Relationship between 'on-treatment platelet reactivity', shear stress, and micro-embolic signals in asymptomatic and symptomatic carotid stenosis.

BACKGROUND: Assessment of 'high on-treatment platelet reactivity (HTPR)' could enhance understanding of the pathophysiology of first or recurrent vascular events in carotid stenosis patients on antiplatelet therapy. METHODS: This prospective, multi-centre study assessed antiplatelet-HTPR status and its relationship with micro-emboli signals (MES) in asymptomatic vs. symptomatic ≥ 50-99% carotid stenosis. Platelet function/reactivity was assessed under 'moderately high shear stress' with the PFA-100® and 'low shear stress' with VerifyNow® and Multiplate® analysers. Bilateral 1-h transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES + ve or MES - ve. RESULTS: Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the 'early phase' (≤ 4 weeks) and 37 patients in the 'late phase' (≥ 3 months) after TIA/ischaemic stroke. Median daily aspirin doses were higher in early symptomatic (225 mg; P < 0.001), but not late symptomatic (75 mg; P = 0.62) vs. asymptomatic patients (75 mg). There was a lower prevalence of aspirin-HTPR in early (28.6%; P = 0.028), but not late symptomatic (38.9%; P = 0.22) compared with asymptomatic patients (56.7%) on the PFA-100®, but not on the VerifyNow® or Multiplate® (P ≤ 0.53). Early symptomatic patients had a higher prevalence of aspirin-HTPR on the PFA-100® (28.6%) vs. VerifyNow® (9.5%; P = 0.049), but not Multiplate® assays (11.9%, P = 0.10). There was no difference in aspirin-HTPR prevalence between any symptomatic vs. asymptomatic MES + ve or MES - ve subgroup. DISCUSSION: Recently symptomatic moderate-severe carotid stenosis patients had a lower prevalence of aspirin-HTPR than their asymptomatic counterparts on the PFA-100®, likely related to higher aspirin doses. The prevalence of antiplatelet-HTPR was positively influenced by higher shear stress levels, but not MES status.

Emergency endovascular management of acute thoracic aortic pathology A safe and feasible option.

Endovascular repair has revolutionised the emergency treatment of thoracic aortic disease. We report our 10 year experience using this treatment in emergency cases. A prospectively maintained vascular database was analysed. Patients' medical records and CT images stored on the hospital PACS system were also reviewed. Statistical analysis was done using IBM SPSS V21. There were a total of 59 thoracic aortic stenting procedures of which 33 (60% males with a mean age of 58 yrs) were performed for emergency thoracic pathologies: traumatic transection (n = 10), ruptured aneurysm (n = 6), non-traumatic dissection (n = 8) and penetrating aortic ulcer (n = 9). All patients had self-expanding endografts implanted. Two patients required debranching procedures before the endovascular treatment. Thirty-day mortality was 12.1% (4/33). 70% of patients received a single device. There were 7 procedure related complications, 6 requiring re-intervention: thoracotomy and drainage in 2 patients, proximal graft extension in 2, open drainage of groin haematoma in 1 and open repair of a common femoral artery pseudo-aneurysm in one patient. In total 23 patients were transferred from 11 centres nationwide. There were no mortalities or other complications related to patient transfer from peripheral centres. Although acute thoracic aortic pathology is life threatening, appropriate blood pressure management and treatment of associated injuries can result in favourable outcomes. Endovascular repair is a safe and effective treatment option which enables patients to be treated with reduced morbidity and mortality. Transfer of patients with acute pathology to a tertiary centre can safely be performed.

Evolution of Carotid Surgical Practice in the last Decade.

Stroke units provide immediate care and appropriate intervention in the evolving stroke. The aims of this study were to review the practice of carotid endarterectomy (CEA) before and after the establishment of a Stroke Unit in St. James's Hospital. Prior to the introduction of the Stroke Unit, 263 CEA's were performed over a five-year period. 139/263 (53%) of these were for symptomatic disease. 229 were performed in the five years since. 179/229 (78%) of these were for symptomatic disease. The 30-day stroke and death rates were < 2% before the introduction of the Stroke Unit, and have remained unchanged. Since the introduction of the Stroke Unit, there has been a slight decrease in the overall number of CEA's performed with a 25% increase in the proportion of endarterectomies performed for symptomatic disease. Despite the reduction in surgery for asymptomatic disease the overall 30-day stroke and death rate remains excellent at 2/229 (2%).

Increased thrombin generation potential in symptomatic versus asymptomatic moderate or severe carotid stenosis and relationship with cerebral microemboli.

INTRODUCTION: The importance of thrombin generation in the pathogenesis of TIA or stroke and its relationship with cerebral microembolic signals (MES) in asymptomatic and symptomatic carotid stenosis has not been comprehensively assessed. METHODS: Plasma thrombin generation parameters from patients with moderate or severe (≥ 50%) asymptomatic carotid stenosis were compared with those from patients with symptomatic carotid stenosis in the early (≤ 4 weeks) and late phases (≥ 3 months) after TIA or stroke in this prospective, pilot observational study. Thrombin generation profile was longitudinally assessed in symptomatic patients with data at each time point. Bilateral transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed whenever possible to classify patients as MES-positive or MES-negative. RESULTS: Data from 31 asymptomatic, 46 'early symptomatic' and 35 'late symptomatic' patients were analysed. Peak thrombin (344.2 nM vs 305.3 nM; p = 0.01) and endogenous thrombin potential (1772.4 vs 1589.7; p = 0.047) were higher in early symptomatic than asymptomatic patients. Peak thrombin production decreased in symptomatic patients followed up from the early to late phase after TIA or stroke (339.7 nM vs 308.6 nM; p = 0.02). Transcranial Doppler ultrasound data were available in 25 asymptomatic, 31 early symptomatic and 27 late symptomatic patients. Early symptomatic MES-positive patients had a shorter 'time-to-peak thrombin' than asymptomatic MES-positive patients (p=0.04), suggesting a more procoagulant state in this early symptomatic subgroup. DISCUSSION: Thrombin generation potential is greater in patients with recently symptomatic than asymptomatic carotid stenosis, and decreases over time following TIA or stroke associated with carotid stenosis. These data improve our understanding of the haemostatic/thrombotic biomarker profile in moderate-severe carotid stenosis.

Fenestrated endovascular repair of complex aortic aneurysms.

BACKGROUND: Fenestrated endovascular aneurysm repair (FEVAR) provides an endovascular solution for patients with large abdominal aortic aneurysms and challenging neck anatomy in addition to repair of endoleaks and pseudoaneurysms. This article reports the midterm outcomes of FEVAR from a single-tertiary referral centre in Ireland. METHODS: From 2006 to 2012, nine consecutive asymptomatic patients with neck anatomy unfavourable for standard EVAR underwent endovascular repair with a customised fenestrated Zenith stent graft. An additional three patients had fenestrated grafts for repair of pseudoaneurysms (n = 2) following open AAA repair and a type I endoleak (n = 1). All patients were prospectively enrolled in a computerised database. Outcomes including mortality, morbidity, renal function, target vessel patency, endoleak and reintervention were analysed. FINDINGS: The mean age and aneurysm size in the primary repair group were 74 years (65-84 years) and 6 cm (5-8.3 cm), respectively, and in the secondary repair group, the mean age was 66 years (61-75 years). No procedures required open conversion, and no visceral arteries were lost. On completion angiography, two patients in group 1 had a type I endoleak and one had a type III endoleak. There were no endoleaks in the secondary repair group. Follow-up ranged from 30 days to 6 years. There was one death within 30 days (8 %) and two deaths at 3 years from non-aneurysm-related causes. Six patients required secondary interventions. Three patients had a transient post-operative creatinine rise of >30 %. CONCLUSION: Our study supports FEVAR as a feasible and effective therapy in the management of patients with complex aortic aneurysms.

Increased endothelial activation in recently symptomatic versus asymptomatic carotid artery stenosis and in cerebral microembolic-signal-negative patient subgroups.

BACKGROUND AND PURPOSE: von Willebrand factor propeptide (VWF:Ag II) is potentially a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). These biomarkers have not been simultaneously assessed in asymptomatic versus symptomatic carotid stenosis patients. The relationship between endothelial activation and cerebral microembolic signals (MESs) detected on transcranial Doppler ultrasound is unknown. METHODS: In this multicentre observational analytical study, plasma VWF:Ag and VWF:Ag II levels in patients with ≥50% asymptomatic carotid stenosis were compared with those from patients with ≥50% symptomatic carotid stenosis in the 'early' (≤4 weeks) and 'late' (≥3 months) phases after transient ischaemic attack or ischaemic stroke. Endothelial activation was also longitudinally assessed in symptomatic patients during follow-up. Transcranial Doppler ultrasound monitoring classified patients as MES-positive or MES-negative. RESULTS: Data from 31 asymptomatic patients were compared with those from 46 early symptomatic and 35 late phase symptomatic carotid stenosis patients, 23 of whom had undergone carotid intervention. VWF:Ag II levels were higher in early (12.8 µg/ml; P < 0.001), late (10.6 µg/ml; P = 0.01) and late post-intervention (10.6 µg/ml; P = 0.038) symptomatic patients than asymptomatic patients (8.9 µg/ml). VWF:Ag levels decreased in symptomatic patients followed up from the early to late phase after symptom onset (P = 0.048). Early symptomatic MES-negative patients had higher VWF: Ag II levels (13.3 vs. 9.0 µg/ml; P < 0.001) than asymptomatic MES-negative patients. CONCLUSIONS: Endothelial activation is enhanced in symptomatic versus asymptomatic carotid stenosis patients, in early symptomatic versus asymptomatic MES-negative patients, and decreases over time in symptomatic patients. VWF:Ag II levels are a more sensitive marker of endothelial activation than VWF:Ag levels in carotid stenosis. The potential value of endothelial biomarkers and concurrent cerebral MES detection at predicting stroke risk in carotid stenosis warrants further study.

Endovascular repair of thoracoabdominal aortic aneurysm (TAAA): early experience.

BACKGROUND: Repair of thoracoabdominal aortic aneurysms (TAAA) represents a considerable technical challenge. Since its first description in 1955, open repair of TAAA has been considered the gold standard of repair. Despite improvements in surgical techniques, spinal cord protection and post-operative critical care support, patients who undergo open repair are faced with a mortality rate of 5-35 %. We report the first Irish experience of endovascular management of TAAAs. RESULTS: To date five patients have undergone endovascular repair; four had hybrid repair and one a fenestrated graft. The mean age of the patients was 66.8 ± 3.4 and the mean aneurysm diameter was 6.74 ± 0.6 cm. All patients were ASA III. Two-stage hybrid repair was associated with an increased risk of complications, prolonged intensive care unit and overall hospital stay. One patient died in the perioperative period due to rupture of their aneurysm between the two stages of their hybrid repair. CONCLUSION: The role of endovascular techniques in the treatment of TAAA continues to evolve. Hybrid and complete endovascular repairs do not replace conventional repair, but provide an alternative for high-risk patients who might otherwise be denied treatment.

Increased platelet activation in early symptomatic vs. asymptomatic carotid stenosis and relationship with microembolic status: results from the Platelets and Carotid Stenosis Study.

BACKGROUND: Cerebral microembolic signals (MES) may predict increased stroke risk in carotid stenosis. However, the relationship between platelet counts or platelet activation status and MES in symptomatic vs. asymptomatic carotid stenosis has not been comprehensively assessed. SETTING: University teaching hospitals. METHODS: This prospective, pilot observational study assessed platelet counts and platelet activation status, and the relationship between platelet activation and MES in asymptomatic vs. early (≤ 4 weeks after TIA/stroke) and late phase (≥ 3 months) symptomatic moderate or severe (≥ 50%) carotid stenosis patients. Full blood count measurements were performed, and whole blood flow cytometry was used to quantify platelet surface activation marker expression (CD62P and CD63) and circulating leucocyte-platelet complexes. Bilateral simultaneous transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed for 1 h to classify patients as MES positive or MES negative. RESULTS: Data from 31 asymptomatic patients were compared with 46 symptomatic patients in the early phase, and 35 of these patients were followed up to the late phase after symptom onset. The median platelet count (211 vs. 200 × 10(9)  L(-1) ; P = 0.03) and the median percentage of lymphocyte-platelet complexes was higher in early symptomatic than asymptomatic patients (2.8 vs. 2.4%; P = 0.001). The percentage of lymphocyte-platelet complexes was higher in early symptomatic than in asymptomatic patients with ≥ 70% carotid stenosis (P = 0.0005) and symptomatic patients recruited within 7 days of symptom onset (P = 0.028). Complete TCD data were available in 25 asymptomatic, 31 early phase symptomatic and 27 late phase symptomatic patients. Twelve per cent of asymptomatic vs. 32% of early phase symptomatic (P = 0.02) and 19% of late phase symptomatic patients (P = 0.2) were MES positive. Early symptomatic MES-negative patients had a higher percentage of lymphocyte-platelet complexes than asymptomatic MES-negative patients (2.8 vs. 2.3%; P = 0.0085). DISCUSSION: Recently, symptomatic carotid stenosis patients have had higher platelet counts (potentially reflecting increased platelet production, mobilization or reduced clearance) and platelet activation status than asymptomatic patients. MES were more frequently detected in early symptomatic than asymptomatic patients, but the differences between late symptomatic and asymptomatic groups were not significant. Increased lymphocyte-platelet complex formation in recently symptomatic vs. asymptomatic MES-negative patients indicates enhanced platelet activation in this early symptomatic subgroup. Platelet biomarkers, in combination with TCD, have the potential to aid risk-stratification in asymptomatic and symptomatic carotid stenosis patients.

A critical evaluation of HIPE data.

Resource allocation and planning of future services is dependent on current volumes, making it imperative that procedural data is accurately recorded. We sought to evaluate the effectiveness of the information gathered by the Hospital Inpatient Enquiry (HIPE) system in recording such activity. Five index vascular procedures (open/endovascular abdominal aneurysm repair, carotid endarterectomy, lower limb angioplasty/bypass) were chosen to reflect activity. The Economic and Social Research Institute (ESRI), and HIPE databases were interrogated to obtain the regional and hospital specific figures for the years 2005, 2006 and 2009, and then compared with the prospective vascular database in St James's hospital. Data for 2006 (the most recent year available) shows significant discrepancies between the HIPE and vascular database figures for St James's hospital. The HIPE and database figures respectively for; open aneurysm 13/30 (-50%), endovascular aneurysm 39/31 (+25%), carotid 62/48 (+29%), angioplasty 242/111 (+100%) and bypass 24/10 (+100%) These inaccuracies are likely to be magnified on a regional and national level when pooling data.

Measurement and optimization of patient radiation doses in endovascular aneurysm repair.

The study assessed radiation exposure during EVAR. Two types of patient dose were estimated: effective dose (ED), which allows estimation of radiation risk to the EVAR patient population; and Peak Skin Dose (PSD), which allows us assess the potential for an individual patient to receive a radiation skin injury. An ancillary aim was to examine dose optimization in EVAR procedures. Based on 111 EVAR cases we estimated average ED as 12.4 mSv. Cumulative patient dose in our centre was lower than other studies because the follow up of EVAR patients is based on ultrasound rather than CT. PSD calculated using a published conversion formula closely matched measurements with calibrated gafchromic film. 99% of patients had an estimated PSD of < 2Gy. Results indicate that skin injuries are possible, but very unlikely in EVAR procedures at our centre. EVAR is a high dose procedure and emphasis on dose optimisation is important. We broke the EVAR procedure into 15 steps and, in a phantom study, showed how skin dose changes as procedure steps are varied. The resulting dose matrix has the potential to be used as an educational tool to promote dose optimization.

Hybrid repair of thoracic aortic arch aneurysm.

INTRODUCTION: Aortic arch pathology requiring surgery most often affects elderly patients with multiple co-morbidities and represents a significant challenge to both patient and surgeon. MATERIALS AND METHODS: This case report describes the repair of an 8.2 cm aortic arch aneurysm arising at the origin of the left subclavian artery using a combined endovascular and open surgical approach. CONCLUSION: Hybrid techniques allow for the treatment of pathology that would otherwise not be amenable to surgery.

Hybrid repair of a symptomatic thoracic intra-mural haematoma.

INTRODUCTION: The repair of thoracic aortic pathology by open techniques is associated with high morbidity and mortality. METHODS: We describe the first case of hybrid thoracic aortic repair performed in Ireland for a symptomatic thoracic intramural haematoma. CONCLUSION: Hybrid repair with extra-anatomical aortic visceral revascularisation and subsequent thoracic endograft exclusion offers an attractive alternative method of repair for thoracic aortic pathology.

Endovascular management of thoracic aortic pathology.

BACKGROUND: Endovascular technology has revolutionised the management of abdominal aortic aneurysmal disease but the less frequent occurrence of pathology in the thoracic aorta has meant that evidence demonstrating the primacy of endovascular treatment strategies in this portion of the vessel is less convincing. Herein we summarise the best available evidence to date. METHODS: A comprehensive search of the surgical and radiological literature using the search term 'endovascular thoracic aorta' was conducted. FINDINGS AND CONCLUSIONS: The vast majority of patients treated by thoracic aortic stent grafting have had their treatment outside the context of a randomised trial. While it would seem that endovascular repair is the treatment of choice for the thoracic aorta, the present evidence is based on single centre case series and is anecdotal at best.

Percutaneous endovascular abdominal aortic aneurysm repair leads to a reduction in wound complications.

INTRODUCTION: While endovascular aortic aneurysm repair (EVAR) has significantly reduced the morbidity associated with open surgery, efforts continue to minimise the surgical insult to the patient. We report our experience of percutaneous EVAR. PATIENTS AND METHODS: Since June 2005, 17/20 EVARs (85%) have been attempted percutaneously by deployment of two Perclose) devices into each femoral artery prior to passage of the device sheath. The sutures are left untied until the sheath is removed at the end of the procedure, when haemostasis is obtained. Patients were entered onto a prospectively maintained database and followed up at regular intervals in a dedicated EVAR clinic. RESULTS: Access and subsequent graft deployment was successful in all the 17 cases. The range of defects closed ranged from 12-24 Fr. Five patients (29%) required open groin exploration at the end of the procedure to achieve haemostasis. There was a significantly lower incidence of wound complications in the percutaneous EVAR group (6 vs. 10% open cutdown cases, P < 0.05, Mann-Whitney U test). CONCLUSION: Percutaneous EVAR is both a feasible and safe method of performing endovascular abdominal aortic aneurysm repair, which is associated with a reduction in wound complication rates.

Prospective randomized controlled trial: conventional versus powered phlebectomy.

OBJECTIVES: Transilluminated powered phlebectomy (TriVex) is a new surgical technique that uses tumescent dissection, transillumination, and powered phlebectomy. The purpose of this study was to compare TriVex with conventional varicose vein surgery in terms of pain, cosmesis, recurrence, complications, and operating time. METHODS: One hundred eighty-eight limbs in 141 patients (33 men, 108 women; mean age, 42.5 years) with varicose veins were randomised to conventional (n = 100) or TriVex (n = 88). Exclusion criteria were venous ulceration or deep venous disease. Varicosities were graded with CEAP and clinical assessment (grades 1-3), and were similar in both groups. Randomization was single blinded. Long or short saphenous vein ligation or stripping was performed as indicated with duplex scanning. Operative time was from skin incision to leg bandaging. Phlebectomy was performed with conventional stab avulsions or TriVex. Patients completed assessment forms preoperatively and postoperatively (2, 6, 26, 52 weeks), and this was supplemented with physician clinical evaluation. Pain was assessed with visual analog score. RESULTS: There was a significant difference in the number of incisions for phlebectomy in the two groups (conventional, n = 29; TriVex, n = 5; P <.0001). TriVex was faster in the grade 3 (extensive) group, but this did not reach statistical significance. There was no difference in mean postoperative pain score over 8 days in the two groups (P =.4624). At 2 weeks there was no significant difference between the groups with regard to bruising (P =.77), cellulitis (P =.33), and numbness (P =.33). At 6 weeks there was no significant difference between the groups with regard to nerve injury (P =.97), residual veins (P =.79), cosmetic score (P =.837), and overall satisfaction (P =.878). At 6 and 12 months, there was no significant difference in cosmesis (P =.955, P =.088, respectively) or recurrence (P =.27, P =.11, respectively). CONCLUSIONS: TriVex is a safe and effective method for excision of varicosities and compares well, after a learning curve, with conventional surgery in regard to complications and recurrence. It has the advantage of a trend toward reduced operating time in extensive varicosities, and significantly fewer incisions, although there was no perceived difference in cosmesis during follow-up.

Low dose intraarterial thrombolysis with tissue plasminogen activator: does it deliver as promised?

The widespread use of intraarterial thrombolytic therapy has been based on perceived benefits over operative treatment and the downgrading of the magnitude of subsequent surgery. Thirty-three patients who had thrombolysis for peripheral artery occlusion were retrospectively analyzed at St. James's Hospital from 1991 to 1997. One patient received streptokinase unsuccessfully. Five other patient's records were inadequate for analysis. Twenty-seven patient's notes were analyzed for risk, duration of occlusion, duration of treatment, dosage of tissue plasminogen activator (tPA) and conduits thrombolysed. There were 15 males and 12 females. The mean age was 62 years (range, 20-87). Fourteen were current or reformed smokers. Five were diabetic. Indications for treatment included acute graft occlusion (n=13), embolus (n=6), and primary and secondary arterial thrombosis (n=8). Duration of occlusion was less than 24 hours in seven, 1 to 7 days in ten, and more than 7 days in ten patients. Twelve (44.44%) patients had complete clot lysis, four (14.81%) had partial clearance, and 11 (40.74%) remained occluded. Eight (29.63%) had serious complications including one death. Eighteen (66.66%) patients needed further surgical intervention to maintain graft patency. Data were analyzed using the chi-square and pooled t test. No significant difference was observed in results from thrombolysis from different conduits, gender, etiology, or smoking history. Increased duration of tPA administration was associated with an increased risk of failure. Administration of total dosages greater than 60 mg was associated with a higher risk of failure. Diabetics had a poor outcome (p=0.0520). Only 44 % of patients successfully underwent lysis. A primary surgical option may be a more sensible course than lysis, given that the vast majority of patients ended up having surgery anyway.

Ultrasound guided human thrombin injection. A new modality in the management of femoral artery pseudo-aneurysms.

OBJECTIVES: We report our initial results of a prospective study of duplex ultrasound-guided injection (UGTI ) of thrombin in the management of femoral artery pseudo-aneurysms. We used human thrombin to avoid the increase in the human antibodies directed against fibrinogen, with the use of bovine thrombus, that preclude further utilisation of the bovine fibrin glue during cardio-thoracic surgery. METHODS: From 1999 to 2001, 19 patients, aged 69 (range 52-85) years presented with 21 femoral pseudo-aneurysms were treated. The mean pseudoaneurysm diameter was 30 (15-55) mm. All but two were secondary to cardiac procedures and the common femoral artery was the injured vessel in all instances. Patients were referred within 2-21 days following their iatrogenic injury. RESULTS: Immediate thrombosis of the sac occurred in 19 (90%) of the 21 pseudo-aneurysms. After a second injection, complete occlusion occurred in the remaining two patients. Two patients (CI 95%; 1-19) with three femoral pseudo-aneurysms developed leg pain. Duplex ultrasound follow-up showed two recurrences (9.5% - CI 95%; 1-19) and both were treated by repeat UGTI. There was no conversion to surgical repair. CONCLUSION: This percutaneous minimally invasive technique is safe and effective in the management of iatrogenic pseudo-aneurysms in this high-risk group of patients. Human thrombin has significant advantages over bovine thrombin.