tbuckley/cabot-search huggingface dataset:
Abstract 14966: Happy Heart Syndrome: The Mid-Ventricular Variant of Takotsubo Cardiomyopathy Triggered by Pleasant Experiences
Authors: Md Rockyb Hasan, Eman Alhussain, Mohammed Abdelsalam, Thien Vo
Journal: Circulation (2023)

Introduction: A joyful event triggered chest pain in an elderly woman, leading to the diagnosis of a mid-ventricular variant of Takotsubo cardiomyopathy (TC). Case presentation: A 65-year-old woman experienced chest pain during a surprise retirement party. The initial electrocardiogram revealed T-wave inversions in leads V1 and V2, and her troponin I level was 6700 ng/ml. A coronary angiogram did not reveal any occlusion in the coronary arteries. However, the left ventriculogram exhibited findings consistent with the mid-ventricular variant of TC. The patient was treated with a diuretic, a beta-blocker, and an ACE inhibitor. A follow-up echocardiogram was scheduled after four weeks. Discussion: TC typically manifests with abnormal apical wall motion on the left ventriculogram, causing "apical ballooning" at end-systole and basal hyperkinesis, unrelated to specific major epicardial coronary artery distribution. Among patients presenting with symptoms resembling acute coronary syndrome (ACS), a study reported that 1.2% showed TC, with 60% exhibiting regional dysfunction in both apical and midventricular regions. In comparison, 40% had isolated dysfunction in the midventricular area. Other rare variants of TC have also been documented, including the inverted Takotsubo or basal variant, biventricular apical dysfunction, and isolated right ventricular Takotsubo syndrome. In a recent study, TC triggered by positive experiences ("happy heart syndrome"), the mid-ventricular variant was found to occur more frequently, representing 35% of the cases. The treatment for TC includes standard management of heart failure and regular follow-up echocardiography is recommended for surveillance. Conclusion: In cardiology, the often-overlooked atypical patterns of left ventricular dysfunction in Takotsubo cardiomyopathy (TC) and the challenges of diagnosing TC in patients with diverse emotional triggers pose difficulties.
Abstract 14621: High-Density Lipoprotein Lipid and Protein Cargo and Cholesterol Efflux Capacity Before and After Bariatric Surgery
Authors: Sohail Zahid, Florencia Schlamp, Michael Gildea, BingXue Lin, manish parikh, Edward Fisher, Thorsten Hornemann, Tomas Vaisar, Sean P Heffron
Journal: Circulation (2023)

Introduction: Cholesterol efflux capacity (CEC) is inversely associated with incident CV events, independent of HDL-C. Obesity is characterized by low HDL-C and impaired HDL function. Bariatric surgery, including Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), improves CV risk, but we have shown that the impact on CEC may differ by procedure over time post-op. Hypothesis: We hypothesized that RYGB and SG significantly affect HDL protein/lipid cargo and mediate CEC. Methods: We prospectively studied severely obese, nondiabetic women undergoing RYGB (n=31) or SG (n=36) before and at 6 and 12 months after surgery. Statistical analyses included Wilcoxon tests of log fold change in HDL proteins/lipids, hierarchical clustering to identify HDL protein/lipid clusters, and network mediation tests to identify cargo associated with CEC changes. Results: Subjects experienced similar weight loss regardless of procedure (38.0±10.4 kg at 12mo). Concentrations of 40 proteins (11 up, 29 down) and 95 lipids (46 up, 49 down) in HDL changed significantly following bariatric surgery. Proteins and lipids clustered into 9 and 14 groups of similar post-operative trajectories, respectively (Figure A). All clusters, other than 2 lipid clusters, showed similar responses regardless of procedure (Figure B). Despite similarities in cargo, changes in CEC differed depending upon time point and efflux pathway (Figure C). Network mediation analyses suggested that changes in 4 protein and 2 lipid clusters associated with post-operative changes in ABCA1-mediated CEC and changes in 1 lipid cluster associated with changes in non-ABCA1-mediated CEC (Figure D). Conclusions: In conjunction with substantial weight loss, bariatric surgery results in altered HDL protein/lipid cargo and CEC, possibly mediated by distinct HDL cargo. Further study of the mechanisms influencing HDL cargo in obesity and after bariatric surgery may lead to better understanding of CEC and management of CVD.
Abstract 13962: Exploring the Therapeutic Potential of SGLT2 Inhibitors and Oral Ketone Ester in HFpEF: A Comprehensive Exploration of Cardiac Function, Structure, and Metabolism in a Rat Model
Authors: Salva Yurista, David Guarin Bedoya, Robert Eder, Shi Chen, William Jiang, Aidan Welsh, Feiyang Liu, Jonah Weigand-Whittier, Yi-Fen Yen, Christopher Nguyen
Journal: Circulation (2023)

Introduction: This study aimed to assess the potential efficacy of the SGLT2 inhibitor empagliflozin and oral ketone ester supplementation as treatments for heart failure with preserved ejection fraction (HFpEF), which is commonly associated with obesity and type 2 diabetes mellitus. Methods: Twenty-week-old obese ZSF-1 rats were initially fed a high-fat diet (HFD) to establish and maintain the phenotype. Subsequently, the rats were randomly assigned to different treatment groups. These groups consisted of a control group receiving only the high-fat diet (HFD), as well as groups receiving empagliflozin, ketone ester (DeltaG®, KE), or a combination of both in addition to the HFD. Cardiac magnetic resonance imaging (CMR) and hyperpolarized carbon-13 (13C) labeled pyruvate magnetic resonance spectroscopy imaging were used to evaluate cardiac function and metabolism. Histological and molecular markers of cardiac remodeling were assessed in the left ventricle. Results: Untreated HFpEF rats exhibited obesity, diabetes, cardiac hypertrophy, atrial enlargement, lung congestion, increased cardiomyocyte size and fibrosis, as well as elevated expression of atrial natriuretic peptide (ANP), col1a1 (fibrosis marker), and TIMP1. The treatment groups displayed decreased body weight, increased circulating ketone levels, and reduced blood glucose levels. All treatment regimens significantly mitigated ventricular hypertrophy, atrial enlargement, and lung congestion. Furthermore, they reduced cardiomyocyte size, ANP expression, fibrosis marker expression, and increased cardiac ATP levels. CMR revealed that the combination of empagliflozin and KE resulted in improvement in diastolic function. Hyperpolarized [1-13C] pyruvate imaging revealed a decrease in lactate/pyruvate ratio in empagliflozin-treated hearts, indicating improved oxidative metabolism. Conclusions: The findings of this study suggest that targeting cardiometabolic dysregulation holds promise as an effective approach for the treatment of HFpEF. While both empagliflozin or KE alone demonstrated improvements in cardiac energetics and remodeling, the combination of empagliflozin and KE yielded the most notable benefits in enhancing cardiac diastolic function.
Abstract 128: Gender Differences in Out-of-Hospital Cardiac Arrest Incidence, Characteristics, and Prehospital Outcome in Qatar
Authors: Emad Awad, Adnaan Azizurrahman, Bothina Mortada, Nooreh Gholami, Asma Bukhari, Hassan Farhat, Guillaume Henri Jean Alinier, Niki Rumbolt, Timothy Morris, Rakan Shami
Journal: Circulation (2023)

Introduction: Research on gender differences in OHCA incidence, characteristics, and outcomes is lacking in the Middle East. We evaluated gender differences in adult non-traumatic OHCA by incidence, characteristics, and achieving prehospital ROSC in Qatar. Methods: We analyzed data obtained from Hamad Medical Corporation on adult, non-traumatic, EMS-attended OHCA in Qatar (2017-2022). We calculated the annual incidence of OHCA and ran descriptive statistics for OHCA characteristics for the full cohort and by gender. This was followed by multivariable logistic regression to examine association between gender and ROSC, adjusting for variables known to be associated with ROSC. Results: We included 4306 OHCA patients, 79.8% were males. The annual incidence of OHCA was 27.4 per 100,000 population. The annual incidence was higher in males than females (30.1 per 100,000 population vs. 20.4 per 100,000 population). Males had higher proportions of OHCA cases in public locations, receiving bystander CPR, and having an initial shockable rhythm. No significant difference was detected in crude ROSC. The adjusted analysis, however, demonstrated that male gender was associated with greater odds of ROSC (OR 1.38, 95% CI 1.15 - 1.66). This advantage of ROSC in males was observed in the full cohort and in subgroups with shockable and unshockable rhythms. Conclusion: Approximately 717 adult patients suffer non-traumatic OHCA in Qatar annually, with a higher occurrence in males. OHCA characteristics were disadvantageous for females. Male gender was associated with greater odds of achieving ROSC, highlighting the need for additional gender-specific research in pre-OHCA care in Qatar.
Abstract 125: The Association of Racial Residential Segregation and Survival to Discharge After Out-of-Hospital Cardiac Arrest in the United States
Authors: Ethan Abbott, David Buckler, Aditya C Shekhar, Benjamin Abella, Lynne Richardson, Brendan G Carr, alexis zebrowski
Journal: Circulation (2023)

Introduction: Racial and economic segregation is associated with poor health outcomes, including out-of-hospital cardiac arrest (OHCA) survival. Prior work identified disparities in OHCA survival for Medicare beneficiaries associated with residential segregation. We sought to use registry data to evaluate this association of racial and economic segregation with OHCA survival to discharge. Methods: We conducted a retrospective analysis of the 2013-2021 Cardiac Arrest Registry toEnhance Survival OHCA dataset. Arrests with missing data, pediatric patients, or EMS-witnessed were excluded. Our primary predictor, the index of concentration at the extremes(ICE), is a validated measure of racial and economic segregation. We examined three ICE measures (race, income, and race + income) calculated from US Census data and binned into tract-level quintiles. The primary outcome was survival to discharge. We performed multi-levelPoisson regression, with hospital random effect, and adjusted for age, gender, race and ethnicity, witness status, location, and bystander CPR to predict relative risk of survival to discharge and good neurological outcome. Results: We identified 624,626 adult OHCA patients with median age 64 years (SD 17), 38%female, 22% Black/African American, 50% White, 6.8% Hispanic/Latino. Overall, 156,712 (25%)survived to hospital admission, 10% survived to hospital discharge and 6.3% had good neurological outcome. Patients residing in the most segregated White and higher income tracts(Q5) had a 7-10% higher likelihood of survival to discharge compared to the most segregatedBlack and lower income communities (Q1) across all three measures (race RR: 1.09, CI 1.05-1.12; income RR: 1.07, CI 1.04-1.10; race + income RR: 1.10, CI 1.06-1.13). Similarly, neurological recovery was higher in Q5 (race RR: 1.20, CI 1.15-1.25; income RR: 1.12, CI 1.08-1.16; race + income RR: 1.19, CI 1.15-1.23) compared to Q1. Conclusion: We identified outcome disparities across three ICE measures for residents of the most segregated and lowest income Black census tracts compared to those in most segregated higher income White census tracts. Future work should focus on interventions for these disparities to improve survival and address health inequities.
Abstract 16163: Low Dose Alteplase for Treatment of Pacemaker Lead Associated Thrombosis
Authors: Aamir hasan, marian mocanu
Journal: Circulation (2023)

Multiple previously published case reports highlighted the thromboembolic risks associated with permanent transvenous pacemaker leads. Even though mostly clinically silent, pacemaker lead associated thrombosis has been linked to fatal outcomes via pulmonary or paradoxical embolism in the case of large mobile RA or RV thrombi formation. There is a lack of consensus on the optimal strategy for managing this condition. Oral and IV anticoagulation, thrombolysis, surgical and percutaneous thrombectomy have been attempted previously with mixed results. A 72 year old gentleman with a history of CAD requiring PCI, paroxysmal atrial fibrillation, and AV node ablation with subsequent biventricular pacemaker implant was admitted to our hospital with a few weeks of worsening dyspnea, now present at rest. Surface echocardiogram showed multiple mobile echo densities in the right ventricle and right atrium, attached to the pacemaker leads, confirmed by TEE, most likely thrombi. The venous duplex was positive for right lower extremity DVT. Bilateral pulmonary emboli with mild right-sided heart strain were noted on CTA chest. The patient was initially treated with IV unfractionated heparin. We subsequently decided to start low-dose tPA infusion for 24 hrs, similar to current off-label protocols for mechanical prosthetic valves or bioprosthetic valve thrombosis. After an initial IV bolus of 5 mg, 1 mg/hour of alteplase was continued for 24 hours. Our team has decided to use percutaneous thrombectomy as a last resort.Follow-up ECHO immediately post tPA infusion showed complete thrombi resolution. The patient was asymptomatic at this point. He was discharged the following day on Lovenox and Coumadin. To our knowledge, this is the first case demonstrating complete resolution of pacemaker lead-associated thrombi by using a 24 hr low dose tPA infusion in addition to IV anticoagulation. This can be entertained as a simple conservative initial strategy in stable patients with pacemaker lead/catheter-associated intracardiac thrombi.
Abstract 15923: Sexually Dimorphic Heart Phenotypes in Mice Lacking Chromatin Factors in Cardiomyocytes
Authors: Andrew K Knutson, Abigail Avelar, Ralph V Shohet
Journal: Circulation (2023)

Introduction: Sex differences in cardiovascular disease have been attributed to differences in lifestyle or sex hormones; less is known of genetic components that cause differences in heart disease between men and women. We have characterized a role for the ZMYND8 chromatin reader in maintaining cardiac function through modulation of enhancer activity in cardiomyocytes. ZMYND8 has been reported to interact with H3K4 histone demethylases KDM5C and KDM5D, which are encoded from genes residing on sex chromosomes ( Kdm5c on X and Kdm5d on Y). KDM5C and KDM5D have diverged over millions of years of sex chromosome evolution and their functional congruency is unknown. Hypothesis: We hypothesize that sex differences in cardiovascular disease are due, at least in part, to differences in functionality of genes residing on the sex chromosomes. Methods: We constructed Zmynd8-cKO mice using the cardiomyocyte-specific Myh6-Cre Tg/0 line and an established Zmynd8 flox allele. We also introduced a Kdm5c flox allele to the Myh6-Cre Tg/0 line to generate Kdm5c-cKO females and Kdm5c-cKO hemizygous males. These mice were evaluated by lifespan analyses, echocardiography, and molecular analyses (RNA-seq and ChIP-seq). Results: While both male and female Zmynd8 - cKO mice develop enlarged hearts, reduced contractility, and illegitimate expression of certain genes normally found in skeletal muscle, female mice have a 10% reduction in lifespan compared to males; this sex difference in lifespan is not seen in Cre-only mice. We tested the necessity for Kdm5c in cardiomyocytes and found that its deletion also leads to premature death in a dosage dependent manner compared to Cre-only mice. Interestingly, Myh6-Cre Tg/0 ; X 5c-flox /Y hemizygous males have a 20% shorter lifespan than Myh6-Cre Tg/0 ; X 5c-flox /X + heterozygous females, suggesting differences between KDM5C and KDM5D functionality. Conclusions: Our results provide evidence of sexually dimorphic heart defects linked to chromatin regulators, including a gene-pair found on the sex chromosomes. We are deliniating the molecular underpinnings of these observations including changes to histone marks and gene expression in these knockout models.
Abstract 19017: Peri-Operative Bridging Requirement for Patients Chronically Taking Direct Oral Anticoagulants (DOACS) or Vitamin-K Antagonists (VKA) Before Undergoing the Elective Procedure: A Systematic Review and Meta-Analysis
Authors: Saad U Malik, Zakaria Alagha, Usman Akbar, Muhammad Ghallab
Journal: Circulation (2023)

Introduction: Many patients undergo elective interventions/surgical procedures while being on direct oral anticoagulants (DOACs) or vitamin-K antagonists (VKA) chronically. There is limited data on peri-procedural management of DOACs in patients undergoing elective procedures. It is also unclear if there is any role of peri-procedural bridging in patients on chronic VKA therapy. We conducted this study to evaluate the efficacy and safety of DOACs (continued vs. interrupted)and VKAs (with vs. without bridging) among patients undergoing elective procedures. Methods: This systematic literature review was conducted according to PRISMA guidelines until 10 th June 2023. The following inclusion criteria were used: adults, chronic use of VKAs or DOACs, elective procedures, and clinical trials. Primary endpoints were major bleeding, stroke, MI, and VTE. A generic variance random effects model was used to estimate odds ratios using CMA III. Heterogeneity and quality of studies were quantified via I 2 statistic and GRADE score, respectively. Results: 14 clinical trials were included (n=15683). There was no difference in the risk of major bleeding (OR: 1.06, 95% CI: 0.65 -1.7, I2: 46%) or risk of stroke(OR: 1.10, 95% CI: 0.66 - 1.84, I2: 0%) whether DOACs were held or continued respectively. Among patients on VKA, there was no difference in risk of major bleeding in bridging vs. no bridging groups (OR: 2.02, 95% CI: 0.87 - 4.71, I2:75%). There was no difference in the rates of stroke (OR: 0.44, 95% CI: 0.12 -1.58, I2: 0%), MI (OR: 1.64, 95% CI: 0.76 - 3.53, I2: 0%), and VTE (OR: 1.26,95% CI: 0.31 - 5.01, I2: 0%). The quality of included studies was low to moderate. Conclusion: Patients undergoing elective procedures and chronically taking DOACs have a similar risk of major bleeding and stroke when DOACs are continued or interrupted peri procedurally. Similarly, among patients on VKA who were bridged or not bridged, there was no difference in risk of bleeding, stroke, MI or VTE.
Abstract 14625: Association of Eicosanoid Metabolites With Cardiac Structure and Function
Authors: Athar Roshandelpoor, Janet Ma, Ilker Demirel, Emily Lau, Mona Alotaibi, Mariana F Ramirez Fernandez Del Castillo, Juhi Parekh, Abigail Pan, Ndidi Owunna, Vinithra Varadarajan, Mohit Jain, Susan Cheng, Joao AC A Lima, Jennifer E Ho
Journal: Circulation (2023)

Introduction: Eicosanoids are bioactive lipids that govern the upstream initiation of pro- and anti-inflammatory activity. They may serve as important pathways by which obesity and cardiometabolic disease lead to the development of heart failure with preserved ejection fraction (HFpEF). Objective: We sought to examine the association of plasma circulating eicosanoid metabolites with subclinical cardiac remodeling as ascertained by cardiac magnetic resonance imaging (CMR) as important determinants of HFpEF risk. Methods: We studied 3880 MESA study participants (mean age 63±10 years, 53% women) who underwent plasma metabolite profiling using a mass spectrometry-based platform and CMR. We used multivariable linear regression to examine the association of eicosanoid metabolites with left ventricular mass index (LVMI, primary outcome), LV end-diastolic volume index (LVEDV), and left atrial volume (LAV). Results: Of 811 eicosanoids, 158 were associated with LVMI (Figure; FDR q &lt;0.05 for all). Specifically, derivatives of eicosadienoic acid (15 oxoEDE), linoleic acid (9,10 diHOME), and arachidonic acid (12(R) HETE) were negatively associated with LVMI and prostaglandin 19R-hydroxy-PGE1 was positively associated with LVMI. Of 158 metabolites, 65 were are also associated with LVEDV including derivatives of linoleic acid (13(S) HOTrE), oxylipin 11-HETE and 15 oxoEDE. Of 158 metabolites, Adrenic acid is also associated with LAV. Conclusions: We found that specific eicosanoids including 15 oxoEDE, 9,10 diHOME, and 12(R) HETE were associated with LVMI, an important measure of subclinical cardiac remodeling and precursor to HFpEF. As causal drivers of HFpEF are poorly characterized, a better understanding of pro- and anti-inflammatory eicosanoid pathways that contribute to cardiac remodeling may have important implications for the prevention of HFpEF.
Abstract 13374: The Intersection of Prenatal Clinical and Demographic Factors in Predicting Fetal Brain Volume and Neurodevelopmental Outcome in Single Ventricle CHD
Authors: Shabnam Peyvandi, Cynthia M Ortinau, Valerie Rofeberg, Zachary Vesoulis, Nicholas Hart, Kaysi Herrera Pujols, David Wypij, Caitlin K Rollins
Journal: Circulation (2023)

Background: Fetuses with single ventricle (SV) CHD have small total brain volumes (TBV) which has been linked to neurodevelopmental impairment (NDI). Evidence suggests a prenatal origin of NDI for CHD. Our primary aim was to use machine learning methods to identify prenatal variables that predict fetal brain growth and in turn early NDI. Methods: This is a multi-center prospective cohort study of maternal-infant dyads with a fetal diagnosis of SV who underwent fetal brain MRI and in-depth prenatal clinical and sociodemographic data collection (self reported race/ethnicity, income, education, area deprivation index, maternal health, genetics, placental health). Infants had ND testing at 12-30 months with Bayley Scales of Infant and Toddler Development. Machine learning models used recursive partitioning to predict 1) gestational-age (GA) and sex-adjusted fetal TBV and 2) ND outcome while including fetal TBV in the models. Results: A total of 67 maternal-infant dyads were enrolled with a mean GA of 33.4 weeks (SD=3.4) at fetal MRI and male predominance (57%); 48 infants had follow-up at median age of 23.5 months (SD=6.3). Key predictors of fetal brain volume were race/ethnicity, maternal age, and cardiac anatomy (Figure 1A). For NDI, fetal brain volume was the strongest predictor of motor outcomes but was not associated with other domains (Figure 1D). Cardiac anatomy was the strongest predictor of cognitive outcome (Figure 1B), while race/ethnicity was the strongest predictor of language (Figure 1C). Cardiac anatomy, maternal age, and cerebral and placental hemodynamics (e.g., middle cerebral or umbilical artery pulsatility) each predicted multiple domains of neurodevelopment. Conclusions: In regression tree modeling, sociodemographic variables are the strongest predictors of fetal TBV, which in turn predicts motor outcome. Prenatal factors predicting NDI across all domains span sociodemographic, cardiac, and placental characteristics.