Risultati per: Linee Guida per le cure post-parto

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

Circulation, Volume 150, Issue Suppl_1, Page A4146198-A4146198, November 12, 2024. Introduction:Lung cancer is divided broadly into two main types: Small cell lung cancer (SCLC) and non-small cell lung cancer-NSCLC. Approximately 70% of SCLC cases have metastasized to other parts of the body including lymph nodes, bone, liver, adrenal glands, and brain [1]. SCLS metastasis to cardiac tissue is rare. Primary cardiac tumors are as rare with a reported prevalence of 0.028% [2]. Here we present a 59-year-old female (59F) with recurrent SCLC metastasis with evidence of a newly diagnosed primary cardiac tumor.Case Presentation:59F with a past medical history of SCLC status-post chemotherapy and radiation presented for evaluation of worsening left upper extremity pain, paresthesia, motor weakness, and neck pain. During the hospital admission, an echocardiogram demonstrated extensive thrombus from the Superior Vena Cava (SVC) into the right atrium (RA) and an irregular echogenic 37 mm x 26 mm mass partially attached to the posterior leaflet of the tricuspid valve. The RA mass was successfully removed by mechanical thrombectomy. Pathological results of the RA mass revealed significant malignant epithelioid and spindled neoplasm with myxoid stroma– concerning for myoepithelial disease.Discussion:Cardiac tumors, although uncommon, should be included in the list of possible diagnoses when observing any abnormal mass detected through cardiovascular or thoracic imaging techniques. Cardiac tumors are likely due to metastatic origins as metastatic cardiac tumors occur 20 times more frequently than primary cardiac tumors[3].When metastatic cardiac tumors are suspected, malignant melanoma and leukemia are the most frequent origins[4]. Rarely does SCLC metastasize to cardiac tissue. Primary cardiac tumors are typically benign (90%), with primary malignant tumors being very rare[5]. Patients may be asymptomatic, or present with nonspecific symptoms such as exertional dyspnea, fevers, arthralgias, or life-threatening cardiac tamponade[6]. For right atrial tumors, treatment strategies are usually dependent on symptomatology, in which removal via aspiration or surgical resection has demonstrated a favorable prognosis[7].Conclusion:Given the rarity of primary cardiac tumors in the setting of metastatic SCLC, there exist no evidence-based guidelines for optimal management of right atrial tumors. In our patient, mechanical aspiration was performed without complications and prevented potential adverse cardiopulmonary events from occurring.

Circulation, Volume 150, Issue Suppl_1, Page AOr110-AOr110, November 12, 2024. Introduction:Lactic acidosis and impaired oxygen extraction due to mitochondrial dysfunction are common post-arrest. Thiamine, a cofactor for pyruvate dehydrogenase, is necessary for aerobic metabolism. In two randomized controlled trials (RCTs) testing the effect of thiamine vs. placebo in out-of-hospital and in-hospital post-arrest patients (NCT03450707 and NCT02974257), no relationship was found between thiamine treatment and the primary outcome of change in lactate over 24 hours. Cellular oxygen consumption rates (OCRs) were measured in a subset of patients at baseline. Maximal and spare OCRs measure the capacity of mitochondria to increase cellular respiration from their basal state when stimulated, and may identify patients likely to benefit from thiamine. We conducted a post-hoc analysis of the two RCTs to evaluate the primary outcome in subgroups defined by baseline OCRs.Hypothesis:Patients with higher maximal and spare OCRs at baseline are more likely to benefit from thiamine treatment, as indicated by lower lactate levels.Methods:Basal, maximal and spare OCRs, collected at enrollment, were measured in peripheral blood mononuclear cells using an XFe96 Extracellular Flux Analyzer and XF Cell Mito Stress Test Kit (Seahorse Bioscience). Lactates (at 6, 12, and 24 hours) were log-transformed and analyzed using a linear mixed model controlling for baseline lactate. In patients who expired

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.

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 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 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 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 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

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 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 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 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 A4144199-A4144199, November 12, 2024. Background:The current standard for children diagnosed with rheumatic heart disease (RHD) is secondary antibiotic prophylaxis (SAP) for at least 10 years or to a minimum age of 21. However, these recommendations were developed prior to the widespread use of echocardiography and based largely on expert opinion. A recent clinical trial in Uganda found that up to 50% of children with early RHD show echocardiographic normalization by 2 years. More research is needed to understand if continued SAP is needed after echocardiographic normalization.Hypothesis:There is a low risk of RHD recurrence in individuals who have had normalization of their echocardiogram following early RHD diagnosis.Aim:To determine the 2-year safety of not providing SAP to children and adolescents with early RHD who have shown echocardiographic normalization.Methods:The GOAL trial in Uganda, 2018-2021, compared SAP with Benzathine Penicillin G (BPG) to no prophylaxis among children with early RHD. GOAL-Post is a non-randomized prospective extension study of the GOAL Trial. Children with echocardiographic normalization at the end of GOAL, regardless of treatment arm, were followed prospectively without SAP, for 2 additional years. Echocardiograms were performed at the end of follow-up, uploaded to a cloud server, and interpreted by a four-person adjudication panel. Recurrence was determined by side-by-side comparison with GOAL enrollment and completion studies.Results:Of 345 eligible participants, 330 (96%) were enrolled, mean age 16 years (SD = 2.3), 56% female, and all completed the two-year follow-up. Only one of 330 (0.3%) progressed to moderate/severe RHD after the 2 years, and an additional 26 participants (7.9%) had evidence of mild RHD, which was clinically comparable to their cardiac status at the start of the GOAL Trial. No participants had clinical signs or symptoms of RHD and no documented rheumatic fever. This means that 99% of children and adolescents who had echocardiographic normalization were safe from moderate/severe RHD and 92% were safe from any RHD, without SAP.Conclusion:These findings suggest that it may be safe to consider stopping of SAP among children who show echocardiographic normalization, providing more individualized recommendations for SAP duration, rather than the current model of long-term SAP for all. Further study is needed including a stoppage of SAP trial, to generate higher quality evidence for this approach.

Circulation, Volume 150, Issue Suppl_1, Page ASu1203-ASu1203, November 12, 2024. Background:A goal of post-resuscitation care among patients successfully resuscitated from in-hospital cardiac arrest (IHCA) is avoidance of fever. However, the incidence of post-resuscitation fever after the initial therapeutic hypothermia trials in 2002 and after the recent Targeted Temperature Management (TTM) trial in 2013 is unknown.Objective:Examine temporal trends in fever during the first 24 hours after return of spontaneous circulation (ROSC) from IHCA during 2005-2013 (after the initial hypothermia trials) and then during 2014-2022 (after the TTM trial).Methods:Within the Get With The Guidelines-Resuscitation registry for IHCA in the U.S., we identified adult patients with ROSC after an index IHCA from 127 hospitals that submitted data on IHCA during both time periods between 2005 and 2022. Patients with sepsis and COVID-19 infection were excluded. We evaluated temporal trends in post-resuscitation fever (defined as >100 °F) during 2005-2013 after the initial hypothermia trials, and then between 2014-2022 after the TTM trial.Results:Among 41,155 patients with ROSC after IHCA, the mean age was 64.8 years (±15.0); 60.0% were male, and 68.6% were of White race. Overall, 11,745 (28.5%) developed post-resuscitation fever (Figure 1). Following the therapeutic hypothermia trials in late 2002, the incidence of fever decreased from 39.1% in 2005 to 29.0% in 2013 (Pfor trend < 0.001) (Figure 2). After the publication of the TTM trial in late 2013, post-resuscitation fever in the years 2014-2022 did not go up but declined more modestly (Pfor trend = 0.003).Conclusions:Between 2005 and 2013, the incidence of post-resuscitation fever after IHCA decreased substantially. Since the publication of the TTM trial in late 2013, fever incidence has not increased; rather, it has remained relatively stable, even as reported use of therapeutic hypothermia has declined.

Circulation, Volume 150, Issue Suppl_1, Page A4140703-A4140703, November 12, 2024. Background:The mRNA vaccines against COVID-19 are highly effective but have been associated with a rare non-infective form of myocarditis, particularly in young males after receiving the second dose. Understanding the mediators of this adverse effect is crucial to enhance the safety of future mRNA vaccines.Hypothesis:Myocardial injury following COVID-19 mRNA vaccination is mediated by overproduced cytokines, and estrogens have a protective effect on this adverse effect.Approach:Candidate cytokine mediators were identified through analysis of proteomics data from plasma samples of vaccinated individuals. Human iPSC-derived macrophages and cardiomyocytes were used to model cytokine-induced effects. An in vivo mouse model of cytokine-induced myocardial injury was employed to assess the impact of the cytokine cocktail and estrogens.Results:CXCL10 and IFN-γ were consistently upregulated in vaccinated individuals on day 1 and further elevated in patients with myocarditis following mRNA vaccination. Consistently, iPSC-derived macrophages exposed to COVID-19 mRNA vaccines produced these cytokines. Next, iPSC-derived cardiomyocytes exposed to these cytokines showed impaired contractility, arrhythmogenicity, and pro-inflammatory gene expression. The phytoestrogen genistein mitigated these effects in vitro, reducing cytokine-induced proteasomal degradation of cardiac proteins and preserving contractile function. In vivo, genistein significantly decreased cardiac injury markers and immune cell infiltration in a mouse model of cytokine-induced myocardial injury.Conclusion:CXCL10 and IFN-γ are key mediators of myocardial injury post-mRNA vaccination. Genistein shows potential as a therapeutic agent to mitigate associated cardiovascular risks.