tbuckley/cabot-search huggingface dataset:
Abstract 13313: Risk of Atherosclerosis in Thoracic Aortic Disease: A Study of Multi-Modal Imaging Data From 40,479 UK Biobank Participants
Authors: Alyssa M Flores, James Pirruccello, Patrick T Ellinor, Mark E Lindsay
Journal: Circulation (2023)

Background: Despite some shared risk factors, aortic aneurysms and atherosclerosis manifest differently across the aorta. While atherosclerosis commonly co-exists with descending and abdominal aortic aneurysms, some observations suggested a decreased risk of atherosclerosis in patients with ascending aortic aneurysms. This has led to the suggestion that drivers of ascending aortic aneurysms may be anti-atherogenic. Aim: Using carotid intima-media thickness (cIMT) as a surrogate for atherosclerosis and deep learning-derived estimates of aortic diameter, this study examines whether ascending aortic aneurysms are protective against atherosclerosis in a longitudinal analysis of UK Biobank participants. Methods: Individuals who underwent both carotid ultrasound and cardiovascular MRI in the UK Biobank (N=40,479) were identified. We derived ascending and descending aortic measurements from a previously developed deep learning model that was trained to quantify dimensions in &gt;4 million MRI images and extract diameter during ventricular systole. Measures of mean cIMT at 2 standardized angles for bilateral carotid arteries were utilized. The relationship between cIMT and aortic diameter was assessed using univariable and multivariable linear regression. β was calculated as μm change in cIMT per cm of aortic diameter. Results: In individuals with an aneurysmal ascending aorta ( &gt; 4.5cm), there was no significant association between aortic diameter and cIMT after accounting for age, sex, height, and weight (adjusted β=-15.4, P=0.26). There was also no significant correlation between ascending aortic diameter at baseline and cIMT progression in follow-up (adjusted β=-2.5; P=0.48). In the entire cohort, larger ascending aortic size was nominally associated with greater cIMT (adjusted β=5.0; P=0.005). As expected, larger diameter in the descending thoracic aorta was associated with higher cIMT (adjusted β=23.9; P=1.9x10 -16 ). Conclusion: Based on multi-modal imaging data from over 40K individuals, we find no evidence of an inverse relationship between ascending aortic aneurysmal disease and atherosclerosis.
Abstract 18692: Relationship Between Fasting Time on Ketogenic Diet and Myocardial Glucose Suppression in Patients Referred for Cardiac Sarcoidosis Evaluation on FDG-PET Imaging
Authors: Abhijit Bhattaru, Mahesh K Vidula, Senthil Selvaraj, Chaitanya Rojulpote, Paco E Bravo
Journal: Circulation (2023)

Introduction: FDG-PET imaging is standard for assessing myocardial inflammation for cardiac sarcoidosis (CS). Preparation with the ketogenic diet (KD) is required to suppress physiologic myocardial glucose uptake (MGU), thereby highlighting pathologic MGU. Incomplete physiologic myocardial glucose suppression (MGS) continues to limit FDG-PET. The effect of fasting time (FT) on MSG remains unexplored. Goal: To identify if FT is an independent predictor of MGS following a KD in patients undergoing FDG-PET imaging. Methods: We prospectively included 442 consecutive patients (59.2 ± 10.9 yrs, 39% female, 55% white) who underwent 590 FDG-PET scans for the evaluation of CS after following a KD at our institution between 2021 and 2023. Time from last meal to FDG injection was documented in all patients. Serum BHB levels were measured in 516 scans. FDG PET images were classified as 1) diagnostic (complete MGS) when there was either no MGU (negative) or multifocal uptake (positive), or 2) nondiagnostic (incomplete MGS) when there was either diffuse left ventricular or nonspecific uptake. Results: The KD was followed for 1, 2 or ≥3 days in 127 (22%), 61 (10%), and 402 (68%) of cases respectively. FDG-PET scans were interpreted as the following: 436 (74%) negative; 109 (18.3%) positive; 13 (2.2%) diffuse; 32 (5.4%) nonspecific uptake. Patients on the KD for only 1 day had higher rates of MGS with increased FT (β = 0.33 ± 0.11, p &lt;0.01); this correlation did not hold true for patients on KD for 2 days (β = -0.005 ± 0.09, p = 0.96) whereas, patients on the KD for 3 or more days showed lower rates of MGS with increased FT (β = -0.18 ±0.07, p&lt;0.01) ( Figure 1 ). When adjusting for BHB level, the correlation between MGS and FT held true (1 day: β = 0.35 ± 0.13, p &lt;0.01; 2 days: β = 0.26 ± 0.28, p = 0.35; 3 days: β = -0.17 ± 0.07, p = 0.02). Conclusion: Fasting time appears to be most beneficial in patients following the KD for 1-day only. Patients following the KD for 2 days or longer may not require overnight fasting.
Abstract 14823: Assessment of the Appropriateness and Prognostic Significance of the Current Universal Diagnostic Definition for Acute Kidney Injury in Patients After Cardiac Surgery and Exploration of Tailored Criteria
Authors: Juntong Zeng, Xiaoting Su, Xiaohong Huang, Zhe Zheng
Journal: Circulation (2023)

Background: Cardiac surgery-associated AKI (CSA-AKI) is prevalent and its diagnosis currently adheres to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, commonly used criteria developed for general populations. Limited evidence exists on their appropriateness and prognostic value for CSA-AKI, which exhibits unique mechanisms and clinical courses. Aims: We aimed to assess the prognostic value of the KDIGO diagnostic criteria for CSA-AKI and explore potentially more prognostically relevant criteria for cardiac surgery. Methods: Patients undergoing coronary artery bypass grafting surgery at a single institution were included and categorized into four groups: no AKI, AKI stage-1, AKI stage-2, and AKI stage-3, based on KDIGO guidelines. Patients of AKI-1 were further divided based on specific criteria met: absolute criteria (0.3mg/dL serum creatinine (SCr) increase over 48-hour intervals), ratio criteria (1.5-1.9 times baseline SCr), and dual criteria (meeting both criteria) AKI-1. The primary outcome was 30-day all-cause mortality. Results: Among 20626 patients, the overall incidence of CSA-AKI was 47.4%, with rates of 44.2% for AKI-1, 2.2% for AKI-2, and 0.9% for AKI-3. The overall 30-day mortality was 0.6%. Among AKI-1, 72.4%, 3.2%, and 24.2% met the absolute criteria, ratio criteria, and dual criteria, respectively. After multivariate adjustment, AKI-2 and AKI-3 were significantly associated with increased 30-day mortality. However, neither AKI-1 nor its subcategories showed prognostic significance. Subsequent restricted cubic spline analysis identified more prognostically relevant cut-off values for AKI-1 criteria as &gt;0.7 mg/dL SCr increase over 48-hour intervals and &gt;1.3 times baseline SCr, respectively. Conclusions: The current universal KDIGO diagnostic criteria may not be suitable for CSA-AKI, especially regarding cut-off values for AKI stage-1, highlighting the necessity of tailored criteria for cardiac surgery.
Abstract 13182: Comparison of Actual and Theoretical Aortic Valve Calcium Score to Assess TAVR Referral Delay in Patients With Atrial Fibrillation
Authors: Rajeev Masson, Bishoy Abraham, Vuyisile T Nkomo, David R Holmes, Sorin Pislaru, Reza Arsanjani, Chieh-Ju Chao, Molly Klanderman, Mahmoud Morsey, Kristen Sell-Dottin, Omar Baqal, Floyd D Fortuin, John Sweeney, Said Alsidawi
Journal: Circulation (2023)

Introduction: Doppler mean gradient (MG) can underestimate the severity of aortic stenosis (AS) in patients with atrial fibrillation (AF) compared to patients in sinus rhythm (SR). Patients with AF and severe AS may experience delayed diagnosis and more advanced disease at time of referral for transcatheter aortic valve replacement (TAVR). Methods: Patients who underwent TAVR from 2013 to 2017 for native valve severe AS were identified from an institutional database. MG and aortic valve calcium score (AVCS) at time of referral were compared in patients in AF and SR. Retrospective theoretical AVCS in AF patients were derived assuming an average progression of 152 AU/year (published data). Results: There were 820 patients included; mean age was 81.3+/- 8.2 years and 41.6% were female. AF was present in 356 patients at time of referral. Patients in AF were older (82.2 vs. 80.5, p = 0.003), had lower MG compared to SR patients (42.0 vs. 44.9, p = 0.002) and a lower peak velocity (4.1 vs. 4.2, p = 0.010) with a similar indexed aortic valve area (0.4 vs. 0.4, p = 0.17). Stratified by sex, the median calcium score for AF patients was higher (by around 300 AU) among both males (AF 2850.0 vs. SR 2561.0, p = 0.044) and females (AF 1942.0 vs. 1610.5, p = 0.025) ( figure 1 ). A density plot of retrospective theoretical AVCS in AF patients (projected assuming referral to TAVR approximately two years prior) resulted in nearly identical median AVCS between the two cohorts ( figure 2 ). Conclusions: Older age and higher AVCS in patients with AF compared to SR suggests that AS was both underestimated and more advanced at time of referral to TAVR. Patients in AF may have severe AS as early as 2 years prior to TAVR referral.
Abstract 15964: Ferroptosis Integrates Mitochondrial Dysfunction and Pathological Inflammation to Promote Pulmonary Hypertension
Authors: Neal T Vogel, Jeffrey Annis, Sasha Z Prisco, Jackson Barnes, Felipe Kazmirczak, Evan Brittain, Kurt W Prins
Journal: Circulation (2023)

Introduction: Ferroptosis is an iron-dependent, mitochondrial-mediated, non-apoptotic, highly inflammatory form of cell death. Ferroptosis plays important roles in numerous disease states via activation of complement and NLRP3 inflammasome, but its role in pulmonary hypertension (PH) is less well defined. Methods: Male Sprague Dawley rats were randomized into 3 groups: control, monocrotaline-vehicle (MCT-V), and MCT rats treated with ferrostatin-1 (MCT-FI). Pulmonary vascular disease severity and right ventricular function were assessed with histology, echocardiography, and pressure-volume loop analysis. Mitochondrial enrichments from lung tissue were subjected to quantitative proteomics. RNAseq evaluated global lung expression changes. KEGG analysis was performed on proteomics and RNAseq datasets to delineate which pathways were most associated with PH severity and modulated by ferrostatin-1 treatment. The hemodynamic effects of single-nucleotide polymorphisms in GPX4 were evaluated in the BioVU dataset. Results: Ferroptosis inhibition reduced right ventricular systolic pressure and improved RV function in MCT rats. Proteomics analysis identified a link between ferroptosis and multiple metabolic pathways that were associated with PH severity. RNAseq demonstrated ferroptosis inhibition partially suppressed complement and inflammatory signaling. Finally, patients with SNP rs1444732 in GPX4 had a higher pulmonary vascular resistance and mean pulmonary arterial pressure. Conclusions: Ferroptosis may integrate disrupted metabolism and inflammation to promote pulmonary vascular disease.
Abstract 15816: Contemporary Nationwide Trends in Major Adverse Cardiovascular and Cerebrovascular Events Among Elderly Chronic Kidney Disease Patients With versus Without Obstructive Sleep Apnea and Associated Sex and Racial Disparities, 2016-2019
Authors: Vamsikalyan Borra, Ikechukwu Ogbu, Gayatri Bondi, Nithya Borra, Naga Vamsi Krishna Machineni, Sai Goutham Reddy Yartha, Sravya Mundla, Karthikeya Ramasahayam, Purnachandra Rao Kuchipudi, CHARU AGARWAL, Prerna Bansal, Sagar Bathija, Rupak Desai
Journal: Circulation (2023)

Background: End-stage renal disease (ESRD) patients with more intensive renal replacement therapy have been shown to alleviate the severity of sleep apnea, specifically obstructive sleep apnea (OSA). Our study aims to analyze the trends in combined cardiovascular events among geriatric CKD patients, comparing those with and without OSA. Methods: We conducted a comprehensive analysis using nationwide data from 2016 to 2019 to identify geriatric CKD patients based on ICD-10 codes. A comparative assessment was performed between elderly CKD patients with and without OSA, examining their baseline characteristics and potential disparities related to sex and race. Results: From 2016 to 2019, 14,157,877 geriatric CKD patients were analyzed. OSA is more prevalent in men (60.5% v/s 50.5%) and in the white race(79.3% v/s 72.5%) compared to the non-OSA group. In the OSA group, men had an increased prevalence of major adverse cardiovascular and cerebrovascular events (MACCE) (12.0% v/s 9.7%) and acute myocardial infarction (AMI)(7.0%-5.2%) with p&lt;0.001. OSA patients had a decrease in all-cause mortality (3.2% v/s 4.7%), AMI (6.3% v/s 7.2%), and cardiac arrest (1.0% v/s 1.3%), with p&lt;0.001. Patient’s on BiPAP/CPAP therapy have further decreased ODD’s of MACCE and is statistically significant, p&lt;0.001. Conclusion: OSA patients with or without BiPAP/CPAP are associated with decreased MACCE in elderly CKD patients. The potential impact of Interventions like BiPAP/CPAP therapy on kidney function and cardiovascular outcomes requires further investigation to better understand and manage chronic kidney disease and OSA cardiovascular paradox.
Abstract 15721: CRISPR Activates Heterochromatic Cardiac Genes in Fibroblasts to Initiate Lineage Conversion Into Cardiac Progenitors
Authors: SUCHANDRIMA DUTTA, JIALIANG LIANG, Wei Huang, Xingyu He, Christian Paul, Yi-gang Wang
Journal: Circulation (2023)

Introduction: Our previous studies have demonstrated that CRISPR activation (CRISPRa) of endogenous genes was sufficient to convert fibroblasts into induced cardiovascular progenitor cells (iCPCs) for myocardial regenerative therapy. However, reprogramming efficiency remains a challenge and little has been elucidated about the epigenetic mechanisms of cellular reprogramming, which will be important for methodological improvements or refinements. Hypothesis: CRISPRa complex can alter the chromatin accessibility and activity of heterochromatic cardiac genes in fibroblasts, directly initiating cardiac reprogramming. Methods: A fibroblast-specific CRISPRa mice model (Pdgfra-cre/ERT; ROSA-dCas9-SunTag) was generated. SgRNAs targeting the promoter region of Gata4, Isl1, Nkx2-5, Baf60c, or Tbx5 genes were transduced through an AAV system in cardiac fibroblast isolated from transgenic mice. iCPCs were confirmed via immunostaining of CPC markers and cardiac electrophysiological assays. iCPCs were collected for RNA-seq, ATAC-seq, and ChIP-seq after reprogramming induction to reveal the epigenetic landscape modulated by CRISPRa. Results: The CRISPRa system was activated in ~80% of fibroblasts after tamoxifen induction and AAV-sgRNA transfection. The reprogrammed iCPCs were characterized by immunostaining of proliferative markers (Ki67 and Pcna), progenitor surface markers (Flk1 and Ssea1), and markers of cardiac tri-lineage cells after induced differentiation. RNA-seq data showed the upregulation of genes associated with cell cycling (Cdkn1b, Aurkb, etc.) and heart development (Myh6, Irx4, etc.) in CRISPRa-induced cells. ATAC-seq showed increased chromatin accessibility at the loci of cardiogenic genes targeted by CRISPRa in fibroblasts. Furthermore, ChIP-seq of Gata4, Nkx2.5, and Tbx5 associated DNA shows that these factors can bind to their own promoter regions in fibroblasts after CRISPRa induction. Conclusions: CRISPRa complexes open the chromatin of the targeted genes in fibroblasts and establish an endogenous autoregulatory loop to ensure stable reprogramming into cardiac progenitors.
Abstract 16589: Predicting Cardiovascular Risk in Participants Treated With Tirzepatide in the SURPASS 1-5 Trials
Authors: Russell J Wiese, Hui Wang, Reema Mody, Brian D Benneyworth
Journal: Circulation (2023)

Predicting atherosclerotic cardiovascular disease (ASCVD) risk considers factors that individually influence the likelihood of experiencing a major cardiovascular (CV) event. Tirzepatide (TZP) is a GIP and GLP-1 receptor agonist that improved risk factors such as lipid profile and systolic blood pressure across the Phase 3 SURPASS T2D program. We compared the effect of TZP versus the comparator on calculated ASCVD risk from baseline to endpoint in each of the 5 SURPASS (S) studies. We assessed the ASCVD risk in T2D participants without CVD history from S 1-5 studies using an American College of Cardiology/American Heart Association risk engine. The risk engine considers the factors: sex, age, race, total cholesterol, high density lipoprotein, systolic blood pressure, antihypertensive medication use, smoking and diabetes status. Risk scores and categories are summarized by treatment group. The baseline characteristics vary between studies (female sex ranges from 44.9% to 54.6%, mean age in years ranges from 53.6 to 64.3) but were similar among treatment groups within each study. The median baseline risk score across the TZP dose range were 6.5-11.5 for S-1, 9.3-10.8 for S-2, 12.4-15.4 for S-3, 22.9-26.0 for S-4, and 14.8-19.1 for S5. At the primary endpoint (40 or 52 Weeks), the ASCVD risk category for 10.9-21.4% of TZP-treated participants improved versus 2.9-12.7% for placebo/comparator (Table). Also, the risk category for 1.2-9.4% of TZP-treated participants worsened versus 6.3-14.9% for placebo/comparator. The median CV risk score was decreased in all TZP treatment groups while the median CV risk score was increased in the placebo/basal insulin groups. In SURPASS-2, the decreases in CV risk score were qualitatively greater in the TZP groups compared to the semaglutide group. TZP treatment lowers CV risk and significantly more participants shift to a lower CV risk category when compared to placebo, basal insulins, and semaglutide.
Abstract 13267: Early Predictors of High-Risk Lymphatic Subtypes on T2-Weighted MRI in Patients After Superior Cavopulmonary Connection
Authors: Jeremiah Joyce, Radhika Rastogi, Erin Pinto, Christopher Smith, Yoav Dori, Aaron G DeWitt, Chitra Ravishankar, David Biko, Danish Vaiyani, Goldberg David
Journal: Circulation (2023)

Introduction: Lymphatic subtype as determined by T2-weighted MRI (T2-CMR) after superior cavopulmonary connection (SCPC) is known to predict clinical outcome after Fontan. Factors related to lymphatic subtype development are not well understood. This study aims to identify early predictors of high-risk lymphatic subtypes. Methods: Retrospective cohort study of consecutive patients with pre-Fontan T2-CMR from 2017 to 2021. Patients divided into two groups based on lymphatic subtype: Group 1 - subtypes 1, 2, and 3; Group 2 - subtypes 3+ (defined as type 3 with history of chylothorax) and 4. Pearson’s chi square, Fisher’s exact, Wilcoxon rank sum, univariate and multivariate logistic regression analysis were performed. Results: We identified 171 patients. The groups differed significantly in total hospital, ICU, and chest tube days, number of catheterizations and number of cardiac surgeries (Table 1). Moderate or greater atrioventricular valve regurgitation (Mod+ AVVR), increased catheterizations and increased chest tube days were associated with high-risk lymphatic subtype. Maintenance of antegrade pulmonary blood flow at the time of SCPC was not significant (Table 2). In multivariate analysis, Mod+ AVVR and number of chest tube days remained in the model after adjusting for other covariates. Overall model significance was 0.007 with an area under the curve of 0.777. Conclusions: Mod+ AVVR and increased chest tube days are predictive of high-risk lymphatic subtype. Further study is needed to determine if lymphatic subtype is acquired via clinical exposure or whether native lymphatic subtype may be predictive of clinical course even prior to cavopulmonary connection.
Abstract 14630: Young Female Presenting With Chest Pain Due to Left Main Aneurysm
Authors: Inderjeet Singh Bharaj, Kirk Thorpe, Oday A Al Rabadi
Journal: Circulation (2023)

Background: Incidence of ACS is increasing in young patients. While atherosclerosis needs to be ruled out, there should be high suspicion for alternate causes. Case: A 36-year-old African American woman with obesity, prediabetes and tobacco use, presented to the ED with chest pain. Initial cardiac investigations unremarkable. CTA chest ruled out pulmonary embolism and aortic dissection. Her pain had resolved and she was discharged home. Within hours, the pain recurred and became progressively worse. She returned to the ED and was found to have an anterior STEMI with a troponin I 0.72 ng/ml. Cardiology was consulted, left heart cath revealed a large left main aneurysm (LMA) with large thrombus burden, with mildly aneurysmal LAD, RCA and LCx, moderate decrease in systolic function and no significant arch or main vessel aneurysms. Case was discussed with cardiothoracic surgery, who recommended medical management. Her symptoms resolved while on anticoagulation. Discussion: Coronary artery aneurysms (CAA) are a rare cause of ACS. The reported incidence of CAA ranges from 0.3% to 5%, most often affecting men. The RCA is the most commonly affected artery followed by the LAD, with the LM being the least common. Risk factors include hypertension, dyslipidemia, smoking, diabetes, and a family history of coronary artery disease. Known etiologies include atherosclerosis, Kawasaki disease, inflammatory, congenital, and degenerative conditions. Transient myocardial ischemia may result from aneurysm-related blood stasis that may predispose to thromboembolic events, coronary spasm, and microvascular dysfunction. Conclusion: Although considered extremely rare, the number of LMA reported has increased in the last decades and may continue to grow with the widespread use of invasive and noninvasive coronary imaging. Considering the rarity of CAA and absence of dedicated studies, both the interventional and the pharmacological management of patients with LMA are challenging.
Abstract 17486: Non-Proportional Hazards in Randomized Cardiology Clinical Trials: A Standardized Universal Secondary Analysis (SUSAN) to Enhance Clinically Meaningful Appraisal of Results
Authors: Anastasios Roumeliotis, Jan G Tijssen, George Dangas
Journal: Circulation (2023)

Introduction: In patients with CAD, more invasive interventions are expected to have more early complications in anticipation of improved longer-term outcomes. This often leads to violation of the proportional hazard (PH) hypothesis, thereby complicating interpretation of results. Hypothesis: Analyzing the early and late post-procedural periods separately may provide important additional information for clinicians beyond the cumulative outcome. Methods: We identified 36 RCTs comparing more versus less invasive strategies for the management of CAD. Of those, 16 exhibited crossover of the Kaplan Meier curves, indicating violation of PH. Hereafter, we focus on 4 landmark trials exhibiting such findings: STICH, EXCEL, FREEDOM, and ISCHEMIA. Complete results in all trials will be presented. Results: Initial evaluation of outcomes violating PH includes assessment using algorithms testing proportionality. Thereafter, focus should be shifted not to the time of crossing of curves, but to identifying the time of trend switch: this signifies transition from the earlier to the later disease states (acute/peri procedure or longer term/chronic phase) and may be accomplished by calculation of instantaneous hazards. Following this, the two clinically relevant periods should be studied individually to quantify the impact of different approaches in each of the periods (Figure). As a final step, the cumulative effect of the intervention on hard endpoints should be calculated using statistical designs not assuming proportionality, such as Restricted Free Survival Time or the Com-Nougue. Conclusions: In addition to the cumulative assessment of the primary endpoint, SUSAN allows analysis of the two post-procedural periods separately, as identified by the point of trend switch. This would be particularly informative for clinicians and patients in reviewing early risks and late benefits; adhering to a standardized method may allow a universal presentation of RCT results.