tbuckley/cabot-search huggingface dataset:
Abstract 4142470: Clinical management of select patients with surgically implanted Impella 5.5 left ventricular assist devices on a cardiovascular step-down unit
Authors: Meg Ospina, Jan Griffin, Adrian Van Bakel, Gregory Jackson, Vishal N. Rao, Jessica Atkins, Jennifer Hajj, Kaylen Dodson, Mary Kathryn Summer, Lindsey Bull, Chakradhari Inampudi, Jeffrey McMurray, Ryan Tedford, Lucas Witer, Krishna Bhandari, JEFFREY YOURSHAW, Brian Houston, Arman Kilic, Anthony Carnicelli
Journal: Circulation (2024)

Introduction: Surgically implanted Impella 5.5 percutaneous left ventricular assist device utilization is increasing. Most centers manage Impella 5.5 patients exclusively in the ICU; however, there are concerns regarding prolonged ICU bed utilization in clinically stable patients. This study evaluates our experience managing Impella 5.5 patients in a stepdown unit (SDU). Methods: In January 2023, select patients with Impella 5.5 at our institution were admitted to a SDU after ≥24 hours in the ICU post implant. Eligible patients had no significant bleeding, device issues, or ongoing hypoperfusion. Demographics, hemodynamics, outcomes, and adverse events ( Fig ) were collected retrospectively and adjudicated by multidisciplinary clinician review. Results: Between Jan 1, 2023 and Mar 31, 2024, a total of 64 patients with Impella 5.5 were managed at our institution. Of these, 42 (66%) were managed in SDU for a median (IQR) of 11 (7, 21) days (range 1-82), totaling 733 of 1055 (69%) Impella-days. SDU patients with Impella 5.5 had a median age of 60 (50, 63) years, were mostly male (55%), non-ischemic (79%), and presented with Stage C (52%) or D (43%) shock. Impella strategy in SDU patients was bridge to transplant in 60% (n=25), to decision in 31% (n=13), to durable LVAD in 8% (n=3), and for VT ablation support in 1% (n=1). Five (12%) patients required transfer back to the ICU for escalation of care. Impella 5.5 patients on SDU experienced a total of 28 adverse events (0.027 events per Impella-day), with &gt;1 adverse event in 16/42 (38%) patients ( Fig ). Twenty-eight (67%) SDU patients underwent heart transplant and 10 (24%) underwent LVAD implant during the hospitalization. One patient died during their hospital course, in whom care was withdrawn due to lack of a destination option. Conclusions: For select patients with Impella 5.5 who met institutional criteria, transfer to a SDU was feasible and safe. This strategy may increase ICU throughput and optimize resource allocation.
Abstract 4142395: Lipid Trends of Adults Who Participate in Hybrid Cardiac Rehabilitation
Authors: Yumin Gao, Jie Ding, Chang Kim, Erin Spaulding, Nino Isakadze, Kerry Stewart, Ashley Broderick, Alexandra Bush, Zane MacFarlane, Mansi Nimbalkar, Anushka Desai, Lena Mathews, Francoise Marvel, Hector Garcia-Garcia, Seth Martin
Journal: Circulation (2024)

Background: Hybrid cardiac rehabilitation (HCR) is an emerging approach to increase participation in cardiac rehabilitation, which targets improvements in functional status and broader risk factor modification including lipid management. However, long-term lipid control trends of patients engaging in HCR remain unexplored. Methods: Using data from a quality improvement program initiated during COVID-19, we conducted a retrospective analysis of 68 adults eligible for HCR from Jan 2021 to Feb 2023 at the Johns Hopkins Health System (Baltimore, MD), utilizing the Corrie digital health platform. This multi-component platform combines expert knowledge with gamified education and virtual coaching to deliver HCR. Patients hospitalized for cardiovascular events qualifying for HCR were recruited for a pilot study of a randomized controlled trial (mTECH REHAB; NCT05238103). We modeled trends in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and triglycerides via mixed-effects regression. Results: Among 68 eligible adults, 41 participated in HCR, with a mean age of 60.1 years, 78.1% male, 24.3% Black, and 14.6% Asian/Mixed. HCR participation was significantly associated with being married (61% vs 33%, p=0.044) or employed (63% vs 26%, p=0.015). On average, 2.3 lipid panels were assessed per person over a median of 12 months (max 30 months) post-discharge. During this period, LDL-C levels decreased from 84.6 mg/dL (95% CI: 75.0-94.1) to 53.0 mg/dL (95% CI: 34.3-71.8) (p for trend = 0.003). Non-HDL-C decreased from 105.9 mg/dL (95% CI: 95.7-116.1) to 74.2 mg/dL (95% CI: 54.1-94.3) (p for trend = 0.005). Levels of HDL-C and triglycerides showed no significant changes (p for trend = 0.724 and 0.607). Among 34 participants with ≥2 lipid panels, the proportion of LDL-C &lt;70 mg/dL increased from 41.2% at hospitalization to 64.7% at the most recent check, and LDL-C &lt;55 mg/dL increased from 14.7% to 38.2%. Conclusion: Improvements in atherogenic lipid levels, in particular LDL-C and non-HDL-C, were observed in adults participating in HCR after a cardiovascular event. Our findings highlight the potential of HCR to support optimal lipid management in adults with cardiovascular disease.
Abstract 4142203: Reducing reperfusion injury in circulatory death hearts with calpain inhibitor
Authors: Qun Chen, Zachary Kiernan, Gina Marie Labate, Mohammed Quader
Journal: Circulation (2024)

Background: Donation after Circulatory Death (DCD) donor hearts are rarely utilized for transplantation following more than 30 minutes of ischemia. Calpains 1 and 2 (CPN1/2) are ubiquitous proteases known to exist in cytosol and mitochondria that significantly contribute to reperfusion injury by degrading the ND5 (NADH dehydrogenase subunit 5) and releasing apoptosis inducing factor (AIF). We elected to study the role of CPN1/2 activation in the mitochondria and their inhibition on DCD heart reperfusion injury. Hypothesis: In the DCD hearts mitochondrial CPN1/2 are activated and administration of MDL-28170 (inhibitor of CPN1/2) during reperfusion will decrease cardiac injury. Methods: Male Sprague-Dawley rats were divided in three groups: control beating-heart donors (CBD n=6) without ischemia, DCD with 35 minutes of global ischemia (n=6), and DCD with 35 minutes of ischemia and 10 minutes of reperfusion (n=7). Hearts were procured and mitochondria isolated. Immunoblotting was used to measure CPN1/2 activation. In a separate group of DCD hearts, to assess the protective effect of MDL, hearts were reperfused for 90 minutes on Langendorff setup with MDL (10 μM n=8) while the control DCD hearts were reperfused without MDL (n=7). At the end hearts were collected to measure infarct size using triphenyl tetrazolium chloride staining. Results: There were no significant differences in either AIF or ND5 contents between CBD and DCD ischemia alone hearts (Panel A and B). However, a marked decrease in the contents of AIF and ND5 occurred in DCD hearts mitochondria following reperfusion (Panel A&amp;B) indicating that CLP1/2 were mainly activated in DCD hearts during reperfusion. Although MDL treatment did not markedly improve cardiac function during reperfusion (Panel C), it did decrease infarct size in DCD hearts (Panel D), indicating that cardiac injury can be decreased by inhibiting CPN1/2 in DCD hearts even following 35 minutes of ischemia. Conclusion: Timely administration of selective CPN1/2 inhibitor is a practical approach to decrease cardiac injury in DCD hearts subjected to prolonged period of ischemia.
Abstract 4142370: KDM2B Antagonizes Trimethylamine N-Oxide-Induced Calcific Aortic Valve Disease by Suppressing Nox4 via JunD Demethylation
Authors: minhui Xu, Jiaying Li, Ying-wen Lin, Xiaolin Duan, Shunyi Li, Gaopeng Xian, Dingli Xu, Qingchun Zeng
Journal: Circulation (2024)

Background and Objective: Calcific aortic valve disease (CAVD) is a debilitating condition characterized by excessive oxidative stress and inflammation. Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, has been implicated in CAVD pathogenesis. Lysine-specific demethylase 2B (KDM2B) possesses antioxidant properties. This study aimed to investigate the protective role of KDM2B against TMAO-mediated CAVD and explores the underlying mechanisms. We hypothesized that KDM2B mitigates TMAO-induced inflammatory and osteogenic response of valve interstitial cells (AVICs) by reconstructing intracellular oxidative balance. Methods and Results: KDM2B expression was diminished in calcified aortic valves and TMAO-treated valve interstitial cells (AVICs) compared to healthy controls, as confirmed by western blot, qPCR, immunohistochemistry (IHC), and immunofluorescence. KDM2B silencing via siRNA exacerbated TMAO-induced inflammation and osteogenic response in AVICs, while KDM2B overexpression (Ad-KDM2B) mitigated these effects. RT-qPCR array identified NADPH Oxidase 4 (Nox4) as a key KDM2B-regulated oxidizing gene. Ad-KDM2B significantly downregulated Nox4 mRNA expression in AVICs. Chromatin immunoprecipitation with qPCR (Chip-qPCR) revealed enhanced JunD binding to the Nox4 promoter upon KDM2B overexpression. KDM2B promoted JunD expression by demethylating H3K4me3, thereby suppressing Nox4 transcription. Western blot, along with alkaline phosphatase and Alizarin Red staining, demonstrated that Nox4 overexpression abolished the protective effects of KDM2B overexpression. In vivo, adeno-associated virus-mediated KDM2B overexpression significantly attenuated aortic valve lesions in mice fed a high-fat, choline diet (HFCD). Conclusion: KDM2B protects against TMAO-induced CAVD by regulating oxidative stress. It achieves this by decreasing H3K4me3 on JunD, thereby preventing Nox4 transcription. KDM2B represents a potential therapeutic target for CAVD.
Abstract 4142546: Single-Nucleus RNA Sequencing Reveals Region-Specific Cell Composition and Transcriptional Variations in Cardiac Sarcoidosis
Authors: Meraj Neyazi, Yuri Kim, Kemar Brown, Syndi Barish, Joshua Gorham, Olivia Layton, Anissa Viveiros, Daniel DeLaughter, Martin Beyer, Viktoria Strohmenger, Daniel Reichart, Dawn Bowles, Carolyn Glass, Gavin Oudit, Jonathan Seidman, Christine Seidman
Journal: Circulation (2024)

Introduction: Sarcoidosis is a granulomatous disease of unknown cause that can affect any organ. Cardiac involvement, indicated by arrhythmias, conduction abnormalities, heart failure, and sudden cardiac death, occurs in about 5% of cases and accounts for 50% of sarcoid-related deaths. Yet, autopsy studies have found cardiac granulomas in 15-90% of patients. The localized nature of granulomas in the heart makes diagnosis difficult. Treatment usually includes immunosuppression and standard cardiac care, but neither is curative or prevents adverse outcomes. Research Questions: We aimed to enhance the understanding of cardiac sarcoidosis pathobiology by performing single-nucleus RNA sequencing on different regions of diseased hearts, focusing on immune dysregulation and the regional impact of granulomas on the myocardium. Methods: We used 10X Chromium V3 chemistry to investigate granulomatous, seemingly unaffected, and scarred regions within the same patients. We conducted a comparative analysis of samples from sarcoidosis patients, normal donor hearts, and patients with DCM due to their similar clinical phenotype. Results: A total of 608,235 nuclei from 21 sarcoidosis patients (41 samples), 12 control subjects (31 samples) and 29 DCM patients (66 samples) were analyzed in this study. On average, sarcoid samples showed fewer cardiomyocytes and pericytes, with more fibroblasts, myeloid, and lymphoid cells, compared to controls. Those sarcoid tissues with a control-like cardiomyocyte proportion displayed a significant reduction in pericytes (14.3% vs. 3.3%, p = 9.1e-9), suggesting microvascular dysfunction even in regions without granuloma and scarring. All sarcoid samples showed a marked increase in a lipogenic and extracellular matrix remodeling fibroblast state (2.6% vs. 10.7%, p = 2.7e-8). Granulomatous regions contained CHI3L1 and DCSTAMP-expressing granuloma-associated macrophages, as well as pro-inflammatory Th17-like T-cells, which have been implicated in various autoimmune diseases, and IL1R1+ Treg cells resembling exhausted Tregs, which have previously been described in tumor microenvironments. Conclusions: This comprehensive single-nucleus profiling highlights considerable regional heterogeneity in cardiac sarcoidosis. Understanding immune dysregulation and the spatial impact of granulomas on the myocardium may lead to optimized therapies for this understudied and potentially lethal disease, which currently has ineffective treatment options.
Abstract 4142177: Structure-Function Alterations in Satellite Glial Cell-Neuronal Communication Underlie Sympathetic Hyperactivity after Myocardial Infarction
Authors: Ruizhu Lin, Yutian Zhao, Kaitlyn Ang, Sachin Sharma, Nigel Arreola, Joseph Ettipio, In Sook Ahn, Carla Valenzuela Ripoll, Ali Javaheri, Xia Yang, Olujimi Ajijola
Journal: Circulation (2024)

Background: Hyperactive cardiac sympathetic signaling characterizes chronic myocardial infarction. Although satellite glial cells (SGCs) regulate cardiac neuronal function, their role in mediating sympathetic hyperactivity following chronic myocardial injury remains poorly understood. Research Questions: The aim of the present study was to investigate the impact of cardiac injury on SGCs and SGC-neuronal communication in the stellate ganglion. Methods: Glial-specific reporter mice (7-9wks) with Cre-dependent tdTomato expression under the glial fibrillary acidic protein (GFAP) + promoter were randomized to sham or myocardial infarction (1, 2 or 4wks) verified by echocardiography. Stellate ganglions from mice received closed chest ischemia reperfusion (CCIR) were subjected to single nuclei RNA sequencing (snRNAseq) to glean transcriptomic profiles of glia and neurons, as well as ultrastructural imaging for high-resolution morphological analyses. Results: Following infarction, progressive LV dysfunction was confirmed by echocardiography at 1, 2, and 4wks in comparison with sham. High-resolution imaging of ganglia showed that SGCs exhibited a diminished cell structure with reduced process length at 4wk post-infarction. SnRNAseq in stellate ganglions of mice revealed two subpopulations of SGCs (GC1&amp;GC2). GC1 exhibited greater expression of satellite glial markers (e.g. ApoE and Fabp7), while GC2 had enriched components related to myelination. In sham mice, GC1 accounted for the majority of SGCs (&gt;75%), whereas CCIR shifted the main type from GC1 towards GC2 over time, with GC2 representing &gt;80% glia 4wks post-CCIR. Pathway analysis of differentially expressed genes (4wk CCIR vs sham) showed enrichment of neural structure-related pathways, including synapses, axons and dendrites, in both GC1 and GC2 compared to sham. Moreover, cell-cell communication analysis indicated that compared to the change of GC1, GC2 became more interactive with sympathetic neurons, which used acetylcholine as the key neurotransmitter. Conclusion(s) In totality, these findings indicate that cardiac injury alters the morphology, distribution, and function of SGCs and their interaction with cardiac sympathetic neurons. These findings implicate a role of SGCs in post-injury sympathetic hyperactivity.
Abstract 4142390: The LAI-OLS registry: Unveiling crucial insights into the challenges of managing LDL cholesterol in Indian patients with CAD
Authors: Kunal Mahajan, Ashu Gupta, Aditya Batra, Vivek Rana, Mukul Kumar, Atit Gawalkar, Tanuj Bhatia, Rahul Yadav, Dhananjay Kumar, Jai Bharat Sharma, Pavan Theja, Ashwani Yadav, munish dev, Surender Himral, Priyanka Thakur, Sakshi Khandelwal, Akshay Pratap, Aziz Khan, Rajeev Agarwala, Raman Puri
Journal: Circulation (2024)

Background: The Lipid Association of India (LAI) recommends intensive lipid-lowering therapy (LLT) for patients with established atherosclerotic cardiovascular disease to achieve a target low-density lipoprotein cholesterol (LDL-C) level below 50 mg/dl. Research Question: The lack of Indian data on achieving LDL-C goals in patients with coronary artery disease (CAD) is a significant knowledge gap that needs to be addressed. Aim: The Lipid Association of India's Optimization of LDL-C in the Stable CAD (LAI-OLS) registry , aimed to assess the achievement of the LAI-recommended LDL-C goals in patients with angiographically proven CAD. Methods: The LAI-OLS registry enrolled 2431 patients with angiographically proven CAD across ten interventional cardiology centers in Northern India over six months (August 2023- January 2024). Interventional cardiologists (ICs) treated all enrolled patients and collected data at a single visit, including the most recent LDL-C and the LLT in the preceding three months of that LDL-C reading. Results The study population had a mean age of 60.6 ± 16.9 years, with a male predominance (80.4%). A substantial proportion of the patients had significant cardiovascular risk factors: 30.7% had diabetes mellitus (DM), 37.9% had hypertension (HTN), 28.6% were obese (BMI &gt; 25 kg/m2), and 17.1% were current smokers. Notably, 74.1% had a history of acute coronary syndrome, and 77.3% had undergone prior percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Rosuvastatin (65.2%) was the most commonly prescribed statin, followed by atorvastatin (34.2%). High-intensity statin (HIS) therapy (20-40 mg rosuvastatin or 40-80 mg atorvastatin) was used in 71.4% of patients. Other lipid-lowering agents (ezetimibe, bempedoic acid, fibrates) were used in a tiny percentage of patients (1.1%), and no patients were on PCSK9 inhibitors. Despite the extensive use of statin therapy, only 26.2% of patients achieved the LAI-recommended LDL-C goal of &lt;50 mg/dl. While 47.1% achieved an LDL-C below 70 mg/dl, it is noteworthy that a small proportion (2.6%) were not taking any lipid-lowering medication. Conclusion: Indian patients with CAD face a high risk due to widespread diabetes, hypertension, and obesity. Despite extensive use of HIS, many fail to meet LDL-C targets. These results highlight the need for early and aggressive combination lipid-lowering therapies, including non-statin drugs, to improve outcomes in this high-risk population.
Abstract 4142298: Association Between Lp(a) and Cardiovascular Events in Individuals with Peripheral Artery Disease in the Mass General Brigham Lp(a) Registry
Authors: Daniel McClintick, David Biery, Adam Berman, Stephanie Besser, Arthur Shiyovich, Avinainder Singh, Daniel Huck, Brittany Weber, Marc Bonaca, Marie Gerhard, James Januzzi, Marcelo Di Carli, Eric Secemsky, Deepak Bhatt, Ron Blankstein, Sanjay Divakaran
Journal: Circulation (2024)

Background: Both lipoprotein(a) [Lp(a)] and peripheral artery disease (PAD) are independently associated with atherosclerotic cardiovascular disease (ASCVD) events. Whether elevated Lp(a) provides additional risk stratification among individuals with PAD is less well-established. Methods: The Mass General Brigham (MGB) Lp(a) registry includes all individuals with Lp(a) measured at two tertiary care centers from 2000-2019. Those with a history of PAD were grouped into quartiles according to Lp(a) percentile: 1 st -25 th (Q1, Lp(a) ≤ 14nmol/L), 26 th -50 th (Q2, 14 - 42nmol/L), 51 st -75 th , (Q3, 42-132nmol/L), and 76 th -100 th (Q4, 132-855nmol/L). Outcomes were major adverse cardiovascular events (MACE: composite of cardiovascular death, myocardial infarction, ischemic stroke, or coronary revascularization) and major adverse limb events (MALE: composite of peripheral revascularization [endovascular or surgical], acute limb ischemia, or major lower extremity amputation). Cox proportional hazard modeling was used to assess the association between Lp(a) and the outcomes of interest. Analyses were adjusted for traditional risk factors. Results: Among 3,791 individuals with PAD, (39% female, median age 68 [IQR: 59-77]), 79% had hypertension, 81% had dyslipidemia, and 37% had diabetes. Relative to Q1, those in Q3 and Q4 had a 19% and 26% increased risk of MACE, respectively (adj. HR: 1.19, 95% CI 1.03-1.37, p=0.018; adj. HR: 1.26, 95% CI: 1.09-1.45, p=0.001, Fig, A ). Individuals in Q4 had a 23% higher risk of MALE (adj. HR: 1.23, 1.03-1.48, p=0.022, Fig, B ) relative to those in Q1. The overall event rate (per 1000 patient years) for MACE increased monotonically across all four subgroups while for MALE was increased only for those in the highest Lp(a) group. Conclusions: In individuals with PAD, Lp(a) levels provide additional prognostic information beyond traditional risk factors. Lp(a) above the 50 th percentile was associated with higher risk of MACE, while levels greater than 75 th percentile were associated with an increased risk of both MACE and MALE.
Abstract 4142443: Multi-Omics Integration of Clinical Risk Factors, Polygenic Risk Score, and Proteomics to Predict Abdominal Aortic Aneurysm in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Aixin Li, Jim Pankow, Kuni Matsushita, Faye Norby, Ron Hoogeveen, Weihua Guan, Pamela Lutsey, Eric Boerwinkle, Joe Coresh, Aaron Folsom, Weihong Tang
Journal: Circulation (2024)

Introduction: Abdominal aortic aneurysm (AAA) is a significant cause of morbidity and mortality in older adults. The AAA screening guidelines from the Society of Vascular Surgery include risk factors such as sex, age, smoking, and family history. This study explored whether integration of a polygenic risk score (PRS) and proteomics with clinical data could improve AAA prediction in the ARIC Study. Methods: Over a median follow-up of 24 years from ARIC visit 2 (1990-92) baseline, we identified 487 clinical AAA cases among 9,373 ARIC participants (7,397 Whites and 1,976 Blacks) through hospital discharge diagnoses or death certificates. We selected AAA-associated clinical risk factors based on literature and our expertise, including age, gender, race, field center, smoking status, smoking pack-years, waist girth, BMI, levels of total and HDL cholesterols, hypertension, diabetes, and eGFR. We calculated the PRS[WT1] based on SNP dosage in ARIC and the latest genome-wide association study for AAA, which reported 141 independent associations from 14 discovery cohorts (PMID: 37845353). ARIC used SOMAscan v4 to measure 4,955 plasma proteins at baseline, of which 24 were significantly associated with clinical AAA (p &lt; 1x10^-5) independent of the clinical risk factors. The prediction equation for AAA risk was constructed in 3 Cox regression models: 1) clinical risk factors measured at baseline, 2) model 1 variables plus PRS, and 3) model 2 variables plus the 24 AAA-associated proteins identified through proteomics analysis. We used the area under the curve (AUC) to evaluate the prediction performance of these models for AAA risk. Results: Participants in the top quintile of PRS showed significantly higher AAA risk compared to the lowest quintile (HR 1.41, 95% CI: 1.03 – 1.85) after adjustment for clinical risk factors. Adding the PRS to clinical risk factors did not improve the AUC: 0.890 (95% CI: 0.869 - 0.945) in model 1 vs 0.891 (95% CI: 0.853 - 0.961) in model 2. Further adding the 24 AAA-associated proteins substantially improved the performance of the prediction model [AL2] (AUC=0.950, 95% CI: 0.939 - 0.986 in model 3), with 289 AAA events in the top quintile of predicted risk compared to 12 in the lowest quintile. Conclusion: A proteomics-integrated approach that combined clinical risk factors and proteomics data enhanced AAA risk prediction and has the potential to improve risk stratification and early intervention for AAA.