tbuckley/cabot-search huggingface dataset:
Abstract 15934: Trends and Disparities in Patients Admitted With Bradyarrhythmias: Insights From the National Inpatient Sample 2016-2020
Authors: Ufuk Vardar, Rohan Gajjar, Naim Battikh, Aneeza Jamshed, IMRAN AZIZ, Dennis Kumi, Mahir Yilmaz, Aviral Vij
Journal: Circulation (2023)

Introduction: Bradyarrhythmias are caused by a dysfunction in the cardiac conduction system at the level of the sinus node, the atrioventricular node, or the His/Purkinje system. We aimed to investigate national trends and outcomes in patients with bradyarrhythmias, grouped as sinus node dysfunction, atrioventricular block, and conduction disorder (with 1:1 AV conduction). Methods: We utilized the National Inpatient Sample (NIS) Database 2016-2020 to identify the cohort with principal diagnosis of sinus node dysfunction (SND), atrioventricular block (AVB), and conduction disorder with 1:1 AV conduction using ICD-10-CM codes. For inpatient mortality analysis, COVID-19 patients were excluded from NIS 2020. Outcome analysis included hospitalization rates per 10,000 admissions and adjusted inpatient mortality rate utilizing predictive margins, during each calendar year stratified by sex, age, race, and median household income (MHOI). Results: There were a total of 1,557,806 hospitalizations (713,321 with SND; 297,037 with AVB and 547,448 with conduction disorder with 1:1 AV conduction) with a principal diagnosis of bradyarrhythmia from 2016-2020. Adjusted rates for hospitalizations per 10,000 admissions significantly increased throughout the years 2016-2020 for all three types of bradyarrhythmias, as demonstrated in Figure 1. Between the years 2016 and 2020, adjusted inpatient mortality rates amongst admissions with SND, AVB and conduction disorder with 1:1 AV conduction were similar, p-trend 0.201, 0.823 and 0.965 respectively; demonstrated in Figure 2. Conclusion: Our findings indicate that, throughout the years of 2016-2020, there was a trend suggesting an increase in hospitalization rates for bradyarrhythmias including sinus node dysfunction, atrioventricular block, and conduction disorder with 1:1 AV conduction. These findings may help the healthcare system recognize and decrease the healthcare burden of bradyarrhythmias.
Abstract 15512: Disrupting the NelfA Dependent RNA pol II Paused Complex in Heart Precipitates Dilated Cardiomyopathy
Authors: Saleena Alikunju, Zhi Yang, Danish H Sayed
Journal: Circulation (2023)

RNA polymerase II (pol II) pausing, a wide-spread genomic phenomenon regulates pol II dependent transcription and plays a critical role in gene expression during development and disease. Negative elongation factor (Nelf) complex consisting of five subunits, namely NelfA, NelfB, NelfC/D and NelfE, in coordination with Drb sensitive inducing factor (DISF) complex has been implicated in mediating pol II pausing. Structural studies show NelfA is indispensable for nucleation of paused complex. We have reported widespread promoter NelfA occupancy on cardiac genome, and showed that it is required for compensatory gene expression in hearts during cardiac hypertrophy. Here, we examine paused complex, with respect to its interactome, influence on gene expression and cardiac function. Immunoprecipitation of chromatin bound NelfA, followed by mass spectrometry in sham and TAC induced hypertrophied hearts identified Nelf proteins, pol II and Supt5, along with novel partners like Trim28 (chromatin remodeler), Adprhl1 (cardiac restricted, nuclear enriched, involved in DNA repair) and Numa1 (nuclear structural protein). Conditional NelfA knockout mice developed progressive dilated cardiomyopathy (LVID’d: 4.72 ±0.1, LVID;s: 3.96±0.13, %EF: 33.7±2.12, %FS: 16.15±1.12, LV vol;d: 104.5±21.9, LV vol;s: 70.26±5.5) compared to Wt-Cre (LVID’d: 4.16 ±0.09, LVID;s: 3.14±0.12, %EF: 49.1±2.3, %FS: 24.6±1.3, LV vol;d: 77.5±13.9, LV vol;s: 40.9±3.9), with sudden death by 3mths of age, in males and females KO mice compared to Wt-Cre. Interestingly, absence of NelfA resulted in decrease in cardiomyocyte size and increase in apoptosis. Single nuclei RNAseq on these hearts show decrease in cardiac-enriched sarcomeric genes, along with increase in genes involved in fibrosis and endothelial dysfunction. Further, ChIP-seq showed reduced Trim28 and NelfE promoter occupancy on essential gene, while below threshold or absent on cardiac-enriched and selected inducible promoters suggesting disruption of paused complex. Thus, we conclude that NelfA induced paused complex plays an essential role in efficient pol II dependent gene transcription and expression in heart, and deconstruction of the paused complex precipitates cardiac dysfunction and dilated cardiomyopathy
Abstract 13625: Laboratory Markers of Effective Endogenous Fibrinolysis in Intermediate-High-Risk Pulmonary Embolism
Authors: Michal Mihalovic, Petr Robert, Denisa Odvodyová, Ivana Malinicova, Katerina Pilikova, Michal Karpisek, Jiri Jarkovsky, Zuzana Motovska
Journal: Circulation (2023)

Introduction: Unselected therapy with fibrinolysis in intermediate risk-pulmonary embolism (iPE) is associated with an unacceptable risk of bleeding. Early identification of iPE patients on anticoagulant therapy with ineffective endogenous fibrinolysis (eFL) could optimize treatment-strategy. Aims: The study aims to determine markers of (in)effective eFL in intermediate-risk PE initially on anticoagulant therapy with UFH. Methods: In course of 24 months, iPE patients were enrolled in the prospective study. At admission, and every 24 hours until day 5, levels of 6 selected markers of eFL (i.e., PAI-1 and tPA active assay and total antigen, TAFI, and PAP) were determined. Upon arrival and following a span of 36 hours,defined i) Clinical (heart rate &gt;100 bpm and spontaneous oxygen saturation &lt;90%), ii) Echo (D-shape, RVd/LVd from PLAX&gt;0.7, RV/RA &gt;30mmHg), and iii) CT (RV/LV&gt;0.9) variables were obtained. An (un)successful therapy was assessed by one point for each clinical, Echo and CT criteria, as at least one parameter from initially altered has adjusted at 36 hours. We performed correlation of laboratory markers with the dynamics of clinical and imaging characteristics. Results: Study population consists of 44 patients, 22 men, mean (SD) age 60 (18.3) yr., first (38), repeat (6) PE. Plasminogen activator inhibitor-1 (PAI-1) active assay showed the most promising results. The cut-off for unsuccessful therapy from AUC for PAI-1 was ≥65 U/ml. Mean (IQR) levels of PAI-1 on day 1 were 119 U/ml (27.1 - 155.8) and were significantly higher on day 1 (p=0.019) and day 2 (p=0.055) in those with/without adjustment of initial pathological findings. PAI-1 elevation was associated with unsuccessful restoration of clinical, Echo and CT parameters at 36 hours (Table1). Overall Tx failure was associated with elevated PAI-1 (p=0.011). Conclusions: PAI-1 active assay could help us in identifying patients who would benefit from early indicated therapeutic fibrinolysis.
Abstract 17654: Sarpogrelate versus Clopidogrel for Arterial Interventions Systematic Review and Meta Analysis
Authors: Naim Battikh, Bisher Sawaf, Sarya Swed, Mohamad Nour Nasif, Hidar Alibrahim, Haidara Bohsas, Noheir Ashraf Ibrahem Fathy I Hassan, Yasmeen Abouainain, Yazan Khair Eldien jabban, Ubaid Khan, Wael Hafez
Journal: Circulation (2023)

Background: Sarpogrelate has been used to alleviate ischemic changes by preventing thrombosis, vasoconstriction, and vascular smoothmuscle proliferation. The worldwide use of Sarpogrelate is arguable due to the lack of reliable data regarding its efficacy and safety.Accordingly, our meta-analysis aims to compare the complications after receiving Sarpogrelate with Aspirin (S&amp;A) vs. Clopidogrel withAspirin (C&amp;A) as part of dual anti-platelet therapy in patients with endovascular intervention. Methods: Multiple electronic databases weresearched to identify relevant articles, including MEDLINE, Cochrane CENTRAL, Scopus, Google Scholar, Web of Science, and EMBASE. Allclinical studies that investigated the complication after performing Sarpogrelate versus clopidogrel with Aspirin for arterial interventionswere included in the meta-analysis. Reviews, case reports, conference abstracts, editorials, and animal studies were all excluded. Data wereanalyzed by using comprehensive meta-analysis studies. A complete quality assessment was performed using the Cochrane Risk of Bias toolversion 2 for randomized clinical trials (RCTs). Results: A total of 2588 studies were screened, with three studies included. Two multicenterRCTs and one retrospective cohort study including 527 patients (251 S&amp;A and 276 C&amp;A) were included. The overall quality was high in 2studies and fair in one. No statistically significant difference in restenosis, mortality, and bleeding risk as follows, respectively: (RR:0.81, 95%CI:0.52-1.2, P-value:0.36), (RR:0.37, 95% CI:0.06-2, P-value:0.25) and (RR:0.4, 95% CI:0.13-1.19, P-value:0.1). Conclusion: The antithromboticeffects of Aspirin with Sarpogrelate after vascular intervention are comparable to those of Aspirin plus Clopidogrel. Further large clinicalstudies are required to identify the actual difference in early and late complications after using Sarpogrelate versus clopidogrel.
Abstract 18912: Interplay Between Cognitive Function and Depressive Symptoms in Patients With Heart Failure
Authors: Muhammad I Amin, Jia Rong Wu, Misook L Chung, Debra K Moser
Journal: Circulation (2023)

Introduction: Mild cognitive impairment (MCI) and depressive symptoms (DS) are common comorbidities in patients with heart failure (HF). MCI and DS are known to be related from cross-sectional studies, but the trajectory of DS over time is unknown in patients with HF and MCI. Objective: To compare the trajectory of DS over a 2-year period based on cognitive function in patients with HF. Methods: We studied 373 patients (age 65 ± 13 years, 60% male, 26% NYHA class III/IV) with HF for 24-months. MCI was assessed using the Mini-Cog Test, and DS using the Patient Health Questionnaire-9; MCI was measured at baseline, and DS at baseline, 12 and 24 months. We used repeated-measures ANOVA for analysis with age and New York Heart Association (NYHA) class as covariates. Results: There was a significant time by group interaction (p = 0.027) in that DS decreased across time from baseline to 24-months in patients without MCI, while DS in patients with MCI, although decreased at 12-months, returned to baseline levels at 24-months (Figure). Although DS were higher in patients with worse NYHA class, they showed the same trajectory across time based on MCI. Conclusions: Although these data suggest that MCI worsens or prevents remission of DS overtime, the interplay between these two conditions requires further study to better understand how MCI and DS affect each other and how they interact to alter outcomes in patients with HF.
Abstract 12855: Early vs. Late Transcatheter Aortic Valve Replacement in Acute Heart Failure Hospitalizations: National Inpatient Sample (2015-2020)
Authors: Anas Hashem, Amani Khalouf, Mohamed Salah Mohamed, Mahmoud Ismayl, Anthony H Kashou, Devesh Rai, Jeremiah Depta, sudarshan balla, Samian Sulaiman, Deepak Bhatt
Journal: Circulation (2023)

Introduction: Data on clinical outcomes of early transcatheter aortic valve replacement (TAVR) (&lt;48 hours) compared to late (≥48 hours) TAVR in patients hospitalized with acute heart failure (AHF) and aortic stenosis (AS) remains limited. We aim to evaluate the differences between early vs. late TAVR regarding major clinical outcomes using a real-world US database. Hypothesis: There is no differences in the clinical outcomes based on the timing of TAVR procedural intervention in patients with acute heart failure. Methods: We used the National Inpatient Sample database by utilizing ICD-10 codes to identify all hospitalizations with a diagnosis of AHF and TAVR (2015-2020). The associations between the time of TAVR and outcomes were examined using multivariable logistic regression. Propensity-score matched (PSM) analysis was utilized to determine the adjusted odds ratio (aOR) of major clinical outcomes. Results: A total of 25,285 weighted hospitalizations of AHF were identified, of which 6,855 patients (27.1%) underwent early TAVR and 18,430 (72.9%) had late TAVR. Compared with early TAVR, Late TAVR was associated with less need for mechanical circulatory support (MCS) (aOR 0.97 [0.96-0.98], p&lt;0.01) and acute hypoxic respiratory failure (aOR 0.99 [0.98-0.99], p&lt;0.01), but higher odds of developing septic shock (aOR 2.06 [1.52-2.80], p &lt;0.01). However, there was no significant difference between both procedures regarding in-hospital mortality (aOR 1.01 [1.00-1.02], p=0.14), cardiac arrest (aOR 0.99 [0.98-1.00], p=0.21), and stroke (aOR 1.01 [1.00-1.02], p=0.18). Conclusions: Most patients with AHF and AS undergo TAVR after 48 hours of their presentation. After PSM, there was no difference in inpatient mortality, cardiac arrest, and stroke between both procedures. Late TAVR was associated with lower odds for MCS and acute hypoxic respiratory failure. The optimal timing of TAVR in patients with AHF and AS needs further study.
Abstract 17052: Are Sex-Specific Thresholds Needed for Donor-Derived Cell-Free DNA in Rejection Surveillance? An Analysis From the Genomic Research Alliance for Transplantation
Authors: Ersilia M DeFilippis, Benjamin A Sweigart, Kiran K Khush, Palak Shah, Sean Agbor-Enoh, Hannah Valantine, Amanda R Vest
Journal: Circulation (2023)

Introduction: Non-invasive methods for surveillance of rejection are increasingly used among heart transplant (HT) recipients, including donor-derived cell-free DNA (dd-cfDNA). The purpose of the current study was to examine patterns of dd-cfDNA seen in quiescence and acute rejection in males and females. Hypothesis: As other cardiac biomarkers differ by sex, we hypothesized that there may be sex-specific differences in performance for detection of acute rejection. Methods: Patients previously enrolled in GRAfT who were ≥18 years at the time of HT were included. Rejection was defined by endomyocardial biopsy with ISHLT acute cellular rejection (ACR) grade ≥2R and/or antibody-mediated rejection ≥ pAMR 1. Median dd-cfDNA levels were compared between sexes during quiescence and rejection. The performance of dd-cfDNA by sex at or after Day 28 was assessed using AUROC. Allograft injury was defined as dd-cfDNA ≥0.25%. Results: After exclusions, 148 patients were included with 1109 dd-cfDNA measurements. Baseline characteristics including demographics and comorbidities were not significantly different between sexes. During quiescence, there were no significant sex differences in median dd-cfDNA (0.038% [IQR 0.001-0.167] in females vs 0.029% [IQR 0.001-0.125] in males, p = 0.21). There were no significant sex differences in median dd-cfDNA for ACR (0.33% [0.210-0.356] in females vs 0.32% [0.210-1.103] in males, p = 0.57). Overall, median dd-cfDNA levels were higher in AMR than ACR but did not significantly differ by sex (0.50% [IQR 0.180-0.820] in females vs 0.63% [IQR 0.316-1.945] in males, p = 0.51). Elevated dd-cfDNA detected ACR/AMR with an AUROC of 0.83 in females and 0.89 in males (Figure). Conclusions: There were no significant sex differences between dd-cfDNA levels during quiescence and rejection. Performance characteristics were similar, suggesting that similar thresholds can be used in men and women for rejection surveillance.
Abstract 18080: Pediatric Sex Detection Through AI-Enabled ECG Analysis: Evaluating Accuracy and the Influence of Pubertal Development
Authors: Donnchadh O'Sullivan, Scott Anjewierden, Grace Greason, Zachi Attia, Francisco Lopez-Jimenez, Paul Friedman, Peter A Noseworthy, Jason Anderson, Anthony H Kashou, Benjamin W Eidem, Jonathan N Johnson, Talha Niaz, Malini Madhavan
Journal: Circulation (2023)

Introduction: Biologic sex and hormonal concentrations shape ECG parameters due to sex hormone effects on cardiac function. AI-enabled ECGs have previously been shown to accurately predict patient sex in adults and correlate with sex hormone levels. Aims: We aimed to test the ability of AI-enabled ECGs to predict pediatric patient sex and explore the influence of pubertal development. Methods: Two AI-enabled ECG models were created using a convolutional neural network trained on pediatric 10-second, 12-lead surface ECGs. The first model was trained de novo using pediatric data. The second model used transfer learning from a previously validated adult data-derived algorithm. We analyzed the first ECG from 89,063 pediatric patients (aged &lt;19 years) recorded from 1988-2022, and divided the cohort into training, validation, and testing datasets. Subgroup analysis was performed on prepubertal (0-7 years), pubertal (8-14 years), and post-pubertal (15-18 years) patients. Results: The cohort consisted of 46.6% males, with 21,434 prepubertal, 26,300 pubertal, and 41,329 post-pubertal children. No significant performance difference was observed between the two models. Both models demonstrated 81% accuracy and an overall AUC of 0.91 in the testing cohorts, with high discriminatory ability in post-pubertal teenagers (AUC = 0.98). (Figure 1) Conclusions: AI-ECG predicts pediatric patient sex with varying performance across pubertal stages. The highest discriminatory ability is observed post-puberty, decreasing in pubertal and prepubertal children. The results suggest hormonal and physiological changes during puberty may influence cardiac electrophysiology measurably. More research is required to interpret CNN-predicted sex discordance with actual sex and its implications for future cardiovascular risk.
Abstract 16725: Cost-Effectiveness Analysis of Intensive Treatment of Systolic Hypertension: Results From Sprint Patient-Level Data
Authors: Zugui Zhang, Brandon K Bellows, Adam P Bress, Andrew E Moran, Yiyi Zhang, Catherine Derington, Paul Kolm, William S Weintraub
Journal: Circulation (2023)

Background: The Systolic Blood Pressure Intervention Trial (SPRINT) showed that treating patients at high risk for cardiovascular events but without diabetes or a history of stroke to a systolic blood pressure (SBP) target goal of &lt;120 mm Hg (Intensive Care, IC), compared with &lt;140 mm Hg (Standard Care, SC), resulted in lower rates of fatal and nonfatal major cardiovascular events and death. We examined the cost-effectiveness of IC vs SC over a life-time horizon, based on patient-level data, from a health-sector perspective. Methods: Patient-level data from SPRINT were used to calculate and estimate cost, effectiveness, quality adjusted life years (QALY), and the incremental cost-effectiveness ratio (ICER). For participants who died during the trial, life years and QALYs were estimated from in-trial analysis; for who survived to the end of the trial, pooled, harmonized data from six epidemiologic cohorts included in the National Heart, Lung, and Blood Institute Pooled Cohorts Study was used to estimate risk of lifetime primary fatal and non-fatal events and calculate life-years. Published utilities estimates were used to calculate QALYs. For participants without SPRINT lifetime primary event estimates, we applied multiple imputation method via machine learning to impute the life-years and QALYs. The ICER was expressed as cost per QALY gained. Results: IC participants were estimated to gain an average of 0.51 QALY (95% CI: 0.21, 0.81) relative to SC participants. Estimated total lifetime costs were $17,449 higher with IC (95% CI: $10,697, $24,201) than SC. The ICER for IC vs SC was $34,214 per QALY gained, with 68.5% of bootstrap-derived estimates &lt;$50,000/QALY. The results from multiple imputation chained equations for addressing missing data showed that IC is cost effectiveness at $50,000/QALY. Across various scenario analyses, we consistently found a more than 60% probability that IC is cost-effective over a lifetime when the willingness-to-pay value exceeds $100,000 per QALY. Conclusions: Based on participant-level trial and epidemiologic cohort data, IC is cost-effective, with significant clinical benefit at acceptable higher lifetime cost. Recommending intensive SBP targets in patients at high CVD risk is an effective, high-value therapy.
Abstract 184: Blood Pressure Matters After Cardiac Arrest: Is Our Target Too Low?
Authors: Rachel Beekman, Noah Kim, Eva Kitlen, Courtney Choy, John Stendahl, EHIMEN ANENI, Jennifer Kwan, Charles R Wira, George Mcginniss, Akhil Khosla, P. Elliott Miller, David M Greer, Nils H Petersen, emily j gilmore
Journal: Circulation (2023)

Introduction: Blood pressure is an important therapeutic target after cardiac arrest (CA), crucial for maintaining cerebral blood flow and preventing secondary brain injury. However, the optimal blood pressure during the post-resuscitation period remains unknown. Hypothesis: Proportion of time with mean arterial pressure (MAP) below a specific threshold will be associated with worse clinical outcomes. Methods: We assessed a retrospective cohort of CA patients admitted to an academic center between January 2014 - August 2022. Patients without a documented initial MAP, those who progressed to brain death, or who died within 96 hours were excluded. Multivariable logistic regression was used to test associations between proportion of time with MAP &lt; 65mmHg or &lt; 80mmHg and outcomes [survival and good neurologic outcome (Cerebral Performance Category 1-2) at hospital discharge]. We adjusted for age, sex, Charlson Comorbidity Score, CA location, initial rhythm, Pittsburgh Cardiac Arrest Category, and peak 24h norepinephrine equivalent. We evaluated the initial 96 hours from CA and the following sub-periods: 1) 0-24h, 2) 25-72h, and 3) 73-96h. Results: Of 817 patients with CA, 411 were included. Over the initial 96 hours, the proportion of time with MAP &lt; 80 was inversely associated with survival and good neurologic outcome (adjusted OR [95% CI] per 10% time 0.83 [0.75 - 0.93] and 0.78 [0.69 - 0.89], respectively); no such association was found for MAP &lt; 65. This inverse association held in period 2 (0.85 [0.78-0.93] and 0.79 [0.71-9.88], respectively) and period 3 (0.87 [0.80-0.94] and 0.85 [0.78-0.93], respectively), but not in period 1 (Figure 1). Conclusion: The proportion of time spent with MAP &lt; 80mmHg was associated with worse outcomes, independent of disease severity. The neuroprotective effect of higher MAP appears to occur between 25-96h from CA. Future prospective studies are needed to further characterize the differential clinical impact of MAP across time.