Risultati per: Circulation

Stroke, Volume 54, Issue Suppl_1, Page A138-A138, February 1, 2023. Introduction:Data on predictors of early stroke recurrence in patients with symptomatic intracranial atherosclerotic disease (sICAD) is limited. We hypothesized that hypoperfusion delay predicts stroke recurrence within 90-days.Methods:We retrospectively collected all patients hospitalized with anterior circulation sICAD over 3 years (April 2019-April 2022) at a comprehensive stroke center. We collected demographics, clinical risk factors, radiological variables, and treatment strategies. Patients with an indication for anticoagulation such as atrial fibrillation and those with intracranial stenting or angioplasty were excluded. The outcome (verified by two independent reviewers) was recurrent stroke within 90 days in the affected artery. We assessed factors associated with stroke recurrence. We measured the effect of hypoperfusion delay volume on stroke recurrence using Cox-regression models.Results:Out of 131 sICAD hospitalizations during the study period, 66 involved the middle cerebral artery (MCA) M1 segment or intracranial internal carotid artery (ICA) and 44 patients met the inclusion criteria. The mean age was 71 years and 41% were women; 75% were treated with best medical management (dual antiplatelet therapy/high intensity statin therapy); and 75% had baseline perfusion imaging performed. Over 90 days, 11/44 (25%) patients had recurrent stroke. Factors associated with recurrence stroke were no best medical management (15.2% vs. 54.5%, p = 0.02), hypoperfusion Tmax >4 sec mismatch volume (p = 0.003), and hypoperfusion delay Tmax >6 sec mismatch volume (p=0.01). Using Youden’s cutoff for Tmax >4 sec mismatch (13 mL) and for Tmax >6 sec mismatch (5 mL), the risk of recurrent stroke at 90 days in separate models was higher in patients with Tmax >4 sec delay mismatch volume > 13 mL (HR 11.98 95% CI 1.48-96.96 p=0.02) and Tmax >6 sec mismatch volume > 5 mL (HR 4.37 95% CI 1.02-18.82, p=0.048). Effect size of the associations did not meaningfully change after adjusting for best medical management.Conclusion:Hypoperfusion delay is associated with an increased recurrent stroke risk within 90 days in patients with sICAD, despite best medical management. Validation by large prospective studies is warranted.

Stroke, Volume 54, Issue Suppl_1, Page AWMP84-AWMP84, February 1, 2023. Introduction:We compared the morphology of intracranial atherosclerotic plaques in the anterior versus posterior circulation, using three-dimensional rotational angiography (3DRA).Methods:We prospectively recruited adult patients with acute ischemic stroke or transient ischemic attack attributed to high-grade (60-99%), atherosclerotic intracranial stenosis as confirmed by 3DRA. We assessed the plaque morphology in 3DRA, including the percentage of luminal stenosis, smooth/irregular/ulcerative plaque surface contour, plaque thickness, length, eccentricity, upstream plaque shoulder angulation, longitudinal distribution of the maximal stenosis, and adjoining branch atheromatous disease (BAD). We compared characteristics of patients with middle cerebral artery-M1 (MCA-M1) and basilar artery (BA) plaques, and the plaque morphology in the two subgroups.Results:Overall, 164 and 17 patients respectively with MCA-M1 and BA plaques were analyzed, with similar age (medians 60 versus 62 years), sex (male 64.6 versus 52.9%) and history of common vascular risk factors. The percentage of luminal stenosis (medians 77 versus 81%), proportion of smooth/irregular/ulcerative plaque surface contour, upstream plaque shoulder angulation (32.1 versus 25.8 °), longitudinal distribution of the maximal stenosis, and presence of adjoining BAD (56.7 versus 64.7%) were similar between MCA-M1 and BA plaques. However, BA plaques were thicker (1.5 versus 1.3mm; p=0.03) and longer (16.4 versus 8.4mm; p

Stroke, Volume 54, Issue Suppl_1, Page AWMP79-AWMP79, February 1, 2023. Introduction:Intracranial atherosclerotic disease (ICAD) remains a major source of stroke worldwide, with high recurrence risk. Prior evaluation of posterior circulation ICAD patients enrolled in the prospective VERiTAS and MYRIAD studies revealed regional hypoperfusion, assessed by large vessel flow measurements using quantitative MRA (QMRA), predicts subsequent vertebrobasilar stroke risk. We examined whether a similar approach to regional flow assessment using QMRA predicted stroke risk in anterior circulation ICAD patients enrolled in MYRIAD.Methods:MYRIAD enrolled patients with recent TIA or stroke attributable to 50-99% stenosis of proximal intracranial artery; the primary outcome was ischemic stroke in the territory of the stenotic artery with 1 year of follow-up. Secondary outcomes included new in-territory infarcts on MRI at 6-8 weeks. Flow was measured in the major intracranial arteries at baseline using QMRA. We designated patients as low- or normal-flow status based on an algorithm assessing distal flow and collateral capacity using age-normalized MCA and hemispheric (aggregate of ipsilateral ACA, MCA, and PCA) flows. Different thresholds for flow status categorization were tested to determine the optimal algorithm for stroke risk prediction.Results:Of 73 enrolled subjects with symptomatic anterior circulation ICAD, 7 (9.6%) patients had recurrent stroke. Z-score thresholds for age-normalized flow ranging from -0.5 to -1.5 were examined. The optimal thresholds identified were as follows: -1 for the MCA and -0.75 for hemispheric flow. 24 (33%) patients were categorized as low-flow status based on these thresholds; recurrent stroke occurred in 21% of low-flow patients vs. 4% of normal-flow patients (OR 6.2 (95% CI 1.1-34.7, p=0.04). However, flow status was not predictive of recurrent infarct on imaging among 61 patients with 6-8 week MRI (32% in low-flow vs. 26% in normal-flow patients).Conclusions:Similar to the predictive value in the posterior circulation, distal flow status assessed through QMRA regional flow measurement appears to be predictive for recurrent clinical (but not imaging-based) stroke. Identification of high-risk patients has implications for future investigation of therapeutic interventions.

Stroke, Volume 54, Issue Suppl_1, Page AWP102-AWP102, February 1, 2023. Introduction:Side-to-side relative reduction in end-diastolic velocity (EDV) of the common carotid artery (CCA) may discriminate ipsilateral anterior circulation large vessel occlusion (LVO), which will contribute faster patient triage for reperfusion therapy. We evaluated the discriminative accuracy of this simple sonographic index for anterior circulation LVO in acute stroke population, including intracerebral hemorrhage (ICH).Methods:Among patients with acute stroke admitted to our institute between 2016-2018, those who underwent both carotid ultrasonography and head MRA or CTA within 24 hours after last known normal time were reviewed. Relative EDV reduction was calculated as a ratio by dividing the CCA EDV lower side by the EDV higher side. Anterior circulation LVO was defined as occlusion of the internal carotid artery (ICA) or M1 segment of the middle cerebral artery on the lower EDV side. Discriminative performance of relative EDV reduction for anterior circulation LVO was assessed by receiver operating characteristics analysis.Results:A total of 688 patients (411 males; median age 77 years; 87 with anterior circulation LVO) were analyzed. When compared to no occlusion, value of relative EDV reduction was remarkably lower in ICA occlusion, followed by that in M1 occlusion (Figure). Area under the curve (AUC) of relative EDV reduction for ICA occlusion was 0.96 (95% confidence interval [CI] 0.94-0.99) with an appropriate cut-off value of 0.50 (sensitivity 94%, specificity 94%). When the discrimination target was set to anterior circulation LVO, the AUC was 0.78 (95% CI 0.72-0.85) with an appropriate cut-off value of 0.67 (sensitivity 69%, specificity 83%). At this cut-point, 51% of patients with M1 occlusion was classified as false negative.Conclusions:The discriminative performance of the relative CCA EDV reduction in acute stroke population was excellent for ICA occlusion and acceptable for anterior circulation LVO.

Circulation, Volume 147, Issue 5, Page 361-363, January 31, 2023.

Stroke, Volume 54, Issue 2, Page 327-336, February 1, 2023. Background:Sex disparities in acute large vessel occlusion (LVO) following endovascular treatment (EVT) have been recently reported. However, there is uncertainty about the effect of sex differences on functional outcomes after EVT, particularly in an Asian population. The present study aimed to compare the clinical and safety outcomes between men and women with anterior circulation LVO treated with EVT.Methods:We analyzed data from the ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke: a Prospective Multicenter Registry Study) Registry, which was conducted at 111 hospitals from 26 provinces in China between November 2017 and March 2019. Men and women with anterior circulation LVO treated with EVT were matched using propensity scores. After a 1:1 propensity score matching, we compared the clinical outcomes including 90-day ordinal modified Rankin Scale distribution (primary outcome), procedure duration, successful reperfusion, symptomatic intracranial hemorrhage, and mortality. Furthermore, we explored sex modification on the primary outcome in subgroup analysis.Results:Of 1321 patients, 483 (36.6%) were women and 838 (63.4%) were men. The mean age for women and men were 68 and 62 years old, respectively. Among 578 patients identified after matching, there were no sex differences (men versus women) in 90-day ordinal modified Rankin Scale distribution (median [interquartile range], 4 [1–5] versus 3 [1–5],P=0.464), successful reperfusion (86.5% versus 91.0%,P=0.089), symptomatic intracranial hemorrhage (6.5% versus 7.9%,P=0.512), and mortality within 90 days (17.7% versus 17.0%,P=0.826). However, men had a longer median procedure duration than women (86 [52–128] versus 72 [48–110] minutes, β=14.51, [95% CI, 4.19–24.84];P=0.006). Subgroup analysis showed that in patients with National Institutes of Health Stroke Scale score

Circulation, Volume 147, Issue 3, Page 271-275, January 17, 2023.

Circulation, Volume 147, Issue 2, Page 178-182, January 10, 2023.

Circulation, Volume 147, Issue 1, Page 1-3, January 3, 2023.

Circulation, Volume 147, Issue 1, Page 4-4, January 3, 2023.

Objective
Mucosal-associated invariant T (MAIT) cells are the most abundant T cells in human liver. They respond to bacterial metabolites presented by major histocompatibility complex-like molecule MR1. MAIT cells exert regulatory and antimicrobial functions and are implicated in liver fibrogenesis. It is not well understood which liver cells function as antigen (Ag)-presenting cells for MAIT cells, and under which conditions stimulatory Ags reach the circulation.

Design
We used different types of primary human liver cells in Ag-presentation assays to blood-derived and liver-derived MAIT cells. We assessed MAIT cell stimulatory potential of serum from healthy subjects and patients with portal hypertension undergoing transjugular intrahepatic portosystemic shunt stent, and patients with inflammatory bowel disease (IBD).

Results
MAIT cells were dispersed throughout healthy human liver and all tested liver cell types stimulated MAIT cells, hepatocytes being most efficient. MAIT cell activation by liver cells occurred in response to bacterial lysate and pure Ag, and was prevented by non-activating MR1 ligands. Serum derived from peripheral and portal blood, and from patients with IBD stimulated MAIT cells in MR1-dependent manner.

Conclusion
Our findings reveal previously unrecognised roles of liver cells in Ag metabolism and activation of MAIT cells, repression of which creates an opportunity to design antifibrotic therapies. The presence of MAIT cell stimulatory Ags in serum rationalises the observed activated MAIT cell phenotype in liver. Increased serum levels of gut-derived MAIT cell stimulatory ligands in patients with impaired intestinal barrier function indicate that intrahepatic Ag-presentation may represent an important step in the development of liver disease.

Circulation, Volume 146, Issue 19, Page 1478-1482, November 8, 2022.

Circulation, Volume 146, Issue Suppl_1, Page A10923-A10923, November 8, 2022. Bone marrow-derived CD51-positive cells (CD51+bMSCs) were candidate progenitor cells for transplantation into acute myocardial infarction (AMI) mice, which could reduce death of cardiomyocytes and promote recovery of cardiac function. However, practical applications were limited by short survival time of resident cells in the injured myocardium and ball-like proliferation potential. Considering exosomes can mimic the biological effects of mother cells, we have discovered that the transplantation of exosomes secreted by CD51+bMSCs (abbreviation: CD51+bMSCs-Exo) to mice with AMI avoided the above problems, and effectively improved heart function via intramyocardial injection but not intravenous injection. The unequal effects were contributed to the different number of exosomes that attached to the injured tissues. Based on the chemotactic characteristics of macrophages to inflammatory tissues, we supposed that the chemotactic capacity of CD51+bMSCs-Exo could be improved when they encapsulated with macrophage membrane expressing multiple receptors (abbreviation: ME complex). The experimental results show that: 1) ME complex migrated to the injured myocardium after intravenous delivery and promoted the recovery of infarcted myocardium.2) Plenty of new blood vessels were emerged in the injured myocardium, which reconstructed coronary microcirculation. 3)Single-cell sequencing data found that sox17 may be an important factor to reconstruct coronary microcirculation in myocardial infarction tissue. We assessed the hypothesis that sox17 can form a positive feedback loop with VEGFR on endothelial cells. +bMSCs-Exo promotes angiogenesis. In conclusion, ME complex activates SOX17/VEGFR of endothelial cells to promote angiogenesis in AMI mice.

Circulation, Volume 146, Issue Suppl_1, Page A15081-A15081, November 8, 2022. Introduction:In the Fontan (FN) circulation pulmonary blood flow (Qp) is passive, resulting in severely decreased shear rate and velocity in pulmonary arteries to the point of stasis. Yield stress (YS) is the shear stress required for blood to transition from stasis to a moving fluid. Therefore, YS may be a determinant of Qp in FN. We evaluated YS in patients with FN and Glenn (GLN) circulations and whether increased YS is associated with decreased Qp.Methods:We enrolled 20 patients with biventricular (2V) congenital heart disease (CHD) and 41 patients with single ventricle CHD (19 FN and 22 GLN) who were undergoing a clinically indicated cardiac catheterization. Two patients were excluded due to pulmonary vascular disease. We obtained blood samples at the time of catheterization and measured blood viscosity across shear rates 1 s-1to 1000 s-1using a Rheolog viscometer We calculated YS by curve-fitting of the viscosity measurements to a Casson fluid model.Hypothesis:We hypothesize that higher yield stress will be associated with lower pulmonary blood flow in Fontan circulation.Results:The FN group was the oldest and had the largest BSA (FN >2V >GLN; pFN >2V; p

Circulation, Volume 146, Issue Suppl_1, Page A15299-A15299, November 8, 2022. Introduction:Fontan-associated liver disease (FALD) contributes to adverse outcomes late after the Fontan procedure. Elevated Magnetic Resonance Elastography-derived Liver Stiffness (MRE-LS) is associated with higher Fontan pressure and Fontan circulatory failure (FCF). How MRE-LS changes over time and if it can predict adverse outcomes has not been studied.Methods:Single center retrospective study of individuals >10 years-old post-Fontan with >1 MRE-LS study between 2010-2020. Absolute change in liver stiffness (shear modulus in kilopascals, kPa) was defined as the difference between first and second MRE-LS measures. Demographic and clinical data were collected. FCF was defined as the composite outcome of death, transplant, VAD placement, or unscheduled cardiac hospitalization following index MRE. To compare the effect of magnitude of change in liver stiffness, patients were ordered from lowest negative to highest positive (Quartile 1-4) change.Results:77 individuals were included (mean age at first MRI 19.9±6.7 years, 47% female). Baseline MRE-LS was 4.4±1.0 kPa, follow-up MRE-LS was 4.1±1.1 kPa with mean time between MRE examinations of 46±27 months. The median annual change in MRE-LS was -0.06 (IQR -0.2-0.05) kPa/year. There was no association between change in MRE-LS and age ventricular dysfunction, or Fontan pressure. FCF occurred in 18 (23%) individuals, and those with FCF had a greater increase in MRE-LS (0.12±0.83 vs -0.42±0.96 kPa, p=0.04, Figure).Conclusions:MRE-LS remains stable over short-term follow-up in most individuals with Fontan circulation. However, those with greater positive change in liver stiffness were more likely to experience adverse outcomes. An increase in MRE-LS is a potential non-invasive biomarker of clinical decompensation.Figure: Probability of endpoint-free survival based on the change in liver stiffness quartiles (4 = largest increase in MRE-LS). Tick marks on curves indicate patients censored.

Circulation, Volume 146, Issue Suppl_1, Page A10926-A10926, November 8, 2022. Introduction:Many prediction algorithms for warfarin maintenance dose (WD) were constructed based on the clinical and genetic information of the patients without extracorporeal circulation devices (ECDs). However, it is unclear whether might be useful for the patients with ECD, such as left ventricular assist devices (LVAD), who still require warfarin.Hypothesis:The WD algorithms constructed using non-ECD patients could be useful for LVAD patients.Methods:An observational study, the Human Genome Research Ethics Committee of OU approved (#756), was conducted at the Osaka University (OU) Hospital on 108 LVAD patients receiving warfarin therapy. Genetic polymorphisms of CYP2C9*1, *3, and VKORC1-1639G >A were tested using TaqMan genotyping assay kits. WD was defined as the administered dose during the periods when the PT-INR value was within its target range. We investigated the difference between the actual warfarin dose (AWD) and the calculated warfarin dose (CWD) using an algorithm proposed by the International Warfarin Pharmacogenetics Consortium (IWPC), which we verified with 125 Japanese non-ECD patients previously (Eur J Clin Pharmacol, 75:901).Results:The percentage of patients whose difference between CWD and AWD was within 20% of AWD showed no significant difference between the LVAD and the non-ECD (%; I, LVAD, 41.7, non-ECD, 49.6, p=0.23). The root mean squared percentage error (RMSPE) to the AWD was similar between the groups (%; LVAD, 42, non-ECD, 37). As the algorithm requires if amiodarone is concomitant with warfarin, we probed the effect of the amiodarone dose on the CWD. Interestingly, RMSPE of the LVAD with ≥ 200 mg/day of amiodarone (≥ 200A) was higher compared to those with < 200 mg/day (