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Ann Thorac Surg 2000;69:1755-1763
© 2000 The Society of Thoracic Surgeons
a Department of Cardiothoracic Surgery, The Mount Sinai Medical Center, New York, New York, USA
b Department of Biomathematics, The Mount Sinai Medical Center, New York, New York, USA
Address reprint requests to Dr Griepp, Department of Cardiothoracic Surgery, The Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1028, New York, NY 10029
e-mail: marekehrlich{at}hotmail.com
Presented at the Forty-sixth Annual Meeting of the Southern Thoracic Surgery Association, San Juan, Puerto Rico, Nov 4–6, 1999.
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Abstract |
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Methods. All 443 patients (300 male, median age 63) undergoing replacement of the ascending aorta with an open distal anastomosis between 1986 and 1998 were included in the analysis. The ascending aorta alone was replaced in 190 (42.9%); 253 (57.1%) also had proximal arch replacement. Median hypothermic circulatory arrest (HCA) time was 25 minutes (range 12 to 68). Either death or permanent neurological dysfunction were considered adverse outcome (AO).
Results. Adverse outcome occurred in 11.5% (51 of 443) of patients overall: in 7.4% of elective (20 of 269) or urgent (4 of 54) operations, but in 17% (19 of 113) of emergencies. Multivariate analysis of the group as a whole revealed that significant (p < 0.05) independent preoperative predictors of AO were age greater than 60 [odds ratio (OR) 2.2], hemodynamic instability (OR 2.7), and dissection (OR 1.9). For the 435 operative survivors, procedural variables predictive of AO were contained rupture (OR 2.8) and HCA time (OR 1.03/min). When only the 271 elective patients were analyzed separately, the need for a concomitant procedure (p = 0.009, OR 3.6) and HCA time (p = 0.002, OR 1.06/min) were the only predictors of AO in multivariate analysis. Transient neurological dysfunction (TND) occurred in 86 of 392 patients (22%). Significant predictors of TND for all patients without AO were age (OR 1.06/y), HCA time (OR 1.04/min), coronary artery disease (OR 2.2), hemodynamic instability (OR 3.4), and acute operation (OR 2.2). Survival of discharged patients was 93% at 1 year and 83% at 5 years.
Conclusions. Early elective operation and shorter HCA time during ascending aorta/hemiarch surgery will reduce both AO and TND.
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Introduction |
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TopAbstractIntroductionPatients and methodsResultsCommentReferences |
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The current study was undertaken to examine both preoperative and procedural predictors of adverse outcome after operations on the ascending aorta with an open distal anastomosis during a period of HCA. We defined adverse outcome as either death or permanent neurological disability, since a successful operation should result not only in survival, but a good quality of life. For most patients, the recitation of a series of separate estimates of the risk of various complications and of mortality is relatively meaningless: what they want to know are the odds that they will emerge from the operation more or less as they were before, but without aneurysm-related symptoms or the threat of imminent aortic rupture.
We also examined factors affecting the incidence of temporary neurological dysfunction because this assessment seems to reflect the adequacy of cerebral protection, and therefore can help in determining how further to improve cerebral recovery following aortic surgery [5]. In addition, recent evidence has suggested that the occurrence of this syndrome is frequently associated with long-lasting albeit subtle cognitive impairment [4].
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Patients and methods |
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TopAbstractIntroductionPatients and methodsResultsCommentReferences |
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There were 300 men and 143 women whose ages ranged from 8 to 88 years (mean 59 ± 15 years); 244 (55.1%) were older than 60 years at the time of surgery. Of the entire cohort, 271 patients (61.2%) were operated on electively, 12.6% urgently (within 72 hours of admission), and 26.2% on an emergent basis (within 24 hours of admission). A total of 211 patients (47.6%) had type A aortic dissections (121 acute and 90 chronic), 143 had degenerative aortic disease, and 47 had atherosclerotic aortas. Thirty-four patients in this series had Marfan’s syndrome. Eight patients had miscellaneous other etiologies such as mycotic aneurysms.
As seen in Table 1, a history of hypertension was the most common preoperative finding, although there was also a relatively high proportion of patients undergoing reoperation and experiencing rupture. If one compares patients with either acute or chronic dissection with patients with degenerative or atherosclerotic aneurysms, it is apparent not only that urgent and emergent operation, rupture, and hemodynamic compromise were more frequently seen among patients with dissection (all p = 0.001), largely because of the inclusion of patients with acute dissections, but also that patients with dissection were older (p = 0.09), more often had a history of hypertension (p = 0.001), and were more likely to have had previous operations (p = 0.001). Interestingly, no difference was found in the incidence of dissection and nondissecting aneurysm in patients with Marfan’s syndrome.
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Operative procedures
As outlined in Table 2, 190 patients had only ascending aorta replacement; 253 (57.1%) had hemiarch replacement. The aortic valve was replaced with a mechanical one in 225 patients (50.8%); a biological valve was implanted in 70 patients (15.8%), and the aortic valve was untouched in 148 patients (33.4%). In more than half of all 443 patients (63.5%), an aortic valve-ascending aorta conduit was implanted utilizing some variant of the Bentall procedure. The button-Bentall was the most common way of implanting the coronary arteries, followed by the Cabrol technique and the classic Bentall. Fourteen patients had aortic valve replacement with a separate ascending aorta conduit (Wheat procedure).
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Table 2 shows other important intraoperative variables. Median circulatory arrest time (HCA) in this series was 25 minutes (range, 12 to 68). Circulatory arrest time was kept below 30 minutes in 68.9% of all patients, and only 25 patients had HCA intervals exceeding 50 minutes.
Definitions of adverse outcome and neurological complications
Adverse outcome was defined as intraoperative or hospital death, or the occurrence of permanent neurological injury. The presence of neurological dysfunction at the time of discharge from the hospital, whether focal injury (stroke) or global (coma), was considered permanent neurological injury.
Transient neurological dysfunction (TND), which could only be assessed in operative survivors without permanent neurological dysfunction, was defined as the occurrence of prolonged postoperative confusion, agitation, or transient delirium. Since 1993, the severity of TND has been graded on a five-point scale, but since this more detailed assessment was not available for all patients, only the presence or absence of TND was scored. Computed tomography, when performed on patients with temporary dysfunction, was usually normal.
Statistical methods
Initially, all patients were treated as a single group, but subsequent analysis indicated that patients with acute dissection differed in significant ways from those with chronic dissection and nondissecting aneurysms, and that these latter groups also differed from one another. Analysis for risk factors was therefore carried out not only for the group as a whole, but separately for patients with acute dissection and for patients with either chronic dissection or chronic nondissecting aneurysms; some comparison of patients before and after 1993, when a more detailed assessment of occurrence of TND was begun, was also carried out. All patients were included in the analysis of preoperative factors impacting on adverse outcome; patients who died in the operating room were excluded from analysis of intraoperative variables, and patients with adverse outcome were excluded from the analysis of transient neurological dysfunction. In addition, an analysis of likelihood of adverse outcome following elective surgery was also carried out.
All putative factors were analyzed initially by chi-square or Kruskal-Wallis tests, as appropriate. Each univariate analysis was followed by stepwise logistic regression to determine independent risk factors. A p value less than 0.05 was considered significant.
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Results |
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Univariate analysis of the group as a whole revealed a number of preoperative, intraoperative, and immediate postoperative factors which were associated with adverse outcome (Tables 3A and 3B). The preoperative risk factors were: age greater than 60 years, hemodynamic compromise, emergent operation, acute dissection, and rupture. If one compares patients with acute or chronic dissection and those without dissection, it is apparent that the distribution of age was significantly different: There was a preponderance of elderly patients with acute and especially with chronic dissections (Table 1). There were also significant differences between etiological groups with regard to a history of hypertension and coronary artery disease, and in the incidence of reoperation. Not surprisingly, comparison of acute and chronic dissection with nondissecting aneurysms also revealed that significantly more patients with acute dissection had emergency operations, hemodynamic compromise preoperatively, and evidence of rupture intraoperatively.
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In univariate analysis of the group as a whole, the occurrence of any postoperative complication also increased the chance of adverse outcome: infection, renal failure, bleeding (requiring reoperation for hemostasis), cardiac problems, or respiratory compromise (prolonged intubation or tracheostomy; Table 3B). With the exception of those related to the heart, all postoperative complications occurred in a significantly higher percentage of patients with acute dissection (p = 0.001) and also tended to occur more frequently in patients with chronic dissection than in those with nondissecting aneurysms.
Multivariate analysis of the group as a whole revealed that statistically significant independent preoperative predictors of adverse outcome were age greater than 60, hemodynamic instability, and presence of dissection (Table 4A). For the 435 operative survivors, additional procedural variables predictive of adverse outcome were contained rupture and HCA duration (Table 4B).
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The 271 elective cases were then considered separately to determine which variables were associated with adverse outcome in this group of patients, in whom accurate assessment of operative risk is most relevant. Univariate assessment revealed a history of coronary artery disease (p = 0.03), etiology of the aneurysm (p = 0.01), need for a concomitant procedure (p = 0.001), coronary artery bypass surgery (p = 0.002), cerebral ischemic time (p = 0.0001), duration of cardiopulmonary bypass (p = 0.02), myocardial ischemic time (p = 0.03), and presence of any complication (p = 0.001) to be associated with adverse outcome. As might have been expected from the considerable overlap with the group comprising all chronic dissections and nondissecting aneurysms, multivariate analysis of all elective patients revealed three risk factors for adverse outcome: performance of a concomitant procedure (p = 0.009, OR 3.6), duration of cerebral ischemia (p = 0.002, OR 1.06/minute), and occurrence of any postoperative complication.
Transient neurological dysfunction
Transient neurological dysfunction, which was evaluated only in patients surviving operation without permanent neurological dysfunction, occurred in 86 of 392 patients (22%). TND occurred in 37% of patients with acute dissection, 25% of patients with chronic dissection, and 14% of patients with nondissecting aneurysms, p = 0.001. Since 1993, when a graded scale of symptoms was introduced and encouraged more careful assessment, 27% of 296 patients were identified as having TND, compared with 12% in the earlier interval, p = 0.001.
Univariate analysis showed that some of the same preoperative factors which were important contributors to adverse outcome were also implicated in the occurrence of TND, as shown in Table 5A: age, etiology, hemodynamic compromise, urgency of operation, and presence of acute dissection. In addition, the presence of coronary artery disease was significant: 41% of patients with a history of coronary artery disease and 42% with concomitant coronary artery bypass operation experienced TND. In this regard, it should be noted that the incidence of coronary artery disease was significantly higher in patients with chronic dissection (28%) than in the other groups.
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When risk factors for TND were considered only in the 292 patients with chronic dissections or aneurysms, a number of preoperative, intraoperative, and immediate postoperative factors were significant in univariate analysis. In addition to age and a history of coronary artery disease (both p = 0.001), a history of hypertension (p = 0.04) or of diabetes (p = 0.01) was an adverse risk factor, but the presence of Marfan’s syndrome significantly lowered the risk of TND (p = 0.03). Intraoperative factors associated with a high risk of TND in patients with chronic lesions included not only cerebral ischemic time (p = 0.001) but also duration of cardiopulmonary bypass (p = 0.02), duration of myocardial ischemia (p = 0.06), and the use of RCP (p = 0.04). Other factors associated with higher risk of TND in this subgroup were hemiarch rather than ascending aorta repair (p = 0.002), use of a biological valve (p = 0.001), and coronary artery bypass grafting (p = 0.001). The occurrence of any postoperative complications was highly correlated with TND (p = 0.001). Especially renal, respiratory, or infectious complications (all p = 0.001), but also cardiac complications (p = 0.01) and bleeding (p = 0.03) were associated with a high incidence of TND; it is admittedly more difficult to evaluate TND in the presence of complications which may require additional sedation for their treatment.
Significant predictors of TND in multivariate analysis of the group as a whole were age, coronary artery disease, hemodynamic instability, acute operation, and HCA duration (Table 6). When only patients with chronic dissections or aneurysms were considered, factors predicting TND in multivariate analysis were age (p = 0.002, OR 1.07/year), coronary artery bypass grafting (p = 0.006, OR 3.1), HCA duration (p = 0.02, OR 1.05/minute), and the presence of any postoperative complication (p = 0.0001, OR 6.8).
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Comment |
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TopAbstractIntroductionPatients and methodsResultsCommentReferences |
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We also wanted to reexamine the syndrome we have termed transient neurological dysfunction because previous studies have consistently shown TND to correlate with duration of cerebral ischemia, in contrast with permanent neurological injury, which is predominantly focal, and for which prolonged HCA has not invariably emerged as a risk factor [5]. In addition to being a reflection of suboptimal cerebral protection, recent evidence has also suggested that TND seems to be a marker of long-lasting but subtle cognitive impairment [4]. Measures aimed at reducing the incidence of TND should therefore contribute toward improving cerebral protection and outcome following ascending aorta/aortic arch operations.
The finding that advanced age is a risk factor for both adverse outcome and transient neurological dysfunction is not unexpected, and is in accord with our own earlier findings and the observations of others [4, 5, 15, 16]. Similarly, the idea that hemodynamic instability, rupture, emergency operation, and the presence of acute dissection increase the risk of surgery on the ascending aorta and aortic arch is also not surprising in light of earlier studies and common sense [17]. The absence of Marfan’s syndrome as a risk factor for adverse outcome is symbolic of the success which has been achieved in a particular group of high-risk patients by early elective intervention, reducing the need for emergency operations with their associated higher mortality and morbidity.
We are somewhat surprised that duration of HCA emerged in this study as a risk factor for adverse outcome as well as for transient neurological dysfunction. Our previous studies, as well as studies by others in which smaller numbers of patients were surveyed, did not identify duration of HCA as a risk factor for stroke: We attributed this to the notion that stroke is predominantly embolic in origin [18]. The fact that we see an impact of prolonged HCA on the incidence of adverse outcome in this study may be a result of increased statistical power derived from combining death and permanent neurological dysfunction as adverse outcome, and of having examined a larger number of patients: others have previously documented a relationship of prolonged HCA and HCA/RCP with both mortality and stroke [10, 16, 19]. The identification of HCA duration as a risk factor for adverse outcome in this series—characterized by thorough cooling to low temperatures and a mean interval of cerebral ischemia well below the consensus estimate of a safe period of circulatory arrest—underscores the continuing need to reduce HCA duration.
The idea that use of RCP can reduce the morbidity and mortality of these operations is not borne out by our data, in which RCP was used in 28 admittedly high-risk patients without evidence of improved outcome. Although several authors have reported excellent results using RCP, comparisons have usually been made to historical controls, and the contribution of other factors to improved results with ascending aorta/aortic arch surgery in recent years has not been acknowledged [9, 13, 20–22]. Some reports have documented that prolonged RCP is a risk factor for stroke and mortality in much the same way as prolonged HCA [19]. Other recent experimental and clinical studies have cast doubt on the ability of RCP to provide meaningful metabolic sustenance even at deeply hypothermic temperatures, leading to the conclusion that the major benefit of RCP is to assure maintenance of deep hypothermia during arrest of antegrade circulation [23, 24].
In addition to its contribution to adverse outcome, the duration of HCA is a concern because of its unquestionably strong impact on the occurrence of transient neurological dysfunction. A recent study documented that TND was much more prevalent among patients with persistent loss of cognitive function on psychometric testing 6 weeks after surgery than among patients with prompt recovery of test scores, suggesting that TND may not be entirely a transient phenomenon, but may be a marker for long-lasting cognitive deficits [4, 25]. Since formal psychometric testing is an expensive and cumbersome tool for assessing the adequacy of cerebral protection during aortic surgery, we urge use of the relatively simple clinical evaluation of TND in the immediate postoperative period as a way of comparing the efficacy of different protocols for cerebral protection.
The emergence of coronary artery disease as an independent risk factor for the occurrence of TND is interesting. We speculate that the presence of coronary artery disease may be an indication of cerebrovascular atherosclerosis in these patients, which puts them at higher risk of cerebral dysfunction postoperatively. It should be noted that more than half of the patients with chronic dissection in this series were undergoing reoperation, often after coronary artery bypass grafting, reinforcing the need to avoid clamp injury during coronary artery procedures to avert the possibility of iatrogenic dissection in these high-risk patients.
Overall, however, the role of prolonged HCA has far less of an impact on adverse outcome and on the occurrence of TND than the need for emergency surgery for acute dissection or rupture. The results of this study reinforce dramatically the notion that elective operation is far safer than emergency surgery on the ascending aorta/proximal aortic arch, and support the idea that elective replacement of the ascending aorta should be undertaken early in patients at risk for rupture or dissection. Earlier elective operation would also help reduce the contribution of age to the risk both of adverse outcome and of TND. Our relatively low incidence of adverse outcome in elective operations encourages this approach, and a recent series of ascending aortic operations suggests that mortality and stroke can each be reduced to below 2% in elective cases [26].
A rational approach to advising patients with chronic aneurysms is to try to balance the likelihood of rupture against the risk of operative intervention, bearing in mind that most patients who experience rupture do not reach a suitable hospital in time to undergo emergency operation. On the basis of data gathered from a large number of patients with chronic ascending aortic aneurysms whom we are following, we estimate that the risk of rupture of an aneurysm with a diameter of 5 cm is 5% to 7% per year; the risk increases to 10% to 15% per year with a 6 cm aneurysm. We therefore currently recommend that patients with few risk factors associated with adverse outcome—younger patients without coronary artery disease, with an uncomplicated lesion likely to require a relative short duration of HCA—undergo elective resection of an ascending aortic aneurysm at a diameter of 5 cm. Patients with a higher operative risk—older patients requiring concomitant procedures and with more complex or extensive lesions—should probably be advised to undergo elective ascending aortic aneurysm repair at a diameter of 6 cm.
In future, we will attempt to construct a more individualized estimate of the risk of adverse outcome based on the results of the multivariate analyses of the patients in this series, relying especially on those risk factors we have identified as important in patients operated on electively, using the characteristics of the aortic lesion to estimate the likely duration of cerebral ischemia, and making an educated guess as to whether or not the patient will require a concomitant procedure. For example, we can use Figure 2 to estimate that the risk of AO following a straightforward uncomplicated elective ascending aneurysm resection would be only 6% if no concomitant procedure were required, versus 18% if coronary artery bypass grafting, mitral valve replacement, or other adjunctive procedure were necessary, whereas a more complex operative repair necessitating a longer cerebral ischemic time would entail a risk of AO of 10% without, and 25% with a concomitant procedure. It is our hope that more refined understanding of operative risk will lead to earlier elective intervention in suitable patients, with fewer emergency operations and, therefore, improved outcomes following resection of ascending aortic aneurysms.
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