Factors associated with high-risk plaque characteristics among patients with medium to severe carotid artery stenosis.

OBJECTIVE: There has been a large discussion in literature regarding the proper management of asymptomatic patients with significant carotid artery stenosis (CAS). This study aims to identify potential risk factors associated with high-risk carotid plaques. METHODS: This is a retrospective study based on a prospective database. Eligible patients had medium to severe symptomatic or asymptomatic carotid stenosis (≥50%, NASCET criteria). This study will analyze patients recruited by our institution as part of the multicenter TAXINOMISIS project (NCT03495830). According to protocol, all patients underwent a colored Duplex ultrasound examination and a magnetic resonance angiography (MRA) at baseline. Carotid plaques were classified according to Gray-Weale ultrasonographic criteria (Types I-V). Main outcomes included the occurrence of symptoms, the high/low echogenicity of the plaque, the existence of intraplaque hemorrhage (IPH) and the existence of lipidic/necrotic core. Secondary, risk factors associated with the aforementioned outcomes were evaluated. RESULTS: A total of 62 patients (mean age: 68.7+/-9.3 years, 66.1% males, 24.2% symptomatic) were recruited by our department. Mean carotid stenosis was 70.81%±13.53%. In multivariate regression analysis, CRP > 2mg/l was strongly associated with symptomatic stenosis (OR=9.92 [1.12-88.178]; P=0.039), and low HDL levels (<1200mmol/l) were associated with lipidic/necrotic plaque core (OR=16.88 [1.10-259.30]; P=0.043). Low HDL levels (OR=7.22 [1.00-51.95], P=0.049) and HbA1c >7% (OR=0.08 [0.01-0.93], P=0.044) were associated with type III/IV plaques whereas HgAbc1 >7% (OR=14.26 [1.21-168.34], P=0.035) was associated with Type V plaques. CONCLUSIONS: This preliminary study has revealed some potential risk factors associated with unstable carotid plaques. This data could help the future development of prognostic models in order to early detect patients that could benefit from further intervention.

Recommendations for multimodal noninvasive and invasive screening for detection of extracranial venous abnormalities indicative of chronic cerebrospinal venous insufficiency: a position statement of the International Society for Neurovascular Disease.

Under the auspices of the International Society for Neurovascular Disease (ISNVD), four expert panel committees were created from the ISNVD membership between 2011 and 2012 to determine and standardize noninvasive and invasive imaging protocols for detection of extracranial venous abnormalities indicative of chronic cerebrospinal venous insufficiency (CCSVI). The committees created working groups on color Doppler ultrasound (US), magnetic resonance (MR) imaging, catheter venography (CV), and intravascular US. Each group organized a workshop focused on its assigned imaging modality. Non-ISNVD members from other societies were invited to contribute to the various workshops. More than 60 neurology, radiology, vascular surgery, and interventional radiology experts participated in these workshops and contributed to the development of standardized noninvasive and invasive imaging protocols for the detection of extracranial venous abnormalities indicative of CCSVI. This ISNVD position statement presents the MR imaging and intravascular US protocols for the first time and describes refined color Doppler US and CV protocols. It also emphasizes the need for the use of for noninvasive and invasive multimodal imaging to diagnose adequately and monitor extracranial venous abnormalities indicative of CCSVI for open-label or double-blinded, randomized, controlled studies.

Direct oral anticoagulants for deep vein thrombosis among patients with hereditary thrombophilia-A cohort study.

OBJECTIVES: to evaluate direct oral anticoagulants (DOACs) in patients with hereditary thrombophilia and deep venous thrombosis (DVT). METHODS: This is a retrospective observational study. RESULTS: In total, 45 patients were treated between 01/2012 and 12/2022 (mean follow-up: 1.5 +/- 0.3 years). The most frequent thrombophilias were heterozygous V Leiden (20%), heterozygous MTHFR C677T (37.8%), heterozygous MTHFR A1298C (24.4%), and hyperhomocysteinemia (26.7%). The patients received rivaroxaban (n = 19), apixaban (n = 15), and dabigatran (n = 11). Three cases presented symptoms' recurrence without evidence of thrombosis' recurrence (two under rivaroxaban and one under apixaban; p > .05). These patients improved under parenteral anticoagulation and were further treated with dabigatran. No other event or major bleeding occurred during the follow-up. The presence of more than two factors was associated with acute recurrence of symptoms (OR = 25.9; 95% CI [1.454-461.262]; p = .026). CONCLUSIONS: DOACs seem to be safe and efficient for patients with hereditary thrombophilia and DVT. The presence of more than two thrombophilia factors is associated with a higher risk for symptom recurrence. Although statistically non-significant, symptoms' recurrence was also observed more frequently among patients under anti-Xa inhibitors than antithrombin inhibitors. This should be verified in larger comparative studies.

Computational modeling of atherosclerotic plaque progression in carotid lesions with moderate degree of stenosis.

Carotid atherosclerotic plaque growth leads to the progressive luminal stenosis of the vessel, which may erode or rupture causing thromboembolism and cerebral infarction, manifested as stroke. Carotid atherosclerosis is considered the major cause of ischemic stroke in Europe and thus new imaging-based computational tools that can improve risk stratification and management of carotid artery disease patients are needed. In this work, we present a new computational approach for modeling atherosclerotic plaque progression in real patient-carotid lesions, with moderate to severe degree of stenosis (>50%). The model incorporates for the first time, the baseline 3D geometry of the plaque tissue components (e.g. Lipid Core) identified by MR imaging, in which the major biological processes of atherosclerosis are simulated in time. The simulated plaque tissue production results in the inward remodeling of the vessel wall promoting luminal stenosis which in turn predicts the region of the actual stenosis progression observed at the follow-up visit. The model aims to support clinical decision making, by identifying regions prone to plaque formation, predict carotid stenosis and plaque burden progression, and provide advice on the optimal time for patient follow-up screening.

Association between periodontal disease and vulnerable plaque morphology in patients undergoing carotid endarterectomy.

BACKGROUND: Periodontal disease (PD) is a chronic inflammatory oral condition with potentially important systemic sequelae. We sought to determine whether the presence of PD in patients with severe carotid disease was associated with morphological features consistent with carotid plaque instability. METHODS: A total of 52 dentate patients hospitalized for carotid endarterectomy (CEA) had standardized assessments of their periodontal status, including measurements of probing pocket depth (PPD), clinical attachment level (CAL) and bleeding on probing (BoP). Carotid plaque morphology was assessed by ultrasound using the gray scale median (GSM) score and by immunohistochemistry using anti-CD68 and anti-alpha-actin antibodies, markers for macrophages and smooth muscle cells (SMCs) respectively. RESULTS: In total 30/52 patients (58%) had PD. Significant associations were noted between low GSM on ultrasound and each mm in PPD (p = 0.001), each mm in CAL (p = 0.002) and with a 10% increase in BoP (p = 0.009). Using the standardized PERIO definition the association remained robust (aOR = 10.4 [95% CI:2.3-46.3], p = .002). Significant associations were also observed with high macrophage accumulation and each individual PD measure (p < 0.01 for PPD, CAL and BoP) and with the PERIO definition (aOR = 15 [95% CI:1.8-127.8], p = .01). Similarly, low SMC density was also significantly associated with individual measures of PD (p < 0.05 for PPD, CAL and BoP), but not with the PERIO definition (aOR 3.4 [95% CI:0.9-12.8], p = .07). CONCLUSIONS: The presence of PD was significantly associated with both ultrasound and immunohistochemistry features of carotid plaque instability in patients undergoing CEA.

The use of Speckle Reduction Imaging (SRI) Ultrasound in the characterization of carotid artery plaques.

BACKGROUND AND PURPOSE: Speckle Reduction Imaging is a new algorithm that improves the image quality of B-mode scanning by reducing the reverberation artifacts. In the present study the value of this method for the characterization of atherosclerotic plaques in the internal carotid artery was investigated. METHODS: Two hundred and twenty two patients (161 men, 61 women; mean age 73 years) referred for carotid ultrasound evaluation were included in the study. Patients with plaques of the internal carotid artery as identified by conventional B-mode scanning were investigated also with the addition of Speckle Reduction Imaging (SRI) with the use of a 4-11-MHz wide band linear transducer. Plaque morphology was rated according to a standardized protocol by two independent observers. RESULTS: For the determination of plaque echogenicity, the reproducibility of SRI (kappa=0.83) was higher than that of conventional B-mode ultrasound (kappa=0.68). The interobserver agreement for plaque surface characterization was also higher for SRI (kappa=0.8) than for conventional B-mode (kappa=0.61). At the evaluation of the image quality through a semiquantitative analysis, SRI was rated superior in the plaque texture resolution, plaque borders determination, vessel wall demarcation and fibrous cap depiction. In addition, the level of "speckle" was reduced with the use of SRI. CONCLUSIONS: SRI is a technique that shows good general agreement with high-resolution B-mode and can be used for the characterization of atherosclerotic plaques in the carotid artery. Furthermore, because this advanced technique allows reduction of ultrasound artifacts, it improves the image quality allowing more precise visualization of plaque morphological details.

Macrophage infiltration and smooth muscle cells content associated with haptoglobin genotype in human atherosclerotic carotid plaques.

We assessed the association between the haptoglobin (Hp) genotype and 2 common indicators of atherosclerotic plaque instability: macrophage infiltration and the smooth muscle cell (SMC) content. A total of 70 consecutive patients who underwent carotid endarterectomy were included in the study. For immunohistochemical study the anti-CD68 and anti-a-actin antibodies were used on adjacent serial sections; 36 plaques from patients with the Hp 1-1 or 2-1 genotype and 34 plaques from patients with the Hp 2-2 genotype were analyzed. The macrophage content (CD68+) was significantly higher in the Hp 2-2 group compared with that in the Hp 1-1 or 2-1 group (P < .001). In plaques from patients with diabetes, the SMC content was significantly lower in the Hp 2-2 group (P = .034). Carotid plaques from diabetic patients with Hp 2-2 genotype had higher macrophage infiltration and lower SMC content. Both parameters are indicators of atherosclerotic plaque instability.

First in vivo application of microwave radiometry in human carotids: a new noninvasive method for detection of local inflammatory activation.

OBJECTIVES: This study investigated whether temperature differences: 1) can be measured in vivo noninvasively by microwave radiometry (MR); and 2) are associated with ultrasound and histological findings. BACKGROUND: Studies of human carotid artery samples showed increased heat production. MR allows in vivo noninvasive measurement of internal temperature of tissues. METHODS: Thirty-four patients undergoing carotid endarterectomy underwent screening of carotid atherosclerosis by ultrasound and MR. Healthy volunteers were enrolled as a control group. During ultrasound study, plaque texture, plaque surface, and plaque echogenicity were analyzed. Temperature difference (ΔT) was assigned as maximal minus minimum temperature. Association of thermographic with ultrasound and histological findings was performed. RESULTS: ΔT was higher in atherosclerotic carotid arteries compared with the carotid arteries of controls (p < 0.01). Fatty plaques had higher ΔT compared with mixed and calcified (p < 0.01) plaques. Plaques with ulcerated surface had higher ΔT compared with plaques with irregular and regular surface (p < 0.01). Heterogeneous plaques had higher ΔT compared with homogenous (p < 0.01). Specimens with thin fibrous cap and intense expression of CD3, CD68, and vascular endothelial growth factor (VEGF) had higher ΔT compared with specimens with thick cap and low expression of CD3, CD68, and VEGF (p < 0.01). CONCLUSIONS: MR provides in vivo noninvasive temperature measurements of carotid plaques, reflecting plaque inflammatory activation.

Late spontaneous recanalization of acute internal carotid artery occlusion.

Spontaneous internal carotid recanalization has been infrequently observed, and when it has been reported, it has most commonly occurred early after a stroke. We report a case of a patient with late spontaneous recanalization of the internal carotid artery (ICA) that occurred within 6 months to 1 year after the initial diagnosis of occlusion during the course of a stroke. This event allowed the patient to undergo a successful surgical intervention. A suggestion is made about the mechanism of this phenomenon and an implication about changes in the follow-up strategies of these patients is presented.