bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 21219: Predictors of Heart Failure Readmission in a High Risk Population
Authors: Carlson Beverly A , Hoyt Helina , Gillespie Kristi , Kunath Julie , Bratzke Lisa
Published: March 2022

Introduction:
High risk for readmission in heart failure (HF) patients is associated with Hispanic ethnicity, multi-morbidity, and hospitals serving low socioeconomic or heavily Hispanic regions or with limited cardiac services. Information for hospitals caring primarily for such high-risk patients is lacking.

Objective:
To explore and describe the characteristics of patients hospitalized for acute heart failure and identify factors associated with 30-day HF readmission in a heavily Hispanic, rural, low-income community hospital near the California-Mexico border.

Methods:
Retrospective chart review of all patients admitted for HF within a two-year period was used to gather patient characteristics, presentation, previous one-year emergency department (ED) and hospital visits, medical therapy, and discharge status. Univariate analyses with student t-tests, Wilcoxon rank, and chi-square analysis as appropriate were used to identify factors associated with 30-day readmission. Logistic regression was used to identify independent predictors.

Results:
A total of 215 patients experienced 288 HF hospitalizations. Patients were primarily Hispanic (72%), male (58%), and obese (56%) with a mean age of 69 years, preserved ejection fraction (52%), and four or more chronic comorbid conditions (80%). In the prior 6 months, most (53%) had an ED visit and 28% had been hospitalized. The sample had high rates of hypertension (89%), diabetes (59%), hyperlipidemia (47%), renal disease (34%), and mental health disorders (18%). Median length of stay was two days and two (.9%) patients died. In the 189 patients discharged alive and with 30-day data, 69% were classified as high risk for early readmission by a commonly used clinical risk assessment metric (LACE score). Ten (5.3%) patients were readmitted for HF within 30 days. Number of ED visits in the previous six months (OR 1.5, p=.009) and atrial fibrillation at discharge (OR 5.7, p=.039) were independent predictors of 30-day HF readmission.

Conclusions:
Prior ED use and atrial fibrillation predicted early HF readmission following hospital discharge. These data provide support for a clinically useful alternative to standardized risk assessment tools in heavily Hispanic, multi-morbid, low-income HF patients.
Abstract 21224: Coronary Microvascular Dysfunction in Patients With Normal and Abnormal Diastolic Function in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Dryer Kathryn , Narang Nikhil , Gajjar Mark , Cheng Jeanette Y , Lee Margaret , Paul Jonathan , Nathan Sandeep , Shah Atman P , Gheorghiade Mihai , Davidson Charles J , Fearon William F , Shah Sanjiv J , Blair John E A
Published: March 2022

Introduction:
A potential mechanism for impaired diastolic relaxation and stiffness in patients with heart failure with preserved ejection fraction (HFpEF) is the presence of coronary microvascular dysfunction (CMD). Invasive studies have demonstrated that HFpEF can be present in patients regardless of the presence or absence of echocardiographic diastolic dysfunction.

Hypothesis:
We hypothesize that CMD is common in HFpEF with normal and abnormal echocardiographic diastolic function.

Methods:
In a prospective study of HFpEF patients (n=30), clinical, echocardiographic, hemodynamic, and coronary physiology (CP) data were evaluated. CP parameters measured included coronary flow reserve (CFR) and index of microvascular resistance (IMR). Echocardiographic diastolic dysfunction (DD) was graded according to current ASE guidelines. Baseline clinical, echocardiographic, hemodynamic, and CP data were compared between grade 0 DD (n=10) and grade 1-3 DD (n=11), excluding patients with indeterminate DD grade (n=10).

Results:
Age, gender, and comorbidities were similar in the grade 0 compared to grade 1-3 DD groups. Median BNP was higher in the grade 1-3 compared to the grade 0 DD group (462 vs. 98, p=0.012). All DD and strain measurements were significantly abnormal in the grade 1-3 compared to grade 0 DD groups, as were mean pulmonary artery, and left-sided filling pressures. Mean IMR was elevated and similar in patients with and without DD (30.5 vs. 27.9, p=0.58), however mean CFR was abnormal and lower in the grade 1-3 compared to grade 0 DD groups (2.05 vs. 3.30, p=0.053).

Conclusions:
Although BNP, LV and left atrial strain, and LV filling pressures were higher in HFpEF patients with abnormal diastolic function compared to "normal" diastolic function, we found that elevated microvascular resistance is present in patients with HFpEF and "normal" diastolic function, but these patients have relatively preserved CFR.
Abstract 21227: Plasma Renin Activity, Response to Aliskiren, and Clinical Outcomes in Patients Hospitalized for Heart Failure: The ASTRONAUT Trial
Authors: Vaduganathan Muthiah , Cheema Baljash , Cleveland Erin , Sankar Kamya , Subacius Haris , Fonarow Gregg C , Solomon Scott D , Lewis Eldrin F , Greene Stephen J , Maggioni Aldo P , Böhm Michael , Zannad Faiez , Butler Javed , Gheorghiade Mihai
Published: March 2022

Background:
The direct renin inhibitor, aliskiren, is known to reduce plasma renin activity (PRA), but whether the efficacy of aliskiren varies based on an individual’s baseline PRA in patients hospitalized for HF is presently unknown. We characterized the prognostic value of PRA and determined if this risk is modifiable with use of aliskiren.

Methods:
This pre-specified neurohormonal substudy of ASTRONAUT analyzed all patients hospitalized for HF with EF≤ 40% with available baseline PRA data (n=1,306, 80.9%). Risk associated with baseline PRA and short-term changes in PRA from baseline to 1-month was modeled with respect to 12-month clinical events.

Results:
Median baseline PRA was 3.0 (interquartile range 0.6-16.4) ng/mL/h with marked regional heterogeneity (P<0.001);
Figure
. Aliskiren significantly reduced PRA early after treatment initiation through 12-month follow-up compared with placebo (P<0.001). The lowest baseline PRA quartile (<0.6 ng/mL/h) was independently predictive of lower all-cause mortality (adj. HR 0.50, 95% CI 0.31-0.81) and the composite of CV mortality and HF hospitalization (adj. HR 0.57, 95% CI 0.40-0.79);
Table
. Delta log-normalized PRA (from baseline to 1 month) was not predictive of either primary endpoint at 12 months (P≥0.43). The prognostic value of baseline PRA and short-term changes in PRA did not vary by randomization to aliskiren or placebo (interaction P≥0.13).

Conclusions:
PRA is reduced early and durably by aliskiren, but this did not appear to translate into improved clinical outcomes in ASTRONAUT. Baseline PRA or short-term reduction in PRA do not identify a subgroup which may preferentially benefit from direct renin inhibition.
Abstract 21244: The Association Between Transthoracic Echocardiography, Transesophageal Echocardiography, and No Ultrasound Use on the Duration of Pulse Checks During Cardiopulmonary Resuscitation
Authors: Fair James , Adler Aaron , Mallin Michael , Ockerse Patrick , Tonna Joseph , Youngquist Scott T
Published: March 2022

Background:
Minimizing compression pauses during cardiopulmonary resuscitation (CPR) reduces total ischemic time and contributes to better outcomes. Guidelines suggest considering ultrasound when available to guide resuscitation management in cardiac arrest and identify cardiac motion. Due to availability and ease of use, transthoracic echocardiography (TTE) is most often employed in cardiac arrest, but requires space on the patient’s chest and clear images can be difficult to obtain.

Hypothesis:
We hypothesized that transesophageal echocardiography (TEE), due to its superior image quality and lack of interference with compressions, may allow for shorter pulse check times.

Methods:
We analyzed a cohort of sequential cardiac arrests treated in the emergency department of a major tertiary care hospital utilizing video recordings of resuscitation attempts. The duration of each pulse check was recorded by blinded reviewers as well as whether TTE, TEE, or no ultrasound was concomitantly employed. A mixed effects linear regression model was used to estimate the average pause time of pulse checks, accounting for the repeated measures design while controlling for victim body mass index.

Results:
A total of 23 cardiac arrest victims were included in the analysis providing 208 pulse checks for analysis. Mean age of victims was 56 years and 42% were female. The mean pulse check duration for palpation alone, TTE, and TEE was 15 sec (95% CI 10-20), 23 sec (95% CI 16-30), and 12 sec (95% CI 7-18), respectively (P 0.00, 0.013, 0.00). TEE was associated with significantly shorter pulse check times when compared to TTE and palpation alone, although the latter difference was not statistically significant (FIGURE).

Conclusion:
In this observational study, pulse check duration was significantly shorter when using TEE during CPR when compared to TTE but not to palpation alone. This factor should be taken into consideration when deciding ultrasound modalities during resuscitation.
Abstract 21261: Circulating Extracellular Vesicles From Mouse and Rat Models of Diabetes Reveal Specific Microrna Signatures as Biomarkers of Diabetic Cardiomyopathy
Authors: Chandy Mark , Njock Makon-Sébastien , Veitch Shawn , Bugyei-Twum Antoinette , Cheng Henry , Momen Abdul , Connelly Kim , Fish Jason , Husain Mansoor
Published: March 2022

Background:
Type-2 diabetes (T2D) is associated with both reduced and preserved ejection fraction heart failure. Obese db/db mice and Goto Kakizaki (GK) rats represents animals models of T2D that develop cardiac dysfunction similar to human diabetic cardiomyopathy, in which dominant early findings are of diastolic (and not systolic) dysfunction. Circulating extracellular vesicles (EV) contain microRNAs (miR) that can be transferred to recipient cells to modulate their function. We explored whether analysis of EV content from animals models of T2D would inform on the pathophysiology, diagnosis and therapeutic targets of cardiac dysfunction.

Hypothesis:
EV from animal models of T2D will have altered miR content that contributes to the pathophysiology of diabetic cardiomyopathy.

Methods & Results:
miR qPCR arrays on circulating EV isolated from plasma of db/db mice reveal several miR (-7, -15, -25, -30e, -148a, -150, -195) modulated during disease progression. These changes in miR content occur prior to echocardiographic evidence of diastolic dysfunction, including global longitudinal strain and strain rate. Among circulating EV miR from the GK rat model, miR-30 was also upregulated (1.42 fold, p=0.03) compared to Wistar rat. In GK rat left ventricle, and in H9C2 rat cardiac myoblast cultured in 25 mM high glucose media, mass spectrometry revealed proteins that were overexpressed in the diabetic heart including oxidative phosphorylation, glycolysis, fatty acid degredation and the citrate cycle. Using a bioinformatics approach, we next identified metabolic pathways affected by miR-30. Based on these findings, in vivo therapy with antagomiR and mimics of miR-30 are underway to test causality and reversibility of the observed cardiomyopathy.

Conclusion:
EV from animal models of T2D have altered miR content, including miR-30. We also identify alterations in the expression of a network of metabolism genes in the heart, which are implicated in diabetic cardiomyopathy. If causality is supported by experiments that enhance or block miR-30 expression in these models of disease, we will have identified a novel biomarker and therapeutic target for diabetic cardiomyopathy.
Abstract 21278: Time to Diagnosis of Acute Coronary Obstruction Following Surgical Repair of Congenital Heart Disease is Associated With Improved Transplant-Listing Free Survival
Authors: Goldsmith Michael P , Gauvreau Kimberlee , Porras Diego
Published: March 2022

Objectives:
Acute coronary artery obstruction (CAO) following surgical repair of congenital heart disease (CHD) is rare but carries a high burden of morbidity and mortality. Prior reports describe the complication in individual populations of CHD, though few have looked at factors associated with outcomes. We hypothesize that increased time from a clinically significant post-operative sentinel event suggestive of coronary ischemia to diagnosis of CAO is associated with worse clinical outcomes.

Methods:
Single center retrospective review of patients diagnosed with acute post-operative CAO by coronary angiography following surgical repair of CHD between January 2000 and June 2016. Sentinel events were identified and timestamped. Characteristics compared by Fisher’s Exact and Wilcoxon Rank-Sum test. Exact logistic regression used for primary analysis.

Results:
A total of 34 patients were identified with acute post-operative CAO, n=32 (94%) had an identifiable sentinel event: n=15 (47%) cardiac arrest, n=12 (38%) persistent ventricular dysfunction, n=5 (16%) malignant arrhythmia. Longer sentinel event to angiography time was associated with composite outcome of death or heart transplant listing (OR 1.08 for each additional hour (1.02-1.17), p = 0.03). This association remained when adjusting for significant covariates of HLHS diagnosis (OR 1.06 (1.01-1.15) p=0.01) and surgical coronary manipulation (OR 1.07 (1.01-1.16), p=0.003). Ultimately in the series, n=27 (79%) required ECMO, n=14 (41%) died, and n=9 (27%) were listed for heart transplant.

Conclusions:
In the largest cohort described to date, time from a significant post-operative event to diagnosis of CAO by angiography was associated with death or heart transplant listing. Given the high burden of ECMO and death in this population, clinicians should maintain a high index of suspicion for CAO in patients who do not follow typical post-operative trajectory and consider early advanced diagnostics.
Abstract 21282: CD14 is a Key Mediator of Foam Cell Formation Induced by Lysophosphatidic Acid and Lipopolysaccharide
Authors: An Dong , Hao Feng , Zhang Fuqiang , Xu Xuemin , Cui Mei-Zhen
Published: March 2022

Lysophosphatidic acid (LPA), a simple lysophospholipid, has potent effects on a variety of cell types. We report here that LPA enhances lipopolysaccharide (LPS)-induced oxidized low density lipoprotein (oxLDL) uptake in mouse primary bone marrow-derived macrophages (BMMs). Our data revealed that both LPA and LPS highly induce the CD14 expression at both messenger RNA and protein levels in BMMs. The role of CD14, one component of the LPS receptor cluster, in LPA-induced biological functions has been unknown. We took several steps to examine the role of CD14 in LPA signaling pathways. Knockdown of CD14 expression nearly completely blocked LPA-, LPS- or LPA plus LPS-induced oxLDL uptake in BMMs, demonstrating for the first time that CD14 is a key mediator responsible for both LPA- and LPS-induced oxLDL uptake/foam cell formation. To determine the molecular mechanism mediating CD14's novel function, we demonstrated that both LPA and LPS significantly induce the scavenger receptor A-1 (SR-AI) expression, and depletion of CD14 levels blocked LPA/LPS-induced SR-AI expression. We further showed that the SR-AI specific antibody, which quenches SR-AI function, blocked LPA and LPS-induced foam cell formation. Thus, SR-AI is the downstream mediator of CD14 in regulating LPA-, LPS-, and LPA/LPS-induced foam cell formation. Taken together, our results provide the first experimental evidence that CD14 is a novel junctional molecule connecting both LPA and LPS pathways and is a key mediator responsible for both LPA- and LPS-induced foam cell formation. The LPA/LPS-CD14-SR-AI nexus might be the new convergent pathway, contributing to the worsening of atherosclerosis.
Abstract 21289: The Presence of Warning Labels on AEDs Decreases the Odds of Device Use by Lay Rescuers
Authors: Carhart Elliot , Murray Aaron
Published: March 2022

Background:
Significant resources have been invested in public access defibrillation programs; however, the true rate of lay rescuer AED use remains unknown. Even in circumstances where the device location is known, numerous potential barriers to lay rescuer use remain. Among these is the presence of warning labels (e.g. “Trained Responders Only”), which may induce anxiety and reinforce a state of low self-efficacy. The purpose of this study was to determine if the presence of warning labels on or near public access defibrillators influences lay rescuer self-reported willingness to utilize such devices in an emergency scenario.

Methodology:
This prospective cross-sectional survey study utilized a simple random sample of adults age 18-65. Healthcare providers were excluded. Participants were asked a series of questions regarding their past experiences with CPR/AED training and were then shown a static picture of an AED. Two versions of the picture were alternated between participants in a random fashion with half of participants seeing a warning label on the device. Participants were asked about their willingness to utilize the device if faced with a victim of cardiac arrest. Comparisons were made between participants in the two groups to determine the potential influence of warning labels on self-reported willingness to render aid. Reported experience and demographics (e.g. age, gender, income, education, etc.) were used for control purposes.

Results:
Most participants (71%, N=500) indicated a willingness to assist, but fewer participants were willing to assist when presented with a warning label (65%) then when no such label was present (75%). The odds of lay rescuer AED use was significantly decreased in the presence of a warning label (OR=0.51, 95% CI=0.34, 0.75).

Conclusion:
The presence of warning labels on an AED decreased the odds of device use by lay rescuers, but it is unknown if actual human performance would be consistent with such responses in the face of an actual emergency.
Abstract 21307: Beta-Blockers Inferior to Calcium Channel Blockers in Hypertrophic Cardiomyopathy
Authors: Gombar Saurabh , Moneghetti Kegan J , Callahan Alison , Jung Ken , Wheeler Matthew T
Published: March 2022

Introduction:
There have been no large, randomized comparison trials in the medical treatment of hypertrophic cardiomyopathy (HCM). Beta-blockers (BB) have been used as first line therapy based on evidence from small studies (combined N<500). Preclinical evidence suggests calcium channel blockers (CCB) may have beneficial molecular effects in sarcomere-mutation driven HCM. We hypothesized that HCM patients treated with CCB would have improved outcomes versus patients treated with BB.

Methods:
We queried claims data of 115 million unique patients from 2007 to 2014 for records with a HCM diagnosis. We divided HCM patients into those prescribed only beta-blockers (N=5141) or those prescribed only calcium-channel blockers (N=993) during the follow up period (4.4 +/- 2.1 years). We evaluated the time to event of atrial fibrillation, ventricular arrhythmia, heart failure, myectomy, ICD implant, or sudden cardiac arrest as well as a combined endpoint. Survival analysis was performed on cohorts matched for age, gender, year of entry, and length of record; logrank test was used to compare groups.

Results:
The cohort treated with BB, when compared to matched patients treated with CCB (n=984 each group), were found to have a significant increase in the rate of new diagnoses of atrial fibrillation, ventricular arrhythmia, heart failure, or myectomy (logrank p all <0.01). Overall (Figure), 152 of 984 patients treated with CCB as compared to 283 of 984 patients treated with BB met the combined endpoint (p<0.001), driven by fewer diagnoses of atrial fibrillation (58 vs 109 outcomes) and ventricular arrhythmias (43 vs 105 outcomes).

Conclusion:
We find that treatment of HCM patients with calcium channel blockers is associated with fewer adverse outcomes when compared to a matched cohort treated with beta-blockers. Further investigation is necessary to determine if these findings warrant a change of current clinical practice.

Figure.
Abstract 21308: Mesenchymal Stem Cells Driven by Exosomal Mir-125b Protect Myocardial Infarction via P53-Mediated Autophagy Signalling
Authors: Hu Xinyang , Xiao Changchen , Xu Yinchuang , Zhu Wei , Wang Jian’an
Published: March 2022

Background and Objectives:
Bone marrow derived mesenchymal stem cells (MSCs) transplantation confers protection against adverse cardiac remodeling mainly through paracrine effects, however, it remains largely unknow whether autophagy is involved in the protection offered by MSCs therapy. In the present study, we used the mice myocardial infarction(MI)model to investigate whether and how MSCs modulates autophagy activity to protect the injured myocardium.

Methods and Results:
Using a well established methodology of MSCs therapy for treating myocardial infarction, we reproduced the data that MSCs can reduce myocardial apoptosis to improve cardiac function post-MI, which was closely associated with attenuated autophagy flux in cardiac tissue. To further investigate how MSCs modulate autophagic activity, we co-cultured MSCs with neonatal mice cardiomyocytes (NMCMs) to test whether NMCMs co-cultured with MSCs exhibited enhanced tolerance to hypoxia. We showed that NMCMs exposed to hypoxia had increased autophagic flux, co-culture with MSCs resulted in a decrease in autophagic flux which was associated with improved apoptosis. Interestingly, NMCMs exposed to hypoxia exhibited up-regulated levels of p53 and its downward target Bnip3 at both mRNA and protein levels. Importantly, NMCMs co-cultured with MSCs had decreased p53 and bnip3 expression levels, suggesting that MSCs protected hypoxic cardiomyocytes via modulating autophagic flux through suppressing p53/bnip3 pathways. Exosome has been considered as the major paracrine components of MSCs, therefore, we extracted the exosomes from MSCs and it displayed the similar effects with MSCs on the autophagy modulation. We found miR-125b was an important component of exosome, inhibition of miR-125b in exosome abolished the effect of autophagy modulation via p53/Bnip3 signal pathway.

Conclusion:
MSCs, can exert the paracrine effects via miR-125b containing exosomes to block p53/Bnip3 pathway and decrease the autophagic related cell death, thus conferring protection for the cardiomyocytes.
Abstract 21309: Transcatheter Aortic Valve Implantation Outcomes in Patients With History of Previous Cardiac Surgery: A National in Patient Sample Analysis
Authors: Nalluri Nikhil , Kumar Varun , Anugula Dixitha , Patel Nileshkumar , Gaddam Sainath , Asti Deepak , Saouma Samer , Royzman Roman , Maniatis Gregory , Kandov Ruben , Tamburrino Frank , Lafferty James C
Published: March 2022

Introduction:
The influence of previous cardiac surgery (CABG, Valve Replacement or both) on In-hospital clinical outcomes in patients(pts) undergoing Transcatheter Aortic Valve Implantation (TAVI) has not been well established.

Methods:
We analyzed the clinical characteristics and periprocedural in-hospital outcomes among pts undergoing TAVI using 2011-2014 HCUP-Nationwide Inpatient Sample database. ICD-9-CM codes were used to identify pts undergoing TAVI with and without history cardiac surgery. Propensity score matching has been attempted to minimize bias. SAS software was used for statistical analysis with p < .05 used to indicate statistical significance.

Results:
Among a total of 8466 pts who underwent TAVI during the study period, 1982 had a history of previous cardiac surgery. It was noted that pts with prior cardiac surgery were dominantly male and had a higher prevalence of unfavorable clinical characteristics except pulmonary hypertension (Table). The propensity-matched analysis for 3834 patients showed that the incidence of periprocedural of stroke (2.61% vs1.62%,p=0.03) was lower in pts with previous cardiac surgery. Whereas the prevalence of In-hospital mortality(3.29% vs 2.35% p=0.07), vascular complications(9.96% vs 9.08%,p=0.34), transfusion(23% vs 20.45%,p=0.055), Acute Kidney Injury (AKI)(18.41% vs 16.95%, p=0.23), and pacemaker implantation(10.64 vs 9.29, p=0.16) were comparable for the two cohorts.

Conclusions:
In Pts with a history of previous cardiac surgery undergoing TAVI there is a lower incidence of periprocedural stroke compared to those without a history of cardiac surgery. The rates of in-hospital mortality, vascular complications, transfusion, Acute Kidney Injury (AKI), and pacemaker implantation were similar between both the groups.
Abstract 21314: Glutaredoxin-1: An Endothelial Protector in Hyperlipidemia
Authors: Han Jingyan , Fan Huijie , Hamburg Naomi
Published: March 2022

Background:
Hypercholesterolemia (HC) dominates the risk factors for atherosclerosis. Sustained oxidative stress is a central mechanism driving endothelial dysfunction (ED) in HC. But the underlying redox mechanism remains unclear. Protein S-glutathionylation, a reversible oxidative modification of cysteine residues is tightly controlled by a specific de-glutathionylation enzyme: glutaredoxin-1 (Glrx-1), which thereby plays a critical role in redox regulation of cellular function.

Methods and Results:
The protein levels of Glrx1 in aorta and lung tissues are inversely correlated with circulating cholesterol in WT and ApoE
-/-
mice. Overexpression of Glrx1 in ApoE
-/-
mice attenuates HC-induced ED as measured by flow-mediated dilation of femoral artery using a new vascular imaging method with optical coherence tomography technique, and impaired eNOS function as evidenced by increased eNOS monomer to dimer ratio and suppressed phosphorylation of vasodilator-stimulated phosphoprotein in the aorta. In HAECs oxidized LDL promotes downregulation of Glrx1 without altering its mRNA level. The consequent elevated PrS-SG inactivates Akt/eNOS and stimulates degradation of Rac1, a key regulator of eNOS. All of these deteriorate effects of oxLDL are prevented by adenoviral overexpression of Glrx1.

Conclusions:
HC-induced downregulation of Glrx1 promotes ED by redox inactivation of eNOS and its upstream regulators: Akt1 and Rac1.
Abstract 21318: Long Non-Coding RNA Promotes Endothelial Homeostasis Through Chromatin Remodeling
Authors: Chen Zhen , Miao Yifei , Lin Feng-Mao
Published: March 2022

Serving as a bioactive interface between the blood flow and the vessel wall, the vascular endothelium senses mechanical and chemical signals under various physiological and pathophysiological conditions, such as atherosclerosis and diabetes complications. Among the extensive mechanistic studies on multiple molecular levels, it is unclear whether and how chromatin remodeling plays a role in regulation of endothelial gene expression. In this study, we explored the role of long non-coding RNAs (lncRNAs)-mediated chromatin remodeling in endothelial transcriptome. Combining RNA-sequencing, chromosome conformation capture technologies, and systems biology approaches, we identified in human endothelial cells (ECs) a set of long non-coding RNAs (lncRNAs) that are differentially regulated by endothelial protective versus detrimental stimuli. Mechanistically, these lncRNAs can act as scaffolds to enhance transcription of key endothelial molecules through mediating the long-range DNA interaction and transcription factor binding. Suppression of these lncRNAs with locked nucleic acid-GapmerRs or CRISPR-Cas9-mediated genomic editing leads to altered endothelial transcriptome and phenotypes. Using mouse models, we demonstrate that some of these lncRNAs and their molecular functions may be conserved across-sepcies. Furthermore, these lncRNAs can be detected in the circulating exosomes, suggesting that they may bear diagnostics and therapeutics potentials. Collectively, these lncRNAs play an essential role in epigenetic regulation of endothelial functions; the identification of these lncRNAs can have significant impacts on understanding of diseases involving endothelial dysfunction.
Abstract 21327:
In vivo
Reduction of Mitochondrial Oxidative Stress Abolishes Arrhythmic Sudden Cardiac Death (SCD) in Non-Ischemic Heart Failure
Authors: Dey Swati , DeMazumder Deeptankar , O'Rourke Brian
Published: March 2022

Intro:
Reactive oxygen species (ROS) are central to SCD pathophysiology, but their effects depend on

where

and

how

ROS are generated. Insight into this has been limited by the lack of adequate experimental methods. Employing innovative approaches, we tested the hypothesis that elevated mitochondrial ROS (mROS) is a principal source of oxidative stress and in vivo reduction of mROS mitigates SCD in non-ischemic heart failure (HF).

Methods:
In a unique guinea pig model that mimics human non-ischemic HF with a high incidence of SCD, we performed a randomized 2x2 crossover study of vehicle (v) and MitoTEMPO therapies (vM/Mv). In the untreated HF model, we performed
in vivo
gene transfer with novel, genetically encoded ratiometric redox sensors targeted to the cytosol (cROS) or mitochondria of cardiomyocytes. In isolated left ventricular (LV) myocytes, we quantified ROS dynamics during field stimulation (1 Hz, 37°C) in the presence or absence of MitoTEMPO.

Results:
Over 4 weeks, 65% of the HF animals experienced SCD. MitoTEMPO therapy abolished SCD and LV dysfunction. Crossover to MitoTEMPO (vM) prevented SCD and improved LV function; the converse (Mv) worsened HF without increasing SCD for up to 5 weeks of follow up, suggesting distinct underlying mechanisms. EKG analysis revealed that MitoTEMPO therapy decreased PVC burden, reduced dispersion of repolarization and decreased QT variability in arrhythmogenic failing hearts. MitoTEMPO therapy also prevented many of the changes in expression proteome and phosphoproteome leading to contractile dysfunction, arrhythmia and SCD. In subcellular studies of LV myocytes, acute MitoTEMPO exposure strongly suppressed both mROS and cROS. Exogenous H
2
O
2
increased ROS in all intracellular compartments, but mROS scavenging was impaired more than cROS, consistent with downregulation of mitochondrial antioxidant enzymes.

Conclusions:
Mitochondria are a principal source of cellular oxidative stress in failing arrhythmogenic hearts, but also are the major sink of ROS. Impaired mROS scavenging cause failing hearts to become more vulnerable to demand-induced oxidative stress and promote arrhythmic SCD. Maintaining global redox balance by enhanced mROS scavenging may be an effective strategy for SCD therapy in HF.
Abstract 21337: Comparison of Cardiac Computerized Tomography Angiography and Transesophageal Echocardiography for Device Surveillance After Endovascular Left Atrial Appendage Closure
Authors: Qamar Sadia , Jalal Sabeena , Nicolau Savvas , McLaughlin Patrick , Tsang Michael , Saw Jacqueline
Published: March 2022

Background:
Surveillance after left atrial appendage (LAA) closure is important to assess for device success and complications. There is limited data on the role of cardiac computerized tomography angiography (CCTA) for LAA device monitoring.

Methods:
We retrospectively analyzed consecutive patients with non-valvular atrial fibrillation who underwent LAA closure who had both trans-esophageal echocardiography (TEE) and CCTA performed post-LAA closure. Prospective cardiac-gated CCTA were performed with Toshiba 320-detector or Siemens 2nd generation 128-slice dual-source scanners. We assessed for residual contrast patency of the LAA by comparing linear attenuation coefficient (Hounsfield unit, HU) in the LAA and left atrium (LA) on CCTA. Residual contrast patency was categorized as due to peri-device leak (presence of ostial gap) or fabric leak (diffusion of contrast through device membrane). We also assessed for device compression, thrombus and pericardial effusion on CCTA. These were compared to TEE findings.

Results:
Sixty-one patients underwent CCTA at median 93.5d (1-267) post-LAA closure (55 WATCHMAN, 4 Amulet, 2 ACP). Post-procedural TEE was done at median 93d (0-289). The median age was 77.5yrs (60-88) and median CHADS-VASc score 4 (2-8). Procedural success was 100%. On TEE, the presence of any peri-device leak was 26 (41.9%), with >3mm leak observed in 10/62 (16.1%), and >5mm observed in none. The presence of residual contrast patency in the LAA was observed in 36/61 (59%) on CCTA, of these, 29 (80.5%) had peri-device leak, and 7 (19.4%) had fabric leak. The median linear attenuation coefficient in patients with residual contrast patency was 328 (133-652) HU, and all had >100 HU in the LAA and HU attenuation ratio LA/LAA of >0.25. Median maximum device compression was 5.7% in those with peri-device leak, and 19.4% (p=0.027) for those without peri-device leak on CCTA. Among patients with peri-device leak on CCTA, 89.6% had peri-device leak on TEE, with corresponding 93.8% sensitivity, 69.9% specificity, and AUC=0.82 (95% CI 0.72-0.93).

Conclusions:
CCTA is more sensitive than TEE for assessing peri-device leak after LAA closure. Greater device compression appears to be associated with lower incidence of peri-device leak.
Abstract 21347: Percutaneous Coronary Intervention With Drug Eluting Stents is as Efficacious as Coronary Artery Bypass Grafting in Unprotected Left Main Disease: A Meta Analysis
Authors: Balasubramanian Senthil S , Vij Aviral , Siddamsetti Sisir , Sethi Ankur , Kodumuri Vamsi
Published: March 2022

Background:
CABG is the preferred revascularization strategy for unprotected left main disease. Multiple small scale trials and registry data showed that PCI with Drug Eluting Stents is a non-inferior strategy and is a Class IIa ACC/AHA recommendation in a high surgical risk patient with favorable anatomy. However, two recent large scale randomized trials have shown conflicting evidence. We conducted a meta-analysis of the existing data to compare the long term outcomes of PCI with DES vs CABG for left main stenosis.

Methods:
4 randomized and 8 non-randomized studies involving 10,284 patients were included. The primary endpoint was a composite of death, stroke or MI at three years or longer. Secondary end points were MACCE (death, stroke, MI or repeat revascularization) and it's individual components. Heterogeneity of the studies was analyzed by Cochran’s Q statistics. The Mantel-Haenszel random effects model was used to calculate the combined odds ratio for outcomes. An independent analysis was performed for the randomized data only.

Results:
There was no significant difference in the primary composite outcome between PCI and CABG at long term follow up. However the MACCE was significantly higher in PCI, primarily driven by significantly high repeat revascularization. The stroke rate was lower in PCI, although not significant. Analysis of randomized data also yielded similar results. A subgroup analysis stratified by SYNTAX score showed that MACCE and repeat revascularization were not significantly different between PCI and CABG in low to intermediate SYNTAX score (<33) while they were significantly higher in PCI in high SYNTAX score.

Conclusion:
There was no significant difference in the primary composite outcome between PCI with DES and CABG at long term follow up. Repeat Revascularization in PCI was also not different from CABG in left main stenosis with low SYNTAX score. PCI with DES can be considered as a reasonable alternate strategy in isolated left main stenosis.
Abstract 21357: Qt Intervals During Nighttime Sleep and Circadian Autonomic Activities in Healthy and Long Qt Syndrome (lqts) Infants
Authors: Yoshinaga Masao , Seki Shunji , Ushinohama Hiroya , Ohno Seiko
Published: March 2022

Background:
Few data were available about the QT intervals during nighttime/daytime sleep and daytime activity, and circadian autonomic nerve activities in healthy and LQTS infants.

Methods:
Holter ECGs were recorded in infants with 12 LQTS infants (2
KCNQ1
, 5
KCNH2
, and 5 not mutation-identified; 12±7 weeks after birth; M/F=6/6) before treatment. Ten age-matched healthy infants (M/F=4/6) were evaluated at the same period (12±3 weeks) and at 40±6 weeks. Three consecutive QT/RR intervals were measured at maximum (max), minimum, and mean heart rates (HRs) at nighttime/daytime and daytime activity and QT intervals were corrected by Bazett’s formula. The power spectral density was computed hourly as low-frequency (LF) and high-frequency (HF) components and was log-transformed. Ln(HF) and the ratio of Ln(LF)/Ln(HF) were used as surrogate markers of para-sympathetic activity and sympathovagal balance, respectively.

Results:
LQTS infants showed a significantly longer QTc value (490±19 ms) at max HR at nighttime sleep than that (478±20 ms,
P
=0.008) at max HR in daytime sleep; On the other hand, healthy infants showed no difference in the QTc values between nighttime and daytime sleep in both early and late infantile periods (439 vs 435 in early and 433 vs 423 ms in late infantile periods, respectively). LQTS infants showed a significantly decreased (or premature) parasympathetic than controls during early infancy during nighttime (Figure). In healthy controls, nighttime parasympathetic activity significantly increased at late infancy. QTc values during nighttime sleep was inversely associated with parasympathetic activity (
P
=0.002) and positively associated with sympathovagal imbalance (
P
<0.001).

Conclusions:
In early infantile periods, parasympathetic activity was not fully functioned, especially in LQTS infants. A long QTc values associated with impaired autonomic activity during nighttime sleep is one of risk factors of lethal arrhythmia in LQTS infants.
Abstract 21380: RBM39 is Vital for Maternal Obesity-Induced Fetal Sheep Cardiac Contractile Dysfunction by Regulating Myocardial Autophagy
Authors: Wang Qiurong , Odhiambo John F , Nathanielsz Peter W , Ford Stephen P , Ren Jun , Guo Wei
Published: March 2022

Maternal obesity becomes pandemics in 21
st
century. Previous epidemiological studies on humans suggested that obesity during pregnancy could result in increased incidences of cardiovascular diseases in the offspring. Studies on animal models also indicated that maternal obesity could induce cardio dysfunction in offspring. However, the mechanisms underlying are still not well elucidated. Previously we have reported that maternal obesity could lead to fetal cardiac contractile dysfunction in sheep. Moreover, from mid- to late-gestation, the cortisol level has been shown increased in fetuses born from obese ewes. Here, we are trying to tie the relationship of upregulated cortisol level in fetuses to maternal obesity-induced fetal cardiac contractile dysfunction. We found that RBM39, a critical transcriptional factor which is activated by hormonal stimulation, was 2.5-fold upregulated in fetal myocardium from obese ewes. Moreover, maternal obesity induced autophagic gene upregulation in fetal myocardium. Meanwhile, the expression of the autophagic cargo protein SQSTM1, also known as ubiquitin-binding protein p62, is also upregulated in maternal obesity fetal hearts. The upregulated SQSTM1 is an indicator of blockade of autophagic flux. Collectively, our studies reveal RBM39 as a transcriptional factor, is activated by increased levels of cortisol in fetuses from mid- to late-gestation. In turn, autophagy pathways have been activated via RBM39 transcriptional regulation in fetal myocardium of fetuses born from obese ewes, as well as the autophagy cargo protein SQSTM1. Therefore, the autophagic flux has been disturbed in the myocardium of fetuses born from obese ewes, which could be a possible mechanism of maternal obesity-induced cardiac contractile dysfunction.
Abstract 21383: Associations of Childhood Traits to Adult Aortic Stiffness and Left Ventricular Hypertrophy Vary by Race: The Bogalusa Heart Study
Authors: Zachariah Justin P , Fernandez Camilo , Barshop Rupert , Harville Emily , Chen Wei , Bazzano Lydia
Published: March 2022

Background:
Aortic stiffness and left ventricular (LV) remodeling increases with age and accumulated CVD risk factors, which vary by race. We hypothesized that childhood risk factors are longitudinally associated with adult aortic stiffness and LV remodeling and that these associations vary by race in the biracial (black vs. white) Bogalusa Heart Study cohort.

Methods:
Participants sampled had at least three Study visits over the life course, ultrasound as young adults for aorta-femoral pulse wave velocity (afPWV), and echocardiographic LV mass (n=1081, 24-44 years old, 31% black, 57% female, and mean follow-up 27 years). Demographic, anthropometric, blood pressure, lipid, glucose and tobacco exposure data were extracted from each visit. Given variable visit intervals and number, separate growth mixed models were used to compute total area under the curve for risk factor traits on the primary outcomes of interest, a) afPWV or b) LV mass indexed to height
2.7
(LVMI). Childhood trait to adult afPWV and LVMI associations, adjusted for cumulative trait levels, were examined with multivariable-adjusted linear regression. Significant race by trait interaction terms (p<0.001) led to race-specific reporting.

Results:
Adult afPWV and LVMI were higher in black (5.4±1.2 m/s and 36.3±11.4 g/m
2.7
) than white (5.2±1.1 and 33.8±9.2) participants (p=0.01). Higher adult afPWV was associated with childhood low density lipoprotein cholesterol (LDL-C, β 0.13;p<0.001) and mean arterial pressure (MAP, 0.1;p=0.02). By race, higher afPWV was associated with childhood LDL-C in blacks (0.17;p<0.01) and whites (0.1;p<0.01) while MAP was associated only in whites (0.08;p=0.04). Adult LVMI was associated with childhood BMI (0.3; p<0.001), triglycerides (TG, -0.08; p=0.04), and afPWV (0.10, p<0.01). By race, higher LVMI was associated with childhood BMI in blacks (0.27; p<0.001) and whites (0.34;p<0.001), while LDL-C (0.1; p=0.02), TG (-0.14; p<0.01), Glucose (0.12; p<0.01), and afPWV(0.11,p<0.01) were associated only in whites.

Conclusions:
Adult aortic stiffness and LV remodeling were associated with childhood traits, even after adjustment for cumulative trait levels. These associations appear to vary by race.
Abstract 21400: Morphological Analysis of Transcranial Doppler Waveforms for Large Vessel Occlusion Diagnosis
Authors: Hamilton Robert , Thorpe Samuel , Thibeault Corey , Martinez Leo , Wilk Seth , Devlin Thomas
Published: March 2022

Introduction:
Underlying cardiac conditions such as atrial fibrillation (AF) and cardiac procedures such as transcatheter aortic valve replacement (TAVR) and coronary artery bypass grafting (CABG) have been shown to lead to large vessel occlusions (LVO) causing significant mortality and morbidity and improved pre, peri, post procedural methods for diagnosis are needed. Transcranial Doppler (TCD) is a rapid, inexpensive and portable tool for assessment of cerebral blood flow velocity (CBFV) that is used clinically and has been shown to have potential as a diagnostic aid for LVO. The utilization of the morphological information from the TCD waveform has shown to provide additional diagnostic capabilities in many neurological conditions and may improve LVO detection over traditional TCD metrics of mean velocity and pulsatility index. However, traditional TCD techniques suffer from a number of limitations including operator skill level and variability due to depth and location selection.

Hypothesis:
The morphology of CBFV waveforms measured with TCD enables detection of LVO while relaxing the need for exact insonation depth relative to occlusion location.

Methods:
Bilateral TCD scans of 17 pts (66.8 ± 15.2 yrs) with confirmed MCA occlusion were performed immediately following CT/CTA. TCD was also performed on 28 healthy out of hospital controls (55.3 ± 9.5 yrs). Waveform morphology was compared between the two groups.

Results:
Morphological analysis wherein MCA data for each subject was randomly sampled across depths showed median AUC of 96.3% for LVO detection, with median SEN of 88.9% and SPE of 96.3%. Fig. 1 shows an example of TCD waveforms for control and LVO subjects with similar traditional TCD metrics, but different subtle morphological profiles.

Conclusion:
Morphological analysis demonstrated high diagnostic accuracy additionally without the need for optimal depth selection, which may reduce the requirement of a trained sonographer.
Abstract 21410: Utility of Ratio of Maximum Leaflet Thickness to Residual Radius in Predicting Aortic Root Rupture or Hematoma During Transcatheter Aortic Valve Replacement
Authors: Sun Yujun , Okoh Alexis , Edwards Isheeka , Kanwal Sunil , Russo Mark , Cohen Marc . , Haik Bruce , Chen Chunguang
Published: March 2022

Introduction:
Aortic root rupture or hematoma (ARR or ARH) is a serious complication of transcatheter aortic valve replacement (TAVR). In addition to excessive oversizing (annular area/TAVR stent area) and aortic annular calcification.

Hypothesis:
We hypothesize that combination of small sinus of Valsalva (SOV) and excessive calcification of aortic leaflets is a significant risk factor for ARR or ARH.

Methods:
Patients who experienced ARR or ARH during TAVR were selected. A matched cohort who had no complications during the procedure were identified from a prospectively maintained database. Dynamic 4-D cardiac computed tomography was used to assess respective thickness of the three aortic cusps, SOV, annular area, LVOT, and the presence and extent of calcification of the LVOT. The ratio of maximum leaflet thickness (MLT) to residual radius (RR): (SOV diameter - TAVR stent diameter)/2), and TAVR stent oversizing: (TAVR stent area - aortic annular area)/TAVR stent area were calculated and severity of annular calcification graded. Stepwise logistic regression using backward selection was used to determine factors associated with ARR or ARH during TAVR.

Results:
Out of 800 TAVR patients, ARR/ARH occurred in 18 (2.2%) during the procedure. There were 19 well-matched (no complication) patients who served as a control group. Baseline clinical characteristics were similar in ARR/ARH - patients and ARR/ARH + patients. LVOT calcification was ≥ moderate in 61 % of ARR+ patients and 31 % in ARR- patients. The overall incidence of bio prosthetic valve oversizing 37% (n=14). On multivariable logistic regression analysis, an MLT/RR ratio > 1.4, prosthetic valve oversizing ≥ 20% and ≥ moderate or greater annular calcification were significantly associated with ARR during TAVR.

Conclusions:
In addition to excessive oversizing of >20% and annular calcification, a high MLT/RR ratio, a parameter for a combination of small sinus of Valsalva and excessive leaflet calcification, is an independent predictor of ARR or ARH.