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

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 A4146295-A4146295, November 12, 2024. Background:Previous studies have highlighted the impact of sex differences on the outcomes of patients admitted for ST-elevation myocardial infarction (STEMI). However, there is limited evidence as to whether there is a difference in the outcomes between females and male STEMI patients who have a concomitant diagnosis of chronic kidney disease (CKD) and end-stage renal disease (ESRD).Research Question:Does sex affect the outcomes for STEMI patients with concomitant CKD and ESRD?Methods:This is a retrospective population-based cohort study that uses the National Inpatient Sample database. CKD patients in the United States hospitalized for STEMI were identified using the International Classification of Diseases, Ninth and Tenth Revision (ICD-9 and 10) codes. Inclusion criteria were adult patients who were hospitalized from 2012 to 2020. A subset of patients with ESRD were also identified. Multivariate regression analysis was performed, with the model adjusted for age and comorbidities. The primary outcome of interest was in-hospital mortality. Secondary outcomes evaluated included ischemic stroke, major bleeding complications, pressor requirement, permanent pacemaker implantation, percutaneous coronary intervention, coronary artery bypass grafting, surgery, pericardiocentesis, mechanical circulatory support, and mechanical ventilation.Results:A total of 1,283,255 STEMI patients without CKD, 158,715 STEMI patients with CKD, and 22,690 STEMI patients with ESRD were identified and analyzed. Among patients with STEMI and CKD, females demonstrated higher in-hospital mortality compared to male counterparts (16.7% vs 12.7%, aOR=1.13, 95% CI: 1.05-1.21, p

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 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 A4125334-A4125334, November 12, 2024. Background:Limited knowledge exists regarding non-acute myocardial infarction-associated cardiogenic shock (nACS-CS) and its associated outcomes within the African American population.Aim:This investigation aimed to examine the clinical outcomes of nACS-CS in the African American population compared to the non-African-American population in the United States.Methods:The National Inpatient Sample (NIS) database was employed to identify hospitalizations with nACS-CS from 2018 to 2020. Patients were categorized as either African Americans or non-African Americans. Statistical analyses, including Chi-square and t-tests, were conducted using STATA version 18.Results:Out of 8,607 nACS-CS hospitalizations, 1,325 (15.4%) involved African Americans between 2018 and 2020 (Figure 1a). African American patients with nACS-CS tended to be younger (60.9±16.6 vs. 65.8±16.7 years; p < 0.05). Moreover, the length of stay for this cohort was notably longer (16.2±0.75 vs. 14.8±0.32 days; p < 0.05). The demographic age group affected by cardiogenic shock exhibited a decreasing trend as time progressed up to 2020 (p-trend

Circulation, Volume 150, Issue Suppl_1, Page A4137045-A4137045, November 12, 2024. The formation of occlusive thrombi resulting in myocardial infarction or stroke present a significant challenge for the healthcare community. Activation of the prostacyclin (IP) receptor has been shown to decrease platelet reactivity, however current IP agonists lack a sustained effect in the blood. We have developed CS585, an IP receptor agonist with sustained anti-thrombotic effects in the blood, which could represent a novel prevention strategy in targeting thrombosis. We sought to assess the anti-thrombotic efficacy and pharmacodynamic stability of IP agonists CS585, iloprost and selexipag, in bothex vivoandin vivomodels.We evaluated the timeframe of effect of CS585, iloprost, and selexipag in mice following a single IV dose. Inhibition of thrombus formation was measuredex vivoin whole blood under arterial shear rates.In vivo, CS585, iloprost, or selexipag, were administered prior to labeling of platelets and fibrin. Thrombus formation at the site of injury was measured using the cremaster arteriole injury thrombosis assay.CS585 administered to mice prior to blood draw decreases platelet adhesion and blood clot formation under arterial shear conditions. These effects are observed up to 24 hours post-administration; however, the effects of iloprost and selexipag return to pre-treatment levels by 24 hours.In vivo, mice administered iloprost or selexipag demonstrated a decrease in platelet accumulation and fibrin formation, however the effects were abrogated post-administration by 10 minutes and 4 hours, respectively. Administration of CS585, however, demonstrated sustained inhibition of thrombus formation at the site of injury, with inhibitory effects observed at 18 hours post-administration.We have used bothin vivoandex vivomodels to demonstrate the anti-thrombotic efficacy of IP receptor agonists. Our results suggest that CS585, a novel IP receptor agonist, sustainably inhibits platelet activation and clot formation for extended periods, in contrast to existing alternatives. This demonstrates a significant improvement in the pharmacodynamic effects of IP receptor agonists in the blood, highlighting CS585 as a novel anti-platelet therapeutic with the potential to treat thrombotic diseases.

Circulation, Volume 150, Issue Suppl_1, Page A4132212-A4132212, November 12, 2024. Background:Atrial fibrillation or flutter (Afib/AFL) incidence rates continue to rise and are linked to significant mortality, particularly in older populations. Our analysis examines Afib/AFL mortality trends across different demographics and regions in the U.S. from 1999 to 2020, highlighting the importance of understanding these patterns.Aim:To guide preventive measures that alleviate the impact of Afib/AFL and identify high-risk populations and regions, we sought to quantify trends associated with Afib/AFL related mortality in the U.S.Methods:We conducted a comprehensive search of death certificates from 1999-2020 using Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research (CDC WONDER) database focusing on Afib/AFL mortality in adults with ICD-10 codes I48. Gender, race, geographical and urban-rural parameters were investigated by calculating annual percent change (APC) and age-adjusted mortality rates (AAMRs) per 100,000 persons using the Joinpoint Regression Program (Joinpoint V 4.9.0.0, National Cancer Institute).Results:A total of 2,581,488 deaths occurred in patients with Afib/AFL from 1999 to 2020. The AAMR displayed an abrupt rise from 2018 to 2020 (APC: 8.51; 95% CI: 4.84-10.47). Men consistently exhibited a higher AAMR (overall AAMR male: 79.4, 95% CI 79.3-79.6; female: 60.8, 95% CI 60.7-60.9). Non-metropolitan areas showed higher AAMRs than metropolitan areas (overall AAMR non-metropolitan areas: 74.9, 95% CI 74.7-75.1; metropolitan: 67.2, 95% CI 67.1-67.2). Disparities were also observed in AAMRs by region with the West region showing the highest mortality rate with a notable rise between 2010 and 2020 (APC: 3.70, 95% CI 3.30-5.37). Non-hispanic (NH) White population showed the highest mortality (overall AAMR: 74.2, 95% CI 74.1-74.3), followed by NH American Indian (AAMR: 50.3), NH Black (AAMR: 45.8), NH Asian (AAMR: 35.0) and Hispanic (AAMR: 37.9) populations.Conclusion:Mortality from Afib/AFL has risen from 1999 to 2020. Men, NH white populations, and residents in non-metropolitan areas and Western U.S. are at higher risk. Targeted interventions and strategic healthcare resource allocation are needed to address these disparities and improve outcomes.

Circulation, Volume 150, Issue Suppl_1, Page A4142312-A4142312, November 12, 2024. Introduction:Patients with cancer have a higher risk for both arterial and venous thromboembolism. Furthermore, this population subset has an increased risk of bleeding when treated with anticoagulation. Left atrial appendage occlusion devices (LAAODs) have emerged as an alternative to oral anticoagulation in patients at high risk for bleeding events. There is a paucity of data regarding the efficacy of LAAODs in cancer patients. In our study, we investigated the readmission rates, predictors, and causes of readmission after LAAODs placement in patients with underlying malignancy.Methods:The National Readmission Database for 2016, 2018, and 2020 was queried to identify hospitalized adults for LAAOD placement with a history of cancer. Multivariate logistic and linear regression analyses were used to adjust for possible confounders.Results:A total of 566 patients were hospitalized for LAAOD placement and had a history of different malignancies with 563 discharged alive. Within 90 days from discharge, 141 patients (25%) were readmitted. Exacerbation of Congestive heart failure (CHF) (7.9%), Sepsis (6.7%), Lower GI bleeding (4.3%), Iron deficiency anemia (3.8%), unspecified gastrointestinal hemorrhage (3.1%), and paroxysmal Atrial fibrillation (2.6 %) were most common causes of readmissions. Independent predictors of readmission included female sex (aOR 1.68, 95% CI: 1.07 – 2.63, P=0.022), acute kidney injury (aOR 4.6, 95% CI: 1.5-8.4, P=0.008), and anemia (aOR 1.71, 95% CI: 1.08-2.7, P=0.023).Conclusion:Predictors of readmission included female sex, anemia, and acute kidney injury during index admission. The most common causes of readmission included Exacerbation of CHF, Sepsis, Lower GI bleeding, and Iron deficiency anemia. Addressing readmission causes and predictors is needed to prevent such a high rate of readmissions after LAAODs placement in cancer patients.

Circulation, Volume 150, Issue Suppl_1, Page A4145617-A4145617, November 12, 2024. Background:Cardiogenic shock (CS) has high morbidity and mortality rates. There is limited understanding of race differences in the management and outcomes of CS.Methods:We queried the US National Inpatient Sample database (years 2016-2021) for CS hospitalizations in adults and categorized them by presence of acute myocardial infarction (AMI) on admission. Using multivariable logistic regression modeling, we adjusted for age, sex, income, insurance, comorbidities, and prior cardiac interventions and compared racial differences in use of and time to interventions, inpatient mortality, and cardiac arrest during hospitalization for AMI-CS and non-MI-CS.Results:Out of a total 1,012,050 weighted hospitalizations for CS, 60% involved non-MI-CS, while 40% were AMI-CS. Among AMI-CS hospitalizations, Black patients were less likely to receive IABP (aOR: 0.87, 95%CI: 0.82-0.93), pLVAD (aOR: 0.79, 95%CI: 0.72-0.86), PCI (aOR: 0.79, 95%CI: 0.75-0.84), and CABG (aOR: 0.77, 95%CI: 0.71-0.83), than White patients (all p

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 A4146104-A4146104, November 12, 2024. Background:There is substantial imbalance between the prevalence and treatment of overweight/obesity. Team-based remote care programs have shown promise in closing healthcare delivery gaps for several cardiometabolic disorders, but whether this strategy can enhance the uptake of guideline-directed therapy for weight management remains uncertain.Methods:In this quality improvement program, we developed and deployed a remote, patient navigator and pharmacist-led, pharmacotherapy-oriented weight management intervention (Supplementary Anti-Obesity Integration into a Longitudinal Weight Loss [SAIL] program). SAIL was conducted within the Partnerships for Reducing Overweight and Obesity with Patient-Centered Strategies 2.0 (PROPS 2.0) program, an ongoing 12-month digital health program pairing an online weight management program (RestoreHealth; HealthFleet, Inc.) with personalized support from health coaches. After 6 months, PROPS 2.0 participants who did not experience weight reduction were offered possible enrollment in SAIL. Pharmacists, enabled by a collaborative drug therapy management program, prescribed, titrated, and monitored anti-obesity medications (AOM) with physician (cardiologist) supervision.Results:Overall, 2,540 invitations for participation in SAIL were sent to the 5,061 patients enrolled in PROPS 2.0, of whom 200 responded. Of the respondents, 98 (49%) were eligible for SAIL, and 75 patients were enrolled. Based randomly by enrollment period, 45 patients participated without a remote physician visit, while 30 had a video telemedicine visit. Among the 75 program participants, 70 (93%) received a prescription for AOM (29/30 with a visit vs. 41/45 without; P=0.64). After a median follow-up of 143 days (IQR 79-193), 61/70 were taking prescribed AOM (26/29 with a visit vs. 35/41 without; P=0.73) (Figure).Conclusion:This study extends prior experiences leveraging remote, team-based care, emphasizing the potential of this approach to enhance weight management. Given the dramatic cardiometabolic detriments of prolonged exposure to overweight and obesity, innovative approaches are necessary to meet demand. Remote and team-based care are proven methods to improve care and outcomes and may provide a novel model for delivering care for overweight and obesity. Further studies are needed to ascertain the effectiveness of this strategy on weight-related health outcomes.

Circulation, Volume 150, Issue Suppl_1, Page A4146872-A4146872, November 12, 2024. Introduction:Increased prevalence and incidence of heart failure has resulted in a significant rise in the number of patients progressing to advanced heart failure (AHF). Heart transplant improves morbidity and mortality in patients with heart failure refractory to medical therapy. We examined resource utilization as measured in 30-day readmission in a contemporary population utilizing the NRD database.Aim:We conducted a thorough analysis to identify trends in 30-day readmissions of HTs and analyze the associated costs.Methods:Using the National Readmission Database from 2010 to 2021, the study focused on new HT recipients. We evaluated various parameters, including readmission rates and the costs associated with 30-day readmissions. Patients aged

Circulation, Volume 150, Issue Suppl_1, Page A4146633-A4146633, November 12, 2024. Background:Catheter-Directed Interventions (CDIs) for Acute Pulmonary Embolism (PE) have been present for years but their use is limited due to paucity of data especially in patients with cancer. We examine the safety and efficacy of CDIs in patients with high-risk PE and cancer.Methods:Nationwide Readmissions Database (2016-2021) was used to analyze cancer patients presenting with high-risk PE (HR-PE) (shock, pressor or mechanical circulatory support requirement). Patients who received systematic thrombolysis were excluded. Mahalanobis Distance Matching within the Propensity Score Caliper was used to match patient who received CDIs vs those who were treated with anticoagulation alone. Inverse Probability weighting (IPW) was utilized, and Pearson’s chi-squared test was applied to the PSM-2 matched cohorts to compare outcomes.Results:Among 265,196 hospitalization of cancer patients with HR-PE, X were treated with systemic thrombolysis and 795 (0.3%) of the patients underwent CDI.After propensity matching (N: 421 in each group), patients receiving CDI had a significantly lower mortality (33% vs. 41.8%, aOR:0.76 (95% CI, p: 0.008); However, bleeding complications including major bleeding (10.7% vs 6.2%, aOR:1.97 (95% CI, p: 0.018) was higher in patients receiving CDIs. No difference was observed in the risk of intracerebral hemorrhage (p >0.05). Readmission rates were similar at 30-day and 90-day intervals (p >0.05). From 2016-2021, mortality associated with HR-PE in cancer has not changed significantly (p >0.05); however, mortality in patients undergoing CDIs has decreased from (43.8% to 22.6%, p-trend: 0.0004). There has been increasing use of mechanical thrombectomy (MT) over thrombolysis in recent years.Conclusion:CDIs for HR-PE in cancer patients are associated with significant reduction in mortality and associated with higher bleeding. Mortality has decreased across the years for patients undergoing CDIs with higher utilization of MT.

Circulation, Volume 150, Issue Suppl_1, Page A4144346-A4144346, November 12, 2024. Background:Stroke is a leading cause of death globally. Atrial fibrillation (AF) is an important modifiable risk factor for stroke. Ascertaining the burden of stroke in AF, its temporal trends and demographic disparities can inform public health policy measures.AimsTo describe national temporal trends of ischemic stroke-related mortality in patients with AF and identify any differences by gender, race, ethnicity, or region.Methods:In this cross-sectional analysis we used death certificate data from the national CDC Wide-Ranging ONline Data for Epidemiologic Research (WONDER) database for adults aged 35-84 years between 1999 and 2020. We queried for both ischemic stroke and AF as contributing or underlying cause of death. Crude and age-adjusted mortality rates (AAMR) were computed for the overall population and stratified by sex, race/ethnicity, geographic region, state, and rural/urban status. Joinpoint Regression Analysis software was used for trend analysis. Average annual percentage change (APC) in AAMR were computed using log-linear regression models.ResultsA total of 32,386 ischemic-stroke related deaths occurred in patients with AF between 1999 and 2020. Overall mortality trends were stable until 2014, sharply rose between 2014 and 2017 (APC 27.6% [95% confidence interval, CI, 18.8-33.4]), slowing down between 2017 and 2020 (APC 2.48 [95% CI, -4.81-7.03]). Overall AAMR per 100,000 was higher in men (1.00 vs 0.86 in women; Figure 1); Non-Hispanic Whites (0.98 versus 0.81 in Non-Hispanic Blacks and 0.70 in Hispanics; Figure 2), individuals in the Western census region (1.07 vs 0.95 in Southern, 0.92 in Midwestern and 0.78 in Northeast regions; Figure 3) and non-metropolitan areas (1.06 versus 0.91 in metropolitan). The rate of increase in AAMR over recent years was significantly greater in Black populations.Conclusion:Stroke mortality in AF rose sharply since 2014. Our findings underscore racial and geographic differences that exist in stroke-related deaths in the US.

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 A4138339-A4138339, November 12, 2024. Introduction:Immune checkpoint inhibitors (ICI), such as anti-PD-1 monoclonal antibodies are increasingly used in anti-cancer therapy. However, several cardiovascular adverse effects can occur with the use of ICIs, including new-onset heart failure.Hypothesis:We hypothesized that prior myocardial ischemic injury could exacerbate cardiac dysfunction and inflammation caused by anti-PD-1 treatment. Moreover, we investigated whether abatacept, a T-cell co-stimulation blocker, can prevent ICI-induced cardiac effects.Methods:To induce reversible cardiac ischemia, C57Bl/6J mice were treated with isoprenaline (ISOP group) or with PBS (CON group), followed by 16 weeks of recovery period. Following this, mice from both groups were divided into three further treatment groups: isotype control, anti-PD-1, or anti-PD-1 combined with abatacept, and were treated for two weeks, with three weekly intraperitoneal injections. Echocardiography was performed to evaluate cardiac function while myocardial inflammation was assessed by qRT-PCR and immunohistochemistry. Flow cytometry and Western blot were used to investigate changes occurring in the thymus.Results:Mice with normal heart function but with prior ischemic injury and anti-PD-1 treatment (ISOP + anti-PD-1) showed significantly decreased fractional shortening and cardiac index on echocardiography, while in animals with abatacept co-treatment (ISOP+anti-PD-1+abatacept) cardiac function was not altered. Increased immune cell infiltration was seen in the myocardium of the ISOP+anti-PD-1 treated group compared to CON animals, including T-cells and macrophages, with increased expression of pro-inflammatory cytokines, while co-treatment with abatacept ameliorated the inflammatory response. In the thymus, increased expression of PD-1 was found after abatacept co-treatment.Conclusion:Prior myocardial ischemic injury was associated with cardiac dysfunction and inflammation after anti-PD-1 treatment, which was ameliorated by abatacept co-treatment. Patients with prior cardiac ischemic events may be at greater risk for developing ICI-induced cardiotoxicity, including new-onset HF.