Cardiovascular Research Articles

Design, optimization, simulation, and implementation of a 3D printed soft robotic peristaltic pump

Abstract This study presents an innovative approach to fluidic pumping using soft robotics, designed to circulate fluid through soft conduits for delicate environments like blood streams where traditional peristaltic pumps may not be feasible. A novel soft robotic peristaltic pump is optimized and implemented, featuring 3D printed ring-shaped actuators and a PDMS pipe housing a Newtonian fluid. The design includes a three-stage actuator ring structure, actuated sequentially for peristaltic motion. A parametric finite element model predicts the required pressure, and the Mooney-Rivlin 5 Parameters hyper-elastic material model ensures accurate material properties. Optimization uses response surface analysis in Minitab and MATLAB Simulink Simscape simulations to achieve maximum flow rate with minimal power and pressure. Experimental validation confirms the simulations, achieving an optimal flow rate of 0.27 ml s−1 at a 450 ms cycle, with minor discrepancies due to friction and measurement errors. This study demonstrates the scalability of linearly sequenced soft squeeze actuators into an effective pump, validated by both simulation and experiments. Future applications include medical devices addressing deep venous thrombosis, with further research exploring control theory for optimization and comparing performance with conventional pumps to enhance practical applicability.

Structural Equation Modelling as a Proof-of-Concept Tool for Mediation Mechanisms Between Topical Antibiotic Prophylaxis and Six Types of Blood Stream Infection Among ICU Patients

Whether exposing the microbiome to antibiotics decreases or increases the risk of blood stream infection with Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter, and Candida among ICU patients, and how this altered risk might be mediated, are critical research questions. Addressing these questions through the direct study of specific constituents within the microbiome would be difficult. An alternative tool for addressing these research questions is structural equation modelling (SEM). SEM enables competing theoretical causation networks to be tested ‘en bloc’ by confrontation with data derived from the literature. These causation models have three conceptual steps: exposure to specific antimicrobials are the key drivers, clinically relevant infection end points are the measurable observables, and the activity of key microbiome constituents on microbial invasion serve as mediators. These mediators, whether serving to promote, to impede, or neither, are typically unobservable and appear as latent variables in each model. SEM methods enable comparisons through confronting the three competing models, each versus clinically derived data with the various exposures, such as topical or parenteral antibiotic prophylaxis, factorized in each model. Candida colonization, represented as a latent variable, and concurrency are consistent promoters of all types of blood stream infection, and emerge as harmful mediators.

Phase angle is a useful predicting indicator for protein-energy wasting and cardiovascular risk among maintenance hemodialysis patients.

Protein-energy wasting (PEW) is a major contributor to the high mortality among maintenance hemodialysis (MHD) patients. Cardiovascular disease (CVD) is the leading cause of death in dialysis patients, and PEW can significantly increase cardiovascular mortality in MHD patients. Previous studies have confirmed that PA may be a good objective indicator for determining the nutritional status and prognosis of MHD patients. Our study aimed to determine the predictive value of phase angle (PA) as detected by bioelectrical impedance analysis (BIA) on PEW and cardiovascular (CV) risk among MHD patients. Our retrospective observational study involved 161 adult patients with HD. The Cardiovascular risk score is a risk model based on the Japan Dialysis Outcome and Practice Patterns Study (J-DOPPS). We established LASSO logistic regression analysis model to identify key parameters related to body composition that can predict PEW in MHD patients. The area under the curve (AUC) values for PA, appendicular skeletal muscle mass index (ASMI), body cell mass (BCM), and mid-arm circumference (MAC) in predicting PEW in male MHD patients were relatively large, with 0.708, 0.674, 0.663, and 0.735, respectively. The predicted PEW values of these parameters were slightly lower in female patients than in men. We incorporated PA, ASMI, BCM, and MAC into a model that predicted the incidence of PEW in maintenance hemodialysis patients using LASSO technology. We discovered that the model predicted a greater AUC of PEW occurrence than any single factor, 0.877 for men and 0.76 for women. The results of the univariate logistic regression analysis showed that the low PA tertile array group had a greater incidence of PEW than the high PA group (P < 0.001). Additionally, we also found that lower PA was associated with higher CV risk scores. The PA detected by bioelectrical impedance analysis could predict the risk of PEW and cardiovascular events among patients with MHD. When used in conjunction, PA, ASMI, BCM, and MAC have a high diagnostic efficacy for PEW in patients on maintenance hemodialysis.

Team-Based Learning &amp; Point of Care Ultrasound (POCUS) to Augment a Preclinical Cardiovascular Physiology Course

Introduction: There has been increasing interest in point of care ultrasound (POCUS) as a learning tool in preclinical medical anatomy and physiology courses. Few interventions have used team-based learning (TBL) to teach cardiac POCUS. This study investigates a novel TBL exercise designed to integrate cardiac anatomy, physiology, and cardiac POCUS education within a first-year cardiovascular (CV) course called Team-Based Learning – Ultrasound (TBL-US). Methods: The TBL-US exercise consisted of four phases: preparation, individual and team readiness assurance, image acquisition and application, and knowledge assessment. Six second-year students were trained to facilitate the session under physician supervision. Pre- and post-session knowledge assessments were administered to determine knowledge acquisition. Pre- and post-session surveys were administered to assess attitudes, beliefs, and confidence surrounding cardiac POCUS. Final exam scores were compared between participants and non-participants of TBL-US and stratified into high- and low-performing subgroups to account for pre-TBL baseline differences in ability between the groups. Results: A total of 54 first-year medical students completed TBL-US. Students showed significant improvement on the post-knowledge assessment compared to the pre-knowledge assessment (70.5% vs. 54.9% [p&lt; 0.001]) and scored significantly higher on the final CV exam compared to non-participants (low-performing group: 85.92% vs. 81.02% [p=0.039], high-performing group: 89.22% vs. 85.95% [p=0.038]). Between 43.3-72.7% of students reported that TBL-US increased their understanding of CV anatomy, physiology, and cardiac POCUS. Discussion: Students found TBL-US to be a valuable teaching modality and improved student knowledge of CV anatomy, physiology, and cardiac POCUS. TBL-US effectively augments the learning of cardiac anatomy and physiology during the preclinical undergraduate medical curriculum.

Integrated multi-omics characterization across clinically relevant subgroups of long COVID

Abstract With SARS-CoV-2 became regional epidemics, substantial amount of patients suffers from post-acute sequelae of COVID-19 (PASC, aka long COVID). Exploring the pathogenesis and especially the heterogenicity features of long COVID subgroups is of paramount importance for etiology understandings. In this study, through integrative multi-omics analyses encompassing transcriptomics, proteomics, and metabolomics, long COVID patients exhibited overall elevated MAPK pathway activation, while patients recovered from long COVID showed down-regulation of this response. Long COVID heterogenicity is described by multi-omics distinct signatures for each subgroup. Multisystemic (MULTI) symptoms subgroup is characterized by enhanced glycerophospholipid and ether lipid metabolism, Neurological (NEU) by augmented glycoprotein synthesis metabolism, Cardio cerebral (CACRB) by increased pyruvate metabolism and suppressed macrophage polarization, Musculoskeletal + Systemic (MSK + SYST) by elevated glycerophospholipid metabolism, and Cardiopulmonary (CAPM) by inhibited NF-κB signaling pathways. ABHD17A, CSNK1D, PSME4 and SYVN1 were general long COVID combination biomarkers, while CRH (MULTI), FPGT (NEU), CBX6 (CACRB) and RBBP4 (CAPM) were selected as serum-specific subgroup proteins. Our study provides commonly shared and distinct pathophysiology explanation underpinning PASC, paving the way for the future diagnosis and therapeutic interventions.

Factors associated with High Viral Loads among HIV Patients Under ARV at Gitwe District Hospital

Background: High viral load is a condition of rapid multiplication in blood stream. The high viral load among HIV patients under ARV may also occur due to the rapid multiplication of virus leading to compromise immune system of living organism up to death. The vast majority of people living with HIV virus face with persistent of high viral load while were under treatments (ARV). Aim: The aim of the study was to evaluate and assess the factors associated with high viral load among HIV patients under ARV at Gitwe District Hospital. Methodology: The retrospective study was conducted to assess high viral load of HIV patients under ARV. The only significance factor for viral load were adherence with (p=0.000173) and ages with (p=0.00023). Results and conclusion: A large of number of PLWH were highly VL tested, and 95 subjects were recorded for study. Among 95 subjects, 54.73% were female and 45.26% male. All data were analyzed using statistical package for social science (SPSS) version 20. The results have showed provider’s advices and ART use, adherence counselling. Keywords: High viral load, HIV, Antiretroviral therapy, Gitwe District Hospital.

Polmacoxib 2mg in patients with mild to moderate idiopathic osteoarthritis of hip/knee-a randomized, double-anonymous study.

Polmacoxib, a new COX-2 inhibitor with carbonic anhydrase (CA) inhibitory action, is expected to help minimize the adverse effects associated with other NSAIDs, like GI (gastrointestinal) and CV (cardiovascular) system- related issues. The comparative efficacy and safety of polmacoxib 2 mg (manufactured by Hetero Labs Limited) versus celecoxib 200 mg (manufactured by Hetero Labs Limited) were assessed in this randomized, double-anonymous, clinical study in Indian adult patients diagnosed with idiopathic osteoarthritis (OA) of the. 18 years and older patients of either sex, clinically and radiographically diagnosed idiopathic knee or hip OA were randomized to receive either polmacoxib or celecoxib in a 1:1 ratio. All patients were assessed with various pain measuring scales and recorded the scores at the end of weeks 3 and 6. The data for all the pain assessment scores were analyzed, and polmacoxib was found to be a non-inferior therapeutic agent compared to celecoxib in terms of safety and efficacy.(https://ctri.nic.in/CTRI/2022/05/042923).

Effect of Different Dietary Patterns on Cardiometabolic Risk Factors: An Umbrella Review of Systematic Reviews and Meta-Analyses

Background/Objectives: Lifestyle interventions such as dietary changes have been proposed to control the cardiometabolic risk factors and thus prevent cardiovascular (CV) disease (CVD). We performed an umbrella review to investigate whether different dietary patterns affect CV risk in individuals with at least one cardiometabolic risk factor (hypertension, dyslipidemia, obesity, diabetes, metabolic syndrome) but not established CVD. Methods: We systematically searched the PubMed and Scopus databases (up to August 2024) for the systematic reviews and meta-analyses of randomized controlled trials (RCTs). Articles should be written in English and refer to a specific dietary pattern (such as Mediterranean diet, etc.). The population studied referred to adults with at least one cardiovascular (CV) risk factor. Results: From 4512 records identified, we finally included 25 meta-analyses with a total of 329 associations. Strong evidence for a benefit was found for LCD with reductions in BW [MD: −4.79 (95% CI −5.85, −3.72) kg, p ≤ 0.001], SBP [MD: −6.38 (95% CI −7.84, −4.93) mmHg, p ≤ 0.001], TG [WMD: −5.81 (95% CI −7.96, −3.66) mg/dL, p ≤ 0.001], and fasting plasma insulin [MD: −15.35 (95% CI −19.58, −11.12) pmol/L, p ≤ 0.001], as well as for low-GI diet for the reduction of BW [SMD: −0.66 (95% CI −0.90, −0.43) kg, p ≤ 0.001]. Conclusions: Across many dietary patterns, LCD showed strong or highly suggestive evidence for a benefit on SBP, BW reduction, and lipid profile improvement. Secondarily, low-GI, DASH, and Portfolio and Nordic diets suggested beneficial effects on controlling CV risk.

Bacteriological Profile and Antibiotic Susceptibility Pattern of Isolates from Suspected Neonatal Septicemia Patients in Different Hospitals of Chattogram

Background: Bacterial blood stream infection is an important cause of morbidity and mortality in neonates. This study was undertaken to identify the bacterial isolates from suspected neonatal septicemia patients and to understand their antimicrobial susceptibility pattern in Chattogram. Materials and methods: A cross-sectional descriptive type of study was done for a period of two years from January 2022 to December 2023. Blood samples from 340 neonates with clinically suspected septicemia were taken for automated culture and susceptibility test was conducted in Bacteriology Laboratory of IbneSina, Chattogram. The samples were collected and processed following standard microbiological techniques and an antibiotic susceptibility test was done on pure culture isolates using disc-diffusion method for the commonly used antibiotics. The data were analyzed by using SPSS version 20 and the results were summarized by using tables and graphs. Results: Out of 340 blood culture done, 62 (18.24%) were positive. Among them 61.3% were of early onset sepsis. The predominant bacteria isolated was Klebsiella spp. 27 (43.6%) followed by Coagulase negative staphylococci 12(19.4%), Salmonella typhi 10 (16.1%), E. coli 6 (9.6%) and Pseudomonas 5 (8.0%). Antibiotic susceptibility tests showed that the most sensitive antibiotics to Gram-negative organisms wereImipenem (81-100%), Tazobactam-Piperacillin (74-100%), Amikacin (67-90%), Ceftriaxone (60-100%) and Levofloxacin (63-80%). Maximum resistance among Gram-negative organisms were seen in Ampicillin (60-100%), Cotrimoxazole (60-100%) and Cefixime (30-80%). Among Gram-positive organisms, all strains (100%) were sensitive to Linezolid and Vancomycin. Other alternates with good sensitivity were Amikacin (92%), Imipenem (83%), Ceftriaxone (83%) and Levofloxacin (75%). While maximum resistance was seen to Ampicillin (83%), Amoxiclav (75%), Cefixime (75%) and Ciprofloxacin (75%). Conclusions: In the present study, most of the pathogens isolated from blood cultures were Gram negative and they showed high resistance to commonly used antibiotics. Therefore, rational use of antibiotics after sensitivity testing should be practiced. IAHS Medical Journal Vol 7(1), June 2024; 68-73

Abstract 4136873: The Role of Socioeconomic Status in the Association Between Cardiovascular Polygenic Risk Score and Cardiovascular Events

Introduction: Polygenic risk scores (PRS) provide a summation of small-effect genetic variants that predict cardiovascular (CV) disease risk. Socioeconomic status (SES) can also impact CV risk, but it is unknown whether SES modifies the effects of PRS on CV events. Hypothesis: The association between CV PRS and CV events is modified by SES. Methods: Participants without CV disease at baseline from the UK Biobank prospective cohort study were followed from recruitment (2006-2010) through 2023. We included participants with genetic data (for CV PRS) and CV risk factors assessed at baseline (hemoglobin A1c, total cholesterol, blood pressure, body mass index, physical activity, tobacco use, and sleep). The CV PRS was centered at zero and standardized to one unit variance within each ancestry group. SES was defined by tertiles of index of multiple deprivation (from housing, crime, income, education, employment, health deprivation and disability, and neighborhood environment). The primary outcome was CV events (myocardial infarction, heart failure hospitalization, stroke, or death). Using Cox proportional hazard models, we estimated the total effect of PRS on CV events, tested for interaction of SES in the association between PRS and CV events, and estimated the direct effect of PRS on CV events by adjusting for age, sex, CV risk factors, and SES. Results: There were 201,374 participants (mean age 55.9 (± 8.1), 53.4% female). CV events occurred in 21,916 (10.9%) participants: 5,754 (2.9 %) myocardial infarctions, 4,061 (2.0%) strokes, 4,312 (2.1%) heart failure hospitalizations, and 12,782 (6.4%) deaths. Each unit of PRS was associated with 1.17 times the risk of CV events (HR 1.17, 95%CI 1.15 to 1.18, p-value &lt; .001, adjusted for age and sex). People with the lowest SES had 1.22 times the risk of CV events (HR 1.22; 95%CI 1.18 to 1.26; p-value &lt;.001) and the middle SES had 1.07 times the risk of CV events (HR 1.07; 95%CI 1.03 to 1.10; p-value &lt;.001) compared to the highest SES, adjusted for age, sex, and CV risk factors. PRS remained associated with CV events (HR 1.15, 95%CI 1.13 to 1.16, p-value&lt;.001) after adjusting for age, sex, CV risk factors, and SES. There was no significant multiplicative interaction between SES and PRS for CV events (interaction p-value = 0.45). Conclusions: SES is associated with CV events but does not modify the effect of PRS on CV events. Genetic risk remains independently important in CV event risk beyond traditional CV risk factors and SES.

Abstract 4124289: Changes in high-sensitivity cardiac troponin I and associated cardiovascular risk: Analyses From the FOURIER Trial

Background: Circulating high-sensitivity cardiac troponin I (hs-cTnI) is associated with the risk of future cardiovascular (CV) events in stable patients (pts). Data are scarce regarding changes of hs-cTnI in a stable setting. Aims: To study baseline and changes of hs-cTnI in pts with atherosclerotic CV disease (ASCVD), and the association with risk of major CV events. Methods: We measured hs-cTnI (Abbott ARCHITECT) at baseline (BL) and 24 weeks (wks) in 20,718 pts enrolled in a nested biomarker study of the FOURIER trial, which tested the PCSK9i evolocumab vs. placebo in pts with ASCVD on statin and LDL &gt; 70 or non-HDL &gt; 100 mg/dL. The primary endpoint was an adjudicated composite of CV death, MI, stroke, hosp. for unstable angina, or coronary revascularization. The HR (95% CI) across percent-change of hs-cTnI was investigated in pts with quantifiable hs-cTnI at BL and 24 wks (lower limit of quantification (LLOQ) 3.6ng/L) using restricted-cubic splines and Cox-PH models, adjusted for sex, age, LDL at BL, prior MI, randomized treatment, eGFR, DM, HTN, prior HF, and BMI. A Generalized Additive Model was used to predict event rates as a function of hs-cTnI BL and absolute change, flexibly evaluated with a non-linear interaction. All models were based on 3-year follow-up using landmark analysis from 24 wks. Results: Median age was 63 yrs (25 th , 75 th percentiles: 56, 69), 75.5% were male, 86.1% had CAD, 13.7% PAD, and 19.0% a prior stroke. Of these pts, 11,021 (46.8%) had hs-cTnI &gt; LLOQ at BL and 24 wks. The median hs-cTnI at 24 wks was 6.6ng/L (5 th , 25 th , 75 th , 95 th percentiles are: 3.7, 4.7, 11.9, 51.1 ng/L). The absolute event rate of the primary endpoint across hs-cTnI BL and depending on absolute hs-cTnI change to 24 wks is shown in Fig. A . Higher Hs-cTnI BL was associated with higher event rates (p &lt; 0.001). Additionally, absolute reductions and increases of hs-cTnI from BL to 24 wks resulted in reduced and increased event rates, respectively, across hs-cTnI BL . Additionally, relative decrease and increase of hs-cTnI from BL to 24 wks were associated with reduced and increased relative risk, respectively (p for overall effect &lt; 0.001, Fig. B ). Conclusion: Changes in hs-cTnI are associated with the risk of future CV events. Serial measurements of hs-cTnI may aid in reclassification of CV risk and the identification of pts whose CV risk changes with time.

Abstract 4136930: Plasminogen Activator Urokinase Receptor (PLAUR) Levels are a Predictor of Adverse Cardiovascular Outcomes in the General Population, Independent of High-Sensitive CRP (hs-CRP)

Background: The gene Plasminogen Activator Urokinase Receptor (PLAUR) encodes the urokinase plasminogen activator surface receptor (uPAR), which upon cleavage releases Soluble Urokinase Plasminogen Activator Receptor (suPAR). SuPAR has emerged as a novel biomarker of inflammation and immunity and is associated with adverse cardiovascular events, particularly coronary artery disease (CAD), regardless of hs-CRP levels, a well-established inflammatory biomarker. However, whether the PLAUR gene predicts adverse cardiovascular events remains uncertain. Methods: We investigated the relationship between PLAUR levels, measured via Olink Immunoassay, in 40,790 individuals from the UK Biobank, and the occurrence of adverse cardiovascular events such as myocardial infarction (MI), as well as all-cause and cardiovascular mortality. Our analysis involved the use of Cox and Fine and Gray proportional hazards models, adjusting for age, sex, race, HDL, LDL, triglyceride levels, BMI, prevalence of hypertension (HTN), prevalence of type 2 diabetes (T2D), smoking history, and use of blood pressure and cholesterol medications. Main Outcomes: The primary outcome was a composite outcome of cardiovascular mortality and MI and the secondary outcome was all-cause mortality. Results: The mean (SD) age was 58 (8) years, 45% men and 94% white. During a median follow-up of 14 (interquartile range 12.3 – 15) years, 7.9% of the population had an MI, 2.7% suffered cardiovascular death, 9.5% all-cause mortality. After adjusting for aforementioned demographic and clinical factors, as well as medication usage, each standard deviation increase in PLAUR levels was associated with a heightened risk of incident non-fatal MI and cardiovascular (CV) death, with a hazard ratio (HR) of 2.31 (95% CI 2.00-2.45), and all-cause mortality, with an HR of 3.81 (95% CI 3.48-4.18). Even after further adjustment for hs-CRP levels, PLAUR levels remained predictive of non-fatal MI and CV death (HR 2.03, 95% CI 1.83-2.26) and all-cause mortality (HR 3.43, 95% CI 3.12-3.77). Furthermore, in a fully adjusted Cox regression model, a significant interaction between PLAUR levels and sex (p = 0.0003) was observed in predicting the primary outcome. The interaction was found to have a stronger predictive value in females compared to males. Conclusion: PLAUR levels are a strong predictor of adverse cardiovascular outcomes in the general population, independent of traditional risk factors and inflammation.

Abstract 4135265: When the Beat Drops: A Pilot Project for a Case-Based Resident’s Guide to Cardiovascular Care

Residents care for patients with a vast array of cardiovascular (CV) diagnoses in settings ranging from primary care clinic to the cardiac intensive care unit. However, the resources available are mainly intended for advanced cardiology trainees. We created a resident-driven, case-based reference for residents to serve as a companion to traditional CV medicine educational resources. Methods: We surveyed residents, fellows, and cardiology attendings to identify topics within CV care for which residents are responsible. We recruited residents from multiple ACGME-accredited Internal Medicine residency programs to write a chapter on each identified topic that would be published on a central website. The chapters included a topic overview with key learning points, a case presentation, review questions, attending pearls, and high-yield articles for further reading. Chapters were reviewed for accuracy and completeness by cardiology fellows, pharmacologists, and attendings. The chapters were sent out to residents weekly via email and through social media platforms. Website analytics were used to track usage and monitor engagement. Each chapter concluded with a brief survey regarding learning gains, comprehension, and if the reader would recommend the resources to others. Results: A total of 52 cases were submitted by resident contributors from four residency programs. Topics included management of arrhythmias, structural heart disease, ischemia, cardiogenic shock, and post-procedure complications. Within the first two months of publication, the website was being accessed throughout 30+ states and 6 countries with more than 2,500 views and 1,500 unique visitors. Topics with high traffic included chapters regarding arrhythmias and post-procedural complications. The website was viewed throughout the entire day with no specific time pattern; however, there were significantly more views on days when each chapter was released via email and social media. Preliminary survey results show that residents and other trainees find this resource useful, and many want to get involved and help create more content. Conclusion: Our resident-created and cardiologist reviewed website is a unique resource created for residents caring for patients with CV disease. Using email and social media marketing has allowed this resource to be widely accessible to a large global audience. Survey feedback suggests the importance of this resource and need for continued CV resources for trainees.

Abstract 4135846: Cardiovascular Effectiveness of Glucagon-like Peptide-1 Receptor Agonists and Empagliflozin Combination Therapy in Adults with Type 2 Diabetes

Introduction/Background: Both empagliflozin and glucagon-like peptide-1 receptor agonists (GLP-1RA) have demonstrated cardiovascular (CV) benefits in clinical trials. However, few trials examined the combination of both therapies and evidence is scarce on whether the addition of empagliflozin to GLP-1RA has further CV benefits. Aim/Goal: We evaluated the risk of CV outcomes in patients with type 2 diabetes (T2D) initiating baseline GLP-1RA therapy that added empagliflozin compared to those that added sulfonylureas (SU). Methods: Using Medicare, Optum, and Marketscan data (2014-22), we identified patients with T2D aged ≥18 years initiating GLP-1RA that subsequently added either empagliflozin or SU. Follow-up began on the date of additional therapy and continued until discontinuation of either drug, a gap in insurance coverage, death, or study end. After propensity score standardized mortality ratio weighting adjusting for 98 covariates, we estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years evaluating a composite of myocardial infarction (MI) or stroke, hospitalization for heart failure (HHF), or all-cause death in the overall population and in patients with history of CV disease. Results: We identified 27,962 patients initiating GLP-1RA + empagliflozin vs 25,137 patients initiating GLP-1RA + SU. After weighting, relative to patients initiating GLP-1RA + SU, those initiating GLP-1RA + empagliflozin had lower risks of MI-stroke [HR 0.70 (0.55, 0.90); RD: -4.3 (-6.6, -2.0)], HHF in the primary hospital discharge position [HR: 0.59 (0.43, 0.81); RD: -3.9 (-5.8, -2.1)]; HHF in any discharge positions [HR: 0.84 (0.72, 0.98); RD: -7.6 (-11.6, -3.6)], and all-cause death [HR: 0.83 (0.62, 1.11); RD: -1.3 (-3.2, 0.56)]. Findings were similar but with larger RDs in patients with baseline CV disease ( Table ). Conclusion: In US clinical practice, patients with T2D initiating GLP-1RA that added empagliflozin had lower risks of MI-stroke, HHF, and death compared to adding SU, which suggests an additive CV benefit when combining GLP-1RA and empagliflozin therapies.

Abstract 4135444: Sex Disparities in Enrollment of Cardiovascular Trials: A Meta-Analysis of ClinicalTrials.gov Listings

Background: Despite increasing recognition of sex differences in the burden of cardiovascular (CV) diseases, women have historically been underrepresented in clinical trials. Aims: The study aimed to systematically quantify the extent of sex disparity in the enrollment of CV trials and explore the annual enrollment trends of women in CV trials. Methods: The analysis included studies that: (1) were registered in ClinicalTrials.gov up to February 2024; (2) were randomized trials involving ≥1 intervention; (3) investigated ≥1 CV condition, as determined by Medical Subject Heading descriptors. The exclusion criteria were: (1) studies without available enrollment information; (2) studies exclusively enrolling men or women; and (3) studies with ≤100 participants. We computed enrollment disparity difference (EDD), defined as the difference between the proportion of women in trial participants and the proportion of women with CV diseases in the general population, based on the Global Burden of Disease estimates matched by country/geographic region and enrollment period. Random-effects meta-analysis was performed to summarize the overall enrollment disparity. Subgroup analysis by trial characteristics was conducted. Meta-regression was used to assess the association of enrollment disparity with the start year of the trials. Results: A total of 1,687 CV trials were identified from 484,781 studies. Among 2,198,317 trial participants for whom sex was reported, 819,570 (37.3%) were women. EDD in CV trials was -0.105 (95% CI, -0.113 to -0.097), indicating that women were under-enrolled by 10.5% (Figure 1). Except for valvular heart disease trials, disparities were evident across other CV disease trials, with the most remarkable under-enrollment of women in peripheral artery disease trials (-0.302 [95% CI, -0.324 to -0.279]). Disparities were more prominent in trials with larger sample sizes, longer study durations, device or procedural interventions, and data monitoring committee oversight (p&lt;0.001 for subgroup differences; Figure 2). There was a significant yet modest improvement in the representation of women over time (increase of 0.0028 [95% CI, 0.0011 to 0.0045] in EDD per start year of trials; p=0.001; Figure 3). Conclusion: Women remain substantially underrepresented in CV trials, particularly in peripheral artery disease trials. The findings underscore the imperative for interventions to mitigate sex inequity in the enrollment of CV trials.

Abstract 4125252: Pre-Hematopoietic Stem Cell Transplantation Echocardiographic Indices and Post-Transplant Cardiovascular Outcomes

Introduction: Hematopoietic stem cell transplantation (HSCT) is associated with adverse cardiovascular (CV) events including the development of heart failure (HF) and arrythmias. While transthoracic echocardiogram (TTE) is routinely obtained prior to HSCT, its role in predicting the incidence of HSCT related CV events is poorly understood. Methods: We used data from the Cardiovascular Registry in Bone Marrow Transplantation (CARE-BMT) study, a multicenter observational study of adult patients (aged ≥18 years) who underwent autologous/allogeneic HSCT for malignant or nonmalignant bone marrow disorders at the University of Michigan Health System (UMHS) and Rush University Medical Center from 2008-2019. In this analysis, we included patients from UMHS with a baseline TTE. Data on pre-HSCT TTE parameters and post-HSCT CV outcomes were collected through manual chart review. Left ventricular (LV) function and dimensions were categorized into normal, mildly abnormal, and moderately/severely abnormal based on American Society of Echocardiography guidelines. The primary outcomes were new-onset HF and atrial fibrillation/flutter post-HSCT. Analyses were conducted using a Fine-Gray model adjusted for the pre-HSCT CARE-BMT CV risk score. Results: Of the 2071 patients (mean age at HSCT 55.5 + 12.9 years; 59.5% male) with a pre-HSCT TTE (median 25 days pre-HSCT), 116 (5.6%) and 128 (6.2%) patients experienced HF and atrial fibrillation/flutter, respectively, over a median period of 2.2 years. Greater abnormalities in left ventricular internal diameter at end-diastole (LVIDd) and end-systole (LVIDs) were linearly associated with a higher risk of HF (P-trend 0.018 and 0.004, respectively) (Table). Similarly, moderately/severely abnormal LVIDd was associated with a 2.41-fold (95% CI: 1.07, 5.43) increase in risk of atrial fibrillation/flutter (Table). Pre-HSCT ejection fraction (EF) was not associated with either endpoint. Conclusion: LV dilation, even when mild, was notably associated with increased risk of developing new HF or atrial arrythmias post-HSCT, regardless of EF. Whether evidence of LV dilation should prompt the initiation of guideline directed medical therapy to minimize the risk of incident HF warrants further study.

Abstract 4124709: Accelerometer-Measured Sedentary Behavior and Future Cardiovascular Disease

Background: Current consensus guidelines emphasize the importance of achieving 150 minutes or more of moderate to vigorous physical activity (MVPA) per week to promote cardiovascular health but give little guidance about sedentary behavior. Research Question: Is sedentary behavior associated with cardiovascular (CV) disease in a manner distinct from insufficient physical activity? Aims: Examine associations between accelerometer-measured sedentary behavior with risk of specific CV outcomes, including potential interactions with MVPA. Methods: Using 89,530 individuals providing one week of accelerometer-based physical activity data from the UK Biobank, we fit Cox models adjusted for demographic and lifestyle factors to assess associations between sedentary time (as a spline term) and incident atrial fibrillation (AF), myocardial infarction (MI), heart failure (HF), and CV mortality. We assessed the potential effect of MVPA on these associations by including MVPA as an adjustment variable, as well as performing subgroup analyses stratified at the guideline-recommended MVPA threshold. Results: Among 89,530 individuals (age 62±8 years, 56.4% women) undergoing accelerometry, median sedentary time was 9.4 hours/day (quartile-1: 8.2, quartile-3: 10.6). In multivariable models, using the second quartile (8.2-9.4 hours/day) as a referent, sedentary time in the top quartile (&gt;10.6 hours/day) was associated with greater risk of HF (hazard ratio [HR] 1.45, 95% CI 1.28-1.65), and CV mortality (HR 1.62, 95% CI 1.34-1.96), with evidence of a threshold effect at 10.6 hours/day. Higher sedentary time was also associated with greater risk of incident AF (HR 1.11, 95% CI 1.01-1.21) and MI (HR 1.15, 95% CI 1.00-1.32), with an approximately linear relation. Associations with HF and CV mortality persisted after adjustment for MVPA, as well as among individuals both above and below the guideline-based activity threshold of ≥150 minutes MVPA/week. Conclusions and Relevance: Sedentary behavior is broadly associated with future adverse CV outcomes. For HF and CV mortality, associations appear distinct from insufficient MVPA, and sedentary time in excess of 10.6 hours/day conferred an increased risk.

Abstract 4134637: Impact of Glucagon-Like Peptide-1 Agonists on Cardiovascular Outcomes in Chronic Kidney Disease Stage 5: A Propensity Score-Matched Analysis

Background: Patients with chronic kidney disease stage 5 (CKD-5) face heightened risks of cardiovascular (CV) complications and mortality. Glucagon-like peptide-1 agonists (GLP-1a), primarily used in type 2 diabetes, are being investigated for potential CV benefits in this population. This study aims to evaluate the impact of GLP-1a treatment on CV outcomes and survival among CKD-5 patients. Methods: This retrospective cohort study utilized data of adult patients diagnosed with CKD-5 between January 2014 and August 2023 from the TriNetX global research network. A propensity score matching analysis of those treated with GLP-1a for at least six months versus those never exposed to GLP-1a therapy was conducted. Results: Our analysis showed significantly reduced odds for the composite primary outcome of acute myocardial infarction (AMI), stroke, and mortality (OR = 0.66, 95% CI: 0.57-0.78, p&lt;0.001), and other CV outcomes such as cardiac arrest, hypertensive crisis, and hypertensive urgency, among the GLP-1a cohort compared with the non-GLP-1a cohort. Kaplan-Meier survival analysis revealed a significantly higher five-year incidence-free probability for the composite primary outcome (63.5% vs. 50.5%, p&lt;0.001) and for other CV outcomes such as hypertensive events, AMI, cardiac arrest, and hemorrhagic stroke for the GLP-1a cohort. Conclusion: The study suggests that GLP-1a therapy in CKD 5 patients may confer certain CV benefits. Further investigations are warranted to elucidate the underlying mechanisms and confirm the therapeutic efficacy of GLP-1a in this patient population.

External validation of a modified cardiovascular sequential organ failure assessment score in patients with suspected infection using the MIMIC-IV database.

We developed a modified cardiovascular (CV) Sequential Organ Failure Assessment (SOFA) score using an emergency department-based cohort data, incorporating norepinephrine equivalent dose and lactate to represent current clinical practice patterns for vasopressor utilization and the diagnostic significance of lactate, respectively. In this study, we sought to validate this modified CV-SOFA score in intensive care unit patients with suspected infection using the Marketplace for Medical Information in Intensive Care (MIMIC)-IV database. This was a retrospective study that utilized data from the MIMIC-IV database. Modified CV/total SOFA score and original CV/total SOFA score were compared for predicting in-hospital mortality. Area under the receiver operating characteristic curve (AUROC) and the calibration curve were employed to evaluate discrimination and calibration, respectively. A total of 29,618 ICU patients with suspected infections was analyzed. The in-hospital mortality rate was 12.4% (n = 3,675). Modified CV-SOFA score (AUROC 0.667; 95% confidence interval [CI] 0.657-0.677 vs. 0.663; 95% CI 0.654-0.673; p = 0.283) and modified total SOFA score (0.784 [95% CI 0.776-0.793] vs. 0.785 [95% CI 0.777-0.793], p = 0.490) did not differ significantly from the original CV-SOFA score and original total SOFA score, respectively. The calibration curve of the original CV-SOFA score was inferior to that of the modified CV-SOFA score. The modified CV- and total SOFA scores were better calibrated than the original CV- and total SOFA scores, but their discriminative performance was not significantly different. Further studies of the modified CV-SOFA score in different settings and populations are required to assess the generalizability of this score.

Abstract 4139141: Predicted efficacy of inclisiran on cardiovascular outcomes in lower extremity peripheral artery disease: results of the In Silico Sirius study

Introduction: Symptomatic lower extremity peripheral artery disease (PAD) patients have the highest risk of cardiovascular (CV) outcomes among patients with established atherosclerotic cardiovascular disease (ASCVD). Inclisiran, an siRNA targeting PCSK9 mRNA, reduces LDL-C levels. In SIRIUS in silico trial (NCT05974345), inclisiran was predicted to lower CV events in ASCVD patients. Research question/Hypothesis: SIRIUS in silico study aims to predict the efficacy of inclisiran on CV outcomes in subgroups of patients with or without PAD. Methods: The SIRIUS in silico trial was conducted using a knowledge-based mechanistic computational model of ASCVD applied to a virtual ASCVD population with LDL-C ≥ 70 mg/dL. Each virtual patient is its own control. This model was previously calibrated and validated before running the trial. SIRIUS compared the efficacy of inclisiran vs placebo on top of High Intensity (HI) statins with or without ezetimibe on 3-Point-MACE defined as a composite of time to first occurrence of CV death, nonfatal myocardial infarction (MI) or nonfatal ischemic stroke (IS) over 5 years. Occurrence of major acute limb events (MALE) was also individually assessed in time-to-first-event analyses. Results: Among 204, 691 virtual SIRIUS ASCVD patients, 28,072 (13.7%) had PAD. At 5 years, the mean predicted percentage reduction in LDL-C with inclisiran as compared to placebo was -49.3% and -49.8% in patients with or without PAD, respectively. The predicted rate of 3P-MACE in the inclisiran arm was consistently lower than in the placebo arm in patients with PAD (17.62% vs 22.88%; Hazard Ratio (HR): 0.75 medium uncertainty) and in patients without PAD (10.33% vs 13.64%; HR: 0.75 low uncertainty). Compared to placebo, inclisiran was also predicted to consistently reduce MALE in patients with or without PAD (2.71% vs 4.11%; HR: 0.65 medium uncertainty and 0.19% vs 0.29%; HR: 0.66 high uncertainty respectively). Conclusion: Pending the results of ORION-4 and VICTORION-2-P, this first In Silico trial in virtual PAD patients predicted a potential effect of inclisiran on 3P-MACE and MALE reductions over 5 years follow-up.