A. Definition and Pathogenesis

1. Dilation of artery to a diameter at least 50% greater than normal
2. True aneurysm requires outpouching of muscle layer
3. Proposed Pathophysiology
   1. Elastin and collagen in the vessel wall form major structural determinants
   2. Elastin gives the artery recoil, and collagen allows maximal distension
   3. Destruction of elastin and collagen lead to dilatation of the artery
   4. Pulse pressure increases in the aorta going from proximal to distal
   5. This may explain the frequencies of aneurysms in the thoracic versus abdominal aorta
   6. The half life of elastin is about 70 years, which can explain increasing age incidence
   7. Hypertension accelerates the progression of aneurysmal dilatation

B. Types

1. Dissecting
   1. Dissection means break in the vessel wall through muscle layer
   2. Blood invades break and causes wall layer expansion and luman compression
   3. Result can be disasterous acute interruption of blood flow distal to dissection
   4. Major morbidity and mortality associated with aneurysm
2. Saccular: usually at vessel bifurcation, ? congenital
3. Fusiform
4. Berry: usually in central nervous system (CNS) circle of Willis
5. Hereditary / Monogenic
   1. Most common are familial intracranial aneurysms - 4X risk increase in relatives
   2. Polycystic kidney disease (PDK) [2]
   3. Osler-Weber-Rendu Syndrome
   4. TGFß receptor mutations - Loeys-Dietz Syndrome, vascular Ehlers-Danlos Syndrome [44]
   5. Ehlers-Danlos Syndrome due to collagen III mutations
   6. Marfan's Syndrome - fibrillin mutations [45]
   7. Collagen structure is disrupted in most of these familial syndromes
6. Acquired
   1. Usually in persons with hypertension and high cholesterol
   2. May occur after chest (blunt) trauma
   3. Infectious or Inflammatory
7. Inflammatory
   1. Takayasu and Giant Cell Arteritis - stenosis and dilatation usually occur together
   2. Syphilis
   3. Polychondritis
   4. Spondyloarthropathy: Reiter's Syndrome and Ankylosing Spondylitis
   5. Behcet's Syndrome, Rheumatoid Arthritis and Systemic Lupus Erythematosus
8. Majority of patients with aneurysms have comorbid conditions
   1. Hypertension
   2. Peripheral, cardiac and/or other vascular disease
   3. Type 2 Diabetes
   4. Renal insufficiency
   5. Advanced Age
   6. These conditions make therapy more difficult
9. Aneurysms may become infected, and may "shower" septic emboli [4]

C. Common Locations

1. Aorta
   1. Ascending thoracic aorta
   2. Proximal descending thoracic
   3. Abdominal (about 90% are infrarenal)
2. Carotids
3. Intracranial

D. Intracranial Aneurysms [5]
[Figure] "Circle of Willis"

1. Introduction
   1. Most commonly berry (saccular) aneurysms in the Circle of Willis
   2. In autosopy series, ~2.5% of adults will have some intracranial aneurysm
   3. In adults undergoing cerebral angiography, 0.5-1.0% will have aneurysms
   4. Usually occur at branching points of major arteries (aa) in base of brain
   5. Magnetic resonance angiography (MRA) can be used to screen for intracranial aneurysms
   6. Arteriovenous malformations (AVM) are also observed [6]
2. Location and Frequency
   1. Anterior communicating artery: 30%
   2. Posterior communicating artery: 25%
   3. Middle cerebral artery: 20%
   4. Internal carotid bifurcation: 7.5%
   5. Basilar tip: 7%
   6. Pericallosal artery: 4%
   7. Posterior inferior cerebellar artery: 3%
3. Histopathology
   1. Typical histology shows very thin or no tunica media, fragmented internal elastic lamina
   2. Intracranial arteries generally lack external elastic lamina (EEL)
   3. This may increase risk of developing aneurysm (extracranial aa typicall have EEL)
4. Etiology and Risk Factors
   1. Gentic factors play role, even in apparently "acquired" aneurysms
   2. Hereditary Disorders (<10% of all intracranial aneurysms)
   3. Familial clustering of intracranial aneurysms supports genetic contribution
   4. Cigarette smoking is consistently found to be a risk factor
   5. Hypertension may play a role in development, though data are not consistent
   6. Women at higher risk than men
   7. Aneurysms >10mm have ~11X increased risk of rupture than <10mm aneurysms [7]
   8. Rupture rate is 6% in first year for aneurysms >24mm [7]
   9. Patients with history of subarachnoid hemorrhage (SAH) have high risk of rupture of small aneurysms (<10mm) [7]
   10. Aneurysms at the tip of the basilar artery have the highest rate of rupture [7]
5. Hereditary Disorders
   1. Ehlers-Danlos Syndrome Type IV
   2. Marfan Syndrome
   3. Autosomal dominant PKD - specific PKD1 and PKD2 mutations increase risk [2]
   4. Neurofibromatosis Type I
6. Symptoms and Morbidity
   1. Subarachnoid Hemorrhage (SAH)
   2. Mass Effect - usually with very large aneurysms
   3. Cerebral ischemia - symptoms referable to areas distal to aneurysm
   4. Many aneurysms are asymptomatic (compare symptom data to autopsy findings)
7. SAH [5,18]
   1. Due to aneurysmal rupture
   2. About 27,000 cases of SAH per year in USA (1:10,000 persons annually)
   3. More common in women than men (2:1)
   4. Fatal SAH occurs in over half of cases
   5. Mean age of patients with SAH is 50 years old
   6. MRA screening of first degree relatives of patients with SAH is not recommended [8]
   7. SAH is graded 1-5 based on clinical description (asymptomatic to deep coma)
   8. Early invasive surgery or endovascular procedure improves outcomes in SAH
8. Screening
   1. Not currently recommended for general population
   2. May be useful in those with family history of aneurysms or SAH
   3. However, general screening of first degree relatives of patients with SAH using MRA is not currently recommended [8]
   4. Patients with predisposing hereditary diseases should also be screened
   5. Computerized tomographic angiography (CTA) and MRA detect intracranial aneurysms accurately except in the setting of SAH, where blood obscures aneurysm
   6. CTA or MRA are recommended initial evaluation for unruptured aneurysms
9. Primary Intracranial Aneurysm Rupture Rates at 5 Years [10]
   1. Aneurysms <7mm: Anterior Circulation: 0% ; Posterior Circulation 2.5%
   2. Aneurysms 7-12 mm: Anterior Circulation: 2.6% ; Posterior Circulation 14.5%
   3. Aneurysms 13-24 mm: Anterior Circulation: 14.5% ; Posterior Circulation 18.4%
   4. Aneurysms >24 mm: Anterior Circulation: 40% ; Posterior Circulation 50%
   5. Anterior included internal carotid, anterior communicating, anterior cerebral, middle cerebral arteries
   6. Posterior included vertebrobasilar system and posterior communicating artery
10. Treatment
    1. Neurosurgical clipping (with craniotomy) has been the most common treatment
    2. Endovascular coiling (stenting) is used as an alternative
    3. In patients with ruptured intracranial aneurysm, endovascular coiling was superior to neurosurgical clipping for 1 year disability free survival (22% risk reduction) [11]
    4. Death or dependency at 1 year after acute rupture were 23.7% for endovascular treatment and 30.6% for neurosurgical clipping [11]
    5. Endovascular coiling superior to neurosurgical clipping in patients with ruptured aneurysm who are candidates for either procedure; benefits up to at least 7 years [43]
    6. SAH should be treated with early neurosurgical clipping or endovascular coiling in young patients (Grade I and II)
    7. Mild intraoperative hypothermia did not improve the neurologic outcome after craniotomy among good-grade patients with SAH due to aneurysms [3]
11. Intracranial aneurysm rupture rate should be evaluated in context of risk or repair

1. Thoracic - ascending, descending
2. Abdominal
3. DeBakey Classification of Aortic Dissection
   1. Type 1: entire aorta affected
   2. Type 2: ascending aorta affected
   3. Type 3: descending aorta affected
4. Svensson Classification of Aortic Dissection
   1. Class 1: classic dissection with true and false lumen
   2. Class 2: intramural hematoma or hemorrhage
   3. Class 3: subtle dissection without hematoma
   4. Class 4: atherosclerotic penetrating ulcer
   5. Class 5: iatrogenic or traumatic dissection

B. Thoracic [13]

1. Ascending (Type A, DeBakey 1 and 2)
   1. About 60% of aortic dissections occur here
   2. Requires cardiopulmonary bypass for correction
   3. Danger of dissection into coronary artery outflow tracts
   4. Marfan's Syndrome is most common predisposing factor
2. Descending (Type B, Debakey 3)
   1. Usually correctable
   2. Complication is injury to spinal artery (artery of Adamkawicz)
3. Causes
   1. Hypertension
   2. Inflammatory: Aortitis (Takayatsu or Giant Cell), polychondritis, Behcet's, Kawasaki's
   3. Degenerative: atherosclerotic, cystic medial degeneration
   4. Infection: syphilis, bacterial, fungal
   5. Developmental: Marfan Syndrome, Ehlers Danlos Syndrome (Type IV), Loeys-Dietz Syndrome
   6. Trauma: blunt and penetrating
   7. Thoracic aortic aneurysms are as common in men as in women [14]
   8. Postpartum: rare but well described [15]
4. Symptoms and Signs of Dissection [16]
   1. Many patients are asymptomatic at presentation
   2. Widened mediastinum on chest radiogrphy ~80% of cases is most sensitive screening
   3. Sudden, knife-like substernal chest pain radiating to back
   4. Diaphoresis
   5. Tachycardia and Hypertension
   6. Unequal radial pulses
   7. Widened mediastinum on chest radiograph
   8. Local Effects: hoarseness, stridor, dysphagia, dyspnea, edema (SVC compression)
   9. Focal neurologic defects
   10. Syncope, especially with cardiac tamponade or stroke present (proximal dissection) [17]
   11. Elderly women are at increased risk for thoracic aneurysmal rupture than men [14]
   12. Clinical exam is insufficiently sensitive to rule out dissecting thoracic aneurysm [16]
5. Diagnosis of Thoracic Aortic Dissection [13]
   1. Gold standard is angiogram (aortography) - sensitivity 90%, specificity 95%
   2. Emergency situations: ultrafast CT or transesophageal echocardiography
   3. Ultrafast CT Scans now availble with increased sensitivity (~90%), specificity (~95%)
   4. MRI generally recommended for all hemodynamically stable patients
   5. Transesophageal echocardiography recommended for all unstable patients
   6. Chest radiograph (CXR) shows widened mediastinum in ~65% of cases [19]
   7. Elective surgery recommended for persons with >5-5.5cm thoracic aneurysm
6. Treatment of Dissection
   1. Overall in hospital mortality <30% (Type A higher risk)
   2. Type A dissections need immediate replacement (high risk fatal rupture)
   3. Emergent use of ß-blockers can often stabilize Type B dissections
   4. Unclear if emergent surgery is required for most Type B dissections
   5. Most Type B dissections are therefore initially treated with medications only
   6. Treatment of certain patients with thoracic aortic dissection with endoluminal stent- graft placement appears safe and effective [20]
7. Complications of Surgery
   1. Each of these organ systems should be evaluated prior to elective surgery
   2. Myocardial infarction
   3. Respiratory failure - much higher in smokers and in persons with COPD
   4. Renal failure - highest risk in patients with pre-existing renal disease
   5. Stroke - evaluate carotids prior to operation (consider endarterectomy if appropriate)
8. Long term survival on leaving hospital is 80% at 5 years and 40% at 10 years
9. Risk of rupture after 5 years [14]
   1. Aneurysms < 4cm 0%
   2. Aneurysms 4-6.9 cm 16%
   3. Aneurysms > 6 cm 31%
10. Prophylactic repair of aortic root should be considered in patients with Marfan's Syndrome and an aortic root diameter of 6.5cm or more [21]

C. Abdominal (AAA) [22]

1. Introduction
   1. Defined as a permanent localized artery dilation leading to >50% increased diameter
   2. AAA 3cm or greater is a risk factor for cardiovascular disease and death in >64 year olds [23]
   3. Screening for AAA is recommended in men 65-75 years old who have ever smoked [41] or have never smoked; benefits of screening sustained for at least 7 years [12]
   4. Cause 1.3% of deaths in men >65 years of age in developed nations
   5. ~15,000 deaths per year from AAA rupture in USA
   6. Most AAA are asymptomatic until rupture
   7. 5-10% of AAA are inflammatory AAA with minimal atherosclerotic component [9]
   8. Repair of large (>5.5cm male; >5.0cm female) or syptomatic AAA strongly recommended
2. Risk Factors For Common AAA
   1. Age - most patients >60 years old
   2. Prevalence of >3cm AAA in >64 year olds is 8.8% [23]
   3. Smoking - strongest risk factor in one large study [24]
   4. Hypercholesterolemia
   5. Hypertension
   6. Any other atherosclerotic disease
   7. Male Sex - 75-80% of AAA patients are male
   8. Non-black race may also be risk factors
3. Pathophysiology of Atherosclerotic AAA
   1. Degradation of elastin fibers and medial shrinkage underlying areas of atherosclerosis
   2. Reduction in extracellular matrix including collagen and elastin leads to wall weakness
   3. Inflammatory infiltrate with activation of proteases and cytokines found
   4. Neovascularization in arterial wall occurs, probably further weakening it
   5. Risk factors contribute to initial damage and progressive disease
   6. Fundamental etiology not yet clear
4. Inflammatory AAA [9]
   1. Usually symptomatic with back or abdominal pain
   2. Typically younger than atherosclerotic AAA patients
   3. Elevated erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP)
   4. Marked thickening of abdominal wall, retroperitoneal fibrosis, adherance to adjacent organs
   5. Likely due to immune response specific to vessel wall
   6. Smoking is a major risk factor
   7. Response to glucocorticoids and/or immunosuppressive agents
   8. Less likely to rupture than atherosclerotic AAA, but >5.5cm aneurysms should be repaired
5. Risk of Dissection or Perforation [25]
   1. Increases significantly when size >5.5 cm
   2. Estimated 1 year rupture risk is 19-30% for 6.5-6.9cm AAA; >30% for 7.0cm or larger
   3. Mortality due to rupture of AAA is 80-90% overall
   4. Of 25% of patients with ruptured AAA who have emergency surgery, about half die
   5. High serum levels of MMP-9 (matrix metalloproteinase 9)
   6. Positive PET scan corresponds to marked inflammation in AAA and is risk
   7. Open surgery or endovascular repair is strongly recommended in high risk patients
6. Symptoms of Dissection
   1. Knifelike pain radiating to back
   2. Hypoperfusion with acidosis, decreased distal pulses
   3. Acute tubular necrosis due to renal hypoperfusion
7. Must rule out dissection in any symptomatic patient with known aneurysm
8. Detection of (Non-Dissecting) Aneurysms [26,27]
   1. Routine screening recommended only in men age 65-75 years who have ever smoked; no recommendation for or against in men 65-75 years who have never smoked [39,41]
   2. Screening is not recommended in asympatomic women
   3. Prevalance in men >64 years old is ~5% (aorta >3cm diameter)
   4. Single ultrasound in high risk patients and in all men >65 years of age [28]
   5. Ultrasound screening men over age 65 reduced AAA rupture rate by ~50%
   6. Followup ultrasound frequency has been reduced based on careful natural history
   7. Size <3-4cm - followup ultrasound at 6 months then annually
   8. Size 4-4.9cm - followup ultrasound every 3-6 months
   9. Size 5.0-5.4cm - followup ultrasound every 3 (or 6) months [29]
   10. Size >5.4cm - recommend intervention
   11. Surgery considered for only for size >5.5cm, expansion >1cm/year, symptoms
   12. Surgery strongly considered for women with >5.0cm AAA [22]
9. Physical Examination (PE) is Unreliable [22,30,31]
   1. PE will miss ~20% of aneurysms >5.4cm [30]
   2. PE has a positive predictive value of ~43%; lower in obese patients [30]
   3. PE has sensitivities of 29% for 3-3.9cm, 50% for 4.0-4.9cm, and 76% for >5cm AAA [30]
   4. PE has a sensitivity as low as 49% (specificity 56-89%) [31]
   5. Use of PE to rule out AAA is not adequate care
   6. Screening men 65-74 years old with ultrasound reduces AAA specific mortality ~45% [12]
   7. All men 65-74 years old should be screened for AAA [12]
10. Treatment of Small (<5.5cm) AAA [22,29,35]
    1. Surgery for <5.5cm AAA increased costs without survival benefit in men [26,32,35]
    2. Immediate repair of 4.5-5.4cm AAA had no clinical benefit and higher costs over surveillance [33,35]
    3. No long term differences in survival for immediate repair of 4.5-5.5cm AAA compared with suveillance [34]
    4. Recommend surveillance every 3-6 months until size reaches 5.5cm
    5. Open surgery or endovascular procedure recommended only after size >5.4cm
11. Summary of Endovascular versus Surgical AAA Repair Results [47]
    1. Open repair was previous standard procedure
    2. Endovascular repair associated with lower initial mortality rate but higher need for reintervention
    3. Long term outcomes with endovascular repair not clearly superior to open repair
    4. Specific studies discussed below

D. Treatment

1. Acute Dissection
   1. This is a surgical emergency with very high mortality
   2. In emergency situation, intravenous medications should be given prior to surgery
   3. Mainstay of medical therapy are ß-adrenergic blockers and nitrates
   4. ß-Blockers - intravenous metoprolol or esmolol
   5. Labetolol, a ß-blocker with alpha-adrenergic blockade also, is often very effective
   6. Nitrates - intravenous nitroglycerin or nitroprusside
2. Medical Management - Chronic Disease
   1. ß-Blockers - oral metoprolol or atenolol or older agent
   2. Nitrates - generally for acute dissection or symptoms, unclear efficacy chronically
   3. Angiotensin converting enzyme (ACE) inhibitors associated with ~18% reduced risk of aortic aneurysm rupture versus other antihypertensives including AT2 blockers [1]
   4. High dose glucocorticoids for Takayasu and Giant Cell Arteritis
3. Endovascular Stents [36]
   1. Expanding wire stents with Dacron Graft covering
   2. Placed with minimal difficulty from femoral artery
   3. Aneurysmal area outside of stent lumin becomes clotted within months in >90% of cases
   4. Well tolerated, no episodes of embolism
4. Elective (Prophylactic) Surgical Correction [26,35]
   1. Based on size; most concerning cases are >5.4cm
   2. Early surgical intervention for <5.5cm increased costs [32] without survival benefit [35]
   3. Most patients are older with comorbid conditions, thus increasing surgical risk
   4. For AAA, open surgery is associated with ~5% mortality risk [15,36]
   5. Balance between risks and benefits of surgery
5. Endovascular Versus Open Surgical AAA Repair Study [46]
   1. Endovascular repair of AAA associated with lower short-term rates of death and complications
   2. Short-term mortality absolute differences of 2-8% versus open repair
   3. Higher mortality benefit in older persons (age >84 years)
   4. Reinterventions higher with endovascular than open repairs (9% versus 1.7%)
   5. Rupture at 4 years more likely with endovascular (1.8%) than open (0.5%) repairs
   6. Hospitalization for bowel obstruction or abdominal wall hernia higher with open (14.2%) than endovascular (8.1%) repairs
   7. Overall, endovascular repairs are associated with better outcomes in most patients
6. Other Studies of Endovascular Versus Open Surgical Repair for AAA
   1. Endovascular aneurysm repair (EVAR) with stent-grafts lower mortality than open repir [35]
   2. EVAR for >5.5cm AAA had 67% lower 30-day mortality (1.7% versus 4.7%) versus open repair in patients >60 years old (mean age 74) [35,36]
   3. EVAR associated with 9.8% secondary interventions versus 5.8% with open surgery [36]
   4. EVAR offered no overall mortality benefit and had greater complications and repeat interventions but had 3% better AAA assocatied survival [37,38]
   5. In long term study with followup 2 years, elective EVAR and open repairs of AAA >5.0cm showed similar morbidity and mortality [40]
   6. In patients who are not candidates for open repair, EVAR lead to a 9% 30 day mortality and no overall benefit on overall mortality at 4 years versus no intervention [42]
   7. Patients who are not candidates for open AAA are not benefited by EVAR [35,42]

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