Risultati per: Circulation

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 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 (

Circulation, Volume 146, Issue Suppl_1, Page A10960-A10960, November 8, 2022. Introduction:Lymphatic complications are common in patients with Fontan circulation. 3D balanced steady-state free precession (3D-bSSFP) angiography by cardiovascular magnetic resonance (CMR) is widely adopted for cardiovascular anatomical assessment. We sought to determine the frequency of thoracic duct visualization using 3D bSSFP images and assess whether thoracic duct characteristics are markers of poor clinical outcomes.Methods:This was a retrospective, single-center study of patients with Fontan circulation who underwent CMR. Patients with repaired tetralogy of Fallot (rTOF) were included as a comparison. Thoracic duct characteristics included maximum diameter and a qualitative assessment of tortuosity (Figure). Clinical outcomes included protein-losing enteropathy (PLE), plastic bronchitis, listing for heart transplant, or death. A composite outcome was defined as presence of any of the above.Results:The study group was comprised of 189 Fontan patients and 36 rTOF patients (median age at CMR 16 years, IQR: 11-23 years). The thoracic duct diameter was larger (median 2.50 vs 1.95 mm, 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 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 A200-A200, November 8, 2022. Introduction:Transesophageal echocardiography (TEE) has been proposed as a tool ideally suited for imaging patients during cardiac arrest (CA) resuscitation, allowing for the evaluation of the area of maximal compression (AMC) during CPR. Previous work has shown that compression of the left-ventricular outflow tract (LVOT) or the aortic root during CPR (AMC-LVOT/Ao) occurs in over 50% of patients; animal trials and small single-center retrospective clinical study have linked this finding to lower rates of ROSC. We aimed to prospectively investigate the AMC and its association with ROSC. We hypothesized that patients who have AMC-LVOT/Ao have lower likelihood of ROSC.Methods:A prospective, observational, multicenter cohort study involving patients with out-of-hospital CA (OHCA) in whom TEE was performed during CPR. The study aimed to compare patients with AMC over the LV (AMC-LV) vs AMC-LVOT/Ao and was conducted through a collaborative research network involving 16 hospitals (NCT04972526). Data was collected on clinical and TEE characteristics and findings. Primary outcome was ROSC. We performed univariate analysis followed by multivariate regression model evaluating variables known to impact resuscitation outcomes.Results:Eighty-four patients were included in the analysis. Mean age 62 (46-72), 28% female, 71% had witnessed arrest, 60% had bystander CPR, 47% had mechanical CPR. Overall 26 patients (32%) had ROSC. Initial AMC during CPR was determined in 55/84 (65%) patients, of whom 33 (60%) had AMC-LV, 18 (33%) had AMC-LVOT/Ao, and 4 (7%) had other locations. There was no significant difference in AMC when analyzed by demographic characteristics, height, weight or between patients who received manual vs mechanical CPR. In multivariate regression controlling for age, race, gender, initial rhythm of arrest, level of TEE operator, doses of epinephrine, now-flow time, and total time of arrest, AMC-LVOT/Ao was significantly associated with lower ROSC probability (OR 0.06, 95% CI 0.01-0.4; p=0.009).Conclusion:In this multicenter, prospective study of patients with OHCA, TEE-guided resuscitation showed a strong association between the AMC and ROSC.

Circulation, Volume 146, Issue Suppl_1, Page A216-A216, November 8, 2022. Introduction:The level of end-tidal carbon dioxide (EtCO2) reflects the blood flow generated by cardiopulmonary resuscitation (CPR). Static EtCO2parameters, such as average EtCO2levels, has been reported to be associated with outcomes following out-of-hospital cardiac arrest (OHCA).Hypothesis:Distinct trajectories of EtCO2during CPR was associated with OHCA outcomes.Methods:This was a retrospective analysis of a prospectively collected database on patients with OHCA who had been resuscitated in the emergency department of a tertiary medical center between 2015 and 2020. Adult patients with ≥3 measurements of EtCO2were included. The primary outcome was the return of spontaneous circulation (ROSC). Group-based trajectory modelling was used to identify the EtCO2trajectories. Multivariable logistic regression analysis was performed to evaluate the association between EtCO2trajectories and ROSC. The predictive performance of the EtCO2trajectories was assessed using the area under the receiver operating characteristic curve (AUC).Results:The study comprised 655 patients with OHCA. In the primary analysis, three distinct EtCO2trajectories, including 10-mmHg, 30-mmHg, and 50-mmHg trajectories, were identified. Compared with the 10-mmHg trajectory, both 30-mmHg (odds ratio [OR]: 4.66, 95% confidence interval [CI]: 3.15-6.90) and 50-mmHg (OR: 7.58, 95% CI: 4.30-13.35) trajectories were associated with a higher likelihood of ROSC. In a sensitivity analysis of excluding EtCO2measured before tracheal intubation or after sodium bicarbonate administration, the predictive ability of the identified EtCO2trajectories remained. As a single predictor of ROSC, EtCO2trajectories had an acceptable discriminative performance (AUC: 0.69, 95% CI: 0.66-0.73).Conclusion:Three distinct EtCO2trajectories during CPR were identified and significantly associated with OHCA outcomes, which may assist in guiding the ongoing resuscitation efforts.

Circulation, Volume 146, Issue Suppl_1, Page A10515-A10515, November 8, 2022. Introduction:The prevalence and significance of mechanical dyssynchrony is not well known in the Fontan population.Methods:Single-center, retrospective analysis of CMRs in Fontan patients compared to healthy controls. Feature tracking was performed on all slices of a short-axis cine stack and dyssynchrony index (DI) was defined as the standard deviation of time-to-peak circumferential strain for all segments. A composite outcome was defined as death, heart transplant listing, or new ventricular arrhythmias.Results:A total of 512 cases (17±9 y) and 42 controls (16±9 y) were included. Figure 1 depicts differences in EDVi, EF, DI, and QRS duration between the cohorts. DI correlated with EDVi(r=0.35; p

Circulation, Volume 146, Issue Suppl_1, Page A218-A218, November 8, 2022. Background:Pulseless electrical activity (PEA) is a heterogeneous clinical state and increasingly observed during resuscitation from cardiac arrest. The aim of this study was to investigate whether the presence or emergence of sinus rhythm in patients with PEA influenced the likelihood of return of spontaneous circulation (ROSC).Methods:Single-lead ECGs were registered during resuscitation from in-hospital cardiac arrests (IHCAs) with PEA. We analyzed evidence of atrial/sinus rhythm as the presence or emergence of P-waves; expressed along the resuscitation timeline as a prevalence (between 0 and 1) during the preceding minute. This information was entered along with QRS-duration as a continuous, time-dependent covariate in an exponential multistate time-to-event model. We employed the software R version 4.1 for the statistical analyses.Results:99 episodes of CA from 90 patients were analyzed. We identified 189 segments of PEA without sinus rhythm and 52 segments with sinus rhythm. Almost none had sinus rhythm initially; usually it emerged as a response to resuscitation. Among segments with sinus rhythm, 22 transitioned to ROSC (42 %) while 55 without sinus rhythm transitioned to ROSC (29 %).According to the exponential model, a one-unit increase in the prevalence of sinus rhythm increased the chance of developing ROSC by a factor of 2.5 (95% CI 1.33-4.72).Conclusion:The emergence of sinus rhythm during treatment of PEA increases the probability of gaining ROSC. Sinus rhythm seems to be an intermediate stage in the development from PEA to ROSC. Sinus rhythm is easy to identify during cardiac arrest and may serve as a marker of treatment response. Occurrence of PEA with atrial rhythm during CA should encourage continuation of resuscitation.Figure:Left column displays rhythms before PEA with SR and right column displays rhythms following PEA with SR.Green: ROSC. Orange: PEA with sinus rhythm. Yellow: PEA. Red: VT/VF. Grey: ASY. Dark grey: Death.