The prevalence and natural history of aortic aneurysms in heart and abdominal organ transplant patients☆☆☆★★★

Methods 

Patients included in this study underwent heart, liver, or kidney transplantation between January 1, 1987, and December 31, 2000, at the University of Washington Medical Center and were 18 years of age or older at the time of the transplant. The diagnosis of an aortic aneurysm was made by computed tomographic scan, ultrasound scan, or at the time of surgery for rupture. Permission to carry out this retrospective review was obtained from the University of Washington Human Subjects Committee. Patients were identified through review of medical records. Data obtained included demographic information (gender and age at transplant), baseline clinical information (type of disease leading to end-stage organ dysfunction, medical comorbidities, cardiac ejection fraction, renal function, and liver function), data on general clinical course (immunosuppressive regimen and cause of death), and information specific to the patient's aortic aneurysm (method of diagnosis, age at time of diagnosis, imaging results, and operative reports). We defined an aortic aneurysm as an abdominal aorta greater than 3.5 cm in diameter.

Baseline characteristics were compared between heart and nonheart transplant patients with Fisher's exact test for dichotomous variables and the Wilcoxon rank-sum test for continuous variables. Statistical analysis was performed with SAS v.8.0 (SAS Institute, Cary, NC). The mean rate of aneurysm expansion (cm/y) was calculated for the total follow-up period and the pretransplant and posttransplant periods. Mean expansion rates were also calculated for patients with heart versus nonheart transplants. Calculation of a mean expansion rate required a minimum of two imaging studies performed at least 1 month apart during the time period of interest.

Results 

Two hundred ninety-six heart transplants, 450 liver transplants, and 811 kidney transplants were performed at the University of Washington Medical Center between January 1, 1987, and December 31, 2000. Eighteen aortic aneurysms were identified among these 1557 patients (13 heart, three liver, and two kidney recipients). Among the heart transplant patients, the overall prevalence of an aortic aneurysm being diagnosed was 4.1%. Routine screening for aortic aneurysms before heart transplantation became more frequent over time. Before 1997, only 11.0% of heart transplant patients were screened for aortic aneurysms before transplantation, but beginning in 1997, 87% of patients were screened. This practice is reflected by a 3.0% prevalence of aortic aneurysm diagnosis in heart transplant recipients for the period from 1987 to 1996 and a 5.8% prevalence for 1997 to 2000. In contrast, the prevalence of aortic aneurysm diagnosis in nonheart transplant patients was 0.4% for the entire study period.

Baseline patient characteristics are shown in Tables I and II.

Table I. Baseline characteristics in 18 transplant patients with aortic aneurysms

	Characteristic	No.
	Male gender	14 (82.4%)
	Transplanted organ/diagnosis
	Heart	13* (72.2%)
	Kidney	2 (11.1%)
	Liver	3 (16.7%)
	Died	5 (29.4%)
	Cause of death related to aortic aneurysm	5 (100%)
	Complications after emergent repair for rupture	3 (60%)
	Intra-abdominal abscess	1/5
	Multisystem organ failure	1/5
	Massive stroke (brain death)	1/5
	No repair	2 (40%)
	*Includes one patient with ascending aortic aneurysm.

Table II. Natural history of aortic aneurysm in 18 transplant patients

	Patient	Transplant type	Diagnosis	Gender	Transplant date	AA diagnosis date	AA location	Initial size (cm)	Final size (cm)	Rupture	Repair	Died
	1	Heart	Ischemic CM	M	7/6/87	7/7/93	IR	5.7	5.7	Yes	Yes	Yes
	2	Heart	Ischemic CM	M	8/28/90	1/20/00	TAAA	6.6	6.6	Yes	Yes	No
	3	Heart	Idiopathic CM	M	6/15/97	7/1/97	IR	3.2	5.2	No	Yes	No
	4	Liver	Alcoholic Cirr	M	6/1/94	11/1/93	IR	5.8	7.0	No	Yes	No
	5	Liver	PSC	F	6/1/89	12/1/99	IR	4.0	5.1	Yes	Yes	Yes
	6	Heart	Ischemic CM	M	8/18/99	10/28/99	TAAA	5.5	6.5	No	No	No
	7	Heart	Ischemic CM	M	9/19/92	4/19/92	IR	3.0	6.5	No	Yes	No
	8	Heart	Ischemic CM	M	5/15/94	6/23/93	IR	3.7	12.5	No	Yes	No
	9	Kidney	Polycystic kidney	M	1/1/89	3/1/00	IR	5.0	5.1	No	Yes	No
	10	Heart	Ischemic CM	M	12/1/99	7/1/97	IR	3.0	6.2	No	Yes	No
	11	Heart	Ischemic CM	M	6/20/00	1/15/97	IR	4.9	5.5	Yes	Yes	Yes
	12	Heart	Ischemic CM	M	8/13/00	5/1/00	IR	3.1	3.8	No	No	No
	13	Kidney	Renal failure NOS	F	4/2/87	1/4/94	IR	—	—	Yes	Yes	No
	14	Liver	Cryptogenic Cirr	F	8/1/92	1/15/00	IR	—	—	No	Yes	No
	15	Heart	Idiopathic CM	M	2/10/92	1/23/99	IR	—	—	Yes	No	Yes
	16	Heart	Ischemic CM	M	1/16/97	8/1/96	IR	3.0	3.8	No	No	No
	17	Heart	Idiopathic CM	F	10/11/87	6/15/90	IR	4.5	7.2	Yes	No	Yes
	18	Heart	Marfan's	M	9/11/95	1/1/91	AscAo	3.5	5.1	No	Yes	No

M, Male; F, female; CM, cardiomyopathy; Cirr, cirrhosis; PSC, primary sclerosing cholangitis; NOS, not otherwise specified; AA, aortic aneurysm; IR, infrarenal; TAAA, thoracoabdominal; AscAo, ascending aorta.

Aneurysm characteristics are shown in Table III.

Table III. Aortic aneurysm characteristics

	Characteristic	No.
	Age at aortic aneurysm diagnosis (y)	58.8 ± 6.6
	Size of aneurysm at time of diagnosis (cm)	4.3 ± 1.3
	Size of aneurysm at time of repair/last study (cm)	6.0 ± 2.1
	Aortic aneurysm location
	Thoracoabdominal	2 (11.1%)
	Infrarenal	15 (83.3%)
	Ascending aorta	1 (5.6%)
	Aneurysm ruptured	7 (41.2%)
	Size at rupture (cm)	6.02 ± 0.86
	Aneurysm repaired	13 (81.3%)
	Time between aneurysm diagnosis and repair (d)	877.5 ± 818.8
	Method of repair
	Open tube	9 (69.2%)
	Endovascular	3 (23.1%)
	Arch repair	1 (7.7%)

Comparison of characteristics between heart and nonheart transplant recipients showed that a greater proportion of heart transplant patients were male (91.7% versus 40.0%; P = .01). There were otherwise no significant differences in the proportion of patients with diabetes or hypertension, in age at aneurysm diagnosis, or in aneurysm size at the time of diagnosis or repair.

Overall and subgroup rates of aneurysm expansion are shown in Table IV.

Table IV. Mean rates of aneurysm expansion

	Patient type	Aneurysm expansion rate (cm/y)
	All patients (after transplant)	0.83 ± 0.49 (n = 12)
	Heart transplant patients	0.78 ± 0.41 (n = 9)
	Nonheart transplant patients	1.00 ± 0.58 (n = 3)
	Before transplant	0.46 ± 0.20 (n = 5)
	After transplant	1.00 ± 0.51 (n = 12)

Discussion 

To the best of our knowledge, this study presents the largest reported series of aortic aneurysms in organ transplant patients and it is the first to describe the clinical course of aortic aneurysms in abdominal transplant patients. The data suggest that transplant patients have high rates of aneurysm rupture and that rupture caries a high risk of fatality. Seven of 17 aneurysms (41%) ruptured, and all five deaths that occurred in this series were caused by rupture. The overall rate of aneurysm rupture was 22.5% per year. Among the transplant patients with ruptured aneurysms, the mean aneurysm size at the time of rupture was 6.02 ± 0.86 cm, with the smallest measuring 5.1 cm. These data do not support previous observations suggesting that aneurysms in transplant patients tend to have rupture at smaller sizes.9, 10 In addition, not enough data were available to confirm whether aortic aneurysms that ruptured had a faster rate of expansion than those that did not rupture. Nonetheless, our data do indicate that the natural history of aortic aneurysms in transplant patients is unfavorable in terms of rupture rate.

The pretransplant rate of aneurysm expansion in our study, 0.46 cm/y, approximates the reported rate of 0.2 to 0.4 cm/y in the general population.11, 12 After a transplant operation, this rate increased to 1.0 cm/y. Although not statistically significant, there was a trend towards higher aortic aneurysm expansion rates after transplantation. Observation of a larger study population is needed to clarify this relationship. There was no statistical difference between the heart and nonheart transplant patients with respect to the rate of posttransplant aneurysm expansion. There have been other reports of increased rates of aneurysm expansion in cardiac transplant patients, ranging from 0.74 cm/y10 to 1.2 cm/y.9 Previous authors have postulated that increased arterial pressure associated with improved cardiac output after cardiac transplantation may contribute to aortic aneurysm expansion.10 As expected, our patients had substantially improved cardiac output after cardiac transplantation. However, the noncardiac transplant patients also had increased rates of aortic aneurysm expansion after transplantation despite not having a similar change in hemodynamics. Therefore, we suggest that the increased rate of aneurysm expansion may not be the result of a unique characteristic of cardiac transplant patients but rather associated with a factor common to transplant patients, such as immunosuppressive medications. There is evidence in animal models for an increased rate of aneurysm expansion with steroid treatment,13 but there are limited clinical data to support the conclusion that steroids increase the rate of aneurysm expansion in humans.14, 15 The etiologic factors predisposing transplant patients to rapid aneurysm expansion and rupture remain undetermined. In addition to the type of immunosuppressive medications, frequency of rejection, infection, insulin resistance, lipid abnormalities, hypertension, and other hemodynamic factors may all play a role. Additional studies are needed to further elucidate the unique relationship between posttransplant status and aortic aneurysms.

The previously reported prevalence of aortic aneurysms in cardiac transplant patients is in the range of 1% to 4%,5, 7, 9, 10 and the prevalence of aortic aneurysms in men aged 65 to 80 years in the general population is 4.3% to 7.7%.16, 17 Because our study is retrospective and not all patients were screened to rule out an aortic aneurysm, our data do not reflect a true prevalence but rather the prevalence of aortic aneurysm diagnosis. As a result, it is difficult to compare our data with these other studies. The prevalence of aortic aneurysm diagnosis in our study was 6.2% in patients who had a heart transplant for ischemic cardiomyopathy compared with a prevalence of 2.7% in patients who had a heart transplant for other indications and a prevalence of 0.4% in patients who had abdominal organ transplants. The higher prevalence in patients with ischemic cardiomyopathy is most likely associated with the similarities of risk factors for aortic aneurysms and ischemic cardiomyopathy.

Changes in screening practice patterns appear to have affected the prevalence of aortic aneurysms in heart transplant patients in our study. Corresponding to the increased frequency of screening for aortic aneurysms from 1997 onwards, the prevalence of diagnosis increased from 3.0% to 5.8%. The earlier (1987 to 1997) and later (1997 to 2000) groups of heart transplant patients were not significantly different with regard to mean age at transplant, presence of comorbidities, or proportion with ischemic cardiomyopathy. None of the patients who had the aortic aneurysm found during the latter period when screening was more common died of aneurysm rupture.

Elective repair of aortic aneurysms in transplant patients can be performed safely, with minimal morbidity and mortality. In this series, eight patients underwent elective repair without any fatalities. Postoperative morbidity included long-term hemodialysis in one patient and a type II endoleak after endovascular repair in another patient. No patient needed greater than 15 days of hospitalization after elective aneurysm repair. In addition, in our series, all of the transplant patients had normal ejection fractions and tolerated aortic cross clamping in the cases of open repairs.

Conclusion 

Aortic aneurysms are a significant clinical problem in organ transplant patients. Compared with patients without transplant, aortic aneurysms in abdominal and heart transplant patients expand more than twice as rapidly. Aortic aneurysms that have been diagnosed in transplant patients have a high rate of rupture, and aneurysm rupture in transplant patients is associated with poor outcomes. Finally, transplant patients appear to do well after elective aortic aneurysm repair. On the basis of these findings, we conclude that early diagnosis and treatment of aortic aneurysms in transplant patients is critical. At the time of initial pretransplant evaluation, we recommend a protocol of screening all cardiac transplant patients over 45 years of age or with ischemic cardiomyopathy. Patients having abdominal transplants do not need to be screened. When a small aortic aneurysm is found in a transplant patient, we recommend close surveillance (imaging every 6 months) and prompt repair of all aortic aneurysms 5.0 cm in diameter or larger.