Feasibility and Intermediate Results of Transcarotid Revascularization with a Prosthetic Conduit.

BACKGROUND: Transcarotid artery revascularization (TCAR) is a hybrid technique with excellent initial outcomes. The technical success and safety of TCAR is heavily dependent on an anatomically suitable common carotid artery (CCA). Many patients do not meet anatomic criteria and therefore are not eligible for this therapy. We sought to extend the eligibility of TCAR to patients with unfavorable CCA anatomy via the adoption of a prosthetic arterial conduit. METHODS: A single-center retrospective study of patients with critical carotid artery stenosis who underwent TCAR via a prosthetic conduit between June 2019 and October 2021 was performed. All patients in the study were considered high-risk for carotid endarterectomy based on anatomic features, such as restenosis post-carotid endarterectomy and neck radiation. Unfavorable CCA anatomy was defined as a clavicle to carotid bifurcation distance <5 cm, a CCA diameter <6 mm, and/or significant atherosclerotic disease at the intended arterial access site. The primary outcome of interest was technical success. Secondary outcomes included perioperative complications, intermediate and long-term patency, intermediate and long-term stroke and/or mortality and in-hospital length of stay. Follow-up ranged from 1 to 29 months. RESULTS: Eight patients underwent 10 TCAR procedures via a prosthetic conduit. A total of 2 procedures (20%) were performed on female patients and 8 procedures (75%) were performed on male patients. The mean age was 65 years old (standard deviation 11 years). Technical success was 100%. The 30-day ipsilateral stroke rate was 0%. The 30-day patency was 90%. There was no re-exploration for hemorrhage and 30 day mortality was 0%. CONCLUSIONS: TCAR is an excellent option for carotid artery revascularization. Unfavorable CCA anatomy has limited its applicability. TCAR via a prosthetic conduit has the potential to expand eligibility for this promising therapy.

AMALRIC TRIANGULAR SIGN AND CAROTID DOPPLER ULTRASONOGRAPHIC FINDINGS IN CENTRAL RETINAL ARTERY OCCLUSION.

PURPOSE: The aim of this study was to determine the incidence of the Amalric triangular sign (ATS) in patients with central retinal artery occlusion and investigate its association with visual function and carotid Doppler ultrasonography findings. METHODS: A retrospective chart review was conducted on 21 eyes from 21 patients with complete central retinal artery occlusion. Best-corrected visual acuity and carotid Doppler ultrasonography findings [peak systolic velocity, end-diastolic velocity, and resistance index (RI) = (PSV - EDV)/PSV] were investigated. RESULTS: Three patients (14%) exhibited the ATS. Best-corrected visual acuity at first visit was significantly worse in ATS-positive patients than in ATS-negative patients (P = 0.024). Doppler waveform analysis of the common carotid artery showed that ATS-positive patients had a significantly lower end-diastolic velocity [P = 0.009, median 10 (range 9-10) vs. 17 (13-24) m/second] and significantly higher resistance index [P = 0.021, median 0.80 (range 0.79-0.83) vs. 0.72 (0.66-0.82)] than did ATS-negative. CONCLUSION: The Amalric triangular sign was observed in three patients with central retinal artery occlusion, who showed worse best-corrected visual acuity at the first visit than did those without the ATS. Carotid Doppler ultrasonography revealed that ATS-positive patients had a significantly higher resistance index and lower end-diastolic velocity at the common carotid artery than did ATS-negative, indicating steno-occlusive changes in the internal carotid artery.

Color Duplex Ultrasonography for the Evaluation of Innominate, Subclavian, and Common Carotid Artery Stenosis.

OBJECTIVE: This study aimed to validate the efficiency of Doppler ultrasonography for predicting the innominate, subclavian, and common carotid artery stenosis. METHODS: This retrospective multicenter study between 2013 and 2022 enrolled 636 patients who underwent carotid Doppler ultrasonography and subsequent digital subtraction angiography. And 58 innominate artery stenosis, 147 common carotid artery stenosis, and 154 subclavian artery stenosis were included. The peak systolic velocity at innominate, subclavian, and common carotid artery, and velocity ratios of innominate artery to common carotid artery, innominate artery to subclavian artery, and common carotid artery to internal carotid artery were measured or calculated. The threshold values were determined using receiver operating characteristic analysis. RESULTS: The threshold values of innominate artery stenosis were peak systolic velocity >206 cm/s (sensitivity: 82.8%; specificity: 91.4%) to predict ≥50% stenosis and >285 cm/s (sensitivity: 89.2%; specificity: 94.9%) to predict ≥70% stenosis. The threshold values of common carotid artery stenosis were peak systolic velocity >175 cm/s (sensitivity: 78.2%; specificity: 91.9%) to predict ≥50% stenosis and >255 cm/s (sensitivity: 87.1%; specificity: 87.2%) to predict ≥70% stenosis. The threshold values of subclavian artery stenosis were peak systolic velocity >200 cm/s (sensitivity: 68.2%; specificity: 84.4%) to predict ≥50% stenosis and >305 cm/s (sensitivity: 57.9%; specificity: 91.4%) to predict ≥70% stenosis. CONCLUSIONS: Symptomatic patients with ultrasonic parameters of velocity at innominate artery ≥206 cm/s, velocity at common carotid artery ≥175 cm/s, or velocity at subclavian artery ≥200 cm/s need to be considered for further verification and whether revascularization is necessary.

Early Atherosclerotic Inflammatory Pathways in Children with Obstructive Sleep Apnea.

OBJECTIVE: To evaluate structural and functional carotid changes and inflammatory profiles in children with obstructive sleep apnea (OSA) and healthy controls. STUDY DESIGN: Patients with OSA and matched controls (ages 5-13 years) were recruited. Proinflammatory cytokines and acute phase reactants were measured at 6:00 p.m. Common carotid artery measures were determined using ultrasound. Confirmatory factor analysis was used to determine subgroups of cytokines and their effects on carotid measures. RESULTS: Ninety-six patients participated (53 healthy controls, 43 patients with OSA). OSA was associated with increased proinflammatory cytokines (cluster of differentiation-40 ligand [CD40-L], interleukin [IL]-6, and IL-8) and high sensitivity C-reactive protein (P < .05 for all). One cytokine subgroup (IL-6 and IL-8) was negatively associated with markers of carotid function, indicating reduced arterial distensibility and increased stiffness (P < .05 for 3 ultrasound measures); and tumor necrosis factor-α had an opposing effect on carotid function compared with this cytokine subgroup (P < .05 for 2 ultrasound measures). Linear regression demonstrated significant associations between and tumor necrosis factor- α and 2 measures of carotid function (P < .05 for each). Children with OSA did not have functional or structural carotid changes compared with controls. CONCLUSION: OSA was not directly associated with structural and functional carotid changes but was associated with upregulation of key proinflammatory cytokines (sCD40-L, IL-6, and IL-8). Together, IL-6 and IL-8 were associated with changes in carotid function. Longitudinal studies are needed to demonstrate that the inflammatory milieu observed in our population is a precursor of atherosclerosis in children.

Carotid artery duplex velocity criteria might be equivocal after left ventricular assist device implantation.

BACKGROUND: Although conventional angiography remains the reference standard for the grading of carotid stenosis, carotid duplex ultrasound (CDUS) is the most commonly used modality for determining the degree of carotid stenosis. The validity of CDUS findings for patients after left ventricular assist device (LVAD) implantation is questionable, because the velocities are often altered secondary to the continuous flow nature of the devices. METHODS: A retrospective review was performed of all patients who had undergone LVAD implantation from January 2007 to December 2019. All patients who had undergone CDUS before and after LVAD implantation were included. Patients receiving extracorporeal membrane oxygenation, those with unusable carotid imaging studies, and those with internal carotid artery (ICA) occlusion were excluded. The peak systolic velocity (PSV) and end-diastolic velocity (EDV) in the ICA and common carotid artery (CCA) and the ICA/CCA ratios were compared before and after LVAD implantation. RESULTS: A total of 36 patients (mean age 59 years; 30 men; 6 women) had undergone CDUS both before and after LVAD implantation (mean, 647 days between imaging studies). A total of 61 ICAs had met the criteria for inclusion. Before LVAD, 7 carotid arteries (13%) had had >50% carotid stenosis and 53 (87%) had had 0% to 50% stenosis. The mean changes in the velocities after LVAD were as follows. The ICA PSV had decreased by 6.12 ± 4.34 cm/s, and the ICA EDV had increased by 13.44 ± 4.23 cm/s. The CCA PSV had decreased by 17.22 ± 4.95 cm/s, and the CCA EDV had increased by 10.83 ± 2.59 cm/s. The mean ICA/CCA ratio had increased by 0.18 ± 0.05. All the mean changes in velocity were significant (P < .01), except for the ICA PSV (P = .167). Among four patients with known stenosis of 60% to 69%, the degree of increase in the ICA and CCA EDVs (75.8 and 13.3 cm/s, respectively) was significantly greater than that for patients with <50% or no stenosis. Carotid artery laterality did not significantly affect the differences in mean velocity. Centrifugal LVADs resulted in a significantly larger increase in the ICA EDV compared with axial LVADs (26.0 vs 6.3 cm/s; P < .01). CONCLUSIONS: LVADs were associated with significant changes in CCA PSV, ICA and CCA EDV, and ICA/CCA ratios. However, the magnitude of these changes in patients with <50% stenosis was minimal and might not be clinically significant. The LVAD type might only have an effect on EDV measurements in the CCA, and the left and right carotid arteries did not appear to have different degrees of change in velocity. The currently used criteria for determining carotid stenosis might result in an under- or overestimation of carotid stenosis in patients with an LVAD.

Ipsilateral carotid bypass outcomes in hostile neck anatomy.

OBJECTIVE: To determine differences in outcomes among patients undergoing ipsilateral carotid bypass with hostile or normal neck anatomy. METHODS: Single-center retrospective review of all ipsilateral extracranial carotid bypasses performed between 1998 and 2018. RESULTS: Forty-eight patients underwent ipsilateral carotid bypass from the common carotid artery to either the internal carotid artery or carotid bifurcation during the study period. Seven patients were excluded owing to either a lack of follow-up or missing data. The indications for intervention included infected patches, aneurysmal degeneration, symptomatic and asymptomatic stenosis or restenosis, carotid body tumors, neck malignancy, and trauma. In 25 procedures (61%), there was a hostile neck anatomy defined as a prior history of external beam neck irradiation or neck surgery. Among this group, 12 pectoralis muscle flaps were performed for reconstructive coverage. Conduits included polytetrafluorethylene (n = 21), great saphenous vein (n = 9), superficial femoral artery (n = 7) and arterial homograft (n = 4). All superficial femoral artery conduits were used in the hostile neck group (P = .03). The overall mean time of follow-up was 22 months, with all bypasses remaining patent with no significant clinical stenosis. The 30-day ipsilateral stroke and myocardial infarction rates were 4.88% each, all within the hostile neck group, with no 30-day mortalities for the entire cohort. One-third of the muscle flaps were performed in the setting of infected patches (P = .02) with no significant differences in perioperative outcomes with use. The overall median hospital length of stay was significantly increased in patients receiving muscle flap coverage (3.0 vs 7.0 days; P = .04). CONCLUSIONS: In patients with a complex carotid pathology, ipsilateral carotid bypass is an effective solution for carotid reconstruction. Different conduits should be used depending on the indication. Muscle flap coverage should be considered in hostile settings when primary wound closure is not feasible.

Endothelial Scaffolding Protein ENH (Enigma Homolog Protein) Promotes PHLPP2 (Pleckstrin Homology Domain and Leucine-Rich Repeat Protein Phosphatase 2)-Mediated Dephosphorylation of AKT1 and eNOS (Endothelial NO Synthase) Promoting Vascular Remodeling.

OBJECTIVE: A decrease in nitric oxide, leading to vascular smooth muscle cell proliferation, is a common pathological feature of vascular proliferative diseases. Nitric oxide synthesis by eNOS (endothelial nitric oxide synthase) is precisely regulated by protein kinases including AKT1. ENH (enigma homolog protein) is a scaffolding protein for multiple protein kinases, but whether it regulates eNOS activation and vascular remodeling remains unknown. Approach and Results: ENH was upregulated in injured mouse arteries and human atherosclerotic plaques and was associated with coronary artery disease. Neointima formation in carotid arteries, induced by ligation or wire injury, was greatly decreased in endothelium-specific ENH-knockout mice. Vascular ligation reduced AKT and eNOS phosphorylation and nitric oxide production in the endothelium of control but not ENH-knockout mice. ENH was found to interact with AKT1 and its phosphatase PHLPP2 (pleckstrin homology domain and leucine-rich repeat protein phosphatase 2). AKT and eNOS activation were prolonged in VEGF (vascular endothelial growth factor)-induced ENH- or PHLPP2-deficient endothelial cells. Inhibitors of either AKT or eNOS effectively restored ligation-induced neointima formation in ENH-knockout mice. Moreover, endothelium-specific PHLPP2-knockout mice displayed reduced ligation-induced neointima formation. Finally, PHLPP2 was increased in the endothelia of human atherosclerotic plaques and blood cells from patients with coronary artery disease. CONCLUSIONS: ENH forms a complex with AKT1 and its phosphatase PHLPP2 to negatively regulate AKT1 activation in the artery endothelium. AKT1 deactivation, a decrease in nitric oxide generation, and subsequent neointima formation induced by vascular injury are mediated by ENH and PHLPP2. ENH and PHLPP2 are thus new proatherosclerotic factors that could be therapeutically targeted.

Metabolic syndrome is related to vascular structural alterations but not to functional ones both in hypertensives and healthy subjects.

BACKGROUND AND AIMS: Metabolic Syndrome (MS) has been related to an impairment in arterial structural and functional properties with heterogeneous results. In this paper we focused on the effects of MS on arterial carotid-femoral PWV and common carotid IMT in two different populations, one of hypertensive patients and one of healthy controls. METHODS AND RESULTS: We enrolled 816 consecutive HT and 536 healthy controls. Vascular structural (IMT) and functional (PWV) properties were evaluated. NCEP-ATP-III criteria were used for diagnosis of MS. MS was diagnosed in 26.9% and 6.9% in hypertensive and control subjects, respectively. PWV was similar in controls with and without MS (7.7 ± 1.9 vs 7.6 ± 1.1 m/s, p = 0.69), while IMT was higher in controls with than those without MS (0.64 ± 0.18 vs 0.57 ± 0.13 mm, p = 0.02). Hypertensives with MS were older (57.9 ± 12.2 vs 52.7 ± 14.1 years, p < 0.001) and showed higher PWV (9.0 ± 2.3 vs 8.4 ± 2.1 m/s, p = 0.001) and IMT (0.72 ± 0.22 vs 0.65 ± 0.17 mm, p < 0.001) than those without MS, however at the age-adjusted analysis only the difference in IMT was confirmed (p = 0.007). Regression models showed that MS was an independent determinant of IMT in both controls (ß = 0.08, p = 0.03) and hypertensives (ß = 0.08, p = 0.01), but not of PWV either in controls (ß = 0.006, p = 0.886 and ß = 0.04, p = 0.19, respectively). CONCLUSIONS: the main finding of our work is that MS is a significant determinant of IMT while this is not the case for PWV. This result have been confirmed both in hypertensive subjects and in healthy controls.

Pemafibrate Prevents Retinal Dysfunction in a Mouse Model of Unilateral Common Carotid Artery Occlusion.

Cardiovascular diseases lead to retinal ischemia, one of the leading causes of blindness. Retinal ischemia triggers pathological retinal glial responses and functional deficits. Therefore, maintaining retinal neuronal activities and modulating pathological gliosis may prevent loss of vision. Previously, pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, was nominated as a promising drug in retinal ischemia. However, a protective role of pemafibrate remains untouched in cardiovascular diseases-mediated retinal ischemia. Therefore, we aimed to unravel systemic and retinal alterations by treating pemafibrate in a new murine model of retinal ischemia caused by cardiovascular diseases. Adult C57BL/6 mice were orally administered pemafibrate (0.5 mg/kg) for 4 days, followed by unilateral common carotid artery occlusion (UCCAO). After UCCAO, pemafibrate was continuously supplied to mice until the end of experiments. Retinal function (a-and b-waves and the oscillatory potentials) was measured using electroretinography on day 5 and 12 after UCCAO. Moreover, the retina, liver, and serum were subjected to qPCR, immunohistochemistry, or ELISA analysis. We found that pemafibrate enhanced liver function, elevated serum levels of fibroblast growth factor 21 (FGF21), one of the neuroprotective molecules in the eye, and protected against UCCAO-induced retinal dysfunction, observed with modulation of retinal gliosis and preservation of oscillatory potentials. Our current data suggest a promising pemafibrate therapy for the suppression of retinal dysfunction in cardiovascular diseases.

Detection of Early Vascular Atherosclerosis in Type 2 Diabetes Mellitus Using Ultrasound Radiofrequency-Data Technique.

OBJECTIVES: To quantitatively evaluate changes in vascular elasticity and intima-media thickness (IMT) of the common carotid artery (CCA) with Ultrasound radiofrequency (RF)-data technology in asymptomatic patients with type-2 diabetes mellitus (T2DM) and controls. MATERIALS AND METHODS: Thirty-seven T2DM patients and 39 controls were enrolled. Arterial elasticity and CCA-IMT were quantitatively assessed by RF-data technology. The CCA diameters in the diastolic and systolic phases, carotid distensibility (CD), IMT, values of stiffness (ß) and local pulse wave velocity (PWVß) were measured and compared between the two groups. RESULTS: The T2DM group had significantly larger CCA diastolic and systolic diameter, lower CD values, higher IMT measurements (all p < 0.001), and higher values of ß and PWVß (all P < 0.05) than the controls. Significant differences were not revealed in the mean values of IMT, ß, PWVß and CD across both sides of the CCA (all P > 0.05). CONCLUSIONS: Higher IMT measurement and lower arterial elasticity of the CCA are significantly pronounced in asymptomatic T2DM patients and may suggest atherosclerotic changes, and the ultrasound RF-data technique may be used as a potential approach for detection of early-stage atherosclerosis.

Acute Endovascular Revascularization for Patients with Common Carotid Artery Occlusion Apparent on Cervical Magnetic Resonance Angiography.

OBJECTIVES: In the endovascular treatment of acute cerebral large-vessel occlusion, cervical magnetic resonance angiography (MRA) is a useful modality for assessing the access route. However, we sometimes encounter cases in which not only the internal carotid artery (ICA), but also the common carotid artery (CCA) is poorly visualized, leading to hesitation over which devices and techniques to choose for revascularization. We retrospectively evaluated such cases, focusing on image findings and treatment results. MATERIALS AND METHODS: Data from 96 patients who underwent acute endovascular revascularization from January 2016 to December 2019 were analyzed. We extracted patients with poor CCA visualization on cervical MRA from 35 cases with ICA occlusion, and examined angiographic findings, treatment methods, and outcomes. RESULTS: Poor visualization of the CCA in cervical MRA was observed in 8 cases. All cases displayed atrial fibrillation or sick sinus syndrome. Angiographic findings showed true CCA occlusion in 2 patients and ICA occlusion in 6 patients. Reasons for the inability to visualize the CCA on cervical MRA were speculated to be stenosis of the external carotid artery (ECA), presence of embolism in the ECA, or severe heart failure. In cases of true CCA occlusion, thrombus was aspirated using the balloon guide catheter and good recanalization was obtained. Seven of 8 patients displayed favorable recanalization, with good prognosis after 90 days in 5 patients. CONCLUSIONS: Poor CCA visualization on cervical MRA does not necessarily represent true CCA occlusion. Aspiration of thrombus from a balloon guide catheter is effective for true CCA occlusion.

Shear-Induced CCN1 Promotes Atheroprone Endothelial Phenotypes and Atherosclerosis.

BACKGROUND: Atherosclerosis occurs preferentially at the blood vessels encountering blood flow turbulence. The matricellular protein CCN1 is induced in endothelial cells by disturbed flow, and is expressed in advanced atherosclerotic lesions in patients and in the Apoe-/- mouse model. The role of CCN1 in atherosclerosis remains undefined. METHODS: To assess the function of CCN1 in vivo, knock-in mice carrying the integrin α6ß1-binding-defective mutant allele Ccn1-dm on the Apoe-/- background were tested in an atherosclerosis model generated by carotid artery ligation. Additionally, CCN1-regulated functional phenotypes of human umbilical vein endothelial cells, or primary mouse aortic endothelial cells isolated from wild-type and Ccn1 dm/dm mice, were investigated in the in vitro shear stress experiments under unidirectional laminar shear stress (12 dyn/cm2) versus oscillatory shear stress (±5 dyn/cm2) conditions. RESULTS: We found that Ccn1 expression was upregulated in the arterial endothelium 3 days after ligation before any detectable structural changes, and intensified with the progression of atherosclerotic lesions. Compared with Apoe-/- controls, Ccn1 dm/dm/ Apoe-/- mice were remarkably resistant to ligation-induced plaque formation (n=6). These mice exhibited lower oxidative stress, expression of endothelin-1 and monocyte chemoattractant protein-1, and monocyte homing. CCN1/α6ß1 critically mediated flow-induced activation of the pleiotropic transcription factor nuclear factor-κB and therefore the induction of atheroprone gene expression in the mouse arterial endothelium after ligation (n=6), or in cultured human umbilical vein endothelial cells or primary mouse aortic endothelial cells exposed to oscillatory shear stress (n=3 in triplicate). Interestingly, the activation of nuclear factor-κB by CCN1/α6ß1 signaling prompted more production of CCN1 and α6ß1. Blocking CCN1-α6ß1 binding by the Ccn1-dm mutation or by T1 peptide (derived from an α6ß1-binding sequence of CCN1) disrupted the positive-feedback regulation between CCN1/α6ß1 and nuclear factor-κB, and prevented flow-induced atheroprone phenotypic alterations in endothelial cells or atherosclerosis in mice. CONCLUSIONS: These data demonstrate a causative role of CCN1 in atherosclerosis via modulating endothelial phenotypes. CCN1 binds to its receptor integrin α6ß1 to activate nuclear factor-κB, thereby instigating a vicious circle to persistently promote atherogenesis. T1, a peptide antagonist selectively targeting CCN1-α6ß1, can be further optimized for developing T1-mimetics to treat atherosclerosis.

Elastin haploinsufficiency in mice has divergent effects on arterial remodeling with aging depending on sex.

Elastin is a primary structural protein in the arterial wall that contributes to vascular mechanical properties and degrades with aging. Aging is associated with arterial stiffening and an increase in blood pressure. There is evidence that arterial aging follows different timelines with sex. Our objective was to investigate how elastin content affects arterial remodeling in male and female mice with aging. We used male and female wild-type (Eln+/+) and elastin heterozygous (Eln+/-) mice at 6, 12, and 24 mo of age and measured their blood pressure and arterial morphology, wall structure, protein content, circumferential stress, stretch ratio, and stiffness. Two arteries were used with varying contents of elastin: the left common carotid and ascending aorta. We show that Eln+/- arteries start at a different homeostatic set point for circumferential wall stress, stretch, and material stiffness but show similar increases with aging to Eln+/+ mice. With aging, structural stiffness is greatly increased, while material stiffness and circumferential stress are only slightly increased, highlighting the importance of maintaining these homeostatic values. Circumferential stretch shows the smallest change with age and may be important for controlling cellular phenotype. Independent sex differences are mostly associated with males being larger than females; however, many of the measured factors show age × sex and/or genotype × sex interactions, indicating that males and females follow different cardiovascular remodeling timelines with aging and are differentially affected by reduced elastin content.NEW & NOTEWORTHY A comprehensive study on arterial mechanical behavior as a function of elastin content, aging, and sex in mice. Elastin haploinsufficient arteries start at a different homeostatic set point for mechanical parameters such as circumferential stress, stretch, and material stiffness. Structural stiffness of the arterial wall greatly increases with aging, as expected, but there are interactions between sex and aging for most of the mechanical parameters that are important to consider in future work.

Does vascular stiffness predict white matter hyperintensity burden in ischemic heart disease with preserved ejection fraction?

The survival rate of patients with ischemic heart disease (IHD) is increasing. However, survivors experience increased risk for neurological complications. The mechanisms for this increased risk are unknown. We tested the hypothesis that patients with IHD have greater carotid and cerebrovascular stiffness, and these indexes predict white matter small vessel disease. Fifty participants (age, 40-78 yr), 30 with IHD with preserved ejection fraction and 20 healthy age-matched controls, were studied using ultrasound imaging of the common carotid artery (CCA) and middle cerebral artery (MCA), as well as magnetic resonance imaging (T1, T2-FLAIR), to measure white matter lesion volume (WMLv). Carotid ß-stiffness provided the primary measure of peripheral vascular stiffness. Carotid-cerebral pulse wave transit time (ccPWTT) provided a marker of cerebrovascular stiffness. Pulsatility index (PI) and resistive index (RI) of the MCA were calculated as measures of downstream cerebrovascular resistance. When compared with controls, patients with IHD exhibited greater ß-stiffness [8.5 ± 3.3 vs. 6.8 ± 2.2 arbitrary units (AU); P = 0.04], MCA PI (1.1 ± 0.20 vs. 0.98 ± 0.18 AU; P = 0.02), and MCA RI (0.66 ± 0.06 vs. 0.62 ± 0.07 AU; P = 0.04). There was no difference in WMLv between IHD and control groups (0.95 ± 1.2 vs. 0.86 ± 1.4 mL; P = 0.81). In pooled patient data, WMLv correlated with both ß-stiffness (R = 0.34, P = 0.02) and cerebrovascular ccPWTT (R = -0.43, P = 0.02); however, ß-stiffness and ccPWTT were not associated (P = 0.13). In multivariate analysis, WMLv remained independently associated with ccPWTT (P = 0.02) and carotid ß-stiffness (P = 0.04). Patients with IHD expressed greater ß-stiffness and cerebral microvascular resistance. However, IHD did not increase risk of WMLv or cerebrovascular stiffness. Nonetheless, pooled data indicate that both carotid and cerebrovascular stiffness are independently associated with WMLv.NEW & NOTEWORTHY This study found that patients with ischemic heart disease (IHD) with preserved ejection fraction and normal blood pressures exhibit greater carotid ß-stiffness, as well as middle cerebral artery pulsatility and resistive indexes, than controls. White matter lesion volume (WMLv) was not different between vascular pathology groups. Cerebrovascular pulse wave transit time (ccPWTT) and carotid ß-stiffness independently associate with WMLv in pooled participant data, suggesting that regardless of heart disease history, ccPWTT and ß-stiffness are associated with structural white matter damage.

Reduced patency in left-sided arteriovenous grafts in a porcine model.

OBJECTIVE: The porcine arteriovenous graft model is commonly used to study hemodialysis vascular access failure, with most studies using a bilateral, paired-site approach in either the neck or femoral vessels. In humans, left- and right-sided central veins have different anatomy and diameters, and left-sided central vein catheters have worse outcomes. We assessed the effect of laterality on arteriovenous prosthetic graft patency and hypothesized that left-sided carotid-jugular arteriovenous prosthetic grafts have reduced patency in the porcine model. METHODS: Arteriovenous polytetrafluoroethylene grafts were placed ipsilaterally or bilaterally in 10 Yorkshire male pigs from the common carotid artery to the internal jugular vein. Ultrasound measurements of blood flow velocities and diameters were assessed before graft placement. Animals were sacrificed at 1 week, 2 weeks, or 3 weeks. Patency was determined clinically; grafts and perianastomotic vessels were excised and analyzed with histology and immunostaining. RESULTS: At baseline, left- and right-sided veins and arteries had similar blood flow velocities. Although internal jugular veins had similar diameters at baseline, left-sided carotid arteries had 11% smaller outer diameters (P = .0354). There were 10 left-sided and 8 right-sided polytetrafluoroethylene grafts placed; only 4 of 10 (40%) grafts were patent on the left compared with 7 of 8 (88%) grafts patent on the right (P = .04). Left-sided grafts had increased macrophages at the arterial anastomosis (P = .0007). Left-sided perianastomotic arteries had thicker walls (0.74 vs 0.60 mm; P = .0211) with increased intima-media area (1.14 vs 0.77 mm2; P = .0169) as well as a trend toward 38% smaller luminal diameter (1.6 vs 2.5 mm; P = .0668) and 20% smaller outer diameter (3.0 vs 3.7 mm; P = .0861). Left- and right-sided perianastomotic veins were similar histologically, but left-sided veins had decreased expression of phosphorylated endothelial nitric oxide synthase (P = .0032) and increased numbers of α-actin-positive smooth muscle cells (P = .0022). CONCLUSIONS: Left-sided arteriovenous grafts are associated with reduced short-term patency compared with right-sided grafts in the Yorkshire pig preclinical model of arteriovenous prosthetic grafts. Laterality must be considered in planning and interpreting surgical preclinical models.

Long-term outcomes of axillary to carotid bypass for symptomatic patients with chronic common carotid artery occlusion.

OBJECTIVE: Relatively little is known about the natural history of atherosclerotic common carotid artery occlusion and optimal treatment of these patients is still unclear. The aim of this retrospective study was to evaluate the immediate- and long-term outcomes of axillary to carotid bypass with polytetrafluoroethylene graft for symptomatic patients with chronic common carotid artery occlusion. METHODS: From March 2001 to December 2017, 58 symptomatic patients (41 men; mean age 64.7 years) with chronic common carotid artery occlusion underwent axillary to carotid bypass at one academic hospital. The clinical data of this patient cohort were retrospectively analyzed. The cumulative graft patency, overall survival, freedom from symptoms, and freedom from ipsilateral stroke were calculated with Kaplan-Meier method. RESULTS: Thirty-three patients presented with transient ischemic attack and 25 patients presented with minor stroke. At 30 days after bypass, the overall perioperative complication rate was 3.4% (2/58). Mild injuries of brachial plexus occurred in one (1.7%) patient and myocardial infarction occurred in one (1.7%) patient. No perioperative stroke or death occurred. The median follow-up was 51 months (range, 12-203) for this series. The cumulative graft patency rates at 1, 3, 5, and 10 years were 100%, 100%, 94%, and 83%, respectively. The cumulative freedom from symptoms rates at 1, 3, 5, and 10 years were 100%, 100%, 94%, and 75%, respectively. The cumulative freedom from ipsilateral stroke rates at 1, 3, 5, and 10 years were 100%, 100%, 94%, and 82%, respectively. The overall survival rates at 1, 3, 5, and 10 years were 98%, 89%, 81%, and 67%, respectively. CONCLUSIONS: Axillary to carotid bypass with polytetrafluoroethylene graft is safe and durable for symptomatic patients with chronic common carotid artery occlusion. The results of this study should be confirmed with a larger, randomized controlled trial in future.

Duration of blood flow reversal during transcarotid artery revascularization does not affect outcome.

OBJECTIVE: Transcarotid artery revascularization (TCAR) has become an increasingly popular alternative for the treatment of carotid bifurcation stenosis. TCAR employs carotid blood flow reversal through an ex vivo common carotid artery to femoral vein shunt for neuroprotection during the placement and angioplasty of the carotid artery stent. There is a lack of data regarding an association between the duration of flow reversal and neurologic complications or other adverse events. We analyzed TCAR flow reversal time in relation to major adverse events. METHODS: There were 307 patients who underwent TCAR at four high-volume academic institutions. Patients were separated on the basis of the duration of carotid flow reversal as follows: group I, ≤8 minutes (n = 138); group II, 9-13 minutes (n = 105); group III, 14-20 minutes (n = 42); and group IV, >20 minutes (n = 22). Adverse events including stroke (assessed by a National Institute of Health Stroke Scale-certified examiner), myocardial infarction (MI), and death at discharge and 30 days were collected in all patients and were compared between groups using one-way analysis of variance and χ2 analysis. RESULTS: There were four strokes in the total cohort, yielding an overall stroke rate of 1.3%. All strokes were minor in nature; two were ipsilateral and two were contralateral. All patients demonstrated full recovery at 30 days. We found no significant difference in the stroke rate between any of the groups: I, 1.5% (2/138); II, 1.9% (2/105); III, 0% (0/42); and IV, 0% (0/22; P = .76). The four strokes occurred in patients with flow reversal time of 6, 7, 11, and 12 minutes. There was also no difference in the 30-day composite stroke/death or stroke/death/MI rates among the groups. CONCLUSIONS: The length of flow reversal during TCAR does not affect rates of stroke, MI, or death. These data suggest that operators should focus on the technical aspects of the procedure during flow reversal rather than on its duration.

Changes in carotid stiffness in patients with familial hypercholesterolemia treated with Evolocumab®: A prospective cohort study.

BACKGROUND AND AIM: Protein convertase subtilisin kexin type 9 (PCSK-9) inhibitors demonstrated efficacy in cholesterol reduction and in the prevention of cardiovascular events. We evaluated changes in lipid profile and carotid stiffness in patients with familial hypercholesterolemia during 12 weeks of treatment with a PCSK-9 inhibitor, Evolocumab®. METHODS AND RESULTS: Patients with familial hypercholesterolemia starting a treatment with Evolocumab® were included. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), small dense LDL (assessed by LDL score) and carotid stiffness were evaluated before starting treatment with Evolocumab® and during 12 weeks of treatment. Twenty-five subjects were enrolled (52% males, mean age 51.5 years). TC and LDL-C were reduced of 38% and 52%, respectively during treatment, with LDL score reduced of 46.1%. In parallel, carotid stiffness changed from 8.8 (IQR: 7.0-10.4) m/sec to 6.6 (IQR: 5.4-7.5) m/sec, corresponding to a median change of 21.4% (p < 0.001), with a significant increase in carotid distensibility (from 12.1, IQR: 8.73-19.3 kPA-1 × 10-3 at T0 to 21.8, IQR: 16.6-31.8 kPA-1 × 10-3 at T12w) corresponding to a median change of 62.8% (p < 0.001). A multivariate analysis showed that changes in LDL score were independently associated with changes in carotid stiffness (ß = 0.429, p = 0.041). CONCLUSION: Small dense LDL reduction, as assessed by LDL score, is associated with changes in carotid stiffness in patients with familial hypercholesterolemia treated with Evolocumab®.

Donepezil down-regulates propionylation, 2-hydroxyisobutyrylation, butyrylation, succinylation, and crotonylation in the brain of bilateral common carotid artery occlusion-induced vascular dementia rats.

Vascular dementia (VaD), caused by stroke or small vessel disease, is the second-most common type of dementia after Alzheimer's disease (AD). Donepezil is an acetylcholinesterase inhibitor that is currently used in patients with mild to moderate AD, and has recently been shown to improve cognitive performance in patients with VaD. In this study, we evaluated the effects of donepezil on VaD, and investigated the underlying molecular mechanisms of action. VaD was established by ligation of the bilateral common carotid artery occlusion (BCCAO). Executive function was tested by the Morris water maze (MWM) test and the attentional set shifting task (ASST). Our results showed that donepezil improved executive dysfunction and cognitive flexibility in BCCAO rats. In addition, we showed that donepezil treatment decreased the level of Aß1-42 in BCCAO rats by enzyme-linked immunosorbent assay. Post-translational modifications (PTMs) are known to be critical mechanisms in the regulation of various cellular processes. Furthermore, PTMs have been linked to the central nervous system, which highlights the importance of PTMs in neurodegenerative diseases. In this study, we used western blot analysis to identify several novel PTMs in the hippocampus of BCCAO rats that were treated with or without donepezil. The data revealed that lysine propionylation, 2-hydroxyisobutyrylation, butyrylation, succinylation, and crotonylation were elevated in the hippocampus of BCCAO rats when compared to sham rats. This increase was abolished by donepezil treatment. Taken together, we speculate that donepezil treatment improves cognitive function in our animal model of VaD, possibly by reducing aberrant acyl-PTMs.

Left Common Carotid Artery Biomechanical Properties in Individuals over 80 years: Women Have Stiffer Vessels.

BACKGROUND: Considering the longevity of the worldwide population, the cardiovascular diseases deserve particular attention, especially the carotid artery disease in the ≥80-year-old population. The stiffness of the common carotid artery, for example, has been showed in numerous clinical studies as a marker of increased risk of stroke, dementia, and depression. Besides, with the emergence of new surgical techniques such as the transcarotid artery revascularization that uses the common carotid artery as a workstation, the biomechanical and histological features of this vessel, more than ever, must be detailed. METHODS: Left common carotid artery fragments from 9 cadaver donors (≥80 years old) were evaluated. Biomechanical (failure stress, tension, and strain) and histological (percentage of collagen and elastic fibers) features of these samples were analyzed with special focus on gender differences. RESULTS: Statistically significant differences in biomechanical and histological features between the genders were observed. The percentage of collagen fiber in intima (P = 0.008) and media (P = 0.041) layers was significantly lower in men than in women. A higher elasticity (failure strain) of the specimens in male gender was also observed (P = 0.025). No significant difference was observed in the layers thickness between the genders regardless which part of the arterial wall was considered. CONCLUSIONS: These biomechanical and histological findings could be the responsible for the higher left common carotid artery stiffness observed among ≥80-year-old women when compared with men in numerous clinical studies in literature.