bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14745: The Histone Reader PHF7 Cooperates With the SWI/SNF Complex at Cardiac Super Enhancers to Promote Direct Cardiac Reprogramming
Authors: Garry Glynnis A , Bezprozvannaya Svetlana , Chen Kenian , Zhou Huanyu , Hashimoto Hisayuki , Morales Maria G , Liu Ning , Bassel-Duby Rhonda S , Olson Eric N
Published: May 2021

Direct cardiac reprogramming of fibroblasts to cardiomyocytes presents an attractive therapeutic strategy to restore cardiac function following injury. Cardiac reprogramming was initially achieved through the overexpression of the transcription factors Gata4, Mef2c, and Tbx5 (GMT), and later, Hand2 (GHMT) and Akt1 (AGHMT) were found to further enhance this process. Yet, staunch epigenetic barriers severely limit the ability of these cocktails to reprogram adult fibroblasts. We undertook a screen of mammalian gene regulatory factors to discover novel regulators of cardiac reprogramming in adult fibroblasts and identified the histone reader PHF7 as the most potent activating factor. Mechanistically, PHF7 localizes to cardiac super enhancers in fibroblasts, and through cooperation with the SWI/SNF complex, increases chromatin accessibility and transcription factor binding at these sites. Further, PHF7 recruits cardiac transcription factors to activate a core regulatory circuit in reprogramming. Importantly, PHF7 is the first epigenetic factor shown to achieve efficient reprogramming in the absence of Gata4. Here, we highlight the underexplored necessity of cardiac epigenetic modifiers, such as PHF7, in harnessing chromatin remodeling and transcriptional complexes to overcome critical barriers to direct cardiac reprogramming.
Abstract 14758: Contrasting Effects of Phospholipid Linked Eicosapentaenoic Acid and Arachidonic Acid on Membrane Structure and Stability
Authors: Sherratt Samuel , Bhatt Deepak L , Mason Preston
Published: May 2021

Background:
Treatment with prescription, high dose, stable icosapent ethyl (IPE), which is metabolized to eicosapentaenoic acid (EPA), significantly reduced clinical events in high-risk patients with either cardiovascular disease or diabetes plus other risk factors (REDUCE-IT). Previous studies suggest that the benefits of EPA, an omega-3 fatty acid (O3FA), correlate positively with its levels and ratio to arachidonic acid (AA) in circulation and cellular membranes. Unlike EPA, AA is an omega-6 fatty acid (O6FA) that, along with its metabolites, contributes to inflammation and diabetes.

Objective:
The purpose of this study was to compare the separate and combined effects of phospholipid-linked EPA and AA on membrane structure.

Methods:
Small angle x-ray diffraction approaches compared the effects of 1-palmitoyl-2-eicosapentaenoyl-sn-glycero-3-phosphocholine (PL-EPA) and 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PL-AA) at a 1:20 ratio in membranes composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol (C) at a 0.3:1 C:PL ratio. As a control, we also evaluated membranes consisting of POPC and C only at the same C:PL ratio. Electron density profiles (electrons/Å
3
vs Å) generated from the diffraction data served to determine membrane structure, including its width or
d
-space, at 1 Å resolution.

Results:
Addition of PL-EPA increased membrane hydrocarbon core electron density over a broad area ± 0-10 Å from the membrane center, indicating a stabilizing effect on surrounding phospholipid acyl chains. By contrast, PL-AA caused a smaller, bimodal increase in electron density centered at ± 7 Å from the center of the membrane corresponding to its terminal double bonds. The membrane widths of the PL-EPA and PL-AA containing membranes were similar at 58 ± 0.7 Å and 57 ± 0.5 Å, respectively. The combination of PL-EPA with PL-AA highly attenuated the stabilizing effects of EPA on the membrane.

Conclusion:
PL-EPA causes membrane stability in a manner that is disrupted by the presence of PL-AA. The contrasting effects of PL-EPA and PL-AA on membrane structure may contribute to differences in biological activity.
Abstract 14759: Burden of Intracranial Hemorrhage in Patients With Acute Myocardial Infarction in the United States, 2000-2017
Authors: Patlolla Sri Harsha , Vallabhajosyula Saraschandra
Published: May 2021

Introduction:
There is a paucity of contemporary data on the burden of intracranial hemorrhage (ICH) complicating acute myocardial infarction (AMI).

Methods:
The National Inpatient Sample database (2000 to 2017) was used to evaluate in-hospital burden of ICH in adult (>18 years) AMI admissions. In-hospital mortality, hospitalization costs, length of stay, and measure of functional ability were the outcomes of interest. The discharge destination along with use of tracheostomy and percutaneous endoscopic gastrostomy (PEG) were used to estimate functional burden.

Results:
Of a total 11,622,528 AMI admissions, 23,422 (0.2%) had concomitant ICH. Compared to those without, admissions with ICH were on average older, female, of non-White race, with greater comorbidities, and higher rates of arrhythmias (all p<0.001). Female sex, non-White race, ST-segment-elevation AMI presentation, use of fibrinolytics, mechanical circulatory support and invasive mechanical ventilation were identified as individual predictors of ICH. The AMI admissions with ICH received less frequent coronary angiography (46.9% vs. 63.8%), percutaneous coronary intervention (22.7% vs. 41.8%), and coronary artery bypass grafting (5.4% vs. 9.2%) as compared to those without (all p<0.001). ICH was associated with a significantly higher in-hospital mortality (41.4% vs. 6.1%; adjusted OR 5.65 [95% CI 5.47-5.84]; p<0.001), and adjusted temporal trends showed a steady decrease in in-hospital mortality over the 18-year period (Figure 1A). AMI-ICH admissions also had longer hospital length of stay, higher hospitalization costs, and greater use of PEG (all p<0.001). In AMI-ICH survivors (N=13, 689), 81.3% had a poor functional outcome indicating severe morbidity and temporal trends revealed a slight increase over the study period (Figure 1B).

Conclusions:
ICH causes a substantial burden in AMI due to associated higher in-hospital mortality, resource utilization, and poor functional outcomes.
Abstract 14763: Patients With a Perceived High-bleeding Risk in a Randomized Controlled Trial of Alert-based Computerized Decision Support for Stroke Prevention in Atrial Fibrillation: An Af-Alert Substudy
Authors: Piazza Gregory , Hurwitz Shelley , Carroll Brett , Goldhaber Samuel Z
Published: May 2021

Introduction:
A perceived increased risk of bleeding is one of the most frequent reasons for failure to prescribe anticoagulation for stroke prevention in atrial fibrillation (AF). We previously conducted a randomized controlled trial of alert-based computerized decision support (CDS) to increase prescription of antithrombotic therapy in 458 high-risk hospitalized patients with AF who were not being anticoagulated.

Hypothesis:
We hypothesized that patients with a perceived high risk for bleeding would have a similar HAS-BLED score and rate of major and clinically-relevant non-major bleeding.

Methods:
To determine the clinical characteristics and outcomes of these patients determined to be high-risk for bleeding, we analyzed the 248 patients in the alert group.

Results:
A perceived high risk of bleeding was the most common reason (77%) for omitting antithrombotic therapy. Median HAS-BLED scores were similar in these patients compared with those who were not deemed to have an increased bleeding risk (3 vs. 3, p=0.44). Despite being categorized as too high-risk for bleeding to receive antithrombotic therapy for stroke prevention at the time of the alert, nearly 12% of these patients were ultimately prescribed anticoagulation over the ensuing 90 days. The frequency of major and clinically-relevant non-major bleeding was similar between the two groups.

Conclusions:
In conclusion, a perceived high risk of bleeding was the most common reason for failure to prescribe antithrombotic therapy after the CDS alert. History of a prior bleeding event or underlying bleeding disorder was not reflected in a higher HAS-BLED score. Implementation of an alert-based CDS with specific attention to assessment of bleeding risk and mitigation warrants further study to encourage adherence to evidence-based clinical practice guideline recommendations for stroke prevention in AF.
Abstract 14769: Outcomes of a Smartphone-based Application With Live Health-coaching Post-percutaneous Coronary Intervention
Authors: Paruchuri Kaavya , Finneran Phoebe , Marston Nicholas A , Healy Emma W , Andreo John , Lynch Ryan , Blood Alexander , Jones-O'Connor Maeve , Lander Bradley , Kelly Noreen , Vivaldi Maria T , Traynor Kate , Wiviott Stephen D , Natarajan Pradeep
Published: May 2021

Introduction:
The period between inpatient hospitalization for symptomatic CAD and post-discharge office consultation remains a vulnerable interval for adverse outcomes. Tools to help guide patients during this susceptible time are needed.

Methods:
We customized content on a digital health platform for hospitalized patients receiving PCI which included education, tracking, reminders and health coaches. We conducted a single-arm open-label pilot study of the application (app) to test feasibility and efficacy at two academic medical centers with 1:3 propensity-matched historical controls (NCT03416920). We assessed whether the app led to excess 30-day hospital readmission, improved outpatient cardiovascular follow up (CVFU) and increased cardiac rehabilitation (CR) enrollment in our health system (MGB). Differences were assessed by Cox Proportional Hazards model.

Results:
118 of 324 eligible (36.4%) were enrolled during incident PCI admission 02/18-06/19. 68 of 118 (57.6%) underwent PCI for MI. Mean age was 62.4 (9.7) years, 87 (73.7%) were male, 40 (33.9%) had DM2, and 59 (50.0%) had previously known CAD. There was no significant difference in all-cause readmission within 30 or 90 days. However, rates of both 90-day CR enrollment and 1-month CVFU were increased. App engagement was high – mean 47% daily and 63% weekly engagement within the first 90 days. Spearman correlation analyses indicated similar engagement across age, sex, and cardiovascular risk factors.

Conclusions:
A post-PCI smartphone app, with live health coaches, deployed upon discharge is feasible with similar engagement across demographics. Compared to historical controls, use of the app did not affect short-term hospital readmission but was associated with two-fold increased attendance in CR. Prospective randomized controlled trials are necessary to test the hypothesis that this digital health platform post-PCI improves cardiovascular outcomes over longer follow-up.
Abstract 14787: Loss of Wnt7a is Associated With Reduced Vegf-a/vegfr2 Mediated Endothelial Tip Cell Formation and Angiogenesis in Pulmonary Arterial Hypertension
Authors: Chakraborty Ananya , Nathan Abinaya , Orcholski Mark , Agarwal Stuti , Shamskou Elya , Yu Joyce , Mallory Alden , Acosta Jose , Gunzman Roberto , Yuan Ke , Rojas Vanesa , Crossno Joseph T , Yung Lai-Ming , Yu Paul B , Spencer Thomas , Winn Robert A , De Jesus Perez Vinicio A
Published: May 2021

Rationale:
Pulmonary arterial hypertension (PAH) is characterized by loss of microvessels. The Wnt pathways control pulmonary angiogenesis but their role in PAH is incompletely understood.

Objective:
We hypothesized that Wnt activation in pulmonary microvascular endothelial cells (PMVECs) is required for pulmonary angiogenesis and its loss contributes to PAH.

Methods:
Lung tissue and PMVECs from healthy donors and PAH patients were screened for Wnt ligand production. Tip cell dynamics were analyzed using 3D spheroid assays and in vivo studies were carried out with tamoxifen-inducible Wnt knockout mice exposed to chronic hypoxia and Sugen-hypoxia (SuHx).

Results:
Healthy PMVECs demonstrated ~6-fold Wnt7a expression that was absent in PAH PMVECs and vascular lesions. Wnt7a expression correlated with formation of tip cells, an endothelial phenotype critical for angiogenesis. To analyze PMVEC tip cell formation, we developed a 3D PMVEC spheroid model combined with live imaging to monitor the behavior of healthy and PAH PMVECs in response to VEGF-A and Wnt7a. We found that PAH PMVECs demonstrated reduced tip cell formation as evidenced by reduced filopodia formation and random motility, which could be partially rescued by recombinant Wnt7a. The mechanism by which Wnt7a promotes VEGF signaling activity is dependent on its capacity to activate the small GTPase cdc42 and facilitate phosphorylation of the Y951 and Y1175 tyrosine residues in VEGFR2 following VEGF-A stimulation. While there was no phenotypic difference between wild type and mice with endothelial-specific Wnt7a knockout (Wnt7a
EC/EC
) under chronic hypoxia and SuHx, we found that global Wnt7a
+/-
mice demonstrated higher pressures and vascular remodeling compared to wild type mice. Interestingly, we found that global Wnt7a knockout (Wnt7a
KO/KO
) mice succumbed 10 days after tamoxifen injection demonstrating interstitial thickening associated with expansion of the pulmonary capillaries, an unexpected phenotype resembling alveolar capillary dysplasia.

Conclusions:
We have identified Wnt7a as a novel angiogenic factor that plays a pivotal role in pulmonary angiogenesis by promoting VEGF-A mediated tip cell formation. Targeting Wnt7a could promote recovery of small vessel loss in PAH.
Abstract 14789: Multimodality Imaging in Mycobacterium Chimaera Cardiovascular Infections
Authors: Tan Nicholas Y , Tarabochia Alex D , Abu Saleh Omar M , Bennett Courtney
Published: May 2021

Introduction:
Mycobacterium Chimaera (MC) infections following cardiovascular surgery are challenging to diagnose given their insidious presentation. We therefore reviewed the various imaging modalities used to diagnose these infections at Mayo Clinic.

Methods:
Cases from 01/01/2010-06/01/2020 were identified using electronic medical records. Demographics and clinical history were collected. Imaging studies, including transthoracic echocardiogram (TTE), transesophageal echocardiogram (TEE), positron emission tomography / computed tomography (PET/CT), cardiac CT (CCT), and cardiac magnetic resonance (CMR) were reviewed.

Results:
A total of 7 patients (85.7% male) were found. 6 underwent aortic valve replacement and 1 received an aortic composite valve conduit. Surgical dates ranged from 01/2010-12/2018. Mean age at presentation was 63.3 years. Mean time from surgery to symptom onset was 28.0 months. All patients underwent TTE and TEE; prosthetic valve endocarditis was identified in 6 cases between both, while CMR established the diagnosis in 1 case. TTE showed prosthetic valve obstruction in 2 cases and an anterior pseudoaneurysm in 1 case. TEE findings included thickened prosthesis and/or vegetations (n=5), thickened posterior root (n=4), and root abscess (n=3). Among the 3 patients who underwent PET/CT, 2 demonstrated increased fluorodeoxyglucose (FDG) uptake around the aortic prosthesis; in addition, 1 had elevated FDG uptake in the myocardium suggesting myocarditis. 1 patient did not have aortic prosthesis FDG uptake. In the 2 patients who had CCT, 1 showed a pseudoaneurysm that prompted suspicion for endocarditis, and the other revealed a fluid collection adjacent to the aortic valve conduit. 2 patients underwent CMR; 1 had aortic prosthesis thickening and patchy areas of myocardial delayed enhancement suspicious for myocarditis, whereas the other showed vegetation and an aortic root abscess.

Conclusion:
TTE plus TEE successfully identified MC prosthetic valve endocarditis in most cases with TEE having higher specificity. Advanced imaging techniques are helpful to support the diagnosis and assess for myocardial and/or aortic involvement. Combining these modalities is therefore crucial in unveiling this elusive organism.
Abstract 14801: Can Plasma Tweak Predict Coronary Slow Flow in Patients With Chronic Kidney Disease?
Authors: Tatlisu Mustafa A , Atici Adem , Ozcan Fatma Betul B , Kirac Eray , Baycan Omer F , Caliskan Mustafa
Published: May 2021

Introduction:
The tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is one of the inflammatory mediators contributing to the atherosclerotic process. TWEAK has been studied in chronic kidney disease (CKD) patients and it has been shown that its level declines as eGFR decreases. Most studies have found that the decreased level of TWEAK was seen in atherosclerosis and was also associated with calcification of the plaque. This prospective study was designed to clarify any relationship between coronary slow flow (CSF) and TWEAK levels.

Hypothesis:
Our hypothesis was to show that the higher level of TWEAK might be seen in the setting of CSF due to lack of calcium deposits and TWEAK is not a reflection of healthy vessels.

Methods:
This prospective study included 93 consecutive patients undergoing invasive coronary angiography (ICA) for any reason except for acute coronary syndromes from May 2019 to March 2020 (Table 1). A total of 93 patients were divided into two groups with regard to having CSF (n=35) or no-CSF (n=58).

Results:
Patients with CSF had higher TWEAK levels than those without CSF (695.2± 225.2 vs 465.8±157.6, p<0.001). As the number of coronary arteries with slow flow increased, the TWEAK level was increased statistically significant (r:0.635/ p<0.001). The TWEAK level of 516 pg/mL was found for the prediction of CSF in ROC analysis.

Conclusions:
Our study has shown that plasma TWEAK level is an independent predictor for the CSF in patients with CKD (Table 2). Our study have found that elevated TWEAK levels may not reflect the healthy vessels as it was hypothesized in the past.
Abstract 14814: By Stanza or Story, the Structure of a Poem
Authors: Simpson Timothy F , Nazer Babak , Divanji Punag
Published: May 2021

A 63-year-old male with recent diagnosis of idiopathic pericarditis presented to the hospital with atrial fibrillation and rapid ventricular rates. He reported one week of palpitations and subacute lower extremity weakness. On exam he was hemodynamically stable with evidence of intra- and extravascular fluid overload. Lab analysis showed elevated creatinine, inflammatory markers, and serum protein gap. Chest radiograph showed bilateral pleural effusions and a focal sclerotic thoracic vertebra. TTE revealed mildly reduced biventricular function, elevated RVSP, and moderate pericardial effusion. The presence of pericardial and pleural effusions with elevated inflammatory markers suggest serositis, and a differential of malignant, autoimmune, and infectious etiologies were considered. Hepatosplenomegaly was noted on CT imaging. Blood, pleural, and pericardial cultures revealed no growth and autoimmune serologies were negative. Given these findings- the differential was narrowed to lymphoma, myeloma with or without amyloidosis, and paraneoplastic syndromes. Electrophoresis revealed presence of an M protein, fat pad biopsy was negative for amyloid fibrils. Bone marrow biopsy revealed an abnormal plasma cell population and biopsy of sclerotic vertebra showed no malignancy. Whole body FDG PET showed no focal uptake in the heart nor elsewhere. VEGF levels were significantly elevated. On the basis of the plasma cell dyscrasia, polyneuropathy, sclerotic bone lesion, elevated VEGF level, hepatosplenomegaly, and pericardial effusion the patient was diagnosed with POEMS syndrome- an extremely rare paraneoplastic syndrome with multisystemic end-organ effects. Cardiac manifestations are infrequent, but include pericardial effusion, myocardial edema and dysfunction, pulmonary hypertension, and volume overload. No specific cardiac therapy exists, but involvement may regress with chemotherapy for treatment of the underlying malignancy. This case demonstrates the importance of recognizing cardiac manifestations as the initial or cardinal presentation of underlying systemic disease, where accurate diagnosis may rely on identification of subtle non-cardiac symptoms, laboratory, and imaging findings as demonstrated here.
Abstract 14824: Identifying Gender Differences in Physical Frailty Phenotypes in Heart Failure: A Focus on Physiological, Clinical, and Symptom Characteristics
Authors: Denfeld Quin E , HABECKER Beth A , Camacho S. A , Davis Mary , Gupta Nandita , Hiatt Shirin O , Medysky Mary E , Purnell Jonathan Q , Winters-Stone Kerri , Lee Christopher S
Published: May 2021

Introduction:
Although women with heart failure (HF) are potentially more likely to be physically frail compared with men with HF, the underlying contributors to this gender difference are poorly understood. The purpose of this study was to characterize gender differences in physical frailty phenotypes in HF with a focus on physiological, clinical, and symptom characteristics.

Methods:
We prospectively enrolled adults with Class I-IV HF. Physical frailty was measured with the Frailty Phenotype Criteria: unintentional weight loss, weakness, slowness, physical exhaustion, and low physical activity; those who met 0-2 criteria were not physically frail, and those who met 3-5 criteria were physically frail. Body composition was measured using dual energy x-ray absorptiometry. Clinical data were extracted from the medical record. Symptoms of dyspnea, sleep-related impairment, pain interference, depression, and anxiety were assessed. Simple comparative statistics and multivariate logistic regression were used to identify gender differences in physical frailty.

Results:
The average age of the sample (n = 115) was 63.6±15.7 years, 49% were women, and 73% had non-ischemic etiology. About 43% of the sample was physically frail. Women were 4.5 times as likely to be physically frail compared with men, adjusting for covariates (OR = 4.52, 95%CI [1.69, 12.08],
p
= 0.003). Both physically frail men and women had significantly more type 2 diabetes and worse dyspnea symptoms compared with non-physically frail men and women, respectively. Physically frail men had significantly lower appendicular muscle mass, higher percent body fat, trunk fat, and appendicular fat, and lower hemoglobin compared with non-physically frail men (all
p
< 0.05). Physically frail women had significantly higher comorbidity burden and worse sleep-related impairment, pain interference, and depressive symptoms compared with non-physically frail women (all
p
< 0.05).

Conclusions:
Women are significantly more likely to be physically frail in HF. Physical frailty in men with HF may be primarily characterized by comorbidities and sarcopenic obesity; whereas physical frailty in women with HF may be predominantly characterized by comorbidities and worse symptoms.
Abstract 14830: Edge-to-edge Transcatheter Mitral Valve Repair is Associated With Lower Pulmonary Artery Pressure in Cardiomems
TM
-monitored Patients With Heart Failure and Mitral Regurgitation
Authors: Shavelle David , Heywood J Thomas T , Srivastava Ajay , Agarwal Rahul , Prillinger Julie , Price Matthew J
Published: May 2021

Introduction:
Transcatheter mitral valve repair (TMVr) reduces heart failure (HF) hospitalizations and improves survival in patients with HF and secondary mitral regurgitation (MR), but the hemodynamics of TMVr are not well studied. Patients with a pulmonary artery pressure (PAP) monitor (CardioMEMS
TM
) provide a unique opportunity to study ambulatory hemodynamics following TMVr.

Methods:
TMVr implants occurring July 2014 to Sept 2019 were identified from Medicare claims data and were linked to PAP data from CardioMEMS
TM
. Patients with CardioMEMS
TM
implant ≥3 mo prior to TMVr and with ≥3 mo PAP data post TMVr were included. Diastolic PAP (DPAP) and area under the curve (AUC) at 3 and 6 mo post TMVr were compared to 4 wks prior to TMVr (baseline). Analysis was repeated for those with elevated baseline DPAP, defined as ≥15 mmHg.

Results:
The cohort included 32 patients (74 ± 8 yrs, 66% male) with high prevalence of hypertension, ischemic heart disease, AF, and kidney disease. LVEF was available in 17 patients (32 ± 14%). Compared to baseline, DPAP was significantly lower at 3 mo (-2.1 ± 4.7 mmHg, p=0.019) and remained lower at 6 mo post TMVr (-2.5 ± 6.7 mmHg, p=0.070). AUC showed a cumulative reduction in DPAP of -129 ± 257 mmHg-days (p=0.008) at 3 mo and -438 ± 719 mmHg-days (p=0.005) at 6 mo post TMVr. Similar trends were observed for mean PAP. Sub-group analyses suggested lower DPAP after TMVr in patients with elevated baseline DPAP (3 mo Δ: -2.6 ± 4.6 mmHg, p=0.009; 6 mo Δ: -3.8 ± 6.3 mmHg, p=0.014, 3 mo AUC: -158 ± 255 mmHg-day, p=0.004; 6 mo AUC: -575 ± 721 mmHg-day, p=0.002).

Conclusions:
In CardioMEMS
TM
-monitored patients with significant MR, TMVr is associated with a clinically relevant and sustained reduction in DPAP, including patients with an elevated baseline DPAP. Although the clinical and survival benefits of TMVr are paramount, these data add to our understanding of the hemodynamic improvements of TMVr. CardioMEMS
TM
is an additional tool to improve filling pressures in those with HF.
Abstract 14844: Ampk is Required for Maintaining Atrial Metabolism and Oxidative Stress
Authors: Ma Yina , Wu Xiaohong , Hu Xiaoyue , Cline Gary , Akar Fadi G , Young Lawrence H
Published: May 2021

Background:
AMP-activated kinase (AMPK) has a critical role in cellular substrate and energy metabolism, regulating fatty acid oxidation, stimulating glucose transport and glycolysis. AMPK is crucial in the LV, preventing ischemic injury and heart failure. Atrial AMPK depletion induces atrial fibrillation in mice, but the role of AMPK in regulating atrial metabolism and oxidative stress is unknown.

Methods:
Atrial AMPK was selectively depleted in mice, utilizing sarcolipin-Cre mediated deletion of floxed α1 and α2 catalytic subunits (AMPKdKO). Floxed littermate mice were controls (CON). Microarray, immunoblotting, liquid chromatography-mass spectrometry (LC-MS), and electron microscope (EM) were used to access the gene, protein, metabolism, and mitochondria changes.

Results:
Pathway analysis of microarray data showed that fatty acid metabolism was downregulated in the AMPKdKO vs. CON atria (n=4 per group, p<0.0001). PGC1-α and downstream genes regulating fatty acid metabolism, including acyl-CoA thioesterase (ACOT), long-chain fatty acid-CoA ligase (ACSL), carnitine palmitoyltransferase 2 (CPT2), and fatty acid binding protein (FABP) were reduced in the AMPKdKO vs. CON atria (at 1 week of age). Atrial long-chain fatty acyl-CoA and acyl-carnitine levels were decreased (by LC-MS) in the AMPKdKO vs. CON atria (at 4 and 8 weeks of age) (n=3-4 per group, p<0.05). EM images showed evidence of swollen, broken and degraded mitochondrial in AMPKdKO atria (at 8 weeks age). Atrial expression of antioxidant enzymes, including SOD2 and PRDX3, was reduced (by immunoblotting) in AMPKdKO vs. CON atria (n=3-4, p<0.05).

Conclusion:
AMPK regulates critical mechanisms regulating atrial fatty acid metabolism and oxidative stress. Loss of atrial AMPK reduces the concentration of critical fatty acid intermediates for oxidative mitochondrial metabolism. These metabolic alterations may contribute to structural and electrical remodeling, and ensuing atrial fibrillation, that results from the loss of AMPK in the atria.
Abstract 14854: A Primary Care Digital Therapeutic for Diabesity
Authors: Wieneke Gitte , Colwell Niall S , Egan Jack , O'Croinín Mícheál , Sheppard Andrew
Published: May 2021

Introduction:
While lifestyle change is a Class I Recommendation for Metabolic Syndrome components and Type II Diabetes, implementation of such change is often not achieved in primary care.

Hypothesis:
Test RediCare ControlDTx, a digital therapeutic which is designed to scale the delivery of lifestyle therapy, in Obese and Type 2 Diabetic subjects.

Methods:
43 subjects, 32 (75%) female and 11 (25%) male were enrolled within a primary care practice. Weight, BMI, Blood Pressure, HbA1c and lipids were analyzed pre and post intervention using a student t-test. The 16-week program combines personalized condition specific video-based health education, health coach support via unlimited one to one online consultations, peer to peer support and asynchronous messaging to optimize compliance. A prescribed dietary protocol based on consuming whole foods while emphasizing the reduction of refined carbohydrates and sugar intake, while exercising resulted in significant reductions in HbA1c, Weight, BMI, Systolic Blood Pressure and Triglycerides.

Results:
are presented in Fig 1 with standard deviations shown in brackets.

In type 2 diabetic subjects, mean triglycerides were 216.4 mg/dL at baseline and 105.0 mg/dL at follow up, a reduction of -111.3 mg/dL (51.56%). Prediabetic subjects mean triglycerides were 137.6 mg/dL at baseline and 99.5 mg/dL at follow up, a reduction of -38.2 mg/dL (-27.72%). The average number of health coach consultations was 1.3 per participant.

Conclusion:
A prescribed primary care digital therapeutic confers statistically and clinically significant reductions in metabolic syndrome and diabetic parameters and is seamlessly integrated into the primary care setting. The digital intervention at <$75 per participant was cost effective in both the health benefits and savings achieved in reduced medication costs.
Abstract 14857: Outcomes of Bloodless Congenital Cardiac Surgery on Cardiopulmonary Bypass
Authors: abdul kayoum anas , Rivera Estefania , Reyes Marcelle , Almasarweh Saleem , ojito Jorge , Burke Redmond , Sasaki Jun
Published: May 2021

Introduction:
Bloodless cardiac surgery defined as blood transfusion-free open-heart surgery, where cardiopulmonary bypass (CPB) circuits primed with crystalloid only and no intraoperative blood transfusion. Limited data have been published in this field.

Hypothesis:
We asked whether blood conservative surgery is feasible in congenital heart disease.

Methods:
We retrospectively reviewed patients who underwent bloodless cardiac surgery for congenital heart disease on CPB between January 2016 and December 2018. Our unique CPB system utilizes assisted venous drainage, bioactive coating, and reduced tubing size to decrease priming volume, and complement activation.

Results:
A total of 164 patients were reviewed (86 male and 78 female) at a median age of 9.6 years (range, 13 months-55 years), weight of 32 kg (IQR, 16-55), preoperative hemoglobin 13.7 g/dl (IQR, 12.6-14.9), and preoperative hematocrit of 40.3% (IQR, 37.2-44.3). Median CPB time was 81.5 minutes (IQR, 58-125), and median hematocrit coming off CPB was 26% (IQR, 23-29.7). Congenital Heart Surgery risk (STAT) category distributed in STAT 1 for 70 (43%), STAT 2 for 80 (49%), STAT 3 for 9 (5%), and STAT 4 for 5 (3%) of the patients. The majority (95%) of patients were extubated in the operating room with low complications rate during the hospital stay (7%). Only 6 (4%) patients needed a blood transfusion in the postoperative period with higher incidence of complications during the hospital course (LR 14.9; p<0.001). The median length of hospital stay was 3.6 days (IQR 2.6-5.6). There was no in-hospital mortality or 30 days mortality after surgery.

Conclusions:
Bloodless congenital cardiac surgery has a high success rate in selected low to medium surgical risk and even higher risk patients (STAT 3 and 4). Our patients had a low rate of complications and short hospital course. The blood product transfusion correlated significantly with a higher rate of complications during the postoperative course.
Abstract 14871: APD588, a Novel, Selective S1P Receptor Modulator, Regulates Inflammatory Responses and Attenuates Cardiac Dysfunction Following Experimental Myocardial Infarction in Mice
Authors: Nguyen Nathalie , Zarak Crnkovic Martina , Neves Liomar A , Wang Hongjian , Martinez Teresa , Gralinski Michael R , Adams John W
Published: May 2021

Recent studies have determined that chronic inflammation contributes to left ventricular (LV) remodeling following myocardial infarction (MI) leading to heart failure (HF). Evidence points to a critical role of T lymphocytes in driving the maladaptive inflammatory process associated with adverse tissue remodeling and cardiac dysfunction. FTY720, a non-selective sphingosine 1-phosphate (S1P) receptor modulator, elicits anti-inflammatory effects via inhibition of lymphocyte egress from secondary lymphoid organs and has been reported to improve cardiac remodeling and function post-MI. We hypothesized that APD588, a next-generation S1P receptor modulator with optimized S1P
1,5
receptor selectivity, would prevent cardiac remodeling and dysfunction following MI through modulation of T lymphocyte-mediated inflammatory responses. Efficacy of APD588 on cardiac function was assessed using C57BL/6N mice (n=7-10 mice/group) with experimental MI induced by coronary artery occlusion. Vehicle (VEH) or APD588 (0.3 mg/kg) was administered orally once daily starting at Day 3 post-MI and continued until Day 28. Blood samples were collected at Days 7 and 28 for lymphocyte count. Echocardiographic measurements, including LV ejection fraction (LVEF), were performed on Days 7, 14, and 28 post-MI. Administration of APD588 following MI resulted in a reduction of lymphocyte count at Days 7 and 28 post-MI, but only reached significance in the latter (VEH: 3.3 ± 0.5 x10
3
/μL; APD588: 1.3 ± 0.2 x10
3
/μL). Decreased cardiac function was observed at Day 7 post-MI (LVEF: 27.7 ± 3.6%, MI vs 45.7 ± 0.6%, Sham). No difference in LVEF was observed 7 days post-MI, however APD588 significantly improved LVEF at Day 28 post-MI, compared to vehicle (APD588: 35.7 ± 3.9%; VEH: 25.3 ± 3.9%). Therapies targeting inflammation in the pathophysiology of HF have shown limited success in the clinic. Novel strategies based on advancements in understanding the underlying immunobiology are warranted. Our results demonstrate that APD588 was effective at regulating lymphocyte activity and improved cardiac functional recovery following MI in mice. This supports the potential of S1P receptor modulation and other T lymphocyte-directed strategies as a targeted anti-inflammatory approach in HF.
Abstract 14888: Extracellular Matrix Quantification of Fully Regenerated Neochorade After Bio-scaffold Mitral Valve Implantation in a Juvenile Non-human Primate Model
Authors: Gonzalez Brittany A , Gonzalez Perez Marcos , Mirza Asad , Scholl Frank , Bibevski Steven , Wagner Krishna Rivas , bibevski Jennifer , Hernandez Lazaro E , Ladich Elena , brehier vincent , Casares Miguel , Morales Pablo , Lopez Jesus , Wagner Joseph , Ramaswamy Sharan
Published: May 2021

Introduction:
To investigate enhanced treatment options for critical mitral valve disease in children, we implanted a bio-scaffold mitral valve comprising of porcine small intestinal submucosa (PSIS) in a juvenile baboon model.

Hypothesis:
New tissue formation would be accelerated at physical connections between the replacement bio-scaffold valve and native cardiac tissues, due to direct extracellular matrix (ECM) communications.

Methods:
Juvenile baboons (n=2) were implanted with a hand-made bicuspid PSIS (Cormatrix, Roswell, GA) mitral valve. The PSIS valves were excised at 11- and 20-months post-implantation. Images of histological stains (Movat’s Pentachrome; Alizée Pathology, Inc., Thurmont, MD) were subsequently spatially mapped for ECM quantification (MATLAB; Mathworks, Natick, MA).

Results:
PSIS bio-scaffold mitral valves (11- and 20-months post-implantation) facilitated complete regeneration of neochordae. The neochordae seamlessly integrated into the papillary muscles and left ventricular insertion sites (
Figure 1A, E
). We also found that with an increase in implantation duration of ~ 9 months, the collagen, proteoglycan and elastin content (per mm
2
;
Figure 1B-D, F-H
) had a fold-change of 6.96, 18.42 and 4.94, respectively.

Conclusions:
Our findings suggest that the PSIS bio-scaffold mitral valve apparatus can regenerate neochordae without the need for any biochemical or biomechanical treatment. Nonetheless, other valve spatial areas of importance (e.g. leaflets) will require additional strategies. As a next step, we will produce oscillatory flow-conditioned, stem cell-derived ECM, to accelerate tissue regeneration. The mechanical parameters that we computed to permit physiological oscillatory flow conditions are an oscillatory shear index (OSI) of 0.23 and time averaged bio-scaffold shear stress (TAB-SSS) of 4.6 dynes/cm
2
.

Acknowledgements:
AHA Award ID: 16GRNT31090009; The Miami Research Heart Institute; FIU-UGS DYF.
Abstract 15102: Benign Cardiac Neoplasms in the United States - A Thirteen-year Review
Authors: Lima Neiberg , Byers-Spencer Kristina , Cwikla Kamil , Huffman Cuyler , Diaz Mireya , Melgar Thomas , Helmstetter Nicholas
Published: May 2021

Introduction:
Benign cardiac neoplasms (BCN) are rare; with varying reported incidence and a paucity of epidemiologic studies. The purpose of our review was to add to the small body of literature describing the characteristics and trends of BCN in the US.

Methods:
This study is a retrospective review of data from the HCUP-NIS Database from 2002-2014. Inclusion criteria consisted of the presence of indication for BCN. Additionally, we queried the database for BCN-associated comorbidities. SAS studio was utilized for analysis.

Results:
The data consisted of 482,872,274 weighted discharges. There were 45,568 weighted discharges that had BCN. Sixty four percent were women. Median cost per admission was 51,799 USD, five times higher than the national average. A total of 1,267 (2.78%) patients died during the admission. Stroke and arterial embolization were reported in 6730 (14.76%) and 573 (1.26%) weighted discharges. Weight loss, fever and endocarditis were reported in 311 (0.68%), 383 (0.84%) and 869 (1.91%) patients, respectively. Pulmonary hypertension co-occurred in 3440 (7.55%) patients. Episodes of atrial tachyarrhythmias, ventricular arrhythmias, syncope and cardiac arrest were reported in 13,184 (28.93%), 1,471 (3.23%), 1,055 (2.32%) and 393 (0.86%) cases. Sinus node dysfunction, severe AV nodal block co-occurred in 1,005 (2.21%) and 930 (2.04%) patients.

Conclusions:
We identified a low incidence of BCN in the US over the 13-year study period. Since the prevalence for BCN is low, clinicians must maintain a high index of suspicion due to the high morbidity and mortality.
Abstract 15116: The Prognostic Value of Left Ventricular Mechanical Dyssynchrony in Patients With Idiopathic Dilated Cardiomyopathy
Authors: Li Yangjie , Xu Yuanwei , Tang Siqi , Zhou Xiaoyue , Chen Yucheng
Published: May 2021

Backgrounds:
The mechanical dyssynchrony has been commonly observed in idiopathic dilated cardiomyopathy (DCM) patients, and several cardiac magnetic resonance (CMR) imaging techniques were used to evaluate the mechanical dyssynchrony. Standard deviation of time-to-peak (T2Psd) and uniformity ratio estimate (URE) indices are two widely used parameters to reflect the incoordinate movement of the left ventricle. However, the prognostic value of mechanical dyssynchrony in DCM patients is not clear.

Methods and Results:
We prospectively enrolled 402 DCM patients undergoing CMR imaging between Jun 2012 to Sep 2018. Mechanical dyssynchrony was measured as T2Psd and URE indices by CMR deformable registration algorithm (DRA) analysis. The primary endpoint was defined as all-cause mortality and heart transplantation, and the secondary endpoint was a combination of primary endpoint, aborted sudden cardiac death, and heart failure readmission. Univariate and multivariate Cox regression analyses were performed to identify the association between variables and outcome. Survival curves were obtained by Kaplan-Meier survival analysis and compared by log-rank test. During a median follow-up of 25.1 months (IQR: 16.2-41.6), there were 57 patients reached primary endpoints, and secondary endpoints occurred in 132 patients. Circumferential uniformity ratio estimate (CURE) at basal, mid and apical level, radial uniformity ratio estimate (RURE)at mid and apical level and longitudinal uniformity ratio estimate (LURE) were significantly worse in patients with primary endpoint compared to patients without primary endpoint. While no significant differences were observed regarding the T2Psd value between patients with and without primary endpoints. In multivariate analysis, CURE at apical level was independently associated with primary endpoints (HR 0.214, P=0.005) and secondary endpoints (HR 0.402, P=0.018). Furthermore, among patients with LVEF <35% or presence of LGE, those with decreased CURE at apical level (<0.917) showed a significantly higher rate of adverse outcome.

Conclusion:
The CURE at apical level is an independent predictor of adverse cardiac events in DCM patients. Compared with T2Psd, URE index is a better predictor of adverse events.
Abstract 15118: Pulmonary Valve Preservation During Tetralogy of Fallot Repair is Associated With Enhanced Pulmonary Valve and Right Ventricular Function
Authors: Guariento Alvise , Avesani Martina , Schiena Chiara A , Doulamis Ilias P , Padalino Massimo A , castaldi biagio , DI SALVO GIOVANNI , Vida Vladimiro L
Published: May 2021

Introduction:
Many centers have recently adopted pulmonary valve (PV) preservation procedures to prevent the detrimental long-term effects of chronic pulmonary regurgitation after tetralogy of Fallot (ToF) repair.

Hypothesis:
Here, we investigated PV and right ventricular function after PV preservation surgical strategies compared to standard transannular patch (TAP) repair.

Methods:
All patients undergoing transatrial-transpulmonary repair for ToF with PV stenosis at our institution between January 2007 and May 2020 were reviewed retrospectively. Patients were divided into 2 main groups, according to the different techniques used: patients undergoing a PV preservation strategy and patients undergoing TAP repair.

Results:
Overall, 82 patients underwent a successful PV preservation strategy while 34 underwent a standard TAP repair. At index surgery, BSA (0.31±0.1 m
2
, P=0.3), age (4.8±0.3 months, P=0.5) and preoperative PV Z-score (-3.20±0.1, P=0.1) did not differ between groups. Five-year actuarial freedom from moderate/severe PV regurgitation was significantly higher in the PV preservation group compared to the TAP (61.3% [95% CI: 48-73%] vs 25.9% [95% CI: 12-43%], respectively; p=0.02). After adjusting for age, gender, BSA, and type of PV, the use of a TAP was still significantly associated with an increased risk for PV regurgitation at follow up (HR: 1.85, 95% CI: 1.09, 3.15; p=0.02). At a mean follow-up of 6.9±0.3 years, patients undergoing PV preservation showed an increased right ventricular fractional area change (46.9±0.8% vs 42.5±1.7%, P<0.001) and tricuspid annular plane systolic excursion z-score (-3.36±0.3% vs -4.7±0.4%, P=0.005), while maintaining better PV competence in terms of pulmonary regurgitation index (87.9±1.2% vs 82.7±2.4%, P=0.02).

Conclusions:
Surgical repair of ToF with PV preservation provides excellent outcomes in terms of PV competence and right ventricular function and should be advocated whenever possible.
Abstract 15126: Myocardial Tissue Reverse Remodeling After Guideline-directed Medical Therapy in Idiopathic Dilated Cardiomyopathy
Authors: Yue Pengfei , Xu Yuanwei , Li Yangjie , Zhou Xiaoyue , Chen Yucheng
Published: May 2021

Background:
The prognosis of idiopathic dilated cardiomyopathy (DCM) patients has improved remarkably in the recent decades with guideline-directed medical therapy (GDMT) and some patients undergo left ventricular reverse remodeling (LVRR).

Objectives:
We aim to study the dynamic changes of myocardial tissue characteristics by cardiovascular magnetic resonance (CMR), and investigate the association between myocardial tissue characteristics and cardiac functional remodeling in DCM patients after treatment.

Methods:
A total of 133 prospectively and consecutively enrolled DCM patients underwent baseline and follow-up CMR examinations with a median interval of 13.7 months (IQR: 12.2-18.5 months). The CMR protocol included cine, late gadolinium enhancement (LGE), pre- and post-contrast T1, and T2 mapping. LVRR was defined as an absolute increase in LV ejection fraction (EF) of >10% to a final value of ≥ 35% with a relative decrease in LV end-diastolic volume (EDV) of >10%.

Results:
Forty-two (31.6%) patients experienced LVRR during follow-up. At baseline, new onset heart failure, lower LVEF and the absence of LGE were independent predictors of LVRR. Patients with LVRR showed significant decrease of myocardial native T1, indexed matrix and cell volumes, while patients without LVRR also showed significant albeit smaller decrease of native T1 and indexed matrix and cell volumes. The changes of myocardial tissue characteristics were significantly correlated with the improvement of LVEF and indexed LVEDV.

Conclusions:
In idiopathic DCM patients, significant improvements in myocardial tissue characteristics were observed and accompanied with the improvement in LVEF and reduction in indexed LVEDV after GDMT.
Abstract 15131: National Rates and Trends of Tobacco and Substance Use Disorders Among Atrial Fibrillation Hospitalizations in the United States
Authors: adalja devina , Doshi Rajkumar P , Dave Mihir , Majmundar Monil , Kumar Ashish , Shariff Mariam , Desai Rupak , Shah Jay , Vallabhajosyula Saraschandra , Gullapalli Nageshwara
Published: May 2021

Introduction:
Atrial Fibrillation (AF) has been associated with various behavioral risk factors such as tobacco, alcohol, and/or substance abuse.

Hypothesis:
The main objective is to describe the national trends and burden of tobacco and substance abuse in AF hospitalizations.

Methods:
The National Inpatient Sample database from 2007 to 2015 was utilized and the hospitalizations with AF were identified using the international classification of disease, Ninth Revision, Clinical Modification (ICD-9-CM) code 427.31 in the primary diagnosis column. They were stratified into without abuse, tobacco use disorder (TUD), substance use disorder (SUD), alcohol use disorder (AUD), and drug use disorder (DUD). We used the Jonckheere-Terpstra trend test to analyze the trend in this study.

Results:
Out of 3,631,507 AF hospitalizations, 852,110 (23.46%) had TUD, 1851,170 (5.1%) had SUD, 155,681 (4.29%) had AUD and 42,667 (1.17%) had DUD. The trends of all increased substantially during the study period
(Figure)
. The prevalence of TUD, SUD, AUD, and DUD was substantially increased across all age groups, races, and gender during the study period. Female sex was associated with lower odds TUD (0.57 (0.56-0.57), P-value <0.001), SUD (0.27 (0.26-0.27), P-value <0.001), AUD (0.22 (0.22-0.22), P-value <0.001), and DUD (0.51 (0.5-0.52), P-value <0.001). Among AF hospitalizations, the black race was associated with higher odds of SUD (1.12 (1.1-1.14), P-value <0.001), and DUD(1.42 (1.38-1.47), P-value <0.001). The younger age group (18-35 years), male, Medicare/Medicaid as primary insurance, and lower socioeconomic status were associated with increased risk of both TUD and SUDs.

Conclusions:
Tobacco and substance use disorder among hospitalized AF patients in the US mainly affects males, younger individuals, white more than black, and those of lower socioeconomic status which demands the development of preventive strategies to address multilevel influences.