Kevin Varty

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.

Endovascular stenting versus open surgery for thoracic aortic disease : Systematic review and meta-analysis of perioperative results

BACKGROUND Endovascular stenting has emerged as an alternative to open repair in patients requiring surgery for thoracic aortic pathology. A number of comparative series have been published but, to date, there has been no meta-analysis comparing outcomes following stenting as opposed to open surgery. METHODS Electronic abstract databases and conference proceedings were searched to identify relevant series. Pooled odds ratios were calculated using random effects models for perioperative mortality, neurological injury, and major reintervention. RESULTS The search identified 17 eligible series, totaling 1109 patients (538 stenting). Stenting was associated with a significant reduction in mortality (pooled odds ratio 0.36; 95% CI 0.228-0.578; P < .0001) and major neurological injury (pooled odds ratio 0.39; 95% CI 0.25-0.62; P = .0001). There was no difference in the major reintervention rate (pooled odds ratio 0.91; 95% CI 0.610-1.619). There was a reduction in hospital and critical care stay although there was evidence of heterogeneity and bias with respect to these outcomes. Subgroup analyses suggested that endovascular repair reduced mortality (pooled odds ratio 0.25; 95% CI 0.09-0.66) and neurological morbidity (pooled odds ratio 0.28; 95% CI 0.13-0.61) in stable patients undergoing repair of thoracic aortic aneurysms. There was no effect on mortality in patients with thoracic aortic trauma but neurological injury was reduced (pooled odds ratio 0.17; 95% CI 0.03-1.03). Endovascular repair did not confer any apparent benefit over open surgery in patients with thoracic aortic rupture. CONCLUSION Endovascular thoracic aortic repair reduces perioperative mortality and neurological morbidity in patients with descending thoracic aortic aneurysms. There may be less benefit in other thoracic aortic conditions.

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.

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.

Association between Biomechanical Structural Stresses of Atherosclerotic Carotid Plaques and Subsequent Ischaemic Cerebrovascular Events – A Longitudinal in Vivo Magnetic Resonance Imaging-based Finite element Study

BACKGROUND High-resolution magnetic resonance (MR) imaging has been used for MR imaging-based structural stress analysis of atherosclerotic plaques. The biomechanical stress profile of stable plaques has been observed to differ from that of unstable plaques; however, the role that structural stresses play in determining plaque vulnerability remains speculative. METHODS A total of 61 patients with previous history of symptomatic carotid artery disease underwent carotid plaque MR imaging. Plaque components of the index artery such as fibrous tissue, lipid content and plaque haemorrhage (PH) were delineated and used for finite element analysis-based maximum structural stress (M-C Stress) quantification. These patients were followed up for 2 years. The clinical end point was occurrence of an ischaemic cerebrovascular event. The association of the time to the clinical end point with plaque morphology and M-C Stress was analysed. RESULTS During a median follow-up duration of 514 days, 20% of patients (n = 12) experienced an ischaemic event in the territory of the index carotid artery. Cox regression analysis indicated that M-C Stress (hazard ratio (HR): 12.98 (95% confidence interval (CI): 1.32-26.67, p = 0.02), fibrous cap (FC) disruption (HR: 7.39 (95% CI: 1.61-33.82), p = 0.009) and PH (HR: 5.85 (95% CI: 1.27-26.77), p = 0.02) are associated with the development of subsequent cerebrovascular events. Plaques associated with future events had higher M-C Stress than those which had remained asymptomatic (median (interquartile range, IQR): 330 kPa (229-494) vs. 254 kPa (166-290), p = 0.04). CONCLUSIONS High biomechanical structural stresses, in addition to FC rupture and PH, are associated with subsequent cerebrovascular events.

Correlation of Carotid Atheromatous Plaque Inflammation Using USPIO-Enhanced MR Imaging With Degree of Luminal Stenosis

Background and Purpose— Inflammation is a recognized risk factor for the vulnerable atherosclerotic plaque. The study explores the relationship between the degree of Magnetic Resonance (MR)–defined inflammation using Ultra Small Super-Paramagnetic Iron Oxide (USPIO) particles and the severity of luminal stenosis in asymptomatic carotid plaques. Methods— Seventy-one patients with an asymptomatic carotid stenosis of ≥40% underwent multi-sequence USPIO-enhanced MR imaging. Stenosis severity was measured according to the NASCET and ECST methods. Results— No demonstrable relationship between inflammation as measured by USPIO-enhanced signal change and the degree of luminal stenosis was found. Conclusions— Inflammation and stenosis are likely to be independent risk factors, although this needs to be further validated.

Preferences for endovascular (EVAR) or open surgical repair among patients with abdominal aortic aneurysms under surveillance

OBJECTIVES There is no evidence about patient preferences for treatment of abdominal aortic aneurysms (AAA) by endovascular aneurysm repair (EVAR) or open surgical repair (OSR). This study examined patient preferences for elective future aneurysm repair and factors that may influence such preferences. METHODS Patients with small AAAs under ultrasound scan surveillance at two United Kingdom (UK) hospitals participated in a semi-structured telephone interview. Features of the two techniques were assessed with regard to their influence on the preferences of participants for EVAR or OSR, using a Likert scale. In addition, participants ranked the relative importance of 14 features against each other. RESULTS Fifty-six out of 100 eligible participants (56%) completed the semi-structured telephone interview. Of those, 84% (47 patients) said they would prefer a future EVAR repair. Patients who expressed a preference for OSR were significantly younger. Risks of major organ failure and death were most commonly judged as important features in influencing patient preference (Likert scale score 5/5). Risk of death was also most frequently ranked above all other features. Postoperative morbidity and mortality were regarded by patients as more important than the need for surveillance and risk of long-term problems with EVAR. Type of incision and radiation exposure were both given low Likert scale scores of 1/5, and the risk of sexual dysfunction was most frequently ranked as the least important feature of either operation, out of 14 other features. CONCLUSION When presented with detailed information about EVAR and OSR, most patients with small aneurysms would prefer EVAR.

VBHOM, a data economic model for predicting the outcome after open abdominal aortic aneurysm surgery.

Vascular Biochemistry and Haematology Outcome Models (VBHOM) adopted the approach of using a minimum data set to model outcome. This study aimed to test such a model on a cohort of patients undergoing open elective and non‐elective abdominal aortic aneurysm (AAA) repair.

Does N-acetylcysteine prevent contrast-induced nephropathy during endovascular AAA repair? A randomized controlled pilot study.

Purpose: To examine if N-acetylcysteine (NAC) reduces the incidence of contrast nephropathy during endovascular abdominal aortic aneurysm repair (EVAR) as evidenced by changes in markers of renal function. Methods: Twenty consecutive men (mean age 72 years, range 65–79) undergoing EVAR were randomized to receive standard intravenous fluid hydration or standard fluid hydration and NAC (600 mg BID orally, 4 doses). Venous blood and urine were collected prior to the procedure and for 5 postoperative days and analyzed blindly for serum creatinine, urinary retinol-binding protein (RBP), and albumin/creatinine ratio (ACR). Results: There were no significant differences in baseline demographics between the groups. No patient developed acute renal failure. In both groups, urinary RBP rose significantly from baseline (median 15 μg/mmol to peak 699 μg/mmol in controls versus 17 to 648 μg/mmol in the treatment group, p<0.003). There were similar significant rises in ACR (p<0.02). There was, however, no significant difference in the postoperative RBP or ACR between the groups at any time point. Conclusion: EVAR causes significant acute renal injury in most patients. This was not attenuated by N-acetylcysteine. The causes of renal injury are probably multifactorial, the long-term clinical significance of which is unclear.

Comparison of the Inflammatory Burden of Truly Asymptomatic Carotid Atheroma with Atherosclerotic Plaques in Patients with Asymptomatic Carotid Stenosis Undergoing Coronary Artery Bypass Grafting: An Ultrasmall Superparamagnetic Iron Oxide Enhanced Magnetic Resonance Study

INTRODUCTION Inflammation is a recognized risk factor for the vulnerable atherosclerotic plaque. The aim of this study was to explore whether there is a difference in the degree of Magnetic Resonance (MR) defined inflammation using Ultra Small Super-Paramagnetic Iron Oxide (USPIO) particles, within carotid atheroma in completely asymptomatic individuals and the asymptomatic carotid stenosis in a cohort of patients undergoing coronary artery bypass grafting (CABG). METHODS 10 patients awaiting CABG with asymptomatic carotid disease and 10 completely asymptomatic individuals with no documented coronary artery disease underwent multi-sequence MR imaging before and 36 hours post USPIO infusion. Images were manually segmented into quadrants and signal change in each quadrant, normalised to adjacent muscle signal, was calculated following USPIO administration. RESULTS The mean percentage of quadrants showing signal loss was 94% in the CABG group, compared to 24% in the completely asymptomatic individuals (p<0.001). The carotid plaques from the CABG patients showed a significant mean signal intensity decrease of 16.4% after USPIO infusion (95% CI 10.6% to 22.2%; p<0.001). The truly asymptomatic plaques showed a mean signal intensity increase (i.e. enhancement) after USPIO infusion of 8.4% (95% CI 2.6% to 14.2%; p=0.007). The mean signal difference between the two groups was 24.9% (95% CI 16.7% to 33.0%; p<0.001). CONCLUSIONS These findings are consistent with the hypothesis that inflammatory atheroma is a systemic disease. The carotid territory is more likely to take up USPIO if another vascular territory is symptomatic.