bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15367: Depression Symptom Patterns as Predictors of Metabolic Syndrome and Cardiac Events in Symptomatic Women With Suspected Myocardial Ischemia: The Women’s Ischemia Syndrome Evaluation (WISE & WISE-CVD) Projects
Authors: Virzi Nicole , Krantz David , Bittner Vera A , Bairey Merz C. Noel , Reis Steven , Handberg Eileen M , Pepine Carl , Rutledge Thomas
Published: June 2023

Introduction:
Ischemic Heart Disease (IHD) risk in women includes biomedical, behavioral, and psychosocial contributors. Among psychosocial contributors, recent studies suggest that depression, especially somatic symptoms of depression such as anhedonia and low energy, may play a disproportionate role in the development of both IHD risk factors and major adverse cardiovascular events (MACE).

Methods:
We examined relationships between cognitive/somatic symptoms of depression and metabolic syndrome (MetS) in two independent cohorts of women with suspected IHD. In the Women’s Ischemia Syndrome Evaluation (WISE, NCT00000554), we also examined depression and MetS as predictors of all-cause mortality and MACE over a median 9.3-year follow-up. The sample from WISE included 641 women with suspected ischemia with or without obstructive coronary artery disease (CAD). The WISE-Coronary Vascular Dysfunction (WISE-CVD, NCT00832702) consisted of 359 women with suspected ischemia and no obstructive CAD (INOCA). Somatic, cognitive, and total depressive symptoms were measured via the Beck Depression Inventory (BDI). MetS was assessed according to the AHA’s ATP-III criteria.

Results:
(See attached table) In both the WISE and WISE-CVD samples, somatic symptoms of depression were associated with MetS diagnosis and MetS severity, while cognitive symptoms were not. Within the WISE sample, using Cox Proportional Hazard Regression, both somatic symptoms and MetS diagnosis were significant predictors of all-cause mortality and MACE, while cognitive symptoms were not.

Conclusions:
In two independent samples of women undergoing coronary angiography for suspected myocardial ischemia, somatic symptoms of depression were uniquely associated with both MetS and all-cause mortality and MACE, and both somatic symptoms of depression and MetS independently predicted all-cause mortality and MACE.
Abstract 15381: Phlegmasia Cerulea Dolens and Concurrent Gastrointestinal Bleeding: A Dangerous Combination With Challenging Management
Authors: Lima Gian , Lederman Yitzchok S
Published: June 2023

Introduction:
Phlegmasia cerulea dolens (PCD) is a rare and life-threatening complication related to extensive deep venous thrombosis (DVT) resulting in acute limb ischemia. Treatment options include anticoagulation, thrombolysis and thrombectomy. Case: A 31-year-old female with a history of ulcerative colitis (UC) on chronic steroids presented with acute dyspnea and tachycardia. She was hemodynamically stable. The initial workup included a lower extremity (LE) Doppler ultrasound (US) which showed an acute occlusive thrombus involving the left posterior tibial and popliteal veins, and a computerized tomography angiography (CTA) of her chest which showed bilateral pulmonary emboli. She was placed on heparin drip for 48 hours but due to an episode of acute gastrointestinal (GI) bleeding due to severe UC, anticoagulation was discontinued after an inferior vena cava filter placement and she was discharged from the hospital. After 1 month, she presented with severe diarrhea, hypotension and tachycardia. A chest CTA showed reduced clot burden compared to prior. On hospital day 2, the patient experienced acute onset of severe left LE pain, bluish skin discoloration and rapidly progressing edema. A repeat US showed progression of DVT to the left common femoral vein. The findings were consistent acute limb ischemia in the setting of PCD. She was managed with emergent thrombectomy, with significant amount of thrombus retrieved. Gastroenterology was consulted and GI bleeding did not recur.

Discussion:
Due to its rarity, there are limited data available to guide PCD management in the setting of elevated bleeding risk such as severe UC. However, after a risk-benefit assessment, we determined that this young patient should be treated with anticoagulation and undergo emergent thrombectomy, which resulted in significant improvement of her symptoms. We highlight the importance of multidisciplinary approach, early diagnosis and prompt treatment in these complex patients.
Abstract 15384: Regional Trends in Watchman Device Placement in United States, Insight From National Inpatient Sample
Authors: Khan Muhammad Z , Munir Muhammad , sattar yasar , Gonuguntla Karthik , Chobufo Muchi Ditah , Alharbi Anas , Skaff Paulina , Khan Muhammad U , balla sudarshan
Published: June 2023

Introduction:
Watchman Implant is a minimally invasive procedure designed to reduce the risk of strokes that originate in the left atrial appendage in patients who cannot receive anticoagulation. Recently, the device is widely adopted in United States(US).

Hypothesis:
Significant variability exists in watchman device implantation across US.

Methods:
National Inpatient sample was used from year 2015-2019. ICD9 & ICD-10 codes were used for data extraction. US population was divided into four regions. Northeast, Midwest, South and West. Mortality and major complications were adjusted for age, sex, race and standard comorbid conditions using logistic regression analysis. Major complication was composite of cardiac arrest, ischemic stroke, hemorrhagic stroke, TIA, arterial embolism, myocardial infarction, major bleeding, pericardial effusion requiring intervention and peripheral vascular complications.

Results:
Total of 62,980 patients were identified (Figure1). There has been gradual increase trend in watchman implants over the years. Median age was 77(71-82) yrs. Mortality was lowest in Midwest (Figure 2), while Major complications were lowest West region (Figure 3).

Conclusions:
Significant variability exists in outcomes across different regions of US. Further studies are needed to determine the significance of these findings.
Abstract 15385: Integrin Alpha 11 is a Critical Regulator of Cardiac Remodelling, Fibrosis and Infarct Formation Following Myocardial Infarction
Authors: Meagher Patrick B , Lee Xavier , Desjardins Jean-Francois , Friedberg Mark K , McCulloch Christopher , Connelly Kim
Published: June 2023

Cardiac fibrosis (CF), a key feature of cardiac remodelling, defined as the accumulation of excessive amounts of extracellular matrix (ECM), in response to injuries such as myocardial infarction (MI). Cardiac fibroblasts within and surrounding the injured area respond to biochemical and mechanical stimuli transforming into myofibroblasts and begin to secrete collagen. Long term collagen production reduces ventricular compliance and ultimately results in further cardiac dysfunction leading to heart failure. Mechanical activation of collagen production is understood to be a significant mediator of cardiac fibrosis. However, the mechanisms via which mechanical stimuli initiate cardiac fibroblast activation are not well understood. Therefore, we sort to investigate the role of Integrin ⍺11, a collagen binding integrin which preferentially binds to type I collagen, in response to cardiac injury. Fibroblast conditional ⍺11 knockout (KO) mice demonstrated similar cardiac function to that of Wildtype littermates (WT). However, interstitial collagen I (P<0.05) and III (P<0.0001) content was reduce along with cardiac myocyte size (P<0.0001). In response to ligation of the left anterior descending aorta ⍺11 KO mice had significantly increased Infarct size 24 hours post MI (WT=39%, ⍺11KO=64% P<0.05). Larger MI’s resulted in increased mortality in ⍺11 KO mice (22% v’s 57%, P<0.05) due to rupture. Cardiac function 2 days following MI measured by echo demonstrated that Fractional Area Change (FAC) (23% ±1.812 v’s 16%±2.311, P<0.05) and Cardiac Output (8.53ml±1.045 v’s 4.98ml±0.67, P<0.05) were significantly worse in ⍺11 KO compared to WT mice. In the later remodelling response 4 weeks post MI, FAC was again significantly worse for ⍺11 KO mice (~9% ±1.659%, P<0.0001) compared to WT (~19% ± 0.9810%). Moreover, ⍺11 KO mice that survived MI had significantly more collagen I (P<0.0001) content in the remote, peri-infarct and infarct zone’s than that of WT along with, a lack of hypertrophic response. In conclusion, the loss ⍺11 results in increased ventricular dilation, impairs cardiac function and, was associated with increased mortality due to rupture following MI. In mice which survived MI ⍺11 deletion led to increased CF and blunted cardiac myocyte hypertrophy.
Abstract 15421: Mice Deficient in Endothelial Cell-Selective Adhesion Molecule Display Coronary Microvascular Rarefaction and Left Ventricle Diastolic Dysfunction
Authors: Buncha Vadym , Fopiano Katie A , Lang Liwei , Arriaga Ricardo A , Bagi Zsolt A
Published: June 2023

Coronary microvascular dysfunction and chronic inflammation play a role in the development of left ventricular diastolic dysfunction (LVDD) in heart failure with preserved ejection fraction (HFpEF). Endothelial cell-selective adhesion molecule (ESAM) is part of the endothelial cell junction complex, which plays a role in the maintenance of cell barrier function, inflammatory cell transmigration and angiogenesis. Here, we examined the role of ESAM in affecting coronary microvascular density and left ventricle diastolic function by employing mice with genetic deletion of ESAM (ESAM
-/-
). Using echocardiography, we found that ESAM
-/-
mice display LVDD, as indicated by a significantly (p<0.05) reduced E/A ratio (E=early, A=late mitral inflow peak velocities), increased E/e’ ratio, isovolumic relaxation time and E wave deceleration time, with no change in the ejection fraction. Using an unbiased, automated tracing and 3D reconstruction of microvascular network revealed that ESAM
-/-
mice have a reduced coronary microvascular density, which was accompanied by myocardial accumulation of myeloperoxidase-positive neutrophils and elevated myocardial levels of inflammatory cytokines and chemokines. ESAM
-/-
mice exhibited a reduced endothelial sprout formation in the carotid artery, whereas in cultured endothelial cells siRNA-mediated ESAM knockdown impaired tube formation. Thus, ESAM deficiency in mice leads to coronary microvascular rarefaction, which likely via a myocardial hypoperfusion-related neutrophil accumulation and inflammatory mediator production impairs LV diastolic function.
Abstract 15445: Combination Therapy With Pde5-mtor Inhibitors Attenuates Cardiotoxicity While Enhancing Cancer Cell Death Following Treatment With Doxorubicin and Human Epidermal Growth Factor Receptor 2 Inhibitor
Authors: Das Anindita , Kraskauskas Donatas , Bhuiyan Nuhash , Samidurai Arun , Kukreja Rakesh C
Published: June 2023

Backgound:
Chemoimmunotherapy with Doxorubicin (DOX) and Trastuzumab (Trast, a monoclonal antibody against human epidermal growth factor receptor 2, ERBB2) has synergistic effects with immense improvement in disease-free survival in breast cancer patients. However, because of the high incidence of heart failure, the concomitant treatment with DOX and trastuzumab has been restricted. In the present study, we examined whether a novel combination therapy with the phosphodiesterase 5 (PDE5) inhibitor (sildenafil, Sild) and mTOR inhibitor (rapamycin, Rapa) can attenuate cardiotoxicity-induced by DOX+Trast.

Methods & Results:
Human ventricular cardiomyocytes (AC16) and ErbB2
+
breast cancer cells (SKBr3) were treated with DOX (1μM), AG-825 (ERBB2 inhibitor, 5μM) and/or Sild (10μM) and Rapa (100 nM) for 24 hours. AC16 cell death was significantly higher with DOX+AG825 as compared to the single drug treatment, which was significantly reduced with Sild+Rapa treatment (Fig.
A
). Contrarily, the enhanced SKBr3 cell death with DOX+AG825 treatment was further increased by Sild+Rapa treatment (Fig.
B
). To evaluate therapeutic effect of Sild+Rapa against cardiotoxicity, C57BL/6J mice were treated for 2 weeks with DOX (6 mg/kg/twice/week, i.p.). After 1week interval, mice were treated with Trast for 2 weeks (2.5 mg/kg/twice/week, i.p.) (Fig.
C
). Rapa (0.25 mg/kg/twice/week, i.p.) and Sild (0.4 mg/ml in drinking water) were administered for 12 weeks. Body weight, left ventricular ejection fraction (LVEF) and E/A ratio as well as survival were significantly decreased in mice with the sequential treatment of DOX and Trast as compared to DOX alone (Fig.
D-G
). Treatment with Sild+Rapa significantly improved body weight and survival with restoration of cardiac function in mice treated with DOX±Trast.

Conclusion:
Combination treatment with Sild and Rapa could be a novel strategy to attenuate cardiotoxicity associated with DOX±Trast and improvement of cancer chemotherapy.
Abstract 15449: Gaps In Diverse Racial/Ethnic Representation in High Impact Studies of Lipoprotein (a) and Atherosclerotic Cardiovascular Disease
Authors: Brar Sumeet S , Rodriguez Fatima , Sarraju Ashish
Published: June 2023

Introduction:
Lipoprotein (a) [Lp(a)] is an emerging target for atherosclerotic cardiovascular disease (ASCVD) with racial/ethnic differences that may link with ASCVD. Compared to non-Hispanic White (NHW) individuals, Asian and Black individuals have high Lp(a) levels. We evaluated diverse racial/ethnic reporting and representation in high impact studies of Lp(a) and ASCVD that inform major Lp(a) scientific statements.

Methods:
We reviewed the 2022 American Heart Association (AHA) Scientific Statement on Lipoprotein (a) and the 2019 Scientific Statement from the National Lipid Association (NLA) on the Use of Lipoprotein (a) in Clinical Practice for all cited observational studies or trials of Lp(a) and ASCVD. For studies of the same cohort, only the one with the largest sample size was included. Meta-analyses were excluded to avoid duplication. Manuscripts and supplements were systematically reviewed for participant race/ethnicity data. Participation (%) was pooled across studies for overall representation. In a sub-analysis of US studies, pooled representation was compared with 2020 US Census data.

Results:
A total of 58 studies met inclusion criteria. Only 33 (57%) reported any race/ethnicity. Reporting studies (participant n=701859) had 92% NHW, 2.6% Black, 0.6% Hispanic, 3.2% Asian, and <0.1% American Indian/Alaskan Native or Native Hawaiian/Pacific Islander participants. No Lp(a) studies disaggregated Hispanic subgroups and 5 disaggregated Asian subgroups. In US studies, Hispanic and Asian representation was lower than 2020 US Census data (Fig).

Conclusions:
High impact studies of Lp(a) and ASCVD underreport and rarely disaggregate participant race/ethnicity and have low overall Black, Hispanic, and Asian representation. Among US studies, Hispanic and Asian groups are underrepresented versus 2020 Census data. Efforts are needed to improve diverse study race/ethnicity reporting and representation for this emerging therapeutic target.
Abstract 15460: Comprehensive Diet and Exercise Intervention During Radiation Therapy Can Improve Metabolic and Inflammatory Markers in Breast Cancer Patients
Authors: Senthilkumar Gopika , Schottstaedt Aronne M , Stolley Melinda , Chitambar Christopher , Visotcky Alexis , Banerjee Anjishnu , Longo John , Kelly Tracy , Currey Adam , Bergom Carmen
Published: June 2023

While radiation therapy (RT) is effective for reducing cancer burden in breast cancer (BC) patients, its side effects promote sedentary behavior and accumulation of adipose mass. Obesity and inactivity further increase the risk for cardiovascular co-morbidities and mortality. To combat these effects, we piloted a 12-week
Stay on Track
(SOT) exercise and diet intervention for breast cancer patients during their RT. We hypothesize that SOT will positively influence body composition and metabolic and inflammatory biomarkers in BC patients. A prospective, randomized control trial for patients with non-metastatic BC undergoing whole-breast RT was conducted. The intervention (
A;
21 patients) group participated in 3 personal excercise training sessions, 3 dietary counseling sessions, and received 3 text message reminders per week to adhere to lifestyle recommendations. The control
(B;
22 patients
)
group received an informative binder. All patients received a Fitbit, and at baseline, 3months, and 6months, measurements of blood biomarkers and dual-energy x-ray absorptiometry (DXA) scans were conducted. A mixed models analysis with a significance value of 0.05 was conducted, and estimated change from baseline with SE’s are reported. There was trend towards lower BMI (-0.95, 0.49; p=0.06) at 6mo and decreased visceral fat (-2.17, 1.22; p=0.081) at 3mo in
A
only.
B
had an increase in HbA1C at 3mo compared to baseline (0.26, 0.10; p=0.01) which stayed elevated at 6mo (0.22, 0.13; p=0.08).
B
also had an increase in glucose levels at 6mo (8.42, 3.94; p=0.04), with a trend towards a decrease in insulin (-14.30, 9.85; p=0.15).
A
had no changes in these levels. There was a significant decrease in leptin levels at 6mo in
B
only (-13583.7, 6184.2, p=0.03). Adiponectin levels trended higher in
A
compared to
B
at 6mo (3143.42, 2265.1; p=0.17). Analysis of inflammatory cytokines showed a decrease in anti-inflammatory IL-1R-a in
B
(-3.46, 1.24; p=0.01), and a reduction in pro-inflammatory IL-8 levels in
A
(-2.77, 1.15; p=0.02). We conclude that SOT may positively influence body composition and metabolic and inflammatory biomarkers in BC patients. Targeted lifestyle interventions during RT are feasible and could help decrease cardiovascular co-morbidities in BC.
Abstract 15470: Mathematical Modeling of the Determinants and Consequences of Mitral Regurgitation: Jacobian Sensitivity Analysis of a Lumped Parameter Model of the Cardiovascular System
Authors: Smith Tyler J , Lee Jeesoo , Markl Michael , Thomas James D
Published: June 2023

Background:
Mitral regurgitation (MR) results in complex changes to hemodynamics, which lumped parameter (LP) models of the cardiovascular (CV) system can model. A previously validated LP model using time varying elastance of the atria and ventricles models pressure, volume, and flow in the four chambers and valves of the heart and arterial and venous compartments. Here we model moderate MR and perform a Jacobian matrix sensitivity analysis to explore impact of CV parameters on MR variables.

Methods:
Using MATLAB app designer, we made an app to give input parameter and output variable specification for the LP model, displaying pressure, volume, and flow curves and specified output variables at equilibrium. Sensitivity analysis was done with a Jacobian matrix, showing the proportional change (Δ) in output variables (

y
i

) to change in each input parameter (

x
j

), [(Δy
i
/y
i
)/(Δx
j
/x
j
)]. We assessed the change in these output variables: LA peak pressure (LAP), Forward Stroke Volume (FSV), and MR Volume (MRVol); in response to changes in these input parameters: LV End Systolic Elastance (LVESE), MR Orifice Area (MROA), and peripheral vascular resistance (PVR) in the setting of moderate MR (MROA=0.3 cm
2
).

Results:
Pressure curves for the left atrium and ventricle and aorta with and without moderate MR are shown, with the Jacobian sensitivity matrix in Figure 1. To use the Jacobian matrix, multiply a small proportional change in the input parameter (rows) with the value under the output variable (columns). For example, a 10% increase in MROA will cause a 3.7% increase in LAP, 0.8% fall in FSV, and 8.3% increase in MRVol.

Conclusion:
This analysis shows how small changes in many parameters impact multiple output variables. MRVol is most sensitive to changes in MROA, while the impact of LVESE (contractility) and PVR (afterload) are appropriately discordant. This model warrants further study to predict instantaneous hemodynamic changes in MR and a host of other entities.
Abstract 15482: Self-Adaptive Deep Learning-Based Segmentation for Uniform and Functional Preclinical and Clinical CT Image Analysis
Authors: Zwijnen Anne-Wietje , Watzema Leon , Ridwan Yanto , Van Der Pluijm Ingrid , Smal Ihor , Essers Jeroen
Published: June 2023

Currently, effective treatment options for heart failure are lacking. Methods to monitor cardiac function longitudinally can accelerate preclinical and clinical research into disease progression and novel drugs. However, manual image analysis of cardiac substructures is resource-intensive and error-prone. While automated methods exist for clinical CT images, translating these to preclinical μCT data is challenging. We aimed at employing deep-learning to automatically extract quantitative data on cardiac functional parameters, developing a uniform method for both μCT and CT images. For this, we collected 110 contrast-enhanced μCT images of wild-type and accelerated aging (Ercc1
Δ/-
) mice, as well as a public dataset of 60 segmented cardiac CT images. Substructures, i.e., the left ventricle, left myocardium and right ventricle, were manually segmented in 24 μCT images to create a training set. After template-based heart detection, two separate segmentation neural network architectures were trained using the nnU-Net framework. Automatic and manual segmentations of the μCT training set were nearly identical (mean Dice score 0.983). The estimated median Dice score (0.940) of the test set results was comparable to existing methods for μCT image segmentation. Also, the automatic volume metrics were similar to manual observations by an expert. In Ercc1
Δ/-
mice, ejection fractions had significantly decreased, and myocardial mass increased by age 24 weeks. The mean Dice score of the CT segmentation results (0.925 ± 0.019, n = 40) was superior to those achieved by state-of-the-art algorithms. While further optimization and validation of the models is recommended, automated data extraction expands the use application of (μ)CT imaging, while reducing subjectivity and workload. In conclusion, the proposed method offers a pipeline to efficiently monitor disease progression in animals and humans, allowing uniform translation from preclinical to clinical studies.
Abstract 15487: Boosting Autophagy for the Reduction of Diabetes-Induced Endothelial Dysfunction
Authors: Forte Maurizio , Schiavon Sonia , Schirone Leonardo , Vecchio Daniele , D'Ambrosio Luca , Frati Giacomo , Sciarretta Sebastiano
Published: June 2023

Introduction:
Diabetes is one of the main cause of endothelial dysfunction. The molecular mechanisms underlying the effects of hyperglycaemia in endothelial cells still need to be clarified. Autophagy, a stress-responsive and self-renewal mechanism exerts beneficial effects in the cardiovascular system. However, its role in diabetes-induced endothelial dysfunction is unknown.

Hypothesis:
Endothelial autophagy is impaired in the presence of diabetes and restoration of autophagy may reduce diabetes-induced endothelial damage.

Methods:
The effects of hyperglycaemia (HG, 30 mM for 6 and 24 hours) on autophagy, mitophagy and endothelial function were evaluated in vitro in human umbilical endothelial cells (HUVEC). Vascular reactivity experiments were performed in mesenteric arteries from wild-type mice (WT) treated with HG and in human saphenous veins from patients with peripheral artery diseases. Autophagy reactivation was carried out through ATG7 overexpression (ATG7ov) or through spermidine (SP) (100 nM), a natural activator of autophagy and inhibitor of p300.

Results:
HG reduces autophagy (0.6 fold p<0.05) and mitophagy (1.5 fold p<0.001) in endothelial cells. HG also inhibits stress-induced autophagy in cells undergoing hypoxia (0.6 fold p<0.05). ATG7ov rescues apoptosis (0.52 fold p<0.05) and angiogenesis (2.3 fold p<0.05) in HUVEC exposed to HG treatment. We found increased expression of the histone acetyltransferase p300 (2.27 fold p<0.05), a known inhibitor of autophagy. Knockout mice of autophagy (Beclin 1 +/-) show a reduction in endothelial-dependent vasorelaxation compared to WT mice in response to HG (-19.16 % +-4.97 SEM vs -48.39 % +-2.18 SEM p<0.001). Autophagy reactivation through ATG7ov or spermidine rescues endothelial-dependent relaxation in WT mice treated with HG (ATG7ov -62.48 % +-5.16 SEM; SP -63.01 +-3.22 SEM; HG -40.67 % +-3.82 p<0.001). Finally, we demonstrated that SP improves vascular function in human veins (-37.6 % +-12.76 SEM vs -12.52 % +-5.6 SEM p<0.001).

Conclusions:
The impairment of autophagy in response to diabetes contributes to endothelial dysfunction. Boosting autophagy with natural activators of autophagy may be a suitable intervention to reduce vascular damage in the presence of metabolic stress.
Abstract 155: Intra-arrest Epinephrine Administration is Associated with Increased Myocardial Injury and Inflammation in a Novel Murine Model of Cardiac Arrest
Authors: Bloom Jason E , Donner Daniel , Shihata Waled , Brown Aascha , Tai Tsin yee , Lambert Gavin W , Chu Po-Yin , Chan William , Stub Dion , Wang Bing , Kaye David M
Published: June 2023

Introduction:
Epinephrine (EPI) is routinely administered in cardiac arrest resuscitation. Using a novel murine model of cardiac arrest, this study aims to assess the effects of epinephrine on myocardial inflammation and injury.

Hypothesis:
Intra-arrest epinephrine use is associated with increased myocardial injury, inflammation and fibrosis.

Methods:
A total of 56 mice were included in the study. Both cardiac arrest (CA) and sham (SHAM) groups received intravenous potassium chloride either as a bolus (CA) or slow infusion (SHAM), inducing ECG-confirmed asystole (CA only) for 4-minutes prior to delivery of intravenous epinephrine (250ul, 30ug/ml) or saline (250ul) and manual chest compressions (300BPM) for 4-minutes (Fig A). Mice were recovered for assessments at 24- or 72-hour timepoints.

Results:
Rates of successful ROSC (n=21(96%) vs. n=14(82%), P=0.18) and survival to recovery (n=11(50%) vs. n=12(71%),P=0.19) were similar in CA treated with (CA+EPI) and without (CA-Epi) EPI, respectively. Greater myocardial injury occurred in CA+EPI, compared to CA-Epi, with increased Hs-Troponin levels measured at 24- (26.0±0.9ng/mL vs. 9.4±5.3,P=0.015) and 72-hours (20.9±8.3ng/mL vs. 5.0±2.4,P=0.012) (Fig B). To examine mRNA expression in cardiac tissue, rt-PCR was performed. At 72-hours, CA+EPI, compared to CA-EPI, was associated with significantly increased expression of inflammatory (TNF-α, IL1β, IL10, F4-80 and CD68) and fibrotic (TGFβ, Col1 and Col3) genes. There was no difference between SHAM-EPI and SHAM+EPI at 72-hours (Fig C).

Conclusion:
In a mouse model of cardiac arrest, the use of epinephrine did not improve rates of ROSC and survival. However, epinephrine exposure was associated with increased biomarkers of myocardial injury, end-organ inflammation, and fibrosis. These findings underscore the need for further pre-clinical studies to assess alternate agents that confer protection to vital organs and improve rates of survival.
Abstract 15503: Myocardial Infarction Increases Diversity of Neutrophil Immunophenotype
Authors: Stephan Jonah , Zoubul Taylor , Brainard Robert , Wysoczynski Marcin
Published: June 2023

Background:
Following myocardial infarction (MI), immune cells are recruited to clear apoptotic cells and facilitate replacement fibrosis. Neutrophils are the first immune cells recruited, and neutrophilia predicts death and adverse outcomes post-MI. Increased demand for neutrophils is met through emergency granulopoiesis.

Methods and Results:
Our prior investigations stimulating emergency granulopoiesis with injections of exogenous granulocyte-colony stimulating factor (G-CSF; 100 μg/kg/d) indicated neutrophil immunophenotypic diversity with the emergence of CD101
Neg
neutrophils in peripheral blood and spleen. In this study, we tested our hypothesis that MI induced emergency granulopoiesis increases neutrophil phenotypic diversity. We used a non-reperfused MI model in C57BL/6J mice (females, 14-20 wk). At 1, 2, 3, and 7 d post-MI, we harvested bone marrow, peripheral blood, spleens, and hearts. Neutrophil immunophenotypes were quantified in dissociated tissues via flow cytometry. Agreeing with previous findings, neutrophil infiltration of the heart was observed at 1-3 d, reaching a climax at 2 d. Our data demonstrates novel CD101
Neg
and CD117
Pos
neutrophils present in the heart 1-3 d post-MI (n=3-6, p< 0.05). Additionally, elevated numbers of neutrophils and CD101
Neg
neutrophil subtypes were observed in bone marrow, peripheral blood, and spleen relative to naïve mice (n=3-10, p<0.05).

Conclusion:
We conclude that post-MI production of neutrophils results in the recruitment of diverse neutrophil subtypes to the heart. Future studies will seek to understand how post-MI activation of emergency granulopoiesis instigates neutrophil diversity and how CD101
Neg
and CD117
Pos
neutrophils are involved in replacement fibrosis.

Figure 1. Presence of CD101
Neg
and CD117
Pos
Neutrophils in the Heart in post-MI.

Gating (A-C) and quantification (E-G) of neutrophil immunophenotypes. (n=6-9, Mixed Affects Two-way ANOVA with Multiple Comparisons).
Abstract 15505: Cardiac-Specific Jarid2 Deficiency, Results in Improved Survival and Myocardial Function Following Experimental Sepsis
Authors: Tsoporis James N , Gupta Sahil , Ektesabi Amin , Izhar Shehla , Lee Youngsook , Parker Thomas G , Leong-Poi Howard , dos Santos Claudia
Published: June 2023

Introduction:
Myocardial depression and associated hemodynamic collapse are among the major causes of death in severe sepsis. Management of severe sepsis is largely supportive.

Hypothesis:
Emerging evidence suggests that the transcriptional repressor Jarid2 may play a regulatory role in sepsis; however, the functional role of Jarid2 in sepsis-induced myocardial dysfunction remains uninvestigated.

Methods:
Using both in
in vivo
(murine model of cecum ligation and puncture (CLP) in 12-week-old C57-wild type (WT) and cardiac specific Jarid2(knock-out, KO)) and
in vitro
(lipopolysaccharide, LPS) treatment of cultured murine cardiac myocytes) approaches we determined whether Jarid2 is a putative novel target for sepsis.

Results:
In response to CLP for 48hrs, WT displayed >60% mortality, survivors developed bacterial peritonitis, a marked inflammatory response (3-5-fold increases in serum and left ventricular (LV) interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha), myocardial dysfunction (20-35% decreases in dp/dt and echo-derived % ejection fraction (EF) and % fractional shortening (FS)), and a 40-50% decrease in LV Jarid2mRNA and protein compared to WT-sham. Jarid2KO mice showed resistance to CLP-induced bacterial peritonitis resulting in improved cardiac function (10-15% decrease in %EF and %FS), and survival (>90%) despite an exacerbated (10-15-fold increase in LV) inflammatory response compared to WT mice. In adult cultured cardiac myocytes derived from WT and Jarid2KO mice, treatment with the endotoxin LPS (1 microgram/mL) for 24 hrs, resulted in an 8-10-fold and 20-35-fold increase respectively, in the inflammatory cytokines TNF-alpha, IL-1beta and IL-6.

Conclusions:
These findings reveal that the loss of Jarid2 enhances bacterial clearance and despite an enhanced inflammatory response, resulted in improved myocardial function and survival following CLP-induced sepsis. As such, Jarid2 may be a novel therapeutic target in the treatment of sepsis-induced myocardial dysfunction.
Abstract 15541: Potentially Adaptive Mt-trna Expression Regulation in Severe Metabolic Dysfunction
Authors: Francois Ashley , Gorr Matthew , MCGRAIL Erin , Stratton Matthew
Published: June 2023

Metabolic dysfunction is increasingly appreciated as characteristic of heart failure, particularly heart failure associated with advanced age. Mice harboring a mutant form of Polymerase Gamma (D257A, POLG), the mitochondrial DNA polymerase, display severe metabolic dysfunction, accelerated aging, and cardiac dysfunction. We recently reported sex specific aspects of cardiac remodeling in this model. We also proposed posttranscriptional/non-canonical activation of the mitochondrial unfolded protein response (mtUPR) in the POLG mutant based on analysis of nuclear encoded gene expression and available mass spectrometry data. Subsequent analysis of mitochondria encoded gene expression in the POLG mutant provides further support for the notion of alternate activation of the mtUPR in the POLG mutant heart. Specifically, we identify a pattern of differential mitochondrial tRNA (mt-tRNA) expression that shows surprising dependence on mt-tRNA chromosomal location as clusters of mt-tRNAs throughout the mitochondrial chromosome show similar expression change. Importantly, specific mt-tRNA expression changes negatively correlate (p=0.0017) with the propensity of the charged amino acid to be found in an amyloid fold. Thus, in addition to the mt-UPR impacting nuclear encoded gene expression, a yet unidentified mechanism exists to minimize protein missfolding in the mitochondria via regulation of mitochondrial tRNA expression.
Abstract 15545: Development and Validation of a Risk Score to Predict Kidney Replacement Therapy in Covid-19 Patients
Authors: Marcolino Milena S , Figueiredo Flávio A , Ramos Lucas Emanuel F , Pires Magda C , Ponce Daniela , Carvalho Rafael L , Menezes Luanna S , Martins Karina Paula M , Viana Rego Souza e Silva Maira V , Nascimento Guilherme F , Oliveira Talita F , Lima Maria Clara P , CAMARGOS BICALHO MARIA APARECIDA C , Anschau Fernando , Pereira Polianna D
Published: June 2023

Introduction:
Acute kidney injury (AKI) is frequently associated with COVID-19 and the kidney replacement therapy (KRT) requirement is associated with disease severity and increased mortality. This study aimed to develop a prognostic score for predicting the need for KRT in inhospital COVID-19 patients.

Methods:
This multicentric cohort included 5,212 adult COVID-19 patients were between March/2020 and September/2020. Demographic data, comorbidities and conditions at hospital admission, laboratory exams, the need for mechanical ventilation, and complications (AKI, KRT, death) were collected from the medical records. The accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC). Risk groups were proposed based on predicted probabilities: non-high (up to 14.9%), high (15.0 - 49.9%), and very high risk (≥ 50.0%).

Results:
The median age of the model-derivation cohort was 59 (IQR 47-70) years, 54.5% were men, 34.3% required ICU admission, 20.9% evolved with AKI, 9.3% required KRT, and 15.1% died during hospitalization. The validation cohort had similar age, sex, ICU admission, AKI, required KRT distribution and in-hospital mortality. Thirty-two variables were tested and four important predictors of the need for KRT during hospitalization were identified using GAM: need for mechanical ventilation, male sex, higher creatinine at hospital presentation, and diabetes. The need for mechanical ventilation at any time of hospitalization was the variable with the highest weight in the score. The presence of this variable alone increases the risk of needing KRT to high. The MMCD score had excellent discrimination in derivation (AUROC = 0.929; 95% CI 0.918-0.939) and validation (AUROC = 0.927; 95% CI 0.911-0.941) cohorts an good overall performance in both cohorts (Brier score: 0.057 and 0.056, respectively). The score is implemented in a freely available online risk calculator (https://www.mmcdscore.com/).

Conclusion:
The use of the MMCD score to predict the need for KRT may assist healthcare workers in identifying hospitalized COVID-19 patients who may require more intensive monitoring, and can be useful for resource allocation.
Abstract 15561: A Rare Case of Air Embolus in the Presence of Bilateral Pulmonary Emboli
Authors: Khan Zohaib V , Zafar Hiba , Patel Kishan V
Published: June 2023

Case Presentation:
A 70-year-old male with cardiac risk factors, cirrhosis, stage II cholangiocarcinoma, and a right internal jugular port-a-catheter, presented to the hospital following an unwitnessed syncopal episode one day after undergoing a therapeutic paracentesis. On presentation he was hemodynamically unstable and endorsed severe substernal chest pain. Diagnostic work-up revealed large bilateral pulmonary emboli, and large amounts of intravascular gas in the right brachial vein, superior vena cava (SVC), right atrium and ventricle (Figure A). He was immediately placed on supplemental oxygen, given intravenous fluids, and started on vasopressors. He was a poor candidate for mechanical thrombectomy thus tissue plasminogen activator (tPA) was administered, and he was admitted to the medical intensive care unit for further management.

Discussion:
Venous air emboli occur as rare complications of trauma or intravascular procedures when air or gas enters the vasculature. Symptoms are generally non-specific making them difficult to recognize. In this patient, a central port-a-catheter had been placed two months prior for chemotherapy administration. A central line provides a direct connection between the air and the vasculature. The sub-atmospheric pressures in the SVC, where these lines often terminate, create a pressure gradient conducive to the development of air emboli. Hypovolemic states as seen in cirrhosis and pulmonary emboli) can further magnify this gradient. Interestingly, the presence of a large venous air embolism and concurrent massive bilateral pulmonary emboli, has rarely been previously reported. Caution should be taken in prevention, early detection, and treatment to avoid potentially fatal complications.
Abstract 15577: Clinical Outcomes in Hypertensive Emergency: A Systematic Review and Meta-Analysis
Authors: Siddiqi Tariq J , Usman Muhammad Shariq S , Rashid Ahmed Mustafa , Ahmed Aymen , Clark Donald , Flack John M , Shimbo Daichi , Jones Daniel W , Hall Michael E
Published: June 2023

Introduction:
Despite the increasing rate of hypertensive emergency (elevated blood pressure with acute target organ damage) presentations in the emergency department (ED), subsequent morbidity and mortality data to support clinical decision making remains scarce. We aim to study the prevalence and prognosis of hypertensive emergencies and hypertension mediated organ damage (HMOD) in patients presenting to the ED.

Methods:
PubMed and Scopus were queried from their inception through the mid of November 2021. Studies were included if they reported the prevalence or prognosis of hypertensive emergencies in patients presenting to the ED. Data from each study was arcsine-transformed and pooled using a random-effects model.

Results:
Fourteen studies (n = 4370 patients) were included in our analysis. Pooled analysis demonstrates that the prevalence of hypertensive emergencies was 0.5% (95% CI: 0.40 - 0.60) in patients presenting to ED. Ischemic stroke 28.1% (95% CI: 18.7 - 38.6), was the most prevalent HMOD, followed by pulmonary edema/acute heart failure 24.1%, (95% CI: 19.0 - 29.7, hemorrhagic stroke 14.6%, (95% CI: 9.9 - 20.0), acute coronary syndrome 10.8%, (95% CI: 7.3 - 14.8), renal failure 8.0%, (95% CI: 2.9 - 15.5), subarachnoid hemorrhage 6.9%, (95% CI: 3.9 - 10.7), encephalopathy 6.1%, (95% CI: 1.9 - 12.4), and the least prevalent was aortic dissection 1.8%, (95% CI: 1.1 - 2.8) (
Figure
). Mortality rate among patients admitted to the hospital due to hypertensive emergency was 9.9% (CI: 1.4 - 24.6).

Conclusions:
Our findings demonstrate substantial morbidity and mortality amongst patients presenting to the ED with hypertensive emergency. Results of studies may help clinicians identify organs at highest risk of damage in patients with hypertensive emergency, aiding the work-up and therefore helping curb the burden of this disease.
Abstract 15578: A Rare Case of Anomalous Left Main Coronary Artery Origin Presenting as ST Elevation Myocardial Infarction
Authors: Zakka Patrick , Eyvazian Vaughn , Assadi Ramin
Published: June 2023

Background:
ST-segment elevation myocardial infarctions (STEMI) are uncommon presentations of coronary artery anomalies and pose challenges in the emergent setting of percutaneous coronary interventions. We describe an extremely rare case of left main coronary artery (LMCA) originating off the right coronary artery (RCA) in a patient who presents with STEMI and was found to have Medina 1,1,1 lesion at the origin of the anomalous (LMCA).

Case Presentation:
An 81-year old male, with a past medical history significant for aortic stenosis and hyperlipidemia, presents to the emergency room for substernal non-radiating chest pressure. His electrocardiogram showed ST segment elevations in inferior and anterior leads. He was taken emergently to the cardiac cath lab. Coronary angiogram revealed a single right coronary ostium with an anomalous LMCA to mid left anterior descending (LAD) artery via dual insertion within a myocardial bridge. There was severe 90% Medina 1,1,1 bifurcating proximal RCA stenosis and 90% proximal LMCA stenosis. The entire left coronary system was fed by the anomalous LMCA, which was inserted into the mid-LAD in a dual insertion, between which there was a myocardial bridge. Cardiothoracic surgery team was consulted, and decision was made to pursue coronary artery bypass grafting (CABG). An intra-aortic balloon pump was placed via right femoral artery and patient was taken for emergent surgery, where he underwent 3 vessel CABG (left internal mammary artery to LAD, saphenous venous graft to obtuse marginal branch and posterior descending artery).

Discussion:
A broad spectrum of coronary anomalies have been reported, but their incidence in STEMI is rare. We discuss a very rare anomaly in which the entire left coronary system branches off the RCA, and culprit lesion was found to be a Medina 1,1,1 lesion. We aim to add to the sparce data pool of STEMI management in patients with anomalous coronary arteries.
Abstract 15588: Effect of Covid-19 on the Mortality of Patients With Congenital Heart Disease
Authors: Yang Yanxu , Huang Eugene , Claxton J'Neka , Kuo Kristina W , Oster Matthew , Kochilas Lazaros
Published: June 2023

Introduction:
Cardiovascular conditions have been recognized as risk factors for poor outcomes in association with COVID-19. However, the effect of the COVID-19 pandemic on different severity types of congenital heart disease (CHD) patients remains unknown. This study aims to examine whether patients with history of interventions for CHD experienced a higher mortality risk during the COVID-19 pandemic.

Methods:
This is a retrospective cohort study using data from the Pediatric Cardiac Care Consortium (PCCC). We included patients having US residence and direct identifiers, who were enrolled between 1982 and 2003 after undergoing transcatheter or surgical interventions for CHD. The observation window (2017-2020) was divided to a pre-SARSV2 and SARSV2 exposure period defined around the state specific onset of COVID-19 disease in 2020. Patients were categorized as having mild, moderate, severe-2 ventricle (2V) or single ventricle (SV) CHD. Standardized mortality ratios (SMRs) were used to describe the observed risk of mortality in CHD patients compared to the age- and sex-adjusted rates from the general U.S. population. Multivariable analysis was conducted using time-varying covariate Cox proportional hazards model with adjustment for age, sex and severity of CHD.

Results:
A total of 50,138 patients with history of interventions for CHD were included. Pooled pre-SARSV2 SMR was 2.38 [95% CI: 2.06, 2.75], while the SARSV2-exposure SMR was 2.07 [95% CI: 1.78, 2.35] (not significantly different). No significant differences in pooled SMRs were found by severity of CHD. The adjusted hazard risk for all-cause mortality in the SARSV2-exposure vs pre-SARSV2 period did not increase for patients with CHD (aHR: 0.59, 95%CI:0.19 - 1.84), and we did not find any differences in risk by severity subgroups or sex of patients.

Conclusion:
In this large cohort study monitoring long term outcomes after interventions for CHD, we could not detect any evidence of increased risk for all-cause mortality among this population during the early part of the COVID-19 pandemic. Additional data will be required over longer period to fully understand the impact of COVID-19 on adults with repaired CHD.
Abstract 15607: Right Ventricular Diastolic Function: A Machine Learning-Based Echocardiographic Classification Scheme
Authors: Shaviv Ella , Vajihi Zara , Sebag Igal , Rudski Lawrence G , Galatas Christos , Hayman Victoria , Murray Nancy , Blais Marie-Josée , Afilalo Jonathan
Published: June 2023

Background:
Right ventricular (RV) diastolic dysfunction is associated with heart failure and adverse cardiac events. Echocardiography guidelines include a limited assessment of RV diastology based on a scheme borrowed from the left ventricle, which is suboptimal.

Hypothesis:
An RV-specific classification scheme could be developed using echocardiographic parameters and machine learning to better reflect right-sided physiology and diagnose diastolic dysfunction.

Methods:
A total of 540 consecutive outpatients undergoing clinically-indicated echocardiograms at the Jewish General Hospital between March and December 2019 were prospectively recruited. Measurements relevant to RV diastology were acquired in triplicate by trained cardiac sonographers and verified by level III echocardiography staff and fellows. A sequential approach of unsupervised and supervised machine learning was used to develop a
de novo
classification model for RV diastology.

Results:
First, to prevent the use of redundant echocardiographic parameters within any given model, a feature-level clustering algorithm classified the 35 candidate parameters into mutually exclusive groups (for example, a group containing various size parameters). Second, a patient-level clustering algorithm analyzed all possible combinations of parameters in order to classify patients into three groups: normal, intermediate, and abnormal diastolic function. Third, a decision tree algorithm analyzed the top performing combinations in order to rank the importance of the echocardiographic parameters in predicting the diastology groups. Finally, after selecting the most predictive parameters - Ep, Ep/Ap, and IVC sniff - the final decision tree algorithm was generated. The prevalence of heart failure increased stepwise from 14% in the normal group, to 19% in the intermediate group, and 32% in the abnormal group.

Conclusions:
Our echocardiographic classification scheme for RV diastology is uniquely tailored to right-sided physiology and identifies patients with increasing rates of heart failure. Further study is warranted to validate this scheme in an independent population and examine its prognostic value for adverse cardiac events.