Detekce nestabilního karotického plátu v prevenci ischemické cévní mozkové příhody Detection of unstable carotid plaque in ischemic stroke prevention Souhrn Aterosklerotická stenóza karotidy je známý rizikový faktor ischemické CMP nebo tranzitorní ischemické ataky. Změny v aterosklerotickém plátu typu krvácení do plátu, neovaskularizace, velký podíl lipidů, tenká nebo prasklá fi brózní čepička či zánět hrají pravděpodobně významnou roli v nestabilitě plátu a jsou spojeny s vyšším rizikem ischemické CMP. V současnosti neexistuje modalita, která by byla schopna současně přesně změřit stupeň stenózy a spolehlivě detekovat nestabilní aterosklerotický plát. K přesné a detailní analýze morfologie plátu je potřeba využít kombinaci jednotlivých metod. CT je široce dostupná a často první zobrazovací metoda plátu se schopností detekovat kalcifi kace, ulceraci plátu a stupeň stenózy. Nicméně rozlišení mezi kumulací lipidů a krvácením do plátu je nízké. MR má schopnost rozpoznat většinu nestabilních morfologických znaků plátu, ale časová náročnost, pohybové artefakty a absence unifi kovaných protokolů jsou komplikací pro širší použití. PET je efektivní nástroj k detekci metabolických procesů v plátu, zejména zánětu, ale prostorové rozlišení je nepřesné. Ultrazvuk je široce dostupná a levná metoda k monitoringu vývoje plátu, zejména za použití 3D módu, ale pro rozlišení jednotlivých znaků plátu je suboptimální. Budoucí vývoj ultrazvukových metod, např. počítačová analýza škály šedi a kontrastní ultrazvuk však výhledový potenciál ultrazvuku významně zlepšuje.

for the ANTIQUE Trial GroupObjectives-Transcranial color-coded duplex sonography (TCCS) enables to measure blood flow characteristics in cerebral vessels, including vascular resistance and pulsatility. The study aims to identify factors influencing pulsatility (PI) and resistance (RI) indices measured using TCCS in patients with carotid atherosclerosis.Methods-Self-sufficient patients with atherosclerotic plaque causing 20-70% carotid stenosis were consecutively enrolled to the study. All patients underwent duplex sonography of cervical arteries and TCCS with measurement of PI and RI in the middle cerebral artery, neurological, and physical examinations. Following data were recorded: age, gender, height, weight, body mass index, systolic and diastolic blood pressure, occurrence of current and previous diseases, surgery, medication, smoking, and daily dose of alcohol. Univariant and multivariant logistic regression analysis were used for identification of the factors influencing RI and PI.Results-Totally 1863 subjects were enrolled to the study: 139 healthy controls (54 males, age 55.52 AE 7.05 years) in derivation cohort and 1724 patients (777 males, age 68.73 AE 9.39 years) in validation cohort. The cut off value for RI was 0.63 and for PI 1.21. Independent factors for increased RI/PI were age (odds ratio [OR] = 1.108/1.105 per 1 year), occurrence of diabetes mellitus (OR = 1.767/2.170), arterial hypertension (OR = 1.700 for RI only), width of the carotid plaque (OR = 1.260 per 10% stenosis for RI only), and male gender (OR = 1.530 for PI only; P <.01 in all cases). Conclusions-The independent predictors of increased cerebral arterial resistance and/or pulsatility in patients with carotid atherosclerosis were age, arterial hypertension, diabetes mellitus, carotid plaque width, and male gender.

Background and aimCarotid plaque progression contributes to increasing stroke risk. The study aims to identify factors influencing carotid plaque thickness progression after changing the preventive treatment to the ‘treating arteries instead of risk factors’ strategy, that is, change in treatment depending on the progression of atherosclerosis.MethodsThe study participants who completed sonographic controls over the course of 3 years were enrolled to the analysis. Duplex sonography of cervical arteries was performed in 6-month intervals with measurement of carotid plaque thickness. Plaque thickness measurement error (σ) was set as 3 SD. Only evidently stable and progressive plaques (defined as plaque thickness difference between initial and final measurements of ˂σ and >2σ, respectively) were included to analysis. Univariate and multivariate logistic regression analysis was performed to identify factors influencing plaque progression.ResultsA total of 1391 patients (466 males, age 67.2±9.2 years) were enrolled in the study. Progressive plaque in at least one carotid artery was detected in 255 (18.3%) patients. Older age, male sex, greater plaque thickness, coronary heart disease, vascular surgery/stenting history and smoking were more frequently present in patients with progressive plaque (p˂0.05 in all cases). Multivariate logistic regression analysis identified only the plaque thickness (OR 1.850 for left side, 95% CI 1.398 to 2.449; and OR 1.376 for right side, 95% CI 1.070 to 1.770) as an independent factor influencing plaque progression.ConclusionCarotid plaque thickness corresponding to stenosis severity is the only independent risk factor for plaque thickness progression after optimising the prevention treatment.Trial registration numberNCT02360137.

BackgroundCarotid endarterectomy (CEA) is a beneficial procedure for selected patients with an internal carotid artery (ICA) stenosis. Surgical risk of CEA varies from between 2 and 15%.The aim of the study is to demonstrate the safety and effectiveness of sonolysis (continual transcranial Doppler monitoring, TCD) using a 2-MHz diagnostic probe with maximal diagnostic energy on the reduction of the incidence of stroke, transient ischemic attack (TIA) and brain infarction detected using magnetic resonance imaging (MRI) by the activation of the endogenous fibrinolytic system during CEA.Methods/designDesign: a multicenter, randomized, double-blind, sham-controlled trial.Scope: international, multicenter trial for patients with at least 70% symptomatic or asymptomatic ICA stenosis undergoing CEA.Inclusion criteria: patients with symptomatic or asymptomatic ICA stenosis of at least 70% are candidates for CEA; a sufficient temporal bone window for TCD; aged 40–85 years, functionally independent; provision of signed informed consent.Randomization: consecutive patients will be assigned to the sonolysis or control (sham procedure) group by computer-generated 1:1 randomization. Prestudy calculations showed that a minimum of 704 patients in each group is needed to reach a significant difference with an alpha value of 0.05 (two-tailed) and a beta value of 0.8 assuming that 10% would be lost to follow-up or refuse to participate in the study (estimated 39 endpoints).Endpoints: the primary endpoint is the incidence of stroke or TIA during 30 days after CEA and the incidence of new ischemic lesions on brain MRI performed 24 h after CEA in the sonolysis and control groups. Secondary endpoints are occurrence of death, any stroke, or myocardial infarction within 30 days, changes in cognitive functions 1 year post procedure related to pretreatment scores, and number of new lesions and occurrence of new lesions ≥0.5 mL on post-procedural brain MRI.Analysis: descriptive statistics and linear/logistic multiple regression models will be performed. Clinical relevance will be measured as relative risk reduction, absolute risk reduction and the number needed to treat.DiscussionReduction of the periprocedural complications of CEA using sonolysis as a widely available and cheap method may significantly increase the safety of CEA and extend the indication criteria for CEA.Trial registrationClinicalTrials.gov, NCT02398734. Registered on 20 March 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1754-x) contains supplementary material, which is available to authorized users.

Purpose Cerebral blood flow volume is an important factor for the accurate diagnosis of neurovascular diseases and treatment indication. This study aims to assess correlations of blood flow volume measurements in cervical and intracranial arteries between duplex sonography and quantitative magnetic resonance angiography (qMRA). Materials and Methods Consecutive patients with suspicion of cerebral vascular pathology underwent qMRA and duplex sonography of cervical and intracranial arteries with measurement of blood flow volume in bilateral common (CCA), internal (ICA) and external carotid arteries, vertebral and basilar arteries, middle, anterior, posterior cerebral and posterior communicating arteries using 2 different ultrasound machines. Ten patients underwent all examinations twice. Correlations between blood flow volume measurements were evaluated using Spearman’s correlation coefficient and inter-class correlation coefficient (ICC). Results In total, 21 subjects (15 males, mean age: 56.3 ± 6.2 years) were included in the study. Duplex sonography inter-investigator correlation was excellent (ICC = 0.972, p < 0.0001) as well as intra-investigator correlations of both qMRA and duplex sonography (ICC ˃ 0.990, p < 0.0001). Mostly high correlations were recorded between qMRA and duplex sonography in particular cervical arteries but only low to moderate correlations were obtained for intracranial arteries. The mean differences between blood flow volume measurements were 10.9 ± 8.1 % in the CCA and its branches when using qMRA and 15.0 ± 11.9 % when using duplex sonography, 13.5 ± 11.8 %/35.4 ± 34.2 % in the ICA siphon and its branches when using qMRA/duplex sonography, and 24.1 ± 19.7 %/44.9 ± 44.0 % in both vertebral arteries and the basilar artery when using qMRA/duplex sonography. Conclusion Duplex sonography as well as qMRA allow for highly reproducible measurement of blood flow volume in cervical and intracranial arteries in routine clinical practice.

Introduction: Dabigatran is direct thrombin inhibitor approved in the prevention of stroke in patients with atrial fibrillation. It was shown in the RELY trial substudy that genetic variants could contribute to interindividual variability in concentrations of the active metabolite of dabigatran and influence the safety of treatment. Carriage of the CES1 rs2244613 minor allele was associated with lower exposure to active metabolite and with a lower bleeding risk compared to wild-type allele. Aim: To determine the influence of gene CES1 polymorphism rs2244613 and through plasmatic concentration of dabigatran on occurrence of major bleeding in stroke patients. Methods: Prospective observational monocentric study in consenting stroke patients initiated on dabigatran. Primary outcome was major bleeding defined using ISTH criteria. DNA analysis of CES1 polymorphism rs2244613 was done with RFLP analysis. Through concentration of dabigatran was measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS) at least 7 days after initiation. Results: 110 patients after cardioembolic stroke, mean age 70,2 (SD 12.7), 56 (50.9%) women, were enrolled. Mean follow-up time was 19.9 months (total 182.2 patient years). 68 (61.8%) patients were wild-type, 37 (33.6%) were minor allele heterozygotes and 5 (4.5%) were homozygous minor allele carriers. Through dabigatran concentration were non-significantly lower in minor allele carriers: 132.8 (SD 98.7) ng/ml in wild-type patients, 112.2 (80.0) in heterozygotes and 95.6 (SD 88.1) in homozygotes. There were 6 episodes of major bleeding, all in patients with wild-type genotype. The patients with dabigatran level above 160 ng/ml (upper quartile) were more likely to have major bleeding, HR 5.74 (95% CI 1.05 - 31.42, p = 0.044). Age and renal function did not correlate with the bleeding. Conclusion: Patients with higher dabigatran concentration had significantly higher major bleeding risk. Minor allele carriers had non-significant trend for having lower through dabigatran level. Personalized dabigatran dosing based on pharmacogenetics and monitoring plasmatic levels should be studied in future trials with the aim to increase the safety of treatment.

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