tbuckley/cabot-search huggingface dataset:
Abstract 15530: Intravenous Thrombolysis in Patients With Ischemic Stroke on Direct Oral Anticoagulants: A Systematic Review and Meta-Analysis
Authors: Rahul Gupta, Amir Hossein Behnoush, Amirmohammad Khalaji, Pegah Bahiraie, Aaqib H Malik, Dhrubajyoti Bandyopadhyay, Akshay Goel, Wilbert S Aronow, NAINESH PATEL, bryan kluck
Journal: Circulation (2023)

Introduction: Current guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who are on direct oral anticoagulants (DOAC). However, studies found conflicting results regarding IVT safety and functional outcomes among patients receiving DOACs. Hypothesis: Herein, we aim to investigate this association through a systematic review and meta-analysis. Methods: A comprehensive literature search was performed in PubMed, Embase, Scopus, and the Web of Science. Studies were included if they compared the outcomes of patients receiving DOACs and those without recent use of DOACs. Random-effect meta-analysis was performed to calculate the odds ratio (OR) and 95% confidence interval (CI) for comparison of modified Rankin Score (mRS) 0-2, all-cause mortality, and symptomatic intracranial hemorrhage (sICH). Results: A total of five studies were included among which 3,408 received DOACs and 244,033 did not. Random-effect meta-analysis revealed that the functional neurological outcome (mRS 0-2) was significantly lower in patients that received DOACs (OR 0.71, 95% CI 0.62-0.81, p&lt;0.01). However, this difference was no longer significant in the subgroup analysis of 90 days mRS 0-2 (OR 0.71, 95% 0.46-1.11, p=0.14). Regarding all-cause mortality, patients on DOAC had a higher overall mortality rate (1.26, 95% CI 1.07-1.48, p=0.01). Nevertheless, this was not true for subgroups of in-hospital and 90-days mortality, which were both insignificant. Finally, sICH did not differ between the groups (OR 0.99, 95% CI 0.70-1.39, p=0.93). Conclusions: Our results demonstrated that the use of IVT in selected patients on DOACs with stroke might be beneficial and not associated with increased risk as there was no difference between the groups in terms of sICH.
Abstract 14226: Prognostic Impact of Hyperkyphosis in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Takuma Iwaya, Hideaki Kanzaki, Yuki Irie, Naonori Kawamoto, Atsushi Okada, Amano Masashi, Makoto Amaki, Kensuke Takagi, Takeshi Kitai, Kengo Kusano, Teruo Noguchi, Satsuki Fukushima, Chisato Izumi
Journal: Circulation (2023)

Introduction: Hyperkyphosis, an excessive forward curvature of the upper spine seen in older people, can lead to pulmonary function decline, decreased physical performance, and frailty. However, there are no data on the prognostic impact of hyperkyphosis in transcatheter aortic valve replacement (TAVR). Hypothesis: Hyperkyphosis may be associated with poor clinical outcomes of TAVR. Methods: This study included 244 patients (age, 83.7 ± 5.4 years; 73.4% female) who underwent transfemoral TAVR at our institution between January 2016 and April 2020. Hyperkyphosis was defined as a Cobb angle of greater than 40°. Results: Hyperkyphosis was present in 47 patients (19.3%), and all had marked descending aortic tortuosity. Vascular and access-related complications were more frequent in the hyperkyphosis group (10.6% vs. 2.5%; P = 0.025). The event-free rate of clinical efficacy, which was a composite of death, stroke, and hospitalization for procedure- or valve-related causes, was lower in the hyperkyphosis group (Log-rank test, P = 0.001). Multivariate Cox regression analysis revealed that hyperkyphosis was an independent determinant of lower clinical efficacy (hazard ratio 2.24, 95% confidence interval 1.05-4.77; P = 0.037). Conclusions: Hyperkyphosis, present in approximately 20% of patients undergoing trans-femoral TAVR, is associated with more perioperative vascular complications and poor clinical outcomes.
Abstract 15621: Pelvic Vein Compression in Patients Diagnosed With Postural Orthostatic Tachycardia Syndrome
Authors: Mariana Garcia, Zakaria Almuwaqqat, Rebecca Steinberg, Catherine McGeoch, Kristina Bortfeld, Siya Thadani, Charles Gilliland, Alexis Cutchins
Journal: Circulation (2023)

Introduction: Postural Orthostatic Tachycardia Syndrome (POTS) is a condition characterized by chronic orthostatic intolerance and a significant increase in heart rate. Patients with POTS often exhibit symptoms suggestive of pelvic venous congestion. While venography is the standard method for diagnosing venous compression disorders in the abdomen and pelvis, its potential use in identifying undiagnosed venous abnormalities and its relationship in POTS patients has not been studied. Research Question: This study aimed to investigate the findings of antegrade venography and intravascular ultrasound in patients diagnosed with POTS with high suspicion of May-Thurner Syndrome (MTS) and/or pelvic congestion syndrome, based on initial diagnostic tools such as ultrasound, and who exhibited symptoms of pelvic venous insufficiency (PVI). Methods: Patients clinically diagnosed with POTS underwent antegrade venography and intravascular ultrasound due to a high suspicion of PVI. Demographic, clinical presentation, and venography findings were extracted from the electronic medical records of patients referred to Emory University for POTS/dysautonomia/long COVID evaluation. Patients were diagnosed with MTS if they demonstrated stenosis of the left common iliac vein of 50-70% with associated symptoms like pelvic pain and lower extremity swelling. Results: We identified 28 patients with POTS who had symptoms of PVI. The mean age was 31.6 years (range 18-54), and 96% were female. Doppler ultrasonography revealed venous reflux in the common femoral vein in 82% of the patients. All participants met the criteria for MTS and were referred for stenting. Additionally, 21% of those evaluated had significant bilateral iliac vein compression. Conclusions: This is the largest cohort of POTS patients with pelvic venous compression to date, and our findings suggest a potential association between venous disease and the pathophysiology of POTS. Further research is needed to establish a causal link and explore the clinical implications of venography findings after intervention with angioplasty and stenting. Understanding the venous component in POTS may aid clinicians in the earlier diagnosis and management of PVI.
Abstract 16825: Brahma Related Gene-1 (BRG1) Protein Mediates Helpful Compensatory Response to Retard Development of Heart Failure
Authors: Patrick S DeSpain, Jacob D Kuempel, Yu Xi, Ashley N Kidwell, Tianru Zhang, Reed A Rivera, Xiuren Zhang, Xu Peng, Carl W Tong
Journal: Circulation (2023)

Background: Chromatin remodeling can modulate transcription by changing gene accessibility. Brahma Related Gene-1 (Brg1) protein, which is an adenosine triphosphate catalytic subunit that supports chromatin remodeling, has been implicated in development of hypertrophic cardiomyopathy. However, contribution of Brg1 to the development of heart failure (HF) has not been clearly elucidated. Hypothesis: We hypothesize that Brg1 mediates compensatory response to cardiac stress; therefore, loss of Brg1 function will accelerate development of HF. Methods: The myosin light chain-2 Cre/loxP system was used to produce cardiac myocyte specific deletion of Brg1(-/-) mouse model with floxed littermates as control. Results: At baseline, Brg1(-/-) hearts showed mildly reduced left ventricular ejection fraction (LVEF). Aging to 12 months caused LV dilation and further reduction of LVEF in Brg1(-/-). We used trans-aortic constriction (TAC) for pressure overload challenge and chose similarly severe TAC induced pressure gradient as indicated by similarly fast peak flow velocities across the constriction. At 2-weeks post-TAC, Brg1(-/-) hearts exhibited severely reduced LVEF, severely dilated LV, and decreased ability to thicken LV wall during systole. In contrast, control hearts did not dilate and maintained its LVEF with increased LV wall thickness. Thus, Brg1 deletion greatly diminished the heart’s ability to compensate for aging and pressure challenge, thereby accelerating development of heart failure with reduced ejection fraction (HFrEF). Separately, RNA sequence analyses of 12-months aged hearts showed Brg1 deletion caused upregulation of 810 genes including HF associated long noncoding RNA XIST and down regulation of 50 genes, while 3-months old hearts were not significantly different. Conclusion: Brg1 mediates compensatory responses that are helpful to the heart to prevent development of HF; therefore, it is a potential treatment mechanism for HF.
Abstract 15639: An Explainable Machine Learning-Based Phenomapping Strategy for Adaptive Predictive Enrichment in Randomized Controlled Trials of Preventive Interventions
Authors: Evangelos K Oikonomou, Phyllis M Thangaraj, Deepak L Bhatt, Joseph S Ross, Lawrence H Young, Harlan M Krumholz, Marc A Suchard, Rohan Khera
Journal: Circulation (2023)

Introduction: Randomized controlled trials (RCT) are the cornerstone of evidence-based preventive cardiovascular care but are resource intensive. We propose a novel machine learning (ML) strategy of adaptive predictive enrichment through computational trial phenomaps to optimize RCT efficiency. Methods: In simulated group sequential analyses of two cardiovascular outcomes RCTs of (1) a drug (pioglitazone vs placebo; IRIS), and (2) a management strategy (intensive vs standard blood pressure reduction; SPRINT), we constructed dynamic phenomaps to infer patient profiles benefiting from the intervention vs control during interim analyses. We examined their ability to adaptively enrich subsequent trial enrollment. We compared the final study size and effect estimates between the adaptive and original study designs. Results: Across 3 interim analyses, our strategy learned dynamic signatures of individualized benefit. By conditioning prospective participant enrollment on dynamic estimates of personalized benefit, our approach enabled a robust reduction in the trial size across simulations (-18% ± 4.7% in IRIS, p=0.008 [ A ] and -27.4% ± 3.4% in SPRINT, p=0.002 [ B ]), also preserving the original average treatment effect (IRIS: hazard ratio of 0.71 ± 0.01 for pioglitazone vs placebo; vs 0.76 in the original trial [ C ]; SPRINT: hazard ratio of 0.72 ± 0.01 for intensive vs standard systolic blood pressure; vs 0.75 in the original trial; all p&lt;0.01 [ D ]). Hierarchical assessment of safety endpoints revealed no safety concerns with adaptive enrichment, whereas post-hoc review of the enriched populations confirmed that no specific demographic groups were excluded from the analysis. Conclusions: We present an explainable ML algorithm for adaptive predictive enrichment in RCTs leveraging phenome-wide computational measures of personalized benefit. These findings propose a new paradigm to maximize clinical trial efficiency through dynamic data-driven inference.
Abstract 365: Prehospital Electrocardiogram Integrated With Computer-Assisted Interpretation Shortens Door-to-Balloon Time in Acute ST-Elevation Myocardial Infarction
Authors: Wei-Tien Chang, ZHI-JIA Wu, Bin-Chou Lee, Ying-Ju Chen, Ming-Chi Tsai, Chien-Kai Chiu, Yu-Chun Chien, Ming-Ju Hsieh, Wen-Chu Chiang, CHIEN-HUA HUANG, Wen-Jone Chen, Matthew Huei-Ming Ma
Journal: Circulation (2023)

Introduction: Prehospital electrocardiogram (ECG) has been shown to expedite reperfusion therapy and reduce mortality in acute ST-elevation myocardial infarction (STEMI). The most challenge part for prehospital ECG is timely accurate interpretation and early activation for primary coronary intervention (PCI). In this study we aimed at constructing a prehospital ECG platform integrated with computer-assisted interpretation for strategic PCI activation in an Urban EMS system, and evaluating its efficacy and impact on door-to-balloon time in patients with STEMI. Methods: A prehospital ECG platform with computer-assisted interpretation and wireless transmission was constructed in 2018 in Taipei, together with EMT training for strategic triage of possible STEMI patients to primary PCI capable hospital. The primary outcomes were door-to-balloon time and scene-to-balloon time compared with those without prehospital ECG at the same period. The secondary outcomes were prehospital management time and transportation time. Results: From Feb. 2019 to July 2020, a total of 1670 patients meeting the predesignated criteria received prehospital ECG. Of these, 217 (13.0%) was interpreted as ST elevation out-of-hospital with notification of PCI capable hospital, and 65 (30.0%) was confirmed as STEMI thereafter. The sensitivity of computer-assisted interpretation of STEMI was 96% and specificity was 91%. Compared to the STEMI patients sent by EMS system to the same PCI hospital without prehospital ECG diagnosis and early activation, those with prehospital ECG showed no difference in prehospital management time and transportation time. However, the door-to-balloon-time (58.3 + 10.8 vs. 72.7 + 11.2, P &lt;0.01) and scene-to-balloon time (75.1 + 12.1 vs. 90.5 + 16.1, P &lt;0.05) were both significantly shorter. Conclusion: Prehospital ECG integrated with computer-assisted interpretation enhanced notification of PCI hospital and proper activation of cardiac catheterization team for STEMI patients in an Urban EMS system. Most importantly, it significantly shortens door-to-balloon-time and scene-to-balloon time without lengthening prehospital management and transportation times.
Abstract 18474: Impact of the Endothelial Nucleotidase on Vascular Function
Authors: Kyle J Gordon, Oscar Bermeo-Blanco, Matthew Gorr, Roman Covarrubias, Richard J Gumina
Journal: Circulation (2023)

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity worldwide. Endothelial dysfunction—marked by poor endothelial-derived vasodilation—is a major prelude to atherosclerotic cardiovascular disease. Endothelial cells (EC) play a vital role in modulating thrombosis, atherosclerosis, and blood flow. One tool the endothelium uses to communicate with surrounding tissues is purinergic signaling. EC express both purinergic receptors to respond to stimuli and ectonucleotidases to facilitate this communication. CD39 is believed to be vital in maintaining homeostasis within the vasculature as it is an ectonucleotidase responsible for converting extracellular ATP and ADP into AMP. However, little is known about the role of endothelial expressed CD39 on vascular function. Hypothesis: We hypothesized that the absence of endothelial CD39 causes an elevation in extracellular adenine-nucleotides, thus causing an elevated endothelial-derived vasodilatory response. Methods: We generated a novel cre-lox endothelial cell-specific CD39 knockout mouse model ( Tie2cre+ CD39flox/flox ) to explore the enzyme’s role in vascular physiology. After validation via flow cytometry and enzyme activity assays, we assessed mouse blood pressure along with EC-derived vasodilatory capacity. Coronary vasodilatory capacity or coronary flow reserve (CFR) was measured via an isoflurane-induced-vasodilation coronary flow model and imaged using transthoracic ultrasound. Results: We noted that the EC specific CD39 knockout mice (EC-cKO) exhibited significantly lower systolic, diastolic, and mean arterial blood pressures at baseline, showing the EC-cKO mice having reduced pressures of over 10mmHg compared to wild-type (EC-WT) (p&lt;0.05). This suggested fundamental differences in vascular function, prompting assessment of CFR. The EC-cKO mice showed a 75.9% increase in CFR (p&lt;0.05) compared to wild-type (EC-WT). Conclusions: The loss of CD39 on EC leads to an overall protective phenotype—EC-cKO mice show drastically lower blood pressures, likely due to improved vasodilatory capacity under healthy conditions. This study shows CD39 inhibition’s potential as a therapeutic target in terms of improving vascular function.
Abstract 16054: Comparing the Efficacy and Safety of Endovascular Therapy versus Surgical Revascularization for Critical Limb-Threatening Ischemia: A Systematic Review and Meta-Analysis
Authors: Mohamed R Abouzid, Junaid Anwar, Shorouk Elshafei, Shereen Naccour, Samar Eldahtoury, Chima Nwaukwa
Journal: Circulation (2023)

Introduction: The purpose of this meta-analysis is to examine the current evidence and compare the clinical outcomes of endovascular therapy and surgical revascularization for the treatment of critical limb-threatening ischemia CLTI. Methods: We conducted a systematic search of electronic databases for studies comparing the outcomes of endovascular therapy versus surgery in patients with CLTI. The primary outcomes were major adverse limb events (MALE) and major adverse cardiovascular events (MACE), while secondary outcomes included risk of bleeding, wound complications, readmission, unplanned reoperation, acute renal failure, and length of hospital stay. Results: A total of 14 observational studies (57,494 patients) were included. The overall effect favors surgery over endovascular intervention in terms of MALE [RR 1.13, 95 % CI (1.01-1.28), P = 0.04]. Endovascular therapy is associated with lower MACE rates compared to surgery [RR 0.62, 95 % CI (0.51-0.76), P &lt; 0.00001]. Furthermore, the risk of bleeding, wound complications, readmission, unplanned reoperation, acute renal failure as well as the length of hospital stay were lower with endovascular intervention. Conclusion: Surgery may be preferred for CLTI patients to endovascular therapy as it has reduced MALE risk. Endovascular treatment may reduce the incidence of MACE, bleeding, readmission, unplanned reoperation, acute renal failure, and the length of hospital stay. Novel endovascular techniques may enhance results, particularly for patients with severe illness or limited surgical choices. The treatment decision should be based on several factors like individual patient characteristics and anatomical considerations.
A decade of the Oesophageal Cancer Clinical and Molecular Stratification Consortium
Authors: C. J. Peters, Y. Ang, F. D. Ciccarelli, H. Coles, H. G. Coleman, G. Contino, T. Crosby, G. Devonshire, M. Eldridge, A. Freeman, N. Grehan, M. McCord, B. Nutzinger, S. Zamani, S. L. Parsons, R. Petty, A. D. Sharrocks, R. J. E. Skipworth, E. C. Smyth, I. Soomro, T. J. Underwood, Paul A. W. Edwards, Aisling M. Redmond, Christine Loreno, Sujath Abbas, Maria O’Donovan, Ahmad Miremadi, Shalini Malhotra, Monika Tripathi, Calvin Cheah, Curtis Millington, Maria Secrier, Sriganesh Jammula, Jim Davies, Charles Crichton, Nick Carroll, Richard H. Hardwick, Peter Safranek, Andrew Hindmarsh, Vijayendran Sujendran, Stephen J. Hayes, Shaun R. Preston, Izhar Bagwan, Vicki Save, Ted R. Hupp, J. Robert O’Neill, Olga Tucker, Andrew Beggs, Philippe Taniere, Sonia Puig, Robert C. Walker, Ben L. Grace, Jesper Lagergren, James A. Gossage, Andrew R. Davies, Fuju Chang, Ula Mahadeva, Vicky Goh, Grant Sanders, Richard Berrisford, David Chan, Ed Cheong, Bhaskar Kumar, L. Sreedharan, Philip Kaye, John H. Saunders, Laurence Lovat, Rehan Haidry, Michael Scott, Sharmila Sothi, Suzy Lishman, George B. Hanna, Krishna Moorthy, Anna Grabowska, Richard C. Turkington, Damian McManus, Freddie Bartlett, R. C. Fitzgerald
Journal: Nature Medicine (2023)
Abstract 237: Effect of Hospital Arrival Time on Mortality Rate in Pediatric Patients With Severe Trauma: A Nationwide Database Study in Japan
Authors: Shingo Ohki, Ryu Matsuo, Nishikimi Mitsuaki, Shinichiro Ohshimo, Nobuaki Shime
Journal: Circulation (2023)

Introduction: Previous studies have reported that hospital arrival during nighttime was associated with worse outcomes in critically ill pediatric patients. However, this “nighttime effect” in pediatric patients with severe trauma has not yet been well-investigated. Hypothesis: We hypothesized that hospital arrival during nighttime is associated with higher mortality rates in pediatric patients with severe trauma. Methods: We conducted a nationwide retrospective cohort study in Japan from 2004 to 2019 using the Japan Trauma Data Bank, a nationwide trauma registry. Patients who were aged &lt;18 years and had an Injury Severity Score (ISS) &gt;15 were included. Patients with cardiac arrest on hospital arrival were excluded. Hospital arrival was categorized into daytime (from 8:00 am to 4:59 pm) arrival and nighttime (from 5:00 pm to 7:59 am) arrival. The main outcome was the in-hospital mortality rate, and the secondary outcome was the emergency department (ED) mortality rate. As a main analysis, an inverse probability of treatment weighting (IPTW) analysis was performed using propensity scores to adjust for confounders such as age, sex, type of injury, transport time, vital signs, and ISS. In addition, we conducted 1) a subgroup analysis in patients who underwent operation (OP) or interventional radiology (IR) during hospitalization and 2) sensitivity analysis using a multilevel mixed-effects logistic regression model. Results: In total, 6,574 pediatric patients with severe trauma were included, and the overall in-hospital mortality rate was 6.5%. The IPTW analysis showed that compared with daytime arrivals, nighttime arrivals were associated with significantly higher in-hospital mortality (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.09-1.83; P = 0.010) and ED mortality rates (OR, 2.42; 95% CI, 1.07-5.45; P = 0.034) in the entire cohort but not in the subgroup who underwent OP or IR during hospitalization. The sensitivity analysis consistently supported the results of the main analysis. Conclusions: Hospital arrival during nighttime was associated with a higher in-hospital mortality rate in pediatric patients with severe trauma. Further investigations are needed to elucidate the reasons for this “nighttime effect.”
Abstract 17802: Racial Disparities in the Association of Pre-Pregnancy Cardiometabolic Risk Factors With Adverse Pregnancy Outcomes
Authors: Kevin M Sun, Theresa Boyer, Vennela Avula, Eunjung Choi, Arthur J Vaught, Chiadi E Ndumele, Erin D Michos, Josef Coresh, Michelle Ogunwole, Allison Hays, Anum S Minhas
Journal: Circulation (2023)

Background/Hypothesis: Racial and ethnic disparities and worsened poor pre-pregnancy cardiometabolic health are individually recognized to increase risk for adverse pregnancy outcomes (APOs). However, the interaction of race and ethnicity with pre-pregnancy cardiometabolic factors in relationship with APO risk is less well understood. Aims: To evaluate racial and ethnic disparities in the risk association of cardiometabolic factors with APOs in a national population. Methods: We analyzed Natality Data from the National Vital Statistics System of the National Center for Health Statistics between 2016-2017. We used multivariable logistic regression to estimate adjusted odds of APOs (preterm birth, gestational diabetes, and pregnancy-induced hypertension) with pre-pregnancy cardiometabolic factors: chronic hypertension, obesity, and diabetes, stratified by race and ethnicity. Population attributable fractions (PAFs) were calculated to assess the proportion of APOs attributable to pre-pregnancy cardiometabolic risk factors. Results: Among 7,460,633 births, presence of pre-pregnancy hypertension, obesity and diabetes were differentially associated with APO risk by race and ethnicity (Table 1). Overall, non-Hispanic Black women had the greatest incidence of preterm birth (16.7%), while American Indian/Native women had the greatest incidence of pregnancy-induced hypertension (10.1%) and gestational diabetes (12.6%). Conclusion: There is heterogeneity by race and ethnicity in the association of pre-pregnancy cardiometabolic factors with APOs. Non-Hispanic Black and American Indian/Native women have the overall greatest burden of most APOs, including preterm birth, pregnancy-induced hypertension, and gestational diabetes. Targeted preventive efforts, with consideration of stressors for individual racial and ethnic groups, should be undertaken to improve cardiometabolic health prior to conception to lower risk of APOs.