bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16717: Features of the Candidate Genes Polymorphisms Accumulation in Population of Hypertensive Patients of Different Age Groups
Authors: Bondar Vadym , Chernyshova Kateryna , Chernyshova Halyna , Bondar Kateryna , Klochko Viktor , Kolomiets Sergei , Maznichenko Iegor , Oliynyk Dmitrii
Published: November 2020

Introduction:
Nowdays the analysis of gene candidates polymorphisms and formation of genetic risk scores are actively being used in diagnostic and preventive management in arterial hypertension (AH).

Hypothesis:
The purpose of the research was to analyze and compare the proportion of modified candidate genes (CG) of AH in different age groups by calculating the gene modification index (GMI) for confirmation of the hypothesis of modified genes accumulation through generations.

Methods:
182 patients with AH were examined, mean age 44,3 [18-75], m/f=95/87, (ESC/ISH 2018). Patients were divided into 3 groups depending on age: 1st group - from 18 to 30 y.o. (n=48, m/f=27/21); 2nd group - from 31 to 55 y.o. (n=74, m/f=34/40); 3rd group - from 56 to 75 y.o. (n=60, m/f=28/32). Patients were analysed on the the following CG by PCR: ADD1: 1378, AGT: 704, AGT: 521, AGTR1: 1166, AGTR2: 1675, CYP11B2: - 344, GNB3: 825, NOS3: -786 , NOS3: 894. The GMI which represents the percentage of "pathological" genotypes. The GMI from 0 to 20% was considered as low genetic risk (GR), from 21 to 40 % - moderate GR, from 41 to 70% - high GR, from 71 to 100% - very high GR.

Results:
In 1 group the average GMI was 64,7% [CI 95%, 29-74], with low GR in 2 (4,2%), moderate GR - in 10 (20,8%), high GR - in 22 (45,8%), very high GR - in 14 (29,2%) patients. In 2 group the average GMI was 56,2% [CI 95%, 18-72], 12 (16,2%) patients had low GR, moderate GR was in 20 (27,1%), high GR - in 26 (35,1%), very high GR - in 16 (21,6%) patients. In 3 group the average GMI was 42,4% [CI 95%, 16-71], low GR was in 16 (26,7%), moderate GR - in 22 (36,7%), high GR - in 14 (23,3%), very high GR - in 8 (13,3%) patients. Analyzing data between the groups, a strong significant difference in GMI was between 1 and 3 groups (64,7% vs 42,4%, p=0,002), high significant differences were also between the 1 and 3 groups, especially in the proportion of patients with high GR (45,8% vs 23,3%, p=0,001) and very high GR (29,2% vs 13,3%, p=0,008) in the group of young patients.

Conclusions:
It was revealed in the research the accumulation of pathological genetic polymorphisms in the population of hypertensive patients through generations. It was found the strong significant difference in the proportion of "pathological" GP between young and older patients.
Abstract 16718: The Impact of Prior Revascularization in Acute Myocardial Infarction Patients With Cardiogenic Shock: Prior Bypass Surgery a Marker of Worse Outcome?
Authors: Gruberg Luis , Gandotra Puneet , Selim Samy , Supariwala Azhar , Ong Lawrence
Published: November 2020

Background:
Cardiogenic shock (CS) in patients with acute myocardial infarction (AMI) is a marker of worse prognosis with extremely high mortality rates. We assessed the impact of previous surgical revascularization by CABG or percutaneous coronary intervention (PCI) on in-hospital outcomes of AMI patients with CS undergoing primary PCI.

Methods:
Between 1/2010 and 5/2019, a total of 1,170 patients were diagnosed with AMI and CS, defined by New York State Percutaneous Coronary Interventions Reporting System (PCIRS) as acute and persistent systolic blood pressure <80 mmHg on mechanical or pharmacological support. Baseline clinical, angiographic and procedural characteristics, as well as in-hospital outcomes were prospectively collected among all patients undergoing primary PCI as part of the New York State PCIRS data collection.

Results:
There were no significant baseline differences between the two groups. Patients with a prior CABG were older and had a history of congestive heart failure. All other risk factors were similar (Table). There was a trend towards higher mortality rates in post CABG patients but longer length of stay in post PCI patients. The combined endpoint of death, reinfarction, acute kidney failure requiring dialysis or stroke (MARCCE) was numerically higher in post CABG patients but did not reach statistical significance.

Conclusions:
The results of this study show that in patients with AMI and CS undergoing PCI: 1) Patients with a prior history of CABG are usually older at presentation and had a prior history of heart failure; 2) there was a trend to higher in-hospital mortality rates in post CABG patient but MARCCE rates were similar in both groups.
Abstract 16726: Impact of Angiotensin Converting Enzyme Inhibitors/angiotensin Receptor Blockers on Mortality and Severity of Covid-19 Pneumonia
Authors: Aggarwal Ankita , Jain Anubhav , Goel Mishita , Tusha Jurgena , Khanam Verisha , Bidhan Sourabh , Khan Ameer , Dhawan Monica , tegeltija vesna , kumar sarwan
Published: November 2020

Introduction:
Coronaviruses are a large family of viruses that have been around for many years and may cause illness in humans or animals. In early December 2019, the first pneumonia cases related to the coranoavirus were found which has since led a pandemic. Coronaviruses bind to their target cells through angiotensin-converting enzyme 2 (ACE2), which is expressed by epithelial cells of the lung, intestine, kidney, and blood vessels.

Hypothesis:
Hypothetically, the increased expression of ACE2 would facilitate infection with COVID-19 and treatment with ACE2-stimulating drugs may worsen the infection with COVID-19. The goal of this study was to analyze the severity of COVID-19 in patients who are on ACEi and ARB therapy.

Methods:
All adult patients admitted with the confirmed diagnosis of COVID 19 pneumonia between March to April 2020 in our community hospital were included in the study. Patients were then be divided into two groups, one group who received ACEi or ARBs and a second group who did not. The baseline characteristics of two groups were compared. Primary outcome was the in-hospital mortality between two groups. Secondary outcomes were severity of pneumonia including rate of intubation, requirement for ICU admission and total length of hospital stay.

Results:
A total of 200 patients were admitted with the time frame studied. After removing for missing data 194 patients were included in the study of which 64 patients received either ACEi or ARB during the hospital stay. There was no difference in the rate of inpatient mortality in patients who received or did not received the drug (32.3% vs 23.5% p- value 0.19). Similarly, there was no difference in the other outcomes including rate of intubation(22.6% vs 24.4% p- value 0.79), requirement for ICU admission(21% vs 33.3% p-value 0.07) and mean total length of hospital stay between the two groups (9.5 days vs 8.4 days p-value 0.34).

Conclusion:
There was no difference in the outcomes. Patients who received ACEi or ARBs did not have worse outcomes. Thus, if indicated for other reasons, these drugs can safely be continued in patients with COVID 19 pneumonia. Further large center studies are however, required to confirm our findings.
Abstract 16733: Immune Response Following Allogenic Cardiac Progenitor Cells Transplantation in Rat Myocardial Infarction Model
Authors: Gunasekaran Muthukumar , Mishra Rachana , Saha Progyaparamita , Shah Aakash , Lauren Davidson , Fu Xuebin , Arfat Yasir M , Abdullah Mohamed , Sharma Sudhish , Kaushal Sunjay
Published: November 2020

Cardiac progenitor cells (CPCs) are well-characterized stem cell type shown to potentiate cardiac regeneration in myocardial infarct (MI) model. However, auto and allo immune response to transplanted adult CPCs (aCPCs) reduces cell retention and MI recovery. We aimed to increase the regenerative potential of aCPCs by reducing immune response directed to the transplanted aCPCs using cyclosporine A (CsA). Adult CPCs isolated from Wister Kyoto rat was transplanted into Brown Norway MI rats. MI rats transplanted with aCPCs+CsA demonstrated significant increase in MI recovery and cell retention compared to MI rats with aCPCs, CsA and Iscove Modified Dulbecco Media controls (p<0.05). MI rats transplanted with aCPCs showed increased infiltration of CD68
+
cells and apoptotic cells in the infarcted myocardium compared to aCPCs+CsA group (p<0.05) analyzed by immunohistochemistry. Sera collected on day 2 and 7 of aCPCs group showed increased inflammatory cytokines (IL-2, IL-17, IFN-γ, TGF-β), antibodies to cardiac SAgs (Troponin-T and Myosin) allo antigens (RT1A, RT1B and RT1D) and reduced anti-inflammatory cytokines (IL-10). In contrast MI rats transplanted with aCPCs+CsA showed reduced inflammatory cytokines, abs to SAgs, allo antigens and increased anti-inflammatory cytokine IL-10 (p<0.05). In conclusion, MI rats transplanted with allogeneic aCPCs with immune suppressant CsA showed increased cell retention, reduced inflammatory cells and cytokines compared to aCPCs, CsA and IMDM control. Therefore, CsA reduces auto and allo immune response and increases regeneration potential by increased transplanted aCPCs retention that resulted in enhanced myocardial recovery.
Abstract 16742: Single-Cell Transcriptional and Epigenomic Dissection of Human Heart in Health and Coronary Artery Disease Reveals Cell-type-Specific Driver Genes and Pathways
Authors: Linna Kuosmanen Suvi , Schmauch Eloi , Galani Kyriakitsa , Boix Carles , Park Yongjin P , Hollmen Maija , Gunn Jarmo , Kiviniemi Tuomas O , Garcia-Cardena Guillermo , Kellis Manolis
Published: November 2020

Genome-wide association studies have uncovered over 200 genetic loci underlying coronary artery disease (CAD), providing great hope for a deeper understanding of the causal mechanisms leading to this disease. However, in order to understand CAD at the molecular level, it is necessary to uncover cell-type-specific circuits and to use these circuits to dissect driver variants, genes, pathways, and cell types, in normal and diseased tissues. Here, we provide the most detailed single-cell dissection of human heart cell types, using cardiac biopsies collected during open-heart surgery from healthy, CAD, and CAD-related heart failure donors, and profiling both transcriptional (scRNA-seq) and epigenomic (scATAC-seq) changes. Using this approach, we identify 12 major heart cell types, including typical cardiovascular cells (cardiomyocytes, endothelial cells, fibroblasts), rarer cell types (B cells, neurons, Schwann cells), and previously-unrecognized layer-specific epithelial and endothelial cell types. We define markers for each cell type, providing the first extensive reference set for the living human heart. In addition, we define differential gene expression patterns in CAD relative to control samples, revealing substantial differences in cell-type-specific expression of disease-related genes, emphasizing, for example, the importance of the vascular endothelium in the pathogenesis of CAD. Strikingly, further clustering of the cell types based on specific subtypes revealed important differences in their expression patterns of disease-associated genes. These changes enrich in known CAD genetic loci, enabling us to recognize their likely target genes from scRNA-seq expression changes, candidate driver variants based on scATAC-seq localization and differential DNA accessibility, and candidate upstream regulators based on their enriched motif occurrences in scATAC loci. Overall, our results highlight the relevance and potential of single-cell transcriptional and epigenomic analyses to gain new biological insights into cardiovascular disease, and to recognize novel therapeutic target genes, pathways, and the cell types where they act.
Abstract 16745: Effect of the Baseline Use of Angiotensin-Converting Enzyme Inhibitors (ACEIs) or Angiotensin-Receptor Blockers (ARBs) on Outcomes of Patients With Suspected or Positive COVID-19 Infection
Authors: Muhlestein Joseph B , Knowlton Kirk U , May Heidi T , Knight Stacey , Bair Tami L , Le Viet T , Horne Benjamin D , Anderson Jeffrey L
Published: November 2020

Introduction:
SARS-CoV-2 requires the ACE-2 receptor to gain cellular entry, leading to concerns as to whether the use of ACEIs/ARBs may adversely affect patients (pts) exposed to the virus. Because of the potential for multiple confounding variables, determining their real impact through observational study may require the use of a carefully adjusted dataset.

Methods:
We collected data, including baseline characteristics and medication use, on 104,018 pts tested at Intermountain Healthcare for SARS-CoV-2 up to June 8, 2020, and determined their hospitalization and intensive care unit (ICU) admission status. We used multivariable regression analysis to ascertain the independent effect of the baseline use of ACEIs or ARBs on the risk of each outcome.

Results:
Tables 1 and 2 show baseline characteristics, including the use of ACEIs/ARBS, of test-positive versus -negative pts and, among test-positive pts, who did or did not require hospitalization and ICU care, respectively. In the entire cohort, test-negative pts were more likely to have multiple comorbidities and on ACEIs/ARBs. In the test-positive group, hospitalized patients were more likely to have comorbidities and to be taking ACEIs/ARBs. However, after multivariable adjustment, the baseline use of ACEIs/ARBs was associated with a reduced likelihood of being test-positive (OR=0.87, p=0.04), a reduced need for hospitalization (OR = 0.58, p=0.004), and a numerically reduced need for ICU placement (OR = 0.74, p=0.32).

Conclusions:
Selection bias regarding viral testing likely influenced the baseline characteristics of the entire tested population. Test-positive patients requiring hospitalization also had more comorbidities and used more ACEIs/ARBs. However, after multivariable adjustment, because of a strong correlation with comorbidities, the use of ACEIs/ARBs became associated with a reduced need for hospitalization and ICU admission. These findings provide further evidence of ACEI/ARB safety.
Abstract 16754: Novel Characterization of Pulmonary Artery Bending, Rather Than Stenosis, Detects Increased Right Ventricular Afterload and is Associated With Increased Right Ventricular Mass in the Post-Arterial Switch Operation Heart
Authors: Delaney Marc A , Mass Paige , Capuano Francesco , Loke Yue-hin , Olivieri Laura
Published: November 2020

Introduction:
Surgical treatment of transposition of great arteries involves the Arterial Switch Operation (ASO) and the LeCompte maneuver, where the pulmonary artery (PA) and its bifurcation are translocated anterior to the neoaortic root, creating relative PA stenosis and exaggerated PA bending. Assessment of branch PA dimensions can identify stenosis, however complex 3-dimensional bending without clear stenosis may contribute to elevated right ventricular (RV) afterload. Initial data suggest elevated RV afterload and RV mass are prevalent in these patients but the etiology and associated risk factors remain unclear.

Hypothesis:
In post-ASO patients, more extreme PA bending, as described by radius of curvature, will be associated with elevated RV afterload and RV mass independently of relative PA stenosis.

Methods:
Retrospective single-center analysis of 22 post-ASO patients was performed, representing native anatomy of D-TGA with (15, 68%) and without (7, 32%) intact ventricular septum, excluding those with PA stent, pulmonary hypertension, or other anatomical confounders. RV systolic pressure (RVSP) was recorded from echocardiography (11, 50%) or catheterization (11, 50%) and correlated to cardiac magnetic resonance (CMR) imaging measurements including: radius of curvature (Rcw) weighted to differential pulmonary blood flow and RV mass indexed to body surface area.

Results:
In ASO patients, receiver operating characteristic curve demonstrated Rcw, but not PA stenosis, moderately detected presence of elevated RVSP (>40 mmHg) (respectively: AUC 0.84, p = 0.03 and AUC 0.49, p =0.60). Patients with elevated RV Mass had more extreme Rcw (when normalized to body surface area), but no difference in PA stenosis via Nakata index (respectively: p = 0.10, p = 0.02).

Conclusions:
Abnormal PA bending as described by Rcw is associated with increased RV afterload and RV Mass. Rcw may serve as a promising future clinical proxy to RV afterload.
Abstract 16757: Immunomodulatory Hydrogel Promotes Survival of Mesenchymal Stem Cells in a Rat Model of Myocardial Infarction
Authors: Olthoff Michaela , Nagaiah Naveen , Franchi Federico , Yan Weiang , Dhingra Sanjiv , Paulmurugan Ramasamy , Rodriguez-Porcel Martin
Published: November 2020

Introduction:
Stem cell (SC) therapy is a potential method of repairing the heart after injury. However, SCs have been shown to have poor survival after transplantation, at least in part, due to a hostile pro-inflammatory ischemic myocardium. Thus, there is significant interest in the identification of strategies that can increase the retention/survival of SCs after transplantation. Here we seek to investigate whether the use of an immunomodulatory hydrogel, containing anti-inflammatory sinapic acid (SA), promotes the survival of SCs after transplantation.

Methods:
Myocardial infarction was induced in rats followed by the delayed delivery of A) mesenchymal stem cells (MSCs), B) MSCs in a hydrogel without SA or C) MSCs in a hydrogel containing SA (10μM). Delivery of MSCs (7.5 x 10
5
in 30μL) occurred 7 days after MI, representing the subacute stage and to minimize acute inflammation. Survival of MSCs, stably expressing firefly luciferase under the constitutive CMV promoter, was followed longitudinally using bioluminescence imaging.

Results:
Panels A-C provide representative images of the viability of MSCs in different groups, with the quantification shown in panel D. There were no differences in survival when MSCs were delivered alone (A) or in a hydrogel without SA (B). However, the survival of MSCs was significantly increased when they were transplanted in a hydrogel with the anti-inflammatory SA (C).

Conclusions:
Here we provide evidence of the potential for an immunomodulatory hydrogel to enhance the viability of MSCs after infarction, which may lead to improvement of cardiac function. Furthermore, use of this hydrogel in combination with stem cells could be a potential therapeutic strategy for ameliorating cardiac repair after significant damage.
Abstract 16765: Sustained Total All-Region Perfusion During the Norwood Operation is Associated With Improved Post-Operative Recovery
Authors: Meza James M , Benkert Abigail , Prabhu Neel , Allareddy Veerajalandhar , McCrary Andrew , Andersen Nicholas D , Turek Joseph W
Published: November 2020

Introduction:
We developed a technique for Stage 1 “Norwood” reconstruction with continuous perfusion of the head, heart, and lower body at mild hypothermia, deemed Sustained Total All-Region (STAR) perfusion.

Hypothesis:
We hypothesized that STAR perfusion would shorten cardiopulmonary bypass and procedural times and expedite post-operative recovery, due to lack of cooling and re-warming and decreased total body ischemia.

Methods:
Between 2012-2019, 65 infants underwent Norwood reconstruction at our institution. Those who underwent prior pulmonary artery banding were excluded, yielding a cohort of 51 infants who underwent primary Norwood reconstruction. Outcomes for patients who underwent Norwood reconstruction using STAR perfusion (n=21) were compared to those who underwent Norwood reconstruction with conventional techniques using regional cerebral perfusion only (n=30). STAR perfusion was performed with innominate artery cannulation as well as olive tip cannulas inserted into the opened descending aorta and native aortic root to provide continuous perfusion of the head, heart, and lower body throughout the procedure (Figure), under mild hypothermia (32-34°C).

Results:
Norwood reconstruction with STAR perfusion was associated with shorter median CPB times vs. conventional perfusion techniques (161 vs. 226 mins,p<0.0001) and elimination of myocardial ischemia (0 vs. 90 minutes cross-clamp time,p<0.0001). Total operative time was reduced by over 3 hours (319 vs 514 mins,p<0.0001), likely in part due to improved post-bypass coagulopathy. Improvements in post-operative recovery were noted with STAR perfusion, including more rapid normalization of serum lactate (19.3 vs. 26.5 hours, p=0.0009), lower peak serum lactate (8.6 vs.10 mmol/dL, p=0.04) and fewer days to chest closure (3 vs. 5 days, p=0.04). Survival to hospital discharge (95% vs 83%, p=0.38) was similar between groups.

Conclusions:
Norwood reconstruction with STAR perfusion is a safe technique that eliminates ischemic time to the heart and lower body and allows for the procedure to be performed at warmer temperatures. We found evidence of reduced CPB and operative times, as well as improved hemostasis, end-organ function, and post-operative recovery with this technique.
Abstract 16778: Ventricular Tachycardia Ablation Outcomes Based on Scar Location in Patients With Ischemic Cardiomyopathy
Authors: Mamillapalli Himanayani , Florea Viorel G , Veligandla Sravya , Murthy Smitha , Li Jian-Ming , Tholakanahalli Venkatakrishna N
Published: November 2020

Introduction:
Catheter ablation of ventricular tachycardia (VT) reduces implantable cardioverter defibrillator (ICD) therapies, improves hospitalization, and improves survival in patients with ischemic cardiomyopathy (ICM).

Hypothesis:
The goal of this study is to evaluate outcomes of patients with VT ablation by scar location in patients with ICM.

Methods:
Consecutive retrospective review of patients with ICM who underwent VT ablation at Minneapolis Veterans Affairs Health Care system between July 2008 and September 2019 were assessed for clinical outcomes.

Results:
Seventy-five patients with ICM underwent VT ablation during the study period. Average age was 67.6 ± 7 years old and 100% Male. Three patients were lost to follow up. Overall mortality was 53.3% and was highest in the inferior wall scar (IWS) group (Figure 1A, Table). Mean survival after ablation was 2.2 years. Most common cause of death was cardiac which included congestive heart failure, myocardial ischemia, and cardiac arrest (VT and pulseless electrical activity) (Figure 1B). On post-ablation echocardiogram, patients with anterior wall scar (AWS) had a lower mean ejection fraction (23%) compared to IWS group (30%) and this was statistically significant (p < 0.03, two-tailed t-test). The average number of ablations for recurrent VT was 1.4 with no significant difference between the groups. Fifty-five percent of patients were on anti-arrhythmics post ablation.

Conclusions:
VT ablation patients with IWS mediated VT have a trend towards higher mortality compared to those with AWS. This may be due to neuroregulatory pathway of VTs based on cardiac innervation.
Abstract 17146: Late Gestation Fetal Growth in Infants Undergoing Stage 1 Palliation for Single Ventricle Heart Disease
Authors: Schneider Kristin , Marcuccio Elisa , Cnota James F , Heydarian Haleh , Khoury Philip R , Hill Garick D
Published: November 2020

Introduction:
Ideal timing for elective delivery of infants with single ventricle heart disease, balancing benefits of fetal growth with risk of fetal demise, remains unclear. Improved understanding of fetal growth in late gestation and postnatal outcomes related to gestational age (GA) may improve insight.

Hypothesis:
Patients with single ventricle heart disease and aortic hypoplasia have decreased fetal growth velocity in late gestation, but longer gestation results in improved outcomes.

Methods:
This was a retrospective cohort analysis of patients in phase 2 of the National Pediatric Cardiology Quality Improvement Collaborative database from 2016-2019 who were anticipated to need stage 1 palliation (S1P) and had a GA of
>
36 weeks. Birth weight (BW) and BW z-scores were compared across GA to normative values. Outcome measures of survival to stage 2 palliation (S2P), post-S1P length of stay, and duration of mechanical ventilation were compared by GA.

Results:
The cohort included 1290 infants. There was an increase in mean BW with increasing GA (2.83 kg at 36-37 weeks, 3.15 kg at 38 weeks, 3.33 kg at 39 weeks, 3.40 kg at
>
40 weeks; p <.0001). BW z-scores were below zero at all points in late gestation (-0.29 at 36-37 weeks, -0.17 at 38 weeks, -0.20 at 39 weeks, -0.52 at
>
40 weeks; p <.0001), with a slower rate of growth beyond 39 weeks GA. Of 1216 patients with available mechanical ventilation data, patients born at later GA had shorter durations of ventilation (11.3 days at 36-37 weeks GA, 9.2 days at 38 weeks, 7.6 days at 39 weeks, 6.6 days at
>
40 weeks; p=0.0001). Among 1083 survivors to discharge or S2P if not discharged, there was no difference in post S1P length of hospitalization across GA (p=0.19). Infants who reached S2P readiness milestones were more likely to undergo S2P if born after longer gestation (p=0.0001).

Conclusions:
Infants with single ventricle heart disease and aortic hypoplasia have decreased growth velocity in late gestation, but growth continues. Infants born after longer gestation have improved outcomes with shorter duration of ventilation and greater likelihood of undergoing S2P.
Abstract 17170: Does Cardiopulmonary Bypass Provide Adequate End-Organ Perfusion?
Authors: Koprivanac Marijan , Aly Ahmed , Magruder Jonathan , Acker Andrew , Grim Joshua , acker michael , Cevasko Marisa , Desai Nimesh
Published: November 2020

Introduction:
Our clinical experience in cardiac surgery teaches us that a subset of patients show signs of unexplained end-organ hypoperfusion after an otherwise unremarkable procedure. The objective of this study is to comprehensively examine cardiopulmonary bypass (CPB) management parameters and end-organ perfusion.

Hypothesis:
Despite advancements in CPB management, CPB does not provide adequate end-organ perfusion.

Methods:
Retrospective analysis was performed using data from 1462 cardiac operations performed from 2/2019 to 4/2020, excluding circulatory arrest and non-CPB cases. CPB management parameters included cardiac index (CI), mean arterial pressure (MAP), vasopressor-phenylephrine use, lines and bladder temperatures, hemoglobin (Hgb), indexed oxygen delivery (iDO
2
), and intravenous fluid infusion. End-organ perfusion markers included lactate levels, mixed venous oxygen saturation (SvO
2
), oxygen consumption (VO
2
), and arterial pH. Results were expressed as means with first standard deviation.

Results:
During CPB, CI, MAP, iDO
2
and Hgb were 2.2 ± 0.4 l/min/m
2
, 67 ± 16 mmHg, 270 ± 71 ml/min/m
2
, and 9.3 ± 1.6 g/dl respectively (Figure 1). Phenylephrine cumulative dose increased with CPB duration, 11 ± 9 mg at 1h and 20 ± 15 mg at 2h. Fluid administration showed similar trend. Core mean temperature was maintained with nadir being 33.5 ± 3.4°C. SvO
2
rapidly increased with institution of CPB, peaking at 85%, and then slowly declined. Inversely, VO
2
dropped and then slowly increased. Lactate continuously increased with duration of CPB.

Conclusions:
Our findings suggest that despite hemodynamic values being maintained at goal by continuously high vasopressor use and fluid administration during CPB, tissue perfusion was inadequate.Our study suggests that, using data-driven approaches, it may be time to revisit the assumptions regarding all aspects of managing CPB.
Abstract 17184: An Increase in the Respiratory Effort Immediately Intensifies the Hemodynamic Congestion; a Mechanism for Progressive Cardiac Decompensation
Authors: Markovitch Noa , Rispler Shmuel , Feld Yair , Solomonica Amir , Yalonetsky Sergey , ROGUIN ARIEL , Kerner Arthur , Landesberg Amir
Published: November 2020

Introduction:
An increase in the pulmonary wedge pressure (PCWP) is associated with an increase in the respiratory effort and the sensation of dyspnea.

Hypothesis:
We investigated the inverse cause and effect relationship, whether an increase in the respiratory effort can by itself aggravate the hemodynamic congestion.

Methods:
We scrutinized the cardiopulmonary interactions by simultaneously measuring hemodynamic and respiratory indices in heart failure (HF) patients undergoing right heart catheterization. The immediate effects of the respiratory effort on the hemodynamic indices were analyzed by asking the patients to perform short events of apnea and intentional vigorous breathing. The cardiac waves are superimposed on the respiratory waves in the PCWP. To quantify the respiratory effort, the PCWP was decomposed into cardiac and respiratory waves. The respiratory effort (PRESP) was defined as the peak to peak swing in the respiratory wave that modulated the PCWP.

Results:
HF patients (n=38) exhibited a high PRESP of 9.0±3.2 mmHg, ~3.5-fold higher than the reported normal respiratory effort. The end-expiratory PCWP rose with PRESP, by 0.83±0.06 mmHg for every 1 mmHg of PRESP (p<0.01). The pulmonary artery pressure (PAP) rose with PRESP by 1.40±0.09 mmHg for every 1 mmHg of PRESP. The changes in the respiratory effort had immediate effect on PCWP, within a single breathing-cycle (t =1.67±0.40 s) in all patients. Interestingly, similar changes in the PCWP with PRESP were obtained in all the patients, independently of the HF etiology.

Conclusions:
An increase in the respiratory effort is not just a result of cardiac decompensation. The respiratory effort has immediate detrimental effects on the PCWP, PAP and the workloads of the heart. The results highlight the existence of a cardiopulmonary vicious cycle the can lead to progressive decompensation, where the respiratory effort plays a pivotal role.
Abstract 17193: Acute and Short-Term Outcomes of Percutaneous Transcatheter Mitral Valve Replacement in Children
Authors: Maschietto Nicola , Prakash Ashwin , Del Nido Pedro J , Porras Diego
Published: November 2020

Introduction:
Despite the improvement of surgical techniques for mitral valve (MV) repair in children, mitral valve replacement (MVR) is sometimes still necessary. MVR and redo-MVR continue to be burdened by early postoperative mortality and long-term morbidity with only about 75% of these patients being alive or transplant-free 10 years after the initial MVR. Although trans-femoral mitral valve replacement (TMVR) is a well-established intervention in high surgical risk adults, only a few pediatric Valve-in-Valve (ViV) case reports have been published.

Hypothesis:
We hypothesized that trans-venous transcatheter mitral valve replacement is feasible, safe, and effective in pediatric patients.

Methods:
Retrospective analysis of pediatric patients who underwent TMVR at Boston Children's Hospital between October 2018 and May 2020

Results:
7 consecutive high surgical risk pediatric patients (median age 9 years, range 8-15) underwent TMVR (6 as ViV, 1 in a native MV). Each patient previously underwent multiple MV surgeries or MVR (median 4, range 2-5) and was highly symptomatic (Ross functional class 3 or 4). The indication for TMVR was mitral stenosis in 5 patients, regurgitation in 1, and mixed disease in 1. TMVR was successful in each patient, effectively reduced the left atrium hypertension (p=0.018), and was carried out without significant complications.

Conclusion:
Trans-venous trans-catheter mitral valve replacement is an attractive alternative to MVR in high surgical risk patients. In this small series, TMVR was acutely effective and safe, with very encouraging early results.
Abstract 17202: Racial/Ethnic Minority Underreporting and Underrepresentation in Guideline-Driving Blood Cholesterol Clinical Trials
Authors: Sarraju Ashish , Valencia Areli , Knowles Joshua , Maron David J , Rodriguez Fatima
Published: November 2020

Introduction:
Cholesterol management is the cornerstone of atherosclerotic cardiovascular disease prevention. Diverse racial/ethnic participation in high-impact cholesterol trials is essential for the generalizability of trials and guidelines across the United States (US).

Methods:
We analyzed randomized clinical trials (RCTs) cited in the 2018 American Multi-society Guideline on the Management of Blood Cholesterol for reporting and representation of racial/ethnic minorities. We extracted participant level racial/ethnic data, including non-Hispanic White (NHW), Black, Hispanic, or Asian groups. For each race/ethnicity, we pooled trial data to assess overall representation compared to the general US population based on 2010 US Census and 2019 US Census American Community Survey estimates.

Results:
Among 71 cited RCTs from 1984 - 2017, 59.1% reported racial/ethnic data. NHW participation was reported in 58%, Black in 34%, Hispanic in 27%, and Asian in 17% (Figure). Four trials disaggregated Hispanic patients and none disaggregated Asians. Black trial representation was significantly lower than the US population per 2010 and 2019 Census data (trial: 5.5%, 2010: 12.6%, 2019: 13.4%,
P
<0.001). Hispanic trial representation was significantly lower compared to the US population (trial: 10.6%, 2010: 16.3%, 2019: 18.3%,
P
<0.001). NHW trial participation was lower compared to the US population (trial 69.2%; 2010: 72.4%; 2019: 76.5%,
P
<0.001), but with smaller relative differences compared to Black and Hispanic representation. Asian participation was higher than US census representation.

Conclusion:
Among guideline-driving cholesterol RCTs, Black and Hispanic participants are significantly underrepresented compared to the general U.S. population. Few studies disaggregate major racial/ethnic subgroups. These findings represent a source of systemic bias that may limit the generalizability of trials and guidelines and potentiate health inequities.
Abstract 17211: Targeting Mitogen-Activated Kinase Alleviates Free Heme-Induced Endothelial Barrier Dysfunction and Vascular Leakage in Lungs
Authors: James Joel , Valuparampil Varghes Mathews , zemskova Marina , Rafikova Olga , Rafikov Ruslan
Published: November 2020

Introduction:
Several studies confirm that free heme in circulation due to hemolysis causes endothelial barrier dysfunction. We recently demonstrated that hemolysis-induced vascular leakage with barrier dysfunction was a contributory factor to the development of pulmonary hypertension (PH). However, the precise molecular mechanisms involved in the pathology of heme induced barrier disruption still remains to be elucidated.

Hypothesis:
Previous studies by us showed that free heme activated the p38/MAPK pathway. Therefore, we hypothesized that targeting mitogen-activated protein kinase kinase 3 (MKK3) a key regulator of this pathway would alleviate heme induced vascular leakage.

Methods:
Barrier dysfunction in human micro-vascular endothelial cells (HLMVEC) was monitored using noninvasive electrical impedance and immunostaining. We used an MKK3 knockout mouse model to assess the efficacy of targeting the p38/MAPK pathway.

Results:
We found a rapid drop in the HLMVEC barrier integrity with heme, in a dose dependent manner (p<0.05). Investigating the barrier proteins showed that heme significantly affected the tight junction proteins, zona occludens-1, claudin1, and claudin5 (p<0.05). We also found the p38MAPK/HSP27 pathway, involved in regulating the endothelial cytoskeleton remodeling, to be significantly altered with heme treatment, both in the HLMVEC and mice (p<0.05). However, heme treated mice showed no significant change in E-selectin, ICAM1 and VCAM1, indicating that the primary rapid target of heme was the p38/MAPK pathway and not the inflammatory pathways. Finally, injecting mice with heme-FITC-dextran and then following its release into the lungs demonstrated that the MKK3 KO significantly prevented heme induced vascular leakage (p<0.05).

Conclusion:
We demonstrate that heme induces a rapid barrier dysfunction by disruption of endothelial barrier proteins via the p38/MAPK pathway. Also, knocking out MKK3, a crucial regulator of the p38/MAPK pathway significantly decreased heme induced vascular leakage, a contributory factor to PH. Taken together, our results show that targeting the MKK3/p38MAPK axis represents a decisive treatment strategy in alleviating heme induced barrier dysfunction in cardiovascular diseases.
Abstract 17220: Functional Roles and Molecular Mechanisms of Calcium Release Signaling in Hypoxic Cellular Responses in Pulmonary Artery Smooth Muscle Cells
Authors: Wang Yong-xiao , Zheng Yun-Min
Published: November 2020

Introduction:
Hypoxia causes contractile and proliferative responses in pulmonary arterial smooth muscle cells (PASMCs), but not systemic artery SMCs, thereby leading to pulmonary hypertension (PH), but not systemic hypertension. However, the underlying mechanisms remain unclear.

Hypothesis:
Ca
2+
release signaling in PASMCs may mediate hypoxic pulmonary artery vasoconstriction, remodeling and hypertension.

Methods:
Single cell RT-PCR and Western blot analysis, FRET and immunoprecipitation, tissue contraction assay, immunohistochemistry staining and pressure-volume loop analysis, and genetic and pharmacological approaches, were, respectively, used to determine targeted molecular expression, interaction and function.

Results:
All ryanodine receptor (RyR1, RyR2 and RyR3) Ca
2+
release channels are expressed in mouse PASMCs. RyR1 or RyR3 knockout (KO) partially inhibits, while RyR2 KO completely blocks, hypoxic cellular responses. SMC-specific RyR2 KO restores abolishes hypoxic pulmonary artery vasoconstriction, remodeling and hypertension in mice. RyR2 KO also inhibits hypoxic nuclear factor (NF)-κB and downstream cyclin D1 activation. FK506 binding protein 12.6 (FKBP12.6) is an endogenous RyR2 inhibitor; its KO or FK506 treatment enhances, and treatment of S107 (a specific RyR2/FKBP12.6 stabilizer) inhibits hypoxic PH. Lentiviral shRNA-mediated SMC-specific Rieske iron-sulfur protein (RISP) knockdown diminishes mitochondrial reactive oxygen species (ROS) generation, RyR2/FKBP12.6 complex dissociation, and RyR2 activation, thereby blocking hypoxic PH.

Conclusions:
RyR1, RyR2 and RyR3 are all involved in hypoxic contractile and proliferative responses in PASMCs, but RyR2 is a most important player. RISP-dependent mitochondrial ROS - FKBP12.6/RyR2 complex dissociation - RyR2 hyperfunction signaling mediate PA vasoconstriction. RyR2 hyperfunction also activates Ca2+-dependent NF-κB/cyclinD1 pathway to provoke PA remodeling; PA vasoconstriction and remodeling together cause PH. Furthermore, RISP-mediated ROS inhibition, RyR2/FKBP12.6 complex stabilization and Ca2+ release blockade may be novel and effective options for the treatment of PH.
Abstract 17230: Transcatheter Leak Occlusion With Endovascular Coils Following Left Atrial Appendage Closure
Authors: Della Rocca Domenico G , Horton Rodney , Di Biase Luigi , Tarantino Nicola , Romero Jorge , Gianni Carola , TRIVEDI CHINTAN G , Mohanty Sanghamitra , Gallinghouse G Joseph , Bassiouny Mohamed , Al-ahmad Amin , Sanchez Javier , Natale Andrea
Published: November 2020

Introduction:
The Transcatheter Leak Closure With Detachable Coils Following Incomplete Left Atrial Appendage Closure Procedures (TREASURE) is a prospective, nonrandomized, single-center study. This study was undertaken to investigate the efficacy of transcatheter leak closure with endovascular coils in patient with incomplete percutaneous/epicardial left atrial appendage (LAA) closure procedures and high thromboembolic (TE)- and bleeding-risk.

Hypothesis:
We report the efficacy of transcatheter leak closure with endovascular coils in patients with incomplete LAA closure.

Methods:
Sixty-five consecutive patients with a clinically relevant residual leak (mean age: 72±8 years; 73.8% males; CHA
2
DS
2
-VASc: 4.7±1.1; HAS-BLED: 3.7±0.7) underwent percutaneous closure of the LAA patency via embolization coils. Trans-esophageal echocardiography (TEE) was performed at 60±15 days post-procedure.

Results:
LAA closure had been previously attempted with a Watchman device in 62 patients, and a LARIAT in 3. Baseline TEE documented a moderate or severe leak in 14 (21.5%) and 51 (78.5%) patients, respectively. Procedure and fluoroscopy times were 69±37min and 22±15min, respectively; the mean volume of iodinated contrast medium used was 82±43mL. Coil deployment was successful in all cases [median n. of coils attempted: 3 (IQR:2-5); median n. of coils deployed: 3 (IQR: 2-4)]. The overall complication rate was 3.1% (1 pericardial tamponade, 1 pericardial effusion). Peri-procedural angiographic and TEE outcomes demonstrated complete obliteration or a negligible residual opacification with a trivial residual jet in 62 cases (95.4%), and a partial occlusion with moderate residual jet in 3 (6.4%). Follow-up TEE after 67±12 days revealed complete LAA sealing or a negligible residual leak in 63 cases (96.9%). Coil deployment led to an average reduction of 90.1% in leak size (p<0.001). After an overall follow-up of 17±4 months, no TE events were documented; 3 patients died from non-cardiovascular and one from cardiovascular causes (heart failure).

Conclusions:
Transcatheter LAA leak occlusion via endovascular coils appears to be a safe, effective, and promising approach in high TE-risk patients with incomplete LAA closure.
Abstract 17234: Elevated Atherosclerotic Biomarkers in Mice With Mild Blast Traumatic Brain Injury and Chronic Variable Stress
Authors: Hood Maureen N , Ho Vincent B , Plavelil Nisha , Wu Tao-Yiao , Luke Michaelson , Oyola Mario
Published: November 2020

Introduction:
Traumatic brain injury (TBI) and stress are significant health concerns that have atherosclerotic cardiovascular disease (ASCVD) effects. Stress and injury can elevate neurochemicals and hormones in the brain that lead to dysfunction of the hypothalamic-pituitary-adrenal axis and the autonomic nervous system increasing inflammation, which plays a role in the development of ASCVD. Animal models can provide a method of separating mild TBI (mTBI) from models of chronic stress.

Hypothesis:
We hypothesize that mild blast TBI (mbTBI) and chronic variable stress (CVS) will result in elevated ASCVD biomarkers in mice.

Methods:
Frozen hearts from C57BL/6J mice (8 weeks, N=16, 8 male/8 randomly cycling female) were obtained through an IACUC approved study. The C57BL/6J mice were part of a mild blast TBI (mbTBI) study utilizing a blast chamber to receive a short duration shock wave (<10 msec, mean peak pressure of blast waves 19.9 psi). A group was subjected to CVS for two weeks prior to the blast, plus one week after blast. All groups were followed for four weeks. Western Blots with relative expression (normalized) were performed using an infrared imaging system. ERK1, ERK2, Galactein 3, Endothelin-1, BDNF, NT-Pro-BNP, and NRG1. ANOVA with Tukey HSD correction and descriptive statistics were performed using SPSS with significance by α of 0.05.

Results:
ERK1: mbTBI and CVS (p<0.05). CVS +mbTBI to CVS (0.015)(
p<0.05
), compared to mbTBI (0.017). ERK2: mbTBI sham = 0.009, CVS only = 0.008, mbTBI only = 0.008 and CVS + mbTBI = 0.012. Galectin-3 (Gal-3): CVS only = 0.144, CVS+mbTBI = 0.168, mbTBI (0.114) to sham (0.111) (
p<0.05
). NT-Pro-BNP: CVS+mbTBI = 0.168, sham 0.076. mbTBI alone (0.077) and CVS alone (0.078). NRG1: mbTBI (0.195) and mbTBI with CVS (0.178). CVS only group (0.157). ET-1: mbTBI sham = 0.068, CVS only = 0.080 mbTBI only = 0.084 and CVS+mbTBI = 0.134. BDNF: CVS only = 0.053, CVS+mbTBI = 0.069. Sham group (0.047), mbTBI (0.038).

Conclusion:
Our results on proteins related to a broad spectrum of vascular growth, innervation, function, inflammation and markers of atherosclerotic plaque development suggest that mbTBI and/or chronic stress may increase risk for developing early ASCVD.
Abstract 17238: Taper With Caution: A Case Report of Treatment Response of a Patient With Cardiac Sarcoidosis to Tapering of Steroid Therapy and Initiation of Methotrexate
Authors: MAHALWAR GAURANGA , BASHIR HANAD , Courson Jeffery , Alameh Anas
Published: November 2020

Introduction:
We present a case of a patient with systemic sarcoidosis with cardiac involvement who presented with palpitations and was noted to be in non-sustained ventricular tachycardia (NSVT) after being tapered down the prednisone dose and being started on methotrexate.

Clinical Course:
49-year-old female presented with symptoms of palpitations for 10 day prior to presentation with associated lightheadedness. Her past medical history included cardiac sarcoidosis, atrial tachycardia and complete heart block with a pacemaker placement. Upon checking her remote pacemaker interrogation during the current admission she was found to have recurrent episodes of non-sustained ventricular tachycardia. Patient was diagnosed with sarcoidosis 4 months prior to presentation and was started on 50 mg of prednisone which was tapered down to 30 mg 2 months prior to patient’s presentation due to weight gain along with initiation of methotrexate therapy .Patient was started on amiodarone 200 mg daily with a loading dose of 400 TID while admitted. Her prednisone was increased temporarily and weekly methotrexate was continued. The patient was found to have resolution of symptoms and did not have recurrence of arrhythmia on telemetry. She was upgraded to ICD placement during the same admission and was discharged with follow up.

Conclusions:
Ventricular tachycardia (VT) resulting from myocardial inflammation is the most common arrhythmia in cardiac sarcoidosis (CS), found in up to 23% of the patients. Antiarrhythmic drugs such as amiodarone are standard treatment for VT in patients with CS. However, corticosteroid therapy has shown to be beneficial for ventricular arrhythmias (VA) as demonstrated in some studies while even worsening ventricular arrhythmias in minority of the patients. In our patient, the tapering of the prednisone dose despite introduction of methotrexate resulted in the recurrence of ventricular tachycardia which eventually resolved with the re-administration of the original dose of prednisone. This indicates that more definitive immunosuppression therapy guidelines are required for patients with CS.
Abstract 17249: Culprit-Only versus Complete Multivessel Percutaneous Coronary Intervention in Patients with ST-elevation Myocardial Infarction: An Updated Meta-Analysis
Authors: Ullah Waqas , Zahid Salman , Narayana Gowda Smitha , Munir Samavia , sattar yasar , Moussa Pacha Houmam , Ghani Ali , Alraies M. Chadi , Fischman David L
Published: November 2020

Introduction:
ST-segment elevation myocardial infarction (STEMI) in patients with concomitant multivessel coronary artery disease (CAD) is associated with poor prognosis.

Hypothesis:
We sought to determine the merits of percutaneous coronary intervention (PCI) of the culprit-only compared with a complete revascularization approach.

Methods:
The MEDLINE (PubMed, Ovid), Embase, Clinicaltrials.org and Cochrane databases were queried with various combinations of medical subject headings (MeSH) to identify articles comparing complete and culprit-only revascularization. Data were compared using a random-effect model to calculate unadjusted odds ratio.

Results:
A total of 26 studies consisting of 26,892 patients, 18,377 in the culprit-only and 8,515 in the complete revascularization group were included. The mean age of patients included in the study was 63 years, comprising 72% of male patients. Baseline characteristics of the two treatment groups were comparable. On a median follow-up of 1-year, culprit-only revascularization was associated with a significantly higher odds of major adverse cardiovascular events (MACE) (OR 1.36, 95% CI 1.10-1.69, p=0.005) (figure), angina (OR 2.28, 95% CI 1.83-2.85, p=<0.00001) and revascularization (OR 1.71, 95% CI 1.18- 2.49, p=0.005) compared to complete revascularization group. The all-cause mortality (OR 1.17, 95% CI 0.89-1.54, p=0.25),, cardiovascular mortality (OR 1.20, 95% CI 0.90-1.61, p=0.22), rate of heart failure (OR 1.17, 95% CI 0.86-1.59, p=0.31), CABG (OR 1.47, 95% CI 0.82-2.64, p=0.19), repeat MI (OR 1.23, 95% CI 0.92-1.63, p=0.17) and stroke (OR 1.27 95% CI 0.68-2.34, p=0.45%) were similar between the two groups.

Conclusions:
In contrast to the culprit-only approach, complete revascularization in patients with the acute coronary syndrome is associated with a significant reduction in MACE, angina and need for revascularization.