Eptifibatide bridging therapy for staged carotid artery stenting and cardiac surgery: Safety and feasibility.

BACKGROUND: Prophylactic carotid artery stenting (CAS) is an effective strategy to reduce perioperative stroke in patients with severe carotid stenosis who require cardiothoracic surgery (CTS). Staging both procedures (CAS-CTS) during a single hospitalization presents conflicting demands for antiplatelet therapy and the optimal pharmacologic strategy between procedures is not established. The purpose of this study is to present our initial experience with a "bridging" protocol for staged CAS-CTS. METHODS: A retrospective review of staged CAS-CTS procedures at a single referral center was performed. All patients had multivessel coronary and/or valvular disease and severe carotid stenosis (>70%). Patients not previously on aspirin were also started on aspirin prior to surgery, followed by eptifibatide during CAS (intraprocedural bolus followed by post-procedural infusion which was continued until the morning of surgery). Pre- and perioperative (30 days) neurologic morbidity and mortality was the primary endpoint. RESULTS: 11 CAS procedures were performed in 10 patients using the protocol. The median duration of eptifibatide bridge therapy was 36 h (range 24-288 h). There was one minor bleeding complication (1/11, 9.1%) and no major bleeding complications during the bridging and post-operative period. There was one post-operative, non-neurologic death and zero perioperative ischemic strokes. CONCLUSIONS: For patients undergoing staged CAS-CTS, Eptifibatide bridging therapy is a viable temporary antiplatelet strategy with a favorable safety profile. This strategy enables a flexible range of time-intervals between procedures.

Vitamin D deficiency is associated with mortality and adverse vascular access outcomes in patients with end-stage renal disease.

BACKGROUND: Plasma 25 hydroxycholecalciferol (vitamin D) deficiency has been associated with adverse cardiovascular outcomes in epidemiologic studies. Chronic kidney disease is associated with loss of 1α-hydroxylase and consequently vitamin D deficiency. We hypothesized that vitamin D deficiency was associated with increased mortality and increased vascular access failure in patients undergoing permanent vascular access for end-stage renal disease. METHODS: This retrospective cohort study analyzed 128 patients undergoing permanent vascular access surgery between 2003 and 2012 for whom concurrent plasma vitamin D levels were also available. Levels were considered deficient at <20 ng/mL. Multivariable analysis was used to determine the association between vitamin D and mortality and vascular access outcomes. RESULTS: The mean age was 66.7 years, 96.8% were male, 32.0% were African American, and 60.9% had diabetes mellitus. In the entire cohort, 55.5% were vitamin D-deficient, despite similar rates of repletion among the vitamin D-deficient and nondeficient groups. During a median follow-up of 2.73 years, there were 40 deaths (31%). Vitamin D-deficient patients tended to be younger (P = .01) and to have higher total cholesterol (P = .001) and lower albumin (P = .017) and calcium (P = .007) levels. Despite their younger age, mortality was significantly higher (P = .026) and vascular access failure was increased (P = .008) in the vitamin D-deficient group. Multivariate logistic regression analysis found vitamin D deficiency (odds ratio [OR], 3.64; 95% confidence interval [CI], 1.12-11.79; P = .031), hemodialysis through a central catheter (OR, 3.08; 95% CI, 1.04-9.12; P = .042), coronary artery disease (OR, 3.08; 95% CI, 1.06-8.94; P = .039), increased age (OR, 1.09; 95% CI, 1.03-1.15; P = .001), and albumin (OR, 0.27; 95% CI, 0.09-0.83; P = .023) remained independent predictors of mortality. Vitamin D deficiency (hazard ratio [HR], 2.34; 95% CI, 1.17-4.71; P = .02), a synthetic graft (HR, 3.50; 95% CI, 1.38-8.89; P = .009), and hyperlipidemia (HR, 0.42; 95% CI, 0.22-0.81; P = .01) were independent predictors of vascular access failure in a Cox proportional hazard model. CONCLUSIONS: Vitamin D deficiency is highly prevalent in patients undergoing vascular access procedures. Patients who are deficient in vitamin D have worse survival and worse vascular access outcomes. Further study is warranted to assess whether aggressive vitamin D repletion will improve outcomes in this population.

Inducible ApoE gene repair in hypomorphic ApoE mice deficient in the low-density lipoprotein receptor promotes atheroma stabilization with a human-like lipoprotein profile.

OBJECTIVE: To study atherosclerosis regression in mice after plasma lipid reduction to moderately elevated apolipoprotein B (apoB)-lipoprotein levels. APPROACH AND RESULTS: Chow-fed hypomorphic Apoe mice deficient in low-density lipoprotein receptor expression (Apoe(h/h)Ldlr(-/-)Mx1-cre mice) develop hyperlipidemia and atherosclerosis. These mice were studied before and after inducible cre-mediated Apoe gene repair. By 1 week, induced mice displayed a 2-fold reduction in plasma cholesterol and triglyceride levels and a decrease in the non-high-density lipoprotein:high-density lipoprotein-cholesterol ratio from 87%:13% to 60%:40%. This halted atherosclerotic lesion growth and promoted macrophage loss and accumulation of thick collagen fibers for up to 8 weeks. Concomitantly, blood Ly-6C(high) monocytes were decreased by 2-fold but lesional macrophage apoptosis was unchanged. The expression of several genes involved in extracellular matrix remodeling and cell migration was changed in lesional macrophages 1 week after Apoe gene repair. However, mRNA levels of numerous genes involved in cholesterol efflux and inflammation were not significantly changed at this time point. CONCLUSIONS: Restoring apoE expression in Apoe(h/h)Ldlr(-/-)Mx1-cre mice resulted in lesion stabilization in the context of a human-like ratio of non-high-density lipoprotein:high-density lipoprotein-cholesterol. Our data suggest that macrophage loss derived in part from reduced blood Ly-6C(high) monocytes levels and genetic reprogramming of lesional macrophages.

Assessing the anatomic applicability of the multibranched endovascular repair of thoracoabdominal aortic aneurysm technique.

BACKGROUND: Multibranched endovascular aneurysm repair (MBEVAR) has the potential to lower the morbidity and mortality rates of thoracoabdominal aneurysm repair, but the applicability of the technique is unknown. Our aim was to estimate the prevalence of anatomic suitability for MBEVAR. METHODS: Retrospective review of patients referred for a prospective trial of MBEVAR between November 2005 and July 2012. Anatomic suitability was assessed on three-dimensional computed tomography scan reconstructions according to the current criteria for a custom-made stent graft or a fixed, off-the-shelf stent graft in both standard (22F) and low-profile (18F) delivery systems. RESULTS: A total of 250 contrast-enhanced computed tomography scans were reviewed, 49 of which were excluded due to inadequate aneurysm size. Of 201 candidates for repair, 149 (74%) were men and 86 (43%) had Crawford classification type IV/paravisceral aneurysms; 109 (58%) were anatomically suitable for a single-stage repair with a custom-made, low-profile stent graft. Another 58 (29%) could have been made suitable for MBEVAR with an adjunct procedure, including angiogram with visceral or renal artery stenting (n = 23), carotid-subclavian bypass (n = 5), or iliac bypass for device insertion (n = 17), or to preserve internal iliac artery flow because of an iliac aneurysm (n = 9), or dissection (n = 8). There was no association between suitability and gender, aneurysm diameter, or type. However, women were significantly more likely to need a conduit or low-profile device (P = .003). Patients with type B aortic dissections were significantly less likely to have anatomy suitable for repair (P = .035) and more likely to require a multistage repair. Thirty-four patients would have been unsuitable for repair because of renal artery anatomy (n = 14), visceral artery anatomy (n = 4), lack of a proximal landing zone due to an arch aneurysm (n = 7), or inadequate access arteries (n = 9). The low-profile device increased the number of patients who would have been suitable for a single-stage repair by 16. The off-the-shelf graft has the advantage of a faster assessment-to-treatment time, but only 64 patients would have been suitable for a single-stage repair and another 30 could have been made suitable with an adjunct procedure. CONCLUSIONS: Most patients would have been suitable or could have been made suitable for a thoracoabdominal stent graft using current anatomic criteria. The applicability of MBEVAR will continue to change as the experience with the technique grows and devices evolve, as evidenced by the potential reduction in iliac bypasses after the introduction of a low-profile device and the ability to treat symptomatic or urgent patients with the off-the-shelf device.

Apolipoprotein E4 domain interaction accelerates diet-induced atherosclerosis in hypomorphic Arg-61 apoe mice.

OBJECTIVE: Apolipoprotein (apo) E4 is an established risk factor for atherosclerosis, but the structural components underlying this association remain unclear. ApoE4 is characterized by 2 biophysical properties: domain interaction and molten globule state. Substituting Arg-61 for Thr-61 in mouse apoE introduces domain interaction without molten globule state, allowing us to delineate potential proatherogenic effects of domain interaction in vivo. METHODS AND RESULTS: We studied atherosclerosis susceptibility of hypomorphic Apoe mice expressing either Thr-61 or Arg-61 apoE (ApoeT(h/h) or ApoeR(h/h)mice). On a chow diet, both mouse models were normolipidemic with similar levels of plasma apoE and lipoproteins. However, on a high-cholesterol diet, ApoeR(h/h) mice displayed increased levels of total plasma cholesterol and very-low-density lipoprotein as well as larger atherosclerotic plaques in the aortic root, arch, and descending aorta compared with ApoeT(h/h) mice. In addition, evidence of cellular dysfunction was identified in peritoneal ApoeR(h/h) macrophages which released lower amounts of apoE in culture medium and displayed increased expression of major histocompatibility complex class II molecules. CONCLUSIONS: These data indicate that domain interaction mediates proatherogenic effects of apoE4 in part by modulating lipoprotein metabolism and macrophage biology. Pharmaceutical targeting of domain interaction could lead to new treatments for atherosclerosis in apoE4 individuals.

ApoE suppresses atherosclerosis by reducing lipid accumulation in circulating monocytes and the expression of inflammatory molecules on monocytes and vascular endothelium.

OBJECTIVE: We investigated atheroprotective properties of apolipoprotein (apo) E beyond its ability to lower plasma cholesterol. We hypothesized that apoE reduces atherosclerosis by decreasing lipid accumulation in circulating monocytes and the inflammatory state of monocytes and the vascular endothelium. METHODS AND RESULTS: We developed mice with spontaneous hyperlipidemia with and without plasma apoE. Hypomorphic apoE mice deficient in low-density lipoprotein receptor (Apoe(h/h)Ldlr(-/-)) were compared to Apoe(-/-)Ldlr(-/-) mice. Despite 4-fold more plasma apoE than WT mice, Apoe(h/h)Ldlr(-/-) mice displayed similar plasma cholesterol as Apoe(-/-) Ldlr(-/-) mice but developed 4-fold less atherosclerotic lesions by 5 months of age. The aortic arch of Apoe(h/h)Ldlr(-/-) mice showed decreased endothelial expression of ICAM-1, PECAM-1, and JAM-A. In addition, Apoe(h/h)Ldlr(-/-) mice had less circulating leukocytes and proinflammatory Ly6C(high) monocytes. These monocytes had decreased neutral lipid content and reduced surface expression of ICAM-1, VLA-4, and L-Selectin. Apoe(h/h)Ldlr(-/-) mice displayed increased levels of apoA1-rich HDL that were potent in promoting cellular cholesterol efflux. CONCLUSIONS: Our findings suggest that apoE reduces atherosclerosis in the setting of hyperlipidemia by increasing plasma apoA1-HDL that likely contribute to reduce intracellular lipid accumulation and thereby the activation of circulating leukocytes and the vascular endothelium.

Efficacy and durability of endovascular thoracoabdominal aortic aneurysm repair using the caudally directed cuff technique.

OBJECTIVE: This study determined early and intermediate results of multibranched endovascular thoracoabdominal (TAAA) and pararenal aortic aneurysm (PRAA) repair using a uniform operative technique. METHODS: Eighty-one patients (mean age, 73 ± 8 years, 19 [23.5%] women) underwent endovascular TAAA repair in a prospective trial using self-expanding covered stents connecting axially oriented, caudally directed cuffs to target aortic branches. Mean aneurysm diameter was 67 ± 10 mm. Thirty-nine TAAA (48.1%) were Crawford type II, III, or V; 42 (51.9%) were type IV or pararenal. Thirty-three procedures (40.7%) were staged. The insertion approach was femoral for aortic components and brachial for branch components. Follow-up assessments were performed at 1, 6, and 12 months, and yearly thereafter. RESULTS: All devices (n = 81) and branches (n = 306) were successfully inserted and deployed, with no conversions to open repair. Overall mortality was 6.2% (n = 5), including three perioperative (3.7%) and two late treatment-related deaths (2.5%). Permanent paraplegia occurred in three patients (3.7%), and transient paraplegia/paraparesis occurred in 16 (19.8%). Four patients (4.9%) required dialysis postoperatively, three permanently and one transiently. Women accounted for 67% of the paraplegia, 75% of the perioperative dialysis, and 60% of the perioperative or treatment-related deaths. During a mean follow-up of 21.2 months, no aneurysms ruptured, but four (4.9%) enlarged: two were successfully treated, one was unsuccessfully treated, and one was not treated. No late onset spinal cord ischemia symptoms developed. Of the five patients starting dialysis during follow-up, two resulted from renal branch occlusion. Sixteen branches occluded (nine renal, two celiac) or developed stenoses (four renal, one superior mesenteric artery), requiring stenting. Primary patency was 94.8%, and primary-assisted patency was 95.1%. Thirty-two patients (39.5%) underwent 42 reinterventions. Of 25 early reinterventions (≤ 45 days), 10 were to treat access or insertion complications, and 5 were for endoleak. Of 17 late reinterventions, eight were for endoleak and five were for branch stenosis/occlusion. New endoleaks developed in two patients during follow-up. Overall, 73 of 81 patients (90.1%) were treated without procedure-related death, dialysis, paralysis, aneurysm rupture, or conversion to open repair. CONCLUSIONS: Total endovascular TAAA/PRAA repair using caudally directed cuffs is safe, effective, and durable in the intermediate term. The most common form of late failure, renal artery occlusion, rarely had a clinically significant consequence (dialysis). The trend toward worse outcome in women needs further study.

Do microemboli reach the brain penetrating arteries?

BACKGROUND: As they are "end arteries," microembolic obstruction of brain penetrating arteries would be expected to create ischemia. Yet the mammalian brain appears to have an impressive tolerance to experimental microembolization with ischemia occurring only after the injection of large numbers of particulates. Potential explanations could be that the majority of these particulates marginate along the pial vasculature or escape the cerebral circulation via arteriovenous (AV) fistulae. METHODS: To test these theories, we first established the level of injury created by the injection of 20, 45, and 90 µm fluorescent microspheres in Sprague-Dawley rats. Brains were examined by immunohistochemistry for injury and for infarction. We then injected 1000 size 20 µm, 500 size 45 µm, and 150 size 90 µm and harvested the brains and lungs for assays of fluorescence. The location of microemboli within the brain was established by determining the percent of 20 and 45 µm fluorescent microspheres entering the superficial versus deeper layers of the brain. The location of larger microemboli was established by 2T-MRI after injection of 60-100 µm microthrombi labeled with supraparamagnetic iron oxide (SPIO) particles. RESULTS: With 20 µm microspheres there were no areas of injury or infarction after injection of 500 and rare areas of injury and no infarctions after injection of 1000 microspheres. With either 250 or 500 size 45 µm microspheres there were a few (≤ 6) small areas of injury per animal with ≤ 2 areas of infarction. After injection, 93%-96% of injected microspheres remained in the brain. Approximately 40% of either fluorescent or SPIO labeled microthrombi were found on the brain surface. CONCLUSIONS: As in humans, the rat brain has an impressive tolerance to microemboli, although this clearly varies with emboli size and number. Wash out of particulates through AV connections is not a major factor in brain tolerance in this model. Approximately 40% of microemboli remain in the larger pial vasculature where the more extensive collateralization may limit their effects on distal perfusion. However, the remaining 60% enter penetrating arteries but few create ischemia.

Assessment of Surgeon Performance of Advanced Open Surgical Skills Using a Microskills-Based Novel Curriculum.

Importance: The increase in minimally invasive surgical procedures has eroded exposure of general surgery residents to open operations. High-fidelity simulation, together with deliberate instruction, is needed for advanced open surgical skill (AOSS) development. Objective: To collect validity evidence for AOSS tools to support a shared model for instruction. Design, Setting, and Participants: This prospective cohort study included postresidency surgeons (PRSs) and second-year general surgery residents (R2s) at a single academic medical center who completed simulated tasks taught within the AOSS curriculum between June 1 and October 31, 2021. Exposures: The AOSS curriculum includes 6 fine-suture and needle handling tasks, including deep suture tying (with and without needles) and continuous suturing using the pitch-and-catch and push-push-pull techniques (both superficial and deep). Teaching and assessment are based on specific microskills using a 3-dimensional printed iliac fossa model. Main Outcomes and Measures: The PRS group was timed and scored (5-point Likert scale) on 10 repetitions of each task. Six months after receiving instruction on the AOSS tasks, the R2 group was similarly timed and scored. Results: The PRS group included 14 surgeons (11 male [79%]; 8 [57%] attending surgeons) who completed the simulation; the R2 group, 9 surgeons (5 female [55%]) who completed the simulation. Score and time variability were greater for the R2s compared with the PRSs for all tasks. The R2s scored lower and took longer on (1) deep pitch-and-catch suturing (69% of maximum points for a mean [SD] of 142.0 [31.7] seconds vs 77% for a mean [SD] of 95.9 [29.4] seconds) and deep push-push-pull suturing (63% of maximum points for a mean [SD] of 284.0 [72.9] seconds vs 85% for a mean [SD] of 141.4 [29.1] seconds) relative to the corresponding superficial tasks; (2) suture tying with a needle vs suture tying without a needle (74% of maximum points for a mean [SD] of 64.6 [19.8] seconds vs 90% for a mean [SD] of 54.4 [15.6] seconds); and (3) the deep push-push-pull vs pitch-and-catch techniques (63% of maximum points for a mean [SD] of 284.0 [72.9] seconds vs 69% of maximum points for a mean [SD] of 142.0 [31.7] seconds). For the PRS group, time was negatively associated with score for the 3 hardest tasks: superficial push-push-pull (ρ = 0.60; P = .02), deep pitch-and-catch (ρ = 0.73; P = .003), and deep push-push-pull (ρ = 0.81; P < .001). For the R2 group, time was negatively associated with score for the 2 easiest tasks: suture tying without a needle (ρ = 0.78; P = .01) and superficial pitch-and-catch (ρ = 0.79; P = .01). Conclusions and Relevance: The findings of this cohort study offer validity evidence for a novel AOSS curriculum; reveal differential difficulty of tasks that can be attributed to specific microskills; and suggest that position on the surgical learning curve may dictate the association between competency and speed. Together these findings suggest specific, actionable opportunities to guide instruction of AOSS, including which microskills to focus on, when individual rehearsal vs guided instruction is more appropriate, and when to focus on speed.

The distribution and size of ischemic lesions after carotid artery angioplasty and stenting: evidence for microembolization to terminal arteries.

BACKGROUND: Much of the brain is perfused by penetrating arteries that are the "single source" of blood to their surrounding tissues. These tissues should be equally vulnerable to ischemia from embolic occlusion, but there are questions about whether emboli have access to the penetrating arteries serving the deep brain tissues. To examine this issue in humans we recorded the number and distribution of new ischemic lesions on diffusion-weighted magnetic resonance imaging (DWMRI) after carotid artery stenting (CAS), a procedure producing showers of numerous small atheroemboli. METHODS: Twenty-nine men (aged 62-81) underwent 30 CAS procedures with distal protection in place, and DWMRI 48 hours after the procedure documented new lesions had developed. Thirteen patients were asymptomatic, and 16 had experienced recent symptoms ipsilateral to the treated carotid stenosis. A DWMRI study was done in each patient ≤72 hours before the procedure. All MRI studies were read by the same neuroradiologist. RESULTS: One patient sustained a minor stroke, which resolved. DWNRI found 131 new lesions (median, 3; range, 1-17; interquartile range, 2-4). Lesion size was <5 mm in 96.6% and 5 to 10 mm in 3.1%. Lesions were ipsilateral in 83.1% and contralateral in 16.9%. Lesions were in the distribution of the middle cerebral artery (91.6%), posterior cerebral artery (6.1%), and superior cerebellar artery subclavian artery (2.0%). Most lesions were in the cortex but at a depth where they were best described as cortical/subcortical (90.8%). The rest were in the periventricular white matter (6.1%) and deep gray matter (3.0%). CONCLUSIONS: The ischemic areas developing after CAS were predominately in the deeper layers of the cortex in the distribution of the middle cerebral artery, but lesions were seen throughout the brain. The distribution of lesions caused by CAS-induced embolization coincided with estimates of blood flow to the respective areas of the brain. These data add to the evidence implicating microemboli in ischemic pathologies throughout the brain.

Long-term follow-up of neck expansion after endovascular aortic aneurysm repair.

OBJECTIVE: This study determined the rate, extent, and clinical significance of neck dilatation after endovascular aneurysm repair (EVAR). METHODS: The study included 46 patients who underwent elective EVAR using bifurcated Zenith stent grafts (Cook, Bloomington, Ind) and had at least 48 months of clinical and radiographic follow-up. Computed tomography images were analyzed on a 3-dimensional workstation (TeraRecon, San Mateo, Calif). Neck diameter was measured 10 mm below the most inferior renal artery in planes orthogonal to the aorta. Nominal stent graft diameter was obtained from implantation records. RESULTS: Median follow-up was 59 months (range, 48-120 months). Neck dilation occurred in all 46 patients. The rate of neck dilation was greatest at early follow-up intervals. At 48 months, median neck dilation was 5.3 mm (range, 2.3-9.8 mm). The extent of neck dilation at 48 months correlated with percentage of stent graft oversizing (Spearman rho = 0.61, P < .001). No type I endoleak or migration >5 mm occurred. CONCLUSIONS: After EVAR with the Zenith stent graft, the neck dilates until its diameter approximates the diameter of the stent graft. Neck dilation was not associated with type I endoleak or migration of the stent graft.

Distal filtration versus flow reversal: An ex vivo assessment of the choices for carotid embolic protection.

OBJECTIVES: Choices for embolic protection during carotid stent procedures include distal filtration (DF) and proximal occlusion with flow reversal (POFR). DF devices are widely used but have produced only modest improvements in clinical outcomes. There is less experience with POFR devices but single center reports suggest reduced emboli detected by transcranial Doppler (TCD). To determine if POFR offers a significant improvement in embolic protection, we tested five DF devices and two POFR devices with 8F and 10F sheath design in an ex vivo angioplasty system using human carotid plaques excised en bloc. Physiologic pressures and flows were used and the efficiency of plaque fragment removal by these devices compared. METHODS: Thirty-three human carotid plaques removed en bloc were secured in tailored polytetrafluoroethylene (PTFE) grafts. The distal PTFE was either 6 mm or 5 mm inner diameter (ID). Saline was delivered through the excised carotid plaque as follows: a cleaning 50 mL flush was done prior to the angioplasty procedure and discarded; further flushes of forward flow were done with five pressurized "pulsations" of 10 mL each (50 mL), peak pressure 140 mm Hg. Balloon angioplasty was done with a 4 mm and then a 6 mm balloon. DF flushes were applied after each angioplasty and "postprocedure" after the device was removed. With POFR, 50 mL were collected through the sheath after balloon angioplasty by either back-pressure of 20 mm Hg, 40 mm Hg or 60 mm Hg, or by aspiration. Postangioplasty pressurized forward flush of 50 or 100 mL was done as described. Each flush was collected, centrifuged, and examined for plaque fragments. Fragments greater than 60 microns were sized and counted on a 100 micron grid. RESULTS: When DF devices were used in 6 mm lumen PTFE, the percent of fragments trapped was poor (13.7% to 27.8%). There were no statistically significant differences between the devices. The capture of fragments improved (22% vs 51.4%, P < .001) when devices appropriate for a 6 mm lumen were used in a 5 mm PTFE "ICA", functionally over-sizing the devices. POFR efficiency improved with increasing back-pressures and with repeated aspirations. Postprocedure, successive flushes of pressurized forward flow yielded additional plaque fragments and when the efficiency of POFR was assessed with forward flushing volumes similar to those used for DF, the efficiencies were similar, although larger fragments were more efficiently removed with POFR. CONCLUSION: In our model, both protection strategies were less than ideal. For POFR, high back pressures or multiple aspirations improve the efficiency of cerebral protection but additional fragments were released by pressurized flow even after aspiration of 150 mL of saline. DF devices create a pressure gradient and fragments apparently went around the device with pressurized flow in our PTFE lumen. Over-sizing of DF devices partially corrected this problem and increased over all DF efficiency to be comparable to POFR for smaller fragments but not for larger fragments.

Outcome of renal stenting for renal artery coverage during endovascular aortic aneurysm repair.

OBJECTIVE: This study was conducted to determine the outcome of adjunctive renal artery stenting for renal artery coverage at the time of endovascular abdominal aortic aneurysm repair (EVAR). METHODS: Between August 2000 and August 2008, 29 patients underwent elective EVAR using bifurcated Zenith stent grafts (Cook, Indianapolis, Ind) and simultaneous renal artery stenting. Renal artery stenting during EVAR was performed with endograft "encroachment" on the renal artery ostium (n = 23) or placement of a renal stent parallel to the main body of the endograft ("snorkel," n = 8). Follow-up included routine contrast-enhanced computed tomography (CT), multiview abdominal radiographs, and serum creatinine measurement at 1, 6, and 12 months, and then yearly thereafter. RESULTS: Thirty-one renal arteries were stented successfully in 29 patients. The 18 patients with planned renal artery stent placement had a proximal neck length <15 mm. Mean proximal neck length was shorter in patients who underwent the "snorkel" technique (6.9 +/- 3.1 mm) compared with those with planned endograft encroachment (9.9 +/- 2.6 mm). None of the patients with unplanned endograft encroachment had neck lengths <15 mm (mean length, 26.3 +/- 10.2 mm). Mean proximal neck angulation was 42.8 degrees +/- 24.0 degrees and did not differ between the groups. One patient had a type I endoleak on completion angiography, and two additional patients had a type I endoleak on the first postoperative CT scan. All type I endoleaks resolved by the 1-month postoperative CT scan. The primary assisted patency of renal artery stents was 100% at a median follow-up of 12.5 months (range, 2 days-77.4 months). In one patient near occlusion of a renal artery stent was noted on follow-up CT scan at 9 months; patency was restored by placement of an additional stent. One patient required dialysis after sustained hypotension from a right external iliac artery injury that resulted in prolonged postoperative bleeding. Mean serum creatinine was 1.1 +/- 0.3 mg/dL at baseline, 1.2 +/- 0.5 mg/dL at 1 month of follow-up, and 1.2 +/- 0.5 mg/dL at 2 years of follow-up. There were no late type I endoleaks (>1 month postoperatively) or stent graft migrations. CONCLUSIONS: Adjunctive renal artery stenting during endovascular AAA repair using the "encroachment" and "snorkel" techniques is safe and effective. Short- and medium-term primary patency rates are excellent, but careful follow-up is needed to determine the durability of these techniques.

Microemboli composed of cholesterol crystals disrupt the blood-brain barrier and reduce cognition.

BACKGROUND AND PURPOSE: Microemboli occur frequently in patients with asymptomatic carotid atherosclerosis. In other vascular beds, microemboli are known to initiate an inflammatory response, causing organ dysfunction. In the current study, we investigated whether emboli composed of cholesterol crystals, a component of human atherosclerotic plaque, could also cause inflammation and brain dysfunction demonstrated by cognitive impairment. METHODS: Cholesterol crystals of 60 to 100 microm were injected via the rat internal carotid artery. T2-weighted magnetic resonance imaging was conducted after 3 days to estimate infarct volume. Brains were examined for matrix metalloproteinase activation at 24 hours and for albumin leakage and microglia and astrocyte activation at 4 days and 1, 2, and 4 weeks after embolization. To determine changes in cognition, behavioral tests including open field, motor learning, and Barnes Maze tests were conducted on young adult and middle-aged rats 4 weeks after either a single injection or after repeated, bilateral injections given at an interval of 2 weeks. RESULTS: Matrix metalloproteinase activation was detected in 50% of the animals examined. Perivascular albumin staining was found at 4 days but rarely persisted beyond 1 week. Activation of microglia and astrocytes occurred in all animals and persisted for up to 8 weeks. Cognitive impairment was observed in middle-aged rats after repeated, bilateral injections but not after single injections. In these animals, areas of inflammation were small and scattered but often involved the striatum and hippocampus. CONCLUSIONS: Cholesterol embolization caused an inflammatory response in the brain with persistent activation of microglia and astrocytes and led to cognitive impairment after repeated injections in middle-aged animals with only small foci of neural injury. These data indicate that microembolization causes inflammation and that minimal neuronal injury can cause cognitive impairment in older animals.

MRI of geometric and compositional features of vulnerable carotid plaque.

Noninvasive imaging of atherosclerotic disease provides a powerful opportunity to gain insight into the complex chain of events underlying atherogenesis, plaque progression, and ultimately those processes that result in atherothrombosis with accompanying clinical symptoms. MRI is particularly attractive because it is noninvasive and is capable of providing a rich array of information on vascular disease. MR methods have been demonstrated to provide information on important features of vascular disease, including the geometric morphology of the flow lumen and the vessel wall, the composition of atheroma, measurement of flow velocities through vessels independent of overlying structures, and more recently insights into the presence and activity of specific molecules that are considered to be important participants in the inflammatory processes and that might differentiate the stable plaque from the vulnerable plaque.

Immediate repair compared with surveillance of small abdominal aortic aneurysms.

BACKGROUND: Whether elective surgical repair of small abdominal aortic aneurysms improves survival remains controversial. METHODS: We randomly assigned patients 50 to 79 years old with abdominal aortic aneurysms of 4.0 to 5.4 cm in diameter who did not have high surgical risk to undergo immediate open surgical repair of the aneurysm or to undergo surveillance by means of ultrasonography or computed tomography every six months with repair reserved for aneurysms that became symptomatic or enlarged to 5.5 cm. Follow-up ranged from 3.5 to 8.0 years (mean, 4.9). RESULTS: A total of 569 patients were randomly assigned to immediate repair and 567 to surveillance. By the end of the study, aneurysm repair had been performed in 92.6 percent of the patients in the immediate-repair group and 61.6 percent of those in the surveillance group. The rate of death from any cause, the primary outcome, was not significantly different in the two groups (relative risk in the immediate-repair group as compared with the surveillance group, 1.21; 95 percent confidence interval, 0.95 to 1.54). Trends in survival did not favor immediate repair in any of the prespecified subgroups defined by age or diameter of aneurysm at entry. These findings were obtained despite a low total operative mortality of 2.7 percent in the immediate-repair group. There was also no reduction in the rate of death related to abdominal aortic aneurysm in the immediate-repair group (3.0 percent) as compared with the surveillance group (2.6 percent). Eleven patients in the surveillance group had rupture of abdominal aortic aneurysms (0.6 percent per year), resulting in seven deaths. The rate of hospitalization related to abdominal aortic aneurysm was 39 percent lower in the surveillance group. CONCLUSIONS: Survival is not improved by elective repair of abdominal aortic aneurysms smaller than 5.5 cm, even when operative mortality is low.

The role of dietary oxidized cholesterol and oxidized fatty acids in the development of atherosclerosis.

The etiology of atherosclerosis is complex and multifactorial but there is extensive evidence indicating that oxidized lipoproteins may play a key role. At present, the site and mechanism by which lipoproteins are oxidized are not resolved, and it is not clear if oxidized lipoproteins form locally in the artery wall and/or are sequestered in atherosclerotic lesions following the uptake of circulating oxidized lipoproteins. We have been focusing our studies on demonstrating that such potentially atherogenic oxidized lipoproteins in the circulation are at least partially derived from oxidized lipids in the diet. Thus, the purpose of our work has been to determine in humans whether oxidized dietary oxidized fats such as oxidized fatty acids and oxidized cholesterol are absorbed and contribute to the pool of oxidized lipids in circulating lipoproteins. When a meal containing oxidized linoleic acid was fed to normal subjects, oxidized fatty acids were found only in the postprandial chylomicron/chylomicron remnants (CM/RM) which were cleared from circulation within 8 h. No oxidized fatty acids were detected in low density lipoprotein (LDL) or high density lipoprotein (HDL) fractions at any time. However, when alpha-epoxy cholesterol was fed to human subjects, alpha-epoxy cholesterol in serum was found in CM/RM and also in endogenous very low density lipoprotein, LDL, and HDL and remained in the circulation for 72 h. In vitro incubation of the CM/RM fraction containing alpha-epoxy cholesterol with human LDL and HDL that did not contain alpha-epoxy cholesterol resulted in a rapid transfer of oxidized cholesterol from CM/RM to both LDL and HDL. We have suggested that cholesteryl ester transfer protein is mediating the transfer. Thus, alpha-epoxy cholesterol in the diet is incorporated into CM/RM fraction and then transferred to LDL and HDL contributing to lipoprotein oxidation. We hypothesize that diet-derived oxidized fatty acids in chylomicron remnants and oxidized cholesterol in remnants and LDL accelerate atherosclerosis by increasing oxidized lipid levels in circulating LDL and chylomicron remnants. This hypothesis is supported by our feeding experiments in animals. When rabbits were fed oxidized fatty acids or oxidized cholesterol, the fatty streak lesions in the aorta were increased by 100%. Moreover, dietary oxidized cholesterol significantly increased aortic lesions in apo-E and LDL receptor-deficient mice. A typical Western diet is rich in oxidized fats and therefore could contribute to the increased arterial atherosclerosis in our population.

Credentialing for carotid artery stenting.

Endovascular treatment of cervical carotid artery stenosis is a rapidly expanding area of clinical competence, and physicians from various subspecialties are already performing carotid artery stenting. As a result of the diverse specialty backgrounds of physicians performing carotid artery stenting, consensus regarding the establishment of credentialing standards remains elusive. In the following manuscript we review the physician credentialing process, published data, and national society position statements applicable to carotid artery stenting.

Cerebral ischemia and infarction from atheroemboli <100 microm in Size.

BACKGROUND AND PURPOSE: To determine the importance of emboli not trapped by carotid angioplasty filtration devices, we examined fragments <100 microm released with ex vivo angioplasty and asked if fragment composition and size correlated with brain injury. METHODS: Human carotid plaques (21) were excised en bloc, and ex vivo carotid angioplasty was performed. Eight plaques were selected as either highly calcified (4) or highly fibrotic (4) by high-resolution MRI (200 microm3). Fragments were counted by a Coulter counter. Before injection into male Sprague-Dawley rats, fragments from calcified and fibrotic plaques were sized with 60-, 100-, and 200-microm filters. Brain ischemia and infarction were assessed by MRI scans (7-T small-bore magnet) and by immunohistologic staining for HSP70 and NueN. RESULTS: All 5 animals injected with 100- to 200-microm calcified fragments had infarctions. One was lethal. After injection of 60- to 100-microm calcified fragments, 7 of 12 animals had cerebral infarctions, whereas only 1 of 11 had infarctions with fibrous fragments (P<0.02). HSP70 staining showed that ischemia was more common and more extensive than infarction. Ischemia was found in 10 of 12 animals after injection of calcified fragments and in 9 of 11 after injection of fibrous fragments. The mean number of 60- to 100-microm fragments released was 375+/-510; the mean number of 20- to 60-microm fragments was 34 196 (range, 2230 to 186 927). CONCLUSIONS: Hundreds of thousands of microemboli can be shed during carotid angioplasty. Fragments from calcified plaques cause greater levels of infarction than fragments from fibrous plaques, although ischemia is common with both fragment types.