tbuckley/cabot-search huggingface dataset:
Abstract 18795: Low Density Lipoprotein Cholesterol Levels at Baseline and the Need for Additional Non Statin Lipid Lowering Therapy for Attaining Lipid Targets in Patients Presenting With Acute Coronary Syndromes- A Retrospective Study
Authors: Akshyaya Pradhan, Ajit Pratap Singh, pradeep Rana, Monika Bhandari, Pravesh Vishwakarma, Abhishek singh, Ayush Shukla, Akhil Kumar Sharma, Gaurav K Chaudhary, Sharad Chandra, rishi sethi, Sudhanshu K Dwivedi
Journal: Circulation (2023)

Introduction: CAD is the leading cause of death globally, with more than 17.3 million deaths per year. Multiple modifiable and non-modifiable factors may contribute to cardiovascular risk; among them, LDL-C levels play a crucial role in the pathophysiology of ACS. Objectives: To study the baseline LDL in ACS patients and Predict the need for additional lipid lowering therapies other than high-dose statins for attaining LDL-C goals. Methods: This is a single-centre retrospective study analysing LDL-C levels at the time of admission for ACS. Results: A total of 1880 ACS patients were enrolled (75.3% STEMI &amp; 19.7% NSTEMI) with a mean age of 56±11.79 years (82% males).The mean LDL-C was 74.73mg/dL, with 79 % of patients having LDL less than 100 mg/dL and 89% of patients having LDL-C levels less than 130 mg/dL. Patients less than 40 years of age had a mean LDL of 88.01 mg/dL, while individuals over 60 years had 69.03 mg/dL (p- &lt;0.001). No significant correlation was observed between angiographic severity and LDL-C levels in 1259 patients who underwent coronary angiography. Most patients (96%) received high-dose statin (Atorvastatin 80 mg and Rosuvastatin 40 mg) on discharge. Considering the expected LDL-C reduction by 50 % with high intensity statins alone, the target LDL-C goals as prescribed by ESC guidelines (&lt; 55 mg/dl) and ACC/AHA guidelines (&lt; 70 mg/dl) would be attained by 79% &amp; 89% of patients respectively on follow up. With high intensity statin plus ezetimibe combination (with an expected 65% LDL-C reduction), 89% patients could achieve LDL-C goal by ESC guidelines criteria and &gt; 99% would attain LDL targets set by ACC/AHA guidelines. Conclusions: In this south Asian cohort of ACS patients, the LDL-C levels at presentation were lower compared to western studies and more than three quarters could potentially achieve their LDL-C targets by high intensity statin alone. The results could have potential implications for non-statin therapy utilization.
Abstract 17213: Machine Learning-Based Prediction of Type A Aortic Dissection
Authors: Juan Velasco, Mohammad Zafar, John A Elefteriades
Journal: Circulation (2023)

Background: Existing risk predictors of aortic dissection have certain limitations. We hypothesized that machine learning models trained on clinical, demographic, and anthropometric features can further improve the prediction of patient outcomes. Objective: This study aims to develop a machine learning model that predicts type A aortic dissection and can help clinical decision making. Methods: This cohort study used the Yale Aortic Institute database. The models incorporated variables spanning demographic, anthropometric, medical history, radiological, and laboratory domains. The models were trained and validated using stratified 10-fold cross-validation. Hyperparameters for each algorithm were tuned through grid-search on the training folds. The models were trained to optimize the area under the receiver operator characteristic curve (AUROC) and were assessed in a held-out test set. Results: A total of 2,109 patients were analyzed in our study. Among them, 271 were diagnosed with type A aortic dissection. The models demonstrated strong performance on the held-out test set. Specifically, the extreme gradient boosting decision tree model achieved an AUROC of 0.821, while the random forest model achieved an AUROC of 0.820. Importantly, these models outperformed the prediction of type A aortic dissection when based solely on the ascending aorta diameter, which had an AUROC of 0.549. Besides the ascending aorta diameter, the key predictors were age, weight, height, family history, smoking, bicuspid aortic valve, and hypertension. Conclusion: We developed a machine learning model that provides an individualized prediction of the development of type A aortic dissection. This approach provides an accessible, efficient, and remote tool to identify high-risk patients.
Abstract 14869: The Role of Female Sex Hormones in Dimorphism of the Immune System in Group 1 Pulmonary Hypertension
Authors: Patricia D Lima, Ruaa Al-Qazazi, Ashley Martin, Danchen Wu, Curtis Noordhof, Rachel E Bentley, Jeffrey Mewburn, Isaac Emon, Oliver Jones, Stephen L Archer
Journal: Circulation (2023)

Background: The right ventricle (RV) fails in pulmonary arterial hypertension (PAH) in part due to inflammation. In male PAH, RV CCR2 + macrophages induce inflammation via NLRP3 inflammasome. Since PAH males have worse outcomes, a cardioprotective role of the female sex hormones is suggested. Hypothesis: Ovariectomy (OVX) in females recapitulates the males’ disease severity by increasing RV inflammation. NLRP3 inhibition ameliorates RV function in male and OVX rats with monocrotaline (MCT)-induced PAH. Methods: PAH was induced with MCT (60mg/kg) in male, female, and OVX female Sprague Dawley rats. 10 days post-MCT, rats (n=6/sex) were treated with the NLRP3 inhibitor, MCC950 (6mg/Kg/day). Control and MCT rats were studied (n=4/sex/group). RV function was assessed by echocardiography and high-fidelity hemodynamics. Inflammatory (His48 lo CD43 lo CCR2 + ) monocytes were quantified via flow cytometry, RV macrophages (CD68 + CCR2 + ) and mitochondrial morphology were quantified by confocal microscopy. RV fibrosis and hypertrophy were measured. Results: MCT rats had higher RV systolic pressure (RVSP), reduced pulmonary artery acceleration time (PAAT), cardiac output (CO), and tricuspid annular plane systolic excursion (TAPSE) vs. controls (Table). The RV end-diastolic pressure (RVEDP) was high in MCT males, while RV-free wall thickening was reduced in males and OVX. MCC950 improved CO in MCT males but reduced RVSP in males and OVX. The number of CCR2 + inflammatory monocytes ( p=0.065 ) and RV macrophages ( p=0.007 ) was higher in MCT males. Fragmented mitochondria ( p=0.004 ), RV fibrosis ( p&lt;0.0001) and cardiomyocyte hypertrophy ( p&lt;0.0001 ) were present only in MCT males. MCC950 reduced fibrosis ( p=0.006 ) and hypertrophy ( p&lt;0.0001) in males. MCC950 tended to improve hemodynamics in OVX. Conclusion: RV inflammation is most severe in males, and female sex hormones are cardioprotective. Inhibition of the NLRP3 is beneficial in MCT males and trend to benefit OVX.
Abstract 13659: Prevalence of Diagnosed Atrial Fibrillation in the United States
Authors: Jean Jacques Noubiap, Janet J Tang, Justin T Teraoka, Thomas A Dewland, Gregory M Marcus
Journal: Circulation (2023)

Background: A study done in 1996-1997 predicted that there would be 3.3 million people with atrial fibrillation (AF) in the United States in 2020. However, contemporary estimates of AF prevalence in the US are lacking. Therefore, we estimated the minimum age-, sex-, and race-stratified prevalence of diagnosed AF in California, and the number of people with diagnosed AF in US. Methods: California’s Department of Health Care Access and Information databases were used to identify adults aged ≥ 20 years who received care in an ambulatory surgery unit, emergency department, or inpatient hospital in California between January 01, 2005, and December 31, 2019. AF was defined based on ICD-9 and ICD-10 codes. We estimated the cumulative number of people diagnosed with AF in California from 2005 to 2019 and accounted for interim mortality using social security death index data. We applied age- and sex-specific AF prevalence data in California to census information on the US population to estimate the number of people with diagnosed AF in US. Results: The estimated population prevalence of diagnosed AF in adults in California was 2.04% in 2019. It was higher in males than females (2.42% vs 1.73%, p &lt; 0.0001), and in Whites (3.82%) compared to Blacks (2.10%), Asian (1.13%), Hispanic (0.93%), &lt; 0.0001. This prevalence increased with age, from 0.04% in the 20-24 age group, to 21.48% in those aged ≥ 85 years. After accounting for deaths, there was an estimated 657,584 people with diagnosed AF in California at the end of 2019. We estimated that at least 5,955,806 people (53.0% males) had AF in the US in 2019. The number of males with AF was higher than females in all age groups, except in those aged ≥ 80 years. The number of affected people increased with age, from 8,074 in those aged 20-24 years, to 1,416,282 in those aged ≥ 85 years. Conclusion: The prevalence of diagnosed AF in the US is higher than previously estimated. More efficient prevention and treatment strategies are needed to curb the burden of AF in the US.
Abstract 17125: Cardiovascular Mortality Defines Severe RV Enlargement in Pre-Capillary Pulmonary Hypertension by a RV to LV Volume Ratio &gt;2.0
Authors: Mahad Raheel, Jiajun Guo, Yucheng Chen, Yuchi Han
Journal: Circulation (2023)

Introduction: Cardiac magnetic resonance imaging (CMR) is emerging as a non-invasive, prognostic tool in pulmonary arterial hypertension (PAH). The right ventricular (RV) end diastolic volume (EDV) to left ventricular (LV) EDV ratio measured by CMR is a parameter to evaluate RV size in relationship to the patient’s own LV and determine severity of dilation in patients with pulmonary arterial hypertension (PAH). An RVEDV/LVEDV greater than 2.3 has been proposed as a cutoff for severe RV enlargement in PAH based on mortality risk 1 . This study aims to confirm this cutoff in pre-capillary (pc) pulmonary hypertension (PH) patients using CMR and mortality data from two additional cohorts. Materials and Methods: In this retrospective study, we analyzed primary outcome cardiovascular mortality and CMR parameters in a database of patients from 2014 to 2021 with pcPH (mean pulmonary artery pressure &gt; 20mmHg, PCWP&lt;15 mmHg, WU≥ 3) determined by right heart catheterization (RHC) from Ohio State University (OSU) (n=42) and West China Hospital (WCH) (n=58). Patients with congenital heart disease, ischemic heart disease, valvular heart disease (moderate to severe AS, AR, MS, or MR), ECV &lt;20 or &gt;28, and WHO group II PH were excluded from the analysis. The optimal cutoff values to classify severe RV enlargement by RVEDV/LVEDV was determined by a receiver operating characteristic (ROC) curve using cardiovascular mortality. Results: The event rates for cardiovascular mortality among the OSU and WCH cohorts were 14/42 and 14/58, respectively. Altmayer identified the optimal cut-off as 2.32 (sensitivity = 87.5%; specificity = 87.0%, AUC=82%) 1 . An RVEDV/LVEDV of 2.01 was the optimal cutoff to predict cardiovascular mortality using the ROC analysis from the OSU cohort (sensitivity= 71.4%, specificity = 82.1%, AUC 80.1%). It was 2.46 from the WCH cohort (sensitivity = 64.3%, specificity = 86.3%, AUC 77.7%). When data from the OSU and WCH cohort were combined, the optimal cutoff was 2.1 (sensitivity = 71%, specificity = 72%, AUC 77.1%). Conclusions: Using data from three different populations of pcPH patients, an RVEDV/LVEDV of at least &gt;2.0 can be used to partition severe RV dilation using cardiovascular mortality.
Abstract 16865: Epicardial Adipose Tissue Density Predicts the Presence of Atrial Fibrillation and Its Recurrence After Catheter Ablation: Three-Dimensional Reconstructed Image Analysis
Authors: Minoru Nodera, Shota Kakehashi, Moe Mukai, Daisetsu Aoyama, Kanae Hasegawa, Hiroyasu Uzui, Hiroshi Tada
Journal: Circulation (2023)

Introduction: Epicardial adipose tissue (EAT) induces inflammation in the atria and is associated with atrial fibrillation (AF). Several studies have examined the relationship between EAT volume (EAT-V) and density (EAT-D) and the recurrence of AF after catheter ablation. However, the conclusions of these studies have not always been consistent, which might be due to the differences in the location and method of EAT measurement. Methods: This study included 43 consecutive patients who underwent catheter ablation for AF and 30 control patients with no documented history of AF who were matched for baseline characteristics. EAT-V and EAT-D around the entire heart, both atria, left atrium (LA), and right atrium (RA) were measured in detail using reconstructed three-dimensional (3D) EAT images from dual-source computed tomography before ablation. Results: None of the measurements of EAT-V differed significantly between patients with AF and controls or between patients with recurrent AF and those without. On the other hand, all measurements of EAT-D were higher in patients with AF than in controls (both atria, p&lt;0.001; RA, p&lt;0.001; LA, p=0.002). All EAT-D measurements were associated with the presence of AF. Among patients with AF who underwent ablation, all EAT-D measurements were higher in patients with recurrent AF than in those without. The difference was significant for EATRA-D (p=0.032). All atrial EAT-D values predicted recurrent AF (EATRA-D: hazard ratio [HR], 1.208; 95% confidence interval [95%CI], 1.053-1.387; p=0.007; EATLA-D: HR, 1.108; 95% CI,1.001-1.225; p=0.047; EATatrial-D: HR, 1.174; 95% CI,1.040-1.325; p=0.010). According to the ROC curve analysis, EATatrial-D&gt; –80.9 HU is associated with AF recurrence with 100% sensitivity and 58% specificity (AUC, 0.75; p&lt;0.05), and EATRA-D &gt; –80.9 HU could distinguish patients with AF recurrence with 86% sensitivity and 61% specificity (AUC, 0.76; p&lt;0.01). However, EATLA-D &gt; –85.3 HU had low accuracy (sensitivity, 100%; specificity, 33%; AUC, 0.65; p=0.209). Conclusion: For predicting the presence of AF, 3D analysis of EAT-D, rather than EAT-V, is useful. Peri-atrial EAT-D is responsible for recurrent AF after ablation and useful for predicting recurrent AF after catheter ablation.
Abstract 16556: Tafamidis: A Game Changer in Transthyretin Cardiomyopathy? A Systematic Review of Efficacy and Safety
Authors: Bilal Hussain, Mohammad Hamza, yasar sattar, Bansari Patel, David Song, Neel N Patel, Sanchit Duhan, Mustafa Sajjad Cheema, Minahil Naeem, Hafiza Hareem Waqar, Sharaad Lactana, M Chadi C Alraies
Journal: Circulation (2023)

Introduction: FDA approval of tafamidis as a treatment for Transthyretin cardiomyopathy (ATTR-CM) was preceded by demonstrating clinical efficacy and safety based on double-blind trials that showed reduction in mortality, and cardiovascular-related hospitalization. We conducted a systematic review to assess the safety and efficacy using present literature. Methods: 7 studies were included in this meta-analysis from PubMed and Embase comparing tafamidis treatment to no tafamidis for ATTR-CM. Mantel-Haenszel method was used to calculate pooled log odds-ratio (OR) for binary outcomes and Hedges’ g using inverse-variance method for continuous outcomes. Results: Tafamidis was associated with decreased odds of mortality (OR 0.55, 95% CI 0.42-0.73, I2=41%, p&lt;0.0001) and reduced CHF exacerbations (OR 0.71, 95% CI 0.51-0.99, I2= 0%, p= 0.04). While, CHR related hospitalizations (OR 0.35, 95% CI 0.07-1.67, I2= 87%, p= 0.19), atrial arrythmias (OR 0.98, 95% CI 0.67-1.42, I2= 0%, p= 0.9), change in left ventricular ejection fraction (OR 0.78, 95% CI -0.32-1.87, I2= 91%, p= 0.16), left ventricular end-diastolic diameter (OR -0.12, 95% CI -0.41-0.18, I2= 0%, p= 0.4), interventricular septal thickness from baseline (OR -0.26, 95% CI 0.56-0.04, I2= 0%, p= 0.08) were not statistically different for tafamidis compared to no tafamidis for ATTR-CM. Conclusion: Tafamidis treatment in ATTR-CM is associated with reduced all-cause mortality and CHF exacerbation. These observations are consistent with the ATTRACT trial supporting the efficacy of tafamidis in the treatment of ATTR-CM.
Abstract 18288: Mice Harboring a Novel De Novo Missense <i>RBFOX2</i> Variant Display Abnormal Heart Development
Authors: Talita Choudhury, Sathiyanarayanan Manivannan, David Gordon, Emily Cameron, Holly Girard, Katherine Myers, Peter White, Vidu Garg
Journal: Circulation (2023)

Hypoplastic Left Heart Syndrome (HLHS) is a complex form of congenital heart disease, characterized by severe underdevelopment of the left ventricle, stenosis or atresia of the mitral and aortic valves, and hypoplasia of the ascending aorta and aortic arch. Despite advances in surgical and palliative strategies leading to improved neonatal survival outcomes, HLHS is still associated with early mortality and long-term morbidity. Elucidation of HLHS etiology is compounded by its complex inheritance mechanism and heterogenous genetic landscape, with studies indicating a multigenic etiology. We performed exome sequencing on a parent-offspring trio in which the proband was affected with HLHS and identified a novel de novo missense variant in the gene, RBFOX2, that was bioinformatically predicted to be pathogenic. RBFOX2 belongs to a family of RNA-binding proteins that is broadly expressed in all tissues and regulates splicing and transcription of many targets, including those involved in heart development. In order to determine the in vivo pathogenicity of the RBFOX2 variant, we generated a knock-in mouse model harboring orthologous missense RBFOX2 variant using CRISPR/Cas9 technology. RBFOX2 KI/KI mice were found to be embryonic lethal. Morphological analysis revealed 100% of homozygous mutants exhibit gross developmental defects. Normal Mendelian ratios are found at E9.5 but homozygous mutants display severe growth retardation from E9.5 to E11.5. Histologic analysis demonstrated underdevelopment of the ventricular chambers starting at E9.5. Overall, these mutant mice, harboring a clinically relevant human HLHS variant in RBFOX2 , display highly penetrant hypoplastic hearts with significant growth retardation. The use of this new murine model will pave the way for better cellular and molecular characterization of the deficits in RBFOX2 function that contribute to HLHS.
Abstract 17943: Biomechanical Finite Element Analysis of Asymmetric Bicuspid Aortic Valve With Different Commissure Positionings for Repair
Authors: Matthew H Park, Yuanjia Zhu, Stefan Elde, Shin Yajima, Y Joe J Woo
Journal: Circulation (2023)

Introduction: While bicuspid aortic valves (BAVs) exist with a wide variety of phenotypes, type 1 valves that require surgery often present with varying levels of cusp fusion, raphe geometry, and commissure positioning angles. Regarding central coaptation angle, BAVs commonly present with asymmetry between fused and non-fused cusps, and surgical debate focuses on whether BAV repair should aim to minimize or accommodate for this asymmetry. We aimed to compare the hemostatic structural integrity of different commissure positionings for repair based on a BAV with an original 150° central angle. Methods: BAV models were designed based on literature of asymmetric valve geometry. The central angle of the pathological valve was 150°, which is common (Fig A). Two subsequent valve geometries were modeled to represent the repair conditions where commissure positioning forces result in central angles of 165° (Fig B) and 180° (Fig C). These models were matched with leaflet surface area and implemented with mechanical parameters of aortic leaflet tissues. Coaptation planes were modeled as encastre boundaries. A hemostatic pressure gradient was applied at 90 mmHg to mimic peak diastolic pressures, and Fusion360 was used for finite element simulations. Results: All three models showed maximum von Mises stresses in the belly regions of the fused leaflet (Fig A-C). Upon running the simulations, the 150° model showed maximum Von Mises stresses of 8103 Pa, the 165° model showed maximum stresses of 5405 Pa, and the 180° model showed stresses of 6116 Pa. Conclusions: By leveraging finite element models and computational biomechanics analyses, we were able to identify differences in BAV leaflet stresses based on alternate commissural positioning of an asymmetric BAV phenotype. Our finding suggests that peak diastolic leaflet forces may be minimized by focusing surgical BAV repair on a moderate reduction of leaflet asymmetry (i.e., 150° to 165°), without imposing perfect symmetry.
Abstract 16599: Deep Learning Prediction of Cardiac Chamber Enlargement on Chest Radiographs
Authors: David M Davila, Rashid Barnawi, Samira Masoudi, Amin Mahmoodi, Albert Hsiao, Lewis Hahn
Journal: Circulation (2023)

Background: Chest radiographs (CXRs) are the most commonly performed radiographic exam. The heart is routinely assessed on frontal CXRs using the cardiothoracic ratio (CTR) to identify cardiomegaly, but the predictive performance of CTR is limited by variability in patient position, lung volumes, and radiographic technique. Thus, CXR may miss a substantial proportion of patients with cardiac disease. Hypothesis: A deep learning (DL) algorithm can accurately identify cardiac chamber enlargement on CXRs and exceed the predictive performance of cardiothoracic ratio. Methods: Frontal CXRs (n=6,228 cases from unique patients, single-site, dated 2014-2022), obtained on the same day as transthoracic echocardiography (reference standard for cardiac chamber enlargement), were randomly grouped for DL model training (n=4,969), validation (n=627), and testing (n=634). A pre-trained EfficientNet-B6 convolutional neural network was modified to predict the presence of one or more enlarged cardiac chambers. The DL model's performance was benchmarked against manual CTR measurements by two radiologists on a random subset of 150 anteroposterior CXRs from the test set. Results: The DL model demonstrated an AUROC (Area under the Receiver Operating Characteristic curve) of 0.78 in the validation set and an AUROC of 0.79 in the unseen test set. The model achieved 73% accuracy, 77% sensitivity, and 67% specificity on the validation set and showed similar results on the test set with 72% accuracy, 77% sensitivity, and 64% specificity. The model outperformed manual CTR measurements for identification of chamber enlargement on the random subset of test set CXRs (AUROC of 0.85 vs. 0.75; p &lt; 0.006, Figure 1). Conclusion: The DL model significantly outperformed traditional CTR assessment for cardiac chamber enlargement on CXR. DL models may improve radiologist identification of cardiac disease on CXR and prompt formal cardiac evaluation.