tbuckley/cabot-search huggingface dataset:
Abstract 4136712: Fontan-specific morbidities impact on heart transplant outcomes: a multicenter study
Authors: Aecha Ybarra, Melissa Cousino, Elizabeth Blume, Maria Bano, Shriprasad Deshpande, Matthew O'Connor, Sharon Chen, Lydia Wright, Steven Kindel, Anna Joong, Michelle Ploutz, Brian Feingold, Chad Mao, Angela Lorts, Kathleen Simpson, Marc Richmond, Shahnawaz Amdani, Jennifer Conway, David Bearl, Joshua Friedland-Little, Adriana Batazzi, Garrett Reichle, Sunkyung Yu, David Rosenthal, Kurt Schumacher
Journal: Circulation (2024)

Introduction: Fontan circulatory failure (FCF) is associated with poor long-term survival. The impact of Fontan-specific morbidities on outcomes in those evaluated for heart transplant (HT) are not well understood. Hypothesis: FCF-specific morbidities, their degree of severity, and the accumulation of morbidities are associated with mortality in individuals undergoing HT. Methods: This 20 center, retrospective cohort study of individuals with FCF from 2008-2023 collected data on FCF-specific morbidities, waitlist (WL), and post-HT outcomes. Each unique FCF morbidity was defined with graded severities (absent, mild, moderate, severe, and life-threatening) via a prior effort. The primary outcome was survival from WL to 1-year post-HT. Appropriate 2-group statistics and multivariable logistic regression compared surviving with those who died. Receiver operating characteristic curve determined the most discriminating value of total cumulative morbidities on mortality. Results: Of the 340 patients included, 51(15%) died between WL and 1 year post-HT. On univariate analysis, 7 of 27 FCF morbidities were associated with the mortality (p &lt; 0.2) including: anatomic Fontan pathway obstruction, clinical hypoxia, chronic pleural effusions, sleep apnea, portal variceal disease, acute kidney injury within 1 year prior to WL, and mental health disorders. On multivariable analysis, only clinical hypoxia and portal variceal disease emerged as independent risk factor for mortality (adjusted odds ratio [aOR]: 2.48, p = 0.03 and aOR 2.74 P=0.02 respectively). When assessing the impact of increasing severity of each morbidity, again worsening clinical hypoxia (aOR 1.42 increase with each increase in grade, p=0.01) and portal variceal disease (aOR 1.80 with each increase in grade, p=0.01) had differential effects on mortality. Risk of death increased with greater number of FCF morbidities. Having 2 or more of the 7 univariately significant morbidities was the value best discriminating survivors from those who died (Area under the curve 0.67; sensitivity 78%, negative predictive value 93%). Conclusion: Clinical hypoxia and portal variceal disease confer independent risk for non-survival in patients with Fontan from WL to 1 year after HT. Additionally, the magnitude of mortality risk for both hypoxia and varices worsens as disease severity worsens. Given the impact, consistent evaluation for these morbidities and timely referral for heart failure evaluation is warranted.
Abstract 4135928: Externally Validated Deep Learning Model for Patent Ductus Arteriosus Detection by Echocardiography in Preterm Infants
Authors: Addison Gearhart, Micaela Elrod, Thomas Gomes, Alexa Golbus, Christopher Baltimore, Cayla Wakser, Jason Graham, Wyman Lai, Andrew Powell, Dane Smith, George Baker
Journal: Circulation (2024)

Introduction: Patent ductus arteriosus (PDA) is a common form of congenital heart disease in premature infants and a source of significant morbidity. Echocardiography is the mainstay modality for diagnosis and monitoring but is resource-intensive and requires expertise for interpretation. Aims: To develop and externally validate a deep learning model to identify PDA in preterm infants by echocardiography. Methods: We trained, validated, and tested a convolutional neural network to detect PDA in raw echocardiogram clips from infants (gestational age &lt;37 weeks) with and without PDAs and no significant additional congenital heart disease at the Medical University of South Carolina (MUSC). For training and validation, we employed a 12-fold cross-validation procedure. Experienced cardiologists defined the ground truth labels. We assessed classification performance on an internal model naïve dataset using the area under the receiver operator curve (AUROC), sensitivity, specificity, positive predictive value, and negative predictive value. For external multicenter testing, we used studies from Children’s Hospital of Orange County (CHOC) and Boston Children’s Hospital (BCH), both of which utilize a different ultrasound system vendor. Results: Training and validation were completed using 1,145 color/color-compare clips (661 clips with PDA and 484 no PDA) from 66 patients. The internal test dataset consisted of 142 clips from 16 patients. The external CHOC and BCH cohorts consisted of 146 clips from 50 patients and 294 clips from 68 patients, respectively. Model performance was similar for internal and external testing (Table 1). Conclusions: Our deep learning model detected the presence of PDA with acceptable performance. This performance generalized well across multiple institutions and ultrasound vendors. This work shows promise for the future development of an automated tool for PDA diagnosis enabling the democratization of pediatric cardiology resources.
Abstract 4135846: Cardiovascular Effectiveness of Glucagon-like Peptide-1 Receptor Agonists and Empagliflozin Combination Therapy in Adults with Type 2 Diabetes
Authors: Phyo Htoo, Julie Paik, Helen Tesfaye, Sebastian Schneeweiss, Robert Glynn, Christina Shay, Niklas Schmedt, Lisette Koeneman, Deborah Wexler, Elisabetta Patorno
Journal: Circulation (2024)

Introduction/Background: Both empagliflozin and glucagon-like peptide-1 receptor agonists (GLP-1RA) have demonstrated cardiovascular (CV) benefits in clinical trials. However, few trials examined the combination of both therapies and evidence is scarce on whether the addition of empagliflozin to GLP-1RA has further CV benefits. Aim/Goal: We evaluated the risk of CV outcomes in patients with type 2 diabetes (T2D) initiating baseline GLP-1RA therapy that added empagliflozin compared to those that added sulfonylureas (SU). Methods: Using Medicare, Optum, and Marketscan data (2014-22), we identified patients with T2D aged ≥18 years initiating GLP-1RA that subsequently added either empagliflozin or SU. Follow-up began on the date of additional therapy and continued until discontinuation of either drug, a gap in insurance coverage, death, or study end. After propensity score standardized mortality ratio weighting adjusting for 98 covariates, we estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years evaluating a composite of myocardial infarction (MI) or stroke, hospitalization for heart failure (HHF), or all-cause death in the overall population and in patients with history of CV disease. Results: We identified 27,962 patients initiating GLP-1RA + empagliflozin vs 25,137 patients initiating GLP-1RA + SU. After weighting, relative to patients initiating GLP-1RA + SU, those initiating GLP-1RA + empagliflozin had lower risks of MI-stroke [HR 0.70 (0.55, 0.90); RD: -4.3 (-6.6, -2.0)], HHF in the primary hospital discharge position [HR: 0.59 (0.43, 0.81); RD: -3.9 (-5.8, -2.1)]; HHF in any discharge positions [HR: 0.84 (0.72, 0.98); RD: -7.6 (-11.6, -3.6)], and all-cause death [HR: 0.83 (0.62, 1.11); RD: -1.3 (-3.2, 0.56)]. Findings were similar but with larger RDs in patients with baseline CV disease ( Table ). Conclusion: In US clinical practice, patients with T2D initiating GLP-1RA that added empagliflozin had lower risks of MI-stroke, HHF, and death compared to adding SU, which suggests an additive CV benefit when combining GLP-1RA and empagliflozin therapies.
Abstract 4136274: A Case of Myocardial Infarction with Non-obstructive Coronary Arteries (MINOCA) Complicated by a Ventricular Septal Defect (VSD)
Authors: Theresa Thai, Jerry Lipinski, Michael Sola, Abdelghani El Rafei, Aken Desai, Christine Sailer
Journal: Circulation (2024)

Case: A 69-year-old woman with a history of hypertension and tobacco use disorder presented with acute chest pain. The patient was found to have classic anterior ST elevation myocardial infarction (STEMI) pattern on electrocardiogram (ECG) with high-sensitivity troponin of 12,772 ng/L and was taken emergently to the catheterization laboratory. Coronary angiography showed tortuous coronary vessels though without evidence of obstructive coronary artery disease, plaque rupture, ulceration, dissection, or vasospasm. Transthoracic echocardiogram showed an apical ventricular septal defect (VSD) with normal left ventricular systolic function of 60%. Cardiac computed tomography (CT), confirmed a discrete apical VSD that was 7.93 mm in diameter and multiple small VSDs distally in the septum. Right heart catheterization revealed severe left-to-right shunting with a ratio of pulmonary blood flow to systemic blood flow (Qp:Qs) of 2.8. Early surgical repair of the apical VSD was pursued despite known high operative risk given the hemodynamic significance of the shunt. The patient developed ongoing hemodynamic instability from cardiogenic shock with inability to ween from intra-aortic balloon pump (IABP). Unfortunately, because of the location of the residual VSDs and elevated panel-reactive antibody testing of 98%, the patient was deemed to not be a candidate for percutaneous closure or heart transplantation, respectively. Discussion: An acquired ventricular septal defect (VSD) is a rare and catastrophic complication of myocardial infarction, typically with a culprit obstructive coronary artery lesion identified on coronary angiography. Acquired VSDs in myocardial infarction with nonobstructive coronary arteries (MINOCA) is an even more rare phenomenon. Possible causes include low flow, inflammation, intimal disruption, or vasospasm of coronary arteries. Our case highlights that MINOCA can present with life-threatening complications similar to obstructive STEMI. The timing of intervention and treatment approach of acquired VSDs remains an area of debate. The life-threatening effects of VSDs make it critical to manage in a multidisciplinary manner involving advanced imagers, interventional cardiologists, cardiothoracic surgeons, and heart failure specialists. This case emphasizes the importance of maintaining a high index of suspicion for abnormal coronary anatomy, even in patients with MINOCA, and prompt interdisciplinary decision making to reduce mortality.
Abstract 4136501: Machine Learning Uncovers the Contribution of Rare Genetic Variants and Enhances Risk Prediction for Coronary Artery Disease in the Japanese Population
Authors: Hirotaka IEKI, Kaoru Ito, Sai Zhang, Satoshi Koyama, Kazuo Miyazawa, HIROKI YOSHIDA, Ryo Kurosawa, Nobuyuki Enzan, Kouichi Ozaki, Yoshihiro Onouchi, Yoichiro Kamatani, Chikashi Terao, Michael Snyder, Issei Komuro
Journal: Circulation (2024)

Background: Genome-wide association studies (GWASs) have enhanced our understanding of the genetic basis of coronary artery disease (CAD), and polygenic risk scores (PRSs) have facilitated the assessment of genetic risk. However, these methods predominantly focus on common variants due to statistical power, potentially leaving rare variants insufficiently analyzed and thus limiting the predictive performance of PRS. Methods: We conducted whole genome sequencing (WGS) of 1,752 Japanese early-onset myocardial infarction (MI) patients and 3,019 controls from Biobank Japan (BBJ). We performed case-control association studies including GWAS and gene-based tests, as well as a novel machine learning-based framework. In this framework, we developed a penalized regression model to predict the CAD status from genome-wide rare nonsynonymous variants. The model identified the minimal set of most distinguishing features (genes) and generated a rare variant-based risk score (RVS). The RVS was evaluated on an independent validation WGS cohort of 200 cases and 824 controls. We also derived a PRS based on CAD-GWAS (25,668 CAD cases vs 141,667 controls from BBJ) to compare the properties and performance between the RVS and PRS. Results: In the case-control studies, only two common variants in chromosome 12 were identified in GWAS, with no genes in gene-based analysis (SKAT-O), suggesting the challenges in rare variant analysis. On the other hand, our machine-learning framework identified 59 CAD-related genes, including LDLR , a causal gene of familial hypercholesteremia. Functional analyses revealed that various biological pathways, including lipid metabolism, immune system, and vessel development, are involved in CAD. For the genetic risk prediction, RVS significantly predicted CAD (area under the curve [AUC], 0.58; p=0.001, pseudo-R 2 , 0.051; p=7.92*10 -9 ). RVS was significantly associated with LDL cholesterol levels and coagulation function (Pearson’s r, 0.21; p=4.5*10 -5 and 0.10; p=0.03, respectively) and MI patients with high RVS (top 5%) showed higher cardiovascular mortality rate (p=0.03, log-rank test), highlighting the clinical importance of RVS. Finally, the combined risk score (CRS) of RVS and PRS significantly improved CAD prediction compared to PRS (AUC, 0.66 (CRS) vs 0.61 (PRS); p=0.007, pseudo-R 2 , 0.093 (CRS) vs 0.040 (PRS); p=0.0018, Figure ). Conclusions: Our machine learning framework successfully characterized rare variants and enhanced genetic risk prediction in CAD.
Abstract 4136294: Carbohydrate intakes and cardiovascular disease risk factors in South Asians: Results from 56,024 participants in Bangladesh, India, Pakistan, and Sri Lanka
Authors: Anwesha Lahiri, Fumiaki Imamura, Anuradhani Kasturiratne, Vinitaa Jha, Prasad Katulanda, Khadija Khawaja, Malay Mridha, Ranjit Mohan Anjana, John Chambers, Nita Forouhi
Journal: Circulation (2024)

Background: Evidence on effects of carbohydrate intake with cardiovascular disease risk factors is inconsistent and has limited generalizability to diverse populations such as South Asians, whose carbohydrate intakes are typically high. Aims: We examined the association of the quantity and types of carbohydrate intake with two risk factors for major cardiovascular events– hypertension (HT) and hypercholesterolemia (HC). Methods: We analyzed cross-sectional data from participants aged ≥18 years in the South Asia Biobank in Bangladesh, India, Pakistan, and Sri Lanka. Using dietary data assessed with interviewer-led 24h diet recalls, we calculated intakes of total and subtypes of carbohydrates and several indices of carbohydrate quality. Primary outcomes were HT and HC, defined by medication use, doctor diagnosis, blood pressure and blood lipid levels. With mixed effects Poisson regression, HT and HC was regressed on quantiles of carbohydrate intakes by country to estimate prevalence ratios (PR) and 95% confidence intervals (CI), followed by meta-analysis pooling country-specific estimates. We examined interactions by diabetes status and adiposity. Results: Of 56,024 adults, 36.6% had HT, 16.1% had HC. In pooled multivariable analyses comparing extreme quantiles, total carbohydrate intake was not associated with HT or HC prevalence. Fructose, free sugar and free sugar-to-fiber ratio were associated with higher prevalence of HT (PRs Q5vsQ1 : 1.03-1.15). Higher intakes of cereal fiber (PR Q4vsQ1 : 0.96, 95% CI: 0.95-0.98) and legume fiber (PR Q4vsQ1 : 0.98, 95% CI: 0.97-0.98) were associated with lower prevalence of HT and higher cereal fiber intake with lower HC prevalence (PR Q5vsQ1 : 0.80, 95% CI: 0.75-0.85). Diabetes and adiposity were observed as effect-modifiers (p&lt;0.001). There were null associations in adults with diabetes but in non-diabetic adults, free sugar intake was related positively with HT (PR Q5vsQ1 : 1.07, 95% CI: 1.05-1.09) while fiber intake was inversely related (PR Q5vsQ1 : 0.98, 0.95-0.97). Starch, sugar and free sugar intake were associated positively with HT prevalence in adults with high body fat (≥20% for men; ≥30% for women) and visceral fat (≥10%) levels (PRs Q5vsQ1 : 1.03-1.20); associations were null for low body and visceral fat levels. Associations varied by country (between-country heterogeneity I 2 &gt;60%). Conclusion: Associations of dietary carbohydrates with HT and HC depended on the quality and type of intake in South Asians.
Abstract 4136032: Digital Biomarkers Associated With Coronary Artery Calcium And Traditional Risk Factors Extracted From Facial Photos Through Multi-Label Deep Learning For Detecting Coronary Artery Disease
Authors: Juntong Zeng, Shen Lin, Runchen Sun, Zhongchen Li, Zhe Zheng
Journal: Circulation (2024)

Background: Biomarkers like coronary artery calcium (CAC) and traditional risk factors are well-validated for coronary artery disease (CAD) assessment but not always available, and with limited workup efficiency and potential radiation risk. Facial features contain biological information related to atherosclerosis. Aims: We aim to extract CAC and traditional risk factor-associated digital biomarkers from facial images and evaluate their value in predicting CAD status compared with conventional clinical approaches. Methods: Suspected individuals referred for confirmatory CAD evaluation across nine centers were included. Participants in one center constituted the derivation set. External validation included one dataset of participants from a different time period in the derivation center and the other dataset from the other eight centers. We developed a multi-label deep-learning model to extract digital biomarkers from facial photos based on a multi-dimensional label of CAC score and eight traditional risk factors to comprehensively represent coronary atherosclerosis risk profile. The extracted digital biomarkers were evaluated for both effectiveness in reflecting components of the multi-dimensional label and clinical value in predicting obstructive CAD. Results: A total of 13248 facial photos from 3312 eligible participants (mean age, 58.5 years; 517 [25.9%] female) were included. In external validation, a set of digital biomarkers (FacialCAD) were extracted, effectively reflecting components of the multi-dimensional label, especially for CAC stratification (CAC&gt;0, AUC 0.919 [0.885 – 0.949]; CAC≥100, AUC 0.906 [0.876 – 0.933]) and nearly perfect prediction for the age and sex. The performance of the FacialCAD in predicting obstructive CAD (AUC 0.721 [0.694–0.748]) significantly outperformed two guideline-recommended CAD models (0.721 vs. 0.653, P&lt;0.001; 0.721 vs. 0.686, P=0.032), with further significant improvement when combined with these models (△AUC= +0.085, P&lt;0.001; △AUC= +0.068, P&lt;0.001). Conclusion: FacialCAD, a set of CAC and risk factors-associated novel digital biomarkers extracted from facial images, exhibited superior and incremental value to conventional clinical approaches in predicting CAD status.
Abstract 4135790: Carotid Plaque Inflammation Is Associated with Atrial Fibrillation
Authors: Valentina Nardi, Ludovica Di Venanzio, Negin Mahmoudi Hamidabad, Elizabeth Copley, Ani Tiwari, Arush Rajotia, Esther Lutgens, Lilach Lerman, Amir Lerman
Journal: Circulation (2024)

Introduction: Atrial fibrillation (AF) is prevalent in patients with atherosclerotic coronary and carotid artery disease and is associated with elevated plasma inflammatory markers, such as Interleukin (IL)-6. In carotid artery atherosclerosis, macrophages are considered a local marker of inflammation. Hypothesis: We hypothesize that AF is independently associated with carotid plaque inflammation. Aims: In patients undergoing carotid endarterectomy (CEA), we aimed to determine whether carotid plaques inflammation is associated with AF. Approach: In this prospective cohort study, consecutive patients with carotid artery disease undergoing CEA were enrolled. From the plaques removed during surgery, fixed in formalin and embedded in paraffin blocks, sections were stained with antibodies against CD68 to detect macrophages (Fig.1A) . Digital copies of the slides were created by Motic Easy Scan and histologically annotated with QuPath. The percentage of CD68+ cells was defined as (CD68+ positive cells/total nuclei) x 100. Flash-frozen plaque segments were analyzed by ELISA for IL-6 concentration. Baseline demographics and clinical data, including AF diagnosis, were extracted from the electronic health records. Results: A total of 106 patients undergoing CEA, with a median age of 73 [67-78] years and comprising 83 (78.3%) males, were included in the study. AF was diagnosed prior to CEA in 13 (12.3%) patients. Univariate logistic regression showed that plaque CD68+ cell content was associated with AF (OR 1.048 [95% CI 1.010 – 1.088]; p = 0.013). Additionally, in Mann-Whitney test IL-6 levels were significantly over twofold higher in plaques of patients with AF compared to those without AF (82.4 [64.9-111.7] pg/mg vs 37.0 [18.4-93.3] pg/mg; p=0.020) (Fig. 1B) . Conclusions: The current study demonstrates an association between carotid atherosclerotic plaque macrophage content, IL6 levels and AF, supporting the role of inflammation in the pathogenesis of AF in these patients. Further studies are needed to determine the potential of plaque inflammation as a therapeutic target in AF.
Abstract 4136290: Toward Quantitative Assessment of Cerebrovascular Autoregulation in Neonates using Ultrafast Ultrasound Power Doppler
Authors: Nikan Fakhari, Julien Aguet, Minh Nguyen, Luc Mertens, Lynn Crawford Lean, Christoph Haller, David Barron, Jonh Sled, Jerome Baranger, Olivier Villemain
Journal: Circulation (2024)

Introduction: Newborns with congenital heart diseases requiring cardiopulmonary bypass are at risk of neurodevelopmental impairment. The impact of deep hypothermia during cardiopulmonary bypass (DH-CPB) on cerebrovascular autoregulation (CAR) that controls brain perfusion in the presence of variable blood pressure is not well understood. Recently, Ultrafast Power Doppler (UPD) showed potential to study CAR in neonates based on the measurement of cerebral blood volume (CBV). However, since CAR relies mainly on the arterial vasoconstriction/vasodilation, the interpretation of brain perfusion based on CBV requires further separation of arterial CBV from total CBV. This study aims to use UPD to monitor CAR during DH-CPB in neonates. Methods: An ultrasonic probe (5.7 MHz) was placed on the anterior fontanel of 6 newborns before, during and after DH-CPB. Using ultrafast sequences generated by a Verasonic Vantage research system, mid-coronal plane images were acquired (PRF of 9 kHz, 5 compounded diverging waves). An adaptive spatiotemporal singular value decomposition was used to separate the blood signal from tissue signal and obtain UPD. CBV was computed in the deep gray matter (DGM). This region was chosen due to its higher susceptibility to hypoxic-ischemic injury. Arterial CBV was isolated from total CBV based on the upward arterial flow obtained using signed-power Doppler (See Fig A). Pearson correlation ® was computed between mean arterial blood pressure (MAP) and arterial CBV to study CAR. Results: Before and after DH-CPB, negative correlations were found between arterial CBV and MAP: -0.30 and -0.43 respectively. This indicates that an increase in MAP is associated with a decrease in cerebral arterial blood volume. This decrease in arterial CBV likely arises from arterial vasoconstriction, suggesting an active CAR response. Conversely, during DH-CPB, no correlation was found (r = -0.02). This means that despite the increase in MAP, arterial CBV remains unchanged. This lack of variation of arterial CBV is likely due to absent arterial vasoconstriction, suggesting an impaired CAR response. Conclusion: Our findings highlight the potential of UPD for continuous monitoring of CAR, paving the way for improving neurovascular management strategies during DH- CPB.