The Greek physician Galen first described superficial false aneurysms arising from venesection in the antecubital fossa and in gladiators injured during battle in the second century A.D.¹ Antyllos, during the same time period, distinguished between true and false aneurysms and attempted surgical treatment with proximal and distal ligation, opening of the aneurysmal sac, and removal of its contents.²

The French physician Jean Francois Fernel, in 1542, described aneurysms, “in the chest, or about the spleen and mesentery where a violent throbbing is frequently observable.”³ In 1543, Andeas Versalius described a thoracic aortic aneurysm. In the late 1500s, Ambroise Paré described a death by a ruptured thoracic aortic aneurysm and either Fernel or Paré proposed that syphilis played a causative role in some aortic aneurysms.¹ In 1760, Morgagni reported the first cases of aortic dissection and in 1773, Alexander Monro described three coats of the arterial wall, and the destruction of the wall in the formation of true and false aneurysms.¹

Peripheral arterial ligation was developed in the 1800s by John Hunter, who demonstrated safe and reproducible means of ligating certain peripheral arteries.⁴ Innovative measures used to cause thrombosis of aneurysms included the insertion of long segments of wire⁵ with the application of an electric current,⁶ and wrapping of aneurysms with cellophane or other irritating materials.^7,8

In 1888, Rudolph Matas introduced obliterative endoaneurysmorraphy in which stitches placed from within the aneurysm sac obliterated the arterial openings.⁹ This allowed closure of large aneurysms that would have been difficult to ligate externally. Recognizing the importance of maintaining arterial continuity for certain aneurysms, he subsequently devised techniques of restorative or reconstructive endoaneurysmorraphy, in which diseased segments of the aneurysm wall were resected and the remaining vessel wall was reconstructed to reestablish flow.¹⁰ The number of aneurysms to which these techniques could be applied, however, was very limited. The broad application of surgical treatment for major arterial aneurysms would have to await the development of satisfactory conduits and the techniques to insert them.

The first report of a descending aortic repair was described by Cooley and DeBakey in 1952. The technique involved lateral resection and aortography performed on a saccular aneurysm without cardiopulmonary bypass (CPB).¹¹ In 1956, Cooley and DeBakey performed replacement of the ascending aorta with a segment of homograft with CPB.¹² Polyester cloth grafts were introduced by DeBakey, who discovered it in a Houston department store, and it soon became the artificial conduit of choice for aortic replacement.¹³ Technical improvements in graft replacements included the impregnation of polyester grafts with albumin, collagen, or gelatin, which has greatly reduced the blood loss through the grafts.¹⁴

Wheat et al in 1964, resected the ascending aorta and entire aortic root except for the aortic tissue surrounding the coronary arteries.¹⁵ They then performed a mechanical valve insertion and fashioned the proximal tube graft to accommodate the coronary arteries, which were left in situ. The first composite aortic root replacement was performed by Bentall and De Bono in 1963 to treat an ascending aortic aneurysm in a patient with Marfan syndrome (MFS) who had severe thinning of the aortic wall in the sinus segment.¹⁶ The original technique involved hand sewing a Starr #13 mechanical prosthesis to a preclotted graft (Fig. 48-1). An inclusion-type technique with aortic wrap in which the coronary buttons were left in situ and anastomosed to holes made in the graft was performed. Due to concerns about coronary malposition, in 1981, Cabrol et al described the use of an 8 to 10 mm Dacron graft to attach to independently mobilized coronary artery buttons.¹⁷ Techniques eventually evolved to the current method of individual coronary button reimplantation as described by Kouchoukos and Karp with end-to-end anastomoses as opposed to the inclusion technique which tended to be prone to pseudoaneurysm formation.¹⁸

The aortic root is in extension of the left ventricular outflow tract and that provides the scaffolding for the elements of the aortic valve and connects to the descending aorta. Its components include the aortic valve cusps, the sinuses of Valsalva, the aortic annulus and subcommissural triangles, and the sinotubular junction (Fig. 48-2).¹⁹ The aortic valve cusps attach to the aortic annulus at hinge point following a semilunar contour being a three-pointed crown type arrangement not a circular or oval ring. The annular tissue itself is typically 50 to 60% fibrous tissue along the hinge point between the aortic and mitral valves as well as the membranous portion of the septum, and the remainder is muscular. Small projections of collagen anchor the aortic root to the ventricular muscle.²⁰ The apices of the attachments of the cusps to the aortic annulus are known as commissures and the most superior aspect of the commissures interrelates with the sinotubular junction. The sinotubular junction is a ridge which marks the beginning of the ascending aorta. The sinotubular junction diameter is typically 15 to 20% smaller than annular diameter in younger patients.²¹ With aging, the sinotubular junction diameter becomes larger. When the sinotubular junction is more than 10% larger than the annular diameter there is frequently resultant aortic insufficiency as the leaflets were no longer coapt due to displacement of the commissures.

Between the sinotubular junction and the aortic annulus are expanded segments of the aorta referred to as the sinuses of Valsalva. The sinuses form a cloverleaf rather than circular alignment when viewed in cross-section (Fig. 48-3).²² Dilatation of the aortic sinuses and annulus is referred to as aortoannular ectasia. Each sinus is named for its corresponding coronary artery (right, left, and noncoronary).

The noncoronary sinus is anatomically related to the left and right atria as well as the transverse sinus. The left coronary sinus anatomically relates to the left atrium and the right coronary sinus is related to the right atrium and right ventricle. The subcommissural triangle between the right and noncoronary arteries is anatomically related to the conduction system within the membranous septum as well as the septal leaflet of the tricuspid valve. The left and noncoronary subcommissural triangles are related to the anterior leaflet of the mitral valve. The ascending aorta starts at the level of the sinotubular junction and ascends to the level of the takeoff of the innominate artery.

The ascending aorta histologically contains a high proportion of compliant elastic tissue allowing it to serve as a reservoir and that stores kinetic energy from the systolic pulse wave as it expands and uses it to maintain flow during diastole via elastic recoil. The ascending aorta is a three layered structure composed of a smooth intimal layer composed of a single layer of endothelial cells adhered to a basal lamina; a medial layer composed of layers of elastin sheets, collagen, smooth muscle cells, and extracellular matrix; and an outer layer of adventitial tissue which includes the vasa vasorum and nerves.²³ The elastin content of the aorta decreases distally and in the abdominal aorta is less than half of that in the ascending aorta.²⁴ The principle biologic causes of aneurysm formation in the ascending aorta are related to degenerative processes in the elastic media, as compared to primarily atherosclerotic changes in the descending and abdominal aortas.²⁵

Ascending aortic aneurysm formation is the result of several biologic and mechanical mechanisms. Disruption of the balance between homeostatic mechanisms within the aortic wall including elastic and collagen elements, proteoglycans, proteolytic enzymes and their inhibitors, and inflammatory mediators causes a spectrum of aortic pathology which manifests in the final pathway as aortic enlargement eventually leading to rupture or dissection. Fragmentation of the extracellular matrix of the aortic media occurs due to matrix-degrading enzymes such as matrix metalloproteinases and cathepsin groups.^26-30 Matrix metalloproteinases comprise a family of proteases that are capable of degrading virtually all components of the extracellular milieu and perform a variety of tasks necessary for normal homeostasis, including maintenance of the dynamic integrity of the extracellular structure within the arteries.^26-28 Aneurysms form as elastic layers fragment, smooth muscle cells become dysfunctional, and eventually elastic and smooth muscle components are replaced with a cystic appearing mucoid material (Fig. 48-4).³¹ This process is referred to as cystic medial degeneration. The term cystic medial necrosis has also been applied to this condition but has been largely abandoned as there is no true necrotic process involved. To a lesser extent, mild degeneration of the aortic wall is common with advanced age and is responsible for the slow dilation of the ascending aorta with age. Smoking tends to exacerbate this degeneration.³²

Mechanical changes to aortic wall characteristics such as alterations in cross-sectional symmetry, compliance, and stress-strain relationships likely predate dilatation. The Young-Laplace relationship describes the relationship between aortic diameter and wall tension where increases in aortic wall diameter lead to increases in wall stress at similar pressures (tension = pressure × radius). Changes in aortic wall compliance, broadly defined as the change in volume of the vessel with a change in pressure, lead to increased stress applied to the aortic wall during the systolic impulse and further exacerbate the biologic derangements leading to aneurysm formation.³³ The coupling between mechanical forces on the arterial wall and the biochemical changes leading to aneurysm formation (mechano-transduction) are not yet clearly elucidated.

Degenerative aortic aneurysms cause asymmetric enlargement of the ascending aorta as the segment of aorta along the inner curvature is adherent to the pulmonary artery.³⁴ Hence, there is significant rightward and anterior displacement of the aortic wall (Fig. 48-5). This causes a relative elongation of the ascending aorta in an asymmetric fashion which tends to push the heart into a horizontal arrangement. This also causes a significant change in the orientation of the aortic valve annulus to more oblique arrangement.³⁴ Aneurysmal widening will typically involve the aorta to the level of the sinotubular junction and frequently involves the noncoronary sinus to a lesser extent.³⁵ This widening at the level of the sinotubular junction is responsible for aortic insufficiency in these cases and frequently placement of tube graft to the sinotubular junction will resolve significant central aortic insufficiency. The left and noncoronary sinuses are fairly normal in these cases. The noncoronary aortic valve cusp may be elongated along its free margin in order to compensate for the asymmetric enlargement of the noncoronary sinus.

Marfan Syndrome

MFS is an autosomal dominant syndrome with complete penetrance. Up to 25% of Marfan cases are from sporadic dictation in the overall incidence is one per 3000 to 10,000 live births.³⁶ Traditionally it is thought to have been caused by alterations in the gene (FBM1) coding the aortic wall protein fibrillin-1 leading to elastin derangement, medial degeneration, and aneurysm formation.^37,38 More recently, homology between fibrillin-1 molecules and latent transforming growth factor (TGF) beta binding proteins has led investigators to infer that altered sequestration of the latent form of TGF beta in the extracellular matrix may increase TGF beta activity which negatively impacts smooth muscle development and the extracellular matrix.³⁹ Approximately 80% of patients with MFS develop aortic root aneurysms and nearly half develop mitral regurgitation.⁴⁰ The clinical manifestations of MFS involve multiple organ systems as it is a systemic disease. Diagnosis has traditionally been made using the Ghent criteria, although it is now made definitively using genotyping.⁴¹ Anatomically, MFS results in severe aortoannular ectasia and can have massively dilated sinuses and aortic annulus (Fig. 48-5).

More recently, reports have shown that the use of angiotensin-converting enzyme inhibitors can prolong the life expectancy of smooth muscle cells in the aortic tissue of Marfan patients via an angiotensin-2 type II receptor blockade mechanism which may antagonize TGF beta.⁴² This has led to the clinical application of the angiotensin receptor blocker losartan as a prophylactic therapy to diminish aortic degeneration and aneurysm formation, which has been shown in animal models to be effective when given in the early stages of the disease.⁴³ A small clinical study of 18 pediatric patients also showed decreased aortic growth rate with treatment of losartan.⁴⁴

Loeys-Deitz Syndome

Loeys-Deitz syndrome (LDS) is a more recently described autosomal dominant syndrome.⁴⁵ Rather than a fibrillin-1 defect, however, there is a mutation in TGF beta receptors 1 and 2. Characteristics of LDS include cleft palate, bifid uvula, scoliosis, orbital hypertelorism, pectus deformities, developmental abnormalities, and congenital heart defects including persistent patent ductus arteriosus and atrial septal defects.⁴⁵ Patients may phenotypically have characteristics that overlapped between LDS and MFS.⁴⁶ Histologically, it is associated with increased medial collagen and a subtle but diffuse form of elastic fiber fragmentation and extracellular matrix deposition.⁴⁷ LDS has a more rapid clinical course than MFS and prophylactic aortic root replacement or reimplantation is often recommended at younger ages and with smaller aortic dimensions.

Ehlers-Danlos Syndrome

Ehlers-Danlos syndrome is caused by either sporadic mutation or inherited autosomal dominant trait resulting in a connective tissue disorder derived from defective type III collagen synthesis. The type IV variant of the Ehlers-Danlos syndrome is associated with spontaneous arterial rupture. Most commonly this occurs in the mesenteric or carotid arteries. However, spontaneous rupture of the descending aorta and aortic arch has been described.⁴⁸ The arterial wall of these patients is extremely thin and friable. Ascending aortic involvement may occur as a consequence of retrograde extension of a primary brachiocephalic branch pathology.

Familial Thoracic Aortic Aneurysms and Dissections

Approximately 20% of patients with thoracic aortic aneurysms have a first-degree relative with an aortic aneurysm.⁴⁹ These families often exhibit strong tendencies for thoracic aortic aneurysm formation without any clearly definable syndromic connective tissue disorder such as MFS or LDS. Grouped together as familial thoracic aortic aneurysms and dissections (FTAAD), mutations in ACTA2, SMAD3, TGFBR1, TGFBR2, TGFB2, and MYH11 have been identified to predispose patients to thoracic aortic aneurysms and dissections in an autosomal dominant manner. These mutations result in incomplete penetrance, variable expression, and variable age of aneurysm onset.^49-55 Genetic testing for patients and family members with multiple first- and second-degree relatives and suspected FTAAD is available. New evidence suggests that these patients are at increased risk for earlier rupture and dissection at diameters less than 5 cm, as seen in patients with LDS and MFS. Genetic testing has the opportunity to stratify these patients and identify those at greatest risk for rupture.

Infectious and Inflammatory Etiologies

Infections and systemic inflammatory disorders can occasionally cause damage to the wall of the ascending aorta leading to aneurysm formation. Frequently, despite high-quality preoperative imaging and even with intraoperative tissue pathology, it is not possible to distinguish definitively between the different possible etiologies.

Ascending aortic aneurysms caused by infection are extremely uncommon. Such mycotic ascending aortic aneurysms are frequently related to concomitant left-sided valvular endocarditis. Most common organisms include, in order of decreasing frequency, Staphylococcus aureus, S. epidermidis, Salmonella, and Streptococcus.⁵⁶ In cases of atherosclerotic aneurysm, if there is intraluminal clot in the ascending aorta, transient bacteremia may lead to infected clot leading to a mycotic aneurysm.⁵⁷

Syphilis, caused by the spirochete Treponema pallidum, was the predominant cause of ascending aortic aneurysms in the pre-antibiotic era and accounted for 5 to 10% of all cardiovascular deaths.⁵⁸ Typically syphilitic aortitis involves the thoracic aorta with a particular predilection for the ascending aorta, likely due to its rich vascular and lymphatic supply. The pathologic process involves a multifocal lymphoplasmacytic infiltrate of the vasa vasorum leading to degeneration of the medial elastic fibers. The intima develops wrinkles, ridges, and plaques described as a “tree bark” appearance.⁵⁹ Inflammation around the coronary artery ostia may lead to high-grade proximal occlusions. The inflammatory process may be either patchy or diffusely involve a large section of aorta. Once established, treatment of syphilis with antibiotics does not reverse the vascular lesions.

Other systemic arteritis conditions may also produce ascending aortic aneurysms. Takayasu’s arteritis, associated with inflammation of the vasa vasorum, medial necrosis and may also have intimal changes similar to syphilis. It is typically seen in females between 15 to 30 years of age and frequently involves occlusive lesions to major branch vessels of the arch.⁶⁰ While syphilis aortitis often leads to rapid aneurysmal degeneration, this is much less common in Takayasu’s aortitis, occurring only in 15% of cases.⁶¹ Giant cell arteritis is a systemic arteritis that occurs in elderly patients, most commonly affecting the temporal artery. It is also more common in females and is also associated with polymyalgia rheumatica. Giant cell arteritis is an inflammatory process with inflammatory infiltration with lymphocytes, plasma cells, and histiocytes. There is variable presence of giant cells.⁶² Aortitis leading to aortic aneurysm may also be associated rarely with Behçet’s disease, rheumatoid arthritis, sarcoidosis, ankylosing spondylitis, lupus erythematosus, and Wegener’s granulomatosis.

Bicuspid Aortopathy

Bicuspid aortic valve is a complex familial syndrome with a male predominance of 3:1.⁶³ It is also associated with Turner syndrome. There is a 9% prevalence of bicuspid aortic valve disease in first-degree relatives of patients with bicuspid aortic valve disease.⁶⁴ More than half of the patients with aortic coarctation have an associated bicuspid aortic valve.⁶⁵ Several genetic defects have been implicated in the formation of bicuspid aortic valve disease however no single genetic etiology has been derived. Aortic dilatation is frequently associated with bicuspid aortic valve disease; however, the mechanism for this occurring is not well delineated. Originally thought to be a sequela of poststenotic dilatation, aortic aneurysm formation in patients with bicuspid aortic valve may occur without any significant aortic stenosis although there is clearly flow perturbation in the proximal sinuses of Valsalva and descending aorta in patients with bicuspid aortic valve.⁶⁶ Recent investigation has shown that embryologically, the aortic valve and ascending aorta arise from the neural crest cells implicating a potential common mechanism for the development of a bicuspid aortic valve and subsequent aneurysm formation.⁶⁷ The aortic wall in the patients with bicuspid aortic valve disease shows increased elastic fragmentation, fibrillin-1 deficiency, matrix disruption, increased levels of matrix metallic proteinases, and smooth muscle cell apoptosis.^67-72

Fazel and colleagues using a cluster-type analysis identified four distinct patterns of aortic dilatation including aortic root alone (13%), ascending aorta alone (10%), ascending aorta and proximal transverse arch (28%), and aortic root, ascending aorta, and proximal transverse arch (45%) (Fig. 48-6).⁷³ This study suggests that for younger patients, definitive treatment of bicuspid aortic valve disease with aortic dilatation requires strategies that address the aortic root, ascending aorta, and proximal transverse hemi-arch. It is advisable to perform an aggressive hemi-arch resecting all aortic tissue along the lesser curve to the level of the subclavian artery take-off in younger bicuspid aortic valve patients to eliminate as much of the diseased aorta as possible. However, total arch replacement with brachiocephalic branch reimplantation is rarely necessary as the aneurysmal component rarely involves the distal aspect of the transverse arch.

Isolated Sinus of Valsalva Aneurysm

Aneurysms of the sinuses of Valsalva (SVA) that occur as isolated lesions are rare abnormalities caused by either a congenital defect in the continuity between the medial layer of the affected sinus and the aortic valve annulus or, less commonly, acquired causes such as endocarditis, syphilis, tuberculosis, focal dissection, iatrogenic causes.⁷⁴ They are more common in males and may be associated with subaortic stenosis, ventricular septal defects, and aortic insufficiency. In over 90% of cases, they involve the right coronary sinus (Fig. 48-7).^75,76 The noncoronary sinus of the second most common location and these aneurysms are extremely uncommon in a left coronary sinus. They are generally asymptomatic until they rupture when they usually cause intracardiac shunts. Right sinus of Valsalva aneurysms typically rupture into the right ventricle, effectively causing a hemodynamic defect similar to a ventricular septal defect. Aneurysms of the noncoronary sinus typically rupture into the right atrium and the left coronary sinus rupture into the pulmonary artery or left ventricle. Occasionally an unruptured left coronary sinus of Valsalva aneurysm may compress the left main coronary artery.⁷⁶

Symptoms

Most ascending aortic aneurysms are asymptomatic when diagnosed, being incidentally noted on chest x-ray or echocardiogram. Anterior chest pain is the most frequent symptom. The pain may be acute in onset signifying impending rupture or a chronic gnawing pain from compression of the overlying sternum. Occasionally signs of superior vena cava (SVC) or airway compression are present. Hoarseness resulting from stretch injury of the left recurrent laryngeal nerve suggests involvement of the distal aortic arch or proximal descending thoracic aorta. Less commonly, aneurysms of the ascending aorta or aortic root can rupture into the right atrium or the SVC, presenting with high-output cardiac failure or bleed into the lungs with ensuing hemoptysis. Acute dissection of the ascending aorta presents with severe tearing pain in over 75% of patients.⁷⁷

Physical Examination

Physical examination is often unremarkable. If there is related aortic insufficiency, a widened pulse pressure or diastolic murmur may be present. If dilation is isolated to the ascending aorta, however, the aneurysm can reach large dimensions without producing physical findings. A thorough vascular examination should be carried out to look for any concomitant peripheral vascular disease, carotid disease, or abdominal aortic aneurysm. Abdominal aortic aneurysms may be present in 10 to 20% of patients with atherosclerotic involvement of an ascending aortic aneurysm.⁷⁸

Electrocardiogram

With significant aortic insufficiency, left ventricular hypertrophy or strain is evident. Patients with generalized atherosclerosis may show evidence of concomitant coronary artery disease or previous myocardial injury.

Chest Radiography

Many asymptomatic ascending aortic aneurysms are first detected on chest x-ray. The enlarged ascending aorta produces a convex contour of the right superior mediastinum (Fig. 48-8A). In the lateral view, there is loss of the retrosternal air space (Fig. 48-8B). Aneurysms confined to the aortic root can be obscured by the cardiac silhouette and may not be evident on chest radiograph.⁷⁹

Echocardiography

Transesophageal echocardiography (TEE) is a portable diagnostic tool that accurately detects and differentiates between ascending aortic aneurysms, dissections, and intramural hematoma (Fig. 48-9).^80-82 TEE is an invasive imaging modality and carries a small risk of esophageal perforation, respiratory compromise, and hemodynamic instability. Imaging of the distal ascending aorta is obscured on TEE by air in the tracheobronchial tree, with up to 40% of its distal extent not well visualized, although this is somewhat mitigated with the use of modern multiplanar probes.⁸³ Although somewhat operator dependent, TEE provides a reliable technique to measure the annular, sinus, sinotubular junction, and ascending dimensions. It is uniquely well suited to examine the most proximal aspects of the aortic root, which are often blurred by motion artifact on computed tomography (CT) scans. Transthoracic echocardiography is far less reliable but may be useful for assessing the severity of aortic regurgitation.

Computed Tomography

Contrast-enhanced CT is the most widely used noninvasive technique for imaging the thoracic aorta. CT scanning provides rapid and precise evaluation of the ascending aorta in regards to size, extent, and location of the disease process (Fig. 48-10). CT scanning detects areas of calcification, and modern scanner accurately identifies dissections and mural thrombus.⁸¹ CT scan technology has evolved with multidetector scanners such that the entire thoracic aorta can be evaluated on one breath-hold and the distance between axial slices can be as small as 0.5 mm. Three-dimensional volume rendering is a highly useful tool for determining true in-plane aortic diameters and the proximal and distal extent of aortic disease relative to the arch vessels, which can aid the surgeon in operative planning (Fig. 48-11). Ideally, the entire thoracic and abdominal aorta should be examined for evidence of concomitant aneurysm disease in the arterial tree. Gating to the electrocardiogram during image acquisition eliminates the motion artifact that may be seen in the most proximal aspects of the aortic root and can also allow for assessment of the coronary arteries.⁸⁵ The main disadvantage of CT scans is the need for contrast solution for optimal resolution, which may be contraindicated in those patients with renal insufficiency or a history of a dye allergy. Noncontrast CT scans allow for assessment of aortic diameters but cannot identify dissection flaps or other acute pathologies.

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) can provide axial and three-dimensional reconstruction of the ascending aorta with the avoidance of iodinated contrast agents and radiation exposure. Contrast-enhanced MR angiography with gadolinium allows more precise measurements of the aorta and its major branches with images comparable to conventional angiography (Fig. 48-12).⁸⁶ MRI scanners are relatively unsuitable for those patients connected to mechanical ventilators or hemodynamic monitoring equipment. MRI is more expensive, less readily available, and requires significantly more acquisition time than CT scanning and is used less frequently.

Elective aortic replacement is used as a means to prophylactically prevent aortic catastrophe such as dissection and rupture which carry high mortality. Recent data from the International Registry of Acute Aortic Dissections (IRAD) show an operative mortality for emergent type A aortic dissection repair of 26%, although this is generally lower in more experienced centers.⁸⁷ Bickerstaff et al examined the natural history of 72 patients that were diagnosed with aortic aneurysms and did not undergo surgery.⁸⁸ Over a 5-year follow-up period, 74% of patients experienced aortic rupture or dissection (Fig. 48-13). Of these 94% died. The overall 5-year survival was only 13% in untreated aneurysm patients compared with 75% in control patients without aortic aneurysms.

Traditionally, the most important criterion for ascending aortic replacement on an elective basis is maximal aortic diameter. In natural history studies by Coady et al, patients with 3.5 to 3.9 cm aortic aneurysms were very unlikely to rupture within 3 to 4 years, and each incremental 1 cm increase from this point increased rupture risk (Fig. 48-14).⁸⁹ Patients with aneurysms greater than 5 cm showed substantially higher dissection and rupture risk within the first year. Using a logistic regression model, they found that the aneurysm with maximal diameter of 6.0 to 6.9 cm had a 4.3 times greater increased risk of rupture or dissection then an aneurysm that is 4.0 to 4.9 cm in diameter. Growth rates for aortic aneurysms less than 4 cm are about 0.1 cm per year and this increases gradually as aortic size increases up to 0.4 cm per year.^90,91 Uncontrolled hypertension, smoking, and presence of connective tissue disorders are associated with more rapid aortic growth.⁹⁰ Patients with MFS are at particularly high risk for rupture or dissection of smaller sizes and dissection is frequently seen with a maximal ascending aortic dimension of less than 5 to 6 cm (Fig. 48-15).⁹² Strikingly the average age of death for untreated patients with MFS is 32 years, with complications of the aortic root being responsible for 60 to 80% of these deaths.⁹³ Marfan’s patients with a family history of early dissection or rupture are at the highest risk for aortic catastrophe occurring at smaller dimensions.⁹⁴

Although size clearly correlates with rupture risk, it is important to note that many aortic dissections occur in ascending aortas that are less than 5.5 cm in diameter. In the IRAD registry, over 59% of 591 enrolled patients with acute type A aortic dissections had maximum aortic dimensions less than 5.5 cm and 40% were less than 5.0 cm (Fig. 48-16).⁹⁵ As the understanding of the biologic mechanisms behind aortic aneurysm formation improves, in the future, serum biologic markers and sensitive imaging techniques that can detect subtle changes in aortic strain characteristics or compliance may provide more accurate identification of the high-risk aorta.

Therapies designed to limit the growth of aortic aneurysms are targeted at mechanisms either to diminish stress on the aortic wall or to prevent deleterious degenerative biochemical changes. In general, patients with aortic aneurysms should avoid high intensity isometric exercise such as weight lifting as aortic pressures may increase rapidly and exert significant stress on the aortic wall. Weight lifting restriction should be less than 1/3 to 1/2 of the patient’s body weight. Additionally exercises with rapid bursts of acceleration and deceleration such as basketball may place excess of stress of aortic wall.

Anti-impulse therapies are the mainstay treatment for thoracic aortic aneurysms. Due to their negative chronotropic and inotropic effects, beta blockers are typically used as a first line treatment.⁹⁶ The primary goals of beta blocker therapy are to decrease the overall blood pressure and to decrease the change in aortic pressure over time (dP/dT) to diminish the stress applied to the aorta in systole thereby limiting damage to the media layer. The rationale for using beta blockers was initially established with an ex vivo plastic model of aortic dissection by Wheat et al in which a tear created in an artificial intimal layer of rubber cement in the plastic tubing propagated less when the pulse pressure was artificially flattened, while variation of mean blood pressure and flow rates had no effect.⁹⁷ Studies performed on turkeys, which are uniquely prone to aortic dissection, showed that the combination of sodium nitroprusside and propanolol were effective at preventing rupture, while lowering blood pressure with nitroprusside alone was ineffective and may have actually increased dP/dT due to reflex sympathetic stimulation causing increased chronotropy and inotropy.⁹⁸ In a landmark study by Shores et al, young patients with MFS randomized to a regimen of beta blocker therapy had significantly less aortic dilatation over a 10-year follow-up period (Fig. 48-17) and also had a lower incidence of a composite end point of death, congestive heart failure, aortic dissection, severe regurgitation, or aortic root surgery versus controls.⁹⁹ These results have been extrapolated to a wider variety of patients with ascending aortic aneurysms in whom beta blockade is used extensively.

Non-Elective Indications

Any new onset of acute dissection, rupture, or intramural hematoma generally warrants immediate surgery. The presence of symptoms of chest pain in patients with ascending aortic aneurysms greater than 4.5 to 5 cm is a sign of impending rupture and should also be managed operatively with expediency. Acute severe congestive heart failure secondary to root dilatation and loss of sinotubular junction either from rapid aneurysm expansion or from chronic dissection also warrants early operative management, although aggressive diuresis and cardiac optimization for 1 to 2 days prior to surgery are frequently helpful.

Elective Indications

Despite the limitations of size criteria, decisions to intervene are still largely decided based on maximal aortic diameter and growth rate. For degenerative aneurysms in the absence of connective tissue disorders or other cardiac pathology, elective repair is reasonable at an absolute maximal diameter of 5.5 cm.¹⁰⁰ Growth rate of greater than 1 cm per year is generally accepted as a strong indication to proceed with surgery for degenerative aneurysms regardless of diameter.¹⁰¹ Some groups have also advocated the use of normalized aortic dimensions to body size to provide a more accurate reflection of the aneurysm dimension for an individual patient.¹⁰²

The aortic ratio is calculated as measured diameter divided by predicted diameter for a given age and body surface area. Using this method, elective replacement is warranted at an aortic ratio of 1.5 in an asymptomatic patient without a connective tissue disorder or other complicating factors.¹⁰³ This leads to intervention at a size of only 4.8 to 5.0 cm in an adult less than 40 years of age with a body surface area of 2 m².¹⁰⁴ Because the ascending aorta normally increases in size with age, the diameter for intervention would be higher in a patient more than 40 years old.

Special Considerations

Patients with MFS are at higher risk for rupture and the ascending aorta should be replaced prophylactically at a diameter of 4.5 cm or an aortic ratio of 1.3 to 1.4.^103,104 Patients with Loeys-Dietz rupture at a smaller dilation than in MFS and should be electively repaired at 4.2 cm.¹⁰⁵ Among patients with bicuspid aortic valves, there remains ongoing debate. The 2013 Society of Thoracic Surgeons Clinical Practice guidelines suggest 5.0 cm (4.5 cm if there is a family history of aortic dissection) whereas the ACC/AHA Valve guidelines recommend 5.5 cm (5.0 cm for a family history of aortic dissection or rapid aortic growth greater than 5 mm/year).^106,107 In the setting of connective tissue disorders, bicuspid aortic valve or chronic dissection, a growth rate of greater than 0.5 cm per year should warrant repair. A chronically dissected aorta, which the external aortic wall is supported only by the residual outer third of the medial and advential layers, should be replaced when aortic diameters reach 4.5 cm or a ratio of 1.3 to 1.4 due to the intrinsic weakness of the aortic wall.^103,108 Pseudoaneurysms, which are frequently from previous aortic suture lines, should be repaired upon diagnosis due to high rupture risk related to their extremely thin walls.

In younger patients, where aortic root reimplantation is preferred to avoid life-long anticoagulation, earlier repair may prevent the development of aortic valve cusp pathology and improve the chances of successful repair. Among patients undergoing aortic valve replacement who have ascending aortic aneurysms, Prenger et al reported a 27% incidence of aortic dissection if the aorta was greater than 5 cm versus 0.6% incidence if aortic size was normal.¹⁰⁹ In general, in the setting of other cardiac surgery, ascending aortas with a maximal dimension of 5.0 cm or a ratio of 1.5 should be replaced.^103,109

Nearly one-third of patients undergoing surgery for thoracic aortic disease have chronic obstructive pulmonary disease.¹¹⁰ Patients with suspect pulmonary function should have spirometry and room air arterial blood gases. Smoking cessation, antibiotic treatment of chronic bronchitis, and chest physiotherapy may prove beneficial in elective situations. Normal renal function should be ensured with the appropriate blood work, and abnormal results should prompt further investigation. Because unaddressed severe carotid disease is a risk factor for stroke during ascending aortic operations, patients over the age of 65 should have duplex imaging of their carotids.¹¹¹ Younger patients with peripheral vascular disease, extensive coronary artery disease, carotid bruits, or history suspicious for cerebral ischemia should be investigated as well. CT or MRI of the thoracic and abdominal aorta is usually indicated. Coronary angiography should be performed in all patients to evaluate for significant coronary atherosclerosis and lesions with greater than 50 to 60% stenosis should be bypassed. Coronary angiography also helps define the coronary anatomy to identify anomalous or intramural coronary arteries which may complicate root replacement.¹¹²

Monitoring and Anesthesia

All procedures are performed using central venous access and a pulmonary artery catheter. Location of arterial line for blood pressure monitoring should be discussed with the anesthesia team preoperatively although generally right radial is preferred. Nasopharyngeal and bladder temperature monitors are used. Bilateral near infrared spectroscopy (NIRS) is employed to provide real-time estimation of cerebral saturation though out the bypass run.¹¹³ Precipitous drops in cerebral saturations are managed with increasing perfusion pressure and hematocrit to the cerebral circulation. In circulatory arrest cases, EEG monitoring is also employed to ensure EEG silence during interruption of cerebral circulation.

TEE plays a critical role in diagnosis, particularly of degree of aortic insufficiency and sinus segment and sinotubular junction anatomy that is not well assessed by CT angiography. It is also critical for hemodynamic management separating from CPB.

Anesthesia management includes fentanyl 25 to 50 μg/kg, midazolam 0.1 to 0.2 mg/kg, isoflurane 0.5 to 1.5%, pancuronium 0.1 to 0.2 mg/kg, and end-tidal concentration in CO₂. Aminocaproic acid is dosed initially as an intravenous bolus of 5 g, followed by a maintenance intravenous infusion of 1 g/h and stopped within 2 hours of patient admission to the intensive care unit. Pharmacologic adjuncts in circulatory arrest cases include 1 g of methylprednisolone, 1 g of magnesium sulfate, 2.5 mg/kg of lidocaine, and 12.5 g of mannitol.¹¹⁴

Myocardial Protection

Typically, 1 L of cold blood hyperkalemic cardioplegia (4°C) is given antegrade into the aortic root. A left ventricular vent is employed to prevent distension. In cases of severe aortic insufficiency, the aorta is opened and the coronary ostia are cannulated directly with handheld cannula. A temperature probe is placed through the anterior myocardium into the septum and a myocardial temperature of 6 to 8°C is achieved. Retrograde cardioplegia is administered at least every 20 minutes and continuously when possible. It is important to give cardioplegia immediately prior to commencing circulatory arrest and at its conclusion.

Circulation Management

Cannulation strategies vary significantly with individual pathology and the modern cardiovascular surgeon must be proficient in several different techniques. With experience, ascending aortas as large as 7 cm may be directly cannulated. This can be done with the traditional stab-technique or using a Seldinger technique over a wire in thin-walled aortas. In aneurysms which terminate prior to the innominate artery, the transverse arch is easily directly cannulated. In cases where antegrade cerebral perfusion is required, either the ascending aorta may be cannulated directly if using selective direct perfusion cannulas or the right axillary artery may be employed. Right axillary artery cannulation, which has grown in popularity in recent years, should be performed through an 8 or 10 mm Dacron graft anastomosed end-to side to the axillary artery as there is risk of dissection from direct cannulation of this friable artery. In some instances, femoral artery cannulation can be employed, but should be avoided in patients with atheroma in the thoracic aorta by CT scan or TEE. A standard two-stage venous cannula is used unless performing concomitant mitral or tricuspid surgery.

The use of deep hypothermic circulatory arrest (DHCA) was first described in conjunction with cardiac operations in the 1960s.¹¹⁵ In the 1970s, there was renewed interest in DHCA after its successful use during repair of complex congenital defects.¹¹⁶ Later, Greipp and Stinson reported the first case series using DHCA during arch aneurysm repairs and supported its efficacy in cerebral protection.¹¹⁷ As interest in DHCA continued to grow; investigators, using dog models, illustrated how profound cerebral hypothermia dramatically decreased cerebral metabolism.^118-120 As knowledge of DHCA physiology increased, it promoted the development of new techniques such as antegrade and retrograde cerebral perfusion (RCP) and allowed for more complex aortic aneurysm repairs.

There are two basic mechanisms that lead to ischemic cerebral injury during repair of proximal aortic aneurysms. While the stroke is one of the most common postoperative complications of aortic aneurysm repairs, its risk is not associated with duration of DHCA.¹²¹ Rather, stroke risk is associated with plaque, clot, and the artheromatous burden in the aortic arch and brachiocephalic vessels.^122,123 The second type of brain injury is temporary neurological dysfunction (TND) and is characterized by confusion, agitation, obtundation, and even transient parkinsonism. Studies suggest that TND results from inadequate cerebral protection during DHCA. In 200 adults who underwent DHCA, 19% of patients had clinical symptoms of TND, which correlated significantly with age and the duration of DHCA (33 min in patients without TND and 47 min in those with TND).¹²² Furthermore, in patients with advanced age, DHCA duration longer than 25 minutes was an independent risk factor for long-term neurocognitive impairment, specifically for worse performance on fine motor and memory testing.¹²⁴ It is posited that due to its high metabolic demand, the hippocampus is acutely sensitive to hypoperfusion, which may be the reason for memory impairment and cognitive dysfunction after DHCA.¹²⁵ Nonetheless, while TND does occur in some patients, clinical studies in adults after DHCA have demonstrated that a safe period of arrest is about 30 minutes at 15°C and 40 minutes at 10°C, after which cerebral anoxia occurs.¹²⁶

Cooling and Rewarming During Deep Hypothermic Circulatory Arrest

Data from Cheung et al have shown that only 60% of subjects undergoing DHCA achieve EEG silence at a core temperature of 18°C or a cooling time of 30 minutes.¹²⁷ In cases where EEG monitoring is not available, a safer technique is to cool for a minimum of 50 minutes, at which point 100% of patients will have EEG silence.¹²⁸ Cooling is performed maintaining less than a 2 to 3°C gradient between arterial inflow temperature and venous return temperature to ensure even cooling. Nasopharyngeal temperature and bladder temperature which correlate with intracranial temperature and core body temperature, respectively, are also monitored during cooling to guide initiation of arrest.

During rewarming, the bladder, nasopharyngeal, and the systemic perfusion temperatures are monitored. The perfusion is kept at a gradient of not more than 10°C above the nasopharyngeal temperature. This ensures that oxygen demand will not exceed oxygen supply during the interval of cerebral vasoconstriction after DHCA.^129-131 Avoiding high perfusate temperatures is important and should not exceed 37°C. The bladder temperature which is raised from 32 to 34°C represents the core body temperature and will lag considerably behind the nasopharyngeal temperature. Monitoring bladder temperature helps to ensure uniform rewarming and minimize rebound hypothermia after CPB.