tbuckley/cabot-search huggingface dataset:
Abstract 4137246: Atrial Fibrillation Wave Vectors Determined by Artificial-Intelligence Indicate Clinical Phenotypes
Authors: Suhaas Anbazhakan, Ricardo Carlos Abad Juan, Samuel Ruiperez-Campillo, Miguel Rodrigo, Sanjiv Narayan
Journal: Circulation (2024)

Background: Atrial fibrillation (AF) is a major cause of morbidity and mortality, which may be reduced by ablation. However, it is difficult to predict patients who will respond, which is currently done using bedside variables since even experts find it difficult to interpret electrical signals (electrograms) or maps in AF, or link them with phenotype, acute or long-term ablation response. Hypothesis: We hypothesized that determining if AF waves consistently propagate away from the pulmonary veins (PV), identified using artificial-intelligence (AI) tools applied to spatial grids in multipolar catheters, may reflect phenotypes of response to ablation or other clinical features. Methods: We studied 26,640 electrograms in N=37 patients at AF ablation ( 66.3 ± 8.6 years, 13.5% women, 59.5% non-paroxysmal AF). We trained AI-algorithms to identify activation patterns and calculate propagation vectors in AF. Each patient had AF recordings from 64-pole basket catheters, from which we calculated AI-based vectors in 48 spatial grids of 3X3 electrodes (covering ~1-3 cm 2 ) over 1 minute (720 per patient). Fig. A illustrates AF waves predominantly exiting the PVs in a 60 year old man. We studied wave maps exiting the PVs in relation to AF type, termination of AF during ablation and 1 year outcome. Results: Ablation success for the cohort was 71.4% at 1 year. Wave direction in AF shifted over time, as expected, but predominant vectors correlated with clinical outcomes. Fig. B showed that AF waves were significantly more likely to exit the PVs for patients with success than failed ablation (&lt;0.05). Fig. C showed that PV wave direction did not differ for AF type, nor for patients with or without acute AF termination by ablation (p=NS). Conclusions: In this study of patients with various types of AF, a novel AI-based approach showed that AF vectors indicating waves exiting the PVs predicted , clinical phenotypes, particularly patients with successful ablation targeting the PVs.
Abstract 4137177: A pharmacovigilance investigation from the FAERS database on patients using pembrolizumab and its association with cardiac arrhythmias
Authors: Prakash Upreti, Predrag Jancic, Stefan Milutinovic, Azeem Rathore, Sameh Nassar, Roshan Karki, Mohan Rao, Brijesh Patel
Journal: Circulation (2024)

Background: Arrhythmia is always a concern in oncological treatments. The advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, enhancing the immune system's ability to combat malignancies. They are being more frequently used, revealing a range of immune-related adverse events (irAEs). This study aims to investigate the incidence of cardiac arrhythmias in patients receiving Pembrolizumab. Methods: We conducted a retrospective analysis of the FDA Adverse Event Reporting System (FAERS) database, focusing on reports submitted between 2006 to 2024. Cases involving patients treated with ICs were identified, and information related to cardiac arrhythmias was extracted using the Medical Dictionary for Regulatory Activities (MedDRA). Patients ≥ 18 years of age treated with ICIs were included in this study. A disproportionality analysis was conducted to identify arrhythmia events associated with pembrolizumab by comparing it with other immune checkpoint inhibitors (nivolumab, ipilimumab, and atezolizumab) and the entire FAERS database using the reporting odds ratio (ROR) and information component (IC). Results: A comprehensive analysis of 61,236 reported cases of pembrolizumab use revealed a total of 3,901 cases with cardiac complications. Among these, 672 cases (17.22 %) of arrhythmias were reported, with 452 individuals (67.26%) requiring hospitalization and 172 cases (25.59%) resulting in fatalities. Atrial fibrillation emerged as the most prevalent arrhythmia (49.7%). The occurrence of ventricular tachycardia with an ROR of 1.67 (1.18–2.35) and an IC of 0.44 (0.01–1.46) and complete atrio-ventricular block with an ROR of 1.57 (1.19–2.08) and an IC of 0.40 (0.04–1.24) were statistically significant. The reported arrhythmias associated with pembrolizumab are tabulated in Table 1 . The majority of events were reported in males, as shown in Figure 1 . Conclusion: This research offers significant insights into the connection between ICIs and cardiac arrhythmias, utilizing real-world data from the FAERS database. Healthcare providers should monitor cardiac events in patients receiving ICIs and aim to achieve a balance between anticancer effectiveness and cardiovascular safety. Further investigation is necessary to better understand the underlying mechanisms of arrhythmia and enhance risk stratification strategies for this specific patient group.
Abstract 4137240: MHCII <sup>hi</sup> LYVE1 <sup>lo</sup> CCR2 <sup>hi</sup> Interstitial Macrophages Promote Medial Fibrosis in Pulmonary Arterioles and Contribute to Pulmonary Hypertension
Authors: Fan Qiu, Hao-Ran Miao, Hong-Liang Hui, Yan-Gui Lin, Hua-Ming Li, Dan Li, Min Luo, Sang-Bing Ong, Xue-Fei Hu, Bo Jiang, Yi-Qian Zhang
Journal: Circulation (2024)

Background: Pulmonary hypertension (PH) is a lethal disease characterized in part by progressive pulmonary arteriole (PA) remodeling. Excessive PA fibrosis and macrophage infiltration are often present in PH, but potential association is obscure. We invesitgated the link between interstitial macrophage (iMΦ) infiltration and PA fibrosis in PH and idiopathic pulmonary arterial hypertension (IPAH). Methods: Lung tissue samples from patients with IPAH (n=11) and experimental PH (sugen-5416 and hypoxia, hypoxia, or monocrotaline, n=5) animals (adult male and female SD rats) were obtained to analyze the extent of fibrosis in PA adventitia and media and their correlation to disease severity. Single-cell RNA sequencing, immunohistological analyses, iMΦs and PA smooth muscle cells (PASMCs) coculture, and transgenic animal experiments were used to investigate the cell heterogeneity and molecular mechanisms by which iMΦs promote PA medial fibrosis. Data in this study were analyzed with unpaired two-tailed t-tests with Welch’s correction, Kruskal-Wallis one-way ANOVA followed by Dunn’s test, RM ANOVA with Geisser-Greenhouse correction, or Pearson correlation test, and p &lt; 0.05 was considered statistically significant. Results: We found that increased collagen deposition and fibrosis in the PA media were correlated with PH severity, and iMΦ medial infiltration may be involved in these pathological processes. Single-cell transcriptomics suggested that ligand-receptor associations between MHCII hi LYVE1 lo CCR2 hi iMΦ and fibroblast-like vascular SMC subclusters contributed to PA medial fibrosis. Mechanistically, MHCII hi LYVE1 lo CCR2 hi iMΦs regulated PASMC phenotypic transition and collagen production through the wingless member 11 (WNT11)/planar cell polarity (PCP) pathway. Deletion of iMΦ-enriched Wnt11 in myeloid cells of PH rats ( Itgam CreERT2 ; Wnt11 fl/fl ) normalized the fibrotic PASMC phenotype and decreased PA medial fibrosis, thereby protecting against PH. Moreover, myeloid-specific C-C motif chemokine receptor 2 ( Ccr2 ) deficiency ( Itgam CreERT2 ; Ccr2 fl/fl ) in PH-PAs inhibited MHCII hi LYVE1 lo CCR2 hi iMΦ infiltration. Conclusions: PA medial fibrosis is a causative factor of PH, and the inhibition of MHCII hi LYVE1 lo CCR2 hi iMΦ pathogenicity or infiltration reverses PA medial fibrosis and thus alleviates PH.
Abstract 4137257: Hepatocyte growth factor -mediated Angiogenesis supersession in Hyperhomocysteinemia
Authors: Xiao Huang, Tianyu Cao, Hong Wang
Journal: Circulation (2024)

Background: Homocysteine (Hcy) is a well-established cardiovascular risk factor. Elevated homocysteine, or hyperhomocysteinemia (HHcy), inhibit the growth of endothelial cells and stimulate vascular smooth muscle cell proliferation. However, the mechanisms of HHcy disrupts angiogenesis remain unclear. Here we examine the molecular pathways involved in HHcy-impaired angiogenesis. Method: We generated Tg-hCBS+ Cbs-/- mice by crossing Cbs knockout mice and Tg-hCBS mice where human CBS cDNA was regulated by a zinc-inducible metallothionein promoter. The model exhibited severe HHcy (＞115 μmol/L). We conducted both in vivo and in vitro experiments, including vasculogenesis assays of retinal and heart tissues, aortic ring assay, and tube formation. Retinas were stained with Isolectin B4 and imaged using a confocal microscope. The Human Angiogenesis RT 2 Profiler™ PCR Array was used to profile 84 key angiogenesis-related genes. Homocysteine metabolites in Cbs mice were measured by HPLC. ChIP-seq data were analyzed using Chip Atlas. Additionally, 91 patients went through coronary angiography were enrolled from the Second Affiliated Hospital of Nanchang University. Participants with CTFC, greater than 27 frames per second were identified as having slow coronary arteries flow (SCF). Results: HHcy caused SCF in patients and impaired vasculogenesis in the retinas of newborn and 12-week-old Tg-hCBS Cbs-/- mice. Capillary density in the hearts of adult Tg-hCBS Cbs-/- mice was reduced. HHcy suppressed tube formation and aortic ring microvessel growth in a concentration-dependent manner. The PCR array revealed significant gene expression changes in Hcy treated human aortic endothelial cells. Notably, genes encoding hepatocyte growth factor (HGF), collagen type IV alpha 3, epiregulin, interferons, and leukocyte cell-derived chemotaxin 1 were downregulated by at least four-fold. In an acute myocardial infarction model, HGF expression was further reduced, and HGF treatment rescued Hcy-inhibited tube formation and microvessel growth. Hcy and S-adenosylhomocysteine levels were negatively correlated with plasma HGF levels. ChIP-seq data identified homocysteine-responsive hypomethylation in ETF, TFII, FOXP3, RXRa, and c-Jun Hcy-hypomethylation Box (-2701/0). Conclusion: HHcy impair angiogenesis via HGF inhibition, which has a rescue effect. Hypomethylation caused by Hcy affects the methylation status of specific CpG sites within the Hcy-hypomethylation box of the HGF gene.
Abstract 4137045: Sustained Anti-Thrombotic Efficacy of CS585, a Novel Prostacyclin Receptor Agonist, Demonstrates Therapeutic Potential
Authors: Livia Stanger, Mariane Flores, Pooja Yalavarthi, Bjorn Dahlof, Michael Holinstat
Journal: Circulation (2024)

The formation of occlusive thrombi resulting in myocardial infarction or stroke present a significant challenge for the healthcare community. Activation of the prostacyclin (IP) receptor has been shown to decrease platelet reactivity, however current IP agonists lack a sustained effect in the blood. We have developed CS585, an IP receptor agonist with sustained anti-thrombotic effects in the blood, which could represent a novel prevention strategy in targeting thrombosis. We sought to assess the anti-thrombotic efficacy and pharmacodynamic stability of IP agonists CS585, iloprost and selexipag, in both ex vivo and in vivo models. We evaluated the timeframe of effect of CS585, iloprost, and selexipag in mice following a single IV dose. Inhibition of thrombus formation was measured ex vivo in whole blood under arterial shear rates. In vivo , CS585, iloprost, or selexipag, were administered prior to labeling of platelets and fibrin. Thrombus formation at the site of injury was measured using the cremaster arteriole injury thrombosis assay. CS585 administered to mice prior to blood draw decreases platelet adhesion and blood clot formation under arterial shear conditions. These effects are observed up to 24 hours post-administration; however, the effects of iloprost and selexipag return to pre-treatment levels by 24 hours. In vivo , mice administered iloprost or selexipag demonstrated a decrease in platelet accumulation and fibrin formation, however the effects were abrogated post-administration by 10 minutes and 4 hours, respectively. Administration of CS585, however, demonstrated sustained inhibition of thrombus formation at the site of injury, with inhibitory effects observed at 18 hours post-administration. We have used both in vivo and ex vivo models to demonstrate the anti-thrombotic efficacy of IP receptor agonists. Our results suggest that CS585, a novel IP receptor agonist, sustainably inhibits platelet activation and clot formation for extended periods, in contrast to existing alternatives. This demonstrates a significant improvement in the pharmacodynamic effects of IP receptor agonists in the blood, highlighting CS585 as a novel anti-platelet therapeutic with the potential to treat thrombotic diseases.
Abstract 4136889: Impact of hypercholesterolemia definitions on prevalence and prognosis of patients without standard modifiable cardiovascular risk factors and ST-segment elevation myocardial infarction.
Authors: Marianne Zeller, Nicolas Danchin, Alexandra Rousseau, Yves Cottin, Dorian Sauze, Pascal Goube, Guillaume CAYLA, Cyril PRIEUR, Vincent Auffret, Tabassome Simon, Philippe Steg
Journal: Circulation (2024)

Background: In patients with acute myocardial infarction (AMI), recent studies have intriguingly reported that up to a quarter of AMI patients have none of the 4 main standard modifiable cardiovascular (CV) risk factors (SMuRFs) (i.e. hypertension (HTN), diabetes mellitus (DM), hypercholesterolemia (HC), and smoking) and have worse mortality. Hypothesis: We tested the hypothesis that the prevalence and prognosis of SMuRF-less patients varies with the definition of risk factors. Aim: Using a French nationwide MI cohort, we aimed to compare SMuRF-less ST-segment elevation MI (STEMI) patients according to 2 HC definitions, given the possibility of using several HC criteria. Methods: The French Cohort of Myocardial Infarction Evaluation (FRENCHIE) is a large ongoing AMI cohort, collecting data from all patients hospitalized for AMI &lt; 48 h of symptom onset in 21 French centers. STEMI patients without prior CAD admitted in 2019 to 2022 were studied. DM was defined as prior DM diagnosis, HbA1c&gt;7% or anti-diabetic medications, ongoing or at discharge, HTN was defined as treated or previous HTN diagnosis and smoking was defined as current smoking within the past month. Restrictive HC (RHC) was defined as either a previous diagnosis of HC or statin therapy. Permissive HC (PHC) was defined as previous diagnosis of HC or lipid-lowering therapy, or LDL-C &gt; 135 mg/dL or total Cholesterol &gt; 213 mg/dL. Results: Among 8008 patients (mean age 61.5± 12.9y, 22.6% women), 41.4% were smokers, 17.4% had diabetes, and 38.5% HTN. According to HC definitions, the prevalence of HC almost doubled, ranging from 30.3% for RHC to 61.0% for PHC. Consequently, the prevalence of SMuRF-less was divided by ≈ two (21.1% vs 11.3%, respectively), depending on the definition of HC used. Age and sex-adjusted logistic regression analysis showed that PHC, but not RHC, was associated with lower odds of in-hospital death ( figure ). Moreover, having multiple SMuRFs was associated with higher risk of mortality than no SMuRF when using RHC, but not with PHC definition. Conclusion: The prevalence and impact on acute mortality of being SMURFless varies largely with the definition of HC. More research is needed, using HC standardized definitions to explore these patients. Frenchie: was supported in part by the RHU iVASC grant ANR-16-RHUS-00010 from the French National Research Agency (ANR) as part of the Investissements d’Avenir program. The FRENCHIE cohort is registered with ClinicalTrials.gov, NCT04050956.
Abstract 4137181: High-Intensity Walking Exercise Minutes and Improved Walking Performance in Peripheral Artery Disease: LITE Randomized Clinical Trial
Authors: Neela Thangada, Shujun Xu, Lu Tian, Lihui Zhao, Mary McDermott
Journal: Circulation (2024)

Background: The LITE randomized clinical trial evaluated the effect of high-intensity vs low-intensity walking exercise on walking ability for peripheral artery disease (PAD). In post-hoc analyses, this study evaluated whether people with PAD who walked more exercise minutes per week had greater six-minute walk (6MW) improvement, compared to those who walked fewer exercise minutes per week. Within each quartile of exercise minutes, change in 6MW was compared between high and low-intensity exercise groups. Methods: People with PAD were randomized to walking exercise that induced ischemic leg symptoms (high-intensity), walking exercise at a comfortable pace without ischemic leg symptoms (low-intensity), or a control group that did not exercise for 12 months. Participants randomized to exercise were asked to walk 5 days/week up to 50 minutes/day. High-intensity exercise was defined and objectively measured using an ActiGraph. Participants wore an ActiGraph during exercise to measure exercise minutes/week. The primary outcome was 12-month change in 6MW. Results: Of 305 PAD participants randomized (47% women, 59% Black), 208 were assigned to exercise and had data available for analyses. The high-intensity exercise group walked fewer exercise minutes/week than the low-intensity exercise group (51.95 vs 136.82, P&lt; 0.0001). In each exercise group, greater exercise minutes/week at target intensity were associated with greater 6MW improvement (Table). Within each quartile of exercise minutes/week, high-intensity exercise improved 6MW significantly more than low-intensity (Table). Conclusion: In the LITE randomized trial, among people randomized to high-intensity and low-intensity exercise, respectively, more minutes of exercise per week were associated with greater 6MW improvement. However, within each quartile of exercise minutes/week, high-intensity exercise improved 6MW significantly more than low-intensity exercise.
Abstract 4137205: Management Patterns and Outcomes in the Use of Invasive Mechanical Ventilation for Patients with Cardiogenic Shock
Authors: Grant Tucker, Christopher Grubb, Neda Bionghi, Catherine Chen, Bethany Lussier, Corey Kershaw, Gregory Ratti, Roma Mehta, Colby Ayers, Nicholas Hendren, Justin Grodin, Jennifer Thibodeau, Ann Marie Navar, Maryjane Farr, Sandeep Das, James de Lemos, Eric Hall
Journal: Circulation (2024)

Background: Approximately half of all patients with cardiogenic shock (CS) require invasive mechanical ventilation (IMV). While there have been significant advances in the management of patients requiring IMV based on data primarily derived from medical intensive care patients with respiratory failure, little is known regarding the management and outcomes of IMV in patients with CS. Methods: We conducted an analysis of patients treated for CS who required IMV at an academic safety net hospital from 2017-2023. Indications for IMV, ventilator settings, and medications were obtained from the medical record. The primary outcome was unsuccessful extubation, defined as reintubation within 48 hours of extubation. Results: A total of 110 patients with CS who received IMV were identified. Median age was 60yo; 28% of the cohort was female, 39% of Hispanic ethnicity, and 38% of Black race. Primary reasons for intubation included ongoing cardiac arrest (35%) and hypoxic respiratory failure (34%). Most patients were on minimal ventilator support at 24 hours after intubation (median FiO2 40% [IQR 30-50%], post-end expiratory pressure [PEEP] 5cm H2O [IQR 5-8]). Mechanical circulatory support (MCS) was present in 40% of patients at 24 hours post-intubation. Protocolized spontaneous breathing trials (SBTs) were delayed in 77% of patients, primarily due to hemodynamic instability (88%). Planned or unplanned extubation occurred in 63% of patients after a median of 4.8 days [IQR 2.1-8.0]. Ten percent of patients transferred hospitals while on IMV, while 27% were palliatively extubated or died on IMV. The majority (58%) of patients undergoing non-palliative extubation were on vasoactive medications preceding extubation, with only 2% on MCS. Most patients (58%) were extubated to nasal cannula or room air. A total of 13% of patients experienced unsuccessful extubation. Conclusions: In a cohort of patients with CS requiring IMV, most patients were on minimal ventilator settings within 24 hours yet remained intubated with SBTs delayed due to hemodynamic instability. Rates of failed extubation were comparable to published data from other forms of critical illness. Further work is necessary to determine optimal approaches to ventilator liberation and circulatory support in intubated patients with CS where hemodynamic derangements rather than respiratory insufficiency represent the primary barrier to extubation.
Abstract 4136822: Implementation of a Community-Engaged Amputation Prevention Intervention in Rural Appalachia
Authors: Samantha Minc, Lauren Wright, Jordyn O'Dell, Christiana Beimel, Paul Rothenberg, Rosalie Hopkins, Gordon Smith, David Armstrong, Ranjita Misra, Monica Peek, Pamela ZimmermanOwen, Geri Dino
Journal: Circulation (2024)

Amputation is a devastating complication of diabetes and peripheral artery disease and a marker for health inequity. Implementation Science (IS) and Community Engaged-Research (CenR) allow for real-world adaptation of evidence-based interventions and provide critical frameworks for reproducibility and sustainability. However, few amputation interventions use these approaches. We describe the feasibility and acceptability of an IS and CEnR driven amputation intervention in a high-risk rural community. A Pre-Post mixed methods design was used (Fig 1). Intervention components were mapped to the Social-Ecological Model (Fig 2) and guided by the CFIR. Community and Project Advisory Boards collaborated on needs assessment, mobilizing resources, intervention adaptation, data review and dissemination. A 3-component intervention was implemented in 2 clinics to improve local foot care. Components included diabetic foot exams (DFEs), a multidisciplinary limb preservation team, and a “hot-foot” hotline. Pre-implementation, a retrospective chart review was performed along with focus groups. DFE training was then conducted at each site. After training, a prospective chart review was performed with clinic check-ins for 12 months. Focus groups were held 6- and 12-months post-implementation. Concurrently, monthly multidisciplinary teleconferences were held, and a “hot-foot” phoneline connected providers to specialty nurses. At baseline, 155/224 (69.2%) patients received an annual DFE, 17% had all four exam components, 15.6% had foot abnormalities identified and 3.6% were referred to specialists. At 12-months 212/268 (79.1%) patients received a DFE, 84.7% had all components, 54.9% had abnormalities and 20.1% were referred. All findings were statistically significant. Clinically there was a significant decrease in patients with foot wounds, infection, and foot-related hospitalization/ED visits. There were no changes in amputations. (Table 1) The virtual teleconference completed 12 sessions. The hotline was used once with clinicians reporting they did not need it. We demonstrate successful, sustained implementation of an amputation prevention intervention in a high-risk rural community using IS and CEnR. This approach was crucial for overcoming barriers to intervention implementation in a resource poor environment. Additional research to assess patient experience, understand key components of the intervention and study scalability and clinical effectiveness is planned.