Robert D. Sayers

In situ replacement of infected aortic grafts with rifampicin-bonded prostheses: The Leicester experience (1992 to 1998)

Abstract Purpose : Prosthetic graft infection after aortic aneurysm surgery is a life-threatening complication. Treatment options include total graft excision and extra-anatomic bypass grafting or in situ replacement of the graft. The latter option is gaining increasing popularity, but the long-term outcome remains uncertain, particularly in light of the increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA). We performed a prospective nonrandomized study to assess the outcome after graft excision and in situ replacement with a rifampicin-bonded prosthesis for the treatment of major aortic graft infection. Methods: In a 6-year period from January 1992 to December 1997, 11 patients (eight men, three women) with major aortic graft infection underwent total graft excision and in situ replacement with a rifampicin-bonded prosthesis. The median age of the patients was 66 years (range, 49 to 78 years). Four patients had a hemorrhage from an aortoenteric fistula, three had a retroperitoneal abscess, two had graft occlusion, one had a perigraft collection shown by means of computed tomography, and one had a ruptured suprarenal false aneurysm. Organisms were cultured from 10 patients. Results: MRSA was isolated in two patients, both of whom had originally undergone repair of a ruptured abdominal aortic aneurysm. Two patients died (18.2%) within 30 days, and three patients (27.6%) had nonfatal complications (peritoneal candidiasis, transient renal impairment, and profound anorexia). Two patients died late in the follow-up period. Seven patients remain alive and clinically free of infection. Conclusion: The long-term results after total graft excision and in situ replacement with a rifampicin-bonded prosthesis appear to be favorable. However, MRSA aortic graft infection appears to be associated with a poor prognosis. (J Vasc Surg 1999;30:92-8.)

Early Results of Fenestrated Endovascular Repair of Juxtarenal Aortic Aneurysms in the United Kingdom

Background— Fenestrated endovascular repair of abdominal aortic aneurysms has been proposed as an alternative to open surgery for juxtarenal and pararenal abdominal aortic aneurysms. At present, the evidence base for this procedure is predominantly limited to single-center or single-operator series. The aim of this study was to present nationwide early results of fenestrated endovascular repair in the United Kingdom. Methods and Results— All patients who underwent fenestrated endovascular repair between January 2007 and December 2010 at experienced institutions in the United Kingdom(>10 procedures) were retrospectively studied by use of the GLOBALSTAR database. Site-reported data relating to patient demographics, aneurysm morphology, procedural details, and outcome were recorded. Data from 318 patients were obtained from 14 centers. Primary procedural success was achieved in 99% (316/318); perioperative mortality was 4.1%, and intraoperative target vessel loss was observed in 5 of 889 target vessels (0.6%). The early reintervention (<30 days) rate was 7% (22/318). There were 11 deaths during follow-up; none were aneurysm-related. Survival by Kaplan–Meier analysis was 94% (SE 0.01), 91% (0.02), and 89% (0.02) at 1, 2, and 3 years, respectively. Freedom from target vessel loss was 93% (0.02), 91% (0.02), and 85% (0.06), and freedom from late secondary intervention (>30 days) was 90% (0.02), 86% (0.03), and 70% (0.08) at 1, 2, and 3 years. Conclusions— In this national sample, fenestrated endovascular repair has been performed with a high degree of technical and clinical success. Late survival and target vessel patency are satisfactory. These results support continued use and evaluation of this technique for juxtarenal aneurysms, but illustrate the need for a more robust evidence base.

Aneurysm Global Epidemiology Study Public Health Measures Can Further Reduce Abdominal Aortic Aneurysm Mortality

Background— Contemporary data from Western populations suggest steep declines in abdominal aortic aneurysm (AAA) mortality; however, international trends are unclear. This study aimed to investigate global AAA mortality trends and to analyze any association with common cardiovascular risk factors. Methods and Results— AAA mortality (1994–2010) using International Classification of Diseases codes were extracted from the World Health Organization mortality database and age standardized. The World Health Organization InfoBase and International Mortality and Smoking Statistics provided risk factor data. Nineteen World Health Organization member states were included (Europe, 14; Australasia, 2; North America, 2; Asia, 1). Regression analysis of temporal trends in cardiovascular risk factors (1946–2010) was done independently for correlations to AAA mortality trends. Global AAA mortality trends show substantial heterogeneity, with the United States and United Kingdom recording the greatest national decline, whereas internationally, male individuals and those <75 years of age demonstrated the greatest reductions. AAA mortality has increased in Hungary, Romania, Austria, and Denmark; therefore, the mortality decline is not universal. A positive linear relationship exists between global trends in systolic blood pressure (P⩽0.03), cholesterol (P⩽0.03), and smoking prevalence (P⩽0.02) in males and females. Body mass index demonstrated a negative linear association with AAA mortality (P⩽0.007), whereas fasting blood glucose showed no association. Conclusions— AAA mortality has not declined globally, and this study reveals that differences between nations can be explained by variations in traditional cardiovascular risk factors. Declines in smoking prevalence correlate most closely with declines in AAA mortality, and a novel obesity paradox has been identified that requires further investigation. Public health measures could therefore further reduce global AAA mortality, with greatest benefits in the younger age group.

In meta-analyses of proportion studies, funnel plots were found to be an inaccurate method of assessing publication bias

OBJECTIVE To assess the utility of funnel plots in assessing publication bias (PB) in meta-analyses of proportion studies. STUDY DESIGN AND SETTING Meta-analysis simulation study and meta-analysis of published literature reporting peri-operative mortality after abdominal aortic aneurysm (AAA) repair. Data for the simulation study were stochastically generated. A literature search of Medline and Embase was performed to identify studies for inclusion in the published literature meta-analyses. RESULTS The simulation study demonstrated that conventionally constructed funnel plots (log odds vs. 1/standard error [1/SE]) for extreme proportional outcomes were asymmetric despite no PB. Alternative funnel plots constructed using study size rather than 1/SE showed no asymmetry for extreme proportional outcomes. When used in meta-analyses of the mortality of AAA repair, these alternative funnel plots highlighted the possibility for conventional funnel plots to demonstrate asymmetry when there was no evidence of PB. CONCLUSION Conventional funnel plots used to assess for potential PB in meta-analyses are inaccurate for meta-analyses of proportion studies with low proportion outcomes. Funnel plots of study size against log odds may be a more accurate way of assessing for PB in these studies.

Association Between the Coronary Artery Disease Risk Locus on Chromosome 9p21.3 and Abdominal Aortic Aneurysm

Background—Recent genome-wide studies have shown a significant association of a locus on chromosome 9p21.3 and coronary artery disease. We performed a case-control study to investigate the association between this locus and abdominal aortic aneurysm (AAA). Methods and Results—A total of 1714 patients (899 patients with AAA and 815 controls) were genotyped for the lead single-nucleotide polymorphism, rs1333049, on chromosome 9p21. The frequency of the C (risk) allele of rs1333049 in the control group was 0.471. There was a significant association between the C allele and AAA (odds ratio, 1.22; 95% confidence interval, 1.06 to 1.39; P=0.004). The genotypic-specific odds ratios (compared with the GG genotype) were 1.17 (95% confidence interval, 0.93 to 1.47; P=0.191) for the GC genotype and 1.50 (95% confidence interval, 1.14 to 1.97; P=0.004) for the CC genotype. In logistic regression modeling, the association of the CC genotype with AAA was independent of the presence of clinical coronary artery disease (odds ratio, 1.46; 95% confidence interval, 1.11 to 1.94; P=0.008). Conclusions—Our study shows that the recently identified chromosome 9 variant that increases risk of coronary artery disease is also associated with the presence of AAA. The findings suggest that the effect of this locus on risk of cardiovascular disease extends beyond the coronary circulation.

A sequence variant associated with sortilin-1 (SORT1) on 1p13.3 is independently associated with abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is a common human disease with a high estimated heritability (0.7); however, only a small number of associated genetic loci have been reported to date. In contrast, over 100 loci have now been reproducibly associated with either blood lipid profile and/or coronary artery disease (CAD) (both risk factors for AAA) in large-scale meta-analyses. This study employed a staged design to investigate whether the loci for these two phenotypes are also associated with AAA. Validated CAD and dyslipidaemia loci underwent screening using the Otago AAA genome-wide association data set. Putative associations underwent staged secondary validation in 10 additional cohorts. A novel association between the SORT1 (1p13.3) locus and AAA was identified. The rs599839 G allele, which has been previously associated with both dyslipidaemia and CAD, reached genome-wide significance in 11 combined independent cohorts (meta-analysis with 7048 AAA cases and 75 976 controls: G allele OR 0.81, 95% CI 0.76-0.85, P = 7.2 × 10(-14)). Modelling for confounding interactions of concurrent dyslipidaemia, heart disease and other risk factors suggested that this marker is an independent predictor of AAA susceptibility. In conclusion, a genetic marker associated with cardiovascular risk factors, and in particular concurrent vascular disease, appeared to independently contribute to susceptibility for AAA. Given the potential genetic overlap between risk factor and disease phenotypes, the use of well-characterized case-control cohorts allowing for modelling of cardiovascular disease risk confounders will be an important component in the future discovery of genetic markers for conditions such as AAA.

Endovascular Aortic Aneurysm Repair in Patients with Hostile Neck Anatomy

Purpose To report a systematic review and meta-analysis of outcomes following endovascular aneurysm repair (EVAR) in patients with hostile neck anatomy (HNA) vs. those with favorable neck anatomy (FNA). Methods Systematic review and meta-analysis of data on EVAR in patients with HNA and FNA was performed by 2 reviewers in February 2013. An eligible study was required to have at least 50 participants and to incorporate one or more of the HNA criteria of neck length <15 mm, neck diameter >28 mm, and/or angulation >60°. Of the 24 full-length articles ultimately reviewed, 8 were excluded, resulting in 16 articles that were suitable for inclusion in the meta-analysis. The study size ranged from 55 to 5183 participants, with a total of 8920 patients in the FNA group and 3039 patients in the HNA group. Mean follow-up ranged from 9 to 49 months. Results Analysis of the pooled data revealed a significant increase in 30-day mortality (2.4% FNA vs. 3.5% HNA; OR 1.60, 95% CI 1.13 to 2.27; p<0.01), intraoperative adjuncts (8.8% FNA vs. 15.4% HNA; OR 1.88, 95% CI 1.15 to 3.07; p=0.01), and 30-day migration (0.9% FNA vs. 1.6% HNA; OR 2.08, 95% CI 1.20 to 3.62; p=0.009) in patients with HNA. A decrease in primary technical success (97.5% FNA vs. 93.8% HNA; OR 0.41, 95% CI 0.18 to 0.93; p=0.03) was significant when all 3 criteria were used to define HNA. For outcomes at >30 days, the increase in secondary interventions (OR 1.29, 95% CI 1.00 to 1.66; p=0.05) approached significance, but aneurysm-related mortality, all-cause mortality, migration, and aortic rupture did not achieve statistical significance. There was no difference in rates of sac expansion. Analysis of endoleak rates revealed a significant increase in 30-day type I endoleaks (OR 2.92,95% CI 1.61 to 5.30; p<0.001) and late type I endoleaks (OR 1.71,95% CI 1.31 to 2.23; p<0.0001) in patients with HNA. Conclusion These results suggest that performing EVAR in patients with HNA increases the technical difficulty and results in poorer short-term outcomes. The higher rates of early and late type I endoleaks, along with secondary interventions, suggest that increased monitoring should be performed in this category of patient to ensure rapid treatment.

Aortomonoiliac endovascular grafting: difficult solutions to difficult aneurysms.

PURPOSE To describe a refined technique for aortomonoiliac endograft exclusion of abdominal aortic aneurysms (AAAs). METHODS A tapered aortomonoiliac graft was prepared from an 8-mm thin-walled expanded polytetrafluoroethylene tube graft predilated proximally to 35 mm and tapered distally to 15 mm. The proximal graft was sutured to a 5-cm-long, predilated Palmaz stent, which was mounted on a 30-mm balloon and backloaded into a 21F packaging sheath. With the patient under general anesthesia and both common femoral arteries exposed, the endograft was anchored in the infrarenal aorta and subsequently passed into one iliac system, where it was anastomosed to the iliac or femoral vessels. The contralateral common iliac artery was occluded, and an extra-anatomic, femorofemoral, or iliofemoral bypass grafting was performed. RESULTS Twenty of the 25 AAAs treated to date with this technique have been successful, with aneurysm exclusion achieved in 18 (2 minor distal endoleaks are scheduled for endovascular repair). The technical failures were analyzed, resulting in enhancements to the technique. Complications included 2 early (< 30 days) deaths, 1 case of minor embolization, 1 transient renal failure, 1 pulmonary embolus, and 1 wound infection. The only late complication was a graft infection localized to the groin. CONCLUSIONS Aortomonoiliac endovascular aneurysm repair is effective in patients with AAAs involving the iliac arteries. Short-term results are acceptable, but long-term efficacy must be addressed before this procedure is widely adopted. Technical changes made in response to early learning curve problems have led to a safer, more reliable procedure.

Current Evidence Is Insufficient to Define an Optimal Threshold for Intervention in Isolated Type II Endoleak After Endovascular Aneurysm Repair

Purpose To report a systematic review and meta-regression of the association between the threshold for intervention in patients with isolated type II endoleak after endovascular aneurysm repair (EVAR) and the fate of the aneurysm sac. Methods Medline, trial registries, conference proceedings, and article reference lists were searched to identify case series reporting sac outcomes following a specific treatment threshold for isolated type II endoleak. Articles were classified by the threshold for intervention as conservative, selective (intervention for >5-mm sac expansion or persistent type II endoleak >6 months), or aggressive (any type II endoleak or persistent for >3 months) and sac outcomes were extracted for review. Standard meta-regression to estimate the pooled odds ratios (OR), presented with the 95% confidence interval (CI), was performed to identify whether an aggressive, selective, or conservative threshold for intervention was associated with sac expansion or sac regression. Results Ten series were analyzed that reported the outcomes of isolated type II endoleak in 231 patients; of these, 56 patients were treated at an aggressive threshold, 104 at a selective threshold, and 71 at a conservative threshold. The majority (194/231,84.0%) demonstrated either stable or shrinking sacs during follow-up. No ruptures occurred. Meta-regression demonstrated no evidence that any strategy, compared to using a conservative approach, reduced sac expansion (aggressive estimated OR 0.70, 95% CI 0.15 to 3.31, p=0.60; selective estimated OR 1.72, 95% CI 0.49 to 6.00, p=0.34) or improved sac regression (aggressive estimated OR 0.55, 95% CI 0.02 to 16.94, p=0.69; selective estimated OR 5.54, 95% CI 0.39 to 79.21, p=0.17). Conclusion There is inadequate information to support any one threshold for intervention. The rarity of rupture and sac expansion confirms the predominantly benign nature of isolated type II endoleak. In the absence of statistical support for a uniform approach to this problem, patient and physician preference remain key. Prospective data are still needed to investigate whether an optimum management algorithm can be devised.

Conservative Management of Type 2 Endoleaks is not Associated with Increased Risk of Aneurysm Rupture

OBJECTIVE Endovascular repair (EVAR) of abdominal aortic aneurysms (AAAs) has led to a reduction in the perioperative mortality when compared with open repair. However, re-intervention for complications, such as endoleak, may be required in up to 20% of the cases. Controversy exists over the management of type 2 endoleaks. This study examined the outcomes of patients with type 2 endoleaks treated conservatively to inform the ongoing management debate. METHODS All patients with a confirmed type 2 endoleak after EVAR for an infrarenal AAA were included in the study. Data regarding device details, endoleak and time point, aneurysm sac growth, intervention and outcome were collected retrospectively from case notes and the vascular research database. RESULTS Forty-one type 2 endoleaks were seen in 369 EVARs performed for infrarenal AAA between March 1994 and June 2006. Twenty-five were isolated type 2 endoleaks and 16 occurred in conjunction with other endoleaks. Of the 25 isolated type 2 endoleaks, 18 (72%) patients demonstrated no increase in sac size, six (24%) patients showed an enlargement of the sac and one patient was lost to follow-up. Only one patient underwent intervention for an isolated type 2 endoleak. After a mean follow-up period of 4 years, approximately half of the patients (48%) remain under observation (with an enlarging or stable sac), whilst the others (48%) have spontaneously sealed. Only five patients under surveillance (20%) have an enlarging sac. There were no ruptured aneurysms or aneurysm-related deaths and no patients required conversion to open repair. CONCLUSIONS In this study, a policy of regular surveillance for type 2 endoleaks was not associated with any adverse events. We therefore advocate the conservative approach for type 2 endoleaks.