Ann Thorac Surg 2008;85:972-977. doi:10.1016/j.athoracsur.2007.10.051
© 2008 The Society of Thoracic Surgeons
Original Articles: Cardiovascular
Long-Term Prognosis of Type A Aortic Dissection in Non-Marfan Patients With Histologic Pattern of Cystic Medial Necrosis
Evaldas Girdauskas, MD*,
Thomas Kuntze, MD,
Michael A. Borger, MD, PhD,
Torsten Doenst, MD, PhD,
Michael Mochalski, MD,
Thomas Walther, MD, PhD,
Volkmar Falk, MD, PhD,
Friedrich W. Mohr, MD, PhD
Department of Cardiac Surgery, Heart Center Leipzig, Leipzig, Germany
Accepted for publication October 12, 2007.
* Address correspondence to Dr Girdauskas, Department of Cardiac Surgery, Heart Center Leipzig, Strümpellstrasse 39, Leipzig, 04289, Germany (Email: evagird{at}centras.lt).
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Abstract
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Background: The aim of this study was to evaluate long-term results of surgery for type A aortic dissection in non-Marfan patients with histologically confirmed cystic medial necrosis.
Methods: We reviewed our institutional database to identify non-Marfan patients who underwent surgery for acute type A dissection between October 1994 and May 2006 (n = 188). Pathology reports and histologic analyses were available in 174 patients, which form the focus of this study. Long-term results of patients with histologic evidence of cystic medial necrosis in their resected aorta were compared with patients with other causes of aortic dissection.
Results: A total of 137 patients (79%) survived to discharge from the hospital. Cystic medial necrosis was present in 89 of these 137 patients (65%, group 1). The remaining 48 patients showed a different histologic pattern (group 2). Long-term follow-up was available in 100% of survivors and was 41 ± 30 months long. Freedom from late death was 82% in group 1 and 74% in group 2 (p = 0.24). Although aortic reoperation was required in more group 1 patients (17% versus 10%), this difference failed to reach statistical significance (p = 0.3).
Conclusions: The aortic reoperation rate after acute type A dissection may be higher among patients having cystic medial necrosis. We recommend that non-Marfan patients with histologically confirmed cystic medial necrosis undergo the same thorough postoperative surveillance as Marfan patients do.
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Introduction
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Cystic medial necrosis as a histologic marker for Marfan syndrome is known to be associated with a high risk of long-term post-surgical aortic complications. However, the histologic pattern of cystic medial necrosis is also common in a large subgroup of younger non-Marfan patients presenting with acute type A aortic dissection [1–3]. There are increasing reports in the literature showing involvement of other vascular territories in patients with histologic signs of cystic medial necrosis: carotid arteries [4–6], coronary arteries [7, 8], abdominal aorta and iliac arteries [9], and multiple visceral arteries [10]. Furthermore, these patients have an increased risk of serious vascular complications during interventional procedures [10–12]. The aim of our study was to evaluate the long-term results with non-Marfan patients operated on for acute type A aortic dissection with histologic evidence of cystic medial necrosis.
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Material and Methods
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We reviewed our institutional database to identify patients who underwent surgery for acute type A aortic dissection between October 1994 and May 2006. A total of 203 consecutive patients underwent emergent surgery for acute type A aortic dissection during this period. Patients with Marfan syndrome (n = 15), defined according to the current Ghent criteria, were excluded from the study. Histologic examination of the aorta was available in 174 of 188 cases (92%), and these patients serve as the focus of the current study. Approval of the Ethics Committee of the University Leipzig (Reg. No. 199-2005) was obtained in October 2005. The individual consent for the study was waived. Histologic examination consisted of light microscopy of the operative material (at the level of sinus of valsalva, of the mid ascending aorta, and the transverse arch) with Van Gieson elastine-halcian blue stain. There was no difference in histologic diagnosis throughout the sampling sites, although some variation in the intensity of pathologic findings was noticed. Cystic medial necrosis was diagnosed if the aorta displayed fragmentation of elastic fibers, accumulation of the extracellular matrix with formation of the cystic structures, and necrosis of nuclei of the smooth muscle cells.
In all, 137 of 174 patients (78.7%) were discharged from the hospital after successful surgery for acute type A dissection. Of these 137 survivors, 89 patients (65%) had histologic pattern of cystic medial necrosis in their resected aorta (group 1). The remaining 48 patients (35%) showed a different histologic pattern—atherosclerotic disease, nonspecific medial degeneration, or no major signs of histologic abnormality (group 2).
Preoperative variables were compared between groups and are displayed in Table 1. The great majority of patients (97% in group 1 and 96% in group 2) presented with a DeBakey type I dissection at the time of diagnosis. The only significant differences included younger age and higher prevalence of aortic insufficiency in group 1.
Intraoperative management was performed using uniform and standardized surgical and anesthetic protocols with only minor changes over time. Briefly, cardiopulmonary bypass (CPB) was instituted using right axillary perfusion and right atrial venous drainage. Core cooling was carried out down to an esophageal temperature of 18°C using a maximal CPB temperature gradient of 6°C. In more recent years, antegrade selective cerebral perfusion (10 mL · kg–1 · min–1) at a core temperature of 23°C to 25°C was used for arch repairs. The aortic root procedure was performed during the cooling phase. The primary aim was to save the native aortic valve when it appeared morphologically normal. Directly before stopping systemic perfusion, ice packs were placed around the patient’s head, and 100 mg dexamethasone was administered intravenously. Distal aortic repair was always performed with an open technique. The proximal hemiarch replacement is the standard procedure in type A aortic dissections in our clinic over the last years. Total arch replacement was reserved for patients with aortic arch entry tears involving the supra-aortic orifices, as well as for patients with an enlarged aortic arch or other indications as described by Crawford and colleagues [13]. The distal extent of the procedure was not different between the two groups (Table 2). Antegrade graft perfusion was always implemented during reperfusion, and the temperature gradient was kept below 6°C.
The most important postoperative in-hospital outcomes are shown in Table 3. The patients in group 2 had more complicated postoperative course with more renal and respiratory problems, as well as longer intensive care unit stays. Perioperative stroke included patients with preoperative focal neurologic deficits (cerebral malperfusion) and those with new postoperative injuries.
All surviving patients underwent strict blood pressure control before leaving the hospital, including β-blockers in all cases. The patients' general practitioners were contacted postoperatively to assure the continuity of adequate hypertension treatment.
Follow-up was performed in 100% of hospital survivors. Follow-up consisted of a telephone interview with the patients and a written questionnaire sent to the patients’ general practitioners. All imaging data obtained during the postoperative course (echocardiography reports, computed tomography/magnetic resonance images) were forwarded to our center for documentation purposes. In addition, 62 of 137 patients (45.3%) were directly examined in our outpatient clinic. The follow-up protocol did not differ between the groups. The primary endpoint of this study was the rate of late aortic reoperations in both groups.
Statistical Analysis
The two-tailed Student’s t test was used for continuous variables, and the 
2 test for categorical variables was used to make univariate comparisons between groups. Survival analysis was performed according to the methods of Kaplan-Meier, and statistical differences were analyzed using the log-rank test. A multivariable analysis, namely, Cox regression, of survival and reoperation-free survival was performed. The risk for late aortic reoperations was estimated using cumulative incidence method. All p values of 0.05 or less were considered statistically significant.
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Results
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Long-term follow-up (range, 1 to 111 months postoperatively) was available in 100% of survivors and was of comparable duration between groups (41.7 ± 32.3 months for group 1 versus 39.6 ± 27.2 months for group 2, p = 0.46). The Kaplan-Meier curve showed a tendency toward better long-term survival in group 1 (Fig 1), although this did not reach statistical significance (log-rank p = 0.06). After 5 years of follow-up, 70% of patients were alive in group 1 versus 57% in group 2. The number of the patients at risk after 10 years of follow-up was too small to make meaningful comparisons.
Analysis of the late deaths showed that 12 of 25 patients (48.0%) in group 1 versus 8 of 19 (42.1%) in group 2 died because of aortic-related causes (Fig 2). Late deaths were classified as aortic related if patients died after referral to the peripheral hospital because of complications related to the primary surgery, if deaths were sudden during the late postoperative course, or if patients died after aortic reoperations. The deaths were classified as cardiac if patients died of known cardiac problems. Noncardiac causes included all patients who died of other known end-stage diseases during the late postoperative course. The cause of death could not be determined in 27.3% of patients.
A Cox regression analysis of long-term survival showed that the only statistically significant factors were preoperative cardiopulmonary resuscitation and postoperative hemodialysis (Table 4). The aortic root replacement and postoperative hemodialysis were the significant factors of reoperation-free survival.
Aortic reoperations (Table 5) were required in 15 of 89 patients (16.9%) in group 1 versus 5 of 48 (10.4%) in group 2 (p = 0.3). The prevalence of proximal reoperations was the same between the groups, whereas there was a tendency toward a higher rate of distal reoperations in the cystic medial necrosis group (11.2% versus 4.2%; p = 0.16). A total of 11 patients had to be reoperated on on the distal aorta owing to progressive enlargement of the false channel (distal disssecting aneurysm). The remaining patient had a pseudoaneurysm at the distal anastomosis associated with systemic fungal infection. The cumulative risk of aortic reoperations at 6 years of follow-up was 18.2% in group 1 versus 14.9% in group 2 (Fig 3). Three patients in group 1 required two distal aortic reoperations during the postoperative follow-up and 1 patient, three redo procedures, with a total number of 20 surgical reinterventions (1.3 procedures per patient). Additionally, four percutaneous therapeutic aortic interventions (stent implantation, fenestration) were required in group 1 during follow-up. The in-hospital mortality for reoperated on patients was 20.0% in both groups. Analysis of the time frame for aortic reinterventions (Fig 4) showed that 8 of 15 patients (53.3%) in group 1 were reoperated on during the first postoperative year versus 2 of 5 patients (40.0%) in group 2. Interestingly, 7 of 89 patients (7.9%) in group 1 were operated on by other surgical disciplines for diseases related to connective tissue disorders: 2 patients for recurrent inguinal hernia, 2 patients for incisional hernia, 1 patient for retinal detachment, 1 patient for degenerative knee disease, and the last patient for the recurrent spontaneous pneumothorax. No such procedure was required in group 2 patients.
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Fig 3. Cumulative (actual) risk of aortic reoperations. (Triangles = cystic medial necrosis [CMN]; squares = no CMN.)
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Fig 4. Aortic reoperations during follow-up. Months after initial surgical procedure are indicated under each set of bars. (CMN = cystic medial necrosis.)
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Imaging data obtained during follow-up were available for 102 of 137 patients (74.5%). The most relevant findings are demonstrated in Table 6. Although progression of the aortic disease (at the proximal and distal site) was more common in the group 1, these differences failed to reach statistical significance. The progression of the aortic disease was defined as a recurrence of aortic insufficiency (moderate or severe) or enlargement of the distal aortic segment more than 20% over the immediate postoperative diameter.
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Comment
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Cystic medial necrosis is often observed in the resected aorta of Marfan patients and is associated with a worse long-term prognosis. In addition, cystic medial necrosis is associated with arterial aneurysms and dissections in other organ systems in patients without Marfan syndrome [4–8]. We hypothesized that cystic medial necrosis, as demonstrated in the aorta of patients undergoing emergency surgery for acute type A aortic dissection, would be associated with a worse postoperative prognosis in non-Marfan patients. To address this question, we compared postoperative survival and aortic events in patients with cystic medial necrosis to those of patients having different histologic findings in their dissected aorta. Our findings may have implications for the postoperative follow-up of non-Marfan patients with cystic medial necrosis.
In patients with cystic medial necrosis, alterations of the aortic root (ie, annuloaortic ectasia) and aortic dissection develop at a younger age because of accelerated degeneration of aortic wall structures [1, 2]. Because of the accelerated disease process, some preoperative risk factors (ie, age, prevalence of aortic insufficiency, coronary artery disease) differed between the two patient groups (Tables 1 and 2). Therefore, it was not possible to eliminate these differences between the two groups. That resulted in a higher rate of composite valve graft root replacement (39.3% versus 18.8%) in the cystic medial necrosis group, and conversely, a higher prevalence of concomitant CABG (27.1% versus 7.9%) in the control group. The trend toward more complicated postoperative course and poorer 5-year survival in the control group was not surprising, because of the older age of patients and more coronary artery disease. These are the limitations of this study and should be considered in the assessment of our long-term results.
The Kaplan-Meier survival curve showed a typical course for aortic dissection patients: the initial high hazard phase during the first year after surgery, the plateau phase lasting until the fourth postoperative year, and the late deterioration because of the increasing number of progressive aortic complications.
Although there was no statistically significant difference in the reoperation rate between the two groups of patients, the findings of this study indicate that patients having histologic evidence of cystic medial necrosis may have a higher risk of late aortic complications after acute type A aortic dissection than patients showing a different histologic pattern. The constellation of higher rate of distal aortic reoperations (11.2% versus 4.2%), higher prevalence of progressive distal aortic disease from the imaging studies (16.9% versus 12.5%), higher total number of surgical aortic reinterventions (1.3 versus 1.0 procedure per patient), higher proportion of aortic reoperations during first postoperative year (53.3% versus 40%), and more aortic-related late deaths (48.0% versus 42.1%) in group 1 points out an increased risk profile of this patient population.
What are the consequences of classifying these patients as a high-risk population for late aortic complications? Firstly, we would recommend that patients having histologic evidence of cystic medial necrosis in their resected aorta should undergo the same thorough postoperative surveillance as Marfan patients do [2]. Such patients would probably benefit from strict control of arterial hypertension and strong consideration of β-blocker usage, as well as serial imaging studies to watch for signs of aortic enlargement. However, severe persistent arterial hypertension is rarely a significant problem among the young population with cystic medial necrosis. Because 50% of our reoperations were performed during the first postoperative year, we recommend performing computed tomography scans every 3 months during the first postoperative half-year in the patients with residual dissected aorta and perfused false channel. The intervals for the subsequent follow-up visits depend on the evolution of the aortic disease during the initial follow-up (ranging from 3- to 12-month intervals thereafter). Secondly, if we proceed in the analogy to our Marfan patients, more aggressive distal repair at the time of primary surgery could be indicated for these otherwise young, healthy patients [14], eliminating the risk of late resternotomy and reducing the potential of downstream aortic reoperations [13]. Three distal aortic reinterventions were required in 28 patients (10.7%) with cystic medial necrosis who underwent total arch replacement during primary surgery versus 6 reinterventions in 31 patients (19.4%) with cystic medial necrosis after isolated ascending replacement in this study. Moreover, replacement of the aortic arch does not increase the perioperative risk of acute type A dissection surgery in our experience.
Histologic examination is the only available method to diagnose cystic medial necrosis, and the results may not be available until after the patients are discharged from hospital. Is there any way to predict cystic medial necrosis preoperatively? In a recent study, echocardiography has been shown to provide a noninvasive and reliable tool for assessment of aortic elastic properties (ie, distensibility, stiffness index) in the Marfan patients [15, 16]. The evaluation of aortic wall elasticity, using a similar protocol, has been performed in patients with bicuspid aortic valve disease. However, there are no reports to date on the echocardiographic aortic indicators of non-Marfan patients with histologic pattern of cystic medial necrosis. This will be the aim of a future study at our center.
In conclusion, the findings of this study suggest that the risk of late adverse aortic events may be higher in patients having histologic pattern of cystic medial necrosis after acute type A dissection surgery. We recommend that non-Marfan patients having histologic evidence of cystic medial necrosis in their resected aorta should undergo the same thorough postoperative surveillance as Marfan patients do. More aggressive distal aortic repair may also be indicated for these patients during their primary surgery. A noninvasive preoperative diagnostic tool would be favorable for surgical planning in this patient population.
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References
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Abstract
Introduction
