tbuckley/cabot-search huggingface dataset:
Abstract 4143070: Institutional Demographics and Outcomes of Admitted Patients with Hypertensive Disorders of Pregnancy
Authors: Marly Azzi, Sanela Potchileev, Luke Burns, Ariel Mueller, Sarosh Rana
Journal: Circulation (2024)

Background: Hypertensive disorders of pregnancy (HDP) serve as the second leading cause of maternal mortality globally and represent a threat to pregnancies across our nation. Blood pressure goals and practice patterns continue to vary broadly between and within institutions. An updated analysis of the management and outcomes of HDP is necessary. The aim is to evaluate maternal and neonatal outcomes for patients admitted due to HDP at our institution. Methods: Patients (≥18 years of age) 23 +0 to 34 +6 weeks’ gestation who were hospitalized at the University of Chicago with a HDP associated condition between January 1 st , 2022, and January 31 st , 2024 were included in this cohort study. Demographics, maternal/neonatal events, and the correlation between interventions received during pregnancy and HDP outcomes were assessed. Results: Our study included 140 patients with HDP, of which 46 (32.9%) had preeclampsia (preE) with severe features (SF), 13 (9.3%) had preE without SF, 10 (7.1%) had gestational HTN, and 26 (18.6%) had cHTN. Our cohort was predominantly African American (n = 86; 61.4%) with median age 31 years (IQR 26, 35). Among patients with a preterm delivery (80.4%), the most common indication for delivery was persistent severe hypertension (81.1%). Modest correlations were observed between birthweight percentile and both systolic BP (Spearman r = -0.189 [95% CI: -0.368, 0.004]; p = 0.06) and diastolic BP (r = -0.197, [95% CI: -0.373, -0.002]; p = 0.047), with BP decreasing as the percentile increased. Figure 1 outlines the latency between admission date and delivery. Patients on an antihypertensive medication at the time of postpartum discharge were less likely to be readmitted within six weeks (9.0% vs 22.0%; p = 0.03) due to BP control as compared to patients who were not on medication. Conclusion: This study demonstrates that severe HTN feature of HDP is most associated with neonatal adverse outcomes and maternal postpartum readmissions. Patients with HDP can benefit from an improved stratification tool during antepartum and at discharge to identify patients at higher risk of neonatal/maternal adverse outcomes.
Abstract 4143098: Development and characterization of an ex vivo human precision-cut lung slice (hPCLS) system for target validation for pulmonary arterial hypertension
Authors: Haejin Kim, Dhawal Jain, Muzaffar Akram, Willa Zhou, Steeve Provencher, Sarah-Eve Lemay, Sebastien Bonnet, Francois Potus, Monica Montesinos, Min Lu, Bryan Goodwin
Journal: Circulation (2024)

Background: Translating therapeutic target biology from in vitro culture systems and animal models to humans remains a significant challenge in drug discovery. Recently, human precision-cut lung slices (hPCLS) have emerged as an innovative ex vivo model to better understand the pathophysiology of pulmonary disease. Given the difficulty in acquiring lung tissue from patients with pulmonary arterial hypertension (PAH), we aimed to develop a hPCLS culture system from healthy donors that replicates the PAH phenotype. Methods: Cryopreserved hPCLS from several healthy donors were obtained from AnaBios. Viability of the hPCLS was assessed using the lactate dehydrogenase (LDH) assay on cultured media. The hPCLS were cultured for seven days with growth factor (GF) cocktails containing various combinations of EGF, FGF, endothelin-1 (ET-1), PDGF-β, activin A, and TGF-β for 7 days to induce PAH-like phenotypes. The stimulated hPCLS were analyzed using RNA sequencing (RNA-seq). Histological analysis assessed pulmonary arterial (PA) medial wall thickness. RNA-seq data from human lungs with and without PAH served as a reference. Gene expression patterns were compared across key disease-associated pathways and processes. The effects of α5β1 integrin inhibition were investigated using the antibody M200 in the PAH-like hPCLS system. Results: LDH activity remained low across all treatment groups over the seven-day period, indicating no tissue toxicity. Histological analysis with H&amp;E and EVG staining showed increased medial wall thickness and elastin deposition in pulmonary arteries stimulated by GFs. RNA-seq analyses revealed gene expression changes in response to several GFs that were consistent with the reference PAH dataset. Key gene sets related to extracellular matrix formation, integrin signaling, proliferation, senescence, and growth factor signaling showed similarities between several GFs and human PAH. Moreover, treatment with the α5β1 antibody, M200, in GF-stimulated hPCLS demonstrated modulation of PAH-like phenotypes. Conclusions: We successfully established a novel ex vivo model using hPCLS from healthy donors that mimics PAH characteristics when stimulated by GFs (ET-1, FGF, PDGF-β, and EGF). This model also demonstrated that α5β1 inhibition reduced PAH-like phenotypes. This hPCLS model, in conjunction with tissue from PAH patients, could be a valuable tool for evaluating new therapies, enhancing the translation from preclinical studies to human applications.
Abstract 4143073: Comparative Clinical Outcomes Following Transcatheter Mitral Valve repair in Patients with a History of Adverse Pregnancy Outcomes Versus Those Without: A National Inpatient Sample Analysis
Authors: Toluwalase Awoyemi, Chinenye Odo, Kayode Ogunniyi, Ikeoluwapo Bolakale-Rufai, Oluwaremilekun Tolu-Akinnawo, Edwin Gwira-Tamattey, Samira Teeri, Habib Alagbo, Emmanuel Daniel, Ugochukwu Ebubechukwu, Ikenna Odoh, Cedrick Mutebi
Journal: Circulation (2024)

Background: Adverse pregnancy outcomes (APO) pose long-term cardiovascular risks. Considering the potential impact of APO on maternal health, this study aims to investigate the characteristics and clinical outcomes of women who have experienced APO and subsequently undergo transcatheter mitral valve repair (TMVr). Methods: This is a retrospective cohort study that analyzed data from 15,220 women who underwent transcatheter mitral valve repair (TMVr) and it was divided into two groups: history of adverse pregnancy outcome (APO, n=3240) and without a history of APO (No APO, n=11,980). Comparative analyses between the APO and No APO groups were performed using t-tests for continuous variables and chi-square tests for categorical variables. Multivariate logistic regression models were employed to adjust for potential confounders and identify independent predictors of in-hospital mortality and other adverse outcomes. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for each variable. Results: Patients with a history of adverse pregnancy outcomes (APOs) were younger (mean age 73.3 vs. 79.0 years, p&lt;0.001) and more frequently identified as Black/African American (20.9% vs. 8.0%, p&lt;0.001). They had a higher mean Charlson Comorbidity Index (3.2 vs. 2.8, p&lt;0.001). After adjustment, these patients were more likely to require mechanical ventilation (OR 0.76, 95% CI 0.61-0.94, p=0.0112) and vasopressors (OR 1.37, 95% CI 1.05-1.79, p=0.0205), experience heart block (OR 2.29, 95% CI 2.00-2.63, p&lt;0.001), and develop acute kidney injury (OR 1.26, 95% CI 1.12-1.42, p=0.0001). However, the adjusted odds of in-hospital mortality did not differ significantly between the groups (OR 0.99, 95% CI 0.73-1.32, p=0.9355). Conclusions: Women with a history of adverse pregnancy outcomes (APOs) undergoing TMVr face higher risks of complications, such as heart block and acute kidney injury, highlighting the importance of incorporating pregnancy history into cardiovascular risk assessment and management for these patients.
Abstract 4143092: Impact of Lifelong Exercise on Left Ventricular Wall Stress
Authors: Lexis Will, Benjamin Levine, Satyam Sarma
Journal: Circulation (2024)

Background: Very high level, lifelong aerobic exercise results in lower ventricular stiffness and left ventricular wall stress (LVWS) LVWS is an important predictor of future heart failure risk. To what degree LVWS changes with various doses of lifelong aerobic exercise is unknown. Objective: The purpose of this study was to determine the impact of lifelong exercise on LVWS. Methods: Seniors (n = 58) who consistently participated in lifelong patterns of exercise training were recruited and categorized into 3 groups: “sedentary” (&lt;1 exercise sessions/week); “moderate” (2 to 3 sessions/week); and “active” (4 to 7 sessions/week). Right heart catheterization and echocardiography were performed at baseline (x 2; once before lower body negative pressure (LBNP) and again before saline infusion) and while manipulating preload using LBNP (-15 mmHg suction) and rapid normal saline (NS) infusion (15 mL NS/kg). LVWS was calculated from pulmonary capillary wedge pressure (PCWP) and LV wall thickness and radius using Law of Laplace and expressed in Pascals (Pa). Strain was calculated using (V−Vmin)/Vmin, where Vmin was the smallest end-diastolic volume measured (during LBNP) and V was the volume during each condition. Results: LVWS increased as preload increased. As shown in the figure, peak LVWS during saline load (top panel: sedentary 3.1 +/- 1.1 Pa, moderate 2.5 +/- 0.7 Pa, active 2.3 +/- 0.5 Pa) and stress-strain slopes (sedentary 12.3 +/- 10.3, moderate 6.5 +/-4.1, active 5.7 +/- 2.7 Pa) were highest in sedentary seniors compared to seniors in the moderate (p=0.008) and active groups (p=0.006). Conclusions: In healthy, older individuals, lower LVWS was apparent even with lifelong, moderate levels of physical activity (2 to 3 sessions/week) and similar to those who exercised at more frequent levels (4-7 times per week). Exercising 2 to 3 times a week may provide a sufficient “dose” to reduce LVWS, highlighting the benefits of even casual training on ventricular structure and potential to mitigate the lifetime risk of heart failure with exercise.
Abstract 4142090: Venous Access Alone <i>vs.</i> Arterial and Venous Access for Patent Arterial Duct Device Closure in Childhood
Authors: Ahmed Hassan, Rajiv Chaturvedi, Lee Benson
Journal: Circulation (2024)

Background: The persistently patent arterial duct accounts for ~12% of congenital heart lesions. Untreated, it may result in heart failure due to volume loading of the left heart, pulmonary hypertension, and infective endarteritis. Percutaneous device closure is the preferred occlusion technique, with the standard approach consisting of femoral artery access for angiography and venous access for device delivery (AA). A venous-only strategy (VA) for angiography and device delivery can also be employed. Hypothesis: We hypothesized that VA would eliminate arterial complications, and reduce procedure times and radiation exposure compared to standard AA. Methods: This retrospective cohort study reviewed isolated arterial duct device closures at the Hospital for Sick Children from January 1, 2011 through December 31, 2022. Exclusions included premature neonates, children requiring arterial access for monitoring and those who underwent other procedures. Children were categorized based upon initial access determined by operator preference, into VA or AA groups. Results: The cohort consisted of 405 children, 252 (62.2%) females, with a median age of 3.1 years (IQR1.30–5.84), median weight 13.2kg (IQR 9.0–19.5), and duct diameter of 2.9mm (IQR 2.0–3.5) with no significant differences between the groups. Type A ducts were more frequent in the AA group (90% vs. 72%). The VA group included 106 children, of which 14 (13.2%) required AA conversion for angiography due to complex anatomy, to assess device positon prior to release, but remained in the VA group for analysis. Children in the VA group had lower dose area product (DAP) (p&lt;0.001), fluoroscopy times (p=0.025), contrast volumes (p&lt;0.001), procedure times (p&lt;0.001), and recovery room lengths of stay (LOS) (p&lt;0.001). Six (5.7%) VA children required admission compared to 44 (14.7%) in the AA group (p=0.015) with no difference in reintervention rates. Weighted regression analysis showed VA was associated with reduced admission likelihood (OR: 0.354 [0.131,0.822], p=0.024), DAP (coef -126.4 [-213.3,-39.4], p=0.004) and contrast volumes (coef 31.2 [-36.6,-25.9], p&lt;0.001) compared to AA. Conclusions: Venous only access was associated with lower DAP and recovery room LOS. Additionally, VA was associated with a lower likelihood of admission with no difference in reintervention rates, suggesting procedural safety. These findings support the consideration of VA as a preferred approach for appropriate cases.
Abstract 4143074: Left Atrial Stiffness in Patients with Cryptogenic Ischemic Stroke
Authors: Jorge Eduardo Hernandez del Rio, Tomas Miranda - Aquino, Christian Gonzalez-Padilla, Oscar Lomeli Sanchez, Daniel Ochoa Castillo, Daniela Alejandra Alonso Diaz, Natalia Gloria Valencia
Journal: Circulation (2024)

Introduction: Atrial fibrillation (AF) is a risk factor for the development of ischemic stroke. Left atrial (LA) function has been described as a predictor of AF, however, atrial stiffness has been little studied. Objectives: To determine if there is a difference in left atrial stiffness between patients with ischemic stroke who presented AF and those who did not, the association of stiffness with AF and the stiffness cut-off points. Methods: An analytical, cross-sectional, single-center study was conducted. Patients older than 18 years with a diagnosis of cryptogenic ischemic stroke who were in sinus rhythm, had no history of atrial fibrillation and underwent an echocardiogram and a 24-hour rhythm Holter during hospitalization were included in the study. The echocardiograms were performed using a Siemens ACUSON SC 2000 machine with a 2.5 MHz sectorial 4v1c transducer. The reservoir LA strain (LASr) was determined using the VVI technique. The left atrial stiffness was obtained through the ratio E/e’ between the LASr. Variables were analyzed using chi-square or Student's t-test. ROC curves were used to determine the cutoff points for predicting AF. The association of variables with the development of AF was analyzed using logistic regression. Results: A total of 96 patients were obtained, of which 35 had documented AF, 16 women and 19 men. Two groups were formed, Group 1: patients with ischemic stroke and AF (35), Group 2: with ischemic stroke without AF (61), which were used as control (Table 1). Among patients with AF, we found they were older and had a higher prevalence of diabetes mellitus, higher E/e' value, LA indexed volume, and greater LA stiffness as well as lower LASr values. LA stiffness (&gt;0.29) and LASr (&lt;36%) were the best predictors of AF in the ROC curves (Image 1) . The association with the development of AF found that LA stiffness was significant in both univariate and multivariate analyses (Table 2). Conclusion: The stiffness of the left atrium is an easy-to-determine echocardiographic parameter that allows us to predict the presence of atrial fibrillation in patients with an ischemic cerebrovascular event who should have a greater intentional search for atrial fibrillation.
Abstract 4143064: Dynamic expression poly(A) binding protein N1 coordinate cardiac growth during development and disease.
Authors: Sandip Chorghade, Joe Seimetz, Subhashis Natua, Bo Zhang, Chaitali Misra, Xander Wehrens, Jiwang Chen, Auinash Kalsotra
Journal: Circulation (2024)

The nuclear poly(A) binding protein (PABPN1) is a ubiquitously expressed, evolutionarily conserved protein that actively involved in 3’-poly(A) tail elongation and alternative polyadenylation (ApA). Here we report that PABPN1 protein expression is post-transcriptionally silenced during postnatal heart development especially in cardiomyocytes but re-expressed during heart failure. Combining single-molecule RNA imaging and nucleo-cytoplasmic fractionations, we demonstrate that PABPN1 silencing in healthy cardiomyocytes occurs through a drastic shift in its mRNA localization: the mRNA is cytoplasmic in neonatal cardiomyocytes but remain incompletely spliced, nuclear speckle-detained, and thus translation-inaccessible in adult cardiomyocytes. Surprisingly during cardiac disease, the stored Pabpn1 mRNA undergoes splicing and transported to cytoplasm for translation. Importantly, cardiomyocyte-specific conditional loss- and gain-of-function studies revealed that persistent expression of PABPN1 in the mouse myocardium provokes major structural and functional abnormalities, resulting in heart failure and death. Using nanopore-based direct RNA and high-resolution illumina sequencing, we identified widespread changes in ApA and poly(A) tail lengths of cardiac transcripts during disease contributing significantly to their expression. Taken together, these results indicate that developmental silencing of PABPN1 through its regulated mRNA splicing and localization is critical for function of the heart while its persistence expression is essential for cardiomyopathy progression.
Abstract 4143155: Sex-Specific Coronary Plaque Characteristics and Risk of Cardiovascular Events: Insights from the ISCHEMIA Trial
Authors: Suvasini Lakshmanan, Yixin Wang, Ying Chen, G B John Mancini, Jonathon Leipsic, Matthew Budoff, Cameron Hague, James Min, Gregg Stone, William Boden, John Spertus, Sripal Bangalore, Judith Hochman, Harmony Reynolds, David Maron
Journal: Circulation (2024)

Background: Artificial-intelligence-enabled analysis of atherosclerotic plaque characteristics on coronary computed tomography angiography (CCTA) may improve sex-specific risk prediction of cardiovascular (CV) events. Aims: The aim of this study was to examine sex differences in CCTA-derived atherosclerotic plaque analysis in ISCHEMIA participants, and to identify any interaction between sex and the prognostic value of quantitative atherosclerosis parameters in predicting CV events. Methods: In a post-hoc analysis, atherosclerosis imaging quantitative CT (QCT) was performed on all available CCTA scans. Interaction analysis was performed to understand the impact of female sex on the relationship between QCT variables and the outcomes of CV death or myocardial infarction (MI), all-cause death, and MI alone over a median follow-up of 3.3 years. Results: Of the 3645 participants with CCTA available for analysis, mean age was 64 and 21% were female. Females had lower total, calcified, non-calcified, and low-density non-calcified plaque volume than males (p&lt;0.001 for all, Table). Percent atheroma volume (PAV=total plaque volume /vessel volume x 100%) was associated with CV death or MI in all participants, and the association was stronger in females (univariate HR: 2.37, 95% confidence interval (CI) 1.79, 3.14, p&lt;0.001) than men (HR: 1.70, 95% CI 1.45, 2.00, p&lt;0.001). There was a significant interaction showing accentuated risk of CV death or MI associated with greater PAV among females vs. males (HR for female*PAV: 1.42, 95% CI 1.03, 1.95, p=0.032, Figure), mainly driven by risk for MI. Conclusions: In ISCHEMIA, females presenting with moderate or severe ischemia and obstructive CAD had less atherosclerotic plaque burden of all subtypes and less adverse plaque characteristics identified by CCTA than men. The risk associated with greater atherosclerotic burden (PAV) was higher among female participants than males for the composite outcome of CV death or MI.
Abstract 4142010: The Evolving Risk of Infective Endocarditis after Transcatheter Aortic Valve Replacement
Authors: Sundos Alabbadi, Josep Rodes-Cabau, Annetine Gelijns, Alan Moskowitz, Torsten Doenst, Jo Chikwe, Nana Toyoda, Shinobu Itagaki, Prof. Dr. med. Markus Krane, Raj Makkar, Emilia Bagiella, Enoch Akowuah, Ranjit Deshpande, Sabine Bleiziffer, Wiphada Bandettini, Shahab Akhter, Patrick OGara, Alexander Iribarne, Natalia Egorova
Journal: Circulation (2024)

Introduction Prosthetic valve endocarditis is a rare complication of aortic valve intervention, associated with high mortality and morbidity. There has been widespread growth in transcatheter aortic valve replacement (TAVR) use over the past decade including expansion to lower-risk and younger patients. Data on trends in incidence and outcomes of infective endocarditis (IE) after TAVR are sparse. Research Question With TAVR expansion, have there been any changes in the incidence of IE and 30-day surgical intervention and mortality, 2013-2022? Methods: Using Medicare data, we analyzed 280,073 TAVR patients. Joinpoint regression was used to evaluate IE incidence, reported as annual percent change (APC). Adjusted Cox models were used to evaluate associations between IE incidence and procedure year, patient characteristics, and 30-day outcomes. Results: IE incidence after TAVR decreased from 13.9/1000 person-years in 2013 to 10.6/1000 p-y in 2017 (APC=-7.7% [CI -12.2- -4.5%],p=0.01) and then was unchanged through 2022 (APC=0.9% [-0.3- 3.1%],p=0.23). Figure 1 depicts risk factors associated with post-TAVR IE. The reduction in non-elective procedures was associated with declining IE rates (p&lt;0.001). After developing IE post TAVR, the 30-day risk-adjusted surgical intervention rate was 3.6% [3.1-4.1%]. In more recent years, patients were more likely to undergo such intervention within 30 days of IE diagnosis (sub-distribution HR (sHR):1.20 [1.12-1.29],p&lt;0.001). Older IE patients (sHR:0.61[0.55-0.67],p&lt;0.001), those on dialysis (sHR:0.48 [0.27-0.86],p=0.01) and those with permanent pacemakers (sHR:0.56 [0.34-0.93],p=0.03) were less likely to undergo intervention. The 30-day mortality risk of patient experiencing IE was 17.6% [16.8-18.5%] and remained similar across years. Conclusion: In Medicare patients, the adjusted risk of IE after TAVR declined over time, which may relate to increasing experience with TAVR, procedural technique, and declining rates of non-elective interventions. Patients with IE were more likely to undergo surgical intervention over time, especially younger and lower surgical risk patients. Mortality rates remained high and did not change, emphasizing the need for more research on management practices.