Analysis of expansion patterns in 4-4.9 cm abdominal aortic aneurysms

Our objective was to analyze the growth pattern of 4-4.9 cm infrarenal abdominal aortic aneurysms (AAAs). We used an observational, longitudinal, prospective study design. We followed 4-4.9 cm AAAs with 6-monthly abdominal computed tomographic (CT) scans (January 1988-August 2004). AAA growth was defined as an increase in aortic diameter > or =2 mm in each surveillance period. We established the aortic expansion pattern in AAA with three or more CT scans as continuous, discontinuous. The latter includes at least one period of nongrowth (<2 mm/6 months). We studied the influence of cardiovascular risk factors (CVRFs), comorbidity, and AAA anatomical characteristics using the chi-squared test, t-test, life tables, and Kaplan-Meier for statistical analysis. We included 195 patients: 183 (93.8%) men, age 71 +/- 8.3 years (50-90). The follow-up period was 50 +/- 36.4 months (6.5-193.7). The growth pattern (n =131) was continuous in 15 (11.5%) and discontinuous in 116 (88.5%) AAA. The mean expansion rate was higher in AAAs with continuous expansion (7.92 +/- 3.74 vs. 2.74 +/- 2.94 mm/year, p < 0.0001). No CVRFs or comorbidity influenced the expansion pattern (p > 0.05). The eccentric thrombus was associated with a greater incidence of continuous growth (p = 0.05), with no influence of aortic calcification (p > 0.1). The expansion of 4-4.9 cm AAA is mostly irregular and unpredictable. We have not found any modifiable risk factors which influence their growth pattern. The eccentric distribution of the thrombus is associated with continuous expansion.     

Aortic necks of ruptured abdominal aneurysms dilate more than asymptomatic aneurysms after endovascular repair

BACKGROUND: Endovascular repair of abdominal aortic aneurysm (AAA) is increasingly used. We evaluated if a difference exists in the rate of change of the aortic neck diameter between non-ruptured and ruptured AAAs after endovascular aneurysm repair (EVAR). METHODS: Details of patients undergoing elective (group I) and emergency (group II) EVAR using Talent stents between October 1999 and September 2005 were reviewed. Top neck diameters were prospectively recorded on the hospital database from computed tomography scans preoperatively and at 1, 3, 12, and 24 months postoperatively. The aortic neck diameter rate of change was calculated for each group. RESULTS: Endovascular repair was performed on 110 elective and 41 emergency patients, of which 100 (80 male) elective and 29 (26 male) emergency patients were included in this analysis. Mean age was similar in each group. Stents were oversized by 20.9% +/- 13.6% in group I and by 24.7% +/- 16.3% in group II (P = .37). The preoperative mean proximal aortic neck was larger in group II (25.0 +/- 3.3 mm vs 23.5 +/- 2.8 mm; P = .029). The growth rate of the top neck diameter was significantly greater at 12 months (1.48 +/- 2.4 mm/year vs 3.89 +/- 6.24 mm/year; P = .04) and 24 months (.99 +/- 1.1 mm/year vs 2.61 +/- 3.3 mm/year; P = .04) in group II than in group I. A decreasing sac size was found in 68.2% of patients whose neck dilated. The complication rate was similar in each group. CONCLUSION: Aneurysm necks in patients with ruptured aneurysms are larger and dilate at a greater rate than those with nonruptured aneurysms. The accelerated rate of expansion in some patients must be borne in mind during follow-up and in secondary endovascular interventions and conversion to open surgery.     

Hyperhomocysteinaemia is associated with the rate of abdominal aortic aneurysm expansion.

OBJECTIVES: Previous literature has suggested an association between AAA and the presence of elevated plasma homocysteine levels (HCY). Homocysteine can stimulate elastolysis in the arterial media via activation of elastase and matrix metalloproteinases. No evidence in the literature exists correlating aneurysm expansion and HCY. The study objective is to identify whether the rate of AAA expansion is related to HCY. METHODS: 108 patients undergoing surveillance for AAA were identified at our vascular surgical unit. AAA size and growth rate were assessed by serial ultrasonographic measurements. Fasting total HCY levels were measured using fluorescence polarisation immunoassays. Demographic details and atherosclerotic risk factors were noted all AAA patients. A multivariate analysis was performed for growth rate vs. HCY, hypertension and hypercholesterolaemia. The correlation between AAA growth rate, AAA size and HCY levels were calculated. RESULTS: 60% of patients with AAA had some degree of hyperhomocysteinaemia (> 15 micromol/l). Multivariate analysis showed HCY to be the only significant factor affecting AAA growth rate. A positive correlation was demonstrated between HCY levels and AAA growth rate using a linear regression model (R=0.28, p=0.003). Median growth rate among patients with hyperHCY was double that of patients with normal HCY (0.5 mm/month vs. 0.25 mm/month, p=0.003). A growth rate of > 10 mm/year was seen in 25% of hyper HCY patients and in only 2% of patients with normal HCY. In addition patients with hyper HCY and larger AAAs (> 4 cm) had a growth rate twice as fast as patients with hyper HCY and AAAs < 4 cm. CONCLUSIONS: A correlation between HCY and growth rate exists, although this is weak due to the multifactorial aetiology of AAAs. HyperHCY patients have faster expansion rates than patients with normal HCY, with significant numbers demonstrating rapid expansion (> 10 mm/year) and therefore an increased risk of rupture.     

The use of statins and fate of small abdominal aortic aneurysms

The aim of this study was to evaluate the value of statins in reducing abdominal aortic aneurysm (AAA) growth rate and improving freedom from aneurysm repair or rupture. One hundred and twenty-one patients with AAA undergoing ultrasonographic surveillance for at least one year were included in this retrospective study. Patients treated with statins had a decreased linear aneurysm growth rate than those not receiving statins (1.9+/-1.8 mm/year vs. 2.6+/-2.4 mm/year, P=0.27), but this difference did not reach statistical significance. Statin users had a better survival freedom from aneurysm repair or rupture (at 5 years: 72.3% vs. 52.5%, P=0.048). The impact of treatment with statins was even more evident in patients with a baseline aneurysm diameter<40 mm (at 5 years: 84.0% vs. 58.8%, P=0.022). When adjusted for age, coronary artery disease and baseline aneurysm diameter, treatment with statins had significantly better survival freedom from aneurysm repair or rupture (P=0.012, RR 0.34, 95% CI 0.14-0.78). The use of statins seems to slightly decrease the AAA growth rate and to significantly improve freedom from aneurysm repair and rupture.     

Expansion rates and outcomes for the 3.0-cm to the 3.9-cm infrarenal abdominal aortic aneurysm

OBJECTIVE: This study was performed for the determination of the expansion rates and outcomes and for recommendations for the surveillance of the 3.0-cm to 3.9-cm abdominal aortic aneurysm (AAA). DESIGN: The study was observational with data from patients screened with ultrasound scanning for AAA at five Veterans Affairs Medical Centers for enrollment in the Aneurysm Detection and Management Trial. The eligibility requirements included: AAA from 3.0 cm to 3.9 cm in diameter and at least one repeat ultrasound scan more than 90 days after the initial screening. Patients also completed a questionnaire for demographic data and the determination of the presence of risk factors associated with AAA. The study endpoints included: 1, both mean and median expansion rates; 2, moderate expansion (>4 mm/year); 3, no expansion; 4, all causes of death; 5, AAA rupture; 6, expansion to 4 cm or more; 7, expansion to 5.0 cm or more; and 8, operative repair. RESULTS: Ultrasound scan screening results identified 1445 patients with 3.0-cm to 3.9-cm AAAs. Seven hundred ninety men met the ultrasound scan criterion of having at least two ultrasound scan studies during the study period, and these 790 men were used for this study. Mean AAA size was 3.3 cm, with an average follow-up period of 3.89 +/- 1.93 years. The median expansion rate was 0.11 cm/year. Expansion rates were significantly different (P <.001) between 3.0-cm and 3.4-cm cm AAA and 3.5-cm and 3.9-cm AAA. There were no reported AAA ruptures during the study period, although cause of death data were available in only 43% of the patients. Few 3.0-cm to 3.9-cm AAAs expanded to 5.0 cm or more during the study period. The patients with 3.0-cm to 3.9-cm AAAs who underwent operative repair during the study period were younger, had larger initial AAA diameters, and had more rapid expansion rates. CONCLUSION: AAAs of 3.0 cm to 3.9 cm expanded slowly, did not rupture, and rarely had operative repair or expanded to more than 5.0 cm in our study of male patients. Expansion rates and the incidence rate of operative repair are more common in the 3.5-cm to 3.9-cm AAA when compared with the 3.0-cm to 3.4-cm AAA.     

Statins are associated with a reduced infrarenal abdominal aortic aneurysm growth.

OBJECTIVE: To evaluate the effect of statins on aneurysm growth in a group of consecutive patients under surveillance for infrarenal aortic aneurysms (AAA). MATERIALS AND METHODS: All patients (59 statin users, 91 non-users) under surveillance between January 2002 and August 2005 with a follow-up for aneurysm growth of at least 12 months and a minimum of three diameter evaluations were retrospectively included in the analysis. Multiple regression analysis, weighted with the number of observations, was performed to test the influence of statins on AAA growth rate. RESULTS: During a median period of 3.1 (1.1-13.1) years the overall mean aneurysm growth rate was 2.95+/-2.8 mm/year. Statin users had a 1.16 mm/year lower AAA growth rate compared to non-users (95% CI 0.33-1.99 mm/year). Increased age was associated with a slower growth (-0.09 mm/year per year, p = 0.003). Female gender (+1.82 mm/year, p = 0.008) and aneurysm diameter (+0.06 mm/year per mm, p = 0.049) were associated with increased AAA growth. The use of non-steroidal anti-inflammatory drugs, chronic lung disease, or other cardiovascular risk factors were not independently associated with AAA growth. CONCLUSIONS: Statins appear to be associated with attenuation of AAA growth, irrespective of other known factors influencing aneurysm growth.     

Abdominal aortic aneurysms following orthotopic heart transplantation

The purpose of these authors' study was to analyze their center's experience with orthotopic heart transplantation (OHT) and abdominal aortic aneurysms (AAA) with particular attention to corticosteroid dosing, hemodynamic parameters, and aneurysm growth rate. A retrospective review of all patients (453) who underwent OHT at their university-affiliated medical center over an 18-year period (1981-1999) was undertaken. Nine (2%) patients who developed AAAs were identified and aneurysm growth was correlated with corticosteroid immunosuppression and hemodynamic parameters. The mean age of OHT patients was 44.5 +/-15 years and the majority were males (371 males, 82%). Median follow-up was 5.7 years. Ischemic cardiomyopathy (IC) was the most common indication for transplantation (45.5% of patients). All AAA patients were male (p=0.157), with a mean age of 58.4 +/-4.8 years (p=0.001), and had undergone OHT for IC (p=0.001). Mean arterial blood pressure and ejection fraction in the AAA patients had increased from pretransplant values of 107 mm Hg and 14.3 +/-5.7% to 142 mm Hg (p=0.017) and 54.1 +/-14.1% (p<0.001), respectively, before aneurysm repair. Mean aneurysm diameter at the time of repair was 6.0 +/-0.8 cm, and the average growth rate was 1.2 +/-0.4 cm/year in the 4 patients in whom it could be measured. Aneurysm repair was performed urgently in 2 patients and electively in 7 patients with 1 early postoperative death (11%). The extent of corticosteroid immunosuppression, corticosteroid pulses, and total corticosteroid dosing did not correlate with the rate of aneurysm growth. Improved hemodynamics and progressive posttransplant hypertension may contribute to aneurysm formation and growth in this group of patients.     

Prediction of rupture risk in abdominal aortic aneurysm during observation: wall stress versus diameter

OBJECTIVES: We previously showed that peak abdominal aortic aneurysm (AAA) wall stress calculated for aneurysms in vivo is higher at rupture than at elective repair. The purpose of this study was to analyze rupture risk over time in patients under observation. METHODS: Computed tomography (CT) scans were analyzed for patients with AAA when observation was planned for at least 6 months. AAA wall stress distribution was computationally determined in vivo with CT data, three-dimensional computer modeling, finite element analysis (nonlinear hyperelastic model depicting aneurysm wall behavior), and blood pressure during observation. RESULTS: Analysis included 103 patients and 159 CT scans (mean follow-up, 14 +/- 2 months per CT). Forty-two patients were observed with no intervention for at least 1 year (mean follow-up, 28 +/- 3 months). Elective repair was performed within 1 year in 39 patients, and emergent repair was performed in 22 patients (mean, 6 +/- 1 month after CT) for rupture (n = 14) or acute severe pain. Significant differences were found for initial diameter (observation, 4.9 +/-.1 cm; elective repair, 5.9 +/-.1 cm; emergent repair, 6.1 +/-.2 cm; P <.0001) and initial peak wall stress (38 +/- 1 N/cm(2), 42 +/- 2 n/cm(2), 58 +/- 4 N/cm(2), respectively; P <.0001), but peak wall stress appeared to better differentiate patients who later required emergent repair (elective vs emergent repair: diameter, 3% difference, P =.5; stress, 38% difference, P <.0001). Receiver operating characteristic (ROC) curves for predicting rupture were better for peak wall stress (sensitivity, 94%; specificity,81%; accuracy, 85% [with 44 N/cm(2) threshold]) than for diameter (81%, 70%, 73%, respectively [with optimal 5.5 cm threshold). With proportional hazards analysis, peak wall stress (relative risk, 25x) and gender (relative risk, 3x) were the only significant independent predictors of rupture. CONCLUSIONS: For AAAs under observation, peak AAA wall stress seems superior to diameter in differentiating patients who will experience catastrophic outcome. Elevated wall stress associated with rupture is not simply an acute event near the time of rupture.     

Optimal interval screening and surveillance of abdominal aortic aneurysms.

OBJECTIVES: to determine safe and optimal intervals of rescreening and surveillance for AAA. METHODS: hospital-based mass screening of 6339 65-73-year-old men from 1994-98. 76.4% attended. One hundred and ninety-one (4%) had AAA53 cm. Twenty-four (0.5%) were initially >5 cm and referred for surgery, while the rest were offered annual control scans to check for expansion. Later, all 348 (7.5%) men who 3 to 5 years ago had an ectatic aorta (infrarenal aortic diameter of 25-29 mm or distal/renal aortic diameter ratio >1.2) were offered rescreening. Of these, 62 (18%) died before rescanning, while 248 of the survivors attended rescreening (87%). Furthermore, a random sample of 380 of those with non-ectatic aortas were offered rescreening. Of these, 49 (13%) died before rescreening (p=0.06), while 275 (83%) of the survivors attended re-screening. RESULTS: none of the controls had developed AAA. Of those who initially had an 25-29 mm aorta, 29% had developed AAA (size range 30-48 mm) with expansion rates varying from 1.0 to 4.7 mm/year. Only 3.5% with a ratio >1.2 developed AAA (size range: 30-34 mm) with expansion rates from 1.3 to 2.4 mm/year. During the fourth year of surveillance some AAA initially sized below 3.5 cm expanded to above 5 cm, while some sized 3.5-3.9 cm did so during the second year, >4 cm did so during the first year of surveillance. CONCLUSION: rescreening for AAA can be restricted to initially ectatic aortas sized 25-29 mm at 5-year intervals. Surveillance of small AAA can be restricted to 1-4 year intervals.     

Selective management of abdominal aortic aneurysms smaller than 5.0 cm in a prospective sizing program with gender-specific analysis

PURPOSE: We present extended follow-up findings of the Kingston prospective sizing program for patients with abdominal aortic aneurysm (AAA) smaller than 5.0 cm in diameter, with gender-specific analysis. METHODS: From 1976 to 2001, 895 patients (688 men, 207 women) with AAA smaller than 5.0 cm were entered, regardless of fitness, in a prospective sizing program in which computed tomography scans were obtained every 6 months. Operations were performed in fit patients with an increase in AAA size to 5 cm (n = 190), AAA expansion greater than 0.5 cm in 6 months (n = 27), or for other reasons (n = 33). Follow-up continued until AAA rupture, surgery, death, or removal from the program. RESULTS: No AAA smaller than 5.0 cm ruptured during prospective follow-up. There was a statistically significant increase in expansion rate relative to size at entry, with the highest mean expansion rate of 0.52 cm/y for AAA 4.5 to 4.9 cm in diameter. There was no significant difference in AAA expansion rate between men and women. The frequency of surgery was inversely related to age at entry, but was positively related to AAA size at entry, with patients with AAA 4.5 to 4.9 cm at entry 6.8 times more likely (95% confidence interval, 4.3-10.7) to undergo surgery than those with AAA 3.0 to 3.4 cm at entry. Women were older than men at entry, and age at entry in those undergoing surgery was significantly greater in women. CONCLUSIONS: The study confirms the results of the United Kingdom Small Aneurysm Trial and the Aneurysm Detection and Management Study, that is, that risk for rupture is extremely unlikely with AAA smaller than 5.0 cm, which enables safe follow-up surveillance programs in both men and women with AAA smaller than 5.0 cm.     

A prospective study to define the optimum rescreening interval for small abdominal aortic aneurysm

A prospective study of 99 patients with small abdominal aortic aneurysms was undertaken using serial ultrasound to assess the optimum screening interval. Fifty-three patients had aneurysms measuring 2.5–3.9 cm and 46 patients aneurysms of 4.0–4.9 cm. Aneurysms measuring 2.5–3.9 cm were screened annually and those >4.0 cm every 6 months. There were eight deaths in the 2.5–3.9 cm group, none attributable to a ruptured aneurysm and five patients have had their aneurysm repaired. Nine patients died in the 4.0–4.9 cm group, one with a ruptured aneurysm measuring 5.6 cm at her previous screening visit and who was unfit for operation. No other patient had an aneurysm which ruptured between scans. There were seven elective repairs in this group. No patient died following elective operation in either group. The mean growth rate of aneurysms in the 2.5–3.9 cm group was 2.2 mm in the first year, 2.8 mm in the second and 1.8 mm in the third. Corresponding growth rates in the 4.0–4.9 cm group were 2.7 mm, 4.2 mm and 2.2 mm. This study supports a policy of annual screening for aneurysms measuring 2.5–3.9 cm and 6-monthly screening for those ⩾ 4.0 cm. Copyright © 1996 The International Society for Cardiovascular Surgery.     

Does the angiotensin-converting enzyme (ACE) gene polymorphism affect rate of abdominal aortic aneurysm expansion?

OBJECTIVES: the tissue renin-angiotensin system (RAS), which plays an important role in vascular structure and function, is regulated in part by an insertion-deletion polymorphism of the angiotensin converting enzyme (ACE) gene. We hypothesised that ACE genotype might affect rate of AAA expansion via modulating long-term structural changes associated with RAS activation. METHODS: fifty-eight patients (50 M, mean age 70 years, mean initial aneurysm size 4.3 cm) with current or previous AAA and serial (>3) annual ultrasound measurements of antero-posterior AAA size provided a sample of leucocyte DNA for ACE genotyping. AAA expansion rate (cm per year) for individual subjects was calculated by linear regression. RESULTS: median AAA expansion rate was 0.28 cm/year (range 0-1.8 cm/year), and the genotype distribution included DD (n=14), DI (n=29) and II (n=15). Corresponding median AAA expansion rates for each of the three genetic subgroups were 0.22, 0.32 and 0.30 cm/year, respectively (p=0.6, nonparametric). CONCLUSIONS: the wide inter-individual variability in AAA expansion rate is likely to reflect complex genetic and environmental interactions, but the lack of any relationship with ACE genotype suggests that differences in vascular ACE activity in aortic tissue are not major determinants of the variability in rate of AAA dilatation.     

The risk of rupture in untreated aneurysms: the impact of size,gender, and expansion rate

OBJECTIVE: The purpose of this study was to establish the risk of rupture as related to size of abdominal aortic aneurysm (AAA), gender, and expansion of the aneurysm. METHODS: Between 1976 and 2001, 476 patients with conditions considered unfit for surgery with AAA 5.0 cm or more were followed with computed tomographic scans every 6 months until rupture, surgery, death, or deletion from follow-up. Surgery was performed for rupture (n = 22), improved medical condition (n = 37), increase in size (n = 95), symptoms (n = 17), and other reasons (n = 24). RESULTS: Fifty ruptures occurred during the follow-up period. The average risk of rupture (and standard error) in male patients with 5.0-cm to 5.9-cm AAA was 1.0% (0.01%) per year, in female patients with 5.0-cm to 5.9-cm AAA was 3.9% (0.15%) per year, in male patients with 6.0-cm or greater AAA was 14.1% (0.18%) per year, and in female patients with 6.0-cm or greater AAA was 22.3% (0.95%) per year. CONCLUSION: The risk of rupture in male patients with AAA 5.0 to 5.9 cm is low. The four-time higher risk of rupture in female patients with AAA 5.0 to 5.9 cm suggests a lower threshold for surgery be considered in fit women. The data regarding risk of rupture in patients with AAA 6.0 cm or more may allow more appropriate decision analysis for surgery in patients with unfit conditions with large AAA.     

Rate of change in abdominal aortic aneurysm diameter after endovascular repair

OBJECTIVE: Untreated abdominal aortic aneurysms (AAAs) enlarge at a mean rate of 3.9 mm/y with great individual variability. We sought to determine the effect of endovascular repair on the rate of change in aneurysm size. METHODS: There were 110 patients who underwent endovascular AAA repair at Stanford University Medical Center and who were followed up for 1 to 30 months (mean, 10 months) with serial contrast-infused helical computed tomography (CT). Maximal aneurysm diameter was determined using two independent methods: (1) measured manually, from cross-sectional computed tomography (XSCT) angiograms and (2) calculated from quantitative three-dimensional computed tomography (3DCT) data as orthonormal diameter. RESULTS: Maximal cross-sectional aneurysm diameter measured by hand (XSCT) and calculated as orthonormal values (3DCT) correlated closely (r = 0.915; P <.001). The XSCT-measured diameter was larger by 2.3 +/- 3. 75 mm (P <.001), and the 95% CI for SE of the bias was 1.85 to 2.75 mm. Preoperative aneurysm diameter (XSCT 59.1 +/- 8.4 mm; 3DCT 58.1 +/- 9.3 mm) did not differ significantly from the initial postoperative diameter. Considering all patients, XSCT diameter decreased at a rate of 0.34 +/- 0.69 mm/mo, and 3DCT diameter decreased at a rate of 0.28 +/- 0.79 mm/mo. Aneurysms in patients without endoleaks had a higher rate of decrease, an XSCT diameter by 0.50 +/- 0.74 mm/mo, and 3DCT diameter by 0.46 +/- 0.84 mm/mo. In these patients, mean absolute decrease in diameter at 6 months was 3. 4 +/- 4.5 mm (XSCT) and 3.3 +/- 5.9 mm (3DCT) and at 12 months, 5.9 +/- 5.7 mm (XSCT) and 5.4 +/- 5.7 mm (3DCT). Aneurysms in patients with persistent endoleaks did not change in mean XSCT diameter, and 3DCT diameter increased by 0.12 +/- 0.52 mm/mo (not significant). Aneurysm diameter remained within 4 mm of original size in 68% (3DCT) to 71% (XSCT) of patients. In one patient, aneurysm diameter increased (XSCT and 3DCT) more than 5 mm. Four patients who had a new onset endoleak had a much higher expansion rate than those with a chronic endoleak (P <.05). CONCLUSIONS: The rate of decrease in aneurysm size (annualized 3.4-4.1 mm/y) after endovascular repair of AAA approximates the reported expansion rate in untreated aneurysms. However, individual aneurysm behavior is unpredictable, and the presence of an endoleak is unreliable in predicting changes in diameter. New onset endoleaks are associated with an enlargement rate greater than that of untreated aneurysms.     

Association of intraluminal thrombus in abdominal aortic aneurysm with local hypoxia and wall weakening

PURPOSE: Our previous computer models suggested that intraluminal thrombus (ILT) within an abdominal aortic aneurysm (AAA) attenuates oxygen diffusion to the AAA wall, possibly causing localized hypoxia and contributing to wall weakening. The purpose of this work was to investigate this possibility. METHODS: In one arm of this study, patients with AAA were placed in one of two groups: (1) those with an ILT of 4-mm or greater thickness on the anterior surface or (2) those with little (< 4 mm) or no ILT at this site. During surgical resection but before aortic cross-clamping, a needle-type polarographic partial pressure of oxygen (PO2) electrode was inserted into the wall of the exposed AAA, and the PO2 was measured. The probe was advanced, and measurements were made midway through the thrombus and in the lumen. Mural and mid-ILT PO2 measurements were normalized by the intraluminal PO2 measurement to account for patient variability. In the second arm of this study, two AAA wall specimens were obtained from two different sites of the same aneurysm at the time of surgical resection: group I specimens had thick adherent ILT, and group II specimens had thinner or no adherent ILT. Nonaneurysmal tissue was also obtained from the infrarenal aorta of organ donors. Specimens were subjected to histologic, immunohistochemical, and tensile strength analyses to provide data on degree of inflammation (% area inflammatory cells), neovascularization (number of capillaries per high-power field), and tensile strength (peak attainable load). Additional specimens were subjected to Western blotting and immunohistochemistry for qualitative evaluation of expression of the cellular hypoxia marker oxygen-regulated protein. RESULTS: The PO2 measured within the AAA wall in group I (n = 4) and group II (n = 7) patients was 18% +/- 9% luminal value versus 60% +/- 6% (mean +/- SEM; P <.01). The normalized PO2 within the ILT of group I patients was 39% +/- 10% (P =.08 with respect to the group I wall value). Group I tissue specimens showed greater inflammation (P <.05) compared with both group II specimens and nonaneurysmal tissue: 2.9% +/- 0.6% area (n = 7) versus 1.7% +/- 0.3% area (n = 7) versus 0.2% +/- 0.1% area (n = 3), respectively. We found similar differences for neovascularization (number of vessels/high-power field), but only group I versus control was significantly different (P <.05): 16.9 +/- 1.6 (n = 7) vs 13.0 +/- 2.3 (n = 7) vs 8.7 +/- 2.0 (n = 3), respectively. Both Western blotting and immunohistochemistry results suggest that oxygen-regulated protein is more abundantly expressed in group I versus group II specimens. Tensile strength of group I specimens was significantly less (P <.05) than that for group II specimens: 138 +/- 19 N/cm2 (n = 7) versus 216 +/- 34 N/cm2 (n = 7), respectively. CONCLUSION: Our results suggest that localized hypoxia occurs in regions of thicker ILT in AAA. This may lead to increased, localized mural neovascularization and inflammation, as well as regional wall weakening. We conclude that ILT may play an important role in the pathology and natural history of AAA.     

Surveillance of small aortic aneurysms does not alter anatomic suitability for endovascular repair

OBJECTIVE: Small abdominal aortic aneurysms (AAAs; 4-5.4 cm) are more likely to be suitable for endovascular aneurysm repair (EVAR) than large aortic aneurysms (>5.5 cm). The purpose of this study was to determine whether small AAA growth is associated with the development of morphologic characteristics that decrease eligibility for EVAR. METHODS: We studied 54 patients who underwent 2 or more computed tomography scans with 3-dimensional reconstruction during surveillance of small AAAs. Morphologic aortic aneurysm features and changes were measured according to Society for Vascular Surgery reporting standards. Suitability for EVAR was determined by neck anatomy (diameter, length, and angulations), iliac artery morphology, and total aortic aneurysm angulation and tortuosity. RESULTS: The median age of the study cohort was 73 years (interquartile range [IQR], 65-77 years). The median follow-up period was 24 months (IQR, 15-36 months). The median small AAA diameter increased from 44.5 mm (IQR, 41-48 mm) to 48.9 mm (IQR, 45.7-52.0 mm). The median aortic neck diameter increased from 23.0 to 24.0 mm (P = .002), whereas median neck length decreased from 26.5 to 20.0 mm (P = .001). Aortic aneurysm median tortuosity index increased from 1.09 to 1.11 (P = .05). No significant changes in iliac artery morphology occurred. Overall, the anatomic suitability for endovascular repair did not significantly change during the study period (74% vs 69%; McNemar test; P = .25). CONCLUSIONS: Changes in aortic morphology are frequently associated with small AAA growth at mid-term follow-up, but such changes are minor and do not affect overall anatomic suitability for EVAR. These data reveal that continued surveillance of small AAAs does not threaten the window of opportunity for EVAR.     

Genotype-phenotype relationships in an investigation of the role of proteases in abdominal aortic aneurysm expansion

BACKGROUND: The aim of the study was to investigate the effect of functional polymorphisms in promoters of matrix metalloproteinase (MMP) 2, MMP-3, MMP-9, MMP-12 and plasminogen activator inhibitor (PAI) 1 genes on the growth rate of small abdominal aortic aneurysms (AAA). METHODS: Some 455 individuals with a small AAA (4.0-5.5 cm) were monitored for aneurysm growth by ultrasonography (mean follow-up 2.6 years). They also provided a DNA sample for analysis of the -1306 C > T, -1171 5A > 6A, -1562 C > T, -82 A > G and -675 4G > 5G alleles of MMP-2, MMP-3, MMP-9, MMP-12 and PAI-1, respectively. Mean linear AAA growth rates were calculated by flexible modelling; the sample size was sufficient to detect variants that influenced the growth rate by 25 per cent. RESULTS: For MMP-2, MMP-9 and MMP-12 genotypes, growth rates were similar to the mean linear growth rate of 3.08 mm per year. For MMP-3, growth rates were 3.05 (for 5A5A), 3.19 (for 5A6A) and 2.90 (for 6A6A) mm per year. For PAI-1, patients with 4G4G, 4G5G and 5G5G genotypes had growth rates of 3.18, 2.92 and 3.47 mm per year, respectively, for aneurysms with a baseline diameter of 45.1, 44.6 and 46.2 mm. The increased growth rate for patients with PAI-1 5G5G genotype was not statistically significant (P = 0.061), although these patients had the lowest plasma PAI-1 concentrations (P = 0.018). CONCLUSION: There was no evidence that any specific MMP polymorphism had a clinically significant effect on AAA expansion. The plasminogen system may have a small but clinically significant role in AAA development. Much larger studies would be needed to evaluate genes of smaller effect.     

Outcomes of original and low-permeability Gore Excluder endoprosthesis for endovascular abdominal aortic aneurysm repair

OBJECTIVE: Because of concern about the percentage of enlarging abdominal aortic aneurysms (AAAs) after endovascular repair with the Excluder device (W.L. Gore & Assoc, Inc, Sunnyvale, Calif), the graft material was modified to reduce its permeability and released for commercial use in mid-2004. We studied all AAA repairs with Excluder endografts performed at our institution, including the original-permeability (OP) version (n = 99) and the low-permeability (LP) version (n = 48). METHODS: All patients were followed up with serial computed tomography (CT) angiography and three-dimensional (3D) reconstruction. Morphologic measurements, including AAA diameter and 3D volume, were prospectively entered into a database to evaluate changes in AAA size over time. Owing to the length of available follow-up for the LP version, the primary end point was AAA size change at 6 and 12 months, evaluated by Mann-Whitney U test for unpaired samples. RESULTS: Preoperative and postoperative anatomy was similar in the two groups, including AAA diameter (OP, 5.6 +/- 1 cm; LP, 5.8 +/- 2 cm; P = .3), aortic neck length (OP, 21 +/- 1 mm; LP, 22 +/- 2 mm; P = .9), postoperative aortic seal zone (OP, 18 +/- 1 mm; LP, 16 +/- 1 mm, P > .1) and iliac seal zone (OP, 33 +/- 1 mm, LP 31 +/- 1 mm, P = .2). The rate of sac shrinkage differed significantly. Orthogonal diameter measurements showed a significant difference in the rate of shrinkage by 12 months postoperatively (OP, -2.1 +/- 1 mm; LP, -5.1 +/- 1 mm; P = .01). By 3D volume, the rate of shrinkage was considerably different between the two groups at both 6 and 12 months (12 months: OP, -6% +/- 1%; LP, -20 +/- 4%; P = .0006). There was no enlargement by diameter in either group at 6 or 12 months postoperative. By standard volume criteria, however, 12 of 99 patients in the OP group and one of 48 patients in the LP group had significant AAA enlargement < or =12 months (P = .04). Of these, four of 12 patients in the OP group had enlargement without apparent endoleak, even on delayed-contrast CT. The remainder had persistent type II endoleaks (8/12 in the OP group and 1/1 in the LP group). Multivariate analysis revealed graft permeability (P < .0001) and endoleak (P < .0001) as independent factors in aneurysm size change. In the OP group long-term, the average AAA enlarged at later time points compared with the prior scan: 24 months, -0.2%; 36 months, +0.2%; 48 months, +2%; and 60 months, +2% (P < .0002). CONCLUSIONS: In early follow-up, the low-permeability Excluder device is associated with a significantly greater aneurysm shrinkage rate than the original version. Clinically important enlargement also appears significantly different within 1 year of implantation. Despite these promising results, longer follow-up is needed to determine whether these differences will persist.     

Three-dimensional analysis of enlarging aneurysms after endovascular abdominal aortic aneurysm repair in the Gore Excluder Pivotal clinical trial

OBJECTIVE: Recent reports have raised concern about the percentage of enlarging abdominal aortic aneurysms (AAAs) after endovascular repair with the Gore Excluder device. As part of the investigation into this issue, a morphologic analysis was performed on enlarging aneurysms in the Excluder Pivotal clinical trial. METHODS: Computed tomographic scans were evaluated on all patients identified with enlarging aneurysms (5-mm increase by Core laboratory or site) and at least 4 years of follow-up in the Excluder Pivotal clinical trial. Three-dimensional reconstruction, a set of 24 standard morphologic measurements, and analysis of potential enlargement mechanisms were performed. RESULTS: Of 112 trial patients with 4 years of follow-up, 38 AAAs (34%) were identified as enlarging. Data were obtained from 196 computed tomographic scans (the mean interval was 47 months from first to last scan). Of the 158 scans with a prior scan for comparison, 41% demonstrated growth relative to the initial scan by diameter criteria, but 79% demonstrated growth relative to the initial scan by 3-dimensional volume criteria (P < .0001 vs diameter; chi2 analysis). This difference was most evident at early time points: at 1 year, diameter criteria indicated that 8% of these AAAs were enlarging, but 56% were already enlarging by volume criteria. On average, enlargement was detected by volume 18 months before it was detected by diameter (P < .0001), and at a smaller diameter (55 +/- 1 mm vs 60 +/- 1 mm; P < .0001). Only 19% of scans (39% of patients) had apparent endoleaks. Scans with apparent endoleaks demonstrated a greater interval rate of growth as compared with those without apparent endoleak (3.6 +/- 0.8 mm vs 1.9 +/- 0.3 mm [P < .02] by diameter; 23 +/- 4 cm3 vs 11 +/- 1 cm3 [P < .001] by volume). Although the etiology of enlargement may be endotension or device permeability in up to 74% of patients, other potential causes of aneurysm enlargement included neck apposition length less than 15 mm (15 patients; 39%), large aortic diameter relative to device (18%), large iliac diameter (5%), and iliac apposition length less than 15 mm (20%). Multiple potential etiologies of enlargement were present in 53% of AAAs. CONCLUSIONS: The etiology of aneurysm enlargement in the Excluder Pivotal trial is likely multifactorial, including endoleak, inadequate attachment site length, and endotension or device permeability. Even by conservative criteria, a substantial percentage of aneurysm growth with the original device is likely due to material permeability. Three-dimensional volume criteria detected aneurysm enlargement more frequently, at a smaller diameter, and on average 18 months sooner than standard diameter criteria, thus suggesting a role in further investigation of this issue.     

The role of aortic neck dilation and elongation in the etiology of stent graft migration after endovascular abdominal aortic aneurysm repair with a passive fixation device

OBJECTIVE: Endovascular repair of abdominal aortic aneurysm (AAA) is complicated by the potential for stent graft migration over time. Factors including the type of fixation, initial proximal fixation length, and dilation and elongation of the infrarenal aortic neck may contribute to device migration. We sought to determine when device migration is a real phenomenon with actual device movement that compromises aneurysm exclusion. METHODS: Computed tomographic (CT) scans and computer reconstructions of all patients undergoing endovascular AAA repair with a passive fixation device at our institution from June 1996 to October 2004 were retrospectively reviewed. The distance from the distal renal artery to the proximal end of the stent graft at the time of initial deployment was determined for each patient. Migration was defined as a distance increase greater than 5 mm in the follow-up period; proximal fixation length, aortic neck enlargement and elongation, and neck angle were then measured. Data were further analyzed with respect to AAA growth, development of endoleak, AAA rupture, and the need for reintervention. RESULTS: A total of 308 patients with endovascular AAA repairs using a passive fixation device had complete postoperative imaging data sets; 48 patients (15.6%) with stent graft migration of 5 mm or more were identified, and 25 (8.1%) of these had a migration of 10 mm or more. Seventeen (35.4%) of 48 migration patients had a total loss of the proximal seal zone (loss patients); their average migration distance was 17.7 +/- 12.0 mm, with a mean neck shortening of 13.6 +/- 14.2 mm, and the average proximal fixation length loss was 14.0 +/- 7.6 mm. Those 31 patients with an intact proximal seal zone (nonloss patients) showed an average migration of 9.4 +/- 3.7 mm, with a mean neck lengthening of 9.6 +/- 8.4 mm and an average proximal fixation length change of 0.7 +/- 8.0 mm. Univariate analysis demonstrated significant differences between the loss and nonloss patients in follow-up duration (65.9 +/- 20.4 months vs 45.9 +/- 26.4 months; P = .01), neck dilatation at the distal renal artery (4.6 +/- 4.5 mm vs 1.8 +/- 1.9 mm; P = .026), stent graft migration distance (17.7 +/- 12.0 mm vs 9.4 +/- 3.7 mm; P = .001), change in aortic neck length (-13.6 +/- 14.2 mm vs 9.6 +/- 8.4 mm; P < .0001), change in proximal fixation length (-14.0 +/- 7.6 mm vs 0.7 +/- 8.0 mm; P < .0001), change in AAA size (1.8 +/- 7.1 mm vs -3.6 +/- 9.7 mm; P = .033), and use of a stiff body stent graft (47.1% vs 19.4%; P = .043). However, only change in aortic neck length was statistically significant on multivariate analysis (odds ratio, 0.75; 95% confidence interval, 0.591-0.961; P = .022). There were no differences between the loss and nonloss patients in time to migration discovery, initial AAA size, initial aortic neck diameter or length, initial device oversizing, initial neck angle, neck angle increase, type II endoleak, or AAA rupture. Eight of the 17 loss patients have been treated with proximal aortic cuffs; the remainder have refused reintervention, died of unrelated causes, or elected to have open repair. CONCLUSIONS: Postoperative elongation of the infrarenal aortic neck may create the radiographic perception of migration without necessarily causing a loss of proximal stent graft fixation. Patients with a total loss of the proximal seal zone actually have infrarenal aortic neck shortening, with a degree of neck dilatation beyond initial device oversizing that may compromise proximal fixation length. Conversely, those with an intact proximal seal zone demonstrate aortic neck elongation equivalent to migration, with no loss of proximal fixation length; these patients have a benign natural history without intervention. Thus, aortic neck dilatation beyond oversizing, aortic neck shortening, and loss of proximal fixation length are more clinically relevant predictors of proximal stent graft failure than simple migration distance.