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Ann Thorac Surg 2005;80:96-100
© 2005 The Society of Thoracic Surgeons

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Original article: Cardiovascular

Midterm Results of Surgical Treatment of Thoracic Aortic Disease in Dialysis Patients

Department of Thoracic and Cardiovascular Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan

Accepted for publication January 20, 2005.

^_* Address reprint requests to Dr Morishita, Department of Thoracic and Cardiovascular Surgery, Sapporo Medical University School of Medicine, South 1 West 16, Central Ward, Sapporo, 060-8543 Japan (Email: kmori{at}sapmed.ac.jp).

	Abstract

Top Abstract Introduction Patients and Methods Results Comment References

 
BACKGROUND: We investigated the influence of dialysis on late aortic events in end-stage renal failure patients who had undergone replacement of the thoracic aorta.

METHODS: Between 1990 and 2003, 28 dialysis patients underwent thoracic aortic aneurysm repair. The cause was non-dissection in 17 patients and dissection in 11 patients. Six patients needed emergency operations. After the initial operation, 10 patients in the dialysis group had a patent false channel distal to the operative area, and 7 patients in the dialysis group had untreated separate aneurysms. These lesions were defined as residual aneurysms. We performed a retrospective case-control analysis of survival and late aortic events (enlargement of the remaining thoracic aorta, sudden death and reoperation) in dialysis patients versus carefully matched non-dialysis patients. Matching criteria included age, sex, cause, operative procedures, operative date, and operative status (elective or emergency).

RESULTS: Survival rates at 1 and 5 years for dialysis patients versus non-dialysis patients were 63 ± 9% vs. 85 ± 7% and 41 ± 11% versus 64 ± 13%, respectively (p = 0.02). Four of nine late deaths in the dialysis group were due to rupture of residual aneurysm. Freedom from late aortic events for dialysis patients versus non-dialysis patients was 91± 6% versus 92 ± 5% and 25 ± 14% versus 68 ± 12% at 1 and 5 years, respectively (p = 0.0073).

CONCLUSIONS: There is a high incidence of late aortic events in dialysis patients undergoing thoracic aortic aneurysm repair. This finding indicates the need for close follow-up examination of dialysis patients who have undergone surgical treatment of thoracic aortic disease.

	Introduction

Top Abstract Introduction Patients and Methods Results Comment References

 
The existence of preoperative renal dysfunction increases operative risk. Svensson and colleagues [1] found that by extensive analysis of 1,509 patients undergoing thoracoabdominal aortic aneurysm repair that preoperative serum creatinine level influenced mortality. Their analysis showed that an increase in creatinine level of 1.0 mg/dL increased operative risk by 1.2 times. Other authors have also shown that preoperative renal dysfunction is associated with early death in patients undergoing thoracic aortic repair [2, 3]. Moreover, diabetes mellitus and primary hypertension, the main causes of chronic renal failure, can adversely affect early results. Therefore treatment of thoracic aortic disease in patients with end-stage renal failure poses significant challenges to surgeons.

On the other hand, little is known about the influence of dialysis on late aortic events, including fatal rupture, and on the requirement for reoperation in dialysis-dependent renal failure patients undergoing thoracic aortic repair. It is well known that dialysis patients present with atherosclerotic disease and die of cardiovascular disease [4]. Some factors that are potentially important for atherosclerotic changes such as diabetes, hypertension, and calcium x phosphate product may exacerbate an existent atherosclerotic disease. Because hemodialysis has become widespread, more dialysis patients will suffer severe cardiovascular complications.

The aim of this study was to verify whether dialysis increases the frequency of late aortic events in patients undergoing treatment of thoracic aortic disease. We performed a retrospective case-control analysis of late results in dialysis-dependent renal failure patients versus late results in carefully matched patients without renal dysfunction after surgical treatment of thoracic aortic disease.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment References

 
Twenty-eight consecutive patients with end-stage renal failure maintained on chronic dialysis who underwent thoracic aortic aneurysm repair between the years of 1990 and 2003 were included in this study. We have recently started endovascular stent-grafting for dialysis patients, but they were excluded from this study because the maximum follow-up period was 6 months. The Institutional Review Ethics Committee approved the study design and waived the need for informed consent from the patients to participate in the study. The 28 patients accounted for 3.8% of all patients who underwent surgical treatment of thoracic aortic disease during the same period. There were 19 men and 9 women whose ages ranged from 48 to 79 years (average age, 67 ± 8 years). The patients received hemodialysis for at least 6 months before thoracic aortic surgery. The cause was atherosclerosis in 16 patients, chronic type B aortic dissection in 4, chronic type A aortic dissection in 3, acute type A aortic dissection in 3, acute type B aortic dissection in 1, and anastomotic pseudoaneurysm in 1. Twelve patients underwent descending aortic replacement, 6 patients underwent thoracoabdominal aortic aneurysm repair, 6 patients underwent arch replacement, 3 patients underwent ascending aortic replacement, and 1 patient required Bentall procedure plus hemi-arch replacement. According to the classification by Crawford [5], the extent of thoracoabdominal aneurysm repair was type III in 3 patients and type IV in 1 patient. Extent of descending aortic replacement was the proximal one third in 2 patients, middle one third in 2, distal one third in 1, proximal two thirds in 3, distal two thirds in 3, and the entire descending thoracic aorta in 1. Six patients needed emergency operations due to acute dissection (n = 4) or rupture (n = 2). One patient had undergone endovascular stent-grafting of the proximal descending thoracic aorta and infrarenal abdominal aorta. Nine patients had undergone prior aneurysm resections; 6 had undergone infrarenal abdominal aortic aneurysm repair, 2 had undergone arch replacement, and 1 had undergone a proximal descending thoracic aorta replacement.

Associated diseases included hypertension in 26 patients (93%), diabetes in 14 (50%), stroke in 4 (14%), ischemic heart disease in 3 (11%), and malignancy in 1. Most of the patients underwent hemodialysis 1 day before surgery and received hemofiltration during cardiopulmonary bypass and after intensive care unit admission. Routine hemodialysis was restarted after extubation had been performed. However, this strategy did not apply to emergency patients.

Control patients were selected from non-dialysis patients who had undergone thoracic aortic aneurysm repair between the years of 1990 and 2003. The patients were matched for age, sex, cause, operative procedures, extent of replaced aorta, and operative status (elective or emergency). With regard to age, a difference of 2 years was accepted. Twenty-four control patients were selected after the previously described matching. When more than 1 patient was eligible to serve as a control, the one whose date of operation was closest to that of the dialysis patient was selected. The control group consisted of 28 patients. Associated disease included hypertension in 20 patients (71%), diabetes in 5 (18%), ischemic heart disease in 4 (14%), stroke in 3 (11%), systemic lupus erythematosus in 1, and malignancy in 1. Eight patients had previously undergone aortic procedures; arch replacement had been previously carried out in 3, abdominal aortic aneurysm repair had been carried out in 3, and the Bentall procedure and thoracoabdominal aneurysm repair had been carried out in 1 patient each. There were no patients with Marfan syndrome in either group.

When patients had an arch aneurysm and thoracoabdominal aneurysm simultaneously, the larger one or the symptomatic one was operated on first. If the smaller one was less than 5 cm in diameter or if the patient refused a second operation, stage 2 repair was not performed. These were regarded as residual aneurysms. There were 7 patients in the dialysis group and 6 patients in the control group with such residual aneurysms. Type A aortic dissection is so extensive that it cannot be entirely exposed through a single-incision approach. Most surgeons usually replace the ascending thoracic aorta or up to the aortic arch in patients with type A aortic dissection. Thus, we have to follow-up patients who have a patent false channel distal to the operative area. Of such distal dissections, one of more than 3 cm in diameter was defined as residual aneurysm. Ten dialysis patients and 8 control patients had such residual distal dissections. The diameters of residual aneurysms at the initial operation in both groups are shown in Table 1. The 31 patients had residual aneurysms of varying sizes elsewhere in the aorta after their initial operations.

Follow-up information on patients who had survived operations was updated during the period from June 10, 2004 to June 28, 2004 and was 100% complete. Follow-up was accomplished by reviewing hospital records of a clinic for outpatients or, if not available, by telephone interview with the patient, his or her family, or the patient’s referring physicians.

All statistical analyses were done with StatView statistical software (SAS Institute Inc, Cary, NC). Fischer’s exact test was used to compare categorical variables. Cumulative survival and freedom from late events were calculated by the Kaplan-Meier method, and their differences were determined by the log-rank test. Significance was considered when p < 0.05.

	Results

Top Abstract Introduction Patients and Methods Results Comment References

 
Mortality and Morbidity
In-hospital mortality rates were 18% (5 of 28) in the dialysis group and 7% (2 of 28) in the control group. However, this difference did not reach statistical significance. In the dialysis group, 4 patients died of sepsis, and 1 patient died due to progressive metastases of renal cancer after emergency graft replacement. In the control group, 1 patient died of respiratory failure and 1 patient died of sepsis. The in-hospital mortality rate of patients who underwent emergency operations was 33% (2 of 6) in each group.

Pulmonary complications occurred in 5 patients (18%) and 8 patients (29%), and spinal cord injury developed in 2 patients (7%) and 1 patient (4%), in the dialysis group and control group, respectively. Both dialysis patients suffering spinal cord injury underwent emergency descending thoracic aorta repair. The control patient with spinal cord injury had graft replacement for a Crawford type III thoracoabdominal aortic aneurysm. Other complications in the dialysis group included cardiac failure in 1 patient and stroke another 1. A 70-year-old dialysis patient who had undergone emergency graft replacement using circulatory arrest needed intraaortic balloon pumping due to low cardiac output. In the control group, 6 patients needed temporary hemodialysis, 2 suffered from stroke, and 1 had renal infarction. Of the 6 patients requiring hemodialysis, 4 had undergone emergency operations. The renal infarction was caused by occlusion of the graft used to reconstruct the left renal artery during thoracoabdominal aortic aneurysm repair.

Late Follow-Up
Overall 1-year, 5-year, and 10-year survival rates for the control group were 85 ± 7%, 74 ± 10% and 64 ± 13%, respectively. Survival rates of dialysis patients were lower, ie, 63 ± 9%, 41 ± 11%, and 41 ± 11% at 1 year, 5 years, and 10 years, respectively (p = 0.02, log rank) (Fig 1). Nine patients in the dialysis group died during the follow-up period. Four of these 9 patients died of rupture of the residual aneurysm. The first patient underwent a distal one third replacement of the descending aorta. He was noted to have an arch aneurysm of 4 cm in diameter. That patient was not followed-up. Forty-two months after the operation, the patient died of a rupture of the arch aneurysm. The second patient with chronic type B aortic dissection was treated with a proximal two third replacement of the descending aorta. The distal dissection was patent on the follow-up computed tomographic scan. The thoracoabdominal part of the dissection was ruptured 21 months after the initial operation. He underwent an emergency operation but died 2 months after the operation. The maximum diameter at the time of rupture was 5.5 cm. The third death resulted from a rupture of a remote aneurysm (arch aneurysm of 4.5 cm in diameter) 9 months after successful thoracoabdominal aneurysm repair of a ruptured case. The fourth patient had a massive hemoptysis 36 months after total arch replacement. An emergency computed tomographic scan showed a distal anastomotic pseudoaneurysm. He underwent emergency endovascular stent-grafting but died of respiratory failure. Rupture occurred at a mean interval of 18 months and in aneurysms with diameters ranging from 5 to 6 cm. The other causes of death were malignancy, stroke, pneumonia, sepsis, and pulmonary embolism. In the control group, 3 patients died of pneumonia, 2 died of rupture of another aneurysm, 1 died of malignancy, and 1 died suddenly. Both patients who died of ruptured aneurysm were noted to have thoracic aneurysm of considerable sizes (6 and 8 cm) during the follow-up period. One patient refused to undergo a second repair and the other experienced rupture before the scheduled operation.

View larger version (15K): [in this window] [in a new window]   Fig 1. Kaplan-Meier survival estimates.

View larger version (16K): [in this window] [in a new window]   Fig 2. Freedom from late aortic events. Late aortic events were defined as the need for reoperation due to residual aneurysm or anastomotic pseudoaneurysm, fatal aortic rupture, sudden death, and expansion of more than 6 cm in diameter of residual aneurysm.

	Comment

Top Abstract Introduction Patients and Methods Results Comment References

A dilated segment of the aorta is believed to be a deleterious factor associated with late rupture and late death. Some surgeons may resect all dilated segments of the aorta at the initial operation. However, we believe that this aggressive approach cannot be justified because preoperative renal dysfunction is highly associated with operative mortality [1, 3, 5, 6]. Extended aortic replacement appears to increase the early mortality rate of dialysis patients due to the large degree of operative invasiveness. Unless operative mortality of an aggressive approach proves to be acceptable, we propose that detailed follow-up examination by computed tomographic scans should be performed and that repair of segments be performed when expanded segments are detected.

The interval for follow-ups needs to be addressed here. In the earlier days of our series, nephrologists followed-up our patients. Because they did not pay attention to residual aneurysms, they did not perform computed tomographic scans. Three patients suffered from fatal rupture of residual aneurysms. In addition, some patients returned to our institution to undergo residual aneurysm repair. We became aware of the high incidence of late aortic events and started postoperative follow-up on a yearly basis with computed tomographic scans, as recommended by Svensson and colleagues [7]. Recently, a dialysis patient died of the rupture of a remote aneurysm 9 months after a successful operation. Since then we have followed-up our patients every 6 months.

Such a close surveillance raises the question of what size of a residual aneurysm should be considered as an indication for repair. Elefteriades [8] recommended intervention for the ascending aorta at 5.5 cm and for the descending aorta at 6.5 cm based on his analysis of 1,600 patients with thoracic aortic aneurysms. However, fatal aortic rupture occurred in patients in this study with residual aneurysms ranging in size from 5 to 6 cm in diameter. We speculate that chronic renal failure has an adverse influence on late aortic condition. Hyperparathyroidism secondary to renal failure is associated with accelerated atherosclerosis. Hypertension exerts forces on a fragile aortic wall. Such a condition may easily lead to aortic rupture. Considering that the mortality rate of patients in our series who underwent 9 elective reoperations was 0%, we recommend a size of 5 cm for resection.

Considering that hypertension or metabolic abnormality may contribute to the high incidence of late aortic events, renal transplantation appears to be optimal to reduce late aortic events. However, our patients did not undergo renal transplantation. The Japanese Society for Dialysis Therapy reported that only 7% of all dialysis patients sought renal transplants. The major reasons for not seeking a transplant were a reasonable stable dialysis condition and uncertainty about transplant [9]. The survival rate of dialysis patients in Japan is not as poor as that of dialysis patients in the United States [10]. The 5-year survival rate for Japanese patients is 61% [11]. On the other hand, the number of kidney transplants in Japan is approximately 600 cases per year, whereas that in the United States exceeds 6,000 cases [12]. The limited number of patients receiving kidney transplants may lead to the atmosphere of not seeking kidney transplants in Japan. In fact, none of the patients in our series wanted kidney transplants. However, this is not the case with dialysis patients in other countries. Because thoracic aortic repair alone cannot improve long-term results, patients eligible for renal transplantation should undergo transplantation.

The control of hypertension is important to manage patients with residual aneurysms, both dialysis patients and patients not undergoing dialysis. Previous studies have shown the effects of beta-blocking agents on prevention of aortic dissection and dilatation in Marfan syndrome patients [13, 14]. Beta-blockers are thought to influence the aorta favorably by reducing the first time derivative of rate pressure change in the aorta as well as blood pressure [7]. Because beta-blockers suppress renin release in hypertension, they appear to be optimal, especially in dialysis patients. End-stage renal failure often induces elevated activation of the renin-angiotensin system. In addition, there is evidence that angiotensin II contributes to aortic disease [15, 16]. Nagashima and associates [17] suggested that an angiotensin-converting enzyme inhibitor prevented aortic disease. We will prescribe these antihypertensive drugs, although we have used calcium channel blockers so far.

Several authors have reported a high mortality rate of dialysis patients undergoing thoracic aortic operations [18–20]. In this case-control analysis, differences between dialysis of the mortality of patients and controls, one did not reach a statistical significance. However, our operative mortality still appears to be high. To improve results, another approach would be necessary. Endovascular stent grafting has emerged as a less invasive management of thoracic aortic disease [21]. Though patients who were considered to be unsuitable for open repair have undergone endovascular repair, early results were acceptable. As of January 2005, we have performed endovascular stent grafting in 3 dialysis patients. Distal endoleak was observed in 1 patient who successfully underwent distal extension. A dialysis patient may require at least a 1 cm longer landing zone than usual due to a stiff and rigid aortic wall. To determine whether this is true or not, a study using more patients and a longer follow-up period will be necessary.

It is important to realize the limits of this study. It was retrospectively designed. Patients were heterogeneous and their number was small. However, this specific patient population is so rare that a sufficient number cannot be collected. Such rareness makes it difficult to draw a definitive conclusion. This case-matched study suggested a high incidence of late aortic events. The results indicate the importance of surveillance. We believe that we should perform long-term serial imaging follow-up to prevent fatal aortic rupture.

In conclusion, there is a high incidence of late aortic events in dialysis patients who have undergone surgical treatment of thoracic aortic disease. This experience suggests the need for close follow-up examination of dialysis patients who have undergone thoracic aortic repair.

	References

Top Abstract Introduction Patients and Methods Results Comment References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Kiyofumi Morishita Yoshihiko Kurimoto Tomio Abe Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Morishita, K. Articles by Abe, T. Search for Related Content PubMed PubMed Citation Articles by Morishita, K. Articles by Abe, T. Related Collections Great vessels