The aortic valve is a complex structure that is best described as a functional and anatomic unit, the aortic root. The aortic root has four components: aortoventricular junction or aortic annulus, aortic cusps, aortic sinuses, and sinotubular junction. In addition, the triangles beneath the commissures of the aortic valve, although part of the left ventricular outflow tract, are also important for valve function.

The aortic annulus unites the aortic cusps and aortic sinuses to the left ventricle. It is attached to ventricular myocardium (interventricular septum) in approximately 45% of its circumference and to fibrous structures (anterior leaflet of the mitral valve and membranous septum) in the remaining 55% (Fig. 30-1). The aortic annulus has a scalloped shape. Histologic examination of the aortic annulus reveals that it is a fibrous structure with strands attaching itself to the muscular interventricular septum and has a fibrous continuity with the mitral valve and membranous septum. The fibrous structure that separates the aortic annulus from the anterior leaflet of the mitral valve is the intervalvular fibrous body. An important structure immediately below the membranous septum is the bundle of His. The atrioventricular node lies in the floor of the right atrium between the annulus of the septal leaflet of the tricuspid valve and the coronary sinus. This node gives origin to the bundle of His, which travels through the right fibrous trigone along the posterior edge of the membranous septum to the muscular interventricular septum. At this point, the bundle of His divides into left and right bundle branches that extend subendocardially along both sides of the muscular interventricular septum.

The aortic cusps are attached to the aortic annulus in a scalloped fashion (see Fig. 30-1). The aortic cusps have a semilunar shape whereby the length of the base is approximately 1.5 times longer than the length of the free margin, as illustrated in Fig. 30-2. There are three cusps and three aortic sinuses: left, right, and noncoronary. The aortic sinuses are also referred to as sinuses of Valsalva. The left coronary artery arises from the left aortic sinus and the right coronary artery arises from the right aortic sinus. The left coronary artery orifice is closer to the aortic annulus than is the right coronary artery orifice. The highest point where two cusps meet is called the commissure, and it is located immediately below the sinotubular junction. The scalloped shape of the aortic annulus creates three triangular spaces underneath the commissures. The two triangles beneath the commissures of the noncoronary cusp are fibrous structures, whereas the triangular space beneath the commissure between the left and right cusps is mostly muscular. These three triangles are seen in Fig. 30-1. The aortic annulus evolves along three horizontal planes within a cylindrical structure. Thus, the annulus of each cusp inserts itself in the aortic root along a single horizontal plane. The sinotubular junction represents the end of the aortic root. It is an important component of the aortic root because the commissures of the aortic valve are immediately below it and changes in the diameter of the sinotubular junction affect the function of the aortic cusps.

The geometry of the aortic root and its anatomic components varies among individuals, but the geometry of these components is somewhat interrelated. For instance, the larger the aortic cusps, the larger are the diameters of the aortic annulus and sinotubular junction. The aortic cusps are semilunar (crescent shape) and their bases are attached to the annulus; the free margins extend from commissure to commissure, and the cusps coapt centrally during diastole. The size of the aortic cusps varies among individuals and within the same person, but as a rule the noncoronary cusp is slightly larger than the right and left. The left is usually the smallest of the three. Because of the crescent shape of the aortic cusps and the fact that their free margins extend from commissure to commissure, the diameter of the aortic valve orifice must be smaller than the length of the free margins. Indeed, anatomic studies of fresh human aortic roots demonstrated that the average length of the free margins of the aortic cusps was one-third longer than the diameter of the aortic orifice. The diameter of the aortic annulus is 15 to 20% larger than the diameter of the sinotubular junction in children, but this relationship changes with age and the diameter of the aortic annulus is often smaller than the diameter of aortic annulus in older persons (see Fig. 30-2).

The aortic annulus, the aortic cusps, and the sinotubular junction play an important role in maintaining valve competence. On the other hand, the aortic sinuses play no role in valve competence, but they are believed to be important in minimizing mechanical stress on the aortic cusps during the cardiac cycle by creating eddies currents between the cusps and the aortic sinuses.

All components of the aortic root are very elastic and compliant in children but compliance decreases with aging as elastic fibers are replaced by fibrous tissue. Expansion and contraction of the aortic annulus during the cardiac cycle are heterogeneous probably because of its attachments to contractile myocardium as well as to fibrous structures such as the membranous septum and intervalvular fibrous body. On the other hand, the expansion and contraction of the sinotubular junction are more uniform. The aortic root also displays some degree of torsion during isovolumic contraction and ejection of the left ventricle. The movements of the aortic annulus, cusps, sinuses, and sinotubular junction also change with aging as elastic fibers are replaced by fibrous tissue.

Anatomically normal aortic cusps may become calcified late in life and cause aortic stenosis. This type of lesion is called dystrophic calcification, senile calcification, or degenerative calcification. The range of histopathologic lesions includes calcification, chondroid and osseous metaplasia, neorevascularization, inflammation, and lipid deposition.

Bicuspid aortic valve is estimated to occur in 0.5% to 1.5% of the population.¹ Males are affected more than females at a ratio of 4:1. There is a relatively high incidence of familial clustering, which suggests an autosomal dominant inheritance with reduced penetrance.² Extensive research in the genetics of bicuspid aortic valve is being presently conducted and this disorder is likely heritable.² Most patients with bicuspid aortic valve have three aortic sinuses and two cusps of different sizes. The larger cusp often contains a raphe instead of a commissure. The raphe extends from the mid portion of the cusp to the aortic annulus, and its insertion in the aortic root is at a lower level than the other two commissures. Bicuspid aortic valves with two aortic sinuses and no raphe are least common and called “type 0”; the most common is with one raphe and is called “type 1”; and finally with two raphes is “type 2.”³ Types 1 and 2 can be subclassified according to the fused cusps: L-R is the most common form (a raphe in between the left and right cusps). Most patients with bicuspid aortic valves have a dominant circumflex artery and a small right coronary artery. Bicuspid aortic valve may function satisfactorily until late in life when it may become calcified and stenotic.⁴ It may also become incompetent, particularly in younger patients and is often associated with dilated aortic annulus and prolapsed cusp.

Other congenital anomalies of the aortic valve are the unicuspid and quadricuspid valves. Subaortic membranous ventricular septal defect can cause aortic insufficiency because of distortion of the aortic annulus and prolapse of the right cusp.

Numerous connective tissue disorders (ankylosing spondylitis, osteogenesis imperfecta, rheumatoid arthritis, Reiter’s syndrome, lupus, etc.) can cause aortic insufficiency. The anorexigenic drugs phentermine and fenfluramine can also cause aortic insufficiency. Rheumatic aortic valve disease is still prevalent in developing countries and can cause aortic stenosis and/or insufficiency by causing fusion, fibrosis, and contraction of the cusps.

Degenerative diseases of the media with aneurysm formation are the most common disorders of the aortic root and ascending aorta. A broad spectrum of pathologic and clinical entities is grouped under degenerative disorders, and it ranges from severe degeneration of the media, which can become clinically important early in life in cases such as Loyes-Dietz syndrome, to cases of the not so important mild dilation of the ascending aorta in elderly patients. Bicuspid and unicuspid aortic valve disease often display premature degeneration of the media with dilation of the aorta. Atherosclerosis, infectious and noninfectious aortitis are other pathologic entities.

Aneurysms of the ascending aorta are often caused by cystic medial degeneration (cystic medial necrosis). Histologically, necrosis and disappearance of muscle cells in the elastic lamina, and cystic spaces filled with mucoid material are often observed. Although these changes occur more often in the ascending aorta, they may affect any portion or the entire aorta. These changes weaken the arterial wall, which dilates and forms a fusiform aneurysm. The aortic root may be involved in this pathologic process, and in patients with Marfan syndrome, the aneurysm usually begins in the aortic sinuses. A large proportion of patients with aortic root aneurysms do not fulfill the criteria of diagnosis of Marfan syndrome, but the gross appearance of the aneurysm and the histology of the arterial wall may be indistinguishable from that of Marfan syndrome. These cases are referred to as forma frusta of Marfan syndrome.

Patients with aortic root aneurysms are usually in their second or third decade of life when the diagnosis is made. These patients develop aortic insufficiency because of dilation of the sinotubular junction and/or aortic annulus (Fig. 30-3). Annuloaortic ectasia is a term used to describe dilation of the aortic annulus.

Other patients have relatively normal aortic roots but develop ascending aortic aneurysms. These patients are usually in their fifth or sixth decade of life. Finally, certain patients have extensive degenerative disease of the entire aorta and develop the so-called mega-aorta syndrome with dilation of the entire thoracic and abdominal aorta. Ascending aortic aneurysm may cause dilation of the sinotubular junction with consequent aortic insufficiency (Fig. 30-3).

Marfan Syndrome

Marfan syndrome is an autosomal dominant variably penetrant inherited disorder of the connective tissue in which cardiovascular, skeletal, ocular, and other abnormalities may be present to a variable degree. The prevalence is estimated to be around 1 in 5000 individuals. It is caused by mutations in the gene that encodes fibrillin-1 (FBN1) on chromosome 15. This is a large gene (approximately 10,000 nucleotides in the mRNA), and identification of the mutation is a complex task. More than 1000 mutations in FBN1 have been identified. The phenotype presents a highly variable degree because of varying genotype expression.

The clinical features of Marfan syndrome were thought to be a result of weaker connective tissues caused by defects in fibrillin-1, a glycoprotein, and principal component of the extracellular matrix microfibril. This concept was inadequate to explain the overgrowth of long bones, osteopenia, reduced muscular mass, and adiposity and craniofacial abnormalities often seen in Marfan syndrome.⁵ Dietz and colleagues^5,6 showed in an experimental mouse with Marfan syndrome that many findings are the result of abnormal levels of activation of transforming growth factor beta (TGF-β), a potent stimulator of inflammation, fibrosis, and activation of certain matrix metalloproteinases, especially matrix metalloproteinases 2 and 9. Excess TGF-β activation in tissues correlates with failure of lung septation, development of a myxomatous mitral valve, and aortic root dilation in mice. This combination of structural microfibril matrix abnormality, dysregulation of matrix homeostasis mediated by excess TGF-β, and abnormal cell-matrix interactions is responsible for the phenotype features of the Marfan syndrome. Ongoing destruction of the elastic and collagen lamellae and medial degeneration result in progressive dilation of the aortic root, as well as a predisposition to aortic dissection from the loss of appropriate medial layer support. Loss of elasticity in the media causes increased aortic stiffness and decreased distensibility.

The diagnosis of Marfan syndrome is made on clinical grounds, and it is not always simple because of the variability in clinical expression. A multidisciplinary approach is needed to diagnose and manage patients afflicted with this syndrome. The revised Ghent criteria to diagnose Marfan syndrome is summarized in Table 30-1.⁷ The most common cardiovascular features are aortic root aneurysm and mitral valve prolapse. These anatomical abnormalities may cause aortic rupture, aortic dissection, aortic insufficiency, and mitral insufficiency.

Loeys-Dietz Syndrome

Mutations in the genes encoding TGF-β receptors 1 and 2 have been found in association with a continuum of clinical features. On the mild end, the mutation have been found in association with presentation similar to that of the Marfan syndrome or with familial thoracic aneurysm and dissection, and on the severe end, they are associated with a complex phenotype in which aortic dissection or rupture commonly occurs in childhood.⁸ This complex phenotype is characterized by the triad of hypertelorism, bifid uvula or cleft palate, and generalized arterial tortuosity with widespread vascular aneurysm and dissection. This phenotype has been classified as Loeys-Dietz syndrome. Affected patients have a high risk of aortic dissection or rupture at an early age and at relatively small diameters. CT angiograms should be obtained from head to pelvis.

Ehlers-Danlos Syndrome

Vascular Ehlers-Danlos syndrome is a rare autosomal dominant inherited disorder of the connective tissue resulting from mutation of the COL3A1 gene encoding type III collagen. Spontaneous rupture without dissection of large- and medium-caliber arteries such as the abdominal aorta and its branches, the branches of the aortic arch, and the large arteries of the limbs accounts for most deaths. Aortic root dilation was present in 28% in a series of 71 patients with Ehlers-Danlos syndrome.⁹ Aortic dissection is uncommon. Diagnosis is confirmed either by biochemical assays showing qualitative or quantitative abnormalities in type III collagen secretion or by molecular biology studies demonstrating mutation of the COL3A1 gene. Varied molecular mechanisms have been observed with different mutations in each family. No correlation has been established between genotype and phenotype. Diagnosis should be suspected in any young person presenting with arterial or visceral rupture or colonic perforation.

Other Aortic Root Aneurysm Associated with Genetic Syndromes

Aneurysm-osteoarthritis syndrome is associated with pathogenic SMAD-3 gene and is clinically characterized by aortic root aneurysm, aortic dissection, arterial aneurysms and dissection, arterial tortuosity, mitral valve prolapse, congenital cardiac defects, and osteoarthritis, soft skin, flat feet, scoliosis and recurrent hernias.¹⁰ Aortic root aneurysms can also be associated with mutations of TGFβ-2 and with mutations of fibrillin-4 gene (FBLN4; cutis laxa syndrome).^11,12

Other Pathologies

Familial thoracic aneurysms can be associated with mutations of various genes (TGFβ1-2, ACTA2, MLCK, SMAD3, TGF2) without systemic syndrome such as those described above. Atherosclerotic aneurysms of the ascending aorta are uncommon. They are more common in the abdominal aorta and to a lesser degree in the descending thoracic aorta. Atherosclerosis often causes irregular and saccular aneurysms of the ascending aorta rather than a more fusiform shape as seen with degenerative diseases.

Infectious aneurysms of the ascending aorta are rare. Syphilis was a common cause of aneurysm of the ascending aorta but it is seldom seen. The spirochetal infection destroys the muscular and elastic fibers of the media, which are replaced by fibrous and other inflammatory tissues. The ascending aorta is the most common site of involvement and the aneurysm is usually saccular. The wall of the ascending aorta is frequently calcified. Syphilitic aortitis also causes coronary ostial stenosis and aortic valve insufficiency. Other bacteria can also cause aneurysm of the ascending aorta.

Various types of aortitis may involve the ascending aorta. Giant cell arteritis is among the more common and it involves medium-sized arteries, but the aorta and its branches are involved in approximately 15% of the cases. The etiology is unknown. The characteristic lesion is a granulomatous inflammation of the media of large- and medium-caliber arteries such as the temporal artery. Occasionally the inflammatory process weakens the aorta leading to aneurysm formation, aortoannular ectasia, and aortic insufficiency.

Ankylosing spondylitis, Reiter’s syndrome, psoriatic arthritis, and polyarteritis nodosa can cause aortic insufficiency because of annuloaortic ectasia. Behçet’s disease can cause aneurysm of the ascending aorta.

Aortic Stenosis

Asymptomatic patients with aortic stenosis have a good prognosis.¹³ Sudden death in asymptomatic patients is uncommon. However, when symptoms develop, the prognosis becomes poor and the average survival is 2 to 3 years for patients with symptoms of angina and syncope, and 1 to 2 years for those with congestive heart failure.¹⁴