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Eur J Cardiothorac Surg 2007;31:963-969. doi:10.1016/j.ejcts.2007.01.034
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved

Surgical and long-term mortality in 2634 consecutive patients operated on the proximal thoracic aorta

^a Department of Cardiothoracic Surgery, Uppsala University Hospital, Sweden
^b Uppsala Clinical Research Center, Uppsala University, Sweden

Received 21 July 2006; received in revised form 19 January 2007; accepted 22 January 2007.

^_* Corresponding author. Address: Thoraxkliniken, Akademiska sjukhuset, SE-751 85, Uppsala, Sweden. Tel.: +46 18 6110000; fax: +46 18 6113926. (Email: christian.olsson{at}surgsci.uu.se).

	Abstract

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion 5. Limitations 6. Conclusions Appendix A References

 
Objective: To assess surgical and long-term mortality in a large, contemporary, unselected cohort of patients undergoing operations on the proximal thoracic aorta. Methods: Patients in the Swedish Heart Surgery register operated 1992–2004 were identified and data cross-linked with the in-hospital and cause-of-death registers. Factors associated with surgical, intermediate, and long-term mortality were studied with separate Cox analyses. Long-term survival was estimated by Kaplan-Meier analysis. Results: 2634 patients (68% men, mean age 60 years) were operated for aortic aneurysm (n = 1821, 69%) or aortic dissection (n = 813, 31%). Overall, increased age, aortic dissection, emergency operation, coronary artery bypass grafting, postoperative stroke, and postoperative renal failure were independently associated with surgical mortality. Only age was independently associated with long-term mortality. Later era of treatment (1998–2004 vs 1992–1997) was associated with lower risk only for aneurysm patients, despite similar changes in surgical approach. Long-term survival for all patients was 83% at 1 year, 77% at 5 years, and 73% at 10 years and identical for aneurysm and dissection when adjusted for surgical mortality. Conclusions: Increased age was associated with increased mortality across follow-up, implicating early surgery when possible. Results improved over time for aneurysms but not dissections; however, long-term survival was equal.

Key Words: Aortic • Aneurysm • Surgery • Survival • Risk factors

	1. Introduction

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion 5. Limitations 6. Conclusions Appendix A References

 
Operations on the proximal thoracic aorta (root, ascending aorta, and arch) have in common the anatomical location of disease, the surgical approach, rationale – prevention or treatment of aortic disease by resection and prosthetic replacement – and techniques, conduct of cardiopulmonary bypass, and potential serious perioperative complications. Subsequent long-term complications affecting the operated proximal aorta [1–3] or the distal aorta [1,4,5] are reported for thoracic aneurysms and dissections alike.

The majority of studies on proximal thoracic aortic operations report the limited experience of single high-volume centers [6–9], multinational multicenter studies [10,11], or results from a very extended period [2,12,13], often in various patient subgroups. Therefore, interpretation of results, generalization, and application to current practice of proximal thoracic aortic surgery has been difficult.

The main purpose of the study was to analyze surgical and long-term outcomes in a contemporary, large, well-defined nationwide cohort of patients with extended follow-up to establish the survival of proximal thoracic aortic operations in an unselected patient population in the current era.

	2. Patients and methods

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion 5. Limitations 6. Conclusions Appendix A References

 
2.1 Patients and study design
Patients operated on the proximal aorta were identified in the Swedish Heart Surgery register by the combination of appropriate procedural and diagnostic codes from the ninth and tenth revisions of the International Classification of Diseases (ICD-9, ICD-10). Patients undergoing minor procedures on the proximal aorta without a concurrent appropriate diagnosis (e.g., aortic valve replacement (AVR) including patch repair of the ascending aorta) were excluded, as were patients undergoing the Ross operation or an operation for primary native or prosthetic valve endocarditis (Fig. 1 ). Simple procedures, e.g. suture repair with or without aortic resection, patch repair, and wrapping, were included provided they were indicated by aortic pathology per se. No lower age limit for inclusion was applied. For patients with undetermined location (proximal/distal aorta) of the operation (i.e., the combination of ICD-9 procedural codes 3145 [resection of aneurysm and implantation of vascular prosthesis] or 3138 [not further specified similar procedure] and 0021 [moderately hypothermic cardiopulmonary bypass] or 0024 [deep hypothermic cardiopulmonary bypass with circulatory arrest]), individual operation notes were reviewed. Cross-linking with the annual national population census and cause-of-death register was made at the time of cross-sectional follow-up. Study closing date was January 1, 2005. Last registered event occurred July 8, 2004. The study was approved by the board of the register and by the regional research ethics committee.

View larger version (18K): [in this window] [in a new window]   Fig. 1. Distribution of patients from the Swedish Heart Surgery register: initially eligible, exclusions, and final study population.

2.3 Definitions
Definitions applied by the register include diabetes = treated with oral medication or insulin; reoperation = pericardium previously entered; reoperation for mediastinitis or sternal insufficiency = reoperation performed at the primary hospitalization; reoperation for bleeding = reoperation performed within 24 h of the primary operation; stroke = established postoperatively, lasting 24 h or permanently, postoperative serum creatinine level = highest serum creatinine level obtained after operation. Postoperative renal failure was defined as new indication for renal replacement therapy. Surgical mortality was defined as death of any cause within 60 days from operation to adequately include deaths related to but remote from operation [14].

2.4 Surgical methods
Operations were performed in up to nine different units; methods varied accordingly. Universally, a median sternotomy was employed, and cardiopulmonary bypass was used. Ascending aortic pathology was addressed by supracoronary graft replacement, separate aortic valve (mechanical or biological) and supracoronary graft replacement, composite graft replacement, or valve-sparing aortic root procedures including the Yacoub and David operations. Free coronary button reimplantation was more common than interposition grafts or inclusion techniques in aortic root replacement. The aortic arch was replaced either as a hemi-arch procedure in conjunction with replacement of the ascending aorta or as total arch replacement with or without additional procedures such as separate arch vessel grafting or elephant trunk. Hypothermic circulatory arrest and concomitant cerebral perfusion (retrograde and selective antegrade cerebral perfusion) were used at the discretion of each center.

2.5 Statistical methods
Parametric statistical methods were used for descriptive statistics. Figures are presented as counts with percentages or means with standard deviations (SDs) if not otherwise indicated. Multivariable backward stepwise Cox proportional hazards analysis was used for time-dependent variables associated with mortality. Results are presented as hazard ratios (HRs) with 95% CL. To account for different hazard phases and changing effects of associated variables during follow-up, Cox analyses were performed independently for early (within 60 days from operation), intermediate (after 60 days but within 5 years from operation), and late (more than 5 years from operation) phases. Actuarial survival was calculated and plotted using the Kaplan-Meier method and compared with the non-parametric log-rank test.

	3. Results

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion 5. Limitations 6. Conclusions Appendix A References

 
Characteristics of the 2634 patients in the register meeting study criteria are presented in Table 1 . Overall, two-thirds were male with a mean age of 60 years, almost 50% were non-electively operated, and nearly 60% underwent AVR, whereas concomitant coronary artery bypass grafting (CABG) was less prevalent. Concomitant procedures and elective operations were much less frequent in aortic dissection patients (Table 1). Mean/maximal follow-up times were 4.4/13.0 years for aneurysms, and 4.1/13.0 years for dissections.

Factors associated with short-term mortality in multivariable Cox proportional hazards analysis are given in Table 2 . For aneurysm patients, emergency operation (HR 3.8), postoperative stroke (HR 2.5), and postoperative renal failure (HR 4.7) were most strongly associated with death, whereas for patients with aortic dissection, concomitant CABG (HR 2.2) and postoperative stroke (HR 1.7) were associated with highest risk. For aortic aneurysms, operation in the later 1998–2004 period was strongly associated with a favorable surgical outcome (HR 0.4); this effect was not present in operations for aortic dissection.

3.3 Long-term mortality and actuarial survival
Overall, 714 of the 2278 operative survivors (31.3%) died during follow-up. Major causes of long-term death were cardiac (33%), aortic (19%), cerebral (12%), and other (36%). In Cox analysis of factors associated with death in the late (after 5 years) follow-up phase, age remained significant irrespective of diagnosis, and the effect of later period remained in the aneurysm group (Table 2). Actuarial survival for all patients and surgical survivors after operations for aortic aneurysm and dissection is illustrated in Fig. 2 . Survival rates at 1, 5, and 10 years are given in Table 3 . The effect of treatment era on survival for aneurysm and dissection, respectively, is illustrated in Fig. 3 .

View larger version (15K): [in this window] [in a new window]   Fig. 2. (A) Long-term survival (Kaplan-Meier) of all patients with thoracic aortic aneurysm and aortic dissection, respectively. (B) Long-term survival (Kaplan-Meier) of all surgical survivors (beyond 60 days) with thoracic aortic aneurysm and dissection, respectively.

View larger version (13K): [in this window] [in a new window]   Fig. 3. Long-term survival (Kaplan-Meier) of patients operated for thoracic aortic aneurysm and dissection in the early (1992–1997) and late (1998–2004) period, respectively.

	4. Discussion

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion 5. Limitations 6. Conclusions Appendix A References

 
This study of proximal thoracic aortic operations in 2634 patients with complete follow-up was one of the most comprehensive to date. It reflected current best practices in unselected patients with a range of diagnoses, acuity, concomitant procedures, and comorbidity.

4.1 Surgical mortality
Surgical mortality was defined as death of any cause within 60 days from operation. The more commonly used 30-day mortality underestimates surgical mortality in thoracic aortic surgery [14], and at 60 days a stable death rate remaining throughout follow-up was established. Thus, 60-day mortality served as a better, robust indicator of procedure-related death.

Overall, emergency status (HR 2.8) was a stronger predictor of operative death than aortic dissection per se (HR 1.5). Emergency cases included the highly lethal thoracic aortic rupture, whereas dissections included a fraction of lower-risk chronic type A dissection (10%): of dissections, 69% were operated emergently, but in 21.3%, the acuity of operation could not be safely determined (Table 1), but it is safe to assume that a majority of these were emergent or acute cases as well. Interestingly, concomitant CABG doubled risk in all patients, but AVR influenced risk only in aortic dissection. AVR, associated either with pre-existing valve disease or aortic valve damage by dissection, often entails technical problems in the frail dissected aorta, and was best avoided if possible in these patients. CABG on the other hand was a marker of coronary artery disease or intraoperative problems mandating coronary revascularization, in either case clearly affecting perioperative mortality.

The major postoperative complications of stroke and renal failure were of much greater importance for 60-day survival, and the effect of stroke extended into the intermediate-term (up to 5 years) follow-up (Table 2). Obviously, stroke victims surviving the initial phase have a worse outcome within a few years from operation, related to neurological sequelae, anticoagulation, or comorbidity.

Increased age is perhaps the most uniformly reported factor associated with surgical mortality [1,6,12,15]. The findings of increased surgical risk with concomitant procedures (AVR, CABG) and aortic dissection/emergency operation also corroborated earlier findings [15–17]. Several putatively important, modifiable (cardiopulmonary bypass time, intraoperative dissection) or non-modifiable (hypertension, shock) variables earlier reported to be associated with surgical risk [1,6,15,16] were not analyzed in this study, and their relative impact could not be evaluated. Evidently, preoperative as well as perioperative variables need to be included in analysis to adequately identify all relevant risk factors, as is not always the case [11,18].

4.2 Long-term mortality
Age was the only variable associated with adverse outcome in all patients at all times after operation. A HR of approximately 1.05 may seem of marginal importance, but equals 1.63, 2.07, and 2.65 for an increase in age by 10, 15, and 20 years, respectively, thus making it an overall important predictor of death at any time. Indirectly, this finding advocated early surgery when possible.

As illustrated by Kaplan-Meier curves in Fig. 2B, successful surgery equalized long-term survival in aneurysm and dissection, respectively. Whereas overall mortality remains higher in aortic dissection, surgical survivors fared better than expected, despite reported risks of late complications including aortic dilatation and rupture [4,19,20]. This finding also advocated an active surgical approach in aortic dissection, but may also reflect the substantial comorbidity of thoracic aortic aneurysm patients, requiring close postoperative surveillance. The absence of difference in long-term survival may challenge our thinking on the long-term fate of the operated aorta. In the present study, there was no evidence for a worse long-term outcome related to a patent false lumen, raising the question of how often it actually contributes to late complications and death. The need for further, more detailed large-scale studies is obvious. Importantly, variables associated with death varied over time, lending support to a hypothesis of different hazard phases postoperatively. It illustrated the selection of patients across time, rendering, e.g. postoperative complications less important in those surviving beyond 5 years from operation. Interestingly, even centers with lower surgical mortality report higher long-term mortality: 57% 10-year survival in a mixed patient population by Shapira et al. [8] and 32–56% 10-year survival in dissection [6,7,12,20] compared to 73% overall and 65% with dissection in this study, with manifold higher numbers at risk throughout follow-up. While obviously not explained by patient selection alone, it could indicate differences in follow-up practices, medical therapy, or attitude toward reinterventions and operations.

4.3 Surgical era and mortality
Disappointingly, later era of operation was associated with lower surgical risk only in aneurysm patients. The use of hypothermic circulatory arrest and concomitant procedures (AVR, CABG, and total arch replacement) increased significantly across time for both aneurysms and dissections (Table 4 ), whereas the use of composite grafts decreased. For dissections, mean age increased, and cerebral complications became more prevalent, contributing to increased surgical mortality. Yet, the patterns for aneurysms and dissections were similar, and the absent improvement in mortality for dissections was not fully understood. Improved perioperative care overall, yet widened surgical indications with more high-risk patients in aortic dissection coheres best with the findings apparent by comparison. Lower volumes of operations for dissection and involvement of more on-duty surgeons with limited experience may also be contributing factors; this variable could not be included in the analysis due to lack of data. Again, this question would be interesting to address in a separate study. Improved outcomes in later treatment eras have been reported by some [7–9], but not all [16,17], previous similar reports.

Despite several common features, head-to-head comparison of outcomes for proximal thoracic aortic aneurysms and dissections is uncommon [1,8,24] due to differences in patient characteristics, presentation, and surgical outcomes. As shown in this study, however, there was good reason to analyze the two in one context: in surgical survivors, late outcomes were very similar and not depending on diagnosis or type of operation. Furthermore, the absence of significant improvement in outcomes for aortic dissection across time was highlighted by the comparison, raising questions about indications for surgery, implementation of improved perioperative techniques, and shortcomings of late follow-up. Importantly, the non-curative feature of operation and important comorbidity were also highlighted: postoperative death rate is still substantial regardless of diagnosis

	5. Limitations

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion 5. Limitations 6. Conclusions Appendix A References

 
Register-based studies carry two major limitations. They are by default retrospective and observational, and they offer limited amounts and quality of variables, e.g. in ICD diagnostic and procedural codes. The possibility of performing randomized controlled trials in thoracic aortic surgery, other than for very limited questions, is minute. Register studies may well be the second best source of information, provided the register is non-administrative, population-based, contemporary, complete, and validated [25]. Data from the Swedish Heart Surgery register, meeting these criteria, abolish the effects of individual high-performance centers, eliminate undue bias, and provide information of relevance and practical use for clinicians, patients, and health care providers. Several potentially important variables were not collected by the register; hence not part of the analyses, e.g. hypertension, left ventricular function, extent of aortic disease, duration of hypothermic circulatory arrest. Follow-up practices including imaging studies, medical therapy, and percutaneous interventions were not reviewed, but may have considerable impact on long-term outcomes.

	6. Conclusions

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion 5. Limitations 6. Conclusions Appendix A References

 
In unselected patients operated on the proximal thoracic aorta, surgical and long-term mortality has decreased across time. However, this benefited only patients operated for thoracic aortic aneurysms. Increased age was the only variable independently associated with death throughout follow-up. In surgical survivors, long-term survival was equivalent for aneurysms and dissections, prompting close and extended follow-up in both instances.

	Appendix A

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion 5. Limitations 6. Conclusions Appendix A References

 
Conference discussion

Dr L. Piazza (Caserta, Italy): I’d like to ask if you observed a different time of the surgery, the time from between the diagnosis and the treatment, in the dissection time.

Dr Olsson: Well, roughly, of course, we can divide dissection cases into acute and chronic cases. And I think the dominating way of handling these cases is to operate type A dissection whenever you diagnose it, as soon as you can. The fraction of chronic cases in this study was about 15%.

Dr L. Von Segesser (Lausanne, Switzerland): One of the problems with the acute dissection is, of course, that some of the patients will have neurologic deficit. And whatever you do, they will still have neurologic deficit. So I think this you cannot get rid of.

Dr Olsson: No. And actually we saw an increase in strokes in the later era in dissection patients. I didn’t show that in the slides, but my interpretation of that is not that we are performing surgery in a worse way than before, but we are treating more sick patients now.

Dr D.C. Miller (Stanford, California, USA): Amen. My mentor, Dr Norman Shumway, who just expired this year, accused all of us ‘young bucks’ many years ago of doing just that. He called it the ‘warm autopsy’. When you’re young, overconfident, and ambitious you just think you can pull anybody through an operation, even if they come to the operating room dead. Alas, we soon learnt the hard way that we are kidding ourselves – this is self-delusion.

Dr A. Garatti (Milan, Italy): You said that the aortic valve replacement was a risk factor for mortality in acute dissection. Do you evaluate if there is a difference in mechanical valve replacement or biological valve replacement, in other words, avoiding anticoagulation does affect mortality or evolution of false lumen in your study?

Dr Olsson: First of all, these were not only acute dissections, they were also chronic dissections.

Second of all, in this material, we have not split between bioprosthesis and mechanical replacement. So I can’t really answer that question supported by any data.

	Acknowledgments

 
The study was financially supported by The Swedish Heart-Lung foundation and by the Erik, Karin, and Gösta Sellander foundation at Uppsala University, Sweden.

	Footnotes

 
^\#9734; Presented at the joint 20th Annual Meeting of the European Association for Cardio-thoracic Surgery and the 14th Annual Meeting of the European Society of Thoracic Surgeons, Stockholm, Sweden, September 10–13, 2006.

	References

Top Abstract 1. Introduction 2. Patients and methods 3. Results 4. Discussion 5. Limitations 6. Conclusions Appendix A References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Elisabeth Ståhle Stefan Thelin Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Olsson, C. Articles by Thelin, S. Search for Related Content PubMed PubMed Citation Articles by Olsson, C. Articles by Thelin, S. Related Collections Great vessels