tbuckley/cabot-search huggingface dataset:
Abstract 18027: Contribution of Sex and Age Differences to Life's Simple 7 Metrics in Cardiac Rehabilitation
Authors: Audry Chacin-Suarez, Helayna Abraham, Thomas P Olson, LaPrincess C Brewer
Journal: Circulation (2023)

Background: Life's Simple 7 (LS7) have been identified as key health factors aimed at achieving ideal cardiovascular health (CVH) and improving healthy life expectancy; however, it is unclear if different patient populations respond similarly to optimization of health behaviors. We sought to quantify the contribution of sex and age differences to changes in LS7 components in patients participating in cardiac rehabilitation. Methods: We included 937 adult patients who participated in CR from January 2018 to September 2020. LS7 metrics at baseline (pre-CR) and completion of CR (post-CR) were collected and changes in LS7 components (body mass index (BMI), diet, smoking, physical activity (PA), blood pressure (PB), cholesterol, glucose) were assessed by sex and age groups (&lt;65 vs ≥65 years old). Each LS7 component was assigned 0 (poor), 1 (intermediate), or 2 (ideal) points and a final score was computed to estimate an individual’s level of CVH (0-14 pts): 0-6 = poor, 7-8= intermediate, 9 -14= ideal. Results: The mean age was 64±13 years, and 34% were female. Patients attended a mean of 11.1±12.5 CR sessions. LS7 components with the highest proportion within the poor category were HbA1c (41%) and BMI (50%) at the time of CR enrollment; neither women nor men showed improvement on either component. The trend towards improvement from poor to intermediate range on cholesterol and BP metrics was seen only in older patients (Table 1). Mean LS7 score improvement was greater in the older group, P=.01 (Fig 1). Both women and men equally improved LS7 scores (Table 2, Fig 2). Conclusions: Patients participating in CR demonstrated improvement in overall LS7 scores regardless of sex and age. However, age disparities exist in LS7 metrics, with exacerbated differences noted by a lack of improvement in LS7 components such as BP and cholesterol in younger patients. Our insights provide opportunities to explore equitable CVH.
Abstract 14386: High Sensitivity Troponin: Implementation Before Education
Authors: Philip Chebaya, Sanchari Banerjee, Nicholas Anand, Hiba Zafar, Andrew Weinberg, Kevin Smith, Vishal Phogat, Danielle Olonoff
Journal: Circulation (2023)

Introduction: Troponin T is strong indicator of Acute Myocardial Injury, however, concerns regarding its sensitivity have led to the inception of high sensitivity troponin (hscTn). The use of hscTn in clinical practice allows for an increased negative predictive value, which in turn can expedite triage and disposition of patients presenting with Acute Coronary Syndrome. The ACC/AHA have developed algorithms to provide a road map to aide in the interpretation of hscTn values and their indications. However, the understanding of the interpretation of test is integral hscTn in guiding management. Hypothesis: Evaluate if the implementation of hscTn within our hospital system decreased the amount of inappropriate diagnostic testing and admissions. Methods: A total of 602 patients consisting of two patient groups seen in our emergency department with the chief complaint of chest pain were studied. The troponin T group consisted of patient admitted between Jan 2021 to June 2021 (n=246) and the hscTn group between July 2021 - December 2021 (n=356). Baseline demographic and clinical comorbid characteristics were compared between both groups. Notable outcomes of interest were rates of admission as well as cardiac testing. Analysis was performed using T test for continuous variables and Chi squared test for categorical variables. Results: Admission rates were significantly increased in the hscTn group in comparison to the regular troponin group with proportions of 60.3% vs 39.7% respectively (p &lt; 0.001). An 11 percent increase in inpatient cardiology consultation of the total visits occurred within the hscTn group vs the regular troponin group. When evaluating admitted patients, based on AHA guidelines for significant hscTn findings only 2% of those patients who were admitted met the criteria. Conclusions: The introduction of hscTn troponin within our hospital did not appear to decrease chest pain admissions regardless of its improved sensitivity and specificity. In contrast, rates were increased even when elevation was not significant, this may not be due to the test's efficacy but instead to the lack of education on its indications.
Abstract 17720: The Role of Soluble Guanylyl Cyclase/NLRP3/RHOA/ROCK Axis in Coronary Artery Spasm: A Potential Biomarker and Therapeutic Target
Authors: Ming-Yow Hung, Chi-tai Yeh, Vijesh Kumar Yadav, Iat-Hang Fong
Journal: Circulation (2023)

Background: Coronary artery spasm (CAS) can lead to potentially life-threatening acute coronary syndrome. The second messenger cyclic guanosine 3',5'-monophosphate (cGMP), which is regulated by BNP-pGC-cGMP and nitric oxide (NO)-soluble guanylate cyclase (sGC)-cGMP pathways, regulate not only vasodilation but also the functions of immune cells. However, the significance of sGC, as a primary receptor for NO, is unclear in CAS. Methods: We investigated sGC and downstream signaling in patient monocyte-derived macrophages (PMDMs) and human coronary artery smooth muscle cells (HCASMCs) using computational biology and bioinformatics to correlate macrophage polarization subsets, Lp(a), and inflammasome signaling axes with CAS. Results: Plasma sGC levels were significantly higher in 30 CAS patients compared to 20 non-CAS controls (P&lt;0.001). RNA-sequencing analysis revealed a significant association of sGC expression with NLR Family Pyrin Domain Containing (NLRP)-3 in HCASMCs and induced expression of inflammatory cytokines-specific surface markers. Lp(a) induction promoted the sGC-NLRP3 mediated lipid metabolism axis in PMDMs at both mRNA and protein levels, with elevated M1 polarization. sGC inhibition in HCASMCs reduced RhoA-GTP activity and its downstream effector ROCK, mitigating the Lp(a) effect, while sGC-specific modulator 1-H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-l-one (ODQ) treatment decreased Lp(a)-induced expression of sGC-NLRP3-inflammasome mediators and induced caspase-1, as well as subsequent cleavage of proIL-1β and proIL-18 in VSMCs. Conclusion: sGC/GC molecule in conjunction with the RHOA/ROCK pathway is an early biomarker for CAS. The sGC-NLRP3-inflammasome mediators signaling axis plays an important role in Lp(a)-regulated macrophage polarization and CAS development.
Abstract 188: Association Between Mean Arterial Pressure and Neurological Outcomes in Comatose Cardiac Arrest Patients: A Multicenter Observational Study
Authors: Byungkook Lee, Dong H Lee
Journal: Circulation (2023)

Aim: The target blood pressure has not been determined in comatose cardiac arrest patients. Therefore, we aimed to investigate the association between mean arterial pressure (MAP) and six-month neurological outcomes in out-of-hospital cardiac arrest (OHCA) survivors who underwent targeted temperature management (TTM). Methods: We analyzed the prospective registry of comatose OHCA survivors who underwent TTM. The arterial blood pressure measured every 1 hr in a 48-hour period after return of spontaneous circulation (ROSC) was recorded between January 2019 and May 2021 in the registry. We calculated the MAP during 48 hr and at every 6 hr. Patients with an MAP &lt; 65 mmHg or missing MAP data for more than 6 hr were excluded. We conducted a multivariable logistic regression analysis to determine the association between MAP and neurological outcomes and conducted a linear mixed models analysis to reveal the interaction between MAP over time and neurological outcomes. The primary outcome was six-month neurological outcomes with Cerebral Performance Category (CPC), which was dichotomized into good (CPC 1 or 2) and poor (CPC 3-5) neurological outcomes. Results: Of the 394 included patients, 255 patients (64.7%) had poor neurological outcomes. MAP did not differ between the neurological outcome groups (poor [89 mmHg, 82-97 mmHg] vs. good [89 mmHg, 84-95 mmHg]; p = 0.498). MAP was not independently associated with poor neurological outcomes (odds ratio, 1.010 [95% confidence intervals, 0.978-1.042]) adjusted with age, sex, body mass index, pre-existing illness (coronary artery disease, diabetes, pulmonary disease, renal impairment), witnessed collapse, first-monitored rhythm, cardiac etiology, downtime, lactate level after ROSC, and sequential organ failure assessment score. Repeated MAP measurements every 6 hr did not differ between the neurological outcome groups (p = 0.403), and the interaction between MAP every 6hr and neurological outcomes was not significant (p = 0.136). Conclusions: MAP during 48 hr after ROSC was not associated with the six-month neurological outcomes. MAP measurements every 6 hr during 48 hr after ROSC did not differ between neurological outcome groups, and the changes in MAP over time were not associated with neurological outcomes.
Abstract 18188: Positron Emission Tomography Has Robust Negative Predictive Value for Development of Clinically Significant Cardiac Allograft Vasculopathy Over Time
Authors: Nikil Prasad, Kevin Clerkin
Journal: Circulation (2023)

Introduction: Cardiac allograft vasculopathy (CAV) affects &gt;50% of OHT recipients by 10 years and is a leading cause of mortality. Standard CAV screening is via invasive coronary angiography (ICA). Recently it has been shown that PET with myocardial blood flow (PET/MBF) has excellent diagnostic ability for CAV, however, its prognostic value is not known. Hypothesis: CAV assessment by PET/MBF can prognosticate lack of significant angiographic progression of CAV over meaningful time scales. Methods: A retrospective analysis of 206 OHT recipients who underwent a PET/CT between ICAs was performed. CAV progression over time was assessed using intra-patient sequences of 1) baseline ICA, 2) interval PET, and 3) subsequent ICA. PET CAV grades were determined using the algorithm in Table 1. For each interval, NPV of CAV development was calculated. Results: Intervals between ICAs of 600, 800, 1000, and 1200 days were included with 77, 114, 106, and 22 patients respectively. Sequences were analyzed if the PET fell within middle third of interval. For development of ISHLT CAV 2/3 on subsequent ICA, PET CAV 0/1 had an NPV of 0.91, 0.94, 0.91, and 0.86 at each respective time point. For development of meaningful ISHLT CAV (presence of ≥ 30% vessel stenosis) on subsequent ICA, PET CAV 0/1 had an NPV of 0.80, 0.85, 0.85, 0.8 respectively (Figure 1). Conclusions: Non-invasive CAV assessment by PET/MBF provides robust NPV for development of varying degrees of clinically significant CAV over intervals up to 4 years. PET may be used as an adjunct to ICA for CAV screening and is a viable alternative among those with reasonable risk profiles. Prospective studies are needed to determine optimal interval lengths.
Abstract 18249: Artificial Intelligence-Based Electrocardiogram Prediction for Duration of Atrial Fibrillation
Authors: Youngjun Park, Kyung Geun Kim, Sunghoon Joo, Mineok Chang, Yeha Lee
Journal: Circulation (2023)

Introduction: Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with poor clinical outcomes, including stroke, acute coronary events, and heart failure. Recent studies have shown that early rhythm treatment of new-onset atrial fibrillation improves the patient's prognosis. However, atrial fibrillation is often asymptomatic, and it is difficult to determine its duration accurately. Recently, AI-based ECG has been studied for various cardiovascular diseases. Hypothesis: We sought to develop and validate a predictive model of the ECG for the duration of atrial fibrillation . Methods: All patients aged 18 years older from the two hospitals with at least one ECG were included in the study. Only patients with sinus rhythm with ECG prior to atrial fibrillation with ECG were selected. An ECG within 1 year from AF was first documented in ECG was defined as new onset AF. After dividing our datasets into training (and test sets, we developed an end-to-end deep neural network to predict for the duration of AF. Performance evaluation was conducted using various metrics, including AUROC, AUPRC, sensitivity, specificity, F1 score. Results: The dataset consisted of 83,525 ECGs from 16,193 patients from two hospitals. The AUROC for discriminating old AF and new-onset AF is 0.8186 (0.8181 - 0.8190) on internal validation set and 0.7967 (0.7966 - 0.7969) on external validation set. Sensitivity, Specificity, and F1 score are 0.7126((0.7118-0.7134), 0.7697 (0.7693-0.7701) and 0.5751 (0.5745-0.5757) on internal validation set and 0.7309 (0.7307-0.7311), 0.7225 (0.7224-0.7227) and 0.6354 (0.6352-0.6356)on external validation set. Conclusions: Our deep learning model can be used to predict atrial fibrillation's duration. Additional studies are ongoing to understand the relative importance of ECG features.
Abstract 14751: A Rare Presentation of 5-Fluorouracil-Induced Cardiotoxicity
Authors: Rachel Moshman, Muhammad Hassan Rehman, Lowell Safren, rido cha
Journal: Circulation (2023)

Background: 5-fluorouracil (5-FU) is associated with numerous cardiotoxic effects, most commonly chest pain and acute coronary syndrome. Less common effects include arrhythmias, myocarditis, pericarditis, and heart failure. We present a rare case of 5-FU causing cardiogenic shock. Case: A 54-year-old man with metastatic esophageal adenocarcinoma presented at 3:50 with chest pain that began the day before at 16:00, shortly after starting a 5-FU pump. Electrocardiogram (EKG) showed normal sinus rhythm with no ST or T wave changes. High sensitivity troponin T was 18 ng/L, followed by 24 ng/L at 1 hour and 81 ng/L at 6 hours. Computed tomography angiography (CTA) ruled out pulmonary embolism. Transthoracic echocardiogram (TTE) showed a globally reduced left ventricular ejection fraction (LVEF) of 35-40%. The patient received metoprolol and was scheduled for coronary CTA to investigate for coronary disease. Over the next few hours, he continued to report chest pain. Repeat troponin at 18:12 was 235 ng/L. Repeat EKG showed new anterior ST depressions. Posterior EKG did not show ST elevations. Repeat TTE revealed LVEF of 15%. The patient underwent left and right heart catheterization at 21:14, which showed normal coronary arteries, pulmonary artery pressure 50/31 mmHg (mean 38 mmHg), pulmonary capillary wedge pressure 36 mmHg, and cardiac index 1.1 L/min/m 2 . An Impella device was placed for circulatory support. He was treated with vasopressors and milrinone. Given concern for 5-FU toxicity, he received the antidote uridine triacetate 10 g IV every 6 hours for 5 days. LVEF improved to 70%. He was treated with nifedipine for possible coronary vasospasm. He was discharged 8 days later with heart failure medications. Conclusion: The incidence of cardiotoxicity from 5-FU ranges from 1.2-18%. Mechanistic theories include coronary vasospasm and direct cellular injury. Symptoms usually present within 12 hours of initiation but may present up to 2 days later. Management includes stopping the offending agent and starting anti-anginal drugs and uridine triacetate. Uridine triacetate is deacetylated to uridine, which prevents cell damage and death via competitive inhibition of 5-FU.
Abstract 18631: Mechanistic Insight on the Protective Role of Microbiome-Derived Butyrate in Pulmonary Hypertension
Authors: Andres Pulgarin, Mohamad Alabdallat, Barbara Methe, Alison Morris, Imad Al Ghouleh
Journal: Circulation (2023)

Introduction: Endothelial cell (EC) dysfunction is increasingly recognized as a precipitating event in Pulmonary hypertension (PH), a progressive, severe disease characterized by high blood pressure in the pulmonary circulation and excessive pulmonary vascular remodeling and inflammation. Microbiome-derived metabolites are altered in PH but their role in this disease remains poorly understood. Butyrate, a microbiome-derived short-chain fatty acid (SCFA) with biological activity, has been associated with benefit in cardiovascular diseases such as atherosclerosis. We aimed to test whether and how butyrate plays a protective role in PH. Results: PH-related inflammatory cytokine IL1β (10 ng/ml) increased expression of mesenchymal markers fibronectin, N-cadherin and transgelin (SM22) in human pulmonary arterial EC (HPAEC), consistent with induction of endothelial-to-mesenchymal transdifferentiation (EndMT). Butyrate (given as sodium butyrate, NaB; 2mM) attenuated this IL1β -induced upregulation (p&lt;0.01, p&lt;0.001, p&lt;0.001 for each gene, respectively). Likewise, butyrate inhibited IL1β-induced upregulation of b-catenin (p&lt;0.001), an important mediator of EndoMT. We previously showed that butyrate reversed IL1 β-induced downregulation of the PDZ protein EBP50, which we showed as a critical modulator of EndMT. In vivo, butyrate (NaB, 150mM) reversed PH phenotypes in wildtype mice (WT) following hypoxia exposure. In contrast, this reversal was attenuated in EBP50 heterozygous mice (Het, 50% EBP50 expression vs. WT) under hypoxia supplemented with butyrate. Similarly, butyrate reduced the number of circulating monocytes in hypoxia exposed WT but not Het mice. Conclusions: Collectively our results demonstrate that butyrate attenuates PH potentially via protecting against pulmonary vascular endothelial reprogramming and myeloid cell induction, through a mechanism that involves EBP50. These findings support the possible therapeutic benefits of butyrate in PH and shed mechanistic insight on the underlying cellular pathways propagating butyrate protection.
Abstract 12859: Clinical Correlates and Prognostic Value of B-type Natriuretic Peptide in Left Ventricular Assist Device Recipients With Cardiogenic Shock: Insights From INTERMACS
Authors: Naman S Shetty, Nirav Patel, Vibhu Parcha, Nehal Vekariya, Rongbing Xie, Garima Arora, Pankaj Arora
Journal: Circulation (2023)

Introduction: B-type natriuretic peptide (BNP) is a robust predictor of outcomes across the heart failure (HF) spectrum. However, data characterizing BNP levels in end-stage HF with cardiogenic shock (CS) is lacking. Furthermore, the prognostic value of BNP in left ventricular assist device (LVAD) receiving Stage D HF patients with CS has not been assessed previously. Methods: Continuous flow LVAD recipients with CS enrolled in INTERMACS between 2005 to 2017 were included. CS was defined as INTERMACS profile 1-3. The primary outcome of the study was long-term mortality. Long-term mortality was assessed in patients alive at 1-month post-surgery. Secondary outcomes included peri-operative mortality (&lt;30 days of surgery), cardiovascular mortality, arrhythmia, and right HF. The cohort was stratified by quartiles of BNP levels. Multivariable Cox proportional hazard models, adjusted for age, sex, body mass index, INTERMACS profile, center volume, implantation year, device strategy, estimated glomerular filtration rate, employment status, and education level, were used to assess the association between BNP levels and outcomes. Results: Among 7,290 LVAD recipients with CS, the median pre-implantation BNP value was 859 (427, 1,614) pg/mL. Males [851(429, 1,557) pg/mL, P =0.07], non-Hispanic Blacks [777 (362, 1,514) pg/mL, P =&lt;0.001], and obese [642 (311, 1,170) pg/mL, P =&lt;0.001] patients had lower BNP values. Over a median follow-up of 14.7 (6.9, 28.7) months, the risk of long-term mortality was similar in the second [HR adj :1.06 (0.94-1.20)], third [HR adj :0.97 (0.85-1.10)], and fourth [HR adj :1.04 (0.91-1.18)] quartiles of BNP compared with the first quartile of BNP. Similarly, the risk of peri-operative mortality, cardiovascular mortality, arrhythmia, and right HF did not vary by the quartiles of BNP. Conclusions: BNP has poor prognostic value in LVAD recipients with CS and the value of routine measurement of BNP in this population needs further investigation.
Abstract 13245: Neural Network-Derived Electrocardiographic Features Predict Future Cardiovascular Disease and All-Cause Mortality
Authors: Arunashis Sau, Antonio Ribeiro, Kathryn A McGurk, Libor Pastika, Nikesh Bajaj, Maddalena Ardissino, Jun Yu Chen, Huiyi Wu, Xili Shi, Katerina Hnatkova, Sean Zheng, Anne Britton, Martin J Shipley, Irena Andršová, Tomas Novotny, Ester Cerdeira Sabino, Luana Giatti, Sandhi Maria Barreto, Jonathan W Waks, Daniel B Kramer, Danilo Mandic, Nicholas S Peters, Declan O'Regan, Marek Malik, James S Ware, Antonio Ribeiro, Fu Siong Ng
Journal: Circulation (2023)

Background Subtle prognostically-important ECG features may not be apparent to physicians. In the course of supervised machine learning (ML), many thousands of ECG features are identified. These are not limited to conventional ECG parameters and morphology. Hypothesis: Novel neural network (NN)-derived ECG features can predict future cardiovascular disease and mortality Methods and Results: We extracted 5120 NN-derived ECG features from an AI-ECG model trained for six simple diagnoses and applied unsupervised machine learning to identify three phenogroups. In the derivation cohort (CODE, 1,558,421 subjects), the three phenogroups had significantly different mortality profiles. After adjusting for known covariates, phenogroup B had a 20% increase in long-term mortality compared to phenogroup A (HR 1.20, 95% CI 1.17-1.23, p &lt; 0.0001). The predictive ability of the phenogroups was retained in a group with physician confirmed normal ECGs. We externally validated our findings in five diverse cohorts (Figure) and found phenogroup B had a significantly greater risk of mortality in all cohorts. Phenome-wide association study (PheWAS) showed phenogroup B had a higher rate of future AF, ischaemic heart disease, AV block, heart failure, VT and cardiac arrest. Phenogroup B had increased cardiac chamber volumes and decreased cardiac output. A single-trait GWAS yielded four loci. SCN10A, SCN5A and CAV1 have roles in cardiac conduction and arrhythmia. ARHGAP24 does not have a clear cardiac role and may be a novel target. Gradient-weighted Class Activation Mapping (Grad-CAM) identified the terminal QRS and terminal T wave as important regions of the ECG for identification of phenogroup B. Conclusion: NN-derived ECG features can be used to predict all-cause mortality and future cardiovascular diseases. We have identified biologically plausible and novel phenotypic and genotypic associations that describe mechanisms for the increased risk identified.