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Ann Thorac Surg 2004;78:1268-1273
© 2004 The Society of Thoracic Surgeons


Original article: cardiovascular

Long-Term Outcome and Prognostic Predictors of Medically Treated Acute Type B Aortic Dissections

Seiji Onitsuka, MD*, Hidetoshi Akashi, MD, Keiichiro Tayama, MD, Teiji Okazaki, MD, Kenji Ishihara, MD, Shinichi Hiromatsu, MD, Shigeaki Aoyagi, MD

Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi,Kurume, 830-0011Japan

Accepted for publication February 10, 2004.

* Address reprint requests to Dr Onitsuka, Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011 Japan
onitti{at}med.kurume-u.ac.jp


    Abstract
 Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 
BACKGROUND: The purpose of this study was to examine the long-term outcome and the prognostic predictors related to the development of complications associated with acute type B aortic dissection.

METHODS: Seventy-six medically treated patients with acute type B aortic dissection were examined between 1990 and 2001. The events associated with aortic dissection included dissection-related death, rupture, visceral ischemia, lower limb ischemia, an increase in the maximum aortic diameter greater than 50 mm, and a mean enlargement rate of greater than 5 mm per year.

RESULTS: Among the 76 patients 10 (13%) underwent chronic phase surgery and 25 (33%) presented with an event. A statistically significant difference was observed between patients with and without events with regard to atherosclerotic factors, blood flow status in the false lumen, maximum aortic diameter upon admission, mean aortic enlargement rate, and blood pressure control during follow-up. Of these factors a patent false-lumen and a maximum aortic diameter greater than 40 mm upon admission were the most strongly associated factors with regard to the development of events. Patients with a patent false-lumen and a maximum aortic diameter greater than 40 mm upon admission were determined to exhibit significantly higher event rates than other patients.

CONCLUSIONS: In determining the appropriate therapeutic approach for acute type B aortic dissection, it is important to pay careful attention to the predictors of a patent false-lumen and a maximum aortic diameter greater than 40 mm at onset to improve the long-term outcome.


    Introduction
 Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 
When patients with acute type B aortic dissection exhibit no complications such as rupture, visceral ischemia, or lower limb ischemia at the time of onset, conservative medical treatment is generally preferred. However, at the time of initial diagnosis, it is difficult to identify which patients will require surgery during the follow-up period. If it were possible to identify, patients with predictors of the complications associated with aortic dissection and thus requiring surgical operation at the time of onset, it would be expected that the medical treatment outcome of acute type B aortic dissection would be improved. The purpose of this study was to examine the long-term outcome and the prognostic predictors related to the development of complications associated with acute type B aortic dissection.


    Patients and Methods
 Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 
Patients
Eighty-one patients were admitted to our hospital and diagnosed as having acute type B aortic dissection during the 11-year period from January 1990 to December 2000. Seventy-six patients were selected for acute phase conservative medical treatment. The study group included 55 men and 21 women with an average age of 65.1 ± 9.9 years (range: 40–85 years) and the mean follow-up period for these patients was 52.4 ± 35.9 months (range: 3.1–120.7 months).

Definitions
"Acute" describes the period within 14 days of the onset of symptoms. "Chronic" describes the situation at least 14 days after the onset of symptoms. The diagnosis was established based on the findings of computed tomography (CT) in all of the patients and digital subtraction angiography (DSA) was performed on those patients with dissection-related complications. Aortic dissections were morphologically classified according to the Stanford (type A, type B) and DeBakey classification (IIIa, IIIb).

Based on the findings regarding the blood flow status in the false lumen obtained by initial CT and DSA, aortic dissections were classified as two types: the early thrombosed false-lumen and the patent false-lumen. In the early thrombosed false-lumen, the false lumen is completely thrombosed and indicates no enhancement. Patients with an ulcer-like projection (ULP) were included in the early thrombosed false-lumen. In the patent false-lumen, blood flow is seen in the false lumen that communicates with the true lumen forming a so-called "double-barrel" aorta. Even if the false lumen were partially thrombosed, the dissection was classified as the patent false-lumen if the contrast agent flowed into the false lumen and extended to central or peripheral areas.

The largest diameter of the dissecting aorta measured on CT images was defined as the maximum aortic diameter (mm). The maximum aortic diameter was measured twice—on the initial CT images obtained upon admission and on the most recent CT images. In patients who underwent surgery during either the acute or chronic phase, the diameter was measured on CT images obtained immediately before surgery. The mean aortic enlargement rate (mm per year) was obtained by dividing the difference in maximum aortic diameter between the initial CT images obtained upon admission and the most recent CT images (mm) by the interval (years) between the initial and most recent CT images. The mean aortic enlargement rate was calculated only when the initial CT images were obtained at least 1 year before the most recent CT images.

Patients were determined to exhibit atherosclerotic factors when they presented with (or indicated a history of) any of the following diseases: hypertension, diabetes mellitus, hyperlipidemia, coronary artery disease, and cerebrovascular disease. Patients who exhibited a history of smoking before onset were classified as "smokers."

Control of blood pressure during the follow-up phase was evaluated based on blood pressure measurements obtained at outpatient clinics at intervals of 2 weeks to 1 month. Control of blood pressure was judged to be favorable when the mean systolic blood pressure was maintained at less than 140 mm Hg and the diastolic blood pressure at less than 90 mm Hg. Otherwise, blood pressure control was judged to be poor.

The complications associated with aortic dissection included dissection-related death, rupture or impending rupture, visceral ischemia, lower limb ischemia, an increase in the maximum aortic diameter greater than 50 mm, and a mean aortic enlargement rate of greater than 5 mm per year. The development of any of these complications was designated as the "event group," and those who did not experience any of these complications were designated as the "nonevent group."

Characteristics
The most commonly observed comorbidity was hypertension, which was observed in 58 patients (76%), followed by chronic heart failure in 9 patients (12%), cerebrovascular disease in 5 patients (7%), operation for cardiovascular disease in 4 patients (5%), malignancy in 4 patients (5%), chronic renal insufficiency in 3 patients (4%) (2 dialysis patients), chronic hepatitis in 2 patients (3%), chronic obstructive pulmonary disease in 2 patients (3%), diabetes mellitus in 2 patients (3%), chronic rheumatoid arthritis in 2 patients (3%), and hyperlipidemia in 1 patient (1%) (Table 1). In our study population, no patients were determined to exhibit Marfan's syndrome, traumatic dissection, or iatrogenic dissection.


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Table 1. Patient Characteristics

 
Treatment
With regard to antihypertensive therapy, patients with acute aortic dissection received calcium-channel blockers by continuous intravenous infusion immediately after admission to our hospital with additional continuous intravenous infusion of nitric acid agents in some cases. When oral administration became possible, patients were switched to oral formulations of these agents. In principle, patients without severe heart failure or obstructive pulmonary disease received oral ß-blockers concurrently with additional {alpha}-blockers and angiotensin-converting enzyme inhibitors as appropriate. While maintaining adequate urine production, blood pressure was controlled with a target systolic blood pressure of 120 mm Hg. After discharge, patients continued to receive oral medications at a local clinic or at our hospital. In addition, surgery was performed in patients with complications such as rupture or impending rupture, an increased aortic diameter, visceral ischemia, and lower limb ischemia. Follow-up was obtained by a review of hospital charts and office records, in-person office visits, and telephone and letter interviews with the patients or their families.

Statistical Analysis
In the statistical analysis, comparisons between the event group and nonevent group were performed using the unpaired Student's t test for continuous measures and the {chi}2 test for nominal variables. For 2 x 2 contingency tables, the {chi}2 test or Fisher's direct method was used. In multivariate analysis, logistic regression was employed. The event-free rate was analyzed by the Kaplan–Meier method and comparisons between groups were performed using the log-rank test as well as the Breslow–Gehan–Wilcoxon test. In addition, changes in maximum aortic diameter over time were evaluated using a regression line. In comparisons between two groups, a risk factor p value less than 0.05 was considered statistically significant. In comparisons between four groups, a Bonferroni comparison method was employed to avoid type I errors, and a risk factor p value less than 0.008 was considered statistically significant. Values are indicated as mean ± standard deviation.


    Results
 Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 
Treatment Outcome
Upon admission 1 out of the 81 patients interviewed had already experienced aneurysmal rupture, was transferred to our hospital in shock, and could not be saved. Of the remaining 80 patients, acute phase surgery was performed in 4 (5%) and acute phase conservative medical treatment was selected for the other 76 (95%), with medical treatment continued during the chronic phase in 66 patients and chronic phase surgery in the remaining 10.

Acute phase surgery was performed in 2 patients with rupture and 2 patients with visceral ischemia involving the superior mesenteric artery and the renal artery. Of these, a total of 3 patients (75%) died during hospitalization: the 2 patients with rupture and 1 patient with occlusion of the superior mesenteric artery. The remaining patient with renal ischemia underwent right axillary-femoral bypass surgery and indicated improved renal function and an increase in urinary volume after surgery. One year later, however, this patient's maximum aortic diameter has increased to 60 mm and surgery has been scheduled.

Chronic phase surgery was performed in 6 patients with increased aortic diameter, 1 patient with rupture of the false lumen of the left iliac artery, 1 patient with impending rupture, 1 patient with visceral ischemia, and 1 patient with lower limb ischemia. Of these 10, 3 patients (30%) who underwent graft replacement for an increase in aortic diameter died during hospitalization.

Among the 66 patients in whom medical treatment was continued during the chronic phase, 50 (76%) of them survived and 14 died. The other 2 patients were lost to follow-up (follow-up was 97.5% complete). Of the 14 patients who died, 4 experienced dissection-related deaths: rupture in 2 patients and sudden death, in 2 patients. In both cases of rupture-induced death the patients had refused to undergo surgery. The other 10 deaths were caused by other factors: acute myocardial infarction in 4 patients, subarachnoid hemorrhage in 1 patient, cerebral stroke in 1 patient, malignancy in 3 patients, and postoperative complications of DeBakey type I aorta dissection in 1 patient.

Examination of Events
Among the 76 patients selected for acute phase medical treatment, 25 (33%) experienced events. The event-free rate was 73% at 5 years (Fig 1). Specifically, these events included dissection-related death in 4 patients, rupture or impending rupture in 5 patients, visceral ischemia in 3 patients, lower limb ischemia in 2 patients, an increase in the maximum aortic diameter greater than 50 mm in 17 patients, and a mean aortic enlargement rate of greater than 5 mm per year in 5 patients, for a total of 36 events in 25 patients. Of these 25 patients, 11 (44%) underwent surgery. Among the 66 patients who did not undergo surgery during the chronic phase, 15 (23%) of them experienced events.



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Fig 1. The complications associated with aortic dissection included dissection related death, rupture or impending rupture, visceral ischemia, lower limb ischemia, an increase in the maximum aortic diameter greater than 50 mm, and a mean aortic enlargement rate of greater than 5 mm per year. Development of any of these complications was classified as patients experiencing an "event." The Kaplan–Meier curve illustrates freedom from the events in all 76 patients.

 
Examination of Predictors: Event Group Versus Nonevent Group
The event group and nonevent group were compared using univariate analysis with regard to the following items: gender, age, atherosclerotic factors, smoking history, DeBakey classification, blood flow status in the false lumen, maximum aortic diameter, mean aortic enlargement rate, ULP, and blood pressure control during the follow-up period. Of these items there were statistically significant differences between the two groups with regard to atherosclerotic factors, blood flow status in the false lumen, maximum aortic diameter, mean aortic enlargement rate, and blood pressure control during follow-up. Compared with the nonevent group, the event group included a significantly larger number of patients with atherosclerotic factors, patent false-lumen, a maximum aortic diameter greater than 40 mm upon admission, a mean aortic enlargement rate, and poor blood pressure control during follow-up. The maximum aortic diameters upon admission in the event group and the nonevent group were 41.0 ± 7.1 mm and 36.3 ± 4.9 mm, respectively, with the event group indicating a significantly larger diameter (p = 0.001). The mean aortic enlargement rates were 5.3 ± 3.1 mm per year and 0.1 ± 2.0 mm per year, respectively, with the event group indicating a significantly higher rate (p < 0.0001). There were no statistically significant differences between the two groups with regard to the length of follow-up or the interval between the initial and most recent CT examination dates (Table 2).


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Table 2. Comparative Studies Between the Event Groupa and the Nonevent Groupa (Univariate Analysis)

 
Examination of Predictors: Multivariate Analysis
The abovementioned factors, which were assessed by univariate analysis, were then evaluated using multivariate analysis to identify correlations with the occurrence of events. The items evaluated included atherosclerotic factors, blood flow status in the false lumen, maximum aortic diameter upon admission, and blood pressure control during the follow-up period; mean aortic enlargement rate was excluded from the analysis because of the limited number of patients who could be followed up. The results indicated that the event occurrence rate was significantly correlated with patent false-lumen (p = 0.001) and a maximum aortic diameter greater than 40 mm upon admission (p = 0.04) (Table 3).


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Table 3. Multivariate Analysis (Performed Using Logistic Regression) for Event Predictors

 
Among the 76 patients, 10 (13%) exhibited both of the factors mentioned above (patent false-lumen and maximum aortic diameter greater than 40 mm upon admission) and 7 (70%) of these patients experienced an event. With regard to the remaining 66 patients, events occurred in 18 (27%). The event-free rate of patients with patent false-lumen and a maximum aortic diameter greater than 40 mm upon admission was significantly lower than that of other patients (p = 0.01). The event-free rates for these patients and for other patients were 50% and 78% at 5 years, respectively (Fig 2).



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Fig 2. Lower line is a Kaplan–Meier curve indicating freedom from events in the group having both a patent false-lumen and maximum aortic diameter upon admission of ≥ 40 mm. Upper line is a Kaplan–Meier curve indicating freedom from events in the group of other patients. Lower patients at risk are that of the group having both a patent false-lumen and maximum aortic diameter upon admission of ≥ 40 mm. Upper patients at risk are that of the other patients. p = 0.01 using the Breslow–Gehan–Wilcoxon test.

 
In addition, no patients with patent false-lumen indicated a reduction in the maximum aortic diameter. A tendency toward an increase was seen in all patients. The mean aortic enlargement rates in the patent false-lumen and the thrombosed false-lumen were 3.8 ± 3.3 mm per year and 0.3 ± 2.7 mm per year, respectively, with the patent false-lumen indicating a significantly higher mean aortic enlargement rate (p = 0.0005).


    Comment
 Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 
Statistically sound criteria for determining whether or not emergency surgery is required and formulating treatment plans without delay can be expected to improve the surgical outcome of patients with acute type B aortic dissection [1–5]. Initial use of transesophageal echocardiography (TEE) as the diagnostic strategy of choice in patients with suspected aortic dissection has been reported [6]. It could be useful to diagnose the morphologic and hemodynamic characteristics by the TEE with high sensitivity and specificity. In this study, we did not use the TEE routinely because CT was performed at the intensive care unit immediately. When patients with acute type B aortic dissection are selected to receive conservative medical treatment upon admission, surgery should be considered later based on factors such as the development of rupture, visceral ischemia, lower limb ischemia, or an increase in the maximum aortic diameter during the follow-up period [3, 7–9]. However the choice between surgical and medical treatment for the patients without these complications is still controversial. The surgical approach of acute type B aortic dissection remains polymorphous. Elefteriades and associates [5] recommended a complication-specific approach to the management of descending aortic dissection: uncomplicated dissection is treated medically, whereas complicated dissection is treated surgically with realized rupture treated by standard graft replacement, limb ischemia treated by fenestration, and enlargement or impending rupture treated by thromboexclusion. Furthermore the endovascular therapy has recently improved and changed the management of type B aortic dissection [10].

In this study, among the 81 patients with acute type B aortic dissection, 76 of them received conservative medical treatment during the acute phase and 66 of them continued to receive medical treatment during the chronic phase. Of these patients 50 (76%) survived. Given these results, can such conservative therapies be considered effective? During conservative treatment 4 patients experienced rupture and sudden death and 10 patients required surgery during the chronic phase. In addition the surgical morbidity and mortality incidences during this chronic phase were high (30%). Some of the other patients who are still receiving conservative treatment are also expected to meet the conditions for surgery during the follow-up period. If it were possible to identify the patients with predictors of dissection-related complications requiring surgery at the time of onset the therapeutic outcome for patients with type B aortic dissections would be expected to improve.

In general, when conservative treatment is selected for patients with acute type B aortic dissection these patients tend to exhibit a comparatively favorable prognosis [8, 11] comparable with that of patients undergoing surgery during the acute phase [4, 12]. However it must be kept in mind that the surgical outcome tends to be poor when the patient is admitted with rupture, visceral ischemia, and lower limb ischemia or when the patient exhibits critical organ failure [3, 5, 9, 13, 14]. It follows that these confounding factors must be eliminated when therapeutic outcomes between the surgical therapy group and the conservative therapy group in patients with type B aortic dissection are compared [5, 7, 12, 14, 15].

The present study examined patients with acute type B aortic dissection who experienced the following six events after onset: dissection-related death, rupture or impending rupture, visceral ischemia, lower limb ischemia, an increase in the maximum aortic diameter greater than 50 mm, and a mean aortic enlargement rate of greater than 5 mm per year. These six events suggested that it was necessary to perform or consider surgery during follow-up. Correlations were evaluated between the occurrence of these events and various factors (ie, gender, age, atherosclerotic factors, smoking history, DeBakey classification, blood flow status in the false lumen, maximum aortic diameter upon admission, mean aortic enlargement rate, ULP, and blood pressure control during follow-up). In other words if these predictors are significantly correlated with the occurrence of events it may be possible to anticipate the necessity for surgical treatment in the chronic phase before the patient satisfies the current criteria for surgical intervention.

Compared with the nonevent group, the event group included a significantly larger number of patients with atherosclerotic factors, patent false-lumen, maximum aortic diameter greater than 40 mm upon admission, and poor blood pressure control during follow-up. The event group also exhibited a significantly larger maximum aortic diameter upon admission and an increased mean aortic enlargement rate compared with the nonevent group. In particular, among those patients who exhibited both a patent false-lumen and a maximum aortic diameter greater than 40 mm upon admission (which were the predictive factors identified by multivariate analysis), greater than 50% experienced events within approximately 5 years. Among the 29 patients who exhibited both thrombosed false-lumen and maximum aortic diameter less than 40 mm upon admission, only 2 (6.9%) of them experienced events during follow-up. Dissection-related complications, such as visceral ischemia and lower limb ischemia, are likely to develop in patients with patent false-lumen. These patients also tend to indicate an increase in maximum aortic diameter.

In conclusion one of the most important factors with regard to improving the prognosis of patients with acute type B aortic dissection is to establish the diagnosis as soon as the patient arrives at the hospital. Based on the findings of physical examination as well as CT, angiographic, and ultrasonographic studies, a valid attempt should be made to accurately determine whether or not emergency surgery is required for rupture, visceral ischemia, or lower limb ischemia and the formulation of a treatment plan should be administered without delay. When conservative medical treatment is selected for patients without dissection-related complications a treatment plan should be formulated according to the blood flow status in the false lumen and the maximum aortic diameter that can be confirmed immediately after onset [16, 17]. When conservative treatment is selected in a patient with atherosclerotic factors who exhibits both the patent false-lumen and a maximum aortic diameter greater than 40 mm upon admission, appropriate blood pressure control and careful CT examination should be performed during follow-up to monitor for potential dissection-related complications. In addition if the patient presents rapid aortic enlargement and poor blood pressure control during follow-up, surgical intervention in the comparatively early phase may be considered.

The recommendations in this report are provisory. An inherent limitation concerning the present study is that it is a retrospective nonrandomized review. It is necessary that we accumulate more experience and more long-term patient follow-up to reassess the predictors influencing the therapeutic outcome of patients with acute type B aortic dissection. Then if those predictors revealed are significantly correlated with the occurrence of dissection-related complications, it may possible to change the management plan and the therapeutic outcome of patients with acute type B aortic dissection can be expected to improve.


    References
 Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 

  1. Haverich A, Miller DC, Scott WC, et al. Acute and chronic aortic dissections—determinants of long-term outcome for operative survivors. Circulation. 1985;72(Suppl 2):22–34
  2. Roberts CS, Roberts WC. Aortic dissection with the entrance tear in the descending thoracic aorta: analysis of 40 necropsy patients. Ann Surg. 1991;231:356–368
  3. Gysi J, Schaffner T, Mohacsi P, et al. Early and late outcome of operated and non-operated acute dissection of the descending aorta. Eur J Cardiothorac Surg. 1997;11:1163–1170[Abstract]
  4. Schor JS, Yerlioglu ME, Galla JD, et al. Selective management of acute type B aortic dissection: long-term follow-up. Ann Thorac Surg. 1996;61:1339–1341[Abstract/Free Full Text]
  5. Elefteriades JA, Hartleroad J, Gusberg RJ, et al. Long-term experience with descending aortic dissection. The complication-specific approach. Ann Thorac Surg. 1992;53:11–21[Abstract]
  6. Torossov M, Singh A, Fein SA, et al. Clinical presentation, diagnosis, and hospital outcome of patients with documented aortic dissection: The Albany Medical Center experience, 1986 to 1996. Am Heart J. 1999;137:154–161[Medline]
  7. Glower DD, Fann JI, Speier RH, et al. Comparison of medical and surgical therapy for uncomplicated descending aortic dissection. Circulation. 1990;82(Suppl 2):39–46
  8. Crawford ES, Svensson LG, Coselli JS, et al. Aortic dissection and dissecting aortic aneurysms. Ann Surg. 1988;208:254–273[Medline]
  9. Glower DD, Speier RH, White WD, et al. Management and long-term outcome of aortic dissection. Ann Surg. 1991;214:31–41[Medline]
  10. Gonzalez-Fajardo JA, Gutierrez V, San Roman JA, et al. Utility of intraoperative transesophageal echocardiography during endovascular stent-graft repair of acute thoracic aortic dissection. Ann Vasc Surg. 2002;16:297–303[Medline]
  11. DeBakey ME, McCollum CH, Crawford ES, et al. Dissection and dissecting aneurysms of the aorta: twenty-year follow-up of five hundred twenty-seven patients treated surgically. Surgery. 1982;92:1118–1134[Medline]
  12. Masuda Y, Yamada Z, Morooka N, et al. Prognosis patients with medically treated aortic dissections. Circulation. 1991;84(Suppl 3):7–13
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  17. Kato M, Bai H, Sato K, et al. Determining surgical indications for acute type B dissection based on enlargement of aortic diameter during the chronic phase. Circulation. 1995;84(Suppl 2):107–112



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