bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14242: Homogeneous Fetal Access to Cardiac Care in a Heterogeneous State
Authors: Garcia Godoy Laura , Madriago Erin J , ronai christina
Published: May 2021

Introduction:
Timely prenatal diagnosis of congenital heart disease (CHD) allows for families to participate in complex decisions and plan for the care of their child. This study sought to investigate if the timing of the first fetal echocardiogram (FE) and the characteristics of fetal counseling were impacted by parental socioeconomic factors.

Hypothesis:
We hypothesized that the scheduling of initial FE would be delayed due to distance from hospital, rurality of maternal home and median income.

Methods:
We performed a retrospective chart review of all fetal patients referred to our institution from 1/1/17 to 12/31/18 with a diagnosis of CHD. We looked at the gestational age at the first FE, age of mother, zip code of residence, rurality index, distance from our hospital and maternal ethnicity. Counseling was evaluated based on documentation in the FE report regarding use of interpreter, time billed for counseling, individuals accompanying mother, and treatment option chosen.

Results:
138 maternal-fetal dyads met inclusion criteria, 29 dyads had a diagnosis of single ventricle heart disease. The median gestational age (GA) at first FE was 24 weeks 4 days. The median income was $57,019 ($42,624-$83,695), and the median distance to the hospital was 51 miles (3.2-379.9miles). There was no difference in income, distance from hospital or rurality index and timing of first FE. There was no significant difference between maternal ethnicity and age of mother, GA at initial FE, number of follow-up FEs or family accompanying mother to the visit. There was no difference in maternal ethnicity and use of interpreter with time counseled. Patients who lived in rural areas did have increased counseling time (p<.05). Importantly, there was no difference between socioeconomic factors and ultimate parental choices (termination, palliative delivery or surgery).

Conclusions:
Oregon comprises a heterogeneous population from a large geographical catchment. While prenatal counseling and family decision making is multifaceted we demonstrated that dyads were referred from across the state and received care in a uniformly timely manner, and once at our center received consistent counseling despite differences in parental socioeconomic factors.
Abstract 14250: Semi-automated Analysis of Tricuspid Regurgitation Doppler Profile for Detection and Evaluation of Pulmonary Hypertension
Authors: Dual Seraina A , Amsallem Myriam , McElhinney Doff , Zamanian Roham , Feinstein Jeffrey , Haddad Francois , Marsden Alison
Published: May 2021

Introduction:
Non-invasive detection of pulmonary hypertension relies on the tricuspid regurgitant (TR) Doppler maximal velocity (Vmax). When the TR signal is incomplete, Vmax must be estimated by extrapolation, which is prone to error. Automatic extrapolation could improve robustness but requires an in-depth understanding of complete TR shape. Semi-automated analysis was used to test the hypothesis that all waveforms can be expressed with a small set of curve parameters.

Methods:
We retrospectively analyzed complete continuous Doppler TR signals from 76 patients (median 50 [39, 56] years-old, 77% female) with pulmonary arterial hypertension in whom echocardiography and invasive hemodynamics were available within 3 months. Semi-automated analysis divided Doppler images into heartbeats (three signals per patient) using the ECG and recognized segmented waveforms for shape analysis. Multiple linear regression modeling assessed the independent association between waveform features (Vmax, velocity-time integral, curve width, skewness (t1,t2), kurtosis and time scale) and age, sex, pulmonary vascular resistance (PVR), TR severity, right ventricular (RV) end-diastolic area index (size), RV strain (function) and right atrial volume index.

Results:
TR waveforms were non-Gaussian with varying skewness, width and kurtosis.
Figure
summarizes the covariates associated with TR waveform features. Vmax was directly related to PVR and RV strain, but not to TR severity. The RR-normalized width was correlated to heart rate, TR severity, RV strain and size (all p<0.0001). Kurtosis was not only associated with heart rate but also with PVR, TR severity, RV strain and size (all p<0.01).

Conclusions:
The non-Gaussian TR Doppler curve shape is influenced by TR severity, RV function and size. The high variability in shape limits the ability to extrapolate signals in the presence of an incomplete envelope. Machine learning algorithms may be valuable to address this issue.
Abstract 14254: Pharmacodynamic Effects of a Single Dose of CK-3773274 in Cats With Hypertrophic Cardiomyopathy
Authors: Oldach Maureen , Hwee Darren T , Ontiveros Eric S , Fousse Samantha L , Gonzalez Carina E , Morgan Bradley P , Malik Fady I , Harris Samantha P , Stern Joshua A
Published: May 2021

Introduction:
Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular (LV) hypertrophy in the absence of known causes. HCM can be due to genetic mutations that affect sarcomeric proteins, leading to myocardial hypercontractility. HCM is often complicated by left ventricular outflow tract obstruction (LVOTO) and patients may be at greater risk of cardiovascular death. Medications targeted to address the pathophysiology of HCM and ameliorate LVOTO are needed. CK-3773274 (CK-274) is a novel small molecule cardiac myosin inhibitor that reduces myocardial contractility
in vitro
and
in vivo
. Cats have naturally occurring HCM commonly complicated by LVOTO and are an excellent large animal model for investigation of HCM therapeutics. In this study, we aim to characterize the pharmacodynamic effect of a single oral dose of CK-274 on cardiac function in cats with hypertrophic cardiomyopathy and LVOTO.

Methods:
Eight purpose-bred cats with naturally occurring HCM and LVOTO due to the A31P mutation in cardiac myosin binding protein C (cMyBP-C) were included in a randomized, controlled, crossover study. Cats were randomized to receive vehicle, 0.3 mg/kg, or 1 mg/kg CK-274 treatment, and received echocardiograms at baseline, 6, 24, and 48 hours post-treatment. All cats were crossed over to all treatment groups.

Results:
CK-274 (1 mg/kg) reduced mean LV fractional shortening at 6, 24 and 48 hours post-treatment (mean reduction 13.6%, p=0.03; 15.4%, p=0.01; 11.6% p=0.02, respectively). CK-274 (1 mg/kg) increased LV systolic internal dimension at 6 and 24-hours post-treatment (mean increase 0.21 cm, p=0.046; 0.25 cm, p=0.03), and did not affect LV diastolic internal dimension. LVOT peak pressure gradient was reduced with CK-274 (0.3 mg/kg) treatment [median pressure gradient at baseline 27.1 mmHg (IQR 18.3-33.3) vs 24 hours post-drug, 7.3 mmHg (IQR 14.2-19.7) p=0.01]. Heart rate did not change for any treatment group over time. No differences were noted following vehicle administration at any time point.

Conclusion:
In HCM affected cats with the cMyBP-C A31P mutation, the cardiac myosin inhibitor CK-274 is well tolerated at the studied doses and caused dose-related changes in LV systolic function and reductions in LVOT peak pressure gradient.
Abstract 14257: Endothelial SOX17 Deficiency Induces Pulmonary Arterial Hypertension
Authors: Dai Zhiyu , Yi Dan , LIU BIN , Li Shuai
Published: May 2021

Introduction:
Pulmonary arterial hypertension (PAH) is a disaster disease characterized by obliterative vascular remodeling and persistent increase of vascular resistance, leading to right heart failure and premature death. Understanding the cellular and molecular mechanisms will help develop novel therapeutic approaches for PAH patients.

Hypothesis:
Human genome-wide association studies identified that SOX17 locus variants are associated with PAH. SOX17 mutation is also found in patients with PAH. We hypothesis that endothelial SOX17 deficiency contributes to the pathogenesis of PAH.

Methods:
Mice with EndoSCL-CreERT mediated deletion of
Sox17
(

Sox17
iCKO

) were generated.

Sox17
iCKO

and

Sox17
f/f

mice after tamoxifen injection were incubated with hypoxia (10% O
2
) for 3 weeks to induced PAH. Hemodynamics and histological examination were measured to determine the PAH phenotypes and vascular remodeling. EC proliferation and apoptosis were assessed in SiRNA-mediated SOX17 knockdown in human lung microvascular endothelial cells (hLMVECs). The RNA-sequencing analysis was performed to understand the molecular mechanisms of SOX17 deficiency in ECs.

Results:

Sox17
iCKO

mice exhibited exaggerative PAH evident by the increase of RVSP and RV hypertrophy after hypoxia treatment compared to

Sox17
f/f

WT mice. SOX17 knockdown in hLMVECs induced cell proliferation and reduced starvation-induced apoptosis. RNA-seq analysis and DAVID pathway analysis demonstrated that there was dysregulation of cell proliferation-related genes, which are enriched in the pathways related to cell cycle, cell division, and mitotic cell cycle. Transcriptional factor, target, and motif discovery analysis of the dysregulated gene set revealed the involvement of transcriptional factors FOXM1 and E2F1. siRNA mediated knockdown of E2F1 but not FOXM1 normalized SOX17 deficiency-induced hLMVECs proliferation and anti-apoptosis.

Conclusions:
Our study demonstrated that endothelial SOX17 deficiency exaggerates hypoxia-induced PAH. Loss of SOX17 promotes EC proliferation and anti-apoptosis via the upregulation of transcription factor E2F1.
Abstract 14278: Microglial Calcium Activity During Ischemic Stroke
Authors: Kearns Kathryn N , Liu Lei , Sharifi Khadijeh A , Stauderman Kenneth A , Park Min S , Tvrdik Petr
Published: May 2021

Introduction:
Ischemic stroke triggers waves of propagating action potentials followed by a loss of homeostatic ion gradients, known as cortical spreading depolarizations (SD). Our data indicate that microglia respond to SD by raising intracellular Ca
2+
, triggering a release of proinflammatory cytokines that may exacerbate post-stroke morbidity.

Hypothesis:
Inhibiting calcium release-activated calcium (CRAC) channels may block microglial Ca2+ influx and activation to potentially provide therapeutic benefit in ischemic stroke.

Methods:
We generated a mouse line expressing the Ca2+ indicator GCaMP5 in cortical microglia. Using two-photon microscopy, we imaged microglia in vivo following physical stroke via middle cerebral artery occlusion (MCAo) or chemical stroke via 1M KCl solution application. Controls were compared to mice treated with lipopolysaccharide (LPS) to mimic the inflammation of ischemic stroke. To study CRAC channels as a therapeutic target, we administered CM-EX-137, a CRAC channel blocker, and compared Ca2+ activity to controls.

Results:
We identified periodical Ca2+ waves in cortical microglia following MCAo (Fig. 1A), or localized KCl application (Fig. 1B-E). Further, when compared to controls, LPS-exposed mice expressed significantly greater microglial Ca2+ activity during KCl-triggered SD (Fig. 1C). Additionally, administration of CM-EX-137 effectively abolished the Ca2+ signals in the microglia and propagation of SD upon application of KCl (Fig. 1E).

Conclusions:
Blocking the Ca2+ influx into microglia after ischemic stroke may decrease the frequency of SD and reduce microglial activation, potentially leading to smaller stroke volumes and improved clinical outcomes.
Figure 1:
Microglial Ca
2+
after SD. (A) Ca
2+
transients in microglia after MCAo. (B) KCl-induced Ca
2+
activity in naïve microglia. (C) KCl-induced Ca
2+
activity after LPS. (D, E) KCl-induced Ca
2+
wave after (D) vehicle or (E) CM-EX-137 administration.
Abstract 14288: Substantial Hospital-level Variation in Troponin Testing After Non-cardiac Surgery
Authors: Azizi Paymon M , Han Lu , Koh Maria , Jerath Angela , Wijeysundera Harindra C , Wijeysundera Duminda N , Austin Peter , Ko Dennis T
Published: May 2021

Introduction:
There is an increasing emphasis in detecting postoperative myocardial infarction (PMI) using routine troponin testing after non-cardiac surgery. However, clinical practice guidelines vary considerably in their recommendations. We conducted a population-based cohort study in Ontario, Canada to assess the degree of hospital-level variation associated with troponin testing after three commonly performed surgeries.

Methods:
We conducted a retrospective cohort study of adults (40-105 y) undergoing major orthopedic, colorectal, or vascular surgery in Ontario, Canada from January 1, 2010 to December 31, 2017. Hierarchical logistic regression modeling was used to model the association of patient, surgery, and hospital factors with postoperative troponin testing, while accounting for clustering at the hospital level.

Results:
We identified 176,454 eligible patients. Canadian Cardiovascular Society guidelines recommended troponin testing for 73.5%, 90.8% and 95.6% of orthopedic, colorectal, and vascular surgery patients respectively, but only 6.7%, 16.6%, and 50.2% were actually tested. Inter hospital variation in testing rates was considerable for the three surgeries (Figure; 0-33%, 0-38% and 18-84%). Even after risk-adjustment, the median odds ratio for testing across hospitals was still 1.74, 1.63, and 2.65 for orthopedic, colorectal, and vascular surgery, respectively. This corresponded to intraclass correlation coefficients of 9.3%, 7.4%, and 24.2% respectively.

Conclusion:
Despite strong recommendations by Canadian guidelines for troponin testing after non-cardiac surgery, testing rates were low overall and varied significantly across hospitals.
Abstract 14299: Deep Convolutional Neural Network Analysis of Echocardiographic Images Improves Prediction of Genotype Positivity in Patients With Hypertrophic Cardiomyopathy
Authors: Morita Sae , Kusunose Kenya , Haga Akihiro , Hasegawa Kohei , Reilly Muredach P , Fifer Michael A , Maurer Mathew S , Shimada Yuichi J
Published: May 2021

Introduction:
Genotyping may provide valuable insights into family screening strategies and prognosis in patients with hypertrophic cardiomyopathy (HCM). On the other hand, genotyping is expensive. Thus, it is important to identify patients who are more likely to be genotype positive. However, conventional prediction models (e.g., the Mayo score) based on clinical and echocardiographic parameters offer only modest accuracy and are subject to inter-observer variability.

Hypothesis:
Deep convolutional neural network (DCNN) analysis of echocardiographic images improves the ability to predict genotype positivity in HCM compared to the conventional model.

Methods:
We included 99 patients with HCM who underwent genetic testing for diagnostic and/or family screening purposes. The age at diagnosis was 46±20 years and 65% were male. In each case, we obtained parasternal short- and long-axis as well as all apical images at end-systole. The DCNN underwent 100 steps to develop the model to predict genotype positivity. In each step, we used 80% of the cohort as the training set and the remaining 20% as the test set (i.e., 5-fold cross-validation). We used the Mayo score as the reference model. We compared the area under the receiver operating characteristics curve (AUC) between a combined model using the reference model plus the DCCN-derived probability and the reference model. We calculated the p value by performing 1,000 bootstrapping.

Results:
Overall, 45 patients (45%) were genotype positive. The model combining the reference and the DCNN-derived models significantly outperformed the reference model (AUC 0.79 [95% CI 0.69-0.87] with the combined model vs. 0.72 [0.61-0.82] with the reference model; p=0.006; Figure).

Conclusion:
Compared to a conventional model based on clinical and echocardiographic parameters, our new model combining the conventional and DCNN-derived models demonstrated superior ability to predict positive genotype in patients with HCM.
Abstract 14304: Assessing the Association of Adherence to Fractional Flow Reserve Treatment Thresholds and Outcomes of Patients With Coronary Artery Disease
Authors: Sud Maneesh , Han Lu , Koh Maria , Austin Peter , Farkouh Michael E , Ly Hung , Madan Mina , Natarajan Madhu K , So Derek Y , Wijeysundera Harindra C , Ko Dennis T
Published: May 2021

Background:
Although fractional flow reserve (FFR) thresholds have been established to guide the use of percutaneous coronary intervention (PCI) or medical therapy, little is known about the adherence to FFR thresholds for PCI in clinical practice and their association with clinical outcomes.

Methods:
Adults undergoing FFR assessment in a single vessel (excluding ST-segment elevation myocardial infarction [MI]) from April 1, 2013 to March 31, 2018 in Ontario, Canada were included. Patients were divided into two cohorts based on FFR ≤ 0.80 (ischemic) and > 0.80 (non-ischemic). Inverse probability of treatment weighting was used to balance confounders between patients treated with PCI vs. no PCI in each cohort. The primary outcome was major adverse cardiac events (MACE) defined by death, MI, unstable angina, or urgent revascularization.

Results:
We identified 9,106 patients who underwent single-vessel FFR measurement. Among the 2,693 patients with an ischemic FFR (mean age 65, 27.0% female), 75.3% of patients received PCI and 24.7% were treated only with medical therapy. Over a median follow-up of 2.6 years in the ischemic cohort, PCI was associated with a 20% lower rate of MACE compared to no PCI (24.0% vs. 31.6%; hazard ratio [HR]: 0.80, 95% CI: 0.66-0.96). However, among 6,413 patients with a non-ischemic FFR (mean age 66, 38.9% female), 12.6% received PCI and 87.4% were treated only with medical therapy. Over a median follow-up of 2.8 years in the non-ischemic cohort, PCI was associated with a 42% higher rate of MACE compared to no PCI (25.6% vs. 17.6%; HR: 1.42, 95% CI: 1.18-1.70). The increased rate of MACE was driven mainly by MI (HR 1.67, 95% CI: 1.20-2.31) but not death (HR 0.99, 95% CI: 0.72-1.35).

Conclusions:
In routine practice, we found 1 in 4 patients did not receive PCI for ischemic lesions while 1 in 8 received PCI for non-ischemic lesions. Performing PCI procedures according to recommended FFR cutoffs was associated with lower rates of clinical events.
Abstract 14310: Elephant Sitting on My Chest: A Tale of Two Vessels
Authors: Dodeja Anudeep K , McConnell Patrick I , Bradley Elisa A , Daniels Curt , Mehta Laxmi S , Sabanayagam Aarthi
Published: May 2021

Introduction:
A dilated main pulmonary artery (MPA) seen in congenital heart disease (CHD) or pulmonary arterial hypertension (PAH) is a rare cause of angina due to left main coronary artery (LMCA) compression.

Case:
A 49 year old male with no prior cardiac history presented with substernal chest pain. He reported exercise intolerance for several years. On exam he had an oxygen saturation of 85%, loud P2, fixed split second heart sound and ejection click. Electrocardiogram showed right ventricular (RV) hypertrophy and no significant ST changes. Laboratory data revealed a negative troponin. An enlarged main and right pulmonary artery (RPA) (Figure 1A) was seen on computed tomography (CT) chest angiography for pulmonary embolism (CTPE) and on echocardiography he had a severely dilated RV with decreased function (Figure 1B,1C). Cardiac catheterization showed a step up in saturations from 56 to 71%, Qp:Qs of 1.5 mean MPA pressure of 53 mmHg, pulmonary capillary wedge pressure of 11mmHg and pulmonary vascular resistance (PVR) of 7WU. A slit-like narrowing of LMCA ostium was seen on coronary angiography and intravascular ultrasound (Figure 1D). He was diagnosed with a sinus venosus defect, anomalous right upper pulmonary venous drainage and suspicion for extrinsic compression of LMCA by the dilated RPA that was confirmed on cardiac CT (Figure 1E-I). He was started on triple therapy for PAH with a significant reduction in PA pressures (mean 36 mmHg and PVR 2.1 WU). Percutaneous stenting of the LMCA was deferred and he underwent successful sinus venosus defect repair with a 5mm fenestrated patch, baffling of the anomalous pulmonary veins and a 32 mm interposition graft in the MPA with reduction plasty of MPA/RPA.

Conclusion:
This is an unusual presentation of unrepaired CHD with angina due to a compressed LMCA from a dilated pulmonary artery. Treatment of the underlying PAH as well as repair of the defect including reduction plasty of the MPA is a consideration for symptomatic relief.
Abstract 14311: Qt Interval Correlation Between Telemetry and 12-lead Electrocardiogram
Authors: Nasser Mohamed Farhan , Jabri Ahmad , Karim Saima , Kaufman Elizabeth
Published: May 2021

Introduction:
QT prolongation is associated with increased risk of ventricular arrhythmias.As many patients with COVID19 may be started on QT prolonging drugs, measuring and monitoring QT is imperative to prevent fatal ventricular arrhythmias. However, we need to limit exposure of staff to patients with confirmed COVID19 and judiciously use personal protective equipment. Thus, it is important to find alternatives to doing frequent 12-lead ECGs.

Hypothesis:
We hypothesize that the QT interval measured from telemetry is similar to the QT interval on 12-lead ECG.

Methods:
Telemetry recordings and 12-lead ECGs were obtained from 15 patients at the same time and identical heart rates. Patients were from two different inpatient units with the same telemetry monitoring service. QT intervals were measured manually using calipers with the tangent method, excluding U waves. Telemetry recordings included lead I and II or a precordial lead. QT from telemetry was compared to the corresponding leads and to the longest QT on the 12-lead ECG. In cases of atrial fibrillation (AF), the QT from all the complexes was averaged.

Results:
Of 15 patients, 2 were in AF and 2 had RBBB. One patient had abnormal T-wave morphology and QT prolongation (abnormal repolarization). In all patients, QT intervals from the same leads as telemetry matched the QT measured from 12-lead. In 14 of 15 patients, telemetry QT matched the longest QT on the 12-lead ECG. However, in the patient with abnormal repolarization, maximum QT on 12-lead ECG was substantially longer than telemetry QT (Figure 1).

Conclusion:
When using the same lead, QT intervals were identical on telemetry and 12-lead ECG. However, in the patient with abnormal repolarization, the longest QT on 12-lead ECG was not represented on telemetry. In patients with abnormal repolarization on 12-lead ECG, we recommend serial 12-lead ECGs while on QT-prolonging drugs. Telemetry may suffice as a surrogate for 12-lead ECG to follow QT intervals in most patients.
Abstract 14369: Assessment of Hemodynamic Response to Exercise in Patients With Advanced Heart Failure
Authors: Buchanan Cole , Coe Gregory , Pratt-Cordova Ashley , Cornwell William K
Published: May 2021

Introduction:
Among patients suffering from HFrEF, outcomes are closely associated with quality-of-life and functional capacity. Data are limited regarding exertional cardiopulmonary performance measures in these patients. The objective of this study was to complete a comprehensive analysis of cardiac function among patients with advanced HFrEF during submaximal and peak exercise through an invasive cardiopulmonary exercise test (CPET) on an upright cycle ergometer.

Methods:
Thirty-five participants with advanced HFrEF (age 59 ± 12) underwent invasive hemodynamic assessment with Swan-Ganz catheter during CPET. Group 1 comprised individuals not on inotropes (N=23, 66%); group 2 was comprised of individuals on inotropes (N=12, 34%). Data were obtained at supine and upright rest, two submaximal levels (steady-states 1-2) of exertion below the ventilatory threshold (VT), and peak exercise.

Results:
Cohort characteristics are displayed in
table 1
. VO
2
max for the overall cohort was severely reduced (11.8 ± 3.3), and was similar between group 1 and 2 (12.1 ± 3.2 v. 10.1 ± 3.5 ml/kg/min, P= 0.71). As displayed in
figure 1
, pulmonary arterial and left-sided filling pressures increased dramatically even during submaximal exercise. Cardiac output increased minimally, with only an ~2-fold change from rest to peak exercise for both groups.

Conclusions:
Among patients with advanced HFrEF, exercise is limited by severe increases in cardiac and pulmonary filling pressures, even during submaximal levels of exercise that mimic real-world activities of daily living, as well as severely impaired inotropic reserve. Inotropes do not appear to improve exertional hemodynamics.
Abstract 14381: Patient-specific Fluid Structure Interaction Simulations of Anomalous Origins of Right Coronary Arteries in Adults Correlate With Measured Instantaneous Wave-free Ratio
Authors: Jiang Michael X , Khan Muhammad O , Ghobrial Joanna , Rogers Ian S , Blackstone Eugene H , Marsden Alison L
Published: May 2021

Introduction:
Anomalous coronaries are associated with ischemia and sudden death, but the recommendation to undergo surgery is often uncertain, especially for asymptomatic individuals with an anomalous aortic origin of the right coronary artery (AAORCA). For risk stratification, dobutamine-stress instantaneous wave-free ratio (iFR) is increasingly used. Meanwhile, advances in fluid-structure interaction (FSI) modeling have enabled the simultaneous simulation of blood flow and tissue deformation that may elucidate the mechanism of ischemia in AAORCA.

Hypothesis:
We hypothesized that the iFR simulated by patient-specific FSI models of AAORCA correlates with the measured iFR at rest and dobutamine-stress, and the hemodynamic mechanism is mainly due to the intramural geometry.

Methods:
Using the Simvascular software package, we constructed 6 FSI models of the AAORCA which encompassed the aortic root, the intramural course (if present), and coronary outlets coupled to lumped parameter networks that included the dynamic microvascular compression. Each model was customized to the patients’ computed tomography angiography, vitals, and cardiac output.

Results:
All 6 AAORCAs had an interarterial course, and all but one had an intramural course. Measured iFRs ranged from 0.98 to 0.95 at rest, and from 0.95 to 0.80 with dobutamine-stress. The FSI model yielded realistic pressures and flows waveforms (Fig. 1). After we tuned the resistances to achieve flow rates at stress to be triple those at rest, the FSI simulations adequately matched the measured iFR (r = 0.85, RMSE = 0.04).

Conclusions:
Patient-specific FSI modeling is a promising non-invasive tool to assess the hemodynamic effects of AAORCA including the intramural course. However, the iFR’s sensitivity to the flow rate suggests a future role for quantitative stress-perfusion imaging to augment the iFR measurements for AAOCA risk stratification.
Abstract 14382: Notch Ligand Delta-like Ligand 1 Promotes Macrophage Activation and Arteriosclerosis
Authors: Koga Jun-ichiro , Katsuki Shunsuke , Matoba Tetsuya , Tsutsui Hiroyuki
Published: May 2021

Introduction:
Macrophage-mediated inflammation promotes various vascular diseases, but how macrophage functions are regulated has not been fully understood. Notch signaling is a fundamental pathway regulating cell differentiation in developmental stages, but its role in adult vascular diseases are largely unknown.

Aim:
The aim of this study is to explore the role of Notch ligands in macrophage activation and subsequent arteriosclerosis.

Methods:
1) To screen the Notch ligands, blocking antibodies of each Notch ligands (Jagged-1, Jagged-2, Dll1, and Dll4) were prepared. After pre-treatment with these antibodies, mouse peritoneal macrophages were stimulated with 10 ng/mL LPS + 10 ng/mL IFN-γ or 10 ng/mL IL-4 for 24 hours. mRNA expressions were quantified by real-time PCR. 2) C57BL/6J mice were subjected to femoral arterial wire injury and blocking antibodies (250 μg/injection) were intraperitoneally injected twice a week for 4 weeks, 3) Apolipoprotein E-deficient mice (

Apoe
-/-

) at 8 weeks of age were fed a high-fat diet and blocking antibodies (250 μg/injection) were intraperitoneally injected twice a week for 12 weeks.

Results:
Blockade of Jagged 2, Dll1 and Dll4 decreased expression of iNOS and IL-1β in macrophages treated with LPS and IFN-γ. In contrast, blockade of Dll1 increased arginase-1 and Ym1 in IL-4 treated macrophages. Immobilized recombinant Dll1 increased prototypical Notch-target gene Hes-1 and induced subsequent IL-1β expression. Therefore, we have tested Dll1 blocking antibodies in
in vivo
models. After femoral arterial injury, administration of Dll1 blocking antibodies attenuated intimal hyperplasia, perivascular fibrosis, and negative remodeling of injured arteries. In

Apoe
-/-

mice, a high-fat diet feeding increased Dll1 expression in atherosclerotic plaques, especially in Mac-3 positive macrophages. Blockade of Dll1 decreased atherosclerotic plaque area and lipid content determined by oil red O staining. In addition, blockade of Dll1 decreased accumulation of Mac-3 positive macrophages to the plaque.

Conclusions:
These results indicate that Dll1 promotes macrophage activation and arteriosclerosis. Dll1 may be a potential therapeutic target for vascular diseases promoted by macrophage-mediated inflammation.
Abstract 14415: Management, Characteristics, and Outcomes of Patients With Acute Coronary Syndrome in a Developing Country
Authors: Elfaituri Muhammed K , Bin Zarti Mohamed Abrahim , Faraj Hazem Abdelkarem , Khaled Ahmed , Zendah Mohammed Abdulhameed , Omran Elham , Msherghi Ahmed , Bheleel Osama
Published: May 2021

Introduction:
Acute coronary syndrome (ACS) encompasses a variety of coronary artery disorders involving myocardial infarction with ST-segment-elevation (STEMI), unstable angina (UA), and myocardial infarction with non-ST elevation (NSTEMI).

Hypothesis:
To gain insight into the epidemiology, evaluation, in-hospital treatment, and commitment to current management guidance of ACS for patients admitted to a tertiary care hospital in a developing country.

Methods:
We performed a retrospective observational study of 50 consecutive patients presenting with ACS between October 2019 and December 2019, and followed for in-hospital mortality at a tertiary care general medical unit. We collected and analysed patient reports on presentation, treatment, in-hospital mortality, and major adverse cardiovascular events (MACE).

Results:
Patients diagnosed with ACS had a mean (SD) age of 59.3 (13.1) years, and were predominantly men (58%). Alcohol and drug consumption, smoking, and morbid obesity were significantly associated with STEMI (P < 0.05). Discharge diagnoses included STEMI (40%), NSTEMI, and unstable angina. Mean (SD) duration of hospital stay was 5.5 (5.8) days. Left ventricular ejection fraction (LVEF) was below 40% in 28% of patients, with a mean (SD) LVEF of 46.0 (15.3) ml. Median time (interquartile range) from the onset of pain to hospital admission was 80 (423) minutes for STEMI and 138 (480) minutes for NSTEMI (P > 0.05). About 72% of patients were admitted to the cardiac intensive care unit, and 34% of STEMI patients received a fibrinolytic. All patients received anti-platelet drugs. MACE were identified in 16.3% of STEMI patients and 10.6% of NSTEMI patients. Body mass index, history of cardiac disease, longer hospital duration, diabetes, and hypertension were significant predictors of in-hospital MACE. All patients were discharged and alive at the study end. All patients received standard of care treatment after discharge.

Conclusions:
Delays in the delivery and application of thrombolytic are coronary therapy require attention in developing countries to improve the care of patients with ACS.
Abstract 14421: Association Between Meeting Daily Step Count Goals With Ambulatory Function and Quality of Life in Patients With Claudication
Authors: Gardner Andrew W , Montgomery Polly , Wang Ming , Shen Biyi
Published: May 2021

Introduction:
The aims were to determine (a) whether patients with peripheral artery disease (PAD) who walked at least 7,000 and 10,000 steps/day had better ambulatory function and health-related quality of life (HRQoL) than patients who walked less than 7,000 steps/day, and (b) whether these group differences persisted after adjusting for covariates.

Hypothesis:
Patients who walk at least 7,000 steps/day have significantly better ambulatory function, as measured by greater 6-minute walk distance (6MWD), and better HRQoL, as measured by a higher distance score on the Walking Impairment Questionnaire (WIQ), than patients who walked less than 7,000 steps/day, and that patients who walked more than 10,000 steps/day would have the best values. Furthermore, group differences in the primary outcomes would persist after adjustment for covariates.

Methods:
Two hundred forty-eight patients were assessed on their daily activity for one week with a step activity monitor, and were grouped according to daily step counts as follows: Group 1 (<7,000 steps/day; n=153), Group 2 (7,000-9,999 steps/day; n=57), Group 3 (>10,000 steps/day; n=38). Primary outcomes were 6MWD and WIQ distance score, which is a disease-specific measurement of HRQoL.

Results:
Groups were different (p<0.05) on ankle/brachial index, and on prevalence of hypertension, diabetes, abdominal obesity, arthritis, and chronic obstructive pulmonary disease. Thus, these variables served as covariates in adjusted analyses, along with age, weight, and sex. 6MWD (mean±SD) was significantly different among the groups in unadjusted (p<0.01) and adjusted (p<0.01) analyses (Group 1=313±90 m, Group 2=378±84 m, Group 3=414±77 m), with Groups 2 and 3 having higher 6MWD than Group 1 (p<0.01). Similar results were found for the WIQ distance score (Group 1=30±30%, Group 2=45±35%, Group 3=47±34%; p<0.01).

Conclusions:
PAD patients who walked more than 7,000 and 10,000 steps/day had greater ambulatory function and HRQoL than patients who walked fewer than 7,000 steps/day, and this finding persisted after adjusting for covariates. The clinical significance is that PAD patients should be encouraged to walk more than 7,000 steps/day because this target is associated with greater ambulatory function and HRQoL
Abstract 14425: Coronary Microvascular Disease in Type 2 Diabetes is Linked to the Upregulation of P53
Authors: Cabrera Jody Tori O , Si Rui , Tsuji Hosokawa Atsumi , Makino Ayako
Published: May 2021

Diabetes mellitus
is a prominent risk factor of coronary microvascular disease (CMD) and the comorbidity of CMD in diabetic patients leads to an increasing occurrence of cardiac mortality. Increased protein
O
-linked β-N-acetylglucosaminylation (
O
-GlcNAcylation), a post-translational modification of proteins, is implicated in the development of vascular complications in diabetes. Therefore, we investigated the molecular mechanisms in which excess protein
O
-GlcNAcylation advances the progression of CMD in diabetes through coronary endothelial cell dysfunction. We hypothesize that excess protein
O
-GlcNAcylation will up-regulate p53 which will induce the development of CMD. We had conducted
in vivo
and
in vitro
experiments in control mice, TALLYHO/Jng (TH) mice, a polygenic type 2 diabetic mouse model, and endothelial cell-specific
O
-GlcNAcase (OGA, a regulatory enzyme that catalyzes the removal of
O-
GlcNAc from proteins)-overexpressing TH mice. We found that compared to control mice, TH mice exhibited a decrease in coronary flow velocity reserve (CFVR, an indicator of coronary microvascular function), reduced capillary density, and increased endothelial cell apoptosis in the left ventricle. In addition, TH mice showed a significant increase of p53 protein expression in mouse coronary endothelial cells (MCECs) compared to control mice. Moreover, overexpression of OGA lowered protein
O
-GlcNAcylation and decreased p53 levels in MCECs. p53 inhibition with pifithrin-α restoratively increased CFVR and cardiac contractility in TH mice. From this data, we conclude OGA overexpression lowers p53 expression levels and thus attenuates endothelial cell apoptosis and restores CFVR and cardiac function in diabetes. The downregulation of p53 through OGA overexpression could be a potential therapeutic target for CMD in diabetic patients.
Abstract 14433: High Intensity Exercise Training Safely Increases Cardiorespiratory Fitness in Patients With Hypertrophic Cardiomyopathy
Authors: Dias Katrin A , Macnamara James P , Hearon Christopher M , Samels Mitchel , Turer Aslan , Link Mark S , Sarma Satyam , LEVINE Benjamin D
Published: May 2021

Introduction:
Patients with hypertrophic cardiomyopathy (HCM) are excluded from high intensity activities due to perceived fear of sudden cardiac death. Observational data from athletes with HCM suggest that engaging in high intensity exercise (HIE) may be safe and is associated with higher cardiorespiratory fitness. Whether HIE can safely elicit a superior increase in fitness compared to moderate intensity exercise in patients with HCM is unclear.

Methods:
Nine HCM patients (49 ± 7 years, 3 female) were assessed for maximal oxygen uptake (VO
2
max, Douglas Bag method), cardiac output (Q
c
, acetylene rebreathing), and peripheral oxygen extraction (av-O
2
diff, Fick equation) before randomization and after 5 months of MIE or HIE training. Patients completed 3-4 sessions of MIE each week, while the HIE group also incorporated 1-2 supervised high intensity interval training sessions/week from month 3 onwards. Arrhythmias were monitored via pre-existing implantable cardiac defibrillators or implantable loop recorders placed prior to training.

Results:
Five months of MIE increased absolute VO
2
max by 3% and relative VO
2
max by 4%, while HIE consistently increased absolute VO
2
max by 6% and relative VO
2
max by 5% (Figure). Maximal Q
c
did not change after MIE but increased in all HIE patients (+1.2L/min, 95% CI -1.4 to 3.9), while maximal av-O
2
diff remained stable in both groups. Training compliance was 84 ± 15% in HIE and 93 ± 11% in MIE. There were no serious exercise-related adverse events in either group though two HIE subjects had arrhythmias at rest: 1) 14-beat run of wide complex tachycardia of uncertain mechanism given underlying conduction disease prior to a training session, and 2) 11 beats of non-sustained ventricular tachycardia prior to post exercise testing.

Conclusions:
Preliminary findings show that five months of HIE safely and consistently increased cardiorespiratory fitness in patients with HCM, though overall the improvements were comparable to MIE.
Abstract 14443: Aortic Root Rotational Position Associates With Aortic Valve Incompetence and Aortic Dilation After Arterial Switch Operation for Transposition of the Great Arteries
Authors: Tseng Stephanie Y , Tretter Justin , Gao Zhiqian , Ollberding Nicholas , Lang Sean
Published: May 2021

Introduction:
Variation in aortic root (AoR) rotational position affects flow dynamics in normal patients. Complications of arterial switch operation (ASO) for transposition of the great arteries (TGA) include aortic dilation and neo-aortic regurgitation (AR). We sought to assess the association of neo-AoR rotational position with neo-AoR and ascending aorta (AA) dilation and neo-AR in TGA after ASO.

Methods:
Patients after ASO for TGA who underwent cardiac magnetic resonance (CMR) from 2005-2020 were retrospectively reviewed. Neo-AoR rotational angle, indexed (to height) neo-AoR and AA dimensions, indexed left ventricular end diastolic volume (LVEDVi), and neo-aortic regurgitant fraction (RF) were obtained from CMR. Multivariable regression analysis for neo-AoR and AA dilation, RF, and LVEDVi were performed.

Results:
A total of 36 patients (78% male) were included. Median age at ASO was 5 days (3, 7) and at CMR was 17.1 years (12.3, 21.9). Rotational angle was 25% counterclockwise (<-9°), 25% central (-9 to +14°), and 50% clockwise (>+15°). There was no material association of neo-AoR and AA size with sex, age, and coronary artery anatomy. A quadratic term for neo-AoR rotational angle - increasing extremes of counterclockwise and clockwise angles - was significantly associated with neo-AoR dilation (p=0.03), AA dilation (p<0.02), and LVEDVi (p<0.01) (Figure 1) and remained significant in multivariable model of neo-AoR dilation (p<0.02), AA dilation (p<0.01), and LVEDVi (p<0.02). Rotational angle was negatively associated with neo-aortic RF (p<0.05) and remained significant in multivariable model (p<0.02).

Conclusions:
In conclusion, both clockwise and counterclockwise neo-AoR rotational position in TGA after ASO are associated with neo-AoR and AA dilation and LVEDVi. Counterclockwise rotational angle was associated with RF. Neo-AoR rotational position likely affects valve function and hemodynamics, leading to risk of neo-AR and aortic dilation.
Abstract 14458: Repeated Social Defeat Exaggerates Fibrin-rich Clot Formation in Fecl3 Induced Arterial Thrombosis Mice Model by Enhancing Nets Formation
Authors: Sugimoto Takeshi , Yamada Hiroyuki , Kubota Hiroshi , Miyawaki Daisuke , Wakana Noriyuki , MATOBA Satoaki
Published: May 2021

Background and Objective:
Depression is an independent risk factor of cardiovascular disease (CVD). We have recently shown that repeated social defeat (RSD) exaggerates atherosclerosis development by enhancing neutrophil extracellular traps (NETs) formation. Here, we investigated the impact of RSD on arterial thrombosis.

Methods and Results:
Eight-week-old male WT mice were exposed to RSD by housing with a larger CD-1 mouse in a shared home cage. They were subjected to vigorous physical contact daily for 10 consecutive days. Control mice were housed in the same gage without physical contact. After social interaction test to confirm depressive-like behaviors, defeated mice (19 of 31) and control mice (12 of 14) were underwent arterial injury at 10 wks of age. A filter paper saturated with 10% FeCl3 was applied on the adventitial surface of left carotid artery for 3 min and analyzed 3 hrs later. The volume of thrombi was comparable between the two groups. However, fibrinogen/fibrin-positive areas in immunofluorescent images significantly increased in defeated mice (48.8% vs. 27.8%, p < 0.01). The number of Ly-6G-positive cells in thrombi was markedly higher in defeated mice (878/mm2 vs. 144/mm2, p < 0.05). Further, Ly-6G-positive cells were co-localized with neutrophil elastase, Cit-H3, and CD42b-positive staining. Percentage of CD42b-positive area in thrombi and in vitro platelets aggregations induced by ADP or collagen were comparable between the two groups. Treatment with DNase I completely diminished the exaggerated fibrin-rich clot formation in defeated mice to an extent similar to that in control mice (22.3% vs. 25.7%, p = ns), although the number of Ly-6G-positive cells in thrombi was not affected. We therefore examined the vulnerability to NETs formation induced by thrombin-activated platelets. Flow cytometric analysis showed that in vitro NETs formation assessed by Cit-H3/MPO double-positive cells was significantly higher in defeated mice (20.7% vs 12.5%, p < 0.01).

Conclusions:
Our findings demonstrate that RSD enhances fibrin-rich clot formation after arterial injury by enhancing NETs formation via platelet-neutrophil interactions, suggesting that NETosis could be a new therapeutic target in depression-related CVD development.
Abstract 14480: Family Planning Care Experiences and Perceptions of Women With Congenital Heart Disease
Authors: Stokes Natalie , Stransky Olivia , WEST Shawn C , Hoskoppal Arvind , Birru Talabi Mehret , Borrero Sonya , Kazmerski Traci
Published: May 2021

Background:
Due to medical advances, women with congenital heart disease (CHD) are living longer, healthier lives and many are considering pregnancy. The hemodynamic changes of pregnancy can present high risks of morbidity and mortality for many women with CHD. As little is known about these women’s reproductive health experiences, this study examines their perceptions of pregnancy and family planning care as related to CHD.

Methods:
Women ages 18-45 years with a diagnosis of CHD associated with a WHO classification II-IV for pregnancy morbidity and mortality participated in individual, semi-structured interviews exploring their experiences and attitudes toward parenthood, pregnancy, contraception and family planning care provision. Interviews were audio-recorded, transcribed verbatim, and analysis was performed by two independent coders using an inductive coding approach.

Results:
Twenty women with CHD participated in interviews (average age 30.1 years, SD 5.85). Nine women had ever been pregnant and 14 considered becoming a parent in the future. We identified 5 key interview themes: (1) Women saw CHD as impacting their reproductive health goals and decisions; (2) Women with CHD desired tailored, disease-specific family planning information; (3) Women with CHD viewed their cardiologist as the primary source for family planning information and prefer provider-initiated reproductive health discussions starting in adolescence; (4) Women with CHD desire coordinated preconception and intrapartum care between their cardiologists and women’s health providers; and (5) Women with CHD perceived a lack of safe contraceptive methods for their condition.

Conclusions:
Women with CHD face a variety of disease-specific family planning concerns and desire coordinated reproductive healthcare from their cardiologists and women’s health providers. As more women with CHD reach childbearing age, these unique needs must be addressed to empower women to make informed family planning decisions. These results provide a foundation for interventions to improve patient-centered interdisciplinary reproductive healthcare for this population.
Abstract 14485: Landscape of Lipid Management Following an Acute Coronary Syndrome: Survey of Canadian Specialists
Authors: Padarath Michelle , Welsh Robert , Gregoire Jean C , Hegele Robert A , Padarath Michelle , Gupta Milan
Published: May 2021

Background:
Following an acute coronary syndrome (ACS), patients are at high risk for subsequent cardiovascular events. LDL-cholesterol lowering remains a pillar in secondary prevention following ACS. There remains significant variability in the application of LDL-lowering therapies in clinical practice.

Methods/Results:
A cross-sectional, online survey of 200 cardiovascular specialists across Canada. The survey consisted of 50 multiple-choice questions and free text entry. The survey was distributed to members of the Canadian Collaborative Research Network with $125 stipend offered. All participants stated that it was standard of practice to obtain a lipid panel during ACS admission, often within the first 24 hours (67.5%, n=135). 68.5% (n=137) stated their hospitals had standing orders for statin initiation at ACS presentation. In very high-risk patients (multiple cardiovascular events, polyvascular disease), the majority (75.5%; n=151) of participants indicated a target LDL-c of <70 mg/dL. Further, 22% (n=44) would target lower LDL-c levels ranging from 19.3-65.7 mg/dL. Only 32.0% (n=64) of participants stated that >70% of their ACS patients were at/below LDL-c targets of <70 mg/dL. Patients presenting with ACS despite high intensity statin with LDL-c above target were most often (80.0%; n=160) started on ezetimibe. Post-discharge, the majority of respondents indicated they would assess the patient in clinic at 1-3 months, and <50% would order a lipid profile prior to that visit. Respondents underestimated the prevalence of familial hypercholesterolemia (FH) in both the general population and in ACS patients. Experience with PCSK9 inhibitors varied with 42.0% (n=84) having prescribed to less than five patients. Forty percent of respondents expressed safety concern at achieved LDL-e levels below 40 mg/dL.

Conclusion:
There is significant variation in practice patterns involving LDL-lowering therapies in the post-ACS period, and probable under-recognition of FH in this very-high risk population. Further evidence to inform guidelines and clinical practice is urgently required.