tbuckley/cabot-search huggingface dataset:
Abstract 15699: A Wolf in Sheep’s Clothing- CD13 Activation Mediates Pericyte to Smooth Muscle Cell Switch in Pulmonary Hypertension
Authors: Joel James, Aleksandr Dekan, Mathews Valuparampil Varghes, Maki Niihori, Odunayo Lawal, DINESH BHARTI, Olga Rafikova, Ruslan Rafikov
Journal: Circulation (2023)

Introduction: Pulmonary hypertension (PH) is a fatal disease lacking effective treatment strategies to prevent its progression or reverse its effects. PH is characterized by vascular remodeling caused by excessive cell proliferation in the vascular layers. Often, pulmonary artery smooth muscle cells (PASMC) are implicated in the proliferative remodeling of the artery. We recently discovered that in PH, PASMC’s highly expressed a pericyte marker, CD13. Previous studies have shown CD13 pathology in cancer. We hypothesized that increased CD13 expression and activation could mediate a phenotype switch from pericytes to proliferative “PASMC like” cells. Methods: In this study, we used rats with a mutation in NFU1G206C, which spontaneously develop PH with severe vascular remodeling. We also used isolated PASMC from PH patients. We used whole lung single cell transcriptomics to uncover the phenotypes of various lung cells. Results: Pericytes of NFU1 rats showed a significant increase in CD13. Additionally, we found a 40-fold increase of CD13 in NFU1 PASMC. scRNA transcriptomics revealed a high similarity of PASMCs with pericytes in the NFU1 rats. Conversely, we also observed that pericytes of NFU1 rats highly expressed canonical SMC markers like SMMHC and CNN3. CellChat analysis revealed pericyte dysfunction with decreased interaction strength and interaction numbers with endothelial cells (ECs). Correspondingly, confocal imaging revealed a severe decrease in pericyte-EC association and a greater coverage area by pericytes in the NFU1 lungs. Treatment of NFU1 rats with a peptide blocking CD13 signaling (B-CD13) significantly attenuated right ventricular systolic pressure, Fulton index and vascular remodeling. Excitingly, treating isolated PASMC from PH patients and NFU1 rats with B-CD13 reverted the high proliferation rates back to control, indicating the pathological role of CD13 in cell proliferation. scRNA analysis of rat lungs treated with B-CD13 showed improvement in pericyte- EC interaction numbers and interaction strength, indicating that CD13 could play an important role in the migratory and proliferative switch of pericytes. Conclusion: Targeting CD13 signaling is a novel strategy to potentially reverse vascular remodeling in PH.
Abstract 18147: Diagnosing Brugada Syndrome in Absence of Electrocardiographic Pattern: Predictive Modeling of Activation Delay in the Right Ventricular Outflow Tract
Authors: Cinzia Monaco, Domenico Della Rocca, Luigi Pannone, Alvise Del Monte, Carlo de Asmundis
Journal: Circulation (2023)

Introduction: Diagnosing Brugada Syndrome(BrS)involves detecting the type1 ECG pattern, spontaneously or drug-induced, which can be challenging(concomitant diseases, ECG phenocopies, unavailability of pharmacological agents, hypersensitivity). Intrinsic cellular changes that cause ECG abnormalities are mainly located in the right ventricular outflow tract(RVOT). Hypothesis: Comparing the activation time(AT)delay between the RVOT and the anterior right ventricle(RVa)in subjects with BrS(with concealed or manifested pattern 1) vs normal controls may provide a cut-off value for a new diagnostic method. Methods: Seventy-five participants(mean age 46±24 y; 45 men), 57 BrS, 10 healthy controls, and 8 RBBB patients, underwent ECGI and ECG recordings. Concealed BrS patients underwent an ajmaline infusion to be studied both in the absence and presence of pattern1. Ventricular epicardium has been divided into 8regions and the mean activation time(ATM)has been calculated for each region. The ATMs were normalized to QRS length (ATM%) and compared across populations. Results: Analysis of ATMs% in RVa did not show differences between groups. Instead, analysis of ATM and ATM% in RVOT, showed significant differences between controls and BrS both with concealed or manifested ECG pattern1 (37.2±6.23vs68.33±14.73 ms, p&lt;0.001; 37.2±6.23vs107.6±21.16 ms, p&lt;0.001). By setting the true negative (controls) and true positive (BrS) populations, the diagnostic performance tests were done: a 45% increase in RVa ATM was the best predictor of delayed RVOT activation in BrS (AUC=0.97,Accuracy=0.92,F-score=0.95). In patients with RBBB the increase between RVa and RVOT remained below the cut-off of 45% Conclusions: In BrS, patients exhibit a pathological delay in the AT of the RVOT, considered significant if it exceeds 45% of the ATM in the RVa. It could be used as alternative diagnostic method when the conventional approach is inconclusive or the ECG pattern is not manifested.
Abstract 17599: Sotatercept for the Treatment of Pulmonary Arterial Hypertension: A Systematic Review and Single-Arm Meta-Analysis
Authors: Nicole Felix, Larissa Teixeira, Luiz Campedelli, Alleh Nogueira, Amanda Godoi, Alice Deberaldini Marinho, Beatriz Deberaldini Marinho, Victor Perim C N, Thomaz A Costa, Michael G Risbano
Journal: Circulation (2023)

Introduction: Pulmonary arterial hypertension (PAH) is associated with progressive clinical worsening and a 50% 5-year survival rate with current PAH therapies. Sotatercept is a first-in-class fusion protein with promising results in preclinical trials, but clinical evidence on its role in treating PAH remains limited. Hypothesis: Sotatercept may provide clinical benefits for patients with symptomatic PAH. Aims: To assess the efficacy of sotatercept in addition to background PAH therapy in this population. Methods: We searched PubMed, Embase, Cochrane and Clinicaltrials.gov in April 2023 for clinical trials assessing efficacy outcomes of sotatercept in patients with PAH. Using a random-effects model, we performed a single-arm meta-analysis of proportions for binary outcomes and applied generic inverse variance weighting formulas to pool arithmetic means and least squares means for continuous outcomes. Statistical analyses were performed using Review Manager 5.4.1 and R software 4.2.2. Results: We included three clinical trials comprising 254 patients with WHO functional class II or III PAH. At 24 weeks, only 2% of patients on sotatercept experienced symptoms of clinical worsening (95% CI 1 to 5; Fig. 1A). Sotatercept was also associated with a reduction in pulmonary vascular resistance (mean change from baseline -199.92 dyn·sec·cm -5 ; 95% CI -256.83 to -143.0; Fig. 1B), while improving 6-minute walk distance (mean change from baseline 45.86 m; 95% CI 28.54 to 63.18; Fig. 1C). Conclusions: These findings suggest that sotatercept may improve exercise capacity while decelerating clinical worsening and attenuating pulmonary vascular resistance in patients with mild to moderate PAH.
Abstract 15510: Generation of the Cardiac Valve Lineage From Human Pluripotent Stem Cells
Authors: Amine Mazine, Alexander Mikryukov, Ian Fernandes, Clifford Liu, Soheil Jahangiri, Marcy Martin, Eric K Gähwiler, Juliana Gomez, Neda Latifi, Michael A Laflamme, Craig A Simmons, Simon P Hoerstrup, Maximilian Y Emmert, Bruce D Gelb, Mingxia Gu, Gordon M Keller
Journal: Circulation (2023)

Background: Heart valves are living structures whose sophisticated functions are mediated by a specialized population of valvular interstitial cells (VICs). Given their central role in valve homeostasis, VICs represent a promising cell population for studying valve diseases and developing novel therapies to treat them. Herein, we describe the generation of VIC-like cells from human pluripotent stem cells (hPSCs). Methods and Results: Using a previously established protocol, we first generated endocardial cells from cardiovascular mesoderm. Within this endocardial population, we identified a subset of cells — marked by the expression of PDGFRβ — that express valvular endocardial cell (VEC) markers and demonstrate VEC-like functional properties, namely the ability to generate calcium transients in response to ATP and the ability to undergo endothelial-to-mesenchymal transition (EndoMT). Through stage-specific manipulation of developmental signaling pathways, we established a protocol that promotes the development of VIC-like cells from these hPSC-derived VEC progenitors (Figure 1A). The cells thus generated transcriptionally matched primary human fetal VICs by scRNAseq. When embedded in a tissue-engineered scaffold, hPSC-VICs secreted collagen and glycosaminoglycans, and demonstrated compact tissue organization analogous to that of native valve leaflets (Figure 1B, C). Finally, we show that VICs generated from an hPSC line with a Noonan syndrome mutation displayed excessive endocardial cell proliferation, diminished EndoMT, and dysregulated pERK activity, recapitulating key aspects of the disease. Conclusions: Together, the findings presented in this report provide a reproducible method for the scaled generation of bona fide VICs from hPSCs. The generation of hPSC-VICs addresses an important gap in the field and provides a platform to study valvulogenesis and heart valve disease, as well as a novel avenue for heart valve tissue engineering.
Abstract 16604: Systemic Lupus Erythematosus and Pregnancy: An Analytical Review of Cardiovascular Disease and Obstetric Complications
Authors: Bilal Hussain, Ahmed M Mahmood, Luay Alalawi, christel cuevas, Sohail Khan, Fahad Waqar, Thomas Alexander, Mohammad M Ansari
Journal: Circulation (2023)

Background Cardiovascular disease in pregnant patients with Systemic Lupus Erythematosus (SLE) is not well studied. Our objective is to study the prognostic implications of SLE in pregnancy in terms of cardiovascular disease (CVD) and obstetric complications. Methods A retrospective cohort analysis was conducted using National Inpatient Sample 2016-2020. Cohorts of patients hospitalized for SLE, pregnancy and CVD were identified using respective ICD-10 codes. Multivariate logistic regression analysis was used to assess prognostic outcomes. Results Among 898825 patients hospitalized for SLE, 30845 patients were pregnant. Out of these patients with SLE and pregnancy, 1710 patients had cardiovascular disease (prevalence 5.5%). Mean age for SLE patients with pregnancy and cardiovascular disease was 30 years, 36.7% were white, and 36.4% were African-American. SLE in pregnancy is associated with five folds higher odds of cardiovascular disease (OR 4.8, CI 4.3-5.5, p&lt;0.001). The strongest association of SLE in pregnancy is with pericarditis (OR 77, CI 34.4-172, p&lt;0.001), followed by myocarditis (OR 35, CI 3.9-312, p=0.001), pulmonary hypertension (OR 12.9, CI 8.6-17.5, p&lt;0.001), ischemic heart disease (OR 9.3, CI 6.7-12.8, p&lt;0.001), stroke (OR 9.3, CI 4.8-18, p&lt;0.001) and congestive heart failure (OR 7.7, CI 5.16-11.5, p&lt;0.001). Table 2 outlines the pregnancy outcomes and complications in SLE. SLE is associated with significantly lower odds of live birth (OR 0.35, CI 0.32-0.37, p&lt;0.001). SLE is associated with significantly higher odds of pregnancy complications (Table 2). Conclusion 5.5% of SLE patients with pregnancy have CVD. SLE in pregnancy is associated with five folds higher odds of cardiovascular disease with strongest association to pericarditis, followed by myocarditis, pulmonary hypertension, ischemic heart disease, and stroke. SLE in pregnancy is associated with lower odds of live birth and higher odds of obstetric complications.
Abstract 17982: Impact of Obstructive Sleep Apnea on Bradyarrhythmia Hospitalizations: Analysis of the National Inpatient Sample 2016-2020
Authors: Ufuk Vardar, Naim Battikh, Prajwal Shrestha, Rohan Gajjar, Mahir Yilmaz, Dennis Kumi, Aneeza Jamshed, Aviral Vij
Journal: Circulation (2023)

Background: Obstructive sleep apnea (OSA) has been associated with many forms of heart rhythm disorders, including bradycardia and cardiac conduction delay. Here, we aimed to investigate the relationship between OSA and bradyarrhythmias. Methods: A retrospective cohort study was conducted using the Nationwide Inpatient Sample from 2016 to 2020. 1,685,704 hospitalizations with a primary diagnosis of bradyarrhythmias (including sinus node dysfunction, atrioventricular block and cardiac conduction disorder with 1:1 AV conduction) were identified and stratified based on the presence of OSA using ICD-10 codes. Multivariate regression analysis was used to adjust for confounders and analyze the variables. Results: Out of the 1,685,704 hospitalizations with bradyarrhythmias, 204,307 (%12.1) had OSA. In-hospital mortality in patients with OSA was significantly lower (3.51% vs 5.64%; p&lt;0.001). When adjusted to patient demographics, comorbidities, and hospital characteristics, independent risk factors for inpatient mortality included congestive heart failure (aOR 1.22, 95% CI 1.17 - 1.27, p-value&lt;0.001), atrial fibrillation (aOR 1.14, 95% CI 1.10 - 1.18, p-value &lt;0.001); however conditions associated with a lower risk for inpatient mortality included previous CABG (aOR 0.91, 95% CI 0.85 - 0.97, p-value 0.004) and previous pacemaker (aOR 0.61, 95% CI 0.58 - 0.65, p-value &lt;0.001). Mean length of stay (LOS) and mean hospital charges (HC) were also lower in the presence of obstructive sleep apnea compared to those without (5.28 vs 6.01 days, p-value 0.002 &amp; $90,549 vs $103,450, p-value &lt; 0.001 respectively). Conclusion: Amongst hospitalizations with a primary diagnosis of bradyarrhythmias, patients with OSA had better outcomes in terms of in-hospital mortality, length of stay and total mean hospitalization charges. This likely suggests that OSA-related bradyarrhythmias are a more benign and modifiable when compared to non-OSA-related bradyarrhythmias.
Abstract 11702: Development of Artificial Intelligence-Based Slow-Motion Echocardiography and Clinical Usefulness for Evaluating Regional Wall Motion Abnormalities
Authors: Yuki Sahashi, Takatomo Watanabe, Susumu Endo, Takeshi Ishihara, Ryo Takeshita, Ayako Sekine, Daisuke Fukuoka, Takeshi Hara, Hiroyuki Okura
Journal: Circulation (2023)

Introduction: Improvement in accuracy and image readability of stress echocardiography needs to be addressed, given that the accuracy depends on the physicians’ experience and image quality. The study aimed to develop an artificial intelligence (AI) based slow-motion echocardiography by inter-image interpolation and evaluate the clinical usefulness for detecting regional wall motion abnormalities (RWMAs). Methods: An AI-based image interpolation pipeline was developed with the optical flow calculation between echocardiographic images and predicting in-between images. In a cohort of patients with RWMA (n=25) and healthy volunteers (n=25), the accuracy for detecting RWMAs and image-reliabilities among four cardiologists was evaluated using slow-motion and conventional exercise stress echocardiography. Results: The development of slow-motion echocardiography were successfully performed at any arbitrary-time steps (e.g., 0.125x, 0.25x, and 0.5x). The accuracy for detecting RWMAs was numerically improved, while not statistically significant (87.5% in slow-motion echocardiography vs 81.0% in conventional stress echocardiography, odds ratio: 1.43 (95% confidence interval 0.78-2.62, p=0.25). Inter-reader agreement analysis demonstrated the level of agreements (Fleiss’s Kappa) for detecting RWMAs was 0.66 (95%CI: 0.55-0.77) in slow-motion echocardiography, and 0.53 (95%CI: 0.42-0.65) in conventional stress echocardiography. As for the four-point scale subjectively-evaluated image readability, the mean score was significantly improved using slow-motion echocardiography (2.11±0.73vs 1.70±0.78, p&lt;0.001). Conclusions: Slow-motion echocardiography was successfully developed. There was no significant improvement in the accuracy for detecting RWMAs using the developed slow-motion echocardiography, while the image readability and inter-reader agreement were improved.
Abstract 17747: Gynecological Manifestations in a Patient With Arrhythmogenic Right Ventricular Cardiomyopathy: A Desmosomal Link?
Authors: Angela Khidhir, Mingma Sherpa
Journal: Circulation (2023)

Introduction: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is inherited cardiomyopathy which is caused by desmosomal protein gene mutations, primarily in the desmoplakin (DSP), plakophilin-2 (PKP2), and desmoglein-2 (DSG2) genes. It is characterized pathologically by myocardial atrophy, fibrofatty replacement, and fibrosis, precipitating ventricular arrhythmias (VA). Desmosomal mutations have been linked to impaired follicular development and leiomyoma formation. However, there is little information about the association of their expression in myocardial with ovarian or uterine tissues. As incidences of ARVC/D in women increase, it is crucial to determine if women with the gynecological manifestations of these mutations are at a higher risk of developing ARCV/D. Case: We report a case of a 32-year-old female who presented with exercise-induced palpitations and syncopal episodes. She has a history of severe dysmenorrhea but has no medical conditions otherwise. On monitoring, she was found to have a high burden of ventricular premature complexes (VPCs). VAs were thought to have precipitated her syncopal episodes. She was started on antiarrhythmics. Echocardiogram demonstrated right ventricular dilatation and wall thinning. The patient later underwent genetic testing, which confirmed ARVC-associated mutations. Her dysmenorrhea was managed with combined oral contraceptives and nonsteroidal anti-inflammatory drugs. Pelvic ultrasound revealed leiomyomas, which were surgically removed. Discussion: This case supports the possible complex interplay between cardiovascular and gynecological conditions in patients with desmosomal mutations. Desmosomes are specialized protein complexes crucial in maintaining tissue's structural and mechanical stability. Mutations in desmosome genes disrupt the normal functioning of these protein complexes, leading to impaired cell-cell adhesion and increased vulnerability to tissue damage. The next step is to conduct studies to better understand the risk of developing cardiovascular disease in patients presenting with these gynecological conditions and vice versa to provide early monitoring and treatment.
Abstract 17471: Adjunctive Hypothermia for Patients With ST-Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention: A Controversy With Disheartening Results!
Authors: Mohamed R Abouzid, Karim Ali, Ahmed Ali, Mohammed Ghanim
Journal: Circulation (2023)

Objective: This meta-analysis aims to assess the effectiveness of hypothermia as an adjunctive therapy in percutaneous coronary intervention (PCI) for patients with ST-segment elevation myocardial infarction (STEMI). Methods: A comprehensive literature search was conducted using electronic databases to identify relevant studies published up until May 2023. Studies investigating the use of adjunctive hypothermia in STEMI patients undergoing PCI were included. Data on clinical outcomes, including mortality, infarct size, left ventricular function, major adverse cardiac events (MACE), and microvascular obstruction, were extracted and analyzed. Results: A total of 8 studies involving 488 patients were included in this meta-analysis. The pooled analysis revealed no significant difference in all-cause mortality between the adjunctive hypothermia group and the control group (risk ratio [RR] = 0.65; 95% confidence interval [CI] 0.30-1.43). There was no significant difference in MACE rates between the two groups (RR = 1.53; 95% confidence interval [CI] 0.66-3.53). Additionally, no significant differences were observed in infarct size, left ventricular function, or microvascular obstruction. Conclusion: While previously believed to show promise, hypothermia as an adjunctive therapy in PCI fails to achieve any significant superiority over standard interventions according to our analysis. Nevertheless, our findings should be interpreted with caution, taking into account the limitations we faced in our analysis such as the small number of studies available in the literature. Continued research efforts on bigger sample sizes are essential to either refine or refute the current findings.
Abstract 17253: Concepts Associated With 30-day Rehospitalization From Unstructured Data Among Patients With Heart Failure
Authors: Youjeong Kang, Caden Stewart, Josef Stehlik, Jincheng Shen, Ramkiran Gouripeddi, Konstantinos Sideris, Julio Facelli
Journal: Circulation (2023)

Introduction: Heart failure (HF) is a diagnosis for which the Centers for Medicare &amp; Medicaid Services mandated public reporting on 30-day risk-standardized rehospitalization rates. Examining risk factors predicting rehospitalization has been widely studied, and most of studies utilized structured data from electronic health records (EHRs) in HF. However, those studies did not use patient-level information that could be captured from unstructured data. Hypothesis: Unified Medical Language System (UMLS) concepts that may be used as factors that could be associated with the likelihood of 30-day rehospitalization among patients with HF by using natural language processing technique. Methods: We obtained notes from patients diagnosed with HF from EHRs from a tertiary hospital between June 1, 2015 and December 31, 2019. We analyzed 14 note types including physician notes, nursing notes and discharge summaries. We used the publicly available natural language processing software MetaMap to extract UMLS concepts that may be used as factors associated with the liekhood of 30-day rehospitalization and the Pandas package in Python for processing and analysis. Results: We identified 350,272 notes among 4,773 patients discharged with HF. The median age of the cohort was 76 years, 54.3% were male, and 89% white, and the 30 day-rehospitalization rate was 12.8%.. A total of 350,272 notes were for 4,164 patients who were not rehospitalized, and 57,212 notes for 609 patients who were rehospitalized. The UMLS concepts identified at a higher rate in notes of rehospitalized patients compared to non-rehospitalized patients included “personal appearance” (7.0% vs 5.5%), “power (psychology)” (3.5% vs 2.5%), and “intrinsic drive” (2.1% vs 1.1%). The UMLS Concepts that were mentioned less in rehospitalized patient notes include “family” (26.3% vs 30.8%), “home environment” (59.9% vs 64%), and “independence” (20.6% vs 24.6%). Conclusions: We identified six UMLS concepts associated with 30-day rehospitalization in patients with HF. Further study is warranted to determine whether incorporation of concepts from unstructured data could improve prediction of 30-day rehospitalization and provide opportunities for patient-level intervention.