bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10461: Single-Cell Transcriptional Analysis of Altered Cardiomyocyte Pdk4 as Indicator of Ischemic Stress Vulnerability in Aging
Authors: Fatmi Mohammad , Ren Di , Wang Hao , Zoungrana Linda Ines , Krause-Hauch Meredith , Li Ji
Published: June 2023

Introduction:
The mechanisms by which aging increases vulnerability to ischemic insult are not well understood. Single-Cell RNA sequencing (scRNA seq) was employed to characterize transcriptional differences in various cell types between aged and young mice which may contribute to aged-related vulnerability to ischemic insult. Pyruvate Dehydrogenase Kinase 4 (Pdk4) has been shown to impact capacity for fatty-acid oxidation (FAO) and consequently adaption to metabolic alterations of ischemic insult.

Hypothesis:
Alteration of Pdk4 expression levels is an adaptive response transcriptionally under pathological stress to maintain metabolic homeostasis during ischemia and reperfusion (I/R).

Methods:
Young (3-5 months) and aged (24-26 months) C57BL/6J mice were subjected to
in vivo
regional 45 min of ischemia and 24 hr of reperfusion (I/R) or sham operations. Bioinformatic analysis was done using Seurat integration vignettes allowing for cell type identification and differential expression testing. Observing genetic expression profiles by cell types. Substrate metabolism was determined with working heart system and Seahorse XF Analyzer.

Results:
Pdk4 was profoundly found in cardiomyocytes versus fibroblasts, endothelial cells and macrophages of both young and aged hearts. Interestingly, I/R stress triggered Pdk4 mRNA expression of young but not aged cardiomyocytes. Moreover, there is a relative higher Pdk4 level in aged versus young cardiomyocytes under sham operations, indicating Pdk4 mRNA respond to pathological stress. The
ex vivo
working heart perfusion data showed that young versus aged hearts exhibited higher FAO in response to I/R. Moreover, Seahorse XF Analyzer showed a higher glycolysis rate in young versus aged cardiomyocytes during I/R. It suggests that an impaired cardiomyocyte Pdk4 mRNA response occurred in aging under I/R stress conditions, this could result in cardiac maladaptive metabolic alterations in aging during pathological stress.

Conclusions:
Alterations in Pdk4 levels of cardiomyocytes regulates cardiac adaptive metabolism in response to pathological stress. This adaptive regulation of cardiomyocyte Pdk4 is impaired in aging that leads to more vulnerability of aged versus young hearts to ischemic insult.
Abstract 10477: Newer Guideline-Directed Medical Therapies Are Underutilized in 2021-22 in Patients With Heart Failure Without Diabetes
Authors: Canonico Mario Enrico , Hsia Judith A , Cannon Christopher P , Bonaca Marc P
Published: June 2023

Introduction:
In 2021-22, Heart Failure (HF) guidelines endorsed quadruple therapy with beta blockers (BB),angiotensin-converting inhibitors/angiotensin receptor blockers (ACEi/ARB) or angiotensin receptor-neprilysin inhibitors (ARNI), mineral receptor antagonists (MRA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) as first-line medications to improve clinical outcomes. AHA 2022 HF guidelines specifically recommended SGLT2i even in patients without diabetes mellitus (DM) irrespective of left ventricular ejection fraction (HF).

Hypothesis and Methods:
Our analysis evaluated the hypothesis that prescription of guideline directed medical therapy (GDMT) is similar in patients with or without DM. We extracted TriNetX data for patients with HF encounters from May 2021-April 2022 in the University of Colorado health system which includes an ethnically diverse population of rural and urban residents. Patient on dialysis were excluded. GDMT use was compared by chi square.

Results:
Among 24890 patients with HF encounters, 9240 (37%) had reduced (HFrEF) and 8680 (35%) preserved ejection fraction (HFpEF) and 6970 (28%) unspecified HF. Mean age was 70
+
14y, 46% were female, 10% Latino in the whole cohort. Diagnosed DM was reported among 3260 (35%) with HFrEF and 3410 (39%) with HFpEF. Older drugs such as BB and ACEi/ARB were widely prescribed in both groups, particularly among patients with DM (Figure, p<0.0001 for both drug classes). MRA were less often prescribed, particularly among patients without DM (Figure, p=0.0089 in HFrEF and p<0.0001 in HFpEF). No difference in ARNI use was detected in patients with vs without DM. SGLT2i prescription was particularly low in patients without DM regardless of HF phenotype (Figure, both p<0.0001).

Conclusion:
Even in 2022, patients without DM were less likely than those with DM to receive BB, ACEi/ARB, MRA and SGLT2i. Efforts to improve use of GMDT for HF could target patients without DM.
Abstract 10537: A Comparison of Endothelial Nitric Oxide Synthase(eNOS)-Based Platelet Subpopulation Ratios and Platelet VEGF Content Within Covid-19
Authors: Asgari Amir , Jurasz Paul
Published: June 2023

Background:
Nitric oxide (NO) regulates both thrombosis and vascular leakage, two of the major complications of severe Covid19. Platelet-derived NO inhibits adhesion/aggregation and within microvascular endothelial cells NO-signalling mediates vascular endothelial growth factor (VEGF/VPF)-induced permeability. Recently, we identified novel platelet subpopulations with a differential ability to produce NO and the presence/absence of endothelial nitric oxide synthase (eNOS). We showed that eNOS-negative (eNOS
neg
) platelets initiate adhesion and aggregation, while eNOS-positive (eNOS
pos
) platelets limit aggregate growth. As inflammatory cytokines are known to counter-regulate eNOS and VEGF expression, we hypothesized that the ratio of eNOS-negative to -positive platelets may be increased in COVID-19 patients along with their VEGF content.

Aims:
To determine the eNOS-positive to -negative platelet ratio and platelet VEGF levels within the blood of hospitalized COVID-19 patients.

Methods:
Platelets were isolated from age- and sex-matched COVID-19 patients (ICU and non-ICU) and COVID-negative healthy controls. Isolated platelets were intracellularly stained for eNOS, VEGF, and for surface CD62P and analyzed using flow cytometry. A multiplex assay was used to measure plasma cytokines.

Results:
The percentage of eNOS
neg
platelets within the blood of COVID-19 patients (ICU and non-ICU) was higher than that within healthy controls and their levels correlated with disease severity (81.2±2.8% ICU vs. 66.0 ±3.1% non-ICU vs. 6.1± 1.3% controls,
P
-value < 0.0001). Accordingly, the percentage of eNOS
pos
platelets in COVID-19 patients was lower compared to controls, while the platelet VEGF content and surface CD62P of COVID-19 patients in ICU was higher than that of healthy controls. Further, COVID-19 patients demonstrated higher TNFα, IL-6, and IL-1β plasma concentrations than controls.

Conclusion:
Preliminary data suggests that eNOS-negative to -positive platelet ratios and VEGF content increase with COVID-19 severity, potentially predisposing patients to thrombosis and enhanced vascular permeability upon platelet activation. These platelet changes may be due to the actions of inflammatory cytokines on megakaryocytes.
Abstract 10580: Machine Learning-Assisted Echocardiographic Identification of Children at High Risk for Treatment-Related Cardiomyopathy: A Proof-of-Concept Study
Authors: Yang Christina , Chen Zih-Hua , Gorantla Lahari , Joshi Sanika A , Longhi Nicolas J , Yang Jamie , Armenian Saro , Bhat Aarti , Border William , Buddhe Sujatha , Leger Kasey J , Leisenring Wendy M , Meacham Lillian R , Nathan Paul , Sachdeva Ritu , Sadak Karim , Chow Eric , Boyle Patrick M , Edwards Lindsay A
Published: June 2023

Introduction:
Childhood cancer survivors require life-long surveillance for treatment-related cardiomyopathy/heart failure (CHF). Ultimately, we aim to use machine learning to aid in echocardiographic discrimination of survivors more likely to develop future CHF. For this feasibility pilot, we built two proof-of-concept deep convolutional neural networks (DCNNs) tasked with binary classification of present/future CHF versus no CHF with the aim of assessing optimal data input format and model architecture.

Methods:
From a robust multi-institutional surveillance echo dataset, we selected pilot data comprising 171 parasternal short axis echo clips, 52 from 5 CHF+ (present and future CHF) and 119 from 21 CHF- patients. We built two DCNN models differing in frame selection for input data (Fig. 1), both tasked with binary classification of CHF+ vs. CHF-. We used holdout subsets in a 10-fold cross-validation framework to test model performance and Student’s t test (paired) to compare model performance.

Results:
Classification performance was similar, with mean AUROC values of 0.59 ± 0.09 and 0.53 ± 0.11 (p=0.14) for the models trained on Type I and Type II montages, respectively (Fig. 2).

Conclusions:
The DCNN framework is feasible for a model tasked with classifying CHF status, and we are optimistic that a similar model can be trained with pre-CHF diagnosis (case) vs control patient images to facilitate machine learning-assisted identification of childhood cancer survivors more likely to develop CHF in the future.
Abstract 10594: Cardiac Tamponade in a Covid-19 Positive Patient With Idiopathic Capillary Leak Syndrome: A Perilous Combination
Authors: Biong Kim Eloise , Lapitan Lois P , Lapitan Raul L
Published: June 2023

Introduction:
Clarkson’s disease, more known as idiopathic systemic capillary leak syndrome (SCLS) is a rare condition characterized by hypotensive episodes due to capillary hyperpermeability and can manifest as fluid accumulation in any organ or potential space. This may cause a range of complications: respiratory failure (from pulmonary edema or pleural effusion), mesenteric hypoperfusion (from hepatic congestion and severe intestinal edema), compartment syndrome and rhabdomyolysis, and even shock from hypovolemia or cardiac tamponade. Very few cases of cardiac tamponade in Clarkson's disease and COVID-19 have been reported, and when present, is certainly a serious and life-threatening complication.

Case Summary:
A 44-year-old female - with prior episodes of angioedema, pleural and pericardial effusions aggravated by menstruation and infection - presented with hypotension and diaphoresis. She was exposed to a COVID patient and eventually tested positive for COVID-19 infection. Persistent hypotension warranted triple inotropic support. Initial laboratories revealed hemoconcentration and hypoalbuminemia. Urinalysis was normal. 2D echocardiography showed normal left ventricular ejection fraction but with large pericardial effusion and signs of cardiac tamponade, hence, she underwent emergency pericardial windowing. She then developed pleural effusion which was drained surgically. Hepatitis, mycoplasmal and Epstein-Barr virus were negative. Direct and indirect Coomb’s test, and Lupus panel were unremarkable. Serum free light chain panel, immunopathology and C1 inhibitor results were non-diagnostic. Patient was managed as a case of idiopathic SCLS or Clarkson's disease. Methylprednisolone pulse therapy (MPPT) and intravenous immunoglobulin (IVIg) were administered. Patient was discharged with tapering doses of oral steroids and scheduled monthly IVIg infusion.

Conclusions:
Cardiac tamponade is a very rare but life-threatening complication of Clarkson’s disease, and on top of a COVID-19 infection, warrants emergent intervention. The pathogenesis is not yet fully elucidated. Diagnosis of SCLS is challenging thus recurrent pericardial and pleural effusions should raise the clinician’s index of suspicion.
Abstract 10611: Inhibition of Sars-cov-2 Viral Channel Activity Using FDA-Approved Channel Modulators Independent of Variants
Authors: Yu Hangang , Sizemore Gina , Martinez Ivan , Stoilov Peter , Perrotta Peter
Published: June 2023

Introduction:
SARS-CoV-2 has undergone mutations, yielding clinically relevant variants such as Delta and Omicron. Early detection of virus and effective therapeutic treatment independent of variants help control virus spread.

Hypothesis:
We hypothesized that in the genome of SARS-CoV-2 two highly conserved viroporins Orf3a and E channels directly related to virus replication may be explored as a target for detection and inhibition of viral replication independent of variants using FDA-approved ion channel modulators.

Methods:
A combination of a fluorescence potassium ion assay with three channel modulators (4-aminopyridine, emodin-Orf3a channel blocker, gliclazide-E channel blocker) in a 96-well plate format was developed to detect SARS-CoV-2 Orf3a/E channel activity. We subtracted the fluorescence signals in the absence and presence of emodin/gliclazide to detect Orf3a and E channel activity. Two FDA-approved drugs, amantadine (an antiviral) and amitriptyline (an antidepressant) that are also ion channel blockers, were used to test whether they can inhibit Orf3a/E channel activity in isolated virus (UV inactivated) and in nasal swab samples from Covid-19 patients. Twenty-one (21) Delta and thirty (30) Omicron nasal swab samples were used. Variants were confirmed by PCR sequencing.

Results:
Orf3a and E form non-voltage-gated ion channels that are highly conserved in SARS-CoV-2 variants. In UV-inactivated SARS-CoV-2 Alpha, Beta, and Delta variants, significant channel activity of Orf3a/E was detected based on an increase in fluorescence induced by 4-aminopyridine, and this increase in fluorescence was inhibited by emodin and gliclazide (IC
50
= 0.42mM). Amantadine and amitriptyline can inhibit Delta virus with amitriptyline being a more potent inhibitor than amantadine. In swab samples of Delta variants, both amitriptyline and amantadine inhibited the channel activity of viral proteins with IC
50
values of 0.73mM and 1.11mM, respectively. In swab samples of Omicron variants, amitriptyline inhibited the channel activity with an IC
50
of 0.76mM.

Conclusions:
We developed an efficient method to screen FDA-approved ion channel modulators that can be repurposed to inhibit SARS-CoV-2 viral replication independent of variants.
Abstract 10619: Pericoronary Fat Attenuation Index on Coronary Computed Tomography Angiography Predicts Hospitalization for Heart Failure in Patients With Suspected Coronary Artery Disease
Authors: Nakashima Mitsutaka , Miyoshi Toru , Nishihara Takahiro , Ichikawa Keishi , Miki Takashi , Takaya Yoichi , Nakayama Rie , Toh Norihisa , TODA HIRONOBU , Yoshida Masatoki , Osawa Kazuhiro , Ito Hiroshi
Published: June 2023

Introduction:
Chronic inflammation is focused as a cause of heart failure (HF). Pericoronary fat attenuation index (FAI) assessed on coronary CT angiography (CCTA), a maker of vascular inflammation, is reported to associate with risk of cardiac mortality. However, relationship between pericoronary FAI and development of HF has not been fully elucidated.

Hypothesis:
Pericoronary FAI predicts hospitalization for HF.

Methods:
A total of 1196 consecutive patients who underwent clinically indicated CCTA and transthoracic echocardiography for suspected CAD were enrolled. Patients with a history of CAD, hospitalization for HF, left ventricular ejection fraction (LVEF) <40%, and hemodialysis were excluded. We assessed pericoronary FAI of proximal 40 mm segments for three major coronary arteries. Association between pericoronary FAI and incidence of hospitalization for HF was analyzed by Cox regression analysis.

Results:
During a median follow-up of 4.3 years, 29 hospitalizations for HF occurred. Pericoronary FAI of three major coronary arteries were significantly corelated each other. Pericoronary FAI of left anterior descending artery (LAD) was higher in patients with hospitalization for HF than in patients without hospitalization for HF (-61.4 ± 7.8 HU and -67.4 ± 7.2 HU, p<0.001). Optimal cut-off value of pericoronary FAI of LAD for predicting hospitalization for HF was -64.8 HU. Pericoronary FAI of LAD (>-64.8 HU) was significantly associated with hospitalization for HF after adjusted by age and gender (HR 4.77, 95%CI 2.10-10.81). In addition, these analyses were performed in 885 patients without significant stenosis (16 hospitalizations for HF occurred). In this cohort, pericoronary FAI of LAD in patients with hospitalization for HF was higher than that in patients without hospitalization for HF (-60.8 ± 7.2 HU and -67.3 ± 7.2 HU, p<0.001), and association of FAI of LAD with hospitalization for HF remained significant. Pericoronary FAI of LAD was significantly correlated with left atrial volume index, left ventricular mass index, LVEF and E/e’, respectively (p<0.001).

Conclusions:
Pericoronary FAI of LAD on CCTA may be a useful clinical predictor of hospitalization for HF in patients suspected CAD without history of CAD and hospitalization for HF.
Abstract 10638: The Effectiveness of Covid 19 Vaccines Against New Onset Atrial Fibrillation in Hospitalized Covid 19 Patients
Authors: Vargas Gustavo A , Azarbal Jilla R , Tang Fei , Hammel Iriana S
Published: June 2023

Introduction:
Cardiovascular complications are prevalent in COVID-19 individuals and have a poor prognosis. A link between atrial fibrillation (AF) and hospitalized COVID-19 patients was reported. Vaccines were shown to be highly effective against COVID-19 infection, poor outcomes and death.

Methods:
In this retrospective cohort study, we used US Veterans Health Administration COVID-19 Corporate Data Warehouse data to evaluate vaccine protection against new onset AF in patients hospitalized with COVID-19 infection. We included veterans without baseline AF who were hospitalized with COVID-19 between January 01, 2021, and November 10, 2021, and obtained their socio-demographic characteristics, diagnoses, vaccination information, symptoms, all-cause death, and diagnosis of AF during hospitalization. We define “fully vaccinated” at the time of infection as follows: for the BNT162b2 vaccine, at least 7 days from receipt of the second dose; for mRNA-1273 and Ad26.COV2.S, at least 14 days from receipt of the second dose and first dose, respectively. Partially vaccinated patients and patients hospitalized before testing positive were excluded. Considering competing risk from death, the Fine-Gray subdistribution hazard model was used to evaluate the effect of vaccination on new onset AF. Statistical analyses were performed using R (the R project for statistical computing, version 4.0.5).

Results:
We identified a total of 23,595 veterans hospitalized with COVID-19 positive infection without baseline AF. 1,807 (7.7%) patients were diagnosed with new onset AF before discharge from the hospital. Among vaccinated patients, 363 (6.0%) developed new onset AF, while among unvaccinated patients, 1,004 (5.7%) developed new onset AF. After adjusting for age, BMI, race, ethnicity, gender, diabetes, hypertension, COPD, CVD, and kidney disease, smoking status, alcohol abuse, substance abuse, vaccination was associated with 12% reduction in the risk of new onset AF (adjusted HR=0.88,95%CI:0.79-0.93).

Conclusion:
For hospitalized patients with COVID-19 infection, vaccination protects against new-onset AF. Further studies are needed to stratify hospitalized patients with COVID-19 at high risk of developing new onset AF.
Abstract 10720: Early Growth Trajectory is Associated With Post-Traumatic Stress in Parents of Infants With Congenital Heart Disease
Authors: Lisanti Amy J , Golfenshtein Nadya , Min Jungwon , Medoff-Cooper Barbara
Published: June 2023

Background:
Parents of infants with congenital heart disease (CHD) have described substantial stress over infant growth. Poor growth trajectory (GT) during early infancy may be a source of traumatic stress. The purpose of this study was to determine if differences exist in parent posttraumatic stress (PTS) between parents of infants with healthy versus poor GTs from hospital discharge to 4 months post discharge.

Methods:
This secondary analysis of a previously reported RCT (REACH telehealth trial NCT01941667) included parents of infants with CHD with stress measures at discharge and study end (n=136). Posttraumatic Diagnostic Scale was used to measure PTS. Weights were converted to weight for age Z scores (WAZ) using World Health Organization standards. WAZ-GT classes were identified using latent class growth modeling. We used multivariate logistic regression modeling to examine associations between WAZ-GT and parental PTS over the study period, adjusting for covariates.

RESULTS
One-quarter of parents (n=37, 28%) demonstrated at least moderate PTS symptom severity at discharge and one-third at study end (n=40, 31%). We identified four distinct classes of infant WAZ-GT (Figure). Among the identified GTs, two were considered healthy growth patterns: “stable around WAZ=0” (n=51, 37.5%) and “maintaining WAZ > 0” (n=12, 8.8%). Therefore, these two patterns were collapsed to serve as one reference group for the analysis. Two additional WAZ-GT classes were identified that reflected poor growth: “partially-recovered” (n=44, 32.4%) and “never-recovered” (n=29, 21.3%). Parents of infants in the "never recovered" GT were at greater risk (OR=4.58; CI=1.54-13.64) for experiencing at least moderate PTS symptom severity at end of study as well as over time from discharge to end of study (OR=3.91; CI=1.60-9.86).
CONCLUSION
Results offer new insights that parents of infants with poor GT are at increased risk for persistent PTS and may need additional screening and intervention.
Abstract 10735: Brash Syndrome: Frequently Under-Recognized and Often Confused With Simple Hyperkalemia
Authors: Patel Kunal N , Joseph Betsy a , Bansal Ankit , Vaithiya Santharaman Aadhithyaraman , Santos Argueta Andrea , kaur Avleen , Patel Vyoma , Singh Karandeep , Patel, MD Keval V
Published: June 2023

Introduction:
BRASH syndrome is a relatively newly recognized and under-reported clinical entity characterized by bradycardia, renal dysfunction, atrioventricular node blockade (AVNB), shock, and hyperkalemia. We report a case of BRASH syndrome that was refractory to medical therapy alone, requiring transvenous pacing, hemodialysis, and vasopressor support.

Case presentation:
An 82-year-old female with hypertension, diabetes, and paroxysmal atrial fibrillation (on metoprolol and verapamil) was found unresponsive at a nursing home. She had refractory shock (99/34 mmHg) and symptomatic bradycardia with heart rate (HR) of 33 BPM. EKG showed atrial fibrillation rhythm with ventricular rate of 31 BMP and peaked T-waves. Labs revealed creatinine of 1.98 mg/dL, potassium of 6.8 mmol/L, and TSH of 2.90 ulU/ml. She had no signs of infection and echocardiogram showed normal left ventricular systolic function. She was intubated for airway protection. AVNB agents were immediately held. Potassium-lowering agents and vasoactive drugs were administered. Temporary transvenous pacemaker was placed due to persistent bradycardia with hemodynamic instability even after transcutaneous pacing. Temporary hemodialysis was started for worsening renal failure and refractory hyperkalemia. She was weaned off vasopressor support, mechanical ventilation, hemodialysis and temporary pacing over the next few days. Renal function improved and HR stabilized at 70 BPM.

Discussion:
In our case, AVNB agent overdose caused bradycardia which in turn led to decreased cardiac output and renal hypoperfusion. Resultant acute kidney injury led to decreased clearance of renally excreted metoprolol and verapamil and worsening hyperkalemia, which locked the patient in a vicious cycle of BRASH syndrome leading to hemodynamic compromise. Therefore, rapid diagnosis and correct management with transvenous pacemaker and renal replacement therapy are crucial to reduce mortality.
Abstract 10742: In-Hospital Virtual Peer-to-Peer Consultation to Improve Guideline-Directed Medical Therapy for Heart Failure: A Pilot Randomized Trial
Authors: Rao Vishal N , Shah Anand , McDermott Jaime , Barnes Stephanie , Murray Evan , Kelsey Michelle D , Greene Stephen J , Fudim Marat , Devore Adam D , BLAZING Michael A , OBrien Cara , Mentz Robert J
Published: June 2023

Introduction:
Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) improves clinical outcomes and quality of life. Optimizing GDMT in the hospital is associated with greater long-term use in HFrEF.

Hypothesis:
A multidisciplinary virtual HF intervention improves GDMT optimization among patients with HFrEF admitted for any cause.

Methods:
In this pilot randomized, controlled study, consecutive patients with HFrEF admitted to non-cardiology medicine services for any cause were identified at Duke Hospital between May to September 2021. Major exclusions were end-stage renal disease, hemodynamic instability, and hospice care. Patients were randomized to a clinician-level virtual peer-to-peer consult intervention providing GDMT recommendations and information on medication costs vs. usual care. Primary endpoints included 1) proportion of patients with new GDMT initiation or use, and 2) changes to HF optimal medical therapy (OMT) scores which included target dosing (range 0-9).

Results:
Of 242 patients identified, 91 (38%) were eligible and randomized to intervention (N=52) or usual care (N=39). Baseline characteristics were similar between intervention and usual care (mean age 63 vs. 67 years, 23% vs. 26% female, 46% vs. 49% Black, mean EF 33% vs. 31%). GDMT use on admission was also similar. There were greater proportions of patients with GDMT initiation or continuation with the intervention compared with usual care (
Figure 1
). After adjusting for OMT score on admission, changes to OMT score at discharge were higher for the intervention group compared with usual care (+0.44 vs. -0.31, absolute difference +0.75, adjusted estimate 0.86 ± 0.42; p=0.041).

Conclusions:
Among eligible patients with HFrEF hospitalized for any cause on non-cardiology services, a multidisciplinary pilot virtual HF consultation increased new GDMT initiation and dose optimization at discharge.
Abstract 10764: A Comparison of Atrial Fibrillation Detection Strategies After Ischemic Stroke- A Retrospective Study
Authors: Salehin Salman , Saleh Mohammed , Rasmussen Peter , Mai Steven , Safder Zaid , Hasan Syed , Chatila Khaled , Khalife Wissam , Sewani Asif
Published: June 2023

Introduction:
In 20-30% cases, the cause of stroke remained unexplained which has led to coining of the term, Cryptogenic Stroke (CS). Similarly, about 48% cases of transient ischemic attacks (TIAs) had no identifiable cause after standard diagnostic workup. Undiagnosed Atrial Fibrillation (AF) is a prime suspect in CS but guidelines do not recommend initiation of anticoagulation unless AF has formally been detected.

Methods:
In a IRB approved retrospective study we included patients with at least one episode of ischemic stroke or TIA without identifiable cause and was monitored with either 48-hour Holter Monitor (HM), 30-day Event Monitor (EM) or Implantable loop recorder (ILR) to diagnose any undiscovered AF. All patients had at least 1 year, and up to 3 years, of follow-up after device placement. SAS Version 9.4 was used for statistical analyses.

Results:
Out of a total of 531 patients, 150 patients were monitored by ILR, 286 by EM and 95 by HM.

Primary Outcome-

detection of AF. The diagnosis of AF within 1 month of the stroke was 5.59% (16/286), 6.32% (6/95) and 9.33% (14/150) in the EM, HM and ILR cohorts, respectively (p=0.33). At 6, 12 and 24 months, ILRs detected AF in 15.33% (23/150), 16% (24/150) and 20% (30/150) of patients respectively (p=.0017, .0008 and .0001, respectively). Hence the Chi-Squared analysis showed no statistically significant difference among 3 devices for the detection of AF within 1 month of the index stroke but a significant difference in AF detection was observed at 6, 12 and 24 months. Similarly, the multivariable logistic regression model demonstrated no significant difference in capturing AF between HM, EM and ILR within 1 month (p=0.29) but showed a significant difference in AF detection when ILR was compared to HM and EM at 6,12 and 24 months (p=0.0027, 0.0012 and <0.0001 respectively).
Secondary Outcome-
Kaplan Meier estimator analysis and Cox proportional Hazard model showed device type had no significant impact on secondary outcomes of the study: 1) Subsequent ischemic stroke or TIA 2) Initiation of anticoagulation 3) Mortality 4) Incidence of major bleeding.

Conclusion:
In conclusion, despite the superiority of AF detection by ILR, it is not superior to HM or EM in lowering the risk of subsequent stroke or TIA, or in reducing mortality.
Abstract 10806: Ten Year Atherosclerotic Cardiovascular Disease Risk in Mid Life Predicts Late-Life Amyloid and Tau Deposition on Brain Imaging
Authors: Saeed Anum , Swanson Justin , Lopez Oscar L , Vu Michael , Mapstone Mark , Cohen Ann , Reis Steven
Published: June 2023

Introduction:
Risk factors of ASCVD have been associated with Alzheimer’s disease (AD) dementia. This association may be mediated by arteriosclerosis (ART), which have been implicated in incident dementia. However, the relationships among ASCVD risk factors, ART, and AD brain biomarkers (amyloid and tau) remains elusive. We investigated the association of the mid-life 10y ASCVD risk and subclinical ASCVD with late-life AD pathology.

Methods:
Participants >65y enrolled in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study between 2003-2005 (mid-life) underwent brain PET scans in 2018-2020 (late-life) to detect and quantify AD-specific amyloid [Pittsburgh Compound B (PiB)] and tau deposition. Mid-life 10-year ASCVD risk was categorized as borderline (5%-7.4%), intermediate (7.5%-14.9%), or high (≥15%). Logistic regression was used to calculate OR (95% CI) for association of late-life cortical amyloid and tau with mid-life ASCVD risk and marker of ART (vascular stiffness).

Results:
In 135 participants (mean age ~79y), global tau uptake had a graded association with increasing mid-life ASCVD risk categories

(OR
ASCVD high vs low risk%
11.00 [2.82-47.49]; p<0.05

) while no significant association was found with PiB uptake on PET (Table) after mean 16y follow up. In fully adjusted models, Tau uptake was mainly driven by Black race (
OR 10.07 [3.25-36.39]
) and age (
OR 1.24 [1.10-1.41]
); all p<0.05. Midlife vascular stiffness showed a trend of association with late-life PiB retention
(OR 1.76 [0.71-4.30]; p 0.05)
but not with Tau
.

Conclusions:
In an asymptomatic middle-aged biracial cohort, 10y ASCVD risk was predictive of late-life tau deposition but not amyloid. Vascular stiffness did not independently predict AD pathology. A simple mid-life ASCVD risk calculation may predict late-life AD risk. Further mechanistic studies are warranted to elucidate the race-related differences in the links between ASCVD risk and Alzheimer’s disease.
Abstract 10848: Adar1 Mediated Rna Editing Contributes to Vascular Remodeling
Authors: Kim Hyunbum , Liu Yu , Klouda Timothy , Schumacher Valerie A , Thompson Alfred A , Wu Joseph C , Li Jin Billy , Raby Benjamin , Yuan Ke
Published: June 2023

Intro:
Adenosine deaminases acting on RNA 1 (ADAR1) catalyzes the conversion of adenosine (A) to inosine (I) on RNA transcripts. Due to the host immune response to non-edited double-stranded RNAs, ADAR1 deficiency has been linked to spontaneous type I interferon (IFN) signaling. Few studies have examined the role of RNA editing in vascular remodeling-associated diseases, including pulmonary arterial hypertension (PAH), a devastating disease that can lead to right heart failure and premature death.

Hypothesis:
ADAR1 mediated RNA editing plays a vital role in vascular diseases, particularly the pathogenesis of PAH.

Methods and Results:
Deeply sequenced RNA-seq data analysis using the SOAP2 program showed that IPAH patient smooth muscle cells (SMCs, N=3) have shown significantly fewer editing sites in transcripts than healthy SMCs (N=3) & decreased levels of ADAR1 mRNA and protein. ADAR1 knockdown in healthy donor SMCs resulted in increased proliferation, migration and contractility, along with upregulated expression of IFN-b signaling-related molecules, such as MDA5 and ISG15. Furthermore, overexpression of MDA5, a dsRNA sensor of ADAR1-mediated immune response, in healthy SMCs induced activation of IFN-b signaling. A novel transgenic mouse model (ADAR1
SMC-KO
) was generated by knocking down ADAR1 (ADAR1
fl/fl
) selectively in smooth muscle actin-positive SMCs (SMA-CreER). Compared to controls, ADAR1
SMC-KO
mice that underwent 3wk hypoxia developed
severe
pulmonary hypertension as evidenced by high RVSP (37mmHg, Fig1A) & RVH(FI: 42%, Fig1B) with the
excessive
vascular remodeling in distal vessels. They also expressed higher expression of IFN-b in serum and increased recruitment of inflammatory cells, including macrophages and monocytes(Fig1C).

Conclusions:
This study reveals a novel molecular mechanism of ADAR1 contributing to abnormal vascular remodeling mediated by upregulation of Type 1 IFN-b, which could be central to the pathobiology of PAH.
Abstract 10884: X-Linked Genetic Associations in Sporadic Thoracic Aortic Aneurysm and Dissection
Authors: Musfee Fadi I , Jun Goo , Mitchell Laura E , Chen Han , Guo Dongchuan , Grove Megan L , Boerwinkle Eric , Milewicz Dianna M
Published: June 2023

Introduction:
The male predominance in sporadic thoracic aortic aneurysm and dissection (TAD) and the high prevalence of TAD in Turner syndrome patients suggest the contribution of X chromosome genes to TAD. However, such role has not been explored.

Methods:
We investigated whether X-linked variation, both common (Minor Allele Frequency (MAF) ≥0.01) and rare (MAF <0.01), was associated with sporadic TAD in three datasets of European descent (dataset-1: 753 cases, 2247 controls; dataset-2: 253 cases, 282 controls; dataset-3: 364 cases, 874 controls). All cases were obtained from McGovern School of Medicine and Baylor College of Medicine; however, controls were obtained from the Atherosclerosis Risk in Communities study (dataset-1), the University of Washington Center for Mendelian Genomics (dataset-2), and the National Institute of Neurological Disorders and Stroke Repository (dataset-3). We applied a sex-stratified logistic regression model, followed by a meta-analysis of sex specific odds ratios for common variants, and an optimized sequence kernel association test model for rare variants. For top (P≤1x10
-3
) common X-linked variants from the three datasets, we performed tissue enrichment analysis using a hypergeometric test.

Results:
The majority of cases (75%) were males. In dataset-2, common variant, rs55936630, in
IGSF1
(P meta-analysis: 2.43x10
-7
), reached X chromosome-wide significance. An additional 125 variants were suggestive of an association (P meta-analysis ≤1x10
-3
) in at least one of the three datasets. Tissue enrichment identified a set of 12 X-linked genes that was significantly enriched in blood vessels (P: 3x10
-2
).
RTL9
(P: 5.15x10
-5
; dataset-1) reached X chromosome-wide significance in rare variants analyses.

Conclusions:
This is the most comprehensive X-chromosome association analysis of TAD to date. Although most of our common variants did not reach X chromosome-wide significance, collectively testing these variants in tissue enrichment analysis identified a set of 12 X-linked genes that was significantly enriched in blood vessels. Among these 12 X-linked genes were
C1GALT1C1
and
DMD
which were previously associated with vasculitis and arterial stiffness, respectively, both of which are risk factors for TAD.
Abstract 10888: Toward a Framework for Comparing Inducibility of Reentrant Arrhythmia in Patient-Specific Computational Models to Clinical Atrial Fibrillation Phenotypes
Authors: Macheret Fima , Bifulco Savannah , Scott Griffin , Kwan Kirsten , Chahine Yaacoub , Afroze Tanzina , Akoum Nazem W , Boyle Patrick M
Published: June 2023

Introduction:
Computational models that incorporate patient-specific left atrial (LA) anatomy and fibrosis from LGE-MRI can assess
in silico
arrhythmia inducibility in atrial fibrillation (AF) patients. Modeling currently relies on a one-size-fits-all approach for electrophysiological properties, limiting the agreement between simulations and patient outcomes.

Hypothesis:
Personalization of conduction velocity (ϴ) in computational models of LA fibrosis-mediated arrhythmia derived from persistent AF (PsAF) patients could improve simulation agreement with clinical arrhythmias.

Methods:
PsAF patients (n=37) were followed ≥2 years after ablation to determine outcomes: AF recurrence, atrial flutter (AFL)-recurrence, or no recurrence (NR). Patient-specific LA models (n=74) were constructed using pre- and ≥90 days post-ablation MRI. Simulated pacing gauged
in silico
arrhythmia inducibility due to AF-like rotors or AFL-like macro-reentrant tachycardias (MTs). A range of possible ϴ values was tested (±10 or 20%; baseline: non-fibrotic, 71.5 cm/s; fibrotic, 47.0 cm/s). Pre-ablation models were deemed to agree if pacing induced ≥1 rotor or MT; post-ablation models agreed if pacing induced ≥1 rotor, MT, or neither in AF, AFL, or NR patients, respectively.

Results:
Fifteen patients recurred with AF and 6 with AFL (57% overall). Arrhythmia was induced in 1078/5550 simulations. Using baseline ϴ, model/clinical agreement was 46% (34/74 models), improving to 65% (48/74) when all ϴ values were considered (p=0.031, Fisher’s exact test, Fig. A). ϴ modulation improved model/clinical agreement in both pre- and post-ablation models (Figs. B, C). Pre-ablation model/clinical agreement was higher for patients with more LA LGE (>17.2%) or higher BMI (>32.0 kg/m
2
) (Fig. D).

Conclusions:
Patient-specific ϴ calibration improved model/clinical agreement by 41%. Improved understanding of factors that influence model ϴ will have immediate clinical implications.
Abstract 10901: Differential Burden of Prediabetes and Diabetes Among Asians Subgroups in a Large US Healthcare System
Authors: Vicks William , Lo Joan C , Rana Jamal S , Gordon Nancy , Ramalingam Nirmala D
Published: June 2023

Introduction:
We previously reported that Chinese, Filipino, and South Asian adults have higher prevalence of prediabetes (PreDM) than non-Hispanic White (White) adults, with nearly twice the burden in healthy BMI ranges. This study further examines the differential burden of diabetes (DM) in these Asian subgroups using Asian specific BMI categories.

Methods:
283,110 White, 33,263 Chinese, 38,766 Filipino, and 17,959 South Asian adults aged 45-64y in a 2016 Northern California health plan with height and weight were examined. PreDM and DM were classified based on lab data, diagnoses, or DM treatment. Modified log Poisson regression was used to determine Asian group vs. White prevalence ratios (PRs) for DM and preDM, adjusted for age and BMI within healthy weight, overweight, and obesity ranges (BMI 18.5 to <25, 23 to <30, ≥30 kg/m2 for Whites; BMI 18.5 to <23, 23 to <27.5, ≥27.5 kg/m2 for Asians).

Results:
Across all BMI categories, DM prevalence was higher for the Asian groups than White adults. DM prevalence was also higher for Filipino and South Asian vs White than Chinese vs White, especially at healthy BMI levels. PRs for South Asian men/women at healthy BMI were 1.8/2.8 for preDM and 5.9/8.0 for DM (Figure). PRs for Filipino men/women at healthy BMI were 1.8/2.6 for preDM and 5.0/7.5 for DM, respectively. For Chinese men/women at healthy BMI, the PRs for preDM were similar (2.1/2.9) to the other Asian groups, but the PRs for DM were lower (2.1/3.4).

Conclusion:
The largest difference in DM prevalence relative to White adults was observed in the healthy BMI range for South Asian and Filipino adults. While PreDM risk in these 2 groups was similar to the preDM risk in Chinese compared with White adults at healthy BMI, their DM risk was 5-8 times greater than White adults at healthy BMI. Our data emphasize the disproportionate metabolic risk among middle-aged adults of different Asian groups and underscore the need for DM screening among high-risk Asian subgroups at healthy BMI levels.
Abstract 10924: Assessing the Mediating Role of Three Key Factors on the Association Between Family Structure Type and Obesity in Children
Authors: Song Minkyoung , Hayman Laura L , Dieckmann Nathan F , Lyons Karen S , Musil Carol M
Published: June 2023

Introduction:
Obesity is a major risk factor for cardiometabolic disease
.
Research shows that children living in grandparent-headed households are more likely to have obesity compared to children living in two-parent headed households. However, little is known about modifiable risk or protective factors that influence that association.

Purpose:
To assess the mediator role of three key factors (families eating meals together, family resilience, and sleep duration; all reported to be associated with childhood obesity) on the association between family structure type and children’s obesity

Methods:
We utilized data from the 2019-2020 National Survey of Children’s Health (n=37,688 to 37,699). Path models were used to assess the mediating (indirect) effect of “frequency of families eating meals together,” “family resilience,” and “child sleeps recommended age-appropriate hours (yes or no)”, on the association between family structure type and obesity. We controlled for child’s sex, age, race/ethnicity, health insurance, number of adverse childhood experiences, and physical activity level.

Results:
We found that family meals was not a significant mediator between family structure type and obesity, whereas family resilience and reaching recommended age-appropriate standards for sleep were both significant mediators. Living in grandparent-headed households was associated with lower family resilience, which in turn was associated with higher odds of having obesity, after adjusting for covariates (indirect effect adjusted Odds Ratio=1.01; 95% confidence interval [1.00, 1.02]). Similarly, living in grandparent-headed households was associated with getting less sleep, which was associated with higher odds of having obesity, after adjusting for covariates (indirect effect adjusted Odds Ratio=1.04; 95% confidence interval [1.03, 1.06]).

Conclusions:
Although the effects were small, our findings suggest that promoting family resilience and adequate sleep could be suitable intervention targets for youth living in grandparent-headed households. Further investigations are required to validate our findings.
Abstract 10933: Artificial Intelligence Enabled Fully Automated Myocardial Strain Quantification for Risk Stratification Following Acute Myocardial Infarction
Authors: Backhaus Soeren J , Aldehayat Haneen , Kowallick Johannes , Evertz Ruben , Lange Torben , Kutty Shelby , Bigalke Boris , Hasenfuss Gerd , Thiele Holger , Stiermaier Thomas , Eitel Ingo , Schuster Andreas
Published: June 2023

Introduction:
Feasibility of automated volume-derived cardiac functional evaluation has successfully been demonstrated using cardiovascular magnetic resonance (CMR) imaging. Notwithstanding, strain assessment has proven incremental value for cardiovascular risk stratification. Since introduction of deformation imaging to clinical practice has been complicated by time-consuming post-processing, we sought to investigate automation respectively.

Methods:
CMR data (n=1095 patients) from two prospectively recruited acute myocardial infarction (AMI) populations with ST-elevation (STEMI) (AIDA STEMI n=759) and non-STEMI (TATORT-NSTEMI n=336) were analysed fully automated and manually on conventional cine sequences. LV function assessment included global longitudinal, circumferential, and radial strains (GLS/GCS/GRS). Agreements were assessed between automated and manual strain assessments. The former were assessed for major adverse cardiac event (MACE) prediction within 12 months following AMI.

Results:
Manual and automated derived GLS showed the best and excellent agreement with an intraclass correlation coefficient (ICC) of 0.81. Agreement was good for GCS and poor for GRS. Amongst automated analyses, GLS (HR 1.12, 95% CI 1.08-1.16, p<0.001) and GCS (HR 1.07, 95% CI 1.05-1.10, p<0.001) best predicted MACE with similar diagnostic accuracy compared to manual analyses; area under the curve (AUC) for GLS (auto 0.691 vs. manual 0.693, p=0.801) and GCS (auto 0.668 vs. manual 0.686, p=0.425). Amongst automated functional analyses, GLS was the only independent predictor of MACE in multivariate analyses (HR 1.10, 95% CI 1.04-1.15, p<0.001).

Conclusions:
Considering high agreement of automated GLS and equally high accuracy for risk prediction compared to the reference standard of manual analyses, automation may improve efficiency and aid in clinical routine CMR examinations.
Abstract 10976: Midlife Caregivers: At Risk for Cardiovascular Disease?
Authors: Smith Jennifer , Fleming Carlie , Anderson Joel G
Published: June 2023

Introduction:
Caregivers remain an invisible population that may be at increased risk for cardiovascular disease (CVD) secondary to the additional stress of caregiving. Some groups of caregivers demonstrate as much as an 82% increased risk of CVD compared with non-caregivers. Purpose/Hypothesis: The purpose of this study was to describe characteristics of midlife caregivers from a large, publicly available dataset and to identify CVD risk factors among a subset of these caregivers.

Methods:
This was a secondary analysis of data from the Midlife in the United States (MIDUS) study. The sample was limited to participants who reported caring for someone else. Data were collected using sociodemographic questionnaires and survey instruments. Key CVD risk factors examined were for a subset of caregivers with complete data for these variables: blood pressure (BP), cholesterol levels, body mass index (BMI), perceived stress (Cohen’s perceived stress scale [PSS]), depression (Centers for Epidemiological Studies Depression Inventory [CESD]), and anxiety (Spielberger Trait Anxiety Inventory).

Results:
In the overall sample of 417 midlife caregivers, the mean age was 52±13 years, 62.1% were female, 62.1% were married, and 18% graduated from a 4-year institution. The most common care recipient was the mother of the caregiver (24.2%), 52.3% lived with their care recipient, and the average number of care hours per week was 25.13 ± 27.23. Care given included help bathing, dressing, and toileting (55.4%), shopping, cooking, laundry, and housework (88.7%), and help with transportation in and out of the home (65.2%). Data regarding CVD risk factors were available for a subset of 66 caregivers. Of those, 71.2% were either overweight or obese, mean systolic BP was 128±20, mean diastolic BP was 78±11, 57.6% had high density lipoprotein cholesterol <60, low density lipoprotein >100 (48.5%), 31.8% had total cholesterol >200, and 13% had triglycerides >150. The average score on the PSS was moderate at 22.5±6.5. Mean depressive symptom score was 8.7±7 and mean anxiety was high at 34.9±9.

Conclusions:
Caregivers at midlife are a unique subgroup, often caring for parents, and show unfavorable levels of CVD risk factors such as low HDL, high LDL, and high perceived stress and anxiety.