Ascending and Arch Aorta Pathology, Natural History, and Treatment

Himanshu J. Patel and G. Michael Deeb Ascending and Arch Aorta : Pathology, Natural History, and Treatment Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 2008 American Heart Association, Inc. All rights reserved. is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231Circulation doi: 10.1161/CIRCULATIONAHA.107.690933 2008;118:188-195Circulation. http://circ.ahajournals.org/content/118/2/188 World Wide Web at: The online version of this article, along with updated information and services, is located on the http://circ.ahajournals.org//subscriptions/ is online at: Circulation Information about subscribing to Subscriptions: http://www.lww.com/reprints Information about reprints can be found online at: Reprints: document. Permissions and Rights Question and Answer this process is available in the click Request Permissions in the middle column of the Web page under Services. Further information about Office. Once the online version of the published article for which permission is being requested is located, can be obtained via RightsLink, a service of the Copyright Clearance Center, not the EditorialCirculationin Requests for permissions to reproduce figures, tables, or portions of articles originally publishedPermissions: by guest on February 12, 2013http://circ.ahajournals.org/Downloaded from Ascending and Arch Aorta Pathology, Natural History, and Treatment Himanshu J. Patel, MD; G. Michael Deeb, MD Aortic aneurysms are the 13th-leading cause of mortalityin the United States.1 The incidence of thoracic aortic aneurysms (TAA) is increasing with improvements in screen- ing, as well as advances in imaging.2 Replacement of the ascending aorta accounts for the majority of thoracic aortic procedures. TAAs are more frequently present in men and typically occur in the 50- to 70-year age range.3 Disease processes affecting the ascending and arch aorta include degenerative aneurysms and aneurysms associated with con- nective tissue disease, as well as acute aortic dissection and its variants of intramural hematoma and penetrating ulcer. Syphilitic aneurysms, once the predominant cause of ascend- ing aneurysms, are exceedingly rare today. In the present review, we will discuss these pathological conditions as well as operative techniques and outcomes after medical and operative therapy. The Spectrum of Thoracic Aortic Pathology Degenerative Aneurysms Degenerative aneurysms comprise the majority of those seen in the ascending aorta and have a specific pathological profile.3 Whereas the elastin content in the ascending aorta is high, that seen in ascending aortic aneurysms is significantly reduced. In addition, the media of the aneurysm displays a loss of smooth muscle cells and fragmentation of the elastic fibers from a process known as cystic medial degeneration. Although this process is seen normally as a consequence of aging, it is accelerated in some and results in the phenotypic expression of an ascending aortic aneurysm. Recent studies have focused on differences in ascending aneurysm patho- genesis for patients with bicuspid and tricuspid aortic valves, with the former suggested as a more-aggressive variant.4 Marfan Syndrome Marfan syndrome is the most common inherited connective tissue disease, with an incidence of 1 in 10 000.5 The basic genetic defect is a mutation of the gene for fibrillin-1, an essential protein of microfibrils. The phenotypic manifesta- tion is that of disorganized elastic fibers, premature cystic medial degeneration, and a resulting complex of ocular, musculoskeletal, central nervous system, and cardiovascular abnormalities. The predominant cause of mortality is from rupture or dissection of the dilated aortic root, which is seen in 75% of patients with Marfan syndrome. In a landmark study, Gott and associates described a multicenter observational analysis of the effects of early operative intervention on the root and ascending aorta in patients with Marfan syndrome.6 In this report, elective aortic root replacement was associated with a 1.5% early mortality rate, and this contrasted with a rate of 11.7% in those undergoing emergency repair. This focus on early interven- tion for aortic pathology, as well as advances in imaging, has extended the median life expectancy of a patient with Marfan syndrome from 42 years in 1972 to 71 years in 2000. Although the therapy for Marfan syndrome involves focusing specifically on the aortic root, any portion of the aorta is at risk for rupture or dissection as a consequence of its weaker nature. Type A Aortic Dissection and Its Variants Type A aortic dissection (AD), defined here as the presence of dissection proximal to the left subclavian artery, represents a true cardiac surgical emergency. Its mortality if left un- treated has been estimated from classical studies at 1% per hour for the first 48 hours and can result in a mortality rate exceeding 80% in the first month. More recent studies evaluating the effects of maximal anti-impulse therapy in nonoperative candidates suggest that the mortality rate with maximal medical management has receded but still exceeds that seen with contemporary reports on operative management.7 The pathogenesis of AD remains debated, with 2 prevailing hypotheses. The first presumes that the initiating event is a tear in the intima (primary tear), which then allows blood to flow into the aortic wall media creating the false lumen. The alternative hypothesis suggests that the initial event is rup- tured vasa vasorum creating intramural hematoma. This hematoma results in increased wall stress during diastole and allows for intimal disruption.8 Although the initiating events remain debatable, the end result remains lethal, with ultimate propagation of a false channel along a predictable spiral course from the right anterior ascending aorta, then curving posteriorly into the arch and down the left aspect of the descending and thoracoabdominal aorta. Risk factors for From the Department of Surgery, University of Michigan Cardiovascular Center, Ann Arbor. Correspondence to Himanshu J. Patel, MD, Assistant Professor of Surgery, Section of Cardiac Surgery, CVC Room 5144, 1500 E Medical Center Dr, SPC 5864, Ann Arbor, MI. E-mail hjpatel@med.umich.edu (Circulation. 2008;118:188-195.) © 2008 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.107.690933 188 Aortic Diseases by guest on February 12, 2013http://circ.ahajournals.org/Downloaded from matao aortic dissection include those contributing to an increased intraluminal pressure (eg, hypertension, hypervolemia) or those diminishing aortic wall strength (eg, connective tissue disease). Presenting symptoms include severe tearing chest or back pain; however, manifestation as a consequence of associated branch vessel compromise (eg, myocardial ische- mia, severe abdominal or lower extremity pain, lower extrem- ity paralysis, and stroke) can also occur.9 It is the latter manifestation that presents the highest risk cohort. In this group with branch vessel ischemia, malperfu- sion can exist by 2 different mechanisms. Two predominant mechanisms exist by which malperfusion can occur, and these have previously been defined by our group.10 In static obstruction, the dissection flap enters the branch vessel lumen without an adequate reentry tear (or a diminutive reentry tear) within the course of that artery. The compromised true lumen of that artery then becomes the sole source of inflow into that end organ. In contrast, in dynamic obstruction, the mobile aortic dissection flap intermittently covers the orifice of the branch vessel during the cardiac cycle, thus impeding arterial inflow into the end organ. The optimal timing of aortic repair in this subset of patients with acute dissection is debated. Although immediate repair with resection of the primary entry tear may eliminate dynamic obstruction, the effects of end-organ ischemia may lead to a severe reperfusion injury and its consequences. We previously suggested a strategy of delay in operation for that group with type A dissection and severe end-organ ischemia and dysfunction.9 In that group, malperfusion was relieved by a percutaneous fenestration procedure, and operative repair was undertaken after resolu- tion of the ischemia-reperfusion injury. Others however have suggested acceptable early results with immediate operative repair.11,12 Regardless of the timing of surgery, the presence of malperfusion remains an important adverse risk factor for mortality, particularly when it involves the mesenteric or cerebral circulation.9–12 Variants of true “double barrel” AD include intramural hematoma (IMH) with or without penetrating ulcer. These variants are often associated with the elderly as well as with women.13 Analysis of a nonoperative strategy has suggested a more benign course for type A IMH when compared with that seen in true aortic dissection, particularly if not associ- ated with a penetrating ulcer. However, recent studies from von Kodolitsch et al, as well as Ganaha and colleagues, emphasized the need to proceed with aortic repair to prevent the risk for progression to a true double barrel dissection or aortic rupture.14,15 The current recommendation is to proceed with aortic repair in the setting of acute type A IMH with or without penetrating ulcer. Natural History of Thoracic Aortic Disease Thoracic aortic intervention is typically undertaken in the asymptomatic setting. Symptoms typically occur in the set- ting of either a complication of the disease (ie, rupture or dissection) or when these complications are imminent. The importance of understanding the natural history of the disease is paramount, because the indications for intervention are typically to improve survival not quality of life. Although the natural history of thoracic aortic disease is not as well characterized as that for abdominal aortic disease, recent reports have yielded important information to assist in deter- mining timing of operative therapy. Recent data have suggested that growth of the ascending and arch aorta is a relatively indolent process.16,17 Previous studies have suggested a mean annual growth rate of 0.07 to 0.2 cm/y for this aortic segment. Risk factors for increased growth have included increasing age, female sex, presence of chronic obstructive pulmonary disease and hypertension, and positive family history, as well as the presence of aortic dissection. Finally, growth rates of TAA have also been shown to be dependent on initial aortic diameter, with larger aneurysms growing faster than smaller counterparts. The importance of aortic diameter in determining risk for complications has been demonstrated in numerous studies. The normal ascending aortic diameter is 2 to 3 cm depending on patient age, size, and sex. The risk for aortic rupture, dissection, or death for the ascending aorta relative to absolute size was recently evaluated by Davies et al.18 They identified that the median aortic diameter at the time of rupture for the ascending or arch aorta was 6 cm. They also demonstrated a progressively increasing risk for rupture, dissection, or death culminating at 15.6% for aortic diameters !6 cm. With these data, the recommendation to intervene was set at 5.5 cm for ascending aortic aneurysms. Whereas the focus of this and other early studies was on determining the absolute size criteria for intervention, more recent reports have suggested that absolute size may not be the only appropriate variable. Indeed, female sex and increasing age have been associated with an increase in event rate.16 In addition, in most natural history studies, those patients presenting with larger aneurysms were often immediately sent for surgery, thus altering the follow-up available for these versus small aneurysms. In recognizing the differences in aortic diameter relative to sex and body size, the Yale group recently suggested the use of an aortic size index, where the maximum aortic diameter was referenced to body surface area.19 In this study, an indexed aortic size !4.25 cm/m2 correlated with an event rate of 20% to 25%. Impor- tantly, even patients presenting with aortic sizes"2.75 cm/m2 displayed an event rate of 4%; those presenting with sizes between 2.75 and 4.25 cm/m2 had event rates approaching 8%. With that data, as well as the recent work from the International Registry of Acute Aortic Dissection (IRAD) consortium demonstrating the propensity for dissection at less than the typical 5- to 5.5-cm intervention target, the impor- tance of adjunctive medical therapy, including control of hypertension and avoidance of strenuous exercise, as well as the need for continued surveillance, is justified to prevent catastrophic complications.20 The natural history of special pathological subtypes has also been recently studied. The known association of bicuspid aortic valve with ascending aortic aneurysms has been asso- ciated with a higher risk for aortic growth (0.19 cm/y versus 0.13 cm/y in nonbicuspid).21 For those patients with aortic stenosis and bicuspid aortic valve disease, the risk for rupture, dissection, or death was higher than in those without aortic stenosis. A family history of aortic aneurysm disease is also a significant risk factor for aneurysm disease. Albornoz et al Patel and Deeb Ascending and Arch Aorta 189 by guest on February 12, 2013http://circ.ahajournals.org/Downloaded from recently demonstrated that of 101 non–Marfan syndrome patients with thoracic aneurysms, 21.5% demonstrated an inherited pattern for TAA with differing penetrance and expression. Those with a familial type presented earlier and displayed higher growth rates than those with sporadic types. In addition, aneurysms frequently coexisted in other loca- tions, including in the abdominal aorta and cerebral circula- tion in this patient group.22 Medical Therapy of Thoracic Aortic Aneurysms Medical therapy for TAA has typically been associated with a dismal prognosis. McNamara and Pressler called to atten- tion the high risk of unrepaired TAAs.23 Recent reports on medical therapy, often focused on patients with Marfan syndrome, have suggested improvements in outcomes for TAA. In a randomized prospective trial, Shores demonstrated that propranolol administration was associated with improve- ments in both aortic growth and 10-year survival for patients with Marfan syndrome.24 Similarly, Zierer et al suggested that the use of !-blockers was associated with a decrease in need for aortic reoperation in patients after repair of aortic dissection.25 In an evaluation of angiotensin-converting en- zyme inhibitors, Yetman and colleagues noted a decrease in aortic growth for Marfan patients receiving enalapril com- pared with those receiving !-blockers.26 Finally, the recent experimental evaluation in a mouse aneurysm Marfan model suggested that losartan use prevents aneurysm formation, likely as a result of its transforming growth factor-! antago- nistic effects.27 This suggestion requires clinical validation in humans. Additional important lifestyle changes include the avoid- ance of strenuous physical activity, particularly weightlift- ing.28 Pregnancy has been associated with a risk for occur- rence of type A dissection, particularly in patients with bicuspid aortic valves or Marfan syndrome.29 As part of the cardiovascular effects of pregnancy, connective tissue changes occur, including dilation of the aorta along with an increase in cardiac output. These considerations led Immer et al to suggest that aortic enlargement "4 cm or an increase in aortic root diameter in patients with bicuspid aortic valve or Marfan syndrome is associated with a dramatic increase in risk of type A aortic dissection, particularly in the third trimester. They stressed the need for close surveillance and suggested the use of cesarian section, selective administration of !-blockers including into the postpartum period, as well as prophylactic aneurysm repair if rapid enlargement is seen.29 The natural history of TAA is that of inexorable expansion. As a result, continued surveillance of small TAAs is manda- tory to identify individuals who should undergo intervention and constitutes an important part of ongoing medical therapy. Our protocol for this surveillance is detailed in Table. Note should be made of the significant interobserver differenc- es—by as much as 5 mm—as detailed by Cayne and associates.30 Therefore, diligent follow-up with standardized protocols is necessary to ameliorate the risk for rupture, dissection, or aneurysm-related death. Operative Therapy for Ascending and Arch Aortic Disease Preoperative Workup Our usual preoperative workup for patients requiring resec- tion of TAA includes obtaining coronary angiography and echocardiography to evaluate the need for concomitant car- diac procedures, as well as to assess the status of the aortic valve and root. Because of the frequent association of aneurysm disease with tobacco use, we routinely obtain pulmonary function testing with consultation from our pul- monary medical colleagues on a selective basis. Severe carotid stenosis represents a risk factor for stroke with operations for TAA, and therefore carotid duplex scanning is also routinely carried out. Finally, given the association of concomitant aneurysmal disease in noncontiguous aortic Table. Suggested Imaging Surveillance for Patients With Thoracic Aortic Aneurysms Aortic Pathology Additional Initial Workup First Follow-Up Imaging Subsequent Imaging Newly diagnosed TAA Echocardiography to evaluate aortic valve structure and function CT scan at 6 months 1) Annual CT scan if stable 2) Annual echocardiography if initial study demonstrated moderate to severe aortic stenosis or insufficiency Rapidly growing TAA 1) Echocardiography CT scan at 3 months unless indication for operation exists 1) CT scan at 6 months if stable, then annually thereafter2) Right and left heart catheterization 2) CT scan every 3 months if growing further3) Carotid duplex 4) Pulmonary function testing Residual distal aortic dissection after repair of type A dissection None CT scan 3 months postoperatively Annual CT scan if stable distal aortic dimension Known TAA in setting of pregrnancy Echocardiography Six to eight weeks with repeat echocardiography 1) Echocardiography every 6 to 8 weeks including into first 3 postpartum months 2) CT scan postpartum, then algorithm per rapidly growing TAA 190 Circulation July 8, 2008 by guest on February 12, 2013http://circ.ahajournals.org/Downloaded from segments, we ensure that a complete computed tomography (CT) evaluation of the aorta is performed before repair of TAA.3 Operative Approach and Outcomes The routine approach for an ascending or arch TAA is via a median sternotomy. In patients presenting with prior sternot- omy and aneurysms adherent to the posterior sternal table, we have found that the “clamshell” incision (bilateral anterior thoracosternotomy) is useful to avoid catastrophic hemor- rhage on reentry into the chest. Cardiopulmonary bypass is used in all patients. Cannulation for cardiopulmonary bypass is often performed via the ascending or arch aorta in elective nondissected pathology. If the procedure is performed for ascending aortic dissection, the site of cannulation typically includes either the femoral or axillary arterial route to avoid inserting large bore cannulae into the weakened aortic wall. Advantages of the axillary cannulation method include the ability to maintain cerebral flow while the patient is on lower-body circulatory arrest for operative procedures on the arch aorta. Recent data have suggested that the axillary method of cannulation may decrease the incidence of post- operative stroke for thoracic aortic operative pro