Jonathan R. Boyle

Remote Ischemic Preconditioning Reduces Myocardial and Renal Injury After Elective Abdominal Aortic Aneurysm Repair A Randomized Controlled Trial

Background— Myocardial and renal injury commonly contribute to perioperative morbidity and mortality after abdominal aortic aneurysm repair. Remote ischemic preconditioning (RIPC) is a phenomenon whereby brief periods of ischemia followed by reperfusion in one organ provide systemic protection from prolonged ischemia. To investigate whether remote preconditioning reduces the incidence of myocardial and renal injury in patients undergoing elective open abdominal aortic aneurysm repair, we performed a randomized trial. Method and Results— Eighty-two patients were randomized to abdominal aortic aneurysm repair with RIPC or conventional abdominal aortic aneurysm repair (control). Two cycles of intermittent crossclamping of the common iliac artery with 10 minutes ischemia followed by 10 minutes reperfusion served as the RIPC stimulus. Myocardial injury was assessed by cardiac troponin I (>0.40 ng/mL), myocardial infarction by the American College of Cardiology/American Heart Association definition and renal injury by serum creatinine (>177 &mgr;mol/L) according to American Heart Association guidelines for risk stratification in major vascular surgery. The groups were well matched for baseline characteristics. RIPC reduced the incidence of myocardial injury by 27% (39% versus 12% [95% CI: 8.8% to 45%]; P=0.005), myocardial infarction by 22% (27% versus 5% [95% CI: 7.3% to 38%]; P=0.006), and renal impairment by 23% (30% versus 7%; [95% CI: 6.4 to 39]; P=0.009). Multivariable analysis revealed the protective effect of RIPC on myocardial injury (OR: 0.22, 95% CI: 0.07 to 0.67; P=0.008), myocardial infarction (OR: 0.18, 95% CI: 0.04 to 0.75; P=0.006) and renal impairment were independent of other covariables. Conclusions— In patients undergoing elective open abdominal aortic aneurysm repair, RIPC reduces the incidence of postoperative myocardial injury, myocardial infarction, and renal impairment.

Neurological complications after left subclavian artery coverage during thoracic endovascular aortic repair: a systematic review and meta-analysis.

INTRODUCTION Recent studies suggest an increased risk of neurologic complications after coverage of the left subclavian artery (LSA) during thoracic endovascular aortic repair (TEVAR). The preventative role of preoperative revascularization of the LSA using carotid-subclavian bypass or transposition remains controversial. We assessed this increased risk and the role of revascularization by undertaking a systematic review and meta-analysis of the literature. METHODS In the absence of any randomized controlled trials, the Pubmed and Embase databases were searched to identify all series reporting TEVAR without LSA coverage compared with LSA coverage with and without revascularization. The incidence of neurologic complications, namely cerebrovascular accident (CVA) and spinal cord ischemia (SCI), were recorded for each group. Pooled odds ratios (POR) were then calculated for postoperative CVA and SCI. RESULTS Compared with patients without LSA coverage, the risk of CVA was increased both in patients with LSA coverage alone (4.7% vs 2.7%; POR, 2.28; 95% confidence interval [CI], 1.28-4.09; P = .005) and in those with LSA coverage after revascularization (4.1% vs 2.6%; POR, 3.18; 95% CI, 1.17-8.65; P = .02). The risk of SCI was also increased in patients requiring LSA coverage (2.8% vs 2.3%; POR, 2.39; 95% CI, 1.30-4.39; P = .005) but not for LSA coverage after revascularization (0.8% vs 2.7%; POR, 1.69; 95% CI, 0.56-5.15; P = .35). CONCLUSION The risk of neurologic complications is increased after coverage of the LSA during TEVAR. Preemptive revascularization offers no protection against CVA, perhaps indicating a heterogeneous etiology. Revascularization may reduce the risk of SCI, although limited data tempers this conclusion. Improved or perhaps compulsory reporting to registries of a minimum data set may help further assess the exact etiology of these complications and identify a higher-risk subset of patients in whom revascularization might prove protective.

Renal Consequences of Endovascular Abdominal Aortic Aneurysm Repair

Endovascular aneurysm repair (EVAR) of abdominal aortic aneurysm (AAA) is less invasive and has a lower operative mortality than conventional surgery. The relationship between renal function and outcome following open AAA repair has been extensively investigated, but less work has been undertaken with respect to renal function and outcome after EVAR. We reviewed the literature (Medline and PubMed databases) between 1991 and 2007 to investigate the relationship between EVAR and renal dysfunction. Our review found that perioperative renal dysfunction is attenuated by EVAR. However, dialysis rates after EVAR are similar to those after open surgery. EVAR patients develop progressive deterioration in renal function over time. The etiology is unclear and probably multifactorial, involving embolization, contrast media, and graft misplacement. The effect of transrenal endograft fixation on long-term renal function is unknown, but the technique may be associated with a significantly increased risk of renal infarction. The etiology of the renal injury during and after EVAR needs further evaluation, and techniques aimed at renal preservation should be pursued.

Endovascular Aneurysm Repair with Preservation of the Internal Iliac Artery Using the Iliac Branch Graft Device

OBJECTIVES Aortoiliac aneurysms comprise up to 43% of the specialist endovascular caseload. In such cases endovascular aneurysm repair (EVAR) requires distal extension of the aortoiliac endograft beyond the ostium of the internal iliac artery (IIA) and into the external iliac artery, conventionally necessitating the embolisation of one or both IIA. This has been associated with a wide range of complications, and the use of an Iliac Branch-graft Device (IBD) offers an appealing endovascular solution. DESIGN Medline, trial registries, conference proceedings and article reference lists were searched to identify case series reporting IBD use. Data were extracted for review. RESULTS Nine series have reported the use of IBD in a total of 196 patients. Technical success was 85-100%. Median operating times were 101-290min and median contrast dose was 58-208g, with no aneurysm-related mortality. Claudication developed in 12/24 patients after IBD occlusion. One type I endoleak and two type III endoleaks occurred and were managed endovascularly. Re-occlusion occurred in 24/196 patients. CONCLUSION IBD was performed with high technical success rates and encouraging mid-term patency. Formalised risk stratification and morphological data are required to identify the group of patients who will benefit most. Cost-effectiveness appraisals are needed for this technique.

Remote Ischemic Preconditioning for Renal and Cardiac Protection during Endovascular Aneurysm Repair: A Randomized Controlled Trial

Purpose: To report a randomized clinical trial designed to determine if remote ischemic preconditioning (IP) has the ability to reduce renal and cardiac damage following endovascular aneurysm repair (EVAR). Methods: Forty patients (all men; mean age 76±7 years) with abdominal aortic aneurysms averaging 6.3±0.8 cm in diameter were enrolled in the trial from November 2006 to January 2008. Eighteen patients (mean age 74 years, range 72–81) were randomized to preconditioning and completed the full remote IP protocol; there were no withdrawals. Twenty-two patients (mean age 76 years, range 66–80) were assigned to the control group. Remote IP was induced using sequential lower limb ischemia. Serum and urinary markers of renal and cardiac injury were compared between the groups. Results: Urinary retinol binding protein (RBP) levels increased 10-fold from a median of 235 µmol/L to 2356 µmol/L at 24 hours (p=0.0001). There was a lower increase in the preconditioned group, from 167 µmol/L to 413 µmol/L at 24 hours (p=0.04). The median urinary albumin:creatinine ratio was significantly lower in the preconditioned group at 24 hours (5 versus 8.8, p=0.06). There were no differences in the rates of renal impairment or major adverse cardiac events. Conclusion: Remote preconditioning reduces urinary biomarkers of renal injury in patients undergoing elective EVAR. This small pilot trial was unable to detect an effect on clinical endpoints; further trials are warranted.

Utility of USPIO-enhanced MR imaging to identify inflammation and the fibrous cap: A comparison of symptomatic and asymptomatic individuals

BACKGROUND AND PURPOSE Inflammation is a risk factor the vulnerable atheromatous plaque. This can be detected in vivo on high-resolution magnetic resonance (MR) imaging using a contrast agent, Sinerem, an ultra-small super-paramagnetic iron oxide (USPIO). The aim of this study was to explore whether there is a difference in the degree of MR defined inflammation using USPIO particles, between symptomatic and asymptomatic carotid plaques. We report further on its T(1) effect of enhancing the fibrous cap, which may allow dual contrast resolution of carotid atheroma. METHODS Twenty patients with carotid stenosis (10 symptomatic and 10 asymptomatic) underwent multi-sequence MR imaging before and 36 h post-USPIO infusion. Images were manually segmented into quadrants and signal change in each quadrant was calculated following USPIO administration. Mean signal change across all quadrants were compared between the two groups. RESULTS Symptomatic patients had significantly more quadrants with a signal drop than asymptomatic individuals (75% vs. 32%, p<0.01). Asymptomatic plaques had more quadrants with signal enhancement than symptomatic ones (68% vs. 25%, p<0.05); their mean signal change was also higher (46% vs. 15%, p<0.01) and this appeared to correlate with a thicker fibrous cap on histology. CONCLUSIONS Symptomatic patients had more quadrants with signal drop suggesting larger inflammatory infiltrates. Asymptomatic individuals showed significantly more enhancement possibly suggesting greater stability as a result of thicker fibrous caps. However, some asymptomatic plaques also had focal areas of signal drop, suggesting an occult macrophage burden. If validated by larger studies, USPIO may be a useful dual contrast agent able to improve risk stratification of patients with carotid stenosis and inform selection for intervention.

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.

Endovascular vs open repair of acute abdominal aortic aneurysms--a systematic review and meta-analysis.

OBJECTIVE To compare the results of emergency open repair of acute (ruptured or symptomatic intact) abdominal aortic aneurysms with that of endovascular repair. METHODS A systematic literature search was performed to identify series that reported comparative outcomes. PubMed, Embase, the randomized controlled trial (RCT) register, and all relevant major journals were searched independently by two researchers. The outcome measures were 30-day mortality, intensive care unit (ICU) stay, hospital stay, blood loss, and operative time. RESULTS Twenty-three studies were identified. Of these, only one was a randomized controlled trial, which is now halted. The total number of patients in the pooled data was 7040 (730 emergency endovascular aneurysm repair [eEVAR]). Emergency EVAR was associated with a significant reduction in mortality (pooled odds ratio 0.624; 95% confidence interval [CI] 0.518 to 0.752; P < .0001). The eEVAR groups ICU stay was reduced by 4 days (pooled effect size estimate -0.70; 95% CI -1.05 to -0.35; P < .0001) and hospital stay with eEVAR was reduced by 8.6 days (pooled effect size estimate -0.33; 95% CI -0.50 to -0.16; P = .0001). In addition, eEVAR was also associated with a significant reduction in blood loss (pooled effect size estimate -1.88 liters; 95% CI -2.49 to -1.27; P < .0001) and reduced procedure time (pooled effect size estimate -0.65; 95% CI -0.95 to -0.36; P < .0001). CONCLUSION This meta-analysis suggests benefits to the selected group of patients undergoing this minimally invasive procedure. There is a reduction in the high mortality, prolonged intensive care requirement and total hospital stay, which are historically associated with open repair. It also indicates that most patients are fit enough to undergo computerized tomography (CT) scanning in acute settings. However, because of heterogeneity and bias in the outcomes these results should be interpreted with caution.

Endovascular AAA Repair Attenuates the Inflammatory and Renal Responses Associated with Conventional Surgery

PURPOSE To quantify the inflammatory and renal parameters in comparative cohorts of patients undergoing surgical or endovascular repair of abdominal aortic aneurysms (AAAs). METHODS Forty-three patients (41 men; ages 58-81 years) underwent endovascular or conventional aneurysm surgery according to aortic morphology. All patients received a standard general anesthetic and had 12 serial blood and urine samples collected during the perioperative period. Samples underwent analysis for the cytokines interleukin (IL) 1beta tumor necrosis factor-alpha (TNF-alpha), and IL-6. White cell and platelet activation were estimated indirectly by measuring sL-selectin and 11-dehydrothromboxane B2, respectively. The urinary albumin:creatinine ratio (ACR) and N-acetyl-beta-D-glucosaminidase (NAG) activity were estimated to assess renal injury. Fibrinogen and fibrinogen degradation products were calculated to assess activation of the clotting cascade. RESULTS Twenty-three patients underwent endovascular AAA repair and 20 had conventional surgery. Concentrations of IL-6 (p < 0.002) and TNF-alpha (p < 0.0004) were significantly higher in the conventional group. The ACR (p < 0.002) and urinary NAGs (p < 0.0009) were also significantly higher in this group, suggesting greater renal injury. Platelet activity was significantly greater in the endovascular group (p < 0.01), perhaps indicating thrombus organization within the aneurysm sac. CONCLUSIONS These data suggest that the inflammatory response associated with conventional aneurysm repair is largely obviated by endovascular techniques. This may potentially translate to a lower incidence of multiple organ failure after endovascular surgery.

Remote Ischemic Preconditioning for Renal Protection During Elective Open Infrarenal Abdominal Aortic Aneurysm Repair: Randomized Controlled Trial

We aimed to determine whether remote ischemic preconditioning (IP) reduces renal damage following elective open infrarenal abdominal aortic aneurysm (AAA) repair. Sequential common iliac clamping was used to induce remote IP in randomized patients. Urinary retinol binding protein (RBP) and albumin-creatinine ratio (ACR) were measured following induction and 3, 24, and 48 hours postoperatively. In controls (n = 22), median urinary RBP increased from 112 µg/mL (interquartile range [IQR] 96-173 µg/mL) preoperatively to 5919 µg/mL (IQR 283-17 788 µg/mL) at 3 hours. Preoperative urinary RBP in preconditioned patients was 96 µg/mL (IQR 50 to 229 µg/mL) preoperatively, rising to 1243 µg/mL (IQR 540 to 15400 µg/mL) at 3 hours. Although control patients’ median urinary RBP level was 5 times greater at 3 hours, there were no statistically significant differences in renal outcome indices. This trial could not confirm that remote IP reduces renal injury following elective open aneurysm surgery.