Aneurysms of the Aorta and Iliac Arteries

Screening

There have been several large ultrasound-based screening programs to detect aortic aneurysms that included over 200,000 persons. Aortic aneurysms were found in 4.9% to 7.6% of ultrasound-screened British men older than 65 years, but only in 1.3% of women. Similar data have been reported from Denmark, Australia, the Netherlands, and Norway. Although most screen-detected aneurysms are small (<4 cm), screening has been shown to decrease aneurysm rupture rate, decrease the number of emergency aneurysm operations and, most importantly, reduce aneurysm-related mortality in men. A small reduction in all-cause mortality has also been attributed to large screening programs. Screening has also been shown to be cost-effective, with cost of $10,754 per quality-adjusted life year (QALY), in 2001 dollars. This compares favorably with a value of $9500 for a three-vessel coronary bypass. Because it is impractical and financially unfeasible to screen all adults, screening programs have been based on known aneurysm-related risk factors. Cigarette smoking is highly correlated with the presence of aortic aneurysms, with an 8 : 1 preponderance of aneurysms in smokers compared with nonsmokers. The relationship between smoking and aortic aneurysm is linear and is several times stronger than the relationship between smoking and peripheral arterial occlusive disease. Aortic aneurysms have been detected by ultrasound screening in 8.8% of male smokers older than 65 years who have peripheral arterial vascular occlusive disease. There is also a well-recognized familial component to aortic aneurysms, present in 15% to 25% of first-degree relatives. Documented coronary artery disease is associated with a greater than twofold increase in the prevalence of aortic aneurysms and future AAA-related events. The current SVS Guidelines recommend ultrasound screening for all men 65 years of age or older and for women 65 years and older who have smoked or have a family history of AAA. These recommendations are somewhat more inclusive than those of the United States Preventive Services Task Force, which did not include women without a family history or men who had never smoked, although it subsequently included men older than 65 years of age who never smoked. Their recommendations led to Medicare offering one ultrasound screening to men 65 to 75 years of age who have smoked at least 100 cigarettes and in both men and women of the same age with a family history of aneurysm. It is reasonable to also recommend screening for all first-degree relatives of any patient with an AAA diagnosis, based on the known genetic relationships. Unfortunately, only 60% to 65% of those eligible have been screened in the large screening programs, and there has been no follow-up on about 35% of the patients whose aneurysms were first detected by the screening.

There has been considerable interest in the use of biomarkers as a means of identifying patients with or prone to develop aneurysms. Increased levels of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), alpha 1-anti-trypsin, IL-6, D-dimer, apolipoprotein A, C-reactive protein (CRP), and others have been found in the blood of patients with aneurysms, but so far none have sufficient sensitivity or specificity to be clinically useful. It is also hoped that biomarkers will be able to identify aneurysms that are likely to grow rapidly or rupture.

Pathogenesis of Aortic Aneurysms

More than 90% of AAAs are associated with atherosclerosis, which, for many decades was considered the primary cause. There are other well-known but uncommon causes of aneurysm of the abdominal aorta, including cystic medial necrosis, dissection, Ehlers-Danlos syndrome, HIV, and syphilis. Aneurysms and occlusive atherosclerosis share most of the same risk factors (e.g., aging, tobacco use, hypertension, male gender, hypercholesterolemia) and atherosclerosis is uniformly present in the wall of aortic aneurysms, but it is believed that several other factors, in addition to atherosclerosis, are involved in aneurysm development. One observation that casts doubt on atherosclerosis being the sole or primary cause of aortic aneurysms is that most patients with aneurysmal disease do not have occlusive vascular disease involving the aorto-ilio-femoral segments. It has been estimated that no more than 25% of aortic aneurysms are associated with significant arterial occlusive disease. Another factor is the negative association of obesity and diabetes with aneurysms (“diabetic paradox”) in contrast to its strong relationship with occlusive vascular disease. This may be an effect of taking the oral hypoglycemic agent metformin. In addition, induction of aneurysms in animals fed an atherogenic diet has not been predictable, although regression of experimental atheromas has led to aneurysm formation in monkeys. Cigarette smoking is the only known modifiable risk factor associated with development, expansion, and rupture of AAA as well as being a causative association in an in vivo mouse aneurysm model. These observations have led to the concept that atherosclerosis is either a coincidental or a facilitating process, rather than the primary cause of AAA and that other biological processes are responsible for the destruction of the media of the aortic wall that characterizes aneurysms.

Mature elastin and collagen are the major structural proteins responsible for the integrity of the aortic wall. Collagen composes approximately 25% of the wall of an atherosclerotic aorta, but only 6% to 18% of an aneurysmal aortic wall. Biochemical studies have shown decreased quantities of both elastin and collagen, but an increased ratio of collagen to elastin in the walls of aneurysms. Elastin fragmentation is the initial structural event in aneurysm formation , and elastin depletion is complete early in aneurysm development. This has been correlated with the histopathologic features of a thin, dilated wall with fragmentation of elastin in the media, its replacement by a much thinner layer of collagen (mostly types I and III), loss of smooth muscle cells, and remodeling of the extracellular matrix. This thinned wall usually contains calcium and atherosclerotic lesions, rendering the wall brittle. Laminated thrombus lines the lumen, often eccentrically, resulting in a nearly normal flow channel ( Figs. 41.1 to 41.3 ; see color plate for Fig. 41.3C ), but possibly making the inner layers of the aortic wall relatively hypoxic. Aneurysms elongate as they dilate, causing them to become bowed and tortuous. It is believed that the weakening and fragmentation of the elastic lamellae is what permits vessels to lengthen excessively and become tortuous. As a result, the failure of elastin to provide sufficient retractive force in both the circumferential and longitudinal directions allows for increased aneurysm diameter and length, respectively.

The aortic wall is composed of lamellar units that consist of collagen (mainly types I and III) and elastin, as well as vascular smooth muscle cells. There are more lamellar units in the thoracic (58) than in the abdominal aorta (40), and there is a further abrupt decrease below the renal arteries (26). This structural factor is believed to have a role in the predilection for aneurysms to develop in the terminal portion of the aorta, combining with the fragmentation of the elastin and the overall thinning of the wall to contribute to its weakening. The large loss of elastin is one of the most consistent biochemical and histochemical findings in human aortic aneurysms. A chronic inflammatory cell infiltrate is also prominent in the media and adventitia. A key unresolved question is what triggers this inflammatory reaction and the subsequent chain of events. Many theories have been proposed, including a reaction to mural atherosclerotic plaque or a latent infectious process (e.g., Chlamydia pneumoniae or oral flora).

These well-established histologic features have prompted a search for nonatherogenic mechanisms that disrupt collagen and elastin in the aortic wall. Several investigators have found excessive (upregulated) collagenase (MMP)-1, -2, -3 activity in the wall of aneurysmal aortas, and others have found increased elastase (MMP-9) activity. These are members of a family of MMPs that are believed to have an essential role in aneurysm formation. MMP-9 is found in abundance in medial smooth muscle cells as well as in inflammatory cells, and increased levels have been found in both the aortic wall and serum in up to 50% of patients with aortic aneurysms, but not in those with aortic occlusive disease. These increased serum levels decline to normal after aortic aneurysm repair. Increased activity of other matrix proteases in aneurysmal aortic tissue has also been reported, as has an increased leukocyte-derived elastase in the blood of smokers with aneurysms. Deficiencies in antiproteases, such as several tissue inhibitors of metalloprotease and α ₁ -antitrypsin, have also been described. α ₁ -Antitrypsin is one of the most important natural antagonists to elastase and is responsible for the association between chronic obstructive pulmonary disease (emphysema patients with reduced α ₁ -antitrypsin levels) and increased prevalence of aortic aneurysm and increased rate of rupture. Another factor is the chronic inflammatory infiltrate that occurs in the outer layers of aneurysmal aortas, consisting of macrophages and T and B lymphocytes. There are also increased levels of cytokines and immunoglobulin (IgG, and IgM) that are not seen in association with aging or with occlusive aortic lesions. These findings may be the explanation for the increased levels of serum inflammatory markers, such as IL-6, C-reactive protein, neutrophil elastase, and others found in patients with aneurysms but not in those with occlusive disease. These inflammatory cells and cytokines are believed to interact in some as yet unexplained way with the connective tissue cells and matrix proteins in the pathogenesis of aneurysms. Most of the research has focused on the aortic media, but the role of the adventitia in aneurysm formation has recently received some interest. Normally, the adventitia, the strongest layer of the aortic wall, is thought to limit maximal aortic diameter. Topical application of elastase to the adventitia leads to aneurysm formation in experimental animals, solely as a result of elastin degradation. Studies such as these have led to speculation about a possible adventitial role in aneurysm formation.

Although not all the studies are conclusive, it is generally agreed that an imbalance between aortic wall proteases and antiproteases is an important factor in the pathogenesis of human abdominal aortic aneurysms. This imbalance causes degradation of the extracellular matrix and loss of structural integrity of the aortic wall, and it is largely responsible for the extensive remodeling of the aorta that occurs during aneurysm formation.

There is also considerable evidence that there is a genetic susceptibility to aortic aneurysm formation. Several investigators have discovered genetically linked enzyme deficiencies that are associated with aneurysms in experimental animals. For example, Tilson and Seashore showed that a deficiency in the copper-containing enzyme lysyl oxidase is the cause of aortic aneurysms in a strain of mice. Lysyl oxidase is important in collagen and elastin cross-linking, and this enzyme defect is sex chromosome linked. In addition, several reports of familial clustering of abdominal aneurysms support the notion of a genetic predisposition to this disease. Approximately 20% to 29% of patients with abdominal aneurysms have a first- or second-degree relative with the same condition. The age- and sex-adjusted increased risk of having an aneurysm is 11.6 times, according to one report. Female siblings are at particularly high risk in some studies, while males are more affected in others. The genetic pattern of increased susceptibility is yet to be completely worked out. Available evidence supports both X chromosome–linked and autosomal dominant patterns of inheritance. Among the mutant suspect genes are the type III collagen gene (COL3A1) and the fibrillin gene (on chromosome 15). Variations on chromosomes 4 and 19, as well as many other gene loci, have been identified in various patients and experimental animals. Many of these control the production of enzymes, enzyme inhibitors, cytokines, cell regulators, and signaling pathways. Each of these findings provides tantalizing clues; it seems likely that multiple gene variations will ultimately be linked to aortic aneurysm formation. So-called familial aneurysms do not appear to be anatomically or clinically distinguishable from those with no familial pattern, except that they develop earlier in life, have a decreased male-to-female ratio of 2 : 1, show more rapid growth, and appear to have an increased risk of rupture. In addition, there is an increased likelihood of developing aneurysmal disease proximal to the infrarenal aorta and an increased incidence of bilateral common iliac aneurysms. The clinical implications of these genetic studies, as limited as they are, strongly support the screening of all first-degree relatives of patients with abdominal aortic aneurysms.

Hemodynamic (mechanical) factors may also contribute to aneurysm development. The abdominal aorta is subjected to large pulsatile stresses as a result of its tapering geometry, relatively increased stiffness distally, and the reflected pressure waves from the peripheral vessels. Reductions in the number of elastic lamellae and the virtual lack of vasa vasorum in the media of the distal abdominal aorta may also be factors favoring aneurysmal formation in this segment of the arterial tree, making the aorta structurally less capable of handling the increased hemodynamic stresses that occur there.

In summary, contemporary concepts of aortic aneurysm formation and growth incorporate two distinctly different pathophysiologic processes: (1) elastin fragmentation as the critical structural defect required for initiation of aneurysm formation; and (2) collagen deposition, degradation, and remodeling governing aneurysm enlargement . These two processes result in a complex remodeling of the aortic wall. The other factors described previously, including inflammation, smoking, biomechanical wall stress, and genetic predisposition, interact with these processes to produce the clinical features that are so well recognized. Clearly, aortic aneurysm formation is far more complex than passive arterial dilation because of age. Therefore, these aneurysms should be referred to as degenerative or nonspecific rather than atherosclerotic aneurysms . They account for more than 90% of aneurysms involving the abdominal aorta.

Aneurysm Enlargement

Once an aneurysm develops, it tends to enlarge gradually yet progressively. The enlargement rate has been well studied and averages 0.2 to 0.3 cm/year for small aneurysms of 3 to 5 cm diameter to 0.3 to 0.5 cm/year for larger aneurysms. In general, large aneurysms grow at a faster rate than smaller aneurysms. Unfortunately the growth rate is nonlinear, making it impossible to predict the rate of enlargement of any individual aneurysm. Some aneurysms remain the same size for many years, whereas others enlarge rapidly. Factors associated with more rapid growth include larger initial size, hypertension, increased pulse pressure, smoking, and cardiac or renal transplant. Smoking has been shown to increase the rate of enlargement by 35% and is the most important modifiable factor controlling aneurysm growth. Interestingly, diabetes mellitus does not appear to be a factor in aneurysm development or growth. Once an aneurysm develops, regardless of the cause, its enlargement is governed by physical principles, especially Laplace's law, which describes the relationship between the tangential stress (T) tending to disrupt the wall of a sphere, the radius (R) , and the transmural pressure (P) : T = PR . Thus, for a given transmural pressure, the wall tension is proportional to the radius. Once dilatation of the aorta has started, Laplace's law explains why aortic enlargement progresses. It also explains why large aneurysms are more prone to rupture than small ones and why hypertension and pulse pressure are important risk factors for rupture. Using Laplace's law, tripling the aortic radius from 2 to 6 cm results in a more than threefold increase in wall tension, and when this tension exceeds the tensile strength of the collagen in the aortic wall, disruption occurs. Although Laplace's law has long been used as the sole explanation for aneurysm enlargement and rupture, it is at best an imperfect explanation because it was derived for perfect cylinders and spheres, and aortic aneurysms do not have uniform shape; it also does not consider the wall thickness, which can be highly variable. In addition, it does not explain why all aneurysms of the same diameter do not rupture or why some small aneurysms rupture and some large ones do not.

Aneurysms usually do not rupture at the point of greatest diameter, as would be predicted by Laplace's law. Recent studies using finite element analysis of computed tomography (CT) scan–derived data have measured peak wall stress and strain patterns and have shown that, in addition to decreased tensile strength, aneurysm walls have increased wall stress, an asymmetrical shape, and a complex radius (actually many radii) of curvature. Wall stress varies with shape and thickness, and the points of maximal stress do not necessarily coincide with the location of maximal diameter. They do, however, correspond closely with the location of rupture. Wall stress data might also explain why eccentric and saccular aneurysms have a greater risk of rupture than those with smooth fusiform shapes. Inclusion of wall thickness in the analyses is reported to improve the predictability of these wall stress measurements on aneurysm expansion and rupture. The influence of calcification and mural thrombus on stress patterns is uncertain but may be important. These stress analyses have been validated by several investigators but have not become widely used clinically for predicting risk of aneurysm rupture.

There has been wide interest in pharmacotherapy to reduce the rate of enlargement of small aortic aneurysms and thereby reduce rupture risk. β-Blockers have been studied in several randomized clinical trials, with disappointing negative results. Similar results have been found with doxycycline, roxithromycin, and angiotensin-converting enzyme (ACE) inhibitors. Both ACE inhibitors and angiotensin receptor antagonists (ARB) have been successful in reducing aneurysm growth in mice but not consistently in humans. Statins, however, in nonrandomized trials, have been found to reduce expansion rate and rupture risk. Unfortunately most of the studies with these agents were not well designed or had insufficient statistical power to permit definitive conclusions, but it seems prudent for patients with small aortic aneurysms to be taking a statin drug for this purpose.

Clinical Manifestations

Seventy to 75% of all infrarenal AAAs are asymptomatic when first detected. Detection of large aneurysms can occur during a routine physical examination, but overall only 50% are palpable. Diagnosis most often occurs during an imaging study performed for some other reason (e.g., upper gastrointestinal series, barium enema, intravenous pyelography, lumbosacral spine radiography, or abdominal CT or ultrasound examination). Occasionally, an aneurysm is first discovered during an unrelated abdominal operation.

AAAs can cause acute symptoms as a result of rupture or expansion, pressure on adjacent structures, embolization, dissection, or thrombosis. Chronic symptoms can be caused by compression of adjacent bowel leading to early satiety and even nausea and vomiting. Because the duodenum crosses in front of the aorta, it is the part of the bowel most frequently compressed. Virtually any type of abdominal, flank, or back pain can be aneurysm-related. This fact often leads to a delay in diagnosis. Chronic abdominal or back pain is the most common symptom, occurring in up to one-third of patients, but is not specific. Large aneurysms can actually erode the spine and cause severe back pain, even in the absence of rupture.

The abrupt onset of severe pain in the back, flank, or abdomen is characteristic of aneurysmal rupture or acute expansion. It is uncertain why pain is produced by an expanding but unruptured (intact) aneurysm. The best explanation is sudden stretching of the layers of the aortic wall, with pressure on adjacent somatic sensory nerves or overlying peritoneum. Tenderness of the palpated aneurysm suggests that abdominal symptoms are arising from the aneurysm, although tenderness by itself is not a reliable indicator of impending rupture. In most surgical series, symptomatic but unruptured aneurysms account for 6% to nearly 40% of cases (average of five series totaling 311 patients: 13.7%). The increased morbidity and mortality for urgent operations on unruptured aneurysms is likely due to lack of patient optimization. The timing of surgical treatment is made more difficult in these cases. A good-quality CT scan may not show any sign of rupture but cannot predict when rupture might subsequently occur.

Ruptured aneurysms constitute between 20% and 25% of most series. The presence of an aneurysm is known in 25% to 33% of patients before rupture occurs. The nature of symptoms and their time course vary depending on the nature of the rupture. Small tears of the aneurysmal sac can result in a small leak confined to the retroperitoneum that temporarily seals, with minimal blood loss; this is usually followed within a few hours by frank rupture, which produces a catastrophic medical emergency. Rupture most frequently occurs through the posterolateral aortic wall on the left side into the retroperitoneal space; less commonly, it occurs through the anterior wall into the free peritoneal cavity. The incidence of this latter type of rupture is higher than indicated in most surgical series, because most of these patients die before reaching the hospital. Rarely, an AAA ruptures into the inferior vena cava or one of the iliac veins, producing an aortocaval (or aortoiliac) fistula , or it ruptures into the gastrointestinal tract, producing a primary aortoenteric fistula .

The classic clinical manifestations of ruptured aortic aneurysm are severe mid or diffuse abdominal pain, shock, and a palpable, pulsatile abdominal mass. The pain may be more prominent in the back or flank, or it may radiate into the groin or thigh. Because the most frequent site of rupture is the left posterolateral wall, pain is more commonly felt on the left side. The pain tends to be severe and steady. The severity of the shock varies from mild to profound, depending on the amount of blood loss. Many patients feel light-headed, sweaty, or nauseated. Abdominal distention is common, often preventing palpation of the expected pulsatile abdominal mass. The duration of symptoms can vary from a few minutes to more than 24 hours. Although aneurysm rupture is usually an acute catastrophic event, it can be contained for prolonged periods. These chronic ruptures have masqueraded as radicular compression, symptomatic inguinal hernia, femoral neuropathy, and even obstructive jaundice. It is thought that chronic, contained ruptures eventually progress to free ruptures, and they should be treated surgically on an urgent basis.

The pain of an expanding but intact aneurysm may closely mimic that of a ruptured one. It tends to be severe, constant, and unaffected by position. The signs of hypovolemia are absent because hypotension and shock do not usually occur in the absence of actual rupture.

The diverse and nonspecific nature of the pain caused by expanding and leaking aneurysms all too often leads to errors in diagnosis, delays in finally establishing the correct diagnosis, and catastrophic rupture in the midst of a diagnostic procedure. Occasionally, a patient with a contained rupture arrives in the emergency room with angina pectoris from blood loss and reflex tachycardia and is rapidly transported to a coronary care unit without the abdominal examination that would identify the true cause of the chest pain. A similar situation can occur with rupture into the vena cava, with the resulting aortocaval fistula presenting as congestive heart failure. Most diagnostic errors such as these are due to failure to palpate the expansile, pulsatile epigastric mass, or failure to consider ruptured aneurysm as a possibility.

Diagnostic Methods

Aortic aneurysms lie against the thoracolumbar spine and project anteriorly in the midline in the epigastrium. Elongated tortuous aneurysms may be located to the right or left or even in the lower quadrants. Except in thin patients, an abdominal aortic aneurysm must be approximately 5 cm in diameter to be detectable on a routine physical examination. As a result, aneurysms are seldom palpated in obese patients unless they are large. The reported accuracy in establishing the correct diagnosis by physical examination alone ranges from 30% to 90% (average 55%), depending on aneurysm size, body habitus, and physician skill. Obesity, ascites, and lack of patient cooperation can impair aneurysmal detection by physical examination. Conversely, tumors or cystic lesions adjacent to the aorta, unusual aortic tortuosity, and excessive lumbar lordosis can all lead to a diagnosis of abdominal aortic aneurysm when none is present. The expansile nature of a pulsatile mass is a key element in deciding whether it is an aneurysm or a transmitted pulsation from an adjacent tumor. However, even when an aneurysm is palpable, determination of its size by palpation is imprecise.

Although physical examination detects some large aneurysms, it is inadequate for diagnosis and planning treatment, so more objective methods are necessary in all AAA patients. Size determination is especially important because it is currently the most important predictor of rupture risk and is usually the basis of management decisions. Plain abdominal and lateral spine radiographs can establish the diagnosis of 67% to 75% of abdominal aortic aneurysms by detecting linear calcification of the aortic wall (see Fig. 41.1 ). Unfortunately, accurate determination of maximal aortic size is possible in only two-thirds of these cases.

Imaging Modalities

Several imaging modalities are widely available to establish the presence of an aortic aneurysm and accurately determine its size. These modalities include ultrasound, CT, and magnetic resonance imaging (MRI).

Real-time B-mode ultrasound is available in most hospitals and clinics and is the imaging method used in the large aneurysm screening and surveillance studies. It uses no ionizing radiation, provides physiologic data as well as structural detail of vessel walls and atherosclerotic plaques, and can accurately measure aneurysm size in longitudinal and cross-sectional directions (i.e., it is three dimensional [3D]; see Fig. 41.2 ). Compared with intraoperative aneurysm measurements, ultrasonic measurements are accurate to within ±5 mm. Many studies have documented the ability of ultrasound to establish the diagnosis (100% sensitivity, 95% to 99% specificity) and accurately determine the size of abdominal and peripheral aneurysms. Transcutaneous ultrasound is not as useful for imaging the thoracic or suprarenal aorta because of the overlying air-containing lung and viscera. Similarly, it is less reliable in defining the relationship between abdominal aortic aneurysms and the renal arteries, although recent developments in 3D ultrasound may improve upon this limitation. Because ultrasonography can obtain images in longitudinal, transverse, and oblique projections, it can be especially helpful in differentiating a tortuous aorta from an aneurysm. Ultrasound imaging is degraded by obesity, intestinal gas, or barium in the bowel. The overlying bowel gas also interferes with evaluation of the iliac arteries. The major advantages of ultrasound are its wide availability, painlessness, absence of known side effects, lack of ionizing radiation, relatively low cost, and ability to image vessels in multiple planes. Most vascular surgery trainees are experienced in performing and interpreting ultrasound studies, which can be helpful in evaluating patients with acute symptoms due to suspected rupture. These factors make ultrasonography the modality of choice for the initial evaluation of pulsatile abdominal or peripheral masses and for follow-up surveillance of aneurysms to determine increases in size and for screening. In addition, the portability of ultrasound machines is advantageous for the emergency department, where it can quickly establish the presence of an aneurysm in most cases, although it is not nearly as accurate (approximately 50%) in demonstrating rupture.

CT uses ionizing radiation to obtain cross-sectional images of the aorta and other body structures. These images provide detailed information about the size of the entire aorta, including the thoracic portion, so that the extent and size of an aneurysm can be accurately measured. Modern multidetector CT scanners using helical (spiral) technology possess sufficient spatial resolution to allow precise identification of the celiac, superior mesenteric, renal, and iliac arteries and their branches, as well as their relationship to the aneurysm and adjacent organs. Major venous structures, including anomalies, can also be identified. The administration of intravenous contrast allows evaluation of the size of the aortic lumen, the location and status of aortic branch vessels, the amount and location of mural thrombus, and in cases of dissection, differentiation of the true lumen from the false lumen (see Fig. 41.3 ; see color plate for Fig. 41.3C ). Contrast-enhanced CT scans are also useful for assessing the retroperitoneum and identifying retroperitoneal hematoma (aneurysmal rupture), renal abnormalities, and the periaortic fibrosis associated with inflammatory aneurysms ( Fig. 41.4 ). Metallic surgical clips and orthopedic hardware create artifacts that can interfere with CT interpretation. CT provides more information about other abdominal and retroperitoneal structures than ultrasound and has emerged as the most frequently used technique to image the abdominal aorta and its branches. One of its most helpful features is the ability to define the often complex relationship of an aneurysm to the renal and other aortic branch vessels and demonstrate their patency. Multiplanar reconstructions are particularly useful in clarifying the true anatomic relationships when there is anterior or lateral displacement of the aorta. Scan times are extremely short, and slices as thin as 1.5 to 2.0 mm can be obtained, allowing 3D reconstruction of the overlapping cross-sectional images, producing a CT angiogram (CTA) (see Fig. 41.3C ). The reconstructed 3D images can be rotated in space and viewed from any projection. CT scans require significant radiation exposure and a relatively large volume of intravenously administered contrast material, which limits their usefulness in the presence of severe renal functional impairment. Non–contrast-enhanced images can be used for determining aortic size and the degree and location of calcification in the aorta and its branch vessels. Overall, CT scans are currently the most useful imaging method for evaluating the abdominal aorta and have nearly obviated the need for catheter aortography in the evaluation of aneurysmal disease. It is also essential in the process of determining an aneurysm's suitability and device sizing for endograft treatment.

MRI is also a useful modality for the evaluation of aortic disease ( Fig. 41.5 ). MRI uses pulsed radiofrequency energy in a strong magnetic field to produce images in longitudinal, transverse, and coronal planes. MRI instruments are not as widely available as ultrasound or CT scanners, and the selection and interpretation of proper scan sequences and images require considerable experience and skill. The spatial resolution has significantly improved, but the presence of implanted metal-containing devices (artificial joints, cardiac pacemakers) or the need for monitoring equipment are contraindications to MRI. Most intravascular stents are MRI compatible. MRI studies are more expensive and require considerably more time than CT or ultrasound, which limits their use in emergency evaluation of possible ruptures. Nevertheless, MRI clearly distinguishes arteries and veins from viscera and other surrounding tissue, and there is excellent agreement between MRI and ultrasound or CT images in determining aortic diameter. MRI is better than ultrasound for demonstrating involvement of branch vessels, especially the renal arteries, with some authors reporting visualization of the renal arteries in more than 90% of cases. Other advantages of MRI over CT are the lack of ionizing radiation, and the relatively large image field. In addition, MRI does not require the use of nephrotoxic contrast agents to achieve intravascular enhancement. Instead, paramagnetic contrast agents, such as gadolinium, are routinely used to improve the imaging of vascular structures. This permits multiplanar image reformatting into MR angiograms (MRAs), similar to those of CT machines. The lack of need for iodinated contrast agents was initially thought to be a significant advantage of MR over CT in patients with abnormal renal function, but gadolinium can cause a severe and often fatal syndrome of nephrogenic systemic fibrosis in a small percentage these patients, which has limited its applicability. MRI machines are able to quantitate blood flow, although this feature is not commonly used clinically. However, adequate visualization of aortic branch arteries is not achieved as frequently with MRA as with CTA, and a significant number of patients cannot undergo MR scanning because of claustrophobia.

Objective documentation of the aortic size should be accomplished with one of these imaging modalities in all patients with suspected AAA. Each method can measure the diameter accurately. The initial scan can be used for comparison with subsequent scans to monitor aneurysmal enlargement. For most routine situations, ultrasonography is the method of choice because of its widespread availability, lower cost, and lack of ionizing radiation. When there is suspicion of suprarenal or thoracoabdominal aortic involvement or dissection, MRI or CT is preferable. For preoperative planning in these complex cases, a multiplanar study with 3D reconstruction (CTA, MRA) will delineate the aneurysm, aortic branch vessels, and neighboring structures. This is especially important if treatment by endografting is being considered. CT and MRI probably have equal capability to demonstrate unexpected features such as venous anomalies, perianeurysmal fibrosis, and horseshoe kidney, although the ureters are not easily identified by MRI. For symptomatic aneurysms, MRI and CT are also better than ultrasound in their ability to identify contained rupture.

Years ago, aortography was an essential step in the evaluation of patients with AAA. The limitations of catheter aortography for the diagnosis and evaluation of aortic aneurysms, like those of plain film radiography, are well known. Because the mural thrombus, which is nearly always present, tends to reduce the aneurysmal lumen size toward normal, aortography is not a reliable method to determine the diameter of an aneurysm or even to establish its presence. Aortography allowed the identification of frequent but unsuspected variations and abnormalities in renal and visceral vessels ( Table 41.3 ). With better noninvasive imaging methods now routinely available, aortography has little use as a diagnostic method for AAA. Aortography is indicated as an initial step in the endovascular treatment of aortic aneurysms but should be performed very selectively in other patients with aneurysms for the following indications: (1) clinical suspicion of visceral ischemia, (2) occlusive iliofemoral vascular lesions, (3) severe hypertension or impaired renal function in a patient in whom a concomitant renal artery stenosis would be repaired if discovered, (4) suspicion of a horseshoe kidney to delineate renal artery anatomy, and (5) the presence of femoral or popliteal aneurysms. With the evolution and availability of CTA and MRA, it is usually possible to obtain this information with fewer risks. Newer CT scanners with large numbers of detectors (128 or more) perform even faster scans, with improved resolution and better 3D images. Sophisticated 3D reconstructions of CT scans are already available online from commercial vendors, making these sophisticated images available to any provider who can transfer the CT data onto a CD or transmit it electronically to the imaging facility.

Molecular imaging is a rapidly developing modality that uses tracers aimed at physiologic processes attempting to provide functional information that is complimentary to the anatomical information of conventional scans. There are a variety of tracers and techniques being evaluated in experimental animals and humans, such as CVA-35, which labels collagen, and F-labeled nanoparticles, targeting macrophages that may be able to predict which aneurysms are at high risk of rupture.

Risk of Aneurysm Rupture

As noted earlier, the majority of AAAs are discovered in asymptomatic patients during an evaluation for an unrelated problem. Because of screening, aneurysms are being discovered at a smaller size than when the original studies in their natural history were first published by Estes, Wright, Szilagyi, and others. Most aneurysms currently detected in screening programs are small (<4 cm), which has led to new concepts in the natural history of these lesions. Although aneurysms can cause symptoms and serious consequences from thrombosis and distal embolization, rupture is the most important risk, and aneurysm diameter is currently the most important factor that determines the risk of rupture. In general, the risk of rupture correlates directly with size: the larger the aneurysm, the greater the risk of rupture. For example, the yearly risk of rupture for abdominal aortic aneurysms, between 4 and 5.4 cm in size is 0.5% to 1%; this increases to 6% to 10% for aneurysms between 6 and 7 cm and to 19% to 35% for aneurysms larger than 7 cm in diameter. Calculated as 5-year rupture rates, these figures become 5%, 50%, and about 95%, respectively. The steepness of the curve plotting these data increases sharply at a diameter of approximately 5 cm, which is the basis for recommendations to defer elective aneurysm repair until a size of 5.0 to 5.5 cm is reached. These data were derived from two randomized, controlled prospective clinical trials that studied survival in patients with asymptomatic small AAAs that were between 4 and 5.4 to 5.5 cm in diameter: the United Kingdom Small Aneurysm Trial, published in 1998, and the Veterans Administration–sponsored Aneurysm Detection and Management (ADAM) trial. These two trials were similar in design, size, and results. The rupture rate for aneurysms in these trials was 0.5% to 1% per year, as noted previously, and neither trial showed a difference in long-term survival, which was the primary end point, between patients allocated to early operation or ultrasound or CT surveillance. The 6-year survival was similar in both trials, 64% in the UK trial and approximately 70% in the ADAM trial. Although 61% of those randomized to surveillance in both studies ultimately underwent aneurysm operation for enlargement or symptoms, long-term survival was not improved by early operation. Furthermore, delaying operation for these small aneurysms was not associated with increased operative or late mortality. These data are consistent with those from older, nonrandomized studies. For example, population-based data from Rochester, Minnesota, showed a mean enlargement rate for aneurysms less than 5 cm in diameter of only 0.32 cm/year, and after 5 years of observation, no aneurysm smaller than 5 cm had ruptured. The ADAM and UK trials enrolled mostly good-risk patients and rupture risk may be higher in high-surgical-risk patients. In both series, there was a higher rupture rate among the ineligible (i.e., high-risk) patients than in those randomized, suggesting that factors other than diameter influence rupture rate.

Other clinical features associated with increased risk of rupture include smoking, chronic obstructive lung disease, hypertension, female gender, transplant recipient, and rapid enlargement (defined as 1 cm/year or more). Cronenwett and associates showed that chronic obstructive pulmonary disease and systolic hypertension are predictors of increased risk of rupture of small abdominal aneurysms. In a subsequent study, they confirmed that the rate of enlargement of small aneurysms was unpredictable, but either increased systolic or decreased diastolic pressure (i.e., increased pulse pressure) was associated with an increased rate of aneurysm expansion. In this study, there was considerable variability in the rate of aneurysm enlargement, although the average rate of expansion was 0.4 cm/year in anteroposterior dimensions and 0.5 cm/year in lateral dimensions. Some clinical and experimental data suggest that the expansion rate of small aneurysms can be diminished by β-adrenergic blockade (propranolol), which should lead to a decreased rate of rupture. Unfortunately, this theory was not supported in three randomized clinical trials. Other studies have shown that aneurysms are frequently elliptical rather than round and that aneurysmal expansion is initially more rapid in the lateral direction. It is interesting to recall that the most frequent site of aneurysm rupture is in the lateral wall. In a review of four series, including their own, Cronenwett and coworkers described the outcome of 378 patients with small aortic aneurysms initially treated nonoperatively. After an average follow-up of 31 months, 27% of the patients were alive with intact aneurysms, 29% had died of other causes, 39% had elective aneurysm operations because the aneurysm diameter reached 5 to 6 cm, and 4% had suffered aneurysm rupture or acute expansion leading to emergency operation. Overall, there was a mean 5-year survival of 54% in these patients, somewhat less than the 6-year survival rates of 64% in the UK trial and 70% in the ADAM trial. In light of these more recent studies, autopsy studies showing high rates of rupture of small aneurysms must be interpreted with caution. Some have shown that 23.4% of aneurysms between 4.1 and 5 cm rupture, and the same is true for up to 10% of aneurysms less than 4 cm in diameter. Data such as these have led surgeons to recommend operation for almost all aortic aneurysms in good-risk patients. However, autopsy studies underestimate aneurysm size because of the lack of a distending blood pressure, and several more recent studies on living patients demonstrate a rupture rate of approximately 1% per year for aneurysms less than 5 cm in diameter, supporting the data from the ADAM and UK small aneurysm trials. In addition, two randomized trials comparing endovascular repair (EVAR) with open repair of small AAAs failed to demonstrate a survival benefit of early repair.

There is little debate about the appropriateness of elective aneurysm surgery for patients with large aneurysms (>5.5 cm in diameter) because of the high risk of rupture and the associated mortality when rupture occurs. This is also valid in so-called high-risk patients because most of these patients will die from rupture and not from the conditions that caused them to be considered high risk. In addition, there is no agreement on what constitutes high risk. Patients who have a large AAA and are “unfit” for surgery constitute approximately 10% of AAA patients. Several reports dealing with these patients showed that rupture occurred in less than 50% and many of those survived emergency repair. EVAR has early survival advantages compared with open repair in these patients. However, a recent report that included 1514 patients from 74 studies demonstrated lower than expected rupture rates ranging from 3.5% per year for 5.5 to 6.0 cm diameter AAAs to 6.3% per year for AAAs greater than 7.0 cm diameter and an overall risk of death from rupture of only 19% compared to 42% from all other causes; 32% were treated for rupture and 42% of these survived. This study is one of many that suggest rupture rates overall are decreasing over time. Several cohort studies indicate that women have a greater risk of aneurysm rupture at a given size than men; therefore it has been suggested that women be offered definitive treatment at a smaller aneurysm size (i.e., 4.5 to 5.2 cm) than men.

It must be emphasized that although the risk of aneurysm rupture correlates most closely with aneurysm size, and the average rate of aneurysmal enlargement is known (0.4 to 0.5 cm/year), it is impossible to predict when a small aneurysm will rupture in a given patient. Perhaps the best explanation relates to the fact that aneurysms rupture at points of peak wall stress, as discussed earlier, and areas of peak wall stress do not necessarily coincide with areas of maximal diameter. Clinical investigations of aneurysm wall stress using finite element analysis of CT-derived data may be better at predicting rupture but are not widely available. For now, diameter remains the best available predictor of risk of aneurysm rupture. The harmlessness of a small, asymptomatic abdominal aortic aneurysm is deceptive. Some do rupture, but still, coronary artery disease, and not rupture, is the most frequent cause of death in patients with small aneurysms.

Risks of Surgical Treatment

The natural history of untreated abdominal aortic aneurysms is well documented. This is especially true for those aneurysms measuring 5.5 cm or less in diameter. Since the first report of successful surgical resection and graft replacement of an infrarenal aortic aneurysm in 1952, many publications have documented the operative and long-term survival after surgical treatment. There has been a steady improvement in operative results for elective operations. Several large, contemporary series have reported operative mortality rates between 0.9% and 5% for large, single medical centers and only somewhat higher rates for community hospitals, and the 1.8% operative mortality in the ADAM trial from selected Veterans Affairs (VA) medical centers compares favorably with these ( Table 41.4 ). Higher mortality rates, ranging from 5% to 8%, have consistently been reported from analyses of large statewide or national data bases and lower operative mortality has been found to be associated with operations performed in high-volume institutions and by high-volume vascular surgeons, although the definitions of the term high volume are not uniform. The recently published SVS guidelines recommend that elective open surgical repair is best performed at high-volume centers with a documented in-hospital mortality of less than 5%. Operative mortality in this range (<5%) justifies elective repair, even for relatively small aneurysms in good-risk patients.

The general improvement in surgical results has occurred despite the fact that more patients are being operated on who are older and have more comorbidities. Preoperative detection and treatment of significant cardiac disease have been important factors, as have improved anesthetic and critical care management and better perioperative drugs such as β-blockers, ACE inhibitors, ARBs, and statins.

Most of the deaths in elective operations occur in so-called “high-risk” patients; unfortunately, there is no consensus on what constitutes high risk. Chronologic age is not as important as physiologic age in assessing operative risk; therefore patients should not be denied elective operation based solely on age. Even octogenarians can undergo elective open aneurysm surgery with acceptable morbidity and mortality rates. Most vascular surgeons have successfully treated ruptured aneurysms in patients previously rejected for elective operation because they were considered too old or too risky.

The major risks for elective abdominal aortic aneurysm resection are similar to those for other major intraabdominal operations and include adequacy of cardiopulmonary and renal function. Recent studies have shown that decreased aerobic fitness and high frailty score both predicted increased morbidity and mortality after open aneurysm repair. High-risk patients are those with unstable angina or angina at rest, cardiac ejection fraction less than 25% to 30%, congestive heart failure, serum creatinine level greater than 3 mg/dL, and pulmonary disease manifested by room air P o ₂ of less than 50 mm Hg, elevated P co ₂ , or both. A substantial percentage of these high-risk patients will die of a ruptured aneurysm and not from the disease that led to their categorization as high risk. With intensive perioperative monitoring and support, aneurysm resection can performed, even in these high-risk patients, with operative mortality of less than 6% as reported by Hollier and colleagues and others. Therefore, even high-risk patients with large abdominal aneurysms should be considered for elective treatment if the appropriate support facilities are available. It is in this group, however, that EVAR is the most attractive in anatomically suitable patients. However, a large number of randomized trials and cohort studies in low- and high-risk patients have shown only a small, statistically insignificant, advantage over open repair in early survival and this advantage disappears by the third postoperative year. Nevertheless, in the United States, 70% to 75% of abdominal aortic aneurysm repairs are now being treated with EVAR, driven largely by patient and physician preference. This has resulted in a higher proportion of open repairs being complex, including para- and juxta-renal aneurysms, which require suprarenal or supraceliac aortic clamping. The results have been quite good, with mortality only slightly higher than for infrarenal AAA, ranging from 0.8% to 6.1% in single-center series and 2.9% to 3.6% from larger databases like the Vascular Study Group of New England (VSGNE). The incidence of renal dysfunction is also higher than for patients who do not require suprarenal clamping but permanent dialysis is uncommon. However, the increasing use of branched and fenestrated endografts has permitted endovascular treatment of juxtarenal, pararenal, and suprarenal aneurysms, which will decrease the need for open repair in a significant proportion of these cases. Nevertheless, there will always be some patients who require open repair, including those with failed EVAR and other uncommon situations. The consistent findings from clinical trials are that 70% to 80% of patients with AAAs are anatomically suitable for endoluminal repair with current commercially available devices (including fenestrated and branched), which can be accomplished with mortality rates equal to or slightly lower than those for open surgical repair. Morbidity rates are clearly lower than those for open surgical repair, hospital stay is shortened, and patient satisfaction and surgeon enthusiasm are high; however, all aortic aneurysms can be treated by open repair. In addition, because of lingering uncertainties about long-term results of EVAR, with late mortality due to rupture being higher than for open repair, there is uncertainty regarding which patients and which aneurysms are best treated in this manner. For these reasons, the indications for endoluminal repair should be the same as those for open surgical repair in terms of aneurysm size and expected longevity. Endovascular aneurysm repair is covered in detail in Chapters 42 and 43 .

Early detection and widespread elective aneurysm treatment programs have led to a decrease in the incidence of aneurysm rupture, but rupture is still highly lethal when it occurs. A substantial percentage (50%) of patients whose aneurysms rupture die before reaching a medical facility. An additional 24% arrive at a hospital alive but die before a definitive operation can be performed; therefore, operative mortality figures underestimate the true significance of aneurysmal rupture. The overall mortality from ruptured aneurysms, as reported in two large community-based studies, ranges from 74% to more than 90%.

The operative results for ruptured aneurysms are not nearly as favorable as those for elective aneurysm repair, but there has been a steady but limited decrease in operative mortality as documented in a 50-year review by Brown and colleagues. They reported an average operative mortality of 47% in 171 studies published between 1950 and 2000, but mortality decreased from 55% at the beginning to 41% at the end of the study, an average decrease of 3.5% per 10 years. This occurred in spite of increasing age of the patients and before the impact of EVAR.

Although there are a few series with better results, nearly 35% of patients die after being operated on for rupture. The nature of the rupture influences the results. Less than 10% of patients presenting in shock with free intraperitoneal rupture survive. Some reports indicate that preoperative cardiac arrest is uniformly fatal, and repair should not be attempted when this occurs. In contrast, patients in stable condition with small, contained leaks have a better than 80% survival rate. Several authors have reported improved mortality rates (30% to 35%) using endovascular treatment for ruptures, and others have reported no survival advantage. There have been three randomized prospective trials (plus many observational studies) comparing open with endovascular treatment of ruptured aneurysms (AJAX [Dutch], ECAR [French], and IMPROVE [United Kingdom]). All three reported no survival benefit of EVAR over open repair, but each of the studies had methodologic problems that have challenged the conclusions. Careful analysis of the data suggests that EVAR, when it can be done, is associated with decreased mortality (27% to 30%). The operative mortality for open repair in some reports is as low as 27%, which is in the same range as most of the EVAR studies. Nevertheless the SVS guidelines give a strong recommendation for EVAR, when it can be done. In one study, endovascular treatment of ruptured aneurysms yielded worse outcomes in nonteaching and low-volume EVAR hospitals.

The factors contributing to failure in the treatment of ruptured abdominal aortic aneurysm have been reviewed by Hiatt and associates. The four most important factors were failure to perform elective aneurysmectomy in patients with known aneurysms; errors in diagnosing rupture when it occurred, leading to delay in operation; technical errors committed during the operation (all venous injuries); and undue delays in induction of anesthesia; these are all preventable. Other series have identified factors leading to death after aortic aneurysm rupture. Repeatedly, delays in performing surgery and the total volume of blood transfused are found to be important. Preoperative cardiac arrest, female gender, age 80 years or older, massive blood loss, and ongoing major transfusion requirements were predictors of 90% to 100% mortality in the series by Johansen and colleagues, which included a highly efficient transport and resuscitation response. Some of the differences in operative mortality among various reports are due in part to inconsistencies in patient categorization or considering all forms of rupture together. Many of these series also fail to separate patients with unruptured but symptomatic aneurysms who undergo emergency operations. The operative morbidity and mortality for symptomatic but not ruptured aneurysms is roughly double that of elective, asymptomatic patients. It has been postulated that the reasons for this increased mortality is the omission of the usual preoperative optimization necessitated by the emergency operation as well as institution-based issues related to emergency procedures during nights and weekends.

Late Survival

The most common cause of death among patients with large abdominal aortic aneurysm is rupture. The objectives of surgical repair are to prevent rupture and thereby prolong life. Without a doubt, surgical repair prevents rupture, and it does prolong life, but what is the long-term outlook for survivors? Several long-term studies using life-table methods have shown 5-year survival rates ranging from 49% to 75% (average, 61%; see Table 41.4 ).

Although these data are far more encouraging than those for the survival of patients not undergoing operation, they do not equal the survival expected for the normal age-matched population. For example, Johnson and coworkers reported a 50% survival of 7.4 years for patients after elective operative treatment for abdominal aneurysm, whereas the age-adjusted figure for the US general population was 15.7 years, and that for North Carolina citizens was 14.5 years. These authors could not identify an influence of age on operative mortality as did Hertzer and colleagues (5-year survival of 82% for ages 45 to 55 years vs. 60% for ages 76 and older), although it affected late mortality as expected. Most of the excess late mortality could be attributed to coronary artery disease and cancer. This has led some centers to pursue an aggressive coronary evaluation and treatment protocol before elective aortic aneurysm operations.

Several large surveys have shown that the safety of vascular surgical procedures in patients who have had previous coronary revascularization is comparable to that in patients with no evidence of ischemic cardiac disease, but this has not been evaluated by randomized clinical trials. It has been estimated that, based on data from the Canadian Aneurysm Study, aggressive cardiac treatment increases the 5-year survival by only 5% to 10%.

Dialysis-dependent renal failure is associated with high perioperative mortality in patients treated by EVAR or open repair and is also associated with significantly shorter survival after 1 and 3 years. This has led some authors to question whether the current recommendations for elective repair should be modified for patients on dialysis.

Overall, aortic aneurysm repair is durable and approximately 70% of patients survive 5 years. Once they get beyond the perioperative period, the survival of those treated for rupture is similar to those with intact aneurysms. Interestingly, aneurysm size appears to be a factor in long-term survival; after treatment, larger aneurysms are associated with a shorter life span. Quality-of-life (QOL) studies have demonstrated that it is well maintained after either open or endovascular repair, although open repair has better QOL than EVAR after the first postoperative year.