tbuckley/cabot-search huggingface dataset:
Abstract 4146276: Conduction Delay Characteristics in the Post-operative Course of the First Porcine-to-Human Cardiac Xenotransplant Recipient
Authors: Justin Brilliant, Devika Haridas, Bartley Griffith, Ubaid Khan, Oneib Khan, Mahdokht Parsirad, Manjula Ananthram, Susie Hong-Zohlman, Erika Feller, Alison Grazioli, Richard Amara, Stephen Shorofsky, Muhammad Mohiuddin, Timm Dickfeld
Journal: Circulation (2024)

Background: The first-ever genetically modified porcine-to-human cardiac xenotransplantation was performed in January 2022 at the University of Maryland, with the recipient surviving 60 days. Aim: Characterize trends in conduction delay observed over the 60-day post-operative course of the first-ever porcine-to-human cardiac xenotransplant recipient. Methods: Daily 12-lead ECGs were evaluated for presence and type of conduction delay. Over the post-operative period, 93 ECGs were obtained. ECGs that could not be assessed for conduction delay due to presence of significant artifact (2 ECGs) or paced rhythm (12 ECGs) were excluded from evaluation. Results: During the 60-day postoperative period, the xenotransplant exhibited alternating conduction block including nonspecific intraventricular conduction delay (NSIVCD), right bundle branch block (RBBB), incomplete RBBB, and left anterior fascicular block (LAFB). Nonspecific intraventricular conduction delay (NSIVCD) was observed on 6 days in total, occurring primarily within the first 9 post-operative days. After day 9, the conduction block alternated between bifascicular block with RBBB+LAFB, incomplete RBBB+LAFB, RBBB, and incomplete RBBB. The predominant pattern of conduction delay was bifascicular block with RBBB+LAFB, occurring over 32 days in this period. Presence of incomplete RBBB+LAFB was noted on 17 days in total. Isolated RBBB occurred on 2 days, and incomplete RBBB on 4 days. There was no evidence of high-grade atrioventricular block observed in this period. Conclusion: Ventricular conduction in the post-operative period of the first porcine-to-human xenotransplant was characterized by an alternating conduction block with NSIVCD in the early postoperative period (through day 9), followed by predominantly bifascicular block with RBBB and LAFB or incomplete RBBB and LAFB. Atrioventricular conduction remained largely intact without evidence of high-grade AV block nor dependence on back-up pacing during the majority of our patient’s post-operative course.
Abstract 4146347: Oxidative Stress Lipids Associate with Mood Disturbance Symptoms and Quality of Life in Acute Ischemic Stroke Patients
Authors: Sarah Martha, Alice Pen, Laura McGuire, Ali Alaraj, Fernando Testai, Hilaire Thompson
Journal: Circulation (2024)

Background: Acute ischemic stroke (AIS) is a leading cause of mortality and disability globally, disproportionately affecting Black and Latinx populations who experience increased morbidity and mortality compared to their white counterparts. At one month, roughly 50% of AIS survivors experience mood disturbances (e.g., anger, irritability, and aggression) and exhibit a lower health-related quality of life (HRQOL) compared to pre-AIS levels. Downstream biomarkers of mitochondrial dysfunction such as oxidative stress may be important pathophysiological mechanisms underlying mood disturbance symptoms, stroke severity, and long-term functional recovery. Purpose: To examine associations among early and late peripheral plasma lipid levels, mood disturbance symptoms (e.g., anger, irritability), and HRQOL outcome over 3 months (baseline/study day 5, and months 1, 3) in persons following AIS. Methods: The pilot study is a non-probability, convenience sample of adult subjects (&gt; 18 years of age) with a diagnosis of AIS. Lipidomics analysis was performed using liquid chromatography-mass spectrometry (LC-MS) of untargeted lipids. The Agilent 6545 LC/Q-TOF platform was used to determine the absolute concentration of lipid species from peripheral plasma samples collected days 1, 3, 5 and months 1 and 3 post-AIS. General linear mixed models were used to test the predictive association of lipidomic biomarker mean value of peripheral plasma lipid levels and symptoms and outcomes over time (baseline and months 1 and 3). Results: We analyzed 82 subjects (age = 64 ± 12.1, 52% male, 78% Black, and 94% with hypertension). Elevated oxidative stress biomarkers (e.g., lipoxygenases, arachidonic acid, glycosylphosphatidylinositol) were associated with higher severity of anger and irritability symptoms, and a poorer HRQOL from baseline to 1- and 3-months post-AIS (p=0.04). Conclusion: An untargeted LC-MS lipidomics approach was used to identify lipids following AIS. Because oxidative stress plays a key regulatory role in complex downstream cellular function, these findings may be of great significance in understanding AIS pathophysiology that has the potential to inform personalized preventive strategies.
Abstract 4146485: Clinical Validation of an AI-enabled ECG Holter Analysis Platform
Authors: Alan Kennedy
Journal: Circulation (2024)

Introduction: The analysis of Holter ECG recordings on a large scale typically demands substantial clinical resources. This investigation aimed to evaluate whether an artificial intelligence (AI)-powered Holter analysis platform could interpret ambulatory ECG recordings with comparable accuracy to that of a board-certified cardiologist. Methods: A total of 328 30-second ECG rhythm strips were analysed from continuous 14-day ECG patch recordings. The recordings underwent independent analysis by the AI platform (PulseAI, Belfast, United Kingdom), six individual cardiologists, and a consensus panel of three cardiologists which served as the gold standard. The presence or absence of five predetermined cardiac arrhythmias were evaluated: atrial fibrillation/flutter (AFIB), ventricular bigeminy, ventricular trigeminy, ventricular tachycardia (VT), and high-grade atrioventricular block (AVB). Results: The comparison between the AI platform's interpretation and that of individual cardiologists revealed no statistically significant differences in sensitivity and specificity (McNemar's Test, p&gt;0.05). For AFIB, the sensitivity was 0.76 for the AI platform compared to 0.74 for individual cardiologists, with specificities of 0.97 and 0.94, respectively. Similarly, for AVB, the sensitivity was 0.85 for the AI platform and 0.83 for individual cardiologists, with specificities of 0.99 for both. For VT, the sensitivity was 0.71 for the AI platform and 0.78 for individual cardiologists, with specificities of 0.98 and 0.99, respectively. For ventricular bigeminy and ventricular trigeminy, the AI platform demonstrated sensitivities of 0.82 and 0.85, respectively, compared to 0.81 and 0.79 for individual cardiologists, with specificities of 0.99 for all comparisons. Conclusions: These results suggest that use of an AI-based platform for Holter ECG analysis can provide rapid ECG interpretation from ambulatory ECG monitors at levels equivalent to those of a board-certified cardiologist. Implementation of this AI-platform could facilitate precise, scalable, and consistent arrhythmia analysis when monitoring patients for arrhythmias.
Abstract 4146402: The efficacy and safety of β-blockers in patients with Chronic Obstructive Pulmonary Disease after Myocardial Infarction: a Systematic review and Meta-analysis.
Authors: Alonzo Prata, Eric Katsuyama, Christian Fukunaga, Pedro Gabriel Scardini, Ana Carolina Coan, Wilson Falco Neto, Julia Fernandes, Rafael Petri Santos Pinheiro, Naieli Andrade, Luciana Gioli-Pereira
Journal: Circulation (2024)

Background: Previous clinical trials demonstrated the efficacy of beta-blockers (BB) after myocardial infarction (MI). However, the effects and safety of BB in patients with chronic obstructive pulmonary disease(COPD) after MI remain a mystery. Therefore, we conducted a systematic review and meta-analysis evaluating beta-blocker use after MI in patients with COPD. Methods: We performed a systematic review and meta-analysis of observational studies that included patients with COPD who received BB after an episode of MI. We searched through Pubmed, Cochrane, and Embase databases. Our primary efficacy outcome was (1) all-cause mortality, and our safety outcome was (2) COPD-related and respiratory adverse events. In our secondary analysis, we evaluated all-cause mortality in patients with a prior history of heart failure (HF). Statistical analysis was done using R Studio 4.3.2. Results: A total of 6 studies were included, encompassing 41840 patients, of whom 16561 (39.5%) were in the beta-blocker group. Most of the participants were male (65%) and the mean follow-up was 5.1 years. In the pooled analysis, all-cause mortality was significantly lower in the BB group (HR 0.81; 95% CI 0.66, 0.98; p = 0.03, Fig 1A). Our secondary analysis in the HF subgroup also showed a significant risk reduction in all-cause mortality(HR 0.80; 95% CI 0.66, 0.97; p = 0.02, Fig 1B.) Regarding COPD-related and respiratory adverse events, the analysis demonstrated a significantly lower incidence in the BB group (HR 0.79; 95% CI 0.74, 0.83; p&lt;0.01; Fig 2 ). Conclusion: In this meta-analysis involving COPD patients following recent MI, BB utilization was linked to reduced all-cause mortality and a decreased risk of COPD-related adverse events. Additionally, BB administration was correlated with reduced all-cause mortality within the HF subgroup of this cohort.
Abstract 4146448: Real-world Outcomes of Nicotine Replacement Therapy in Acute Coronary Syndrome
Authors: Jasninder Dhaliwal, Manraj Sekhon, Arush Rajotia, Kamleshun Ramphul, Swaiman Singh
Journal: Circulation (2024)

Introduction: Acute Coronary Syndrome (ACS) is a major global health issue, with smoking as a significant modifiable risk factor. Smoking cessation reduces recurrent coronary events, making it crucial in ACS management. Current protocols recommend smoking cessation education during hospitalization and referral to smoking cessation or outpatient cardiac rehabilitation programs, where nicotine replacement therapy (NRT) and bupropion are available. NRT, including patches, gum, and lozenges, helps alleviate withdrawal symptoms by providing a controlled nicotine dose. Hypothesis: We hypothesize that cautious initiation of NRT during hospitalization benefits ACS patients, with the benefits outweighing the risks. This study seeks to provide clarity and contribute to evidence-based guidelines for ACS management. Methods: In this retrospective cohort study, data were gathered from the TriNetX database. The study compared two cohorts: 122,198 patients who received NRT and were hospitalized for acute myocardial infarction (AMI) or unstable angina (UA), and 160,387 patients who did not receive NRT but were admitted for the same conditions. The follow-up period began on the day of the index event and continued for 30 days. Cardiovascular outcomes were compared between propensity score-matched patients with and without NRT. Results: Patients receiving NRT had a reduced risk of several cardiovascular outcomes compared to those who did not receive NRT, including atrial fibrillation and flutter (RR [95% CI]=0.822[0.792-0.854, p&lt;0.01]) and ventricular fibrillation and flutter (RR [95% CI]=0.715[0.654-0.781, p&lt;0.01]). The risk of death was also reduced (RR [95% CI]=0.701[0.678-0.726, p&lt;0.01]). Hospital readmissions were less frequent in the NRT group (RR [95% CI]= 0.960[0.955-0.965, p&lt;0.01]). Additionally, the risk of cardiac arrest was lower (RR [95% CI]= 0.698[0.660-0.738, p&lt;0.01]), and supraventricular tachycardia (SVT) was less common (RR [95% CI]= 0.883[0.827-0.942, p&lt;0.01]). These results highlight the potential benefits of NRT in reducing the risk of various cardiac events following AMI or UA. Conclusions: The cautious initiation of NRT during hospitalization can benefit ACS patients where the benefits outweigh the risks. This study aims to provide clarity and contribute to evidence-based guidelines for ACS management.
Abstract 4146535: Prevalence and In-hospital Outcomes of Cardiac events in Women with underlying Infertility Condition:A National Inpatient Database Analysis
Authors: Sujana Sanka, Priya Hotwani, Dhairya Nanavaty, Rishav Sinha, Himaja Dutt Chigurupati, Sivaram Neppala, Jawad Basit, M Chadi Alraies
Journal: Circulation (2024)

Introduction: Cardiovascular(CV) disease is one of the leading cause of death in females in USA out of which 44% suffer. According to the latest CDC guidelines, 13.4 % are suffering from the infertility.It includes the most common conditions including endometriosis, poly cystic ovarian syndrome. Studies shows a mutlitude of factors including genetic abnormalities, hormonal imbalances like chronic anovulation or increased androgens predispose the women to subsequent health conditions.Literature review suggests that long term cv risks are less understood in the infertile women. Aim: The aim of the study is to identify the CV outcomes including coronary heart disease(CAD) , acute coronary syndrome(ACS), and heart failure in women with underlying infertility condition. Methods: The NIS 2020 was queried for the female adult population (age&gt;18 years) with a primary or secondary diagnosis of infertility. Prevalence of CV risk factors were compared between females with and without infertility problem. The association of cardiac diagnoses including CAD, ACS and was analysed. Multivariate regression analysis was performed taking all-cause mortality as a primary outcome. Results: A total of 3870 adult patients with a primary or secondary diagnosis of infertility were identified and the mean age was 36 years.In adult population without infertility condition, patients with an underlying infertility were found to have an increased association with DM (48.16%vs 23.11%; P&lt;0.001),HLD(56.14% vs 30.72%; P&lt;0.001),hypothyroid(17.47% vs 10.47%; P&lt;0.001),metabolic syndrome(0.23% vs 0.16%; P&lt;0.001) while we found decreased association in tobacco abuse( 14.18% vs 17.12%; P&lt;0.001),HTN(1.47% vs 37.95%; P&lt;0.001). The prevalence of CAD(46.64% vs 12.59%; P&lt;0.001), ACS(46.64% vs 12.59%; P&lt;0.001) was also found to be significantly higher in women with infertility. In the female subpopulation with infertility, approximately 5.91% of patients died. However, the odds of mortality was significantly increased if patients had underlying ACS (OR- 2.77; C.I.-2.72 -2.87; P&lt;0.001) or CAD (OR- 3.97; C.I.: -3.93-4.02; p&lt;0.001). There was no statistically significant increased mortality with HF( OR:1). Conclusion: In our study, infertility in women was associated with higher prevalence of CAD and ACS. The odds of mortality also increased if women with infertility condition if they developed ACS or CAD. Further clinical research and studies are warranted to understand its CV outcomes.
Abstract 4146419: Maternal Gestational Diabetes Leads to Disturbed Fetal Vascular Function and Increased LOX-1 Expression
Authors: Clara Hengst, Maria de Leyre Villar Ballesteros, Heike Brendel, Philine Sophie Carstens, Deborah Effenberger, Jennifer Mittag, Sindy Giebe, Alexander Fruehauf, Cahit Birdir, Paul Taylor, Henning Morawietz
Journal: Circulation (2024)

Introduction/Background: Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and a major risk factor for endothelial dysfunction and cardiovascular diseases in later life. The underlying pathophysiology is not well-understood. An important mediator of endothelial dysfunction and atherosclerosis is the lectin-like receptor for oxidized low-density lipoprotein, LOX-1. Research Question/Hypothesis: We hypothesize that maternal GDM leads to impaired fetal vascular function and increased endothelial LOX-1 expression. Goals/Aim: Our aim is a better understanding of the impact of maternal GDM on fetal vascular function and LOX-1 as potential mediator of endothelial dysfunction. Methods/Approach: We obtained maternal and fetal vessels of mature human placentas from normoglycemic mothers (n=32) and patients with insulin-treated GDM (iGDM) (n=8) or diet-treated GDM (dGDM) (n=8). Groups were defined by oral glucose tolerance test and clinical data of mothers and newborns. Vascular function of fetal vessels from mothers with iGDM, dGDM, or normoglycemic controls was analyzed by Mulvany Myograph. Gene expression was quantified by real-time PCR in RNA from fetal vessels of cotyledone base and maternal spiral arteries of patients. Results/Data: Birth weight to placenta weight-ratio showed a significantly reduced placenta efficiency in the iGDM group ( P &lt;0.0016), but not in the dGDM group, compared to control. We observed a significant reduction of insulin-mediated vasodilatation in fetal arterial vessels of the chorionic plate from iGDM ( P &lt;0.0003) and dGDM patients ( P &lt;0.0421), compared to control. NO synthase inhibition significantly reduced insulin-dependent vasorelaxation in the control, but not GDM groups. This was independent of eNOS mRNA expression. We could show a significant LOX-1 overexpression in fetal placental vessels of iGDM patients, compared to normoglycemic mothers. In addition, the mitochondrial uncoupling protein 2 (UCP2) was elevated in fetal vessels of iGDM mothers compared to control. This supports a fetal compensatory mechanism in response to impaired vascular function in spiral arteries of the mother. Conclusions: In conclusion, the endothelial function of the fetus is more severely affected by maternal iGDM, compared to dGDM. Furthermore, iGDM might have an adverse effect on placenta efficiency. The LOX-1 receptor could be a promising therapeutic target in the treatment of vascular dysfunction in GDM.
Abstract 4146352: Development and Validation of Machine Learning-based Ischemic Outcome Prediction Using Clinical and Genetic Data in Patients with Percutaneous Coronary Intervention
Authors: Caroline Grant, Gurukripa Kowlgi, Ryan Lennon, Larisa Cavallari, Craig Lee, Amber Beitelshees, Dominick Angiolillo, Francesco Franchi, Julio Duarte, Joe Rossi, George Stouffer, Eric Klee, Rajiv Gulati, Amir Lerman, Charanjit Rihal, Michael Farkouh, Arjun Athreya, Naveen Pereira
Journal: Circulation (2024)

Introduction: Identifying patients at risk for ischemic events after percutaneous coronary intervention (PCI) relies on traditional analysis of limited clinical and imaging variables. Machine learning (ML) has shown promise in effectively predicting cardiovascular risk in population studies. While existing ML models mainly predict mortality and incorporate clinical variables, there is a lack of tools that have utilized genetic data and that predict ischemic events. Aims: This study aims to develop and validate a ML model incorporating genotyping and clinical data to enhance prediction of ischemic outcomes for PCI patients utilizing large prospectively derived diverse datasets. Methods: Patients from the TAILOR-PCI trial (n=5302) were utilized for model development. 50% of the sample was utilized for Boruta feature selection and 50% for training and testing using cross validation. Features included demographics, medical history, medications, PCI characteristics, and genetic data (specifically, CYP2C19 *2, *3, *17 alleles). The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia at 12 months. Multiple ML classification algorithms, including Support Vector Machine (SVM) polynomial, Random Forest, Light gradient boost, XG Boost, among others, were benchmarked for their prediction performance on rare events. The top performing classifiers were externally validated on an independent dataset from the PRECISION PCI study (n=3,745). Results: Mean participant age of the training set was 64.2 ± 11.0 years, with 75.4% being male. During follow-up of 12 months, among 4,572 patients in the entire cohort 343 (7.5%) met the primary outcome. The SVM polynomial model demonstrated the highest area under the curve (AUC) of 0.67 for predicting the primary outcome with test dataset. The sensitivity, specificity, precision, and recall were 0.87, 0.28, 0.07, and 0.87 respectively (Figure). Peripheral arterial disease, body mass index, and age were among the top variables by feature importance. Conclusion: ML models incorporating both clinical and genetic data are feasible and highly promising in predicting major adverse cardiac events that may help guide use of anti-platelet drug therapy. The AUC values are reasonable given imbalances and misclassifications in datasets, and further model optimization with prospective utilization of the model will be paramount.
Abstract 4146342: Endothelial cells injured by hyperglycemia are rescued by P53 silenced bone marrow derived mesenchymal stromal cells (BM-MSC) derived secretome by improving cellular mitochondrial function.
Authors: Sabyasachi Sen, Seshagiri Nandula
Journal: Circulation (2024)

Introduction: Diabetes is associated with endothelial cell dysfunction. Studies have demonstrated that endothelial progenitor cells (EPCs) and mature endothelial cells (EC) are susceptible to apoptosis in hyperglycemic environment, however EPC start to undergo apoptosis within 48 hrs whereas ECs take upto 4 weeks. We in the past have shown that p53 gene silencing prevents EPC senescence in hyperglycemia and helps vascular regeneration. We have also shown that p53 silenced hematopoeitic CD34+ve EPC therapy helped tissue and vascular regeneration in hyperglycemia (25mmol). Our goal was to test whether conditioned media (CM) obtained from p53 silenced human stem cells (non-hematopoitic source) can also improve cell survival&amp;regeneration. Methods: We examined BM-MSCs and Adipose tissue MSCs (ADMSCs) derived CM to explore cell free therapeutics. Ad-human-P53 (TP53)-shRNA was used to silence P53 and Ad-scrambled-null-shRNA was used as control. To collect CM, the MSCs were cultured for 5 days, in serum-free media, followed by transduction with Ad-p53sh or Ad-null. After transduction, cells were cultured in 2% exosome free FBS media for only 48h and the collected supernatant was concentrated 10-fold to obtain the CM. Endothelial regeneration was tested following CM treatment on human endothelial cells (HECs) using endothelial wound healing assay kit (Cell Biolabs CBA-120-T). We compared CM obtained from null and p53sh BM-MSCs and ADMSCs on HEC , which was exposed to hyperglycemia for 2-3 weeks, using wound-healing assay (n=5). Results: Anti-apoptosis/ Proliferation capacity of the p53sh BMMSC-CM was 2.5-fold more compared to p53sh-ADMSC-CM. Post BM-MSC-CM treatment of hyperglycemia exposed endothelial cells, we noted a 4-fold increase in VEGFA mRNA expression and 2.2-fold increase mitochondrial-SOD (SOD2), compared to null transduced BMMSC derived CM. Other mitochondrial genes are being investigated and indicate a similar trend. Furthermore exosomes derived from p53 BMMSC-CM appear to have the protective effect on hyperglycemia exposed HEC vs non exosomal portion. Conclusion: p53sh-BMMSC-CM appears to have better anti-apototic effect compared to p53sh-ADMSC-CM. This finding allows us to generate relatively larger quantities of CM vs CM from p53sh EPCs. Cell-free CM or exosomes from CM obtained from p53sh BM-MSC cells may have a therapeutic role in treating vascular complications of diabetes with mitochondrial function improvement as a possible mechanism.