Peter Gaines

Global experience in cervical carotid artery stent placement

The purpose of this article is to review and update the current status of carotid artery stent placement in the world. Surveys to major interventional centers in Europe, North and South America, and Asia were initially completed in June 1997. Subsequent information from these 24 centers in addition to 12 new centers has been obtained to update the information. The survey asked the various questions regarding the patients enrolled, procedure techniques, and results of carotid stenting, including complications and restenosis. The total number of endovascular carotid stent procedures that have been performed worldwide to date included 5,210 procedures involving 4,757 patients. There was a technical success of 98.4% with 5,129 carotid arteries treated. Complications that occurred during the carotid stent placement or within a 30‐day period following placement were recorded. Overall, there were 134 transient ischemic attacks (TIAs) for a rate of 2.82%. Based on the total patient population, there were 129 minor strokes with a rate of occurrence of 2.72%. The total number of major strokes was 71 for a rate of 1.49%. There were 41 deaths within a 30‐day postprocedure period resulting in a mortality rate of 0.86%. The combined minor and major strokes and procedure‐related death rate was 5.07%. Restenosis rates of carotid stenting have been 1.99% and 3.46% at 6 and 12 months, respectively. The rate of neurologic events after stent placement has been 1.42% at 6–12‐month follow‐up. Endovascular stent treatment of carotid artery atherosclerotic disease is growing as an alternative for vascular surgery, especially for patients that are high risk for standard carotid endarterectomy. The periprocedure risks for major and minor strokes and death are generally acceptable at this early stage of development and have not changed significantly since the first survey results. Cathet. Cardiovasc. Intervent. 50:160–167, 2000. ©2000 Wiley–Liss,Inc.

Multicenter evaluation of carotid artery stenting with a filter protection system

OBJECTIVES The aim of this study was to evaluate the feasibility and safety of carotid artery stenting (CAS) with a filter protection system. BACKGROUND Neurologic events linked to the embolization of particulate matter to the cerebral circulation may complicate CAS. Strategies designed to capture embolic particles during carotid intervention are being evaluated for their efficacy in reducing the risk of these events. METHODS Between September 1999 and July 2001, a total of 162 patients (164 hemispheres) underwent CAS with filter protection (NeuroShield, MedNova Ltd., Galway, Ireland) according to prospective protocols evaluating the filter system at three institutions. RESULTS Angiographic success was achieved in 162 of the procedures (99%) and filter placement was successful in 154 (94%) procedures. Carotid access was unsuccessful in two cases (1%) and filter placement in eight cases (5%). Of the latter, five procedures were completed with no protection and three were completed using alternative protection devices. On an intention-to-treat basis, the overall combined 30-day rate of all-stroke and death was 2% (four events: two minor strokes and two deaths). This includes one minor stroke in a patient with failed filter placement and CAS completed without protection. There was one cardiac arrhythmic death and one death from hyperperfusion-related intracerebral hemorrhage. There were no major embolic strokes. CONCLUSIONS Carotid artery stenting with filter protection is technically feasible and safe. Early clinical outcomes appear to be favorable and need to be confirmed in a larger comparative study.

Long-term risk of carotid restenosis in patients randomly assigned to endovascular treatment or endarterectomy in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): long-term follow-up of a randomised trial

Summary Background In the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), early recurrent carotid stenosis was more common in patients assigned to endovascular treatment than it was in patients assigned to endarterectomy (CEA), raising concerns about the long-term effectiveness of endovascular treatment. We aimed to investigate the long-term risks of restenosis in patients included in CAVATAS. Methods 413 patients who were randomly assigned in CAVATAS and completed treatment for carotid stenosis (200 patients had endovascular treatment and 213 patients had endarterectomy) had prospective clinical follow-up at a median of 5 years and carotid duplex ultrasound at a median of 4 years. We investigated the cumulative long-term incidence of carotid restenosis after endovascular treatment and endarterectomy, the effect of the use of stents on restenosis after endovascular treatment, risk factors for the development of restenosis, and the effect of carotid restenosis on the risk of recurrent cerebrovascular events. Analysis was by intention to treat. This study is registered, number ISRCTN01425573. Findings Severe carotid restenosis (≥70%) or occlusion occurred significantly more often in patients in the endovascular arm than in patients in the endarterectomy arm (adjusted hazard ratio [HR] 3·17, 95% CI 1·89–5·32; p<0·0001). The estimated 5-year incidence of restenosis was 30·7% in the endovascular arm and 10·5% in the endarterectomy arm. Patients in the endovascular arm who were treated with a stent (n=50) had a significantly lower risk of developing restenosis of 70% or greater compared with those treated with balloon angioplasty alone (n=145; HR 0·43, 0·19–0·97; p=0·04). Current smoking or a history of smoking was a predictor of restenosis of 70% or more (2·32, 1·19–4·54; p=0·01) and the early finding of moderate stenosis (50–69%) up to 60 days after treatment was associated with the risk of progression to restenosis of 70% or more (3·76, 1·88–7·52; p=0·0002). The composite endpoint of ipsilateral non-perioperative stroke or transient ischaemic attack occurred more often in patients in whom restenosis of 70% or more was diagnosed in the first year after treatment compared with patients without restenosis of 70% or more (5-year incidence 23% vs 11%; HR 2·18, 1·04–4·54; p=0·04), but the increase in ipsilateral stroke alone was not significant (10% vs 5%; 1·67, 0·54–5·11). Interpretation Restenosis is about three times more common after endovascular treatment than after endarterectomy and is associated with recurrent ipsilateral cerebrovascular symptoms; however, the risk of recurrent ipsilateral stroke is low. Further data are required from on-going trials of stenting versus endarterectomy to ascertain whether long-term ultrasound follow-up is necessary after carotid revascularisation. Funding British Heart Foundation; UK National Health Service Management Executive; UK Stroke Association.

Endovascular treatment with angioplasty or stenting versus endarterectomy in patients with carotid artery stenosis in the Carotid And Vertebral Artery Transluminal Angioplasty Study (CAVATAS): long-term follow-up of a randomised trial

Summary Background Endovascular treatment (angioplasty with or without stenting) is an alternative to carotid endarterectomy for carotid artery stenosis but there are scarce long-term efficacy data showing that it prevents stroke. We therefore report the long-term results of the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS). Methods Between March, 1992, and July, 1997, patients who presented at a participating centre with a confirmed stenosis of the internal carotid artery that was deemed equally suitable for either carotid endarterectomy or endovascular treatment were randomly assigned to either treatment in equal proportions by telephone or fax from the randomisation service at the Oxford Clinical Trials Unit, UK. Patients were seen by an independent neurologist at 1 and 6 months after treatment and then every year after randomisation for as long as possible, up to a maximum of 11 years. Major outcome events were transient ischaemic attack, non-disabling, disabling, and fatal stroke, myocardial infarction, and death from any other cause. Outcomes were adjudicated on by investigators who were masked to treatment. Analysis was by intention to treat. This study is registered, number ISRCTN 01425573. Findings 504 patients with stenosis of the carotid artery (90% symptomatic) were randomly assigned to endovascular treatment (n=251) or surgery (n=253). Within 30 days of treatment, there were more minor strokes that lasted less than 7 days in the endovascular group (8 vs 1) but the number of other strokes in any territory or death was the same (25 vs 25). There were more cranial nerve palsies (22 vs 0) in the endarterectomy group than in the endovascular group. Median length of follow up in both groups was 5 years (IQR 2–6). By comparing endovascular treatment with endarterectomy after the 30-day post-treatment period, the 8-year incidence and hazard ratio (HR) at the end of follow-up for ipsilateral non-perioperative stroke was 11·3% versus 8·6% (HR 1·22, 95% CI 0·59–2·54); for ipsilateral non-perioperative stroke or TIA was 19·3% versus 17·2% (1·29, 0·78–2·14); and for any non-perioperative stroke was 21·1% versus 15·4% (1·66, 0·99–2·80). Interpretation More patients had stroke during follow-up in the endovascular group than in the surgical group, but the rate of ipsilateral non-perioperative stroke was low in both groups and none of the differences in the stroke outcome measures was significant. However, the study was underpowered and the confidence intervals were wide. More long-term data are needed from the on going stenting versus endarterectomy trials. Funding British Heart Foundation; UK National Health Service Management Executive; UK Stroke Association.

Filter-Protected versus Unprotected Carotid Artery Stenting: A Randomised Trial

Background: Our aim was to determine whether filter protection reduces embolisation to the brain during carotid artery stenting (CAS). Methods: Thirty patients with symptomatic carotid artery stenosis ≧70% (North American Symptomatic Carotid Endarterectomy Trial) were randomly assigned to filter-protected or unprotected CAS. Diffusion-weighted magnetic resonance imaging (DWI) of the brain was performed before and at 3 time points after CAS. In a subset of patients, high-intensity transient signals on transcranial Doppler (TCD) were recorded with categorisation of emboli. Data were independently reviewed off-site. Results: There were no significant differences in mean age, proportion of octogenarians or presenting symptoms between the groups. On procedural DWI (1–3 and 24 h after stenting), there were 7/24 (29%) and 4/22 (18%) new lesions in protected and unprotected patients respectively (p = 0.38). At 30 days there were 9/33 (26%) and 4/33 (12%) lesions in protected and unprotected patients, respectively (p = 0.1). On TCD there were significantly more signals in total as well as particulate emboli during filter-protected CAS (426.5 and 251.3) than during unprotected CAS (165.2 and 92) – p = 0.01 and 0.03, respectively. Conclusions: Filter-protected CAS is associated with an increase in new lesions on DWI and significantly higher rates of total and particulate microembolisation on TCD than unprotected CAS. The clinical significance of these findings requires further study.

Clinical demonstration that catheter-delivered ultrasound energy reverses arterial vasoconstriction

OBJECTIVES This study was designed to describe the clinical effects of ultrasound energy on guide-wire-induced arterial vasoconstriction. BACKGROUND We have previously shown that ultrasound energy (20 kHz) delivered by a wire probe produces dose-dependent, endothelium-independent smooth muscle relaxation capable of reversing both receptor-mediated and voltage-dependent vasoconstriction in vitro. METHODS A high intensity, low frequency ultrasound catheter system was used to recanalize total occlusions in the superficial femoral arteries of two patients. After recanalization, the proximal residual stenoses were each less than 15%. However, distal arterial vasospasm was found angiographically in a popliteal artery of one patient and in an anterior tibial artery of another. Subsequently, the ultrasound catheter probe was advanced to the sites of arterial vasospasm (diffuse in one, focal in one). RESULTS After 30 and 90 s, respectively, of exposure to ultrasound energy with a frequency of 19.5 kHz, peak tip amplitude of 111 microns and power output at the transducer of 25 W, the vasospasm resolved in each arterial segment. CONCLUSIONS Our findings are the first reported clinical cases documenting that catheter-delivered low frequency, high intensity ultrasound induces arterial vasodilation at the site of vasoconstriction. These biologic effects appear to be relatively unique for an angioplasty device and may have potential clinical importance.

Nanoparticles from photocopiers induce oxidative stress and upper respiratory tract inflammation in healthy volunteers

Abstract Photocopiers emit large quantities of nanoparticles (NPs); however, their toxicological properties have not been studied. Here we investigate for the first time early human responses following a days exposure to NPs from photocopiers. Nine healthy subjects spent 6 h at a busy photocopy centre on 2–3 randomly selected days. Matched nasal lavage and urine samples were collected before and at different time points post-exposure. Nasal lavage samples were analysed for 14 cytokines, inflammatory cells and total protein. Urine samples were analysed for 8-hydroxydeoxyguanosine (8-OH-dG). Exposure assessment was conducted using a suite of instruments. The mean total particle number on exposure days was >5 times higher than background, with size distributions in nanoscale range (peak 30–40 nm). Following exposure, 8-OH-dG and several pro-inflammatory cytokines were elevated 2–10 folds compared with pre-exposure levels and remained elevated for up to 36 h. We conclude that NPs from photocopiers induce upper airway inflammation and oxidative stress.

The Costs of Managing Lower Limb-threatening Ischaemia

One hundred and fifty consecutive patients presenting with limb-threatening ischaemia were studied prospectively to determine treatment and rehabilitation costs in the first year. Limb salvage was attempted in 104 (69%) patients but failed in 13%. Mortality at 1 year was 27%. The cost of treatment, inpatient stay, occupational therapy, physiotherapy, convalescence, disablement services, home adaptations, home care, district nursing, transportation and outpatient visits were determined for each patient. The patients were classified according to their presentation and initial treatment into five groups (number of patients) whose median management costs (interquartile range) for 12 months were: Gp 1 (23 - Revascularisation for acute ischaemia = 3970 pounds (2984-5511) Gp 2 (29) - Angioplasty for critical ischaemia = 6611 pounds (3630-10,200) Gp 3 (52) - Reconstruction for critical ischaemia = 6766 pounds (4337-9677) Gp 4 (34) - Primary amputation = 10,162 pounds (7894-13,026) Gp 5 (12) - Primary bilateral amputations = 13,848 pounds (11,440-18,056) At 1 year, there was no significant difference in the cost of managing a patient with a critically ischaemic limb by angioplasty or surgical reconstruction. The cost of revascularisation for acute ischaemia was comparatively low because these patients required minimal rehabilitation. The median cost of managing a patient following amputation was almost twice that of successful limb salvage justifying an aggressive revascularisation policy. However, justification of such a policy on economic grounds requires salvage failure episode to be minimised as they increase costs considerably.

Experienced Endovascular Interventionalists Objectively Improve their Skills by Attending Carotid Artery Stent Training Courses

OBJECTIVE Carotid artery stenting (CAS) is an advanced endovascular intervention with a steep learning curve. Virtual reality (VR) simulation has been proposed as a means to train and objectively assess technical performance. AIM To objectively assess psychomotor skills acquisition of experienced interventionalists attending a two-day CAS course, using a VR simulator. METHODS Both cognitive and technical skills of 11 interventionalists were trained in a two-day course using didactic sessions, case reviews, supervised VR simulation and live-cases. Pre- and post-course skills were assessed through performance on the same CAS procedure using metrics derived from the simulator. RESULTS Significant differences were noted between pre- and post-course performance for procedure (36 vs. 20min., p=0.005), X-ray (20 vs. 11min., p=0.016) and delivery-retrieval time of the embolic protection device (12 vs. 9min., p=0.007). Advancement of the guiding catheter without a leading wire occurred to a greater extent pre- versus post-course (199 vs. 152mm., p=0.050) as did spasm of the internal carotid artery (4 vs. 2, p=0.049). CONCLUSIONS This study has objectively proven a benefit for experienced interventionalists to attend CAS courses for skills acquisition measured by a VR simulator. These data can be used to offer participants an insight into their skills and objectively audit course efficacy.

Clinical Risk Associated With Contrast Angiography in Metformin Treated Patients: a Clinical Review

Recently, concern has been expressed about the hazards of lactic acidosis following the use of intravascular iodinated contrast agents in patients taking metformin. In response the Royal College of Radiologists have issued guidelines for the management of these patients. We have reviewed the reported cases of lactic acidosis and identified that in all cases underlying renal impairment existed. To examine this further we reviewed the notes of 33 in-patients receiving metformin who underwent contrast angiography in our hospital. Twenty-nine patients had a normal serum creatinine prior to the procedure and none had a rise following angiography. Four patients had an abnormal serum creatinine prior to angiography, all four patients showed significant deterioration and all four patients died, two from unrelated causes and two from acute renal failure and acidosis. These data strongly highlight the hazards of intravascular contrast radiology in diabetic patients with pre-existing renal impairment. We have failed to find evidence in support of the Royal College of Radiologists recommendation; instead we recommend that in those patients taking metformin with evidence of renal impairment metformin should be stopped and diabetic control obtained using alternative therapy before proceeding with angiography. Patients with normal renal function taking metformin are not at risk of lactic acidosis following the use of iodinated contrast agents for angiography.