bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17085: The Modified US Heart Allocation System Improves Waitlist Mortality for Patients With Hypertrophic Cardiomyopathy
Authors: Helmers Mark R , Fowler Cody , Altshuler Peter , Iyengar Amit , Han Jason J , Patrick William , Birati Edo , Atluri Pavan
Published: May 2021

Introduction:
On October 18, 2018, the US donor heart allocation policy was restructured to better stratify patients, decrease status exemptions, and improve inequities. Previously, HCM patients experienced significant waitlist mortality and functional decline, often requiring status exemptions to be transplanted. This study aims to examine changes in waitlist mortality and transplant rates of HCM patients in the new system.

Methods:
Retrospective analysis was performed of the UNOS Transplant Database for all isolated adult single-organ heart transplant patients listed between April 20, 2008 and December 6, 2019. Redo heart transplants were excluded. Patients were grouped by diagnosis (HCM or ICM & NICM) and divided into eras based on allocation system. Era 1 spanned April 20
th
, 2008 to October 17
th
, 2018 and Era 2 spanned October 18
th
, 2018 to December 6
th
, 2019.

Results:
During the study period, 28,930 patients were listed, with 26,354 in Era 1 (750 HCM, 2.8%) and 2,576 in Era 2 (107 HCM, 4.2%). Across eras, no differences in age, ethnicity, gender, dialysis, and mechanical ventilation were noted among HCM patients (p>0.05). ECMO usage for HCM at listing was 1.3% in Era 1 vs 2.8% in Era 2 (p=0.557). Use of bridge-to-transplant LVADs remained low in HCM patients (Era 1: 4.3% vs Era 2: 1.9%, p=0.505). Status upgrades for HCM patients decreased from 49% to 39% (p=0.06). Waitlist survival was improved in Era 2 for HCM patients (Figure 1, p=0.001). Transplant rates trended higher in Era 2 for HCM (Figure 1, p=0.344). Thirty-day mortality post-transplant in HCM patients was 2.36% in Era 1 and 1.47% in Era 2 (p=0.643).

Conclusions:
The new allocation system has led to significantly increased one-year waitlist survival and a near-significant decrease in status upgrades for HCM patients. Moreover, HCM patients trended towards higher transplant rates and shorter waitlist times in the new system. Continued investigation of listing practices and outcomes of HCM patients is warranted.
Abstract 17087: Mesenchymal Stem Cell-Derived Extracellular Vesicle Therapy Delivered in a Hydrogel Preserves Hemodynamic Function Following Myocardial Infarction
Authors: Helmers Mark R , Jarmula Jakub , Kim Samuel , Schiazza Alexis , Altshuler Peter , Burdick Jason A , Atluri Pavan
Published: May 2021

Introduction:
Mesenchymal Stem Cell (MSC)-derived Extracellular Vesicles (EVs) are an emerging regenerative therapy for treatment of ischemic cardiomyopathy. In this study, we determine the efficacy of MSC-EV therapy in a shear-thinning hydrogel (STG) delivered via intramyocardial injection to the border zone of rat hearts following myocardial infarction (MI).

Hypothesis:
MSC EV-loaded STGs will preserve hemodynamic function and minimize ventricular scar formation in a rat model of acute MI.

Methods:
EVs were isolated from MSCs by PEG precipitation, and the EV proteome was characterized by MaxQuant 1.5.1.2 and Metacore analysis software. Varying concentrations of EVs were administered to rats following induction of acute MI by ligation of the left anterior descending artery. EVs were delivered in either sterile phosphate buffered saline (PBS) or STG for sustained EV release. Chronic injury was assessed at 4 weeks post-MI through transthoracic echocardiography, intraventricular pressure-volume loop displacement, and histology.

Results:
MSC EV proteomic analysis highlighted upregulation of VEGF angiogenic cascades and ILK-mediated proliferative pathways. The mean left ventricle ejection fraction (LVEF) for each treatment group at four weeks is displayed in Table 1. A 20 ug dose of MSC EVs in STG improved LVEF by 19.12% (p<0.05) compared to PBS, with a 90 ug dose of MSC EVs in STG increasing LVEF by 23.56% (p<0.01) (Fig. 1).

Conclusions:
Intramyocardial injection of MSC EVs in STG post-MI showed concentration dependent improvements in hemodynamics. These findings show that high doses of MSC EV in STG may have potential as a therapy for ischemic cardiomyopathy. Proteomic analysis revealed that angiogenesis, recruitment of cardiac progenitor cells, and immune modulation may be mechanistic drivers of MSC-EV therapy.
Abstract 17095: Association of Cigarette and Electronic Cigarette Use Behaviors With Levels of Inflammatory and Oxidative Stress Biomarkers Among United States Adults, Path 2013-2014
Authors: Stokes Andrew , Wilson Anna E , Xie Wubin , Orimoloye Olusola A , Fetterman Jessica L , Defilippis Andrew P , Keith Rachel J , Benjamin Emelia J , Robertson Rose M , Bhatnagar Aruni , Hamburg Naomi M , Blaha Michael J
Published: May 2021

Introduction:
Electronic cigarette (e-cigarette) use has increased rapidly in recent years; however, the cardiovascular risks of e-cigarettes remain unclear. Using data from the Population Assessment of Tobacco and Health Survey, this study assesses the cross-sectional association of cigarette and e-cigarette use behaviors with markers of inflammation (high-sensitivity C-reactive protein [hsCRP], soluble intercellular adhesion molecule [sICAM], interleukin-6 [IL-6], fibrinogen), oxidative stress (8-isoprostane [F2PG2a]), and nicotine exposure (cotinine).

Methods:
We analyzed data from adults (18+ years) who provided urine and blood specimens at wave 1 (2013-2014). Biomarkers were examined as continuous and categorical variables using the clinical cut points of ≥3 mg/L for hsCRP >10 ng/mL for cotinine, and the upper quartiles of fibrinogen (≥381mg/dL), IL-6 (≥2.32 pg/mL), sICAM (≥288.77 ng/mL), and 8-isoprostane (≥788 pg/mL). Progressively adjusted negative binomial and generalized structural equation models were used, as well as sensitivity checks to assess the robustness of associations.

Results:
Of the 7,019 participants (58.6% non-users, 1.8% current vapers, 29.7% current smokers, 9.9% dual users), 67.2% had ≥1 high inflammatory or oxidative stress marker. Current vapers had increased risk of high hsCRP (IRR 1.28; 95% CI,1.02-1.59) and sICAM (IRR 2.01; 95% CI,1.42-2.85) compared to non-users. Relative to current smokers, current vapers who were former smokers had lower risk of having ≥1 high inflammatory or oxidative stress marker (IRR 0.80; 95% CI,0.69-0.94). Dual users had higher levels of all 5 inflammatory and oxidative stress markers compared to never smokers in both continuous and categorical models, with similar levels compared to current smokers. Current smokers and dual users had higher levels of cotinine compared to exclusive vapers.

Conclusions:
This study suggests that current vapers may have lower levels of inflammatory and oxidative stress markers compared to current smokers, but only after complete cessation of combustible cigarettes. Our findings strengthen the need for longitudinal studies investigating the association of vaping with markers of cardiovascular risk, particularly among dual users.
Abstract 17258: The Relationship Between D-Dimer Levels and Deep Venous Thrombosis in COVID-19: An Analysis From a Quaternary Academic Medical Center in New York City
Authors: Madhavan Mahesh V , Gupta Aakriti , Bikdeli Behnood , Redfors Björn , Hennessey Jessica , Lawlor Matthew , Poterucha Timothy J , Nalbandian Ani , Driggin Elissa , Elias Pierre , Ranard Lauren S , Nabavi Nouri Shayan , Jianhua Li , Finn Matthew T , Ingrassia Joseph , Eisenberger Andrew , Masoumi Amirali , Uriel Nir , Leon Martin B , Kirtane Ajay J , Parikh Sahil , Sethi Sanjum
Published: May 2021

Background:
D-Dimer values may be elevated in hyperinflammatory or prothrombotic states and are frequently measured in patients with coronavirus disease 2019 (COVID-19). Many institutional algorithms and ongoing studies suggest using D-Dimer cutoffs to initiate anticoagulation. The relationship between D-Dimer levels and deep venous thrombosis (DVT) has not been extensively studied specifically in patients with COVID-19.

Methods:
We retrospectively studied patients hospitalized at our institution between 2/1/20-5/19/20 for COVID-19 who underwent lower extremity venous doppler imaging. After stratifying by presence of DVT, baseline characteristics, vital signs, and laboratory values were assessed. We assessed the association between peak D-Dimer levels and diagnosis of DVT during admission. Upper limit D-Dimer value for the hospital’s laboratory assay was >20 mg/dL.

Results:
Of the 2677 patients admitted, 514 underwent lower extremity imaging, out of whom 186 (36.2%) were diagnosed with DVT. Other than history of cancer, which was more common in patients with a diagnosis of DVT (14.7% vs. 6.3%, p<0.01), baseline characteristics and presentation vital signs were similar between groups. Median peak D-Dimer levels were similar in patients with and without diagnosis of DVT [18.5 mg/dL, IQR: 6.4-20.0 vs. 12.2 mg/dL, IQR: 3.7-20, p = 0.80]. Density plots of initial D-Dimer values grouped by presence of DVT are presented in Figure 1.

Conclusions:
In this analysis of patients hospitalized with COVID-19, DVT was frequently diagnosed in patients who underwent imaging. There was considerable overlap of peak D-Dimer values in patients with and without documented DVT. As such, elevation in D-Dimer values alone should not prompt routine initiation of therapeutic anticoagulation in COVID-19 patients. Data from prospective clinical trials and registries regarding optimal antithrombotic practices in this patient population is needed.
Abstract 17319: Management of Advanced Heart Failure Patients With the Combined Use of CardioMEMS™ and Telehealth: A Single Center Experience in a Veteran’s Affairs Population
Authors: Patel Nishi , Alam Amit , Banerjee Subash , Minniefield Nicole , Hall Shelley , Joseph Susan , Wencker Detlef , Cheeran Daniel , Gong Timothy
Published: May 2021

Background:
Due to the Coronavirus Disease of 2019 pandemic many clinics began to utilize virtual visits in lieu of traditional office visits. It is unclear what effect this will have on outcomes and admission rates for heart failure (HF). We describe our approach and outcomes in managing HF in a Veteran’s Affairs population with previously implanted CardioMEMS™ during this time.

Methods:
Starting February 15
th
2020, virtual visits were utilized in patients with CardioMEMS™ during which their symptoms were discussed and medications adjusted. Patients also received weekly phone calls to ensure that they had medications and to adjust diuretics based on pulmonary artery (PA) pressure readings. They received text message reminders if a reading was missed. A nurse was also tasked to follow up on lab results. Data was collected by reviewing the charts of CardioMEMS™ patients followed in our clinic by cardiology fellows and divided into pre pandemic period of July 1
st
2018 to February 14
th
2020 and a post pandemic period of February 15
th
2020 to May 15
th
2020. Data collected included baseline demographics, number of in-office and virtual visits, hospital admissions for HF, PA pressures, and compliance with CardioMEMS™ readings. Phone calls to adjust diuretics or review labs were not counted as virtual visits.

Results:
In the pre-pandemic period we identified 49 patients with prior CardioMEMS™; baseline demographics are shown in Table 1A. Table 1B shows our results comparing the pre pandemic and post pandemic periods when our telemedicine program was started. Although in the post pandemic period our encounter rate was lower, our virtual program was able to maintain stable PA pressures and a lower overall hospital admission rate. Compliance with CardioMEMS™ also increased though this was not statistically significant.

Conclusion:
Both CardioMEMS™ and virtual visits may be used effectively to maintain low PA pressures and reduce hospital admissions for in patients with chronic HF.
Abstract 17335: Cluster Analysis of Cardiac Resynchronization Response Parameters Predicts Long-Term Survival With Heart Failure
Authors: Bilchick Kenneth C , Gao Xu , Bivona Derek , Malhotra Rohit , Mangrum Michael , Darby Andrew , Mehta Nishaki M , Mason Pamela K , Epstein Frederick H , Holmes Jeffrey W , Mazimba Sula
Published: May 2021

Introduction:
Machine learning methods such as cluster analysis can identify commonality in patterns of short-term response measures after cardiac resynchronization therapy (CRT) to predict classes of patients with distinct long-term prognoses.

Hypothesis:
Distinct response clusters identified within 6 months of CRT implantation would provide independent prognostic value relative to known pre-CRT patient characteristics.

Methods:
Patients with heart failure (HF) undergoing CRT had assessments of left ventricular end-systolic volume fractional change (LVESV-FC), peak VO
2
, and B-type natriuretic peptide (BNP) based on cardiac magnetic resonance (CMR), echocardiography, exercise testing, and blood tests before and 6 months after CRT. Statistical methods included multivariate multiple linear regression, cluster analysis based on a mixture model, survival analysis, and receiver operating characteristic (ROC) analysis.

Results:
During a median of 5.0 years of follow-up after CRT, the cohort of 146 patients (age 66.0 ± 11.3 years, 34.9% female) had a death rate of 28.1%. A significant correlation was observed for BNP response and LVESV-FC (r=0.42, p>0.01), but not for the other response comparisons. Three clusters of patients (1: n=27; 2: n=82; 3: n=37) were identified. Kaplan-Meier analysis (Figure) demonstrated the best long-term survival in cluster 2, intermediate survival in cluster 3, and the worst survival in cluster 1 (p<0.0001). ROC curve comparisons for 4-year survival based on pre-CRT findings with or without the 6-month response cluster showed that the cluster increased the AUC from 0.818 to 0.870 (p=0.069).

Conclusions:
Response clusters based on 6-month parameters were strongly associated with long-term survival and improved prognostication compared with just pre-CRT predictors alone. This response clustering approach based on machine learning promises to be very useful for clinical risk stratification in heart failure after CRT.
Abstract 17345: Dysregulated Phenylalanine Catabolism is a Key Determinant of Cardiac Aging
Authors: Czibik Gabor
Published: May 2021

Introduction:
Cardiac aging is characterized by cardiomyocyte hypertrophy and myocardial interstitial fibrosis with impaired contractility and relaxation. Recent metabolomics studies revealed an age-dependent increase in the plasma levels of essential amino acid phenylalanine (Phe), which is predictive of heart failure hospitalization. The present study aimed to dissect 1) the basis for increased Phe levels with age and 2) how Phe may promote age-related cardiac dysfunction.

Methods:
To establish a role for Phe in driving cardiac aging, wild-type (WT) male mice were treated twice a day with Phe (200 mg/kg) for a month. The impact of Phe on cellular senescence, redox biology and epigenetics were explored in cultured cardiomyocytes (primary adult rat and AC-16 human cardiomyocytes) treated with Phe.
In vivo
cardiac structure and function, together with Phe catabolism were monitored in WT and in p21
-/-
mice (in pursuit of p21 induction with Phe and age) up to 24 months of age. Finally, we treated aged WT mice with tetrahydrobiopterin (BH4; 10 mg/kg), the essential cofactor for Phe-degrading enzyme phenylalanine hydroxylase (Pah). The effect of aging and Phe treatment on hepatic Phe catabolism was explored
in vivo
and
vitro
in AML-12 hepatocytes.

Results:
Natural aging induced a progressive increase in plasma Phe levels concomitant with cardiac dysfunction, whilst p21 deficiency prevented these changes. Phe treatment triggered cellular senescence, along with complex redox and epigenetic changes
in vitro
and induced an age-mimicking cardiac deterioration in young WT mice
in vivo
. Pharmacological restoration of Phe catabolism with BH4 reversed the rise in plasma Phe and senescent cardiac alterations in aged WT mice without affecting myocardial NOS activity. Key observations were reproduced in corresponding human samples and collectively they pointed to hepatic Phe catabolic decline with ensuing elevated plasma Phe levels compromising cardiac integrity.

Conclusions:
Our findings established a pathogenic role for increased Phe levels in cardiac aging, highlighting modulation of Phe catabolism as a potential therapeutic target for age-associated cardiac impairment.
Abstract 17367: Propitious Temporal Changes in Clinical Outcomes After Transcatheter Compared to Surgical Aortic Valve Replacement; A Meta-Analysis
Authors: Panchal Ankur , Kyvernitakis Andreas , Doyle Mark , Biederman Robert W
Published: May 2021

Introduction:
Treatment for severe aortic stenosis has rapidly evolved over the past decade, in both transcatheter aortic valve replacement (TAVR) technique and surgical aortic valve replacement (SAVR), resulting in improved clinical outcomes. We sought to determine and compare the temporal changes and 1-year outcomes between these groups.

Methods:
We searched the Medline MESH database using the keywords “aortic stenosis”, “atrial fibrillation” and “stroke”. We performed a meta-analysis and created funnel plots to compare TAVR with SAVR population for post-procedural stroke, all-cause and cardiovascular (CV) mortality at 1-year.

Results:
Out of >50 studies, we included 20 meeting criteria for analysis with total population of >65000 patients, of which 61067 had TAVR and 4162 had SAVR. AFib prevalence was higher in TAVR vs SAVR patients (38% vs 27%; p< 0.0001). By funnel plotting, post-procedural stroke at 1-year was 3.1% in TAVR and 5% in SAVR patients (NS). All-cause mortality at 1 year was 12.5% in TAVR and 10.3 % in SAVR patients, and CV mortality at 1-year was 7.4% in TAVR and 6.2% in SAVR patients (NS for both).

Conclusion:
While there is a trend over the last 14 years for overall improvement in both SAVR and TAVR outcomes, via meta-analysis, despite a higher prevalence of AFib in TAVR vs SAVR, there is statistical overlap in the confidence intervals supporting no distinct separation in stroke risk, all-cause mortality or adjudicated CV mortality at 1 year between groups. To our knowledge, this represents the largest study over the longest time period that points towards potential benefit at the individual level but as a socio-economic consideration, no distinction between SAVR vs TAVR.
Abstract 17371: In-Hospital Outcomes of Ablation for Ventricular Tachycardia in Heart Failure With Reduced Ejection Fraction
Authors: Patel Raj , Ludhwani Dipesh , Patel Harsh P , Thakkar Samarthkumar J , shah Love , Kutom Fadee , Jani Chinmay , Doshi Rajkumar P , Arora Shilpkumar , Sheth Aakash , Patel Rushin , Shah Priyal , Nayak Hemal
Published: May 2021

Introduction:
Ventricular tachycardia (VT) is a significant cause of morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF).

Hypothesis:
Data on efficacy, safety, and outcomes of catheter ablation for VT in HFrEF have not been studied well.

Methods:
The 2002-2014 Nationwide Inpatient Sample (NIS) was used to identify all hospitalizations with a principle diagnosis of VT (International Classification of Diseases, Ninth Edition, Clinical Modification [ICD-9-CM] code 427.1) and a secondary diagnosis of HFrEF. Patients who underwent catheter ablation were identified using ICD-9-CM procedure code 37.34.

Results:
Of 228,557 patients with HFrEF & VT, 5845 (2.56%) underwent catheter ablation. The prevalence of Diabetes Mellitus (DM) and Chronic Kidney disease (CKD) was higher in the reference population contrary to a higher prevalence of prior myocardial infarction (MI), coronary bypass and AICD in those undergoing CA. The frequency of complications in the ablation group was 19.47%, the most common being post-operative hemorrhage (8.3%). This was followed by myocardial infarction (5.34%), pericardial complications (3.38%), and neurological complications (2.14%) (Figure 1.). The odds of in-hospital mortality were lower in the CA group compared to the reference group (5.08% vs 9.42%, p<0.05).

Conclusions:
Compared to medical therapy, VT ablation in HFrEF is associated with lower mortality though with significant complication rate. This suggests a need for future studies identifying the safety measures in VT ablations and instituting appropriate interventions to improve overall VT ablation outcomes.
Abstract 17373: The Association of Professional American-Style Football Career Length With Left Ventricular Geometry in Retired National Football League Players
Authors: Smith Genevieve , Fernandez Camilo , Stewart Gregory W
Published: May 2021

Introduction:
There is widespread interest in the long-term cardiovascular (CV) implications of professional football. Studies have suggested that retired National Football League (NFL) players have a high prevalence of hypertension, which may increase risk for left ventricular hypertrophy (LVH). However, it is unknown if football-specific factors, such as professional football career length (NFLYrs), are associated with long-term CV outcomes, including changes in left ventricle (LV) geometry. Thus, we examined the association of NFLYrs with LV geometry patterns in a retired NFL player cohort.

Methods:
We analyzed data on 1349 retired NFL players (aged 53.1 ± 12.8 years, 55.1% African-American) that underwent comprehensive health screening with the NFL Player Care Foundation. Echocardiography was used to estimate LV mass, which was then indexed to height
2.7
. Relative wall thickness was computed to classify LV geometry patterns into normal, concentric remodeling (CR), eccentric hypertrophy (EH), and concentric hypertrophy (CH). Three binary logistic regression models (Model 1: CR; Model 2: EH; Model 3: CH), using normal geometry as reference, were fitted to assess the association of NFLYrs with each LV geometry pattern, adjusting for traditional cardiometabolic risk factors.

Results:
Increasing NFLYrs was independently associated with CR (odds ratio [OR]: 1.48, 95% confidence interval [CI] 1.03 – 2.11, p = 0.0334), while no associations were observed with EH (OR: 0.49, 95% CI 0.22 – 1.09, p = 0.0801) or CH (OR: 1.04, 95% CI 0.61 – 1.77, p 0.8927). Mean arterial pressure was independently associated with increased odds of CR (OR: 1.03, 95% CI 1.01 – 1.05, p – 0.0017), EH (OR: 1.06, 95% CI 1.02 – 1.09, p = 0.0013), and CH (OR: 1.06, 95% CI 1.04 -1.09, p < 0.0001).

Conclusion:
NFL career length is not associated with increased odds for EH and CH later in life. In contrast, increased NFLYrs is associated with CR, likely an adaptive response to intense athletic training. Cardiovascular risk factors such as high blood pressure in the retirement period appear to be more important for long-term LVH risk in NFL athletes, underscoring the need for preventive initiatives aimed at decreasing risk for future CV outcomes in athletes transitioning out of professional sports.
Abstract 17377: Quantification of Arterial Stenosis Severity Based on the Changes in the Perfusion Wave Dynamics; a Novel Technology for Monitoring Peripheral Artery Disease
Authors: Heitner Tomer , Livneh Amit , Lorber Jonathan , Karmeli Ron , Landesberg Amir
Published: May 2021

Introduction:
Current screening modalities for peripheral artery disease (PAD) lack sensitivity especially in the elderly and diabetics, and there is an unmet need for early detection of restenosis after revascularization.

Hypothesis:
We have hypothesized that arterial stenosis is associated with adaptive arteriolar vasodilatation, which alters the downstream perfusion dynamics and prolongs the initial phase of the perfusion upstroke. These changes can be utilized for quantification of the arterial stenosis severity.

Methods:
We measured the lower leg perfusion with impedance plethysmography and compared it with other modalities used in the clinic and the gold-standard angiography. The various phases of the perfusion wave were identified by analyzing the first and second derivatives of the plethysmography. The signals were acquired from PAD patients before and after they underwent revascularization, to validate the ability to detect stenosis and successful revascularization.

Results:
Eighteen consenting patients were recruited (61±10 years old) and nineteen legs were treated. The perfusion upstroke encompasses 2 or 3 distinctive phases. An initial slow phase that is followed by a brisk upstroke and a final sallower augmentation in some patients. The slow phase duration (SPd) was 113±45 ms in extremities with above-knee (AK) arterial stenosis (n=17) while significantly shorter SPd of 26±0 ms was observed in limbs without AK stenoses (P = 0.011). In the AK extremities, the SPd significantly decreased to 52±40 ms after successful revascularization (P<0.01). Moreover, in AK cases with a satisfactory post-operative result (Duplex assessment), the SPd dramatically decreased from 103±35 ms before revascularization to 35±18 ms afterward (P<0.01, n=12).

Conclusions:
Analysis of the perfusion dynamic provides a gamut of precious indices. The SPd is a novel index that can detect and quantify the severity of arterial stenosis. The technology can significantly improve the surveillance of PAD patients and may be used for early detection of restenosis.
Abstract 17379: Relationship Between Myocyte Branching and Location Within Myocardial Sheetlet
Authors: Wilson Alexander J , Sands Gregory B , Ennis Daniel B
Published: May 2021

Introduction:
Cardiomyocytes form a continuously branching syncytium that also form sheetlets four to six cells thick. Myocytes and sheetlets have essential structural and functional roles, but descriptions of their complex branching structure are limited. Herein, we characterize the branching structure of cardiomyocytes within a myocardial sheetlet segment.

Hypothesis:
Due to topological constraints, cardiomyocytes on the sheetlet surfaces branch within the fiber-sheetlet plane more than myocytes on the interior of the sheetlet.

Methods:
Rodent myocardium was stained for collagen and the left ventricular free wall was imaged using extended volume confocal microscopy (0.4 μm
3
voxel size), a and sheetlet portion segmented (146 х 214 х 339 μm
3
, approx. 5 by 10 by 3 cells). The centerline of each myocyte was tracked, with branch-points identified where the cell bodies of adjacent cardiomyocytes merge. This produced a connected network (Figure) with five cell-layers along the normal axis: lower surface, lower interior, middle interior, upper interior, and upper surface.

Results:
The cardiomyocyte branching frequency varied between cell-layers (Figure); the sheetlet-surface cell-layers branched within their own cell-layer more frequently than myocytes in the sheetlet interior (0.28 vs 0.11 branches per 100 μm). Cardiomyocytes on the sheetlet surface also branched less frequently with cardiomyocytes of a different cell-layer, compared with cardiomyocytes in the sheetlet interior (0.31 vs 0.67 branches per 100 μm). Cardiomyocytes in the middle interior cell-layer had the highest number of branches between cell-layers (0.86 per 100 μm), and the lowest number of branches within their own cell-layer (0.03 per 100 μm).

Conclusion:
Analysis of confocal images revealed differences in cardiomyocyte branching between cell-layers of a sheetlet segment, and confirmed that sheetlet boundaries provide a topological constraint for cardiomyocyte branching.
Abstract 17381: Comparative Analysis of Mechanical Circulatory Support in Patients With Acute Coronary Artery Syndrome Induced Cardiogenic Shock
Authors: Ullah Waqas , Zahid Salman , sattar yasar , Moussa Pacha Houmam , Darmoch Fahed , Banisad Ali , Alhatemi Gaith , Sohaib Roomi , Panchal Ankur , Fischman David L , Alraies M Chadi
Published: May 2021

Introduction:
The relative safety of contemporary, real-world use of percutaneous ventricular assist device (pVAD) and intra aortic balloon pump (IABP) in patients with acute coronary artery syndrome (ACS) induced cardiogenic shock remains unknown.

Hypothesis:
Outcomes of pVAD and IABP in ACS

Methods:
Data were obtained from the Nationwide Inpatient Sample (NIS) database (2011-2014) using ICD-9 codes. Patients with the renal transplant or chronic kidney disease were excluded. Categorical and continuous data were compared using unadjusted odds ratio (uOR) and independent t-test analysis, respectively. Univariate and multivariate logistic regression analysis was performed to obtain adjusted odds ratio (aOR), controlled for patient comorbidities.

Results:
A total of 165,006 (pVAD 3104, IABP 161902) patients with cardiogenic shock following ACS were included. The proportion of demographics and baseline comorbidities for pVAD vs. IABP were significantly different between the two groups, including age (65 vs. 63 years, p=<0.001, female (33.6% and 27.9%, p=<0.001), caucasian (77.8% vs 72.8%, p=<0.001), respectively. The undusted odds for In-hospital mortality (41.2% vs 29.6%%, uOR, 1.67; 95% CI, 1.55-1.78, P=< 0.001), acute kidney injury (47.6% vs 28.7% uOR, 2.25; 95% CI, 2.09-2.41, P=<0.001) and major bleeding (21% vs 14.8% uOR, 1.54; 95% CI, 1.40-1.68, P=< 0.001) were significantly higher in patients undergoing pVAD compared to IABP. (Figure 1) However, there was no difference in the odds of vascular complications between the two groups (3% vs 2.6%, uOR 1.16; 95% CI, 0.94-1.42, P=0.18. The adjusted odds based on baseline characteristics including hypertension, diabetes, renal failure, anemia, bleeding disorders, age, race and hospital area did not deviate from unadjusted odds ratios.

Conclusions:
Compared to the IABP, pVAD might have higher odds of in-hospital all-cause mortality, acute kidney injury and major bleeding in ACS induced cardiogenic shock.
Abstract 17395: Women Veterans’ Knowledge of Cardiovascular Disease Risk: Higher Than National Samples and an Opportunity for Innovations
Authors: Bean-Mayberry Bevanne , Chanfreau Catherine , Clair Kimberly , Schweizer Catherine A , Dyer Karen , Brunner Julian , Moreau Jessica , Huynh Alexis , Moin Tannaz , Finley Erin , Hamilton Alison , Farmer Melissa
Published: May 2021

Introduction:
One in three American women die of cardiovascular disease (CVD) annually, and evidence shows that while American women’s understanding of CVD increased the last 2 decades, knowledge gaps remain.

Objective:
The objective of this analysis was to assess women Veterans’ knowledge in a similar manner to national samples and uncover gaps to target health education or innovations.

Methods:
Across four VA primary care clinics, we surveyed women Veterans exposed to at least one component of a CV toolkit designed to increase patient engagement and reduce CV risk. Survey included AHA validated measures of leading cause of death, heart attack symptoms, what to do if having a heart attack and risk factors, traumatic life events, depression, provider trust and demographics.

Results:
Among 140 respondents (average age 61, range 29-88), 65% identified as white, 22% black, 5% Asian, and separately 9% Hispanic. For personal risk, 96% reported at least one CV risk factor, and 60% had 3+ risks. Regarding trauma exposures, 36% reported unwanted or attempted sexual contact and 67% reported experiencing at least one traumatic event (e.g., earthquake/flood, seeing a death/injury, physical or sexual abuse, etc.). More than half (56%) reported depression history. Trust in VA providers was high (mean 9 [SD 1.8], range 1-10). Regarding knowledge, 64% correctly identified heart disease as the leading cause of death, 68% correctly identified all 5 symptoms of a heart attack, (97% knew at least one symptom), and 94% identified correct action to take if someone is experiencing a heart attack (call 911).

Conclusions:
Nearly all had a CVD risk, over half reported 3+ risks, depression and trauma. Despite multiple conditions and complex histories, women Veterans displayed higher levels of knowledge about CVD causing death and all 5 heart attack symptoms compared to national samples (Mosca 2006; 55% for cause of death; Fang 2019; 50.2% for all symptoms). Responses for calling 911 were similar to national data (Fang 2019; 94.7%).High levels of provider trust and baseline knowledge in women Veterans offer an opportunity to create novel VA interventions that account for women’s trauma/mental health needs combined with traditional CVD risks to change the trajectory of CVD outcomes.
Abstract 17411: De Novo Protein Synthesis of Alpha-Toxin Activated Platelets
Authors: Buerke Michael , Bingener Linda , Boettger Priyanka
Published: May 2021

Introduction:
Endovascular infections with bacteria are often devastating with subsequent high morbidity and mortality. Exo- and or endotoxins of bacteria can activate endothelial cells, leukocytes and platelets. Platelets are first line defence they accumulate at sites of vascular injury or infection. Platelet activation is a necessary step in thrombus formation. Nevertheless, stimulation of platelets will result in de novo protein synthesis despite missing nucleus since platelets armed with translational equipment.

Methods:
In the present study we determined the effect of staphylococcus aureus α-toxin on platelet activation and
de novo
protein synthesis analysed with 2-D gels, proteomics and phosphorylation analysis.

Results:
α-toxin induced platelet activation resulted in modulation of de novo protein synthesis of DJ-1 Protein, ras suppressor protein1, PLEK protein, fumaryl aceto acetase sowie das coronin actin binding protein. This synthesis was time- and concentration-dependent and was markedly increased when platelets adhered to collagen or fibrinogen and required ligation of α
IIb
β
3
. Accumulation of protein synthesis in platelets was blocked by global translational inhibitors and attenuated by inhibitors that regulate signalling through the mammalian Target of Rapamycin (mTOR). In addition with phosphorylation analysis we were able demonstrate modulation of threonine phosphorylation of fumaryl aceto acetase, phosphor threonin signal of coronin actin binding protein, phosphorylation of peroxiredoxin-6, phosphorylation of tropomyosin-2, phosphothreonin signal of

H
+
transporting two sector ATPase

upon α-toxin stimulation.

Conclusion:
Interactions with staphylococcus aureus α-toxin and platelets might lead to their activation and de novo protein synthesis. These results suggest that platelets have an important role in inflammation besides their aggregating duties in inflammatory disease.
Abstract 17412: Rapid Liposome Mimicking SARS-CoV-2 to Elucidate Thrombosis in Endothelialized Microfluidic Chip
Authors: Lai Angela , Satta Sandro , Cavallero Susana , Williamson Cayden , Hsiai Tzung K
Published: May 2021

Introduction:
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), poses the worst global health crisis in modern times. Thrombotic complications such as VTE, pulmonary embolism, and risk of stroke affect more than 30% of critically ill COVID-19 patients. Unfortunately, the flow dynamics and endothelial dysfunction underlying this outcome remains poorly understood. We hereby developed liposome-nanoparticles exposing functional S-Spike (Lipo-S) to simulate the cell internalization route of SARS-CoV-2. We propose to elucidate thrombosis development in a microfluidic channel lined with HAECs exposed to Lipo-S alone, or in combination with chimeric-lentiviral vectors (ch-Lenti) expressing SARS-CoV2-ORF sequences to recapitulate SARS-CoV-2 infection.

Methods:
Non-PEG liposomes (100 nm) with chemically attached S-Spike proteins on their surface were developed in house. Furthermore, singular regions of SARS-CoV-2-ORFs were cloned and inserted in ch-Lenti. After exposure to Lipo-S and/or ch-Lenti vectors HAECs coverage and response will be elucidated by staining of VE-Cadherin and confocal imaging. To mimic the progression of thrombosis, whole human blood containing platelets stained with CD41-PE antibody and fluorescently labeled fibrin will be flowed with an arterial shear rate of 25 dyne/cm
2
through the microfluidic chip for 15 minutes. The chip will be fixed and imaged to characterize the clot.

Results:
Lipo-S showed stronger interaction for ACE2 protein compared to non-coated liposomes measured by ELISA. Our previous work showed feasibility of measuring platelet and fibrin by quantifying coverage and projecting maximum intensity of the image stack for each component.

Conclusion:
This novel platform will uncover mechanisms underlying COVID19 infection-mediated thrombosis, lending itself for testing therapeutics targeting selected targets with the advantage of capturing the cellular response on a rapid and small scale.
Abstract 17419: Gender Differences in Outcomes With Patients Undergoing Percutaneous Left Atrial Appendage Occlusion: Insights From the NCDR LAAO Registry
Authors: Darden Douglas J , Duong Thao , Munir Mohamad B , Han Frederick , Reeves Ryan , Du Chengan , Wang Yongfei , Minges Karl E , Curtis Jeptha P , Freeman James V , Hsu Jonathan C
Published: May 2021

Introduction:
Left atrial appendage occlusion (LAAO) has emerged as an alternative to anticoagulation in select patients with atrial fibrillation (AF), however women are underrepresented in trial data and sex-specific sub analyses are limited.

Hypothesis:
Women will be more likely than men to experience adverse events following left atrial appendage occlusion (LAAO) procedure.

Methods:
Using the National Cardiovascular Data Registry LAAO Registry, patients undergoing Watchman implantation between January 2016 and December 2018 were included. Unadjusted and multivariable adjusted logistic regression analyses were performed to assess the association between gender and in-hospital outcomes, including any complication, major adverse events (pericardial effusion, major bleeding, stroke, and device embolization), hospital stay > 1 day, and mortality.

Results:
A total of 20,388 (41.3%) women and 28,969 (58.7%) men underwent Watchman implantation. Compared with male patients, women were older (76.5 vs 75.8 years, p<0.001) with a higher CHA2DS2-VASc score (1.5 vs 1.4, p<0.001), and higher prevalence of paroxysmal atrial fibrillation (59.0% vs 50.0%, p<0.001), prior stroke (27.5% vs 26.7%, p=0.003) and uncontrolled hypertension (29.3% vs 26.7%, p<0.001). Women had a lower prevalence of congestive heart failure (34.5% vs 39.7%, p<0.001), diabetes (34.8 vs 39.7%, p<0.001), and coronary artery disease (35% vs 55.7%, p<0.001). There were no differences with increased thromboembolic risk or history of major bleed, while women were more likely to have a high fall risk (39.8% vs 33.5%, p<0.001) and labile INR (9.1% vs 8.3%, p=0.003) as an indication for occlusion. After multivariable adjustment, women were more likely to have any complication (OR 1.62, 95% CI 1.62 - 1.77, p<0.001), major adverse event (OR 1.81, 95% CI 1.61 - 2.04, p<0.001), hospital stay >1 day (OR 1.46, 95% CI 1.38 - 1.54, p<0.001), and higher mortality (2.01, 95% CI 1.31 - 3.09, p=0.001).

Conclusion:
Women have a significantly higher risk than men of in-hospital adverse events and mortality following Watchman implantation. Further examination of the risk-benefit relationship of LAAO in women is warranted.
Abstract 17473: GRK2 in the Mitochondria: Uncovering Novel Mechanisms in Heart Failure
Authors: Ferrero Kimberly M , Kayki Mutlu Gizem , Pfleger Jessica M , Tilley Douglas G , Koch Walter J
Published: May 2021

Introduction:
During heart failure, levels and activity of G protein-coupled receptor kinase 2 (GRK2) increase. GRK2 is canonically studied in the phosphorylation of GPCRs and β-adrenergic desensitization. Noncanonical activities of GRK2 are being uncovered, however. Our lab has recently discovered that in cardiac myocytes, GRK2 translocates to the mitochondria (
mtGRK2
) following injury and is associated with negative effects on metabolism and cell survival.

Hypothesis:
GRK2 plays a role in regulating mitochondrial function following cardiac stress and contributes to HF pathogenesis in a novel manner, by interacting with a novel group of mitochondrial proteins involved in pro-death signaling, bioenergetics and substrate utilization.

Methods:
Mitochondrial translocation of GRK2 was validated with either protein kinase C inhibitor (chelerythine) administration or hypoxia/reoxygenation stress in primary neonatal rat ventricular myocytes or a cardiac-like cell line. Immunoprecipitation of the GRK2 interactome basally and under stress conditions was conducted endogenously
in vitro, in vivo
, and with purified recombinant GRK2 peptides. Proteins were separated via SDS-PAGE and potential binding partners were identified by mass spectroscopy (LCMS) and proteomics analysis conducted with Ingenuity Pathway (IPA; Qiagen) software to determine which partners in the GRK2 interactome were potentially involved in mitochondrial dysfunction.

Results:
Subunits of Complexes I, II, IV and V of the electron transport chain were identified as potential mtGRK2 interacting partners. Several mtGRK2-ETC interactions were increased following oxidative stress-induced translocation of GRK2. Finally, mtGRK2 appears to phosphorylate some of the interactome partners identified in mitochondrial dysfunction.

Conclusions:
The phosphorylation of subunits of the ATP synthesis machinery by mtGRK2, or other mechanisms of interaction between these proteins, may be regulating some of the phenotypic effects of HF previously observed by our lab, such as increased ROS production and reduced fatty acid metabolism. Further research is essential to elucidate the novel role of GRK2 in regulating mitochondrial bioenergetics and cell death in failing hearts.
Abstract 17500: A Crisis of the Heart
Authors: Njoroge Joyce , Crawford Michael H
Published: May 2021

A 59 year old female with past medical history of metastatic neuroendocrine tumor without cardiac involvement was admitted for transarterial catheter embolization (TACE) procedure of liver lesions. During the TACE procedure, she developed hypertensive urgency treated with intravenous beta blocker therapy and continuous octreotide for carcinoid reaction. The following day she developed acute pulmonary edema and labile blood pressures requiring low dose norepinephrine. Octreotide infusion was up-titrated to 500 mcg/hour with concern for carcinoid crisis. On physical exam, she was tachycardic and regular without notable murmurs or extra cardiac sounds, no elevated jugular venous distension, and no lower extremity edema. She had bilateral crackles on pulmonary exam and was diaphoretic and delirious. There were sub-millimeter lateral ST- segment elevations on her electrocardiogram but her troponin levels were elevated to 14 ng/dL. Point of care cardiac ultrasound demonstrated severely impaired left ventricular systolic function without regional wall motion abnormalities. Coronary angiogram revealed diffuse coronary vasospasm and elevated left ventricular end-diastolic pressure. On right heart catheterization, she had elevated filling pressures, pulmonary arterial oxygen saturation of 25%, and cardiac index of 1.42 L/min/m2. Our patient was diagnosed with cardiogenic shock secondary to octreotide mediated coronary vasospasm causing diffuse myocardial injury. Continued multidisciplinary discussions were needed to determine appropriate vasopressor and inotropic agent use to support cardiac function without triggering further hormonal dysregulation during carcinoid crisis. Her cardiac function eventually improved with left ventricular Impella support and gradual down-titration of octreotide dose. Norepinephrine, epinephrine, and phenylephrine were avoided in favor of vasopressin, and dobutamine was switched to milrinone to prevent further sympathetic activation. She was able to wean off Impella and pressor support and had improvement of her left ventricular function on repeat echocardiography one month later. She has not had recurrence of heart failure symptoms and continues to follow up with oncology via tele-visits.
Eplerenone Improves Pulmonary Vascular Remodeling and Hypertension by Inhibition of the Mineralocorticoid Receptor in Endothelial Cells
Authors: Kowalski Jessica , Deng Lisa , Suennen Chiara , Koca Duygu , Meral David , Bode Christoph , Hein Lutz , Lother Achim
Published: May 2021

Pulmonary hypertension is characterized by progressive remodeling of the pulmonary arteries, however, this is not therapeutically targeted yet. Aldosterone and the MR (mineralocorticoid receptor) are key drivers of cardiovascular disease, and there is a growing body of evidence suggesting a role in pulmonary hypertension. Thus, the aim of this study was to investigate the impact of cell type-specific deletion of MR on pulmonary vascular remodeling. To induce pulmonary hypertension, mice were exposed to chronic hypoxia for 6 weeks. Treatment with the MR antagonist eplerenone attenuated pulmonary vascular remodeling, hypertension, and right ventricular dysfunction. In contrast, aldosterone infusion via osmotic minipumps induced pulmonary vascular remodeling. We created 4 different mouse models with cell type-specific MR deletion in smooth muscle cells, endothelial cells, macrophages, or fibroblasts and exposed them to chronic hypoxia. MR deletion from endothelial cells fully recapitulated the beneficial effects of eplerenone while MR deletion from other cell types had no detectable effect on pulmonary vascular remodeling. RNA-seq from isolated MR-deficient and wildtype pulmonary endothelial cells revealed differentially expressed genes as potential downstream mediators of MR related to pulmonary hypertension, including genes related to the endothelin signaling pathway. MR antagonists improve hypoxia-induced pulmonary vascular remodeling via inhibition of MR in endothelial cells but independent from MR in smooth muscle cells, fibroblasts, or macrophages. The results from this study provide the basis for future investigation of potential downstream mediators of MR involved in pulmonary hypertension and further support the clinical evaluation of MR antagonists in pulmonary hypertension.
ʿĪsā b. Hišām’s Shiism and Religious Polemic in the Maqāmāt of Badīʿ al-Zamān al-Hamaḏānī (d. 398/1008)
Authors: Stewart Devin
Published: May 2021

This study reads the Maqāmāt of Badīʿ al-Zamān al-Hamaḏānī (d. 398/1008) against the background of the sectarian milieu of the fourth/tenth century. It begins with a thorough review of the preceding scholarship on al-Hamaḏānī’s sectarian allegiances, and it confirms the contention that Hamaḏānī was a Sunni by conviction. It then proposes that the names and attributes of the narrator of al-Hamaḏānī’s Maqāmāt, ʿ Īsā b. Hišām, reflect an attempt by al-Hamaḏānī to satirize Shii values and practices. It then considers references to Shiism in six of al-Hamaḏānī’s maqāmāt: the Ḥulwāniyya, Māristāniyya, Iṣfahāniyya, Maḍiriyya, Aḏarbayjāniyya, and Kūfiyya, along with several other references to Shiism in the collection. The study further proposes a possible connection between the portrayal of ʿĪsā b. Hišām and the famed Twelver scholar Ibn Bābawayh al-Qummī (d. 381/991).
Digressions in the Islamic Archive
Authors: Keegan Matthew L.
Published: May 2021

This essay critiques the view that al-Ḥarīrī’s Maqāmāt faced a hostile reception among piety-minded Muslims by offering a preliminary examination of al-Panǧdīhī’s unstudied sixth-/twelfth-century commentary on al-Ḥarīrī’s Maqāmāt. Al-Panǧdīhī’s commentary was the first digressive commentary on a prose adab text, and its digressions consist mainly of Qurʾānic quotations, ḥadīṯ of the Prophet Muḥammad, and stories about other prominent Muslims—what I term the Islamic archive. Al-Panǧdīhī argues in his elaborate preface that al-Ḥarīrī’s collection trains the reader to understand this archive better. Because al-Panǧdīhī’s commentary has never been printed and because scholars have tended to focus on the origins of the maqāma rather than its reception, this key text and its interpretive implications have been overlooked.