bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14620: LncExACT1 Acts as a Pivotal Switch Between Physiological and Pathological Cardiac Growth
Authors: Li Haobo , Trager Lena E , Liu Xiaojun , Hastings Margaret H , XIAO CHUNYANG , Li Guoping , Yeri Ashish , Rodosthenous Rodosthenis , Silverman Michael G , DAS Saumya , Ambardekar Amrut V , Bristow Michael R , Rosenzweig Anthony
Published: May 2021

Rationale:
Pathological hypertrophy commonly leads to heart failure (HF) and loss of cardiomyocytes, while physiological hypertrophy protects the heart and enhances cardiomyogenesis. The mechanisms underlying these differences remain unclear. While long noncoding RNAs (lncRNAs) are important in cardiac development and disease, their role in physiological hypertrophy is unknown.

Objective:
To investigate the role of lncRNAs in physiological hypertrophy.

Methods and Results:
Mice underwent voluntary wheel running for eight weeks or transverse aortic constriction (TAC) for two or ten weeks. RNAseq identified a novel set of lncRNAs altered in exercised hearts, which we termed
l
ong
n
on
c
oding
Ex
ercise-
A
ssociated
C
ardiac
T
ranscripts (lncExACTs). lncExACT1 was highly conserved and uniquely downregulated in exercised hearts but upregulated in pathological animal models and hearts from HF patients vs controls (1.8-fold;
p
<0.001, N=24) as well as plasma from HF patients with reduced (2.9-fold;
p
=0.032, N=16) and preserved ejection fraction (3.4-fold;
p
=0.006, N=18). In mice, AAV9 lncExACT1 overexpression increased cardiac lncExACT1 7-fold at 16 weeks and increased heart (HW) and lung (LW) weight relative to tibial length (TL), reduced fractional shortening (FS) and increased relative wall thickness (RWT) (
p
<0.05 for all). These changes were associated with a pathological gene expression pattern. In contrast, antisense lncExACT1 inhibition reduced cardiac expression 2-fold at 2 weeks and increased HW/TL without an increase in LW/TL, improved cardiac function, and increased RWT (
p
<0.05 for all). LncExACT1 inhibition induced a physiological gene expression pattern and increased markers of cardiomyogenesis. LncExACT1 inhibition reduced TAC-induced HW/TL and fibrosis, while increasing FS (
p
<0.05 for all). Mechanistic studies revealed that lncExACT1 works by binding miR-222 and as a novel regulator of Hippo/Yap1 signaling through modulation of dachsous cadherin-related 2.

Conclusions:
lncExACT1 acts as a master switch toggling the heart between physiological and pathological growth and provides a potentially tractable therapeutic target for harnessing the beneficial effects of exercise.
Abstract 14622: Longitudinal Changes in Left Ventricular Diastolic Function in Late Life: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Zhao Li , Claggett Brian , Matsushita Kunihiro , Kitzman Dalane W , Folsom Aaron R , Konety Suma H , Mosley Thomas , Skali Hicham , Shah Amil M
Published: May 2021

Introduction:
Diastolic dysfunction is a potent risk factor for heart failure (HF). However, there is limited data regarding longitudinal changes of diastolic function in the very old, who are at the highest risk for HF.

Methods:
We studied 2,559 community-based elderly participants in the prospective ARIC study who underwent protocol echocardiography, were in sinus rhythm at study Visits 5 (2011-2013) and 7 (2018-2019), and did not have an interval myocardial infarction. The primary diastolic measures were Tissue Doppler e’, E/e’ ratio, and left atrial volume index (LAVi).

Results:
Mean age at Visit 5 was 74±4 years, 59% were women, and 25% black. At Visit 5, mean e’ was 5.8±1.4 cm/s, E/e’ 11.8±3.6, and LAVi 24.3±6.7 ml/m
2
. Over a mean of 6.5±3.1 years, e’ decreased by 0.6±1.4 cm/s, E/e’ increased by 3.1±4.5, and LAVi increased by 1.4±7.7 ml/m
2
. Using validated ARIC-based cut-points, there was significant increase in the proportion of participants with abnormal e’ (18% at Visit 5 to 34 % at Visit 7), E/e’ (20% vs 46%), LAVi (17% vs 25%; all p<0.01), and in the number of abnormal diastolic measures (
Figure
). Compared to participants free of cardiovascular (CV) risk factors or CV diseases (n=237), those with CV risk factors or diseases at Visit 5 (n=2,210) demonstrated greater increases in E/e’ (2.3±3.9 vs 3.1±4.5 respectively; p=0.006) and LAVi (0.0±7.0 vs 1.5±7.7 ml/m
2
; p=0.008) while increases in E/e’ (5.0±5.1; p<0.001) and LAVi (4.6±8.7 ml/m
2
; p<0.001) were the most prominent in those who developed HF between Visits 5 and 7 (n=60).

Conclusions:
Diastolic function progressively worsens over 6.5 years in late life, particularly among persons with CV risk factors. Further studies are necessary to determine if risk factor prevention or control will mitigate these changes.
Abstract 14626: Propofol and Dexmedetomidine Related Transient High-grade Symptomatic Av Block
Authors: Talib Usama , Sneha Lakshman , Estevez Anneris
Published: May 2021

Introduction:
Dexmedetomidine and propofol are both associated with risk of sinus bradycardia and hypotension. High grade AV block has rarely been reported with these medications. We present a case of high grade AV block (Mobitz II) in the setting of co administration of dexmedetomidine and propofol resulting in hypotension, that resolved with discontinuation of propofol.

Case:
85 year old female with history significant for hypertension and CLL was admitted to the ICU with ARDS secondary to COVID-19 requiring mechanical ventilation. Along with management of ARDS, dexmedetomidine and propofol were administered for adequate sedation while trying to limit high dose of propofol. On day one of administration of the combination (16 mcg/kg/min propofol and 0.6 mcg/kg/hr dexmedetomidine), patient developed Mobitz II AV block associated with hypotension with systolic pressure in 60s. Propofol was discontinued and AV block and hypotension resolved. Patient continued to improve and was eventually extubated and transferred to the telemetry floor. Her telemetry during hospital course did not reveal any further high grade AV block and thus patient did not require placement of a pacemaker.

Discussion:
Optimizing sedation in intubated patients and knowledge of associated adverse effects is warranted to minimize mechanical ventilation time and prevent life threatening complications. Dexmedetomidine has been associated with a reduction in mechanical ventilation duration but an increased risk of bradycardia and hypotension as compared to midazolam and propofol. (1) Hypotension is common with propofol but sinus bradycardia and arrythmias have also been reported. (2) Rarely propofol can precipitate high grade AV block that can be life threatening if not promptly addressed. (3) Co administration of dexmedetomidine and propofol can be associated with exaggeration of individual side effects. Mindfulness of such adverse effects can not only help prevent life threatening complications but also decrease chances of unnecessary pacemaker placements.

Conclusion:
Propofol though associated with sinus bradycardia, may result in high grade AV block when co-administered with dexmedetomidine that is usually reversible with discontinuation of the offending drug.
Abstract 14646: Left Ventricular Global Longitudinal Strain and CT Derived Extracellular Volume Predicts Outcomes in Patients With Low-flow, Low-gradient Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement
Authors: Shah Maulin B , Oskouie Suzanne , Flint Nir , Mirocha James , Han Donghee , Thompson Louise , Friedman John , Makkar Raj , Siegel Robert , Tamarappoo Balaji K
Published: May 2021

Introduction:
Low-flow, low-gradient aortic stenosis (LFLG-AS) is associated with impaired left ventricular (LV) function and afterload mismatch. Indications and timing for transcatheter aortic valve replacement (TAVR) in LFLG-AS do not account for the presence of subclinical LV remodeling. We evaluated whether combining LV global longitudinal strain (GLS) and CT-derived extracellular volume (ECV), both markers of LV remodeling, provides incremental prediction of adverse outcomes in patients with LFLG-AS undergoing TAVR.

Methods:
We retrospectively evaluated patients with LFLG-AS undergoing TAVR in whom pre-TAVR CT-based ECV measurements were available. GLS was measured in pre-TAVR echocardiograms using speckle tracking. Cox regression analysis was performed with a primary outcome of heart failure hospitalization (HFH) or death. Four sub-groups were identified for analysis based on optimal cutoff points: Group 1 (n=64): ECV< 33 + GLS≥
Abstract 14653: Genome-wide Association Study of Peripheral Artery Disease and Critical Limb Ischemia Identifies Novel Genetic Loci and Coagulation Pathways
Authors: Krittanawong Chayakrit , Narula Jagat , Johnson Kipp W , Narula Navneet , Berger Jeffrey S , Olin Jeffrey W , Al-Mulla Fahd , Al-Ozairi Ebaa , DO Ron , Nadkarni Girish
Published: May 2021

Introduction:
The pathogenesis of peripheral artery disease (PAD) and critical limb ischemia (CLI) are poorly understood.

Hypothesis:
We hypothesize that genetic factors related to abnormalities in coagulation or fibrinolysis, in addition to atherosclerosis, could play an important role in PAD patients and PAD with CLI patients.

Methods:
A genome-wide association study (GWAS) was performed testing for associations between single-nucleotide variants (SNVs) and PAD case-control (3,190 cases and 463,495 controls) and subgroup analysis of PAD with CLI case-control (142 cases and 3,048 controls) in the UK Biobank cohort. To further validate the results, we selected SNVs with the most significant Cochrane-Armitage trend p values without evidence of strong linkage disequilibrium (r2 > 0.8) for PAD with CLI case-control in the BioMe Biobank. We tested for association using BOLT-LMM with adjustment for age, sex, BMI, and the first ten principal components to control for population structure. The SNV association tests' significance level was set at P < 5x10–8 after Bonferroni correction.

Results:
363 SNVs from 81 genetic loci reached the threshold for statistical significance based on a Bonferroni correction (p <5x10–8). (Figure) We then performed a subgroup analysis between PAD patients and PAD with CLI patients in the UK Biobank. We identified 63 SNVs with 52 genetic loci independent for PAD with CLI in the UK Biobank. We further validated those 63 SNVs with 52 genetic loci in the BioMe Biobank. In the validation cohort, 2 genetic loci (
PLG
and
CDKN2B
) were independent for PAD with CLI. On pathway analyses, we identify several new loci that implicate thrombotic, inflammation, glycosaminoglycan synthesis, coagulation, and fibrinolytic pathways involved in PAD along with known atherosclerosis pathways (p <0.05).

Conclusions:
We show that
PLG
gene related to coagulation pathways in PAD may play an important role in coagulation-related PAD pathogenesis.
Abstract 14682: Impact of Atrial Fibrillation in Aortic Stenosis Patients: Insights From the United States Readmissions Database
Authors: Shekhar Shashank , Saad Anas M , Isogai Toshiaki , Gad Mohamed M , Ahuja Keerat , Kaur Manpreet , Verma Beni R , Vaidya Prashansha , Abdelfattah Omar M , Kassis Nicholas , Reed Grant W , Puri Rishi , Krishnaswamy Amar , Kapadia Samir R
Published: May 2021

Introduction:
Even though atrial fibrillation (AF) is present in >30% of patients with aortic stenosis (AS), it is not typically included in the decision-making algorithm for the timing or need for aortic valve replacement (AVR), either by transcatheter (TAVR) or surgical (SAVR) approaches. Large scale data on how AF affects outcomes of AS patients remain scarce.

Methods:
From the Nationwide Readmissions Database (NRD), we retrospectively identified AS patients aged ≥18years, with and without AF admitted between January and June in 2016 and 2017 (to allow for a six month follow up), using the International Classification of Diseases-10
th
revision codes. Multivariable logistic regression was performed to examine the predictors of in-hospital mortality during index hospitalization. In-hospital complications and 6 month in-hospital mortality during any readmission after being discharged alive were compared in patients with and without AF, for patients undergoing TAVR, SAVR or no-AVR.

Results:
We identified 403,089 AS patients, of which 41% had AF. Patients with AF were older (median age in years: 83 vs. 79) and were more frequently females (52% vs. 48%; p<0.001).
Table
summarizes outcomes of AS patients with and without AF. TAVR in patients with AF was associated with higher in-hospital mortality and follow-up mortality as compared to patients without AF. Although AF did not influence in-hospital mortality in SAVR population, follow-up mortality was also significantly higher after SAVR in patients with AF compared to patients without AF. For patients not undergoing AVR, in-hospital and follow-up mortality were higher in AF population compared to no AF and was higher than patients undergoing AVR (Table).

Conclusions:
AF is associated with worse outcomes in patients with AS irrespective of treatment (TAVR, SAVR or no-AVR). More studies are needed to understand the implications of AF in AS population and whether earlier treatment of AS in patients with AF can improve outcomes.
Abstract 14685: Long-term Outcomes of Aortic Body Tumors: A Nationwide Study
Authors: Aranda-Michel Edgar , Okusanya Olugbenga T , Kilic Arman , Serna-Gallegos Derek , Brown James A , Bianco Valentino , Habertheuer Andreas , Sultan Ibrahim
Published: May 2021

Introduction:
Aortic body tumors are rare intrathoracic tumors. The majority of existing literature for aortic body tumors exists as case reports or a limited series. Our aim was to analyze a large national database, providing a contemporary view of this cancer.

Methods:
The national cancer database, which includes data from 1,500 cancer centers was queried to retrospectively review all aortic body tumors between 2004 and 2015. The cohort was divided into patients who underwent surgery versus those who were treated with chemotherapy or radiation. Cohorts were assigned a year range based on when they were diagnosed. Survival between these cohorts were compared using Kaplan-Meier survival estimates. Cox multivariable analysis was performed using baseline variables (age, year range, metastasis, surgery, radiation, and chemotherapy). Overall survival of the cohort was analyzed via Kaplan-Meier survival estimates.

Results:
A total of 87 patients who were diagnosed with an aortic body tumor were identified. The mean age was 51 ± 15.7 years and the majority of patients were female (51.7%). Most patients were treated at an academic/research center (62.7%) or a comprehensive community cancer program (25.4%). A significant portion of patients (19.5%) had metastatic disease on diagnosis. The treatment modalities utilized were surgery (54%), radiation (44.8%), and chemotherapy (20.7%). Long-term survival was 35.5% with a median survival of 8.25 years
(Figure 1A)
. Overall survival was significantly higher in the surgery cohort (p<0.001)
(Figure 1B)
. On Cox multivariable analysis
(Figure 1C)
, surgery (HR 0.32, p=0.01) was associated with increased survival. An independent predictor of mortality was having a metastasis on diagnosis (HR 8.49, p=0.001).

Conclusion:
The overall prognosis of aortic body tumors is poor, with metastasis on presentation significantly increasing mortality. Surgery provides a substantial benefit to these patients; however, this may be a result of selection bias. Aggressive surveillance in predisposed populations may be warranted given the grave prognosis once metastasis occurs.
Abstract 14689: Optimal Prenatal Care Coordination is Associated With Fewer Pre-operative Risk Factors in Babies With a Prenatal Diagnosis of HLHS
Authors: Schidlow David N , Gauvreau Kimberlee , Bucholz Emily M , Bennett Amy , Lafranchi Terra , Pruetz Jay , ronai christina , Vergales Jeffrey , BROWN David W
Published: May 2021

Introduction:
Prenatal diagnosis (PD) of congenital heart disease permits coordination of care to optimize postnatal outcomes. Using phase II registry data from the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC), we sought to identify associations between prenatal care coordination (PNC) and pre-operative status among infants with HLHS and variants intended for Stage I Norwood or hybrid palliation.

Hypothesis:
We hypothesized that suboptimal PNC would be associated with worse pre-operative status.

Methods:
The NPC-QIC database was queried for all instances of prenatally diagnosed HLHS and variants intended for Stage 1 Norwood or hybrid palliation from 2016 through 2019. Demographic and clinical data pertaining to the prenatal period through the first birthday were obtained. Optimal PNC was defined as (1) a completed interdisciplinary case conference prior to delivery and (2) a note in the medical record documenting closed-loop communication between the OB and cardiology teams. Associations between PNC and outcomes were identified.

Results:
Among 1441 registry patients with HLHS and variants, 1242 (86%) had PD. Among patients with PD, optimal PNC was achieved in 68%. Preoperatively, infants without optimal PNC were more likely to have any adverse event (50% vs 40%, p<0.001), receive inotropes (19% vs 13%, p=0.007), require mechanical ventilation (22% vs 16%, p=0.016), and were less likely to feed enterally (53% vs 67%, p <0.001). Lower socio-economic status (SES) was associated with a lower likelihood of PD (p<0.001), and African-American race was associated with a lower likelihood of optimal PNC (p=0.006).

Conclusions:
Among prenatally diagnosed infants with HLHS and variants, optimal PNC was associated with fewer preoperative risk factors. There also appear to be disparities in PD related to SES and in PNC related to race. Additional study is required to understand the complex interplay between PNC and clinical outcomes, as well as identify and address barriers to PD and optimal PNC.
Abstract 14694: Coronary Artery Fistula Presenting With Complete Heart Block and Syncope
Authors: Alameh Anas , Daoud Ansaam , Jabri Ahmad
Published: May 2021

Introduction:
Coronary artery fistula (CAF) is an anomalous connection between one or more coronary arteries and a cardiac chamber or great vessel. The incidence of coronary fistulas is estimated to be 0.2-0.4% of all cardiac malformations. We present a 75 year old female who presented with a complete heart block, which was most likely caused by a fistula between the coronary vasculature and the pulmonary trunk.

Clinical presentation:
A 75 year old female with a past medical history of hypertension, hyperlipidemia, and COPD presented with two episodes of syncope. Clinical examination was unremarkable. The EKG showed complete third degree heart block requiring transcutaneous pacing. Echocardiography showed normal left ventricular size and function, with an ejection fraction of 55%. The right ventricle size and function were also normal. No hemodynamically significant valvular disease was seen. Left heart catheterization showed occluded middle right coronary artery, 50% stenotic lesion in the left anterior descending artery (LAD), and an abnormal termination of the first diagonal branch of the LAD (D1) into the pulmonary trunk indicative of a fistula. The fistula was the presumed cause of the complete heart block in this patient. The fistula was managed by observation rather than surgical intervention while a dual chamber pacemaker was placed to address the complete heart block.

Conclusions:
Coronary artery fistulas are either congenital or acquired. They are rare and usually asymptomatic but can present with a myriad of symptoms. Our case describes a patient presenting with complete heart block and syncope, with a fistula detected on coronary angiography. This is considered the gold standard for diagnosing CAF. Disrupted coronary flow leading to ischemic complete heart block is the presumed process leading to syncope in this patient. Other modalities that can assist in this diagnosis include echocardiography, computed tomography, or magnetic resonance imaging.
Abstract 14703: Sex Disparities in Management and Outcomes of Cardiac Arrest Complicating Acute Myocardial Infarction in the United States
Authors: Verghese Dhiran , Patlolla Sri Harsha , Vallabhajosyula Saraschandra
Published: May 2021

Background:
Sex disparities exist in acute cardiovascular care. Despite sex-specific cardiac arrest (CA) research being identified as a priority by professional societies, there are limited studies on this topic.

Objectives:
To assess sex disparities in management and outcomes of CA complicating acute myocardial infarction (AMI) in a contemporary United States population.

Methods:
Adult admissions with a primary diagnosis of AMI and concomitant diagnosis of CA were identified using the National Inpatient Sample. Outcomes of interest included sex disparities in in-hospital mortality, coronary angiography (CAG), percutaneous coronary intervention (PCI) and mechanical circulatory support (MCS) use.

Results:
Between January 1, 2000 and December 31, 2017, 11,622,528 admissions for AMI were identified, of which 584,216 (5.0%) were complicated by CA. Men had higher prevalence of CA compared to women (5.4% vs 4.4%,
p<
0.001) in both STEMI and NSTEMI (2017 vs 2000, STEMI-men: 12.3% vs 7.8%, STEMI-women: 10.4% vs 7.5%, NSTEMI-men: 3.1% vs 2.7%, NSTEMI-women: 2.4% vs 2.5%). Women with AMI-CA were on average older (70.4 vs 65.0, p<0.001), of black race (12.6% vs 7.9%, p<0.001) and had higher comorbidity. Women were more likely to present with NSTEMI (36.4% vs 32.3%, p<0.001) and a non-shockable rhythm (47.6% vs 33.3%, p<0.001). Women less frequently received CAG (56.0% vs 66.2 %), early CAG (32.0% vs 40.2%), PCI (40.4% vs 49.7%), MCS (17.6% vs 22.0%), and CABG (all p<0.001). Women had significantly higher unadjusted in-hospital mortality (52.6% vs 40.6%, p
<
0.001). In a multivariable logistic regression analysis, female sex was associated with higher in-hospital mortality (OR 1.13 [95% CI 1.11-1.14];
p<
0.001). When stratified by type of rhythm, type of AMI, presence of cardiogenic shock and location of CA, women consistently received less frequent CAG and experienced higher in-hospital mortality.

Conclusion:
In the largest 18-year study evaluating management and outcomes of CA in AMI, we identified the presence of significant sex disparities. Women with AMI-CA were older, with higher rates of non-shockable rhythm, were less likely to undergo therapeutic procedures including CAG, PCI, and MCS. Women had higher unadjusted and adjusted in-hospital mortality.
Abstract 14710: Cardiovascular Interventions in Face of Covid-19 Pandemic in a Low to Middle Income Country of South Asia Region -
A Pre and Post Covid Era Comparison!
Authors: Shams Pirbhat , Faheem Osman , adnan ghufran , Ali Jamshed , Khan Maria
Published: May 2021

Introduction:
Worldwide, cardiologists have reported decline in cardiac catheterization lab (CCL) activation. In this study, we analysed the impact of COVID19 outbreak on cardiology intervention in a tertiary care centre of epicentre of Pakistan.

Methods:
A retrospective study was conducted on patients admitted via emergency department (ED) and undergoing cardiovascular intervention. Data for CCL procedures was obtained from electronic register for March-April 2019 (pre-COVID era - pCE) and March-April 2020 (COVID era - CE). Comparison was made between the two era for number of times CCL was activated with regard to left heart catheterization (LHC), percutaneous coronary intervention (PCI) or cardiac implantable electronic devices (CIED). This study also compared numbers for coronary artery bypass grafting (CABG) and cardiac imaging.

Results:
A total of 239 and 106 patients were admitted via ED in pCE and CE respectively (Reduction =R=55.6%). Total procedures performed dropped from 183 to 73 (R = 60.11%). Numbers for primary PCI were 34 (pCE) and 16 (CE) with R = 52.94%. 41 patients underwent LHC in pCE in comparison to 13 patients in CE (R = 68.29%). PCI other than primary was performed in 30 (pCE) and 24 patients (CE) with R = 20%. CABG numbered to 26 (pCE) and 12 (CE) with R = 53.85%. CIED was implanted in 12 and 2 patients in pCE and CE respectively (R = 83.33%). Additionally cardiac imaging modality was used in 38 (pCE) and 6 patients (CE) with R = 84.21 %.

Conclusion:
There is significant reduction in rate of primary PCI, LHC, CABG, CIED and non-invasive imaging procedures during CE. South-asia region carries huge burden of undiagnosed cardiovascular disease. Significant drop in cardiovascular procedure in CE is alarming and warns us for need of preparedness for times of increased late presentations or cardiovascular morbidity or mortality. This highlights the importance of urging public to report for their cardiac symptoms in face of COVID-19 pandemic.
Abstract 14712: Cardiometabolic Differences Between Male and Female Obese-insulin Resistant Rats Following Sex Hormone Deprivation
Authors: Shinlapawittayatorn Krekwit , Pongkan Wanpitak , Sivasinprasasn Sivaporn , Chattipakorn Siriporn , CHATTIPAKORN Nipon
Published: May 2021

Introduction:
Male gender and menopause increase the risk for cardiovascular incidence. However, less is known about gender differences in cardiometabolic disorders, particularly under obese-insulin resistant and sex hormone-deprived conditions.

Hypothesis:
Male have worse cardiometabolic disorders than female under obese-insulin resistant and sex hormone-deprived conditions.

Methods:
Adult Wistar rats of both sexes (n=20) were randomly assigned into four groups (n = 5/group): male normal diet sham (M-NDS), male high fat-diet with orchiectomy (M-HFO), female normal diet sham (F-NDS) and female high fat-diet with ovariectomy (F-HFO). Rats were fed either a normal diet (19.77% of energy fat) or a high-fat diet (57.60% of energy fat) for 12 weeks following the induction of sex hormone deprivation by either bilateral orchiectomy or ovariectomy. Temporal determinations of metabolic parameters, heart rate variability (HRV), left ventricular (LV) function, and cardiac mitochondrial function at 4, 8, and 12 weeks were done after starting each feeding program.

Results:
Insulin resistance was initially observed after 8 weeks of high-fat diet consumption in both M-HFO and F-HFO groups. In addition, M-HFO had depressed HRV, impaired LV performance indicated by decreased ejection fraction (%EF) and cardiac mitochondrial dysfunction indicated by increased mitochondrial ROS level, depolarization and swelling, as early as week 4, whereas F-HFO exhibited them at week 8 or 12. Moreover, at week 12, M-HFO have worse cardiometabolic disorders than F-HFO, particularly %EF and HRV.

Conclusions:
Under sex hormone-deprived condition, male are generally more susceptible to cardiometabolic disorders and cardiac mitochondrial dysfunction, especially in the presence of obese-insulin resistant condition.
Abstract 14715: Diabetes and Relative Rates of Cardiovascular Events in Women Compared With Men
Authors: Angoulvant Denis , Ducluzeau Pierre Henri , Renoult Pierre Peggy , Fauchier Gregoire , Herbert Julien , Spiesser Pascal , Bodin Alexandre , Bisson Arnaud , Fauchier Laurent
Published: May 2021

Data are inconsistent regarding sex-differences in the relative rates of cardiovascular events associated with diabetes. We aimed to investigate whether diabetes confers higher relative rates of cardiovascular events in women compared with men using contemporary data, and whether these sex-differences depend on age.

Methods:
All patients seen in French hospitals in 2013 with at least 5 years or follow-up (or dying earlier) without a history major adverse cardiovascular event, were identified and characterized by individual-level linkage of French nationwide administrative registers. They were categorized by diabetes-status and followed-up until 31 December 2019. Using Cox models, we calculated overall and age-dependent incidence rates, incidence rate ratios, and women-to-men ratios for myocardial infarction, heart failure, ischemic stroke, or cardiovascular death (MACE-HF).

Results:
The study included 3,381,472 individuals among whom 482,848 (14.3%) had diabetes (88.1% with type 2 diabetes). Among 482,848 (45% women) patients with diabetes, the absolute rate of MACE-HF was higher in men than in women (9.7 vs. 7.4 per 100 person-years). Corresponding absolute rates in men and women without diabetes were 4.9 vs. 3.1 per 100 person-years. Comparing individuals with and without diabetes, women had higher incidence rate ratio (IRR) of MACE-HF than men (IRR 2.42 95% confidence interval [CI] 2.40-2.44) in women vs. 1.99, 95% CI 1.98-2.01 in men) with a women-to-men ratio (WMR) of 1.22 (CI 1.20-1.23, p<0.001). The IRRs of MACE-HF for diabetes vs no diabetes were highest in women aged 45 and in the youngest men and decreased with advancing age for both men and women, but the IRRs were higher in women across all ages, with the highest WMR between age 45 and 70 years. This effect was more apparent for myocardial infarction (women-to-men ratio 1.43, 95%CI 1.39-1.47 after adjustment) than for ischemic stroke (WMR 1.10, 95%CI 1.07-1.13 after adjustment) or overall MACE-HF (WMR 1.16, 95%CI 1.15-1.18 after adjustment).

Conclusion:
Although men have higher absolute rates of cardiovascular complications, the relative rates of cardiovascular complications associated with diabetes are higher in women than in men across all ages in recent years.
Abstract 14720: Pre-clinical Safety Assessment of SLN360, a Novel Short Interfering Ribonucleic Acid Targeting
LPA
Authors: Rider David , Swerdlow Daniel , Eisermann Mona , Loeffler Kathrin , Hauptmann Judith , Morrison Eliot , Wikstrom Lindholm Marie , Schubert Steffen , Campion Giles
Published: May 2021

Introduction:
SLN360 is a liver-targeted N-acetyl galactosamine (GalNAc)-conjugated siRNA with a promising profile for addressing Lp(a)-related cardiovascular risk. We previously reported the pharmacodynamic effects of SLN360 in female (F) cynomolgus monkeys (cynos)
1
. Here we describe the findings from key pre-clinical safety studies.

Methods:
SLN360 was tested in vitro in primary human hepatocytes for
LPA
knockdown and effects on hypothetical off targets identified through in silico screening. An
in vivo
biodistribution study was performed in rats over 21 days (4 males [M]/4 F per timepoint; single 10 mg/kg s.c. injection). In a GLP safety study, healthy cynos received 5 once weekly s.c. injections of saline control or SLN360 (3 M / 3 F per group, up to 200 mg/kg) followed by an 8-week recovery period (2 M / 2 F in saline and top dose). A standard battery of safety assessments was performed.

Results:
In vitro, SLN360 reduced
LPA
expression in primary human hepatocytes with no effects on any hypothetical liver-expressed human off-target genes at concentrations >300-fold the human
LPA
IC
50
. SLN360 showed a typical rodent GalNAc distribution pattern, with significant levels in liver and kidney (peak 126 or 246 mg/g tissue at 6h respectively; estimated liver half-life of 56 hours). Levels in other organs (including reproductive organs) were <1% of peak liver levels. In cynos, no clinical observations were observed following 5 s.c. doses of SLN360. Liver
LPA
mRNA levels were significantly reduced by 98% at day 30 and 95% after the 8-week recovery period, while serum Lp(a) was undetectable at both timepoints. Findings were restricted to the liver (increased weight and diffuse hepatocyte hypertrophy) and lymph nodes (vacuolated macrophages) at day 30. These were considered non-adverse due to reversibility after recovery. No dose-related changes in clinical chemistry, hematology, circulatory and ECG parameters, respiratory rate, neurobehavior, plasma cytokines, complement activation or CRP were noted. The NOAEL was defined as 200 mg/kg, >60-fold the active dose in cynos.

Conclusions:
Overall, the off-target profile, biodistribution and NOAEL of SLN360 indicate suitability for entry into clinical studies.
1
Aleku et al., 2019. Circulation. 2019, 140:A9538.
Abstract 14730: Oral Semaglutide Provides Less Value for Money Than Subcutaneous Semaglutide for the Prevention of Major Adverse Cardiovascular Events, but Significantly More Value for Money for the Prevention of Cardiovascular Mortality
Authors: Arbel Ronen , Aboalhasan Enis , Hammerman Ariel , Azuri Joseph
Published: May 2021

Introduction:
Semaglutide, a subcutaneous Glucagon-Like Peptide-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in patients with Type 2 diabetes mellitus (T2DM). An oral version of semaglutide is now available, and patients may prefer it over a subcutaneous injection. The value for money of the oral version for the prevention of MACE is not clear.

Hypothesis:
Oral semaglutide provides less value for money than subcutaneous semaglutide for the prevention of MACE, but more value for money for the prevention of the single endpoint of cardiovascular mortality (CVM).

Methods:
We calculated the cost needed to prevent (CNT) one MACE, by multiplying the one-year number needed to treat to prevent one event, by the annual cost of the therapy. Efficacy estimates were extracted from published RCT data. The CNT to prevent one event of the single endpoint of CVM was analyzed as a secondary outcome. We performed a sensitivity analysis to mitigate primary differences between the RCTs. Drug costs were calculated as 75% of the US National Average Drug Acquisition Cost listing in June 2020.

Results:
The CNT to prevent one MACE with subcutaneous semaglutide in SUSTAIN-6 is $641,823 ($402,021-$3,533,533) compared to $855,040 (95% CI: $420,840-∞) with oral semaglutide in PIONEER 6. The lower cost of subcutaneous semaglutide was confirmed in a sensitivity analysis simulating the effects of the drugs in both RCTs. The CNT to prevent one CVM with semaglutide is $16,342,560 ($2,020,704.00-∞) compared to $1,315,720 (95% CI: $921,004-$8,392,414) with oral semaglutide.

Conclusions:
Subcutaneous semaglutide prescribed for the prevention of MACE in patients with T2DM is moderately cost-saving compared to oral semaglutide for the same purpose. However, for the prevention of CVM, the oral version provides significantly better economic value.
Abstract 14736: Aquaporin 1 Modulates H
2
o
2
-mediated Endothelial Inflammaging
Authors: Saeedi Saravi Seyed Soheil
Published: May 2021

Background:
Aquaporin 1 (AQP1), a key regulator of endothelial cell function, transports hydrogen peroxide (H
2
O
2
) into the cells. H
2
O
2
-mediated inflammation has been implicated in endothelial dysfunction, yet specific roles of AQP1-mediated signaling pathways underlying age-dependent endothelial dysfunction remains incompletely understood.

Methods:
In these studies, we dissected AQP1-regulated inflammation modulation of eNOS signaling pathways in human aortic endothelial cells (HAEC) from passages 5 to 15 by exploiting siRNA approaches, live cell fluorescence imaging with genetically-encoded H
2
O
2
biosensor HyPer, biochemical and
in vitro
endothelial function assays.

Results:
We discovered that AQP1 expression remarkably increases in senescent HAEC (P.15) in association with significant increased SA-βgal activity compared to young cells (P.5). H
2
O
2
levels were increased in senescent cell cytosol revealed by fluorescence HyPer imaging. We found that senescence-associated increase in AQP1-mediated H
2
O
2
led to enhanced TNF-α, unlike HO-1, transcription (p<0.01). Moreover, immunofluorescence assay documented that AQP1 gene knock-down significantly ameliorated senescence-associated elevation of adhesion molecule ICAM-1. Immunoblot analyses demonstrated that increased AQP1 protein levels in senescent HAEC leads to significant increase in caveolin-1 phosphorylation (2-fold) and decreases in phosphorylation of AMPK (Thr172; 4-fold) and eNOS (Ser1177; 2-fold) compared to young ECs (for each, p<0.05, n>6). We discovered that AQP1 knock-down improved the reduced angiogenesis and wound healing capacity in association with eNOS down-regulation in senescent endothelial cells.

Conclusion:
These results establish that AQP1 plays a crucial role in the regulation of H
2
O
2
-mediated inflammation-associated endothelial senescence, and AQP1 deletion improves endothelial dysfunction by ameliorating ROS-modulated inflammaging.
Abstract 14744: Native Bicuspid Pulmonary Valve in D-loop Transposition of the Great Arteries: Outcomes of the Neo-aortic Valve Function and Root Dilation After Arterial Switch Operation
Authors: Irwin Jane Margaret , Binney Geoffrey , Gauvreau Kimberlee , Emani Sitaram , Blume Elizabeth , BROWN David W
Published: May 2021

Introduction:
Neo-aortic root dilation (ARD) is common after arterial switch operation (ASO) for D-loop transposition of the great arteries (TGA). We sought to compare short and long-term outcomes for bicuspid native pulmonary valve (BNPV) patients to those with normal trileaflet variants (TNPV).

Methods:
A retrospective cohort of TGA patients undergoing ASO at Boston Children’s Hospital from 1989-2018 was analyzed, matching BNPV patients 1:3 with TNPV patients by year of ASO; those with >mild subpulmonary stenosis or complex TGA were excluded. Categorical and continuous variables were compared using Fisher’s exact and Wilcoxon rank sum tests, respectively. Kaplan-Meier analyses with log-rank test compared groups for time to first reoperation on the neo-aortic valve, first occurrence of ≥moderate neo-aortic regurgitation (AR), and ARD defined as root z-score ≥4. Hazard ratios were estimated based on the Cox proportional hazards model.

Results:
A total of 83 BNPV patients were matched with 217 TNPV. BNPV patients were more likely to have a VSD (75% vs 44%, p <0.001). Early surgical outcomes including hospital LOS (11 vs 10 days) and 30-day mortality (3.6% vs 2.8%) were similar. During median 10 years follow-up, neo-aortic valve reoperation occurred in 4 BNPV (6%) vs 6 TNPV (3%) patients, with no statistically significant difference in time to reoperation. More BNPV patients had AR at discharge (4.9% vs 0%, p=0.014) and during follow-up (13.4% vs 4.3%, HR 3.9, p=0.004), with shorter time to first occurrence of AR (Figure 1A); this remained significant after adjusting for presence of VSD. Similarly, ARD was more common in BNPV (45% vs 37%, HR 1.64, p=0.02) with shorter time to first occurrence (Figure 1B).

Conclusions:
While patients with BNPV have similar short-term ASO outcomes, AR and ARD occur more frequently and earlier compared with TNPV patients. Further long-term studies are needed to determine whether this results in greater need for neo-aortic valve reoperation.
Abstract 14752: Hepatic Steatosis in Patients With the Fontan Circulation
Authors: Katz David , Peck Daniel , Lubert Adam , Possner Mathias , Zafar Faizeen , Trout Andrew , Palermo Joseph , Anwar Nadeem , Dillman Jonathan , Powell Adam , Xanthakos Starva , Opotowsky Alexander , Veldtman Gruschen , Alsaied Tarek
Published: May 2021

Introduction:
Hepatic steatosis is a leading cause of chronic liver disease, and it is most commonly attributed to nonalcoholic fatty liver disease (NAFLD). The interplay between hepatic steatosis and the development of liver disease following the Fontan procedure is not well understood. This study examined the prevalence and associations of hepatic steatosis in patients with a Fontan circulation.

Methods and Results:
This was a single-center retrospective study of 95 patients with a Fontan circulation who had a liver magnetic resonance imaging (MRI) performed between 2012 and 2019. Average age at MRI was 21.5 ± 8.5 years. Percent liver fat signal was determined using magnetic resonance chemical shift-encoded proton density fat fraction imaging. Hepatic steatosis was defined as liver fat greater than or equal to 5%; this was present in 10.5% of the population. The presence of hepatic steatosis was associated with higher body mass index (BMI) (29 ± 4 vs. 24 ± 6 kg/m
2
, p = 0.01), a higher frequency of obesity (50 vs. 12%, p = 0.02), lower high density lipoprotein (HDL) cholesterol (35 ± 9 vs. 43 ± 14 mg/dL, p = 0.05), and greater subcutaneous fat (2.6 ± 0.7 vs. 1.8 ± 1.0 cm, p = 0.04). Percent liver fat was positively associated with AST, triglyceride, and alkaline phosphatase levels. There was no association between hepatic steatosis and cardiovascular imaging or hemodynamic variables. Hepatic steatosis was not associated with the development of the composite outcome of: death, heart transplant, or escalation of diuretics (10 vs. 25%, p = 0.44).

Conclusions:
Risk factors for hepatic steatosis in patients with Fontan circulation are similar to the general population: obesity and dyslipidemia.
Abstract 14767: Thrombolysis of Stroke Mimics via Telestroke
Authors: Howell Ravyn , Yadav Randheer S , Lakhani Sushil , Heaton Sharon , Wiles Karen L , Lee Vivien H
Published: May 2021

Introduction:
Telestroke allows stroke expertise for thrombolysis decision making remotely using high-quality bidirectional audiovisual technology.

Hypothesis:
Intravenous tissue plasminogen activator (IVtPA) is administered via telestroke network to a proportion of patients without a stroke diagnosis (i.e. stroke mimic)

Methods:
Our academic comprehensive stroke program telestroke program includes 26 spoke Emergency rooms (ERs) through which IVtPA is administered throughout central Ohio. From July 1, 2016 to Sept 30, 2017, nearly all patients who received IVtPA at the outside hospital telestroke ERs were transferred to our institution for post-IVtPA care. Data was collected on final diagnosis, demographics, National Institutes of Health Stroke Scale (NIHSS), door to needle (DTN) time, and outcomes.

Results:
Among 270 acute ischemic stroke patients who received IVtPA via telestroke, we identified 64 (23.7%) with a stroke mimic diagnosis. Stroke mimics were younger (mean age 56.4 vs 68.2, p <0.0001), more likely female (60.9% vs 45.6%, p 0.03), and had higher DTN times (85.3 vs 69.9 minutes, p 0.0008). The increase in DTN was due to longer time to recommend by the telestroke neurologist for stroke mimic (65.0 vs 53.2 minutes, p 0.0034). The stroke mimic diagnosis included Migraine 26 (40.6%), Factitious disorder 12 (18.8%), Encephalopathy 7 (10.9%), and Unmasking 6 (9.4%). The stroke mimics did not differ from each other based upon initial NIHSS, DTN, or sex. Compared to the other stroke mimics, Migraine and Factitious disorder patients were younger (51.2 vs 63.9 years, p <0.0006), more likely to have a personal history of migraines (42.1% vs 0%, p < 0.0001), and more likely to have functional exam findings (42.1% vs 3.8%, p 0.0007). There were no hemorrhagic complications in the stroke mimic patients. Among all stroke mimics, 26 (40.6%) had a history of similar prior episodes and 10 (15.6%) would have future recurrence of another similar episode, with 2 patients receiving IVtPA again in the future (1 Migraine and 1 Factitious disorder).

Conclusions:
In a tertiary academic telestroke network, nearly one-quarter of patients receive IVtPA for a non-stroke diagnosis, with migraine and factitious disorder being the most commonly seen.
Abstract 14768: Echocardiographic Strain Outcomes of Cardiac Resynchronization Therapy in Patients With Chemotherapy Induced Cardiomyopathy
Authors: Ezzeddine Fatima M , Saliba Antoine N , Jain Vaibhav , Villarraga Hector R , Herrmann Joerg , Asirvatham Samuel , Cha Yong-mei
Published: May 2021

Introduction:
Several chemotherapy agents, especially anthracyclines, are associated with the development of non-ischemic cardiomyopathy. When chemotherapy-induced cardiomyopathy (CHIC) is associated with left bundle branch block (QRS >150 ms) and a left ventricular ejection fraction (LVEF) of 35% or lower, cardiac resynchronization therapy (CRT) is often utilized to improve cardiac function and relieve symptoms.

Hypothesis:
CRT is associated with improvement in left ventricular strain in patients with CHIC.

Methods:
The study included 22 patients with CHIC and 44 age- and gender-matched controls with other types of NIC who underwent CRT implantation between 2004 and 2017. LVEF, left ventricular global longitudinal strain (GLS), systolic strain rate (SRS), and early diastolic strain rate (SRE) were assessed at baseline and 6-18 months after CRT. CRT response was defined as LVEF improvement by >5% after CRT.

Results:
CRT responders had a significant improvement in left ventricular GLS as compared to CRT non-responders in the control group, but not in the CHIC group (Table 1). The mean change in LVEF after CRT was similar between the CHIC and control groups (10 ± 10% versus 11 ± 11%, p= 0.67). The mean change in GLS after CRT was also similar between the two groups (-2.15 ± 4.32 versus -3.57 ± 4.02, p= 0.19). The proportion of patients whose LVEF increased by more than 5% was similar between the two groups (59% in the CHIC group versus 68% in the control group, p= 0.46). The mean changes in LV myocardial systolic and early diastolic strain rates were similar between the CHIC and control groups. Mean SRS decreased by 0.13 ± 0.14 in the CHIC group and by 0.34 ± 1.28 in the control group (p=0.45). Mean SRE increased by 0.06 ± 0.18 in the CHIC group and by 0.07 ± 0.22 in the control group (p=0.86).

Conclusions:
CRT is associated with improvement in left ventricular strain in patients with CHIC. Prospective studies are needed to further evaluate the echocardiographic strain outcomes of CRT in CHIC.
Abstract 14773: Biventricular Conversion After Fontan Completion: A Preliminary Experience
Authors: Doulamis Ilias P , Marathe Supreet P , Piekarski Breanna L , Beroukhim Rebecca S , Marx Gerald R , Del Nido Pedro J , Emani Sitaram M
Published: May 2021

Hypothesis:
Biventricular conversion (BiVC) following takedown of Fontan circulation is feasible and results in improved hemodynamics.

Methods:
Retrospective analysis of patients who had takedown of Fontan circulation and conversion to BiV circulation at a single center from September 2007 to April 2020. Failing Fontan physiology was defined as Fontan circulation pressure >15 mmHg.

Results:
There were 23 patients (median age: 10.0 (7.5-13.0) years); 15 (65%) had failing Fontan physiology and 8 (35%) underwent elective takedown of their Fontan circulation. Of the 15 patients with failing Fontan physiology, 4 had exercise intolerance or cyanosis, 3 had hepatic congestion or cirrhosis, 3 had end-organ damage and 1 patient had protein losing enteropathy; the rest 4 patients had no other sign of SVP complications. A subset of patients (n=6) underwent recruitment of the non-dominant ventricle prior to conversion. HLHS (p<0.01) and sub-/aortic stenosis (p<0.01) were more common in these patients. BiVC with or without staged ventricular recruitment led to a significant increase in indexed end-diastolic volume (p<0.01), indexed end-systolic volume (p<0.01) and ventricular mass (p<0.01) of the non-dominant ventricle (14 RV, 9 LV). There were 1 (4%) early and 4 (17%) late deaths. All who underwent elective BiVC survived, while 2-year survival rate for patients with a failing Fontan circulation was 72.7% (95% CI: 37-90%) (Figure 1). The overall, 1-year reintervention free survival was 44.1% (95% CI: 21-65%). Left dominant atrioventricular canal defect (p<0.01) and early year of BiVC (p=0.02) were significant predictors for mortality.

Conclusions:
BiVC is feasible in patients with failing Fontans, and has promising outcomes after elective takedown of Fontan circulation. A staged approach for ventricular recruitment does not seem inferior to primary BiVC. The optimal timing for BiVC in Fontan patients needs further evaluation.