bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11197: Nano-Triciribine Reduces SARS-CoV-2 Infection by Sequestering ACE2 and the Novel Host Factor LDLR
Authors: Condor Capcha Jose Manuel , Iansen Irion Camila , Lambert Guerline , CHAHDI AHMED , Buchwald Peter , Dykxhoorn Derek , Farzaneh Hamidreza , deo Sapna , Daunert Sylvia , Young Karen C , Shehadeh Lina A
Published: March 2022

Introduction:
People with previous CVD hospitalized for COVID-19 have elevated death rate. We reported that patients with diabetes and HF higher protein levels of the low density lipoprotein receptor (LDLR). We hypothesized that LDLR is a novel host factor for the SARS-CoV-2-Spike (S2S) protein that may be regulated by the Akt inhibitor Triciribine (TCN), a drug being tested in Phase III studies for breast cancer. We also hypothesized that nano-formulation of Triciribine (NanoTriciribine; NTCN) would enhance its efficacy and allow for intranasal delivery.

Methods:
Interactions between the recombinant proteins Spike-RBD (receptor binding domain), ACE2, LDLR and its ectodomains (EGFA-EFFB, C2-C5 and C2) were analyzed by binding assays and co-IP in HepG2, HK2, and 293T cells. Viral entry assays were performed with 2 S2S pseudoviruses using 293T cells + hACE2 and TMPRSS2 or Furin protease. The effect of NTCN or the LXR agonist GW-3965 on viral uptake (pseudotyped VSVΔG-GFP*S2S or chimera VSV-S2S-eGFP virus) was assessed. Akt, pAkt, ACE2, and LDLR levels were determined in 293T+hACE2 by flow cytometry. Assays were done in triplicates and 1-way-ANOVA with Tukey’s correction was used for statistics.

Results:
RBD protein binds modestly to the human LDLR (EC
50
:10μM) and its C2-C5 ectodomain (EC
50
:13.8μM). Co-IP revealed a novel and strong LDLR-ACE2 interaction in several human cell lines. LDLR overexpression in human cells increased the uptake of VSVΔG-GFP*S2S (FC=2.32;p<0.001) and chimera virus (FC=.33; p<.0001). NTCN and TCN each reduced pAkt/Akt ratio. 1μM TCN or NTCN reduced LDLR (7.2%;p<.01 & 15.6%;p<0.0001) and ACE2 (32%;p<0.05 & 44.7%;p<.01) cell surface expression, respectively. 1μM NTCN or GW-3965 reduced S2S viral entry by 64.2% (p<.0001) and 40.7% (p<.01), respectively, confirming a role for LDLR in S2S infection. In hACE2tg mice, chimera VSV-S2S caused significant lung infection as measured by qPCR, GFP expression in proximal and distal lung airway epithelial cells, and electron microscopy. Intranasal delivery of NTCN was well tolerated.

Conclusions:
LDLR enhanced S2S viral entry supporting the elevated COVID-19 susceptibility seen in patients with heart disease. NTCN is a promising candidate for prophylactic treatment against COVID-19.
Abstract 11211: Guideline Directed Medical Therapy After Peripheral Vascular Intervention and One-Year Mortality in Patients with Peripheral Artery Disease in the Vascular Quality Initiative Medicare Linked Database
Authors: Provance Jeremy B , Smolderen Kim G , Mao Jialin , Goodney Philip P , Henke Peter , Sedrakyan Art , Bogra Pragati , Mena-hurtado Carlos
Published: March 2022

Introduction:
Guideline directed medical therapy (GDMT) for patients with peripheral artery disease (PAD) includes statin, antiplatelet, ACE inhibitors (angiotensin converting enzyme inhibitors) and ARBs (angiotensin-receptor blockers) therapy if hypertensive. Undertreatment with GDMT is still common, and therefore we sought to quantify the association of receiving GDMT vs. not and subsequent mortality in patients undergoing peripheral vascular interventions (PVIs).

Methods:
The Vascular Quality Initiative linked with Medicare claims data through the VISION platform and contains data for PVIs between 2010 and 2018. Patient-level GDMT at discharge following the index PVI was defined as documentation of all of the following: statin, antiplatelet, and ACE/ARB therapy if hypertensive. Patients with less than three GDMT medications were the comparator. Mortality follow-up was censored to 12 months. Kaplan Meier curves were constructed for one-year mortality. The association between the receipt of GDMT following undergoing a PVI and mortality was quantified with a Cox proportional hazards model, adjusting for demographics, clinical history, and disease severity.

Results:
A total of 29,676 patients undergoing PVI were analyzed. Of those, 42.2% were female and the mean age was 71.9 (± 10.3) years. GDMT was administered in 64.9% of discharges. One-year mortality rates for those receiving no GDMT vs. complete GDMT was 23.4% vs. 17.3% (P < 0.001) (Figure 1). Not being on GDMT was associated with an increased risk of mortality (Unadjusted HR = 1.24, 95% confidence interval [CI 95%] 1.21-1.27; Adjusted HR = 1.22, 95% CI 1.19-1.25).

Conclusions:
Over a third of patients did not have documented GDMT after discharge for PVI, which was associated with an increased risk of mortality. There is a potential opportunity to improve outcomes for patients with PAD, who are at an increased risk of cardiovascular diseases, by improving adherence to evidence-based medical therapy.
Abstract 11214: Ibrutinib Decreases Mitochondrial Oxidative Phosphorylation and Metabolic Gene Expression in Atrial-Like Engineered Heart Tissue
Authors: Rennison Julie H , Lovano Beth , Castel Laurie , Lin Cheryl R , Cheng Feixong , Moudgil Rohit , Smith Jonathan D , Barnard John , Chung Mina K , Van Wagoner David R
Published: March 2022

Introduction:
Ibrutinib is a Bruton kinase inhibitor which treats many hematological malignancies, but also precipitates atrial fibrillation (AF). The precise mechanism(s) remain to be elucidated.

Hypothesis:
We hypothesized ibrutinib treatment would decrease mitochondrial function and metabolic gene expression in human inducible pluripotent stem cell-derived atrial cardiomyocytes grown as atrial-like engineered heart tissues (aEHTs).

Methods:
aEHTs were treated with vehicle or 1 μM ibrutinib daily, for 72 hours. Oxidative phosphorylation was assessed (n=5/group) using an Oroboros Oxygraph. Gene expression was evaluated by RNAseq (n=3/group).

Results:
Oxidative phosphorylation in the presence of complex I and complex II substrates, and maximal oxidative capacity, was decreased in ibrutinib-treated aEHTs compared to vehicle (Panel A). Subunit expression of complex I (NDUFA6, NDUFA9, NDUFS1, NDUFS2, NDUFS4, ND3, ND4, ND5, ND4L), complex II (SDHA, SDHB, SDHD), complex III (UQCR10, UQCRB, UQCRC1, UQCRC2, UQCRFS1), and complex IV (CO2, COX10, COX7A2, CYCS) was decreased. Ingenuity Pathway Analysis of genes differentially expressed identified TCA Cycle and Glycolysis I (Panel B), pathways that provide reducing equivalents to the electron transport chain, as pathways that were decreased by ibrutinib. These changes were accompanied by decreased AMPK Signaling, including key metabolic regulators (PRKAA2, PRKAB2, PRKAG2, SIRT1, and PPARGC1A), and Calcium Signaling. Tumor protein (TP53), nuclear protein 1 (NUPR1), and erb-B2 receptor tyrosine kinase (ERBB2) were identified as top upstream regulators.

Conclusions:
Ibrutinib treatment decreased oxidative phosphorylation and gene expression of electron transport chain subunits and key modulators of atrial metabolism. Together, these data identify metabolic pathways that are altered by ibrutinib in aEHTs and metabolic regulators that could be targeted for AF therapeutic intervention.
Abstract 11215: Cardiac Resynchronization Therapy via Left Bundle Branch Pacing Vvrsus Optimized Biventricular Pacing with Adaptive Algorithm in Heart Failure with Left Bundle Branch Block: A Prospective, Multi-Center, Observational Study
Authors: Chen Xueying , SU YANGANG
Published: March 2022

Objectives:
The purpose of our study was to evaluate the feasibility and efficacy of cardiac resynchronization therapy (CRT) via left bundle branch pacing (LBBP-CRT) compared with optimized bi-ventricular pacing (BVP) with adaptive algorithm (BVP-aCRT) in heart failure with reduced left ventricular ejection fraction≤35% (HFrEF) and left bundle branch block (LBBB).

Methods:
One hundred patients with HFrEF and LBBB undergoing CRT were prospectively enrolled in a non-randomized fashion and divided into 2 groups (LBBP-CRT, n=49; BVP-aCRT, n=51) in 4 centers. Implant characteristics and echocardiographic parameters were accessed at baseline and during 6-month and 1-year follow-up.

Results:
The success rate for LBBP-CRT and BVP-aCRT was 98.00% and 91.07 %. Fused LBBP had the greatest reduced QRS duration compared to BVP-aCRT (102.61±9.66ms vs 126.54±11.67ms, P<0.001). Higher absolute LVEF and ΔLVEF was also achieved in LBBP-CRT than BVP-aCRT at 6-month (P=0.008,P=0.020) and 1-year follow-up (P=0.021,P=0.015). There was no significant difference in response rate between two groups while higher super-response rate was observed in LBBP-CRT as compared to BVP-aCRT at 6-month(53.06% vs 36.59%, p=0.016) and 12-month(61.22% vs 39.22%, p=0.028) during follow-up. The pacing threshold was lower in LBBP-CRT at implant and during 1-year follow-up(both p<0.001). Procedure-related complications and adverse clinical outcomes including heart failure hospitalization and mortality were not significantly different in 2 groups.

Conclusions:
The feasibility and efficacy of LBBP-CRT demonstrated better electromechanical resynchronization and higher clinical and echocardiographic response, especially higher super-response than BVP-aCRT in HFrEF with LBBB.
Abstract 11222: A Combined, Fully Automated Electrocardiogram and Echocardiogram Strategy for Detection of Hypertrophic Cardiomyopathy
Authors: Goto Shinichi , Ichihara Genki , Ikura Hidehiko , Katsumata Yoshinori , Itabashi Yuji , Macrae Calum , Deo Rahul C
Published: March 2022

Introduction:
Hypertrophic cardiomyopathy (HCM) is a disorder characterized by abnormal thickening of the heart muscle and may affect up to 1 in 200 people in the general population. Detection of HCM, like other rare diseases, is challenging both because of its low prevalence and the fact that there are other more common diseases such as aortic valve stenosis (AS) and hypertension that also manifest as cardiac hypertrophy. Distinguishing among such conditions, though challenging for human interpretation, may be feasible with artificial intelligence (AI)-based approaches, but strategies to date have looked only at data from single centers using single modalities.

Methods:
Here we developed and validated a robust approach to accelerate detection of HCM using a combination of fully automated interpretation of electrocardiograms (ECG) and echocardiograms using convolutional neural networks and evaluated it on data from multiple institutions in multiple countries. The ECG model was trained on 4,935 ECGs from Brigham and Women’s Hospital (BWH) and was tested on an internal test set of 1,950 ECGs along with 842 and 1,103 ECGs from 2 different academic medical centers (AMC) in the United States (US). The echocardiogram model was trained on 4,483 studies from BWH and was tested on an internal test set of 1,945 studies, 1,025 and 554 studies from 2 AMCs in the US, and 239 studies from an AMC in Japan.

Results:
Both models had excellent accuracy for detecting HCM with C-statistics of 0.84-0.91 and 0.91-0.94 for the ECG and echocardiography models, respectively. The echocardiography model, which uses only a single commonly acquired view, discriminates HCM from AS and HTN with C-statistics of 0.92 and 0.86, respectively. Simulating deployment on 13,906 and 7,775 patients with ECG-echocardiography paired data for AMC2, and AMC3 indicated a positive predictive value (PPV) for the ECG model of 7% and 8% at 50% and 59% recall, respectively. Pre-screening with ECG enhanced the echocardiography model performance from PPV 43% and 36% to PPV 71% and 73% at 46% recall, respectively, for AMC2 and AMC3.

Conclusions:
We have developed a robust pipeline to augment detection of HCM, and that could enable patient identification in less specialized settings.
Abstract 11227: Ischemia Mediated Contractile Dysfunction Modulates Functional Mitral Regurgitation - Multiparametric Strain and Tissue Characterization Data from the Society of Cardiovascular Magnetic Resonance (scmr) Registry
Authors: Maciejewski Abigail , Kochav Jonathan , Kim Jiwon , Tak Katherine , Judd Robert M , Kim Han , Heitner John F , Shah Dipan J , Shenoy Chetan , FARZANEH-FAR Afshin , Polsani Venkateshwar R , Parker Michele , Khalique Omar , Leon Martin B , Ratcliffe Mark B , Levine Robert , Zoghbi William A , Devereux Richard B , Kim Raymond J , Weinsaft Jonathan W
Published: March 2022

Introduction:
LV ischemia has been linked to functional mitral regurgitation (FMR) but ischemia is present many pts without FMR. CMR concomitantly assesses MR, ischemia and LV function but has not been used to test factors modifying impact of ischemia on FMR.

Methods:
Vasodilator stress CMR was performed in CAD pts in a multicenter registry, in whom advanced (≥moderate) FMR was confirmed by core lab. LV ischemia was categorized by subpapillary involvement (subtending mitral apparatus). To test mechanism by which ischemia impacts FMR, LV strain was measured in pts with ischemia and <5% LV infarct, with and without (1:2) FMR, matched for ischemia extent/distribution. Followup was done for mortality.

Results:
2639 pts were studied; 7% had advanced FMR. While FMR pts had more ischemia in subpapillary (21.8 ± 28.3 vs 13.4 ± 21.9%) and nonpapillary (19.2 ± 25.5 vs 13.0 ± 22.2%) regions (p<0.001), multivariate analysis showed only subpapillary ischemia (OR 1.13 per 5% LV [1.05, 1.21] p=0.001) to be associated with FMR (nonpapillary p=NS). Wall motion scores in ischemic subpapillary segments were higher in pts with FMR (1.7±0.9 vs 0.8±0.9, p<0.001) paralleling strain subgroup data (n=114): FMR prevalence increased stepwise with impaired radial and circumferential strain (
Figure
). Adverse mitral remodeling associated with impaired strain; mitral tenting area (OR -0.01 per % [-0.02, -0.004] p<0.01) and papillary fractional shortening (OR 0.36 per % [0.26, 0.47] p<0.001) each associated with subpapillary radial strain controlling for nonpapillary strain (p=NS). On follow up (median 4.7 [2.2, 7.7] yr), FMR, age, subpapillary ischemia and infarction each independently predicted death (p<0.001): When categorized as dysfunctional or non-dysfunctional, only ischemic/dysfunctional myocardium (HR 1.15 per 5% LV [1.05, 1.14] p<0.001) associated with death.

Conclusions:
Ischemia mediated LV dysfunction on multiparametric CMR modulates likelihood of FMR and adverse prognosis.
Abstract 11230: Coordinate Cistrome Regulation by Reprogramming Factors During Direct Human Cardiac Reprogramming
Authors: Tang Yawen , Zhou Xinyue , Zhang Jianyi , Lu Rui , Zhou Yang
Published: March 2022

Introduction:
Direct cardiac reprogramming of somatic cells into induced cardiomyocytes (iCMs) through overexpressing cardiac enriched transcription factors is considered as a promising strategy for regenerative medicine and an important cell model to study cell fate determination. In addition to our published cocktail using MEF2C, GATA4, and TBX5 and microRNA miR-133 (MGT133), we found that addition of TBX20 significantly enhanced cardiac reprogramming and generated human iCMs (hiCMs) more similar to functional cardiomyocyte identity. However, it is largely unknown how the reprogramming factors coordinately regulate direct lineage conversion.

Methods:
To determine the regulatory networks orchestrated by transcription factors, we performed CUT&TAG or CUT&RUN for MEF2C, GATA4, TBX5, TBX20 and histone marks H3K27me3, H3K27ac and H3K4me3 in hiCMs generated with MGT133 or MGT133+TBX20. We also performed time course RNA-seq and ATAC-seq analyses to profile transcriptome and chromatin accessibility changes during reprogramming process.

Results:
We mapped the genome wide binding of each reprogramming factor and determined the co-occupancy of TBX20 and MGT at a majority of cardiac gene promotors, especially at genes related to cardiac cell structure and contractility, such as MYBPC3, SCN5A and MYH7. Interestingly, TBX20 itself is not able to target cardiac genes unless is expressed together with MGT. Meanwhile, expression of TBX20 led to significantly increased chromatin occupation of MGT factors and upregulation of cardiac-specific genes. Our immunoprecipitation assay further confirmed the physical interaction of TBX20 with MGT. Intriguingly, in addition to targeting cardiac-lineage genes, TBX20 also binds to many fibroblast-specific genes, such as LAMB1 and IGFN1. While binding of TBX20 augments chromatin accessibility at cardiac-specific genes loci, it decreases the chromatin openness at fibroblast genes.

Conclusions:
TBX20 cooperates with MEF2C, GATA4, and TBX5 to target cardiac-specific genes and facilitate gene transcription and serves as a transcription repressor of non-cardiac lineage genes. These results provided significant insight into cistrome regulation during human direct cardiac reprogramming.
Abstract 11232: Role of Line-1 Retrotransposition in Atherosclerosis
Authors: Pulgarin Andres , Cuevas Rolando A , St Hilaire Cynthia , Bruemmer Dennis , Al Ghouleh Imad
Published: March 2022

Introduction:
LINE-1 (L1) retrotransposons are a class of transposable elements comprising ~21% of the human genome. L1-retrostransposed elements move within the genome, where they profoundly alter gene function. Somatic L1 insertions, or retrotranspositions (RTNs), were implicated in multiple diseases including cancer. However, this literature has been mainly confined to epithelial tissue, and the role of L1 in cardiovascular diseases is unknown. Specifically, whether L1 presence and activity in vascular cells has a functional role in atherosclerosis, a disease characterized by extensive vascular remodeling, inflammation and plaque formation, remains unexplored.

Hypothesis:
L1 expression and RTN in vascular endothelial cells (ECs) leads to endothelial activation in atherosclerosis.

Methods:
L1 mRNA expression was analyzed by qRT-PCR in postmortem coronary artery specimens from patients with atherosclerosis and non-diseased controls. Immunofluorescence (IF) in coronary tissue was performed for ORF1p, a L1 encoded polypeptide required for active RTN. In vitro, qRT-PCR was used to assess L1 expression in primary human aortic ECs (HAEC) treated with proatherogenic inflammatory stimuli TNFα, IL6, oxidized LDL (oxLDL) and IL1β. Active RTN was assessed by FACS and IF in a purpose-built human umbilical vein EC line (CRL2922) L1 RTN detection system.

Results:
L1 mRNA was increased in atherosclerotic human coronary arteries and positively correlated with age and histologically-assessed disease severity. ORF1p expression increased in EC of atherosclerotic plaques indicative of increased L1 activity. L1 expression and retrotransposition was induced in ECs in vitro by TNFα, IL-6 and oxLDL. Finally, de novo L1 insertion alone resulted in upregulation of genes involved in EC activation and atherosclerosis (ICAM1, MCP-1, IL6, NOR), and this effect was further enhanced by co-treatment with TNFα, IL-6 and oxLDL.

Conclusions:
Our results identify a disease-related increase in L1 in the vascular endothelium under atherosclerotic conditions that contributes to EC activation. These data support a permissive environment during atherosclerosis for L1 activity and unveil a previously unrecognized role for L1 in this disease’s pathophysiology.
Abstract 11235: Timing of Repair in Post-Infarction Ventricular Septal Defect
Authors: Jaswaney Rahul , Arora Shilpkumar , Shah Nischay , Osman Mohammed Najeeb , Abu-Omar Yasir , Shishehbor Mehdi H
Published: March 2022

Background:
Post-infarction ventricular septal defect (PIVSD) formation is a rare but devastating complication of ST-elevation myocardial infarction (STEMI).

Objective:
To determine the association of the timing of VSD repair on in-hospital mortality in patients with PIVSD.

Methods:
This retrospective cohort study identified 10,902 patients with VSD and STEMI from the Nationwide Readmissions Database from 2003-2018. VSD repair was identified by appropriate ICD9 and ICD10 codes. Patients were stratified based on intervention timing: 0-7 days, 8-14 days, and > 14 days after admission. The primary outcome was in-hospital mortality. Outcomes of patients who received VSD repair were compared patients who did not receive VSD repair within the same time-point. Multivariate logistic regressions were used to adjust for demographic, comorbid, and socioeconomic factors. Analysis was stratified by clinical presentation of cardiogenic shock.

Results:
In patients in shock, there was a significant decrease in in-hospital mortality with VSD repair at 0-7 days (50.8% vs. 60.4%; OR 0.76; 95% CI 0.68-0.86, p<0.001) as compared to at risk patients who did not undergo VSD repair (Table 1). There was no difference in in-hospital mortality in patients receiving VSD repair at 8-14 days or at > 14 days as compared to who did not undergo VSD repair. In patients not in shock, there was an increase in in-hospital mortality in patients who received VSD repair from 0-7 days (23.8% vs 36%; OR 1.59; 95% CI 1.33-1.90; p<0.001) at compared to those who did not receive VSD repair. There was no significant difference in outcomes in patients not in shock who received VSD repair at 8-14 days or at >14 days as compared to those at who did not receive VSD repair at this timepoint.

Conclusions:
Early PIVSD repair was associated with a significantly decreased rate of in-hospital mortality in patients in shock, but was associated with significantly higher rate of in-hospital mortality in patients not in shock
Abstract 11236: Preserved Cardiac Reserve and Cardiorespiratory Fitness in Patients with De Novo versus Acute on Chronic HFrEF
Authors: Del Buono Marco , Mihalick Virignia , Damonte Juan Ignacio , Billingsley Hayley , Vecchie Alessandra , TRANKLE Cory R , Kadariya Dinesh , Wohlford George F , Ho Ai-Chen , Talasaz Azita , Carbone Salvatore , MARKLEY ROSHANAK , Turlington Jeremy , Lu Juan , Federmann Emily , Arena Ross , VAN TASSELL Benjamin W , Abbate Antonio , Canada Justin M
Published: March 2022

Hypothesis:
There is limited understanding on the potential differences in the pathophysiology between
de-novo
heart failure with reduced ejection fraction (HFrEF) and acute on chronic HFrEF.

Objective:
the aim of this study was to assess differences in cardiorespiratory fitness (CRF) parameters between
de-novo
heart failure and acute on chronic HFrEF using cardiopulmonary exercise testing (CPX).

Methods:
We retrospectively analyzed CPX data measured within 2 weeks of discharge following acute hospitalization for HFrEF. The predicted peak oxygen consumption (VO
2
) was calculated using the FRIEND formula. Circulatory power, a measure of cardiac reserve, was calculated as the product of peak VO
2
and peak systolic blood pressure. Peak O
2
pulse, a surrogate measure of exercise stroke volume, was calculated by dividing peak VO
2
by the maximum heart rate (HR). Left ventricular ejection fraction (LVEF) was calculated using Simpson method during echocardiography. Data are reported as median and interquartile range or frequency and percentage (%).

Results:
We included 102 patients: 32 (31%) women, 81 (79%) Black, 57.0 [ 51-64] years of age, BMI of 34 [29-39] Kg/m
2
. Of these, 26 (25%) had
de-novo
HFrEF and 76 (75%) had acute on chronic HFrEF. When compared with acute on chronic, patients with
de-novo
HFrEF had a significantly higher peak VO
2
(16.5 [12.2-19.4] vs 12.8 [10.15-15.32] mL·kg
-1
·min
-1
,
p
<0.001), %-predicted peak VO
2
(58% [51-75] vs 49% [42-59])
p
=0.012), peak HR (134 [117-147] vs 117 [104-136] bpm,
p
=0.004), peak O
2
pulse (12.2 [10.5 -15.5] vs 9.9 [8.0-13.1] mL/beat,
p
=0.022) and circulatory power (2823 [1973-3299] vs 1902 [1372-2512] mmHg·mL·kg
-1
·min
-1
, p=0.002). No significant difference in resting LVEF was found between groups.

Conclusion:
Patients with
de-novo
HFrEF patients have better CRF parameters than those with acute on chronic HFrEF. These differences are not explained by resting left ventricular systolic function but may be related to greater preservation in cardiac reserve during exercise in
de-novo
HFrEF patients.
Abstract 11238: Impact of Baseline Heart Failure and Heart Failure Subtype on Brain Natriuretic Peptide Levels in Patients with Acute Pulmonary Embolism
Authors: Cash Ayla , Niedoba Matthew , Katterle Konrad , Pasadyn Vanessa , Brewster Pamela , Mann Alexandria , Gupta Rajesh
Published: March 2022

Introduction:
Among patients with acute pulmonary embolism (PE), elevated levels of brain natriuretic peptide (BNP) correlate with right ventricular dysfunction and increased morbidity and mortality. Suggested BNP cut-offs for PE risk stratification in the general population range from 90-100 pg/mL. It is unclear whether this BNP cut-off should be used for PE risk stratification among patients with heart failure (HF), who may have elevated BNP at baseline.

Methods:
Patients diagnosed with acute PE between 2010 and 2015 at the University of Toledo Medical Center were identified. Patients were categorized as: no HF, heart failure with reduced ejection fraction (HFrEF), or heart failure with preserved ejection fraction (HFpEF). No HF was defined as having no prior history of HF and an ejection fraction (EF) ≥ 50%. HFrEF was defined as history of HF and an EF < 50%. HFpEF was defined as history of HF and an EF ≥ 50%. HF was defined as subjects with HFrEF or HFpEF.

Results:
One hundred and eighty-three patients with acute PE were identified for this study. One hundred and forty-two patients were classified as no HF (median BNP 112 [interquartile range (IQR) 49-355] pg/mL), while 41 were classified as HF (median BNP 422 [IQR 179-940] pg/mL) (p<0.0001). When HF was further sub-categorized, we found significant differences in BNP levels between subjects with HFrEF (median BNP 923 [IQR 464-2296] pg/mL) vs. subjects with HFpEF (median BNP 247 [IQR 88-726] pg/mL) (p=0.002). Median BNP among patients with HFrEF was significantly higher compared to patients with no HF (p<0.0001). Median BNP among patients with HFpEF was not significantly different compared to patients with no HF (p=0.416).

Conclusions:
Patients with HFrEF who present to the hospital with acute PE have significantly higher median BNP compared to patients with HFpEF or no HF. These results suggest that risk stratification for PE using current BNP cut-off guidelines may not be optimal for patients with HFrEF.
Abstract 11239: Changes in Clinical Outcomes for Patients Enrolled in a Non-Academic Multidisciplinary Cardio-Obstetrics Program
Authors: Benson Gretchen A , Shaw Kirsten , Wagner William , Sidebottom Abbey , Baechler Courtney , Hayes Joy , Okeson Brynn , Saxena Retu
Published: March 2022

Introduction:
Cardiovascular disease (CVD) is the leading cause of maternal death. Maternal mortality has steadily increased in the US. More than 60% of deaths due to CVD are preventable. In 2018, a non-academic multidisciplinary cardio-obstetrics (CVOB) program was formed at a Midwest hospital system. Cardiologists and Maternal Fetal Medicine specialists work together to provide evidence-based care to pregnant women with cardiac risk. To assess program effectiveness, we compared women seen by the CVOB program in 2018/2019 with a sample of pregnant women seen by cardiology in 2016/2017 prior to the program’s inception.

Hypothesis:
Women seen by the CVOB program will have improved outcomes - measured by gestation at delivery, length of stay (LOS) and readmission rates - over pre-program controls.

Methods:
A retrospective chart review was conducted of 102 patients who received care from the CVOB program in 2018/2019. These women were matched 1:1 based on mWHO categories with women who were seen by cardiology in 2016/2017.

Results:
Women who received care in the CVOB program had more cardiology tests during pregnancy relative to pre-program controls (median of 8 tests vs 5; p <0.001). Women in the CVOB program had a longer LOS (median of 3.08 vs 2.55 days; p=0.02). Women in the CVOB program were less likely to have inpatient or ED visits in the 6 months postpartum (24% vs 72%; p <0.001). Gestational age was similar at time of delivery.

Conclusions:
In a multidisciplinary, non-academic CVOB program; there was a trend towards an increase in LOS after delivery, as well as in increase in ICU utilization. However, there were fewer readmissions or emergency visits in the post-partum period. A multidisciplinary CVOB program is feasible in a non-academic setting. The development of the program led to a decrease in the rates of readmission and ED visits in the postpartum period.
Abstract 11241: Longitudinal Myocardial Mechanics in Covid-19 Survivors with Normal Left Ventricular Ejection Fraction, a Single Center Study
Authors: Jain Vaibhav , Quintero-Martinez Juan , Madera Sandra C , Young Katie , Kane Garvan , Pellikka Patricia A , Michelena Hector I , Pislaru Sorin , Villarraga Hector R
Published: March 2022

Introduction:
Subclinical cardiovascular involvement in COVID-19 patients has not been well described. 2D-Speckle Tracking Echocardiography derived global longitudinal strain (GLS) and systolic and early diastolic strain rate (SRs, SRe) measurements are more sensitive than standard echocardiographic parameters to diagnose subclinical mechanical dysfunction in patients with normal Left Ventricle Ejection Fraction (LVEF).

Hypothesis:
Evaluate subclinical myocardial mechanical function and reserve in active COVID-19 systemic disease patients with normal LVEF vs controls and between survivors and non survivors of COVID-19 in the longitudinal domain of contractility.

Methods & Results:
166 adult patients with active COVID 19 having normal LVEF were included and compared to 89 healthy volunteers. Baseline parameters were recorded. Peak GLS, SRs and SRe, were measured offline. Mean age was 62.53 ± 18.96 years and 87 (52%) were males and Mean LVEF was 62±5%. COVID-19 patients had higher GLS compared to controls (-20.93%±0.30 vs. -18.48%±0.40; p value <0.0001), SRs was similar (-0.97 s
-1
±0.10 vs. -0.98 s
-1
±0.02, p value 0.2528) and SRe was lower (0.85 s
-1
±0.0 vs. 1.05 s
-1
±0.02; p value <0.0001) respectively. After adjusting for age and sex, GLS, SRs and SRe was significant (p<0.001). GLS, SRs and SRe were similar in survivors vs. non survivors (p NS), both groups had elevated biomarkers (cardiac troponin, NT-pro BNP, CRP), but non survivors had higher levels (3.22±0.18 vs 3.62±0.28, p = 0.2371, 5.86±0.19 vs 7.15±0.27, p = 0.0004, 3.75±0.14 vs 4.31±0.21, p = 0.0422, 7.64±0.17 vs 8.26±0.25, p=0.0487 respectively) (Table 1).

Conclusions:
In our cohort, COVID-19 patients had better systolic reserve and abnormal relaxation compared to controls. There was no significant difference in strain (GLS) and strain rate (SRs & SRe) amongst survivors and non survivors in the longitudinal domain of contractility despite of higher inflammatory biomarkers in non-survivors.
Abstract 11246: Racial Distribution and Regional Comparison in Hospital Outcomes Among Patients with Peripartum Cardiomyopathy in the United States
Authors: Fatuyi Michael , Pereira Leanne , Akuna Emmanuel , Zain elabidin Awfa , Namdarizandi Vahid , Yusuf Mubarak , AKPALA LORETTA , Otulana Rukayat , Ansari Asimul H
Published: March 2022

Introduction:
Peripartum cardiomyopathy (PPCM) is a rare entity, first described over two centuries ago, associated with left ventricular systolic dysfunction in the last month of pregnancy and up to 5 months postpartum, in the absence of another identifiable etiology for heart failure. Black women are disproportionately affected by this condition. Our study sought to evaluate the racial distribution of each region and regional differences in-hospital outcomes among patients with PPCM in the United States.

Methods:
Data were obtained from the nationwide inpatient sample database (NIS) for 2016 and 2017. We included data on all adult females (aged 18 - 49 years) hospitalized with a principal diagnosis of PPCM using ICD-10 codes. Our primary outcome was in-hospital mortality. Secondary outcomes included: length of stay, cardiac arrest, and cardiogenic shock. Multivariable logistic and linear regression models were constructed to evaluate the relationship between PPCM and regional in-hospital clinical outcomes. A p-value <0.05 was considered statistically significant.

Results:
A total of 3,030 hospitalizations for PPCM were included. Regional distribution for the northeast, midwest, south, and west were 12.0%, 20.8%, 50.0%, and 17.2%, respectively with a mean age of 31 years (CI of 28-34, P < 0.01) across all regions. Inpatient mortality was 0.82% overall. Using northeast as the reference of comparison, there was no statistically significant difference in mortality across the regions. There was white predominant in the midwest and west compare to black predominant in the south and northeast (Table 1). In addition, we found no differences in the average length of stay, rates of cardiac arrest, or cardiogenic shock.

Conclusion:
There were no regional differences in hospital outcomes among patients admitted with PPCM in the US
Abstract 11260: Psychosocial Factors Amongst Women with MINOCA
Authors: Hausvater Anais , Spruill Tanya , Park Ki , Smilowitz Nathaniel , Shah Binita , Marzo Kevin , Jhalani Nisha , Giesler Caitlin , Mehta Laxmi S , Ahmed Bina , Bairey Merz C Noel , Thomas Dwithiya , Trost Jeff , Mehta Puja , Har Bryan , Bainey Kevin R , Xia Yuhe , Zhong Hua , Hada Ellen , Hochman Judith S , Reynolds Harmony
Published: March 2022

Introduction:
Women are particularly vulnerable to high stress and depression after myocardial infarction (MI), and both are associated with increased post-MI mortality. MI with non-obstructive coronary arteries (MINOCA) disproportionately affects women. Little is known about the degree to which stress and depression levels around the time of MI relate to the type of MI in women. We aimed to determine whether psychosocial factors differ between women with MINOCA and those with MI and obstructive CAD (MI-CAD).

Methods:
Women with MI enrolled in a multicenter study completed baseline measures of perceived stress (Perceived Stress Scale [PSS-4]), depressive symptoms (Patient Health Questionnaire [PHQ-2]), major life stressors (life events checklist [LEC]) and psychological resilience (Brief Resilience Scale [BRS]) at the time of hospitalization for acute MI. PSS-4 and PHQ-2 were repeated at 2-months post-MI. Psychosocial measures were compared between patients with MINOCA and those with MI-CAD at baseline and 2-month follow-up using t-test and chi-square.

Results:
This study compared 172 MINOCA patients and 314 MI-CAD patients. Women with MINOCA were younger (59.4±12.5 vs 64.2±12.9 years, p<0.001) and less likely to be non-Hispanic white (52.3% vs 64.3%, p=0.004). Women with MINOCA were less likely to have high stress (PSS-4 ≥6) at the time of MI (51.0% vs 63.0% vs, p=0.021) and at 2-months post-MI (32.5% vs 46.3%, p=0.019) compared to women with MI-CAD. There was no difference in the proportion with depressive symptoms (PHQ-2 ≥2) at the time of MI (36.2% MINOCA vs 42.7% MI-CAD, p=0.23) or at 2-months post-MI (39.0% vs 39.5%, P>0.99). MINOCA patients reported fewer major life stressors than MI-CAD patients (LEC 2.67±1.93 vs 3.13±1.80, p=0.015). The frequency of low psychological resilience (BRS<18) (24.3% vs 21.6%, p=0.60) did not differ between MINOCA and MI-CAD patients.

Conclusions:
Stress and depression are common among women at the time of, and 2-months post-MI. MINOCA patients reported lower stress levels at the time of and following MI compared to MI-CAD patients and fewer traumatic life events, but depressive symptoms and resilience did not differ by MI type.
Abstract 11261: Impact of Baseline Heart Failure on RV:LV Diameter Ratio in Patients with Acute Pulmonary Embolism
Authors: Cash Ayla , Pasadyn Vanessa , Katterle Konrad , Niedoba Matthew , Brewster Pamela , Mann Alexandria , Gupta Rajesh
Published: March 2022

Introduction:
Among patients with acute pulmonary embolism (PE), an elevated right ventricular to left ventricular diameter (RV:LV) ratio is associated with increased morbidity and mortality. RV:LV cut-offs used to identify PE patients at elevated risk for adverse events range from 0.9-1.0. It is unclear whether this cut-off should be used for PE risk stratification among patients with heart failure (HF), who may have abnormal cardiac chamber dimensions.

Methods:
Patients diagnosed with acute PE between 2010 and 2015 at the University of Toledo Medical Center were identified. Patients were categorized as: no HF, heart failure with reduced ejection fraction (HFrEF), and heart failure with preserved ejection fraction (HFpEF). No HF was defined as having no prior history of HF and an ejection fraction (EF) ≥ 50%. HFrEF was defined as history of HF and an EF < 50%. HFpEF was defined as history of HF and an EF ≥ 50%.

Results:
One hundred and eighty-three patients were identified for this study. Twelve patients were excluded due to missing EF records. Among the remaining 171 patients, 142 were categorized as no HF, 13 were categorized as HFrEF, and 16 were categorized as HFpEF. There were no significant differences in mean RV diameter between HFrEF [39.1 mm, standard deviation (SD) ± 5.9], no HF [36.9 mm, SD ± 7.5], or HFpEF [38.5 mm, SD ± 6.6] (p=0.575). However, mean LV diameter among patients with HFrEF was significantly higher [52.2 mm, SD ± 7.2] compared to no HF [38.1 mm, SD ± 8.3] and HFpEF [42.1 mm, SD ± 6.6] (p<0.001). Median RV:LV ratio was 0.77 [interquartile range (IQR) 0.65-0.89] for HFrEF, 0.91 [IQR 0.79-1.17] for no HF, and 0.89 [IQR 0.80-1.04] for HFpEF (p=0.024).

Conclusions:
Patients with HFrEF who presented to the hospital with acute PE had significantly higher mean LV diameter and lower RV:LV ratio compared to patients with HFpEF or no HF. These results suggest that risk stratification using current RV:LV ratio guidelines may underestimate PE risk among patients with HFrEF.
Abstract 11264: Medicaid Expansion and Association with Cardiovascular Care: A Systematic Review
Authors: Jiang Ginger , Wasfy Jason
Published: March 2022

Background:
One of the goals of the Affordable Care Act was to improve health outcomes through expanding insurance, including through Medicaid expansion. It remains unclear whether Medicaid expansion was associated with improvement in cardiovascular (CV) outcomes.

Objectives:
To systematically review the available literature on the association of Medicaid expansion with cardiovascular outcomes.

Methods:
In adherence with guidelines established by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), we performed systematic searches in PubMed, the Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases for studies that evaluated the relationship between Medicaid expansion and CV outcomes.

Results:
A total of 24 studies met inclusion and exclusion criteria. Of these, 22 studies utilized a quasi-experimental study design. The median number of post-expansion years evaluated was 2 (range, 0.5-4) and the median number of expansion states included was 23 (range, 1-33). Commonly assessed outcomes included access to cardiovascular care (25.5%), morbidity/mortality (19.1%), disparities in care (12.8%), and preventive care (42.6%). Medicaid expansion was generally associated with improved access to CV care, reduction in overall CV mortality, and some increase in screening and treatment of CV comorbidities, but was not commonly associated with improvement in disparities in care.

Conclusions:
Current literature demonstrates in general that Medicaid expansion was associated with improved access to care, some improvement in clinical outcomes outside of acute care settings, and some improvements in prevention and screening. In general, Medicaid expansion has not been associated with reductions in disparities. Conclusions are limited because quasi-experimental comparisons of expansion and non-expansion states cannot account for unmeasured state-level confounders.
Abstract 11267: Ibrutinib Treatment Results in Arrhythmia in Atrial-Specific Human Ipsc-Derived Cardiomyocytes
Authors: Fleming Matthew R , Hall Lynn , Short Laura , Shaffer Christian , Glazer Andrew , Moslehi Javid J , Roden Dan M
Published: March 2022

Introduction:
Cardiovascular sequelae of targeted cancer therapies may provide novel insights into cardiovascular biology and disease pathogenesis, including atrial fibrillation (AF). The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has revolutionized treatment for B-cell malignancies but increases the incidence of AF compared with conventional chemotherapy. Recent data in mouse models have shown that ibrutinib mediated-AF likely results not from inhibition of BTK (“on target” effect), but from off-target inhibition of a different kinase, C-terminal Src kinase (CSK). The signaling pathway by which CSK inhibition results in AF remains unknown and thus may represent a novel mechanism for AF molecular pathogenesis.

Methods:
To study how CSK inhibition results in AF in a human derived model, we created atrial specific cardiomyocytes from human induced pluripotent stem cells (hiPSC-aCMs) from a healthy control. We studied cellular monolayers of hiPSC-aCMs using extracellular field potential (EFP) recordings obtained by the Nanion CardioExcyte 96 system after 24 hour exposure to vehicle, ibrutinib, or the second generation BTK inhibitor acalabrutinib.

Results:
Chamber specificity of hiPSC-aCMs was confirmed by Western blot analysis of subtype-specific markers. Treatment with ibrutinib for 24 hours resulted in striking increase in beat-to-beat variability in spontaneous contraction, an in vitro correlate of arrhythmogenic behavior (mean coefficient-of-variance/second following treatment 0.835 for ibrutinib vs. 0.198 for acalabrutinib vs. 0.165 for DMSO vehicle control, p<0.001). Arrhythmogenic behavior was not seen with acalabrutinib, which does not appear to increase the incidence of AF in clinical trials.

Conclusion:
These experiments provide a novel method of screening for arrhythmogenic potential of targeted cancer therapies and validate atrial-specific hiPSC-CMs as a model system for the study of CSK mediated AF.
Abstract 11271: Three-Dimensional Deep-Tissue Imaging of the Right Ventricle Reveals Decreased Capillary-Cardiomyocyte Contact Surface in Decompensated Right Heart Failure
Authors: Ichimura Kenzo , Boehm Mario , Zhang Fan , Andruska Adam , Dufva Melanie J , Reddy Sushma , Kheyfets Vitaly O , Metzger Ross , Spiekerkoetter Edda F
Published: March 2022

Introduction:
Right ventricular (RV) function determines the prognosis of pulmonary hypertension. Capillary rarefaction using 2D imaging has been proposed as the hallmark of RV failure, although this paradigm is controversially discussed. By applying 3D deep-tissue imaging, we characterized the adaptive and maladaptive response of the capillaries in the pressure-overloaded RV in hypertrophy and failure.

Methods and Results:
Mice subjected to pulmonary artery banding (PAB) were harvested after 3 weeks (w) (compensated RV hypertrophy) and 7w post-surgery (decompensated RV failure). Hearts were sectioned into 250 μm and capillaries were stained with isolectin B4. Samples were imaged with confocal microscopy and reconstructed into 3D using Imaris imaging software (Fig. A, n=4). In the RV free wall, mean capillary length decreased, and branching, tortuosity, mean and total capillary diameter increased 3w post-PAB. Mean and total diameter, and total length decreased at 7w resulting in a reduced capillary volume normalized to heart volume at 7w vs 3w, but not significantly reduced vs baseline suggesting that this is not the mechanism of RV failure (Fig. B). However, most strikingly we uncovered by sparsely labeling cardiomyocytes that the capillary-cardiomyocyte contact surface was maintained at w3, yet significantly decreased in areas of interstitial fibrosis in the decompensated RV at 7w compared to baseline and 3w (Fig. C, D).

Conclusions:
3D deep-tissue imaging uncovered the remarkable adaptive response of the RV microvasculature in the pressure-overloaded RV to maintain an adequate capillary-cardiomyocyte contact by increasing capillary branching, length and diameter. These mechanisms failed in the decompensating RV when interstitial fibrosis impaired the capillary-cardiomyocyte interaction. Our method offers the unprecedented opportunity to study microvascular adaption in the pressure overloaded RV and is readily transferable to human tissue.
Abstract 11279: Coronary Microvascular Dysfunction in Patients with Elevated Filling Pressures During Exercise
Authors: Allan Tess , Tessema Frazer , Shirkhodaie Camron , Arévalo Cynthia M , Blair John
Published: March 2022

Introduction:
Ischemia due to coronary microvascular dysfunction (CMD) may cause a loss of lusitropy and resultant elevated filling pressures which can worsen with exercise. CMD is prevalent in patients with heart failure with preserved ejection fraction (HFpEF) and exercise studies are useful in diagnosing early HFpEF. The relationship between CMD and early HFpEF is not well characterized.

Hypothesis:
CMD is prevalent in patients with elevated pulmonary capillary wedge pressure (PCWP) at rest and those with normal resting PCWP but elevated post-exercise PCWP.

Methods:
All patients without obstructive CAD who underwent cardiac catheterization with coronary physiology and exercise bicycle studies at the University of Chicago Medical Center between 2015-2021 were included. Elevated resting PCWP was defined as
>
15 and elevated post-exercise PCWP was defined as
>
25. Patients were separated into three groups: elevated resting PCWP (group 1), normal resting & elevated exercise PCWP (group 2), and normal resting and exercise PCWP (group 3).

Results:
A total of 22 patients (mean age 56
+
10 years, 77% female) were studied. There were 9 patients in group 1, 8 patients in group 2, and 5 patients in group 3. A diagnosis of HFpEF was present in all patients in groups 1 and 2 and no patients in group 3. There was a nonsignificant trend towards lower median CFR in groups 1 (2.1 IQR 1.6-2.8) and 2 (2.3 IQR 1.75-3.65) compared to group 3 (3.8 IQR 1.8-5.5; Figure 1). Similarly, there was a nonsignificant trend towards higher median IMR in groups 1 (23.2 IQR 16.9-41.3) and 2 (25.9 IQR 19.0-35.2) compared to group 3 (14.4 IQR 11-25; Figure 1).

Conclusion:
Like patients with elevated resting PCWP, patients with normal resting and elevated post-exercise PCWP tend to have lower CFR and higher IMR than those patients with normal pre and post-exercise PCWP. This may indicate that CMD plays a role in the development of early HFpEF though more patients are needed to further characterize this relationship.