Sanjay D. Patel

Factors Influencing the Frequency of Fluorescence Transients as Markers of Peri-Infarct Depolarizations in Focal Cerebral Ischemia

BACKGROUND AND PURPOSE Peri-infarct depolarizations (PIDs) that occur in ischemic boundary zones of the cerebral cortex of experimental animals have been shown to promote rather than simply to indicate the evolution of the lesion and are especially prominent in the rat. To study the influence of one factor, species, on PID incidence, we compared the frequency of PIDs in a primate species, the squirrel monkey, with that in the cat after middle cerebral artery occlusion. Plasma glucose was reviewed as a possible cause of interexperiment variability in the cat experiments. METHODS In open-skull experiments under chloralose anesthesia, changes in cortical fluorescence believed to indicate NADH/NAD(+) redox state, as markers of PIDs, were recorded by serial imaging of the cortical surface in vivo for 4 hours after middle cerebral artery occlusion. RESULTS Fluorescence transients occurred in squirrel monkeys at a frequency (mean+/-SD) of 0.7+/-0.8 hours(-1) (n=5), which was not significantly less than in that observed in cats (1.3+/-1.6 hours(-1), n=8). Data from the cat experiments indicated a relationship between number of transients (dependent) and plasma glucose, with a striking increase in PID frequency in association with values of mean postocclusion plasma glucose <4.1 mmol/L (Mann-Whitney U=15.0, P=0.034); this observation agrees well with other published findings. CONCLUSIONS Transient changes in fluorescence strongly suggestive of peri-infarct depolarizations, either transient or terminal, occur and propagate in the ischemic cerebral cortex of a nonhuman primate. The results also suggest that the relationship of frequency of peri-infarct depolarizations with plasma glucose requires further examination, to confirm the finding and to determine a safe lower limit for a target range for control of plasma glucose if insulin is used in the management of patients with cerebral ischemia.

The role of endothelial cells and their progenitors in intimal hyperplasia

Intimal hyperplasia leading to restenosis is the major process that limits the success of cardiovascular intervention. The emergence of vascular progenitor cells and, in particular, endothelial progenitor cells has led to great interest in their potential therapeutic value in preventing intimal hyperplasia. We review the mechanism of intimal hyperplasia and highlight the important attenuating role played by a functional endothelium. The role of endothelial progenitor cells in maintaining endothelial function is reviewed and we describe how reduced progenitor cell number and function and reduced endothelial function lead to an increased risk of intimal hyperplasia. We review other potential sources of endothelial cells, including monocytes, mesenchymal stem cells and tissue resident stem cells. Endothelial progenitor cells have been used in clinical trials to reduce the risk of restenosis with varied success. Progenitor cells have huge therapeutic potential to prevent intimal hyperplasia but a more detailed understanding of vascular progenitor cell biology is necessary before further clinical trials are commenced.

A novel approach to the management of a ruptured Type II endoleak following endovascular repair of an internal iliac artery aneurysm

Endovascular repair of isolated iliac artery aneurysms is an established safe and effective management option. Type II endoleak is a potential complication, but rarely results in significant morbidity or mortality. We report a case of a patient who presented with a ruptured internal iliac artery aneurysm secondary to a Type II endoleak. To our knowledge this and the following method of managing this have not been previously reported. Established methods of managing endoleaks, such as intravascular transfemoral embolisation and open or laparoscopic ligation, were not possible. Therefore, we resorted to a novel approach to this type of aneurysm and successfully performed a transcutaneous direct puncture and embolisation of the superior gluteal artery.

Results of complex aortic stent grafting of abdominal aortic aneurysms stratified according to the proximal landing zone using the Society for Vascular Surgery classification

BACKGROUND Advances in endovascular technology have led to the successful treatment of complex abdominal aortic aneurysms. However, there is currently no consensus on what constitutes a juxtarenal, pararenal, or suprarenal aneurysm. There is emerging evidence that the extent of the aneurysm repair is associated with outcome. We compare the outcomes of 150 consecutive patients treated with a fenestrated or branched stent graft and present the data stratified according to the Society for Vascular Surgery classification based on proximal anatomic landing zones. METHODS A prospectively collected database of consecutive patients undergoing fenestrated or branched stent graft insertion in a tertiary center between 2008 and 2013 was retrospectively analyzed. Aneurysms were subdivided into zones according to where the area of proximal seal could be achieved in relation to the visceral arteries. Zone 8 covers the renal arteries, zone 7 covers the superior mesenteric artery, and zone 6 covers the celiac axis. Patient demographics, operative variables, mortality, and major morbidity were analyzed by univariate and multivariate analysis to assess for differences between zones. RESULTS During the study period, 150 patients were treated. There were 49 in zone 8, 76 in zone 7, and 25 in zone 6. Prior aortic surgery had been performed in 19 patients, which included 11 patients with previous endovascular aneurysm repairs. There was significantly increased blood loss (P < .001), operative time (P < .0001), total hospital stay (P = .018), and intensive care unit stay (P < .0001) as the zones ascended the aorta. There were 14 inpatient deaths recorded across all zones with a 30-day mortality rate of 8%. Logistic regression analysis for 30 day mortality showed a significant increase as the zones ascended (P = .007). Kaplan-Meier analysis showed that 5-year survival significantly deteriorated as the zones ascended (P = .039), with no significant difference in the freedom from reintervention curves between zones (P = .37). CONCLUSIONS We have shown that the extent of the aneurysm repair as determined by the proximal sealing zone is associated with outcome. Mortality, operative duration, blood loss, and hospital stay all significantly increased as the zones ascended. These data also validate the use of the proposed new classification based on aortic anatomy.

Comparison of angioplasty and bypass surgery for critical limb ischaemia in patients with infrapopliteal peripheral artery disease.

Both infrapopliteal (IP) bypass surgery and percutaneous transluminal angioplasty have been shown to be effective in patients with critical limb ischaemia (CLI). The most appropriate method of revascularization has yet to be established, as no randomized trials have been reported. The aim of this study was to compare the outcomes of patients with similar characteristics treated using either revascularization method.

Atherosclerotic Plaque Analysis: A Pilot Study to Assess a Novel Tool to Predict Outcome Following Lower Limb Endovascular Intervention.

INTRODUCTION Atherosclerotic plaque analysis using computed tomography angiography (CTA) has been found to be accurate and reproducible in the coronary and carotid arteries. The aim of our study was to assess the utility of this technique in predicting outcome following lower limb endovascular interventions. METHODS Pre-procedural CTA was retrospectively analysed in 50 patients who had undergone femoropopliteal (F-P) angioplasty (and/or stenting). Plaque analysis was performed using TeraRecon workstation by two observers blinded to the long-term outcome. Using the Hounsfield units (HU) scale atherosclerotic plaque composition was subdivided into volumes of soft (-100-100 HU) fibrocalcific (101-300 HU) or calcified (300-1000 HU) components. The relationship between plaque composition, clinical and procedural variables, and the study end points (vessel patency, binary restenosis rate, and Amputation-Free Survival [AFS]) were assessed using multivariate analysis. RESULTS The technical success rate of the endovascular procedure was 98%, with 48% of patients receiving F-P stents. The AFS was 90%, primary patency 84%, assisted primary patency 88%, and binary restenosis 44% all at 1 year. A significantly greater total volume of calcified plaque (1.1 [.01-3.2] cm(3) vs. .11 [0-1.86] cm(3), p < .001) was found in patients developing restenosis (>50%) compared with those who did not. Patients with a calcified plaque volume greater than 1.1 cm(3) had a significantly worse AFS than those with a volume less than 1.1 cm(3) (p = .0038). Multivariate analysis showed that the percentage calcified plaque (p = .003, HR 11.4, 95% CI 1.45-37.29) was an independent predictor of binary restenosis at 12 months, and that absolute volume of calcified plaque (p = .001, HR 3.56, 95% CI 1.64-7.7) was independently associated with AFS. CONCLUSIONS The burden of calcified plaque, but not soft or fibrocalcific plaque is related to restenosis, reintervention, and AFS. Computed tomography plaque analysis may form an important non-invasive tool for risk stratification in patients undergoing F-P endovascular procedures.

The efficacy of salvage interventions on threatened distal bypass grafts.

OBJECTIVE Infrapopliteal bypass is an established and effective method for limb salvage in patients with critical limb ischemia. Secondary interventions maybe required to maintain graft patency. The aim of this study was to look at the frequency and outcomes of such interventions. METHODS Consecutive patients undergoing bypasses onto the infrapopliteal vessels for critical limb ischemia (Rutherford 4-6) at a single institution were analyzed between 2009 and 2013. The primary end points were graft patency, amputation-free survival (AFS), and freedom from reintervention at 12 months by Kaplan-Meier analysis. RESULTS A total of 114 infrapopliteal bypasses were performed in 102 patients. Distal anastomosis was on to the anterior tibial (n = 31), posterior tibial (n = 27), peroneal (n = 24), tibioperoneal trunk (n = 23), or dorsalis pedis artery (n = 9). Primary patency, assisted primary patency, and secondary patency was 57%, 76%, and 82%, respectively, at 12 months and 44%, 70%, and 80%, respectively, at 36 months. AFS was 80% at 12 months and 65% at 36 months. Endovascular salvage interventions were performed on 58 grafts (51%) including angioplasty of inflow/proximal anastomosis (33%), outflow/distal anastomosis (46%), and graft stenosis (20%), with a further 12 grafts (11%) undergoing thrombolysis for occlusion. Surgical salvage interventions included jump grafts (n = 7), revision of anastomotic stenosis (n = 3), and thrombectomy (n = 2). AFS was similar in salvaged threatened and acutely occluded grafts compared with nonthreatened grafts (P = .064) and better in grafts requiring reintervention later (>6 months from bypass) compared with those requiring early reintervention (<6 months; P = .047). CONCLUSIONS Secondary interventions in threatened distal bypass grafts are successful at maintaining graft patency and AFS when compared with nonthreatened grafts, and are associated with a low morbidity rate.

Hematopoietic Progenitor Cells and Restenosis After Carotid Endarterectomy

Background and Purpose— Hematopoietic progenitor cells (HPCs) may attenuate the response to vascular injury by maintaining endothelial integrity and function. Our aim was to determine whether circulating HPC number and function correlate with restenosis after carotid endarterectomy. Methods— HPC number (CD34+/CD133+ cells), early colony-forming units, migratory capacity, and senescence were analyzed in blood collected preoperatively, 1 day, and 6 weeks postoperatively. Mobilizing cytokine levels were also measured. Stenosis was assessed by duplex scanning. Results— HPC numbers (P<0.001) and early colony-forming unit count (P=0.001) fell rapidly 24 hours postoperatively. Restenosis at 6 months correlated negatively with the magnitude of postoperative falls in HPC numbers (R=−0.38, P=0.013) and early colony-forming unit counts (R=−0.42, P=0.008). The migratory capacity of preoperative HPCs correlated negatively with restenosis (R=−0.48, P=0.007). Preoperative SDF1 levels correlated with falls in HPC number (R=0.42, P=0.044) and early colony-forming unit counts (R=0.56, P=0.004). Conclusions— HPC function appears to be linked to the development of carotid artery restenosis after endarterectomy. These data support the concept that HPCs have a role in regulating remodeling of the injured arterial wall.

Cystic Adventitial Disease of the Common Femoral Artery Presenting with Acute Limb Ischemia

Cystic adventitial disease (CAD) is a recognized cause of chronic lower limb ischemia. We present a case of CAD presenting as acute lower limb ischemia. A 54-year-old woman presented with a 48-hr history of sudden-onset right leg and foot pain associated with paresthesia and weakness. Duplex ultrasound and computed tomography angiogram showed acute occlusion of the common, superficial, and profunda femoral arteries. On surgical exploration, a mucinous cystic structure was found occluding the common femoral artery (CFA), which was later confirmed on histology as CAD. Because of the extent of the cyst, we treated this with an interposition graft, and the patient initially made a good recovery. However, 2 months later, she presented again with acute lower limb ischemia, and investigation and surgical exploration confirmed further cystic degeneration of the remaining part of the CFA. This case highlights a rare presentation and shows the importance of a high index of suspicion when investigating and treating young patients with lower limb symptoms, particularly when interpreting imaging.

Bone marrow mononuclear cells drive thrombus resolution

Objective: ESCT and NASCET established the role of CEA in appropriate patients but reported a 5–7% 30-day stroke/death risk. Strategies reducing this would be important. The GALA Trial was conceived following analysis of non-randomised and randomised studies suggesting a 50% risk reduction for LA CEA. Method: A total of 3526 patients (symptomatic or asymptomatic disease) were randomised to GA or LA (95 centres, 24 countries). Primary outcome events were stroke, myocardial infarction or death (randomisation −30 days post-surgery). The data were analysed by intention-to-treat analysis. Results: Events occurred (99·9% follow-up) in 84/1752 (4·8%) GA and 80/1771 (4·5%) LA patients (not significant: three events prevented per 1000 LA patients [95% CI −11, +17]; risk ratio 0·94 [95% CI 0·70, 1·27]). There were no differences for individual outcome events: stroke 70 (4·0%) GA versus 66 (3·7%) LA (three prevented per 1000 LA patients [95% CI −10 to +16]); death 26 (1·5%) GA versus 19 (1·1%) LA (four prevented per 1000 [95% CI −3 to +12]); myocardial infarction LA 9 (0·5%) versus GA 4 (0·2%) (three more per 1000 LA patients [95% CI −2 to +8]). In patients with contralateral carotid occlusion (pre-defined sub-group), outcome events occurred in 15/150 (10%) GA versus 8/160 (5%) LA, p = 0·098. Further 1-year survival data indicate fewer subsequent events (stroke, death, MI) in LA patients (p = 0·094). Conclusion: These data show that CEA outcomes have improved by up to a third since earlier trials and that both LA and GA are safe. For patients with contralateral carotid occlusion, LA might offer a benefit and trends suggesting improved 1-year survival following LA surgery require further analysis.