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Circulation. 2006;114:I-357-I-364
doi: 10.1161/CIRCULATIONAHA.105.000620
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*Aortic Aneurysm

(Circulation. 2006;114:I-357 – I-364.)
© 2006 American Heart Association, Inc.


Surgery for Aortic and Peripheral Vascular Disease

Role and Results of Surgery in Acute Type B Aortic Dissection

Insights From the International Registry of Acute Aortic Dissection (IRAD)

Santi Trimarchi, MD; Christoph A. Nienaber, MD; Vincenzo Rampoldi, MD; Truls Myrmel, MD; Toru Suzuki, MD; Eduardo Bossone, MD; Valerio Tolva, MD; Michael G. Deeb, MD; Gilbert R. Upchurch, Jr, MD; Jeanna V. Cooper, MS; Jianming Fang, MD; Eric M. Isselbacher, MD; Thoralf M. Sundt, 3rd, MD; Kim A. Eagle, MD, on behalf of the IRAD Investigators

From the Cardiovascular Center "E. Malan" (S.T., V.R., V.T.), Policlinico S. Donato, S. Donato Milanese, Italy; University of Rostock (C.A.N.), Rostock, Germany; Tromsø University Hospital (T.M.), Tromsø, Norway; University of Tokyo (T.S.), Japan; National Research Council (E.B.), Lecce, Italy; University of Michigan (M.G.D., G.R.U., J.V.C., J.F., K.A.E.); Ann Arbor, Michigan; Massachusetts General Hospital (E.M.I.), Boston, Massachusetts; Mayo Clinic (T.M.S.), Rochester, Minnesota.

Correspondence to Santi Trimarchi, Cardiovascular Center "E. Malan", Policlinico San Donato, via Morandi 30, 20097 S. Donato Milanese, Italy. E-mail satrimarchi{at}yahoo.it


*    Abstract
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Background— The clinical profiles and outcomes of patients treated surgically for acute type B aortic dissection (ABAD) are often reported for those in small series or for those cared for at a single institution over a long time period, during which a continuous evolution in techniques has occurred. Accordingly, we sought to evaluate the clinical features and surgical results of patients enrolled in the International Registry of Acute Aortic Dissection by identifying primary factors that influenced surgical outcome and estimating average surgical mortality for ABAD in the current era.

Methods and Results— A comprehensive analysis of 290 clinical variables and their relation to surgical outcomes for 82 patients who required surgery for ABAD (from a population of 1256 patients; mean±SD age, 60.6±15.0 years; 82.9% male) and who were enrolled in the International Registry of Acute Aortic Dissection was performed. The overall in-hospital mortality was 29.3%. Factors associated with increased surgical mortality based on univariate analysis were preoperative coma or altered consciousness, partial thrombosis of the false lumen, evidence of periaortic hematoma on diagnostic imaging, descending aortic diameter >6 cm, right ventricle dysfunction at surgery, and shorter time from the onset of symptoms to surgery. Factors associated with favorable outcomes included radiating pain, normotension at surgery (systolic blood pressure 100 to 149 mm Hg), and reduced hypothermic circulatory arrest time. The 2 independent predictors of surgical mortality were age >70 years (odds ratio, 4.32; 95% confidence interval, 1.30 to 14.34) and preoperative shock/hypotension (odds ratio, 6.05; 95% confidence interval, 1.12 to 32.49).

Conclusions— The present study provides insights into current-day clinical profiles and surgical outcomes of ABAD. Knowledge about different preoperative clinical conditions may help surgeons in making treatment decisions among these high-risk patients.


Key Words: aorta • aortic diseases • disease management • treatment outcome


*    Introduction
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Acute type B aortic dissection (ABAD) is a serious cardiovascular condition associated with high morbidity and mortality.1–4 Distal or descending thoracic aortic dissection generally is associated with better survival compared with that involving the ascending aorta.5,6 The introduction of newer management strategies that have shown the potential to improve outcomes has reduced the role of surgery to &15% of cases.7,8 Despite improved surgical techniques and perioperative care, operative mortality in this subgroup remains high, between 25% and 50%.9 Recent reports on ABAD are limited by small number of patients, are long-term, single-institution series, or both, wherein more recent advances in diagnosis or treatment are not fully represented.10,11

The International Registry of Acute Aortic Dissection (IRAD) represents a unique opportunity to study large groups of consecutive patients treated for aortic dissection by 18 aortic referral centers around the world. We completed a comprehensive analysis of 290 clinical variables and their relation to surgical outcomes. The aim of this analysis was to identify the primary factors that influence surgical outcomes in this specific cohort, to show an accurate average surgical mortality for ABAD in the current era, and to facilitate a preoperative risk stratification for improving preoperative decision making.


*    Methods
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Patient Selection
Patients operated on for ABAD and who were enrolled in the IRAD between January 1, 1996 and April 30, 2003 were included in the present analysis. IRAD is an ongoing, multinational, multicenter registry started in 1996 that includes consecutive patients with acute aortic dissection at 18 large referral centers (IRAD centers; see Appendix). The rationale for this registry has previously been described.12 ABAD was defined as any acute aortic dissection involving the descending aorta without any entry tear in the ascending aorta and/or in the aortic arch and presenting within 14 days of symptom onset.6,12 Intramural hematoma was defined as the presence of a regionally thickened aortic wall without any evidence of a double lumen and/or intimal flap regardless of imaging modality.13,14 For this analysis, both classic dissection and acute intramural hematoma progressing to surgery were considered in the study cohort. Indications for surgery at IRAD centers generally included rupture with hypotension or shock, uncontrollable hypertension despite medical therapy, visceral and/or limb ischemia, extension of dissection, and recurrent and/or refractory pain. The institutional review boards for research at all IRAD centers approved the study protocol.

Data Collection
Data were collected on a standardized data form of 290 clinical variables, including patient demographics, history, clinical presentation, physical findings, imaging studies, medical and surgical management, in-hospital mortality, and adverse events. Completed data forms were forwarded to the coordinating center at the University of Michigan. Data forms were reviewed for analytical internal validity and scanned electronically into an Access (Microsoft Corp, Redmond, Wash) database. For this analysis, 82 patients with distal aortic dissection who were treated surgically were analyzed.

Statistical Analysis
Data are shown as frequencies and percentages, and as mean±SD or median and interquartile range. Missing data were not defaulted to negative, and denominators reflect only reported cases. Associations of death among nominal variables were compared with the {chi}2 test and Fisher’s exact test when appropriate and among continuous variables with Student’s t test. Stepwise multivariate logistic-regression variables were fitted from variables found to have marginal associations with death on univariate testing (P<0.20). Odds ratios (ORs), 95% confidence intervals (CIs), probability values, and c-statistics are reported. SAS 8.1 software (Cary, NC) was used for all analyses.

The authors had full access to the data and take full responsibility for its integrity. All authors have read and agree to the manuscript as written.


*    Results
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Patient Population
Of 1256 patients with acute aortic dissection enrolled in IRAD from 1996 to April 2003, 476 patients (37.8%) had ABAD, of whom 82 (17.2%) were surgically treated and included in this analysis. In the surgical cohort, mean±SD age was 60.6±15 years with a predominance (82.9%) of male patients; 49 (63.6%) had been transferred to an IRAD center from a referral hospital for definitive treatment. Among this group of surgical patients, Marfan syndrome was present in 11.3% (Table 1).


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TABLE 1. Demographics of Surgical ABAD Patients in IRAD

Presenting Signs and Symptoms
An abrupt onset of pain was noted in 83.8% of patients, and any type of pain was reported in 92.6% of patients: chest pain in 59.3%, abdominal pain in 36.7%, and leg pain in 9.3%. Preoperative malperfusion was detected in 30% of patients, a pulse deficit in 23.4%, mesenteric ischemia or infarction in 14.5%, acute renal failure in 12.5%, and limb ischemia in 16.9%. Neurological symptoms were noted in 12.3%, including coma/altered consciousness in 3.8%, spinal cord ischemia in 6.2%, and ischemic peripheral neuropathy in 2.5% (Table 2). Preoperative hypertension appeared at presentation in 45.6% of patients, hypotension in 7.6%, and shock or tamponade in 6.3% before surgery. Hemodynamic status was documented on arrival in the referral hospital and at surgery (Table 3). Surgical intervention was indicated for aortic rupture in 23.1% of patients, for visceral ischemia in 23.9%, for limb ischemia in 15.5%, for extension of dissection beyond the intimal tear compromising additional arteries in 52.1%, for recurrent pain in 26.8%, for refractory pain in 14.1%, and for untreatable hypertension in 15.5%. In almost one third of patients, >1 surgical indication was noted.


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TABLE 2. Presenting Symptoms and Signs of Surgical ABAD Patients in IRAD


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TABLE 3. Preoperative Hemodynamic Status of Surgical ABAD Patients in IRAD

Diagnostic Evaluation
The diagnosis of ABAD was made by 1 (typically >1) imaging method, including transesophageal echocardiography in 62.2%, computed tomography in 93.9%, aortography in 42.7%, and magnetic resonance in 24.4%. Chest radiography showed a widened mediastinum in 62.7% of patients, whereas no abnormalities were noted on chest x-ray in 17.3%. Tomographic imaging revealed intramural hematoma in 7.8% of patients, pleural effusion in 20.5%, and periaortic hematoma in 23.1%. The mean aortic diameter was 41.2 mm in the aortic arch and 52.9 mm in the descending aorta (Table 4).


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TABLE 4. Diagnostic Methods and Types of Evidence of ABAD Patients in IRAD

Surgical Strategy
The descending aorta was replaced in 52 patients (69.3%), partial arch in 14 (20.6%), and the complete arch in 5 (7.5%). Surgical fenestration was used in 6 cases (9.0%), whereas surgical approaches to the peripheral vessels were used in 15 (20.3). In association with surgical procedures, visceral or iliac stenting was performed in 6 (9.0%) patients. An open procedure was used in 82.2% of cases (60 patients), with hypothermic circulatory arrest in 48% (36 patients) and cerebral perfusion in 12 patients (17.1%). Mean hypothermic circulatory arrest time was 40 minutes (range, 29 to 61) in patients who survived 37 minutes versus 54 minutes (P=0.01) in patients who expired in-hospital. Reoperation was required for bleeding in 5 patients (7.1%; Table 5). The mean interval between the onset of symptoms and initial surgery was 71.2 hours, 41.3 hours in nonsurvivors and 96.0 hours in survivors (P<0.04). Surgery was reported to be delayed for a variety of reasons, including the need to obtain confirmatory imaging studies, to perform coronary angiography, until a surgeon or operating room became available, or for resolution of a comorbid medical condition. Delayed surgery (>48 hours) was performed in 61.2% of patients.


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TABLE 5. Surgical Procedures of ABAD Patients in IRAD

Hospital Outcomes
The overall in-hospital mortality was 29.3%. In patients who underwent surgery by 48 hours, in-hospital mortality was 39.2%, and for those who underwent surgery by 49 hours or more, mortality was 18.1% (P<0.05). Causes of death were aortic rupture in 61.9% of patients, neurological in 14.3%, and unspecified in 23.8%. Considering the various indications for surgery, nonsignificant differences in mortality have been shown except for rupture, which is correlated with shock and periaortic hematoma (P<0.02). Postoperative complications, most of which were correlated with postoperative death, were new neurological deficits in 23.2% of patients (P<0.02; cerebrovascular accident in 9.0% [P<0.3], coma in 7.5% [P<0.02], and paraplegia in 4.5% [P>0.99]), visceral ischemia/infarction in 6.8% (P<0.05), acute renal failure in 18.3% (P<0.02), hypotension/shock in 21.3% (P<0.001), cardiac tamponade in 3.3% (P<0.06), and limb ischemia in 3.4%. Independent predictors of surgical mortality were age >70 years (OR=4.32; 95% CI=1.30 to 14.34) and preoperative shock/hypotension (OR=6.05; 95% CI=1.12 to 32.49). Univariate predictors of death after surgery (P<0.05) were preoperative coma or altered consciousness, partial thrombosis of the false lumen, periaortic hematoma at the diagnostic examinations, descending aortic diameter >6 cm, right ventricular dysfunction at surgery, and shorter time from the onset of symptoms to surgery. Predictors of a more favorable outcome included radiating pain, normotension at surgery (systolic blood pressure 100 to 149 mm Hg), and hypothermic circulatory arrest time <40 minutes. Among nonsurvivors, the mean time of death occurred 19.8 hours (5.6 hours to 75.1 hours) after the onset of surgery. Mean hospital length of stay was 16 days, 26 days for survivors and just 2 days for patients who died (P<0.0001).


*    Discussion
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In ABAD, medical management (eg, antihypertensive, cardiac output suppressive) is currently the preferred method of treatment for uncomplicated patients,8 including those with stable hemodynamic status, no branch vessel involvement, and no periaortic hematoma. Such a cohort has a very low mortality rate, &1%.7 Complicated forms of ABAD often require more aggressive approaches. The recent evolution of therapeutic options has led to the availability of percutaneous catheter-based techniques of fenestration or stent-grafts15 as alternatives to surgical management. Actually, percutaneous procedures are preferred for treating uncomplicated patients16; for this specific cohort, a randomized, controlled trial of endovascular management versus medical management is ongoing.

Currently, surgery for ABAD is generally indicated for patients with persistent symptoms despite medical treatment, a rapidly expanding false lumen, impending or frank rupture, or major-organ malperfusion that cannot be resolved by percutaneous therapy.7,10,14,17

The results of surgery remain suboptimal in the current era, with reported in-hospital mortality rates of 25% to 50%.9 Single centers have described no surgical mortality in 34 consecutive patients10 or in specific series not including patients with preoperative thoracoabdominal malperfusion syndromes.11 The findings of a single center report on favorable patients cannot be compared with those of IRAD, wherein the overall surgical mortality was 29.3%. IRAD collects data on all patients treated by participating centers, wherein different approaches in diagnosis and management are expected and potential biases of patient selection in small series are minimized.

Surgical results for ABAD, similar to those for type A, are largely related to the preoperative conditions of the patients, which are also frequently the primary cause of postsurgical death10,11,18. In this cohort of patients, preoperative hemodynamic status was the primary factor in determining surgical outcome. Patients with severe hypotension or shock on admission and/or at surgery had the worst prognosis, with a mortality of 60% (P<0.0001). Conversely, normotension at surgery was associated with fewer adverse outcomes (P<0.002). We also noted that in evaluating different indications for surgery, only aortic rupture with shock yielded significant results in terms of operative mortality (Figure 1). This defines multiple subgroups of surgically treated ABAD patients who clearly cannot be considered in the same way.


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Bar graph showing the incidence of mortality in ABAD IRAD patients with different indications for surgical treatment.

In addition, the presence of radiating pain predicts a positive surgical outcome (P<0.05), perhaps in part due to a quicker diagnosis and specific treatment (mean time interval from symptom onset to diagnosis in patients with radiating pain was 61.9 hours versus 71.1 hours in those who did not have such pain, P<0.6, NS). In effect, in the group of patients who died, we also noted a more frequent atypical presentation characterized by less pain, less abrupt onset, less chest pain, more abdominal pain, less radiation and/or migration pain, and more ECG changes. All of these findings may have led to a delay in diagnosis, thereby postponing delivery of definitive therapy.

As previously shown for patients with type A dissections enrolled in IRAD,18 the mean interval time from onset of symptoms to surgery was longer for survivors compared with those who died (96 versus 41.3 hours; P<0.04). Accordingly, mortality was significantly higher in patients who underwent surgery within 48 hours (mortality rate with surgery <48 hours was 39.2% versus 18.2% at surgery >48 hours; P<0.05). We also noted that the median time interval between confirmed diagnosis and surgery was shorter in patients with a fatal outcome (24 versus 72 hours, P=0.06, NS). These data highlight the notion that presentation with hemodynamic instability leads to a faster diagnosis and, when possible, more rapid surgical treatment. However, in such urgent situations when patients arrive earlier at the operating room, there is a referral bias because these operations are being attempted in patients with a much greater preoperative, intraoperative, and postoperative risk of death.

Diagnosis and treatment decisions in ABAD are clearly related to comorbid conditions. For instance, >40% of these patients presented with ECG alterations, such as left ventricular hypertrophy with T wave negative, myocardial ischemia, and/or myocardial infarction, and almost 30% of this cohort were older than 70 years. In this last group, surgical mortality was 50% (P<0.008), and age >70 years remained an independent predictor of surgical mortality, even though it has been reported that visceral and/or renal malperfusion is less likely to occur in elderly compared with younger patients7. Higher mortality among the elderly is frequently due to factors associated with generalized arteriosclerosis, such as hypertension and diabetes, and to preoperative hypotension or shock, probably indicating either rupture or impending rupture.7,19,20 In the IRAD series, we noted that in 25% of patients, an aortic aneurysm was known, which likely also conferred a greater propensity for rupture. Interestingly, all 9 Marfan patients, typically younger, survived surgery (11.3%, P<0.06). Although neurological signs occurred in >10% of patients, surgical mortality was predicted only by extreme conditions, such as preoperative coma (P<0.02), which in many centers represents a contraindication to surgery.

For patients presenting with life-threatening complications, stent-grafting has been reported to have potential advantages over surgery.15,16,21 However, those studies included both complicated and uncomplicated patients and may have been limited by referral bias. Complications of stent implantation, such as occlusion of the left subclavian artery, inadequate device placement, and insufficient seal of the proximal endograft neck with type 1 endoleak, have been documented, with a significant incidence of surgical conversion or of long-term endovascular graft failure.22 Such complications can be difficult to treat through a percutaneous approach, leading to a more complex surgical intervention with higher risk than a primary surgical approach.23 Clearly, more studies will be needed to resolve this debate.

IRAD data also show that imaging variables are useful in predicting surgical outcomes. Periaortic hematoma is correlated with higher surgical death (P<0.02), whereas pleural effusion is not a predictor, often being due to a serous pleural reaction to the acute aortic event. Periaortic hematoma generally is associated with hypotension or shock and indicates a frank or contained rupture of the aorta in ABAD, a catastrophic complication that rapidly leads to death. In addition, partial aortic thrombosis of the false lumen was associated with higher operative mortality (P<0.03), in contrast to the presence of a widely patent false lumen. Although thrombosis of the false lumen can possibly lead to the stabilization of aortic diameter, it may also be correlated with a higher incidence of malperfusion. IRAD also verified that descending aortic diameter is predictive of surgical outcome. We observed that a diameter >6 cm is associated with a higher mortality rate (P<0.04). Larger aortas experience much higher wall stress and are more prone to rupture.24

The site of origin of ABAD at the level of the left subclavian artery is also associated with higher risks, probably because of the necessity of an extended procedure. In the IRAD experience, an open procedure was adopted in >80% of cases, and a partial or total arch was replaced in one quarter of patients. In this setting, adoption of the open technique permits avoidance of aortic clamping between the left common carotid artery and left subclavian artery, which is particularly unsafe in cases of fragile acute aortic dissected tissue. Also, hypothermic circulatory arrest may have been helpful in improving surgical results (P<0.07). In addition, a shorter hypothermic circulatory arrest time was correlated with outcome, with a mean of 37 minutes for survivors and 54 minutes for those who did not survive (P<0.001). Hypothermic cardiopulmonary bypass with circulatory arrest has also been reported to be an important adjunct for operations on the distal aortic arch, descending thoracic aorta, and thoracoabdominal aorta for preventing spinal cord injures and renal and visceral organ system failure.25 In type B IRAD surgical patients, cerebral perfusion showed a trend for improved outcome (P<0.17), even when used sparingly (17.1%). Utilization of antegrade cerebral perfusion from a left thoracotomy has not been widely adopted by the surgical community, but it seems safe and feasible in more complicated interventions.23

Similar to previous experience,10 operative risk for paraplegia was acceptable (4.5%) in IRAD and was not correlated with higher mortality, as opposed to new postoperative signs such as neurological deficits (P<0.02), coma (P<0.02), visceral ischemia/infarction (P<0.05), and acute renal failure (P<0.02). Most often, these appear as signs of preoperative, irreversible, ischemic end-organ insults and/or continued malperfusion. In fact, in patients who did not survive, the mean hospital stay was significantly shorter than in patients with a favorable outcome (2 versus 26 days; P<0.0001).

Study Limitations
IRAD is an observational study based on patients treated in tertiary referral centers, and therefore its findings may not necessarily be applicable to the total population. In-hospital death was the outcome parameter that was assessed in this registry analysis. Although assessment of mortality is necessary and important to patients, it is not sufficient for full evaluation of outcomes of patients with ABAD. Nonfatal adverse events, functional status, and resource use must also be taken into consideration. Further studies are needed to address the best therapeutic strategy for complicated ABAD, optimal medical and percutaneous therapies, and factors associated with optimal short- and long-term outcomes.

Conclusions
Complicated ABAD remains a challenging problem. In the centers participating in the IRAD, surgical treatment of distal aortic dissections was associated with a 29.3% hospital mortality. Similar to type A dissections, preoperative evaluation of ABAD patients permits an assessment of surgical risk. Moreover, different indications for surgery produce different operative results. Although the time interval between the onset of symptoms and therapy is a major factor in determining outcome, this notion is complicated by the observation that earlier surgery is attempted in patients with extreme conditions. The present study suggests that in ABAD patients who require surgery, use of an open procedure and reduced circulatory arrest time are correlated with better surgical outcomes. Aortic stent-graft implantation represents a promising alternative to conventional surgical repair, which needs to be evaluated in studies on long-term outcome.


*    Appendix
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The IRAD Investigators
Coprincipal 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.

Coinvestigators
Eduardo Bossone, MD, National Research Council, Lecce, Italy; Arturo Evangelista, MD, Hospital General Universitari Vall d’Hebron, Barcelona, Spain; Rosella Fattori, MD, University Hospital S. Orsola, Bologna, Italy; Dan Gilon, MD, Hadassah University Hospital, Jerusalem, Israel; Stuart Hutchison, MD, St. Michael’s Hospital, Toronto, Ontario, Canada; Alfredo Llovet, MD, Hospital Universitario 12 de Octubre, Madrid, Spain; Rajendra H. Mehta, MD, MS, University of Michigan, Ann Arbor, Mich; Truls Myrmel, MD, Tromsø University Hospital, Tromsø, Norway; Patrick O’Gara, 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, Robert-Bosch Krankenhaus, Stuttgart, Germany; Toru Suzuki, MD, University of Tokyo, Tokyo, Japan; Santi Trimarchi, MD, Policlinico San Donato, San Donato Milanese, Italy.


*    Acknowledgments
 
Sources of Funding

We acknowledge the University of Michigan Faculty Group Practice and the Varbedian Fund for Aortic Research for the support.

Disclosures

None.


*    Footnotes
 
Presented at the American Heart Association Scientific Sessions, Dallas, Tex, November 13–16, 2005.


*    References
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*References
 
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*Aortic Aneurysm