Aortic aneurysm

Aortic Aneurysm Overview

An aortic aneurysm is a dilation of the aorta in which the aortic diameter is ≥ 3.0 cm, usually representing an underlying weakness in the wall of the aorta at that location. While the stretched vessel may occasionally cause discomfort, a greater concern is the risk of rupture which causes severe pain, massive internal hemorrhage which are often fatal. Aneurysms often are a source of blood clots (emboli) stemming from the most common etiology of atherosclerosis.

Classification

There are 2 types of aortic aneurysms: thoracic and abdominal. These can be further classified according to the respective part of the vessel that's been affected:

• Thoracic aortic aneurysm, which occur in the thoracic aorta (runs through the chest);
• Abdominal aortic aneurysm, which occur in the abdominal aorta, are the most common.
  • Suprarenal - not as common, often more difficult to repair surgically due to the presence of many aortic branches;
  • Infrarenal - often more easily surgically repaired and more common;
  • Pararenal - aortic aneurysm is infrarenal but affects renal arteries;
  • Juxtarenal - infrarenal aortic aneurysm that affects the aorta just below the renal arteries.

Thoracoabdominal aortic aneurysm may also be classified according to Crawford classification into 5 subtypes/groups:

• Type 1: from the origin of left subclavian artery in descending thoracic aorta to the supra-renal abdominal aorta.
• Type 2: from the left subclavian to the aorto-iliac bifurcation.
• Type 3: from distal thoracic aorta to the aorto-iliac bifurcation
• Type 4: limited to abdominal aorta below the diaphragm
• Type 5: from distal thoracic aorta to celiac and superior mesenteric origins, but not the renal arteries.

Historical Perspective

Aortic aneurysm was first recorded by Antyllus, a Greek surgeon, in the second century AD. In the Renaissaince era, in 1555, Vesalius first diagnosed an abdominal aortic aneurysm. The first publication on the pathology with case studies was published by Lancisi in 1728. Finally, in 1817, Astley Cooper was the first surgeon to ligate the abdominal aorta to treat a ruptured iliac aneurysm. In 1888, Rudoff Matas came up with the concept of endoaneurysmorrhaphy.

Pathophysiology

The aortic aneurysms are a multifactorial disease associated with genetic and environmental risk factors. Marfan's syndrome and Ehlers-Danlos syndrome are associated with the disease, but there are also rarer syndromes like the Loeys-Dietz syndrome that are associated as well. Even in patients that do not have genetic syndromes, it has been observed that genetics can also play a role on aortic aneurysms' development. There has been evidence of genetic heterogeneity as there has already been documented in intracranial aneurysms. The genetic alterations associated with these genetic syndromes are the following:

Genetic diseases associated with aortic aneurysms

Disease	Involved Cellular Pathway	Mutated Gene(s)	Affected Protein(s)
Ehlers-Danlos syndrome type IV	Extracellular Matrix Proteins	COL3A1	Collagen type III
Marfan's syndrome	Extracellular Matrix Proteins	FBN1	Fibrillin-1
Loeys-Dietz syndrome	TGF-β Pathway	TGFBR1/TGFBR2
Aneurysm-Osteoarthritis Syndrome		SMAD3	SMAD3
Autosomal Dominant Polycystic Kidney Disease	Ciliopathy	PKD1PKD2	Polycystin 1 Polycystin 2
Turner Syndrome	Meiotic Error with Monosomy, Mosaicism, or De Novo Germ Cell Mutation	45X 45XO	Partial or Complete Absence of X Chromosome
Bicuspid Aortic Valve with TAA	Neural Crest Migration	NOTCH1	Notch 1
Familial TAA	Smooth Muscle Contraction Proteins	ACTA2	α-Smooth Muscle Actin
Familial TAA with Patent Ductus Arteriosus	Smooth Muscle Contraction Proteins	MYH11	Smooth Muscle Myosin
Familial TAA	Smooth Muscle Contraction Proteins	MYLK	Myosin Light Chain Kinase
Familial TAA	Smooth Muscle Contraction Proteins	PRKG1	Protein Kinase c-GMP Dependent, type I
Loeys-Dietz Syndrome variants	TGF-β Pathway	TGF-βR1TGF-βR2SMAD3TGF-β2TGF-β3

These genetic diseases mostly affect either the synthesis of extracellular matrix protein or damage the smooth muscle cells both important component's of the aortic wall. Injury to any of these components lead to weakening of the aortic wall and dilation - resulting in aneurysm formation.

The aorta is the largest vessel of the body, but it is not homogenous. Its upper segment is composed by a larger proportion of elastin in comparison to collagen, therefore being more distensible. The lower segment has a larger proportion of collagen, therefore it is less distensible. It is also where most of the atherosclerotic plaques of the aorta are located. Historically it was thought that abdominal and thoracic aortic aneurysms were caused by the same etiology: atherosclerotic degeneration of the aortic wall, but recently it has been theorized that they are indeed different diseases.

The aortic arch mostly derives from the neural crest cell which differentiate into smooth muscle cells. These smooth muscle cells are probably more adapted to remodel the thoracic aorta and manage the higher pulse pressure and ejection volume due to increased production of elastic lamellae during development and growth. The abdominal aorta remains with cells of mesodermal origin, which are more similar to that of the original primitive arterial. That difference results in the neural crest cell precursors of the thoracic aorta being able to respond differently to various cytokines and growth factors than the mesodermal precursors of the abdominal aorta, such as homocysteine and angiotensin II.

When neural crest vascular smooth muscle cells are treated with TGF-β they demonstrate increased collagen production, while mesodermal vascular smooth muscle cell did not. Not coincidently, mutations of the TGF-β receptor can cause thoracic aortic aneurysm but do not cause abdominal aortic ones.

The thoracic and abdominal aorta are very structurally different. While they both have three layers: intimal, medial and adventitia, the media of the thoracic aorta is comprised of approximately 60 units divided into vascular and avascular regions. The abdominal aorta consists of about 30 units and is entirely avascular - being dependent on trans-intimal diffusion of nutrients for its smooth muscle cells to survive. It is believed that both differences explain why the abdominal aorta is more likely to form aneurysms.

The development of aortic aneurysms is defined by: inflammation: infiltration of the vessel wall by lymphocytes and macrophage; extracellular matrix damage: destruction of elastin and collagen by proteases (also metalloproteinases) in the media and adventitia; cellular damage: loss of smooth muscle cells with thinning of the media; and insufficient repair: neovascularization.

In summary:

• The pathogenesis of aortic aneurysm is characterized by progressive dilation, rupture, and may present with dissection;
• The pathological processes that lead to abdominal and thoracic aortic aneurysms may be very different from one another;
• The fibrillin-1 gene mutation has been associated with the development of thoracic aortic aneurysms in Marfan's syndrome;
• Other gene mutations coding for collagen, elastin and other elements of the extracellular matrix have been associated with the development of aneurysms in some genetic disorders, including Ehlers-Danlos syndrome and others;
• Mutations in the TGF-β pathway have also been described in the pathogenesis of aortic aneurysms in multiple genetic disorders, including Loeys-Dietz syndrome.

Differentiating Aortic Aneurysm from other Diseases

Thoracic aortic aneurysms: differential diagnosis include other causes of chest pain: acute aortic dissection, acute pericarditis, aortic regurgitation, heart failure, hypertensive emergencies, infective endocarditis, myocardial Infarction, pulmonary embolism, superior vena cava syndrome.

Abdominal aortic aneurysms: differential diagnosis include causes of pulsatile abdominal mass and/or abdominal pain such as ruptured viscus, strangulated hernia, ruptured visceral artery aneurysms, mesenteric ischemia, acute cholecystitis, ruptured hepatobiliary cancer, acute pancreatitis, lymphomas, and diverticular abscess.

These conditions can be easily differentiated using abdominal or thoracic imaging.

Epidemiology and Demographics

In the United States alone 15,000 people die yearly due to aortic aneurysms and it is the 13th leading cause of death. 1-2% of the population may have aortic aneurysms and prevalence rises up to 10% in older age groups. The disease varies according to where it takes place. In the thorax, the aortic arch is the less affected segment (10%) and the most common is the ascending aorta (50%). Regarding abdominal aneurysms, the infrarenal segment aortic aneurysms are three times more prevalent than the aortic aneurysms and dissections.

Regarding other factors as age, abdominal aortic aneurysms usually present 10 years later than thoracic aortic aneurysms. Both lesions are more present in men, but the proportion is much higher regarding abdominal aortic aneurysms (6:1 male:female ratio) in comparison to thoracic ones.

Abdominal aortic aneurysms also affect patients differently regarding race, as they are more prevalent among whites than blacks, asians and hispanics. It also seems to be declining in prevalence as evidenced by a Swedish study that found out a 2% prevalence of abdominal aortic aneurysms in comparison to earlier studies which reported 4-8%, probably due to risk-factor modification.

Risk Factors

Many risk factors are common between both forms of aortic aneurysms, but some are specific for each presentation:

• Abdominal aortic aneurysm: smoking, male gender, age (>65 years), race (white), family history, other aneurysms.
• Thoracic aortic aneurysm: smoking, age (>65 years), hypertension, atherosclerosis, family history, Marfan's syndrome, bicuspid aortic valve.

Natural History, Complications and Prognosis

Even though the majority of the aortic aneurysms remain asymptomatic for years, their natural history is dissection or rupture. According to Laplace's law, as the aneurysms grow larger they have a higher rate of expansion. Due to that, the frequency of monitoring changes with the diameter of the abdominal aortic aneurysm, being every 3 years for aneurysms with a 3-3.4cm diameter, yearly for diameters of 3.5-4.4cm, and every 6 months for larger than 4.5cm. For the thoracic one, up to 80% of the aneurysms will eventually rupture, and patients present with a 10-20% five-year survival rate if they remain untreated. Risk of rupture doubles every 1cm in growth over the 5cm diameter in descending thoracic aorta.

Besides rupturing and dissection of the aorta, aortic aneurysms can also present with systemic embolization and aortic regurgitation (if the thoracic aortic aneurysm is located in the ascending aorta). The altered blood flow in the aneurysm can also lead to the formation of blood cloths and embolization.

Diagnosis

Diagnostic Criteria

Abdominal aortic aneurysms: are considered a dilation of the abdominal aorta which presents with a permanent vessel diameter larger than 30mm (normal abdominal aortic diameter ranges from 15 to 25mm). They can be diagnosed by abdominal ultrasound imaging, CT scan or MRI.

Thoracic aortic aneurysms: generally an aneurysm is diagnosed when the axial diameter of the ascending aorta is larger than 5cm and 4cm for the descending aorta. When larger than normal but not reaching aneurysmal definition the terms dilatation and ectasia can be used. The transthoracic ultrasound is not used due to the fact that thebones of the chest wall and the air inside the lungs makes the assessment of the aorta difficult. Instead it is chosen the CT scan, MRI or angiography for diagnosis.

Symptoms:

Aortic aneurysms are largely an asymptomatic condition, but symptoms present differently according to the affected segment of the aorta.

Thoracic aortic aneurysms: patients are usually diagnosed in these contexts:

• Incidental finding as part of a routine examination (transthoracic echocardiography, computerized tomography of the chest, cardiac magnetic resonance imaging, routine chest radiograph);
• Acute presentation with thoracic aortic dissection or aneurysm rupture;
• Screening due to a relative of a patient presenting with aortic disease;
• Part of a known congenital cardiac condition.

The aneurysms tend to grow slowly and most of them will never rupture. As they grow, however, their symptoms become more evident and present with mass effects over surrounding structures and pain. They may present with thoracic symptoms: interscapular or central pain, ripping chest pain and dyspnea. Atypical presentations include hoarseness, dizziness and dysphagia, due to esophageal compression. Aneurysm rupture lead to massive internal bleeding, hypovolemic shock and it is usually fatal.

Abdominal aortic aneurysms: as the thoracic aneurysms, they begin asymptomatic but may cause symptoms as they grow and compress surrounding structures.Even though they usually remain asymptomatic, when they rupture they present with an ensuing mortality of 85 to 90%., and symptomatic patients require urgent surgical repair.

When symptomatic, abdominal aortic aneurysms present with:

• Pain: in the chest, abdomen, lower back, or flanks. It may radiate to the groin, buttocks, or legs. The pain characteristics vary and may be deep, aching, gnawing, or throbbing It may also last for hours or days, not affected by movement. Occasionally, certain positions can be more comfortable and alleviate the symptoms;
• Pulsating abdominal mass;
• Ischemia: "cold foot" or a black or blue painful toe. This is usually the presentation when an aneurysm forms a blood cloth and it releases emboli to the lower extremities;
• Fever or weight loss if caused by inflammatory states such as vasculitis.

If ruptured, the abdominal aortic aneurysm can present with sharp abdominal pain, often radiating to the back, discoloration of the skin and mucosa, tachycardia and low blood pressure due to hypovolemic shock.

Differential diagnosis include causes of pulsatile abdominal mass and/or abdominal pain such as ruptured viscus, strangulated hernia, ruptured visceral artery aneurysms, mesenteric ischemia, acute cholecystitis, ruptured hepatobiliary cancer, acute pancreatitis, lymphoma, and diverticular abscess.

Treatment

Medical Therapy

Focus is to reduce systemic blood pressure, inhibit MMP (zinc endopeptidases that degrade the extracellular matrix in aortic aneurysms), and contain the progression of atherosclerosis:

• Beta-blockers may help in reducing the rate of expansion of the aortic aneurysm, reducing shear stress - studies have been mostly on Marfan patients and they found a low compliance with propranolol due to a significant effect on quality of life;
• Tetracyclines inhibit the MMP endopeptidases, and has been used in conditions in which MMP are overexpressed such as rheumatoid arthritis. There are studies in humans showing that doxycycline reduced the rate of expansion of aortic aneurysms. Roxithromycin, a macrolide has been also show to reduce the expansion of the aortic aneurysms.
• Statins may also be helpful due to their pleiotropic effecs, reducing the oxidative stress by blocking the reactive oxygen species on aneurysms, suppressing the NADH/NADPH oxidase system.
• Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers promotes vascular hypertrophy, cell proliferation and production of extracellular matrix. It also activates the NADH/NADPH oxidase system, both stimulating and inhibiting MMPs and degradation of extracellular matrix. There is a controversy of which class is more effective, and ongoing trials are being run to further clarify these questions.

Surgery

Indication for elective surgical treatment is commonly discussed

• The mainstay of therapy for AAA is aneurysmal repair if diameter>5.5cm or size increased>0.5cm over 6 months.
• Surgical repair is indicated in cases of TAA dissection and progressive enlargement.

Prevention

• Smoking cessation is an important measure to prevent AAA progression and rupture.

Related Chapters

• Aortic Dissection
• Thoracic Aortic Aneurysm
• Abdominal Aortic Aneurysm
• Aneurysm