tbuckley/cabot-search huggingface dataset:
Abstract 4141217: Lipid Profiles and Prognosis in Heart Failure: A Participant-Level Pooled Analysis of the PARADIGM-HF and PARAGON-HF Trials
Authors: Sara Siqueira, Maria Pabon, Brian Claggett, Milton Packer, Carolyn Lam, Jean Rouleau, Michael Zile, Marty Lefkowitz, Akshay Desai, Pardeep Jhund, John McMurray, Muthiah Vaduganathan, Scott Solomon
Journal: Circulation (2024)

BACKGROUND: Higher total cholesterol (TC) and LDL-C levels may improve outcomes in heart failure (HF) patients. Elevated remnant cholesterol (RC) is a novel potential atherosclerosis risk factor, but its role in HF is underexplored. AIM: To investigate classical (TC, LDL-C, triglycerides (TG), and HDL-C) and novel (RC) lipid parameters (LP) as risk determinants for CV events in HF patients across the LVEF spectrum. METHODS: We pooled participant-level data from the PARADIGM-HF (LVEF ≤40%) and PARAGON-HF (LVEF ≥45%) trials to assess the association of LP with CV outcomes. RC was calculated as TC minus the sum of HDL-C and LDL-C. Lipid levels were classified per the National Lipid Association and RC by quartiles. The associations with time to first HF hospitalization and myocardial infarction (MI) were evaluated by adjusted Cox proportional hazards models stratified by trial. Restricted cubic splines accounted for potentially non-linear relationships. RESULTS: Of 12,819 participants with available lipid data, 1,967 (15.3%) experienced HF hospitalization and 442 (3.4%) had an MI. Over a median follow-up of 2.6 years, various LP were not consistently or significantly associated with risk of HF hospitalization, while higher RC and TC were linked to increased risk of MI (Table 1) . When evaluating LP continuously, there was a significant non-linear association between RC and risk of HF hospitalization, with a nadir in risk at ~ 20-30 mg/dL (Figure 1) . In contrast, higher levels of RC, LDL-C, and TC were linearly and significantly associated with risk of MI. None of the results were modified by LVEF. CONCLUSION: In a global HF population, higher RC levels were consistently associated with increased risk of MI, while the relationship between RC and the more frequent endpoint of HF hospitalization appeared to be more complex and inconsistent. These data might explain why previous interventional lipid lowering trials have not modified disease course in HF.
Abstract 4140703: CXCL10 and IFN-γ Mediate Myocardial Injury Post-COVID-19 mRNA Vaccination
Authors: Masataka Nishiga, Xu Cao, Amit Manhas, Arianne Caudal, Gema Mondejar-Parreno, Shane Zhao, James Jahng, Mingqiang Wang, Pj Utz, Kari Nadeau, Joseph Wu
Journal: Circulation (2024)

Background: The mRNA vaccines against COVID-19 are highly effective but have been associated with a rare non-infective form of myocarditis, particularly in young males after receiving the second dose. Understanding the mediators of this adverse effect is crucial to enhance the safety of future mRNA vaccines. Hypothesis: Myocardial injury following COVID-19 mRNA vaccination is mediated by overproduced cytokines, and estrogens have a protective effect on this adverse effect. Approach: Candidate cytokine mediators were identified through analysis of proteomics data from plasma samples of vaccinated individuals. Human iPSC-derived macrophages and cardiomyocytes were used to model cytokine-induced effects. An in vivo mouse model of cytokine-induced myocardial injury was employed to assess the impact of the cytokine cocktail and estrogens. Results: CXCL10 and IFN-γ were consistently upregulated in vaccinated individuals on day 1 and further elevated in patients with myocarditis following mRNA vaccination. Consistently, iPSC-derived macrophages exposed to COVID-19 mRNA vaccines produced these cytokines. Next, iPSC-derived cardiomyocytes exposed to these cytokines showed impaired contractility, arrhythmogenicity, and pro-inflammatory gene expression. The phytoestrogen genistein mitigated these effects in vitro, reducing cytokine-induced proteasomal degradation of cardiac proteins and preserving contractile function. In vivo, genistein significantly decreased cardiac injury markers and immune cell infiltration in a mouse model of cytokine-induced myocardial injury. Conclusion: CXCL10 and IFN-γ are key mediators of myocardial injury post-mRNA vaccination. Genistein shows potential as a therapeutic agent to mitigate associated cardiovascular risks.
Abstract 4140852: Total Burden of Posttraumatic Stress Disorder on Incident Cardiovascular Disease Among Women Veterans
Authors: Ramin Ebrahimi, paul dennis, Carlos Alvarez, jean beckham, Annie Shroyer, Jennifer Sumner
Journal: Circulation (2024)

Introduction: Posttraumatic stress disorder (PTSD) is an independent cardiovascular disease (CVD) risk factor with high prevalence in women, particularly women veterans (WV). While the impact of PTSD on ischemic heart disease (IHD) and stroke has been well established, its impact on a comprehensive set of CVD outcomes has not been studied in WV, a growing population at high risk for CVD in the U.S. The goal of this project was to investigate the impact of PTSD on a comprehensive set of CVD conditions in WV. Methods: National Veterans Health Affairs (VHA) electronic health records were used to identify all women who visited any VAs from 1/1/2000 to 12/31/2019. PTSD and CVD were identified based on International Classification of Disease versions 9 and 10 diagnoses ( 1 inpatient or 2 outpatient encounter documentations). Incident CVD outcomes included first onset of IHD, stroke, cardiomyopathy/heart failure (HF), pulmonary arterial hypertension/pulmonary hypertension (PH), atrial flutter/fibrillation (AF), peripheral arterial disease (PAD), venous thromboembolism (VTE), and aortic stenosis (AS). Propensity score matching and Cox survival analyses were performed to assess associations of PTSD with incident CVD outcomes. Results: We identified 622,312 WV, with 140,210 (22.53%) with PTSD. After 1:1 matching, 202,896 patients were included in the final analysis. WV had a mean age of 39.1 years, and the mean [MOU1] follow-up was 5.72 years. Table 1 reveals the association of PTSD with an incident CVD composite and the different component outcomes individually. Conclusion: In a large sample of WV, we demonstrate significant and clinically relevant associations of PTSD with a comprehensive set of incident CVD outcomes. The potential association with some of the specific outcomes warrant further investigation. Maybe more of a call to action for PTSD screening and treatment to potentially offset CVD risk instead?
Abstract 4141561: Impact of Snowfall on Emergency Medical System and In-hospital Mortality in Patients with Acute Coronary Syndrome
Authors: Yuki Mori, Toshiyuki Nagai, Sakae Takenaka, Kohei Saiin, Akinori Takahashi, Yoshifumi Mizuguchi, Takao Konishi, Seiji Yamazaki, Mitsunori Kamigaki, Daisuke Hotta, Kandoh Kawahatsu, Tsutomu Fujita, Takehiro Yamashita, Toshihisa Anzai, Takao Makino
Journal: Circulation (2024)

Background: Acute coronary syndrome (ACS) requires rapid transportation by the emergency medical system (EMS) and emergent percutaneous coronary intervention (PCI). In snowy areas, traffic conditions due to snowfall may delay EMS transport times and increase short term mortality of ACS. However, there is a paucity of data showing how snowfall affects the EMS and clinical outcomes in patients with ACS. We sought to investigate the impact of snowfall on the EMS transport time and in-hospital mortality in patients with ACS. Methods: We examined 2,387 consecutive ACS patients who were transported via EMS to 29 acute cardiac care facilities in Sapporo city (fifth largest in Japan) between April 2013 and March 2023. The patients were divided into two groups according to hospital arrival at snowy or non-snowy day. Results: The median age was 68 years, 1,754 (74.6%) patients were male, and 34.9%, 70.1%, and 69.2% had diabetes mellitus, hypertension, and dyslipidemia, respectively. There were no significant differences in gender, Killip classification, blood pressure, heart rate, or laboratory findings between the groups. Patients in snowy day group had longer time from EMS call to hospital arrival than those in non-snowy day group (33 [26–40] vs 29 [24–36] min, P &lt;0.001). Quantity of snowfall was associated with a delayed time from EMS call to hospital ( Figure ). The proportion of emergent PCI and door-to-balloon time were similar between the groups. In-hospital death occurred in 125 patients (5.3%). The proportion of in-hospital death was higher in snowy day group compared to non-snowy day group (4.6% vs. 7.3%, P = 0.011). The snowfall was independently associated with a higher incidence of in-hospital death ( Table ). Conclusions: The snowfall was significantly associated with prolonged transfer time in EMS and higher in-hospital mortality in patients with ACS. These findings are relevant for developing traffic obstacles prevention strategies and ensuring timely treatment.
Abstract 4141557: Does Copayment for Cardiac Rehabilitation Impact Attendance? An Analysis from the American Association of Cardiovascular and Pulmonary Rehabilitation Registry
Authors: Quinn Pack, Maryam Naser, Michel Farah, Yu Zhang, George Howard
Journal: Circulation (2024)

Introduction: Improving cardiac rehabilitation (CR) attendance is a national priority. However, insurance companies often charge copays for CR, and patients commonly report copays as a barrier to attendance. Aim: To describe the prevalence of copays, their amounts, and the associations with attendance and drop-out in a national sample. Methods: We analyzed the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) registry through the AACVPR Data Analytic Center. We included patients from 2012 to 2021 who had a value for copayment (including 0) and excluded patients with missing copay data. We described copay magnitude, prevalence, and associations with baseline factors, patient characteristics, region, and if copays were cited as a reason for drop out. In multivariable models, we analyzed if a copay of any amount was associated with CR attendance and if a dose-response existed. In all models, we adjusted for age, education, AACVPR risk category, surgical diagnosis, tobacco use, distance to CR, insurance, and median household income. Results: Among 489,507 total patients, 59838 were included in analyses, of which 16339 (27.3%) had a copay. Patients with copays had lower educational attainment and were more likely to have Medicare or Medicaid insurance. The median (IQR) copay was $24 (20, 34). Medicare, Medicaid, Private, and Other insurances charged a median (IQR) copay of $20 (20-25), $3.7 (3, 12), $30 (20-40), and $25 (20 to 36), respectively. Copays were more common in Florida, New York, and the Rocky Mountain States, (&gt;40% of patients) and more expensive in the northeast (median &gt;$34). In multivariable models, the presence of a copay was associated with attendance at 5 (4.3 to 5.6, p &lt; 0.001) fewer sessions of CR. When considering copay amount, every $10 increase in copay was associated with 0.5 (0.4 to 0.6, p &lt; 0.001) fewer sessions of CR. Finally, copays were cited as the reason for early drop out in 21% of cases, with 2.2 (p&lt;0.001) fewer sessions of CR compared to drop out for other reasons. Conclusion: In this national sample, copays for CR are common, costly, and associated with fewer sessions of CR. Policy makers should reconsider these policies to promote CR participation.
Abstract 4141532: Time-Restricted Eating Improves Heart Rate, Symptoms, and Quality of Life Metrics in Patients With Postural Orthostatic Tachycardia Syndrome
Authors: Marissa Dzotsi, Allyssa Strohm, Emily Manoogian, Satchidananda Panda, Taylor Doherty, Pam Taub
Journal: Circulation (2024)

Introduction/Hypothesis: Time-restricted eating (TRE) is a lifestyle intervention in which there is an extended fasting period overnight of about 14 hours with a 10-hour eating window. Clinical and animal studies have shown that TRE decreases inflammation, and improves immune autonomic and mitochondrial function and cardiometabolic parameters. Patients with POTS have derangements in many of these parameters resulting in the hypothesis that TRE could be beneficial for patients with POTS. Methods/Approach: 20 participants aged 18-70 (M=36 years ±11.79), all on pharmacological therapy for POTS, met inclusion criteria: ≥12-hour dietary window and established POTS diagnosis (≥30 bpm increase in upright heart rate). After a 2-week baseline period of monitoring via myCircadianClock App, to ensure baseline eating window was ≥12 hours, participants entered a 12-week TRE intervention, consuming calories within an 8-10 hour eating window. Pre/post-intervention assessments included a 10-minute stand test and QOL questionnaires (SF-36 and MALMO POTS). Results/Data: Orthostatic assessments comparing pre and post-intervention standing tests revealed reduction in heart rate increase. 19 of the 20 participants experienced this improvement, with the mean decrease in heart rate change (Figure 1A) averaging approximately 11 bpm (p &lt; 0.001). Additionally, outcomes from the MALMO POTS Symptom Score Survey (MALMO) (Figure 1B) and the Short Form (36) Health Survey (SF-36) showcased substantial enhancements in participants' QOL. These improvements were evidenced by reductions in POTS symptom severity (p &lt; 0.0001) and notable enhancements in physical functioning (p = 0.015) and energy/fatigue levels (p &lt; 0.01). Conclusion: In this pilot study, TRE improved heart rate, symptoms and QOL in patients with POTS, who are on background medical therapy, suggesting this lifestyle intervention could be beneficial for patients with POTS.
Abstract 4141630: Development of a Model for MEPPC Using hiPSC-HPCs and Bioprinted Purkinje Networks
Authors: Pengfei Ji, Bo Sun, Gabrielle Monaco, Jeffrey Heinle, Andrew Landstrom, Ravi Birla
Journal: Circulation (2024)

Introduction: Multifocal Ectopic Purkinje-related Premature Contractions (MEPPCs) is marked by early and frequent spontaneous membrane depolarization of the His-Purkinje cells (HPCs), which can trigger life-threatening arrhythmias and sudden death. It has been postulated that MEPPC-associated variants in SCN5A result in increased sodium influx leading to early depolarization and triggered arrhythmias. Hypothesis: Our central hypothesis is that MEPPC is caused by a gain-of-function in I NAV that leads to spontaneous HPC automaticity and triggered arrhythmogenesis originating from the CCS, which propagates into the surrounding myocardial tissue. Aims: The goals of this study are to develop a rigorous method to generate HPCs from human induced pluripotent stem cells (hiPSCs) and characterize he hiPSC-HPCs using IHC, qPCR and electrophysiology. A second objective of this study is to develop a method to bioengineer 3D Purkinje networks using state-of-the-art advances in laser based bioprinting. Methods: To generate hiPSC-HPCs, 90% of confluent hiPSCs were transitioned to GSK-3 inhibitor CHIR99021 followed by Wnt inhibitor IWP2 to generate cardiac progenitor cells. Subsequently, hiPSCs were exposed to sodium nitroprusside on day 5, which led to spontaneous beating after 10 days, followed by a change in cell morphology, transitioning to large and cylindrical cells indicative of HPCs. To generate 3D Purkinje networks, we used a commercial laser based bioprinter, the Lumen X. We optimized our bioink formulation and selected 90% PEGDA as our base polymer, supplemented with 10% GELMA. Results: Robust expression of both CNTN2, an HPC-specific marker, and HCN4, unique to cardiac nodal and conduction cells, was observed by IHC ( Fig. 1A ). We successfully bioprinted Purkinje networks ( Fig. 1B ) and cell viability was confirmed using a live/dead assay. Phenotype of hiPSC-HPCs within the bioprinted Purkinje networks was confirmed using CNTN2 staining ( Fig. 1C ), a marker specific for Purkinje cells. Conclusion: Our results demonstrate our ability to successfully reprogram hiPSCs to form HPCs and our ability to utilize these cells to bioprint human 3D Purkinje networks.
Abstract 4140908: ST Elevation Myocardial Infarction in the Setting of Severe Ectasia and Aneurysm of the Left Anterior Descending Coronary Artery.
Authors: Derek Ugwendum, Muhammed Atere, Divine B Arrey Agbor, Merschelle Tindoy, Meena Farid, Akua Aboah Taylor, Gautham Upadhya, Francesco Rotatori, Sean Galligan, Ricardo Castillo, Richard Grodman
Journal: Circulation (2024)

Background: Coronary artery aneurysm seen in patients undergoing coronary angiography is an uncommon disorder with poorly understood pathophysiology. Patients have variable clinical presentations and often poor long-term outcomes. Management of these patients still pose a clinical dilemma given there are no standardized treatment guidelines Description of case and discussion: A 44-year-old male with a significant past medical history of hypertension, diabetes mellitus, and hyperlipidemia presented in the emergency room (ER) for acute onset chest pain. His pain was retro-sternal, non-radiating, and pressure-like in nature. Pain was initially rated as 2/10 intensity which progressed to 9/10 later in the day with associated diaphoresis. He took acetaminophen which provided no relief. His electrocardiogram (EKG) showed ST elevation in the inferior and lateral leads. Initial troponin was negative. The cardiac catheterization laboratory was activated and the patient was administered loading doses of Aspirin, ticagrelor and a bolus of intravenous (IV) heparin. An emergent left heart catheterization and coronary angiogram was performed which revealed a 100% thrombotic occlusion of the mid LAD as well as severe ectasia of the proximal vessel. There was mild ectasia of the left circumflex and right coronary arteries without any significant stenosis. There were no collaterals to the distal LAD consistent with an acute presentation. At the level of the occlusion (mid LAD), there was an aneurysm measuring up to 10 mm in diameter by angiography. Intravenous eptifibatide was administered with the continuation of IV heparin. The thrombotic occlusion was managed medically with a plan to repeat angiography in 24-48 hours. Transthoracic echocardiography revealed a preserved left ejection fraction at about 55-60% with mild hypokinesis of the apex. Repeated angiography in 48 hours revealed a mostly patent LAD with diffuse TIMI 2 flow and sub occluded distal LAD at the apex. He was discharged home with dual antiplatelet therapy, a statin, and a beta blocker. Two weeks later he was seen on outpatient setting and his medications were transitioned to Rivaroxaban and clopidogrel Conclusion: Large LAD aneurysms are not common and they carry long term complications which includes thrombosis (as seen in our patient), fistula formation, and rupture. Management of this condition is still challenging as there are no standardized management guidelines.
Abstract 4141584: Associations of the Glasgow Prognostic Score with Adverse Outcomes in Patients with Acute Coronary Syndrome and Atrial Fibrillation
Authors: Hanyang Liang, Zhang Han, XingHui Shao, Juan Wang, Shuang Wu, Si-qi Lyu, Wei Xu, YANMIN YANG
Journal: Circulation (2024)

Introduction: Glasgow Prognostic Score (GPS), including c-reactive protein and albumin, has been used to assess inflammatory status in many diseases. The aim of this study was to evaluate the associations of GPS on prognosis in patients with acute coronary syndrome (ACS) and atrial fibrillation (AF). Methods: We conducted a prospective observational study and consecutively recruited 1153 patients with AF combined with ACS. The primary endpoint was all-cause mortality and the secondary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs). Three multivariable adjusted Cox proportional hazards models were performed to evaluate the associations between GPS and endpoints. Results: Patients were divided into 3 groups: GPS=0 (c-reactive protein≤10mg/L and albumin ≥35g/L, n=812), GPS=1 (c-reactive protein &gt;10mg/L or albumin &lt;35g/L, n=264), GPS=2 (c-reactive protein &gt;10mg/L and albumin &lt;35g/L, n=77). During a median follow-up of 34.0 months, log-rank analysis showed that higher GPS was associated with decreased overall survival (P&lt;0.001, Figure 1A) and a higher incidence of MACCEs (P&lt;0.001, Figure 1B). After adjustment for confounders including demographics, comorbidities, and treatments, multivariable Cox models showed that GPS=1 was independently associated with increased risk of all-cause mortality and MACCEs (Table 1). Conclusions: Hypoalbuminemia or elevated c-reactive protein is independently associated with worse prognosis in patients with ACS and AF, suggesting that inflammatory status plays an important role in the prognostic assessment of ACS patients with AF.
Abstract 4141606: Is 70% Achievable? Hospital-Level Variation in Rates of Cardiac Rehabilitation Use among Medicare Beneficiaries
Authors: Quinn Pack, Taylor Keys, Aruna Priya, Penelope Pekow, Steven Keteyian, Mike Thompson, Thomas D'Aunno, Peter Lindenauer, Tara Lagu
Journal: Circulation (2024)

Background: Hospitalization is an opportunity to refer and recruit eligible patients to cardiac rehabilitation (CR). Despite national goals to enroll 70% of CR-eligible patients, enrollment remains low, and little is known about how hospitals influence CR enrollment at the national level. Methods: We included fee-for-service Medicare beneficiaries older than 65 years who were hospitalized in 2017 for acute myocardial infarction (AMI), coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or heart valve repair/replacement. We examined the role of the hospital in CR enrollment using three different methods: 1.) a risk-standardized model to assess comparative hospital rates with bootstrap methods to group hospitals as above, at, or below national rates of CR (as might be done for quality incentives); 2.) a linear regression model to identify hospital factors associated with rates of risk-standardized CR; and 3.) a hierarchical generalized linear model to allow calculation of the hospital Median Odds Ratio (MOR). Results: At 3,420 hospitals, we identified 264,970 eligible patients. While a minority of hospitals (1,446; 38%) performed cardiac surgery, these hospitals cared for the vast majority (242,875; 92%) of all eligible patients, and subsequent analyses were limited to these hospitals. The median risk-standardized CR enrollment rate was low (22%) and varied 10-fold across hospitals at the 10 th and 90 th percentiles (3%, 42%). Bootstrap methods to group hospitals as above, at, or below national average demonstrated that about one-fifth of hospitals [301, 21%] had worse performance than the national mean and about one-third [453, 31%] had better performance than the national mean. Factors associated with higher hospital performance were Midwest location, higher number of hospital beds, directly affiliated CR program, and &lt;1 mile distance between the hospital and closest CR facility. The national hospital MOR was 2.1, similar in effect size as Midwest location. Discussion: The referring hospital plays a key role in facilitating CR enrollment after discharge, Fewer than 1% of US hospitals achieved a risk-standardized CR enrollment rate of &gt;70%. Hospitals with cardiac surgery capability care for more than 90% of all CR-eligible patients, and may be a logical place to focus improvement efforts.