tbuckley/cabot-search huggingface dataset:
Abstract 17102: Establishing Outcome-Based Severity Partitions for LV Dilation
Authors: Cecilia Wallace, Yuanwei Xu, Yangjie Li, Yucheng Chen, Yuchi Han
Journal: Circulation (2023)

Background: The 2015 American Society of Echocardiography chamber quantification guideline 1 included healthy population-based normal controls for left ventricular (LV) size, but not severity partitions due to the lack of data to support mild, moderate, and severe categories. In this study, we propose using adverse outcomes to define “severe” in non-ischemic dilated cardiomyopathy (DCM). Methods: 778 adults with DCM were enrolled prospectively and underwent CMR from June 2012 to August 2020 at West China Hospital and followed for a median of 49 months 2 . 72 healthy Chinese adults served as controls. We evaluated “severe” increase in LV end-diastolic volume indexed to body surface area (EDVi), LVEDV/right ventricular (RV) EDV, and “severe” decrease in LV ejection fraction (EF) using receiver operator characteristic (ROC) and area under the curve (AUC) analysis based on cardiovascular outcome. We defined “moderate” as control mean +½ the standard deviation (SD) distance between control mean and “severe” and “mild” as between control mean +2 SD and “moderate”. Results: Of 778 participants, 190 experienced heart failure death, sudden cardiac death, or heart transplant. For LVEDVi, the “severe” dilation cut point was 184 mL/m 2 , 10.9 SD from control mean (71 ml/m 2 ). Thus, “moderate” dilation starts at 128 ml/m 2 (control mean +5.4 SD) and “mild” starts at 92 ml/m 2 (control mean +2 SD). The LVEDV/RVEDV ratio partitions are similar to RVEDV/LVEDV partitions for pulmonary arterial hypertension 3 . It is well known that LVEDVi and LVEF have sex-based differences with females having smaller hearts and higher EF 4 . the volume ratio is slightly lower in females as compared to the males (Table 1). Conclusion: Severity of LV dilation and dysfunction based on LVEDVi, LVEF, and LVEDV/RVEDV can be determined by finding upper limits of normal, using outcomes to determine “severe” category, and using the SD distance between severe and control mean to determine mild and moderate categories.
Abstract 17638: Left Atrial Scar Burden Among Patients With Persistent Atrial Fibrillation Undergoing Catheter Ablation and Its Association With Patient Risk Factors and Risk of Recurrence
Authors: Matthew Pulaski, Christopher Thorne, Ian Ling, Allyson Varley, Victor Nauffal, Jose Osorio, Brahim Redouane, Esseim Sharma, Andrew Zadeh, Matthew J Singleton, Paul Zei, Ivan C Ho, Anil Rajendra, Junaid Zaman
Journal: Circulation (2023)

Introduction: Left atrial (LA) scar at time of catheter ablation (CA), assessed by bipolar voltage &lt;0.5mV may indicate more advanced AF substrate. It is not known which risk factors are associated with scar burden and whether this is linked to worse clinical outcomes. Hypothesis: We hypothesized that patient demographics and comorbidities are associated with greater scar burden at time of CA and predispose to AF recurrence. Methods: The Real-AF registry is a prospective, observational, multicenter registry of patients undergoing CA with follow-up at 6 and 12 months. LA scar burden was calculated from CARTO as total % LA area &lt; 0.50mV bipolar using the Pentaray catheter at first CA for persistent AF. We evaluated 1503 patients among this cohort using logistic regression modeling of age, sex, CHA2DS2-VASc and LVEF &lt;= 35%, BMI and their association with LA scar burden categorized as 0 to 5% vs &gt;= 6%. In 783 patients with 12-month clinical outcomes a Kaplan-Meier estimator was used to analyze risk of AF recurrence in these two cohorts. Results: Each additional year in age is associated with 1.07 greater odds (p&lt;0.001, 95% CI=1.05, 1.08) of scar area &gt;= 6%. Women had 2.08 greater odds (p&lt;0.001, 95% CI=1.63, 2.65) of abnormal scar area compared to men, while patients with CHF had 1.67 greater odds (p&lt;0.001, 95% CI=1.30, 2.16). Patients with LA scar burden &gt;= 6% experienced significantly higher recurrence of AF compared to those with a lower scar burden (HR=1.8, p=0.0094) including after controlling for operator-specific effects (HR=1.9, p=0.0088), see figure 1. Conclusions: In a large multicenter registry of persistent AF patients undergoing CA, LA scar &gt;=6% was associated with female sex, greater age, and CHF. An increased scar burden is associated with worse 12 month clinical outcomes from CA.
Abstract 15093: Serum Apolipoprotein-A2 Levels Are a Stronger Predictor of the Residual Cardiovascular Event Risk After Percutaneous Coronary Intervention
Authors: Takumi Akiyama, Ryutaro Ikegami, Naoki Kubota, Toshiki Takano, Shintaro Yoneyama, Takeshi Okubo, Makoto Hoyano, Kazuyuki Ozaki, Takayuki Inomata
Journal: Circulation (2023)

Introduction and Aim: Apolipoprotein-A2 (apoA2) is the second major apolipoprotein that constitutes high-density lipoprotein cholesterol (HDL-C) particles, following apolipoprotein-A1 (apoA1). HDL-C can be divided into two main subfractions: those containing both apoA1 and apoA2, and those containing only apoA1. It is believed that HDL-C particles with apoA2 exhibit superior functionality in lipid metabolism compared to those without apoA2. However, the clinical impact of apoA2 on future cardiovascular events in patients who have undergone percutaneous coronary intervention (PCI) remains unclear. The aim of our study is to test the hypothesis that apoA2 would be a stronger predictor of residual cardiovascular risk compared to other apolipoproteins in the statin era. Methods: We examined 638 patients who underwent PCI with a second-generation drug-eluting stent for acute or chronic coronary syndrome and had their apolipoproteins measured between 2016 and 2021 (median follow-up period of 17.7 months). The patients were divided into two groups based on the median serum apoA2 values. We assessed the incidence of major adverse cardiovascular events (MACEs), including cardiovascular death, non-fatal acute coronary syndrome, ischemic stroke, exacerbation of heart failure, or target vessel revascularization. Results: A total of 563 patients (88%) received statin treatment, and the median serum low-density lipoprotein cholesterol was 93 mg/dL. A total of 138 patients (21.6%) experienced MACEs, and Kaplan-Meier analysis revealed that the lower apoA2 group had a significantly higher incidence of MACEs compared to the higher apoA2 group (23.6% vs. 19.7%, p=0.036). However, the other apolipoproteins, including apolipoprotein-A1, B, C2, C3, or E, showed no significant difference in MACEs. Multivariate Cox hazard analysis indicated that apoA2 was an independent predictor of MACEs (hazard ratio 1.51; 95% confidence interval 1.06-2.14, p = 0.022). Furthermore, apoA2 levels exhibited the strongest inverse association with high-sensitivity C-reactive protein levels (ρ= -0.48, p&lt;0.0001). Conclusions: Serum apoA2 level may be the strongest predictor of residual cardiovascular event risk after PCI among apolipoproteins.
Abstract 15854: Pulmonary Arterial Waveform Analysis and Supervised Machine Learning Predicts Outcomes in Heart Failure: An Analysis of the CHAMPION Trial
Authors: Katherine Kearney, Alexander Padayachee, Audrey Adji, Edmund Lau, Christopher S Hayward
Journal: Circulation (2023)

Introduction: Pulmonary artery (PA) pressure monitors have been shown to prevent hospitalizations in heart failure patients using mean pressure values. PA waveform analysis offers an overall assessment of right ventricular load that combines resistance and compliance. Hypothesis: We hypothesised that clinical outcomes can be predicted from PA waveform analyses from patients with an implanted PA monitor. Methods: The CHAMPION trial database was analysed. Information about the demographics and data collection methods for this cohort have been published previously. All waveforms were analysed automatically using Python. Tau or RC time, respiratory rate, respiratory range, P asymptote, mean pulmonary arterial pressure (mPAP), diastolic pulmonary arterial pressure (dPAP) and systolic pulmonary arterial pressure (sPAP) were derived from the raw waveforms. Tau and P asymptote were calculated using phase plane analysis. Outcomes of hospitalization or mortality were adjudicated as part of the original trial. Statistics were performed in R. A decision tree statistical approach using the XGBoost algorithm was used. Contribution to the model was assessed using Shapley Additive Explanations (SHAP) values. The dataset was split into 70% train and 30% test sets. Results: 296,948 PA pressure traces from 547 patients were analysed. 3 patients had insufficient quality of trace to analyse. There were 1340 outcome events throughout the follow up period, median 664 days. The trained algorithm was able to predict clinical outcomes in the test dataset with 100% accuracy. The most significant contributors according the mean SHAP value were RC time (SHAP = 1.1), respiratory range (SHAP = 1.1) and heart rate (SHAP = 1.1). Conclusions: Detailed analysis of the PA waveform from PA pressure monitors is feasible and yields clinically relevant information. A supervised machine learning algorithm trained on this data can accurately predict hospitalization or mortality events in heart failure patients.
Abstract 14518: Interactive Effects of Statins, Obesity, and Cardiorespiratory Fitness in Type 2 Diabetes Mellitus Incidence
Authors: Peter F Kokkinos, charles J faselis, Jonathan Myers, Immanuel B Samuel, Carl J LAVIE, Jared Gollie, Michael J Lamonte, Andreas Pittaras, Sabyasachi Sen, Eric Nylen
Journal: Circulation (2023)

Introduction: Statin therapy and obesity are associated with increased risk of developing type 2 diabetes mellitus (T2DM). Conversely, cardiorespiratory fitness (CRF) is inversely related to T2DM incidence. The interaction between statin therapy, obesity, and CRF has not been addressed. Hypothesis: Obesity and statins will be associated with increased risk of T2DM, while CRF will mitigate this increased risk. Methods: From the ETHOS cohort, we identified 570, 054 patients (age 60.7±10.1 years) with no T2DM. All completed a standardized exercise treadmill test (ETT) with no evidence of ischemia. Subsequently, 322,805 (56.6%) were treated with statins for at least 8 months (mean 9.5±5.9 years) and 247,249 were not. Participants were classified based on body mass index (BMI) as normal weight (BMI&lt;25.0 kg/m 2 ), overweight (BMI 25.0-29.9 kg/m 2 ), Obese-I (BMI 30.0-34.9 kg/m2), and Obese-II (BMI ≥35.0 kg/m 2 ). We established five CRF categories based on age-specific quintiles of peak metabolic equivalents achieved: Least-Fit (n=95,071); Low-Fit (n=133,404); Moderate-Fit (n=110,973); Fit (n=158,004) and High-Fit (n=72,602). Adjusted Cox proportional hazards models were constructed to evaluate the association between BMI, statin therapy and T2DM risk, and the interaction with CRF status. Results: During the follow-up period (median 10.3 years), 44,662 developed T2DM (7.4 events/1,000 person-years of observation). The risk of developing T2DM was 44% higher in those treated with statins [Hazard Ratio (HR) 1.44; 95% confidence interval (CI) 1.41-1.48)] compared to those not on statin therapy. The risk increased progressively with higher BMI levels and was nearly 3 times higher for those in the Obese-II category (HR 2.96, CI 2.85-3.06). When T2DM risk was assessed across CRF categories within BMI groups, we noted a progressive decline in T2DM risk with increased CRF regardless of statin therapy or BMI status. The adjusted risk was approximately 25% to 40% lower for those in the two highest CRF categories. Conclusions: Statin therapy and obesity were associated with increased risk of developing T2DM. This risk was mitigated significantly with increased CRF regardless of BMI status.
Abstract 13519: US Population Eligibility and Estimated Impact of Tirzepatide on Obesity Prevalence and Preventable Cardiovascular Disease Events in US Adults
Authors: Nathan D Wong, Hridhay Karthikeyan, WENJUN FAN
Journal: Circulation (2023)

Background: Tirzepatide, a novel GIP-GLP-1 receptor agonist therapy, has been shown to be beneficial for weight loss and reduction of cardiovascular disease (CVD) risk factors in adults with obesity in the SURMOUNT-1 trial. We estimated US population eligibility for tirzepatide and the impact on reduction of CVD events in US adults with obesity. Methods: We applied SURMOUNT-1 eligibility criteria (body mass index [BMI] &gt; 30 kg/m 2 or BMI &gt; 27 kg/m 2 with at least one risk factor or CVD, excluding diabetes) to US adults aged &gt; 18 years in the US National Health and Nutrition Examination Survey (NHANES) 2015-2018 to estimate the US eligible population using NHANES sample weighting. Tirzepatide 15 mg group weight changes in the SURMOUNT-1 trial were applied to estimate the population impact on weight and obesity, and in those aged 30 to 74 years without prior CVD, the estimated 10-year CVD risks utilizing the BMI-based Framingham CVD risk scores. The difference in the estimated risks with and without tirzepatide “treatment” multiplied by the eligible weighted population represented the estimated “preventable” CVD events. Results: We identified 4015 US adults weighted to an estimated population size of 93.4 million [M] (38% of the US adult population) who fit SURMOUNT-1 trial eligibility criteria, of which 51% were female and 89% were without prior CVD. Applying tirzepatide 15 mg SURMOUNT-1 treatment effects on weight loss resulted in an estimated 70.6% (65.9 M) and 56.7% (53.0 M) showing &gt; 15% and &gt; 20% weight reductions, respectively, translating to a 58.8% (55.0 M) reduction in obesity (BMI &gt; 30 kg/m 2 ) prevalence and 36.4% (34.0 M) increase in normal weight (BMI &lt;25 kg/m 2 ) prevalence among the eligible population. Among those without CVD, estimated 10-year CVD risks were 10.1% “before” and 7.8% “after” tirzepatide “treatment” reflecting a 2.3% absolute (and 23% relative) risk reduction (number needed to treat [NNT]=43) translating to an estimated 1.95 million preventable CVD events over 10 years. Conclusions: Tirzepatide treatment in eligible US adults may reduce obesity prevalence nearly 60% representing 55M adults and prevent up to 2M CVD events over 10 years, suggesting a dramatic impact on societal burden and healthcare costs in those with these conditions.
Abstract 18799: <i>Edn1</i> is a Disease-Specific Marker in Endothelial Cells During Atherosclerosis
Authors: Danielle Dy
Journal: Circulation (2023)

Introduction: Coronary artery disease (CAD) is the leading cause of mortality in the United States. Multiple cell types contribute to the atherosclerotic plaques causing CAD, influencing its growth and propensity to rupture. Endothelial-to-mesenchymal transition (EndMT), the process by which endothelial cells (ECs) acquire characteristics of mesenchymal cells and loose canonical endothelial features, is correlated with an unstable plaque phenotype, although this transition remains poorly characterized. Hypothesis: A specific population of ECs may undergo EndMT, potentially contributing to the progression of atherosclerosis. Methods: We induced endothelial-specific lineage-tracing in Tg Cdh5-CreERT2 , ApoE -/- mice, followed by 16 weeks of high-fat diet (HFD) to produce atherosclerosis. Aortic roots were collected from male and female disease-condition animals (n=13) and a baseline cohort that was not fed HFD (n=6). Single cell RNA sequencing was performed and analyzed using the Seurat package. RNAscope staining of transverse sections (n=10 per genotype per sex) was performed to characterize the lesion. Results: We identified multiple endothelial subtypes within the aortic root. One population, characterized by the marker Klk10, appears to give rise to a disease-specific population characterized by expression of Edn1. Upstream regulator analysis of differentially expressed genes between Edn1+ and Klk10+ populations predict this EC transition to be driven by EndMT-associated transcription regulators including SNAI2, TWIST2, STAT3, SNAI1, YAP1, and TEAD2. This analysis also predicted upregulation of pulmonary fibrosis idiopathic signaling, wound healing signaling, pathogen induced cytokine storm signaling, and hepatic fibrosis signaling pathways. This EndMT process, characterized by a single, linear trajectory, was the only disease-associated EC transition state identified in the atherosclerotic aortic root. Conclusions: We identified ECs undergoing EndMT in a mouse model of atherosclerosis and determined that this transition is the primary EC cell state transition during disease. We localized this process in situ in the atherosclerotic lesion and identified potential key transcriptional drivers of this process.
Abstract 13200: Changes in Thrombi-Inflammatory Biomarkers Associated With Therapeutic Heparin in Non-Critically Ill Patients Hospitalized With COVID-19: A Pre-Specified Secondary Analysis of the ACTIV4a and ATTACC Randomized Clinical Trial
Authors: Lana Wahid, MD, Joshua Froess, Thomas L Ortel, Ryan Zarychanski, Michelle N Gong, Mary Cushman, Lucy Kornblith, Lana Castellucci, Michael E Farkouh, Ewan Gologher, Bryan J McVerry, Grant V Bochicchio, Abhijit Duggal, Yonatan Greenstein, Nicholas Hanna, Kristin Hudock, David T Huang, Robert Hyzy, Akram Khan, Vidya Krishnan, Matthew Kutcher, George Lim, Jose Luis Lopez-Sendon Moreno, Michael A Matthay, Ambarish Pandey, John Quigley, Lewis Satterwhite, Robert J Widmer, Jenny Jenny Wilson, Judith S Hochman, Jeffrey S Berger, Matthew D Neal, Patrick R Lawler
Journal: Circulation (2023)

Background: SARS-CoV-2 infection potentiates thromboinflammation contributing to poor outcomes in COVID-19. In non-critically ill patients hospitalized for COVID-19, therapeutic-dose heparin improves clinical outcomes. We hypothesized therapeutic-dose heparin impacts thromboinflammatory biomarkers in patients hospitalized for COVID-19 infection. Methods: We conducted a pre-specified secondary analysis of a multi-platform open-label, randomized trial comparing therapeutic-dose versus usual-care thromboprophylaxis-dose heparin in non-critically ill patients hospitalized for COVID-19. Inflammatory markers were analyzed using Wilcoxon rank-sum test and compared based on treatment. Ordinal logistic regression models evaluated for relative D-Dimer change (measured at baseline, day 1, day 3). Odds ratio of a 3-level ordinal outcome (death, survival with organ support, or survival without organ support through 21 days) was determined for relative change. Results: Of 1510 patients, 528 had a D-Dimer on baseline and day 1, and 432 on baseline and day 3. Median age was 60 years (IQR: 50-69) with 41% female and 66% under-represented minorities. Compared to usual-care, therapeutic-dose heparin was associated with a greater drop in D-Dimer at days 1 and 3; other biomarkers were unaffected by treatment (Table 1). D-Dimer at baseline and day 1 had an OR 0.93 (95% CI: 0.88, 0.98) whereas baseline and day 3 had an OR 0.86 (95% CI: 0.78, 0.94) of the ordinal outcome translating in a higher odds of surviving without the need for organ support (adjusted for treatment, gender, and age). Conclusion: In this randomized controlled trial therapeutic-dose heparin was associated with an early reduction in D-Dimer and clinical improvement, suggesting thromboinflammatory mechanisms whereby treatment conferred a clinical benefit. Temporal changes in D-dimer could predict treatment response or may signal need for alternative therapies.
Abstract 17853: Efficacy of Grace Score for Prediction of Mortality in Patients of Acute Coronary Syndrome: A Meta-Analysis
Authors: Jawad Basit, Zaofashan Zaheer, Farah Yasmin, Laiba Khan, Huzaifa Ahmad Cheema, Mohammad Hamza, Muhammad Aamir, Usman Akbar, kuldeep dhama, Shanjeev Kumar K Rajeshkumar Chitra, Sajeel Saeed, Mohammad E Rehman, Jahanzeb Malik, Sardar Muhammad Alamzaib, yasar sattar, M Chadi C Alraies
Journal: Circulation (2023)

Introduction: The Global Registry of Acute Coronary Syndrome (GRACE) is a validated risk prediction model for acute coronary syndromes (ACS). However, discrimination ability of this model for predicting mortality in ACS remains unclear. The aim of this meta-analysis is to determine the predictive accuracy of GRACE score for mortality in ACS patients. Methods: A comprehensive literature search was conducted across MEDLINE, Embase &amp; the Cochrane Library from inception till May 2023. All studies that reported the C-statistic for predicting in-hospital, 6-month, 1 year &amp; 2-year mortality in ACS patients were included. The generic inverse variance weighted random effects method was used to pool C-statistics &amp; corresponding standard errors (SEs) from each study. Subgroup analysis was conducted based on whether the patients required percutaneous coronary intervention (PCI) or not. Results: A total of 22 studies with a patient population of 132856 were included. For in-hospital mortality (n=99774), the GRACE score showed a good discrimination ability to predict mortality (summary C-statistic 0.86 [0.85-0.87], I 2 =58%). The pooled C-statistic for 6-month mortality (n=24174) was 0.80 (0.70-0.84; I 2 =93%). For 1-year mortality (n=13517), the predictive accuracy of the GRACE score was moderate (summary estimate= 0.77 [0.70-0.83]; I 2 =94%). The GRACE score proved to be moderately accurate in predicting 2-year mortality (n=4972) in ACS patients [0.75 (0.66-0.83); I 2 =66%]. All the findings were consistent across the two subgroups of PCI vs no PCI (p for interaction &gt;0.05). Conclusion: The GRACE score is a simple scoring system that demonstrated good predictive ability for in hospital mortality, &amp; at 6-months while moderate predictive ability for the risk of death at 1-year, &amp; 2-year in patients of ACS with &amp; without PCI.