Risultati per: Gestione del dolore post-operatorio

Circulation, Volume 150, Issue Suppl_1, Page A4116298-A4116298, November 12, 2024. Background:Utreglutide (GL0034), a novel, once weekly glucagon-like peptide-1 receptor agonist (GLP-1RA), previously demonstrated significant reductions in body weight (BW) after a single dose ascending study in individuals with obesity.BW reductions after pharmacological treatment of obesity with GLP-1RA is associated with blood pressure (BP) lowering effects.Aim:This phase I study assessed the safety, tolerability, and cardio-metabolic effects of utreglutide after multiple ascending doses in post-menopausal female volunteers with overweight and obesity.Methods:In this randomized, double-blind, placebo-controlled study 12 post-menopausal female volunteers with overweight/obesity, aged 18 to 65 years old with a body mass index (BMI) ≥26 kg/m2were randomized (9:3) to subcutaneous utreglutide fixed doses (4 × 450 µg); or placebo once weekly for four weeks. Safety, tolerability, and key cardio-metabolic parameters were assessed. Biomarker measurements included oral glucose tolerance test (OGTT) insulin and glucose area under the curve (AUC), systolic- and diastolic BP, lipid profile (triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), and non-high-density lipoprotein (non-HDL), creatinine, potassium, BW and leptin.Results:Utreglutide was generally well tolerated and related adverse effects were mainly gastrointestinal with dose-dependent nausea, vomiting and decreased appetite. Reductions in OGTT AUCs of insulin (p

Circulation, Volume 150, Issue Suppl_1, Page A4142315-A4142315, November 12, 2024. Introduction:Although atrial fibrillation (AF) catheter ablation (AFCA) may reduce the risk of ischemic stroke (IS), those patients still have some risk. It is unclear whether post-AFCA IS has a genetic background as generally diagnosed IS. We explored the post-AFCA IS-associated single nucleotide polymorphisms (SNPs), and their polygenic risk score (PRS) has an incremental benefit to predict post-AFCA IS in addition to CHA2DS2VASc scores in the two independent cohorts.Methods:We developed PRS for post-AFCA IS from the UK Biobank (N=2,063) and validated from the independent Yonsei AF ablation cohort (N=2,897) after excluding the procedure-related IS (

Circulation, Volume 150, Issue Suppl_1, Page A4144997-A4144997, November 12, 2024. Introduction:Myocardial injury in patients hospitalized with acute on chronic heart failure concurrent with index SARS-CoV-2 (CoV-2) infection is well described, though studies incorporating pre- and post-acute COVID-19 (PAC) are lacking. We address this gap by estimating intensity of acutely decompensated heart failure (ADHF) using time-series pro-BNP levels across hospitalizations pre- vs. respectively index and initial readmission (PAC1).Hypothesis:Case time series analysis will reveal association (p

Circulation, Volume 150, Issue Suppl_1, Page A4146008-A4146008, November 12, 2024. Objective:Inflammation is associated with pathologies including post operative acute kidney injury (AKI). AKI is one of the common post operative conditions which prolongs hospitalization, intensive care unit stay and causes higher health costs and mortality. Pre-operative neutrophil to lymphocyte ratio (NLR) has predictive value for post-operative AKI after coronary artery bypass grafting (CABG). Hence, we aimed to evaluate the association of pre-operative NLR and post-operative AKI in patients undergoing CABG.Methods:A comprehensive literature review was conducted using PubMed, Google Scholar and SCOPUS databases from 2000 until 2024 using related keywords to identify studies reporting association of pre-operative NLR and post-operative AKI in patients undergoing CABG. The data was extracted and independently reviewed by four authors using standard forms. A random-effects model was used to calculate odds ratios (OR) and heterogeneity was assessed using I2 statistics. The sensitivity analysis was performed using the leave-one-out method.Results:Our final analysis included 6 retrospective studies which included 1757 patients with CABG. The mean age of the included patients was 64 years and 63.4% were males. Initial unadjusted analysis showed higher odds of post-operative AKI in patients having higher pre-operative NLR values with unadjusted OR 1.67, 95% CI 1.20-2.34, p

Circulation, Volume 150, Issue Suppl_1, Page A4140630-A4140630, November 12, 2024. Introduction:Efforts to stratify mortality risk in pulmonary hypertension (PH) have focused on the minority of patients in WSPH group 1. Metabolomic studies in group 1 identify histidine, polyamines, tRNA metabolites, and homoarginine as predictors of mortality. Little is known about the role of metabolomics to predict mortality in the larger group of PH patients.Question:Which serum metabolites predict a composite of mortality or transplant in pre-capillary, post-capillary, and combined pre- and post-capillary PH (Cpc-PH), irrespective of WSPH group?Aims:To identify predictive metabolites in the Pulmonary Vascular Disease Phenomics Program (PVDOMICS) cohort and understand the pathobiology relating predictors to mortality/transplant.Methods:We generated peripheral venous metabolomic data in 649 PH subjects. We defined pre-capillary PH as pulmonary vascular resistance (PVR) >2 WU and pulmonary capillary wedge pressure (PCWP)≤15 mmHg (n = 453), post-capillary PH as PVR≤2 WU and PCWP >15 mmHg (n=25), and Cpc-PH as PVR >2 WU and PCWP >15 mmHg (n = 171). We used Cox models with multiple testing correction to identify predictive metabolites in each group. We then correlated select predictors with hemodynamic, laboratory, and echocardiographic data.Results:The hemodynamic groups included a mix of WSPH groups. We identified 249 predictors in pre-capillary PH, 0 in post-capillary PH, and 7 in Cpc-PH. Homoarginine predicts mortality/transplant in pre-capillary PH (HR=0.56, p

Circulation, Volume 150, Issue Suppl_1, Page A4147497-A4147497, November 12, 2024. Background:There is strong data about the neuroprotective effects of targeted temperature management (TTM) in patients post cardiac arrest, however, there is limited literature on the cardiac effects. We evaluate the impact of targeted normothermia (TN) vs targeted hypothermia (TH) on left ventricular ejection fraction (LVEF). We hypothesized that targeted hypothermia would be more cardioprotective than targeted normothermia, thus manifesting in improved LVEF and/or reduced incidence of new heart failure at various points in time.Method:We queried the TriNetX Global collaborative network for adult (≥18 years) patients with LVEF >50% who suffered a Cardiac arrest (CA) and Coma within one day of CA, and we created two groups: therapeutic hypothermia and therapeutic normothermia. TTM was identified with International Classification of Diseases 10th edition (ICD-10) Procedure codes 6A4Z0ZZ, 6A4Z1ZZ, and SNOMED code 308693008 and the TN group excluded patients with documented temperature ≥ 99.6 °F or ≤ 97.6 °F within 1 day of CA. Similarly, the TH group was identified using the same ICD codes and excluded patients with documented temperatures ≥96.7°F or ≤ 91.3°F within 1 day of CA being excluded. Propensity Score Matching (PSM) done for age, race, sex, and multiple cardiovascular comorbidities. Outcomes were measured at 3-, 12-, and 36 months post-CA included the risk of LVEF ≤ 50%, new onset heart failure, and new prescription of loop diuretic.Results:After PSM 510 patients were analyzed, with 255 well-matched subjects in each group. At 3 months there were no significant odds of TH causing a decrease in cardiac ejection fraction to 50% or less (Odds Ratio [OR] 0.90, 95% CI: 0.37 – 2.18) compared to TN. No significant difference was seen at 12 months (OR 0.897, 95% CI: 0.37 – 2.18) or 36 months (OR 0.71, 95% CI: 0.32 – 1.60). Other outcomes at 3 months without significant difference include new HF (OR 0.97, 95% CI: 0.39 – 2.43), and new loop diuretic (OR 0.77, 95% CI: 0.33 – 1.80). These odds were similarly not significant at 12 and 36 months.Conclusions:In post-CA patients who received TTM, no cardioprotective effects were appreciated between hypothermia compared to normothermia at 3-, 12-, and 36 month follow up. There was no difference in new diagnosis of HF post-CA or new loop diuretic prescription. With the understanding that TN has fewer side effects than TH then the results reinforce the use of TN post cardiac arrest.

Circulation, Volume 150, Issue Suppl_1, Page A4146928-A4146928, November 12, 2024. Background:Post-operative atrial fibrillation (POAF) is a common and serious complication following cardiac surgery, leading to increased morbidity and healthcare costs. Inflammation, particularly mediated by cytokines like IL-17A, is believed to play a significant role in the pathogenesis of POAF. We aim to investigate the association between blood IL-17A levels and the incidence of POAF.Hypothesis:We hypothesize that elevated IL-17A levels in the blood are associated with a higher incidence of POAF in patients undergoing cardiac surgery.Methods:Blood samples were collected from 16 patients undergoing open heart surgery. Patients were monitored during the index hospitalization for the surgery. IL-17A levels in the blood were quantified using Olink proteomics, where oligonucleotide-labeled antibodies bind to target proteins, forming a new PCR target sequence by a proximity-dependent DNA polymerization event. Quantitative PCR measured the amplicons, and the Olink NPX Manager Software calculated Normalized Protein Expression Units (NPX) by normalizing the Cq values to interpolate controls. Statistical analysis was performed using Student’s t-test to compare clinical variables and IL-17A levels across the two groups.Results:Our cohort had an average age of 63.8 ± 4.7 with 14% female participants, an average weight of 83.9 ± 14.6 kg, and an average BMI of 28.8 ± 4.7. The POAF group was slightly older (64.8 ± 3.8 years vs. 62.7 ± 4.6 years) but had a similar BMI compared to those who did not develop AF. Hypertension and hyperlipidemia were present in all POAF patients (100%) compared to 81.8% in those without AF, while anemia was more common in the POAF group (40% vs. 18.2%). IL-17A levels were significantly elevated in the POAF group (0.75 ± 0.10 NPX) compared to the non-POAF group (0.35 ± 0.05 NPX) with a p-value < 0.05. Cardiac function assessments showed non-significant differences in left atrial volume index (LAVI) (46.2 mL/m^2 vs. 36.3 mL/m^2) and left ventricular mass index (LVMI) (114.4 g/m^2 vs. 89.3 g/m^2) in the POAF group. These findings suggest a significant association between elevated IL-17A levels and POAF, with trends of differences in left atrial remodeling between the two groups.Conclusion:Elevated blood IL-17A levels are associated with an increased risk of developing POAF. This suggests that IL-17A may serve as a critical biomarker and potential therapeutic target for preventing POAF in patients undergoing cardiac surgery.

Circulation, Volume 150, Issue Suppl_1, Page A4120229-A4120229, November 12, 2024. Background:In SURMOUNT-4, participants with obesity demonstrated a mean weight reduction of 21% during the 36-week lead-in with the maximum tolerated dose (MTD) of tirzepatide (TZP). During the 52-week double-blind period, participants who switched to placebo (PBO) experienced a 14% weight regain, while those who continued TZP achieved an additional 6% weight reduction. This post hoc analysis assessed whether participants who shifted to a lower BMI category had improved cardiometabolic factors.Methods:Shift in BMI category (

Circulation, Volume 150, Issue Suppl_1, Page A4138507-A4138507, November 12, 2024. Background:SARS-CoV2 infection has been associated with cardiovascular consequences, including myocarditis and cardiac arrhythmias. Myocarditis secondary to SARS-CoV2 infection and cardiac arrhythmias may often go unrecognized and can present with late and nonspecific symptoms. Predicting those at risk allows for prompt treatment and prevention of their potentially life-threatening consequences.Methods:The National COVID Cohort Collaborative (N3C) database was used to identify patients aged 0-30 years with COVID-19 index date between 1/1/2020 and 3/31/2022, whose sites provided data for at least six months beyond the index date. Outcomes included myocarditis and new arrythmias within 6 months of the index visit. Patients with known cardiac comorbidities were excluded. Predictors included gender, race, COVID severity as an ordinal scale, vaccination status, clinical comorbidities, and Area Deprivation Index (ADI). The data were stratified by age groups (0-4, 5-17, 18-30). Random forest models were used for data analysis and SHapley Additive exPlanations (SHAP) method was applied to optimize results. These analyses were conducted using the NCATS N3C Data Enclave.Results:Of the 1,487,741 patients in our study population, 4,105 (0.28%) had the measured outcomes; 404 had myocarditis only, 3,634 had arrhythmia only and 67 had both. Severity of COVID (SHAP 0.2344 for 0-4 years, 0.2114 for 5-17, 0.1370 for 18-30) was identified as the most important risk factor for de-novo myocarditis and arrhythmias overall. Increase in ADI (indicating lower socioeconomic status) was the second most important risk factor for the 0-4 and 5-17 age groups (SHAP: 0.0370, 0.0223). Among the 18-30 age group, race (SHAP 0.0321) and gender (SHAP 0.0289) were the second and third most important risk factors, with White and Black patients more likely to develop an event and Hispanic patients less likely. Women were less likely to develop a cardiac outcome than men.Conclusion:The severity of COVID was identified as the most important risk factor for the occurrence of myocarditis or cardiac arrhythmia within 6 months of infection. ADI, race, and gender were also identified as important, though less influential, risk factors.

Circulation, Volume 150, Issue Suppl_1, Page ASu1206-ASu1206, November 12, 2024. Introduction:Critical care after advanced cardiac life support can be pivotal for survival and outcomes in patients with out-of-hospital cardiac arrest (OHCA). Prior studies have demonstrated improvements in survival after OHCA with shorter door-to-therapeutic hypothermia (TH) initiation times. Post-cardiac arrest consult teams (PCACT) can facilitate TH to goal 33°C and other aspects of post-arrest care. However, the effects of such a service on TH have not been consistently quantified.Hypothesis:More OHCA patients would undergo TH and reach goal temperature sooner following implementation of a PCACT.Aims:We aim to evaluate the effectiveness of a PCACT in optimizing TH in survivors of OHCA.Methods:We conducted a retrospective chart review of 305 patients admitted between January 1, 2021 and December 31, 2022. Implementation of a dedicated PCACT, comprised of a neurointensivist and an advanced practice provider or neurocritical care fellow, occurred on January 1, 2022. The PCACT was active on weekdays only. One year before and after this date were designated as “pre-PCACT” and “post-PCACT”, respectively. De-identified patient demographics, clinical features of cardiac arrest, and TH data were collected and compared using Wilcoxon rank-sum and Chi-squared tests for continuous and categorical variables, respectively.Results:Of the 305 patients admitted during the study period, 149 were in the pre-PCACT group and 156 were in the post-PCACT group. Baseline demographics between the two groups were similar except that the post-PCACT group had more patients with non-shockable rhythms (64% vs. 54%,p=0.001). Patients were not cooled to 33°C more frequently (50 vs. 52%) pre- or post-PCACT. TH to 33°C was performed in 156 (51%) patients, 78 patients (50%) pre- and post-PCACT implementation. There were no baseline demographic or temperature differences between the two groups amongst patients undergoing TH to 33°C. Post-PCACT patients were quicker to reach 33°C (1.6 vs. 3 hours,p=0.001). After PCACT implementation, this difference was noted during weekdays but not during weekends (1.3 vs. 2.7 hours,p=0.05).There were no differences in survival or neurologic outcomes pre- and post-PCACT introduction, nor between patients who were or were not cooled to 33C.Conclusion(s):Implementation of a PCACT may streamline care to reduce time to goal temperature during TH. However, further study is required to determine whether a PCACT can improve outcomes.

Circulation, Volume 150, Issue Suppl_1, Page A4142266-A4142266, November 12, 2024. Introduction:Supraventricular tachycardia (SVT) is common and poorly tolerated in patients who have undergone Fontan procedure. Recurrence rates after catheter ablation in these patients are high. Recent data on the outcomes of SVT ablation and the predictors of recurrence in this population is lacking.Objective:Our study aimed to characterize clinical variables in patients with a Fontan undergoing EP ablation, investigate long-term outcomes, and determine factors that are associated with recurrence.Methods: Charts of patients who had undergone Fontan procedure and underwent SVT ablation between January 1, 1995, and October 1, 2023, at a tertiary care center were reviewed. Demographic, clinical, and outcome variables over 5 years were compared between patients with and without SVT recurrence.Results:Mean age of 25 patients (56% male) at time of SVT ablation was 31.5 ± 7.2 years. Ablation success rate was 92%. Recurrence occurred in 12 (48%) patients, with 7 (28%) requiring repeat ablations repeat within 5 years. Rate of recurrence did not differ between those who had the procedure before or after 2018. During the 5-year follow up period, 13 (59%) patients with follow up had cardiovascular (CV) hospitalization and 1 patient died. Atrial Tachycardia (70%) and Typical Atrial Flutter (65%) were the most common SVTs ablated. A trans-baffle puncture during the ablation was performed in 6 (23%) patients. Tricuspid atresia and elevated BNP levels were associated with increased risk of SVT recurrence (Table).Conclusion:Recurrence and cardiac hospitalization rates after SVT ablation in this population remain high. This study underscores the need for risk stratification in patients with Fontan physiology undergoing SVT ablation and informs future research directions for enhancing ablation outcomes.

Circulation, Volume 150, Issue Suppl_1, Page A4143067-A4143067, November 12, 2024. Background:Atherogenesis often develops in regions with disturbed blood flow (d-flow), involving increased ERK5 and p53 SUMOylation due to SENP2 T368 phosphorylation, leading to increased ERK5 and p53 SUMOylation, contributing to endothelial cell (EC) activation. Conversely, laminar flow (l-flow) induces SENP2 S344 phosphorylation, reducing ERK5 and p53 SUMOylation, thereby suppressing EC activation. The presence of senescent ECs in atherosclerotic plaques suggests that d-flow-induced EC senescence may contribute to atherogenesis, possibly due to metabolic changes. EC glycolysis is crucial for NO production and atheroprotection, however, it is inhibited by l-flow, indicating that l-flow protective effects extend beyond glycolysis.Methods:In ECs from wild-type mice exposed to l-flow, the expression of DDIAS increases, regulated by SENP2 S344 phosphorylation. DDIAS interacts with ACLY, a key regulator of fatty acid metabolism and vascular function. We performed LC-MS and IC-MS analyses on ECs with DDIAS knocked down or control siRNA exposed to l-flow, using13C2-gucose or13C5-glutamine to trace metabolic changes. HMG-CoA, acetyl-CoA, and CoQ levels were measured using LC-MS and triple quadrupole LC-MS/MS.Results:L-flow enhances glycolysis and glutaminolysis, significantly increasing TCA cycle intermediates through upregulated glutamine pathways. DDIAS expression and its interaction with ACLY are also increased by l-flow. Without DDIAS, the ACLY-mediated mevalonate pathway is inhibited, reducing l-flow-induced antioxidant mechanisms. Thus, the DDIAS-ACLY complex is crucial for the antioxidant response triggered by L-flow, which is essential for supporting angiogenesis after hindlimb ischemia. L-flow-induced increases in HMG-CoA and CoQ are inhibited by DDIAS depletion, highlighting the importance of DDIAS in maintaining the balance of metabolic and antioxidant pathways under L-flow.We are investigating the role of DDIAS-ACLY complex on l-flow-mediated upregulation of glycolysis and glutaminolysis.Conclusion:DDIAS plays a key role in mediating l-flow atheroprotective effect by directly interacting with and activating ACLY, essential for the mevalonate pathway and subsequent HMG-CoA and CoQ biosynthesis. Under l-flow conditions, ECs preferentially utilize glutamine over glucose for TCA cycle intermediates, underscoring the importance of the DDIAS-ACLY complex in supporting EC protection and function through enhanced metabolic pathways.

Circulation, Volume 150, Issue Suppl_1, Page AOr108-AOr108, November 12, 2024. Background:Addition of resuscitative endovascular balloon occlusion of the aorta (REBOA) to automated head-up position (AHUP) cardiopulmonary resuscitation (CPR), the combination of active compression decompression CPR, an impedance threshold device, and controlled gradual elevation of the head and thorax, increases cerebral perfusion pressure. Optimal management of REBOA deflation after prolonged AHUP-CPR and ROSC is unknown.Hypothesis:We hypothesized that partial deflation of REBOA, rather than full deflation after ROSC, would result in better hemodynamic parameters.Aims:To compare hemodynamic parameters 1 minute before and 1 minute after complete (100%) versus partial (50%) REBOA deflation after prolonged AHUP-CPR and ROSC.Methods:Yorkshire pigs weighing ∼40 kg were anesthetized and ventilated. After 10 minutes of untreated ventricular fibrillation, AHUP-CPR was started and continued for a median time of 44 minutes. After ROSC, REBOA deflation was initiated in two ways: complete (100%) or partial (50%) deflation over 5 seconds. The following hemodynamic parameters were measured 1 minute before and 1 minute after deflation: mean aortic pressure (MAP), cerebral perfusion pressure (CerPP), and coronary perfusion pressure (CorPP). Data, in mmHg, are presented as mean ± SD, and compared using a paired t-test.Results:13 pigs were included, with 8 pigs in the 100% deflation group and 5 in the 50% deflation group. After ROSC in the 100% deflation group, MAP was 81.5±36.0 before deflation vs. 43.0±14.4 after (p=0.01), whereas in the 50% deflation group, MAP was 90.5±33.0 vs. 83.4±33.3 (p=0.02). CerPP was 72.3±34.4 before deflation vs. 35.9±14.6 (p=0.01) in the 100% deflation group, and 84.6±31.2 vs. 77.6±31.8 (p=0.02) with 50% deflation. Similarly, CorPP was 74.1±37.3 before deflation vs. 36.1±15.8 (p=0.01) after in the 100% deflation group, and 83.0±32.7 vs. 76.1±33.0 (p=0.02) in the 50% deflation group. The differences from before to after deflation were markedly less in the 50% deflation group versus the 100% deflation group: MAP (7.0±4.3 vs. 38.5±25.7, p=0.02), CerPP (7.1±4.4 vs. 36.3±24.4, p=0.02), and CorPP (6.0±4.2 vs. 39.8±25.2, p=0.02), respectively.Conclusion:In this porcine model of prolonged cardiac arrest, partial deflation of the REBOA balloon post ROSC resulted in strikingly higher hemodynamics compared with complete deflation. These findings highlight the need to develop a post-ROSC REBOA deflation strategy when used during AHUP-CPR.

Circulation, Volume 150, Issue Suppl_1, Page A4147346-A4147346, November 12, 2024. Background:Although recent studies have suggested the advantages of utilizing optical coherence tomography (OCT) for image guidance during percutaneous coronary intervention (PCI) with drug-eluting stent implantation over conventional angiography, the specific impact on post-procedural lesion complications has remained uncertain. To address this gap, we conducted an updated systematic review and meta-analysis focusing on post-procedural lesion complications associated with OCT-guided versus angiography-guided procedures in lesions undergoing PCI with drug-eluting stent implementation.Methods:We searched systematically through Pubmed, Embase, and Cochrane for randomized controlled trials(RCTs), which included lesions undergoing PCI and drug-stent deployment guided by OCTversus angiography. Our primary outcome of interest was (1) stent malposition under OCT analysis. We also included the following secondary outcome: (2) dissections under OCT analysis. We excluded studies that did not use OCT imaging to analyze post-procedure lesions. Risk Ratios(RRs) with 95% confidence interval (CI) were pooled across studies using a random effect model.Results:Five RCTs comprising 3,266 lesions undergoing OCT or Angio PCI-guided and drug stent implementation were included, of whom 1,549(48,34%) underwent OCT. The number of moderate-severe calcified lesions was 370 (11.33%). Our results show a significant association with decreased stent malposition risk in the OCT group, showed a significant decrease in post-procedure risk regarding stent malpositioning ( RR: 0.80; 95% CI: 0.75-0.84; P

Circulation, Volume 150, Issue Suppl_1, Page AOr107-AOr107, November 12, 2024. Background:Innate T cells have both deleterious and protective roles in a range of diseases. Natural killer T (NKT) cells are a major type of innate T cell, but their role and clinical relevance after cardiac arrest (CA) are undefined.Hypothesis:In patients after CA, an early increase in diverse NKT (dNKT) cells correlates with good neurological outcomes. dNKT cells improve outcomes after CA by reducing inflammatory responses in the brain.Aims:To investigate the clinical relevance of dNKT cells after out-of-hospital CA (OHCA) and their roles in a murine CA model.Methods:A clinical retrospective cohort study of complete blood cell counts with differentials after OHCA. Single-cell RNA-seq and flow cytometry of circulating T cells in OHCA patients. Good neurological outcomes were defined as a Cerebral Performance Category of 1 or 2 at 30 days post-CA. Single-nucleus RNA-sequencing(-seq) of hippocampal cells (50,332 nuclei), RT-PCR, and flow cytometry of the brain 24 hours post-CA in mice.Results:In a large OHCA patient cohort (N=1,955), the percentage of lymphocytes early (less than 12 hours) after CA was independently associated with good neurological outcomes (adjusted odds ratio [95%CI], 1.08 [1.03-1.14], P=0.005). Transcriptional profiling of T cells in OHCA patients at single-cell resolution showed an increase in an innate T cell-like NCAM1+subset in patients with good neurological outcomes. This subset expressed cytotoxic, cytokine, and chemokine genes. Flow cytometry identified an early increase in circulating dNKT cells in patients with good neurological outcomes post-CA. In a murine model of CA, type II dNKT cells migrated to the brain after CA. NKT cell-deficient mice (Cd1d-/-) had increased neuronal injury and mortality after CA. Cd1d-/-mice had increased molecular and cellular inflammation compared to wild-type mice 24 hours post-CA. Global transcriptomic analysis of murine brain at single-nucleus resolution indicated NKT cells suppressed inflammatory axes post-CA in multiple cell types, including astrocytes, microglia, and inhibitory neurons. Treatment with sulfatide (a lipid antigen for dNKT cells) improved neurological function after CA.Conclusions:Early abundance of dNKT cells was associated with good neurological outcomes after OHCA. dNKT cells are neuroprotective after CA by suppressing inflammatory axes in the brain. Immunomodulation of dNKT cells via endogenous lipids is a potential treatment approach after CA.

Circulation, Volume 150, Issue Suppl_1, Page A4135273-A4135273, November 12, 2024. Background:Heart failure with reduced ejection fraction (HFrEF) often necessitates the use of cardiac implantable electronic devices (CIED) such as cardiac resynchronization therapy defibrillators (CRT-D) or implantable cardioverter-defibrillators (ICD). These devices are proven to reduce mortality, prevent hospitalizations, and improve symptoms and quality of life. Frailty, characterized by an age-associated decline in physiological reserve, significantly impacts outcomes in these patients. This study uses the Hospital Frailty Risk Score (HFRS) to assess the effect of frailty on mortality and post-procedural complications in HFrEF patients undergoing CIED implantation.Hypothesis:Frail patients with HFrEF have worse in-hospital outcomes after CIED placementMethods:We conducted a retrospective cohort study using the 2020 National Inpatient Sample database from the Healthcare Utilization Project. Our population included patients aged 18 years or older with HFrEF who underwent CRT-D or ICD placement, identified using ICD-10 procedure codes. The primary risk factor was frailty, classified by an HFRS score of ≥5 (frail) or