tbuckley/cabot-search huggingface dataset:
Abstract 19060: Single-Nuclei RNA-Seq Provides Novel Insights Into Cellular Composition and Transcriptional Changes in Human Right Ventricular Failure
Authors: Rajarajan A Thandavarayan, Rajasekaran Mahalingam, Rahul Neupane, Krupa R Mysore, Keith Youker, Erik Suarez, Ioannis Karakikes, Guha Ashrith
Journal: Circulation (2023)

Introduction: Right ventricular failure (RVF) is a common consequence of pulmonary hypertension, but effective treatment options are currently lacking. To develop precise molecular and cellular targets for therapeutic development, a comprehensive investigation of cell type-specific responses and cellular heterogeneity in RVF is needed. Hypothesis: Cellular heterogeneity exists within the myocardium of RVF patients with pulmonary hypertension, and identifying specific genes contributing to failure can be aided by studying these distinct subpopulations. Methods: To test this hypothesis, we performed single-nucleus transcriptome analysis of 120,000 nuclei from ventricle samples of RVF patients with advanced or end-stage pulmonary hypertension with severe right heart failure undergoing heart double lung transplantation and normal control (NC) subjects. Single nuclei RNA sequencing was performed using 10x genomics, and bioinformatics tools were used for analysis. Results: Unsupervised clustering of 120,000 nuclei led to the identification of transcriptionally distinct subpopulations within 6 major cell types. We identified a unique fibroblast subpopulation expressing SERPINE1 in RVF and observed extensive crosstalk between the fibroblast cells and the other cardiac cell types through Visfatin signaling. In addition, other major cardiac cell types, such as cardiomyocytes, endothelial cells, and macrophages within the failing hearts also exhibited significant alterations in the signaling pathways compared with the control hearts. Conclusions: Our study provides novel insights into the single-cell landscape within the myocardium of RVF patients, revealing remarkable changes in the expression patterns of fibroblast genes. The identified sub-cluster of the fibroblast cell population could serve as a specific and potential therapeutic target in the clinic.
Abstract 13478: Causes of Long-Term Mortality in Patients With Microvascular Obstruction Following ST-Segment Elevation Myocardial Infarction
Authors: Giselle Fisher, Bethany White, Brynn Okeson, Evan Walser-Kuntz, Jay H Traverse
Journal: Circulation (2023)

Introduction: The presence of microvascular obstruction (MVO) following ST-segment elevation myocardial infarction (STEMI) portends a poor prognosis and is associated with adverse left-ventricular (LV) remodeling and an increase in mortality in the subsequent year of follow-up. However, the long-term effects of MVO on mortality have not been previously described. Methods: We analyzed the long-term follow-up and cardiac MRIs of 475 patients (Average age = 60 years, 76% male) for the presence (n=337) or absence (n=138) of MVO at a single institution following STEMI and successful reperfusion with primary percutaneous intervention (PCI). Causes of death were determined from the patient's electronic medical record or death certificate. Results: The infarct-related artery was more likely to be the LAD in patients with MVO and the RCA in patients without MVO. Patients with MVO had greater ischemic times (159 vs. 141 mins; p = 0.012) and were more likely to have TIMI 0 flow on presentation (71 vs 54%; p &lt;0.002). Patients with MVO had greater infarct size by cardiac enzymes resulting in greater LV end-diastolic volume index (LVEDVI) (80 vs.75 ml/m2), LV end-systolic volume index (LVESVI) (39 vs 30 ml/m2) and LV mass (146 vs 134 g) and reduced LVEF (48 vs 58 %; all p &lt; 0.01) by cardiac MRI performed 1-3 days following STEMI and PCI . During long-term follow-up a total of 56 patients with MVO died compared to 18 patients without MVO. Patients with MVO died sooner after STEMI (5.9 vs 7.8 years) and were more likely to die from cardiovascular causes such as progressive heart failure or sudden cardiac death (Table). LVEF before death was lower in the MVO group (46 vs 52%). Conclusions: There is significant long-term mortality associated with MVO following STEMI with the majority of patients dying from cardiovascular causes. In contrast, patients with STEMI without MVO rarely died from a cardiac etiology but from cancer and natural causes.
Abstract 15775: Prehospital Scene Delays in the Prehospital Care of ST-Segment Myocardial Infarction (STEMI)
Authors: Aditya C Shekhar, Joshua Kimbrell, Michael McCartin, Ira J Blumen
Journal: Circulation (2023)

Introduction: Emergency medical services (EMS) are an important link in the chain of care for patients experiencing time-sensitive cardiovascular emergencies, including ST-segment elevation myocardial infarction (STEMI). Recent quality initiatives have focused on reducing delays in STEMI care in both the prehospital and in-hospital environments. For instance, “door-to-balloon times” are tracked to ensure minimal delays from the time a STEMI patient enters a hospital to revascularization. In the prehospital realm, comparably less research has investigated factors contributing to delays in care for STEMI patients. Prolonged “scene times” - the time spent with a patient prior to transport - represents one area where focus is needed. Methods: As part of an ongoing initiative, EMS providers are encouraged to limit scene times to under 20 minutes for STEMI patients. We queried data from the Minnesota State Emergency Medical Services Regulatory Bureau (EMSRB) to ascertain what percentage of EMS encounters involving STEMI patients within the state’s MNSTAR EMS database between 2018 and 2021 had a scene time of greater than 20 minutes. Encounters involving helicopter emergency medical services (HEMS) were excluded. Results: Between 2018 and 2021, there were a total of 5178 STEMI patient encounters meeting eligibility criteria. Approximately 67.6% (n~3501) of patient encounters involved a scene time less than or equal to 20 minutes. Rural communities were associated with prolonged scene times when compared with metropolitan communities. Conclusions: Our preliminary analysis of EMS data from Minnesota shows one-third of STEMI encounters had scene times greater than 20 minutes. Thus, reducing prehospital scene times by EMS may be one method to streamline the care for STEMI patients. Further research should investigate what factors influence EMS crews to spend more than 20 minutes on scene with STEMI patients.
Abstract 16995: Distensibility and Aortic Growth Rate Predict Type B Aortic Dissection in Marfan Syndrome
Authors: Carlos Alberto Campello Jorge, Prabhvir Marway, Nic Tjahjadi, Heather Knauer, Himanshu J Patel, C A Figueroa, Nicholas S Burris
Journal: Circulation (2023)

Introduction: Marfan syndrome (MFS) is associated with high aortic growth rate (GR) and incidence of aortic dissection (AD), including delayed type B AD (TBAD) after prophylactic root repair. Elevated aortic stiffness has been investigated as a biomarker in MFS, but it remains uncertain how stiffness relates to GR and risk of AD. Vascular deformation mapping (VDM) is a technique that uses clinical CT angiography (CTA) to yield accurate, 3D maps of aortic growth over surveillance (VDM-G). This technique can also be used to assess aortic stiffness via quantification of cyclic wall stretch between systole and diastole (VDM-D) using multi-phasic dynamic CTA. Research Question: Is distensibility of the descending thoracic aorta associated with aortic GR or development of TBAD in MFS patients? Goal: The aim of this study was to analyze stiffness of the descending thoracic aorta in MFS and its association with aortic GR and occurrence of TBAD. Methods: We identified 36 adult MFS patients with dynamic CTA studies (&gt;1 year interval) between 2004-2020. Growth was quantified by VDM-G, and linearized descending aortic stiffness by VDM-D - via calculation of distensibility - as the ratio of cyclic aortic surface area change (AR) over pulse pressure [(AR-1)/PP]. Results: Patients were 38.9 ± 12.1 years old, 58% were male and 25 (69%) had prior ascending repair. Mean CT follow-up interval was 5.7 ± 3.4 years and 8 developed TBAD during follow-up with pre-dissection diameter of 31.12 ± 6.01 mm at tear location. Age (β -0.4, 95%CI: -0.07, -0.01, p=0.015) and baseline diameter (β 0.10, 95%CI: 0.02, 0.18, p=0.017 ) independently predicted GR on multivariable analysis, but distensibility did not (p=0.38). Both distensibility (OR 0.02, 95% CI: 0.00, 0.68, p=0.03) and GR (OR 8687.05, 95% CI: 1.43, 5x10^7, p=0.04) were independent predictors of TBAD during follow-up, but diameter was not (p=0.49). Conclusion: Aortic stiffness and growth rate are likely predictors of type B aortic dissection in MFS.
Abstract 15595: In-Hospital Outcomes in Patients With Psoriasis Who Undergo Transcatheter Aortic Valve Replacement
Authors: Ryan M Severdija, Michael Dangl, Fatemah Akbar, Rosario Colombo
Journal: Circulation (2023)

Background Psoriasis is a chronic inflammatory condition associated with an increased prevalence of aortic stenosis (AS). There is paucity of evidence regarding transcatheter aortic valve replacement (TAVR) outcomes in patients with psoriasis. Methods: The National Inpatient Sample Database was queried from 2016-2019 for relevant ICD-10 diagnostic and procedural codes. Beeline characteristics and in-hospital TAVR outcomes were compared in patients with and without psoriasis. Multivariate logistic regression was performed for select outcomes to adjust for differences in baseline characteristics. A p value &lt;0.05 was considered significant. Results: 227,920 hospitalizations for TAVR were identified of which 1,510 (0.6%) were patients with psoriasis. See Table 1 for baseline characteristics. Patients with psoriasis were more likely to be white, and have concurrent diagnoses of hypertension, diabetes mellitus, hyperlipidemia, coronary artery disease, obesity, tobacco use disorder, COPD, and thrombocytopenia. Adjusting for baseline characteristics, those with psoriasis were found to have higher rates of in-hospital all-cause mortality OR 2.20 [1.57-3.09], and major bleeding events OR 1.38 [1.13-1.69]. Conclusions: Psoriasis is associated with worse outcomes and higher in-hospital mortality in TAVR. Further studies are warranted to optimize outcomes in this higher risk cohort. Table 1. Patient Characteristics. Values are reported as mean ± standard deviation or median [interquartile range] for continuous variables. Categorical variables are represented as n (%). Between-group comparisons were performed for continuous data using T-test for parametric and Mann-Whitney U test for nonparametric variables, respectively. Categorical variables were compared using Chi squared test. A p-value &lt;0.05 was considered significant (bold).
Abstract 13569: Impact of Intense Smartphone Application Based versus Routine Outpatient Follow-Up on Short Term Clinical Outcomes in Acute Decompensated Heart Failure (ADHF)
Authors: Ajit Pratap Singh, rishi sethi, Sudhanshu Dwivedi, Sharad Chandra, Akshyaya Pradhan
Journal: Circulation (2023)

Introduction: Heart failure (HF) poses a global health burden, with about 26 million people affected and an estimated health expenditure of US$31 billion worldwide . The outcome of HF patients with reduced ejection fraction (HFrEF) has improved significantly due to the availability of evidence-based therapies. Still, the readmission rates, and subsequent mortality, have remained unchanged in the last two decades. Despite immense positive evidence, &lt; 25% of patients with HFrEF are on the appropriate target doses of medical therapy. Objectives: Impact of intense versus routine outpatient follow-up on clinical outcomes and patient satisfaction in Acute decompensated heart failure (ADHF) patients over a 3-month follow-up.METHODS: This is a prospective open-label randomized study analyzing readmission rates and achieving target doses of GDMT. Results: A total of 226 subjects (Intense smartphone application-based follow-up -112) (routine outpatient follow-up -114) were enrolled in the study. The mean age was 53 and 54 years in intense follow-up and routine follow up, respectively. Both study arms were well-matched and randomized. There was a significant reduction in rehospitalization rate in the intense follow-up arm (28 vs. 57) p - 0.005. Subjects on smartphone application-based follow-up had better drug compliance and a rapid escalation of GDMT to reach target doses. Number of patients on target dose of GDMT at three months Conclusion: Intense smartphone application based follow-up was feasible and safe for ADHF patients. The incidence of 30-day and three months readmissions improved. They also showed improved BP, HR, and NT Pro-BNP levels. Drug dosages were up-titrated periodically in these subsets of patients based on their cardiac function and laboratory parameters. Newer apps should be designed to incorporate artificial intelligence (AI) with features more likely to improve key patient-reported and clinical outcomes.
Abstract 13282: Parental Allostatic Load Predicts Time to the Onset of Cardiovascular Disease in Offspring
Authors: James M Muchira, Mulubrhan F Mogos, Boniface Kimathi, Mariann R Piano
Journal: Circulation (2023)

Background: Allostatic load, a measure of cumulative stress-related physiologic dysregulation, is associated with major cardiovascular disease (CVD) events. However, despite evidence of familial aggregation of CVD risk factors, the impact of parental allostatic load on the onset and timing of CVD in offspring remains unknown. Hypothesis: We hypothesize that offspring of parents with lower allostatic load will have longer CVD-free survival time. Aim: To examine whether CVD-free survival in offspring is associated with parental allostatic load and potential sex-specific differences. Methods: A secondary data analysis of 6,145 offspring-mother-father trios derived from the Framingham Heart Study Original (exam 10) and Offspring Cohorts (exam 1). Allostatic load was defined as an index (0-16) of 8 variables (systolic and diastolic blood pressure, total cholesterol, HDL, LDL, total cholesterol/ HDL ratio, fasting blood glucose and body mass index). Kaplan-Meier plots, and Irwin’s restricted mean and multivariable-adjusted Cox proportional hazards regression models were used to examine sex-specific differences and the association between parental allostatic load and offspring’s CVD-free survival. Results: Parents mean age (SD) was 60.8 (8.1) and offspring’s 34.8 (10.5). 22.8% of parents (n=458) and 12.1% (n=412) of offspring had high allostatic load (&gt;8). In a total of 118,132 person-years of follow-up among the offspring, 1060 incident CVD events occurred. The overall CVD incidence rate was 8.9 per 1000 person-years (95% confidence interval [CI] 8.4-9.5) and sons had a higher CVD incident rate than daughters (11.0 vs 7.2, p&lt;0.001). Offspring of mothers with low allostatic load lived 4 more years free of CVD compared to offspring of mothers with high allostatic load. Similarly, offspring of fathers with low allostatic load lived 3 more years free of CVD. The hazard rate of having incident CVD among offspring of mothers and fathers with high (compared to low) allostatic load was 1.58 (1.28-1.95) and 1.39 (95% CI: 1.11-1.75), respectively. Conclusion: Parents' allostatic load has a significant impact on the cardiovascular health of their offspring, with those of mothers with high allostatic load being at a higher risk of developing CVD at a younger age.
Abstract 15497: Association of Blood Cell-Based Inflammatory Markers and C-Reactive Protein With Mortality in Acute Coronary Syndrome Patients: Analysis From the ATLAS ACS-TIMI 46 Trial
Authors: Gerald Chi, Ginger Jiang, Cecilia Bahit, Serge Korjian, Laith Allaham, Elliot S Barnathan, Alexei Plotnikov, Charles Gibson
Journal: Circulation (2023)

Background: Inflammation has been implicated in the pathogenesis of acute coronary syndrome (ACS). The comparative performance of blood cell-based inflammatory markers in mortality prediction among ACS patients remains unclear. Methods: In this multinational, double-blind, phase 2 trial, patients with recent ACS were randomized to receive rivaroxaban or a placebo. The relationship of inflammatory markers (including neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR], systemic immune-inflammation index [SII], and C-reactive protein [CRP]) with 6-month all-cause mortality was assessed using logistic regression, and the optimal cut points were determined by the Youden index. The discriminative performance of the combinations of inflammatory markers was compared by the c statistic. Results: A total of 2918 patients were analyzed. A higher risk of mortality was observed in patients with elevated NLR (≥3.691; OR=3.732; 95% CI=1.930 to 7.217; p&lt;0.0001), elevated PLR (≥14.18; OR=2.915; 95% CI=1.447 to 5.873; p=0.0028), decreased LMR (&lt;3.125; OR=3.179; 95% CI=1.643 to 6.152; p=0.0006), elevated SII (≥875.7; OR=2.494; 95% CI=1.285 to 4.840; p=0.0069), or elevated CRP (≥26 mg/L; OR=3.435; 95% CI=1.771 to 6.662; p=0.0003). The discriminative capacity of CRP plus NLR (c statistic=0.7326) was greater than CRP or NLR alone (c statistic=0.6444 and 0.6443) but not significantly affected by further inclusion of PLR, PLR plus SII, or PLR plus SII plus LMR into the model (c statistic=0.7430, 0.7412, and 0.7406) (Figure 1). Conclusion: NLR calculated from differential white blood cell count provides incremental prognostic value to CRP in predicting mortality among ACS patients. Future studies may consider NLR and CRP conjunctively in constructing mortality risk assessment models.
Abstract 13362: Proteomic Architecture of Frailty Across the Spectrum of Cardiovascular Disease
Authors: Andrew Perry, SHilin Zhao, Priya Gajjar, Venkatesh L Murthy, Benoit Lehallier, Patricia Miller, Sangeeta Nair, Colin Neill, Jeffrey Carr, William F Fearon, Samir R Kapadia, Dharam J Kumbhani, Linda D Gillam, Joann Lindenfeld, Laurie Farrell, Megan M Marron, Qu Tian, Anne Newman, Joanne Murabito, Robert E Gerszten, Matthew G Nayor, Sammy Elmariah, Brian R Lindman, Ravi V Shah
Journal: Circulation (2023)

Introduction: With an aging population, understanding how frailty affects treatment response is paramount to improve patient-centered outcomes. Hypothesis: We hypothesized that circulating proteomic correlates of frailty will identify novel pathways for therapeutic investigation and provide prognostic information. Methods: From a multicenter, prospective cohort of 809 participants (median age 83 years; 44% women) with symptomatic, severe aortic stenosis (AS) and systematic assessments of frailty, we measured &gt;900 circulating proteins (Olink). We used principal component analysis (PCA) to define composite “axes” of 12 measures of frailty (Figure). Using ordinary and penalized regression (LASSO), we related proteins to both individual measures of frailty and the composite axes. Prioritized proteins were then examined for their relation with age and morbidity in external, published datasets. LASSO model coefficients were used to calculate protein “scores” of frailty, which were tested for their relation with all-cause mortality in the AS cohort and cause specific mortality in &gt;1,800 participants from the Framingham Heart Study (FHS; mean age 55 years, 54% women). Results: PCA identified 3 axes of frailty (“patient reported outcomes”, “body composition” and “physical function”) that explained ≈49% of variance. Proteins related to axes of frailty were (1) related to inflammatory and metabolic phenotypes and (2) weakly related to age, in &gt;35,000 community dwelling Icelanders (mean age 55±17 years). The protein score of physical function was associated with all-cause post-transcatheter aortic valve implantation (TAVI) mortality in the AS cohort (HR 0.68 [0.59-0.79]) and non-cardiovascular mortality in FHS (0.83 [0.75-0.91]). Conclusions: Circulating proteins capture frailty phenotypes that are weakly related to age, and provide prognostic information in both older adults undergoing TAVI and younger community dwelling adults.
Abstract 16873: Takotsubo Variant is Associated With Worse Right and Left Ventricular Systolic Function Than Other Stress Cardiomyopathy Variants
Authors: Maroun Chedid, Kevin Buda, Mengistu Simegn, omer iqbal
Journal: Circulation (2023)

Introduction: Stress cardiomyopathy (SCM) is usually associated with reduced systolic function on echocardiogram. However, the prevalence of systolic dysfunction between different variables of SCM has not been established. Hypothesis: Whether Takotsubo variant SCM is associated with worse systolic function compared to other SCM variants. Methods: We conducted a retrospective cohort study evaluating echocardiograms of all patients with SCM between 2010 and 2022 at Hennepin Healthcare, MN, USA. The diagnosis of SCM was made based on the International Takotsubo (InterTak) diagnostic criteria. Results: Between January 2010 and December 2022, 296 patients presented with SCM. The majority of patients (N= 173, 58.4%) had the apical (Takotsubo) variant, compared to 78 (26.3%) patients with the midventricular variant and 45 (15.2%) with the basal variant. The three groups had no significant difference in the left ventricular outflow tract and septal diameters. Patients with the apical variant had a lower ejection fraction on presentation compared to mid-ventricular and basal variants (28.1% vs. 36.8% and 35.7%, respectively, p&lt;0.001). Patients with Takotsubo CM had the lowest cardiac output and cardiac index among the three groups ( table 1 ). Right ventricular systolic function, evaluated by Tricuspid Annular Plane Systolic Excursion (TAPSE), was lowest in patients with apical SCM (mean TASPE 1.58 cm, p=0.027). All patients had similar ejection fraction recovery at follow-up (mean EF &gt; 55%, p=0.793, mean follow-up time &lt; 4 weeks, p=0.913). Conclusion: Takotsubo variant is associated with worse right and left ventricular systolic function compared to other SCM variants, with similar systolic function recovery at follow-up.