tbuckley/cabot-search huggingface dataset:
Abstract 4139026: Prevalence of Familial Hypercholesteremia (FH) Among Participants in the ACCELERATE Trial: Implications for Opportunistic FH Screening and Prognostication
Authors: Ashish Sarraju, Julie St John, Abhayjit Singh, Josh Knowles, Fatima Rodriguez, Dennis Bruemmer, Leslie Cho, Luke Laffin
Journal: Circulation (2024)

Background: Familial hypercholesteremia (FH) leads to elevated low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (ASCVD). Although treatable, FH is underdiagnosed. Lipid lowering therapy may mask diagnostic pretreatment LDL-C levels. Participants of ASCVD trials may be enriched for FH, so ASCVD trial enrollment may be a unique contact point to opportunistically diagnose FH. Hypothesis: The population of the ACCELERATE trial of evacetrapib and ASCVD outcomes is enriched for FH. Methods: ACCELERATE is a phase 3 cardiovascular outcomes trial which randomized 12,092 patients with high-risk vascular disease to receive evacetrapib or placebo. FH was not reported. Using participant-level data, we estimated pretreatment LDL-c using validated corrections based on type and dose of statin therapy. We defined severe hypercholesterolemia as pretreatment LDL-C ≥ 190 mg/dl and FH as severe hypercholesterolemia with total cholesterol &gt; 290 mg/dL in a first or second degree relative, consistent with Simon Broome register criteria. We compared trial prevalence to general prevalence (severe hypercholesterolemia ~7%, FH ~0.4%). We evaluated the adjusted association of severe hypercholesterolemia with the primary trial endpoint of ASCVD events using multivariable Cox proportional hazards regression. Results: Data were available for 11,993 participants (99%). The prevalence of severe hypercholesteremia was 15% (1809/11993). The prevalence of FH was 2.1% (255/11993). Pretreatment LDL-C ≥ 190 mg/dL, as compared with pretreatment LDL-C &lt; 190 mg/dL, was significantly associated with a higher incidence of the primary ASCVD trial endpoint (15% vs 13.5% respectively, adjusted hazard ratio 1.19; 95% CI 1.03-1.38, P=0.021; Figure ). Conclusion: In a participant-level analysis of a rigorous, independently adjudicated ASCVD outcomes trial, severe hypercholesterolemia and FH were more prevalent in the trial population than the general population based on pretreatment LDL-C calculation. Severe hypercholesterolemia was significantly associated with higher ASCVD incidence. ASCVD trial enrollment may be a novel high-yield contact point for index FH case identification using simple pretreatment LDL-C calculation.
Abstract 4140005: Trends in Stimulant-Involved Cardiovascular Disease Mortality, 1999 – 2023
Authors: Rebecca Arden Harris
Journal: Circulation (2024)

Introduction: Cocaine and methamphetamine, stimulants with potent central nervous system effects, are known to be cardiotoxic. They increase the risk of hypertension, coronary artery disease, coronary vasospasm, arrhythmias, cardiomyopathy, cardiac arrest, and stroke. Despite these well-documented risks, the National Survey on Drug Use and Health reports that illicit stimulant use is increasing. Research Question: How have mortality rates changed over time when cardiovascular disease (CVD) is the underlying cause of death and illicit stimulant use is a contributing factor? Aims: To describe trends in cardiovascular mortality rates from 1999-2023 and to stratify the analysis by race, ethnicity, sex, age, CVD subcategories, and stimulant type. Methods: We leveraged CDC WONDER data to model age-adjusted CVD mortality rates from 1999 to 2023 using joinpoint regression. For each stimulant type, demographic group, and CVD subcategory, we report annual percent changes (APCs) for each time segment and average annual percent changes (AAPCs) to estimate overall trend direction and magnitude. Results: From 1999 to 2023, stimulant-involved CVD mortality rates increased significantly, with an AAPC of 6.4%, contrasting sharply with the 2.0% decline in overall CVD mortality rates (Table). Each subcategory of CVD mortality (ischemic heart disease, hypertension; cerebrovascular disease) showed AAPC increases when stimulants were involved, with hypertensive diseases experiencing the largest AAPC rise at 9.1%. Stratifying by drug type, methamphetamine-involved CVD death rates increased by 14.9% AAPC, compared to a 3.1% increase for cocaine-involved deaths. Demographic stratification revealed additional differences. Non-Hispanic White individuals had the highest AAPC (9.2%), followed by Asian/Pacific Islander (5.6%), Hispanic (5.4%), Non-Hispanic Black (3.0%), and American Indian/Alaskan Native individuals (1.9%). A higher AAPC also was observed among those aged ≥65 years (14.6%). Conclusions: Cardiovascular deaths where stimulants were a contributing cause have increased rapidly over the past 25 years despite the overall decline in the CVD mortality rate during the same period. The largest increases were seen in hypertensive diseases, methamphetamine-involved deaths, non-Hispanic White individuals, and older individuals. This study extends our understanding but is limited by potential inaccuracies in the recorded causes of death.
Abstract 4140291: Unraveling the potential receptors involved in mediating globular CTRP9's protective effects in the cardiovascular system
Authors: Kayleigh Wyatt, Huilan Tan, Yalin Wu, Taslima Akter Shila, Amr Mahmoud, yanwen liu, Xinliang-Xin Ma, Jianli Zhao, Yajing Wang
Journal: Circulation (2024)

Improved reperfusion strategies have significantly reduced mortality rates after acute myocardial infarction. However, chronic heart failure cases are rising. Cardiokines and adipokines, as paralog family members, share similarities in multiple aspects and play critical roles in protecting against heart failure by blocking its progression. It has been debated and remains elusive whether the CTRP family has its own receptors or shares them with other family members during disease conditions. Our previous research has indicated that globular CTRP9 (gCTRP9) plays a vital role in protecting the cardiovascular system by promoting cell proliferation and energy production in ischemic-injured hearts. However, the signal transduction mechanisms are not yet fully understood. To address this gap in knowledge, we aimed to identify the potential cell membrane receptor for CTRP9 by analyzing the interaction between CTRP9 and three candidate receptors, namely Cadherin-13, adiponectin receptor 2, and adiponectin receptor 1. We utilized Surface Plasmon Resonance to examine the binding specificity, kinetics, and affinity of CTRP9 at a concentration of 50 µg/ml with varying levels of Cadherin-13 and Adiponectin Receptor 1, ranging from 0.1 to 100 µg/ml. Our results showed that gCTRP9 exhibited saturation on the carboxyl chip, indicating its ability to bind to specific mobile receptors on the surface. Notably, we observed a significant binding affinity between CTRP9 and Adiponectin Receptor 1 in a dose-dependent, suggesting a stronger interaction between Adiponectin Receptor 1 and CTRP9. In contrast, Cadherin-13 also exhibited some binding affinity with CTRP9, although the response was comparatively lower. Importantly, no binding signals were detected between CTRP9 and Adiponectin Receptor 2. In conclusion, our study provides evidence that Adiponectin Receptor 1 is a potential cell membrane receptor for gCTRP9, playing a crucial role in transmitting signals that protect injured or diabetic cardiomyocytes. Further research is needed to fully understand the downstream signaling pathways and mechanisms by which gCTRP9 and Adiponectin Receptor 1 interact to exert their protective effects on the cardiovascular system.
Abstract 4140035: Sex Differences in Nature History and Clinical Prognosis in Asymptomatic Significant Pulmonary Regurgitation Patients
Authors: Wenhao Zhu
Journal: Circulation (2024)

Background: There are limited data on the sex differences in the nature history and prognostic factors of asymptomatic pulmonary regurgitation (PR) patients. Objectives: This study aims to investigate the sex-specific differences in the nature history and clinical prognosis of PR. Methods: Asymptomatic PR patients undergoing cardiac magnetic resonance at our hospital between 2013 to 2023 were consecutively screened and followed until 2024; baseline characteristics and multimodality imaging variables at the first CMR examination time were assessed. The primary objective was the composite of cardiovascular death, cardiac hospitalization, and pulmonary valve replacement (PVR) events. Results: Overall, 173 males and 141 females were included. At baseline, females had lower QRS duration, right ventricular (RV) end-diastolic volume index (EDVi), and RV end-systolic volume index (ESVi) than males (All P &lt; 0.05). The risk of the primary objective was higher in females (unadjusted HR: 1.697; 95% CI: 1.157, 2.489), it was even more pronounced after multivariable adjustment. This sexual disparity persisted in adult patients, irrespective of the primary diagnosis. Secondly, QRS &gt; 160ms, RVESVi ≥ 80ml/m 2 , and RVEDVi ≥ 150ml/m 2 were not sex-specific, whereas RV eject fraction &lt; 47% had predictive value only in females. Additionally, all risks related to these factors were higher in females. Conclusion: Females have a paradoxical increase in PVR events despite milder RV remodeling at baseline and they maintained a higher risk compared with males across longer QRS, larger RVEDVi and RVESVi, and lower RVEF; these findings suggested that this sexual disparity cannot be ignored when discussing thresholds.
Abstract 4139032: Torsemide versus furosemide for hospitalization in patients with heart failure: a meta-analysis and trial sequential analysis
Authors: Lucas Barbosa, Beatriz Araujo, Ivo Queiroz, Giulia Almiron
Journal: Circulation (2024)

Background: Furosemide is the most commonly used loop diuretic in patients with heart failure (HF). However, recent studies suggest that torsemide might be a better option, potentially reducing hospitalization rates. This meta-analysis aimed to compare the effectiveness of torsemide versus furosemide in patients with HF. Methods: We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) comparing torsemide versus furosemide in HF patients. We pooled risk ratios (RR) for binary outcomes, and mean differences (MD) for continuous outcomes with 95% confidence intervals (CI) with a random-effects model. We performed a trial sequential analysis (TSA) to assess the random risk of HF-related hospitalizations. We used R version 4.3.2 and TSA version 0.9.5.10 for statistical analyses. Results: Our meta-analysis included 9 RCTs comprising 4077 patients, of whom 2014 (49.4%) were randomized to torsemide. The mean age was 65.9 years old. Torsemide significant reduced the HF-related hospitalizations (RR 0.61; 95% CI: 0.45 to 0.83; p&lt;0.05; Figure A), cardiovascular hospitalization (RR 0.73; 95% CI: 0.61 to 0.89; p&lt;0.05; Figure B), and all-cause hospitalization (RR 0.95; 95% CI: 0.90 to 0.99; p&lt;0.05; Figure C). However, there were no significant differences in all-cause mortality (RR 0.98; 95% CI: 0.88 to 1.11; Figure D) between groups. Additionally, for the primary endpoint, TSA suggested a low risk of type 1 error; therefore, this result may be conclusive (Figure E). Conclusion: In patients with heart failure, torsemide significantly reduced the incidence of hospitalizations. However, it appears not to have significant benefits in mortality rates.
Abstract 4140006: Risk of Acute Ischemic Stroke with Early Versus Late Initiation of Mechanical Circulatory Support in Patients with Acute Myocardial Infarction Complicated by Cardiogenic Shock: A Propensity-Matched Analysis
Authors: Rui Yan, Guangzhi Cong, Shaobin Jia, Xueping Ma, Bo Shi, Congyan Ye, Shizhe Fu, Kairu Wang, Haowei Li, Baotong He, Zefeng He, Israel GITANGAZA, Abdul Rehman
Journal: Circulation (2024)

Background: Mechanical circulatory support (MCS) devices have been widely used for managing acute myocardial infarction complicated by cardiogenic shock (AMI-CS). However, their use additionally elevates acute ischemic stroke (AIS) risk. There is insufficient data on the risk of AIS associated with early versus late initiation of MCS in AMI-CS cases. Aims: This study aimed to assess the timing of MCS initiation associated with the risk of AIS in patients with AMI-CS. Methods: A retrospective of the National Inpatient Sample data analysis (January 2016–December 2020) identified AMI-CS hospitalizations: categorized into early MCS initiation (&lt;48 h) and late MCS initiation (&gt;48 h). The primary outcome was AIS; the secondary outcomes included in-hospital mortality, acute kidney injury (AKI), cardiac arrest, major bleeding, and blood transfusion. The outcomes were compared using logistic multivariate regression and 1:1 propensity score-matching analyses between the groups. Results: From 2016 to 2020, the use of IABP decreased from 35.89% to 30.21%, whereas Impella use increased from 8.49% to 15.27% and ECMO use increased from 2.05% to 2.90% . The incidence of AIS in patients with AMI-CS receiving MCS remained stable over the study period; 3.55% in 2016 and 4.54% in 2020 (P trend = 0.277). Among 78,405 weighted patients with AMI-CS receiving MCS, 82.77% (n=64,895) and 17.23% (n=13,510) underwent early and late MCS initiation, respectively. The patients with late MCS initiation had higher risks of AIS (5.74% vs. 3.60%; adjusted odds ratio [aOR] 1.46; 95% confidence interval [CI], 1.19-1.79; p&lt;0.001), AKI (61.73% vs. 50.40%; aOR, 1.41; 95%CI 1.27-1.55; p&lt;0.001), and major bleeding (43.19% vs. 29.72%; aOR, 1.12; 95%CI 1.01-1.23; p=0.028). A propensity-matched cohort, adjusted for risk factors indicated that late MCS initiation remained associated with increased risks of AIS (aOR, 1.39; 95%CI 1.08-1.78; p=0.010), AKI (aOR, 1.37; 95%CI 1.23-1.53; p&lt;0.001), and major bleeding (aOR, 1.14; 95%CI 1.02-1.28; p=0.027). Furthermore, subgroup analysis revealed that an AMI-CS hospitalization with late MCS was consistently associated with a high AIS risk among all subgroups. Conclusions: Among patients with AMI-CS, late initiation of MCS was associated with increased risks of AIS, AKI, and major bleeding. Further studies are needed to decipher the optimal timing of MCS initiation to improve outcomes in this critically ill population.
Abstract 4138182: Evaluation of ACTION-ICU Score as a Predictor of Complications Requiring Intensive Care in a Mexican Cohort of Patients with Non-ST-Segment Elevation Myocardial Infarction
Authors: Jose Martin Alanis Naranjo, Julio Cesar Rivera Hermosillo, Jose Evodio Villegas Mayoral
Journal: Circulation (2024)

Introduction: The ACTION-ICU Score is a tool to assess the risk of complications associated with non-ST-segment elevation myocardial infarction (NSTEMI) requiring intensive care unit (ICU) admission. Limited studies have investigated the effectiveness of risk scores in predicting the need for ICU care in patients with NSTEMI. We evaluated the performance of the ACTION-ICU Score in Mexican patients with NSTEMI. Methods: A retrospective cohort study of patients over 18 years old who were admitted to a coronary care unit in Mexico City, Mexico, between January 1, 2017, and December 31, 2023, with a diagnosis of NSTEMI according to the fourth universal definition of myocardial infarction; patients with cardiac arrest or shock on admission were excluded from the study. The ACTION-ICU score was applied to all patients based on the collected data. The cut-off score for ICU admission is 5, with a 9.3% risk of complications. During hospitalization, the composite primary outcome included cardiac arrest, shock, heart block requiring a pacemaker, respiratory failure, stroke, or death. The score's performance was estimated with a conditional multivariable logistic regression analysis, and the area under the curve (AUC) was calculated. Results: Among 345 patients with NSTEMI, 41 (14.2%) developed the primary outcome. The most common complications were shock (12.5%) and respiratory failure (8.1%). Regarding the score, heart failure was the variable with a significant risk of developing the primary outcome [OR: 4.78; 95% CI 2.17-10.5, p-value &lt;0.01]. A score of 0 to 5 points was present in 187 patients (54.2%), ten of whom (5.3%) developed the primary outcome. The score had an AUC of 0.77 [CI 0.64-0.97, p-value 0.01], better than the original study. Conclusion: The ACTION-ICU score identifies Mexican patients with NSTEMI who need ICU care, providing a valuable tool for predicting complications and implementing best practices in medical units with limited resources.
Abstract 4138864: Characterizing Coronary Artery Outcomes with Real World Use of Etanercept for Kawasaki Disease with Coronary Involvement
Authors: Ryan Rogers, Aaron Olson, Eyal Sagiv, Michael Portman
Journal: Circulation (2024)

Background: The Etanercept as Adjunctive Treatment for Acute Kawasaki Disease study, a phase 3 randomized placebo-controlled clinical trial, evaluated etanercept, a TNF-alpha inhibitor, as an adjunct to IVIg for Kawasaki Disease (KD). In children presenting with coronary artery (CA) aneurysm, etanercept resulted in reduction in progression of CA dilation and earlier aneurysm regression compared to placebo. Following study conclusion, our institution implemented etanercept as a first line IVIg adjunctive treatment for patients presenting with early CA aneurysm formation. Hypothesis: Real world use with etanercept as adjunct to IVIg in children with KD and CA aneurysm shows high patient compliance, is safe and results in early CA regression. Methods: We reviewed charts and echocardiograms for all children admitted to Seattle Children’s Hospital from 5/2019 to 4/2024 and treated with etanercept for KD with CA aneurysms at presentation (Z-score ≥2.5 per AHA aneurysm definition). Etanercept is injected subcutaneously at 0.8 mg/kg with IVIg at diagnosis and then with 2 repeat weekly doses at outpatient visits. Results: Thirty-six patients with KD and CA aneurysms received at least one dose of etanercept. Sixteen (44%) were &lt;1 year of age, 17 (47%) were diagnosed with incomplete KD and 5 (14%) were ‘IVIg refractory.’ Four patients responded to a second IVIg dose and two patients received additional biologic agents. Thirty-two patients completed the 3-dose course of etanercept, with outpatient doses administered 6.6±1.5 days (mean±SD) and 13.5±2.3 days after the first. Seven patients had giant CA aneurysms (Z-score ≥10) requiring anticoagulation. In patients with giant aneurysms and at least 6-month follow-up, all aneurysms regressed to below the threshold for requiring anticoagulation beyond aspirin. Of 31 children with long-term follow-up echocardiograms available, 19 had complete resolution (Z-score &lt;2.5) of CA dilation by 6 months, 22 by 1 year, and 29 by 2-year follow-up. No severe or serious adverse events were attributed to etanercept. Conclusions: Etanercept for KD with early CA aneurysms was delivered safely and with high compliance. CA aneurysm regression occurred in most patients with marked reduction in giant CA aneurysms by 6 months. These real-world data support the use of etanercept as an intensification therapy for preventing persistence of CA aneurysms in KD.
Abstract 4139936: Effectively Communicating the Seriousness of High Cholesterol at Diagnosis to Improve Shared Decision-Making and Adherence: Findings from the Patient-Led “Insights from Patients Living with Elevated Cholesterol” (IPEC) Study
Authors: Neil Johnson, Joe Vandigo, Fernanda De Carvalho, Celina Gorre, Tanya Hall, Susan Hennessy, Dhruv Kazi, Kornelia Kotseva, Patsy Petrie, David Kelly, Elisabeth Oehrlein
Journal: Circulation (2024)

Background: Shared decision-making aims to improve health outcomes by empowering patients to make informed decisions with their healthcare providers. While decision aids guide treatment choices, they may not help providers effectively communicate the importance of treatment and the risks of non-adherence. We explored patient perspectives on shared decision-making and communication of CVD risks upon diagnosis with elevated LDL-C, a significant risk factor for CVD. Aims: To learn from people with high cholesterol about their experiences, decisions, and perspectives on being diagnosed and living with high LDL-C, including awareness of the association between high LDL-C and other risk factors for heart disease and stroke. Methods: The design and interpretation of this cross-sectional, qualitative study were guided by a global multi-disciplinary steering committee. Fifty people with confirmed high LDL-C in Brazil, Australia, and the United States participated in 60-minute interviews between November 2023-March 2024. Half were required to have an ASCVD-related hospitalization. Interview transcripts were thematically analyzed. Results: Table 1 describes participant characteristics. During their high-LDL-C diagnosis encounter, participants often described being overwhelmed by multiple concurrent diagnoses, unfamiliar medical terms, and concerns about elevated cardiac risk. Most participants stated that their primary source of information, upon diagnosis and throughout their experiences with high LDL-C, is their HCP. Some described underestimating cardiac risks if treatment plans included lifestyle changes only or if discussions focused primarily on comorbidities. Reflecting on time between diagnosis and an ASCVD event, many participants acknowledged they had not taken their care plan as seriously as they should have. Participants offered messages and suggestions for communicating effectively with others with high LDL-C at diagnosis and regularly after diagnosis (see Table 2). Conclusions: Findings highlight an opportunity to improve cardiovascular care by overcoming indifference towards high LDL-C. Effective communication by healthcare providers at diagnosis and beyond, such as emphasizing the severity of high cholesterol and providing a realistic care plan, is crucial.