tbuckley/cabot-search huggingface dataset:
Abstract 4142294: Anticoagulation for the Prevention of Stroke Recurrence in Embolic Stroke of Undetermined Source: a meta-analysis
Authors: Kuan Yu Chi, Junmin Song, Talal El Zarif, Dimitrios Varrias, George Ntaios, Yu-Cheng Chang, Cho Han Chiang, Adam Gershon, Pawel Borkowski, Michele Nanna, MD, FACC, Michael Nanna
Journal: Circulation (2024)

Background: The 2021 AHA/ASA stroke guideline highlighted the importance of identifying clinical factors to discern patients with embolic stroke of undetermined source (ESUS) who may benefit from anticoagulation as a key area for future investigation. Research Question: Which subsets of patients with ESUS potentially benefit from anticoagulation for secondary prevention? Aims: To identify potential subsets of ESUS who may benefit from direct oral anticoagulants (DOAC). Methods: Electronic databases were searched from January 1 st , 2014 to May 10 th , 2024 to identify randomized controlled trials (RCTs) comparing DOACs and aspirin for secondary prevention after ESUS. The efficacy outcome was comparative ischemic stroke recurrence between DOACs and aspirin. The safety outcome was major bleeding.Random-effects meta-analysis using restricted maximum likelihood method was performed, with a prespecified subgroup analysis based on participants with evidence of patent foramen ovale (PFO) and with signs of, or risk factors for atrial cardiopathy. Results: We identified four RCTs including 13,970 participants. Overall, DOAC did not lead to a significant reduction in the unselected ESUS population (RR, 0.92; 95% CI, 0.80 to 1.05; I 2 = 0%; Figure A). In patients with signs of or risk factors for atrial cardiopathy, there was a significant 16% reduction in recurrent ischemic stroke with DOAC (RR, 0.84; 95% CI, 0.70 to 0.99; I 2 = 0%; Figure A). Notably, a significant 36% reduction in stroke recurrence was observed in the subgroup using criteria more specific to atrial pathology for signs of atrial cardiopathy (RR, 0.64; 95% CI, 0.43 to 0.97; I 2 = 25%; Figure A). Conversely, no difference was noted in the subgroup using cardiac biomarkers criteria for signs of atrial cardiopathy (RR, 1.05; 95% CI, 0.78 to 1.43; I 2 = 0%; Figure A). The risk of major bleeding outside ICH was significantly higher with DOACs than with aspirin (RR, 1.63; 95% CI, 1.08 to 2.47; I 2 = 0%; Figure B). Conclusions: The use of DOAC was associated with a significantly lower risk of ischemic stroke recurrence in patients with ESUS presenting with signs of or risk factors for atrial cardiopathy, especially in those meeting criteria more specific to atrial pathology.
Abstract 4142708: DIgital REgistry for CardiomeTabolic conditions – Diabetes Mellitus (DIRECT-DM): A Large, Pragmatic, Multisite, Diverse Longitudinal Registry of Type 2 Diabetes
Authors: Aline Pedroso Camargos, Lovedeep Dhingra, Arya Aminorroaya, Rohan Khera
Journal: Circulation (2024)

Background: Despite the rising prevalence of T2DM, contemporary information on its longitudinal care and outcomes is limited and largely derived from small, self-selected cohorts. We describe the development and patterns of care of a digital pragmatic cohort of all T2DM patients seeking care in the multisite network of an integrated health system. Methods: DIRECT-DM is a digital registry of T2DM patients seeking care across multiple hospitals and community practices in CT and RI from 2013 to 2023. From 223,932 individuals with T2DM, those with regular care (≥1 visit every 2 years) were included in the longitudinal cohort. Mortality was derived from the CT Death Index, healthcare resource utilization (HRU) was tracked across all care settings, and exposomic drivers of outcomes were linked via zip-code-based community and environmental characteristics, including data drawn from census, surveys, and air quality metrics. In this report, we describe the cohort’s characteristics, patterns of HRU, particularly in those with CV disease and factors associated with HRU using multivariate Poisson regression. Results: DIRECT-DM included 106,881 T2DM individuals with a median age of 63 years (IQR 52-73), 50% women and 16% Black, who were followed for a median of 5.4 years (3.1-7.5), and 9% died. There were 2.3M healthcare visits, including 1.5M hospitalizations, 250K emergency department visits, and 1.9M outpatient visits with 11.4% of CV-related principal diagnoses. In the DIRECT-DM cohort, where 31.5% had established CV disease, the burden of HRU increased with the comorbidities burden, with those having CV disease experiencing the highest HRU (3.7 median visits/year for ASCVD [1.9-6.8] and 4.4 [2.2-8.0] for HF). However, for the same age, sex, and comorbidity profile, lack of health insurance (IRR 0.94; 0.92-0.97), low income (IRR 0.97; 0.96-0.98), and Black vs. White race (IRR 0.98; 0.98-0.99) were associated with lower HRU. Conclusions: DIRECT-DM is a pragmatic T2DM registry in a diverse high-risk population, identifying key factors associated with HRU among T2DM patients. While there was an expected increased HRU in established CV disease, there was a lower-than-expected HRU among racially and socioeconomically disadvantaged populations.
Abstract 4142629: Trends in Ischemic Heart Disease-Associated Mortality in Individuals with Diabetes Mellitus Type II
Authors: Sara Rahman, Abdullah Nofal, Maheen Khurram
Journal: Circulation (2024)

Introduction: Over 9 million people are estimated to die annually due to Ischemic Heart Disease (IHD). It also serves as an inviolable risk factor for diabetes mellitus type II-related mortality. However, trends in IHD-related mortality tend to show disparities, which if addressed, can improve outcomes. Research Question: What are the trends in IHD-associated mortality in individuals with diabetes mellitus type II in the USA? Goal: Determining trends stratified by age, gender, race, geographical location, and metropolitan status in IHD-associated mortality in diabetic individuals. Methodology: The CDC Wonder database was used to extract crude mortality rates (CMRs) and age-adjusted mortality rates (AAMRs) per 100,000 population from 1999 to 2020. Annual percentage change (APC) was determined using Joinpoint regression analysis to identify temporal trends. Results: The overall AAMR doubled from 1999 (AAMR: 6.61) to 2020 (AAMR: 12.50). It increased from 1999-2005 (APC: 3.67), followed by a decrease during 2005-2014 (APC: -1.09), and finally a steep incline till 2020; 2014-2018 (APC: 5.53) and 2018-2020 (APC: 12.70). Men had a higher AAMR than women, 11.57 versus 6.19. Older adults aged 85+ had the highest CMR (137). NH American Indians or Alaska Natives had the highest AAMR (12.01), followed by Hispanic or Latino (9.73), NH Black or African American (8.81), NH White (8.44), and NH Asian or Pacific Islander (6.69) populations. Stratified by census regions, the highest death rate was in the Midwestern region (AAMR: 10.07), followed by the Western, Southern, and Northeastern regions; AAMR: 9.74, 7.81, and 6.29, respectively. Among the states, West Virginia had the highest AAMR of 16.61, while Nevada had the lowest AAMR of 3.47. Non-metropolitan areas consistently showed higher rates (AAMR: 10.87). Conclusions: Rising trends were observed in IHD-related fatalities in type ll diabetes patients between 1999 and 2020. Amongst various groups, the highest AAMRs were found in those over 85 years, men, American Indians or Alaska Natives, and residents of the Midwest, West Virginia, and non-metropolitan areas. These findings can aid in developing targeted interventions and strategies to counter the alarming rise in mortality rates.
Abstract 4142625: Ultrasonic Evaluated Endothelial Dysfunction Highly Predicts Future Diabetic Evolution And Development Of Fatal Events
Authors: Tatsuaki Murakami
Journal: Circulation (2024)

Introduction: Although diabetes mellitus (DM) and endothelial dysfunction are thought to affect atherogenic processes, we know little about the clinical impact of endothelial dysfunction on evolutional mechanisms of DM. Hypothesis: This study assessed hypothesis that endothelial dysfunction accelerates diabetic evolution and adverse clinical events. Methods: Endothelial dysfunction was graded by reactive changes in lumen diameter of right brachial artery following transient forearm occlusion (FMD; flow-mediated endothelium-dependent vasodilation) in consecutive 518 patients with stable coronary artery disease using high-resolution ultrasonography. The enrolled patients were categorized into 3 groups according to the values of FMD, and their glucose tolerance and adverse clinical events were followed-up for 36 months or more. We prospectively followed up diabetic evolution, which was defined as newly diagnosed DM by 75g-OGTT or new administration of an antidiabetic agent. Results: For a mean follow-up period of 60 months with 100% follow-up, the patients with severe endothelial dysfunction (FMD&lt;4%; Group-L, n=174), more frequently manifested diabetic evolution [Group-L versus Group-M with mild endothelial dysfunction (4%≤FMD&lt;8%, n=171) plus Group-H with preserved endothelial function (FMD 8% or more, n=173): 25 (14.4%) versus 12 (7.0%) plus 7(4.0%), p&lt;0.001, by Kaplan-Meier analysis]. The patients in Group-L more frequently resulted in fatal events [Group-L versus Group-M plus Group-H: 15(8.6%) versus 4(2.3%) plus 2(1.2%), p&lt;0.001]. HbA1c significantly elevated in Group-L (5.9±0.6 to 6.2±0.9, p=0.009) but not in Group-M or in Group-H. Cox proportional hazard model analysis including clinical variables showed that severe endothelial dysfunction was a significant predictor for future diabetic evolution (hazard ratio=2.69, p=0.011) and all-causal death (hazard ratio=5.87, p=0.009). Conclusions: This is the first clinical ultrasonic vascular investigation demonstrating that endothelial dysfunction accelerates diabetic evolution and causes excess of fatal events and strategies based on practical status of endothelial dysfunction are required for metabolic and prognostic management.
Abstract 4142748: Direct Oral Anticoagulants Versus Aspirin for Secondary Stroke Prevention in Patients with Embolic Stroke of Undetermined Source: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Authors: Juan Armando Talavera, Larissa Teixeira, Thomaz Costa, Denilsa Navalha, Tathiane Gibicoski, Nicole Fernandez, Luciana Armaganijan, Guilherme Dagostin de Carvalho
Journal: Circulation (2024)

Background: Embolic stroke of undetermined source (ESUS) represents approximately 20% of ischemic strokes. The optimal treatment strategy for secondary prevention remains uncertain for patients with ESUS. We aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the safety and efficacy of direct oral anticoagulants (DOACs) versus aspirin therapy in patients with a history of ESUS. Methods: PubMed, Embase, Cochrane and Web of science databases were systematically searched for eligible trials until March 2024. The primary outcome of interest was recurrent stroke. Major bleeding and clinically relevant non-major bleeding (CRNMB) were assessed as safety outcomes. We pooled hazard rations (HRs) with 95% confidence intervals (CIs) for analysis. Results: Four RCTs comparing direct oral anticoagulants (DOACs) versus aspirin were included comprising 13,970 patients, of whom 6,989 (50%) were randomized to the DOACs group. The mean follow-up was 16 months. Compared to aspirin, DOACs did not reduce the incidence of recurrent stroke (HR: 0.95; 95% CI: 0.81-1.09; p=0.44), ischemic stroke (HR: 0.91; 95% CI: 0.79-1.06; p=0.23), all-cause mortality (HR: 1.11; 95% CI: 0.87-1.42; p=0.40), and major bleeding (HR: 1.56; 95% CI: 0.85%-2.86; p=0.15). However, patients in the DOACs group presented significantly higher incidence of CRNMB (HR: 1.54; 95% CI: 1.23-1.92; p=0.0002) when compared with the aspirin group. Conclusion: Compared with aspirin, DOACs use was associated with an elevated risk of CRNMB and did not demonstrate superior efficacy in preventing recurrent stroke among patients with ESUS. &lt;div class="acfifjfajpekbmhmjppnmmjgmhjkildl" id="acfifjfajpekbmhmjppnmmjgmhjkildl"&gt; &lt;/div&gt; &lt;div class="acfifjfajpekbmhmjppnmmjgmhjkildl" id="acfifjfajpekbmhmjppnmmjgmhjkildl"&gt; &lt;/div&gt;
Abstract 4142220: Recovery of Anthracycline-Induced Cardiomyopathy- A Contemporary Cohort Study
Authors: Osnat Itzhaki Ben Zadok, Panagiotis Simitsis, Anju Nohria
Journal: Circulation (2024)

Background: There are limited data regarding left ventricular ejection fraction (LVEF) recovery rates among patients with anthracycline-induced cardiomyopathy (AIC). Aims: To assess the rate of LVEF recovery and its predictors in a contemporary and heterogenous cohort of patients with AIC. Methods: A retrospective cohort study of adult patients with new onset cardiomyopathy determined to be secondary to anthracyclines after a comprehensive work-up for potential etiologies within Massachusetts General Brigham between 2010 and 2023. LVEF recovery was defined as an absolute LVEF increase of ≥10% from LVEF at detection of AIC to a final LVEF ≥50%. Time to LVEF recovery within the first 3 years post-diagnosis was assessed using Cox proportional hazards regression analysis with all-cause death/mechanical circulatory support/heart transplant as competing risks based on the Fine-Gray method. Non-fatal cardiovascular (CV) events included acute decompensated heart failure, acute coronary syndrome and malignant arrhythmias requiring admission. Results: The cohort included 167 patients with AIC. The median age at anthracycline exposure was 60 (Q1, Q3: 48, 69) years, 53% (n=88) were females and majority had lymphoma (n=92, 55%) and breast cancer (n=39, 23%). The median time from first anthracycline exposure to detection of AIC was 631 (Q1, Q3: 219, 3569) days and median LVEF was 38 (Q1, Q3: 29, 45) %. A total of 42% (n=70) were managed by dedicated cardio-oncologists and neurohormonal therapy was prescribed in 86% (n=144). LVEF recovered in 38% (n=63) at a median time of 349 (Q1:Q3: 137, 691) days from AIC detection. Statin use was associated with a higher likelihood of recovery (HR=2.162, 95%CI:1.207-3.875, p=0.009), while age&gt;60 at time of anthracycline exposure, non-white race, longer duration between anthracycline exposure and detection of AIC, increased LV end-diastolic diameter, and lymphoma vs. other cancers had lower adjusted odds of LVEF recovery. Patients with recovered LVEF were less likely to experience CV events during follow-up (HR=0.455; CI 0.22-0.95, p=0.036). LVEF recovery, as a time-dependent variable, was not associated with all-cause or cardiovascular death. Conclusion: In a contemporary cohort of patients with AIC, 38% experienced LVEF recovery and lack of recovery was associated with a higher burden of CV events requiring admission. Routine screening for AIC may improve the likelihood of recovery and improve outcomes.
Abstract 4142660: Mast cell MRGPRX2 receptor-mediated neuroimmune interaction induces ventricular arrhythmias after acute myocardial infarction via the overactivation of cardiac sympathetic nerves system
Authors: Changyi Wang, Hong Jiang, Lilei Yu
Journal: Circulation (2024)

Background: Previous study has shown mast cell (MC) can modulate cardiac sympathetic nerve activity, associated with ventricular arrhythmias after myocardial infarction (MI). However, the key receptor that play a role in this remain unknown. Hypothesis: MRGPRX2 is a newly identified MC receptor that primarily mediates neuroimmune responses. We hypothesized it plays an important role in ventricular arrhythmias after MI. Methods: Cardiac sympathetic ganglion tissues and blood were collected from normal, acute MI and chronic MI models for preliminary detection of MRGPRX2 expression. Plasma of acute MI and normal coronary arteries patients was collected for the determination of relevant indices. Knockdown of MRGPRX2 in cardiac sympathetic nerve to explore its role and mechanisms in ventricular arrhythmias after acute MI. Results: In normal models, expression of MRGPRX2 and FcεRI receptors in cardiac sympathetic nervous were significantly higher than other common MC receptors. We found increased expression of MRGPRX2, corresponding ligand neuropeptide Y (NPY) and MC inflammatory factors in acute MI models. No similar trend was observed for IgE-FcεRI pathway. Clinical data showed serum MRGPRX2 levels were higher in acute MI group than in the control group [1.002 (0.675-1.301) vs. 0.661 (0.562-0.887), P &lt;0.05], and were positively correlated with serum NPY and inflammatory factors levels. In acute MI models, knockdown of MRGPRX2 reduced the sympathetic indexes of heart rate variability and serum NPY, resulting in suppressed cardiac sympathetic activity. And it suppressed local inflammation and sympathetic remodeling. Moreover, it could improve ventricular electrophysiological stability, evidenced by the prolonged ventricular effective refractory period, elevated action potential duration, increased ventricular fibrillation threshold, consequently showing antiarrhythmic effects. Conclusion: MRGPRX2 receptor-mediated neuroimmune disorders induce ventricular arrhythmias after MI, suggesting that MRGPRX2 is a potential target for therapy.
Abstract 4142349: Multidisciplinary Approach to Definitive Management of Chylopericardium with Percutaneous Thoracic Duct Embolization
Authors: Nelish Ardeshna, Janki Thakker, Natasha Rana, Laith Derbas, Bulent Arslan, Jeffrey Soble, Neeraj Jolly, Steve Attanasio
Journal: Circulation (2024)

Background: Conservative management of chylopericardium with pericardiocentesis, TPN, and octreotide has a high rate of recurrence. On the other hand, surgical management is invasive and can also result in treatment failure as well. Percutaneous approach has rarely been studied in this population. Case: A 26-year-old female was admitted for recurrent idiopathic chylopericardium after failing management with pericardiocentesis. On presentation, echocardiogram demonstrated a 5.4 cm pericardial effusion without hemodynamic compromise. Fluid studies showed turbid white fluid with a triglyceride level of 1,622 mg/dL. A pericardial window was performed, and patient was started on octreotide with fat-free diet. However, high chylous output continued for one week. After multidisciplinary discussion with cardiology, thoracic surgery, radiology, and interventional radiology, a nuclear medicine lymphangiogram was completed. This demonstrated a focal area of intense tracer activity at the level of pulmonary trunk. Subsequent lymphangiogram showed dilated lymphatic channels with reflux and stasis in this area. The thoracic duct was successfully embolized. Chylous output significantly decreased, and patient was discharged. An echo at one month follow-up showed complete resolution of pericardial effusion. Discussion: Although the clinical presentation was consistent with chylopericardium, management was complicated after patient failed treatment with several approaches. At this stage, invasive surgery to ligate the thoracic duct versus continued drainage in the outpatient setting was being considered. A collaborative approach guided the right imaging modality and therapeutic intervention to definitively manage chylopericardium efficiently without significant morbidity. Furthermore, it suggested that percutaneous thoracic duct embolization may be a viable treatment option for recurrent idiopathic chylopericardium refractory to conventional management. Conclusion: A multidisciplinary approach with nuclear medicine testing and percutaneous intervention can be an effective approach to certain cases of idiopathic chylopericardium.
Abstract 4142541: Chronic heart failure associates with activation and clonal expansion of T cells with predicted autoreactive capacity
Authors: Wesley Abplanalp, Maximilian Merten, Tina Rasper, Sebastian Cremer, David John, Thimoteus Speer, David Leistner, Jedrzej Hoffmann, Halvard Bonig, Christoph Knosalla, Evgenij Potapov, Tamim Sarapki, Emina Mustafic, Alexander Berkowitsch, Andreas Zeiher, Stefanie Dimmeler
Journal: Circulation (2024)

Background: Chronic heart failure (HF) is characterized by adverse remodeling and persistent inflammation, leading to impaired heart function and poor prognosis. While the acute immune response post-myocardial infarction (MI) is well-studied, the role of the immune system in chronic HF remains unclear. This study aims to elucidate the response of T cells to HF. Methods and Results: In a cohort of 188 HF patients and healthy controls (HC), flow cytometry of peripheral blood revealed an increase in T cell memory/effector cells (HF=65%, HC=53% activated T cells) and a reduction in naïve T cells in HF patients. Additionally, antigen-presenting cells (APCs) displayed a higher immune stimulatory profile (e.g., HLA-DR, ICAM-1, TREM-1). Immune secretome analysis supported the chronic inflammatory state with significantly elevated serum levels of sICAM-1, IL6, and TNFRI in HF patients. Phenotyping of peripheral blood T cells showed a decline in T central memory cells (TCM) and an increase in CD4+ Th17 and CD8+ T effector memory cells in HF patients compared to healthy controls. This decline in TCM cells and the increased expression of the homing marker CCR5 on T cell subsets were associated with poor prognosis in HF. T cell receptor (TCR) sequencing revealed reduced TCR diversity (p=0.03) and clonal expansion in circulating and cardiac T cells of HF patients. Epitope prediction modeling identified 22 unique human-derived epitopes specific to HF, suggesting potential autoreactivity. Single-cell RNA sequencing (scRNA-seq) of CD45+ sorted cardiac and circulating cells confirmed clonal TCR expansion in the heart and blood of HF patients. Post-MI mouse models demonstrated an accumulation of pro-inflammatory Th17 T cells in the heart at days 14, 28, and 48, with later time points showing more pronounced pro-inflammatory profiles. Conclusion: Chronic HF is associated with persistent T cell activation and clonal expansion, potentially contributing to adverse remodeling and poor prognosis through autoimmune mechanisms. These findings provide insights for therapeutic cardio-immunological interventions targeting T cell responses in HF.
Abstract 4142334: 90 days readmission rates, predictors, and causes of readmission in heart failure patients with history of irradiation: nationwide retrospective analysis
Authors: Taha Teaima, Andres Quevedo Ramirez, Vivek Jha, Joshua Ibarra, Raquel Soon-Shiong, Javier Gomez Valencia
Journal: Circulation (2024)

Introduction: Radiation therapy (RT) is an important part of treatment strategies in cancer patients, but it carries multiple significant cardiovascular risks. Data regarding the effects of RT in heart failure patients is limited. In our study, we investigated the readmission rates, predictors, and causes of readmission in heart failure patients with a history of RT. Methods: The National Readmission Database for 2018 and 2020 was queried to identify hospitalized adults with Congestive heart failure (CHF) and a history of RT. Multivariate logistic and linear regression analyses were used to adjust for possible confounders. Results: A total of 2,607 patients were hospitalized for acute exacerbation of congestive heart failure and had a history of RT with 2,497 discharged alive. Within 90 days from discharge, 874 (35%) were readmitted. Exacerbation of CHF with a history of CKD or hypertension (27%), Sepsis (6.6%), Pneumonia (3.1%), and acute kidney injury (2.3%) were the most common causes of readmissions. Independent predictors of readmission included presence of anemia (aOR 1.46, 95% CI: 1.1 - 1.92, P=0.007), discharge against medical advice (aOR 2.9, 95% CI: 1.07-7.97, P=0.03), and presence of atrial flutter/Fibrillation (aOR 1.36, 95% CI: 1.03-1.81, P=0.03). Conclusion: Predictors of readmission included discharge against medical advice, anemia, and atrial flutter/ Fibrillation. The most common causes of readmission included Exacerbation of CHF, Sepsis, Pneumonia, and acute kidney injury. Addressing readmission causes and predictors is needed to prevent such a high rate of readmission.