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

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 A4146424-A4146424, November 12, 2024. The role of genetic ancestry (GA) in hypertensive pregnancy disorders in Latin-American women is poorly understood.Using data from amulti-center case-control study (GenPE) of preeclampsia (PE) in young Colombian women(median age = 19) of predominantly low socioeconomic status (2364 controls and 1811 cases), who identify as Afro-Caribbean (AFR-C), White Hispanic (HISP), Amerindian, and Mixed ethnicity,we evaluated associations between 1) reported ethnicity, and 2) empirically estimated GA, with PE. We performed 3-way admixture mapping using European (EUR), African (AFR) and Amerindian (AMR) ancestry references from the Human Genome Diversity Project using the FLARE software to estimate local and global ancestry in GenPE samples. Statistical significance threshold, for three-way local ancestry analyses, was empirically estimated using STEAM (P = 3.45×10-6).In multivariable logistic regression modelsfor reported ethnicity,AFR-C were 33% more likely to have PE (OR = 1.33; P = 0.02) than HISP women.In models evaluating empirically estimated global GA,AFR was positively associated (OR per 10% increase in ancestry = 1.05; P = 0.002), while AMR (OR = 0.91; P = 0.035) and EUR (OR = 0.95; P = 0.009) were inversely associated with PE. Additionally,adjusting for reported ethnicity in models evaluating global GA and PEchanged estimates only marginally for AFR (OR = 1.04; P = 0.025) and EUR (OR = 0.92; P = 0.009).Evaluation of GA and PE in a subset of women who reported AFR-C ethnicity, showed stronger estimates for all global ancestries: AFR (OR = 1.11; P = 0.013, EUR (OR = 0.82; P = 0.026), and AMR (OR = 0.83; P = 0.01).Association analyses with AFR local GA identified three loci associated with PE.The top locusat chromosome 11, rs2021740 (a smooth muscle enhancer inOTOG1and nearMYOD1), each additional allele of AFR origin associated with 27% increased odds of PE (OR = 1.27; P = 1.13×10-7).The A-allele for this variantis found in greater frequency in AFR reference populations (22%) than in EUR (5%).Subgroup analyses with HELLP syndrome(279 cases and 2364 controls) shows intriguingly opposite findings with increased risk for global AMR and EUR ancestry and decreased risk for AFR ancestry.Using a genetically diverse hispanic population, we showgenetic ancestry is associated with PE independent of reported ethnicityand further demonstrate thepower of admixture mapping to identify a candidate locus for PE.

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 A4136289-A4136289, November 12, 2024. Background:Aortic valve calcium (AVC) is associated with an increased risk of cardiovascular disease, non-cardiovascular disease such as dementia, and all-cause mortality. Traditional atherosclerotic cardiovascular disease risk factors are associated with both AVC and chronic kidney disease (CKD), but whether there is an association between AVC and CKD is unknown.Objectives:To ascertain whether AVC quantified by cardiac CT scanning is independently associated with the long-term risk of incident CKD among individuals without a previous history of cardiovascular disease.Methods:We examined 6,346 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac CT scanning at Visit 1 (2000-02) and had an eGFR of ≥ 60 mL/min/1.73 m2. AVC was quantified using the Agatston method and categorized as 0, 1-99, and ≥100. Incident CKD was defined as an eGFR < 60 mL/min/1.73 m2accompanied with an at least 40% decline in eGFR from baseline, and/or a diagnosis of CKD and indicators of end stage renal disease extracted from hospital records using the International Classification of Disease (ICD) codes. We performed Kaplan-Meier survival curve analyses along with multivariable Cox proportional hazard regression models, adjusted for age, gender, race/ethnicity, highest level of education and traditional cardiovascular risk factors along with coronary artery calcium (CAC), lipoprotein (a) (Lp[a]), and the APOE-ε4 genotype to examine the association between AVC (categorical and log-transformed) and incident CKD.Results:Participants had a mean age 62.2±10.1 years, 53% were women, and AVC >0 was present in 795 (12%) participants. During a median follow-up time of 16.9 years, 982 (15%) participants developed incident CKD. AVC examined as a continuous variable was associated with a significantly increased risk of developing CKD (per log-unit [AVC+1] HR 1.06 [95% CI: 1.02-1.10];p= 0.005). There was a stepwise increased risk for CKD with higher AVC levels (Figure). Similarly, in the multivariable adjusted Cox models, participants with AVC ≥100 had a higher risk of incident CKD, compared with the AVC=0 group (HR 1.48 [95% CI: 1.15-1.89];p= 0.002). The observed associations remained after further adjusting for CAC score (p= 0.024), Lp (a) (p= 0.004), and the APOE-ε4 genotype (p= 0.004).Conclusions:In a multi-ethnic cohort of participants free of CKD at baseline, AVC was independently associated with a higher risk of incident CKD.

Circulation, Volume 150, Issue Suppl_1, Page ASu904-ASu904, November 12, 2024. Background:The relationship between base-excess (BE) values, which take into account the time interval from cardiac arrest to blood test, and neurological outcome after out-of-hospital cardiac arrest (OHCA) is not well understood. The purpose of this study was to evaluate the association between BE on arrival at the hospital and neurological outcomes in OHCA patients.Methods:The CRITICAL study, a prospective, multicenter observational study in Osaka, Japan, registered consecutive OHCA patients who were transported to 16 participating critical care centers from 2012 to 2021. We included adult patients aged 18 years with witnessed OHCA whose BE values on hospital arrival was available, and divided patients into quartiles based on BE values of initial blood test on arrival at the hospital: Q1 (BE ≤ −21.1 mmol/L), Q2 (−21.1 < BE ≤ −15.7 mmol/L), Q3 (−15.7 < BE ≤ −10.4 mmol/L), and Q4 (BE > −10.4 mmol/L). The primary outcome was one-month survival with favorable neurological outcome, defined as cerebral performance category scale 1 or 2.Results:A total of 23,854 patients were registered, and 6,066 of them were eligible for analyses. Neurologically favorable outcome was the lowest in the Q1 group (3.2% [49/1,528]), followed by the Q2 (4.7% [70/1,493]), Q3 (9.8% [148/1,515]), and Q4 (23.5% [359/1,530]) group. In the multivariable logistic regression analysis, the adjusted odds ratio of Q1 compared with Q4 for one-month favorable neurological outcome was 0.13 (95% CI 0.090–0.18). The proportion of one-month favorable neurological outcome decreased progressively across decreasing quartiles (p for trend < 0.001). In subgroup analysis, there was an interaction between presence of return of spontaneous circulation (ROSC) before blood test and neurological outcome (p for interaction < 0.001). The neurological outcome worsened as the BE values decreased among those who achieved ROSC before the blood test (p for trend < 0.001), but not in those without ROSC (p for trend = 0.078). There was not a significant interaction between BE values without ROSC before blood test and time from witness to blood test (p for interaction = 0.501).Conclusions:We demonstrated that lower BE values at hospital arrival were associated with worse neurological outcome. The BE values may be one of the effective prognostic indications for neurological outcome, especially in OHCA patients with ROSC before hospital arrival.

Circulation, Volume 150, Issue Suppl_1, Page A4145056-A4145056, November 12, 2024. Introduction:Iron deficiency anemia (IDA) affects millions of people with heart failure (HF) and is of a higher proportion in patients admitted for HF than those seen as an outpatient. The cause of IDA in patients with HF is postulated to be related to the chronic inflammatory process that occurs resulting in decreased erythropoiesis. This could also be a side effect of the extensive treatment. The fate of patients admitted for exacerbation of heart failure, especially those with IDA could be fatal. This study uses the NIS HCUP database to assess the outcome of patients admitted from 2016 to 2019 with heart failure and co-existing iron deficiency anemia.Research question/ hypothesis:Patients with HF and co-existing IDA have worse outcomes than those without.Method:We used the NIS HCUP 2016 to 2019 database for the analysis. The primary outcome was inpatient mortality. Secondary outcomes such as mean length of hospitalization (LOS), mean total hospital charges (THC) adjusted for inflation and proportion of complications were computed. Data was analyzed using regression models adjusted for significant, confounding, sociodemographic and comorbid conditions.Discussion/ Results::The total population of hospitalizations for HF from 2016 to 2019 was 1270784 with 6.9% having IDA. A higher proportion of hospitalizations with IDA were women. The mortality from the HF admission was 39350 patients. IDA was associated with lower adjusted odds of inpatient mortality (2.5 vs 3.2%, aOR: 0.75, 95% confidence interval (CI) of 0.68-0.84. However, patients with IDA had significantly longer mean LOS and higher THC compared to patients without IDA. Patients with IDA also had increased adjusted odds or requiring pressors, developing acute kidney failure and respiratory failure.Conclusion::Although IDA did not appear to impact mortality in patients with HF, it was associated with higher inpatient complications and higher healthcare cost utilization. Researchers postulate that limitation of different codes being used when data is recorded could have contributed to the unimpacted mortality. Further studies are needed to decipher other factors. Addressing comorbid IDA in the outpatient setting may significantly decrease the cost associated with hospitalization for HF by decreasing the length of hospitalization and the hospital charges associated with those hospitalizations.

Circulation, Volume 150, Issue Suppl_1, Page A4141762-A4141762, November 12, 2024. Introduction:Chronic heart failure (HF) is linked to elevated serum TNF-α levels and affects multiple signaling pathways in non-cardiomyocytes, such as immune cells, intestinal epithelial cells, lymphatic endothelial cells, vascular cells, and their interactions. The combined dysbiosis of host transcriptomics and gut microbiota concerning altered TNF-α signaling in older adults with HF remains unknown.Methods:We recruited 10 older adults with heart failure (HF) (6 females) and 16 healthy controls (HCs) (10 females) from the Northeastern U.S. Non-fasting peripheral blood and stool samples were collected. Serum TNF-α was assayed using Enzyme-linked Immunosorbent Assay (ELISA) kits. Differentially expressed genes (DEGs) between HF and HCs were investigated using the R package “DESeq2” after aligning the raw blood RNA sequence data to the reference database and undergoing quality control. The QIAGEN Ingenuity Pathway Analysis (IPA) was used to analyze the canonical pathways associated with the DEGs. The 16S rRNA V4 gene regions of stool samples were sequenced and processed using the Mothur 1.42.3 pipeline. The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict the metagenomic functions of different gut microbiota compositions.Results:The mean ages of the HF and HC subjects were 73.50 (SD = 8.33) and 63.19 (SD = 7.75), respectively. HF subjects had significantly higher serum TNF-α levels than HCs (p < 0.05). Among the DEGs, HF subjects had 18 downregulated genes (e.g.,AK5,FAM167A,RGCC, andSARDH) and 3 upregulated genes (SMPD3,TMIGD3, andFRRS1) compared with HCs. TNF signaling (p < 0.01) was one of the significantly different canonical pathways in the DEGs between HF and HCs. HF subjects had significantly enrichedMogibacteriumand diminishedSutterellathan HCs (p < 0.05) and lower P53 signaling pathway activity than HCs (p < 0.05) among the predicted functions in stool samples.Conclusions:By analyzing serum TNF-α, whole transcriptomics, and gut microbiota, we identified higher serum TNF-α, differentially expressed genes (DEGs) and their canonical pathways, and distinct compositions and predicted functions of gut microbiota in older adults with HF compared to healthy controls. These findings suggest that TNF-α signaling may be a potential target for developing precise HF interventions and highlight the need for further large-scale multi-omics analysis in understanding and treating HF.

Circulation, Volume 150, Issue Suppl_1, Page A4141344-A4141344, November 12, 2024. Background:Leadless pacemakers offer a safe and effective alternative pacing strategy, crucial for patients with end-stage renal disease (ESRD) overcoming vascular access isues. However, there is limited data available on their use in this population.Methods:We utilized the Nationwide Readmission Database to extract data on all adult patients with ESRD who received either traditional transvenous or leadless pacemaker implantation from 2016 to 2021. We then compared in-hospital mortality, in-hospital complications, healthcare resource utilization, and 30-day readmission rates between these two groups.Results:A total of 6,384 patients (81.2%) were included in the transvenous pacemaker cohort, while 1,481 patients (18.8%) were in the leadless pacemaker cohort. In ESRD patients, leadless pacemaker implantation was associated with higher in-hospital complications compared to transvenous pacemakers, including cardiac complications (aOR 4.12, CI 1.70-9.98, p

Circulation, Volume 150, Issue Suppl_1, Page A4143692-A4143692, November 12, 2024. Hypothesis:Small prospective and dataset-based studies predicted the rates of sudden cardiac death (SCD) are higher in the African American (AA) population as compared to White Americans (WA). However, there is a lack of long-term data over two decades lookingfor racial differences in SCD.Aim:Our study aims to analyze and quantify the racial differences in age-adjusted mortality rates(AAMR) related to SCDs between AA and WA to further explore potential contributing factors, such as socioeconomic status, sex, and varied comorbidity burdens, to these differences.Methods:We analyzed the Centers for Disease Control and Prevention (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) database, containing death certificate records for various causes of mortality in the US from 1999 to 2020. We searched the CDC WONDER database for patients, 18-45 years old whose cause of death was SCD corresponding to ICD-10 code; I46.1. We searched for AAMR and stratified patients based on race and gender on a total population of 48668 (41975 WA; 6693 AA). Temporal trends were analyzed by fitting log-linear regression models using the Joinpoint Regression Program.Results:We calculated annual percent change (APC) with 95% confidence intervals (CIs) in AAMR for the line segments linking joint points. The AAMR for SCDs in AA males ranged from 2.1% in 2000 to 0.9% in 2020 with an APC of 0.68 between 1999 and 2009, -26.72 between 2009 and 2012, and 4.34 between 2012 and 2020 suggest that the rate peaked between 2008 and 2010, followed by a significant decline in the following years. WA males had consistently lower rates compared to AA males. The AAMR for WA males peaked at 1.5% in 2000 followed by a stepwise decline until it reached a rate less than 0.9% in 2020, with APCs -1.32 between 1999 and 2009, -19.58 between 2009 and 2012. [Figure A]. AA females had APCs of 2.01, -31.88, and 1.73 while WA females had APCs of -2.32, -21.38, and 0.43 between 1999 and 2009, 2009 and 2012, and 2012 and 2020, respectively [Figure B]. Rates in AA females had a similar progression to that in AA males [Figure C].Conclusion:Racial disparities in SCDs related AAMR in the US suggest the role of a complex interplay between healthcare delivery, underlying pathological processes, and race. AA demonstrated higher age-adjusted SCD rates than WA. These findings should be used to guide policymaking and address areas of unmet need in providing racially equitable healthcare for all patients.

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

Circulation, Volume 150, Issue Suppl_1, Page 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 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 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 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.