The relationship between peri-operative systemic inflammation and survival in patients with abdominal aortic aneurysm.

OBJECTIVE: An association between pre-operative markers of systemic inflammation and inferior mortality following AAA repair has been observed. The prognostic value of the post-operative inflammatory response remains unreported in patients with AAA. The present study aimed to describe the association between the peri-operative inflammatory response & mortality in patients undergoing endovascular aneurysm repair (EVAR) and open surgical repair (OSR) for infrarenal AAA. MATERIALS & METHODS: Consecutive patients undergoing either emergency (EVAR or OSR) or elective (OSR) intervention for infrarenal AAA were retrospectively recruited from 3 centres. Pre-operative systemic inflammation was assessed using the modified Glasgow Prognostic Score (mGPS). Post-operative day 3 CRP (≤ 300mg/L, > 300mg/L) was chosen as the covariate of interest. The primary outcome was thirty-day mortality in the emergency cohort and twelve-month mortality in the elective cohort. RESULTS: There were 167 emergency cases (120 (72%) OSR) and 207 elective (207 (100%) OSR) cases, with a median (IQR) follow-up of 85 (52) months in the emergency cohort and 63 (57) months in the elective cohort. There were 56% vs. 44% of patients in the emergency cohort day 3 CRP ≤300mg/l vs. >300mg/L compared with 82% vs. 18% of patients in the elective cohort (p < 0.001). On univariate binary logistic regression analyses in the emergency cohort, open repair (p < 0.05), pre-operative mGPS 2 (p < 0.05), post-operative mesenteric ischaemia (p < 0.01), and day 3 post-operative CRP > 300mg/L (p < 0.05) were associated with increased odds of thirty-day mortality. On multivariate binary logistic regression analyses, only pre-operative mGPS 2 (OR 2.11, 95% CI 1.12 - 3.98, p < 0.05) retained independent association with thirty-day mortality. In the elective cohort, mean (95% CI) survival in the day 3 CRP ≤300mg/l vs. >300mg/L was 112.0 (101.8 - 122.2) months vs. 67.2 (54.1 - 80.2) months (p < 0.001). On univariate binary logistic regression analyses in the elective cohort, age ≥ 75 (p < 0.05), ischaemic heart disease (p < 0.05), and day 3 post-operative CRP > 300mg/L (p < 0.001) were associated with increased odds of twelve-month mortality. On multivariate binary logistic regression analyses, both age ≥ 75 (OR 5.15, 95% CI 1.25 - 21.30, p < 0.05) and day 3 post-operative CRP > 300mg/L (OR 15.68, 95% CI 3.61 - 68.15, p < 0.001) retained independent association with twelve-month mortality. CONCLUSIONS: Pre- and post-operative markers of systemic inflammation were independently associated with inferior survival following emergency and elective repair of AAA respectively. Further investigation of the peri-operative systemic inflammatory response is warranted in this patient group, with a particular focus on identifying targets for intervention.

The relationship between computed tomography-derived body composition, systemic inflammation, and survival in patients with abdominal aortic aneurysm.

OBJECTIVE: Patient selection and risk stratification for elective repair of abdominal aortic aneurysm (AAA), either by open surgical repair or by endovascular aneurysm repair, remain challenging. Computed tomography (CT)-derived body composition analysis (CT-BC) and systemic inflammation-based scoring systems such as the systemic inflammatory grade (SIG) appear to offer prognostic value in patients with AAA undergoing endovascular aneurysm repair. The relationship between CT-BC, systemic inflammation, and prognosis has been explored in patients with cancer, but data in noncancer populations are lacking. The present study aimed to examine the relationship between CT-BC, SIG, and survival in patients undergoing elective intervention for AAA. METHODS: A total of 611 consecutive patients who underwent elective intervention for AAA at three large tertiary referral centers were retrospectively recruited for inclusion into the study. CT-BC was performed and analyzed using the CT-derived sarcopenia score (CT-SS). Subcutaneous and visceral fat indices were also recorded. SIG was calculated from preoperative blood tests. The outcomes of interest were overall and 5-year mortality. RESULTS: Median (interquartile range) follow-up was 67.0 (32) months, and there were 194 (32%) deaths during the follow-up period. There were 122 (20%) open surgical repair cases, 558 (91%) patients were male, and the median (interquartile range) age was 73.0 (11.0) years. Age (hazard ratio [HR]: 1.66, 95% confidence interval [CI]: 1.28-2.14, P < .001), elevated CT-SS (HR: 1.58, 95% CI: 1.28-1.94, P < .001), and elevated SIG (HR: 1.29, 95% CI: 1.07-1.55, P < .01) were independently associated with increased hazard of mortality. Mean (95% CI) survival in the CT-SS 0 and SIG 0 subgroup was 92.6 (84.8-100.4) months compared with 44.9 (30.6-59.2) months in the CT-SS 2 and SIG ≥2 subgroup (P < .001). Patients with CT-SS 0 and SIG 0 had 90% (standard error: 4%) 5-year survival compared with 34% (standard error: 9%) in patients with CT-SS 2 and SIG ≥2 (P < .001). CONCLUSIONS: Combining measures of radiological sarcopenia and the systemic inflammatory response offers prognostic value in patients undergoing elective intervention for AAA and may contribute to future clinical risk predication strategies.

The prognostic value of preoperative systemic inflammation-based scoring in patients undergoing endovascular repair of abdominal aortic aneurysm.

OBJECTIVE: Abdominal aortic aneurysm (AAA) is a common condition that is predominantly managed in the United Kingdom by endovascular aneurysm repair (EVAR). Activation of the systemic inflammatory response (SIR) appears to offer prognostic value in patients with vascular disease. The present study examines the relationship between the SIR and survival in patients undergoing standard and complex endovascular aneurysm repair (EVAR and fenestrated/branched [F/B]-EVAR). METHODS: Consecutive patients undergoing elective EVAR and F/B-EVAR were retrospectively identified from three tertiary vascular centers over a 5-year period. Neutrophil:lymphocyte ratio and modified Glasgow Prognostic Score were calculated from preoperative blood results and combined into the systemic inflammatory grade (SIG). The primary outcome was all-cause mortality during the follow-up period, which was compared between subgroups of SIGs. RESULTS: There were 506 patients included in the final study, with a median follow-up of 68.0 months (interquartile range, 27.3 months), and there were 163 deaths during the follow-up period. Mean survival in the SIG 0 vs SIG 1 vs SIG 2 vs SIG 3 vs SIG 4 subgroups was 80.7 months (95% confidence interval [CI], 76.5-85.0 months) vs 78.7 months (95% CI, 72.7-84.7 months) vs 61.0 months (95% CI, 51.1-70.8 months) vs 65.1 months (95% CI, 45.0-85.2 months) vs 54.9 months (95% CI, 34.4-75.3 months) (P < .05). In the entire cohort, age (P < .001), body mass index (P < .05), high creatinine (P < .05), and SIG (P < .05) were associated with survival on univariate analysis, with retained independent association for age (hazard ratio, 1.72; 95% CI, 1.29-2.31; P < .001) and SIG (hazard ratio, 1.20; 95% CI, 1.02-1.40; P < .05) on multivariate analysis. Increasing SIG (area under the curve, 0.68; 95% CI, 0.58-0.78; P < .01) predicted 1-year mortality. CONCLUSIONS: Markers of the SIR such the SIG may be used to identify patients at higher risk of adverse outcome in patients undergoing EVAR and F/B-EVAR for abdominal aortic aneurysms. These findings warrant further investigation in large prospective cohort studies.

Novel conformable stent-graft repair of abdominal aortic aneurysms with hostile neck anatomy: A single-centre experience.

OBJECTIVES: Abdominal aortic aneurysms (AAAs) demonstrating hostile neck anatomy (HNA) are associated with increased perioperative risk and mortality. A number of these patients are not suitable for standard endovascular aneurysm repair (EVAR) and are high risk for open surgery. We present our experience with the first implantations in Scotland of a novel conformable aortic stent-graft designed to overcome some of the challenges of HNAs. METHODS: From May 2018 to March 2022, 24 consecutive patients with non-ruptured AAAs demonstrating HNAs (neck length < 15 mm, or angulation > 60°) were treated with GORE Excluder Conformable AAA endoprosthesis (CLEVAR) (CEXC Device, W.L. Gore and Associates, Flagstaff, AZ, USA) at a Scottish vascular centre. We assessed clinical outcomes and technical success of CLEVAR during deployment, primary admission and the post-operative period at 3- and 12-month clinical follow-up alongside CT angiography. RESULTS: Twenty-four patients (20 males, mean age 75.6) were included. Primary technical success of proximal seal zones and CLEVAR deployment (no type 1/3 endoleaks, no conversion to open repair, AAA excluded and patient leaving theatre alive) was achieved in 100% of patients. All patients were alive and clinically stable at 3- and 12-month follow-up. There were five patients requiring re-intervention; at the 3-month follow-up, one patient (4.2%) developed a type 1b endoleak requiring graft limb extension, one patient developed a right common femoral artery dissection requiring open repair and one patient required a limb extension of the right iliac limb due to risk of developing a type 1b endoleak. At the 12-month follow-up, two patients required embolization of type 2 endoleaks and no patients demonstrated type 1 or type 3 endoleaks.Conclusions: In-hospital and post-operative 3- and 12-month clinical and angiographic outcomes demonstrate safety and efficacy with CLEVARs in treating unruptured AAAs with HNA. Further research involving larger heterogenous sample sizes is warranted to determine long-term clinical outcomes.

Evaluation of the prognostic value of computed tomography-derived body composition in patients undergoing endovascular aneurysm repair.

BACKGROUND: Endovascular aneurysm repair (EVAR) is the most common mode of repair of abdominal aortic aneurysms (AAA) in the UK. EVAR ranges from standard infrarenal repair to complex fenestrated and branched EVAR (F/B-EVAR). Sarcopenia is defined by lower muscle mass and function, which is associated with inferior perioperative outcomes. Computed tomography-derived body composition analysis offers prognostic value in patients with cancer. Several authors have evaluated the role of body composition analysis in predicting outcomes in patients undergoing EVAR; however, the evidence base is limited by heterogeneous methodology. METHODS: Six hundred seventy-four consecutive patients (58 (8.6%) female, mean (SD) age 74.4 (6.8) years) undergoing EVAR and F/B-EVAR at three large tertiary centres were retrospectively recruited. Subcutaneous and visceral fat indices (SFI and VFI), psoas and skeletal muscle indices, and skeletal muscle density were measured at the L3 vertebral level from pre-operative computed tomographies. The maximally selected rank statistic technique was used to define optimal thresholds to predict mortality. RESULTS: There were 191 deaths during the median follow-up period of 60.0 months. Mean (95% CI) survival in the low SMI versus high SMI subgroups was 62.6 (58.5-66.7) versus 82.0 (78.7-85.3) months (P < 0.001). Mean (95% CI) survival in the low SFI versus high SFI subgroups was 56.4 (48.2-64.7) versus 77.1 (74.2-80.1) months (P < 0.001). One-year mortality in the low SMI versus high SMI subgroups was 10% versus 3% (P < 0.001). Low SMI was associated with increased odds of one-year mortality (OR 3.19, 95% CI 1.60-6.34, P < 0.001). Five-year mortality in the low SMI versus high SMI subgroups was 55% versus 28% (P < 0.001). Low SMI was associated with increased odds of five-year mortality (OR 1.54, 95% CI 1.11-2.14, P < 0.01). On multivariate analysis of all patients, low SFI (HR 1.90, 95% CI 1.30-2.76, P < 0.001) and low SMI (HR 1.88, 95% CI 1.34-2.63, P < 0.001) were associated with poorer survival. On multivariate analysis of asymptomatic AAA patients, low SFI (HR 1.54, 95% CI 1.01-2.35, P < 0.05) and low SMI (HR 1.71, 95% CI 1.20-2.42, P < 0.01) were associated with poorer survival. CONCLUSIONS: Low SMI and SFI are associated with poorer long-term survival following EVAR and F/B-EVAR. The relationship between body composition and prognosis requires further evaluation, and external validation of the thresholds proposed in patients with AAA is required.

Hypoplastic internal carotid artery stenosis with a low-lying carotid bifurcation causing cerebral ischemia.

Congenital abnormalities of the internal carotid artery (ICA) are infrequent and can be associated with aberrations of the Circle of Willis. A 47-year-old gentleman presented with transient neurological symptoms and cerebral infarction and carotid Doppler showed a stenotic right ICA. Subsequent computed tomographic angiography showed a hypoplastic ICA with a low-lying bifurcation at the C6 level and aplasia of the anterior communicating artery. This patient was commenced on aggressive medical therapy and at 7-month follow-up was symptom-free. This case report highlights the need for a centralized registry with long-term follow-up data in order to identify optimal management.

Randomized controlled trial of aspirin and clopidogrel versus aspirin and placebo on markers of smooth muscle proliferation before and after peripheral angioplasty.

OBJECTIVE: In peripheral arterial disease (PAD) patients, a limiting factor in the success of percutaneous transluminal angioplasty (PTA) is the development of restenosis secondary to vascular smooth muscle cell (SMC) proliferation. Following endothelial damage and platelet activation, there is release of factors and adhesion molecules which affect SMC proliferation. The aim of this study was to determine the effect of combination antiplatelet therapy (clopidogrel and aspirin compared with aspirin and placebo) on the ability of plasma from PAD patients undergoing PTA to stimulate SMCs in vitro. We further aimed to investigate the effect of combination treatment on the levels of circulating adhesion molecules and factors, which are known to mediate SMC proliferation in experimental models. METHODS: Fifty patients were randomized to receive blinded clopidogrel or placebo, for thirty days, in addition to their daily 75 mg aspirin. To measure proliferative capacity, diluted plasma was incubated for 15 minutes with 24 hour-growth-arrested rat vascular smooth muscle cells, and extracellular regulated kinase (ERK)1/2 activation was analyzed by Western blotting at baseline, one hour pre-PTA, one hour, 24 hours and 30 days post-PTA. Plasma platelet-derived growth factor (PDGF), sE-selectin, intracellular adhesion molecule-1 (sICAM-1), and von Willebrand factor (vWF) were measured by ELISA, at the same five timepoints. Platelet activation was measured by flow cytometry of ADP-stimulated platelet fibrinogen binding at baseline and one hour post-PTA. RESULTS: ADP-stimulated platelet fibrinogen binding was significantly inhibited by clopidogrel before and after PTA. ERK 1/2 activation was significantly increased post-PTA in both the aspirin/clopidogrel and aspirin/placebo groups (P < .001). There was a statistically significant decrease in PDGF (P = .004), and increase in vWF (P = .026), following loading with clopidogrel. sICAM-1 levels significantly decreased (P = .016) in the aspirin/placebo group following PTA. There were no other significant changes and also there was no statistically significant difference between the two treatment groups for each of ERK 1/2, sICAM-1, sE-selectin, or vWF. CONCLUSIONS: This is the first study to show in-vitro ERK 1/2 activation (a surrogate marker of SMC proliferation) increases post-PTA. Combination antiplatelet therapy had no significant effect on this, although it did reduce PDGF. Further work is required to evaluate potential therapeutic treatments, which may reduce peripheral PTA-induced smooth muscle cell activation. CLINICAL RELEVANCE: High rates of restenosis remain the major limitation of peripheral arterial angioplasty and stenting.The restenotic lesion occurs secondary to platelet activation, released circulating factors, and subsequent smooth musclecell proliferation and migration into the intima. Methods to limit the restenotic lesion are poorly understood. This paperinvestigates the effect of PTA on smooth muscle cell activation and the release of factors in plasma which mediate SMCproliferation. It also examines the effect of combination antiplatelet therapy as a potential therapeutic strategy.