tbuckley/cabot-search huggingface dataset:
Abstract 4143921: Adaptation of Prompt-enabled Segment-Anything-Model Enhance the Accuracy and Generalizability of Cine Cardiac Magnetic Resonance Segmentation
Authors: Zhennong Chen, SEKEUN KIM, Hui Ren, Sunghwan Kim, Siyeop Yoon, Quanzheng Li, Xiang Li
Journal: Circulation (2024)

Introduction: Accurate segmentation of cine cardiac magnetic resonance (CMR) throughout the cardiac cycle is essential for comprehensive cardiac functional analysis. However, current deep-learning (DL) approaches often suffer from reduced accuracy on unseen datasets due to generalizability issues. The Segment-Anything Model (SAM) is a new prompt-enabled segmentation foundation model trained on one billion natural images, known for its generalizability and user-defined prompts. Hypothesis: Adapting SAM for cine CMR segmentation can improve accuracy and generalizability on previously unseen CMR data. Methods: We adapted SAM for cine CMR segmentation by incorporating a temporal attention mechanism to maintain temporal consistency across the cardiac cycle and parameter-efficient transfer learning to segment the left ventricle (LV) and myocardium (MYO). User-defined bounding box prompts were used around MYO at end-diastole and end-systole phases to guide the segmentation region. The model can output segmentations for all phases throughout one cardiac cycle at once. We evaluated the model using a multi-center, multi-vendor (M&amp;M) international dataset of 136 cine CMR cases, which was unseen during model training.The trained model was applied to this dataset without fine-tuning to assess generalizability. We compared SAM with three state-of-the-art (SOTA) cine CMR DL segmenters. Segmentation accuracy was evaluated using the Dice coefficient. Clinical parameters, including LV end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF), were compared between manual and automatic measurements. Results: The adapted SAM with box prompts demonstrated superior generalization compared to SOTA methods (p&lt;0.01 by one-sided Wilcoxon test). The Dice coefficient was 0.937±0.024 for LV and 0.870±0.029 for MYO, with no significant differences across different centers and vendors, except for one center. The agreement for LVEDV and EF was high, with r = 0.995 and bias = 4.21±6.75 ml for LVEDV and r = 0.97 and bias = -0.50±3.75% for EF. Using bounding box prompts around the MYO region enhanced its segmentation accuracy from 0.853±0.032 to 0.870±0.029 (p&lt;0.05) compared to no prompts. Conclusion: Adapting SAM with box prompts enhances accuracy and generalizability in cine CMR segmentation..
Abstract 4143932: Exploring P300/CBP as therapeutic approach for right ventricular dysfunction in PAH
Authors: Alice Bourgeois, Sarah-Eve Lemay, Yann Grobs, Charlie Theberge, Melanie Sauvaget, Sandra Martineau, Megan Gilbert, Sandra Breuils Bonnet, Francois Potus, Steeve Provencher, Olivier Boucherat, Sebastien Bonnet
Journal: Circulation (2024)

Pulmonary arterial hypertension (PAH) is characterized by vascular obstruction leading to progressive elevation of pulmonary artery pressure. In the face of pressure overload, the right ventricle (RV) initially compensates (adaptive hypertrophy), but ultimately transitions to a decompensated state (marked by cardiomyocyte apoptosis and fibrosis), leading to premature death. The histone acetyltransferases P300/CBP have been identified as key pathogenic factors promoting the activation of a fetal gene program, supporting vascular remodeling in the lungs of PAH patients. Previous studies have also implicated P300/CBP in the control of pathological cardiac hypertrophy and fibrosis. However, their role in RV failure associated with PAH has never been explored. We hypothesized that P300/CBP contribute to maladaptive RV remodeling in PAH and thus represent a potential therapeutic target. We show by Western blot (WB) and immunofluorescence (IF) that P300 expression is upregulated in compensated and decompensated RV from PAH patients, monocrotaline (MCT)- and pulmonary artery banding (PAB)-exposed rats (p&lt;0.05), whereas CBP expression remains unchanged. RV fibroblasts (RVfbs) isolated from compensated or decompensated RV display a pro-fibrotic phenotype (increased COL, Fn, MMP and aSMA expression, WB p&lt;0.05) associated with an increase in P300/CBP expression (WB, p&lt;0.01). In vitro, pharmacological (CCS-1477) or molecular (combined siRNA) inhibition of P300/CBP decreases proliferation/survival (WB PCNA, Survivin, p&lt;0.05) and activation (WB pSMAD2/3, aSMA, Fn, Col1, MMP2, p&lt;0.05) of RVfibs. These effects were associated with a reduction in H3K27 acetylation (WB, p&lt;0.05). In addition, P300/CBP inhibition prevents phenylephrine-induced hypertrophy in H9C2 cells and in isolated adult rat cardiomyocytes (IF, p&lt;0.05). Using human precision-cut RV slices stimulated with phenylephrine and TGFb, we show that P300/CBP inhibition attenuates fibrosis [Masson’s trichrome staining (MT), p&lt;0.05] and cardiomyocyte (CM) hypertrophy [hematoxylin and eosin staining (HE), p&lt;0.05]. In vivo, administration of CCS-1477 in a PAB rat model reduces fibrosis (MT, p&lt;0.05), CM surface area (HE, p&lt;0.01), and improves RV function (TAPSE, cardiac output, stroke volume, p&lt;0.05). Our finding provide evidence that targeting P300/CBP may represent a promising avenue to counter maladaptive RV remodeling in PAH.
Abstract 4143815: Structural, Hospital, and Clinical Factors Do Not Completely Explain Major Lower Limb Amputation Disparities among Patients Hospitalized with Peripheral Artery Disease
Authors: Katharine McGinigle, Corey Kalbaugh, Samantha Minc, Paula Strassle
Journal: Circulation (2024)

Background: Racial and ethnic disparities in major lower limb amputation (MLLA) in patients with peripheral artery disease (PAD) are well documented. Rural/urban differences have also been observed. Disparities in the prevalence of PAD, progression to chronic limb-threatening ischemia, and access to vascular centers and revascularization may explain observed differences. Research Question/Hypothesis: Are MLLA disparities still present after accounting for clinical presentation, hospital characteristics, and social drivers of health? We hypothesized that race, ethnicity and rurality differences in MLLA rates would disappear after accounting for these factors. Methods: We conducted a retrospective cohort study of 2017-19 PAD-related hospitalizations in adults ≥40 years old living in Florida, Georgia, Maryland, Mississippi, and New York using HCUP State Inpatient Databases, which include all community hospital admissions in each state, regardless of insurance status. Patients were excluded if they were not a resident or if they were admitted for lower limb trauma, malignancy, or non-vascular wounds. We used machine learning (LASSO) to predict the probability of revascularization and MLLA for each hospitalization, using clinical presentation, chronic conditions, hospitalizations and surgery within past year, hospital characteristics, and social drivers of health. We calculated observed-to-expected (O/E) ratios across race, ethnicity, and rurality. Bootstrapping (n=1000) was used to estimate confidence intervals. Results: 1,577,061 hospitalizations (990,152 patients) were included; there were 100,549 revascularizations (6.4%) and 21,233 MLLA (1.4%). No meaningful disparities were seen for revascularization. More than expected MLLA were performed in Black patients, both rural (O/E:1.26, 95% CI:0.98-1.54) and non-rural (O/E:1.12, 95% CI:1.09-1.15), and rural Hispanic patients (O/E:1.50, 95% CI:0.89-2.12), Fig . Conclusions: Even after accounting for clinical, hospital, and structural factors, MLLA disparities were observed among Black and rural Hispanic patients. These results suggest other factors, such as implicit bias in healthcare, play a role in the elevated limb amputation rates in minority and rural patients.
Abstract 4143936: More Than a Portion of Probiotics a Day is Associated with a Decreased Likelihood of Having Hypertension
Authors: Ben Thiravetyan, Tulaton Sodsri, Vitchapong Prasitsumrit, Terasut Numwong, Sireethorn Wonghanchai, Nutchapon Xanthavanij, Watsachon Pangkanon, Prin Vathesatogkit
Journal: Circulation (2024)

Background: Probiotic consumption may have the potential to improve blood pressure in patients with hypertension. However, there is limited evidence regarding the specific daily dosage of probiotics that is directly associated with a reduced probability of hypertension occurrence in the general population. Aim: The study aims to evaluate the relationship between the amount of probiotics consumed per day and hypertension. Methods: A cross-sectional analysis of data from a survey of employees at the Electricity Generating Authority of Thailand (EGAT) was conducted. Baseline characteristics, hypertension status, and probiotic consumption were collected in 2017. Two tablespoons of kimchi or pickles, 200 mL of fermented milk, or 200 mL of yogurt constitute one portion. The mean portion per day was calculated by summing up all the probiotics consumed per day. Logistic regression models comparing participants among the non-probiotic group, the less than one portion of probiotics per day group (&lt; 1 portion/day), and the more than one portion of probiotics per day group (≥ 1 portion/day) were analyzed to explore the association between the amount of probiotic consumption and hypertension. Results: The study included 1218 participants. The mean (SD) age was 73.3 (4.3) years, with 870 (71.4%) being male and 1014 (83.2%) having hypertension. Of all, 545 (44.7%) were non-probiotic users, 539 (44.3%) were using &lt; 1 portion/day, and 134 (11.0%) were using ≥ 1 portion/day. For the ≥ 1 portion/day group, after univariate analysis, individuals were statistically 0.56 times less likely to have hypertension compared to those in the non-probiotic group, while those in the &lt; 1 portion/day group did not meet statistical significance. Multiple logistic regression analysis also demonstrated that consuming ≥ 1 portion/day of probiotics was significantly associated with a decreased likelihood of having hypertension, with an odd ratio of 0.55 (95%CI 0.31-0.96). Conclusion: Consuming ≥ 1 portion/day of probiotics is associated with a decreased likelihood of having hypertension. Further studies with larger sample sizes are required to determine the optimal amount of probiotic intake as a supplementary treatment for hypertension.
Abstract 4143958: NADPH oxidase-4 is an early driver of cardiac myofibroblast differentiation and cellular senescence in dilated cardiomyopathy
Authors: Samuel Berhanu, Andrew Antolic, Yoon Shin, kosuke kato, Jennifer Kleinhenz, Zhe Jiao, Louise Hecker, Michael Burke
Journal: Circulation (2024)

Background: Myofibroblasts mediate tissue fibrosis and are a driver of disease progression in heart failure (HF). Reactive oxygen species (ROS) generated by NADPH oxidase-4 (NOX4) are required for transforming growth factor-beta (TGFb)-induced myofibroblast activation. Therapeutic targeting of NOX4 inhibited fibrosis development and reversed existing fibrosis in an aging model of lung fibrosis. However, the cell-specific roles of NOX4 in the heart have not been fully explored. Objective: We sought to define the cardiac cell-type specific expression and role of NOX4 activation in the progression to HF. Methods: Mice carrying a mutation in the phospholamban gene (PLNR9C) develop progressive dilated cardiomyopathy (DCM), fibrosis and HF. Cardiac cells were isolated using the Langendorff hanging heart method followed by flow cytometry. Single nucleus RNA-sequencing (snRNA-seq) was performed to define cell-specific gene expression. Immortalized mouse cardiac fibroblasts were treated with TGFb to establish longitudinal gene expression patterns with differentiation to myofibroblasts. Results: Nox4 was upregulated in hearts (mRNA 8.5-fold; protein 3.1-fold; n=4, p&lt;0.01) and isolated cardiac fibroblasts (mRNA 6.1-fold; protein 2.5-fold; n=3, p&lt;0.01) from PLNR9C mice with HF but not age-matched wild type (WT) mice or young PLNR9C mice prior to the onset of DCM. Using snRNA-seq, we identified fibroblasts as the primary cell type expressing Nox4 in the heart in WT and PLNR9C mice; notably there was almost no expression of Nox4 in cardiomyocytes. This was consistent with published data in mouse heart analyzed from the NCBI GEO database. Fibroblasts from PLNR9C hearts with DCM had elevated ROS levels (Amplex Red assay 2.5-fold, p&lt;0.01, n=3) and displayed a senescent phenotype, with elevated levels of the senescence markers p16 (2.1-fold, p&lt;0.01, n=3) and b-galactosidase (1.7-fold, p&lt;0.01, n=3), compared to fibroblasts from age-matched WT mice. In immortalized cardiac fibroblasts activated with TGFb, Nox4 increased 12 hours prior to expression of myofibroblast-specific genes (Postn, Col3a1). Co-treatment with siRNA targeting SMAD3 or the bromodomain and extraterminal (BET) inhibitor JQ1 blocked TGFb-induced Nox4 expression and fibroblast to myofibroblast differentiation. Conclusions: These data identify NOX4 as a putative proximal mediator of cardiac fibroblast activation in mice with genetic DCM and suggest that cardiac fibroblasts develop a premature aging phenotype in HF.
Abstract 4143980: Bleeding with the FXI Inhibitor Abelacimab compared with Rivaroxaban in Patients on Antiplatelet therapy: A Prespecified Analysis of the AZALEA-TIMI 71 Trial
Authors: Samer Al Said, Siddharth Patel, Robert Giugliano, David Morrow, Erica Goodrich, Sabina Murphy, Bruce Hug, Sanobar Parker, Shih-Ann Chen, Shaun Goodman, BOYOUNG JOUNG, Robert Kiss, Jindrich Spinar, Wojciech Wojakowski, Jeffrey Weitz, Dan Bloomfield, Marc Sabatine, Christian Ruff
Journal: Circulation (2024)

Background: Combining antiplatelet (APT) with anticoagulant therapy increases the risk of bleeding. In AZALEA-TIMI 71, the novel factor XI inhibitor abelacimab reduced the risk of bleeding compared with rivaroxaban in patients with atrial fibrillation (AF). In this analysis, we investigated whether the safety of abelacimab vs rivaroxaban was modified by antiplatelet therapy. Methods: AZALEA-TIMI 71 randomized 1,287 patients with AF to abelacimab (90 or 150 mg subcutaneously monthly) or rivaroxaban (20 mg orally daily), with stratification by planned use of concomitant APT. The primary outcome, major or clinically relevant non-major (CRNM) bleeding, was compared using Cox proportional hazards adjusted for age, sex, and BMI, with an interaction term for randomized treatment and APT use. Results: Of 1,287 patients, 318 (25%) were on APT at baseline (16% aspirin only, 8% P2Y 12 only, 2% DAPT) and were younger (median age 72 vs 75 years) and had a higher prevalence of CAD (74% vs 40%), prior MI (36% vs 16%) and PAD (15% vs 11%) than those not on APT (p&lt;0.05 for each). The rate of major or CRNM bleeding tended to be higher in those on APT than those not taking APT in the rivaroxaban group (10.6% vs. 7.7%), but not in the abelacimab group (Fig). Both abelacimab doses significantly reduced major or CRNM bleeding compared with rivaroxaban regardless of APT use [60-66% in patients not on ATP and 70-74% in patients on ATP] (Fig). Given the higher rates of bleeding in patients on both rivaroxaban and APT, the corresponding absolute risk reductions with abelacimab tended to be greater in patients on APT (7.1-8.1%) compared to those not on APT (4.6-5.0%) (Fig). Conclusion: Inhibition of FXI with abelacimab results in substantial reductions in bleeding compared with rivaroxaban regardless of concomitant APT use. These data support the potential advantage of FXI inhibitors in patients who require concomitant APT.
Abstract 4143905: Distribution of Coronary Artery Plaque Volume by Artificial Intelligence Quantitative Coronary CT Angiography in General Population: Results from the Miami Heart Study
Authors: Keishi Ichikawa, Rachelle Bishay, Srikanth Krishnan, Travis Benzing, Sina Kianoush, Jairo Aldana, Miguel Cainzos, Theodore Feldman, Jonathan Fialkow, Khurram Nasir, Matthew Budoff, Shai Ronen
Journal: Circulation (2024)

Background: Coronary computed tomography angiography -derived plaque burden is associated with the risk of cardiovascular events and is expected to be utilized in clinical practice. Understanding of CT quantitative plaque volume compares to normative values in the general population is clinically important for determining management. This study aimed to investigate the distribution of coronary artery plaque volume in general population and to develop nomographic quantitative plaque volume using the Miami Heart Study, a large community-based cohort study. Methods: A total of 2,301 asymptomatic subjects without coronary artery disease (CAD) enrolled in the Miami Heart Study were included. Quantitative assessments of atherosclerotic plaque volume (total, calcified, and non-calcified plaque) were performed using artificial intelligence-guided quantitative coronary computed tomography angiography analysis (AI-QCT). The percentiles of the plaque distribution by gender and age were estimated with nonparametric techniques. Results: The mean age was 53.5 years and 50.4% were male. The majority of study participants were Hispanic/Latino (47.2%) and White (85.5%). In terms of traditional risk factors, approximately one-third of the cohort were current or former smokers, 4.3% had diabetes, 24.9% had hypertension, and 34.9% had high cholesterol or lipid abnormalities. Overall, 93.1% of men and 84.6% of women had any plaque using AI-QCT. The median total plaque volume was 54 mm 3 (IQR 16-126 mm 3 ) and increased with age. Male subjects had more median total plaque volume, calcified plaque volume, and noncalcified plaque volume than female subjects (80 mm 3 vs 34mm 3 , 4 mm 3 vs 2 mm 3 , and 66 mm 3 vs 27 mm 3 , respectively). Younger individuals tend to have a higher percentage of noncalcified plaque. Conclusions: In this asymptomatic population without known CAD, 93.1% of men and 84.6% of women had CAD detected using AI-QCT. Additionally, we developed age- and sex-specific nomograms for atherosclerotic plaque volume. Our data enhance the understanding of plaque volume distribution in general population and should be an important indicator in clinical practice.
Abstract 4143989: Differences in Patient-Centered Outcomes Between Patients with Heart Failure and With and Without Renal Dysfunction
Authors: ISSAHAKU AWAL, Geunyeong Cha, Ashmita Thapa, JungHee Kang, Misook Chung, Martha Biddle, Jia-Rong Wu, Abigail Latimer, Jessica Thompson, Debra Moser
Journal: Circulation (2024)

Background: Heart failure (HF) is not a homogeneous condition, and comorbidities, such as renal dysfunction, commonly complicate the clinical picture. However, differences in patient-centered outcomes (PCO), such as depressive symptoms, health-related quality of life, functional status, adherence, and self-care behaviors, have not been explored in patients with HF with and without renal dysfunction. Hypothesis: We hypothesized that there is a significant difference in PCO between patients diagnosed with heart failure with renal dysfunction and those without renal dysfunction. Methods: A secondary data analysis was conducted using the RICH Heart Program Heart Failure Database. We included 517 patients (61 ± 13 years old, 66% male, 66% NYHA class III/IV) with HF with (22%) and without (78%) renal dysfunction. Depressive symptoms were measured using the Patient Health Questionnaire-9, health-related quality of life using the Minnesota Living with Heart Failure Questionnaire, functional status using the Duke Activity Status Index, adherence using the Medical Outcomes Study Specific Adherence Scale, and Self-care using the Self-care of Heart Failure Index. Independent samples t-tests were conducted to compare PCO between the two groups. Results: All PCO were significantly different between the two groups. Compared to patients without renal dysfunction, those with renal dysfunction had worse depressive symptoms (8.1 ± 5.9 vs 10.0 ± 6.0, respectively, p = 0.001), poorer health-related quality of life (50.5 ± 24.9 vs 58.0 ± 25.6, p = 0.005, respectively), and lower functional status (11.7 ± 11.7 vs 77.0 ± 7.1, p &lt; 0.001, respectively). Patients with renal dysfunction had better scores on self-reported adherence (29.2 ± 6.0 vs 25.6 ± 7.7, p &lt; 0.001), self-care maintenance (61.6 ± 21.1 vs 54.3 ± 23.2, p = 0.03), and self-care management (60.9 ± 23.0 vs 53.8 ± 22.9, p = 0.04) than those without. Conclusions: Even though patients with HF and renal dysfunction reported better adherence and self-care behaviors, they still had higher levels of depressive symptoms, worse health-related quality of life, and lower functional status. This suggests that knowledge of their comorbidity prompted better self-care, but other PCO remained poor. Increased attention to promoting specific self-care behaviors that focus on renal dysfunction in the context of HF should be tested to determine if PCO can be improved in this patient population.
Abstract 4143816: Effects of epicardial adipose tissue on cardiac function and exercise hemodynamics in patients with Heart Failure with Preserved Ejection Fraction
Authors: Diana De Oliveira Gomes, Tiffany Brazile, James MacNamara, Sauyeh Zamani, Christopher Hearon, Denis Wakeham, Michael Nelson, Benjamin Levine, Satyam Sarma
Journal: Circulation (2024)

Background: Obesity is a risk factor for developing Heart Failure with Preserved Ejection Fraction (HFpEF). Epicardial adipose tissue (EAT), an ectopic fat depot located between the epicardium and the pericardium, has emerged as a potential risk factor for various cardiovascular diseases, including HFpEF. Previous studies have linked increased EAT thickness, measured by echocardiography, to elevated cardiac filling pressures and systolic and diastolic dysfunction. Compared to echo, a volumetric assessment of EAT with MRI has greater accuracy, precision, and reproducibility. This study aimed to assess the relationship between EAT and cardiac function and exercise hemodynamics in patients with HFpEF. Methods: We studied 32 patients with HFpEF (19 women; BMI, 37±6kg/m 2 ; age, 69±6years). Total and visceral fat were assessed with dual-energy x-ray absorptiometry. MRI was used to quantify EAT volume across short-axis slices and assess global longitudinal strain(GLS). We assessed ventricular filling pressures (right heart catheterization), oxygen uptake (VO 2 ), cardiac output (Qc, Direct Fick), and diastolic function (echocardiography) on a seated upright cycle ergometer at rest, 20 Watts, and peak exercise (87±35 Watts). Correlation analyses were performed to examine the relationship between variables. Results: EAT was moderately correlated with visceral adiposity (r=0.57, P&lt;0.001) but not with total body fat (Figure, Panel A). EAT was not associated with markers of diastolic function (early tissue Doppler relaxation velocity [e'], mitral inflow velocity ratio [E/A], early mitral inflow/e' ratio [E/e']), cardiac filling pressures (right atrial pressure and pulmonary capillary wedge pressure) or mean pulmonary artery pressure at rest or during exercise. In addition, there was no association between GLS and total EAT (r=-0.06, P=0.735) or EAT located over the left ventricle (r=-0.05, P=0.749). EAT was not associated with exercise capacity (Figure, Panel B). Conclusions: In patients with HFpEF, total EAT volume quantified with MRI did not correlate with measures of cardiac function at rest or during exercise. Our results suggest ventricular EAT does not impact cardiac function directly in patients with obesity and HFpEF.