Elective Surgery for Thoracic Aortic Aneurysms: Late Functional Status and Quality of Life

Elective Surgery for Thoracic Aortic Aneurysms: Late Functional Status and Quality of Life Andreas Zierer, MD, Spencer J. Melby, MD, Jordon G. Lubahn, BS, Gregorio A. Sicard, MD, Ralph J. Damiano, Jr, MD, and Marc R. Moon, MD Divisions of Cardiothoracic Surgery and Vascular Surgery, and Center for Diseases of the Thoracic Aorta, Washington University School of Medicine, St. Louis, Missouri Background. Elective surgical treatment for thoracic aortic aneurysms is unique in that it is often performed on asymptomatic patients. Although it has been found to improve survival, the impact of elective surgery on late functional status and quality of life have yet to be examined. Methods. Over a 5-year period, 110 asymptomatic patients underwent elective thoracic aortic replacement for ascending, descending, or thoracoabdominal aneurysms. Mean age was 67 9 years (53 > 70 years). Functional status, physical and psychological quality of life (Medical Outcome Study 36-Item Short Form Health Survey, in which 50 represents normalized age-matched US population), and survival (Kaplan-Meier) were assessed. Results. Return to normal activity level was independent of age (p > 0.59) and procedure (p > 0.18). At 35 20 months, psychological quality of life was similar between surgical groups (p > 0.71), but physical quality of life was lower after thoracoabdominal versus ascending or descending aneurysms (p < 0.02). Age did not impact physical quality of life (40 13 > 70 years versus 42 11 < 70 years, p > 0.58), but older patients had improved psychological quality of life (52 9 > 70 years versus 47 8 < 70 years, p > 0.03). Overall survival was 79% 4% at 2 years and 70% 5% at 4 years, but was lower with thoracoabdominal versus ascending or descending aneurysms (p < 0.002). Multivariate analysis identified thoracoabdominal (p < 0.004), advanced age (p < 0.03), chronic renal failure (p < 0.03), and congestive heart failure (p < 0.001) as predictors of late death. Conclusions. Advanced age did not impair return to normal functional status, and older patients had improved psychological quality of life. Survival and physical quality of life were lowest with thoracoabdominal versus ascending or descending aneurysms. Thus, patients with asymptomatic thoracic aneurysms should not be denied elective replacement based on age alone, as functional recovery was not significantly impaired. (Ann Thorac Surg 2006;82:573 8) 2006 by The Society of Thoracic Surgeons Repair of thoracic aortic aneurysms is generally indicated for patients who are symptomatic if they present with aneurysm-related pain, symptoms of compression of surrounding structures, or dissection [1, 2]. However, the decision for patients found to have asymptomatic thoracic aortic aneurysms is not as clear. To address this uncertainty, researchers have compiled databases in an attempt to construct mathematical formulas to determine when the risk of surgical intervention outweighs the risk of living with an aneurysm that may be growing [3, 4]. The Mount Sinai group has developed a mathematical model to predict the risk of developing a complication of the aneurysm, such as dissection or rupture, for patients with descending thoracic aneurysms based on aneurysm size, age, and the presence of chronic obstructive pulmonary disease (COPD) or atypical chest or back pain not directly attributable to the aneurysm [5]. Accepted for publication March 14, 2006. Presented at the Poster Session of the Forty-second Annual Meeting of The Society of Thoracic Surgeons, Chicago, IL, Jan 30 Feb 1, 2006. Address correspondence to Dr Moon, Division of Cardiothoracic Surgery, Washington University School of Medicine, 3108 Queeny Tower, 1 Barnes- Jewish Plaza, St. Louis, MO 63110-1013; e-mail: moonm@wustl.edu. In general, our current recommendation for surgical intervention for patients with asymptomatic thoracic aortic aneurysms is an aneurysm size greater than 5.5 cm in the ascending aorta and 6.5 cm in the descending aorta. Other indications for resection of asymptomatic thoracic aortic aneurysms include, enlargement of more than 7 to 10 mm per year, or localized saccular aneurysms that might put the patient at a higher risk of rupture [6, 7]. At these hinge points, it is our impression that the overall benefit of primary elective thoracic aneurysm repair outweighs the risk of natural complications and may lead to improved survival in patients who are otherwise reasonable surgical candidates [8]. Nevertheless, elective surgery of the thoracic aorta can be associated with a significant risk of major complications, and the dilemma presented to the surgeon and asymptomatic patient is a difficult one that is further complicated by the fact that late functional status and quality of life (QOL) after elective repair have yet to be examined. The purpose of the current investigation was to evaluate functional recovery and late QOL after elective replacement of asymptomatic thoracic aortic aneurysms in order to include this information in future guidelines for elective surgical intervention. 2006 by The Society of Thoracic Surgeons 0003-4975/06/$32.00 Published by Elsevier Inc doi:10.1016/j.athoracsur.2006.03.042

574 ZIERER ET AL Ann Thorac Surg ELECTIVE THORACIC ANEURYSM REPAIR AND QOL 2006;82:573 8 Table 1. Demographics for Patients Undergoing Elective Ascending, Descending, or Thoracoabdominal (TAA) Aortic Replacement Material and Methods Ascending Descending TAA Number of patients 29 33 48 Age (years) 70 10 63 13 70 8 Male 15 (52%) 19 (58%) 20 (42%) History of smoking 16 (55%) 25 (76%) 41 (85%) Hypertension 18 (62%) 26 (79%) 39 (81%) COPD 4 (14%) 10 (30%) 15 (31%) Aneurysm size (cm) 6.0 1.1 6.7 1.0 6.0 1.0 COPD chronic obstructive pulmonary disease. This retrospective review includes 110 consecutive asymptomatic patients who underwent elective aortic replacement for treatment of a thoracic aortic aneurysm between January 1998 and April 2003 at Washington University School of Medicine (Barnes-Jewish Hospital). The study was approved by the Washington University Institutional Review Board and informed consent and permission for the release of information were obtained from each patient. There were 54 males (49%) and 56 females (51%) with a mean age of 67 9 years (53 patients 70 years). Twenty-nine patients (26%) underwent ascending, 33 (30%) descending, and 48 (44%) thoracoabdominal (TAA) aortic aneurysm replacement. The extent of aneurysm in the TAA group was Crawford type I in 8 patients, type II in 26, type III in 14, and type IV in none. Selected preoperative patient characteristics are summarized in Table 1. Hypertension, smoking history, and COPD were the most common preoperative comorbidities. Mean aneurysm size ( 1 SD) was 6.0 1.1 cm for ascending, 6.7 1.0 cm for descending, and 6.0 1.0 cm for TAA. Fifteen patients were identified with asymptomatic coronary artery disease by routine preoperative cardiac catheterization and underwent concomitant coronary artery bypass grafting. Patients who underwent simultaneous valve replacement or valve sparing aortic root replacement were excluded (all patients with Marfan syndrome were excluded). Follow-Up Patients were mailed a postoperative questionnaire to determine their current health status and the timing of their return to a normal level of activity. To assess health-related QOL, patients were asked to complete the Medical Outcome Study 36-Item Short Form Health Survey (SF-36) [9, 10]. The SF-36 measured eight quality of life health domains: physical functioning, role limitations due to physical problems (role limitation-physical), bodily pain, general health perception, vitality, social functioning, role limitations due to emotional problems (role limitation-emotional), and mental health. Raw data were transformed to generate a score for each domain that ranged from 0 (worst) to 100 (best). A physical composite score and a psychological composite score were calculated using standard weighted averages of the eight health domains. To facilitate comparison between groups, all scores were normalized so that the scores of an age-matched general US population had a mean of 50 and a standard deviation of 10 [10]. At35 20 months postoperatively, 84 patients (76%) were alive, and of these, 70 (84%) completed the SF-36 surveys during a 2-month midterm closing interval (November 2003 to December 2003). The midterm period was selected for QOL assessment to allow better recollection by the patients of their postoperative recovery. Long-term survival was then reassessed during a 2-month late closing interval (July 2005 to August 2005) and was 100% complete. Data Analysis Perioperative mortality included any death that occurred during the initial hospitalization or within 30 days of operation for discharged patients. Cumulative survival rates were calculated using Kaplan-Meier analysis, and survival curves were compared using the log-rank test. Continuous data are reported as mean 1 SD and were compared using Student s t test. Categorical variables were analyzed using the 2 test or Fisher s exact tests as appropriate. Odds ratios (OR) are reported with 70% confidence intervals (CI). Multivariate analysis (stepwise backward regression) was used to determine the preoperative and intraoperative risk factors that were significant, independent predictors of late death and impaired functional status at 12 months (SigmaStat 2.03; SPSS, Chicago, Illinois). Eighteen variables were analyzed as follows: age, year of operation, sex, hypertension, diabetes mellitus, COPD, cerebrovascular disease, peripheral vascular disease, chronic renal insufficiency, history of myocardial infarction, smoking history, coronary artery disease, chronic pulmonary hypertension, congestive heart failure, aortic dissection, New York Heart Association (NYHA) class, concomitant coronary artery bypass grafting, and location of the aneurysm (ascending, descending, or TAA). Comparison of the age-matched general US population to the treated patients was made using a two-tailed one-sample t test. Statistical differences were considered significant at a p value less than 0.05. Results No perioperative deaths occurred in the ascending or descending groups, but there were 4 deaths (8%) with TAA replacement. Two patients died of cardiac failure with a perioperative myocardial infarction, and the other 2 patients died as the result of sepsis with multisystem organ failure. Surgical outcomes are summarized in Table 2. None of the patients with ascending or descending aneurysm had paraplegia, as compared with 10% of the patients (5 of 48) in the TAA group. No patient with ascending aneurysm, 6% of patients with descending aneurysm, and 8% of TAA patients had a perioperative cerebrovascular accident. At 3 months postoperatively, a return to normal activ-

Ann Thorac Surg ZIERER ET AL 2006;82:573 8 ELECTIVE THORACIC ANEURYSM REPAIR AND QOL 575 Table 2. Surgical Outcomes for Patients Undergoing Elective Ascending, Descending, or Thoracoabdominal (TAA) Aortic Replacement Ascending Descending TAA Perioperative 0/29 (0%) 0/33 (0%) 4/48 (8%) mortality Myocardial 0/29 (0%) 0/33 (0%) 2/48 (4%) infarction Reoperation for 3/29 (10%) 3/33 (9%) 4/48 (8%) bleeding Cerebrovascular 0/29 (0%) 2/33 (6%) 4/48 (8%) accident Paraplegia 0/29 (0%) 0/33 (0%) 5/48 (10%) ity levels was reported by 31% of patients (22 of 70) overall compared with 61% (43 of 70) at 6 months. At 12 months, 85% of ascending, 85% of descending, and 83% of TAA patients had returned to their normal level of activity (p 0.18 between surgical groups; Fig 1). Return to normal activity level at 12 months was independent of age (83% for patients 70 years old and 88% for patients 70 years old; p 0.59; Fig 2). Multivariate analysis identified two factors to be independent predictors of impaired late functional status at 12 months: NYHA class III or IV (p 0.001, OR 4.3 [2.0 to 9.4]), and COPD (p 0.034, OR 5.0 [2.3 to 11.1]). Average QOL scores for all 70 patients were 38 13 physical functioning, 41 12 role limitation-physical, 47 11 bodily pain, 46 11 general health perceptions, 48 10 vitality, 46 12 social functioning, 42 14 role limitation-emotional, and 52 9 mental health. For the entire group, psychological QOL scores were similar to the age-matched US population (50 9, p 0.65), but physical scores were diminished (42 11, p 0.03). Figures 3 and 4 demonstrate QOL scores for the eight domains of the SF-36 survey based on procedure type Fig 2. Return to normal functional activity level after thoracic aortic aneurysm repair depending on age: less than 70 years old (solid circles) and greater than 70 years old (open circles). and age, respectively. Psychological QOL scores were similar between surgical groups: 50 8 for ascending, 49 10 for descending, and 51 10 for TAA patients (p 0.71). However, physical QOL was lower after TAA (37 13) compared with more proximal replacement procedures (44 11 for ascending, 45 10 for descending; p 0.02). Interestingly, patients less than 70 years old had lower psychological QOL scores when compared with older patients (47 9 versus 52 9, p 0.03), but age did not impact physical composite QOL (42 11 versus 40 13, p 0.58). When treated patients were asked about their current health status at follow-up, 75% ascending, Fig 1. Return to normal functional activity level after thoracic aortic aneurysm repair depending on procedure performed: ascending (solid circles), descending (open circles), and thoracoabdominal (open triangles) aortic replacement. Fig 3. Medical Outcomes Survey Short Form-36 scores (mean) for patients undergoing ascending (n 20 [solid circles]), descending (n 25 [open circles]), or thoracoabdominal (n 25 [open squares]) aortic replacement, normalized to age-matched general US population (mean of 50 [horizontal line]). The eight SF-36 domains are physical functioning (PF), role limitation-physical (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitation-emotional (RE), and mental health (MH).

576 ZIERER ET AL Ann Thorac Surg ELECTIVE THORACIC ANEURYSM REPAIR AND QOL 2006;82:573 8 Fig 4. Medical Outcomes Survey Short Form-36 scores (mean) for patients less than 70 years old (n 40 [solid circles]) and 70 years or older (n 30 [open circles]) undergoing aortic replacement normalized to age-matched general US population (mean of 50 [horizontal line]). The eight SF-36 domains are physical functioning (PF), role limitation-physical (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitationemotional (RE), and mental health (MH). TAA repair, the incidence of paraplegia was 5% for a combined series of type I IV aneurysms [12], but the rate can be as high as 10% to 30% depending on the extent of resection required to achieve complete extirpation of the aneurysmal aorta [14 16]. Delayed-onset paraplegia or paraparesis is becoming more identified and may account for 20% to 40% of postoperative spinal events [17 19]. In the current series, the incidence of paraplegia and stroke was consistent with our previous reports [17], but these adverse neurologic events certainly remain the most feared and devastating surgical complications in thoracic aortic aneurysm surgery. To justify an elective procedure, considering its welldocumented risks in an asymptomatic patient, relative guidelines have been established to facilitate the surgeon s decision as to when the expected benefits of surgery exceed its operative risks. In the current series, overall 4-year survival was 77% 7%, but clearly other factors should be considered in addition to survival 68% descending, and 68% TAA patients rated their current level of health as excellent or good (p 0.39 between groups; Fig 5A). No ascending, 8% of descending, and 20% of TAA patients reported their current health status as poor, significantly worse in the TAA group (p 0.04). Current health status was not significantly different when comparing patients less than 70 years of age to older patients (Fig 5B). At late follow-up, 75 patients (68%) were alive an average of 54 19 months postoperatively. Four-year survival was lower among patients who underwent TAA (53% 7%) versus ascending (77% 9%) or descending (91% 5%) replacement (p 0.002; Fig 6). For patients 70 years of age or older, 4-year survival was lower (64% 6%) than for patients less than 70 years old (79% 8%, p 0.008; Fig 7). Multivariate analysis identified TAA (p 0.004, OR 4.6 [2.9 to 7.3]), advanced age (p 0.03), chronic renal failure (p 0.03, OR 6.1 [2.5 to 14.9]), and congestive heart failure (p 0.001, OR 33.9 [11.2 to 102.8]) as predictors of late death. Comment Elective surgical treatment for thoracic aortic aneurysms is unique among major cardiac surgical procedures in that it is often performed on asymptomatic patients. Techniques used in thoracic aortic aneurysm repair have improved throughout the years [11, 12], improvements that have not only reduced operation-related complications, but have also decreased hospital length of stay and potentially cost [1, 13]. However, these challenging procedures are still accompanied by the risk of several serious perioperative complications. In a recent review of Fig 5. (A) Current health perception based on procedure performed: ascending (solid bar), descending (striped bar), or thoracoabdominal (TAA) (dotted bar) aortic replacement. The TAA group is significantly different than the ascending and descending groups combined (*p 0.04). (B) Current health perception based on patients age: less than 70 years old (solid bar), and 70 years or older (striped bar).

Ann Thorac Surg ZIERER ET AL 2006;82:573 8 ELECTIVE THORACIC ANEURYSM REPAIR AND QOL 577 alone. It was the goal of this report to examine late functional status and quality of life, which have not previously been factored into the equation. This could be particularly helpful for patients of advanced age, especially where restricted agility and the presence of severe comorbidities may influence the surgeon s evaluation of the potential benefit of an elective procedure. Another reason that this information is of clinical relevance is the availability of less-invasive treatment options. Reports about the use of endovascular stentgraft repair of descending aneurysms and TAA have demonstrated good short-term and midterm results [20]. In our series, multivariate analysis identified congestive heart failure to be the strongest independent predictor of late death after elective surgery. The endovascular approach is associated with a hastened functional recovery and seems to be a reasonable alternative in selected patients, especially those with compromised cardiac, pulmonary, or renal status and those who have previously undergone complex thoracic aortic operations that may increase their surgical risk substantially. However, long-term results and the need for reinterventions have yet to be defined [21, 22]. The impact of elective surgery on postoperative QOL in the current series was variable. Based on the extent of aorta resected, psychological composite QOL scores were not significantly different when compared with the agematched normalized population. However, younger patients had diminished psychological scores compared with older patients, but age did not impact physical scores. In contrast, physical composite scores were significantly impaired after TAA, but not ascending or descending replacement. Patients with TAA also had diminished late survival compared with those with more proximal aneurysms, and the procedure-related risk for Fig 7. Long-term Kaplan-Meier survival for patients less than 70 years old (solid line) and 70 years or older (dotted line) undergoing aortic replacement. The numbers of patients at risk at 2 and 4 years are indicated for patients less than 70 years old (top) and for patients 70 years old or older (bottom). neurologic complications was highest with TAA. Future studies will address whether the best treatment option for the patient with TAA may be a less-invasive endovascular approach, in an attempt to reduce the perioperative and late impact of treatment for these high-risk patients. Survival of patients over 70 years of age was lower compared with patients less than 70 years old, but still improved compared with historic survival rates reported for patients whose thoracic aneurysms did not undergo repair [23]. Surprisingly, advanced age did not influence return to normal activity levels at 12 months postoperatively, and there was no difference between patients less than 70 years and those 70 years or older when asked about their current health status at follow-up. In summary, the current report demonstrated that survival and physical QOL after elective surgery were lowest with TAA when compared with more proximal aneurysms. However, advanced age did not influence postoperative health status, QOL, or return to normal functional activity. Thus, patients with asymptomatic thoracic aneurysms should not be refused elective replacement based on age alone, as survival is likely improved and functional recovery is not substantially impaired. Fig 6. Long-term Kaplan-Meier survival after ascending (solid line), descending (dotted line), and thoracoabdominal (dashed line) aneurysm repair. The numbers of patients at risk at 2 and 4 years are indicated for ascending (middle), descending (top), and thoracoabdominal (bottom) aneurysm repair. References 1. Moon MR, Sundt TM III. Influence of retrograde cerebral perfusion during aortic arch procedures. Ann Thorac Surg 2002;74:426 31. 2. Moon MR, Sundt TM III, Pasque MK, et al. Does the extent of proximal or distal resection influence outcome for type A dissections? Ann Thorac Surg 2001;71:1244 50. 3. Davies RR, Goldstein LJ, Coady MA, et al. Yearly rupture or dissection rates for thoracic aortic aneurysms: simple prediction based on size. Ann Thorac Surg 2002;73:17 28.

578 ZIERER ET AL Ann Thorac Surg ELECTIVE THORACIC ANEURYSM REPAIR AND QOL 2006;82:573 8 4. Elefteriades JA. Natural history of thoracic aortic aneurysms: indications for surgery, and surgical versus nonsurgical risks. Ann Thorac Surg 2002;74:S1877 80. 5. Juvonen T, Ergin MA, Galla JD, et al. Prospective study of the natural history of thoracic aortic aneurysms. Ann Thorac Surg 1997;63:1533 45. 6. Moon MR, Sundt TM III. Aortic arch aneurysms. Cor Artery Dis 2002;13:85 92. 7. Moon MR, Miller DC. Aortic arch replacement for dissection. Op Tech Thorac Cardiovasc Surg 1999;4:33 57. 8. LeMaire SA, Miller CC III, Conklin LD, Schmittling ZC, Coselli JS. Estimating group mortality and paraplegia rates after thoracoabdominal aortic aneurysm repair. Ann Thorac Surg 2003;75:508 13. 9. Ware JE Jr, Snow KK, Kosinski M, Gandek B. CSF-36 Health Survey: manual and interpretation guide. Boston: New England Medical Center, The Health Institute, 1993. 10. Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). Conceptual framework and item selection. Med Care 1992;30:473 83. 11. Kouchoukos NT, Dougenis D. Surgery of the thoracic aorta. N Engl J Med 1997;336:1876 88. 12. Coselli JS, Conklin LD, LeMaire SA. Thoracoabdominal aortic aneurysm repair: review and update of current strategies. Ann Thorac Surg 2002;74:S1881 4. 13. Huynh TT, Miller CC III, Estrera AL, Sheinbaum R, Allen SJ, Safi HJ. Determinants of hospital length of stay after thoracoabdominal aortic aneurysm repair. J Vasc Surg 2002;35: 648 53. 14. Crawford ES, Crawford JL, Safi HJ, et al. Thoracoabdominal aortic aneurysms: preoperative and intraoperative factors determining immediate and long-term results of operations in 605 patients. J Vasc Surg 1986;3:389 404. 15. Hollier LH, Money SR, Naslund TC, et al. Risk of spinal cord dysfunction in patients undergoing thoracoabdominal aortic replacement. Am J Surg 1992;164:210 4. 16. Cambria RP, Clouse WD, Davison JK, Dunn PF, Corey M, Dorer D. Thoracoabdominal aneurysm repair: results with 337 operations performed over a 15-year interval. Ann Surg 2002;236:471 9. 17. Maniar HS, Sundt TM III, Prasad SM, et al. Delayed paraplegia after thoracic and thoracoabdominal aneurysm repair: a continuing risk. Ann Thorac Surg 2003;75:113 20. 18. Safi HJ, Miller CC III, Azizzadeh A, Iliopoulos DC. Observations on delayed neurologic deficit after thoracoabdominal aortic aneurysm repair. J Vasc Surg 1997;26:616 22. 19. de Haan P, Kalkman CJ, de Mol BA, Ubags LH, Veldman DJ, Jacobs MJ. Efficacy of transcranial motor-evoked myogenic potentials to detect spinal cord ischemia during operations for thoracoabdominal aneurysms. J Thorac Cardiovasc Surg 1997;113:87 101. 20. Neuhauser B, Perkman R, Greiner A, et al. Mid-term results after endovascular repair of the atherosclerotic descending thoracic aortic aneurysm. Eur J Vasc Endovasc Surg 2004;28: 146 53. 21. Fann JI, Miller DC. Endovascular treatment of descending thoracic aortic aneurysms and dissections. Surg Clin North Am 1999;79:551 74. 22. Criado FJ, Abul-Khoudoud OR, Domer GS, et al. Endovascular repair of the thoracic aorta: lessons learned. Ann Thorac Surg 2005;80:857 63. 23. Perko MJ, Norgaard M, Herzog TM, Olsen PS, Schroeder TV, Pettersson G. Unoperated aortic aneurysm: a survey of 170 patients. Ann Thorac Surg 1995;59:1204 9.