Bechara
Aortic Center, Vascular Surgery, Loyola University Medical
Center, Maywood, IL, USA
(*)
Table 32.1 Lesion histology and classication [4]
Histology and
classication Characteristics
Type I– Initial Isolated macrophage foam cells
Type II– Fatty
streak
Type
III– Intermediate
Type
IV– Atheroma
Type
V– Fibroatheroma
Type
VI– Complicated
Mainly intracellular lipid accumulation
Type II changes + small extracellular lipid
pools
Type II changes + core of extracellular lipid
Lipid core and brotic layer, or multiple lipid
cores and brotic layers, or mainly calcic, or
mainly brotic
Surface defect, hematoma-hemorrhage,
thrombus
lipid accumulation, type V due to accelerated smooth muscle and collagen increase, and type VI due to thrombosis
and hematoma.
Cardiovascular disease associated with atherosclerotic
changes is still the leading cause of death in the world, with
the exception of the sub-Saharan African region. Because of
the advancement in understanding atherosclerotic disease,
there has been a growth in disease prevalence, which places
a nancial burden to the health system. Describing specic
costs goes beyond the scope of this chapter.
Despite the different manifestations of atherosclerotic disease and the systems affected, such as aortoiliac disease,
aneurysms, symptomatic carotid disease, or coronary artery
disease, the lesions associated with it have a lot in common. It
starts with the accumulation of cholesterol in the arterial wall
with different degrees and characteristics of plaque that ultimately lead to the ischemic manifestations of the disease.
Medical advances in diagnosis and imaging have helped
us obtain a better understanding of the progression of the disease, which in turn has helped develop new treatment and
management strategies. Regardless of the treatment, either
open or endovascular, medical management is added to
ensure long-term results. Newer imaging techniques can
detect unstable plaques that are more likely to result in rupture, thrombosis, and distal embolization. New risk factors
© Springer Nature Switzerland AG 2019
R. S. Dieter et al. (eds.), Diseases of the Aorta, https://doi.org/10.1007/978-3-030-11322-3_32
427
428
R. D. Li et al.
https://t.me/med1917
for late progression have been identied separate from the
traditional risk factors. These are elevated blood levels of biomarkers like inammatory cytokines, metalloproteinases,
insulin, glucose, and other smooth muscle growth factors.
In a retrospective study by DeBakey etal. on the patterns
of atherosclerosis in which they describe a review of 13,827
patients who were admitted one or more times at the
Methodist Hospital in a medical center in Houston, Texas,
between 1948 and 1983, they described ve categories of
distribution of disease: (I) coronary arteries, (II) major
branches of the aortic arch, (III) visceral arterial branches of
the aorta, (IV) terminal abdominal aorta and its major
branches, and (V) a combination of two or more of these
categories at the same time. In this review, they described the
progression of the disease as well as re-occurrence and
development of disease in new sites other than the ones for
which the patient had been originally treated [5]. Criqui etal.
published on the mortality over a period of 10 years in
patients with peripheral arterial disease and found that there
was a high risk of death from cardiovascular causes in
patients with large-vessel peripheral arterial disease [6].
When planning for treatment, it is important to evaluate
the type of lesion; a stable plaque that is causing some degree
of ischemia distally is much safer than a plaque that has lots
of atheroma debris under a thin cap. This is also affected by
the vascular bed in which the lesion is located, as described
by Herisson etal. where they compared carotid and femoral
atherosclerotic plaques and found that those plaques in the
carotid arteries had more frequent brous cap atheroma
whereas the plaque in the femoral arteries was more brocalcic, and due to these characteristics, the results with treatment were different [7].
Endothelial dysfunction has been linked to the development of atherosclerotic lesions. Studies have found that
ow- induced vasodilation is an endothelium-dependent
process in humans, and it is mediated by nitric oxide.
Interestingly, ow-induced vasodilation is markedly reduced
in young patients with CAD [8]. These ndings propose that
not only the vessels with atherosclerotic disease have endothelial dysfunction, but that it is more of a diffuse process
and could perhaps be used as an early marker for the progression of disease.
More recently, some studies have shown a connection
between diseases that affect the endothelial function,
advanced glycation end products, and protein kinases with
alteration in vasodilation and contribution to the progression
of atherosclerosis [9, 10].
The subendothelial space is where the atherogenic particles will deposit and where macrophages and smooth muscle
cells take in the particles and start the atherogenic process
[11]. It is in this space where the proteoglycans present interact with low-density lipoprotein and its associated apolipoproteins [12].
Aortic Thrombus
Arterial embolization is a problem that carries increased
morbidity and mortality. Among the complications associated with distal embolization are acute ischemia with an
approximate rate of 13–14% and mortality with a rate of
9–12% [13]. The main cause of embolic events has been
associated with alteration in cardiac rhythm either as a consequence of myocardial infarction, atrial brillation, endocarditis, or after prosthetic valve replacement. When it
comes to noncardiac pathology, the origin of these emboli
is within the aorta, and it is due to aneurysmal degeneration, dissection, ulcers, or trauma. When they are found,
most of them are in the abdominal aorta and the rest in the
thoracic aorta [14].
On a paper published in the Journal of Vascular Surgery,
it was found on autopsies that 0.45% of the patients who had
a normal aorta had some degree of mural thrombus. From
those patients, only 17% had evidence of distal embolization. Also, they found that 20% of those mural thrombi were
present in the thoracic aorta [15]. Some studies have indicated that up to 15% of emboli may originate from a noncardiac, unidentied focus [16].
Emboli may originate from any segment of the aorta from
the arch to the aortoiliac bifurcation. These emboli can cause
cerebrovascular accidents, mesenteric ischemia, renal ischemia, and acute limb ischemia. Frequently, the thrombus is
found because of the embolic event. These embolic events
can occur spontaneously or as a complication from certain
procedures such as endovascular interventions [17].
Diagnosis can be made with transesophageal echocardiogram if the thrombus is present within the thoracic aorta and
the heart. Katz etal. [18] recommend a ve-point grading
system for aortic atheroma on transesophageal echocardiography reporting patients with a mobile atheroma had a 47%
incidence of stroke (Table32.2).
The increased use of CT angiography has helped in the
diagnosis as well as planning of management when indicated.
There are other imaging modalities that can be used such as
contrast-enhanced ultrasound, intravascular ultrasound,
magnetic resonance imaging, multiple-row detector CT, and
positron emission tomography [19] (Figs.32.1, 32.2, 32.3,
32.4 and 32.5).
Table 32.2 TEE grading of aortic atheroma [18]
Grade Description
1 Normal aorta 0
2 Extensive intimal thickening <3mm 0
3 Protrudes <5mm into aortic lumen 5
4 Protrudes >5mm into aortic lumen 10.5
5 Mobile atheroma 46.5
Incidence of
stroke (%)
32 Management ofAortic Atherothrombi
https://t.me/med1917
Fig. 32.1 This patient presented with blue toe syndrome (emboli to the
feet) and was treated medically
429
a
b
Fig. 32.2 This patient developed acute left lower extremity. She was
found to have a 6cm abdominal aneurysm (AAA) and diffuse atherosclerotic disease and was treated with open AAA repair and left leg
embolectomy
Management of aortic thrombus is not well established
due to the lack of available data. Usually, the initial management consists of systemic anticoagulation if no contraindications are present, aspirin, and then surgical
intervention or long-term anticoagulation. In a study by
Pagni etal., they found that half of the patients who developed aortic thrombi without any predisposing condition
had some sort of underlying and sometimes unrecognized
hypercoagulable state. They also found that small lesions
of less than 1 cm tended to respond more favorably to
anticoagulation than larger lesions did [17]. The treatment
will be detailed below and should aim at prevention of
embolization and possible stabilization and resolution of
the clot.
Fig. 32.3 This patient presented with abdominal pain and bilateral
renal infarcts. CT scan shows heavy thrombus burden at the level of the
superior mesenteric artery and renal arteries (a). She was treated with
oral anticoagulation. (b) is her repeat scan after 4weeks showing reduction in the thrombus burden. She had no further embolic episodes
If the lesions are larger or freely mobile, surgical intervention might be warranted. Traditionally, open thrombectomy has been used. With the progress made in endovascular
procedures, these have become more common. The location
of the lesion determines the type of endograft to be used.
Medical Treatment
Atherothrombosis is the unhealthy coupling of atherosclerosis
and thrombosis. Atherosclerosis leads to many systemic diseases such as coronary artery disease, cerebrovascular diseases, aortic atherosclerosis, and peripheral arterial disease.
Disease in one vascular bed increases the risk of disease in
others which is known as “cross-link” [20]. One of the most
detrimental consequences of atherosclerotic plaque is an
embolic event especially in those suffering from signicant
aortic atherosclerosis. These embolic events may be spontaneous or induced by mechanical interventions such as guidewire
or catheter manipulation during cardiac or peripheral vascular
catheterization. The risk of embolism in aortic atherosclerosis
is drastically increased for plaques that are mobile and/or protruding, especially if it is >4 mm in thickness [21]. These
430
https://t.me/med1917
R. D. Li et al.
Fig. 32.4 A young female presented with recurrent blue toe syndrome despite optimal medical management. The thoracic thrombus was covered
with a stent graft, and no further emboli occurred. She did well and was discharged home 3days later
including antiplatelet therapy, antihypertensive, anticoagulation, and statin medications.
Dual antiplatelet therapy has been shown to be an effective treatment choice for secondary prevention. One of the
most commonly used dual antiplatelet therapy medications
is aspirin and clopidogrel. Aspirin binds to and irreversibly
inhibits cyclooxygenase (COX), which is the rst-step
enzyme in the biosynthesis of prostaglandins in platelets.
This effectively shuts down the formation of thromboxane
A2 which is a potent platelet agonist and vasoconstricting
substance. Clopidogrel is an adenosine diphosphate receptor antagonist on platelets that ultimately blocks platelet
activation and aggregation. The Antithrombotic Trialists’
Collaboration meta-analysis demonstrated aspirin alone
Fig. 32.5 Transesophageal echocardiogram of a complex atheroma in
aortic arch
yielded an absolute reduction of 3.1% in vascular event
rates vs. control (12.9% vs. 16%) [23]. In the Clopidogrel
versus Aspirin in Patients at Risk of Ischemic Events
(CAPRIE) trial, a randomized comparison of clopidogrel
thromboemboli tend to lodge in small or medium arteries
which often lead to stroke or TIA, limb ischemia, renal infarction, intestinal ischemia, or other organ ischemia [22]. Since
atherothrombosis is a progressive process with an inammatory component where platelet adhesion, activation, and
aggregation are the nal stage that ultimately is responsible for
arterial occlusion and ischemia, many drugs have been
designed to target the various stages to provide primary and
secondary prevention in the treatment of atherothrombosis
75mg and aspirin 325 mg, ADP receptor antagonists such
as clopidogrel were associated with a signicant absolute
reduction of 0.51% in the rate of the primary composite
endpoint of MI, ischemic stroke, or vascular death compared with aspirin (5.32% vs. 5.83%; p = 0.043) [24].
However, evidence from the Clopidogrel and Aspirin for
Reduction of Emboli in Symptomatic Carotid Stenosis
(CARESS) trial demonstrated that the combination of clopidogrel and aspirin was more effective than aspirin alone in
32 Management ofAortic Atherothrombi
https://t.me/med1917
431
reducing asymptomatic embolization [25]. The Clopidogrel
for High Atherothrombotic Risk and Ischemic Stabilization,
Management, and Avoidance (CHARISMA) trial evaluated
the effects of dual antiplatelet therapy with clopidogrel and
aspirin in a broad population of high-risk patients including
established MI, stroke, or PAD.While this trial attempted to
explore the primary prevention of dual antiplatelet therapy
which remained unclear, it did further concur the secondary
prevention benets shown in previous trials [26].
Several studies have demonstrated possible efcacy of
warfarin for secondary prevention in patient with aortic
plaque. SPAF-III trial compared adjusted-dose warfarin with
INR 2–3 to low-dose warfarin with INR 1.2–1.5 plus aspirin
for the prevention of stroke in patients with atrial brillation
with at least one thromboembolic risk factor. They found that
those treated with adjusted-dose warfarin had 4% incidence
of stroke vs. 16% incidence in those with low-dose warfarin
plus aspirin, which demonstrated a 75% risk reduction [27].
In another study in patients who had undergone transesophageal echo found to have protruding plaque, there were no
embolic events in 27 patients who were treated with warfarin
compared to clinical embolic events in 5 of the 23 patients
who were treated with antiplatelet therapy [28]. Thus, these
studies demonstrated a possible efcacy for warfarin in
plaque stabilization.
Another important target for treating atherothrombosis is
lipid-lowering therapy, specically statins. Statins are coenzyme A reductase inhibitors which reduce atherothrombotic
events through a variety of mechanisms including reduction
of cholesterol biosynthesis, modulation of lipid metabolism,
and a notable way to prevent thrombosis by improving endothelial homeostasis by increasing the bioavailability of nitric
oxide that subsequently orchestrates the paracrine antiatherosclerotic functions of the endothelium [29]. Tunick etal.
demonstrated in their retrospective analysis of 519 patients
that statin therapy was associated with an absolute reduction
of 17% in thromboembolic events (12% vs. 29%) compared
to those who were not treated with statins. This signied the
clinical benet of statin-induced plaque stabilization [30].
Other studies attempted to evaluate possible regression of
aortic plaque with imaging such as MRI.One trial was able
to demonstrate the maximal wall thickness of thoracic aorta
was reduced by 13.8% in combination therapy of atorvastatin and etidronate vs. 12.3% in patients who took atorvastatin vs. only 2.2% in those who took etidronate for
12 months. In the abdominal aorta, combination therapy
showed 11.9% reduction in vessel wall thickness vs. 0.9% in
atorvastatin group and 5.5% in the etidronate group [31].
Thus, statin therapy is imperative in the prevention and treatment of atherothrombosis.
The renin-angiotensin system (RAS) has been shown as a
key pathway modulating atherosclerotic plaque vulnerability. It is a series of enzymatic reactions that leads to the gen-
eration of angiotensin II which promotes vasoconstriction,
aldosterone secretion, water and sodium reabsorption, thirst,
activation of the sympathetic nervous system, and cardiac
ionotropic and chronotropic actions [32]. There is emerging
evidence indicating RAS might regulate all stages of atherogenesis, from initiation to disease progression including
determining plaque vulnerability and rupture. Many studies
have shown direct relationship between inammation and
the RAS where activation of NF-kB by angiotensin II in
endothelial cells and vascular smooth muscle cells induces
the upregulation of cell adhesion molecules, which favor
adhesion, tissue recruitment, and accumulation of inammatory cells. These inammatory cells can lead to intraplaque
proliferation of macrophages and further increase cytokine
and chemokine expression which result in a positive feedback response. The persistent proinammatory state plays an
essential role in the conversion of a stable atherosclerotic
plaque into a vulnerable phenotype [32]. Thus, angiotensinconverting enzyme (ACEi) inhibitors play an important protective role where it antagonizes atherogenesis and
atheroprogression. While the exact mechanism behind atherosclerotic plaque stabilization with ACEi is not fully
understood, ACEi are known to reduce formation of Ang II
and increase bradykinin levels which result in increased NO
release, thus attenuating the oxidation of LDL and inhibiting
MMP-9 activity [33].
The current guideline for medical management of aortic
atherosclerotic disease is consistent with the American
College of Chest Physicians (ACCP) guidelines for antithrombotic and thrombolytic therapy for valvular disease,
ischemic stroke, and peripheral artery disease.
• For patients with no contraindications (low risk of major
bleeding) with stroke and complex aortic plaque, or
patient without stroke but atheroma with a mobile compo-
nent, medical therapy includes lipid-lowering therapy
plus aspirin monotherapy, or clopidogrel 75 mg daily
monotherapy is appropriate.
• For patients without stroke and simple plaque (<4 mm
without a mobile component), the evidence behind medi-
cal therapy is limited; however, they still recommend
lipid-lowering therapy plus aspirin or clopidogrel
monotherapy.
While warfarin may play a more signicant role in patient
with atrial brillation or mechanical prosthetic valves in the
setting of aortic atherosclerotic disease, it is generally not
recommended in patients with stable aortic atheroma and
thromboembolism. Based on nonrandomized retrospective
studies, oral anticoagulation has shown benet in patients
with mobile thrombi in the aortic arch; thus, the 2012 ACCP
currently recommends oral anticoagulation in the setting of
cryptogenic stroke and mobile aortic arch thrombi pending
432
https://t.me/med1917
R. D. Li et al.
ongoing randomized controlled trials comparing oral anticoagulant with antiplatelet therapy [34].
There are many different targets in the attenuation of the
progression of atherothrombosis. Atherosclerotic plaque stabilization remains to be one of the most important goals in
the treatment of atherothrombosis whether it is through primary prevention or by secondary prevention using dual antiplatelet therapy, anticoagulation with warfarin, lipid-lowering
drugs with statins, or ACEi. It is crucial to initiate the appropriate treatment to minimize the detrimental consequences
of atherothrombosis.
Surgical Intervention
Surgical management is another approach in the treatment of
aortic atherothrombosis. Surgical interventions for aortic atherosclerosis include aortic replacement with interposition
graft, thrombectomy if focal, and endovascular stenting.
Wareing etal. assessed a strategy for reduction of stroke incidence in patients undergoing cardiac surgery by screening for
ascending aorta atherosclerosis and carotid disease. For the
purpose of this chapter, we will focus on atherosclerosis of
the aorta and not the carotid arteries. They found that none of
the 27 patients with moderate or severe atherosclerosis of the
ascending aorta who had ascending aortic replacement had
stroke, while 6.3% of 111 patients with moderate or severe
disease who had only minor interventions had stroke. This
study suggested that screening and aggressive surgical treatment could reduce the frequency of stroke in cardiac surgical
patients [35]. However, interposition graft requires signicant
consideration for myocardial, brain, spinal cord, and lower
body protection and rigorous surgical technique. Thus, careful selection of surgical candidates needs to be done to limit
mortality and morbidity. Another study compared interposition graft in severe atherosclerosis group versus arterial cannulation in mild or moderate atherosclerosis group and found
that there was no signicant difference in mortality and stroke
rate but there was a statistically signicant difference in operation time, ICU stay, and hospital stay that were all longer in
the interposition graft group [36]. This raises the question if
interposition graft would ultimately be the optimal surgical
option for patients with aortic atherosclerosis.
Another option for treating severe ascending aorta atherosclerosis is endarterectomy. In one study, arch endarterectomy was performed in 268 patients undergoing heart surgery
who were found to have >4mm aortic plaque in an effort to
reduce intraoperative stroke risk; however, these patients
ended up having higher rates of stroke than those who did
not have endarterectomy (35% vs. 12%) as well as higher
mortality rate and longer hospital stay [37]. Thus, aortic arch
endarterectomy should not be recommended in patients with
aortic atherosclerosis.
We have no randomized studies to suggest surgical treatment for emboli from sources such as the descending thoracic aorta or the abdominal aorta, but the same principles
apply. It is indicated for those who fail medical therapy and
are at low risk of complications. In addition, endovascular
therapy has replaced open surgical treatment for these anatomic areas when it is feasible. Endovascular treatment
allows for intervention in patients who previously were considered as nonsurgical candidates as well as carries a lower
morbidity rate. The early results have shown 100% technical
success, no early recurrences, and no wire- or device-related
complications. However, several conditions should be considered when approaching aortic atherosclerotic lesions [38]:
• Careful manipulation of wires to prevent iatrogenic
emboli
• Use of angiography and/or intravascular ultrasonography
to accurately identify and exclude the affected segment of
the aorta
• Planning of at least 1–2 cm proximal and distal landing
zones
• Postprocedural evaluation of mesenteric and lower
extremity vessels
Conclusion
Aortic atherosclerotic plaques are important potential
sources of systemic emboli which can lead to signicant
consequences such as stroke, transient ischemic attack, renal
infarction, and embolization to other arterial beds that could
lead to end-organ ischemia and, occasionally, require intervention such as renal thrombectomy for acute renal injury or
popliteal thrombectomy for acute limb ischemia. The risk of
thromboembolism in aortic atherosclerosis is increased when
there is a complex plaque which is dened as thickness>4mm or ulceration. Secondary prevention with various medications that target the atherosclerotic process has
been used to prevent thromboembolism. These medications
include lipid-lowering therapy with statins, anticoagulation
therapy such as warfarin, antiplatelet therapy including aspirin and clopidogrel, and antihypertensive medications such
as ACE inhibitors. Surgical treatment, open and endovascular, should be reserved for those who fail medical treatment
and at low risk for complications.
References
1. Kips JG, Segers P, Van Bortel LM. Identifying the vulnerable
plaque: a review of invasive and non-invasive imaging modalities.
Artery Res. 2008;2:21–34.
32 Management ofAortic Atherothrombi
https://t.me/med1917
433
2. Kronzon I, Tunick PA.Aortic atherosclerotic disease and stroke.
Circulation. 2006;114:63–75.
3. Capmany RP, Ibañez MO, Pesquer XJ. Complex atheromatosis of the aortic arch in cerebral infarction. Curr Cardiol Rev.
2010;6:184–93.
4. Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull W,
etal. A denition of advanced types of atherosclerotic lesions and
a histological classication of atherosclerosis. A report From the
Committee on Vascular Lesions of the Council on Arteriosclerosis,
American Heart Association. Circulation. 1995;92:1355–74.
5. DeBakey ME, Lawrie GM, Glaeser DH.Patterns of atherosclerosis
and their surgical signicance. Ann Surg. 1985;201:115–31.
6. Criqui MH, Langer RD, Fronek A, Feigelson HS, Klauber MR,
McCann TJ, etal. Mortality over a period of 10 years in patients
with peripheral arterial disease. N Engl J Med. 1992;326:381–6.
7. Herisson F, Heymann MF, Chetiveaux M, Charrier C, Battaglia S,
Pilet P, etal. Carotid and femoral atherosclerotic plaques have different morphology. Atherosclerosis. 2011;216:348–54.
8. Lieberman EH, Gerhard MD, Uehata A, Selwyn AP, Ganz P, Yeung
A, etal. Flow-induced vasodilation of the human brachial artery is
impaired in patients <40 years of age with coronary artery disease.
Am J Cardiol. 1996;78:1210–4.
9. Ren X, Ren L, Wei Q, Shao H, Chen L, Liu N.Advanced glycation
end-products decreases expression of endothelial nitric oxide synthase through oxidative stress in human coronary artery endothelial
cells. Cardiovasc Diabetol. 2017;16:52.
10. Yang L, Cong HL, Wang SF, Liu T.AMP-activated protein kinase
mediates the effects of lipoprotein-associated phospholipase A2
on endothelial dysfunction in atherosclerosis. Exp Ther Med.
2017;13:1622–9.
11. Camejo G, Hurt-Camejo E, Wiklund O, Bondjers G.Association of
apo B lipoproteins with arterial proteoglycans: pathological signicance and molecular basis. Atherosclerosis. 1998;139:205–22.
12. Camejo G, Fager G, Rosengren B, Hurt-Camejo E, Bondjers
G. Binding of low density lipoproteins by proteoglycans synthesized by proliferating and quiescent human arterial smooth muscle
cells. J Biol Chem. 1993;268:14131–7.
13. Eliason JL, Wainess RM, Proctor MC, Dimick JB, Cowan JA Jr,
et al. A National and Single Institutional Experience in the contemporary treatment of acute lower extremity ischemia. Ann Surg.
2003;238:382–90.
14. Abbott WM, Maloney RD, McCabe CC, Lee CE, Wirthlin
LS. Arterial embolism: A 44-year perspective. Am J Surg.
1982;143:460–4.
15. Verma H, Meda N, Vora S, George RK, Tripathi RK.Contemporary
management of symptomatic primary aortic mural thrombus. J Vasc
Surg. 2014;60:1524–34.
16. Khouzam RN, Salama L, Sou MK, Khandekar A, Al-Mawed
S.Showers of emboli from a large aortic root thrombus. J La State
Med Soc. 2014;166:138–42.
17. Pagni S, Trivedi J, Ganzel BL, Williams M, Kapoor N, Ross C,
Slater AD.Thoracic aortic mobile thrombus: is there a role for early
surgical intervention? Ann Thorac Surg. 2011;91:1875–81.
18. Katz ES, Tunick PA, Rusine H, Ribakove G, Spencer FC, Kronzon
I. Protruding aortic atheromas predict stroke in elderly patients
undergoing cardiopulmonary bypass: experience with intraoperative transesophageal echocardiography. J Am Coll Cardiol.
1992;20:70–7.
19. Owen DRJ, Lindsay AC, Choudhury RP, Fayad ZA.Imaging of
Atherosclerosis. Annu Rev Med. 2011;62:25–40.
20. Ellahham S.Role of antiplatelet agents in the primary and secondary prevention of atherothrombotic events in high risk-patients.
South Med J. 2008;101:273–83.
21. Karalis D, Quinn V, Victor MF, Ross JJ, Polansky M, Spratt KA,
etal. Risk of catheter-related emboli in patients with atherosclerotic
debris in the thoracic aorta. Am Heart J. 1996;131:1149–55.
22. Tunick PA, Kronzon I.Atheromas of the thoracic aorta: clinical and
therapeutic update. J Am Coll Cardiol. 2000;35:545–54.
23. Antithrombotic Trialists’ Collaboration. Collaborative metaanalysis of randomised trials of antiplatelet therapy for prevention
of death, myocardial infarction, and stroke in high risk patients.
BMJ. 2002;324:71–86.
24. CAPRIE Steering Committee. A randomised, blinded, trial
of clopidogrel versus aspirin in patients at risk of ischaemic
events (CAPRIE). CAPRIE Steering Committee. Lancet.
1996;348(9038):1329–39.
25. Markus HS, Droste DW, Kaps M, Larrue V, Lees KR, Siebler
M, Ringelstein EB. Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid stenosis evaluated using
Doppler embolic signal detection: the Clopidogrel and Aspirin for
Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS)
trial. Circulation. 2005;111(17):2233–40.
26. Bhatt DL, Fox KA, Kacke W, Berger PB, Black HR, Boden WE,
etal. A global view of atherothrombosis: baseline characteristics
in the Clopidogrel for High Atherothrombotic Risk and Ischemic
Stabilization, Management, and Avoidance (CHARISMA) trial.
Am Heart J. 2005;150:401.
27. Adjusted-dose warfarin versus low-intensity, xed-dose warfarin
plus aspirin for high-risk patients with atrial brillation: stroke
prevention in atrial brillation III randomized clinical trial. Lancet.
1996;7:633–8.
28. Ferrari E, Vidal R, Chevallier T, Baudouy M. Atherosclerosis
of the thoracic aorta and aortic debris as a marker of poor
prognosis: benet of oral anticoagulants. J Am Coll Cardiol.
1999;35:1317–22.
29. Vaughan CJ.Prevention of stroke and dementia with statins: Effects
beyond lipid lowering. Am J Cardiol. 2003;91:23–9.
30. Tunick PA, Nayar AC, Goodkin GM, Mirchandani S, Francescone
S, Rosenzweig BP, et al. Effect of treatment on the incidence of
stroke and other emboli in 519 patients with severe thoracic aortic
plaque. Am J Cardiol. 2002;90:1320–5.
31. Corti R, Fayad ZA, Fuster V, Worthley SG, Helft G, Chesebro
J, et al. Effects of lipid-lowering by simvastatin on human
atherosclerotic lesions: a longitudinal study by high-resolution, noninvasive magnetic resonance imaging. Circulation.
2001;104:249–52.
32. Da Silva AR, Fraga-Silva RA, Stergiopulos N, Montecucco F, Mach
F.Update on the role of angiotensin in the pathophysiology of coronary atherothrombosis. Eur J Clin Investig. 2015;45:274–87.
33. Yoshida H, Kisugi R. Mechanisms of LDL oxidation. Clin Chim
Acta. 2010;411:1875–82.
34. Lansberg MG, O’Donnell MJ, Khatri P, Lang ES, NguyenHuynh MN, Schwartz NE, et al. Antithrombotic and thrombolytic therapy for ischemic stroke: antithrombotic therapy and
prevention of thrombosis, 9th ed: American College of Chest
Physicians Evidence- Based Clinical Practice Guidelines. Chest.
2012;141:e601S–36S.
35. Wareing TH, Davila-Roman VG, Daily BB, Murphy SF, Schechtman
KB, etal. Strategy for the reduction of stroke incidence in cardiac
surgical patients. Ann Thorac Surg. 1993;55:1400–7.
36. Yamanaka K, Nishina T, Kanemitsu N, Hirose K, Mizuno A,
Nakatsuka D, et al. Total aortic arch replacement for severe atherosclerotic aortic aneurysms: consecutive 135 cases study. Kyobu
Geka. 2013;66:948–51.
37. Stern A, Tunick PA, Culliford AT, Lachmann J, Baumann FG,
Kanchuger MS, et al. Protruding aortic arch atheromas: risk of
stroke during heart surgery with and without aortic arch endarterectomy. Am Heart J. 1999;138:746–52.
38. Scott DJ, White JM, Arthurs Z.Endovascular management of a
mobile thoracic aortic thrombus following recurrent distal thromboembolism: a case report and literature review. Vasc Endovasc
Surg. 2014;48:246–50.
Aortic Disease inPregnancy
https://t.me/med1917
CarolineA.Ball andSaraSirna
33
Introduction
Pregnancy represents a unique physiologic period, with signicant implications on the cardiovascular system [1].
Although rare, aortic disease is a known potential complication of pregnancy. Aortic dissection and rupture can be of
particular concern for pregnant women with underlying connective tissue disorders [2]. In the next chapter, we will
explore aortic disease in pregnancy, including pathophysiology, epidemiology, and specic conditions. We will pay particular interest to aortic dissection and rupture, given the
increased incidence in pregnancy, and the devastating potential consequences.
Vascular Changes inPregnancy
Pregnancy causes a unique set of physiologic changes
(Table33.1), which place an increased burden on the cardiovascular system and the aorta [3]. Throughout a normal pregnancy, there is a decrease in systolic, diastolic, and mean
blood pressures. Compared to baseline, there is a 20–25%
increase in heart rate over the course of pregnancy. Cardiac
output also increases throughout pregnancy. Peripheral vascular resistance decreases, and there is systemic vasodilation
in addition to increased vascular distensibility [2, 4].
Pregnancy is associated with an increase in vasomotor
sympathetic activity [5], in addition to hormonal changes.
Estrogen and progesterone increase vasodilation [4], as does
relaxin, a hormone produced by the placenta [6]. Relaxin
affects the cardiovascular and renal systems, increasing cardiac output and renal blood ow. Pregnancy increases angiotensinogen, total blood volume, plasma volume, and red
blood cell mass. It is also associated with an increased left
ventricular thickness and wall mass [4].
C. A. Ball (*) · S. Sirna
Department of Medicine, Division of Cardiology,
Loyola University Chicago, Maywood, IL, USA
Table 33.1 Physiologic changes of pregnancy
Parameter Expected change
Systemic
vascular
resistance
Blood pressure Decrease in systolic and diastolic blood pressure
Heart rate Increases by 20–25% over the course of
Cardiac output Increases throughout pregnancy
Plasma volume Increases throughout pregnancy
Aortic root
diameter
The aorta undergoes structural changes during pregnancy,
as well. The changes described above cause increased shear
stress on the aortic wall, predisposing the aorta to aneurysmal dilation and dissection [7]. In late pregnancy, the gravid
uterus can cause aorto-iliac compression, resulting in
increased peripheral resistance [8]. Pregnancy also affects
the structural integrity of the aorta. Circulating estrogen and
progesterone cause reticulin ber fragmentation and elastin
ber disorganization [8]. Pregnancy is also associated with
fragmentation of the reticulum bers of the aorta, loss of the
normal corrugation of elastic bers, and hypertrophy and
hyperplasia of the smooth muscle cells [3, 9, 10]. The aortic
root increases in diameter by at least 1mm during a normal
pregnancy. The peak diameter occurs in the third trimester
[1]. In women with hypertension during pregnancy, the
increase of the diameter is more pronounced [9].
Decreases throughout pregnancy
over the course of pregnancy, with a nadir in the
second trimester
pregnancy
Increases throughout pregnancy
Epidemiology
Aortic dissection is a rare occurrence in normal pregnancy.
In the United States, the incidence of aortic dissection in
pregnancy is 0.0004%, based on data from the Nationwide
Inpatient Sample database from 1988 to 2008. The study
identied 44 cases of aortic dissection out of 10 million
© Springer Nature Switzerland AG 2019
R. S. Dieter et al. (eds.), Diseases of the Aorta, https://doi.org/10.1007/978-3-030-11322-3_33
435
436
C. A. Ball and S. Sirna
https://t.me/med1917
pregnancies. Seven of the 44 patients who experienced a
dissection had Marfan syndrome [11]. Aortic dissections
that occur during pregnancy represent 0.1% of all cases of
aortic dissection in the United States [11]. The risk of aortic
dissection increases over the course of the pregnancy, with
the greatest risk in the third trimester and postpartum [8].
Despite its rarity, the consequences to both mother and child
can be devastating [12].
For women with underlying conditions that affect the
aorta, the physiologic changes of pregnancy can further
increase the risk of aortic dissection and rupture. For example, the risk of aortic dissection in women with Marfan syndrome increases eightfold during pregnancy, particularly in
the postpartum period [13].
There is limited data available on the incidence of aortitis
in pregnancy. Takayasu arteritis, a rare form of large-vessel
vasculitis, which is known to affect women of childbearing
age, is neither affected nor worsened by pregnancy [7, 14].
However, hypertension is not uncommon in patients with
Takayasu arteritis, and close monitoring of blood pressure is
recommended.
Management ofAortic Disease inPregnancy
Management of aortic disease in pregnancy is based primarily on case series and expert opinion. Management decisions
depend on the stage of the pregnancy, the condition of the
mother and child, as well as the disease process involved.
Treatment should involve a team approach, including
maternal- fetal medicine specialist, cardiologists, and cardiovascular and vascular surgeons [7].
Aortic dissection in pregnancy presents a potentially lifethreatening situation to both mother and child. For women
with known genetic syndromes that cause thoracic aortic
aneurysm or dissection, screening can be done both before
and during pregnancy to mitigate risk. Screening and preconception strategies for particular genetic syndromes will be
described later. American College of Cardiology/American
Heart Association guidelines recommend that all pregnant
women with known thoracic aortic dilatation or a familial or
genetic predisposition for aortic dissection should undergo
strict blood pressure control [15] (Table33.2). Additionally,
all pregnant women with known aortic root or ascending aortic dilatation should undergo monthly or bimonthly echocardiographic measurements of the ascending aortic dimensions
until delivery. Pregnant women with aortic aneurysms should
be delivered at a center where cardiothoracic surgery is available [15]. Women with an aortic diameter>= 45mm at the
time of delivery should undergo elective cesarean section [7].
For women presenting with type A aortic dissections, surgical treatment should be undertaken immediately, regardless of the trimester. For women presenting with type B
Table 33.2 Antihypertensive medication use in pregnancy
US FDA
Medication Mechanism of action
Methyldopa Central alpha
adrenergic agonist
Labetalol Peripherally acting
Nifedipine Calcium channel
Hydralazine Arteriolar smooth
Clonidine Selective central
Data from: [
FDA Pregnancy Categories: A = Adequate, well-controlled studies
have failed to demonstrate a risk to the fetus in the rst trimester of
pregnancy, and there is no evidence of risk in later trimesters.
B= Animal reproduction studies have failed to demonstrate a risk to
the fetus, and there are no adequate and well-controlled studies in
pregnant women. C = Animal reproduction studies have shown an
adverse effect on the fetus, and there are no adequate and well-controlled studies in humans, but potential benets may warrant use of the
drug in pregnant women despite potential risk. D=There is positive
evidence of human fetal risk based on adverse reaction data from
investigational or marketing experience or studies in humans, but
potential benets may warrant use of the drug in pregnant women
despite potential risks. X=Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human
fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in the use of the drug in pregnant women clearly outweigh potential benets [19]
nonselective
beta-blocker
blocker
muscle relaxation
alpha
2
agonist
17, 18]
-
2
-adrenergic
Priority of
therapy
First line B
Second
line
Second
line
Second
line
Third line C
pregnancy
category [
C
C
C
19]
aortic dissection, medical management is recommended,
unless the dissection is complicated by malperfusion [7].
Surgical intervention for pregnant women with aortic dissection requires careful discussions between the surgical,
obstetric, and anesthesia teams. European Society of
Cardiology guidelines recommend surgical repair of an aortic dissection while the fetus is in utero for type A dissections
that occur before the fetus is viable. After the fetus is considered viable, prompt cesarean delivery is recommended prior
to surgical repair of the aortic dissection so as to prevent
cesarean delivery while on aortopulmonary bypass [16].
For women with Takayasu arteritis in pregnancy, steroids
are the recommended treatment, despite their potential role
in increasing the risk of aortic dissection [14].
Pregnancy andAortic Disease inSpecic
Conditions
As described above, women with underlying aortopathies
have an increased risk of aortic dissection and rupture during
their pregnancy. There are recommendations available for the
management of aortic disease in several of these conditions.
Соседние файлы в папке Библиотека им академика М.И. Перельмана