Alterations in matrix structure are fundamental to aneurysm development. A pathologic hallmark of aneurysms, especially those resulting from Marfan syndrome, is cystic medial necrosis (defined by elastic tissue damage, smooth muscle loss, and the accumulation of basophilic substance in the media). This change occurs to a mild degree as part of the normal aging process and may explain the association between age and the propensity for aneurysms. Marfan syndrome is an autosomal dominant disorder characterized by mutations in the fibrillin-1 molecule, the main protein component of the microfibril. Microfibrils are extracellular matrix structures displaying a diameter of less than 20 nm and lacking the characteristic 67-nm banding periodicity of interstitial collagen fibers. They form a meshwork in tissues into which elastin is embedded. In the wall of the proximal aorta, the presence of the elastinassociated microfibrillar network gives the aorta added elasticity and compliance. More
than 100 mutations have been identified in individuals affected with Marfan syndrome and other Marfan syndrome-related “fibrillinopathies,” such as MASS (mitral valve prolapse, aortic dilatation, and skin and skeletal manifestations), isolated ectopia lentis, annuloaortic ectasia, and neonatal Marfan syndrome (9,10). It has been demonstrated that FBN1 mutations can occur in individuals with thoracic aneurysms who otherwise do not meet any criteria for Marfan syndrome (11). This missense mutation, although rare, is associated with reduced synthesis of fibrillin-1 in dermal fibroblasts.

Recent advances have demonstrated that the most likely mechanism of vascular damage in Marfan syndrome is mediated by markedly elevated levels of transforming growth factor β (TGF-β), due to impaired TGF-β binding by the mutant fibrillin, an important function of normal fibrillin (12). Treatment of Marfan mice with a drug known to decrease TGF-β levels (losartan) normalizes the arterial wall of these animals (12). Beyond a potentially dramatic treatment for Marfan syndrome patients, this new insight has the potential to abrogate the effect of TGF-β in all aortic aneurysmal disease. The magnitude of the role of TGF-β on aneurysmal disease not due to Marfan has yet to be clarified.

Another disorder, Ehlers-Danlos syndrome type IV, the vascular type, results from mutations in the gene for type III procollagen (COL3A1). Affected patients are at risk for arterial, bowel, and uterine rupture. In this disorder, dissections of the aorta are common, but aneurysmal dilation of the aorta is relatively uncommon (13).

A substantial body of evidence implicates the increased expression and activation of a family of degrading enzymes called matrix metalloproteinases (MMPs) in the pathogenesis of abdominal and thoracoabdominal aneurysms. MMP-2, MMP-9, and membrane-bound MMP (MT-MMP) have so far been implicated (14,15,16,17,18). The evidence for a causative role for these enzymes comes from studies in which interruption in the
activity of these key enzymes by drugs (19,20,21) or targeted gene-disruption approaches (22) reduces aneurysm development. Correlative human studies have noted an increase in progression of aneurysm size and risk for rupture with an increase in the levels of these enzymes within the aortic wall (23,24). These findings have justified a large multicenter trial for the treatment of small aneurysms with tetracyclines, which are MMP inhibitors (21).

With progressive dilation of the aorta, circumferential wall-shear stress, as defined by the Laplace law, increases (wall tension and diameter). The pulsatile load (dP/dT) tends to be greatest in the dilated portions (25). Thus modalities such as β-blockers that reduce dP/dT would be expected to reduce aneurysmal wall stress and the propensity for rupture (26).

Widening of the mediastinum and unfurling of the ascending aorta on the chest radiograph may be the first clue to the presence of an ascending aortic or aortic arch aneurysm. The chest radiograph may, however, appear completely normal in many cases of ascending aortic aneurysms and in almost all cases of descending thoracic aneurysms and TAAs. Conversely, the presence of mediastinal widening secondary to aneurysmal enlargement cannot always be differentiated from that of tumors or other enlargements of the mediastinum.

Transesophageal echocardiography (TEE) with color-flow Doppler imaging is emerging as an invaluable initial study in the diagnosis and follow-up care of patients with ascending aortic and aortic arch aneurysmal disease, because it simultaneously provides important information on the status of the aortic valve, the aortic arch, and left ventricular function. For suspected dissection of the proximal aorta, a TEE is often the initial diagnostic modality of choice in many institutions.
Intraoperative monitoring with TEE during ascending aortic repair is helpful in the detection of early prosthetic complications and the adequacy of reparative procedures on the valve. In the follow-up of patients with composite graft replacement of the ascending aorta, TEE is excellent for monitoring the size of the graft and the anastomotic junction, as well as in the simultaneous evaluation of the prosthetic valve. Because patients with an ascending aortic or aortic arch aneurysm are at risk for recurrence of aneurysmal disease in the distal thoracic or abdominal aorta, three-dimensional contrast-enhanced magnetic resonance angiography (MRA) or computed tomographic (CT) scanning should be considered as a periodic surveillance adjunct in addition to TEE (35). For patients with descending thoracic aneurysms, TEE cannot provide complete information, because very often the aneurysm extends beyond the field of view. TEE is therefore not useful in the initial diagnosis or follow-up of patients with descending thoracic and TAA. However, in combination with CT scanning and angiography, it may be of use in monitoring placement of endovascular grafts and in the evaluation of early endoleaks (36).

CT techniques are commonly used in the diagnosis of thoracic aortic disease, owing to the widespread availability of CT scanners. They are of particular value in documenting growth rates of aneurysms and in determining timing for surgery, as well as obtaining detailed information on precise extent of the aneurysm (37). Computed tomographic angiography (CTA) combines a rapid bolus intravenous injection with a timed breathheld spiral CT acquisition during peak arterial opacification.

Three-dimensional reformatting with maximal intensity projections, curved planar reformations, and shaded surface displays afford excellent visualization of the aorta and major branch vessels. In the patient with a diagnosis of acute rupture, a non-contrast-enhanced CT scan is often the initial diagnostic test of choice, owing to its ready availability (38). Once the rupture is documented, no further studies are indicated, and prompt operative repair should be undertaken. If the rupture is not readily evident, contrast material is administered more completely to delineate the pathologic process and evaluate the possibility of other scenarios, such as dissection, dissecting intramural hematoma, or penetrating aortic ulcer. CTA is often necessary for endovascular planning and is a valuable adjunct in the follow-up of patients after surgery or endovascular graft placement. In the latter case, curved planar reformations are helpful in visualizing the internal anatomy of grafts and stents. The main disadvantage of CTA is its reliance on ionizing radiation and the use of contrast agents with its implications for renal dysfunction.

Magnetic resonance (MR) imaging has emerged as a powerful noninvasive tool for the assessment of the thoracic and thoracoabdominal aorta. It obviates the need for iodinated contrast agents and catheter-based arteriography, with their associated risks of nephrotoxicity and atheroembolism, respectively. MR protocols used in the systematic evaluation of the thoracic aorta include three-dimensional contrast-enhanced MRA (Fig. 29.4) and T₁– weighted spin-echo techniques (black blood) in multiple planes to assess the extent of the aneurysm (Fig. 29.5) and provide information about the involvement of great vessels and their relation to the aneurysm. Three-dimensional contrast-enhanced MRA data-set acquisition is fast (less than 1 minute) and provides detailed images of the thoracic and abdominal aorta. Multiplanar reformations of the image data sets aid in the display of the often complex, tortuous anatomy of aneurysms. The inclusion of post-gadolinium T₁-weighted images to the protocol may additionally provide information on inflammatory involvement of the vessel wall in cases of suspected aortitis.