An update of the Italian Stroke Organization-Stroke Prevention Awareness Diffusion Group guidelines on carotid endarterectomy and stenting: a personalized medicine approach

Although proof-based medicine has generated much valid evidence for the drawing up of guidelines and recommendations for best clinical practice in symptomatic and asymptomatic carotid stenosis, whether and when it is better to employ endarterectomy or stenting as the intervention of choice still remain matters of debate. Moreover, guidelines have been targeted up to now to the 'representative' patient, as resulting from the statistical analyses of the studies conducted on the safety and efficacy of both interventions as well as on medical therapy alone. The Italian Stroke Organization (ISO) and Stroke Prevention and Awareness Diffusion (SPREAD) group has thus decided to update its statements for an 8th edition. To this end, a multidisciplinary team of authors representing Italian scientific societies in the neurology, neuroradiology, vascular and endovascular surgery, interventional cardiology, and general medicine fields re-examined the literature available on stroke. Analyses and considerations on patient subgroups have allowed to model the risks/benefits of endarterectomy and stenting in the individual. Accordingly, the guideline's original methodology has been revised to follow the new SIGN (Scottish Intercollegiate Guideline Network) Grade-like approach, integrating it with new considerations on Precision, or Personalized Medicine. Therefore, this guideline offers recommendations on precision medicine for the single patient, and can be followed in addition to the more standard guidelines.

Aorfix™ device for abdominal aortic aneurysm with challenging anatomy.

Anatomical characteristics of abdominal aortic aneurysms (AAA) are the most critical factors for successful endovascular aortic repair (EVAR). Of these, severe proximal aortic neck angulation and iliac axis tortuosity increase the complexity of EVAR. Neck angulation seems to have a pivotal potential for fixation failure, a situation that may lead to complications, including endoleak and late rupture. Bench-test studies identified that the relative stiffness of a stent-graft was responsible for its inability to conform to neck angulation, therefore creating leaks through gaps between the stent graft and the neck. Aorfix™ stent graft (Lombard Medical, Didcot, UK) is a flexible stent-graft designed and manufactured with the purpose of overcoming the issue of stent-graft stiffness. Many studies have shown good results in term of procedural success and mid-term type-I endoleak. PYTHAGORAS trial evaluated mainly patients with highly angulated infrarenal neck and showed that high performance of Aorfix™ stent graft did not present any significant difference between neck >60° and <60°. In the series of 27 patients treated at our Institution we had a primary technical success of 96.3% and an assisted primary technical success of 100%. In this review we will analyze the available data in literature regarding Aorfix™ stent graft and will discuss the outcome of the patients treated with Aorfix™ stent graft at our centre.

From the abluminal biodegradable polymer stent to the polymer free stent. Clinical evidence.

The implementation of methods of the coronary angioplasty was one of the most important achievement in the field of treatment of coronary artery disease. Abluminal biodegradable polymer stents (BDS) and polymer free stent are the newest and the most promising research concerning coronary stent technology. In this article we discuss the perceived need for BDS-polymer free stents, the current clinical evidence, limits and future perspectives.

Current concepts on the management of concomitant carotid and coronary disease.

In the absence of randomized data, the optimal management of patients with severe carotid and coronary artery disease (CAD), especially those undergoing coronary bypass grafting (CABG), remains unsettled. As a general rule, in patients with multilevel atherosclerotic disease the symptomatic vascular discrict should be treated first. The entirely surgical approach with carotid endarterectomy (CEA) and CABG is associated with high event rates. Therefore, whenever in the work-up prior to cardiac surgery severe carotid disease is identified, the indication for CABG should be reassessed and the feasibility of percutaneous coronary intervention (PCI) as an alternative treatment should be explored. If PCI is not an option, carotid artery stenting (CAS) prior to open heart should be considered if the expertise is available. Although perioperative stroke is multifactorial and the value of revascularization of asymptomatic carotid disease prior to open heart surgery remains controversial, treatment of patients with severe bilateral carotid stenosis appears reasonable for perioperative stroke prevention. The aim of carotid revascularization in patient with unilateral severe carotid stenosis should more long-term stroke prevention than merely perioperative stroke reduction. The main advantage of CAS compared with CEA in patients with advanced CAD is the reduction of perioperative myocardial infarction, an event associated to long term mortality.

SPREAD Italian Guidelines for stroke. Indications for carotid endarterectomy and stenting.

This multidisciplinary guideline provides an overview of the current evidence on the benefits obtained by endoarterectomy and stenting for the surgical treatment of patients with symptomatic and asymptomatic carotid stenosis. A hundred forty-six authors, 37 Italian scientific societies and two Italian patients' associations participated in drafting the Stroke Prevention and Educational Awareness Diffusion (SPREAD) document, which has become the national guideline for the prevention and treatment of stroke in Italy. For the surgical therapy section of this document, the main trials on carotid endoarterectomy and stenting were critically reviewed following The Scottish Intercollegiate Guideline Network Oxford Centre for Evidence-Based Medicine methodology in order to formulate recommendations and syntheses for these procedures. The final document was peer reviewed and approved by all the participants. Recommendations and syntheses are presented for the referral of patients to either carotid endoarterectomy or stenting on the basis of whether carotid stenosis is symptomatic or asymptomatic, on the presence of various risk factors such as degree of arterial narrowing, and on concomitant pathology (cardiopathy and acute stroke).

Clinical endpoints in peripheral endovascular revascularization trials: a case for standardized definitions.

BACKGROUND: Endovascular therapy is a rapidly expanding option for the treatment of patients with peripheral arterial disease (PAD), leading to a myriad of published studies reporting on various revascularization strategies. However, these reports are often difficult to interpret and compare because they do not utilize uniform clinical endpoint definitions. Moreover, few of these studies describe clinical outcomes from a patients' perspective. METHODS AND RESULTS: The DEFINE Group is a collaborative effort of an ad-hoc multidisciplinary team from various specialties involved in peripheral arterial disease therapy in Europe and the United States. DEFINE's goal was to arrive at a broad based consensus for baseline and endpoint definitions in peripheral endovascular revascularization trials for chronic lower limb ischemia. In this project, which started in 2006, the individual team members reviewed the existing pertinent literature. Following this, a series of telephone conferences and face-to-face meetings were held to agree upon definitions. Input was also obtained from regulatory (United States Food and Drug Administration) and industry (device manufacturers with an interest in peripheral endovascular revascularization) stakeholders, respectively. The efforts resulted in the current document containing proposed baseline and endpoint definitions in chronic lower limb PAD. Although the consensus has inevitably included certain arbitrary choices and compromises, adherence to these proposed standard definitions would provide consistency across future trials, thereby facilitating evaluation of clinical effectiveness and safety of various endovascular revascularization techniques. CONCLUSION: This current document is based on a broad based consensus involving relevant stakeholders from the medical community, industry and regulatory bodies. It is proposed that the consensus document may have value for study design of future clinical trials in chronic lower limb ischemia as well as for regulatory purposes.

Are there predictive risk factors for complications after carotid artery stenting?

AIM: The aim of this study was to identify predictive risk factors for complications during and after carotid artery stenting (CAS). METHODS: A multivariate analysis was performed on the databases of 4 European high-volume centers regarding risk factor distribution between patients presenting with or without neurological complications 30 days after CAS. The cumulative 30-day neurological complication rate (death, major stroke, minor stroke and transient ischemic attack) was 2.8% in the total examined cohort of 3 179 consecutive CAS procedures. The following risk factors were taken into consideration for statistical analysis: age, symptomatic, male gender, nicotine abuse, hypertension, hypercholesterolemia, polyvascular disease, diabetes, restenosis after carotid endarterectomy (CEA)/CAS, calcified internal carotid artery. RESULTS: Symptomatic (P=0.02) or hypercholesterolemic (P=0.02) patients are at significantly increased risk for neurological events 30 days after CAS. Asymptomatic women and men without hypercholesterolemia have the lowest risk on any 30-day neurological complications after CAS. CONCLUSIONS: CAS is a safe technique in experienced hands. Preprocedural neurological complaints and hypercholesterolemia can be defined as predisposing factors for 30-day neurological complications after CAS.

Does free cell area influence the outcome in carotid artery stenting?

OBJECTIVES: To identify if carotid stent design, especially free cell area, impacts on the 30-day rates for stroke, death and TIA after carotid artery stenting (CAS). MATERIAL AND METHODS: A CAS database of 3179 consecutive CAS patients was retrospectively assessed. The distribution of neurological complications were analysed for association with the different stent types and designs. Events where subdivided into procedural and postprocedural events. RESULTS: The overall combined rate of TIA, stroke and death was 2.8% at 30 days (late events 1.9%). The post-procedural event rate analyzed for differences stents varied from 1.2% using BSCI Carotid Wallstent to 5.9% using Medtronic Exponent. The late event rates varied from 1.2% to 3.4% for free cell areas <2.5mm(2) and >7.5mm(2) respectively (p<0.05). Post-procedural event rate was 1.3% for closed cells and 3.4% for open cells. All these differences were highly pronounced among symptomatic patients (p<0.0001). CONCLUSIONS: After carotid stenting, complication rates vary according to stent type, free cell area and cell design. In the symptomatic population (and also in the total population), post-procedural complication rates are highest for the open cell types and increase with larger free cell area.

PRIAMUS--proximal flow blockage cerebral protectIon during carotid stenting: results from a multicenter Italian registry.

AIM: The aim of this Italian prospective registry was to evaluate the applicability and efficacy of the Mo.Ma Device (Invatec, Roncadelle, Italy) for the prevention of cerebral embolization during carotid artery stenting (CAS) in a real world population. METHODS: In 4 Italian centers, 416 patients (300 men; mean age 71.6+/-9 years) between October 2001 and March 2005 were enrolled in a prospective registry. Two-hundred and sixty-four symptomatic (63.46%) with >50% diameter stenosis and 152 (36.54%) asymptomatic patients with >70% diameter stenosis were included. The Mo.Ma Proximal Flow Blockage Embolic Protection System was used to perform protected CAS, achieving cerebral protection by endovascular clamping of the common carotid artery (CCA) and of the external carotid artery (ECA). RESULTS: Technical success, defined as the ability to establish protection with the Mo.Ma device and to deploy the stent, was achieved in 412 cases (99.03%). The mean duration of flow blockage was 4.91+/-1.1 min. Transient intolerances to flow blockage were observed in 24 patients (5.76%), but in all cases the procedure was successfully completed. No peri-procedural strokes and deaths were observed. Complications during hospitalization included 16 minor strokes (3.84%), 3 transient ischemic attacks (0.72%), 2 deaths (0.48%) and 1 major stroke (0.24%). This resulted in a cumulative rate at discharge of 4.56% all strokes and deaths, and of 0.72% major strokes and deaths. All the patients underwent thirty-day follow-up. At thirty-day follow-up, there were no deaths and no minor and major strokes, confirming the overall cumulative 4.56% incidence of all strokes and deaths rate, and of 0.72% rate of major strokes and deaths at follow up. In 245 cases (58.89%) there was macroscopic evidence of debris after filtration of the aspirated blood. CONCLUSIONS: This Italian multicenter registry confirms and further supports the efficacy and applicability of the endovascular clamping concept with proximal flow blockage in a broad patient series. Results match favorably with current available studies on carotid stenting with cerebral protection.

Does carotid artery stenting work on the long run: 5-year results in high-volume centers (ELOCAS Registry).

AIM: Although the first long-term results of Carotid Artery Stenting (CAS) became available only recently, CAS has become an accepted treatment for carotid artery disease. We report CAS data up to 5 years, both late stroke rate and patency rates as observed in 4 high-volume European centers. METHODS: Between February 1, 1993 and December 31, 2004, 2 172 patients were selected over the 4 participating centres, with intention to treat endovascularly. Conscientious follow-up was done according to the in-hospital stipulations of each centre and was entered into a database both retrospectively and prospectively. Long-term restenosis and stroke-death rates were investigated and statistically analysed and stratified using the Kaplan-Meier method. RESULTS: Of the 2 172 patients with intention to treat 2 165 (99.7%) were technically successful. Of these 306 (14.1%) were performed without and 1 859 (85.9%) with embolic protection device (EPD); 96 patients (4.4%) received balloon dilation only and stenting was performed in 2 069 (95.6%) cases. Kaplan-Meier analysis of major stroke/all death and of significant restenosis (>50%) for the total population showed stroke/death rates of 4.1% (nar=1 356), 10.1% (nar=476) and 15.5% (nar=138); and restenosis rates of 1% (nar=1 363), 2% (nar=480) and 3.4% (nar=139), after 1, 3 and 5 years respectively. CONCLUSIONS: The patency and stroke/death rates resulting from our database analysis are pleasing and indicate that CAS also on longer term is a valuable treatment method for carotid artery disease. Due to the fact that our dataset contains prospective as well as retrospective data, it may have its limitations. Until this moment, data indicating that certain patient subgroups are at increased risk for neurological complications and in-stent restenosis during and after CAS are sparse. Further multivariant analysis on this unique dataset is mandatory in order to identify any potential links in between plaque morphology, preprocedural neurological complications, risk factor distribution, procedural steps and clinical outcome.

Multicenter registry to evaluate the efficacy of the NIROYAL stent in de novo or restenotic coronary stenosis.

The purpose of this registry was to document the safety and efficacy of elective deployment of the NIROYAL stent (Boston Scientific SCIMED, Maple Grove, Minnesota) in coronary arteries. This was a prospective, multi-center international registry. NIROYAL stents (9, 16, 25 and 32 mm-long) were manually crimped onto coronary balloons and deployed in de novo or restenotic lesions in 165 male and female patients with angina pectoris and a reference vessel diameter of 2.0-4.5 mm. Stent deployment was successful in 98.8% of the lesions. Mean percent diameter stenosis decreased from 83.5+/-10.8% to 2.7+/- 6.2% after intervention. The interventional procedure of the treatment site was successful in 97.6% of patients. At six-month clinical follow-up, 88.5% had event-free survival [i.e., did not experience a major adverse cardiac event (MACE)] and 95.2% had no anginal symptoms. Furthermore, 87.3% of the patients were free of target vessel failure (defined as a composite of acute procedural failure, target vessel revascularization, myocardial infarction or death at six months). Only three MACE were observed within the first 30 days after stent implantation. A low left ventricular ejection fraction and the percentage stenosis pre-procedure were identified as statistically significant (p<0.05) predictive factors for MACE. The incidences of MACE and target vessel failure after six months follow-up were lower than that seen in other studies, and target lesion revascularization rates were low.

Clinical Experience with the NIR Stent: Retrospective Observation on Acute Results and Follow-up in 709 Patients.

The NIR stent is an expandable cellular coronary prosthesis with high flexibility and excellent trackability. The very low crossing profile, associated to the high flexibility, makes this stent suitable for complex and distal lesions. The aim of this study was to evaluate the feasibility, safety, and long-term (clinical follow-up) efficacy of elective and/or urgent deployment of the NIR stent in a broad patient group with coronary artery disease. Between June 1996 and May 1997, 986 NIR stents were implanted in 781 vessels (de novo or restenotic lesions in native vessels, saphenous vein grafts and internal mammary conduits) of 709 consecutive patients (498 men, 211 women) undergoing coronary angioplasty in two Villa Maria Group Catheterization Laboratories. Procedural angiographic success was achieved in 98.4% of all the lesions treated, ranging from 100% success rate in type A lesion to 97.6% in type C lesions (overall procedural success, 98.4%). Major adverse cardiac events (MACE) were considered from PTCA/stenting time to the patient discharge. The in-hospital MACE were limited and occurred in 15 patients: urgent surgical revascularization 0.8%, death 0.7%, sub-acute stent thrombosis 0.5% (overall in-hospital MACE rate 2.1%). Clinical follow-up data were obtained at 8.6 +/- 2.8 months following the stenting procedure. The event-free survival rate was 87.9%. The late MACE rate evaluation showed death, target lesion revascularization 9.9% (over-all late MACE rate 12.1%). The NIR stent performances in this broad patient population were excellent, showing very high procedural success rate both in normal and complex coronary anatomy. On the basis of the previous data, we can define NIR stent a safe multifunctional device suitable both for easy and complex situations. The clinical late results are very promising in term of event-free survivals and late MACE.

Endovascular treatment of carotid atherosclerotic disease: early and late outcome in a non-selected population.

BACKGROUND: Carotid angioplasty and stenting are still not widely accepted treatments for carotid stenosis. This registry was aimed at investigating the efficacy of endovascular therapy of the extracranial carotid arteries in a non-selected population. METHODS: One hundred nineteen consecutive patients (93 males and 26 females, mean age 70.4 +/- 7.2 years) were enrolled to undergo percutaneous angioplasty and/or stenting of the extracranial carotid artery. The primary endpoint of this study was to evaluate the feasibility, safety and efficacy of carotid elective angioplasty and stenting in a "real life group" of patients (> 50 years, without strict target vessel selection or inclusion criteria) with carotid occlusive disease. During a 6-12 month follow-up period late major adverse events were evaluated, either related to the endovascular treatment or due to other pathological conditions. RESULTS: Percutaneous procedure was effective in 118/119 patients (99.16%). Procedural success rate was 99.16%, in-hospital major neurological symptomatic complications 0%, in-hospital minor neurological symptomatic complications 3.36% (two minor strokes, one transient ischemic attack and one subarachnoid hemorrhage). The follow-up observation time ranged from 6 to 36 months following the percutaneous procedure. Overall follow-up data showed absence of late major adverse events related to carotid disease (stroke, permanent neurological damage, death), in-stent restenosis 5.04%, balloon expandable stent crush 0.84%, stent migration 0.84%. CONCLUSIONS: Our data confirm that percutaneous dilation and stenting of the carotid artery represent an effective method which, during the periprocedural phase and the follow-up, does not expose the patient to any greater risk of complications than traditional surgery.

The use of coronary angioplasty devices in carotid endovascular interventions: encouraging results in 21 consecutive patients.

Severe atherosclerotic lesion of carotid artery is the main cause of stroke and transient ischemic attack (TIA). Its incidence may reach 5-7% per annum in patients with carotid artery stenosis higher than 70% with or without symptoms. While time-honored carotid endarterectomy is still regarded as the "gold standard" therapy for most of the patients, carotid angioplasty with stent may be the only alternative to this treatment when endarterectomy is too risky or impossible. Although percutaneous angioplasty has been fully acknowledged as far as coronary or peripheral artery disease is concerned, the issue is still controversial in the endovascular treatment of carotid artery disease with regard to its indications, devices to be used and long-term results. Assessment of risk relating to carotid angioplasty with stent in comparison to carotid endarterectomy continues to be difficult, since materials and methods for this approach have not been standardized yet. Our initial experience in carotid angioplasty with stent performed in 21 consecutive patients by using devices for coronary angioplasty is extremely encouraging.

Femoral Arterial Hemostasis using the Angio-Sealª System after Coronary and Vascular Percutaneous Angioplasty and Stenting.

The procedures of left cardiac catheterization and revascularization by angioplasty are associated with a substantial risk of hemorrhagic complications. This risk increases clearly in patients with an intravascular stent who require early high doses of anticoagulant therapy. The first purpose of our study was to evaluate the effectiveness of a mechanical system of femoral hemostasis (Angio-Sealª, Sherwood Davis & Geck, St. Louis, Missouri) deployed in a group of 411 consecutive patients (302 males, 109 females, mean age 59 +/- 15) who successfully underwent percutaneous angioplasty (PA) and application of an intravascular stent (378 coronary, 33 vascular). The arterial closure system consists of a small absorbable anchor and a collagen pad connected to a suture thread which, at the end of the procedure, is positioned by percutaneous introduction at the site of the femoral puncture. All the patients studied received long-term platelet anti-aggregant therapy (ticlopidine 500 mg/day and ASA 150 mg/day) for 3Ð4 days before and for one month after the procedure, and an anticoagulant regimen of heparin sodium administered via intravenous bolus (10,000 IU) during the procedure, followed by subcutaneous heparin calcium (12,500 IU/day) for 21 days. Thirteen patients were treated intravenously with 10 mg abciximab and seven received pre-procedure coumadin. The ACT when the hemostasis system was positioned was 355 +/- 43 seconds. Successful hemostasis was reached in more than 95% of the patients (394/411 pts., 95.86%). In 17 (4.14%) of the 411 patients studied, the system failed; nine (2.19%) of these were attributed by the operator to a failure of the positioning device procedure, and the remaining 8 (1.95%) were attributed to a malfunction of the system. Overall complications were observed in 23/411 (5.6%) of the patients (pts) studied; eighteen were minor non-surgical hemorrhagic complications (bleeding and/or hematoma) which occurred primarily in the first 4 hours. In 4 cases (1%) vascular surgery was necessary for femoral pseudoaneurysm repair (2 pts) and femoral hematoma (2 pts). One patient (0.24%) complained of severe claudication related to a severe stenosis in the femoral artery caused by a malpositioning of the anchor. This patient was successfully treated with balloon angioplasty and stenting of the femoral artery. The average time to early mobilization was 9 hours, and all the patients without complications were completely mobile within 12 hours after the procedure; 380/411 (92.46%) of the patients were discharged 18Ð24 hours after percutaneous angioplasty. The second purpose of our study was to compare data from 411 consecutive patients treated with the Angio-Sealª device after coronary and vascular angioplasty and stenting (Angio-Seal group), to a group of 387 consecutive patients where the femoral arterial hemostasis was obtained using manual compression after coronary angioplasty and stenting (manual compression group). We found significant differences (p < 0.01) in the most important elements concerning general patient management after the interventional procedure, with excellent improvements using the Angio-Seal device, including: successful hemostasis (95.86% vs. 88.37%); reduction of non-surgical hematomas (1.22% vs. 4.65%); reduction of surgical hematomas (0.49% vs. 2.84%); mobilization time (9 +/- 3 hours vs. 19 +/- 8 hours); and discharge within 18Ð24 hours (92.46% vs. 0.00%).

Hemodynamic evaluation of the Carbomedics R, St Jude Medical HP and Sorin-Bicarbon valve in patients with small aortic annulus.

UNLABELLED: A Doppler echocardiographic study was performed to evaluate the hemodynamic performance of three 19 mm size currently used bileaflet valve prosthesis (St Jude Medical Hydrodinamic Plus, Sorin-Bicarbon and Carbomedic Reduced) implanted in aortic position. METHODS: Patients, 30, with the same profile receiving 19 mm size valve (ten for each valve type) were selected when body surface area (BSA) was > 1.7 m2. Doppler echocardiography was carried out at rest and after exercise, 60 days after surgery. Peak (Pg) and mean (Mg) gradients across the valve were recorded: the effective orifice area (EOA), and performance index (PI) were calculated. RESULTS: No significant differences were observed between St Jude Medical and Sorin Bicarbon as far as peak and mean gradient, effective orifice area and performance index at rest and after exercise. A significant difference (P < 0.05) was demonstrated in the above mentioned parameters when Carbomedics-R valve were tested. This type of valve showed a lower EOA and PI with higher Pg and Mg gradient both at rest and after exercise. CONCLUSION: The St Jude Hydrodymanic plus (Hp) and Sorin Bicarbon valves had similar performance and a better hemodynamic trend when compared to the Carbomedics-R valve in patients with large body surface areas. The Carbomedics-R valve shows a ineffective use of the total area of the prosthesis both at rest and after exercise.