Effect of CYP2C19 Polymorphisms on the Platelet Response to Clopidogrel and Influence on the Effect of High Versus Standard Dose Clopidogrel in Carotid Artery Stenting.

OBJECTIVES: Genetic background has been identified to be a major predictor of post-clopidogrel platelet inhibition in patients undergoing coronary stenting. However, there is a lack of data on clopidogrel response regarding genotype in patients undergoing carotid artery stenting (CAS). The influence of the most common allelic variants of CYP2C19 phenotypes and genotypes on response to baseline clopidogrel and on the pharmacodynamic effect of dose adjustment (high or standard dose of clopidogrel) in patients with high on-treatment reactivity after CAS was investigated. METHODS: Platelet reactivity was assessed before and 30 days after carotid stenting using the VerifyNow P2Y12 assay to obtain P2Y12 reactivity unit (PRU) values. RESULTS: A total of 209 patients (79.4% male, 44.1% currents smokers) were treated by CAS. Smokers improved responsiveness to clopidogrel (p = .034). With respect to CYP2C19 enzymatic function, 61 subjects (29.1%) were ultra-rapid metabolizers, 95 patients (45.5%) were extensive metabolizers, 51 (24.4%) were intermediate metabolizers, and two (0.96%) were poor metabolizers. Baseline PRU was significantly higher among intermediate-poor metabolizers compared with ultra-rapid (p = .001) or extensive metabolizers (p = .005). At 30 days follow up, in non-responding patients with the intermediate-poor metabolizer phenotype, the PRU value and inhibition percentage were significantly reduced with standard dose (p = .008; p = .0029) and high dose of clopidogrel (p = .00 0; p = .000). However, high dose clopidogrel did not achieve a more intense pharmacodynamic effect at 30 days (p = .994) compared with standard dose. CONCLUSIONS: In patients undergoing carotid stenting, those with the CYP2C19*2 allele had increased basal PRU values and in fact clopidogrel non-responders increased significantly among intermediate-poor metabolizers. Although high dose and standard dose clopidogrel therapy was effective in lowering the 30 day PRU values in patients with high on-treatment reactivity who are intermediate-poor metabolizers, the use of high dose clopidogrel did not result in statistically significantly greater reductions in reactivity compared with the standard dose.

[Filter content after carotid angioplasty and stenting: relation to ischemic lesions in diffusion-weighted imaging]. / Contenido en filtros tras angioplastia y colocación de stent carotídeo: relación con lesiones isquémicas en la resonancia magnética de difusión.

OBJECTIVES: To evaluate the relation between the material retrieved from distal filters after carotid angioplasty and stenting and the development of ischemic brain lesions in diffusion-weighted imaging (DWI). To determine the influence of demographic, clinical, and procedural variables in the pathogenesis of emboli and in ischemia after carotid angioplasty and stenting. MATERIAL AND METHODS: We submitted the contents of the filters of 76 patients (60 men; mean age, 68.39 years; range, 46-82) who had undergone angioplasty and stenting for severe stenosis of the internal carotid artery for histologic analysis evaluating volume (< 1 λ = 0.001 ml = 1 µl; 1-10 λ; and > 10 λ) and the composition of the particles. All patients underwent DWI before and 24 hours after the procedure; we recorded whether lesions appeared and their number, size, and distribution. We correlated the findings with demographic, clinical, and procedural variables. RESULTS: Symptoms were present before the procedure in 58 (76.3%) patients. Particles were present in 49 (64.5%) of the filters; most particles (77.5%) were 1 λ with a predominance of fibrin-platelet aggregates, cell remnants, and cholesterol crystals. DWI after the procedure detected lesions in 12 (15.8%) patients. We found no statistically significant correlation between filter contents and lesion detection after the procedure or between filter contents and other variables. CONCLUSIONS: Ischemia after carotid angioplasty and stenting does not depend solely on the embolic load and its nature. We consider that the lower prevalence of postprocedural lesions in our series compared to others suggests that appropriate patient selection and experience minimize the negative influence of some variables like age in their development.

Early treatment of obstructive apnoea and stroke outcome: a randomised controlled trial.

The aim of the present study was to assess the impact of nasal continuous positive airway pressure (nCPAP) in ischaemic stroke patients followed for 2 yrs. Stroke patients with an apnoea-hypopnoea index ≥ 20 events·h⁻¹ were randomised to early nCPAP (n = 71; 3-6 days after stroke onset) or conventional treatment (n = 69). The Barthel Index, Canadian Scale, Rankin Scale and Short Form-36 were measured at baseline, and at 1, 3, 12 and 24 months. The percentage of patients with neurological improvement 1 month after stroke was significantly higher in the nCPAP group (Rankin scale 90.9 versus 56.3% (p < 0.01); Canadian scale 88.2 versus 72.7% (p < 0.05)). The mean time until the appearance of cardiovascular events was longer in the nCPAP group (14.9 versus 7.9 months; p = 0.044), although cardiovascular event-free survival after 24 months was similar in both groups. The cardiovascular mortality rate was 0% in the nCPAP group and 4.3% in the control group (p = 0.161). Early use of nCPAP seems to accelerate neurological recovery and to delay the appearance of cardiovascular events, although an improvement in patients' survival or quality of life was not shown.

Silent ischemia after neuroprotected percutaneous carotid stenting: a diffusion-weighted MRI study.

BACKGROUND AND PURPOSE: To assess by diffusion-weighted MR imaging (DWI) the efficacy of cerebral protection devices in avoiding embolization and new ischemic lesions in patients with severe internal carotid artery (ICA) stenosis undergoing carotid artery stent placement (CAS). METHODS: One hundred sixty-two CASs in the extracranial ICA were performed with the use of distal filters. Mean age of the patients was 68.5 years (range, 33-86) and 122 patients (75.3%) were symptomatic. MR imaging was performed in all patients during the 3-day period before CAS, and DWI was obtained within 24 hours after the procedure. Ninety-five patients (58.6%) were monitored by transcranial Doppler ultrasonography for microemboli detection in the territory of the middle cerebral artery (MCA), ipsilateral to the vessel being treated. RESULTS: Twenty-eight patients (17.3%) showed 58 new ischemic foci in DWI, and 13 patients (46.4%) had multiple foci. Location of new lesions was mainly in the vascular territory supplied by the treated vessel (19 patients; 67.9%), but also in the contralateral MCA (1 patient; 3.6%), and the posterior fossa (4 patients; 14.3%). A significant relationship (P < .03) was found between occurrence of transient ischemic attack (TIA) and appearance of new lesions. Microembolic signals (MES) were detected in 88 patients (92.6%), with no relationship between number of MES and the appearance of new ischemic foci. CONCLUSION: New ischemic foci were observed in 17.3% of the patients undergoing neuroprotected CAS. Appearance of new ischemic lesions were only significantly related to the occurrence of TIA but not to the number of MES registered or other variables. Despite the encouraging results, the incidence of new ischemic lesions should promote research for safer techniques and devices.

[Vascular risk factors in patients with infratentorial vertebrobasilar ischemia]. / Factores de riesgo vascular en pacientes con isquemia en el territorio vertebrobasilar infratentorial.

INTRODUCTION: Arteriosclerosis is the commonest aetiology of vertebro-basilar ischemia (VBI). In the literature few studies mention the risk profile of cerebrovascular accidents at this site. MATERIAL AND METHODS: In order to establish whether this profile has specific characteristics, we carried out a transversal study of 70 patients with VBI of artherothrombotic origin situated in the brain stem or cerebellum, determining the prevalence of the main risk factors (RF). The results were compared with a control group of individuals who had no cerebral vascular pathology and also with another group who had arteriosclerotic obstructive lesions of the carotid artery as an example of involvement of another vascular territory. RESULTS: In the the group of patients with VBI we found greater prevalence of hypertension, smoking, ischaemic cardiopathy, peripheral vascular disease and excessive alcohol consumption together with raised levels of arterial hypertension, haematocrit, haemoglobin and total cholesterol as compared with the control group and within a similar range to the group of patients with ischemia of the carotid territory. We underline the high prevalence of diabetes in patients with VBI (45.7%), considerably greater than that of the control group (12.5%), than those with carotid pathology (20.4%) and that described in the literature (17-25%). CONCLUSIONS: According to our results, the prevalence of RF in VBI and in carotid pathology is similar, except in the case of diabetes. This may play a more decisive role in territory such as the vertebro-basilar, where vascularization is basically by small calibre vessels.

[Restenosis and remodeling after percutaneous transluminal carotid angioplasty]. / Reestenosis y remodelado tras angioplastia transluminal percutánea carotídea.

INTRODUCTION: The characteristics of restenosis and remodeling after carotid percutaneous transluminal angioplasty (PTA) were badly known. OBJECTIVE: To describe these characteristics in our series of carotid PTA. PATIENTS AND METHODS: A total of 78 cases of PTA for symptomatic > 70% atherosclerotic stenosis of the extracranial internal carotid artery, were selected from our series of PTA if follow-up was > 12 months. All of them were followed with extracranial continuous-wave Doppler. RESULTS: Restenosis of any degree was found in 17 cases (21.79%) and always asymptomatic. A restenosis > or = 70% was found in 5 cases (6.4%). Restenosis was mainly found in cases without residual stenosis nor dissection after PTA (p = 0.002). Restenosis was found in 16 cases (94.11%) in the first 6-months, with no progression thereafter. Remodeling of residual stenosis was frequent (17 cases; 53.11%) and found mainly during the first month after PTA. Its incidence was highest in patients with dissection treated with heparin. In cases with restenosis, remodeling was infrequent, incomplete and occurred after 18-24 months. CONCLUSIONS: 1. Significant restenosis after PTA due to myointimal proliferation, was infrequent. All cases were asymptomatic, under antiplatelet treatment. A new interventional procedure might not be necessary. 2. Complete remodeling was frequently found after 1-month control, mainly in arteries with some residual stenosis and dissection after PTA.

[Hyperperfusion syndrome as a complication of percutaneous transluminal angioplasty of the internal carotid artery]. / Síndrome de hiperperfusión como complicación de la angioplastia transluminal percutánea de la arteria carótida interna.

INTRODUCTION: The hyperperfusion syndrome (HS) is described as an infrequent complication of carotid endarterectomy. It may also occur in percutaneous transluminal carotid angioplasty with a similar causal mechanism and clinical features to those seen in HS related to carotid endarterectomy. CLINICAL CASE: We describe the case of a 69 year old man who developed HS at the time of transluminal carotid angioplasty and 'stenting' of symptomatic, pre-occlusive stenosis of the left internal carotid artery. This complication was not detected on the postoperative arteriography. On CT the presence of a hemispheric hematoma was confirmed. It is thought that HS is caused by a fault in autoregulation of the cerebral blood flow following correction of vascular stenosis in previously ischemic territory. CONCLUSIONS: Most of the early complications of transluminal carotid angioplasty are ischemic. HS is rare but is a possible complication of transluminal carotid angioplasty and therefore meticulous control of the blood pressure is necessary. A CT scan after any atypical complication of angioplasty may be considered to be essential.

[Chlamydia pneumoniae and arteriosclerosis]. / Chlamydia pneumoniae y arteriosclerosis.

INTRODUCTION: The relationship between Chlamydia pneumoniae and atherosclerosis has been assessed in several studies. Development and conclusions. Their results suggest a possible role of Chlamydia pneumoniae in the origin and development of the disease, while the actual link between them are still unknown. However, the presence of Chlamydia pneumoniae in patients with atherosclerosis could be just a coincidence.

[Cardiac disease in intracerebral hematomas]. / Enfermedad cardíaca en los hematomas intracerebrales.

INTRODUCTION AND OBJECTIVE: The Central Nervous System (CNS) plays an essential role in the regulation of the cardiac function. There is strong evidence that many CNS lesions, mainly those of hemorrhagic origin, may induce repolarization abnormalities and enlargement of the QT interval (ECG changes) and several types of arrhythmias. In some cases these changes have been related to sudden death. The imbalance between the sympathetic and parasympathetic systems, favoring the former, seems to be the etiopathogenic factor. MATERIAL AND METHODS: We have carried out a study on thirty-two in-patients suffering from non-severe intracerebral hemorrhage, by means of a Holter ECG examination within the first 72 hours and a second record after two months. We have assessed any significative differences on the ECG findings in relation to the location of the hematoma (left or right hemispheres) and the presence of a personal history of arterial hypertension and/or heart disease. RESULTS: One or more ECG changes were present in 69.2% of the patients and 73% showed one or more rhythm abnormalities. There was a higher incidence of supraventricular arrhythmias associated with the right hemisphere hematomas, with an statistical significance for the atrial extrasystolia. No differences were found between the group with a previous history of hypertension and/or heart disease and the one without these conditions. There were two cases of sudden death, both with left hemisphere hematomas, and in one of them the previous rhythm abnormalities were recorded. CONCLUSIONS: This study corroborates the hypothesis that right hemispheric hematomas induce supraventricular arrhythmias more frequently. The possible association between severe ventricular arrhythmias and sudden death with left-hemisferic hematomas should be studied in a higher number of patients. We recommend monitoring every acute case of intracerebral hematoma when possible.

[Recurrent spontaneous carotid dissection]. / Disección carotídea espontánea recurrente.

INTRODUCTION: Arterial dissection is the cause of 20% of the stroke occurring in adults under the age of 45. The existence of recurrence has been discussed in recent studies, and the overall frequency estimated as 4% to 8%, with a risk of 1% per year. The course of the condition is usually oligosymptomatic, so that a high index of suspicion is necessary for diagnosis to be made. We consider that different connective tissue disorders and anomalies of the vascular wall predispose to dissection. It would seen reasonable to think that these same anomalies may lead to recurrence. However, this cannot always be demonstrated. A family history of dissection is also an important factor in recurrence. CLINICAL CASES: We present two cases of recurrent spontaneous dissection of the carotid artery from a series of 22 patients with dissection, during the period 1990-1997. In the first case, the second dissection occurred 15 days after the first and in the second case, seven months later. In both cases the recurrence was in the contra-lateral carotid artery. In the second case the vascular tree was noted to have been formed of ecstatic, tortuous vessels. CONCLUSIONS: Our series shows results similar to others published. In one of these, an underlying arteriopathy which predisposed to the condition was shown. Both followed satisfactory courses. In case 2 a high index of clinical suspicion was necessary, since the recurrence presented as headache alone.

[Cardioembolic stroke in atrial fibrillation and new anticoagulation criteria: a therapeutic dare]. / Ictus cardioembolico por fibrilacion auricular y nuevos criterios de anticoagulacion: un reto terapeutico.

INTRODUCTION: Atrial fibrillation (AF) increases five times the risk of stroke. The new risk stratification scheme for establishment of oral anticoagulation CHA2-DS2-VASc performs better in risk stratification of stroke compared to the prior CHADS2 scale. AIM: To evaluate in patients with known AF and cardioembolic stroke, the indication of oral anticoagulation under previous risk embolism according to the CHADS2 scale and new classification CHA2-DS2-VASc, assessing the risk of bleeding with HAS-BLED scale. PATIENTS AND METHODS: We included 164 patients with atrial fibrillation and cardioembolic stroke, 87 of them with known AF. It was recorded previous anticoagulant treatment and criteria for prior anticoagulation taking into account CHADS2 scales and CHA2-DS2-VASc, including hemorrhagic risk scale HAS-BLED. In anticoagulated patients INR level was recorded in acute stroke phase. RESULTS: There were no significant differences in baseline patients characteristics according to previous anticoagulation, except higher percentage of previous stroke in anticoagulated patients (47%). 41.3% were anticoagulated with known AF prior to stroke. From 52 non-anticoagulated patients, 61.5% met criteria for anticoagulation prior to stroke as CHADS2. Using CHA2-DS2-VASc, this percentage increased to 94.2% (p <0.001). 78.8% of non-anticoagulated had a low risk of bleeding according to the scale HAS-BLED. In anticoagulated patients, 67.6% had suboptimal INR at the time of stroke. CONCLUSION: In our study, we found low compliance scales of thromboembolic risk stratification in patients with AF for an optimal treatment strategy. It should be increased its use for primary prevention of stroke and optimization of anti-coagulant therapy in patients with AF.

Internal carotid artery stenting in patients with near occlusion: 30-day and long-term outcome.

BACKGROUND AND PURPOSE: The natural history of the carotid NO is poorly characterized, and the management of patients remains controversial. We report the results and complications associated with CAS and follow-up. MATERIALS AND METHODS: Between March 2000 and March 2009, 116 of 836 CAS procedures were performed in patients with carotid NO (13.9%). A total of 99 men (85.3%) and 17 women (14.7%) with a mean age of 65.8 years were included. Presenting symptoms were TIA in 44 patients (37.9%) and minor stroke or noninvalidating stroke in 61 (52.6%). One hundred five patients (90.5%) were symptomatic. RESULTS: A distal filter was used for cerebral protection in 92 patients (79.3%). Transient hemodynamic alterations were frequent during balloon inflation: hypotension (37.1%), bradycardia (48.3%), and asystole in 24.1%. Four patients (3.4%) developed a TIA after CAS. Stroke in progression was arrested in the 1 patient (0.9%). The median follow-up period for patients was 36 months. Asymptomatic restenosis >70% occurred in 5 patients (4.3%); asymptomatic occlusion occurred in 3 patients (2.6%). During follow-up, 3 patients (2.6%) experienced a stroke, 1 ipsilateral (at 19 months) and 2 contralateral (at 6 and 30 months, respectively). Thirteen patients (11.2%) died, 7 from vascular causes. CONCLUSIONS: Our study showed that carotid NO is an under-recognized condition, and CAS would seem to be beneficial when performed by an experienced neurointerventional team.

Volume and composition of emboli in neuroprotected stenting of the carotid artery.

BACKGROUND AND PURPOSE: Periprocedural microembolization is a major and permanent risk for patients treated by angioplasty and stent placement of high-grade carotid stenoses. Little is known however about the characteristics and significance of these embolized particles. Our aim was to assess the volume and composition of debris captured by filters during carotid angioplasty and stent placement (CAS) of severe internal carotid artery (ICA) stenoses. MATERIALS AND METHODS: Institutional review board approval and informed consent from all subjects were obtained. Two hundred one patients (mean age, 66.2 years; range, 35-82 years) with > or = 70% stenosis of the ICA underwent filter-protected CAS. Ultrastructural and semiquantitative analysis of the volume of filters was obtained. Multifactorial statistical analysis was performed to determine factors related to debris volume and composition. RESULTS: Transient ischemic attack occurred in 6 patients (3%), and a major stroke, in 1 (0.5%). Debris was found in 117 filters (58.2%), with volume <1 lambda (0.001 mL) in 71%. The number of balloon dilations, age older than 65 years, and calcified plaques in pre-CAS angiography were significantly associated with the presence of particulates inside the filters (P < .03, P < .004, and P < .05, respectively). CONCLUSIONS: Vessel wall and atheromatous plaques are the main source of microemboli during CAS. Embolization is mainly related to the number of balloon dilations during CAS. Planning a proper and individualized strategy for the procedure in each patient is essential to minimize the potential effects of manipulation during CAS.