tbuckley/cabot-search huggingface dataset:
Abstract 15120: Effect of Prolonged Left Ventricular Global Longitudinal Strain Reduction After Exercise on the Development of Cardiovascular Events
Authors: Katsuhisa Ishii, Shunsuke Usami, Minako Kinoshita, Kotaro Miyagawa, Mamoru Hayano, Takeshi Hatani, Yuya Aono, Hidenobu Seo, Satoshi Asada, Shuichiro Kaji
Journal: Circulation (2023)

Introduction: Recently, it has also been reported that patients with ischemic heart disease have prolonged left ventricular (LV) GLS reduction after exercise. Hypothesis: To investigate the influence of prolonged LV GLS reduction after exercise on the development of cardiovascular events. Methods: One hundred thirty-three consecutive patients with at least one of the following coronary risk factors: hypertension, hyperlipidemia, or diabetes mellitus underwent echocardiography (ARTIDA; Canon medical, Japan) before and 30 minutes after Master double exercise and LV GLS was measured offline (Vitria; Canon medical, Japan). Patients with obvious LV wall motion abnormalities, significant valvular heart disease, or atrial fibrillation were excluded. The incidence of cardiovascular events was determined from the patients' medical records. Patients were divided into three groups based on the occurrence of cardiovascular events up to 6 months after the examination: non-events group, minor cardiovascular event group (chest pain, palpitations, other additional tests), and major cardiovascular event group (coronary revascularization, cardiac hospitalization). The LV GLSs before and 30 minutes after exercise were compared in each patient group. Results: Mean age was 63±11.5years (female: 25%). Patients had hypertension (53%), hyperlipidemia (47%), and diabetes (65%). Of the 133 eligible patients, non-event group (n=68), minor cardiovascular event group (n=50), and major cardiovascular event group (n=15). LV GLS before exercise was not significantly different between the groups, however LV GLS at 30 minutes after exercise were significantly lower in the cardiovascular event groups and were proportional to the severity of the event. (Figure) Conclusions: The prolonged reduction in LV GLS after exercise could be a useful predictive index for the development of cardiovascular events.
Abstract 14343: Early Genetic Screening and Cardiac Intervention in Patients With Genetic Cardiomyopathies Within a Multidisciplinary Care Model
Authors: Chandu Sadasivan, Luke R Gagnon, Kaiming Wang, Deepan Hazra, Tara Dzwiniel, Susan Christian, Jissy Thomas, Anita Y Chan, David I Paterson, Wayne Tymchak, Gavin Y Oudit
Journal: Circulation (2023)

Introduction: Patients with genetic cardiomyopathies are a heterogeneous group of patients who experience significant morbidity and mortality. Early cardiac assessment and intervention coupled with access to genetic counselling and testing may improve clinical outcomes and prevent progression to end-stage heart failure. Methods: Our prospective cohort study was conducted at our multidisciplinary Cardiomyopathy Clinic and patients with suspected genetic cardiomyopathy (CM) or a family history of CM ( n =405) were recruited. Patients with genetic analysis completed ( n =228) were categorized into dilated cardiomyopathy (DCM) ( n= 118), hypertrophic cardiomyopathy (HCM) ( n= 55), infiltrative cardiomyopathy (CM) ( n= 18), and Stage A/at-risk for CM ( n= 37). Continuous variables were analyzed using Wilcoxon signed-rank test or paired t test, while categorical variables were compared using Pearson chi-square tests. Results: There was a median follow-up time of 13 months (IQR: 7 - 21 months) with an increase in genetic testing, cascade family screening, optimization of guideline-directed medical therapy, and usage of device therapies compared to prior to clinic enrolment. In patients with genetic testing, 29.4% ( n= 67) had positive genotypes (pathogenic or likely pathogenic variants), 11.8% ( n= 27) had variants of unknown significance (VUS), and 58.8% ( n= 134) had negative or inconclusive genotypes. Optimization of medical and device therapies resulted in improvements in left ventricular ejection fraction from 30.5% (20.8 - 42.5%) to 45.5% (34.0 - 48.5%, P&lt; 0.001), reduced left ventricular mass index from 121.2 g/m 2 (116.2 - 146.4 g/m 2 ) to 107.0 g/m 2 (88.9 - 134.7 g/m 2 , P&lt; 0.001), and reduced E/e’ ratio from 12.6 cm/s (9.2 - 15.3 cm/s) to 10.9 cm/s (9.0 - 14.2 cm/s, P= 0.015). These improvements were driven by patients with negative genotypes (no variants or VUS) relative to those with positive genotypes. Additionally, patients with normal blood pressure (SBP &lt; 120 mmHg and DBP &lt; 80 mmHg) at follow-up had improvement in LVEF ( P&lt; 0.001) and LVMI ( P= 0.005). Conclusion: Our findings demonstrate the efficacy of a combined cardiovascular genetics clinic in improving the clinical trajectories of patients with genetic cardiomyopathies.
Abstract 16389: Inflammatory Chronic Kidney Disease is Associated With Incident Heart Failure: A Pooled Cohort Analysis
Authors: Arsalan Hamid, Abdul Mannan Khan M Minhas, Maria Clarissa Tio, Mohammad S Khan, Muhammad Shariq S Usman, Daisuke Kamimura, Tariq J Siddiqi, Ambarish Pandey, Javed Butler, Michael E Hall
Journal: Circulation (2023)

Introduction: High sensitivity C-reactive protein (hsCRP), a biomarker of inflammation, can risk stratify patients for cardiovascular disease including heart failure (HF). It is not well established if inflammation increases the risk of HF in patients with chronic kidney disease (CKD) and if hsCRP can be utilized to risk stratify patients with CKD for their risk of incident HF. Aims: We assessed the role of hsCRP in risk stratifying patients with CKD for incident HF. Methods: We studied participants of 3 major epidemiologic cohorts: Atherosclerosis Risk in Communities Study, Multi-Ethnic Study of Atherosclerosis, and Jackson Heart Study. High inflammation was classified as hsCRP &gt;3 mg/L and CKD was classified as estimated glomerular filtration rate &lt;60 mL/min/1.73m2. Participants were stratified into 3 groups: neither CKD nor high inflammation, CKD without high inflammation, or CKD with high inflammation. Cox hazards models adjusted for age, sex, race, body mass index, smoking, alcohol use, diabetes, hypertension, and coronary disease were utilized for analysis. Results: 8,692 participants with 460 incident HF events followed over a median 8.32 years were included in our analysis. Participants with CKD without high inflammation (HR = 1.45; 95% CI 1.14 to 1.85) and CKD with high inflammation (2.05; 1.61 to 2.61) were associated with an increased risk of incident HF compared with participants without CKD or high inflammation (referent, Figure). Furthermore, participants with CKD and a hsCRP &gt;3 mg/L had an increased risk of incident HF (1.41; 1.06 to 1.88) compared with participants with CKD but hsCRP ≤3 mg/L (referent). Conclusions: Patients with CKD and high levels of inflammation carry a 2-fold increased risk of incident HF. In patients with CKD, hsCRP levels &gt;3mg/L may be useful to risk stratify patients with increased risk of developing HF.
Abstract 13107: Addressing Sudden Cardiac Arrest: An Analysis of the Efficacy and Implementation of Automated External Defibrillators in New Jersey Schools
Authors: Ezra Schneier, Mira Blecherman, Themba Nyirenda, george kipel
Journal: Circulation (2023)

Introduction: Out of hospital sudden cardiac arrest is a major health concern with a low survival rate. Proper Automated External Defibrillator use has been shown to decrease mortality associated with OHCA. In 2014, New Jersey passed Janet’s Law to mandate automated external defibrillator access in all public and private schools. Our project surveyed NJ schools to evaluate the implementation of AEDs and to analyze their usage and outcomes. Hypothesis: Schools that were adherent to AED placement and training as outlined in Janet’s Law will likely have more positive outcomes from sudden cardiac arrests on school properties than schools that do not. Methods: An observational, cross sectional study was conducted via an online form (Redcap 12.4.2) sent to New Jersey public school nurses. Data was collected from February to June 2023 and analyzed using SAS version 9.4. Results: 301 (99.7%) responses reported having automated external defibrillators. 85.3% of schools provided AED staff training. 42 schools (14.4%) utilized an AED in a cardiac emergency, most often occurring to students in classrooms. An AED was administered by school employees 95.8% of the time. In 80.5% of cases, the patient was resuscitated on scene with no long term neurological complications. 87.2% of schools have an emergency response plan. Conclusions: Our data highlights the impact of proper AED utilization to positively influence out of hospital sudden cardiac arrest outcomes in pediatric populations. Despite Janet’s law being an unfunded mandate, we found near complete compliance among New Jersey schools. The majority of reported sudden cardiac arrests occurred in a classroom setting, necessitating available resources throughout school facilities. In these events, the percentage of positive patient outcomes in our study was significantly higher than the national average with excellent neurological recovery. This discovery may be a product of excellent response rates by trained staff as mandated in Janet’s law. Our findings highlight the need for awareness, training, and accessibility regarding AEDs.
Abstract 15791: Higher Diet Quality Associates With Lower Inflammation in Black Adults With Heart Failure
Authors: Erica Davis, Sandra B Dunbar, Melinda Higgins, Erin Ferranti, Brittany Butts
Journal: Circulation (2023)

Introduction: Heart failure (HF) is associated with a chronic inflammatory state. Diet-derived metabolites, such as trimethylamine-N-oxide (TMAO), may be associated with chronic inflammation. Most Americans consume a pro-inflammatory diet with high intakes of sugar and processed foods, but adherence to high quality diet patterns may be beneficial in HF-associated inflammation. The Healthy Eating Index (HEI) and the Alternative Healthy Eating Index (AHEI) measure adherence to the Dietary Guidelines for Americans with greater adherence associated with lower inflammation and better HF outcomes but is understudied in Black adults. Hypothesis: Higher adherences to the HEI or the AHEI is inversely associated with TMAO and inflammation measured by TNF-α. Methods: Participants included Black adults living with HF (N=36, mean age 57 years, 64% women); HEI and AHEI diet scores were derived from a food frequency questionnaire (FFQ). TMAO and TNF-α were analyzed with dried blood spots and immunoassays. A lifestyle factor (LIS) score consisting of alcohol intake, body mass index, physical activity, and smoking was measured. Analyses included correlational and regression analyses. Results: Regression models explained the variance of TMAO and TNF-α levels. HEI and related covariates (AHEI, LIS) explained 15.9% change in TMAO levels: F(3,30)=3.09, p&lt;.042. Standardized beta coefficients were at least 0.3 and higher. HEI scores and related covariates explained 17.2% change in TNF-α levels: F(4,29)=2.71, p&lt;.050. There was an inverse correlation between AHEI scores and TNF-α: r=-.36, p=.031. Conclusions: Higher diet quality, as measured by the HEI/AHEI, was associated with lower levels of TNF-α. The anti-inflammatory benefits of adherence to healthy eating patterns are important in the self-management of HF, yet these foods may include precursors for TMAO levels. Thus, healthy eating should be balanced with an overall dietary plan that attends to the quantity and nature of foods consumed by those with HF. Interventions which promote adherence to high quality diet patterns are needed in adults with HF, particularly in Black adults who bear an excess burden of disease. More research to understand which specific diet components decrease inflammation in HF are warranted.
Abstract 17284: Prognostic Impact of Silent Cerebral Microbleeds in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Yumiko Kanzaki, Tomohiko Watanabe, Kazushi Sakane, Hideaki Morita, Masaaki Hoshiga
Journal: Circulation (2023)

Introduction: Cerebral microbleeds (CMBs) are known to be associated with age, various cardiovascular risk factors, cognitive impairment, the use of antithrombotic drugs, and future neurological or cardiovascular events. Transcatheter aortic valve implantation (TAVR) has emerged as a rapidly evolving treatment for patients with severe aortic stenosis (AS). However, data on CMBs in those patients are scarce. Hypothesis: We hypothesized that the presence of CMBs in patients with severe aortic stenosis (AS) undergoing TAVR may be associated with some clinical factors or have prognostic implications. Methods: A retrospective analysis was conducted on data from 137 consecutive patients (mean age: 84 ± 5 years, 55 male) with severe AS who underwent T2*-weighted brain magnetic resonance imaging (MRI) prior to TAVR. The brain MRI was assessed by researchers blinded to the patients' clinical information. Additionally, conventional echocardiography was performed to evaluate left ventricular function and valvular abnormalities. Results: CMBs were identified in 42 out of 137 patients (31%). No significant differences were observed between patients with and without CMBs in age, gender, serum BNP levels, or antiplatelet/anticoagulant therapy. However, there were significant differences in left ventricular ejection fraction (LVEF) and left ventricular end-systolic volume (LVESV) between the two groups (LVEF: 58 ± 14% vs. 64 ± 10%, p = 0.01; LVESV: 38 ± 25 ml vs. 28 ± 16 ml, p &lt; 0.01, respectively). Over a median follow-up period of 618 days, patients with CMBs had a higher incidence of major adverse cardiac events (defined as death or heart failure re-hospitalization) compared to those without CMBs (24.0% vs. 13.0%, log-rank test, p = 0.04). (Figure). Conclusions: Our study reveals a high prevalence of CMBs in patients with severe AS. The presence of CMBs is associated with lower LVEF, increased LVESV, and poor prognosis following TAVR.
Abstract 17130: Metabolic and Epigenetic Coupled Regulation in Angiogenic Transdifferentiation and Vascular Recovery
Authors: Li Lai, Shuang Li, Alexander J Lu, Kaylee Carter, Eric Nagueh, John P Cooke
Journal: Circulation (2023)

Recent studies from our group and others have characterized the phenomenon of "angiogenic transdifferentiation” from fibroblasts to endothelial cells as a novel endogenous mechanism for microvasculature expansion and perfusion restoration in murine models of hindlimb ischemia and myocardial infarction. Metabolic regulation of epigenetic reprogramming has emerged as a key regulatory process controlling cell fate transition. To study the comprehensive role of metabolism in this healing process, we conducted liquid chromatography-mass spectrometry (LC-MS) based untargeted and targeted metabolomics during transdifferentiation. Our analysis revealed the upregulation of key metabolites, including UDP-GlcNAc (substrate for post-translational modification O-GlcNAcylation) and acetyl-CoA (substrate for histone acetylation). With our in vitro transdifferentiation protocol, we found that pharmacologic or genetic inhibition of OGT (O-GlcNAc transferase, the enzyme responsible for protein O-GlcNAcylation) or ACL (ATP citrate lyase, the enzyme converting citrate to acetyl-CoA) in human BJ fibroblasts impairs transdifferentiation. Employing a preclinical peripheral arterial disease (PAD) hindlimb ischemia model with fibroblast lineage tracing mice, we discovered that O-GlcNAcylation and ACL were accumulated in fibroblast lineage cells in ischemic limbs, and pharmacologic inhibition of OGT or ACL diminished the transdifferentiation cell population in the ischemic tissue. Furthermore, we identified fibroblast-specific OGT or ACL KO impaired vascular recovery post femoral artery ligation in the mice. Finally, we showed that metabolism-dependent post-translational modifications on histones (acetylation of H3K9, H3K27, H3K14) or histone chaperons (O-GlcNAcylation of HIRA, a histone H3.3 chaperone) mechanistically enhanced chromatin openness, thereby facilitating cell fate plasticity and vascular regeneration. In conclusion, our studies demonstrate the significant regulatory potential of metabolic factors in angiogenic transdifferentiation which presents an innovative avenue to enhance vascular recovery in ischemic vascular diseases such as PAD.
Abstract 13322: Administrating the Anti-Apoptosis Inhibitor of Macrophage Antibody Prevents Aortic Aneurysm Progression in Mice
Authors: Taro Fujii, Aika Yamawaki-Ogata, Sachie Terazawa, Yuji Narita, Masato Mutsuga
Journal: Circulation (2023)

Introduction: Our previous report has shown that macrophages play vital roles in developing aortic aneurysms (AA). Apoptosis inhibitor of macrophage (AIM) secreted from macrophages is known to induce apoptosis resistance of macrophages and exacerbate chronic inflammation, which leads to arteriosclerosis. However, it is unclear the role of AIM in AA. Hypothesis: We hypothesized that administering the anti-AIM antibody could prevent eventual AA progression via inhibiting chronic inflammation and promoting apoptosis of macrophages. Methods: The AA was induced in apolipoprotein E deficient mice by subcutaneous angiotensin II (ATII) infusion. Along with ATII infusion, an anti-murine AIM monoclonal antibody or anti-murine IgG antibody was injected intraperitoneally. Mice were divided randomly into two groups: (i) AIM group; weekly anti-AIM antibody injection (n=10), and (ii) IgG group; anti-IgG antibody injection as control (n=14). All animals were euthanized 4 weeks after study initiation. Results: There were two deaths in the control group and one in the AIM group. None of the deaths were aorta-related. Compared with the IgG group, the AIM group exhibited reduced AA enlargement (aortic diameter at four weeks: AIM 2.1 vs. IgG 2.7 mm, p = 0.012), less loss of construction of the elastic lamellae, reduction protein expression levels of various inflammatory response including IL-6, TNF-α and MCP-1, a decrease in the number of AIM-positive cells and inflammatory M1 macrophages (AIM: 1.4 vs. 8.0 %, p = 0.004, M1 macrophages: 24.5 vs. 55.7 %, p = 0.017), and higher expression of caspase-3 (22.8 vs. 10.5 %, p = 0.019) in the aortic wall. Conclusions: Our results suggested that anti-AIM antibody therapy mitigated AA progression by controlling inflammation and promoting apoptosis.
Abstract 17315: Black Patients With Heart Failure Living in Distressed Communities Disproportionately Experience Excess Risk of Mortality After Emergency Department Visit for Dyspnea
Authors: Karina Kraevsky-Phillips, Clifton W Callaway, Richard A Henker, Paul Scott, Salah S Al-Zaiti
Journal: Circulation (2023)

Introduction: Dyspnea is a frequent reason for seeking emergency care in patients with heart failure (HF). Social determinants of health play an important role in long term survival in this population. We sought to explore the association between community’s economic well-being and post-visit survival in patients with HF evaluated in the emergency department (ED) for dyspnea. Methods: This was a retrospective cohort study enrolling all consecutive patients with a history of HF and an ED visit for a chief complaint of dyspnea at one of 40 UPMC-affiliated hospitals in Western PA between 1/2018 and 12/2021. We automatically extracted limited tabular data from electronic health records (e.g., demographics, visit dates) and performed manual chart review to determine home community status according to Economic Innovation Group’s Distressed Communities Index (i.e., prosperous/comfortable vs mid-tier/at-risk/distressed). Primary outcome was all cause death, established by documented death in UPMC network inpatient or outpatient charts and through a manual obituary search to ascertain missing death dates through 5/2023. We used Cox regression to identify independent predictors of time-to-event (death) and plotted significant predictors using Kaplan-Meier analysis. Results: The sample included 1248 patients (age 73 ± 13, 53% female, 15% Black). Around 59% of patients lived in distressed communities, and 62% died during a mean follow up of 996 days. In multivariate Cox regression, age (HR=1.032, 95% CI 1.025-1.038) and non-Black race (HR=2.304, 95% CI 1.264-4.202) were associated with excess risk of mortality. There was a significant independent interaction between race and residence, with Black individuals living in distressed communities experiencing excess risk of death compared to their counterparts (HR=1.926, 95% CI 1.083-3.424). This interaction was not evident among individuals who were not Black. Conclusion: While elderly patients, who are predominantly White, experience excess risk of HF mortality irrespective to area of residence, Black patients living in distressed communities experience excess risk of mortality, independent of age, sex, and other potential risk factors.
Abstract 15636: NFATC1 Modulates Atrial Excitability and Arrhythmogenesis
Authors: Natalia S Torres, Christopher Kauffman, YUEQIN YANG, Alexandra Acuna, Karishma Shah, Scott Cho, Martin Tristani-Firouzi
Journal: Circulation (2023)

Transcription factors have emerged as important loci for atrial fibrillation (AF) susceptibility. We identified a novel mutation (M527L) in a conserved site of the transcription factor NFATC1 in a multigenerational family with an autosomal dominant young onset AF (&lt;40 years old) phenotype. M527L reduces NFATC1 nuclear translocation (nuclear/total cellular ratio: M527L 0.50±0.02; WT 0.64±0.04, p&lt;1E-5; n=10/each), DNA binding (M527L 0.69±0.02; WT 0.83±0.01, p=0.02; n=3/ each), and transcriptional activity (M527L 0.0003±0.00005; WT 0.0009±0.0002, p=0.01; n=5/each) in expression systems, underscoring the functional consequences of this mutation. To study the broader role of NFATC1 in atrial excitability we employed a CRISPR/Cas9 strategy to create an nfatc1 null (KO) zebrafish. KO fish exhibited reduced survival, with ~80% of juvenile fish succumbing to sudden death (log rank test p=0.0001), with no observable change in body or heart gross morphology. Explanted juvenile atria displayed spontaneous tachyarrhythmias or irregular rhythm (29 /40 KO atria vs 11/28 WT atria; Chi-Squared, p=0.0013) accompanied by irregular Ca 2+ handling (10/11 KO atria vs 5/16 WT atria). Furthermore, we found an abbreviated action potential duration in KO atrium (80±1 ms in KO (n=607) vs 91±1 ms in WT (n=441), p=0.0001), but not ventricle (186±3 ms in KO (n=109) vs 191±2 ms in WT (n=160), p=0.8). Taken together, our data suggests that NFATC1 is a modulator of atrial excitability and plays a role in AF susceptibility. Experiments are ongoing to further define the mechanisms underlying arrhythmia susceptibility and to identify the gene networks downstream of NFATC1 in the atria.