Natural history, pathogenesis, and etiology of thoracic aortic aneurysms and dissections

Aortic Aneurysm: The natural history of TAA is diverse reflecting a spectrum of etiologies. Perhaps the most well-documented risk factor for aortic rupture is increasing aneurysm size. Our recent review documented rupture or dissection of ascending or arch aneurysms at a median size of 6 cm and descending or thoracoabdominal aneurysm ruptured or dissected at a median size of 7.2 cm. This observational data taken together with multivariable and logistic regression analysis enabled us to establish recommendations for intervention in TAA based on sound statistical evidence. Other important risk factors for aneurysm growth include hypertension, COPD, presence of a chronic dissection, and infection of the aortic wall. Arteriosclerosis has been described in the literature as a risk factor for aneurysms and dissections; however, this concept is seriously challenged today. We agree with with Dr. M. David Tilson that arteriosclerosis may well be a concomitant process and not a direct cause of aneurysm formation and growth. There is a wide range of growth rates in the literature for aortic aneurysms, mostly related to the method of growth rate calculation. We recently reported an improved statistical methodology for calculating aortic growth rates. Most recent evidence from our Yale series using this method indicates an annual mean growth rate of 0.12 cm/y for TAA. The pathogenesis of aortic aneurysm is related to defects or deficiencies in structural proteins: elastin, collagen, or fibrillin. Extracellular matrix proteins such as laminin, glycosaminoglycans, proteoglycans, and fibronectin may also play a role in aneurysm formation. Dr. John V. White from Temple University (Philadelphia, PA) has contributed significantly to our understanding of a structural basis for aneurysm formation and growth. Eventual loss of the structural integrity of the adventitia, not the media, is required for aneurysm formation. Recent investigations into the etiologic basis of aortic aneurysm have led to significant changes in our understanding of aneurysm formation. The causes are thought to be multifactorial, with genetic, environmental, and physiologic influences. Aneurysms of the ascending aorta are most commonly related to degenerative changes in the medial layer of the aortic wall, annuloaortic ectasia, or metabolic derangements (i.e., Marfan and Ehlers Danlos syndromes). A mutation in fibrillin has been demonstrated in patients with Marfan syndrome, and the gene has now been isolated. Histologic specimens from patients with Marfan syndrome reveal cystic medial necrosis. Aneurysms of the descending aorta are commonly associated with atheromatous disease; however, atherosclerosis as an underlying cause remains controversial. Other etiologies include cystic medial necrosis, chronic dissections, aortitis, and trauma. We now realize that hereditary factors are involved in aortic aneurysm formation. In patients with TAA, our group recently demonstrated a 19% genetic predisposition to the development of familial TAA in patients with known TAA. Pedigree analysis demonstrates more than one possible mode of transmission of aortic aneurysms. Autosomal dominant appears to be the primary mode (38.5%), but X-linked dominant and recessive patterns are also apparent. This suggests genetic heterogeneity may play an important role in aortic aneurysm formation. Aortic Dissection: Acute aortic dissection is the most lethal event affecting the human aorta. Dissections involve an intimal tear, usually transverse, with layer separation progressing rapidly along the outer, thinner one-third of the aortic media. In ascending aortic dissections, the false lumen occupies the right anterior portion of the aorta, and the medial half of the aorta remains intact. Untreated type A dissections are associated with a very high mortality. During the first 24 to 48 hours, the mortality approximates 1% to 2% per hour. In an effort to understand the natural history of interval or permanent nonoperative management of type A dissections, our group recently reviewed such experience at Yale-New Haven Hospital. We demonstrated that type A dissection patients who are referred or diagnosed several days after presentation have successfully surmounted the early danger period and can safely be operated on semi-electively (rather than emergently). In addition, this study showed that selected patients who are not considered operative candidates and who survive the initial type A dissection without complication may be treated with aggressive medical therapy and achieve an acceptable early mortality and short-term outcome, better than previously expected. In a recent review from Stanford, the operative mortality rates for acute type A dissections was approximately 7% ± 5%; chronic type A dissections had an 11% ± 7% operative mortality. The 5-year actuarial survival rate for discharged patients was 78% ± 6% for type A dissections. Approximately one-third of dissections involve the descending thoracic aorta (Stanford type B). Direct aortic replacement in the setting of acute descending aortic dissection carries a very high mortality rate and paraplegia rate, therefore initial management is with antiimpulse therapy for uncomplicated type B dissections. Rupture and vascular occlusion are typically managed with direct aortic replacement and fenestration, respectively. Actuarial survival for patients with type B dissection is 65% at 1 year and 50% at 5 years. For medically treated patients, survival is 73% at 1 year and 58% at 5 years. Finally, for surgically treated patients, representing a group with more serious life- threatening complications, survival is 47% at 1 year and 28% at 5 years. Erdheim was the first to coin the phrase 'cystic medial necrosis,' describing the combination of loss of smooth muscle cells and mucoid degeneration of the aortic media. Although his theory was believed for many years, it can no longer be regarded as the common structural disorder underlying aortic dissection. In the ascending and descending aorta, there appear to be separate underlying disease processes that lead to a weakened vessel wall and an increased susceptibility to dissection. In patients with type A dissections, elastic tissue degeneration is the more common histologic observation. Fragile and irregular elastic fibers interconnecting the lamellar units, especially in the outer media, have been demonstrated in ascending dissections, which weaken the aortic wall. In type B dissections, patients are often not affected with connective tissue disorders, and medial degeneration appears to be primarily responsible. Investigators have shown that this loss of smooth muscle cells may not represent a pathologic entity, but relate to the normal aging process. Though the exact causes of acute aortic dissection are debated, there are several well-established factors that are known to predispose an individual to the disorder. Systemic hypertension is regarded as the single most important predisposing factor in the pathogenesis of their disease. Aortic dissection is also a known pathology of patients with connective tissue disorders such as Ehlers-Danlos Syndrome or Marfan syndrome. Other factors known to predispose to dissection include bicuspid aortic valve, aortic coarctation, and surgical manipulation of the thoracic aorta during cannulation and cross clamping. Heritability of aortic dissections in absence of known connective tissue disorders has not been widely addressed in the literature. Most studies addressing inheritance have been case reports. A defect in the fibrillin gene responsible for Marfan syndrome may also be a cause of inherited dissection in patients without other Marfan characteristics, but the precise genetic defect has not been isolated. Pedigree analysis in several studies, however, suggests an autosomal dominant pattern of inheritance.