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J Thorac Cardiovasc Surg 1994;107:1323-1333
© 1994 Mosby, Inc.
SURGERY FOR ACQUIRED HEART DISEASE |
New York, N.Y.
From the Departments of Cardiothoracic Surgery and of Biomathematics, The Mount Sinai Medical Center, New York, NY.
Address for reprints: Otto E. Dapunt, MD, The Mount Sinai Medical Center, Department of Cardiothoracic Surgery, Box 1028, One Gustave L. Levy Place, New York, NY 10029-6574.
Abstract
Because improved understanding of the natural history of thoracic aneurysms would enhance our ability to determine in which cases the risk of surgical treatment is justified, the rate of enlargement of thoracic aneurysms and thoracoabdominal aneurysms was studied in 67 patients by means of serial computer-generated three-dimensional reconstructions of computed tomographic scans. Patients were followed for a mean of 1.5 ± 0.15 years (0.2 to 5.35 years) with an average interval between examinations of 0.9 ± 0.1 year (0.2 to 5.0 years). Thirty-nine patients continue to be followed; 7 were lost to follow-up; 14 died during follow-up (4 after aneurysm rupture), and 10 underwent an operation. Indications for operation included the presence of pain, an absolute aortic diameter larger than 8 cm, an increase in aortic diameter of more than 1 cm per year, or marked irregularity of aneurysm contour. Aortic diameter and volume data were generated from the aortic silhouette obtained by tracing each computed tomographic slice with a translucent digitizing tablet. Estimated change in aortic diameter after 1 year was 0.43 cm; estimated change in aortic volume was 88.1 ml. The impact of possible risk factors on the enlargement of aneurysms was examined by analysis of variance (p < 0.05). A significantly higher rate of aneurysm expansion was found in patients with a larger aortic diameter (>5 cm) at diagnosis (change in diameter = 0.17 cm versus 0.79 cm; change in volume = 40 ml versus 141.8 ml), and in smokers (change in diameter = 0.35 cm versus 0.70 cm; change in volume = 78.3 ml versus 120.8 ml). Changes in diameter and volume for aneurysms of different initial diameters and volumes was predicted by exponential regression by the equations: change in diameter = 0.0167 (initial aortic diameter) 2.1; change in volume = 0.0356 (initial aortic volume) 1.322. No correlation was noted between the rate of enlargement and age, sex, or the presence of dissection. A history of hypertension correlated with a greater aortic diameter at diagnosis but did not significantly affect the rate of enlargement. The rate of aneurysm enlargement for patients who underwent operation (change in diameter = 1.11 cm; change in volume = 178 ml) or had rupture of the aneurysm (change in diameter = 0.7 cm; change in volume = 124 ml) was compared with those without operation or rupture (change in diameter = 0.28 cm; change in volume = 57 ml) by one-way analysis of variance: all parameters were significantly greater (p < 0.05) in patients requiring operation and those in whom rupture occurred. By allowing more complete surveillance of aneurysm behavior, use of three-dimensional reconstructions of computed tomographic scans enables recognition of potentially threatening patterns of aneurysm progression and thereby permits further refinement of operative indications for thoracic and thoracoabdominal aneurysms. (J THORACCARDIOVASCSURG1994;107:1323-33)
Surgery for thoracic aortic aneurysms, especially those of the descending thoracic aorta, continues to have both a high operative mortality and the potential for serious morbidity, the risk of paraplegia being as high as 38% depending on the extent of aneurysmal disease. 
1 An improved understanding of the natural history of thoracic aneurysms would enhance our ability to determine in which cases the risk of operation is justified.
Virtually all of what is known concerning the natural history of aneurysms and the risk factors associated with rupture has come from studies of abdominal aneurysm behavior.
In 1966 Szilagyi and associates 2 retrospectively analyzed 223 cases in which aneurysms were not operated on. Five-year survival for the patients with large aneurysms (>6 cm) was less than 10%, whereas 5-year survival was almost 50% in patients with smaller aneurysms (<6 cm). The risk of rupture over a 10-year period was 20% for small aneurysms but twice as high (43%) for larger aneurysms.
Bernstein and associates 3 were the first to perform serial studies of patients with abdominal aneurysms by using ultrasound. Average growth rate was 0.4 cm per year with considerable variability between individuals. In a later study, these authors reported on 99 patients with an average follow-up of 2.4 years. 4 Operation was advised if symptoms developed or if the aneurysm exceeded 6 cm in diameter. Using this approach, the authors had only a 3% rate of unexpected rupture: they emphasized the need for careful serial follow-up of the patients to keep the rate of unexpected aneurysm rupture to a minimum when using relatively conservative guidelines for operative intervention.
By means of sophisticated multivariate analysis and use of actuarial techniques, Cronenwett and coworkers 5 were able to construct a predictive table of the relative risk of rupture of abdominal aneurysms over a 5-year time span. Risk factors found to correlate significantly with rupture included diastolic blood pressure greater than 100 mm Hg, initial anteroposterior diameter greater than 5 cm, and evidence of chronic obstructive pulmonary disease (forced expiratory volume in 1 second 50% of predicted normal values). In a patient with all three risk factors, the likelihood of rupture was estimated to be as high as 98% after 3 years, in comparison with 0% risk of rupture in a patient without any of these factors.
More recently, Guirguis and Barber 6 undertook a prospective analysis of 300 consecutive patients with abdominal aneurysms who were initially treated non operatively. The mean initial aneurysm diameter was 4.1 cm. Among the 208 patients who had more than one noninvasive measurement of the aneurysm, the median increase in diameter was 0.3 cm per year: it ranged from 0.2 cm per year in patients with aneurysms smaller than 4 cm, to 0.4 cm per year in patients with aneurysms from 5 to 6 cm, and 0.8 cm per year in patients with aneurysms larger than 6 cm in diameter. The 6-year cumulative risk of rupture in patients with aneurysm diameter smaller than 4 cm was 1%; in aneurysms between 4.0 and 4.9 cm it was 2%. In those patients with aneurysm diameter larger than 5 cm, however, the 6-year cumulative risk of rupture was 20%, confirming the influence of aneurysm size on the probability of spontaneous rupture.
In contrast with the research on abdominal aneurysms, the few studies dealing with the natural history of thoracic aortic aneurysms derive from either autopsy or retrospective analyses, and most were initiated before the widespread availability of modern noninvasive technologies for serial assessment of aneurysm enlargement. 7-10 Although the prospective studies of abdominal aortic aneurysms and the retrospective studies of thoracic aneurysms have been helpful in identifying factors relating to risk of rupture and in developing general guidelines for elective surgery, they have not provided a sufficiently detailed knowledge of the patterns of thoracic aneurysm enlargement or the necessary understanding of the critical sequence of events leading to rupture that would allow accurate prognostication in individual cases.
It is for this reason that we have undertaken to study the usual pattern of aneurysm progression in patients being observed with descending thoracic and thoracoabdominal aortic aneurysms. Using data gathered from computer generated three-dimensional reconstructions of the aorta from serial sections of computed tomographic (CT) scans, we have correlated the rate of enlargement of aneurysms with various suspected risk factors for rupture. We have also demonstrated the value of this three-dimensional computer reconstruction technique in advancing our understanding of the natural history of thoracic aortic aneurysms and in observing patients with these difficult lesions.
PATIENTS AND METHODS
For the purpose of this study, the aorta was considered ectatic or aneurysmal if it had reached a maximal diameter of 3.5 cm or more or if it measured twice the diameter of the adjacent normal aorta. Sixty-seven patients with thoracic aortic aneurysms who did not meet our criteria for elective operation at initial evaluation, and who had at least two CT studies of the aorta, were studied to determine the rate of enlargement of the descending thoracic aorta and aortic arch. The study comprised 24 women and 43 men. Mean age was 65.1 ± 13 years (29 to 82 years). Seventeen patients had aneurysms limited to the descending thoracic aorta; in 17 there was chronic type B dissection; 22 had both descending and ascending aortic lesions; 7 had thoracoabdominal aneurysms, and 4 had involvement of the distal aortic arch and the proximal descending thoracic aorta. Patients with lesions limited to the ascending aorta were not included in the study.
Patients were followed up by clinical examination and CT scans of the aorta at regular 6- or 12-month intervals. Mean follow-up time was 1.5 ± 0.15 years (0.2 to 5.35 years). The mean interval between examinations was 0.9 ± 0.1 years (0.2 to 5.0 years). Indications for operative treatment included (1) the presence of pain as a sign of rapid expansion or impending rupture, (2) an absolute aortic diameter of more than 8 cm, (3) an increase in diameter of more than 1 cm per year, and (4) marked irregularity of aneurysm contour suggestive of localized wall weakness.
Thirty-nine patients continue to be followed; seven have been lost to follow-up, and 10 underwent an operation, having met one or more of the operative criteria outlined earlier. Of the patients who underwent operation after entry into the study, five had begun having pain; in five the aneurysm had expanded beyond 8 cm in diameter; in six the growth rate exceeded 1 cm per year; and ominous irregularities of contour were noted in two. Only one of the patients who ultimately underwent an operation had an aneurysm diameter less than 4 cm at the onset of the study: because this patient's aneurysm was primarily in the arch, where we cannot measure diameters reliably, its rapid expansion was reflected in volume data. Data collected after the operation were not included in the study.
Fourteen patients died during follow-up. In four cases death was caused by aneurysm rupture; four patients died suddenly for unexplained reasons; three patients died after an elective aneurysm operation; and three deaths were attributable to causes unrelated to the aneurysm. In none of the patients whose aneurysm ruptured was the diameter less than 5 cm at the onset of the study.
Three-dimensional reconstructions of the aorta
A computer program was developed that allows three-dimensional reconstruction of the aorta from serial sections of CT scans. Data are obtained by tracing the outline of the aneurysm from each CT slice by means of a translucent digitizing tablet and a digitizing puck.
As seen in Fig. 1, the computer program permits the following: (1) A three-dimensional reconstruction of the aorta as a series of stacked cylinders that can be viewed from any angle desired (usually a left anterior oblique projection); (2) determination of the diameter of each aortic slice; (3) portrayal of the four different aortic segments in different colors (ascending in red, arch in black, descending in blue, abdominal in green); (4) an indication of the largest diameter in each segment; (5) the volume of each segment, calculated by multiplying the area of each slice by its height (usually 1 cm) and summing the numbers of slices per segment; (6) calculation of the total volume of the aorta; (7) determination of the tortuosity index, a ratio of the measured length of the descending aorta to its theoretical height.
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In certain cases it is difficult to define precisely the borders of each aortic segment: this is particularly true in the region of the left ventricular outflow tract–ascending aorta junction, particularly if the aortic valve anulus is not calcified. A similar problem exists in the aortic arch. In contrast, the descending thoracic aortic segment is clearly demarcated by the underside of the arch cranially and the crura of the diaphragm caudally.
For the reasons described, diameter data were analyzed only for the descending thoracic aorta. For calculation of aortic volume expansion, however, arch volumes were included. Volume increase was studied in 54 patients: volume calculations for the remaining 13 patients, who did not have at least two complete CT studies of the descending thoracic aorta and aortic arch, were excluded.
Statistical analysis
Data gathered from office records and three-dimensional studies were entered into a standard spreadsheet program. The change in diameter and volume over time was estimated by linear regression analysis. Exponential regression analysis was used to predict aneurysm expansion at a given initial diameter or volume. The impact of six risk factors believed to be associated with aneurysm enlargement was examined by one-way and multifactorial analysis of variance. For this analysis, data were expressed as yearly rates regardless of the interval between serial examinations.
Three-year survival estimates were calculated by life-table analysis (Kaplan-Meier). Log-rank and Wilcoxon tests were used to compare survival of patients with and without those risk factors believed to be associated with aneurysm enlargement.
RESULTS
The change in maximal diameter and in volume of both the descending thoracic aorta and aortic arch with time are shown in Figs. 2 and 3. After 1 year, estimated change in maximal diameter was 0.43 cm, and estimated change in volume was 88.1 ml.
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Table I).
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Table II depicts the averages of various measurements in the three outcome groups: those patients whose aneurysms ruptured (including four who died suddenly without an alternative explanation), those who underwent operation, and those without operation or rupture. Patients whose aneurysm ultimately ruptured or who underwent operation started with higher initial diameters, had higher final diameters at the end of follow-up, and showed accelerated aneurysm expansion. All parameters of aneurysm size and growth were significantly greater in the patients whose aneurysm ruptured or who underwent operation than in the control subjects (one-way analysis of variance, p < 0.05).
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(Table III).
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Available information concerning the natural history of abdominal aortic aneurysms reveals that the rate of enlargement ranges from 0.22 to 0.57 cm per year. 2-6,11-14. It has clearly been shown that a larger aneurysm diameter correlates with a higher rate of expansion, a greater likelihood of rupture, and a shortened survival. 2,5 Nevertheless, it has also been ascertained that even relatively small aneurysms carry a significant risk of rupture and death. Because elective operations for abdominal aneurysms can be carried out with acceptably low mortality and morbidity, there is little disagreement concerning the advisability of early elective operation for even small abdominal aneurysms.
In contrast with the abundant information about abdominal aortic aneurysms, only a few reports of the natural history of thoracic aortic aneurysms have been published, and most of them are retrospective analyses. McNamara and Pressler 8 examined 22 patients with nondissecting aneurysms of the thoracic aorta in whom 5-year survival was only 15%. More than 50% of the deaths were due to aneurysm rupture, and all but one of the ruptured aneurysms had diameters in excess of 10 cm.
Another series of patients was collected retrospectively by Crawford and DeNatale 15 in 1986: they studied the outcome of 94 patients with thoracoabdominal aortic aneurysms who had not been treated surgically for a variety of reasons. Although a few of the patients had been followed for longer periods, most had been observed for 5 years or less. Seventy-five of these patients had died by 2 years of follow-up, with half of the deaths attributable to aneurysm rupture. Five-year survival was 19%. In this series, as in another study by Bickerstaff and associates, 9 the likelihood of rupture was higher in patients with dissections than in patients with nondissecting aneurysms (57% versus 34%).
The poor outcome in these studies, compared with the results of surgical series, would seem to justify a policy advocating elective repair of even relatively small descending thoracic aneurysms and type B dissections. 1,16,17 However, although the hospital mortality associated with elective surgery of descending thoracic and thoracoabdominal aneurysms has fallen significantly in recent years—our current overall survival in 63 patients over the past 3 years is 81%—the potential morbidity (especially paraplegia) is still a considerable deterrent to an aggressive surgical approach. This dreaded complication ranges from 0.5% to 38%, despite many and varied approaches to spinal cord preservation. 1,18-20 In view of the risk of paraplegia, it seems imperative to select only those patients for operative repair in whom rupture is truly imminent. At present, however, we lack the information that would allow us to evaluate risk of rupture accurately.
In the past few years, with the increase in the number of patients in whom we have elected to defer operation, we saw the opportunity to undertake a systematic analysis of serial data routinely obtained during the course of follow-up of these patients that would enable us to construct a more detailed picture of the natural history of thoracic aortic aneurysms. The need for a method for the accurate tracking of aneurysm enlargement, such as the three-dimensional reconstruction that we have developed, became obvious when a significant proportion of these patients had several conventional CT studies, not always precisely comparable, on which clinical decisions about aneurysm progression (and likelihood of rupture) had to be made.
The three-dimensional reconstruction method offers several practical and theoretical advantages over conventional CT studies of thoracic aneurysms. On the practical side, the three-dimensional method allows the important findings from each study to be displayed on a single sheet of paper (see Fig. 1). The data, stored on floppy computer disks, are readily accessible at any time and can be easily compared with previous and future studies, making review of multiple CT studies no longer such a time-consuming and cumbersome task.
One of the theoretical advantages of the three-dimensional method is that it allows appreciation of longitudinal as well as transverse increases in aneurysm size. This is not essential in the abdominal aorta, where the diameter is an accurate reflection of the essentially spherical shape of the abdominal aneurysm. However, in the thoracic aorta, aneurysm expansion may involve significant elongation without substantial increase in aortic diameter: using the three-dimensional reconstruction technology, this expansion will be reflected by changes in volume as well as in the tortuosity index. In addition, three-dimensional reconstructions permit visualization of the entire aorta from each study at a glance, making it more difficult to overlook secondary areas of dilatation and easier to appreciate localized aortic abnormalities such as eccentric outpouchings.
In our study, diameter and volume data were analyzed to evaluate the normal pattern of descending aortic aneurysm enlargement. Our findings (0.32 cm per year increase in diameter, 53 ml per year in volume) correlate with a recent review of serial CT scans in 170 patients with aortic aneurysms of different locations 21 in which the diameter of the descending thoracic aorta increased at an average of 0.34 cm per year. These authors documented that thoracic aneurysms expand more rapidly than abdominal aneurysms: mean growth rate was 0.42 cm per year for 84 thoracic aneurysms compared with 0.28 cm per year for abdominal aneurysms.
Our growth rate data also corroborate the findings of Guirguis and Barber's recent study 6 of abdominal aneurysms, in which it was demonstrated that the rate of diameter increase in larger aneurysms is higher than the rate of enlargement in smaller aneurysms. In fact, our data suggest that a large diameter (>5 cm) at diagnosis is the best predictor of a high expansion rate in thoracic aneurysms.
In addition to identifying aneurysm diameter as a major risk factor for subsequent expansion and rupture, we have also documented that thoracic aneurysms enlarge more rapidly in patients with a history of smoking. This may be a consequence of the adverse effects of cigarette smoking on connective tissue: an increase in proteases and a decrease in protease inhibitors have both been observed in smokers with abdominal aortic aneurysms, and both may contribute to the accelerated damage to the aorta that is observed in smokers. 22
It is possible that factors that appear to have an impact on initial diameter of aneurysms (hypertension and age) will emerge as significant influences on aneurysm enlargement as the number of patients in our ongoing natural history study becomes larger. It is also possible, however, that the failure of hypertension to emerge as a significant influence on aneurysm expansion rate reflects the effectiveness of treatment of hypertension, instituted once the existence of the aneurysm has been recognized, in preventing accelerated expansion and enhanced risk of rupture.
Surprisingly, the presence of dissection did not correlate with accelerated aortic expansion in our study. Although we are reluctant to conclude unequivocally that the probability of rupture is equal for patients with dissecting and nondissecting aneurysms on the basis of our data with such small numbers of patients, our present policy is to use the same operative indications for the management of both uncomplicated chronic type B dissections and nondissecting thoracic aortic aneurysms.
Sterpetti and colleagues 12 have emphasized that, based on the law of Laplace, the diameter of the aneurysm is the most important determinant of the probability of rupture. The data from the few instances of rupture that did take place in our study tend to validate the assumption that accelerated expansion of aneurysms usually occurs before rupture (see 
Table II).
As demonstrated by Bernstein and Chan 4 for abdominal aneurysms, our data suggest that a relatively cautious approach in advising operation for descending thoracic and thoracoabdominal aneurysms, coupled with scrupulous ongoing surveillance, is not associated with excessive mortality. Careful serial follow-up, with elective operations when indicated, resulted in a low risk (6%) of unanticipated aneurysm rupture. Three-year survival probability for all patients in the study was 77%, which is only modestly lower than the expected survival (85%) in a comparable group of individuals of the general population, as reported in an epidemiologic study by Bickerstaff and colleagues 9 in 1982.
The results of our study have permitted the refinement of guidelines for the management of patients with descending or thoracoabdominal aortic aneurysms. Although we continue to use our previously outlined operative indications, we have expanded our operative criteria to include some additional patients: those with smaller aneurysms (diameter < 5 cm) are operated on if they show signs of rapid expansion (increase in diameter >1 cm per year or increase in volume >180 ml per year).
Our data suggest that patients with small aneurysms, unless they are expanding rapidly, carry a low risk of rupture and can be observed at regular 6- or 12-month intervals. The symptom-free patient with a larger aneurysm diameter (5 cm to 8 cm), without evidence of rapid expansion, presents more of a dilemma. If the aneurysm is not enlarging significantly more than average, the patient's condition can be monitored at 3- to 6-month intervals. If the aneurysm is localized to the proximal descending aorta (even if it is 8 cm in diameter), surgical intervention is more readily recommended because the risk of paraplegia is relatively low in these cases. Surgical therapy is more strongly considered if risk factors such as smoking or poorly controlled hypertension are present. In patients with extensive thoracic or thoracoabominal aneurysms in whom the risk of postoperative paraplegia is high, we would favor a nonoperative approach at the same maximal diameter and rate of enlargement that would prompt operation in a more localized lesion in a less vulnerable part of the aorta.
Use of three-dimensional reconstructions of the aorta from CT scans allows more complete surveillance of aneurysm behavior and earlier recognition of morphologic factors predisposing to rupture, permitting further refinement of operative indications for these troubling lesions.
Appendix: DISCUSSION
Dr. H. Storm Floten (Portland, Ore.).
In the past 5 years, 102 patients have undergone profound hypothermia and circulatory arrest for various abnormalities of the ascending aorta and arch at our institution. Five of them died, for 4.9% mortality. Among the 97 survivors, only one had a transient embolic neurologic event. In the same time frame, 23 patients had elective resection of aneurysms isolated to the descending thoracic aorta with one death, for a 4.3% surgical mortality. However, we do not have a series of medically observed patients to compare with your 67 retrospectively selected patients in whom surgical treatment was initially deemed unsuitable; therefore, I will direct my comments toward your hard work in this area.
Two factors in possible expansion rate have not been adequately addressed. A history of hypertension needs definition. Does this mean systolic or diastolic hypertension, diastolic blood pressure greater than 100 mm Hg as a risk factor, or systolic blood pressure?
Second, aneurysm location—ascending, descending, thoracoabdominal—may also affect the rate of expansion and should be considered as a risk factor, for the usual pathology differs in the different locations.
From your analysis, including smoking as a risk factor is questionable. Although smoking was associated with expansion by univariate analysis, it falls out as a risk factor for expansion when size of initial aneurysm is taken into account by multivariate analysis. Therefore, the smokers had larger aneurysms at the initial evaluation. The p value for smokers was 0.8 on multivariate risk analysis. On multivariate analysis, initial aneurysm diameter greater than 5 cm was the only independent predictor of accelerated expansion, and this point should be emphasized.
According to your raw data, 10 of 67 patients crossed over to surgical treatment because of pain, size greater than 8 cm, diameter increase of 1 cm per year, or irregular contour. Of the remaining 57 patients, seven were lost to follow-up, leaving 50 patients to be followed up medically for a mean of 1
years. Four of these 50 died of known aneurysm rupture and another four died suddenly of unexplained reasons. It is reasonable therefore to consider that there might be a total of eight ruptures among the 50 patients being followed up, which would be a 16% rupture rate over a mean time frame of 1 years. This suggests that waiting for the asymptomatic 5 cm aneurysm to enlarge to 8 cm may be unwise. It could not be justified by your 30% surgical mortality rate in this series, because if emergency and thoracoabdominal procedures are excluded, surgical mortality for elective aneurysm resection confined to the chest approaches 5% as it does in most institutions. This surgical and medical mortality data coupled with an initial aneurysm diameter greater than 5 cm being the only significant predicting factor for accelerated expansion leads us to at least consider resection of 5 cm aneurysms confined to the chest. The increased operative mortality and morbidity of thoracoabdominal aneurysm resection truly is another beast to contend with and needs to be addressed independently.
It will be interesting to know the outcome of the remaining 36 patients being followed up conservatively. I compliment the authors on their hard work to try to answer the long-standing question of when a thoracic aneurysm should be resected electively. The method you have described has great worth in monitoring aneurysms of smaller size and thoracoabdominal aneurysms of greater size in which mortality and morbidity of resection completely changes the thinking and the approach to the problem.
Dr. Dapunt, how did you define hypertension? Did you consider location to be a risk factor? Do you have a pathologic or physiologic hypothesis for smoking being a risk factor for aneurysm expansion?
Dr. Dapunt.
In our retrospective study, the history of hypertension was defined as a diastolic pressure of more than 100 mm Hg, if that information was available from the office records. As we continue with our natural history prospectively, more sophisticated analyses of blood pressure will be performed, and other potential risk factors will be included in the multifactorial analysis, for example, chronic obstructive pulmonary disease, as has been shown for abdominal aneurysms.
The location of the aneurysm was not considered as a risk factor. Patients were operated on if the aneurysm had reached 8 cm in maximal diameter or had increased more than 1 cm per year. However, as a conclusion of our study, we would recommend surgical intervention for patients with aneurysms between 5 cm and 8 cm in largest diameter if they involve the proximal descending thoracic aorta and thus pose a low risk of postoperative paraplegia. On the other hand, we still think there is a role for a conservative approach so long as there is such a high risk of paraplegia for extended thoracoabdominal aneurysms, for dissections in particular. So long as there is no method to prevent paraplegia, we should be cautious in advising operation for such extended aneurysms.
The effect of smoking on aneurysm expansion can be a reflection of the adverse effect of cigarette smoking on connective tissue. It has been shown for abdominal aneurysms that protease and antiprotease relationship is altered in these patients, and this might cause accelerated damage to the aortic wall as well. This could explain the effect of smoking on the rate of enlargement.
Dr. Edward Verrier (Seattle, Wash.).
The only part of the presentation that I have difficulty with is the graphs concerning aneurysm enlargement. The increase in size of an aneurysm is particularly important to clinical decision making. I believe most of us recommend operative intervention if an aneurysm enlarges. The lines that you appear to draw through what appeared almost to be a scattergram end up being particularly important in terms of those decisions. It seems to me that there was tremendous variability in the amount of expansion for various aneurysms on those graphs, and yet a regression line sort of goes through the middle of widely disparate data points. What was the statistical analysis of that line generation, and how do you interpret that? How much importance is it to the individual patients?
Dr. Dapunt.
I agree with your observation that the rate of aneurysm enlargement seems to be highly variable among patients and also, as we could show in our study, among the different follow-up intervals in the same patient. Given this fact, which has been shown by other authors too, we thought the only possibility of predicting the expected expansion rate would be an estimation by linear regression. Just taking the average of the normalized data—we had to normalize all data to a yearly rate to control for different intervals between follow-up examinations—might overestimate the expected rate of enlargement. As you have seen in one of the graphs, an exponential regression line seems to fit better to the data distribution if you look at the patient with the given initial diameter and then look at the predicted increase rate in diameter and volume.
Dr. Verrier.
It depends on how tight the variability is in that line.
Dr. Dapunt.
Yes. The scatter in the data is certainly a problem.
Dr. D. Craig Miller (Stanford, Calif.).
I also have trouble with your trying to fit a nonlinear function to a linear curve; we all know it is not a linear function, which is a problem, but I still think you have provided us with very meaningful information.
I have one question. Did you look at renal function as a predictor of aneurysm size increase? Renal dysfunction has not only been shown in patients with abdominal aneurysms in the studies by Jack Cronenwett from Dartmouth to be a factor, but it also enters into your operative risk decision making.
Dr. Dapunt.
The data had to be gathered from office records where information about renal function was not included, so I cannot answer this question.
Footnotes
Read at the Nineteenth Annual Meeting of The Western Thoracic Surgical Association, Carlsbad, Calif., June 23-26, 1993. 
References
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B. W. Andrus, D. J. O'Rourke, L. J. Dacey, and R. T. Palac Stability of Ascending Aortic Dilatation Following Aortic Valve Replacement Circulation, September 9, 2003; 108(90101): II-295 - 299. [Abstract] [Full Text] [PDF]
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M. P. Ehrlich, M. Schillinger, M. Grabenwoger, A. Kocher, E. M. Tschernko, P. Simon, A. Bohdjalian, and E. Wolner Predictors of Adverse Outcome and Transient Neurological Dysfuntion Following Surgical Treatment of Acute Type A Dissections Circulation, September 9, 2003; 108(90101): II-318 - 323. [Abstract] [Full Text] [PDF]
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M. Schoder, F. Cartes-Zumelzu, M. Grabenwoger, M. Cejna, M. Funovics, C. G. Krenn, D. Hutschala, F. Wolf, S. Thurnher, G. Kretschmer, et al. Elective Endovascular Stent-Graft Repair of Atherosclerotic Thoracic Aortic Aneurysms:Clinical Results and Midterm Follow-Up Am. J. Roentgenol., March 1, 2003; 180(3): 709 - 715. [Abstract] [Full Text] [PDF]
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C. A. Anderson, R. J. Rizzo, and L. H. Cohn Ascending Aortic Aneurysms Card. Surg. Adult, January 1, 2003; 2(2003): 1123 - 1148. [Full Text]
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J. S. Coselli and P. L. Moreno Descending and Thoracoabdominal Aneurysm Card. Surg. Adult, January 1, 2003; 2(2003): 1169 - 1190. [Full Text]
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S. D. Moffatt and R. S. Mitchell Endovascular Stent Management of Thoracic Aneurysms and Dissections Card. Surg. Adult, January 1, 2003; 2(2003): 1191 - 1204. [Full Text]
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U. Herold, J. Piotrowski, D. Baumgart, H. Eggebrecht, R. Erbel, and H. Jakob Endoluminal stent graft repair for acute and chronic type B aortic dissection and atherosclerotic aneurysm of the thoracic aorta: an interdisciplinary task Eur. J. Cardiothorac. Surg., December 1, 2002; 22(6): 891 - 897. [Abstract] [Full Text] [PDF]
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K. Kallenbach, K. Pethig, M. Schwarz, A. Milz, A. Haverich, and W. Harringer Valve sparing aortic root reconstruction versus composite replacement - perioperative course and early complications Eur. J. Cardiothorac. Surg., July 1, 2001; 20(1): 77 - 81. [Abstract] [Full Text] [PDF]
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M. Genoni, M. Paul, R. Jenni, K. Graves, B. Seifert, and M. Turina Chronic {beta}-blocker therapy improves outcome and reduces treatment costs in chronic type B aortic dissection Eur. J. Cardiothorac. Surg., May 1, 2001; 19(5): 606 - 610. [Abstract] [Full Text] [PDF]
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C. B. Higgins Cardiac Imaging Radiology, October 1, 2000; 217(1): 4 - 10. [Abstract] [Full Text]
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W. S. Ring Congenital Heart Surgery Nomenclature and Database Project: aortic aneurysm, sinus of valsalva aneurysm, and aortic dissection Ann. Thorac. Surg., April 1, 2000; 69(4): S147 - 163. [Abstract] [Full Text] [PDF]
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W. Harringer, K. Pethig, C. Hagl, G. P. Meyer, and A. Haverich Ascending Aortic Replacement With Aortic Valve Reimplantation Circulation, November 9, 1999; 100 (2009): II-24 - II-28. [Abstract] [Full Text] [PDF]
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I. Shimada, S. J. Rooney, P. A. Farneti, P. Riley, P. Guest, P. Davies, and R. S. Bonser Reproducibility of thoracic aortic diameter measurement using computed tomographic scans Eur. J. Cardiothorac. Surg., July 1, 1999; 16(1): 59 - 62. [Abstract] [Full Text] [PDF]
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W. Harringer, K. Pethig, C. Hagl, T. Wahlers, J. Cremer, and A. Haverich Replacement of ascending aorta with aortic valve reimplantation: midterm results Eur. J. Cardiothorac. Surg., June 1, 1999; 15(6): 803 - 808. [Abstract] [Full Text] [PDF]
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M. A. Ergin, D. Spielvogel, A. Apaydin, S. L. Lansman, J. N. McCullough, J. D. Galla, and R. B. Griepp Surgical treatment of the dilated ascending aorta: when and how? Ann. Thorac. Surg., June 1, 1999; 67(6): 1834 - 1839. [Abstract] [Full Text] [PDF]
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M. A. Coady, J. A. Rizzo, G. L. Hammond, G. S. Kopf, and J. A. Elefteriades Surgical intervention criteria for thoracic aortic aneurysms: a study of growth rates and complications Ann. Thorac. Surg., June 1, 1999; 67(6): 1922 - 1926. [Abstract] [Full Text] [PDF]
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R. B. Griepp, M. A. Ergin, J. D. Galla, S. L. Lansman, J. N. McCullough, K. H. Nguyen, J. J. Klein, and D. Spielvogel Natural history of descending thoracic and thoracoabdominal aneurysms Ann. Thorac. Surg., June 1, 1999; 67(6): 1927 - 1930. [Abstract] [Full Text] [PDF]
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I. Shimada, S. J. Rooney, D. Pagano, P. A. Farneti, P. Davies, P. J. Guest, and R. S. Bonser Prediction of thoracic aortic aneurysm expansion: validation of formulae describing growth Ann. Thorac. Surg., June 1, 1999; 67(6): 1968 - 1970. [Abstract] [Full Text] [PDF]
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T. Juvonen, M. A. Ergin, J. D. Galla, S. L. Lansman, J. N. McCullough, K. Nguyen, C. A. Bodian, M. P. Ehrlich, D. Spielvogel, J. J. Klein, et al. RISK FACTORS FOR RUPTURE OF CHRONIC TYPE B DISSECTIONS J. Thorac. Cardiovasc. Surg., April 1, 1999; 117(4): 776 - 786. [Abstract] [Full Text] [PDF]
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T. Juvonen, M. A. Ergin, J. D. Galla, S. L. Lansman, K. H. Nguyen, J. N. McCullough, D. Levy, R. A. de Asla, C. A. Bodian, and R. B. Griepp Prospective Study of the Natural History of Thoracic Aortic Aneurysms Ann. Thorac. Surg., June 1, 1997; 63(6): 1533 - 1544. [Abstract] [Full Text]
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M. A. Coady, J. A. Rizzo, G. L. Hammond, D. Mandapati, U. Darr, G. S. Kopf, and J. A. Elefteriades WHAT IS THE APPROPRIATE SIZE CRITERION FOR RESECTION OF THORACIC AORTIC ANEURYSMS? J. Thorac. Cardiovasc. Surg., March 1, 1997; 113(3): 476 - 491. [Abstract] [Full Text]
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J.-i. Hayashi, S. Eguchi, K. Yasuda, S. Komatsu, K. Tabayashi, M. Masuda, R. Yozu, K. Amemiya, E. Takeuchi, S. Nakano, et al. Operation for Nondissecting Aneurysm in the Descending Thoracic Aorta Ann. Thorac. Surg., January 1, 1997; 63(1): 93 - 97. [Abstract] [Full Text]
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J. S. Coselli Thoracoabdominal Aortic Aneurysms Ann. Thorac. Surg., January 1, 1996; 61(1): 269 - 270. [Full Text]
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