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

Circulation, Volume 150, Issue Suppl_1, Page A4135861-A4135861, November 12, 2024. Background:Lipoprotein (a) (Lp[a]) is associated with an increased risk of cardiovascular disease and mortality, as well as heart failure and myocardial fibrosis. However, the link between Lp(a) and cardiac remodeling as a pathway to adverse cardiac outcomes remains unknown.Objectives:This study investigated the relationship between Lp(a) levels and longitudinal changes in the left ventricular (LV) remodeling over a decade among individuals without a previous history of cardiovascular disease.Methods:2,366 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac MRI at Visit 1 (2000-02) and Visit 5 (2010-12) and had available Lp(a) at baseline were examined. Lp(a) was analyzed as a continuous and a categorical variable based on quartiles (Q1[38.8 mg/dL]). Multivariable linear regression analysis was used to examine the association of Lp(a) with changes in cardiac MRI measures of LV remodeling (Table).Results:Participants had a mean age 60±9 years and 53% were women. Over 10-year follow-up, LV indexed volumes decreased, while LV indexed mass and mass to volume ratio increased across all the Lp(a) quartiles. However, LV ejection fraction only decreased in the third and fourth Lp(a) quartiles. Lp(a) examined as a continuous variable was associated with an increase in LV end-systolic indexed volume (per log-unit Lp[a]; β 0.32 mL/m2;P= 0.01), LV indexed mass (per log-unit Lp[a]; β 0.38 g/m2;P= 0.02), and a decrease in LV ejection fraction (per log-unit Lp[a]; β -0.29 %;P= 0.02) over 10 years after adjusting for sociodemographic and traditional cardiovascular risk factors (Table). Similarly, the fourth Lp(a) quartile was associated with an increase in LV end-systolic indexed volume (β 1.07 mL/m2;P= 0.01), LV indexed mass (β 1.17 g/m2;P= 0.02) and a decrease in LV ejection fraction (β -1.01 %;P= 0.01) compared to the first Lp(a) quartile after controlling for risk factors. The observed associations remained significant after further adjusting for aortic valve calcium score at Visit 1 (Table- Model 3), and baseline coronary artery calcium score and interim myocardial infarction (Table- Model 4).Conclusions:In a multi-ethnic cohort of participants free of cardiovascular disease at baseline, higher Lp(a) levels were independently associated with an increase in LV end-systolic volume and LV mass as well as a decrease in LV ejection fraction over the span of a decade.

Circulation, Volume 150, Issue Suppl_1, Page A4139407-A4139407, November 12, 2024. Background:Higher aortic valve calcium (AVC) burden is associated with an increased risk of cardiovascular disease (CVD) and non-CVD. Despite shared risk factors between AVC and chronic kidney disease (CKD), the association of AVC with incident albuminuria is unknown.Methods:We examined 5,464 MESA participants who had AVC quantified by cardiac CT at Visit 1 (2000-02), an eGFR of ≥60 mL/min/1.73 m2, a normal spot urine albumin to creatinine ratio (ACR) ( 0. During a median follow up of 14.2 years, 921 (17%) developed albuminuria. There was a significantly increased rate of incident albuminuria with higher AVC values (p < 0.001) (Figure). In multivariable adjusted models, a higher risk of incident albuminuria was observed when AVC was examined as a continuous variable (per log-unit [AVC+1]) HR 1.05;p= 0.03 and for participants with AVC ≥100 HR 1.43; (p= 0.02) compared to AVC=0, but not for participants with AVC 1-99 (HR 1.13;p= 0.29). A significant progression in log transformed ACR was observed for AVC as a continuous variable (β 0.03;p< 0.001) along with participants who had AVC 1-99 (β 0.13;p< 0.001), and AVC ≥100 (β 0.16;p= 0.001), compared to AVC=0. The associations between continuous AVC and incident albuminuria remained after further adjusting for CAC score (p= 0.04), Lp(a) (p= 0.03), and the APOE-ε4 genotype (p= 0.04). The signal was consistent for ACR progression after further adjusting for CAC score (p< 0.01), Lp (a) (p< 0.01), and the APOE-ε4 genotype (p< 0.01).Conclusions:In a multi-ethnic cohort of participants free of CVD and CKD at baseline, AVC was independently associated with a higher risk of incident albuminuria and progression of ACR.

Circulation, Volume 150, Issue Suppl_1, Page A4134768-A4134768, November 12, 2024. Backgrounds:Heart failure (HF) associated with coronary artery disease (CAD) is a significant contributor to mortality in the elderly population of the United States. This study examines trends in HF in CAD-related mortality among adults aged 65 and older, focusing on geographic, gender, and racial/ethnic disparities from 1999 to 2020.Methods:A retrospective analysis was performed using the CDC WONDER database death certificates from 1999 to 2020. Age-adjusted mortality rates (AAMRs), annual percent change (APC), and average annual percentage change (AAPC) were calculated per 100,000 persons, stratified by year, sex, race/ethnicity, and geographical region.Results:Between 1999 and 2020, there were 6,571,263 deaths attributed to coronary artery disease (CAD) and 6,135,540 deaths related to Heart Failure (HF) in the US. Among adults aged 65 and older, HF in CAD caused 1,597,451 deaths, with 37.1% occurring in medical facilities and 30.3% in nursing homes. The AAMRs for HF in CAD decreased from 241.7 in 1999 to 156.2 in 2020 (AAPC: -2.23, p < 0.000001). This reduction was significant from 1999 to 2014, followed by a slight increase from 2014 to 2020. Men consistently had higher AAMRs than women (227.4 vs. 137.1), with women experiencing a more significant decline in rates (AAPC: -3.23, p < 0.000001). Racial disparities revealed the highest AAMRs among Whites (183.0), followed by American Indians/Alaska Natives (153.7), Blacks (134.6), Hispanics (123.7), and Asians/Pacific Islanders (81.6). The most significant reductions were observed in Hispanics (AAPC: -2.68, p < 0.000001). Geographically, AAMRs varied, ranging from 92.1 in Hawaii to 257.3 in West Virginia, with the Midwest showing the highest mortality (191.0). Nonmetropolitan areas exhibited higher AAMRs than metropolitan areas (202.6 vs. 166.1), although both showed moderate declines over time, more pronounced in urban areas (AAPC: -2.41, p < 0.000001).Conclusion:The study uncovers notable variances in HF in CAD-related mortality among elderly individuals in the United States based on race, gender, and geographic location. While the decrease in AAMRs from 1999 to 2014 indicates progress in cardiovascular care, the subsequent rise from 2014 to 2020 and enduring disparities call for specific public health measures to tackle these inequalities.

Circulation, Volume 150, Issue Suppl_1, Page A4139206-A4139206, November 12, 2024. Introduction:Maintaining LDL-C at goal levels is critical in populations at high risk for cardiovascular events, including people with heterozygous familial hypercholesterolemia (HeFH) and/or premature coronary artery disease (CAD). Despite multiple approved LDL-C lowering therapies for these populations, most patients are not at guideline-directed treatment goal.In vivobase editing to inactivate hepaticPCSK9has the potential to provide lifelong LDL-C lowering after a single course of treatment. Success of the base editing approach is contingent on safe and effective hepatocyte delivery and precise, consistentPCSK9editing.Aim:We set out to develop a base editing medicine to inactivatePCSK9with broad utility across diverse genetic backgrounds. Here we describe the investigational therapy, VERVE-102, and the design of the ongoing, phase 1b Heart-2 trial.Approach:VERVE-102 consists of an mRNA encoding an adenine base editor and guide RNA (gRNA) targetingPCSK9packaged in a novel, proprietary GalNAc lipid nanoparticle (LNP). VERVE-102 creates a precise A-to-G DNA edit to introduce a premature stop codon and thereby inactivatePCSK9in hepatocytes. In a DNA sequence analysis of 784,318 individuals from diverse ancestries, the 20 base-pair sequence targeted by the gRNA was identical in 99.97% of individuals. LNP delivery to hepatocytesin vivooccurs through either endogenous LDL receptor (LDLR) uptake or GalNAc-mediated endocytosis via the asialoglycoprotein receptor (ASGPR) and as such, may address the LDLR deficiency seen in a fraction of patients with HeFH. Heart-2 is a single ascending dose trial of VERVE-102 in males and females aged 18–65 with HeFH and/or premature CAD who require additional LDL-C lowering despite maximally tolerated oral lipid-lowering therapies. Participants receive a single intravenous infusion of VERVE-102 with 3 to 9 participants per dose cohort. The primary endpoint is safety and tolerability. Secondary endpoints include pharmacokinetics of VERVE-102 and changes from baseline in blood PCSK9 and LDL-C.Discussion:VERVE-102 was designed to access hepatocytes via either LDLR- or ASGPR-mediated uptake to enable robust LNP delivery and subsequentPCSK9editing. Consistency of the gRNA target site suggests that potential therapeutic benefits should apply broadly across ancestries. The ongoing Heart-2 clinical trial is intended to support selection of a safe and effective dose for future clinical investigation of VERVE-102.

Circulation, Volume 150, Issue Suppl_1, Page A4141571-A4141571, November 12, 2024. Background:Although ambient air pollution exposure has been linked with increased mortality in many cardiovascular or pulmonary diseases, its relationship with pulmonary arterial hypertension (PAH) is still unknown. The present study aims to investigate the association of ambient particulate matter (PM) exposure with pulmonary hemodynamics and long-term survival in patients with PAH in China.Methods:This retrospective multi-center cohort study included 1511 participants who underwent invasive right heart catheterization and were eventually diagnosed with PAH from January 2014 to December 2020. The primary outcome was transplant-free survival from the time of diagnosis. The association of PM2.5and PM10with all-cause death or lung transplantation was assessed by fitting Cox proportional risk models. Generalized linear models were used to examine the relationship between PM exposure and pulmonary hemodynamic severity at baseline. Restricted cubic splines were used to describe exposure-response curves. Mediation analysis with bootstrap method was used to explore whether potential variables mediated the associations.Results:During a median follow-up of 36.7 months, all-cause death or lung transplantation occurred in 149 patients. Per 10 µg/m3increase of PM2.5and PM10were associated with 14.5% and 7.9% increased risk of primary outcomes adjusting for potential confounding variables, respectively. PM2.5and PM10were associated with European Society of Cardiology risk stratification and with pulmonary hemodynamics at baseline, in particular pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP), cardiac index, and mixed venous oxygen saturation (SVO2). Effect of PM may be mediated in part by impaired glucolipid metabolism and inflammation-associated lymphocyte.Conclusions:Particulate matter exposure was associated with disease severity and pulmonary hemodynamics at baseline in patients with PAH, and higher chronic exposure to PM2.5and PM10independently predicted shorter transplant-free survival.

Circulation, Volume 150, Issue Suppl_1, Page A4141341-A4141341, November 12, 2024. Background:Aortic valve calcification (AVC) is the primary underlying process leading to aortic stenosis. Whether polygenic risk scores (PRS) are associated with AVC beyond traditional atherosclerotic cardiovascular disease risk factors (ASCVD) is unknown.Methods:This study included 6,812 Multi-Ethnic Study of Atherosclerosis participants who had AVC measured via CT at Visit 1 and single-nucleotide polymorphism (SNP) genotype data. Using previously published PRS for coronary artery disease (CAD), coronary artery calcium (CAC), and ASCVD risk factors we calculated a weighted PRS for each participant that was standardized within each ancestry group. The cross-sectional association of the individual PRS with AVC >0 was examined using multivariable logistic regression modeling with Bonferroni correction.Results:The mean age was 62 years old, 53% were women, and 913 (13.4%) of participants had AVC >0 at baseline. The PRS for CAD (HR 1.17, 95% CI 1.07-1.26), SBP (HR 1.13, 95% CI 1.04-1.24), LDL-C (HR 1.16, 95% CI 1.07-1.26), and lipoprotein(a) [Lp(a)] (HR 1.11, 95% CI 1.02-1.20) were significantly associated with AVC, while the other PRS including CAC (HR 1.02, 95% CI 0.94-1.10) and CRP (HR 0.97, 95% CI 0.89-1.05) were not (Table). In sex stratified analyses, the PRS for CAD, LDL-C, and Lp(a) were significantly associated with AVC >0 for both women and men (p0. Additionally, the lack of association for the CAC PRS with AVC >0 demonstrates that significant differences exist in the calcification pathways for AVC and CAC.

Circulation, Volume 150, Issue Suppl_1, Page A4125533-A4125533, November 12, 2024. Background:In the United States, over 38 million people have diabetes mellitus (DM) and more than 6 million have heart failure (HF). DM and HF often coexist, and each condition independently increases the likelihood of developing the other. Approximately 40% of individuals with HF also have DM, and this prevalence is even higher among older adults and hospitalized patients. While there has been concern regarding the increasing burden of disease for both conditions individually over the last decade, a comprehensive examination of mortality trends associated with their coexistence has not been thoroughly explored.Methods:This study analyzed death certificates from the CDC WONDER database, specifically focusing on mortality caused by the simultaneous presence of HF and DM among individuals aged 75 years and older. The data covers the period from 1999 to 2020. Age-adjusted mortality rates (AAMRs) per 100,000 individuals and annual percent change (APC) were computed and categorized based on year, gender, and race/ethnicity.Results:Between 1999 and 2020, a total of 663,016 deaths were reported in patients with coexisting HF and DM. Overall, AAMR increased from 154.1 to 186.1 per 100,000 population between 1999 and 2020, with an initial increase from 1999 to 2005 (APC: 0.80; 95% CI: -0.17 to 2.94), a significant decline from 2005 to 2011 (APC: -2.82; 95% confidence interval (CI): -5.47 to – 1.71), a subsequent increase from 2011 to 2018 (APC: 0.61; 95% CI: -0.59 to 2.18), and finally a steep increase from 2018 to 2020 (APC: 11.30; 95% CI: 6.98 to 14.11). Gender-based analysis revealed that older men had consistently higher AAMRs than older women (Men: 185; 95% CI: 184.3 to 185.6; vs Women: 135.4; 95% CI: 135 to 135.8). Furthermore, we found that AAMRs were the highest among non-Hispanic American Indian or Alaska natives (214.4; 95% CI: 207.5 to 221.4) followed by non-Hispanic African Americans (179.9; 95% CI: 178.5 to 181.4), Hispanics (159.5; 95% CI: 158 to 161.1), non-Hispanic White (152.9; 95% CI: 152.5 to 153.3), and non-Hispanic Asian or Pacific Islander populations (104.1; 95% CI 102.4 to 105.8) (Figure 1).Conclusion:The mortality rate due to coexisting HF and DM has increased in the elderly population over the past decade. Males and non-Hispanic American Indians or Alaskan Natives had the highest AAMRs in our study.

Circulation, Volume 150, Issue Suppl_1, Page A4139353-A4139353, November 12, 2024. Background:Coronary Artery Disease (CAD) in obese population is the most common cause of mortality worldwide. This study examines the variation in cardiovascular mortality rates due to CAD in obese adults aged 25 and above from 1999 to 2020.Methods:We performed a retrospective cohort study using death certificate data from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research (CDC WONDER) database from 1999 to 2020. We calculated age-adjusted mortality rates (AAMRs), annual percent change (APC), and average annual percentage change (AAPC) per 100,000 persons. The information was categorized based on year, gender, ethnicity, and geographic area.Results:Between 1999 and 2020, CAD in obesity accounted for 102,434 deaths among adults (≥25 years) in the United States. Majority of deaths occurred in medical facilities (49.0%), followed by decedents’ homes (36.8%). The overall AAMR for CAD in obesity-related deaths increased from 1.5 in 1999 to 3.3 in 2020, with an AAPC of 3.46 (95% CI: 2.83 to 3.92, p < 0.000001). Men exhibited higher AAMRs compared to women (men: 2.7; women: 1.6), with significant increases for both sex. The increase was more prominent in men (AAPC: 4.34, 95% CI: 3.73 to 4.83, p < 0.000001). Racial/ethnic disparities were evident, with American Indian or Alaska Native individuals having the highest AAMR (2.9), followed by Black or African American (2.4), White (2.3), Hispanic or Latino (1.3), and Asian or Pacific Islander (0.5). All racial groups experienced an increase in AAMR from 1999 to 2020, most pronounced in American Indian or Alaska Native individuals (AAPC: 5.06, 95% CI: 2.90 to 8.64, p < 0.000001). Geographically, AAMRs ranged from 1.0 in Alabama to 4.3 in North Dakota, with the Midwestern region having the highest mortality (AAMR: 2.6). Nonmetropolitan areas exhibited higher AAMRs than metropolitan areas (nonmetropolitan: 2.8; metropolitan: 2.0). (Figure 1)Conclusion:This study highlights significant demographic disparities in mortality rates due to CAD in obesity among adults aged 25 and older. Despite an overall increase in mortality rates, the significant rise in recent years, particularly among certain racial groups and geographical regions, emphasize the need for targeted interventions and equal healthcare access to improve outcomes for affected populations.

Circulation, Volume 150, Issue Suppl_1, Page A4139239-A4139239, November 12, 2024. Objective:Identification of individuals with reduced or preserved ejection fraction heart failure (HFrEF/HFpEF) within claims data is typically based on ICD-10-CM diagnosis codes that use systolic and diastolic HF (SHF/DHF) nomenclature. The objective of this study was to assess the performance characteristics of using ICD-10-CM diagnostic codes from claims data for HFrEF and HFpEF classification relative to a reference standard using EF results or clinician documentation within an integrated claims/EMR database.Methods:EMR data from the Healthcare Integrated Research Database (HIRD®) were searched to identify patients with EF assessment between 01/01/2016 and 01/31/2023. HFrEF was defined as EF ≤ 40% or documented reduced EF, while HFpEF was defined as EF ≥ 50% or documented preserved/normal EF. The most recent EF assessment date or EMR entry date (if EF assessment date not available) was set as the index date. Claims submitted from 7 days to 6 months post index date were then reviewed to identify SHF and DHF diagnoses as well as comorbid conditions. Analyses were performed to determine sensitivity, specificity, and positive/negative predictive values (PPV/NPV), accuracy and F1 scores of the claims-based algorithm, with a sensitivity analysis performed using the subset of patients with a known EF assessment date available.Results:A total of 45,272 patients had EF assessment in the EMR data with either a SHF or DHF diagnoses in the claims data. Mean (SD) age was 71.7 (12.7) years, 51.2% were male. The most common comorbidities of interest included hypertension (89.5%), dyslipidemia (71.9%), atrial fibrillation (45.9%), type 2 diabetes (43.7%), and chronic kidney disease (39.6%). Counts by heart failure classification and algorithm performance characteristics are in Table 1. Sensitivity analyses for those with known EF assessment dates showed similar results.Conclusions:Overall performance of the claims-based algorithm was good to very good, although EF data integrated with claims data can improve HF classification. Future claims-based algorithm development could also incorporate treatments and comorbidities to improve performance.

Circulation, Volume 150, Issue Suppl_1, Page A4147046-A4147046, November 12, 2024. Background:Stroke is one of the leading causes of death for older individuals with hypertension. This research investigates the variations in stroke mortality rates and trends among 65-year-old hypertension patients in the US from 2000 to 2020.Methods:The CDC WONDER database’s mortality data from 2000 to 2020 was used for a retrospective analysis. Average Annual Percentage Change (AAPC) and Annual Percent Change (APC) were used to evaluate trends and produce age-adjusted mortality rates (AAMRs) per 100,000 people. Data was stratified by year, sex, race/ethnicity, and geographical regions.Results:Between 2000 and 2020, 598,341 deaths among individuals 65 years of age or older in the United States were related to stroke due to hypertension. Most occurred in nursing homes/long-term care facilities (36.7%). The overall AAMR for stroke in hypertension-related deaths dropped from 86.6 in 2000 to 51.8 in 2020, with an AAPC of -2.86 (95% CI: -3.18 to -2.61, p < 0.000001). Between 2000 and 2012, the AAMR had a considerable reduction (APC: -2.30, p < 0.000001). Subsequently, from 2012 to 2018, there was a more dramatic decrease (APC: -6.85, p < 0.000001) than a notable rise (APC: 6.45, p = 0.024) from 2018 to 2020. Older women had higher AAMRs than older men (women: 66.5; men: 60.1). Both sexes experienced decreases, with the decline more prominent in women (women: AAPC: -3.20, p < 0.000001; men: AAPC: -2.22, p < 0.000001). There were notable racial differences: Black people had the highest AAMRs (31.0), followed by White people (21.8), American Indians and Alaska Natives (18.6), Asians and Pacific Islanders (12.9), and Hispanics (12.5). All racial groups experienced decreases in AAMRs, most pronounced in Asians (AAPC: -4.62, p < 0.000001). Geographically, Massachusetts had the lowest (36.3), and Mississippi had the highest (117.7) AAMRs. The Western region had the highest average AAMR (71.8), while nonmetropolitan areas exhibited higher AAMRs than metropolitan areas (nonmetropolitan: 25.9; metropolitan: 20.7).Conclusion:The study uncovers significant variations in mortality rates among elderly individuals in the US due to stroke and hypertension. The recent uptick emphasizes the necessity for targeted efforts to tackle these disparities and improve the health outcomes of affected communities.

Circulation, Volume 150, Issue Suppl_1, Page A4141689-A4141689, November 12, 2024. Background:Female patients referred for coronary artery bypass grafting (CABG) are generally older and have more comorbidities than their male counterparts. Although higher perioperative mortality among female patients has been reported, there is a lack of large-scale, real-life data on this outcome and its trend.Aim:To study the mortality rate among female patients undergoing CABG from 2015-2020 and compare it with that of their male counterparts.Methods:The National Inpatient Sample from January 2015 to December 2020 was utilized to identify the study population using the International Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification. The primary outcome was the overall in-hospital mortality of CABG based on sex, and the secondary outcome was the mortality trend between the groups.Results:We evaluated 929,759 patients who underwent CABG, of whom 230,000 (24.3%) were female. The female patient group was slightly older than the male patient group (66.4 vs 65.4 years, P

Circulation, Volume 150, Issue Suppl_1, Page A4141628-A4141628, November 12, 2024. Introduction:Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality worldwide. Lipid-lowering therapies (LLTs) are a key element to reduce the risk of recurrence of ASCVD events. However, despite concordant guidelines, LLTs are often underused in real-life setting.Research questions:The aim of this study is to describe the use of LLTs and its impact on morbi-mortality in the year following a first ASCVD event.Methods:This retrospective study used the national health data system (SNDS), collecting health insurance claims and hospital discharge data from 99% of the French population. Incident cases in 2021 were identified, corresponding to all adults with a first ASCVD event, based on ICD-10 hospital coding. ASCVD includes coronary artery disease [myocardial infarction, unstable angina or coronary revascularization], cerebrovascular events [ischemic stroke, carotid revascularization] and peripheral artery disease (PAD) requiring artery revascularization. In patients discharged alive from the index event, longitudinal analyses were performed at 1-year from discharge to describe LLT use, occurrence of major ASCVD events and all-cause mortality.Results:In 2021, 195,211 newly diagnosed ASCVD cases were identified among 43,1M adults (mean age: 70.3 (±13.7) yo; 62% of male). The first ASCVD event was myocardial infarction (N=51,614) or ischemic stroke (N=52,865) in 53.5% of incident cases. The remaining 46.5% corresponded mostly to coronary revascularization procedures (N=83,910), followed by PAD (N=26,925). In-hospital mortality was 5.5% (N=10,673). In patients analyzed at 1 year (N=180,875), 16.9% did not receive any LLT. This value rose to 26.7% among patients who had no received LLT prior to the ASCVD event. After a myocardial infarction, patients were more likely to receive LLT (91.9%) compared to after an ischemic stroke (72.9%) or revascularization for PAD (68.0%). Finally, 1-year all-cause mortality was higher in non-LLT compared to LLT patients (20.9% vs 4.0%). Additional data on the recurrence of ASCVD events as a function of LLT use are currently being analyzed and will be presented at the congress.Conclusion:Contrary to recommendations, the underuse of LLTs after a first ASCVD event remains very high, particularly after a stroke. This is associated with a significantly higher mortality at 1 year, justifying the need to reinforce implementation of the guidelines in real life for a better management of residual lipid risk.

Circulation, Volume 150, Issue Suppl_1, Page A4139238-A4139238, November 12, 2024. Intro:Myocarditis is an inflammatory cardiac condition that may progress to dilated (DCM) or arrhythmic (ACM) cardiomyopathy. Prior cohort studies indicate genetic factors significantly influence myocarditis susceptibility and outcomes; yet, this has not been studied at a population level, which holds potential for clinical risk prediction.Objective:To investigate DCM and ACM gene variant burden and clinical consequences by a multi-population approach encompassing diverse genetic ancestries.Methods:Individuals with exome sequencing (ES) in UKBB and AoU were included, and poor-quality samples excluded. Individuals with myocarditis were identified by ICD code and compared with myocarditis-neg population. Cardiomyopathy (CM) genes in ClinGen DCM- and ARVC-associated genes with at least moderate evidence of disease causality were included and filtered by our previously published variant pipeline and ClinVar 2* criteria for pathogenic/likely pathogenic (P/LP). Cardiac phenotype and CM variant burden were analyzed by chi-squared analysis.Results:200,580 individuals in UKBB and 230,013 in AoU had ES. 137 in UKBB and 284 in AoU had myocarditis. Myocarditis cohorts in both populations had increased phenotypic burden of CM, ventricular arrhythmia, and HF vs myocarditis-neg. Myocarditis-pos showed increased CM (16.8% vs 0.2%); VA (10.9% vs 0.9%) and HF (32.8% vs 3.1%) in UKBB (p

Circulation, Volume 150, Issue Suppl_1, Page A4144617-A4144617, November 12, 2024. Introduction:Over the past two decades, treatment advances for atrial fibrillation (AF) and stroke have improved overall survival (OS). However, a significant proportion of the population still faces high mortality, suggesting an uneven distribution of improvements. This study analyzes mortality after stroke in older adults with AF in the United States (US), highlighting disparities and trends.Method:A retrospective analysis was conducted using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database, extracting data through ICD-10 code I48, I63.1, I63.2, I63.4, I63.5, I63.8, I63.9, I64, I69.4, to find stroke-related deaths among people diagnosed with AF, aged ≥65 years old from 1999 to 2019. We examined demographic disparities in mortality rates by age, gender, race, geographic region, rural/urban classification, and place of death. Results were reported as age-adjusted mortality rates (AAMR) with 95% confidence intervals (CI). Joinpoint regression assessed trend changes and average annual percentage change (AAPC).Results:Between 1999 and 2019, 398,571 individuals aged 65 and older died from AF and stroke in the US, with an AAMR of 45.6 per 100,000 (95% CI: 45.5-45.8). The AAMR declined from 47.0 in 1999 to 45.7 in 2019. Mortality rates showed disparities: females had a higher AAMR than males (46.4 vs. 43.4), non-Hispanics higher than Hispanics (46.7 vs. 27.9), and Whites higher than Blacks (48.5 vs. 32.8). The West was the most affected region (53.9), while the Northeast was the least affected (42.1). State variations were most pronounced in Vermont and Oregon (84.9 and 78.6) and lowest in Louisiana and Nevada (28.3 and 27.0). Rural areas had higher AAMR than urban areas (51.1 vs. 44.4). Most deaths occurred in inpatient settings (39.3%), followed by nursing homes (32.6%). The age group 85 years and older accounted for the majority of deaths (56.5%).Conclusions:Overall mortality due to stroke and AF has decreased, yet disparities persist. Focused action is needed to mitigate these deaths. Expanding access to healthcare in rural areas and promoting stroke prevention programs are vital for improving survival rates.

Circulation, Volume 150, Issue Suppl_1, Page A4138722-A4138722, November 12, 2024. Introduction:Multidisciplinary team (MDT) discussions are integral to Transcatheter Aortic Valve Implantation (TAVI) decision making. Large language model (LLM) ubiquity and low-code no-code platforms have enabled clinician lead solution development. Specialised chatbots or ‘agents’ have evolved into multi-agent systems that can personify human collaboration. We assess the performance of an artificial intelligence (AI) multi-agent TAVI MDT.Methods:Four de-identified TAVI cases from two metropolitan Australian hospitals were assessed by a mock human TAVI MDT (h-MDT) and an AI multi-agent TAVI MDT (ai-MDT). The ai-MDT was created with Agentflow within Flowise AITM and had a hierarchical multi-agent architecture suited to complex reasoning required for TAVI MDT simulation (figure). LLM limitations necessitated the ai-MDT rely on imaging reports rather than clinical images. The h-MDT and ai-MDT consisted of similar team members. Outputs from the h-MDT and ai-MDT was adjudicated by a panel of four blinded TAVI doctors that determined if output was human vs AI and assigned a SMIC score (4-12, 4=good, 12=poor) that assessed structure, missing information, incorrect information and clinical utility. Time durations for h-MDT and ai-MDT were recorded.Results:Adjudicators differentiated human vs. AI output 100% of the time and ai-MDT output had better SMIC scores than h-MDT (U-stat 213, p=0.0011). ai-MDT outperformed h-MDT in the domains of structure, missing information and clinical utility but was not statistically different in the incorrect information domain (U-stat 132, p=0.88). The average time for each case in h-MDT was 15 minutes and 45 seconds compared to 97 seconds for ai-MDT.Conclusion:This demonstrates the potential of using LLM based multi-agent systems as a clinical adjunct in highly specialized multidisciplinary clinical meetings. AI responses were superior for structure, clinical utility and missing information and non-inferior for incorrect information compared to humans, which highlights that hallucinations remain an issue with generative AI. Time was saved but image interpretation still requires human input, for now. Cognitive AI continues to require human supervision for implementation.

Circulation, Volume 150, Issue Suppl_1, Page A4135095-A4135095, November 12, 2024. Background:While anticoagulation is crucial for atrial fibrillation (AF) patients to prevent ischemic events, those with thrombocytopenia have a potential increased risk of bleeding. This study examines the outcomes of hospitalized AF patients with thrombocytopenia.Methods:The National Inpatient Sample (NIS) from 2016-2020 was analyzed to identify adult patients with AF and thrombocytopenia (using the proper ICD-10 codes). Multivariate logistic and regression analyses were performed after adjusting for multiple patient and hospital confounders to compare outcomes between patients with and without thrombocytopenia. The primary outcome was all-cause inpatient mortality. Secondary outcomes included major bleeding (defined as gastrointestinal, intracranial, pulmonary, or unspecified bleeding), hypovolemic shock, packed red blood cell (pRBC) transfusion, ischemic stroke, length of stay (LOS), and total charges.Results:Among 2,016,244 AF admissions, 75,545 patients (3.75%) had thrombocytopenia. Thrombocytopenia was associated with increased inpatient mortality (adjusted odds ratio [aOR] 2.47, 95% CI 2.21-2.77, p < 0.001). Thrombocytopenia was also associated with increased risk of major bleeding (aOR 1.99, 95% CI 1.8-2.19, p < 0.001), hypovolemic shock (aOR 3.11, 95% CI 2.29-4.24, p < 0.001), pRBC transfusion (aOR 3.07, 95% CI 2.8-3.37, p < 0.001). There was no significant difference in ischemic stroke risk (aOR 0.67, 95% CI 0.37-1.21, p < 0.19) but thrombocytopenia was associated with longer LOS (aMD 1.5 days, 95% CI 1.41-1.59, p < 0.001) and higher total charges (aMD $16,508, 95% CI 14,805-18,211, p < 0.001).Conclusions:Thrombocytopenia in hospitalized AF patients is associated with increased mortality, bleeding risk, and healthcare costs, with no clear impact on ischemic stroke. These findings highlight the need for careful risk-benefit assessment and individualized management strategies for this vulnerable patient population.