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

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 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 A4147674-A4147674, November 12, 2024. Background:Leadless pacemaker (LP) is a novel pacemaker offering an innovative approach to bradyarrhythmia treatment. Aveir LP and Micra LP are the two leadless pacing systems available in the United States. Aveir LP was approved by the Food and Drug Administration (FDA) in April 2022. Data regarding the adverse events (AE) following implantation of Aveir LP is scarce, largely limited to single centers, and no real-world comparative analyses were done previously.Methods:We queried the FDA Manufacturer and User Facility Device Experience (MAUDE) database between April 2022 and December 2023 to assess the safety and AE following implantation of Aveir LP. “AVIER” and “MICRA” were the key terms used to search the MAUDE database. The event types “death” and “injury” were included in our search to capture major clinical events related to the patient. Disproportionality analysis was performed using the reporting odds ratio (ROR) to compare the adverse events of Aveir LP with Micra LP. A signal to noise ratio was considered to be significant if the confidence interval (CI) did not cross the number “one”.Results:Our search resulted in 207 event reports for Aveir LP and 1969 event reports for Micra LP. Major device related adverse events with Aveir LP were capturing problem (33.8%) followed by dislodgement (16.9%), and sensing problem (7.2%). Most encountered device related AE with Micra LP were capturing problem (37.8%), pacing problem (11.5%), and sensing problem (9.3%). Frequencies of all the analyzed AE are shown in Figure 1. The reporting of pericardial effusion (ROR 2.84, 95% CI 2.18-3.71), and dislodgment (ROR 1.85, 95% CI 1.26-2.73) were significantly higher with Aveir, whereas cardiac arrest (ROR 0.18, 95% CI 0.04-0.74) was disproportionately lower. Overall, patient related AE were significantly higher (ROR 1.53, 95% CI 1.20-1.95) and device related events were significantly lower (ROR 0.65, 95% CI 0.51-0.83) with Aveir LP compared to Micra LP (Figure 2).Conclusion:This is the first real-world comparative analysis of two leadless pacing systems available in the United States. Our analysis showed that, when compared to Micra LP, the newer Aveir LP had lower device related events but higher patient related events, largely driven by pericardial effusion. These events could be attributed to the operator learning curve and long-term data are needed to further verify these findings.

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 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 A4147547-A4147547, November 12, 2024. Background:Paroxysmal atrial fibrillation (PAF) is an intermittent irregular arrhythmia that terminates within seven days. Prior studies have shown that females with atrial fibrillation are at increased risk of mortality and readmissions compared to men. Given the dramatic rise in PAF diagnoses over the past several years, the impact of sex on clinical outcomes in this patient population requires further analysis. This study aims to investigate sex-based disparities in clinical outcomes over recent years for patients with PAF.Methods:In this large scale, retrospective cohort study, patients who were admitted with PAF were analyzed from 2016 to 2020 using the National Readmissions Database. The study population was divided into male and female groups. Diagnoses were classified according to the International Classification of Diseases Tenth (ICD-10) Revision codes. The primary outcome was 30-day readmissions. Secondary outcomes included inpatient mortality and length of stay.Results:During the study period, a total of 548,617 patients with PAF meeting inclusion criteria were admitted. Of this population, 55.3% were female (n = 303,412) and 44.7% (n =245,205) were male. The mean age was 73.7 ± 11.9 years for females and 65.7± 13.6 years for males. After adjusting for baseline characteristics, female sex was associated with a higher 30-day readmission rate (HR: 1.06, CI: 1.03-1.09, p < 0.001). Multivariate regression analysis for inpatient mortality and length of stay was higher for females than males (p < 0.01 for both).Conclusion:Female patients experienced worse overall outcomes compared to male patients with higher readmission rates, inpatient mortality, and longer length of stay. These data suggest that targeted intervention for females may be required to improve these outcomes.

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 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 A4147256-A4147256, November 12, 2024. Introduction:Studies suggest a complex relationship between body mass index (BMI) and percutaneous coronary intervention (PCI) outcomes. However, the effect of obesity on in-hospital outcomes of PCI with mechanical circulatory support (MCS) for acute myocardial infarction complicated by cardiogenic shock (AMICS) has not been established.Objective:To characterize outcomes of PCI with MCS for AMICS in patients with and without obesity.Methods:In the National Inpatient Sample (NIS) 2016-2020, we identified patients with AMICS treated with MCS with obesity (BMI 30.0-39.9) or normal BMI (20.0-24.9). The primary outcome was in-hospital mortality. Secondary outcomes included cardiac arrest, stroke, acute kidney injury, bleeding, acute respiratory failure, palliative consults, hospital length of stay (LOS), and total charges. Multivariate logistic regression models adjusted for baseline characteristics and estimated odds ratios (ORs) with 95% confidence intervals (CIs).Results:5270 patients met study criteria (4870 obese). Obese and normal weight patients had a mean age of 69.8 vs. 63.5 years and male sex 78.1% vs. 71.3%. Obese patients had more hypertension, diabetes, dyslipidemia, and previous myocardial infarction (Table 1A). There was no difference in mortality [OR 0.84, CI (0.41-1.71), P=0.623] or the secondary outcomes (Table 1B). Normal weight was associated with longer LOS (13.0 vs. 8.5 days) and higher charges ($325,926.3 vs. $294,629.1).Conclusion:There were no significant differences in in-hospital mortality or secondary outcomes between obese and normal-weight AMICS patients treated with PCI and MCS. PCI with MCS may be performed safely in AMICS patients with and without obesity.

Circulation, Volume 150, Issue Suppl_1, Page A4146016-A4146016, November 12, 2024. Introduction:Atrial Fibrillation is the most common arrhythmia, causing an irregular and rapid heart rate. This occurs due to electric and structural remodeling of the atria, which creates the rapidly discharging foci.Aims:This study aims to explore the national mortality trends resulting from Atrial Fibrillation and Flutter in the United States from 1999-2022 while also studying the discrepancies among the various socio- demographic groups.Methods:The death certificate data from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiological Research (CDC Wonder) database were explored to investigate the Atrial fibrillation and flutter mortality from 1999 to 2022, focusing on the Age-Adjusted Mortality Rate (AAMR) per 1,000,000 individuals. We employed Joinpoint Regression Analysis to compute Annual Percent Changes (APC) with a 95% Confidence Interval. The data was further stratified into epidemiological groups of age, gender, ethnicity, and census region.Results:There was a steady rise in mortality from 1999 to 2017 (APC: 2.96), followed by a rapid surge in mortality trends from 2017 to 2022 (APC: 7.35). The mortality rate rose fairly equally among both genders over the years, with males having a slightly steeper incline (Male AAPC: 4.27, Female AAPC: 3.43). African Americans had the greatest number of deaths due to atrial fibrillation and flutter and the greatest rise was during recent years from 2017 to 2022 (APC: 9.64). The atrial fibrillation and flutter related mortality was the greatest among 25-34-year-olds, with the mortality decreasing among the older populations. All US Census regions had similar mortality rates and trends.Conclusion:This study reveals an overall rise in mortality associated with atrial fibrillation and flutter. It also highlighted disparities across gender, age, and geographic regions. These findings emphasize the need for further research and the development of targeted interventions to reduce mortality and alleviate the burden of this debilitating condition.

Circulation, Volume 150, Issue Suppl_1, Page A4137925-A4137925, November 12, 2024. Introduction:Thoracic endovascular aortic repair (TEVAR) has emerged as a promising treatment option for patients with type B aortic dissection (TBAD). However, there is a lack of evidence regarding the long-term morbidity of initial TEVAR compared to optimal medical therapy (OMT) in acute uncomplicated TBAD (uTBAD).Objective:To evaluate real-world data(RWD) on the long-term outcome of Japanese patients with acute uTBAD using a nationwide claims database.Methods:This retrospective cohort study utilizes JMDC, a nationwide claims database under Japan’s universal healthcare system. We included patients who were initially hospitalized with a diagnosis of acute TBAD. We defined acute uTBAD by excluding those who died within one month, suffered aortic rupture, traumatic thoracic aortic injury, underwent open-chest surgery, experienced stroke or paralysis, or had less than six months of history in the JMDC. Patients who underwent TEVAR within three months of the index hospitalization (TEVAR group) were compared with those who received optimal medical therapy (OMT group). Propensity score (PS) matching was performed based on age, sex, and year of hospitalization. Using the Kaplan-Meier method, we calculated the cumulative rate of all-cause mortality and aorta-related events.Results:Of 18,445 patients diagnosed with aortic disease between January 2005 and December 2020, 641 were included in the study (OMT group: n=580, TEVAR group: n=61). After PS-matching, demographics of the groups (OMT_PSM: n=183 vs. TEVAR_PSM: n=61) were female (12.6% vs. 13.1%), median age (54 years [IQR, 48-60] vs. 54 years [IQR, 50-61]) and follow-up time (18 months [8-32] vs. 19 months [9-32]), respectively. Kaplan-Meier curves for the aortic-related events (Figure1, 2) are shown as long-term outcomes.Conclusions:This study successfully demonstrated that the estimated 5-year aortic-related event rate in acute uTBAD patients undergoing OMT is approximately 20%, demonstrating the relevance of the RWD source. However, the number of death events in the TEVAR and OMT groups was not sufficient to provide statistical power. Therefore, further studies are warranted to evaluate the long-term prognosis of initial TEVAR for uTBAD.

Circulation, Volume 150, Issue Suppl_1, Page A4144043-A4144043, November 12, 2024. Introduction:Artificial intelligence-powered coronary artery calcium scan (AI-CAC) provides more actionable information than currently reported. We have previously shown in the Multi-Ethnic Study of Atherosclerosis (MESA) that AI-enabled left atrial (LA) volumetry in CAC scans (AI-CAC) enabled prediction of atrial fibrillation (AF) as early as one year. Furthermore, we have shown adding AI-CAC LA volumetry to CHA2DS2-VASc risk score improved stroke prediction in MESA. We have recently reported that AI-CAC left ventricular (LV) volumetry and mass significantly predicted incident heart failure (HF) and outperformed NT-proBNP. In this study, we compared LV volume measured by AI-CAC versus cardiac magnetic resonance (CMR) imaging and NT-proBNP for predicting HF. Additionally, we compared AI-CAC vs. NT-proBNP for detection of left ventricular hypertrophy (LVH) defined by the 95th percentile of CMR LV mass.Methods:We used 15-year outcomes data for incident HF from 3078 asymptomatic MESA participants (52.3% women, age 62.2±10.3 years) who underwent both CAC scans and CMR at the baseline examination. We applied the AutoChamberTM(HeartLung.AI, Houston, TX) component of AI-CAC to 3078 CAC scans.Data on CMR semi-automated LV volume, NT-proBNP, and Agatston CAC score were obtained from MESA. Discrimination was assessed using the time-dependent area under the curve (AUC) for incident HF.Results:Over 15 years of follow up, 133 cases of HF were diagnosed. The AUC for AI-CAC (0.789) and CMR (0.793) were not significantly different (p=0.67) but were significantly higher than NT-proBNP (0.719) and Agatston score (0.664) (p

Circulation, Volume 150, Issue Suppl_1, Page A4144822-A4144822, November 12, 2024. Background:The relationship between anion gap (AG) and short-term mortality in intensive care unit (ICU) sepsis patients complicated by pulmonary hypertension (PH) remains unclear.Methods:Retrospective analysis of incident sepsis patients complicated by PH first admitted to ICU in MIMIC database (2008 to 2019) were enrolled. Short-term outcomes include in-hospital mortality and 28-day mortality. According to the AG value (17.0 mmol/L), patients were divided into high and low AG groups. The Kaplan-Meier survival curve was used to compare the cumulative survival rates of the high and low groups using the log-rank test. Multivariable Cox regression analyses were constructed to assess the relationship between AG and short-term outcomes in sepsis patients complicated by PH.Results:2012 sepsis patients with pulmonary hypertension were included. The in-hospital mortality rates (11.4%) and 28-day mortality rates (12.8%) in the high AG group were higher than those in the low AG group (5.0% or 7.2%, respectively;P< 0.001). The Kaplan-Meier curve showed that the in-hospital and 28-day cumulative survival rates were lower in the high AG group than that in the low AG group (P< 0.001). Multivariable Cox regression analysis confirmed that elevated AG was an independent risk factor of in-hospital mortality, 28-day mortality, length of stay in ICU and hospital. The relationship between elevated AG and in-hospital mortality remain stable after subgroups analyses.Conclusions:Elevated serum AG is associated with increased risk-adjusted short-term mortality in sepsis patients complicated by PH, and it may remind clinicians to identify patients with poor prognosis as early as possible.

Circulation, Volume 150, Issue Suppl_1, Page A4143840-A4143840, November 12, 2024. Introduction:Transthyretin (TTR) dissolution into monomer form and subsequent misfolding causes amyloidosis through deposition of beta-pleated sheets in end organs. Genetic sequence variations can decrease the stability of TTR leading to earlier disease manifestation, a condition known as hereditary TTR amyloidosis (hATTR). The most common variant in the U.S. – V142I, is most prevalent in individuals of African descent. We sought to explore the relationship of V142I and cardiac manifestations of hATTR, using the Million Veteran Program (MVP) dataset.Methods:We identified all V142I carriers in the MVP dataset who had a first visit before January 2008. Carriers were matched with controls at a 1:5 ratio based on age, sex, and race. The outcome studied was development of heart failure (HF)/cardiomyopathy (CM). Cumulative incidence and multivariable Cox proportional hazards regression models were performed to compare V142I carriers with the matched control group.Results:A total of 2,658 V142I carriers (3.1% of veterans of African descent in MVP) and 13,467 matched control patients were included in our final study cohort. Carriers at baseline had a median age of 53 [46-60] years, 87.2% were male, 3.5% had HF, 34.0% had type 2 diabetes mellitus (T2DM), 8.0% had bilateral carpal tunnel syndrome (BCTS), 5.2% had spinal stenosis (SS), and 19.4% had neuropathy. Patients in the control group at baseline had a median age of 53 [46-60] years, 87.2% were male, 3.4% had HF, 33.6% had T2DM, 7.9% had BCTS, 5.0% had SS, and 19.6% had neuropathy. Cumulative incidence of HF/CM at age 70, 80 and 90 years was 23.8%, 48.0%, and 68.8% for cases, and 23.7%, 40.5%, and 56.7% for controls (p=0.006), respectively(Figure).In a multivariable Cox proportional hazards regression model, carrier status was associated with higher incidence of HF/CM – HR of 1.13 (CI: 1.03-1.23, p=0.004). T2DM, hypertension, Charleston comorbidity index and current smoking were also associated with the outcome.Conclusions:We report on higher risk of developing HF/CM in V142I variant carriers compared to controls in the MVP cohort. Further research is needed to determine the most effective diagnostic and treatment approaches in veterans who may be V142I carriers at risk of developing HF/CM.

Circulation, Volume 150, Issue Suppl_1, Page A4143707-A4143707, November 12, 2024. Introduction:The population of men and women who are overweight (defined as a BMI 25-29.9 kg/m2) continues to grow at fast pace. The prevalence and prognostic implications of a high coronary artery calcium (CAC) score in this group are poorly defined.Aims:Using a multiethnic cohort of men and women, we compared the ASCVD event-risk at follow up in normal weight, overweight, and obese individuals, overall and further stratified by CAC scores.Methods:Individual-level pooled analysis of participants from MESA, JHS, HNR, and FHS free of ASCVD at baseline and in whom CAC and BMI data were available. Participants with BMI 0, and 22% had CAC≥100 (17% prevalence among individuals with normal weight). The distribution of CAC by BMI categories is presented in the Figure. The incidence of ASCVD events among overweight participants was: 3.8 per 1000 person-years for those with CAC=0, 8.1 for CAC >0 –

Circulation, Volume 150, Issue Suppl_1, Page A4137177-A4137177, November 12, 2024. Background:Arrhythmia is always a concern in oncological treatments. The advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, enhancing the immune system’s ability to combat malignancies. They are being more frequently used, revealing a range of immune-related adverse events (irAEs). This study aims to investigate the incidence of cardiac arrhythmias in patients receiving Pembrolizumab.Methods:We conducted a retrospective analysis of the FDA Adverse Event Reporting System (FAERS) database, focusing on reports submitted between 2006 to 2024. Cases involving patients treated with ICs were identified, and information related to cardiac arrhythmias was extracted using the Medical Dictionary for Regulatory Activities (MedDRA). Patients ≥ 18 years of age treated with ICIs were included in this study. A disproportionality analysis was conducted to identify arrhythmia events associated with pembrolizumab by comparing it with other immune checkpoint inhibitors (nivolumab, ipilimumab, and atezolizumab) and the entire FAERS database using the reporting odds ratio (ROR) and information component (IC).Results:A comprehensive analysis of 61,236 reported cases of pembrolizumab use revealed a total of 3,901 cases with cardiac complications. Among these, 672 cases (17.22 %) of arrhythmias were reported, with 452 individuals (67.26%) requiring hospitalization and 172 cases (25.59%) resulting in fatalities.Atrial fibrillation emerged as the most prevalent arrhythmia (49.7%). The occurrence of ventricular tachycardia with an ROR of 1.67 (1.18–2.35) and an IC of 0.44 (0.01–1.46) and complete atrio-ventricular block with an ROR of 1.57 (1.19–2.08) and an IC of 0.40 (0.04–1.24) were statistically significant. The reported arrhythmias associated with pembrolizumab are tabulated inTable 1. The majority of events were reported in males, as shown inFigure 1.Conclusion:This research offers significant insights into the connection between ICIs and cardiac arrhythmias, utilizing real-world data from the FAERS database. Healthcare providers should monitor cardiac events in patients receiving ICIs and aim to achieve a balance between anticancer effectiveness and cardiovascular safety. Further investigation is necessary to better understand the underlying mechanisms of arrhythmia and enhance risk stratification strategies for this specific patient group.