Abstract 4143906: Prophylactic Administration Of Colchicine Mitigates Atrial Fibrillation Vulnerability Post-Catheter Ablation In Rats: Exploring Sex-Specific Variations.

Circulation, Volume 150, Issue Suppl_1, Page A4143906-A4143906, November 12, 2024. Background:Atrial Fibrillation (AF) is the most diagnosed cardiac arrhythmia in clinical practice. Catheter ablation (ABLA) is a method used to manage AF by cauterizing the left atrium (LA) to isolate arrhythmogenic areas. However, ABLA is paradoxically associated with atrial inflammation and AF recurrence, with 10% of patients experiencing recurrence within 30 days and over 50% after 12 months. Studies suggest that AF prevalence is generally lower in women than in men, but females with AF are more prone to severe complications. Colchicine has been proposed for its anti-inflammatory and cardioprotective effects.Hypothesis:Early colchicine treatment prevents ABLA-triggered atrial fibrosis, inflammation, and arrhythmogenic substrates.Methods:Male and female Wistar rats (225-275g) were randomly assigned to four groups: Sham or ABLA, with or without colchicine treatment (1 mg/kg/day; intraperitoneally) starting 2 hours before surgery. Sham animals underwent surgery without ABLA.In vivoelectrophysiological studies and echocardiography were performed on days 1 (D1) and 3 (D3) post-ABLA. On D3,ex-vivooptical mapping was conducted on Langendorff-perfused hearts, and atrial fibrosis, gene, and protein expression were assessed using Masson’s trichrome staining, qPCR, and immunoblotting, respectively.Results:ABLA animals displayed a significantly higher susceptibility to atrial arrhythmias compared to Sham animals, and among ABLA rats, females were 20% less vulnerable to AF than males at D3 post-ABLA. The LA from ABLA rats exhibited significantly slowed conduction velocity, increased fibrosis areas, and enhanced levels of inflammatory markers compared to Sham. Colchicine significantly reduced the incidence of AF post-ABLA with more efficacy in females than males. Moreover, colchicine normalized LA conduction, fibrosis, and inflammation in LA ABLA compared to Sham. Consistent with contemporary knowledge about male and female differences in AF incidence, our data suggest that endogenous female sex hormones combined with colchicine administration may contribute to significantly reducing AF incidence.Conclusion:Initiating Colchicine treatment prior to ABLA may lower post-ABLA-induced LA inflammation and AF occurrence. Delving into the variances in male and female responses to colchicine intervention could offer new insights into addressing post-ABLA AF incidence.Bas du formulaire

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Novembre 2024

Abstract 4144388: Impact of Left Atrial Myopathy and Post-Ablation Remodeling on Quality of Life: A DECAAF II Subanalysis

Circulation, Volume 150, Issue Suppl_1, Page A4144388-A4144388, November 12, 2024. Background:Atrial fibrillation (AF) is associated with adverse remodeling of the left atrium (LA). The impact of the extent of atrial myopathy and post-ablation remodeling on quality-of-life (QoL) outcomes have not been studied.Objective:The aim of our study was to investigate the association between atrial myopathy and post-ablation remodeling on quality-of-life outcomes in patients with persistent AF.Methods:We conducted an analysis of DECAAF II participants who underwent late-gadolinium enhancement MRI (LGE-MRI) before and after AF ablation. We assessed atrial myopathy and post-ablation atrial remodeling, scar formation, and fibrosis coverage with ablation. QoL metrics were assessed using the Short Form Survey (SF-36) and Atrial Fibrillation Severity Scale (AFSS). Uni- and multivariable regression models were developed for this analysis.Results:613 patients with persistent AF were included in our analyses. At baseline, AFSS burden and total AFSS score were 18.94±7.35 and 12.24±8.17, respectively. Following ablation, all QoL and AFSS metrics improved in both the pulmonary vein isolation (PVI) and MRI-guided fibrosis ablation groups. On average, one unit of post-ablation reduction in left atrial volume index (LAVI) was associated with an improvement of 0.085 in total AFSS score (p=0.001), 0.01 in shortness of breath with activity (p

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Novembre 2024

Abstract 4147168: Left Atrial Remodeling By Cardiac MRI In Mitral Stenosis Patients Pre- and Post- Balloon Mitral Valvuloplasty

Circulation, Volume 150, Issue Suppl_1, Page A4147168-A4147168, November 12, 2024. Background:Mitral stenosis (MS) is associated with adverse left atrial (LA) structural changes. Mechanical relief of this obstruction via balloon mitral valvuloplasty (BMV) may be associated with LA reverse remodelling.Objective:To study LA and RV remodelling in isolated severe rheumatic MS patients before and 9-12 months after successful BMV.Methods:We included 49 patients with isolated severe rheumatic MS in sinus rhythm who underwent successful BMV. CMR was done at baseline and 9-12 months post BMV. Thirty age- and gender- matched healthy controls were included for comparison. Indexed LA volumes (Vmax, Vmin,&Vpre-A) were obtained from CMR cine images. LA phasic functions were evaluated using both volumetric and deformation indices. Deformation analysis including LA strain (global, passive,&active strain)&strain rate (SRs, SRe, and SRa ) measurements were performed using specialized MASS (R) software for CMR feature tracking.Results:At baseline, there was significant impairment of LA volumes and functions in severe MS patients compared to healthy controls. Following BMV, there was statistically significant reduction in all LA indexed volumes compared to baseline (p-value

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Novembre 2024

Abstract 4142266: Long-term Outcomes and Predictors of Recurrence in Atrial Arrhythmia Ablations Post-Fontan Procedure: A Retrospective Analysis

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.

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Novembre 2024

Abstract Or108: Optimizing Post-resuscitation Care after Resuscitative Endovascular Balloon Occlusion of the Aorta and Automated Head-up Position Cardiopulmonary Resuscitation.

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.

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Novembre 2024

Abstract 4125252: Pre-Hematopoietic Stem Cell Transplantation Echocardiographic Indices and Post-Transplant Cardiovascular Outcomes

Circulation, Volume 150, Issue Suppl_1, Page A4125252-A4125252, November 12, 2024. Introduction:Hematopoietic stem cell transplantation (HSCT) is associated with adverse cardiovascular (CV) events including the development of heart failure (HF) and arrythmias. While transthoracic echocardiogram (TTE) is routinely obtained prior to HSCT, its role in predicting the incidence of HSCT related CV events is poorly understood.Methods:We used data from the Cardiovascular Registry in Bone Marrow Transplantation (CARE-BMT) study, a multicenter observational study of adult patients (aged ≥18 years) who underwent autologous/allogeneic HSCT for malignant or nonmalignant bone marrow disorders at the University of Michigan Health System (UMHS) and Rush University Medical Center from 2008-2019. In this analysis, we included patients from UMHS with a baseline TTE. Data on pre-HSCT TTE parameters and post-HSCT CV outcomes were collected through manual chart review. Left ventricular (LV) function and dimensions were categorized into normal, mildly abnormal, and moderately/severely abnormal based on American Society of Echocardiography guidelines. The primary outcomes were new-onset HF and atrial fibrillation/flutter post-HSCT. Analyses were conducted using a Fine-Gray model adjusted for the pre-HSCT CARE-BMT CV risk score.Results:Of the 2071 patients (mean age at HSCT 55.5+12.9 years; 59.5% male) with a pre-HSCT TTE (median 25 days pre-HSCT), 116 (5.6%) and 128 (6.2%) patients experienced HF and atrial fibrillation/flutter, respectively, over a median period of 2.2 years. Greater abnormalities in left ventricular internal diameter at end-diastole (LVIDd) and end-systole (LVIDs) were linearly associated with a higher risk of HF (P-trend 0.018 and 0.004, respectively) (Table). Similarly, moderately/severely abnormal LVIDd was associated with a 2.41-fold (95% CI: 1.07, 5.43) increase in risk of atrial fibrillation/flutter (Table). Pre-HSCT ejection fraction (EF) was not associated with either endpoint.Conclusion:LV dilation, even when mild, was notably associated with increased risk of developing new HF or atrial arrythmias post-HSCT, regardless of EF. Whether evidence of LV dilation should prompt the initiation of guideline directed medical therapy to minimize the risk of incident HF warrants further study.

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Novembre 2024

Abstract 4147346: Efficacy of OCT versus angiography in post-procedural lesions complications after percutaneous coronary intervention with drug-stent implementations: A systematic review and meta-analysis

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

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Novembre 2024

Abstract 4142315: Genetically enhanced CHA2DS2VASc score predicts post-ablation ischemic stroke in patients with atrial fibrillation

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 (

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Novembre 2024

Abstract 4144997: Pro-B-Type Natriuretic Peptide Kinetics across Pre-, Index, and Post-Acute COVID-19 in Hospitalized Acute on Chronic Heart Failure Patients: A Learning Health System Science Initiative

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

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Novembre 2024

Abstract 4145353: Sex Differences in Post-PCI Myocardial Injury and Long-Term All-Cause Mortality

Circulation, Volume 150, Issue Suppl_1, Page A4145353-A4145353, November 12, 2024. Background:Myocardial injury complicating percutaneous coronary intervention (PCI) is associated with mortality, but sex differences in outcomes are uncertain. We explored sex differences in the incidence and long-term outcomes of post-PCI myocardial injury (PPMI).Methods:Adults who underwent PCI at NYU between 2011-2020 were included in this retrospective analysis. Patients with ACS as the indication for PCI were excluded. PPMI was defined as a peak CKMB concentration >99% of the upper reference limit. The incidence of PPMI by sex was compared by Chi-square tests. Independent predictors of elevated CKMB post-PCI were evaluated with linear regression models in subgroups by sex. Cox proportional hazard models were generated to evaluate relationships between PPMI and all-cause mortality by sex.Results:Of 10,807 adults undergoing PCI, 24.9% (2,694) were female. Females were older than males at the time of PCI (68.9 vs. 65.8, p

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Novembre 2024

Abstract 4140722: Racial Disparity among the clinical outcomes in post Ablation Atrial Fibrillation patients: A Global Retrospective Study

Circulation, Volume 150, Issue Suppl_1, Page A4140722-A4140722, November 12, 2024. Background:Racial disparities have been well described in cardiovascular disease. However, the impact of race on the outcomes post atrial fibrillation (AF) ablation is not well understood.Objective:This study aim to investigate the clinical outcomes post AF ablation among Black and White patients.Method:The TriNeTX Global Collaborative Network database was used to identify patients aged ≥18 years of age from January 2000 to April 2023 which included atrial fibrillation post-ablation patients. Patients were categorized into two groups, one with Black or African American race and another with White race groups. Both groups were followed for 12 months. We used the international Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes to identify comorbidities, and ICD-10 Procedure coding system for procedures. Propensity score-matched analysis (PSM) (1:1) was performed on age, gender, BMI, smoking, hypertension, diabetes mellitus, chronic kidney disease, hemoglobin level and left ventricular ejection fraction. The primary outcome was all-cause mortality (ACM), while secondary outcomes were ischemic stroke, hemorrhagic stroke, acute myocardial infarction (AMI), MACE (composite of ACM, heart failure, AMI, and ischemic stroke) and heart failure (HF).Result:After 1:1 propensity score matching, the study cohort comprised 10, 335 Black patients and 10,335 White patients. The mean age of patients was comparable between both groups (65.2 and 64.9 years). Post ablation, Black patients were having a significantly higher risk of ACM (RR 1.131, 95% CI: 1.002-1.277), HF (RR 1.473, 95% CI: 1.290-1.683), AMI (RR 1.312, 95% CI: 1.117-1.342), and MACE (RR 1.416, 95% CI: 1.250-1.603) as compared with white population. However, the risk of ischemic stroke (RR 1.069, 95% CI: 0.878-1.301) and hemorrhagic stroke (RR 1.466, 95% CI: 0.908-2.369) were found comparable between Black and White patients post ablation.Conclusion:These findings suggest that Black patients post AF ablation were having a higher risk of mortality and MACE.

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Novembre 2024

Abstract 4147291: Examination of pre-mRNA from cardiomyocytes at single-cell resolution from post-infarcted mouse hearts

Circulation, Volume 150, Issue Suppl_1, Page A4147291-A4147291, November 12, 2024. Background:RNA-seq provides a powerful tool to dissect cellular heterogeneity in diseased hearts. It generates reads from both mature RNA and pre-mRNA. Traditionally, only mature RNA transcripts are considered for analysis, but studying both species of transcripts from single-cell RNA-seq of cardiomyocytes in post-infarcted hearts can reveal novel insights into the dynamic transcriptional changes and regulatory mechanisms that occur during heart repair and regenerationResearch question:Do nascent transcriptional events from pre-mRNA forecast the biological processes in failing hearts better than the mRNA and unravel the complexity of cardiomyocyte diversity?Aim:Execute an exon-intron analysis on cardiomyocyte single-cell RNAseq data obtained from post-infarcted mouse heartsMethods:Cardiomyocytes from mice (n=4) post-LAD ligation were isolated and single-cell RNAseq was performed using MegaKit v.2 (Parse Biosciences) on a NovaSeq 6000. Data was analyzed via theParsepipeline andSeurat v5. Pre-mRNA reference was built withAGAT. Gene set enrichment was done usingfgsea. Sham mice without ligation (n=4) served as controlsResults: We analyzed at least 70K cells for each transcript type and compared their enrichment profiles for post-infarcted hearts to sham. Infarction resulted in enrichment for biological processes predominantly for development and fatty acid metabolism, especially from pre-mRNA mapping (mRNA vs pre-mRNA;p=4.2 x 10-18vs 4.8 x 10-32). At the level of individual clusters, cardiomyocyte heterogeneity was revealed with cells enriched for distinct processes. Common to both types of transcripts were terms enriched for cell death (mRNA vs pre-mRNA;p=7.6 x 10-3vs 4.2 x 10-3), tissue remodeling (p=4.3 x 10-4vs 9.6 x 10-4), and respiratory&metabolic activity (p=8.9 x 10-5vs 7.2 x 10-8).However, compared to mRNA, the pre-mRNA had more cell clusters enriched for terms related to increased protein production activity (p=7 x 10-4), activation of key signaling pathways (p=8.5 x 10-4), and defense response (p=2.1 x 10-6). These additional processes show adaptive mechanisms that promisingly forecast cardiomyocyte repair and could be visualized by mapping pre-mRNAConclusion:Examining pre-mRNA offers a realistic view of stressed cardiomyocytes’ transcriptional dynamics. This study could identify new biomarkers to predict the onset of heart failure. Further insights into transitioning cells could aid in developing therapies for regeneration

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Novembre 2024

Abstract 4138507: Uncovering Risk Factors for Myocarditis and Cardiac Arrhythmia in Youth Post-SARS-CoV-2 Infection: Insights from the N3C Database and Advanced Machine Learning

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.

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Novembre 2024

Abstract Or107: Sulfatide-specific natural killer T cells regulate early inflammation and ameliorate post-cardiac arrest brain injury

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.

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Novembre 2024

Abstract 4141173: CMR can discriminate need for biopsy and rejection therapy in children post heart transplant

Circulation, Volume 150, Issue Suppl_1, Page A4141173-A4141173, November 12, 2024. Background:Heart transplantation remains definitive therapy for children with heart failure, but the burden of acute graft rejection remains. While adult data has shown cardiac magnetic resonance (CMR) offers reliable, non-invasive identification of graft rejection1-3, endo-myocardial biopsy (EMB) continues to be the gold-standard in children.Hypothesis:CMR can establish the presence/absence of rejection, guiding need for EMB and rejection therapy.Aims:To assess the (1) strength of CMR parametric mapping in discriminating presence of rejection (defined as need for new therapy), and (2) the ability of CMR to identify patients without rejection, negating the need for EMB.Methods:Pediatric heart transplant patients referred for EMB underwent concurrent noncontrast CMR with volumetry, flows, MOLLI T1 and T2 parametric mapping at 1.5T. Average and peak segmental native T1 and T2 were measured in 6 slices, and regions of sub-segmental ‘hotspot’ elevation (3 continuous voxels T1 >1050 ms or T2 >60 ms) were identified. Rejection treatment was per institutional protocol, blinded to CMR results, categorized as (A)new IV therapy, (B)oral augmentation of maintenance, or (C) no change. Sensitivity, specificity and ROC analyses were performed.Results:95 encounters in 34 patients (median age 13.1y (IQR 7.5-16.3), BSA 1.37 m2 (1.1-1.6), 47% female) were completed, with treatment groups A 13%, B 5%, and C 82%. Significantly higher T1 and T2 values were found in the rejection groups. ROC curve analysis identified elevated peak T1 levels as the strongest predictor of rejection (AUC = 0.848, 95% CI: 0.746, 0.950, p1099 ms. Subsegmental hotspots were present in all encounters with rejection requiring new therapy (100% sensitivity), however the type/ number of hotspots did not correlate with rejection. New rejection therapy was not initiated in any patient encounter without hotspots (NPV 100%).Conclusions:Elevated segmental T1 CMR values can identify children with graft rejection, and absence of subsegmental hotspot elevations can reliably identify patients without rejection. CMR is a promising non-invasive test to aid in graft surveillance and direct invasive testing and therapy.

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Novembre 2024

Abstract Su1101: Evaluating Participant Comfort Levels Pre and Post Community-Based CPR and AED Education

Circulation, Volume 150, Issue Suppl_1, Page ASu1101-ASu1101, November 12, 2024. Introduction:Bystander cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use are interventions that can increase survival rates of out-of-hospital cardiac arrests (OHCA). However, willingness and comfort levels of such interventions amongst laypersons vary greatly, especially in racial and ethnic minoritized groups including African Americans and Hispanics.Research Question:To assess the comfort level and perceived barriers of participants before and after community-based CPR and AED education.Methods:We conducted a family-centered quasi-experimental study in primarily Black and Hispanic churches around the Will and Dupage counties of Illinois. Informed consent was obtained. Participants watched an instructor-facilitated CPR and AED 10-minute educational video. Comfort levels pre- and post-training were assessed on a scale of 1 (least confident) to 5 (extremely confident) and reported as percentages. A semi-structured questionnaire was used to assess perceived barriers to performing CPR.Results:Out of 27 participants who completed training assessment, majority were females 55.6% (n=15), with 44.4% (n=12) males; 66.7% (n=18) African Americans, and 33.3% (n=9) Hispanic or Latino. 70.4% (n=19) of the participants spoke English while 29.6% (n=8) spoke Spanish. Before training, 73% (n=19) and 81% (n=21) of participants were not confident in administering CPR or using AED respectively on someone in cardiac arrest. After training, confidence level increased to 100% for both CPR and AED use. Perceived barriers to CPR prior to training included participants not knowing how to perform CPR correctly (65%), concern that they may further harm someone (4%), concerns about potential legal liability (4%), and loss of recall on how to perform CPR (4%), while 23% had no barrier.Conclusion:Comfort levels of individuals performing CPR and AED use increased significantly after community-based CPR and AED education. Data collection is ongoing to assess comfort level with a larger number of participants. Implementing community-based CPR training in churches allows for community-oriented CPR trainings and may help improve bystander comfort level and willingness to perform CPR during OHCA, especially in minoritized communities.

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Novembre 2024