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Ann Thorac Surg 1999;67:1030-1037
© 1999 The Society of Thoracic Surgeons
a Department of Cardiothoracic Surgery, Boston Medical Center, Boston, Massachusetts, USA
Accepted for publication September 22, 1999.
Address reprint requests to Dr Shapira, Department of Cardiothoracic Surgery, Boston Medical Center, 88 E Newton St, Boston, MA 02118
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Abstract |
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 Top Abstract IntroductionPatients and methodsResultsCommentAcknowledgmentsReferences |
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Methods. One hundred eight consecutive patients undergoing 111 proximal aortic operations over 10 years were studied. The cohort was divided into two groups: early, 1987 to 1993 and late, 1994 to 1997.
Results. Baseline patients profiles, indications for operation (aneurysm, 66 patients; dissection, 45 patients), priority of the operation, and surgical procedures were comparable for both groups. Mortality and morbidity for the entire cohort were 13.5% (15 of 111) and 66% (73 of 111), respectively. Compared with the early group, the late group was characterized by significantly higher use of noninvasive diagnostic modalities (69% versus 10%), exclusive use of heparin-bonded circuits and collagen-impregnated grafts (100% versus 0% for both), use of antifibrinolytic agents (79% versus 8%), and the introduction of retrograde cerebral perfusion (43% versus 0%) (p < 0.00001 for all). These changes in practice were associated with a substantial decrease in operative mortality (26% [13 of 49] versus 3% [2 of 62], p = 0.001), overall morbidity (77% [38 of 49] versus 56% [35 of 62], p = 0.02), blood transfusions (55.6 ± 48 donor units versus 29.3 ± 35 donor units, p = 0.003), and a shorter hospital stay (21.6 ± 31 days versus 12.1 ± 15 days, p = 0.07). Average long-term follow-up for 99% (107 of 108) of patients was 29.6 ± 30 months (1 to 120 months). Ten-year actuarial survival was 57.3% ± 8% with 93% being in New York Heart Association functional class I or II.
Conclusions. Recent advances, particularly noninvasive diagnosis and improved operative management, have led to a substantial reduction in mortality and morbidity after proximal aortic operation. Improved short- and long-term outcomes were achieved both in acute dissection and aneurysm procedures, although patients remain at risk for long-term distal aortic complications.KEY WORDS: Proximal aorta, Diagnosis, Management, Surgery, Clinical Outcomes.
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Introduction |
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-amino caproic acid (Amicar) and aprotinin (Trasylol) [11]. These advances resulted in further reduction in operative mortality of 1.7% to 5% for aneurysm repair [12–16], but mortality remained high (20% to 27%) in acute dissection [17, 18]. The purpose of this study was to evaluate the impact of these changes on short- and long-term clinical outcomes of an unselected consecutive group of patients undergoing operation of the proximal aorta in a single tertiary care teaching institution over a 10-year period. |
Patients and methods |
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TopAbstractIntroductionPatients and methodsResultsCommentAcknowledgmentsReferences |
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Preoperative diagnosis
At the early phase of the study aortography was performed routinely in each patient for either acute dissection or aneurysms. More recently, contrast-enhanced computerized tomography of the chest and transesophageal echocardiography have become the diagnostic procedures of choice in acute dissection. Magnetic resonance imaging and magnetic resonance angiography are now frequently used as the sole diagnostic procedures in patients with chronic aneurysms in preparation for elective operations. Thus, aortography is reserved for those few patients in whom the diagnosis is uncertain, or the anatomy of the arch or other major branch vessels needs to be further clarified.
Operative management
Cardiopulmonary bypass
Operations were performed using cardiopulmonary bypass with femoral artery/bicaval cannulation. In the early period conventional cardiopulmonary bypass circuits were used. In 1994 we switched completely to "tip-to-tip" heparin-bonded cardiopulmonary bypass circuits (Duraflo II; Baxter, Irvine, CA). Full anticoagulation (3 mg/kg of heparin, target activated clotting time >480 seconds) was used with conventional circuits. Low anticoagulation (1 mg/kg of heparin, target activated clotting time >280 seconds) was used with heparin-bonded circuits, unless deep hypothermia and circulatory arrest were indicated. In the latter circumstances standard full systemic anticoagulation was used. Other major modifications in the conduct of cardiopulmonary bypass implemented in recent years include: (1) changing to near-normothermic bypass (34°C) versus moderate hypothermia (28 to 30°C), unless deep hypothermia and circulatory arrest were indicated; (2) switch from femoral arterial cannulation throughout the operation to antegrade perfusion through the graft once the distal anastomosis is completed; (3) liberal use of deep hypothermia and circulatory arrest; (4) introduction of retrograde cerebral perfusion as an adjunct to deep hypothermia and circulatory arrest (the technique was adopted from Ueda and colleagues [7]); and (5) routine use of -amino caproic acid (Amicar) or aprotinin (Trasylol) to reduce bleeding and blood product use [9, 10, 19]. Myocardial protection was achieved by intermittent antegrade and retrograde cold (4°C) blood cardioplegia enhanced with topical cooling.
Acute dissection
In all patients the segment of the proximal aorta containing the intimal tear was transected, the layers of the aortic wall were reapproximated, reinforced with two strips of Teflon felts both proximally and distally, and an interposition graft was implanted. The aortic valve was preserved in most cases by resuspension of the commissures. Aortic valve replacement or a total aortic root replacement were indicated only in a few patients with acute dissection. A major modification in the operative management of acute dissection implemented in recent years was the routine use of deep hypothermia and circulatory arrest in every case to afford an "open" distal anastomosis. This allowed direct inspection of the aortic arch in search of a second intimal tear and minimized the risk of iatrogenic injury to the aorta by the cross-clamp.
Aneurysm
The surgical technique selected for the specific patient was determined based on the surgical anatomy of the ascending aorta and the aortic valve. Interposition graft alone was used for isolated ascending aortic aneurysm without involvement of the sinuses of Valsalva. Interposition graft and aortic valve repair/replacement were selected for patients with aortic valve disease and separate ascending aortic aneurysm. In patients with Marfan syndrome or other patients with involvement of the sinuses of Valsalva the entire root was replaced. In the early phase a modified Bentall operation was performed in all of these patients [20]. The technique of coronary reimplantation was the "button" technique in most patients. The Cabrol technique was used in 2 patients [20]. More recently, aortic valve sparing procedures, as described by Yacoub [15] and David [16] and their colleagues, were performed in selected patients with aortic insufficiency secondary to annular ectasia and in whom the aortic valve was otherwise structurally normal. The "exclusion" technique was used for distal anastomosis. The distal aorta was completely transected and the graft was sutured to the distal aorta end-to-end.
Grafts
In the early phase albumin-soaked Dacron grafts (Cooly) were used. These were replaced by collagen-impregnated Dacron grafts (Hemashield; Meadox Medicals, Oakland, NJ) in the early 1990s. Cryopreserved allografts were used in selected patients.
Data collection
Hospital data
All clinical data were retrospectively collected and entered into a database. Data collected included (1) demographic information; (2) comorbid risk factors; (3) operative data; (4) postoperative complications (eg, mortality) and significant morbidity (reoperation for bleeding, mediastinal infection, pneumonia, respirator dependent > 72 hours, transient ischemic attack or cerebrovascular event, myocardial infarction [new Q wave, elevation of creatine kinase MB fraction 
50 U, new wall motion abnormality in echocardiogram], low cardiac output state [a newly placed intraaortic balloon pump or the use of inotropes for more than 24 hours to maintain a cardiac index > 2.0], and other major complications; (5) bleeding and transfusion requirements; and (6) total hospital and intensive care unit length of stay.
Long-term follow-up
All clinical records were reviewed. Direct telephone contact with the patient or family, and the primary care physician or the cardiologist was made in 99% of patients. Data obtained included survival, functional status and long-term medical management, readmissions and reinterventions, and any operation-related complications.
Statistical analysis
Statistical analysis was performed by the Department of Biostatistics at the Boston University School of Medicine. Data are expressed as mean ± standard deviation. Median and range values were added for selected variables. Statistical analysis was performed using SAS software, release 6.12 for Windows. Univariate analyses were carried out among 3 dependent (outcome) variables and 92 independent (predictor) variables. Two-tailed student’s t test was used to analyze continuous variables. Categorical data were analyzed using 
2 with Yate’s correction or Fisher’s exact test when appropriate. A p value of less than 0.05 was considered significant. Multivariate analyses were performed to identify independent predictors of adverse outcomes. Multiple logistic regression analyses were used for categorical outcome variables, and linear regression analyses for continuous variables. A stepwise backward selection method was used to select the variables in the models, with a significance level of 0.1 for entry into the model, and a significance level of 0.05 for staying in the model. The Kaplan-Meier method was used to analyze actuarial survival and postoperative events. The log rank test was used to compare survival curves with a p value of less than 0.05 considered significant.
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Results |
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TopAbstractIntroductionPatients and methodsResultsCommentAcknowledgmentsReferences |
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Operative data
Operative profiles are summarized in Table 2. The indication for operation was acute Stanford type A aortic dissection in 45 patients (40%) and chronic ascending/arch aortic aneurysm in 66 patients (60%). Aortic pathology included atherosclerosis (63 patients), non-Marfan cystic medial necrosis (35), Marfan disease (9), chronic dissection (2), and unknown (2 patients). In 59 patients (53%) the operation was nonelective and in 16 (14%) it was a reoperative procedure. Aortic pathology was similar between the study groups.
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Hospital outcomes
Hospital outcomes are summarized in Table 3. Hospital mortality and overall morbidity for the entire cohort were 13% and 66%, respectively. Respiratory complications were the most frequent, and 25% of patients required ventilatory support for more than 3 days. Nine percent of patients had a postoperative stroke. Reexploration for bleeding was performed in 17 patients (15%). Eighty-nine percent of patients required allogeneic blood transfusion of an average of 41 ± 43 donor units (0 to 213 donor units). Total hospital and intensive care unit length of stay were 16 ± 23 days and 8.1 ± 23 days, respectively.
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Univariate and multivariate analyses of three major hospital outcomes—mortality, postoperative stroke, and blood transfusion—were performed. Variables identified as predictors of hospital mortality in a univariate analysis include acute dissection and prolonged cardiopulmonary bypass time, whereas aortic valvar insufficiency, use of aprotinin, and heparin-bonded cardiopulmonary bypass circuits were associated with reduced mortality. However, in a multiple logistic regression analysis (Table 4 ) only prolonged cardiopulmonary bypass time remained an independent predictor of hospital mortality (odds ratio, 1.013; confidence interval [CI], 1.003 to 1.023; p = 0.02). Cardiopulmonary bypass time was longer in the early group, but the difference was not statistically significant (Table 2). In both groups cardiopulmonary bypass times were longer for patients undergoing arch repair (data not shown). However, the number of patients in the latter group (n = 14) was too small to allow a meaningful analysis. Patients requiring concomitant coronary artery bypass grafting did not have significantly longer cardiopulmonary bypass times, and mortality in this group was similar to the entire cohort (data not shown).
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The predictors of allogeneic blood transfusions in a univariate analysis included advanced age, female gender, small body surface area, acute dissection, nonelective procedure, the procedure interposition graft, lower systemic temperature during bypass, the use of circulatory arrest, and prolonged cardiopulmonary bypass time. In the univariate analysis, the use of heparin-bonded cardiopulmonary bypass circuits was the only factor associated with reduced blood transfusions. Independent predictors of increased allogeneic blood transfusions in multivariate logistic and linear regression analyses (Table 4) include advanced age (odds ratio, 1.078; CI, 1.015 to 1.144; p = 0.02), acute dissection as the indication for operation (odds ratio, 2.549; CI, 1.035 to 5.218; p = 0.01), the use of circulatory arrest (odds ratio, 3.359; CI, 1.925 to 11.342; p = 0.011), reoperation (odds ratio, 3.896; CI, 2.187 to 15.305; p = 0.002), and the use of conventional (non–heparin-bonded) cardiopulmonary bypass circuits (odds ratio, 3.431; CI, 3.024 to 6.473; p = 0.0009).
Long-term follow-up
Average long-term follow-up for 99% (107 of 108) of patients was 29.6 ± 30 months, range 1 to 120 months. Fourteen patients died during the follow-up period. Causes of late deaths included malignancy (4 patients), congestive heart failure (2), ruptured descending thoracic aortic aneurysm (2), cerebrovascular accident, pulmonary fibrosis, and ruptured abdominal aortic aneurysm (1 patient each). In 2 patients the cause of death is unknown. Actuarial survival (including hospital mortality) at 1, 5, and 10 years were 81 ± 3%, 57 ± 8%, and 57 ± 8%, respectively (Fig 1 ). At the time of follow-up 93% (73 of 78) of patients were in New York Heart Association functional class I or II—a significant improvement compared to the preoperative status where 77% of patients were in New York Heart Association functional class III or IV. By design the length of follow-up in the late group was much shorter. Therefore, survival curves were not compared between these two groups. We did compare the long-term survival of patients operated on for acute dissection to that of patients operated on for chronic aneurysm. Although 1-year survival of patient with chronic aneurysm was slightly better (85 ± 1% versus 75% ± 7%), 5- and 10-year survival rates were similar (Fig 2 ). The incidence of persistent false lumen in patients initially operated on for acute dissection was 61% (65% in the early group and 57% in the late group, p = not significant). Of note all three late deaths secondary to distal aortic pathology occurred in patients originally operated on for acute dissection. Two of these patients had documented persistent false lumen. The aneurysm size in these patients at the time of rupture was 4.8 cm and 5.2 cm.
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Comment |
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TopAbstractIntroductionPatients and methodsResultsCommentAcknowledgmentsReferences |
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Improvement was observed not only in operative mortality, but also in most major clinical end points. We observed marked reduction in stroke rate, the incidence of respiratory complications, the rate for reexploration for bleeding and allogeneic blood product use. Improvements in clinical outcomes resulted in shorter intensive care unit and hospital lengths of stay, which translated to tremendous cost savings. Undoubtedly, multiple factors account for these improved clinical outcomes. These include advances in diagnosis, major modifications in operative, and perioperative management as well as implementation of early extubation and "fast track" protocols (dictated by economic factors), and obviously increased surgeon and team experience.
Until the mid-1990s angiography has been considered as the gold standard for the diagnosis of acute and chronic aortic diseases. In addition to its inherent morbidity as an invasive procedure, it may lead to delay in therapy. Thus, noninvasive modalities, such as transesophageal echocardiogram, magnetic resonance imaging, and contrast-enhanced computed tomography, have emerged as the diagnostic procedures of choice [3, 4]. These procedures are noninvasive, much less time consuming, and are very accurate. The sensitivity of all three noninvasive modalities in acute dissection is similar in the range of 94% to 98% [3]. Magnetic resonance imaging is more specific (98%) compared to computerized tomography (87%) or transesophageal echocardiogram (77%), with the latter having more false positives [3]. Rizzo and colleagues [4] have clearly demonstrated that achieving rapid noninvasive diagnosis of aortic dissection and avoidance of routine angiography, improve survival by expediting surgical intervention and decreasing the risk of aortic rupture. We have observed one death related to procedural delay, and now routinely use transesophageal echocardiogram for the diagnosis of acute dissection, particularly in hemodynamically unstable patients. Magnetic resonance angiography has become our procedure of choice in stable patients and in patients scheduled for elective aneurysm operation. Aortography is reserved for those few patients in whom the diagnosis is uncertain, or the anatomy of the arch and other major branch vessels needs to be further clarified.
One of the major modifications in operative technique was the frequent use of deep hypothermia and circulatory arrest for arch repair or to perform an "open" distal anastomosis, particularly in acute dissection. The value and safety of this strategy have been shown by several investigators [5, 6]. Open distal anastomosis allows inspection of the arch in search for a primary or secondary intimal tear, and eliminates clamp-induced injuries. Whether use of the open distal anastomosis technique reduces the incidence of persistent false lumen in patients operated for acute dissection remains controversial. Ergin and colleagues [21] reported the lowest incidence of persistent false lumen (47%), which they attributed to the open technique. However, Barron and colleagues [18], using a very similar technique, reported an incidence of 72%. In this study the incidence of persistent false lumen in long-term follow-up was 61%.
Despite the increased use of deep hypothermia and circulatory arrest, postoperative stroke rate dropped from 12% in the early group to 6% in the late group. This did not reach statistical significance most likely because of the small number of patients in the two groups. Similar to many reports advanced age was a significant independent predictor of postoperative stroke [5, 6]. However, the use of circulatory arrest per se, or the circulatory arrest time were no longer predictors of stroke as previously reported by Svensson and colleagues [5] in a large series. This may be attributed to the protective effect of the retrograde cerebral perfusion technique. Favorable impact of retrograde cerebral perfusion with reduction of postoperative stroke rate was recently reported by Safi and colleagues [8].
Another important trend in recent years is the effort to preserve the native aortic valve whenever possible. This approach is widely accepted in acute dissection, where reconstruction of the aortic wall and resuspension of the aortic valve will restore aortic valve competence in most patients [22]. The management of patients with trileaflet aortic valve having severe aortic insufficiency secondary to annuloaortic ectasia (particularly Marfan) is still controversial. The traditional approach of total root replacement has been recently challenged by valve-sparing techniques described by Yacoub [15] and David [16] and their colleagues. Our experience with the latter techniques is limited to only 4 patients, but the short- and long-term reports recently reported by these investigators are very encouraging.
Several modifications in the operative management account for the decreased bleeding complications and reduced allogeneic blood product use. These include improved graft technology, the switch to exclusion type of distal anastomosis and the "button" technique for coronary reimplantation, the use of antifibrinolytic agents, and the introduction of heparin-bonded cardiopulmonary bypass circuits with reduced anticoagulation. The introduction of the collagen-impregnated Hemashield graft is undoubtedly an important component secondary to a significantly decreased pore size. The tube graft exclusion anastomoses and the button coronary reimplantation techniques advocated by Crawford and Crawford [23] and adopted by others, not only reduce bleeding complications, but also prevent late false aneurysm formation [12, 24].
The use of heparin-bonded cardiopulmonary circuits with reduced systemic anticoagulation has been shown to be effective in patients undergoing coronary artery bypass grafting and valve operation [9, 10]. We have used this strategy exclusively in all patients undergoing major aortic operation since 1994, including patients operated with deep hypothermia and circulatory arrest. This strategy proved to be very safe in the present study, and in a multivariate analysis use of heparin-bonded circuits was found to be a strong independent predictor of reduced blood transfusions.
Antifibrinolytic agents have been extensively used in recent years and have been shown to effectively reduce bleeding. We have predominantly used aminocaproic acid and modified the drug administration in patients with heparin-bonded circuits to prevent hypercoagulability [9]. Although we have used aprotinin in selected patients without noticeable adverse effects (such as stroke or renal failure), its use is still controversial, particularly in the setting of deep hypothermia and circulatory arrest [25].
The long-term survival in our study was overall similar to that reported in other series, although we did not observe the significant drop in survival 7 to 8 years after operation reported by some investigators [12, 15–18, 21, 24]. Although overall survival of patients undergoing operation for acute dissection was similar to that of patients operated for aneurysms, distal aortic pathology was more frequent in patients with acute dissection. Most likely this is related to both baseline abnormal aortic wall characteristics as well as persistent false lumen in many of these patients. Two of 3 patients who developed long-term distal aortic complications had persistent false lumen. Thus, future efforts should focus on methods aimed at reduction of the incidence of false lumen. Also, meticulous long-term follow-up is mandatory. The size criteria for reoperation is still controversial, but should probably be lower for patients originally operated on for acute dissection, particularly if persistent false lumen is documented. The quality of life in surviving patients is excellent with most patients being in functional class I and II at the time of follow-up.
The major limitations of the study are related to its retrospective nature with the two groups operated in sequence, rather than parallel, and the relatively small number of patients. However, the differences in outcomes between the groups were substantial, and therefore, we were able to show statistical significance in both univariate and multivariate analyses.
In summary, recent advances, particularly noninvasive diagnosis and improved operative management have led to a substantial reduction in mortality and morbidity after proximal aortic operation. Lower complication and allogeneic blood transfusion rates translated into reduced intensive care unit and hospital length of stay, and therefore, to reduced cost. Improved short- and long-term outcomes were achieved both in acute dissection and aneurysm operation, although patients remain at risk for long-term distal aortic complications.
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Acknowledgments |
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TopAbstractIntroductionPatients and methodsResultsCommentAcknowledgmentsReferences |
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TopAbstractIntroductionPatients and methodsResultsCommentAcknowledgmentsReferences |
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