tbuckley/cabot-search huggingface dataset:
Abstract 16882: Comparison of Regadenoson and Adenosine in First Pass Quantitative Perfusion Cardiovascular Magnetic Resonance in Subjects With Suspected Coronary Microvascular Disease
Authors: Patricia Rodriguez-Lozano, Shuo Wang, Haonan Wang, Ming-Yen Ng, Paul Kim, Amita Singh, Saima Mushtaq, Sin Tsun Hei, Yuko Tada, Elizabeth Hillier, Christian Østergaard Mariager, Michael Salerno, Gianluca Pontone, Javier Urmeneta, Ibrahim M Saeed, Hena Patel, Simon Madsen, Vicente Martinez, Alicia Maceira, Jose Monmeneu, Aju P Pazhenkottil, Mitchel Benovoy, Alborz Amir-Khalili, Martin A Janich, Andrew E Arai, Matthias G Friedrich, Amit R Patel
Journal: Circulation (2023)

Introduction: Regadenoson and adenosine are commonly used vasodilators in myocardial perfusion imaging for detection of coronary artery disease. There are no comparative studies of the vasodilator properties of two agents in subjects with suspected coronary microvascular disease (CMD). We aimed to compare the potency of two vasodilators by quantifying myocardial perfusion in subjects with suspected CMD. Methods: Subjects with angina and more than two risk factors for CMD (females, or males with diabetes, metabolic syndrome, HTN, hyperlipidemia, and smoking) who had no obstructive coronary disease by invasive coronary angiography or CT angiography were enrolled for first-pass perfusion images using dual sequence. Stress perfusion images were acquired on 1.5T or 3.0T GE Healthcare during adenosine infusion or regadenoson. Rest perfusion images were acquired either 10 minutes following the cessation of adenosine or reversal with aminophylline. Myocardial blood flow (MBF) in ml/min/g and myocardial perfusion reserve (MPR) were quantified using Fermi deconvolution. Results: A total of thirty-two subjects were recruited with a mean age of 62±11 years, 53% men, history of hypertension in 91%, diabetes in 72%, hyperlipidemia in 75%, and tobacco use in 16%. Twenty (63%) of subjects underwent adenosine, while twelve (38%) of subjects underwent regadenoson. Regadenoson produced similar stress MBF compared to adenosine (2.30 ± 0.54 vs. 2.35 ± 0.61 ml/min/g, p = 0.66). Rest MBF was higher in the regadenoson group compared to adenosine group (1.35±0.35 vs. 1.12±0.26 ml/min/g, p=0.07). MPR was non-significantly lower in regadenoson compared to adenosine 1.72±0.70 vs.1.89±0.53 ml/g/min, p=0.13). Conclusions: Based on fully quantitative perfusion using CMR, regadenoson and adenosine have similar vasodilator efficacy in subjects with risk factors for CMD. However, resting blood flows are slightly higher when regadenoson is used which may impact quantification of MPR.
Abstract 17020: Education of Children Improves Awareness of Hypertension, a Novel Method to Improve Health Equity
Authors: Cherylann Rocha, Amy C Ladd, Kristine C Olson, Unice Davis, Grace Smith, Arianna Martinez, Sarah Neely, Ralph Dagostino, Greg G Hundley, Phillip Duncan, Sangeeta Shah
Journal: Circulation (2023)

Introduction: Approximately 45% of the U.S. population has hypertension (HTN), with increased prevalence in Black adults in urban areas. HTN is a risk factor for heart disease, stroke, and renal failure. Increasing awareness of HTN during early education may improve health equity. Hypothesis: We hypothesized that a science-based educational program administered to primary school students can increase knowledge of HTN with the objective of increasing awareness and health equity. Methods: We engaged 95 4th graders in an urban, public school system (44% White, 43% Black, 13% Other) with an innovative, experiential educational program administered across four, one-hour sessions as part of their curriculum. We taught and assessed students’ awareness of HTN across four topics: (1) knowledge of BP &amp; HTN, (2) organ systems impacted by HTN, (3) habits to maintain a healthy BP, and (4) their competence to operate a BP monitor according to AHA recommendations. Assessments were completed via surveys of 21 individual data points and administered pre-and post-program with each child as their own control. Paired t-tests were used to analyze the pre- and post-survey data. Results: Of the 95 students who underwent the program, 71 children had both pre- and post-program results. Comparison of pre-and post-program data showed a statistically significant improvement in students’ knowledge about healthy nutrition, organs affected by HTN, and understanding of blood pressure/HTN (53% to 90%, 20% to 75%, and 40% to 77%, respectively)[p&lt;0.001 for all; Table below] Conclusions: Implementing an educational program focused on knowledge of nutrition, organ systems, and BP to 4th-grade students significantly raised awareness of HTN. This innovative program in an urban public school is feasible and may be the first step to decreasing the morbidity of a highly prevalent and modifiable disease in a community.
Abstract 17006: Clinical Characteristics and All-Cause Mortality After Non-Major Bleeding in Patients With Atrial Fibrillation Taking or Not Oral-Anticoagulant: The Fushimi AF Registry
Authors: Kenjiro Ishigami, Yumiko Nakanishi, Syuhei Ikeda, KOSUKE DOI, Takashi Yoshizawa, Yasuhiro Hamatani, Yuya Ide, Akiko Fujino, Mitsuru Ishii, Moritake Iguchi, Nobutoyo Masunaga, Masahiro Esato, Hiromichi Wada, Koji Hasegawa, Mitsuru Abe, Masaharu Akao
Journal: Circulation (2023)

Background: The use of oral anticoagulants (OAC) in atrial fibrillation (AF) patients increases the risk of bleeding. However, the relationship between OAC use before and after non-major bleeding and all-cause mortality remains unknown. Purpose: We aimed to investigate the association between OAC prescription before and after non-major bleeding and all-cause mortality in AF patients. Method: In the Fushimi AF Registry, follow-up data were available in 4,496 patients by the end of February 2022. Patients were divided into four groups based on OAC prescription before and after non-major bleeding: G1 (OAC prescribed both before and after), G2 (OAC prescribed before but not after), G3 (OAC not prescribed before but prescribed after), and G4 (OAC neither prescribed before nor after). Non-major bleeding was defined as all bleeding except for major bleeding according to the criteria of the International Society on Thrombosis and Haemostasis. Result: During the median follow-up of 1,448 days, 733 patients experienced non-major bleeding. G1 had 452 patients, G2 had 54, G3 had 63, and G4 had 164. G1 and G2 were more often non-paroxysmal AF and had significantly higher prevalence of previous stroke or systemic embolism, heart failure and dyslipidemia and had higher CHADS2 scores than G3 and G4. All-cause mortality after non-major bleeding occurred in 91 patients in G1, 54 in G2, 63 in G3, and 164 in G4. (G1: 5.1%, G2: 13.0%, G3: 7.1%, and G4: 6.8% per patient-year, p=0.0004). Multivariate analysis showed that the G2 group had a higher incidence of all-cause mortality as compared with G1 (HR 2.49, 95%CI 1.58-3.93; p&lt;0.0001), G3 (HR 2.44, 95%CI 1.23-4.84; p=0.011), and G4 (HR 1.71, 95%CI 1.00-2.93; p=0.0502) [Figure]. Conclusion: Discontinuation of OAC therapy after non-major bleeding in Japanese AF patients was associated with increased all-cause mortality.
Abstract 16974: Sudden Cardiac Death With Heart Failure Despite Improvement in LV Ejection Fraction: A Population-Based Study
Authors: Harpriya Chugh, Audrey Uy-Evanado, Arayik S Sargsyan, Habiba Aziz, Jonathan Jui, Kotoka Nakamura, Kyndaron Reinier, Sumeet S Chugh
Journal: Circulation (2023)

Introduction: Individuals with heart failure (HF) and severely reduced LVEF (≤35%) have increased risk of SCD and qualify for primary prevention ICD implantation. Guideline-directed medical therapy can improve LVEF in ICD patients but influence on SCD risk remains controversial. Hypothesis: In a subgroup of HF patients, improvements in LVEF may not eliminate risk of SCD.Aim: To identify and characterize a subgroup of HF patients who suffer SCD despite improvements in LVEF. Methods: From a large, prospective population-based study of SCD in the Northwest US (population ~1 million, 2002-2018), we identified all consecutive patients with an established diagnosis of HF and LVEF≤35%. In the sub-group of patients with at least 2 prior LVEF evaluations (earliest and latest in relation to SCD), individuals with significant improvement in LVEF over time (latest LVEF &gt;35%) were compared to those without improvement in LVEF (latest LVEF ≤35%). Results: A total of 1622 individuals suffered SCD with a known diagnosis of HF (65% male, age 72±14) of which 434 had at least 2 LVEF evaluations over time prior to their SCD. Of these 100 (23%) had LVEF ≤35% at their earliest evaluation (mean LVEF 27±6). A subgroup of 46% (n=46) had significant improvement in LVEF between earliest vs latest evaluation (28±6 vs. 49+9, by 20±10, p&lt;0.001) with no improvement observed in the remainder (54%, 25±6 vs. 24±7, by -1±7, p = 0.23). Comparisons of the clinical profile (demographic, coronary disease, comorbidities and medications) did not yield any identifiable differences between the subgroups with and without improvement in LVEF (Table; p&gt;0.05 for all). Conclusions: Approximately half of individuals with SCD and a history of HF and LVEF ≤35% had significant improvements in LVEF, but this group could not be distinguished from those without improvements in LVEF by readily available clinical variables. These findings highlight the need for novel markers of SCD risk beyond the LVEF for this subset of HF patients.
Abstract 16961: Characterization of Extracellular Vesicles and RNA Content and Its Relevance to Thrombo-Inflammatory Biomarkers in Patients With Acute Pulmonary Embolism
Authors: Fakiha Siddiqui, Chongyu Zhang, Srdjan Nikolovski, Bulent Kantarcioglu, Amir Darki, Debra Hoppensteadt, Lonnie Saetern, Alfonso J Tafur, Manuel Monreal, Keith Jones, Jawed Fareed
Journal: Circulation (2023)

Introduction: Pulmonary embolism (PE) is a complex disease with significant morbidity and mortality rates globally. Previous studies have shown that extracellular vesicles (EV) carrying disease specific ribonucleic acids (RNA’s) may contribute to pro-inflammatory and pro-coagulant state in VTE. This study aimed on profiling EV related parameters, RNA content, and thrombo-inflammatory markers in patients with acute PE compared to healthy individuals. Materials &amp; Methods: Prospective cohort of patients with PE (n=72) were compared with normal healthy individuals (n=19) and further stratified by PE severity. Blood samples were collected under an IRB-approved project from Loyola University Chicago. Plasma samples were analyzed for the EV parameters, RNA parameters, and thrombo-inflammatory markers (D-Dimer, PAI-1, and CRP) respectively. Results: PE cohort includes 72 patients (41 male, and 31 female) with a median age of 67-years (interquartile range; IQR= 53-76), and a median body mass index (BMI) of 27.5-kg/m 2 (IQR= 24.7-35.7). Compared to controls, EV concentration, and EV/ng RNA were significantly (p= &lt;0.05) lower, while D-Dimer, CRP and PAI-1 were significantly (p= &lt;0.05) higher in patients with PE. In correlation analysis, varying levels of positive and negative correlations between the EV, and RNA parameters, and thrombo-inflammatory markers were noted (Figure 1). Upon stratification on PE severity, D-dimer was higher in massive PE compared to low-risk (p= 0.012), and sub-massive PE (p=0.036) respectively. Conclusion: These studies demonstrate significant changes in extracellular vesicles, RNA content and thrombo-inflammatory markers in acute PE patients compared to healthy controls. These changes may be due to the drivers of VTE pathogenesis or the result of a consumption process in acute PE. Further large scales studies on disease specific exosomes and RNA signatures are warranted to understand their relevance.
Abstract 18666: SR-BI and Tyrosine Kinase Inhibitors: A Novel Pathway for Atherosclerotic Cardiovascular Disease Therapeutic Development
Authors: Holly C Sucharski-Argall, Sallie J Jurs, Aaron D Argall, Jordan L Williams, Revati S Dewali, Emma K Dudley, Luke Comisford, Nondyce C Gulik, Alaina A Lah, Kristin I Stanford, Peter J Mohler, Sara N Koenig
Journal: Circulation (2023)

Introduction: Cardiovascular disease (CVD) is the leading cause of death in the U.S., where coronary artery disease (CAD) accounts for 42.1% of all CVD deaths. Current therapeutics focus on lowering LDL-C, as previous attempts to raise HDL-C were not successful in altering CVD outcomes. However, the therapeutic potential of HDL has not been fully explored. Variants in SCARB1, the gene that encodes HDL receptor Scavenger Receptor B1 (SR-BI), are associated with dyslipidemia and atherosclerotic CVD (ASCVD), and we first to identified Mendelian inheritance of SCARB1 variants that cause severe early-onset CAD and dyslipidemia. Limited clinical evidence suggests imatinib reduces total cholesterol in chronic myeloid leukemia (CML). Additionally, TKI treatment in atherosclerotic mice reduced total cholesterol (imatinib) and atherosclerotic lesions (dasatinib). Yet, no data is available on the effects of TKIs on HDL and RCT. Hypothesis: Our findings suggest that HDL function (vs. HDL-C concentration) in reverse cholesterol transport (RCT) may be a promising target for cholesterol-based therapy and studying TKIs in RCT may provide a novel mechanism for therapeutic development. Methods: We performed a high throughput drug screen with 788 FDA-approved compounds, using HepG2 cells to measure endogenous HDL binding. We identified four compounds that significantly increased HDL binding, of which, imatinib was the only one to increase SR-BI. Wildtype C57Bl/6 mice on a high fat, high cholesterol diet, underwent imatinib treatment for 4 weeks and measured biweekly serum lipids. Results: We have found that imatinib and dasatinib significantly enhance HDL binding, where imatinib increased SR-BI, ABCA1, and ABCG1 in vitro. Furthermore, in vivo imatinib treatment decreased plasma total cholesterol, HDL-C and triglyceride levels, and elevated hepatic SR-BI. Knockdown of SR-BI in HepG2 cells ameliorated the imatinib-induced HDL binding increase suggesting an SR-BI-specific mechanism. Mass spectrometry revealed a novel SR-BI methionine oxidation site with imatinib treatment. Conclusions: Our data supports the exploration of TKI-mediated SR-B1 regulation, HDL metabolism, and RCT mechanism to identify new therapeutic targets for dyslipidemia and ASCVD.
Abstract 16968: Hypoxia-Lactate Dehydrogenase A-Lactate Axis Mediated Metabolic Adaptation of Macrophage Promotes Vascular Remodeling of Pulmonary Hypertension
Authors: Na Wang, Qiang Li, Feilong Wang, Yingqun Ji
Journal: Circulation (2023)

Introduction: Early recruitment of inflammatory macrophages with subsequent adaptation into pro-fibrotic phenotype have been reported essential for the development of PH. However, the underlying mechanism remains undetermined. Hypothesis: With enhanced glycolysis under hypoxic conditions, lactate dehydrogenase A(LDHA) mediated accumulation of lactate facilitates metabolic adaptation of macrophages and promotes the development of PH. Methods: Circulating monocytes, lactate, LDHA expression level were analyzed from patients with PH. The expression of LDHA, iNOS, and Arg1 in macrophages within lung tissue were examined on histopathology from patients with IPAH. Mice with myeloid specific knockout of Ldha were generated, and hemodynamic measurement, echocardiogram, histopathological examinations were conducted to evaluate pulmonary vascular remodeling using Su/Hx PH model. Bone marrow derived macrophage (BMDM) and vascular smooth muscle cells (SMCs) from mice were harvested for the mechanism study. Results: Lactate, monocytes and LDHA expression in PBMC were elevated in PH patients. On histopathology, perivascular macrophages infiltration with overexpression of LDHA, iNOS and Arg1 was noticed from lung tissue of IPAH patients, similar seen in both MCT-PH rats and Su/Hx mice. Mice with myeloid knockout of Ldha ( Ldha lyz2-/- ) shown decreased RVSP and improved right heart function on Echocardiogram. In vitro, inflammatory BMDM shown significantly elevated expression of LDHA and lactate under hypoxia, along with oversecreted growth factors including PDGF-β and promoting SMCs proliferation, which can be reversed by Ldha depletion. Conclusions: The hypoxia-LDHA-lactate axis plays a crucial role in metabolic adaption of macrophages under hypoxia condition, promoting SMCs proliferation and pulmonary vascular remodeling process. These findings suggest that targeting LDHA-lactate axis might exert therapeutic potential for PH.
Abstract 18629: Discriminative Accuracy of Cha <sub>2</sub> Ds <sub>2</sub> Vasc Score, and Development of Predictive Accuracy Model Using Machine Learning for Ischemic Stroke in Cardiac Amyloidosis
Authors: Waqas Ullah, Abhinav Nair, Eric Warner, Salman Zahid, Daniel Frisch, Indranee Rajapreyar, Rene Alvarez, Mohamad A Alkhouli, Sridhara Yaddanapudi, mathew S Maurer, Yevgeniy Brailovsky
Journal: Circulation (2023)

Background: Cardiac amyloidosis (CA) in conjunction with atrial fibrillation (AF) presents unique management challenges. CHA2DS2VASc score in these patients is believed to underestimate the risk of ischemic stroke, necessitating a better predictive model in these patients. Methods: Data was obtained from the National Readmission Database (NRD). Outcomes between CA-AF and no-CA-AF were compared using multivariate regression analysis to calculate adjusted odds ratios (aOR). AutoScore; an interpretable machine learning framework, was used to develop a stroke risk prediction model, the predictive accuracy of which was evaluated with an area under the curve (AUC) using the receiver operating characteristic analysis. Results: A total of 11,860,804 (CA-AF 22,687 [0.19%] and no-CA-AF 11,838,117) patients were identified from 2015-2019. The adjusted odds of mortality (aOR 1.41 and 1.29), stroke (aOR 1.78 and 1.74), non-intracranial hemorrhage (aOR 2.10 and aOR 1.85), and intracranial hemorrhage (aOR 14.4 and aOR 4.26) were significantly higher in CA-AF compared with non-CA-AF at both index admission and 30-days, respectively. The CHA 2 DS 2 VASc score had a poor discriminative accuracy for stroke at 30-days in CA-AF (AUC 49%, 95%CI 47%-51%, p=0.54). The machine learning autoscore integrative model revealed that the predictive ability of our newly proposed E-CHADS score (end-stage renal disease (ESRD), congestive heart failure, hypertension, active cancer, dementia, and diabetes mellitus) for 30-day risk of ischemic stroke in CA-AF was excellent (for a cutoff of 52 points random forest score) with an AUC of 80% (95%CI 74%-86%) Conclusion: Cardiac amyloidosis carries a high risk of ischemic stroke that is not accurately predicted by the CHA 2 DS 2 VASc score. Our proposed model (E-CHADS) identifies 3 new variables (ESRD, dementia, and cancer) that have higher discriminative accuracy for ischemic stroke in these patients.
Abstract 17019: The Missense W792R Mutation in C6 Domain of Cardiac Myosin Binding Protein-C Alters Morphology and Contractility in Mouse Myocardium
Authors: John C Ralphe, Jasmine A Giles, Emily T Farrell, Ella C Harbaugh, Willem J de Lange, Richard L Moss
Journal: Circulation (2023)

Background: Mutations in cardiac myosin binding protein C (cMyBP-C) are a common cause of hypertrophic cardiomyopathy (HCM) in humans. While many known cMyBP-C mutations lead to haploinsufficiency, others lead to amino acid substitutions which may impact protein function in unique ways The W792R mutation introduces a charge change and is known to be pathogenic in humans. This mutation, located remotely from both the regulatory amino terminus, and the C-terminus, has an unknown impact on the final protein structure and function. Goal: Generate a murine knock-in model to fully characterize the impact of the W792R mutation on cardiac morphology and function in vivo. Methods: We generated a W792R knock-in (KI) mouse and produced heterozygous (HT) and homozygous (KI) offspring, and wild-type (WT) littermate controls. We performed histology, RNA and protein expression analyses, and mechanics on isolated trabeculae at postnatal day 12 (KI n=5; HT n=3; and LC n=4). One-way ANOVA used to compare KI and HT to WT samples, with p-values &lt; ; 0.05 as significant. Results: The KI mice did not live past ~20 days old with massive hypertrophy, dilated atrium, myofibrillar disarray and fibrosis. Full-length mutant protein was expressed and incorporated into the sarcomere. Survival and morphology in the HT was similar to WT. Post-natal day 10 KI mice demonstrated severely enlarged atria and ventricles, interstitial fibrosis, a trend towards increased Ca 2+ sensitivity (pCA 50 KI 5.8 vs HT 5.65 vs LC 5.67 mM; p &gt; 0.05), a trend towards increased cross-bridge cycling kinetics (k tr KI 24.00 + 2.42 vs HT 24.33 + 1.08 vs LC 21.25 + 0.87; p &gt; 0.05) and increased levels of β-myosin heavy chain expression compared to both LC and HT mice. Conclusions: In our mouse HCM model, homozygous expression of the W792R-cMyBP-C mutation recapitulates severe human HCM and provides mechanistic insights into the pathology of this mutation. The trend towards accelerated crossbridge kinetics suggest that the W792R mutation disrupts the inhibitory effects of cMyBP-C on myosin-actin binding implicating the potential application of current myosin ATPase inhibitors in the treatment of patients carrying this mutation. Ongoing work will expand sample sizes to evaluate significance of findings.
Abstract 16979: Posterior Wall Ablation With Cryoballoon in Persistent Atrial Fibrillation
Authors: Miaoli Bloemhard, Victor Berkland, Hannah Bernstein, Carly Robinson, Rahul Iyer, Dali Fan, Bilal Munir, Uma N Srivatsa
Journal: Circulation (2023)

Background: Posterior wall ablation (PWA) in addition to pulmonary vein isolation (PVI) has been suggested to improve outcomes in persistent atrial fibrillation (PeAF). Endocardial radiofrequency ablation is frequently inadequate to achieve electrical silence of PW. Aim: To contribute to the real-world data of the efficacy of PWA with cryoballoon in treating PeAF. Methods: This is a single-center, retrospective study including patients with PeAF referred for catheter ablation between 2015-2019 who underwent either PVI or PVI+PWA. PeAF was defined in accordance with current guidelines. PWA was achieved by cryoballoon; repeat map was used to confirm electrical silence (&lt;0.05mV). Time to ablation (TTA) was defined as the time between first documented AF diagnosis and ablation. Patients were monitored for recurrence of AF or other atrial arrhythmia, defined as atrial tachycardia or flutter, through 1-year follow-up. Results: A total of 119 patients were included, 43 (36.13%) underwent PVI alone and 76 (63.87%) underwent PVI+PWA. PVI and PWA groups had similar baseline characteristics (Table 1). All patients in PWA cohort had complete electrical silence in PW. One-year follow-up occurred at a mean of 370.46 + 91.70 days after ablation. PWA was associated with decreased AF recurrence at 1-year follow up (35.90% in PVI vs 16.44% in PWA, OR 0.35, 95%CI 0.14-0.86, p = 0.023). In multivariate logistic regression, when controlling for age, longstanding persistent AF and TTA the association of PWA with decreased AF recurrence became stronger (OR 0.27, 95%CI 0.10-0.73, p = 0.010). PWA was not associated with a significantly increased rate of other atrial arrhythmia at 1-year follow-up (23.08% in PVI vs 13.70% in PWA, OR 0.53, 95%CI 0.19-1.44, p = 0.212). Conclusion: In comparison to PVI alone, PWA leads to decreased AF recurrence without increase in other arrhythmia at one year follow-up in PeAF. Cryoballoon technique may offer a more complete ablation in PW contributing to efficacy.