O diametro de 3cm na aorta toracico, com ou sem acometimento do segmento anular, é considerado aneuristmático, mesmo que o diâmetro médio em ressecções cirúrgicas seja maior que 5cm. O aneurisma de aorta torácica pode acometer a raiz da aorta, aorta ascendente, o arco da aorta e aorta descendente. Existe principalmente uma combinação desses sítios. A combinação da dilatação do arco da aorta e do segmento ascendente é conhecido como ectasia anulo-aórtica.
Existem dois tipos básicos de aneurisma de aorta: os inflamatórios e os não inflamatórios (principalmente ateroscleróticos).
As dissecções de aorta ascendente são frequentemente superpostos a aneurismas não-inflamatórios, designados de forma geral como aneurismas dissecantes. Entretanto, dissecções ocorrem frequentemente na ausência de um aneurisma pre-existente.
O termo pseudo-aneurisma denota a ruptura da parede da aorta com cicatrização e formação de aneurisma dentro da parede fibrosa da aorta, geralmente entre a média e a adventícia.
Causes of non-inflammatory thoracic aneurysms include inherited syndromes, specifically Marfan syndrome, familial non-Marfan dissections, and Loeys-Dietz syndrome. The major associations are bicuspid aortic valve and systemic hypertension. Approximately 25% of patients with thoracic aortic aneurysms have no known cause or association. Pathologically, non-inflammatory aneurysms demonstrate degrees of cystic medial degeneration, depending on etiology or association.
The majority of surgically resected thoracic aortic aneurysms involve the ascending aorta (Figures 1 and 2). In a series of 513 ascending aneurysms at the Mayo Clinic (Homme, Aubry et al., 2006), 89% were non-inflammatory. Of these, 13% of patients had inherited connective tissue disease, mostly Marfan syndrome; 25% of patients had bicuspid aortic valves; and 51% had no association other than hypertension, which occurred in approximately 60%. Ninety percent of descending thoracic aortic aneurysms are atherosclerotic. They are less frequently resected than ascending aortic aneurysms, as they are frequently treated medically, especially those causing chronic dissections (Bergholm e Hallen, 1984).
Thoracic aortic aneurysms can be divided in 4 main categories regarding their association with genetic diseases:
– Sporadic cases with genetic polymorphisms that may predispose the formation of thoracic aortic aneurysm. Approximately 20% of these patients have a family history, generally autosomal dominant
– Cases associated with bicuspid valve disease with familial aggregation; these comprise approximately 10% of patients
– Marfan syndrome; these comprise less than 10% of patients
– Other genetic conditions, including Ehlers-Danlos syndrome type IV and Loeys-Dietz syndrome (<1% of cases)
Many patients with aortic aneurysm and dissection do not fit any syndrome of collagen vascular disease, such as Marfan syndrome, yet as many as 20% of those will have at least one first-degree family member with a known aneurysm in the arterial tree. (Biddinger, Rocklin et al., 1997; Albornoz, Coady et al., 2006) (Pannu, Tran-Fadulu et al., 2005) Patients with a family history are significantly younger than patients without a family history, but older than full-blown Marfan syndrome. Radiological screening in family members of patients presenting with aneurysms of complications thereof have identified a pool of patients with asymptomatic aortic dilatation. (Milewicz, Chen et al., 1998) The inheritance is autosomal-dominant. In addition, there is an increased risk of abdominal aortic aneurysm, cerebral and other aneurysms. (Albornoz, Coady et al., 2006) A variety of loci have been recently associated with familial non-Marfan thoracic aortic aneurysms, and include TAAD1, FAA1, FBN1. Three genomic loci include 5q13–14, termed the TAAD1 locus, 11q23–24, the FAA1 locus, and 3p24–25, the TAAD2 locus. The latter was sequenced for the gene transforming growth factor-β receptor type 2 (TGFBR2), which may be responsible for 5% of familial thoracic aortic aneurysms (see Loeys-Dietz syndrome, below). Recent studies have demonstrated unique polymorphisms in the THBS2 as is a risk for thoracic aortic aneurysms, with some other variants being protective. (Kato, Oguri et al., 2008) This area of research is rapidly advancing, and it is expected that many other more specific genes will be identified and be used in the screening of patients and family members.
Bicuspid aortic valve disease is a common congenital cardiac defect that affects approximately 1.3% of the general population (see chapter 30), but 14% of patients with proximal aortic dissections (Larson e Edwards, 1984). The much less common unicuspid aortic valve is also associated with thoracic aortic aneurysm. This condition happens in multiple members of the same family. Epidemiological studies have pointed an autosomal dominant inheritance, but no specific genetic aberration has been identified to date. (Huntington, Hunter et al., 1997) Aneurysms in patients with bicuspid aortic valve are not due to flow-related disturbances secondary to valvar insufficiency or stenosis but due to an unknown genetic association; for this reason, the aorta is often wrapped at valve replacement to prevent progressive dilatation. (Bauer, Pasic et al., 2002). One-third of patients with bicuspid aortic valve and aortic aneurysms have aortic valve stenosis, and the other 2/3 have valve insufﬁciency, with a small number having normal valve function. (Bauer, Pasic et al., 2002; Auriemma, Bortolotti et al., 2004) Among patients with ascending aneurysms and aortic insufficiency, two-thirds can be treated with ascending aortic aneurysm repair, and the remainder require valve replacement (David, Feindel et al., 2006).
Marfan’s syndrome is a disorder characterized by abnormalities of the eyes, skeleton, and cardiovascular system. Marfan syndrome is an autosomal dominant disease, with 25% of patients having no family history (presumed de novo mutations). Cardiovascular manifestations of Marfan syndrome include aortic root dilatation, ascending aortic dilatation, aortic dissections, other sites of aortic aneurysm, ad mitral valve prolapse (Figure 6). The histologic feature of aortic aneurysms in Marfan syndrome is loss of elastic laminae with pooling of proteoglycans, so-called cystic medial degeneration. The histologic findings are also seen to lesser degrees in familial non-Marfan aortic dissection and those associated with bicuspid aortic valve.
In the absence of surgical treatment, patients with Marfan’s disease have a 50 percent risk of developing aortic dissection during their lifetime. The aortic dilatation observed in Marfan syndrome is the result of defects in a specific component of the elastic fiber, fibrillin-1 (Hasham, Willing et al., 2003) which is encoded by the FBN1 gene on chromosome 15. An online Marfan database (http://www.umd.be/) contains more than 250 mutations. Mutations in the FBN2 gene, for fibrillin 2, also predispose for aortic dilatation, without a risk increase for dissection as in patients with FBN1 mutations. A second less prevalent locus was indentified in MSF-like patients at 3p24.2-p25, coded MFS2. Patients bearing this mutation have not met the criteria for MFS, but seem to have a high incidence of thoracic aortic aneurysm.
Loeys-Dietz syndrome is an autosomal dominant connective tissue disorder that is a rare cause of thoracic aortic aneurysm. It results from genetic mutations in the transforming growth factor beta receptors 1 and 2 (TGFBR1 and TGFBR2). The syndrome is characterized by hypertelorism, bifid uvula, cleft palate, and arterial tortuosity with aneurysms and dissections. Loeys-Dietz syndrome has an earlier onset than Marfan syndrome, with recommendations for prophylactic aortic root replacement at younger ages and with smaller aortic dimensions. Histologically, there is diffuse medial degeneration, which may be subtle. (Maleszewski, Miller et al., 2009)
Ehlers-Danlos syndrome type IV (vascular type) is due to defects in the type III procollagen (COL3A1). It causes vascular fragility with aneurysm formation, rupture and dissections. The aorta is involved in a small percentage, since this disease affects most often smaller arteries. Usually there are multiple rupture sites in the aorta. Patients with Ehlers Danlos syndrome type IV may also have thoracic aortic aneurysms; however, the typical complication is rupture in normal caliber artery. Coronary artery dissections, aortic rupture, iliac and femoral rupture, and coronary and other muscular arterial aneurysms are among the different complications seen in these patients. Generally fewer than 1% of patients in series of thoracic aneurysm have Ehlers Danlos syndrome. See chapter 50 for a further discussion. Other rarer genetic diseases that predispose to thoracic aortic aneurysm are polycytic kidney disease and Ehlers-Danlos type VI (kyphoscoliotic type).
Osteogenesis imperfecta shares some clinical features with Ehlers Danlos syndrome. It is a heterogeneous disorder of type I collagen affecting approximately once in 60,000 births with a wide range of severity. Clinical manifestations include bone fragility with repeated bone fractures, skeletal malformations, and blue sclerae. All forms are the result of mutations in COL1A1 or COL1A2, the genes that encode the proalpha1(I) and proalpha2(I) chains of type I collagen, respectively. The leading cause of death in adults is respiratory insufficiency caused by kyphoscoliosis; cardiac manifestations include aortic root dilatation, aortic insufficiency, and mitral valve prolapse, occurring in approximately 7-12% of patients. The histologic findings in the aortic wall have not been well described, but as in the case of other non-inflammatory aneurysms are non-specific.
Rare causes of non-inflammatory thoracic aortic aneurysm include post-traumatic pseudoaneurysms, most frequently seen in the proximal descending thoracic aorta at the site of the ligamentum arteriosum, where blunt chest trauma results in separation of the aortic wall. (Numata, Ogino et al., 2003) Congenital aneurysms of the thoracic aorta may occur in association with aberrant right subclavian artery with diverticulum of Kommerell (Kouchoukos e Masetti, 2007).
Uncomplicated thoracic aortic aneurysms can be divided grossly into saccular and fusiform. Fusiform aneurysms are most common, and affect the entire circumference of the aorta and have tapered borders. Among the types of thoracic aneurysms, only infectious (mycotic) aneurysms and post-traumatic pseudoaneurysms are typically saccular, both of which have a propensity for the distal thoracic aorta. Only rarely are aneurysms secondary to medial weakness due to medial degeneration saccular.
At autopsy, the gross appearance of thoracic aortic aneurysm depends on the type. Proximal aneurysms demonstrate diffuse ectasia of the ascending aorta. Aneurysms of the proximal portion of the aorta may stretch the aortic ring, resulting in aortic insufficiency (annuloaortic ectasia). Involvement of the aortic root is typical of Marfan syndrome, syphilitic aneurysms, and a significant proportion of non-infectious aortitis. Syphilitic aneurysms tend to demonstrate massive aneurysm formation, and marked thinning of the aortic wall. In non-inflammatory aneurysms, the arch is generally spared, but aortitic aneurysms (Mennander, Miller et al., 2008) and atherosclerotic aneurysms frequently extend to the arch vessels.
The adventitial appearance of thoracic aneurysm is generally unremarkable, unless there is rupture of a true or false lumen, resulting in soft tissue hemorrhage, or if there are adhesions and edema in the case of infectious aneurysm. One form of non-inflammatory aneurysm of the ascending aorta is the so-called “egg-shell” aorta in cases of diffuse intimal calcification of atherosclerotic intima.
Aortic dissection. Dissections are a common complication of non-inflammatory thoracic aortic aneurysm, occurring in approximately 20% of aneurysm repair, either as acute or chronic lesions. The rate is similar among the various etiologies. Because rare examples of thoracic aortic aneurysm with dissection lack an intimal tear, it is believed that the initiation of the dissection may involve leaking or rupture vasa vasorum, which are present predominantly in the proximal aorta.
Dissecting aortic aneurysms represent one of the most dramatic specimens in gross pathology. The aneurysm involves the root in most cases of Marfan’s syndrome, but typically spares the root in patients with bicuspid aortic valve or idiopathic aneurysms. Aortic dissections have been studied extensively for centuries with uncountable descriptions in the medical and lay literature. The most common used classification is the one by DeBakey and colleagues from 1965. (Debakey, Henly et al., 1965) Three major types are described (Figure 3):
– Dissection involving both the ascending and descending aorta (Type I).
– Dissection only in the ascending aorta (Type II).
– Dissection involving only the descending aorta (Type III)
A modified system refers to Types I and II of DeBakey as type A, and type III as type B. Dissections are characterized by splitting of the aortic wall within the media, typically outer media, or the medial-adventitial interface. The blood flow dissects the new plane and forms a new path, called the false lumen. In the great majority of the cases, an intimal tear is seen on gross inspection, most often found in the proximal aorta, just distal to the aortic valve. The second most common location is just distal to the arch vessels, in the ascending aorta. The dissection plane can extend to any of the branches of the aorta, thoracic or abdominal causing symptoms specific to that location. The outer wall of the false lumen is usually thinner than the inner dissected wall, thus rupture to adjacent structures (commonly causing hemopericardium, left pleural hemothorax or extension of the blood into the mediastinum) is frequent. The distal portion of the false lumen will demonstrate a second communication with the true lumen, in the form of a re-entry tear. The intimal tears associated with aortic dissections heal over time, in cases of prolonged survival, and have a white fibrous surface.
The aortic media in non-inflammatory thoracic aortic aneurysms may be normal, show underlying cystic medial necrosis, and in either case show superimposed acute or healed dissection. The histopathologic hallmark of non-inflammatory thoracic aortic aneurysms is cystic medial degeneration, or the pooling of proteoglycans (mucoid material) and pseudocysts formation in the media, accompanied by extensive loss of elastic lamellae. These changes result in the medial weakening that progresses to aneurysm, dissection, or both. However, in a significant proportion of cases of thoracic aneurysms with or without dissections, the media appears histologically normal (Figure 28). The greatest degrees of cystic medial necrosis occurs in patients with Marfan syndrome, followed by non-Marfan familial dissection. Older patients with non-hereditary thoracic aortic aneurysms, and those associated with bicuspid aortic valve, have relatively small degrees of cystic medial necrosis. (Homme, Aubry et al., 2006) Figures 29 to 33 show histologic examples of cystic medial degeneration.
Cystic medial necrosis may also occur as a post-inflammatory change in aortitis (see chapter 42). Disorganized media in areas of healed aortitis may also show proteoglycan pooling (Homme, Aubry et al., 2006; Burke, Tavora et al., 2008). A related histologic finding is so-called “medionecrosis” a finding also seen in aging aortas and in patients with hypertension. Medionecrosis, or laminar medial necrosis, is defined as coagulative necrosis of medial smooth muscle cells, resulting in loss of nuclei and collapse of the elastic lamellae (Homme, Aubry et al., 2006), a finding that is not specific for any specific etiology for thoracic aneurysms and has been described in aortitis as well (Figure 34).
Acute or healed dissections are seen histologically in approximately 20% of resected non-inflammatory thoracic aortic aneurysm (Figures 35-41). Acute dissections result in hemorrhage into the adventitia, with the dissection plane typically in the outer third adjacent to the adventitia, or less commonly in the center of the media. The reaction of the extravasated blood depends on the age of the lesions. Typically, there is an inflammatory infiltrate in the adventitial fat, often rich in eosinophils, in the first few days; thereafter, the response is similar to hematoma formation elsewhere, with macrophages, endothelial cells, reactive fibroblasts and mesothelial cells (if near the pericardium), all occurring with the first 2 weeks, with eventual fibrosis within the false lumen wall. The lining of the chronic false lumen is typically composed of dense amorphous elastic tissue, without the formation of distinct elastic laminae.
Aneurysms associated with uni- and bicuspid aortic valve disease usually show focal loss of elastic laminae and some associated intimal fibrosis, which is usually mild. Marfan syndrome patients usually reveal severe elastic fiber degeneration of the aortic media, which can be prominent at and around the sites of gross tears. If a healing process, such as remote tear, is present, intimal thickening and fibrosis can occur. The adventitia is usually normal in cases without a history of rupture. There are only few reports of histologic findings in Ehlers Danlos syndrome and most show mild histologic change characterized by loss of elastic fibers and medionecrosis. The intima and adventitial layers are usually spared. Intimal tears are common, and may cause intimal fibrosis, which is believed to be post-healing.