Risultati per: Caratterizzazione dell'asma in base all'età di insorgenza: uno studio di coorte multi-database

Circulation, Volume 150, Issue Suppl_1, Page A4136032-A4136032, November 12, 2024. Background:Biomarkers like coronary artery calcium (CAC) and traditional risk factors are well-validated for coronary artery disease (CAD) assessment but not always available, and with limited workup efficiency and potential radiation risk. Facial features contain biological information related to atherosclerosis.Aims:We aim to extract CAC and traditional risk factor-associated digital biomarkers from facial images and evaluate their value in predicting CAD status compared with conventional clinical approaches.Methods:Suspected individuals referred for confirmatory CAD evaluation across nine centers were included. Participants in one center constituted the derivation set. External validation included one dataset of participants from a different time period in the derivation center and the other dataset from the other eight centers. We developed a multi-label deep-learning model to extract digital biomarkers from facial photos based on a multi-dimensional label of CAC score and eight traditional risk factors to comprehensively represent coronary atherosclerosis risk profile. The extracted digital biomarkers were evaluated for both effectiveness in reflecting components of the multi-dimensional label and clinical value in predicting obstructive CAD.Results:A total of 13248 facial photos from 3312 eligible participants (mean age, 58.5 years; 517 [25.9%] female) were included. In external validation, a set of digital biomarkers (FacialCAD) were extracted, effectively reflecting components of the multi-dimensional label, especially for CAC stratification (CAC >0, AUC 0.919 [0.885 – 0.949]; CAC≥100, AUC 0.906 [0.876 – 0.933]) and nearly perfect prediction for the age and sex. The performance of the FacialCAD in predicting obstructive CAD (AUC 0.721 [0.694–0.748]) significantly outperformed two guideline-recommended CAD models (0.721 vs. 0.653, P

Circulation, Volume 150, Issue Suppl_1, Page A4140013-A4140013, November 12, 2024. Background:Prior research has noted disparities in sleep duration among demographic groups and those with cardiometabolic disorders. However, these are mostly based on self-reported data. The NIH All of Us Fitbit database offers a new method for objective and reliable sleep assessment.Goals:The study aimed to objectively assess sleep duration using the All of Us Fitbit database across various demographic variables and cardiometabolic disorders.Methods:All of Us participants with at least one year of Fitbit data were identified. Fitbit’s “minutes asleep” parameter was extracted daily over the first year of Fitbit use and averaged. The average total minutes asleep (TMA) was compared across self-reported age, sex and race groups. For those individuals who also shared their electronic health record (EHR) data, TMA was compared between those with and without hypertension, diabetes, and sleep apnea. T-test and ANOVA were used for comparisons.Results:The first year of Fitbit data for 13,039 participants (51 [16]* years, 69% female, 82% White) was analyzed, with sleep information available for 330 [104] days (90% complete data). TMA decreased with age, with the 18-44, 45-64, and 65+ groups averaging 366 [64], 348 [72], and 339 [85] minutes respectively (p

Circulation, Volume 150, Issue Suppl_1, Page A4132152-A4132152, November 12, 2024. Background:Hypertrophic cardiomyopathy (HCM) is associated with increased mortality mainly due to sudden cardiac arrest. However, it is not clear how HCM affects in-hospital mortality among patients hospitalized due to other cardiovascular conditions requiring intervention.Methods:National Inpatient Sample (NIS) database was queried from 2016 to 2020 to identify hospitalized patients with a diagnosis of HCM. Patients with HCM were stratified based on their concomitant cardiovascular conditions necessitating interventions.Results:Data pertinent to 278,995 admission cases with HCM was analyzed. Of this, 15,035 cases had concomitant non-ST elevation MI (NSTEMI), and 1,230 cases had ST-elevation MI (STEMI). Additionally, 15,100 cases were diagnosed with aortic valve diseases (AVD), 33,580 had concomitant mitral valve diseases (MVD), 5,580 cases had tricuspid valve diseases (TVD), and 16,815 cases had pulmonary valve diseases (PVD). Cardiovascular procedures were more common among HCM patients with concomitant STEMI (43.5%) followed by HCM patients with AVD (17.1%) and HCM patients with NSTEMI (16.9%). Stratification of mortality rate based on cardiovascular procedures and the underlying indication revealed CABG to have the highest mortality rate for HCM patients with STEMI (25%), followed by PCI for HCM patients with STEMI and HFrEF (12.5%). HCM patients with NSTEMI undergoing revascularization had higher mortality when PCI was performed for HFrEF cases and when CABG was performed for HFpEF cases. For HCM patients with AVD requiring repair or replacement, TAVR was superior to SAVR if performed in patients with HFpEF but was inferior among HFrEF subgroup in terms of in-hospital mortality. For subgroup of HCM patients with MVD, transcatheter replacement was associated with a lower mortality than surgical repair regardless of concomitant heart failure. Data was insufficient for HCM patients with concomitant TVD or PVD undergoing repair or replacement procedures.Conclusions:Among hospitalized patients with HCM, concomitant HFrEF but not HFpEF is associated with a significantly higher mortality rate regardless of the underlying cardiovascular conditions requiring revascularization or heart valvular repair. A more comprehensive preoperative risk assessment could delineate the ideal procedures for HCM patients with certain comorbidities and specific need.

Circulation, Volume 150, Issue Suppl_1, Page A4146331-A4146331, November 12, 2024. Background:Acute Myocardial Infarction (AMI) in malignancy is a significant cause of mortality globally. This study analyzed demographic trends and disparities in mortality rates due to AMI in malignancy among adults aged 65 and older from 1999 to 2020.Methods:A retrospective analysis was performed using death certificate data from the Centers for Disease Control and Prevention database from 1999 to 2020. The analysis utilized ICD* codes I21 for AMI and C00-C97 for malignancies. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 persons, and trends were assessed using Average Annual Percentage Change (AAPC) and annual percent change (APC). Data were stratified by year, sex, race/ethnicity, and geographical regions.Results:Between 1999 and 2020, AMI in malignancy caused 172,691 deaths among U.S. older adults aged ≥65 years. The majority of deaths occurred in medical facilities (56.9%) and at decedents’ homes (24.2%). The overall AAMR for AMI in malignancy-related deaths decreased from 30.2 in 1999 to 14.2 in 2020, with an AAPC of -3.90 (p < 0.000001). Men showed higher AAMRs than women (28.6 vs. 12.3), with a more pronounced decrease in men (AAPC: -4.22, p < 0.000001) compared to women (AAPC: -3.78, p < 0.000001). Racial disparities were significant, with Black individuals having the highest AAMR (22.7), followed by Whites (19.3), American Indians or Alaska Natives (14.4), Hispanics (12.2), and Asians or Pacific Islanders (10.8). The decline in AAMR throughout the study was most pronounced in Black individuals (AAPC: -4.30, p < 0.000001). Geographically, the highest AAMRs were observed in Arkansas (32.3) and the lowest in Nevada (8.1). The Northeastern U.S. had the highest regional AAMR (20.2), followed by the Midwest (19.9), South (18.3), and West (17.4). Nonmetropolitan areas had higher AAMRs than metropolitan areas, though both saw significant declines from 1999 to 2020 (Metropolitan: AAPC: -3.97, p < 0.000001; Nonmetropolitan: AAPC: -2.64, p < 0.000001).Conclusion:This study reveals significant demographic disparities in mortality rates related to AMI in malignant older adults. These findings emphasize the need for targeted interventions and improved access to care to reduce mortality and enhance outcomes in this vulnerable population.

Circulation, Volume 150, Issue Suppl_1, Page A4124226-A4124226, November 12, 2024. Introduction:Exposure to ambient air pollution may increase the risk of cardiovascular disease events and mortality, but prior publications have primarily included administrative cohorts with outcomes that have not been individually reviewed and with air pollution estimates created without cohort-specific exposure monitoring. Multi-Ethnic Study of Atherosclerosis (MESA) is a multi-site cohort study designed specifically to prospectively collect and adjudicate cardiovascular disease (CVD) events. MESA Air recruited additional participants into sub-cohorts for enhanced air pollution variation and sample size.Research Question:The aim of this analysis was to characterize the relationship between long-term exposure to nitrogen dioxide (NO2) and fine particulate matter (PM2.5) and all-cause mortality and CVD events.Methods:Air pollution exposure was assessed using address history with a purpose-built exposure model incorporating cohort-specific monitoring including measurement and validation at participant homes. We used Cox models to assess the risk of rolling 2-year average exposures on all cause-mortality and on a composite CVD endpoint (definite angina, probable angina with revascularization, myocardial infarction, atherosclerosis or other CVD death, resuscitated cardiac arrest, and stroke). Models were stratified for baseline hazard by age, sub-cohort, and recruitment year and were additionally adjusted for age, sex, race/ethnicity, field center, smoking/second-hand smoke, pack-years, physical activity, education, income, neighborhood socioeconomic status, and statin use.Results:MESA Air participants were aged 44-87 years at enrollment between 2000 and 2007; follow-up averaged 14 years. 6,915 participants had follow-up for events, NO2exposure, and covariate information. We observed 1,442 deaths and 985 CVD events. The interquartile range over all 2-year averages was 10.5-23.1 ppb for NO2and 10.1-14.9 µ/m3for PM2.5. The adjusted hazard ratio (aHR) for a 10 ppb increment in NO2was 1.38 (95% CI: 1.17, 1.64) for all-cause mortality and 1.16 (95% CI: 0.95, 1.42) for incident CVD events. The aHR for a 5 µg/m3increment in PM2.5was 1.20 (95% CI: 0.99, 1.46) for all-cause mortality and 1.15 (95% CI: 0.95, 1.39) for incident CVD eventsConclusions:These results add to growing literature demonstrating an association between air pollution exposure, mortality, and CVD in a cohort with well-characterized clinical endpoints and cohort-specific exposure assessment.

Circulation, Volume 150, Issue Suppl_1, Page A4117772-A4117772, November 12, 2024. Background:Aortic valve calcium (AVC) is strongly associated with an increased risk for severe aortic stenosis (AS). The prevalence of AVC increases with age affecting 40-50% of individuals ≥80 years. The impact of age on the progression of AVC and its association with incident AS remains unknown.Methods:Our study included 6,810 participants (52.9% women) free of cardiovascular disease between ages 45 and 84 from the Multi-Ethnic Study of Atherosclerosis. AVC was measured using non-contrast cardiac CT at Visit 1. Progression was calculated as the change in AVC divided by years between CT scans with up to 10 years between scans. Long term incident AS was adjudicated using medical chart review and echocardiogram data from Visit 6 with a median follow up of 16 years. Multivariable adjusted 1) linear regression was used to examine AVC progression and 2) multivariable adjusted Cox proportional hazards ratios (HR) were used to examine the association of AVC with incident AS.Results:The prevalence of AVC >0 was 4.9% among participants 0, the median AVC was 34.1 (IQR 13-1,113) for participants 0 was associated with significantly increased risk of incident AS for both younger (HR 13.37; 95% CI 5.67-31.52) and older participants (HR 10.59, 95% CI 6.77-16.56).Conclusion:We observed a similar progression of AVC for younger versus older persons after adjusting for baseline AVC burden. Additionally, AVC >0 independently conferred at least a ten-fold higher risk for severe AS among both younger and older participants. These findings demonstrate that the AVC progression is primarily associated with baseline AVC burden and that AVC is a strong marker of risk for severe AS for both younger and older persons.

Circulation, Volume 150, Issue Suppl_1, Page A4141384-A4141384, November 12, 2024. Introduction:Recent transcriptomic and metabolomic studies have suggested heart failure with preserved ejection fraction (HFpEF) myocardium exhibits metabolic insufficiency. Here we integrated targeted gene expression and proteomics to identify which fuel use pathways are likely compromised in HFpEF.Hypothesis:We hypothesize HFpEF has depressed gene/protein/metabolite levels related to metabolism of fatty acids, branched chain amino acids, and anaplerosis.Methods:Myocardial septal biopsies from HFpEF patients and non-failing controls were studied by Western blot for key proteins in fuel metabolism and cross-related to metabolomics (38 HFpEF, 20 control) and bulk RNAseq (41 HFpEF, 24 control). Protein abundance between groups was tested using Welch’s t-test.Results:Protein levels of CPT1 and CPT2 enzymes needed for acylcarnitine formation and rate-limiting for fatty acid metabolism, were similar in HFpEF vs controls. Proteins related to fatty acid uptake (ACSL1, P=0.002) and oxidation (ACAD [ACADM, P=0.02; ACADVL, P=0.009], HADH [HADHA, P

Circulation, Volume 150, Issue Suppl_1, Page A4115235-A4115235, November 12, 2024. Intro:The AHA endorses screening youth athletes to identify risk for sudden cardiac arrest (SCA). Rates of SCA can be predicted by social determinants of health (SDOH) such as education level and proportion of Black residents in ZIP Code. The Child Opportunity Index (COI) quantifies neighborhood factors that influence health and development. The link between COI and youth cardiac screening findings and outcomes remains unclear.Hypothesis:Cardiac screening data will differ significantly by COI.Aims:To identify differences in cardiac screening data in children of varying COI.Methods:The HeartBytes Database, including sports exams, self-reported physical activity (PA), and zip codes from Simon’s Heart screenings was augmented with COI index zip code data. Chi-squared and logistic regression were used to analyze demographics, cardiac risk factors, and screening results.Data:Screening data of 11,431 youth athletes (median age 14.3 (IQR = 3), BMI 20.6 (4.8), 53.7% male, 70.6% White) was analyzed. The majority of children had very high overall COI (Figure 1). Hypertension, hyperlipidemia, Kawasaki disease, and heart infection were similar across COI levels (p > 0.05). Levels of physical activity varied significantly across levels of overall COI, with the highest levels reported in the lowest COI group (50.4% with >10 hours PA/week) (Chi-Squared; p = 0.007). Positive screening rates varied significantly by level of COI (p = 0.013) (Figure 2). The overall level of education, health environment, and socioeconomic COI did not predict positive screening outcomes in logistic regression analysis (all p >0.05).Conclusion:Prevalence of cardiac risk factors did not vary significantly across COI levels, however, positive screening rates were highest in moderate and very low COI levels. Simon’s Heart engaged communities across the COI spectrum; however, a majority of children had high or very high COI. Further efforts are needed to expand access to underserved populations of lower COI.

Circulation, Volume 150, Issue Suppl_1, Page A4134249-A4134249, November 12, 2024. Background:Inflammation plays a role in the development of cardiovascular disease (CVD). We have defined various non-cardiovascular and non-cancer conditions, both infectious and non-infectious, with a common basis of inflammation; collectively termed Chronic Inflammatory-Related Disease (ChrIRD). We have previously described that ChrIRD is common, associated with baseline inflammatory marker levels, associated with high mortality, and has a bidirectional association with CVD. The clinical implications of these data require further study.Aims:We hypothesize that many traditional risk factors for CVD are also associated with ChrIRD and that ChrIRD has additional unique risk factors. We also hypothesize that the treatment of traditional CVD risk factors is associated with a decreased likelihood of ChrIRD.Methods:We studied MESA participants free of overt CVD or significant illness at baseline. ChrIRD was determined based on review of ICD codes for hospitalizations and deaths. Incident CVD was adjudicated by review of medical records. We performed proportional hazards regression (time-dependent for CVD) to identify factors associated with a first diagnosis of ChrIRD. All variables were simultaneously entered into the model.Results:Participants (n=6155) had mean age 62±10 years and 47% male gender. ChrIRD was observed in 24% and CVD in 18%; including 8% with both conditions. Participants with a diagnosis of CVD, older age, higher heart rate, higher BMI, current or ever smoking status, higher HDL, higher baseline IL6 and GlycA levels, and NSAID use had increased likelihood of ChrIRD. Whereas those with female sex, higher total cholesterol, and statin use had a decreased likelihood of ChrIRD. Participant race/ethnicity, blood pressure, diabetes status, antihypertensive use, aspirin use, baseline CRP level, and baseline D-dimer level were not associated with ChrIRD. Regression results are summarized in Table 1.Conclusions:ChrIRD shares some risk factors with CVD, while other risk factors are opposite.Better understanding of ChrIRD could eventually lead to improved patient care.

Circulation, Volume 150, Issue Suppl_1, Page A4144108-A4144108, November 12, 2024. Background:The CHA2DS2-VASc risk score is a clinical tool for stroke prediction. It is mainly used in patients with atrial fibrillation (AF) but is also applied to the non-AF population. We previously reported that artificial intelligence (AI)-enabled left atrial (LA) volumetry from coronary artery calcium (CAC) scans (AI-CAC) predicts AF as early as one year and outperformed CHARGE-AF and NT-proBNP. In this report, we compare AI-CAC LA volumetry to the CHA2DS2-VASc risk score and evaluate the incremental value of incorporating AI-CAC LA volume to CHA2DS2-VASc for incident stroke prediction in the non-AF population.Methods:We applied the AutoChamberTMLA volumetry component of AI-CAC to CAC scans of 5830 people without AF (52.2% women, age 61.7±10.2 years) enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) baseline (2000-2002). We used the 15-year outcomes data for incident stroke (ischemic and hemorrhagic) and assessed discrimination using the time-dependent area under the curve (AUC) between AI-CAC LA volume vs. CHA2DS2-VASc risk score. Notably, the CHA2DS2-VASc score in this non-AF population ranges from 0 to 5, whereas in the AF population it typically ranges from 0 to 9 points.Results:252 cases of stroke accrued over 15 years. The median and mean ± SD of CHA2DS2-VASc score at baseline were 1.0 and 1.58 ± 1.15, respectively. The cumulative incidence of stroke for the 95thpercentile of AI-CAC LA volume (n=291) vs. CHA2DS2-VASc 4 or 5 points (n=364) was 13.0% and 13.7%, respectively. AI-CAC LA volume significantly improved the AUC of CHA2DS2-VASc for stroke prediction at 2-year follow-up (0.76 for CHA2DS2-VASc vs. 0.81 for CHA2DS2-VASc plus LA volume, p=0.03), 5-year follow-up (0.73 vs. 0.77, p=0.01), 10-year follow-up (0.70 vs. 0.75, p

Circulation, Volume 150, Issue Suppl_1, Page A4146507-A4146507, November 12, 2024. Background:Atrial flutter (AFL) is a common supraventricular tachyarrhythmia characterized by a rapid and regular atrial rate. Although the global burden of atrial flutter on the general population has risen dramatically over the past four decades, the impact of sex on clinical outcomes for these patients is poorly characterized. This study aims to investigate sex disparities in clinical outcomes over recent years for patients admitted with atrial flutter.Methods:In this large scale, retrospective cohort study, adult patients who were admitted with AFL were analyzed from 2016 to 2021 using the National Readmissions Database. The study population was divided into male and female groups. Diagnoses were classified using the International Classification of Diseases, 10th edition codes. The primary outcome was 30-day readmissions. Secondary outcomes included inpatient mortality and length of stay.Results:A total of 132,027 patients with AFL meeting inclusion criteria were included in the study. Of these, 82,988 (62.9%) were male and 49,040 (37.1%) were female. The mean age was 63.0 ± 11.5 for males vs 67.2 ± 11.4 years for females. Readmissions were higher in females (10% vs 9%) than males. Cox regression analysis showed higher readmission events in females (HR: 1.07, 95% CI: 1.01-1.13, p < 0.010) when compared to males. Multivariate regression analysis for inpatient mortality and length of stay was higher for females than males (p < 0.01 for both).Conclusion:Women experienced higher readmission rates and had worse outcomes including inpatient mortality and higher length of stay compared to their male counterparts. These findings suggest that female patients may require closer monitoring and targeted intervention to improve these outcomes.

Circulation, Volume 150, Issue Suppl_1, Page A4144428-A4144428, November 12, 2024. Background:Leadless pacemaker implantation (LPI) is common among patients with sick sinus syndrome (SSS) or atrioventricular block (AVB). Our study explores 30-day readmission rates (30-dr) following LPI for SSS and AVB, comparing outcomes between male and female patients.Methods:Using the Nationwide Readmissions Database, we conducted a retrospective analysis of patients who underwent LPI for SSS, and second or third-degree AVB between 2017 and 2021. Our study cohort was stratified by gender. The primary outcome was 30-dr, while secondary outcomes included inpatient mortality, length of stay (LOS), complications, and total hospital charge (THC).Results:Among the 17,759 patients meeting the inclusion criteria, 54.1% (n = 9,613) were males and 45.9% (n = 8,146) were females, with a mean age of 76.4 ± 12.6 years. The mean age was 75.5 ± 12.4 years for males and 77.4 ± 12.6 years for females (adjusted Wald test, p < 0.01).Logistic regression analysis revealed that females had higher odds of readmission (OR 1.21, 95% CI 1.06 - 1.39, p < 0.01) compared to males. However, inpatient mortality and LOS did not differ significantly between the two groups (p > 0.05, all). In addition, males had a higher rate of complications leading to hemodialysis and the use of mechanical ventilators (p < 0.05, all), while women had higher complications in pericardial effusions and tamponade (p < 0.05, all). The mean THC was higher in males ($50,589 vs 47,681), compared to females (adjusted Wald test, p = 0.02).Conclusion:Our study revealed that female patients have a higher risk for 30-dr after LPI for SSS and AVB,. While the difference between two groups was not significant for inpatient mortality and LOS, the males had higher THC. Moreover, the nature of complications differed between males and females as well. This highlights the need for tailored interventions to minimize readmissions in this patient population.

Circulation, Volume 150, Issue Suppl_1, Page A4145765-A4145765, November 12, 2024. Background:The incidence burden of maternal hypertensive disorders has increased by 30% globally. This study analyzed the trends in prevalence and death rates from maternal hypertensive disorders across various states in the United States from 1990 to 2021.Methods:Using the Global Burden of Disease (GBD) database, we compared the following levels, stratified by state, between the beginning of 1990 and the end of 2021: hypertensive disorders of pregnancy, percentage prevalence change, mortality percentage change by age-standardized rates per 100,000 population, and age-stratified changes in the rate of incidence and mortality. The analysis was conducted using Microsoft Excel (16.7).Results:The analysis revealed notable interstate variability in the prevalence and death rates of maternal hypertensive disorders (Figure 1). Nevada exhibited the highest increase in prevalence (0.87%), followed by Hawaii (0.65%) and Idaho (0.54%). In contrast, Mississippi experienced the largest decrease in prevalence (-0.22%), followed by Louisiana (-0.20%) and Maine (-0.19%). Regarding death rates, the District of Columbia saw the most significant decrease (-0.67%), followed by New York (-0.45%) and New Jersey (-0.42%). Conversely, West Virginia had the highest increase in death rates (0.89%), followed by Alaska (0.52%) and Kentucky (0.51%). The analysis of Age stratified subgroups in each state showed the maximum increase in mortality change in the age group of 40–44 years, followed by 35–39 years, with West Virginia having the highest percentage change mortality rates (2.55%; age group 40–44 years) and District of Colombia showing a sharp decrease in the percentage mortality rates (-0.72%; age group 30-34 years). Incidence percentage changes showed similar patterns, with Virginia showing a (3.41%; 40–44 years), closely followed by New York (3.31%; 40–44 years).Conclusion:The data reveal significant disparities in both the prevalence and death rates of maternal hypertensive disorders across different states. Additionally, an increase in mortality and incidence rate changes of hypertension in pregnancy was observed in higher age groups, particularly among women aged 35–39 and 40–44. These findings highlight the need for tailored, state-specific public health strategies to effectively address targeted interventions for older age groups and mitigate the impact of maternal hypertensive disorders.

Circulation, Volume 150, Issue Suppl_1, Page A4142154-A4142154, November 12, 2024. Introduction:With the increasing popularity of glucagon-like peptide 1 receptor agonists (GLP1-RAs), numerous safety concerns arose pertaining to suicide, hair loss, and aspiration risks. We attempted to validate these concerns.Methods:We queried the FDA Adverse Event Reporting System (FAERS) database; a post-marketing pharmacovigilance database, from Q4/2003 till Q3/2023 to analyze public reports of these adverse events with GLP1-RAs and other diabetes medications, including sodium-glucose transporter 2 inhibitors (SGLT2is), dipeptidyl peptidase 4 inhibitors (DPP4is), sulfonylureas, metformin, and insulin. OpenVigil 2.1 is an online tool that was utilized to perform disproportionality analysis. A positive signal signifying disproportionate reporting was detected if the proportional reporting ratio (PRR) > 2 and chi-squared (χ2) > 4 for any drug-event pair. The studied medications were arranged in descending order according to the corresponding reporting odds ratio (ROR), which is a measure of the likelihood of reporting a certain event with a certain drug in comparison to all other drugs in the database.Results:No positive signals were observed between GLP1-RAs and either suicide, hair loss, or aspiration events. Semaglutide [ROR= 0.601 (95% CI 0.51 – 0.71)] and liraglutide [ROR= 0.282 (95% CI 0.228 – 0.35)] had higher suicidal events than DPP4is and SGLT2is. GLP1-RAs were the most reported class with hair loss [ROR= 0.605 (95% CI 0.6 – 0.64)], and semaglutide, liraglutide, and dulaglutide were the three leading medications. GLP1-RAs ranked lower with aspiration events, which were led by sitagliptin and DPP4i as a group. Only metformin and glyburide generated positive signals with suicide risk.Conclusion:GLP1-RAs exhibit higher reporting of suicide, hair loss, and aspiration events when compared to several other antidiabetic medications, despite not meeting the criteria for positive signals yet. This warrants intensive monitoring and reporting.

Circulation, Volume 150, Issue Suppl_1, Page A4120687-A4120687, November 12, 2024. Background:There are currently no approved medical therapies for acute fulminant myocarditis (AFM). Janus kinase (JAK) inhibitors target the JAK-STAT signaling pathway, which is crucial in immune activation. We report the first use of ruxolitinib, a JAK inhibitor, for treatment of AFM. Multi-omics single-cell technologies, including RNA-seq, T-/B-cell receptor seq, and CITE-seq, were employed to analyze immune profiles pre- and post-ruxolitinib treatment.Results:A 20-year-old female presented with AFM with cardiogenic shock and was supported by VA-ECMO and impella CP. Endomyocardial biopsy showed lymphocytic myocarditis. The patient received pulsed steroids and was listed for orthotopic heart transplant. Due to deteriorating conditions, ruxolitinib (10 mg BID) was added with immediate improvement in cardiac and inflammatory biomarkers and hemodynamics. ECMO was decannulated on day 6 and impella CP was removed on day 8. Repeat TTE on day 9 showed normalization of cardiac function (LVEF 58%, increased from 10%). She was discharged on ruxolitinib and is doing well in follow-up. Multi-omics single-cell technologies were employed on PBMCs collected at four time points: prior to ruxolitinib treatment (but after treatment with corticosteroids), and post-ruxolitinib treatment on day 5, day 8, and 2-months. At baseline, prior to treatment, scRNA-Seq and CITE-seq analysis revealed upregulated JAK-STAT signaling in pathogenic immune cells such as NK cells, CCR2+/CCR5+/HLA-DR+monocytes and activated T cells. Ruxolitinib treatment significantly decreased these pathogenic immune cells, with inhibition of STAT1/STAT3 signaling. Ruxolitinib also significantly decreased key cytotoxic genes PRF1, GZMB, and TBX21 in T and NK cells. TCR sequencing revealed clonal expansions of activated T cells with high levels of pro-inflammatory genes (IL2/IL6/IFNg) at baseline which were dramatically reduced post-treatment with ruxolitinib. Longitudinal data indicated normalization of naive T and B cell levels and clonal diversity, mirroring her clinical improvement.Conclusions:Ruxolitinib significantly modulates immune profiles and disrupts pathogenic signaling in AFM. This first reported use of ruxolitinib in AFM, coupled with our multi-omics analysis, highlights profound immune reprogramming and supports targeted immune modulation for rapid recovery, underscoring ruxolitinib’s therapeutic efficacy.

Circulation, Volume 150, Issue Suppl_1, Page A4148110-A4148110, November 12, 2024. Background:Critical Limb Ischaemia (CLI) is a concerning medical emergency condition with notable mortality among older adults. This study highlights the trends and demographic disparities in mortality rates due to CLI in patients aged 55 and older in the United States from 1999 to 2020.Aim:This study aimed to evaluate patterns and geographical variations in mortality associated with CLI among adults in the United States.Methods:Death certificates from CDC WONDER database from1999 to 2020 were analyzed to investigate mortality related to CLI among adults. Age-adjusted mortality rates (AAMRs) per 100,000 persons were calculated, stratified by year, sex, race/ethnicity, and geographical regions.Results:CLI caused a concerning 620,205 deaths among US adults aged 55+ between 1999 and 2020, primarily in hospitals (42%). The overall AAMR for CLI-related deaths showed decline from 51.6 in 1999 to 40.1 in 2020, with an AAPC of -1.51 (95% CI: -1.75 to -1.25, p < 0.000001). The AAMR experienced a steeper decrease from 1999 to 2011 (APC: -3.31, p < 0.000001), followed by a slight increase from 2011 to 2020 (APC: 0.94, p = 0.031174). Men had higher AAMRs than women, though both sexes experienced reductions (men: 48.3; women: 32.6). The AAMR for men decreased from 64.9 in 1999 to 42.8 in 2011, increasing to 50.1 by 2020. For women, the AAMR decreased from 42.9 in 1999 to 28.3 in 2014, followed by a slight increase to 32.3 by 2020. Racial/ethnic disparities were apparent, with Black individuals having the highest AAMRs (58.7), followed by Whites (39.0), American Indians/Alaska Natives (38.0), Hispanics (28.5), and Asians/Pacific Islanders (13.8). All racial groups experienced decreases in AAMRs. Geographically, AAMRs varied from 20.4 in Utah to 53.2 in Ohio. The highest mortality noted in the Midwestern region (AAMR: 43). Nonmetropolitan areas unveiled higher AAMRs than metropolitan areas (nonmetropolitan: 43.5; metropolitan: 38.2). Both regions showed a decrease in AAMRs from 1999 to 2020 (metropolitan AAPC: -1.36, p < 0.000001; nonmetropolitan AAPC: -0.81, p = 0.001399).Conclusion:Our analysis highlights significant demographic and geographic differences in older adult mortality due to CLI in the U.S. Continued decreases over time but recent upturn in mortality rates emphasizes need for focused interventions to close these gaps and to improve population health outcomes for affected populations.