doi: 10.1161/CIRCULATIONAHA.106.681510
(Circulation. 2007;116:I-150 – I-156.)
© 2007 American Heart Association, Inc.
Surgery for Aortic Disease |
Acute Type B Aortic Dissection: Does Aortic Arch Involvement Affect Management and Outcomes?
Insights From the International Registry of Acute Aortic Dissection (IRAD)
On Behalf of the International Registry of Acute Aortic Dissection (IRAD). See Appendix for list of investigators.
Correspondence to Thomas T. Tsai, MD, MSc, University of Michigan Cardiovascular Center, 1500 E. Medical Center Dr, Ann Arbor, MI 48109-5853. E-mail hsianshi{at}umich.edu
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Abstract |
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Background— Stanford Type B acute aortic dissection (TB-AAD) spares the ascending aorta and is optimally managed with medical therapy in the absence of complications. However, the treatment of TB-AAD with aortic arch involvement (AAI) remains an unresolved issue.
Methods and Results— We examined 498 patients with TB-AAD enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2003. Kaplan-Meier mortality curves were constructed and multivariate regression models were performed to identify independent predictors of AAI and to evaluate whether AAI was an independent predictor of follow-up mortality. We found that 371 (74.5%) patients with TB-AAD did not have AAI versus 127 (25.5%) with AAI. Independent predictors of AAI were a history of previous aortic surgery (OR 3.4; 95% CI, 1.6 to 7.6; P=0.002), absence of back pain (OR 1.6; 95% CI, 1.1 to 2.5; P=0.05), and any pulse deficit (1.9; 95% CI, 1.1 to 3.3, P=0.03). Mortality for patients without AAI was 9.4%±4.3% and 21.0%±6.9% at 1 and 3 years versus 9.2%±7.7% and 19.9%±11.1% with AAI, respectively (mean follow-up overall, 2.3 years, log rank P=0.82). AAI was not an independent predictor of long-term mortality.
Conclusions— Patients with TB-AAD and aortic arch involvement do not differ with regards to mortality at 3 years. Whether or not AAI involvement impacts other measures of morbidity such as freedom from operation or endovascular intervention deserves further study.
Key Words: aorta • surgery • risk factors • mortality
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Introduction |
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Acute aortic dissection is a life-threatening cardiovascular disease associated with considerable morbidity and mortality.1–4 Patients with type B acute aortic dissection (TB-AAD), defined by the absence of false lumen propagation in the ascending aorta, have better survival compared with those involving the ascending aorta (type A).5,6 In the current era, patients with uncomplicated aortic dissections confined to the descending aorta (type B) are usually treated with medical therapy.7,8 Surgery or endovascular therapy is reserved for patients presenting with evolving complications such as signs of imminent rupture, expansion, retrograde dissection, or malperfusion syndromes.4,9–11 However, the management of TB-AAD with involvement of the aortic arch is not specifically addressed in the current classification systems, and management of these patients remains unresolved. Previous studies have shown that involvement of the aortic arch has been associated with higher mortality than dissections limited to the descending aorta only.12,13
The International Registry of Acute Aortic Dissection (IRAD) represents 21 large referral centers from around the world with consecutively enrolled patients presenting with TB-AAD.1 It includes information on presentation, in-hospital clinical outcomes, and follow-up data.14,15 The purpose of this study was to evaluate differences in demographics, medical history, presentation, management, and outcomes of patients with TB-AAD with a dissection distal to the left subclavian artery without aortic arch involvement (AAI) compared with patients with AAI. Additionally, we report predictors of AAI and the impact of AAI on follow-up mortality.
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Methods |
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The International Registry of Acute Aortic Dissection (IRAD) is a multinational registry designed to provide a representative population of patients with acute aortic dissection. Treatment during the index hospitalization or in follow-up was not standardized but at the discretion of each patient’s treating physician. Full details of the IRAD methods have been previously published.1,16 The authors had full access to the data and take responsibility for its integrity. All authors have read and agree to the manuscript as written.
Study Population
We examined data on all patients with TB-AAD enrolled in IRAD centers between January 1, 1996 and December 31, 2003 (15 centers). TB-AAD was defined as any nontraumatic dissection sparing the ascending aorta presenting within 14 days of symptom onset.6,17 Patients were identified prospectively at presentation or retrospectively via discharge diagnoses, imaging, and hospital databases. Diagnosis was based on imaging, surgical visualization, or on autopsy.
Of the 503 patients enrolled in IRAD with TB-AAD, 5 were excluded because proximal extent of dissection was unknown. Of the remaining 498 patients with TB-AAD, 127 (23.9%) had AAI. To minimize follow-up bias, our long term follow-up analysis included 232 patients discharged alive from the 8 of 15 referral centers with >80% follow-up.14,15 Median follow-up time was 2.6 years.
Data Collection
Data on 290 variables were recorded on a standardized form which included information on patient demographics, history, clinical presentations, physical findings, imaging study results, details of medical and surgical treatment, and patient outcomes including mortality. Data forms were reviewed for internal consistency and validity and then scanned electronically into an Access database.
Imaging was interpreted at each patient’s respective tertiary care center by specialized radiologists and echocardiographers and entered into the data form. Spiral computed tomography, transesophageal echocardiography, magnetic resonance imaging, or angiography was obtained. TB-AAD with AAI was defined as involvement of the aortic arch on cross sectional imaging either by an intimal tear in the aortic arch or extension of the dissection flap within the arch.
Yearly follow-up data were obtained up to 5 years after discharge using standardized data forms. Collected data included variables on clinical, imaging, and vital information. When applicable, additional data on mortality was obtained through the Social Security Death Index. At each enrolling hospital, study investigators obtained approval from their ethics or institutional review board to participate in IRAD and its follow-up study.
Statistical Analysis
We compared patients with TB-AAD without AAI versus patients with TB-AAD and AAI. Summary statistics between the 2 groups are presented as frequencies for categorical variables and mean±standard deviation for continuous variables. In all cases, missing data were not defaulted to negative and denominators reflect only cases reported. Bivariate analysis was performed using Chi-squared or 2-sided Fisher exact tests and Student t test to assess differences between clinical variables in patients with and without aortic arch involvement. Stepwise logistic regression was used to identify variables independently associated with AAI. Initial modeling used variables marginally suggestive of an unadjusted association to AAI (P<0.20). Variables were reviewed a priori for clinical significance before testing. Multistage Cox proportional hazards analysis modeled the association between follow-up death and AAI to assess the incremental impact of demographic, comorbid conditions (atherosclerosis, history of known aortic aneurysm, history of hypertension, history of prior cardiac surgery), and in-hospital variables on follow-up death. Kaplan-Meier mortality curves were constructed and differences tested using the log-rank test. SAS Version 8.2 (SAS Institute) and Stata 9 (Stata) was used for all analyses.
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Results |
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Baseline and Imaging Characteristics
The mean age was 64.2±13.5 years (Table 1) with the majority being men (68.9%); 197 (39.6%) were older than age 70 and 384 (77.9%) had a history of hypertension. Atherosclerosis (35.8%) and a history of prior cardiovascular surgery (18.4%) were not uncommon.
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In more than 95% of patients, the diagnosis of TB-AAD was confirmed by cross sectional imaging within 1 day of presentation (0.42±2.36 days). The remaining cases were confirmed within 7 days. With regards to AAI on cross sectional imaging, 371 (74.5%) were categorized without AAI with a dissection distal to left subclavian artery and 127 (25.5%) had a TB-AAD with AAI. In patients without AAI, an intimal tear was seen in the descending aorta in 41.0%, multiple locations in 3.8%, and was not visualized in 55.2% of patients. The proximal dissection flap began in close proximity to the left subclavian level in 64.4%, descending aorta in 30.8%, and in the abdominal aorta in 4.8%. The distal extent remained in the descending aorta in 24.8% propagating to the abdominal aorta in 75.2%. In patients with AAI, the intimal tear was seen in the arch in 37.7%, descending aorta in 22.3%, at multiple locations in 2.3%, and not seen at all in 37.7%. The proximal extent of the dissection flap involved the arch in all cases and remained distally confined to the arch in 2.4%, propagating to the descending aorta in 29.5%, abdominal aorta in 65.9%, and unknown in 2.2%. A mean of 1.5±1.1 studies per patient was performed with computed tomography being the most common, used in 67.5% of patients (Table 2).
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Management and Outcomes
A total of 78 (15.7%) patients received surgery for the repair of their TB-AAD, whereas 66 (13.3%) were managed with endovascular treatment (stenting or fenestration) and 354 (71.1%) treated with medical therapy alone. There was no significant difference in management strategies between patients with and without AAI (Table 3).
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The overall in-hospital mortality rate was 12.3% (61/498). When stratified by patients with TB-AAD without AAI compared with patients with AAI, there was no significant difference in in-hospital mortality according to Kaplan-Meier mortality curves out to 30 days (log rank P=0.58; Figure 1). Patients treated with surgery were significantly more likely to die in the hospital compared with patients treated with medial therapy alone or endovascular treatment (30.8% versus 8.8% versus 9.1%, P<0.001). However, regardless of in-hospital treatment, there was no significant difference in in-hospital mortality when comparing patients without AAI and patients with AAI (Table 3). Furthermore, in patients who survived to hospital discharge, the mortality curves were similar in patients without AAI with a 1- and 3-year follow-up mortality of 9.4%±4.3% and 21.0%±6.9% versus 9.2%±7.7% and 19.9%±11.1% in patients with AAI (log rank P=0.82; Figure 2).
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Clinical Features of Type B Aortic Dissection With Arch Involvement
Patients with AAI did not differ with regards to demographics when compared with patients without AAI but did have a significantly higher prevalence of a history of prior aortic dissection (13.4% versus 4.2%, P<0.001). On presentation, patients with AAI were less likely to present with back pain (60.8% versus 70.7%, P=0.04) or have a normal chest x-ray (11.7% versus 21.8%, P=0.02) but had larger arch diameters on cross sectional imaging (Table 2). Additionally, patients with AAI were more likely to present with arch vessel involvement (10.6% versus 1.9%, P<0.001) and aortic regurgitation (27.9% versus 12.7%, P<0.001). After multivariate adjustment including age and gender, clinical variables independently associated with AAI in patients with TB-AAD include a history of prior aortic surgery, the absence of back pain, and any pulse deficit on physical examination or on arrival (Table 4).
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Predictor of Follow-Up Mortality
In multistage Cox regression, the association between AAI and follow-up mortality was not significant after adjustment for demographic characteristics alone or after adjustment for demographics, comorbid conditions, and treatment strategy (Table 5).
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Discussion |
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Although in-hospital outcomes are generally acceptable in patients with initially uncomplicated TB-AAD, short- and long-term prognosis after discharge remains unclear. Recent contemporary results from IRAD showed that patients surviving to hospital discharge still have a 3-year follow-up mortality that approaches 1 in 4 patients regardless of in-hospital treatment.14 Given the high follow-up mortality despite the access to contemporary imaging and management, the debate on optimal treatment of acute type B dissection is unsettled. Stent grafts to cover the primary tear and expanded indications for surgery have both been considered and promoted.18 Other centers have used expanded surgical indications in patients with TB-AAD with a focus on younger patients, patients with Marfan syndrome, and arch involvement.11,19,20 At present, however, there is no evidence-based data to support either of those strategies.
Predictors and Incidence of Arch Tears
We found that more than 1 in 4 patients (25.5%) with TB-AAD had involvement of the aortic arch on cross sectional imaging. Of those, at least 37% (8.6% overall) had the site of intimal tear in the arch. This is within the broad range of studies reporting AAI in 5.4% to 74.2% of patients with TB-AAD.13,21–23 The highest incidence was reported by Sueyoshi et al on the growth rate of the aortic diameter in patients with TB-AAD from 2 centers in Japan.24 The large range of aortic arch involvement is largely a function of a differing spectrum of in-homogeneous definitions. In some studies arch involvement is meant to describe the site of primary tear in the arch whereas others are less restrictive and include any extent of the dissection flap in the arch regardless of the site of primary tear.
We found that prior aortic surgery (aortic aneurysm repair or aortic dissection repair), the absence of back pain, and the presence of pulse deficits at presentation were independent predictors of patients with aortic arch involvement of their TB-AAD even after adjusting for age, sex, and comorbid conditions. This suggests that patients with prior aortic disease necessitating surgery may have diseased segments of aorta left behind, such as the arch, that are at increased risk of tearing or further expansion during follow-up. Furthermore, patients with an ascending aortic graft with disease in the native arch tissue may only dissect in antegrade fashion. Also, the absence of typical back pain associated with the tearing of the descending aorta may have been superceded by the jaw and neck pain associated with arch involvement. Additionally, pulse deficits in neck vessels may herald AAI into the carotid or brachiocephalic vessels.
In-Hospital and Follow-Up Mortality
In our analysis, no difference in in-hospital mortality was apparent between patient with TB-AAD with and without AAI. Furthermore, in those patients with AAI who survived to hospital discharge there was no significant difference in mortality compared with patients with and without AAI (Figure 2). Patients with and without AAI had 3-year follow-up mortality of 19.9%±11.1% and 21.0%±6.9%, respectively. Finally, in patients with TB-AAD, AAI was not an independent predictor of follow-up death compared with patients without AAI despite adjustment for age and gender as well as comorbid conditions and in-hospital management type. This analysis had 76% power to detect a HR=2.0 of the risk of death among patients with AAI versus patients without AAI.
On aggregate, our study does not support previous investigations that link AAI in patients with TB-AAD with worse long term survival. Therefore, given the lack of association between AAI and long-term survival, management based on conflicting observational evidence would not appear justified. However, we are unable to comment on the relationship of AAI and a dissection related event such as aortic rupture or follow-up surgery. In the current era, we believe that patients with uncomplicated TB-AAD regardless of AAI should be treated by medical therapy with endovascular interventions or stent graft placement, or surgery reserved for patients with recurrent pain, aortic expansion, dissection progression, or end-organ malperfusion syndromes.
Limitations
Several considerations are important in interpreting results of this registry. First, our cohort represents patients treated at centers specialized in aortic diseases. As a result, these findings may not reflect management or represent patients treated and followed at community hospitals. Second, imaging across centers was not standardized in terms of choosing a definitive method, however all imaging was performed with the latest generation tomographic equipment by skilled personal with expertise in aortic diseases. Nevertheless, image interpretation across modalities remains subject to misclassification of AAI when limited expertise is applied. However, follow-up mortality was recorded independent of data form completion, thereby minimizing any systematic classification bias. Third, to minimize selection bias, we only included patients from the 8 of 15 centers with >80% follow-up when performing our survival analysis. However, these patients resembled those from the centers with <80% follow-up with regard to mortality rates (33% versus 26%, P=0.17). Additionally, there was not a significant difference in the percentage of patients lost to follow-up when grouped by the presence of aortic arch involvement (19.2% versus 20.7%, P=0.64). This suggests a nondifferential loss to follow-up between groups and therefore limits the bias attributable to any particular group. Finally, data available to us on follow-up mortality did not include information on cause of death. We were therefore unable to evaluate cause-specific mortality or other nonfatal end points such as freedom from reoperation, rupture, or redissection. However, previous studies have shown that the majority of deaths in these patients are attributable to aorta-related complications such as rupture, extension of dissection, and perioperative mortality from subsequent aortic or vascular repairs.13,20,25,26
Conclusion
Aortic arch involvement occurred in 25.5% of patients presenting with TB-AAD and is not associated with higher follow-up mortality compared with patients without AAI. Previous aortic surgery, absence of back pain, and pulse deficits are independent predictors of AAI. Aortic arch involvement in patients presenting with TB-AAD does not appear to increase the risk of either in-hospital or follow-up mortality. Whether or not AAI involvement impacts other measures of morbidity such as freedom from late complications or major adverse vascular events deserve further study.
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Appendix I |
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TopAbstractIntroductionMethodsResultsDiscussionAppendix IReferences |
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The International Registry of Acute Aortic Dissection (IRAD) Investigators
Co-Principal Investigators
Kim A. Eagle, MD, University of Michigan, Ann Arbor, Mich; Eric M. Isselbacher, MD, Massachusetts General Hospital, Boston, Mass; Christoph A. Nienaber, MD, University of Rostock, Rostock, Germany.
Co-Investigators
Eduardo Bossone, MD, National Research Council, Lecce, Italy; Arturo Evangelista, MD, Hospital General Universitari Vall d’Hebron, Barcelona, Spain; Rossella Fattori, MD, University Hospital S. Orsola, Bologna, Italy; James Froehlich, MD, University of Michigan, Ann Arbor, Mich; Dan Gilon, MD, Hadassah University Hospital, Jerusalem, Israel; Stuart Hutchison, MD, St. Michael’s Hospital, Toronto, Ontario, Canada; James L. Januzzi, MD, Massachusetts General Hospital, Boston, Mass; Alfredo Llovet, MD, Hospital Universitario "12 de Octubre", Madrid, Spain; Debabrata Mukherjee, MD, University of Kentucky, Lexington, Ky; Truls Myrmel, MD, Tromsø University Hospital, Tromsø, Norway; Patrick O’Gara, MD, and Joshua Beckman, MD, Brigham and Women’s Hospital, Boston, Mass; Jae K. Oh, MD, Mayo Clinic, Rochester, Minn; Linda A. Pape, MD, University of Massachusetts Hospital, Worcester, Mass; Udo Sechtem MD, and Gabriel Meinhardt, MD, Robert-Bosch Krankenhaus, Stuttgart, Germany; Toru Suzuki, MD, University of Tokyo, Tokyo, Japan; Santi Trimarchi, MD, Policlinico San Donato, San Donato, Italy.
Data Management and Biostatistical Support
Jeanna V. Cooper, MS and Dean E. Smith, PhD, University of Michigan, Ann Arbor, Mich.
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Acknowledgments |
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Sources of Funding
IRAD has been supported by grants from the University of Michigan Faculty Group Practice and the Varbedian Fund for Research in Aortic Diseases. Thomas T. Tsai is supported by a training grant from the National Institutes of Health (#5T32HL007853-08).
Disclosures
None.
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Footnotes |
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Presented at the American Heart Association Scientific Sessions, Chicago, Ill, November 12–15, 2006.
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References |
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