tbuckley/cabot-search huggingface dataset:
Abstract 17126: Role of Aldehydes, Transient Receptor Potential Ankyrin 1, and Catecholamines in Electronic Cigarette-Induced Endothelial Dysfunction in Mice
Authors: Lexiao Jin, Daniel Riggs, Andre Richardson, Jordan Lynch, Laura Fryar, Whitney Theis, Gregg Shirk, Alexis Miller, Pawel Lorkiewicz, Sanjay Srivastava, Aruni Bhatnagar, Daniel J Conklin
Journal: Circulation (2023)

Although Electronic Nicotine Delivery Systems (ENDS)-derived aerosols induce endothelial dysfunction (ED), the mechanisms and constituents responsible for ED are unknown. Because ENDS use propylene glycol and vegetable glycerin (PG:VG) that thermally decompose into aldehydes, we hypothesized that acrolein and formaldehyde stimulate ED via the sensory transient receptor potential ankyrin-1 (TRPA1) receptor and the autonomic nervous system (ANS). To test this, female wild-type (WT) and TRPA1-null mice were exposed to either filtered air, PG:VG-derived aerosol, acrolein (AC; 1 ppm), or formaldehyde (FA, 5 ppm). Biomarkers of exposure (AC: 3HPMA; FA: 4TCA) and of harm (aortic ED; urinary catecholamines) were measured. The PG:VG and AC exposures significantly increased urinary 3HPMA levels; and the PG:VG and FA exposures significantly increased urinary 4TCA levels vs air controls. Both PG:VG and FA exposures (6h/d x 4d) in WT mice led to aortic ED (-64.6±3.8; –66.7±5.5 % ACh, respectively) vs air control (-81.5±1.5 % ACh); yet AC exposure did not induce ED (-76±2.9 % ACh). Exposures in TRPA1-null mice to PG:VG, AC, or FA did not lead to ED (-93.0±3.6; –82.8±3.1; -86.6±2.8 % ACh; respectively). As an index of ANS activation and a potential mediator of ED, urinary catecholamines (dopamine, DA; norepinephrine, NE; epinephrine, EPI; serotonin, 5HT) and metabolites were measured by UPLC-MS/MS in early (0-3h) and late (3-18h) post-exposure (PE) samples. In WT mice, PG:VG significantly increased early PE urine levels of NE (and two NE metabolites; +1.5-2.5x), DA metabolite (+1.5x), but not EPI nor 5HT; FA exposure increased DA (+3x), EPI (+2.5x), NE and NE metabolites (+1.2-2.5x), 5HT and 5HT metabolite (+2.5x) only in late PE; while AC exposure decreased early PE DA (-73%) and 5HT (-42%) levels. In TRPA1-null mice, PG:VG and AC exposures increased early PE levels of NE (+2x) and depressed EPI and 5HT levels (-40%); whereas FA exposure increased NE (+2x), EPI (+4x), and 5HT (+1.5) levels in late PE. Aldehydes induce ED through time-dependent mechanisms mediated in part by TRPA1 activation and ANS stimulation. These data indicate that ENDS use may increase cardiovascular disease risk via aldehydes generated by PG:VG independent of nicotine and flavorants.
Abstract 15007: Time to SGLT2i Initiation in Patients With Heart Failure
Authors: Jungyeon Moon, Jacob A Udell, Alice Chong, Jiming Fang, Peter Austin, Dennis T Ko, Therese Stukel, Clare Atzema, Gillian Booth, Karen Tu, David Naimark, Cynthia Jackevicius
Journal: Circulation (2023)

Introduction: SGLT2i, initially introduced as antidiabetic agents, have shown cardiovascular benefits for heart failure (HF) patients, irrespective of their diabetes status. Given the growing evidence from post-hoc analyses of landmark trials advocating for early initiation, this study aims to investigate the temporal trends in the timing of SGLT2i initiation after HF hospitalization. Methods: A cross-sectional study was conducted using administrative health data from Ontario, Canada. Our cohort included patients aged ≥65 years who filled an SGLT2i prescription after their HF hospitalization in Ontario, Canada between 4/2016-3/2021. We computed the median number of days to the first SGLT2i prescription after the HF discharge date, exclusively for patients who started SGLT2i. Patients were further stratified based on their diabetes status. Results: We identified 64,183 HF patients, of which 5,257 filled an SGLT2i prescription after discharge (mean age was 82.49; 46.9% men; 49.6% had diabetes). The number of patients starting an SGLT2i increased from 889 (16.9%) in 2016/17 to 1,206 (22.9%) by 2020/21. The median time from discharge following the index HF admission to first dispensation of an SGLT2i prescription decreased 7-fold over this period, from 1,082 days to 156 days (Figure 1). In 2016/17, patients with diabetes started an SGLT2i at a median of 930 days, and patients without diabetes at 1,640 days. However, by 2020/21, the median initiation times were closer at 143 and 189 days, respectively. Conclusions: Our findings demonstrate a substantial reduction in the time to SGLT2i initiation for patients after HF admission, suggesting increased clinician recognition of their cardiovascular benefits. However, initiation remains delayed, especially for patients without diabetes. To optimize patient outcomes, it is crucial to encourage early initiation of SGLT2i therapy in hospitalized HF patients and address potential barriers to SGLT2i initiation.
Abstract 18865: Cardiac Arrest on Weekends Are More Fatal Than Weekdays - A Study From National Database
Authors: Durgesh Agrawal, Mansoor Ahmad, Vien T Truong, Avilash Mondal, Aanchal Sawhney, Pooja Panjwani, Krunalkumar Patel, Abhishek Dutta, Smriti Bhatia, Muhammad Saad Siddique, Sunil Dhar, Federico Viganego, Thomas Metkus, Sonela Skenderi
Journal: Circulation (2023)

Introduction: The overall survival of cardiac arrest patients is very poor. There is a higher incidence of cardiac arrest on weekends especially on Saturdays as per national statistics. Also, hospitals experience reduced staffing on the weekends. We examined the outcomes of cardiac arrests on weekends compared to weekdays. Hypothesis: There is no difference in mortality in cardiac arrests which happen over the weekday compared to over the weekend. Methods: This retrospective cohort study used a national inpatient sample database to identify patients from 2016 to 2019 presenting with cardiac arrest on weekdays vs on weekends. SAS 9.3 was used for data analysis. The data were weighted to generate national estimates of the entire US hospitalized population. Results: Out of 57,300 patients who presented with cardiac arrest during the study period, 41,410 were on weekdays (72.2%; mean age 65.9; 56.2% males) and 15,890 were on weekends (27.8%, mean age 65.2; 56.7% males). Inhospital mortality was less on weekdays than on weekends (72.4% vs 76.2%). The younger age group (18-40 years) had a higher share of of cardiac arrest on weekends when compared to weekdays (8.2% vs 7.1%). Weekday admissions had a higher rate of prior MI (8.9% vs 7.6%) and a higher rate of comorbities including DM (39.4% vs 36%), CHF (32.2% vs 28.9%), Renal Failure (29.5% vs 26.6%), CAD (34.8% vs 31.7%). Weekend admissions had a higher rate of smoking history (16.9% vs 15.1%). All p values &lt;0.001. Conclusions: Cardiac arrest on weekends has a higher mortality rate compared to weekdays. We found a higher burden of comorbidities on patients with weekday cardiac arrest.
Abstract 14599: A Pilot Rheumatic Heart Disease Screening Program Using Portable, Handheld Echocardiography in Rivas, Nicaragua
Authors: Sugi Min, Bryan Carrillo, Kimberly Lopez, René Francisco Guido, michael yeung, Carlos Espinoza, Matthew Lawlor
Journal: Circulation (2023)

Introduction: Portable, handheld echocardiography offers several advantages for rheumatic heart disease (RHD) screening in low-resource settings. Analyses of focused protocols using handheld echocardiography have yielded acceptable sensitivity and specificity for diagnosis of RHD, including in those performed by non-expert sonographers. Previous studies estimate high burden of RHD in Nicaragua. We conducted a pilot community-based RHD screening program using handheld echocardiography in Rivas, Nicaragua using contemporary RHD diagnostic criteria. Methods: Non-expert sonographers were trained using the GE Vscan Extend TM device and a simplified version of the 2012 World Heart Federation criteria for diagnosis of RHD. Referral criteria for complete echocardiogram included the presence of a mitral regurgitant jet of &gt; 2.0 cm, aortic regurgitant jet &gt; 1.0 cm, or any morphologic abnormality of the mitral or aortic valve, as well as left ventricular dysfunction or significant congenital heart disease. Participants were recruited by convenience-based sampling in communities throughout Rivas, Nicaragua. Participants were notified at the point-of-care of need for complete echocardiogram. All studies were overread asynchronously by expert readers for diagnostic accuracy. Results: Between March 2022 and April 2023, 494 screening echocardiographic studies were performed and evaluated for diagnostic accuracy. The median age was 36.3 years (IQR 19.2, 56.2), 22% of participants were &lt;18 years of age, and 60% of participants were female. There were 17.6% of participants referred for complete echocardiogram at the point-of-care compared with 13.0% meeting referral criteria on expert review. Negative and positive predictive values for non-expert vs. expert assessment were 92.4% and 62.1%, respectively. Cohen’s kappa for inter-rater reliability was 0.338, suggesting fair agreement. Conclusions: This pilot program demonstrated the feasibility of a screening program for RHD in rural Nicaragua with non-expert sonographers. Lessons from this program are intended to inform future epidemiological studies to determine the population prevalence and longitudinal outcomes of RHD in this region.
Abstract 16327: Machine Learning-Based Prediction of Clinical Frailty Scale Based on Gait Analysis in Elderly Patients With Heart Failure
Authors: Motoki Nakao, Toshiyuki Nagai, Yoshifumi Mizuguchi, Yuki Takahashi, Takahiro Abe, SHIGEO KAKINOKI, Shogo Imagawa, Kenichi Matsutani, Takahiko Saito, Masashige Takahashi, Kenji Hirata, Takahiro Ogawa, Takuto Shimizu, Manabu Otsu, Kunihiro Chiyo, Toshihisa Anzai
Journal: Circulation (2023)

Background: Although frailty assessment is recommended for guiding treatment strategies and outcome prediction in elderly patients with heart failure (HF), most frailty scales are subjective, and the scores vary among raters. We sought to develop a machine learning-based automatic rating method/system/model of the clinical frailty scale (CFS) for patients with HF. Methods: We prospectively examined 358 elderly (≥75 years) with symptomatic chronic HF patients (mean age 82.3±5.2 years, left ventricular ejection fraction 58 [IQR 45-67]%) from six sites between January 2019 and September 2022. The CFS was evaluated based on the modified Delphi method by 10 independent trained cardiologists as the gold standard. We obtained body-tracking motion data using OpenPose ® , a deep learning-based pose estimation library, on a smartphone camera. Predicted CFS was calculated from 128 key features, including gait parameters, using the extremely randomized trees (ERT) model. To evaluate the performance of this model, we calculated Cohen’s weighted kappa and intraclass correlation coefficient (ICC) between the predicted and actual CFSs. The studied patients were divided into derivation (from a university hospital) and validation (from other five sites) cohorts. Results: In the derivation (n = 181) and validation (n = 177) cohorts, the ERT model showed sufficient agreement between the actual and predicted CFSs (kappa 0.864, ICC 0.864 and kappa 0.796, ICC 0.796, respectively) ( Figure ). During a median follow-up period of 421 (IQR 280-616) days, the higher predicted CFS was independently associated with a higher risk of all-cause death (HR 1.97, 95% CI 1.21-3.20) adjusted for the MAGGIC mortality risk prediction score, N-terminal pro-brain natriuretic peptide, and serum albumin levels. Conclusions: Machine learning-based algorithms that automatically rate the CFS are feasible, and the predicted CFS is associated with the risk of all-cause death in elderly patients with HF.
Abstract 13633: Modern Treatment Patterns in Incident Pulmonary Arterial Hypertension (PAH) Patients: Real-World Data From the Pulmonary Hypertension Association (PHA) Registry
Authors: Carly J Paoli, Noah Kime, Kayleen Williams, Gabriela Gomez-Rendon, Adriano Tonelli, Hector Cajigas, Stephen Mathai, Sarah L Khan, Sandeep Sahay
Journal: Circulation (2023)

Purpose: New 2022 European Society of Cardiology/European Respiratory Society PAH guidelines recommend treatment guided by a multi-parameter risk assessment. 1 Patients with low/intermediate risk without cardiopulmonary comorbidities should start dual PAH combination therapy; those with cardiopulmonary comorbidities should be reassessed early for rapid escalation to dual therapy. Initial triple therapy is recommended for high-risk patients. We examined use of dual and triple PAH therapy in the US (before guideline update). Methods: We used the Pulmonary Hypertension Association Registry (PHAR), a prospective US registry of pulmonary hypertension (PH) patients, enrolled within 6 months of their first outpatient visit at one of 54 participating PH care centers in the US, between Sep 2015-Jun 2022. We included adults (≥18 years at enrollment) with incident PAH (newly diagnosed and treated within 6 months of enrollment) and ≥1 follow-up clinic visit post baseline visit. Chronic thromboembolic PH patients were excluded. Results: We analyzed (descriptive statistics) 794 incident patients (baseline characteristics in Table 1). Treatment patterns at baseline (n=794)/last follow-up visit (n=610) were 289 (36.4%)/102 (16.7%) on monotherapy, 419 (52.8%)/314 (51.5%) on dual combination, 83 (10.5%)/179 (29.3%) on triple combination therapy, respectively. Mean time from enrollment to dual and triple combination therapy was 86.1 (standard deviation [SD]: 209.0) and 346.1 days (SD: 430.8), respectively. Conclusions: Among incident PHAR patients, half received initial dual and 10% triple upfront combination therapy. At last follow-up, most (&gt;80%) patients had escalated to dual/triple combination therapies. Clinical Implications: At PH care centers, most incident PHAR patients are escalated to dual and triple therapy (at last follow-up) per current guidelines. Reference 1. Humbert M, et al. Eur Heart J. 2022;43:3618-731.
Abstract 16079: Outcomes Among Heart Failure Patients With Non English Language Preference
Authors: Zara Latif, Tracy Makuvire, Anna Modest, Pablo A Quintero Pinzon, Rishi K Wadhera, Eli Gelfand, Fatima Rodriguez, Haider Warraich
Journal: Circulation (2023)

Introduction: Non-English Language Preference(NELP) has been associated with inequitable care with prior studies highlighting increased risk of readmissions and lower patient satisfaction with care. However, outcomes of patients with heart failure with reduced ejection fraction (HFrEF) who identify as NELP in the United States have not been previously reported. Aims: To evaluate clinical outcomes of HFrEF patients with NELP compared to English-speaking patients. Methods: We performed a single center propensity score matched retrospective cohort study of HFrEF patients who received care between 2010-2022. We compared 5-year mortality, guideline directed medical therapy (GDMT) utilization, length of stay, and readmissions between NELP and English-speaking HFrEF patients. In secondary analyses, we divided NELP by major language group (Spanish, Russian, Other). Results: Our cohort consisted of 2136 English-speaking patients (mean age 82 years, 42% female) and 961 NELP patients (mean age 83 years, 41% female). NELP HFrEF patients had higher rates of angiotensin converting enzyme inhibitor/angiotensin receptor blocker and sodium glucose cotransporter 2 inhibitor use compared to English speakers (Table). Unadjusted 5-year mortality among NELP patients was lower compared to English speakers with a hazard ratio of 0.8 (95% CI 0.68-0.94), but this difference was attenuated after adjusting for race.NELP patients were more likely to have ED visits (69% vs. 65%) but less likely to have inpatient admissions (82% vs 85%) (both p&lt;0.05). In our secondary analysis, Spanish speakers were more likely to be on more GDMT classes compared to English speakers while Russian speakers had increased risk of readmissions and longer length of stay compared to English speakers. Conclusions: NELP patients are heterogeneous with multiple group differences in GDMT use and admissions.Further research is needed to provide culturally-competent, equitable care for HFrEF patients.
Abstract 18602: A Rare Case of Ehrlichiosis Induced Myocarditis
Authors: Christopher Watson, Josue Sanchez, Jasmyn Atalla, Ritu Modi
Journal: Circulation (2023)

Description of Case: A 64-year-old female presented with progressively worsening shortness of breath, headaches, weakness, intermittent confusion, and persistent fevers. Laboratory work-up revealed leukopenia, thrombocytopenia, elevated transaminases, negative viral panel, and elevated CRP. Chest CT revealed ground glass opacities and bilateral interlobular thickening. TTE obtained was normal. She was started on empiric meningitis treatment. She was transferred to the ICU after becoming more hypoxic and hypotensive. Further history revealed recent tick exposure while visiting the eastern North Carolina woods. Doxycycline was started for suspected tick-borne disease on day 2 of her ICU stay. LP was non-revealing. Her course was complicated by development of inferolateral ST segment elevation on EKG. Initial troponin I level was 155.66 ng/mL peaking at 209.24 ng/mL (reference range &lt;= 0.03 ng/mL). Cardiac catheterization revealed no epicardial coronary disease. Repeat TTE showed a decreased LVEF at 25-30% and global hypokinesis. Cardiac MRI revealed evidence of an inflammatory myocardial process, myocardial edema and epicardial fibrosis. The patient had a positive Erhlichia chaffensis IgG antibody titer and Ehrlichia chaffensis DNA polymerase chain reaction was positive. She demonstrated improvement with continuation of doxycycline. Heart failure guideline directed medical therapy was initiated prior to her discharge. Discussion: Ehrlichia infections occur primarily in areas of south and central United States. Transient flu-like symptoms are the most typical manifestations, but more severe complications can occur such as meningoencephalitis, respiratory failure, coagulopathy, myocarditis and death. There are only a few documented cases of myocarditis due to Ehrlichia infections. If not recognized early, myocarditis can be a serious and fatal complication of ehrlichiosis, even in immunocompetent patients. A high level of suspicion for this should be kept in the differential for patients with cardiac manifestations presenting from endemic areas, especially during warmer seasons. Doxycycline therapy should be started promptly for clinical suspicion of Ehrlichia infection.
Abstract 15461: Proteomic Profiling Identifies Metabolic and Extracellular Matrix Markers That Predict MACE in Individuals With Type 2 Diabetes: An EXSCEL Substudy
Authors: Kristin M Corey, Maggie Nguyen, Megan E Ramaker, Harald Sourij, Michael Felker, Naveed Sattar, Robert J Mentz, Adrian F Hernandez, Jennifer Green, Rury Holman, Svati H Shah
Journal: Circulation (2023)

Background: Patients (pts) with type 2 diabetes mellitus (T2DM) are at greater risk for major adverse cardiovascular events (MACE; e.g. stroke, myocardial infarction, and cardiovascular death). Given marked heterogeneity of risk, better multi-marker models are required to improve risk prediction. Methods: We evaluated 5473 pts with T2DM in the EXSCEL trial of exenatide, a GLP1-RA, vs. placebo by profiling ~5000 proteins at baseline and 12 months. Multivariable Cox proportional hazards models (adjusted for age, race, sex, study treatment, BMI, eGFR, BP, HbA1c, CHF and CV disease) were used to test for association between individual proteins with MACE. Pathway analysis using gene set enrichment (GSEA) was performed and LASSO, elastic net, random forest, and gradient boosted decision tree models were used to predict MACE on a held-out test set (N=1094). Protein importance scores and coefficients were analyzed to determine proteins predicting MACE. Linear mixed models (LMM) were performed to assess treatment effect on protein levels. Results: Over a median of 3.2 (IQR 2.2-4.4) years, 813 (6.72%) pts experienced MACE. A total of 1278 individual proteins were associated with MACE (FDR adjusted p &lt;0.05). GSEA identified 8 pathways enriched in these proteins including fatty acid metabolism (p=0.01) and cardiac muscle contraction (p=0.04). LASSO outperformed other models in discrimination for MACE (AUC = 0.75) and prioritized tetranectin (an adipocyte secretory protein associated with insulin resistance and fibrinolysis) and fibulin-1 (a regulator of extracellular matrix) as highly predictive of MACE. Both proteins were highly associated with MACE in Cox proportional hazards models (tetranectin: FDR adjusted p=8.86e-26, HR = 0.11 (95%CI 0.07-0.16), fibulin-1: FDR adjusted p=6.72e-14, HR = 6.49 (95%CI 4.13- 10.19). LMM showed treatment modification in tetranectin levels (p=0.0018) with exenatide. Conclusions: Leveraging a large trial of a GLP1-RA in pts with T2DM, we identified proteomic models highly discriminative of MACE. Models using proteins involved in molecular pathways of fatty acid metabolism and cardiac contraction may have clinical utility in identifying higher risk pts and for understanding beneficial molecular mechanisms of GLP1-RA.
Abstract 14844: Coronary Artery System Dominance Influences the Distribution of Calcified Plaques in Coronary Tree
Authors: Leili Pourafkari, April Kinninger, Venkat Sanjay Manubolu, Hooman Fazlalizadeh, Keishi Ichikawa, Jairo Aldana, Sion Roy, Matthew J Budoff
Journal: Circulation (2023)

Introduction: Left dominant coronary system associates with worse prognosis likely due to less well-balanced myocardial perfusion. Larger proportion of coronary flow enters left coronary in left dominant systems potentially leading to higher shear stress. In left dominant coronary systems, resultant alterations in flow hemodynamics could affect development of calcified plaques in left anterior descending artery (LAD). Hypothesis: Coronary artery dominance with resultant alterations in blood flow hemodynamics in coronary arteries could affect the distribution of calcified plaques in the coronary tree Methods: We performed a large retrospective single-center cohort study, including consecutive patients who underwent CTA from September 2006 to December 2022 in Los Angeles, California to determine whether left dominant coronary anatomy was associated with higher LAD calcium percentage (LAD calcium score divided by total calcium score) compared to right dominant coronary system. Subjects with coronary artery calcium score (CAC) above zero were enrolled. Multivariable linear regression was used to evaluate the association between the LAD calcium percentage by subjects with left versus right coronary system dominancy. Results: Among the cohort of 9,560 subjects,6,796 subjects had with CAC above zero. The average age was 64.8±10.7 years, 68% male, and 9% had left dominant coronary systems. Controlling for age, gender, BMI, hyperlipidemia, hypertension, family history of cardiovascular disease and past smoking, those with a left dominant coronary system had 10.1% higher (CI 7.5%-12.8%, p&lt;0.001) percent of calcium localized in LAD than those with right dominant systems (Table 1) Conclusions: Coronary system dominance affects the distribution of atherosclerotic burden. Left dominant coronary system compared to right dominant coronary system is associated with higher percentage of calcified plaques localized to LAD.