bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 21216: Racial Differences for Ablation in Atrial Fibrillation
Authors: Joy Parijat S , Kabra Rajesh
Published: March 2022

Introduction:
Catheter ablation procedures are utilized for rhythm control of atrial fibrillation (AF) but the utilization of this procedure based on race remains uncertain.
Purpose:
We investigated trends in admissions due to AF and utilization of AF ablation, based on race.

Methods:
The 2000-2013 National Inpatient Sample (NIS) from Healthcare Utilization Project (HCUP) was analyzed for hospitalizations in patients with known history of AF based on ICD-9-CM codes. Observations with unknown or missing race were excluded.

Results:
35,761,659 adults (mean age 75.9 ± 11.8) with known AF were hospitalized (49.0% males and 51.0% females). AF was the primary reason for admission in 4,158,058 (11.6%) patients that consisted of 86% whites, 7% Blacks, 5.3% Hispanics, 1.4% Asians and 0.3% Native Americans. Of these patients admitted primarily for AF, ablation procedures were performed in 96,250 (2.31%) patients. The proportion who underwent ablation during an admission for AF, was lowest among blacks (whites 2.46%; blacks 1.11%; Hispanics 1.5%, Asians 2.15% and Native Americans 3.25%). There is a rising trend of ablation procedures among patients admitted due to AF: 0.5% in the year 2000 to 2.82% in 2013 (p trend < 0.001). The difference in the proportion of black vs. non-black patients having ablation has increased from 0.43% in the year 2000 to 1.42% in the year 2013. On multivariable analysis, adjusting for relevant patient-related factors, the likelihood of black patients being hospitalized primarily for AF was higher than non-blacks (OR: 1.04, p < 0.001). However, adjusting for the same patient-related factors, the likelihood of black patients undergoing ablation, during admission for AF remained lower than non-blacks (OR: 0.51, p < 0.001).

Conclusion:
For patients hospitalized due to AF, ablation of AF is being increasingly utilized. Black patients are more likely to get hospitalized due to AF but less likely to undergo ablation than non-black patients.
Abstract 21236: Novel Immune Regulatory Defects Contribute to Abdominal Aortic Aneurysm Formation
Authors: Green Linden A , Murphy Michael P , Babbey Clifford M
Published: March 2022

Abdominal aortic aneurysm (AAA) is a significant and serious health problem with an incidence as high as 9% and is associated with 15,000 deaths each year in the U.S. Recently AAA has increasingly been considered to be an autoimmune disease, where a pro-inflammatory cascade with cytotoxic and proteolytic features results aortic wall degradation and aneurysm formation, but the underlying causes of this imbalance remain unknown.

Regulatory T cells prevent both the activation and effector function of reactive T cells sensitized to auto-antigens. Critical in this process are Type 1 regulatory T-cells (Tr1) which are antigen-specific and identified by expression of CD49b and lymphocyte activation gene 3 (LAG-3). Tr1 cells exhibit strong immunosuppressive activity and are able to restore tolerance in several immune-mediated diseases, through the secretion of high amounts of IL-10. Most importantly IL-10 is essential in the induction as well as immune suppressor activity of Tr1 cells. We found that AAA patients have a decreased number of Tr1 cells compared to risk-factor matched controls, and that those cells are functionally defective, producing reduced levels of IL-10 and having impaired immune suppression abilities. Moreover, naive CD4+ T cells from AAA patients were resistant to Tr1 induction
in vitro
, and AAA plasma likewise impaired the induction of Tr1 cells from healthy CD4+ T cells. Plasma miRNA analysis revealed a profile of expression changes in AAA patients that inhibit IL-10 expression. Together, these results suggest a critical defect of Tr1 cells in AAA, driven by impaired IL-10 expression, which could contribute to AAA disease pathology.
Abstract 21256: Cardiac ECM Environment Improves iPSC-Derived Cardiomyocyte Differentiation
Authors: Czirok Andras , Isai Dona G , Rajasingh Sheeja , Filla Mike , Johnson Rajasingh
Published: March 2022

Introduction:
Generation of induced pluripotent stem cells (iPSCs) and their differentiation into cardiomyocytes (CMCs) have created exciting possibilities in cardiac medicine. However, the long-term impact of iPSC-derived CMC implantation on cardiac function remains elusive. After the first month following injection, only less than 10% of the implanted cells remain alive. In contrast, during development mesodermal precursors differentiate into a functional myocardium without substantial cell loss.

Hypothesis:
The poor survival of iPSC-derived CMCs is mainly attributable to the lack of evolutionarily determined microenvironment in which the normal differentiation process takes place. Thus, we hypothesize that the embryonic or adult heart-derived extracellular matrix (ECM) provides a better culture environment for CMC differentiation.

Methods:
We utilized a highly efficient, viral-free combination of DNA and mRNA transcription factor approach to generate iPSCs and functional CMCs from adult human cells. To analyze CMC contractility, we recorded cultures using both time-lapse and high frame-rate video microscopy. ECM from adult and embryonic chicken hearts was extracted using a high salt/urea protocol, and lyofilized. iPSCs were grown on a variety of substrates, including rehydrated cardiac ECM or electrospinned films. The quality of differentiation was characterized by molecular markers, electron microscopy and tracking beat frequencies.

Results:
Heart ECM extracts provide a supportive environment for CMC differentiation. When grown on ECM extracted from adult chicken hearts, the maturation of iPSCs-derived cardiomyocytes exceeds those that were cultured using matrigel environments. For example, in vitro beat rates are higher on heart ECM (Figure, red symbols) than on matrigel (black).

Conclusions:
Culture environments containing heart-derived matrix is a promising avenue to improve the quality of iPSC-derived cardiomyocytes.
Abstract 21266: Valve Oversizing in Transcatheter Aortic Valve Replacement: Impact on Outcome
Authors: Stathogiannis Konstantinos , Toutouzas Konstantinos , Drakopoulou Maria , Latsios George , Synetos Andreas , Michelongona Archontoula , Kaitozis Odysseas , Trantalis George , Penesopoulou Vasiliki , Tsiamis Eleftherios , Tousoulis Dimitrios
Published: March 2022

Introduction:
In transcatheter aortic valve replacement (TAVR), prosthesis oversizing prevents paravalvular regurgitation. Although the estimated extent of oversizing depends on annular measurements, oversizing strategies are not well established.

Hypothesis:
The aim of our study was to evaluate the impact of different degrees of valve oversizing based on multislice computed tomography (MSCT) on the outcome of patients.

Methods:
Patients with severe and symptomatic aortic stenosis scheduled for TAVR with a self-expanding valve, were prospectively enrolled. All patients underwent pre-procedural MSCT. According to the measurements, patients were classified into three groups for the degree of oversizing: normal (10-15%), moderate (15-20%) and severe (>20%) depending on the ratio between valve prosthesis diameter and the perimeter-derived annulus diameter based on MSCT. The main endpoint was mid-term mortality and secondary endpoints were the Valve Academic Research Consortium (VARC-2) end-points.

Results:
Overall, 177 patients (mean age: 79±7years, mean logEuroscore 24.9±10%, NYHA III-IV: 90%) were consecutively included in the study. Mean annulus area was 23.3±2.5mm
2
and mean perimeter was 74.36±7.27mm. Ninety-one patients (51%) had normal oversizing, 67 patients moderate (38%) and 19 patients (11%) severe oversizing. There were no cases of annular rupture. The primary clinical end-point occurred in 38 patients (21%) during a follow-up period of 24±12 months. While all-cause mortality rates were similar in all groups (24.1% for normal sizing versus 21.9% for moderate oversizing versus 22.9%, for severe oversizing, p=0.93), post-procedural new pacemaker (PPM) implantation rate was significantly higher in severe compared to the moderate and normal oversizing groups respectively (63.2%, versus 38.8%, versus 30.8%, p=0.03). Patients with normal oversizing had a trend of higher rate of significant paravalvular leak (at least moderate) compared to patients with moderate and severe oversizing (18.7%, versus 7.5%, versus 5.3%, p=0.058).

Conclusions:
Despite a higher rate of pacemaker implantation, a higher extent of valve oversizing in patients undergoing TAVR, seems to reduce the degree of paravalvular leak.
Abstract 21273: Burden of Arrhythmias in Hypertrophic Obstructive Cardiomyopathy in United States From 2000 Through 2014: A National Population-Based Cohort Study
Authors: Tripathi Byomesh K , Arora Shilp , Krittanawong Chayakrit , Virk Hafeez UH , Badal Madan , Mishra Abhishek , Kumar Varun , Lahewala Sopan , Patel Nirali , Patel Prashant , Kulaski Edo
Published: March 2022

Background:
Hypertrophic obstructive cardiomyopathy (HOCM) is the leading cause of sudden cardiac death (SCD) in young adults and ventricular arrhythmias are known to cause SCD in these high-risk patients. The risk of SCD increases with increasing age. This data is first of its kind to address the trends in the prevalence of arrhythmias in HOCM population.

Methods:
The study cohort was extracted from Nationwide inpatient sample (NIS) from 2000 to 2014. Appropriate international classification of diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes were used to diagnose HOCM (425.1 and 425.11) and arrhythmias (427.xx). P-values for trends were generated by Cochrane-Armitage test for categorical variables and simple linear regression for continuous variables.

Results:
We noted 49.13 % incidence of any arrhythmias in HOCM patients with a relative increase of 27.92% over study period (2000-2014). Atrial fibrillation was most prevalent arrhythmia in this patient population (33.39%).Highest increase in incidence over study period was observed in bundle branch blocks ( relative increase 189.64%), atrioventricular blocks ( relative increase 119.85%), premature atrial/ventricular complex ( relative increase 123.28%), atrial flutter ( relative increase 66.86%), ventricular tachycardia (relative increase 60.54%) and atrial fibrillation ( relative increase 24.31%).

Conclusion:
Patients with HOCM are at increased risk of arrhythmias. Even after improvement in the early diagnosis and treatment of these high-risk patients, the burden of arrhythmias i.e., AF, ventricular arrhythmias, premature arrhythmias and atrioventricular blocks has increased exponentially through 2000-2014. It was also accompanied by increase in-hospital mortality in HOCM population.
Abstract 21281: Cardiosphere-Derived Cell and Mesenchymal Stem Cell Extracellular Vesicles Contain Distinct RNA Cargo
Authors: Walravens Ann-Sophie , Kelly Lauren , Peck Kiel , Marbán Linda , de Couto Geoffrey , R.-Borlado Luis
Published: March 2022

Introduction:
Cardiosphere-derived cells (CDCs) possess regenerative, immunomodulatory and cardioprotective characteristics when delivered to the heart post-myocardial infarction (MI). CDCs derived from different donors possess variable regenerative potency in a MI model. We previously demonstrated that human CDC-derived extracellular vesicles (CDC-EVs) recapitulate the effects of CDCs in acute and chronic in vivo MI models. We are testing the hypothesis that a distinct cargo profile defines the functional efficacy between CDC-EVs and mesenchymal stem cell-derived EVs (MSC-EVs). Also, we assessed the immunomodulatory role of CDC-EVs derived from potent and non-potent CDCs in comparison with MSC-EVs.

Methods:
CDCs or MSCs were cultured in serum-free medium for 15 days and the conditioned media was concentrated by ultrafiltration to isolate EVs. The miRNeasy Serum/Plasma kit was used to extract total RNA from EVs followed by small RNA sequencing (NextSeq 500, Illumina) (CDC-EVs,
n
=12; MSC-EVs,
n
=4). We performed an
in vitro
and
in vivo
macrophage assay to assess the immunomodulatory role of EVs.

Results:
RNA sequencing analysis of CDC-EVs and MSC-EVs revealed a greater overall abundance of Y-RNA fragments and miRNA in CDC-EVs. Examining the specific Y-RNA classes, we found that MSC-EVs contained an expression profile with lower Y4 (p<0.05) but higher Y5 (p<0.05) Y-RNA fragments. Four miRNAs (miR-146a, miR-151, miR-409, miR-423) were highly enriched in CDC-EVs while miR-10a and miR-4792 were more abundant in MSC-EVs. EVs from potent CDCs showed a stronger upregulation of anti-inflammatory genes in activated macrophages (
in vitro
) and prevented accumulation of macrophages (
in vivo
) when compared with EVs obtained from non-potent CDCs or MSCs.

Conclusions:
We demonstrated that CDC-EVs contain a unique RNA cargo set that can differentiate CDC-EVs from MSC-EVs. The higher presence of Y-RNA in CDC-EVs as compared to MSC-EVs could be responsible for the ability of CDCs to regulate stem cell activation and tissue regeneration. The highly enriched panel of miRNAs observed in CDC-EVs and the ability to reduce the inflammatory reaction by macrophages, in contrast to MSC-EVs, suggest that they may support some of the functional benefits observed post-MI.
Abstract 21286: Outcomes and Trends of Percutaneous Coronary Interventions in Chronic Total Coronary Occlusion
Authors: Lahewala Sopan , Patel Nirali , Patel Prashant , Arora Shilpkumar , Tripathi Byomesh , Kumar Varun , Badheka Apurva
Published: March 2022

Background:
Percutaneous coronary intervention (PCI) of Chronic Total Coronary Occlusion (CTO) remains challenging, with observed success rates that are significantly lower than those for non-occluded lesions.

Methods:
HCUP’s Nationwide Inpatient Sample (NIS) database from 2008-2014 was utilized. CTO was identified using the ICD-9-CM diagnostic code 414.2, while PCI was identified using appropriate ICD 9 procedural codes. Complications were identified using previously published ICD9 codes and patient safety indicators tagged by data vendor. Cochran-Armitage test for trend was used to test the statistical significance.

Result:
878112 CTO admissions were identified during study period, of which 47.6% went for revascularization with PCI (26.7% female, 69.8% white, 51.1% age ≥ 65). Compared to 2008, there was a relative decline of 5.7%(p < 0.0001) in 2014. Population undergoing PCI showed significant relative increase in comorbidities (p- trend < 0.0001) such as heart failure (+68.6%), renal failure (+ 50.7%), chronic pulmonary disease (+22.2%). In-hospital mortality (+ 101%) and complication rates (+ 29.4%) increased during the study period (p < 0.0001). There was a significant increase in Renal and respiratory complication rates (relative increase 466.7% & 201.7%, p < 0.0001), while cardiac complication did not show any relative change during study period and vascular complications showed decline of 29.6% from 2008 to 2014 (p < 0.0001).

Conclusion:
PCI in CTO is increasingly being done in sicker patients with higher burden of comorbidities. Improvement in interventional technical expertise has led to decline in vascular complications and steady rate of cardiac complications, though overall mortality and complications has risen mainly driven by non cardiac non vascular complications.
Abstract 21287: Myocardial Oxygen Delivery is Progressively Impaired During Development of Pulmonary Hypertension
Authors: van Duin Richard W , Cai Zongye , Duncker Dirk J , Merkus Daphne
Published: March 2022

Introduction:
Pulmonary hypertension (PH) increases afterload of the right ventricle (RV), initially resulting in RV hypertrophy. Eventually the RV is unable to cope with the high afterload, resulting in RV failure and death. The transition of RV hypertrophy to failure is incompletely understood.

Hypothesis:
The increased workload together with the RV hypertrophy increases oxygen demand of the myocardium, which is insufficiently compensated by an increase in myocardial oxygen supply through the right coronary vasculature. This mismatch between oxygen supply and demand is exacerbated during physical activity when oxygen demand increases.

Methods:
PH was induced by banding of the confluent of the inferior pulmonary vein in juvenile swine (N=5), while 5 healthy swine served as controls. Swine were chronically instrumented to measure pressure in the RV, pulmonary artery, left atrium and aorta, and right coronary blood flow (CBF) rest and during graded treadmill exercise.

Results:
Pulmonary venous banding (PVB) resulted in PH as evidenced by an increase in pulmonary artery pressure (PVB: 29±1 mmHg (week 5) and 39±3 mmHg (week 12); CON 20±1 mmHg and 21±1 mmHg, both P<0.05) that was accompanied by RV hypertrophy (RV/bodyweight 1.18±0.05 (CON), 1.70±0.15 (PVB), P=0.06). The relation between myocardial oxygen delivery (CBF*arterial oxygen content) and Myocardial work (heartrate*pulmonary artery pressure) was not different between CON and PVB at week 5 , but rotated downwards at week 12 weeks (Figure), indicative of a mismatch between oxygen supply and demand. Histology revealed an increase in cardiomyocyte size (717±35 vs 598±30 μm
2
, P<0.05), whereas capillary density and interstitial fibrosis were not changed.

Conclusions:
Progression of PH leads to a mismatch between myocardial oxygen supply and demand, particularly during exercise. This mismatch between supply and demand may cause myocardial ischemia and contribute to the transition of RV hypertrophy to failure.
Abstract 21290: Adipose Tissue Factors and the Adipokine Resistin-Induce Vascular Endothelial Dysfunction via Arginase Upregulation
Authors: Atawia Reem T , Chen Jijun , Toque Haroldo A , Lemtalsi Tahira , Caldwell Ruth B , Caldwell Robert W
Published: March 2022

Introduction:
Obesity is a major contributor to cardiovascular disorders, for which endothelial cell (EC) dysfunction is a hallmark. Obesity-induced EC dysfunction has been linked to dysregulation of the visceral adipose tissue (VAT) resulting in increased secretion of the pro-inflammatory cytokine resistin and alterations in endothelial nitric oxide (NO) producing capacity. However, mechanisms underlying this pathology are not well understood.

Hypothesis:
Resistin impairs vascular EC function via upregulation of endothelial arginase1 (ARG1) expression and activity, thus limiting L-arginine availability for NO synthesis.

Methods:
To determine the effect of obesity on EC function, conditioned media prepared from VAT (VAT CM) of high fat diet-induced obese mice, VAT CM from lean mice or resistin (100 ηg/ml) were used to treat mouse aortic endothelial cells (MAEC) and aortic rings for 24 hr.

Results:
VAT CM from obese mice increased endothelial ARG1 mRNA by 34% and decreased NO level by 32% (p<0.05), vs VAT CM from lean mice. Aortic rings incubated with obese VAT CM markedly reduced endothelium-dependent vasorelaxation (EDV) to acetylcholine. Moreover, resistin levels were 143% higher in obese VAT CM compared to lean VAT CM. In MAEC, resistin increased ARG1 mRNA by 30% and decreased NO production by 39% (p<0.05). Co-treatment with the specific ARG inhibitor (ABH, 100 μM) or supplementing EC with L-arginine increased NO to near normal levels. Incubation of aortic rings with resistin also impaired EDV. This dysfunction was largely prevented by co-treatment with ABH or in aortic rings from EC specific-ARG1 knockout mice. The resistin-induced increase in ARG1 expression in MAEC is attributed to Toll-like receptor 4 (TLR4)-induced activation of p38 MAPK pathway as co-treatment with specific TLR4 inhibitor (CLI-095) inhibited p38 activation and ARG1 expression (34% and 33%, respectively, p<0.05) and increased NO production by 38% (p<0.05). Additionally, co-treatment with a specific p38 inhibitor prevented resistin-induced increase in endothelial ARG1 expression.

Conclusions:
VAT factors and particularly resistin induce vascular endothelial dysfunction via elevated arginase expression/activity.
Support :
NIH EY11766 & HL70215 & AHA fellowship
Abstract 21292: Total Laser Cycles - A Novel Measure of Transvenous Lead Extraction Difficulty
Authors: Elsaid Ossama , O'Sullivan David , Zweibel Steven , Cronin Edmond
Published: March 2022

Background:
Several variables have been identified as predictors for difficult or complicated transvenous lead extraction (TLE), including age and number of implanted leads, as well as patient’s age; however, a standard measure of TLE difficulty has not been described.

Objective:
Total laser cycles (TLC) delivered during laser-assisted TLE is an objective variable that could reflect the difficulty of TLE. This study investigated whether TLC is correlated with known predictors of difficult TLE.

Methods:
In a retrospective study of TLE procedures using the laser sheath, we analyzed TLC delivered and compared it to established predictors of procedural failure and complications.

Results:
Of 166 patients undergoing TLE, the laser sheath (SLS II or Glidelight, Spectranetics Inc,) was used as the primary extraction sheath in 130 patients, and 100 patients had complete TLC data available. The mean age of the oldest lead (AOL) was 7.1 ± 3.2 years, and 1.6 ± 0.7 leads (range, 1-4) were extracted per procedure. Two-thirds of procedures involved ICD leads. Clinical success was 97.5%, with one patient (0.6%) experiencing a major complication. Median TLC delivered was 1165 (IQR, 567-2062; range, 49 - 9522) Hz. TLC was positively correlated with AOL (ρ=0.203, p=0.042), and the combined age of leads extracted (ρ=0.287, p=0.004) Fig 1. TLC was also positively correlated with number of leads extracted per procedure (ρ=0.240, p=0.016). There was negative and non-significant correlation between TLC and patient’s age (ρ=-0.114, p=0.257).

Conclusion:
TLC showed significant correlation with known predictors of difficulty during TLE using the laser sheath. TLC can hence be used as an objective method to report the difficulty of TLE.

Figures:

Figure1: Panel A showing the correlation between age of oldest lead (AOL) and total laser cycles (TLC); Panel B showing the correlation between combined age of leads (CAL) and total laser cycles (TLC)
Abstract 21299: Drug of Abuse is Associated With Clinical Aspects and Outcomes of Injection Drug Use Endocarditis
Authors: Barnes Erin W , Peacock James E , Bachmann Laura
Published: March 2022

Introduction:
Wake Forest Baptist Medical Center has perceived a rise in the number of injection drug use associated endocarditis cases. Many of these patients report injection of the prescription opioid oxymorphone, a drug specifically linked to a microangiopathic hemolytic anemia when injected and large HIV outbreak in Indiana.

Hypothesis:
1) The number of IDU-IE cases at our institution is increasing 2) The characteristics of these patients will differ from the classically taught phenotype of a mostly male, right sided predominant, low morbidity and mortality disease process 3) Those who injected oxymorphone will have differing clinical characteristics and clinical outcomes than those who did not inject oxymorphone.

Methods:
Retrospective analysis of IE cases at an academic medical center from 1/1/2004 to 9/30/2015 stratified by IDU and reported intravenous oxymorphone use.

Results:
Three hundred seven cases of IE were identified which included 92 IDU cases: 46 oxymorphone-exposed and 46 oxymorphone-unexposed . As compared to the non-IDU group, the IDU group was younger (31.3 +/-9.2 vs 54.2 +/-15.8, p<0.0001), predominantly Caucasian (95.7% vs 78.1%, p=0.0002), and female (58.7% vs 35.4%, p=0.02). When comparing the oxymorphone-exposed to oxymorphone-unexposed group, age (31.3+/-9.2 vs. 33.2+/-9.2, p=.32), race (95.7% Caucasian both groups), and gender (58.7% female vs. 41.3% p=0.1) were equivalent. As compared to the oxymorphone-unexposed group, the oxymorphone exposed group had significantly more MRSA (63% vs 48.9%, p=.007), tricuspid valve involvement (52.2% vs 30.4%, p=.03), and hepatitis C antibody seropositivity (78.3% vs 52.2%, p=.01). The oxymorphone unexposed group had significantly more aortic valve disease (23.9% vs 2.2%, p=.004), cardiac surgery (37% vs 13%, p=.008), and ICU admission (73.9% vs 54.4%, p=.05) than the oxymorphone exposed group. Inpatient mortality was comparable (6.5% exposed vs 8.7% unexposed, p=1.0) whereas one-year mortality was 19.6% in the oxymorphone exposed group and 13% in the oxymorphone unexposed group (p=.06).

Conclusions:
Our results support the hypothesis that there may be differences in clinical characteristics and outcomes of IDU-IE which are associated with the specific drug of abuse.
Abstract 21304: Calmodulin Modulates the Functional Effects of cMyBP-C on the Thin Filament
Authors: Yang Yuanzhang , Azimi Vahid , Hoye Elaine , Belknap Betty , White Howard D , Harris Samantha P
Published: March 2022

Introduction:
Cardiac myosin binding protein-C (cMyBP-C) is an essential regulator of heart muscle function that is necessary for both normal contraction and for increased contractility in response to inotropic signals. Effects of cMyBP-C on contraction are complex and attributable to dynamic interactions with both actin and myosin. For instance, cMyBP-C binding to actin can exert either activating or inhibitory effects on contraction by shifting tropomyosin on the thin filament or by blocking myosin heads, respectively. Recently, calmodulin (Ca
2+
/CaM) was also shown to bind cMyBP-C at a unique sequence within the regulatory M-domain of cMyBP-C (Lu et al,
JBC
287:31596, 2012). Importantly, the binding site for CaM overlaps with a conserved actin binding site that we found was important for mediating the activating and inhibitory effects of cMyBP-C on the thin filament (Bezold et al.
JBC
288: 21496, 2013).

Hypothesis:
Here we hypothesized that CaM competes with actin for cMyBP-C binding and thus influences the functional effects of cMyBP-C that are mediated through the thin filament.

Methods:
Recombinant N’-terminal domains of cMyBP-C were used in co-sedimentation binding assays, pull-down assays, and actomyosin ATPase assays to determine effects of CaM binding on cMyBP-C function.

Results:
We found that CaM binds to N’-terminal domains of cMyBP-C in the presence of Ca
2+
(Ca
2+
/CaM) with an affinity comparable to cMyBP-C binding to actin (3-10 UM). We further show that Ca
2+
/CaM reduces apparent binding affinity of cMyBP-C for actin, consistent with Ca
2+
/CaM competing with actin for binding to cMyBP-C. Also consistent with reduced binding of cMyBP-C to actin, Ca
2+
/CaM reversed the inhibitory effects of cMyBP-C N’-terminal domains on actin activated myosin ATPase rates. However, apo-CaM showed reduced binding affinity for cMyBP-C, did not compete with actin, and did not reverse the activating effects of cMyBP-C on the thin filament at low Ca
2+
.

Conclusions:
These data suggest that Ca
2+
/CaM is a novel modulator of cMyBP-C function that can temporally tune the complex effects of cMyBP-C on contraction, potentially as Ca
2+
rises and falls during a single heartbeat.
Abstract 21310: ApoCIII RX19 Mutation Lowers the Production of ApoCIII and Increases the Clearance of VLDL-TG
Authors: Reyes-Soffer Gissette , Matveyenko Anstasiya , Khavandi Maryam , Karmally Wahida , Ramakrishnan Rajasekhar , Holleran Stephen , Ginsberg Henry , Pollin Toni
Published: March 2022

The APOCIII R19X mutation (rs76353203), has been found in ~5% of the Lancaster Old Order Amish. It is a C ->T substitution at the 55th nucleotide in human aolipoprotein C-III mRNA that prevents translation of mature apoC-III protein. The mutation decreases apoC-III levels by ~50% and confers favorable lipid profiles and less coronary artery calcification, providing evidence that ApoC-III deficiency is cardioprotective. This conclusion is supported by recent data in Danish and U.S. cohorts showing a 40% reduction in myocardial infarction rates in people with this mutation. The mechanisms whereby apoc-III deficiency exerts its effects are not fully understood. The aim of this study was to describe the fractional clearance rates (FCR) and production rates (PR) of apoB containing lipoproteins, apoCIII, and very low density lipoprotein (VLDL) tryglyceride (TG) in five Amish sibling pairs (CT vs. CC) discordant for the APOC3 R19X mutation and matched for age and sex.

Methods:
Sib pairs completed a 24-hr stable isotope kinetic study using leucine and glycerol. Blood samples were collected over 24-hr period. We measured plasma lipids and apoCIII by Elisa. We determined the FCR and PR of VLDL apoB, apoCIII, and VLDL-TG.

Results:
The CT subjects had a 38% decrease in baseline TG levels compared to CC. ApoCIII levels were reduced by 42% in the CT vs. CC. We observed reductions in VLDL-Chol (49%), IDL-Chol (52%), VLDL-TG(44%), and IDL-TG(39%) in the CT when compared to CC. The changes in plasma levels were due to an increase in the VLDL apoB FCR (p = 0.001) without significant changes in production. VLDL-TG FCR increased by 76% in the CT when compared to CC (p=0.03). We observed no differences in post-heparin plasma levels of hepatic and lipoprotein lipase activity in the CT vs. CC. The plasma changes in apoCIII were due to and increased FCR in the CT compared to CC.

Conclusions:
Reductions in plasma TG levels in heterozygous apoC-III deficient individuals is due to enhanced FCRs of VLDL-apoB and VLDL-TG.
Abstract 21316: Mitochondrial DNA Copy Number and Ventricular Remodeling: Multi-Ethnic Study of Atherosclerosis
Authors: Ambale Venkatesh Bharath , Ostovaneh Mohammad , Heckbert Susan , Vargas Jose , Arnett Donna , Rich Stephen , Taylor Kent , Hundley Gregory , Post Wendy , Gomes Antoinette , Bluemke David , Wu Colin , Arking Dan , Guallar Eliseo , Lima Joao A
Published: March 2022

Introduction:
The effect of mitochondrial DNA copy number (mtDNA-CN), which reflects energy reserves and oxidative stress, on left ventricular (LV) remodeling in the general population may provide insights into heart failure development.

Hypothesis:
Lower mtDNA-CN values from blood samples will be associated with concentric remodeling.

Methods:
Longitudinal analyses of MESA participants with mtDNA-CN and MRI-measured LV mass to volume ratio (MVR) at baseline and the 10-year follow-up (n=2735) were performed. mtDNA-CN was estimated using 25 high-quality mitochondrial single nucleotide polymorphisms from the Affymetrix 6.0 array. Analyses were adjusted for age, sex, and field center, and standardized. LV mass and volumes were measured from cine images. Concentric remodeling was assessed by higher MVR. The association of mtDNA-CN with MVR, adjusted for the ASCVD/AHA risk score as a time-varying covariate, was assessed with mixed-effects models. Longitudinal change in MVR and LV ejection fraction (LVEF) was assessed with an interaction term of mtDNA-CN and time.

Results:
Population average age (SD) was 60 (9) years, with 48% males, 42% Caucasians, 12% Chinese, 22% African-American and 21% Hispanics. Mean MVR was 0.95 (0.18) g/ml at baseline and 1.05 (0.23) g/ml at follow-up. Lower mtDNA-CN was associated with higher MVR values (coef=-0.006, p=0.01, Fig 1), as well as greater longitudinal change in slope of this association (interaction term coef =-0.008, p=0.03) with small effect sizes (Cohens f2= -0.018 and -0.019 respectively). The longitudinal change reflected greater increase in concentric remodeling in those with low mtDNA-CN at baseline. mtDNA-CN values were not associated with LVEF.

Conclusions:
Lower mtDNA-CN was associated with both high levels at baseline and longitudinally increasing levels of concentric remodeling in a multiethnic population free of CVD at baseline. Altered myocardial energy reserves may contribute to concentric remodeling
Abstract 21323: Intralipid Fails to Rescue Bupivacaine-Induced Cardiac Arrest in Pregnant Rats
Authors: Sherman Caitlin , Cao Nancy , Moazeni Shayan , Vaillancourt Mylene , Marijic Buljubasic Anamaria , Marijic Buljubasic Andriana , Eghbali Mansoureh , Umar Soban
Published: March 2022

Background:
Pregnant patients routinely get neuraxial anesthesia. Bupivacaine is one of the most commonly used local anesthetics in obstetric anesthesia. Studies have suggested that pregnancy increases Bupivacaine cardiotoxicity. We and others have previously shown that Intralipid (ILP) rescues the heart from Bupivacaine cardiotoxicity in male rats. ILP mediates its cardioprotective effects via glycogen synthase kinase-3b (GSK-3b) phosphorylation. We aimed to investigate Bupivacaine cardiotoxicity and potential for ILP’s rescue in pregnant rats, that has not been studied before.

Methods:
Late pregnant rats (200-300 g, n=12) at day 20 of pregnancy were used for the study. A group of pregnant rats received Bupivacaine bolus (10 mg/kg, IV over ~20 seconds, n=7) to induce asystole under anesthesia. Resuscitation with ILP 20% (5 ml/kg bolus, and 0.5 ml/kg/min maintenance, n=7) and chest compressions were initiated. The ejection-fraction (EF%), and heart rate (HR) were calculated from echocardiography and EKG at baseline and at 1, 5, and 10 min after ILP treatment. A group of pregnant rats that did not undergo Bupivacaine-induced cardiac arrest and ILP rescue served as sham controls (n=5). Hearts were collected and Western blot was performed to assess GSK-3b phosphorylation.

Results:
All 7 late pregnant rats developed cardiac arrest a few seconds after Bupivacaine. Interestingly, 6 out of the 7 rats were not rescued with ILP using the same dose as in male rats. In these 6 rats, the average baseline EF and HR were 67.344.47% and 34130.44 bpm. One, five and ten minutes after ILP administration, the EF and HR were 0. Western blots showed that pregnant rats which were not rescued by ILP failed to have GSK-3b activation (pGSK/GSK=0.80±0.51 vs. 1.00±0.56 in late pregnant sham controls; p=0.578). In the late pregnant rat that recovered with ILP, baseline EF and HR (66.302.99% and 31034 bpm), were not different than the rats that did not recover.

Conclusions:
ILP failed to rescue Bupivacaine-induced cardiac arrest in pregnant rats. This failure of rescue is most likely attributed to the inability of ILP to activate GSK-3b, a known mediator of ILP’s cardioprotection.
Abstract 21329: Derivation and Validation of Simple Stroke Risk Score in a Thai Population
Authors: Chamnan Parinya , Konepan Panpaporn , Arayawichanont Arkhom , Boongird Prasert , Laptikultham Somsak , Nitiyanant Wannee , Aekplakorn Wichai ,   HCUR Study Investigators
Published: March 2022

Introduction:
Most stroke risk prediction equations were developed in Western populations. These risk scores perform less well in Asian populations, who have different background risk.

Hypothesis:
This study aimed to develop and validate a new stroke risk algorithm for estimating 5-year risk of developing stroke in a Thai general population using large electronic health records.

Methods:
This retrospective cohort was derived from the linkage of health checks data with diagnostic information from electronic health records of 483,285 men and women residing in Ubon Ratchathani. It was randomly and evenly divided into the derivation and validation cohorts. An outcome of interest was first recorded diagnosis of stroke over a period of 6 years between January 2006 and December 2012. A Cox proportional hazards model was used to estimate effects of risk factors on stroke risk and to derive a risk equation in the derivation cohort. Measures of discrimination, global model fits and calibration were calculated in the validation cohort.

Results:
The derivation cohort comprised of 241,643 individuals aged ≥30 years, who contributed 1,393,990 person-years of follow-up and 1,884 incident cases of stroke, while the validation cohort comprised of 241,642 individuals (1,393,420 person-years), with 1,915 incident cases of stroke. The risk equation was 0.0584 x Age (years) + 0.4538 x Sex (Male=1) + 0.0040 x Systolic BP (mmHg) + 0.2886 x Hypertension (present=1) + 0.5214 x Diabetes (present=1) + 0.0266 x Body mass index (kg/m
2
) - 0.0039 (if exercise 1-2 days/week) or -0.2827 (if exercise 3-5 days/week) or -0.3179 (if exercise >5 days/week). The stroke risk equation had a reasonably good discriminatory ability in the validation cohort, with the area under the receiver operating characteristic curve of 0.756 (95%CI 0.750-0.772). The risk equation had good global model fit as measured by Bayesian information criteria. The Gronnesby and Borgan test showed good calibration, with chi-square statistic of 701.43 (p<0.001).

Conclusions:
This simple stroke risk score is the first risk algorithm to estimate the 5-year risk of stroke in a Thai general population. The risk score does not need laboratory tests and can therefore be used in clinical settings and also by the public.
Abstract 21336: Comparison of the Serial Levels of the Sofa and Apache II Score for Predicting Neurologic Outcome of out of Hospital Cardiac Arrest Survivors With Targeted Temperature Management
Authors: KIM SANG-IL , Kim Won Young , kim Youn-Jung , Ryoo Seung Mok
Published: March 2022

Introduction:
Sequential organ failure assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APAHCE) II score are known as useful prediction tools for mortality in critically ill patients. This study aimed to compare the prognostic value of serial levels of SOFA and APAHCE II score for the neurologic outcome in comatose out-of-hospital cardiac arrest (OHCA) survivor treated with targeted temperature management (TTM).

Methods:
This single-center, registry-based, retrospective cohort study which included consecutive adult (≥18 years) comatose OHCA survivors with TTM was conducted in January 2010 and December 2015 at a tertiary care university-affiliated hospital emergency department. SOFA and APACHE II score were calculated at initial (D0), day 1(D1), day 2(D2), day 3(D3), day 5(D5), day 7(D7) after intensive care unit (ICU) admission. The primary outcome was 28-day good neurologic outcome and secondary outcome was 28-day survival. Prognostic value of SOFA and APACHE II score was analyzed using receiver operating characteristic curve.

Results:
A total of 143 patients, 62 patients (43.4%) had a survival and 34 patients (23.8%) had good neurologic outcome at day 28. SOFA and extracerebral SOFA scores did not show difference between good neurologic outcome two groups. Both SOFA and APACHE II score had significantly higher in non-survival group than survival group. However, for neurologic outcome, APACHE II score had a significant difference between good and poor neurologic outcome groups at D0, D1, D2, D3, D5, D7, but SOFA did not. APACHE II score at D3 had a highest prognostic values for predicting poor neurologic outcome (area under the cure of 0.793 [95% CI; 0.702-0.884]), its optimal cut-off point was 15.

Conclusions:
In the present study, illness severity during early post cardiac arrest period, as assessed by APACHE II score was associated with poor neurologic outcome; especially APACHE II score after ICU day 3 may help clinicians assess the neurologic outcome of post cardiac arrest patient.
Abstract 21338: Temporal Trends of In-Hospital Complications Associated With Catheter Ablation of Atrial Fibrillation in United States
Authors: Lahewala Sopan , Tripathi Byomesh , Arora ShilpKumar , Patel Neil , Kumar Varun , Patel Nirali , Patel Prashant , Nalluri Nikhil , Patel Smit , Syed Amer , Patel Nileshkumar , Deshmukh Abhishek
Published: March 2022

Introduction:
Catheter ablation is widely accepted intervention for atrial fibrillation (AF), but data is limited on contemporary trends in major complications and mortality due to the procedure.

Methods:
HCUP’s Nationwide inpatient sample (NIS) database was utilized from 2011-14 to identify the AF patients treated with Catheter Ablation using ICD-9- CM codes. χ 2 test was utilized to compare categorical variables, the student’s t-test for continuous variables and hierarchical mixed-effects logistic regression models for multivariate predictors of post-procedural complications.

Results:
In total 50,969 patients were identified undergoing AF ablation during the study period (37.6% female, 51.4 age ≥ 65). Overall complication rate was 5.5% with relative increase over study period (+56.4%, p < 0.001). In subgroup analysis of complication trends significant relative increase seen in respiratory (+352.7%, p < 0.001), neurological (+43.9%, p = 0.003) and vascular (+38.7%, p = 0.003) complications. While cardiac complications (+9.1%, p = 0.323) and In-hospital mortality (+ 60%, p = 0.173) showed insignificant change. On multivariate analysis of mortality and complication significant increased risk was associated with female gender (OR, 95% CI, p-value) (1.40, 1.17-1.68, p < 0.001), as well as higher comorbidity burden (CCI ≥ 1). While higher hospital volume (≥ 50 procedures) was associated with significantly decreased complication rates.

Conclusions:
Patients undergoing AF ablation showed an insignificant change in mortality, with increase trends of complication. Which was likely related to higher comorbidity burden over study period.
Abstract 21339: Deciphering Endocrine Factors Underlying Regulatory-Gene Network Signaling Between Metabolic and Vascular Tissues in Coronary Artery Disease
Authors: Koplev Simon , Björkegren Johan L
Published: March 2022

Introduction:
Endocrine proteins play central roles at all stages of coronary artery disease (CAD) development from endothelium activation, leukocyte migration to foam cell formation, smooth muscle cell migration and the formation of advanced atherosclerotic plaques. Although some endocrine factors already have been identified, the systemic landscape of endocrine signaling acting between fat, liver, skeletal muscle and the arterial wall in CAD remains largely unknown.

Hypothesis:
Systemic endocrine signaling underlying cross-tissue metabolic and arterial wall networks is essential for CAD development.

Methods:
We studied the underlying endocrine signaling between tissues by inferring 89 cross-tissue and 135 tissue-specific regulatory-gene networks (RGNs) from genotype and RNA-seq data in seven tissues including blood, arterial and metabolic tissues isolated from 672 CAD patients in the Stockholm Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) study. Within the cross-tissue RGNs, we detected 1,358 transcripts encoding secreted proteins and identified their cross-tissue target transcripts. Next, we validated these endocrine factors and their cross-tissue regulatory interactions using expression data from mice and experimentally in relevant cell models.

Results:
As judged from a super-network containing all RGNs, a majority of identified endocrine factors in cross-tissue RGNs were found between visceral abdominal fat and liver. However, one RGN active in visceral abdominal fat contained the endocrine factors: ALB, APOH, APOC3, APOA2, AHSG, AMBP, FGA, FGB, FGG, and GC, targeting an arterial wall RGN enriched for blood microparticle genes and for CAD risk genes identified by genome-wide association studies, and was associated with SYNTAX scores of the STARNET patients.

Conclusions:
Previously unknown endocrine factors acting in cross-tissue RGNs contribute to CAD and may be useful as targets for novel CAD therapies.
Abstract 21344: Mutations in
CACNA1C
and
KCNE2
Genes are Associated With Brugada Syndrome and Epilepsy
Authors: Hu Dan , Wu Yuesheng , Pfeiffer Ryan , Carrier Tabhita , Viskin Sami , Barajas Martinez Hector
Published: March 2022

Introduction:
Cardiac arrhythmias are generally associated with abnormal mutations in ion channel genes. Epilepsy is a disorder of neuronal function, which also involves abnormal channel function. Our

Hypothesis:
now increasing by demonstration that the etiologies of Brugada syndrome (BrS) and epilepsy may partly overlap. However, only a few genetic studies have addressed a possible link between cardiac and neural channelopathies.

Methods:
The suspected case and family were underwent thorough medical examination. Fifteen candidate genes were screened for ion channels by direct sequencing. Ion channel variants were cloned by site-directed mutagenesis and studied using patch clamp and confocal microscopy techniques in TSA201 cells.

Results:
A 36 y/o male with epilepsy showing typical type 1 Brugada pattern ECG during flecainide challenge test and under antiepileptic medication (valproic acid). Cardiac evaluation included a normal echocardiogram and exercise stress test. We identified two mutations (D2130N and A1717G) in
CACNA1C
and one in
KCNE2
(T10M). All mutations are highly conserved. The variants in
CACNA1C
were located in C terminal and the one in
KCNE2
was in N terminal. Functional studies in
CACNA1C
mutants were co-expressed with
CACNB2b
and
CACNA2D1
. At 0 mV, peak ICa densities were reduced by 85% and 70% in D2130N and A1717G
vs.
WT respectively. Significant kinetic alterations included a negative shift in V1/2 of inactivation, and positive shift in V1/2 of activation, for D2130N and A1717G, respectively. Confocal study showed D2130N and A1717G conjugated to YFP trafficked normally to the cell membrane. We found a gain-of-function in Ito current when T10M-
KCNE2
was co-expressed with
KCND3
channels by 55% relative to WT.

Conclusion:
Our results suggest for the first time that several mutations in
CACNA1C
leads to a loss of function in ICa and thus can contribute to the development of BrS phenotype. T10M-
KCNE2
produces a gain of function in Ito, which further aggravates BrS. Meanwhile, as previously reported, T10M-
KCNE2
also produces a loss-of-function of IKr, so it is reasonable to deduce that the mutation is probably responsible for the epilepsy. It once again provides the evidence that anti-epilepsy drug could unmask potential Brugada ECG.
Abstract 21348: The Difference of Antiplatelet Prescription Between Gender and the 1-Year Mortality in Patients With STEMI in Developing Country
Authors: Panthong Sowitchaya , Kittipibul Veraprapas , Suttirut Paramaporn , Lertsuwunseri Vorarit , Srimahachota Suphot , Ariyachaipanich Aekarach
Published: March 2022

Introduction:
There were inequalities in treatments prescribing to women resulted in poorer outcome in woman compare to men in many conditions include ST-elevation myocardial infarction (STEMI).

Hypothesis:
This study aims to described the difference of dual antiplatelet therapy (DAPT) prescription between gender and its effect on outcome.

Methods:
We conducted a retrospective study of consecutive patients presented with STEMI who underwent primary percutaneous coronary intervention at a tertiary care hospital in Thailand from January 2011 to December 2015. Patients’ baseline characteristics, usage of antiplatelet and mortality were collected. Chi-square and Log-rank were used to analyze.

Results:
Total of 755 patients (74.8% male) were included. Women were significantly older (68.1 ± 13.4 vs 57.6 ± 12.7, p <0.005), had lower hemoglobin at baseline (12 ± 1.9 vs 14.3 ± 2, p <0.005) and had more comorbidities include diabetes mellitus (46.6% vs 26.2%, p<0.005), hypertension (76.8% vs 49.2%, P<0.005) and chronic kidney disease (7.6% vs 3%, p=0.009). At the time of discharge, aspirin and clopidogrel were less commonly prescribed in women (86% vs 92.7%, p = 0.015 and 85.5% vs 91.1%, p=0.049, respectively) but the usage of DAPT was not statistically different between female and male (85.3% vs 90.9%, p=0.061) (Table). The 1-year survival is lower in women (79.5% vs 88.6%, p = 0.001). Patients who were discharged with DAPT had lower 1-year mortality than those without DAPT (2.6% vs 16.7%, p=0.003). Men, but not women, who were discharged with DAPT have the 1-year survival rate higher than those without DAPT.

Conclusions:
In conclusion, aspirin and clopidogrel but not DAPT were less commonly prescribed for women. The 1-year mortality was high in female which reflects the same disparity in outcomes that was found in western countries. There may be different effect of DAPT on males and female.