tbuckley/cabot-search huggingface dataset:
Abstract 15746: Longitudinal Remodeling in Persistent Heart Failure With Reduced Ejection Fraction and Improved Ejection Fraction
Authors: Erick Romero, Alexander Baltodano, Dev Patel, Camryn Sellers-Porter, Maya Deshmukh, Pablo Acevedo, Nathan Shimamoto, Martin Cadeiras
Journal: Circulation (2023)

Background: Among patients with heart failure (HF) with reduced ejection fraction (HFrEF), a subpopulation improves ventricular function, HF with improved ejection fraction (HFimpEF). This study aimed to investigate the longitudinal remodeling trajectories associated with HFimpEF and with HFrEF. Methods: This was a retrospective cohort study, UC Davis Medical Center (2014 to 2022). The inclusion criteria included HF related ICD codes, a left ventricular ejection fraction (LVEF) ≤40%, and a B-type natriuretic peptide (BNP) ≥100 pg/mL. Longitudinal BNP and echocardiographic data were retrieved from electronic medical records. The HFimpEF group was defined as follows: an initial LVEF ≤40% with a subsequent &gt;40% with a minimum 10% improvement after ≥3 months. Those not meeting these criteria were classified as persistent HFrEF. Longitudinal assessments were performed using linear mixed models, adjusted for baseline values. Results: The study included 1307 patients. The cohort median age was 65, 68% male, 57% white, with 39% developing HFimpEF. Compared to persistent HFrEF, the HFimpEF group exhibited evidence of reverse remodeling with increasing trends in LVEF, interventricular septal end diastole (IVSd), and decreasing trends in left ventricular internal dimension in systole (LVIDs) values with a p= &lt;.01 between groups (Figure). However, BNP did not present significant changes over time, presenting sustained initial measurements ( p =0.08). Conclusion: Patients with HFimpEF in this cohort had different longitudinal remodeling patterns compared with persistent HFrEF. The HFimpEF group had increasing trends of LVEF, IVSd and decreasing trends of LVIDs. Suggesting reverse remodeling and lower longitudinal levels of BNP.
Abstract 15826: Single-Cell Analysis of Right Ventricle Combined With AI: Implications for Pulmonary Arterial Hypertension
Authors: Aleksandr Dekan, Joel James, Maki Niihori, Ruslan Rafikov, Olga Rafikova
Journal: Circulation (2023)

Background: Pulmonary arterial hypertension (PAH) significantly compromises the functionality of the right ventricle (RV). Our recently established NFU1 mutation-based rat model spontaneously develops PAH and successfully recapitulates main features of human PAH, such as gender dimorphism, right ventricle (RV) hypertrophy and dysfunction with RV-pulmonary artery uncoupling. Objective: We aimed to discern unique transcriptional differences between in WT and NFU1 rats on the single cell level, which may shed light on potential therapeutic targets for RV hypertrophy in PAH. Methods: We performed a single-cell transcriptomics analysis of WT and NFU1 RV collected from WT and NFU1 G206C rats to determine potential targets for treating RV dysfunction. The single-cell data was processed, and cells were annotated. Differentially expressed (DE) genes in cell types between the WT and NFU1 were determined using a two-sided Wilcoxon rank sum test. Finally, PandaOmics AI was employed to select through RV transcriptomics data (Boucherat, 2022) and extract the top 300 human targets from our key gene findings in the rat model. Results: We identified several cell types in rat scRNA-seq data, among which cardiomyocytes and endothelial cells had the highest number of human-relevant rat targets. Endothelial cells had 6 targets, Hsp90aa1/b1, Fabp4, Fhl2, Tnni3, Atp2a2, Ndufa4. These genes can affect endothelial cell proliferation, vascular integrity, intracellular transport, and angiogenic phenotype. Cardiomyocytes had 24 identified targets responsible for increased mitochondrial metabolism (Ndufv1, Nme2, Mrpl15), calcium release and muscle contraction (Ryr2, S100a1, Atp2a2), and others. Conclusions: A distinct disparity is observed in the transcriptional landscape in RV in NFU1 model of PAH. This could either indicate an adaptive response by the RV to increased afterload or be tied to its distinctive embryological/developmental origin, morphology, and functional properties. Novel cell-type-specific potential targets responsible for RV hypertrophy and dysfunction in PAH were discovered.
Abstract 14671: Investigating Health Disparities in Arrival From Last Known Well Times in Queens, NY
Authors: Stanley Pierre, Anna Huang, Shaun-marie Wilson, Vanessa Jules, Holson Holson, Denise Chuang, Debashree Sengupta, Jason Punsalan, Suja Mohan, Susan Thomas, Gilbert Merisier
Journal: Circulation (2023)

Background: Stroke is a leading cause of death in the US and the third leading cause of disability worldwide, so timely access to care must be considered as it is a salient predictor of prognosis and outcomes. 1,2 Specifically, because the recommended treatment window for IV tPA (alteplase) is within 4.5hr of last known well (LKW), it is imperative for patients to present to the facility within 3.5hr from symptom onset to receive treatment. 3 There are known health disparities in stroke treatment/outcomes 4 , and this study seeks to explore the population of patients that disproportionately have unknown or LKW &gt;4.5hr to arrival, and the impacts of such. Methods: Stroke patients entered into the Get With The Guidelines™-Stroke excluding patients whose symptoms began after hospital arrival and were discharged from October 2021 to December 2022 from NYC Health + Hospitals/Queens were included. Arrival from LKW time was categorized into ≤0-4.5hr and &gt;4.5hr. Covariates collected and included are age, Hispanic ethnicity, sex, race, final clinical diagnosis of stroke, and history of previous stroke. Logistic regression models were used to analyze data and results are presented as adjusted odds ratios at 0.05 significance. Results: A total of 342 patients were included in this study with 211 patients arriving after 4.5hr. The median time to arrival from LKW was 829min. Notably, patients identifying as Asian were more likely to arrive within 4.5hr of LKW (3.21 adjusted OR, 95% CI 1.30-7.91, p = 0.01) compared to their Black counterparts. White patients were also more likely to arrive within the 4.5hr treatment window compared to Black patients (11.69 adjusted OR, 95% CI 3.39-40.36, p = 0.0001). Increase in age was associated with decrease in timely arrival from LKW (0.98 adjusted OR, 95% CI 0.96-0.99, p = 0.04). Clinically, those that were diagnosed with ischemic stroke were more likely to arrive within 4.5hr of LKW (2.55 adjusted OR, 95% CI 1.37-4.77, p = 0.003) as well as those with a history of previous stroke (2.74 adjusted OR, 95% CI 1.39-5.40, p = 0.004). Conclusion: There are health disparities in stroke treatment because of prolonged patient arrival from or unknown LKW, and these findings will help inform further practices in community education and outreach.
Abstract 15132: Proteomic Signatures of Human Immunodeficiency Virus-Associated Subclinical Left Atrial Dilation
Authors: Tess E Peterson, Virginia S Hahn, Sabina Haberlen, Michael Plankey, Frank Palella, Joel Bader, Joseph Margolick, Gregory Kirk, Damani Piggott, Todd T Brown, Wendy S Post, Katherine C Wu
Journal: Circulation (2023)

Introduction: Persons living with HIV (PLWH) receiving combination antiretroviral therapy (cART) are at higher risk of heart failure (HF) and preceding cardiac abnormalities, including left atrial (LA) dilation, compared to persons without HIV (PWOH). Mechanisms of this excess risk are unclear. We assessed whether plasma proteomic signatures of immune activation are cross-sectionally associated with LA volume index (LAVi) and augmented among PLWH. Methods: We performed Olink proteomics on plasma obtained concurrently with cardiac magnetic resonance among PLWH and PWOH. Proteins were analyzed individually and as clusters agnostically defined using weighted gene co-expression network analysis. Associations with HIV serostatus and LAVi were estimated using multivariable linear regression with robust variance. We explored protein relationships using annotated enrichment analysis. Results: Among 352 participants (age 55±6 years; 25% female; 70% Black), mean LAVi was 29±9 mL/m 2 and 60% were PLWH (88% on cART; 73% with undetectable plasma HIV RNA). Of 2594 proteins, 104 were independently associated with LAVi (false discovery rate, FDR&lt;0.05). We identified 49 of these as candidate contributors to the association between HIV seropositivity and higher LAVi (36 when excluding PLWH with detectable HIV RNA), enriched in T-cell activation and leukocyte cell adhesion regulators. We identified one protein cluster positively associated with LAVi and HIV seropositivity regardless of HIV suppression status, enriched in TNF signaling, ephrin signaling and extracellular matrix (ECM) organization. Conclusion: Proteomic signatures that may in part account for HIV-associated elevation in LAVi are enriched in pathways of immune activation, cytokine signaling and ECM organization, even among virally suppressed PLWH on cART. These findings support a link between persistent immune activation and subclinical LA dilation which may portend future risk for HF among PLWH.
Abstract 18126: A Rare Case of a Left Ventricular Papillary Fibroelastoma With an Initial Presentation of Unilateral Vision Loss
Authors: Bernard Brown, sabu john
Journal: Circulation (2023)

A 59-year-old female with hypertension presented with acute onset of decreased vision in the right eye. She reported waking up 3 days prior to admission with sudden onset of shadow in the right eye appearing like a falling curtain which eventually progressed to total visual loss. She also complained of headaches and palpitations. The patient denied pain, nausea, vomiting, photophobia, changes in speech, aphasia, facial weakness, arm or leg weakness or numbness. She states that this is her first experience of vision loss. At the time of admission, she was hypertensive to 170/100s and started on amlodipine 5mg and losartan 25mg. Neurology and ophthalmology were consulted for concerns of stroke and new vision loss. She was started on heparin drip, aspirin 81mg, atorvastatin 80mg, and methylprednisolone 1g. Ocular examination revealed right brachial retinal artery occlusion. MRI brain showed chronic microvascular changes, but no acute intracranial hemorrhage or infarction. CT angiogram of the neck showed mild soft plaque in right carotid bifurcation. Transthoracic echocardiogram revealed a 1.6cm x 1.6cm left ventricular mobile mass which appeared to be attached to the posteromedial papillary muscle and left ventricle ejection fraction of 60%. The patient underwent open heart surgery for removal of the mass. The mass was confirmed to be a papillary fibroelastoma attached to the left ventricular trabeculum. The mitral valve and subvalvular apparatus were not involved. New onset of stroke or acute vision loss is generally a result of thromboembolism. Most times it can be caused by a clot formed in a patient with atrial fibrillation. In other cases, it can be due to a ruptured cholesterol plaque. However, primary cardiac tumors are rare, especially ones on the papillary muscle. We presented a rare case of papillary fibroelastoma that possibly embolized causing acute unilateral vison loss. This case reinforces the importance of cardiac imaging in new stroke or acute vision loss.
Abstract 17668: Association of Female Sex With Outcomes in Older Patients With STEMI
Authors: Minji Seok, Amer Muhyieddeen
Journal: Circulation (2023)

Introduction: Acute coronary syndrome is increasingly affecting the aging population. Despite this, we have observed that older patients presenting with acute coronary syndromes often experience poorer outcomes in the setting of age-related comorbidities and undergo decreased rates of reperfusion therapy. In this analysis, we aimed to uncover any sex differences in outcomes amongst older female patients admitted with ST-Elevation Myocardial Infarction (STEMI). Methods: We utilized the National Inpatient Sample data from 2020 to isolate cases where patients were primarily admitted for STEMI. From this pool, we then identified two subsets: individuals who were aged 65 and over and females. We implemented both logistic and linear regression analyses and accounted for any potential confounding factors. We considered our findings to be statistically significant if the 2-tailed p-value was &lt;0.05. Results: During 2020, there were a total of 159,890 hospitalizations for STEMI. Among these cases, 46.3% or 74,013 involved patients over 65 years old. After adjusting for various factors such as race, hospital characteristics (including bed size, location, and teaching status), insurance coverage, income level, and Elixhauser comorbidities, we noted a number of significant findings for women over the age of 65 admitted due to STEMI. These included a heightened in-hospital mortality rate (aOR 1.36, 95% CI 1.23- 1.52), reduced usage of mechanical ventilation (aOR 0.86, 95% CI 0.78 - 0.96), less likelihood to receive mechanical circulatory support (aOR 0.64, 95% CI 0.53 - 0.78), and a decreased probability to undergo PCI (aOR 0.87, 95% CI 0.81 - 0.94). Conclusion: In hospital admissions for STEMI, we observed that older female patients experienced increased complications during hospitalization and were less likely to undergo invasive reperfusion therapy. Additional research would be required to identify if these sex differences can be attributed to variations in initial presentation before STEMI or if changes in clinical management by sex are contributing to adverse outcomes.
Abstract 13229: Coiled-Coil Domain-Containing Protein 80 Protects Against Aortic Dissection by Maintaining the Contractile Smooth Muscle Cell Phenotype
Authors: Linghong Shen, Qingqing Xiao, Xiaoxiao Yang, Bin Cai, Yi Li, Xiying Huang, Ke Xu, Weifeng Zhang, Xiaolei Wang, Xia Wang
Journal: Circulation (2023)

Background: Aortic dissection (AD) is a life-threatening medical emergency characterized by adverse vascular remodeling. Effective prevention and treatment options are lacking for AD. Coiled-coil domain-containing protein 80 (CCDC80) plays an essential role in regulating vascular remodeling. In the present study, we aimed to define the role of CCDC80 in the formation and development of AD. Methods: The expression and subcellular localization of CCDC80 were determined in human and mouse AD. CCDC80 knockout mice (CCDC80 –/– ) and vascular smooth muscle cell (VSMC)-specific CCDC80 knockout mice (CCDC80 fl/fl SM22α Cre + ) were treated with angiotensin II (Ang II) or Ang II combined with β-aminopropionitrile monofumarate (BAPN) to induce AD models. RNA-Seq analysis combined with immunoprecipitation and blockage of the JAK2/STAT3 signaling pathway in CCDC80 –/– mice were used to evaluate the effect of CCDC80 deficiency on this pathway. Results: CCDC80 was downregulated in VSMCs in human and mouse AD. CCDC80 – / – mice challenged with Ang II and BAPN developed AD with higher frequency and severity compared with their littermate controls (66.7% vs. 100%, p &lt; 0.05). Remarkably, compared with littermate controls treated with Ang II, CCDC80 –/– mice (8.3% vs. 87.5%, p &lt; 0.05) and CCDC80 fl/fl SM22α Cre + mice (12.5% vs. 80%, p &lt; 0.05) frequently developed AD with severe elastin fragmentation and collagen deposition. CCDC80 interacted with JAK2; CCDC80 deficiency could promote VSMC phenotype switching, proliferation, and migration as well as matrix metalloproteinase production by activating the JAK2/STAT3 signaling pathway. The JAK2/STAT3 pathway-specific inhibitor ameliorated adverse vascular remodeling and reduced AD formation (90% vs. 55%, p &lt; 0.05) in CCDC80 knockout mice. Conclusion: CCDC80 deficiency exacerbates the progression of AD by activating the JAK2/STAT3 pathway involved in regulating the phenotype switching and function of VSMCs. Our findings suggest that CCDC80 is a potential target for the prevention and treatment of AD.
Abstract 11601: Does Artificial Intelligence Dream of Elevated Natriuretic Peptide in Chest Radiography?
Authors: Eisuke Kagawa, Masaya Kato, Noboru Oda, Eiji Kunita, Michiaki Nagai, AYA YAMANE, Shogo Matsui, Yuki Yoshitomi, Shunsuke Ishida, Genki Kurimoto, Keigo Dote
Journal: Circulation (2023)

Introduction: Heart failure pandemic is a medical issue, and its diagnosis can be challenging. Hypothesis: To assess the hypothesis that the artificial intelligence (AI) model for predicting elevated brain natriuretic peptide (BNP) levels from chest X-ray images has sufficient performance and could improve the diagnostic performance of human. Methods: Patients who underwent chest radiography and BNP testing on the same day were enrolled in this study. The chest X-ray images were labeled based on plasma BNP levels &gt;= 200 pg/mL. We trained models that predicted the label, and the final ensemble model was constructed. Humans were trained and tested to predict labels, followed by the same test, referring to the prediction of the AI model. Diagnostic performance was assessed. Results: Among the 1607 patients, 10103 chest X-ray images and BNP values were collected. We assembled 31 models as the final model with an accuracy of 0.855, precision of 0.873, recall of 0.827, receiver-operating-characteristics area-under-curve (AUC) of 0.929, and precision-recall AUC of 0.934. The accuracy of the testing by 35 individuals significantly improved from 0.708±0.049 to 0.829±0.069 (P &amp;lt; 0.001) with AI assistance. The accuracy of the experts was higher than that of non-experts (0.692±0.042 vs. 0.728±0.051, P = 0.030); however, with the AI assistance, the accuracy of the non-experts was rather higher than that of the experts (0.851±0.074 vs. 0.803±0.054, P = 0.033). Conclusions: The AI model can predict elevated BNP levels from chest X-ray images and could improve the diagnostic performance of humans.
Abstract 15566: Dissecting the Genetic Architecture of Intracranial Aneurysms
Authors: Shaunak Adkar, julie lynch, Sharika Bamezai, Sabina Sorondo, Ryan Choi, John Cabot, Michael Levin, Scott M Damrauer, Saiju Pyarajan, Philip S Tsao, Stephen Skirboll, Nick J Leeper, Derek Klarin
Journal: Circulation (2023)

Introduction: The genetic risk of intracranial aneurysm (IA) development has been ascribed largely to smoking and hypertension. The contribution of IA risk loci to aberrant gene programs within cerebrovascular cell types remains unclear. Hypothesis: We hypothesized that candidate causal genes at IA susceptibility loci are enriched within extracellular matrix producing cell types. Methods: We identified participants enrolled in the Million Veterans Program (MVP) with and without IA. Thirty-two million genotyped and imputed variants were tested for association with IA using mixed effect regression modeling, controlling for age, sex, and population structure prior to external replication and meta-analysis. Candidate causal genes were prioritized through expression quantitative trait loci colocalization and transcriptome wide association studies. We constructed a cerebrovascular single nucleus RNA sequencing (snRNA-seq) dataset and integrated IA summary statistics to compute a ‘disease relevance score’ per nucleus using the scDRS pipeline. Cell type level analysis was used to assess association of cerebrovascular cell types with IA. Results: We identified 3165 participants (2280 European, 627 African, and 258 Hispanic ancestry) with and 592927 without IA in the MVP. After replication and meta-analysis with data from an additional 12273 cases and 591046 controls, we identified 22 loci (5 novel) associated with IA. We prioritized 16 candidate causal genes. Gene expression analysis of snRNA-seq genes revealed enrichment of several candidate genes, including EDNRA and PLCE1 within smooth muscle cells (SMCs) and pericytes. Integration of summary statistics and snRNA-seq data revealed significant association of matrix-producing pericytes and smooth muscle cell populations with IA. Conclusion: Here, we identify novel loci associated with IA and found enrichment of candidate causal genes in pericytes and SMCs. Integration of summary statistics with cerebrovascular snRNA-seq reveals association of cell-types involved in matrix production, suggesting an intrinsic deficit in matrix production and vascular integrity that may drive IA pathogenesis independent of systemic hypertension.
Abstract 18097: The Burden of Ischemic Heart Disease in North Africa and Middle East Region From 1990-2019: Results From the GBD Study
Authors: Arya Aminorroaya, Sahar Saeedi Moghaddam, Hamed Tavolinejad, Zahra Aryan, Behnam Heidari, Hedyeh Ebrahimi, Mohammadreza Naderian, Parnian Shobeiri, Ali Ghanbari, Nazila Rezaei, Mohammad-Reza Malekpour, Rosa Haghshenas, Negar Rezaei, Bagher Larijani, Farshad Farzadfar
Journal: Circulation (2023)

BACKGROUND: Despite the substantial burden of IHD in North Africa and Middle East (NAME) region, temporal trends of the burden of IHD were not systematically evaluated in this region and its countries previously. Methods: We reported deaths, premature mortality, YLLs, YLDs, and DALYs of IHD in NAME region and its 21 countries during 1990-2019 using the results of the Global Burden of Disease Study 2019. Premature IHD mortality was defined as IHD death in males &lt;55 and females &lt;65 years of age. Results: IHD accounted for 0.8 million deaths and 18 million DALYs in NAME in 2019. From 1990-2019, the age-standardized death rate of IHD significantly decreased by 29% (-37 to -22) and reached 219 (194 to 247) per 100,000 in NAME in 2019 (Fig A) compared with the global estimates of -31% (-35 to -27) and 118 (108 to 126), respectively. From 1990-2019, the age-standardized DALY rate of IHD significantly decreased by 33% (95% CI: -41 to -25) and reached 4159 (3651 to 4752) per 100,000 population in NAME in 2019 (Fig B) compared with the global estimates of -29% (-33 to -24) and 2243 (2099 to 2385), respectively. The reduction in age-standardized DALY was mostly derived from the reduction in YLL (-34%) rather than YLD (-4%) compared with worldwide estimates of -29% and -6%. While the decreasing pattern in the age-standardized DALY and death rate of IHD was consistently observed across all 21 NAME countries, it was not statistically significant for Egypt, Libya, Saudi Arabia, Syria, Tunisia, and Yemen (Fig C, D). In 2019, 27% of IHD deaths in females and 18% of IHD deaths in males were premature in NAME, which was higher than the worldwide estimates of 17% and 15%, respectively. Turkey, Iran, and Lebanon showed the greatest reduction in IHD premature mortality during 1990-2019. CONCLUSIONS: Despite the improvements, IHD still remains the leading cause of lost death and DALYs in NAME. People are more likely to die prematurely due to IHD with more pronounced sex disparities in NAME compared with the global average.