bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18814: Glycoprotein VI is Critical for the Detection and Progression of Abdominal Aortic Aneurysms
Authors: Benson Tyler W , Pike Mindy M , Spuzzillo Anthony , Hicks Sarah , Pham Michael , Bhandari Rohan , Brunner Seth , Wadding-Lee Caris , Conrad Kelsey , Russell Hannah , Coughlin Taylor , Aggarwal Anu , Lyden Sean , Mani Kevin , Bjorck Martin Gustaf , Wanhainen Anders , Mix Doran S , Lipworth Loren , Robinson Cohen Cassianne , Shim Sharon , Edwards Todd I , Tranter Michael , Gardiner Elizabeth , Mackman Nigel , Cameron Scott J , Owens A. Phillip
Published: December 2023

Objective:
Abdominal aortic aneurysms (AAA) frequently feature the formation of a nonocclusive intraluminal thrombus (ILT) along the site of aortic dilation. Platelets are known to maintain hemostasis and propagate thrombosis through several redundant activation mechanisms, yet the role of platelet activation in the pathogenesis of AAA associated ILT is still poorly understand. Thus, we sought to investigate how platelet activation via the glycoprotein VI (GPVI) platelet receptor impacts the pathogenesis of AAA.

Methods and Results:
RNA sequencing of age-matched control human aortic tissue, AAA aortic tissue, and AAA ILT demonstrates that platelet transcripts comprised 25% of significantly enriched genes AAA thrombus compared to AAA tissue and control aortic wall, with GPVI increased by 9.1 Log2-FC (P = 3.21E
-08
). Examination of soluble GPVI (sGPVI), a specific marker of platelet activity, in 2 independent AAA patient cohorts is predictive of AAA case status, associates strongly with aneurysm growth rate, and better predicts the presence of a fast-growing AAA when compared to D-dimer. To determine if GPVI blockade ameliorates AAA progression, mice were subjected to either the angiotensin II (AngII) infusion or the topical elastase models of aneurysm formation. Following model initiation, aortic diameter was monitored by weekly ultrasounds. After two weeks, mice which developed an aneurysm (defined as an aortic diameter of >1.2mm) were randomized into control (IgG-50μg) or treatment (JAQ1-50μg, monoclonal GPVI antibody) groups. Treatment with JAQ1 blunted GPVI mediated platelet activation, attenuated aneurysm progression, and increased survival in both murine AAA models versus control.

Conclusions:
The highly specific platelet activation biomarker soluble glycoprotein VI strongly predicts both AAA case status and growth rate with potential use in identifying high risk patients. Specific blockade of GPVI-mediated platelet activation attenuates progression of established aneurysms in two independent murine models. Thus, our work demonstrates that specific targeting of GPVI to blunt platelet activation in AAA could be a potential therapeutic for a pathology with no current pharmacological treatments.
Abstract 18826: Atrial Fibrillation, Atrial Myopathy, and the Risk of Recurrent Stroke or Transient Ischemic Attack After Cryptogenic Stroke
Authors: Raco Joseph , Shah Ravi , Farbaniec Michael , Maheshwari Ankit
Published: December 2023

Background:
The annual risk of recurrent stroke after cryptogenic stroke (CS) is estimated at 3-6%. Atrial myopathy, characterized by left atrial structural and electrophysiological remodeling, is associated with atrial fibrillation (AF) and stroke.

Hypothesis:
Atrial myopathy is associated with an increased risk of recurrent stroke or transient ischemic attack (rCVA) within one year.

Methods:
Patients with interpretable echocardiograms who received an implantable loop recorder for CS at a tertiary care medical center (2015-22) were included and followed for at least 1 year. Left atrial emptying fraction (LAEF) and reservoir strain (LARS) were calculated from two-dimensional transthoracic echocardiograms. Covariates including congestive heart failure, hypertension, age, diabetes, sex, stroke/transient ischemic attack, vascular disease, carotid artery stenosis, and rCVA were ascertained by review of hospital medical records. Incident AF post CS was obtained from review of loop recorder data. Odds ratios were calculated using logistic regression models. Two-sided student's T-test was used to compare means of continuous variables.

Results:
159 patients (mean age 74.4 years, 52.1% female) were followed for at least one-year post CS. Patients with rCVA had significantly lower LAEF (p=0.012) and near-significantly lower LARS (p=0.088) compared to those who did not. The odds of rCVA were 4.82 (2.22, 7.11)-fold greater in those found to have new AF independent of LAEF, LARS, and remaining covariates including carotid artery stenosis. Patients on anticoagulation at time of rCVA had trends towards reduced stroke severity (p=0.184).

Conclusions:
Atrial myopathy characterized by AF or reduced LA function is associated with rCVA post CS.
Abstract 18841: Long-Term Cardiovascular Outcomes of Immune Checkpoint Inhibitors-Related Myocarditis: A Large Single-Center Analysis
Authors: Braghieri Lorenzo , Gharaibeh Ahmad M , Nkashama Lubika , Abu-Shawer Osama , Honnekeri Bianca , Puthenpura Max , Calabrese Cassandra , Menon Venu , Funchain Pauline , Moudgil Rohit
Published: December 2023

Introduction:
Immune checkpoint inhibitors (ICI) have revolutionized the oncology landscape. Despite ICI-related cardiovascular adverse events being rare, they are often fatal in the short-term. Whether ICI-related myocarditis portends a worse long-term prognosis is unclear.

Aims:
To determine the long-term cardiovascular (CV) comorbidity burden and CV mortality after ICI-related myocarditis.

Methods:
The ICI-related adverse event registry, which includes 4195 patients who received ICI between 2011 and 2019, was screened to identify patients with ICI-related myocarditis. ICI-related myocarditis was defined according to Bonaca criteria by two independent Authors and discrepancies were further adjudicated by a staff cardiologist. Controls were randomly selected. Patients’ demographics, comorbidities, cancer history, labs, and myocarditis features on presentation were collected. Primary outcomes were freedom from CV comorbidities (a composite of atrial fibrillation, stroke, myocardial infarction, and heart failure) and freedom from CV death (CVD) at 2 years from the initiation of ICI. ICI-related myocarditis was treated as a time-varying covariate. Freedom from primary outcomes was analyzed via Kaplan-Meier analysis and Cox proportional models with backward regression were used to account for confounding.

Results:
A total of 76 patients developed ICI-related myocarditis at a median time of 167 days (36.8% female, mean age 69, 47% primary lung cancer). Overall, 65% and 75% of patients had EKG changes and new wall motion abnormalities, respectively. Mean LVEF was 43%, median NTproBNP was 2057, and median peak TnT was 0.81 on presentation. At 2-years follow-up, patients who developed ICI-related myocarditis had significantly lower freedom from CV comorbidities (67% vs 86.8%, p<0.001) and CVD (93.4% vs 99.3%, p=0.003). On multivariable analysis, development of ICI-related myocarditis was an independent predictor of CVD (HR 8.28, p=0.048), but not cardiovascular comorbidities (HR 2.21, p=0.08).

Conclusions:
This is the largest case-control study on ICI-related myocarditis demonstrating significantly worse long-term CV outcomes. Future studies are needed to optimize the management of ICI-related myocarditis survivors.
Abstract 18853: Rescue of Pulmonary Hypertension-Induced Right Ventricular Failure by Silencing Snai1 Induces Alterations in Methylation Status of Critical Genes Regulating Endothelial-to-Mesenchymal-Transition and Fibrosis
Authors: Banerjee Somanshu , Clark Varina R , Martineau Sandra , Hong Jason , Razee Asif , Provencher Steeve , Breuils Bonnet Sandra , Bonnet Sebastien , Umar Soban
Published: December 2023

Introduction:
Pulmonary hypertension (PH)-induced RV failure (PH-RVF), a significant prognostic determinant, is characterized by RV endothelial-to-mesenchymal transition (EndMT), fibrosis, and remodeling. However, the regulatory control of RV EndMT and fibrosis remains unclear.

Hypothesis:
TGFβ1-Snai1-LOXL2 axis regulates RV EndMT and fibrosis in PH-RVF. Key gatekeeper transcription factor (TF) Snai1 mediates RV EndMT and fibrosis via differential methylation changes in EndMT and fibrotic genes and may serve as a novel therapeutic target.

Methods:
Male rats received s.c. Monocrotaline (MCT, 60mg/kg, n=9; 30-days), Sugen (20mg/kg, n=9; 3-wk hypoxia+2-wk normoxia; SuHx) or PBS (CTRL, n=9). For Snai1-knockdown (KD), MCT rats received siSnai1 (n=6; 5nM every 3-4d, IV) or scramble (n=7) from day 14-30. Echo, cath, RV-RNASeq, qPCR, WB, IF validation, and RV-DNA methylome RRBS-Seq were performed. Differentially methylated sites (DMS) and regions (DMR) were assessed. Secondary RNASeq analysis was performed on human decompensated-RVF vs Control (dRVF; GSE198618) and human RVs were assessed for EndMT, fibrosis, myofibroblast (MFB) transition, and Snai1+LOXL2. Snai1-KD was performed on human coronary artery endothelial cells (HCAECs) and human cardiac fibroblasts (HCFs) under hypoxia+TGFβ1.

Results:
MCT and SuHx had increased RVSP and Fulton index and decreased RVFAC (all p<0.001). RNASeq showed EndMT and Snai1 as the top-upregulated pathway and TF respectively in MCT and SuHx and human dRVF. RV EndMT, fibrosis, MFB transition, TGFβ1-Snai1-LOXL2, and peri-nuclear colocalization of Snai1+LOXL2 were increased in MCT, SuHx and dRVF patients. Snai1-KD rescued PH-RVF via significantly reducing Snai1+LOXL2. RV-RNASeq demonstrated EndMT as the top-downregulated pathway and decreased fibrotic DEGs. RV RRBS-Seq showed significant DMS and DMR remodeling of Dnmt3a, Kdm1a, Snai1, TGFβ1/2, and other critical EndMT and fibrotic genes. Snai1-KD inhibited hypoxia+TGFβ1-induced EndMT in HCAEC and MFB transition in HCF by decreasing Snai1+LOXL2 expression and reversing EndMT and fibrotic DEGs respectively.

Conclusions:
Rescue of PH-RVF by silencing Snai1 induces alterations in methylation status of critical genes regulating EndMT and fibrosis.
Abstract 18864: A Novel Technique to Improve Vector Uptake for Cardiac Gene Therapy
Authors: Mazurek Renata , Mavropoulos Spyros Archimedes , Sakata Tomoki , Ravichandran Anjali , Marx Jonas , Ishikawa Kiyotake
Published: December 2023

Introduction:
Cardiac gene therapy with adeno-associated virus (AAV) has promise. However, clinical trials with intracoronary (IC) delivery have been challenged by low efficacy.

Hypothesis:
We predicted that AAV uptake could be enhanced using a catheter-based mechanical cardiac support device (MCS) to facilitate IC delivery with brief coronary balloon occlusions in a pig model of myocardial infarction (MI).

Aims:
We aimed to: 1) confirm that MCS could support hemodynamics during coronary balloon occlusions, and 2) determine whether this technique could improve vector uptake and cardiac gene expression after HF onset.

Methods:
A week after MI, 12 Yorkshire pigs (36.6±1.45 kg, male n=6) received AAV6 encoding for luciferase by one of four delivery methods (n=3/group) (Figure 1). Tissues were harvested 1 mo later for analysis. A similar experiment was conducted with gold nanoparticles (GNPs) in place of AAV by either continuous or CAO+CSO delivery (n=4) with same-day cardiac harvest. GNP presence was seen by electron microscopy.

Results:
MCS maintained blood pressure and prevented arrhythmias during coronary balloon occlusions. Application of MCS during continuous infusion did not significantly alter AAV genome uptake (vg) or luciferase expression (luc). CAO+CSO delivery increased both vg and luc across heart regions, with notable significance at the infarct-border region vs continuous delivery (vg: p=0.027; luc: p=0.032). Vg was also positively associated with luc (Figure 2). Improved uptake was further supported by greater GNP presence with CAO+CSO delivery.

Conclusion:
MCS can be utilized to optimize IC gene delivery in a safe and clinically-applicable way.
Abstract 18887: Trends and Outcomes of Use of Inotropes in Cardiac Arrest Survivors With Ventriculartachycardia/Fibrillation
Authors: Dutta Abhishek , Patel Krunalkumar , Truong Vien T , Mondal Avilash , Ahmad Mansoor , Agrawal Durgesh , Parajuli Tilachan , Majeed Chaudry N , Metkus Thomas , Qureshi Waqas , Dhar Sunil
Published: December 2023

Introduction:
Cardiac arrest remains a public health crisis with only 10% overall survival rate. Patients with arrest secondary toventricular tachycardia (VT)/ventricular fibrillation (VF) have relatively better survival rates. Post-arrest shock is usuallycardiogenic due to structural defects at baseline. The outcomes of inotrope use in this population is not well known.

Hypothesis:
We hypothesized that the use of inotropic support is not associated with better survival outcomes.

Methods:
This is a cohort study of 387 cardiac arrest patients in a tertiary care center enrolled from January 2012 to December2016 who were able to survive for 24 hours post-cardiopulmonary resuscitation after a VT/VF arrest. We compared thebaseline characteristics and 30-day outcomes of cardiac arrest patient who required inotropes and who did not requireinotropes. Results:Out of 338 cardiac arrest survivors with VT/VF arrest, 99 (29.3%) patients were treated with inotropes. 90 (90.9%) ofpatients in the inotrope group were simultaneously on vasopressors. 30-day mortality was higher (67.7%) in theinotrope group compared to patients with no inotrope use (46.2%). The neurological outcome was worse (cerebralperfusion category ≥3) in patients on inotropes (86.9 vs 63.6%).

Conclusions:
We observed that mortality was higher in VT/VF cardiac arrest survivors who were on inotropes. These patients hadhigher incidence of vasopressor use and were more likely hemodynamically unstable. Further studies are needed toinvestigate the use and outcomes of inotropes in these subsets of patients.
Abstract 18888: Demographic and Racial Trends of Ischemic Heart Disease Related Mortality in Patients With Cancer
Authors: Mannumbeth Renjithlal Sarath Lal , Eid Mohamed M , Shanker Dinesh Abhijeeth , Eid Fahad , Barssoum Kirolos , Cordeiro Nikhil , NISHA PILLAI
Published: December 2023

Introduction:
We aim to assess the demographic and racial trends of mortality associated with Ischemic heart disease in patients diagnosed with neoplasia, between 1999 and 2020.

Methods:
A cross-sectional analysis of the Centers for Disease Control and Prevention Wide-Ranging Online Data for the Epidemiological Research database (CDC-WONDER) was conducted to investigate the trends in mortality associated with Ischemic heart disease (ICDcodes - I20-I25) in patients with diagnosis of neoplasm or cancer during the time of death (ICD codes C00-D48). The study calculated age-adjusted mortality rates (AAMR) per 100,000 individuals and corresponding annual percentage changes (APC), along with 95% confidence intervals, using jointpoint regression analysis. Demographic and racial trends were evaluated.

Results:
359,383 Ischemic heart disease-related deaths occurred in cancer patients from 1999 to2020. Annual trends show that the AAMR decreased from 8.3 (95% CI 8.2-8.4) in 1999 to 3.3(95% CI 3.3-3.4) in 2020. The overall AAMR from 1999-2020 had an Annual PercentageChange (APC) decrease of -5 (95% CI: -5.3 to -4.7). When stratified by sex, males had a worseAAMR at 7.6 (95% CI: 0.6-0.6), and females were found to have an AAMR of 3.1 (95% CI: 0.5-0.5). When stratified by ethnicity, AAMR was highest among African Americans at 5.4 (95% CI:5.3-5.4), followed by white at 4.9 (95% CI 4.9-5.0), followed by American Indian or Alaskan Native at 2.7 (95% CI 2.6-2.9), followed by Asian or PacificIslander at 2.5 (95 % CI 2.5-2.6).

Conclusions:
In the United States, there has been a general decrease in IHD-associated Mortality in cancer patients from 1999 to 2020. Similar to the IHD-related mortality in the general population. Our data shows that the AAMR is worse in men, black population. In the setting of worse AAMR in specific populations, further research is needed to identify the causes and potential strategies to improve AAMR in cancer patients.
Abstract 189: How Quickly Does Arterial Blood Pressure Recover After Pauses in Mechanical Chest Compressions in Humans With Out-of-Hospital Cardiac Arrest?
Authors: Yin Rose T , Berve Per Olav , Skaalhegg Tore , Elola Andoni , Taylor Tyson G , Walker Rob G , Aramendi Elisabete , Chapman Fred W , Wik Lars
Published: December 2023

Introduction:
Conventional wisdom says that arterial blood pressure (ABP) recovers slowly after interrupting CPR chest compressions (CCs). An oft-cited animal study with manual compressions and 15:2 compression:ventilation ratio showed that all 15 compressions were needed to restore pre-pause invasive pressure, implying that even short pauses substantially reduce CPR blood flow. Whether this holds true for humans receiving mechanical chest compressions is unknown. We measured recovery of ABP after pauses in mechanical compressions by LUCAS in patients treated for out-of-hospital cardiac arrest (OHCA).

Methods:
We analyzed data from a subset of patients enrolled in both groups of a prospective, randomized LUCAS 2 Active Decompression trial performed by an anesthesiologist-staffed rapid response car program in Oslo, Norway from 2016 to 2018. Only patients with an ABP signal and at least one CC pause longer than 2 sec were included. All CCs were mechanical. Arterial cannulation was verified, and CC pauses were identified by physician review of the patient care record and physiological signals. Pauses were excluded if ROSC or a LUCAS “soft start” occurred or epinephrine had been applied within 5 minutes of the pause. Peak compression (cAP), mean (mAP), and mean decompression arterial blood pressures (dAP) for 10 CCs before and after each pause were measured with custom MATLAB code.

Results:
We included 56 patients with a total of 148 pauses (mean pause duration: 10.63 ± 3.05 sec). Pre-pause mean cAP, mAP, and dAP were 95.6 ± 0.3, 49.9 ± 0.1 and 30.5 ± 0.1 mmHg. Post-pause dAP for each compression was not significantly different than pre-pause dAP (Fig. 1A,B). cAP and mAP recovered to >90% of pre-pause pressure within 2 CCs. Pause duration was not predictive of post-pause pressures (Fig. 1C).

Conclusions:
ABP generated by mechanical CPR recovered quickly after pauses. Consequently, short pauses (such as pauses for 30:2 CPR) may pose less hemodynamic concern than previously thought.
Abstract 18912: Interplay Between Cognitive Function and Depressive Symptoms in Patients With Heart Failure
Authors: Amin Muhammad I , Wu Jia Rong , Chung Misook L , Moser Debra K
Published: December 2023

Introduction:
Mild cognitive impairment (MCI) and depressive symptoms (DS) are common comorbidities in patients with heart failure (HF). MCI and DS are known to be related from cross-sectional studies, but the trajectory of DS over time is unknown in patients with HF and MCI.

Objective:
To compare the trajectory of DS over a 2-year period based on cognitive function in patients with HF.

Methods:
We studied 373 patients (age 65 ± 13 years, 60% male, 26% NYHA class III/IV) with HF for 24-months. MCI was assessed using the Mini-Cog Test, and DS using the Patient Health Questionnaire-9; MCI was measured at baseline, and DS at baseline, 12 and 24 months. We used repeated-measures ANOVA for analysis with age and New York Heart Association (NYHA) class as covariates.

Results:
There was a significant time by group interaction (p = 0.027) in that DS decreased across time from baseline to 24-months in patients without MCI, while DS in patients with MCI, although decreased at 12-months, returned to baseline levels at 24-months (Figure). Although DS were higher in patients with worse NYHA class, they showed the same trajectory across time based on MCI.

Conclusions:
Although these data suggest that MCI worsens or prevents remission of DS overtime, the interplay between these two conditions requires further study to better understand how MCI and DS affect each other and how they interact to alter outcomes in patients with HF.
Abstract 18918: Outcomes of Patients With Transcatheter Aortic Valve Replacement (TAVR) and Cardiac Resynchronization Therapy (CRT): A Retrospective Analysis
Authors: Umrani Rohan , Matsumura Martin , Khalid Yaser , Roy Trinava , Dasu Neethi , Dasu Kirti
Published: December 2023

Introduction:
Many patients with TAVR have a pre-existing reduced LVEF <35% and left bundle branch block (LBBB) requiring CRT-D for potential improvement in LV function and secondary prevention of sudden death. Few studies have examined patient outcomes in this specific subpopulation. The aim of our study was to see if this patient population had worse outcomes compared to patients with TAVR without CRT-D.

Hypothesis:
We hypothesized that patients undergoing CRT would have better outcomes.

Methods:
Patients aged >18 years with TAVR and CRT versus TAVR alone were identified from the United States National Inpatient Sample (2015-2020). ICD 9 and 10 codes were utilized and multivariate regression analysis was used to estimate the odds ratios of in-hospital mortality, average length of stay (LOS), and hospital charges (TOTHC), after adjusting for age, gender, race, insurance, and hospital demographics (type, size, region, and teaching status). Propensity matching was performed using the Kernel method. Weighted analysis utilizing Stata 17 MP was performed.

Results:
This study identified approximately 324,563 patients with TAVR, of which 2,613 patients had CRT. The analysis revealed mortality (OR: 2.59, p<0.025, CI: 1.13-5.94), length of stay (LOS) (+5.69 days, p<0.0001, CI: 4.44-6.95), and TOTHC ($165,520, p<0.0001, CI: 134,551-196,489) were increased for patients with TAVR and CRT compared to patients with only TAVR. Secondary analysis is described in Table 1.

Conclusions:
Our study revealed that patients with TAVR and CRT had worse outcomes including increased mortality, LOS, and TOTHC. Despite CRT, this patient subpopulation had worse outcomes compared to those with only a TAVR. We suspect that these patients either have a poor functional status at baseline or CRT may not have as much benefit for patients with TAVR. Further studies are required to further evaluate this patient population.
Abstract 18926: Skeletonization Mitigates Risk of Deep Sternal Wound Infection in Patients With Diabetes Undergoing CABG With Bilateral Internal Mammary Arterial Grafting
Authors: Chinedozi Ifeanyi D , Holmes Sari D , Hashmi Fayyaz , Athipathy Nikhita , Matthew Thomas , Sulague Ralf Martz , Kang Jin Kook , Nair Shuait , Sangalang Janelle J , Fonner Clifford Edwin , Alejo Diane , Lawton Jennifer S ,   Maryland Cardiac Surgery Quality Initiative (MCSQI)
Published: December 2023

Background
Bilateral internal mammary artery (BIMA) grafting may provide benefits compared to single artery coronary artery bypass grafting (CABG). However, many surgeons cite deep sternal wound infections (DSWI) as a deterrent for use of BIMA in patients with diabetes (DM).

Aim
To evaluate the effect of DM and skeletonization on the incidence of DSWI in patients with BIMA grafting.

Hypothesis
Skeletonization reduces risk of DSWI in DM patients with BIMA.

Methods

A retrospective analysis from 11 hospitals in the Maryland Cardiac Surgery Quality Initiative was performed. Of 27,930 adult non-emergent CABGs between 2017 and 2022, 2,010 patients (7%) received BIMA grafting among whom 764 (38%) had DM. Effect of DM and skeletonization of ≥ 1 IMA on DSWI in BIMA patients was evaluated by chi-square analyses and multivariable logistic regressions adjusting for DSWI-specific STS risk score.

Results
There was no significant difference in preoperative glycosylated hemoglobin (HgbA1c) level for DM patients with and without BIMA (7.2 [6.5-8.4] vs 7.2 [6.5-8.5], P=0.842. BMI was significantly higher in DM vs non-DM patients (30 [27 - 33] vs 28 [25 - 31], respectively, P<0.001]. Skeletonization of ≥ 1 IMA in DM patients reduced DSWI vs. no skeletonization (0.3% vs 4.1%, respectively, P=0.023) but did not alter DSWI in non-DM patients (0.4% vs 1.2%, P=0.280). In patients with skeletonization of ≥1 IMA, there was no difference in DSWI between patients with and without DM (0.3% vs 0.4%, respectively, P>0.999; Figure 1). After adjusting the DSWI-specific STS risk scores, skeletonization remained independently associated with reduced DSWI risk in DM patients with BIMA (OR=0.09,
P
=0.044).

Conclusions
Skeletonization of ≥1 IMA was associated with lower risk of DSWI in BIMA patients with DM. This supports the use of BIMA with skeletonization in patients with DM barring other prohibitive risk factors, and may encourage its increased usage in skeptical surgeons.
Abstract 18928: Phenotypic Manifestations of Polygenic Risk for Ischemic Stroke in Adults Free From Disease
Authors: Barber Jacob L , Rao Prashant , Mi Michael Y , Tahir Usman A , Dev Prasun K , Bouchard Claude , Clish Clary B , Robbins Jeremy M , Sarzynski Mark A , Gerszten Robert E
Published: December 2023

Introduction:
Ischemic stroke is a complex heritable disease with a substantial proportion of risk attributable to polygenic factors. Little is known about how polygenic risk for stroke may manifest as intermediate phenotypes.

Hypothesis:
Polygenic liability for ischemic stroke will be associated with cardiometabolic phenotypes even in young adults free from disease.

Methods:
Polygenic risk derived from a multi ancestry population (GIGASTROKE ~1.2 million SNPs) was applied to 454 White adults from the HERITAGE Family Study with imputed whole genome data available. Participants (mean age = 31.5 ±14.5 years, 51% female) underwent robust cardiometabolic profiling including deeply phenotyped cardiopulmonary exercise tests, body composition, lipid panels, inflammatory markers, and measures of glucose homeostasis. General linear models adjusted for age and sex were used to test the association between z-scored polygenic risk of stroke (SPRS) and 130 phenotypes. A false discovery rate of <5% was used to determine significance.

Results:
SPRS did not associate with demographic traits or measures of body composition. SPRS was positively associated with several blood pressure related phenotypes with the strongest association between SPRS and systolic blood pressure response to acute exercise (β=0.01, p=2.86e-05), which persisted after adjustment for resting systolic blood pressure. Additionally, 19 total phenotypes were nominally associated (p<0.05) with SPRS including multiple apoB related plasma lipid traits (
Table 1
). Interestingly, SPRS was also inversely associated with hematocrit (β= -0.06, FDR=0.004).

Conclusions:
Genetic risk of ischemic stroke is associated with hemodynamic traits even in a cohort of relatively young adults free from overt cardiometabolic disease. Additionally, blood pressure response to acute exercise may represent an early manifestation of genetic liability to stroke.
Abstract 18935: A Prospective Evaluation of a Community-Based Outreach Initiative for Black Women With Severe, Uncontrolled Hypertension
Authors: Granger Bradi B , Caesar Awanya , Muhirwa Amnazo , Guggenheim Dana , Hatch Daniel , Thompson Julie , Biola Holly
Published: December 2023

Introduction:
Despite American Heart Association evidence-based guidelines for care, inequities in prevalence and management of HTN disproportionately impact minority populations. Though studies have evaluated strategies to improve management of HTN and self-measurement of blood pressure (SMBP), existing strategies have not included a patient-partner who is a peer in literacy level, socio-economic status, and the lived experience of hypertension.

Hypothesis:
This pilot study was designed to evaluate a community-based intervention using patient-selected partners to improve blood pressure at 12 months. Secondary aims were to improve engagement in care, BP cuff distribution and use, and patient-centered goal setting for Life’s Essential Eight.

Methods:
We used a prospective, pre-post cohort design to evaluate the peer-partnership intervention. The team-based intervention included:1)Distribution of blood pressure cuffs and provision of skill-based training for BP self-monitoring to women at a federally qualified health center (FQHC).2) Implementation of coaching and feedback with patients on SMART goal setting for Life’s Essential Eight, to improve goal concordance and goal achievement.

Results:
Participants included Black women (n=335), average age 56 (SD 9.6). Preliminary results on key process measures indicate early signs of adoption: patient engagement in calls completed (n=426), cuffs distributed (n=186), SMART goals set (187, 56%), and partnerships established with family or community sites (n=91, 27%). Blood pressure was significantly reduced overall from baseline to 12 months (pre-systolic mean 172.05 (SD 13.3) mmHg versus post-systolic mean 140.3 (SD 20.9) mmHg; p<.0001) Focus groups evaluating patient perceptions of the added value of peer-partnership are ongoing.

Conclusions:
Community-based partnerships may improve SMBP skills, goal setting, and communication among patients in minority and low socioeconomic groups.
Abstract 18941: Pediatric Electrocardiogram-Based Deep Learning to Predict Left Ventricular Dysfunction and Remodeling
Authors: Mayourian Joshua , La Cava William G , Ghelani Sunil J , Mannix Rebekah , Bezzerides Vassilios J , Pu William T , Geva Tal , Dionne Audrey , Alexander Mark E , Triedman John K
Published: December 2023

Background:
Artificial intelligence-enhanced ECG algorithms show promise to detect a range of adult phenotypes, inclusive of ventricular dysfunction and remodeling. However, it remains unclear whether similar approaches provide meaningful and generalizable predictions in children.

Methods:
We trained a convolutional neural network on paired ECG-echos (≤ 2 days apart) from patients ≤ 18 years old without major congenital heart disease to detect human expert classified greater than mild left ventricular (LV) dysfunction, hypertrophy, and dilation (individually and as a composite outcome). Model performance was assessed by calculating area under the receiver operating curve (AUROC) in an internal test set and external setting (emergency department).

Results:
The main cohort comprised of 119,787 ECG-echo pairs (61,722 patients; median age 8.3 [IQR, 2.9-13.8] years; 55% male). Training, internal test, and external test sets comprised of 92,377, 24,343, and 3,067 ECG-echo pairs with 8.2%, 7.7%, and 10.0% composite outcome rates, respectively. During internal testing, AUROCs of 0.84 [95% CI, 0.83-0.85], 0.87 [95% CI, 0.85-0.88], 0.86 [95% CI, 0.84-0.87], and 0.84 [95% CI, 0.83-0.86] were achieved for the LV composite outcome, dysfunction, hypertrophy, and dilation, respectively (Figure). During external testing, AUROCs of 0.80 [95% CI, 0.77-0.83], 0.84 [95% CI, 0.80-0.88], 0.77 [95% CI, 0.72-0.82], and 0.86 [95% CI, 0.82-0.89] were achieved, respectively (Figure). Similar model performance was achieved when using quantitative z-score cutoffs for each outcome. Exploratory saliency mapping provides insight into notable ECG components that influence model predictions.

Conclusions:
Our artificial intelligence-enhanced pediatric ECG algorithm shows promise to inexpensively screen for and diagnose LV dysfunction or remodeling in children. Prospective trials to guide model implementation for supporting clinical decision making are warranted.
Abstract 18948: Prospective Associations Between the Life's Essential 8 Cardiovascular Health Construct, Leptin, and Inflammatory Markers Among Women Across the Menopausal Transition: Findings From the AHA Research Goes Red Weight Study
Authors: Aggarwal Brooke A , Scaccia Samantha , Wang Pengchen , Allison Matthew A , Catov Janet M , Reynolds Harmony , Vaidya Dhananjay
Published: December 2023

Introduction:
The menopausal transition is a key period of potential detrimental changes in adiposity. The hormone leptin may be relevant to obesity, inflammation, and cardiovascular health (CVH).

Hypothesis:
Among women across the menopausal transition, lower levels of circulating leptin, C-reactive protein (CRP) and interleukin 6 (IL-6) will be associated with better Life’s Essential 8 (LE8) CVH score.

Methods:
Participants were women ages 45-55y (N=291, mean age=50 ± 3.2yr, 74% with overweight/obesity, (n=98 pre-, n=94 peri-, n=99 post-menopausal) from the AHA Research Goes Red Weight Study, a 1-yr prospective observational study utilizing Verily’s online platform. At baseline and 1yr, women completed a 1-wk food record using the NIH ASA 24-Hour Dietary Assessment Tool and fasting blood samples were drawn. The LE8 CVH and component scores (range: 0-100, high: 80-100, moderate: 50-79, low: 0-49) were computed. Associations between leptin, inflammatory markers, and CVH scores were tested using multivariable linear regression models adjusted for age, race/ethnicity, education, employment, insurance, and menopausal status.

Results:
The mean (SD) overall LE8 CVH score at baseline was 68.0 (15.3) and did not vary by menopausal status. Individual LE8 scores were lowest for the diet metric [mean (SD)=40.2 (31.5)]. Pre-menopausal women had better scores on the blood glucose metric compared to post-menopausal [mean (SD)= 88.0 (24.4) vs. 76.2 (26.5), p=.02]. Compared to peri- and pre-menopausal women, leptin values were highest in post-menopausal women (55 ± 29.5 mg/mL vs. 41 ± 29.5 vs 39 ± 25.6, p=.047). In cross-sectional analyses, and after adjustment for confounders, higher overall LE8 CVH scores were associated with lower levels of leptin (B= -0.17, p<0.0001), CRP (B= -0.34, p=0.009), and IL-6 (B= -2.85; p=0.02). In multivariable prospective analyses, lower CRP at baseline predicted better LE8 CVH scores at 1 yr (B= -0.22; p=.02), with a similar trend for an association between lower baseline leptin and better LE8 CVH scores at 1 yr (B= 0.04; p=.066).

Conclusions:
In a national sample of women across the menopausal transition, those with lower leptin and inflammatory markers had more favorable CVH scores as measured by the recently updated LE8 construct.
Abstract 18955: Post Webinar Survey Responses Regarding Maternity and Legal Rights for Cardiologists
Authors: Bullock-Palmer Renee P , Sanghavi Monika , Tamirisa Kamala , Mehta Laxmi S , Reza Nosheen , Quesada Odayme , Shah Sonia , Volgman Annabelle S , Gulati Martha , Lee Jessica , Grapsa Julia A , Lundberg Gina P
Published: December 2023

Introduction/Background:
Women are under-represented in cardiology and cardiology subspecialties. Work life challenges are often a stated reason why women do not choose cardiology. Pregnancy and motherhood represent a time of significant challenges to women in cardiology due to lack of support and discrimination. The American Heart Association (AHA)Women in Cardiology (WIC) Committee recently held a case-based webinar to increase awareness about the issues, discuss available resources for support, and understand laws protecting women against discrimination.

Goals/Aims:
The goal of the survey was to understand the current landscape of perceived institutional support during the maternity period and gauge awareness of the laws protecting women against discrimination.

Methods/Approach:
After the webinar, an email survey was sent to all those who registered on behalf of the AHAWIC Committee within 7days of the event.

Results/Data:
There were 189registrants for the webinar, of which 29(15%)responded to the survey. Of those who responded, 72%were female, 48%were <40years of age, 33%of the attendees were mothers, and 20%reported fertility issues. Almost all respondents reported working in a hospital-based practice (90%),59%were attending physicians and 38%were trainees. Only 28%reported that their work environment was very supportive of mothers and only 31%were aware of maternal legal rights in the workplace. After the webinar, 76%planned to learn or implement new maternal rights related policies in their workplace (Figure 1).

Conclusions:
Pregnancy and motherhood represent a challenging time in the career of a female cardiologist or trainee. Perceived support in the workplace is low. Very few women know their legal rights, but a majority had a plan to learn more after the webinar. This survey highlights opportunities for the cardiology community and national societies to help support women cardiologists.
Abstract 18976: In-Hospital Outcomes in Patients Undergoing Protected Left Main Percutaneous Coronary Intervention With Percutaneous Left Ventricle Assist Device Protection
Authors: Legutko Jacek , Kleczynski Pawel , Niewiara Luke , Pawlik Artur , Weglan Katarzyna , Kwiatkowska Ewa , Stanislaw Bartus
Published: December 2023

Introduction:
Left main disease (LMCA) is a known risk factor for patients’ poor outcomes. Percutaneous revascularization of LMCA in heart failure patients is associated with a particularly high periprocedural risk. Percutaneously introduced left ventricle assist devices (pLVAD) are a potential tool to improve patient outcomes in these high-risk procedures.

Hypothesis:
Our study aimed to assess short-term clinical outcomes of protected left main percutaneous coronary intervention with the use of a pLVAD.

Methods:
A prospective registry of patients with chronic heart failure, undergoing protected LMCA PCI included 66 patients, 89% male, the median age of 71.5 y.o, 40 (60.6%) after prior myocardial infarction, 31 (47%) after prior PCI and 12 (18.2%) after CABG, with CTO RCA in 17 (25.6%) of cases. Percutaneous LVAD was used in all patients, 72% access site was the right femoral artery, additional plaque modification techniques were used in 46 (69.7%) patients, IVL was applied in 25 (37.9%) of cases and high-speed rotational or orbital atherectomy was used in 21 (31.2%) of cases. Median of 3 [2;4] DES was implanted.

Results:
During the in-hospital follow-up, a significant improvement of the left ventricle ejection fraction was observed (median LVEF 30% post PCI vs22% at baseline, p<0.001) as well as a significant decrease of NTproBNP levels (765 [IQR: 194, 6,370] at discharge vs 7113 pg/ml [IQR:1,945, 15,646] at baseline, p=0.01]. There was 1 in-hospital death due to cardiogenic shock. A safety monitoring revealed 11 hematomas, including 3 cases that needed vascular surgery. Bleeding according to BARC 3a was recorded in 17/66 (28%) and BARC 3b in 3/66 (5%) of cases.

Conclusions:
Percutaneous LVAD support is a feasible method to perform protected left main PCI with a good safety profile when applied by experienced operators

A significant improvement of the LVEF can be observed after left main revascularization Further research is needed to confirm the presented results.
Abstract 18979: Calm Before the Storm: Exploring the Risk of Torsades De Pointes With Dexmedetomidine Administration
Authors: Amirian Aslan , Soni Bosky , Rajak Kripa , Halder Anupam
Published: December 2023

Introduction:
Corrected QT interval (QTc) prolongation is the known side effect of multiple medications especially in antipsychotic and antiarrhythmic family. Patients with either inherited or secondary prolonged QTc should be monitored closely as they can develop life threatening complications like Torsades de-pointes and ventricular fibrillation. Here we present a case of cardiac arrest secondary to dexmedetomidine.

Case:
A 49-year-old female with history of bipolar disorder was admitted to intensive unit for seizure after intentional ingestion of uncounted amount of diphenhydramine pills. Patient was intubated for airway protection and started on propofol. Her vitals at the time of admission included the pulse rate of 76, blood pressure of 102/49 mmHg. Her urine drug screen was positive for TCA and cannabinoids. Her ECG at the time of admission was significant for prolonged QTC of 600msec that improved to 460msec in the consecutive ECGs after administration of total of 4mg intravenous magnesium. Continuous EEG was negative for seizure and she was weaned off sedation. After awakening, she became agitated, after pushes of benzodiazepines, was eventually started on dexmedetomidine. Twenty minutes after starting low dose dexmedetomidine, patient was noted to be in cardiac arrest. Reviewing telemetry prior to event, revealed the R on T phenomenon and Torsades de pointes that lasted for few seconds with progression into ventricular fibrillation.

Discussion:
Currently dexmedetomidine is labeled with a low to possible risk of Torsade de pointes and QTC prolongation. Dexmedetomidine induced Torsade de pointes might be explained by bradycardia in patients which causes further prolongation of QT interval. Studies have shown that continuous IV infusion of dexmedetomidine at rate of 0.3 mcg/kg/hour can worsen QTC prolongation.

Conclusions:
In this case we present a case of VFib arrest secondary to Torsade after twenty minutes of infusion of dexmedetomidine without any sign of bradycardia prior to the event. This carries a significant importance as it shows this drug carries a potential risk of QTc prolongation similar to previous studies. Whether this side effect is dose dependent or not requires further investigation.
Abstract 19006: Human Epididymis Protein 4 and Carcinoembryonic Antigen-125: Promising Blood Biomarkers to Identify Diffuse Myocardial Fibrosis in Patients With Severe Aortic Stenosis
Authors: Zanuttini Antonela , Hecht Sebastien , Giuliani Carlos , Bernard Jeremy , Tastet Lionel , Abu-Alhayja'a Rami , Beaudoin Jonathan , Arsenault Benoit J. , De Larochelliere Robert , Paradis Jean-Michel , Clavel Marie-Annick A , Rodes Josep , Cote Nancy , Pibarot Philippe
Published: December 2023

Introduction:
Cardiovascular magnetic resonance (CMR) T1 mapping, extracellular volume (ECV) and late gadolinium enhancement (LGE) demonstrate strong agreement with endomyocardial biopsy in evaluating myocardial fibrosis. Human epididymis protein 4(HE4) has been shown as a blood biomarker to identify fibrosis, but the relationship with other blood biomarkers is not well established yet.

Hypothesis:
determine the correlation between different blood biomarkers and myocardial fibrosis by CMR in patients undergoing transcatheter aortic valve implantation(TAVI).

Methods:
Forty-three patients were included. The cohort was divided into two groups based on the threshold values of HE4(128.5 pmol/l) and/or CA-125 (19.5 U/ml), before TAVI. Native T1 mapping and ECV were measured at 1280 ms and 26%, respectively, corresponding to the median of the population studied. LGE was qualitatively measured.

Results:
Patients with higher HE4 plasma levels (> 128.25 pmol/l) and/or CA-125 (>19.5 U/ml) prior to TAVI had more comorbidities and had higher median native T1 mapping values, 1278 ms (1239.25-1280.25) vs 1352 ms (1303.50 -1376.00), p < 0.001, and LGE positive, 10 (55.6%) vs 10 (90.9%); p= 0.046, respectively. HE4 (r=0.34, p=0.03) and CA-125 (r=0.371, p=0.034) correlated with prolonged T1 mapping. No significant correlation was found with other biomarkers: troponin T (r = 0.14, p = 0.41), Nt-proBNP (r=0.28, p=0.089), IL-6 (r=0.189, p= 0.250), procalcitonin, (r =0.132, p =0.420). The addition of elevated plasma levels of HE4 and CA-125, provided significant C-statistics for myocardial fibrosis, AUC [95%CI]: 0.74 [0.58- 0.89], p= 0.008, regarding HE4 AUC [95%CI]: 0.69 [0.52- 0.85], p=0.039, and CA-125 AUC [95%CI]: 0.72 [0.57- 0.88], p= 0.014. On univariable analysis, high plasma levels of HE4 and/or Ca-125 were independently associated with diffuse fibrosis by native T1 mapping OR:9.37, [95% CI: 2.07 - 42.33], p = 0.004 and there was a trend toward focal fibrosis by LGE + OR: 8.00, [95% CI: 0.83 - 76.36], p = 0.071.

Conclusion:
Elevated HE4 and/or Ca-125 plasma levels correlated with prolonged native T1 mapping. The combination of HE4 values ≥ 128 pmol/l and CA-125 ≥ 19.5 U/ml may provide a useful screening biomarker to identify diffuse myocardial fibrosis in AS.
Abstract 19030: Growth Arrest-Specific 5, a Novel Regulator of Adipose Tissue Browning
Authors: Mehdi Dilbar , Chen Shiyou
Published: December 2023

Background:
Obesity is a global epidemic with significant health risks, including type 2 diabetes and cardiovascular diseases. Increasing white adipose tissue (WAT) browning has shown metabolic benefits in both animal models and humans. Long non-coding RNAs (lncRNAs), have been implicated in various diseases, including metabolic disorders. Growth arrest-specific 5 (GAS5), a tumor suppressor lncRNA decreased in type 2 diabetic patients, has been found to be involved in adipocyte differentiation, however, the role of GAS5 in WAT browning has not yet been established. We hypothesized that in the presence of an adipose tissue browning stimuli, GAS5 promotes WAT browning

Methods:
In vitro
approaches through knocking down or overexpressing GAS5 were used to determine its role in regulating thermogenic genes and thermogenesis. To test the role of GAS5 in adipose tissue browning
in vivo
, adenovirus AAV8 expressing GAS5 was administered specifically in epidydimal adipose tissues followed by the treatment of browning stimuli CL-316,243.

Results:
Knockdown of GAS5 increased Smad3 phosphorylation, which was blocked by Smad3 inhibitor, SIS3. Conversely, overexpression of GAS5 inhibited Smad3 phosphorylation. On the other hand, Smad3 overexpression blocked the stimulatory effects of GAS5 on the expression of thermogenic genes PGC-1α and UCP1. Moreover, overexpression of GAS5 inhibited, while knockdown of GAS5 enhanced, Smad3 nuclear translocation and tis binding to PGC-1α promoter.
In vivo
experiments with GAS5 overexpression in epididymal adipose tissues revealed that GAS5 promotes CL-316,243-induced WAT browning in mice.

Conclusions:
Our study demonstrates that GAS5 promotes WAT browning by suppressing Smad3 signaling, which in turn increases thermogenesis via stimulating PGC-1α and UCP1 expression. These findings establish GAS5 as a novel regulator of WAT browning with potential implications for mitigating obesity and associated metabolic disorders.
Abstract 19033: Increased Prevalence of Gaps in Care for Patients With Congenital Heart Disease Are Associated With Social Determinants of Health Including Childhood Opportunity Index
Authors: Alberts Adam , Brewer Benjamin , Zadokar Varsha , beaty claude , Chen Ming-Hui H , De Ferranti Sarah D , Chowdhury Devyani , Zaidi Abbas H
Published: December 2023

Background:
Lifelong continuity of care is imperative for patients with congenital heart disease (CHD). Unfortunately, gaps in care (GIC) are common.

Hypothesis:
Social determinants of health are associated with GIC in patients with CHD.

Methods and Results:
A total of 2511 patients followed at Nemours Cardiac Center (NCC) with CHD were seen in the clinic between January 2005 and December 2022. Patients were divided into 3 cohorts based on anatomic complexity described in 2018 AHA/ACC adult congenital guidelines as simple, moderate, and complex CHD. Patient characteristics were analyzed, including race, ethnicity, gender, language, insurance status, and Childhood Opportunity Index (COI) based on home address zip code. GIC of > 3 years were identified in 56% (n=1168) of patients. Linear regression model showed that the proportion of GIC stayed consistent for complex CHD with an increase of 0.1% per year and had a significant increase for those with simple and moderate CHD (Figure 1) with a yearly increase of 1.1% and 0.6% respectively. On the multivariable model GIC were associated with a non-Delaware residence (P<0.001), simple to moderate CHD (P<0.001), having less than two caregivers listed (P<0.001), not having public insurance (P<0.001), being none-white (P<0.007), age (P<0.001) Overall COI (P<0.007) with a c-Statistic of 0.692.

Conclusions:
Over half of the patients with CHD experienced a substantial GIC. GIC were consistent for those with complex CHD but increased significantly for those with simple to moderate CHD over almost two decades and were associated with various SDOH factors including COI. Providing consistency in practice, minimizing practice variation especially for those with mild and moderate CHD and understanding the role of SDOH factors can help decrease GIC and improve patient care for this vulnerable population.