Risultati per: Analisi sull’uso dei farmaci anti-osteoporotici in sette database europei

Circulation, Volume 150, Issue Suppl_1, Page ASu703-ASu703, November 12, 2024. Introduction:Out of hospital cardiac arrest (OHCA) is a leading cause of death in the United States, with upwards of 360,000 OHCAs annually. Receiving bystander cardiopulmonary resuscitation (CPR) almost doubles an individual’s odds of survival compared to those who don’t receive bystander CPR. Unfortunately, in the US, bystander application of CPR only occurs in 40% of OHCA. Improving the rate of bystander CPR and AED use will improve survival rates for OHCA.Minoritized populations experience worse outcomes from OHCA. Compared to non-Hispanic whites, they are less likely to survive to hospital discharge. A cross-sectional study of witnessed OHCA patients found that Black and Hispanic patients had lower rates of bystander CPR. Less is known about disparities in care for Asian American persons who experience OHCA. Studies using the Resuscitation Outcomes Consortium Epidemiologic Registry (ROC) and the Cardiac Arrest Registry to Enhance Survival (CARES) have concluded discrepant results, with ROC finding that Asian Americans were less likely to receive bystander CPR and CARES finding that they were just as likely to receive bystander CPR compared to non-Hispanic Whites. To that end, we sought to evaluate the association between bystander CPR and Asian race after witnessed OHCA.Objective:To evaluate the association between race/ethnicity and the odds of receiving bystander cardiopulmonary resuscitation (bCPR) after witnessed out-of-hospital cardiac arrest (OHCA).Methods:Data were obtained from the National Emergency Medical Services Information System (NEMSIS) database for adults (≥18 years) with a witnessed non-traumatic OHCA in the year 2022. Patients were separated into two groups: Non-Hispanic White and Asians. The primary outcome was the odds of receiving bCPR. Exclusions included traumatic etiology, do-not-resuscitate orders, and arrests witnessed by healthcare providers. Pearson’s chi-square test was used to test significance.Results:A total of 73,215 witnessed OHCA activations were included in this study. Overall, bystander CPR rates were lower for the Asian group (59.8%) compared to the Non-Hispanic White group (65.0%). Pearson’s chi-square test showed a statistically significant difference between the bCPR rates of the Asian group and Non-Hispanic White group, with a p-value of less than 0.001.Conclusion:Racial/ethnic disparities exist for Asian individuals in the odds of receiving bCPR after a witnessed non-traumatic OHCA.

Circulation, Volume 150, Issue Suppl_1, Page A4140981-A4140981, November 12, 2024. Introduction/Background:Patients with hematological malignancies are at a higher risk of developing atrial fibrillation. Additionally, it can predispose to an increased risk of bleeding limiting anticoagulation for stroke prevention. LAAO has been successfully utilized among patients with atrial fibrillation and contraindication to anticoagulation.Research Question:What are the outcomes and in-hospital complications of left atrial appendage occlusion (LAAO) among patients with atrial fibrillation and hematological malignancy?Methods:The National Inpatient Sample (NIS) was analyzed from 2015-2020 to identify admissions for LAAO among patients with and without a hematological malignancy. Baseline characteristics were compared between the two groups and multivariate logistic regression was used to analyze hospitalization outcomes.Results:We identified 89,920 weighted admissions for LAAO procedures of which 1,665 patients (1.85%) had a hematological malignancy. In the adjusted analysis, the odds of MACCE (aOR 1.86, 95% CI 1.10-3.14, p 0.0205), cardiogenic shock (aOR 3.76, 95% CI 1.95-7.24, p

Circulation, Volume 150, Issue Suppl_1, Page A4147077-A4147077, November 12, 2024. Background:Tricuspid regurgitation (TR) worsens heart failure symptoms and perpetuates right ventricular failure (RVF). Given the limited efficacy of medicines and high risk of surgical mortality, percutaneous therapeutic options are gaining importance. The TRILUMINATE study reported an 86% reduction in TR severity and 4% mortality rate using Triclip G4 tricuspid transcatheter edge-to-edge repair (T-TEER) system with improvement in health status. Triclip subsequently gained FDA approval for TR on April 2, 2024.Objective:To evaluate reported device and patient related adverse events during early experience with Triclip system for T-TEER.Methods:The events reported for Triclip since it gained FDA approval were extracted from the FDA MAUDE database. Previously published reports, duplicates and events before FDA approval were excluded. Grades of TR at baseline and after T-TEER associated with single leaflet device attachment (SLDA) were compared using Wilcoxon rank sum test.Results:After excluding 14 reports, 45 were included, dating from 04/02/24 to 05/31/24. Of these, 31 (67.4%) featured patient complications, with SLDA being the most frequent (n=24, 53%).(Figure-1) Cause of SLDA was reported in 8 reports.(Figure-2) SLDA led to regression of TR to pre-procedure levels in 10 patients and Polymorphic VT in one patient. Other patient issues included damage to leaflets (n=7, 15.6%) which necessitated surgery in one case and prompted consideration of the same in another. There were 4 reports of clip entrapment in the chordae. Device-related issues included 3 cases of leaks in the steerable guide catheter affecting its ability to hold the column, knotting on the lock line, difficulties with positioning the second clip above the valve, clip reopening beyond the expected 5°, clip opening while locked but staying closed post-deployment, delays in clip delivery, and challengers in guiding catheter positioning. No acute deaths were reported in the MAUDE database within 2 months of device approval.Conclusion:Our research findings summarize the reported adverse events during the early period following FDA approval of Triclip G4 T-TEER system. This provides valuable insights into common failure modes and complications, offering guidance on their optimal utilization. Multiple adverse events can be noted soon after approval of the Triclip, underscoring the importance of good initial training and proctoring.

Circulation, Volume 150, Issue Suppl_1, Page A4147863-A4147863, November 12, 2024. Background:Ischemic heart disease (IHD) affects over 120 million people and is the leading cause of death globally. Our study aims to assess the trends in IHD-related mortality in the regions of the Americas.Research Questions/Hypothesis:Has IHD-related mortality decreased from 2000 to 2019 in all regions of the Americas?Aims:Analyze differences in IHD-related mortality in different regions of the Americas.Methods:We analyzed the Pan American Health Organization (PAHO) database for IHD-related mortality rates in 2000, 2010, and 2019. The age-standardized mortality rates per 100,000 population were extracted, and trends were analyzed by gender and region.Results:The IHD-related mortality was consistently higher in males as compared to females in the last 2 decades. The mortality rate decreased in males in all regions from 2000 to 2019 apart from the Mexico, Central America and Latin Caribbean region where it increased from 115.12 in 2000 to 119.50 in 2019.The greatest decrease in IHD-related mortality in males was seen in the North America region from 164.49 in 2000 to 93.73 in 2019. This opposite trend was seen in females where mortality decreased in all regions from 2000 to 2019.Conclusion:The sociodemographic and temporal trends highlighted by this study need to be further investigated, and targeted policy measures are required to reduce the disparities in IHD-related mortality.

Circulation, Volume 150, Issue Suppl_1, Page A4124307-A4124307, November 12, 2024. Background:Obesity is considered a significant risk factor for numerous cardiovascular conditions due to its effects on cardiac structure and function. The prevalence of atrial fibrillation (AF) is elevated among patients with obesity due to the dysregulation of several mechanisms. Weight loss has been shown to reverse cardiac remodeling, leading to a lower recurrence of AF despite the better prognosis in obese patients described as the obesity paradox.Methods:We utilized the National Inpatient Sample 2016-2019 to extract patients ≥18 years of age admitted with AF as the primary diagnosis based on ICD 10 codes. We performed univariate and multivariate regression analysis for known coronary risk factors. We divided patients based on their body mass index (BMI), and our primary outcomes were determining the odds of electrical cardioversion (ECV) and cardiac ablation (CA) due to AF.Results:The analysis included 1,625,809 weighted patients. Patients include underweight (6.66%), normal BMI (4.03), overweight (6.51%), obesity class I (20.65%), obesity class II (21.45%), and obesity class III (40.7).After multivariate regression analysis, patients with obesity class I, II, or III had higher odds of ECV, irrespectively of coronary risk factors (OR 1.3, 95% CI 1.25-1.37, OR 1.3, 95% CI 1.32-1.43, OR 1.3, 95% CI1.29-1.38, respectively, with statistically significant P values). However, underweight or normal BMI patients had fewer odds of ECV (OR 0.5 95%CI 0.49-0.61 and OR 0.6 95%CI 0.58-0.74, respectively, with P values

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 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.

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 A4146535-A4146535, November 12, 2024. Introduction:Cardiovascular(CV) disease is one of the leading cause of death in females in USA out of which 44% suffer. According to the latest CDC guidelines, 13.4 % are suffering from the infertility.It includes the most common conditions including endometriosis, poly cystic ovarian syndrome. Studies shows a mutlitude of factors including genetic abnormalities, hormonal imbalances like chronic anovulation or increased androgens predispose the women to subsequent health conditions.Literature review suggests that long term cv risks are less understood in the infertile women.Aim:The aim of the study is to identify the CV outcomes including coronary heart disease(CAD) , acute coronary syndrome(ACS), and heart failure in women with underlying infertility condition.Methods:The NIS 2020 was queried for the female adult population (age >18 years) with a primary or secondary diagnosis of infertility. Prevalence of CV risk factors were compared between females with and without infertility problem. The association of cardiac diagnoses including CAD, ACS and was analysed. Multivariate regression analysis was performed taking all-cause mortality as a primary outcome.Results:A total of 3870 adult patients with a primary or secondary diagnosis of infertility were identified and the mean age was 36 years.In adult population without infertility condition, patients with an underlying infertility were found to have an increased association with DM (48.16%vs 23.11%; P

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.

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 A4134396-A4134396, November 12, 2024. Backgrounds:Ischemic heart disease (IHD) remains a leading cause of mortality globally and has a high prevalence in the United States, necessitating an understanding of long-term trends to inform interventions. This study examines IHD-related mortality trends among US adults from 1999 to 2020, considering demographic and geographic disparities.Aim:This study aimed to evaluate patterns and geographical variations in mortality associated with IHD among adults in the United States.Methods:Death certificates from the CDC WONDER database spanning from 1999 to 2020 were analyzed to investigate mortality related to IHD among adults aged 35 years and above. Age-adjusted mortality rates (AAMRs) per 100,000 persons and annual percent change (APC) were calculated, stratified by year, sex, race/ethnicity, and geographic region.Results:Ischemic Heart Disease (IHD) caused 12,756,359 deaths among U.S. adults aged 35 and above from 1999 to 2020. Annual trends in age-adjusted mortality rates (AAMRs) showed a decline from 48.7 in 1999 to 28.9 in 2020, with notable fluctuations. Men consistently had higher AAMRs than women. NH Black or African American individuals exhibited the highest AAMRs. Geographically, significant disparities existed among states and regions, with the Northeast having the highest mortality. Nonmetropolitan areas consistently had higher AAMRs compared to metropolitan areas, showing varying trends over the study period.Conclusion:Fluctuations in mortality trends among IHD patients were observed over the study duration, revealing significant disparities across demographic and geographic parameters. Targeted interventions are imperative to alleviate the burden of IHD and mitigate mortality rates in the United States.

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 A4141387-A4141387, November 12, 2024. Background and Objective:To investigate the differences in Ambulatory Blood Pressure Monitoring (ABPM) parameters in patients affected by VEGFR-TKI and tumors, and to summarize the relationship between VEGFR-TKI, tumors, and blood pressure.Methods:43 patients who received VEGFR-TKI anti-tumor treatment and developed induced hypertension were selected for ABPM. Additionally, 94 cases of tumor-associated hypertension and 96 cases of primary hypertension were randomly selected for comparison. The ambulatory blood pressure-related parameters between the VEGFR-TKI-related hypertension group and the tumor-associated hypertension group, as well as between the tumor-associated hypertension group and the primary hypertension group, were analyzed.Results:Compared with the tumor-associated hypertension group, the VEGFR-TKI-related hypertension group showed higher 24-hour average diastolic blood pressure [(85.37±13.21) vs. (80.41±10.71) mmHg,t=2.332,P=0.021], daytime average diastolic blood pressure [(85.98±13.19) vs. (80.69±10.98) mmHg,t=2.452,P=0.015]. Multivariate linear regression analysis revealed that after adjusting for tumor type and BMI, the use of VEGFR-TKI remained independently associated with nighttime average diastolic blood pressure (B=5.921,P=0.021). Compared with the primary hypertension group, the tumor-associated hypertension group exhibited significantly reduced nighttime systolic blood pressure decline rate [(1.10±9.01) vs. (6.33±6.87),t=-4.508,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 A4142847-A4142847, November 12, 2024. Background:Clonal hematopoiesis of indeterminate potential (CHIP) can contribute to cardiovascular risk. The Interleukin-6 receptor (IL6R) polymorphism (D358A) modifies the risk of coronary artery diseases among CHIP carriers in human cohorts. However, the effects of the IL6R D358A on IL-6 pathways are discordant with the canonical expectation, that the classical IL-6 signaling pathway is anti-inflammatory while the trans-signaling pathway is pro-inflammatory.Hypothesis:DNMT3A, the most frequent driver gene for CHIP, changes the inflammatory consequence of IL-6 classical signaling from anti-inflammatory to pro-inflammatory to worsen atherosclerosis.Method:We investigated if an anti-IL6R antibody modifies atherosclerosis associated with myeloidDnmt3adeficiencyin vivo.Ldlr-/-mice were transplanted with 10% bone marrow cells fromDnmt3a-/-mice/90% of wild-type (WT) cells compared with 100% WT transfer. After engraftment, mice consumed a high-fat diet, and received an anti-IL6R antibody for 10 weeks to assess aortic root atherosclerosis vs. control antibody treatment. We also investigated the differences between IL-6 classical- vs trans-signaling pathways and whetherDnmt3adeficiency in bone marrow-derived macrophages (BMDM) modifies the IL-6 pathways. RNA-seq was performed in BMDM stimulated with IL-6, which activates the classical IL-6 pathway, or IL-6/IL6R conjugate, which activates trans-signaling. We further compared IL-6 vs control stimulation betweenDnmt3a-/-and WT BMDM using RNA-seq, and the major finding was replicated by quantitative PCR. In addition, IL-1β was quantified in the conditioned medium.Result:Anti-IL6R antibody treatment reduced atherosclerosis in the mice with myeloidDnmt3adeficiency. IL4R expression rose significantly in BMDM stimulated by IL-6 compared to IL-6/IL6R conjugate. IL4R induction by IL-6, but not the IL-6/IL6R conjugate, fell significantly inDnmt3a-/-BMDM compared to WT. IL-1β secretion declined with IL-6 stimulation and was higher in IL6R deficient BMDM, but IL-6 stimulation and deletion ofIL6Rdid not affect IL-1β secretion inDnmt3a-/-BMDMs.Conclusion:These data suggest that DNMT3A tonically limits the IL-6 classical pathway to limit atherogenesis in an IL-4 signaling-dependent manner. These findings promote understanding of the CHIP-atherosclerosis association and inform the development of management strategies for CVD risk in CHIP carriers.