Risultati per: Circulation

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 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 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 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 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 A151-A151, November 8, 2022. Background:Survival with favorable neurological outcomes is one of the goals in patients with out-of-hospital cardiac arrest (OHCA). Although previous studies have shown that a chance of neurologically intact survival was significantly lower at nighttime than at daytime in patients with OHCA, details are uncertain. The aim of this study was to evaluate the effect of time from collapse to prehospital return of spontaneous circulation (ROSC) on neurologically favorable survival in patients with OHCA at nighttime versus daytime.Methods:Using a nationwide OHCA registry database from 2005 to 2020 in Japan, a cohort of 1,902,986 patients with OHCA were retrospectively screened. In the present study, a total of 128,180 patients with witnessed OHCA who achieved prehospital ROSC were included. Nighttime was defined as 6:00 pm through 5:59 am. Neurologically favorable survival was defined as cerebral performance category score of 1 or 2 at 1 month.Results:Patients with witnessed OHCA at nighttime were likely to be younger (70.3±16.0 vs. 72.7±15.3 years, 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 A320-A320, November 8, 2022. Introduction:Literature on neuroprognostication suggests that gray-white matter ratio (GWR) measured from head computed tomography (CT) within two hours after return of spontaneous circulation (ROSC) can’t adequately predict neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients. However, severe cerebral edema may predict poor outcomes within two hours after ROSC.Hypothesis:We evaluated if GWR measurements obtained early after OHCA (≤ 2 hours) indicated poor neurological outcomes in patients with severe cerebral edema.Methods:We conducted a multicenter, retrospective cohort study using data from five hospitals collected between 2007 and 2019 in Japan. Inclusion criteria: adult comatose OHCA survivors with head CT within two hours after ROSC. Exclusion criteria was trauma, stroke, or pre-existing neurological disorders. Primary outcome was poor neurological outcome, defined as Cerebral Performance Category (CPC) score ≥ 3 at one month after admission. GWR was measured at the levels of the basal ganglia (BG), corpus callosum (CC), and posterior internal capsule (PIC). The prognostic value of GWR for predicting poor outcome was assessed using a receiver operating characteristic (ROC) curve analysis, area under the curve (AUC) with sensitivity/specificity.Results:A total of 377 patients were included. Of those, 281 (74.6%) exhibited poor neurological outcome at one month after admission. GWR values did not alter by the time of obtaining head CT: 1.22 (0-30 min: n=194); 1.22 (31-60 min: n=127); 1.22 (61-120 min: n=56). Using a cut-off GWR value of

Circulation, Volume 146, Issue Suppl_1, Page A219-A219, November 8, 2022. Purpose:Effectiveness of cardiopulmonary resuscitation (CPR) is associated to return of spontaneous circulation (ROSC), but the alignment of the characteristics of compressions (rate and depth) to AHA recommendations has not been proven to improve outcome. In this study the power of the near infrared spectroscopy to discriminate productive CPR, i.e. chest compression sequences leading to ROSC, was evaluated.Material and methods:The cerebral oxygen saturation (rSO2) measured in both cerebral lobules was recorded with the Nonin SenSmart 100X oximeter by Emergentziak-Osakidetza, the emergency service of the Basque Country, in the out-of-hospital cardiac arrest (OHCA). Concurrently, the ECG and bioimpedance were recorded by the Lifepak 15 desfibrillator. Chest compressions were delivered by Lucas 2 & Lucas 3 devices. Sequences of compressions longer than 30 s were extracted, and changes in the left (rSO2,L) and right (rSO2,R) lobes were automatically computed by signal processing. The increase of rSO2, measured every 4 s during the CPR-sequence, was adjusted with linear regression and compared for ROSC/no-ROSC patients as registered in the emergency department (ED).Results:Chest compression intervals were identified in the bioimpedance, and 403 CPR-segments were extracted from 115 patients (80 from 43 patients with ED-ROSC) with a mean(std) duration of 2.46(1.07) min. The median(IQR) increase of brain saturation per patient, rSO2,Land rSO2,R, were 2.1(1.1-5.5) and 1.9(0.9-3.8) points. The figure shows the linear adjustment of the evolutions for both ROSC/no-ROSC groups, with slopes of: 1.81 vs 1.23 min-1for ΔrSO2,L(p >0.05), 1.78 vs 0.95 min-1(p

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 A11115-A11115, November 8, 2022. Introduction:The ventricular fibrillation (VF) often occurs in acute heart failure patients with Impella support, percutaneous transvalvular left ventricular assist device. Although Impella can preserve blood pressure in some VF patients, the hemodynamic mechanism of Impella during VF remains unclear.Aim:In this study, we examined the impact of Impella on hemodynamics and cerebral and coronary blood flows in a goat model of VF. We also addressed the optimal blood volume status to maintain the Impella circulation during VF.Methods:In six goats, we inserted Impella CP via the left carotid artery. We simultaneously recorded right (RAP) and left atrial pressure (LAP), central blood pressure at ascending aorta (CBP), and the blood flows of pulmonary artery (PA), left coronary circumflex artery (LCX), and right carotid artery (CA). The VF was induced by direct current. We compared the impact of Impella support level (P0, P4 and P8) on hemodynamics and each blood flow. Under P8-Impella supported VF condition, we withdrew blood continuously and observed the left ventricular (LV) suction point at which a frequent negative LV pressure occurred.Results:As shown in Fig. 1 and 2, Impella maintained hemodynamics flow-dependently, indicating the establishment of acute Fontan circulation. In P8-Impella support, systemic (PA flow), LCX and CA blood flows were preserved by 50.1±27.7, 50.7±12.5 and 67.3±5.6%. from baseline, respectively. The blood volume reduction induced the suction of Impella (Fig. 3) at RAP below 9.9±1.9 mmHg.Conclusions:Impella establishes the acute Fontan circulation and preserves hemodynamics including coronary and cerebral blood flows during VF. The optimal blood volume status should be considered to maintain the Impella operation during VF.

Circulation, Volume 146, Issue Suppl_1, Page A221-A221, November 8, 2022. Introduction:Several factors are known to influence return of spontaneous circulation (ROSC) following out-of-hospital (OHCA) and in-hospital cardiac arrest (IHCA). Machine learning (ML) methods are capable of analyzing large datasets to elucidate the clinical and prognostic value of specific variables. In cardiac arrest, ML may help identify predictors of ROSC in OCHA and ICHA.Purpose:The present systematic review summarizes the literature on ML algorithms used to predict ROSC in OHCA and IHCA.Methods:PubMed, EMBASE, Web of Science, and Cochrane were searched to identify articles. Studies on human subjects with OHCA or IHCA which used ML methods to predict ROSC were included.Results:A total of 4,094 studies were identified through a literature search. Ten were included in the final analysis with a total sample size of 240,798 patients (240,798 (93%) male). Studies used logistic regression (n=7), random forest models (n=2), or deep learning (n=1). Sociodemographic variables beyond age (n=8) and sex (n=5) were not used. Variables used for predicting ROSC included age (n=8), type of rhythm (n=7), witnessed arrest (n=5), and time to emergency services arrival (n=5). Most models were built using data from OHCA patients (n=7), with only three focused on IHCA. Studies utilized a variety of parameters for reporting the prognostic value of their models, including predictive accuracy (69%-99%), area under the receiver operating characteristic curve (0.71-0.83), sensitivity (50.2%-76.0%), and specificity (61.0%-92.9%).Conclusion:Despite the prevalence of cardiac arrest and advances in AI, only ten studies examined ML in the prognostication of ROSC. Logistic regression was predominantly used in the included studies, and there is a paucity of data on the efficacy of deep learning models. Furthermore, heterogeneity in the predictive efficacy of studied ML models merits additional work and the need for large-scale trials comparing ML to conventional methods and clinician judgment. Critically, there is also a need for greater data inclusivity in model development, understanding that marginalized populations are less likely to receive CPR.

Circulation, Volume 146, Issue Suppl_1, Page A13035-A13035, November 8, 2022. Mechanical circulatory support (MCS) is rarely used in adults with congenital heart disease and even more uncommon among those with single ventricle (e.g. Fontan) circulation. As survivorship among Fontan patients increases, evaluation for MCS is warranted. This systematic review’s objective is to study the outcomes of adult Fontan patients supported by MCS. METHODS We searched the literature in English in PubMed and Google Scholar in May 21 & 2, 2022 using MeSH terms: “VAD,” “Fontan,” and “circulatory assist device.” The search yielded 2785 results. After screening for title, abstract, patient age ( >18 y/o), and extractable individual patient data, 23 reports met the criteria. Ultimately, 15 full texts were reviewed and included in this report. RESULTS We identified 18 patients on MCS, including 7 on short-term devices (Impella), 4 on paracorporeal pulsatile devices (PPDs), and 7 on durable continuous flow ventricular assist devices (VADs). Short-term pumps were used for cardiogenic shock (5, with 3 survivors) or support of high-risk ablation procedures. PPDs were used as a bridge to transplantation, mean patient age of 23.5±3.4 years old; all survived after a mean time on MCS of 172±158 days.In the VAD cohort (7 patients, 85.7% males, age 25.1±4.0), 5 received Heartmate 3, one received Heartmate II, and one Heartware (Table 1). Indications for VAD included cardiogenic shock (4 patients, 2 on VA ECMO) or heart failure. VADs dramatically increased cardiac index from 1.6±0.14 to 3.6±0.1 L/min/m2, p=0.0003, and decreased Fontan pressure from 21.4±3.3 to 13.0±1.4 mmHg, p=0.02. Heartmate 3 mean speed was 6460±568.3 rpm. All patients survived, with mean time on VAD lasting 459.5±452.2 days. CONCLUSIONS Implanted mostly for catastrophic indications, adult Fontan patients demonstrated improved hemodynamics and excellent survival following MCS use. These improvements are promising, and earlier implantation prior to catastrophic events may lead to better outcomes.