bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17153: Trends in Coronary Revascularization Among Cancer Patients in the United States, 2005-2014
Authors: Rubens Muni , Saxena Anshul , McGranaghan Peter , Ramamoorthy Venkataraghavan , Das Sankalp , Appunni Sandeep , Suarez Deborah , Puebla Brittany , Guida Alexandra , Veledar Emir
Published: July 2021

Introduction:
Although co-existing coronary artery disease (CAD) and cancers are increasing, trends of coronary revascularization in patients with cancer history is scarce. Hence, we examined trends, costs, hospital length of stay and in-hospital mortality among cancer patients who underwent percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) surgery in the United States.

Methods:
The current study was a retrospective analysis of the National Inpatient Sample, collected during the period 2005-2014. Coronary revascularizations were identified among patients ≥45 years by procedure codes 36.01-36.07, 36.09, or 00.66 for PCI, and 36.1x for CABG surgery. Cancer hospitalizations were identified if any of the CCS codes were 11-43.

Results:
A total of 8,428,811 weighted coronary revascularizations were done during the study period, and 636,819 (7.6%) were among cancer patients. Of this, 454,138 (71.3%) were PCI and 182,681 (28.7%) were CABG. About 35.0% were in the age group 65-74 years and 41.0% in the age group ≥70 years. Majority of patients had Medicare coverage (72.0%), followed by private insurance (22.15%). Among patients with history of cancer, coronary revascularizations increased significantly from 6.5% to 8.5% (relative increase, 30.8%;
P
trend
<0.001). PCI increased significantly from 4.7% to 6.0% (relative increase, 27.7%;
P
trend
<0.001) and CABG increased significantly from 1.8% to 2.5% (relative increase, 38.9%;
P
trend
=0.056) during the study period. The median (interquartile range [IQR]) length of stay decreased significantly from 2.8 (0.86-6.3) to 3.2 (1.6-6.4) days (relative decrease, 14.3%;

P
trend

=0.003) and overall in-hospital mortality rate increased significantly from 1.7% to 2.4% (relative decrease, 41.2%;
P
trend
=0.031). Median cost of hospitalizations increased significantly from $51,206 to $87,935 (relative increase, 71.7%;
P
trend
=0.047).

Conclusion:
Cancer patients had increasing number of coronary revascularization interventions and adverse hospital outcomes. Prevention and management of risk factors, early disease diagnosis, and advanced treatments should be implemented to improve CAD outcomes in this population.
Abstract 17227: Atrial Fibrillation in the Presence of Post-ST Segment Elevation Myocardial Infarction Left Ventricular Thrombus is Associated With Worse Outcomes
Authors: Leow Aloysius Shen-Ting , Sia Ching-Hui , Yeo Leonard Leong-Litt , Tan Benjamin Yong-Qiang , Kaur Rajinderdeep , Sim Hui-Wen , Yeo Tiong-Cheng , Chan Mark Yan-Yee , Tay Edgar Lik-Wui , Loh Joshua Ping-Yun
Published: July 2021

Introduction:
Left ventricular (LV) thrombus is a complication of ST-segment elevation myocardial infarction (STEMI) that leads to a higher risk of stroke. Atrial fibrillation (AF) is another independent risk factor for stroke, however there is a dearth of studies examining the outcomes of patients with concomitant AF and LV thrombus.

Hypothesis:
This study aims to investigate the impact of the presence of concomitant AF in post-STEMI patients with an LV thrombus on stroke and mortality outcomes.

Methods:
We screened 6007 transthoracic echocardiogram reports containing the “thrombus” keyword from July 2006 to September 2017. Relevant clinical data was collected from 196 post-STEMI patients positive for an LV thrombus, stratified into non-AF and AF groups.

Results:
AF patients (69.6 ± 11.8 years) were significantly older (p < 0.01) than non-AF patients (55.5 ± 12.2 years) and more were found to have chronic kidney disease (p = 0.02), hypertension (p = 0.04) and dyslipidaemia (p = 0.03), with significantly higher baseline HAS-BLED score (p < 0.01) and CHA2DS2-VASc score (p < 0.01). Fewer AF patients were treated with triple therapy (p = 0.04). Despite this, there was no difference observed in resolution of the LV thrombus on repeat imaging (p = 0.30). However, Kaplan-Meier analysis showed a higher incidence of stroke (p = 0.02) and all-cause mortality (p < 0.01) in AF patients.

Conclusion:
Post-STEMI patients with LV thrombus formation and AF have significant differences from non-AF patients and are associated with poorer outcomes. These findings should be validated in larger cohorts.
Abstract 17239: Grandparents as Agents of Change for Addressing Childhood Obesity: Preliminary Data From a Caregiver Weight Loss Intervention
Authors: Song MinKyoung , Lyons Karen S , Stoyles Sydnee , Hansen Lissi , Lee Christopher S
Published: July 2021

Introduction:
Much interventional research seeks to reduce childhood obesity by capitalizing on parents’ influence as caregivers. However, few studies have investigated whether grandparent-caregivers might have a similar influence on children’s weight-related health. This dearth of evidence is surprising since there has been a rapid increase in grandparent caregiving in the U.S.

Purpose:
Examine for a ripple effect on weight-related outcomes in children whose grandparent-caregivers have been enrolled in a weight loss program.

Methods:
We recruited 9 grandparent-grandchild (aged 6 to 12 years) dyads where both members had overweight or obesity. We collected data on weight/height, physical activity/sedentary time, and dietary behaviors at baseline and at 8 weeks. Physical activity and sedentary time data were collected using accelerometers over two, seven-day cycles (after baseline and 8-weeks’ visits). Dietary data were collected using the Block Food Screener. Spearman’s rank-order correlation was used to quantify associations in changes between the dyad members.

Results:
Mean age was 64.3 ± 5.2 years and 9.0 ± 1.7 years for grandparents and grandchildren, respectively; 88.9% of grandparents and 66.7% of grandchildren were female. At 8 weeks: (1) there was a positive association between changes in grandparents’ BMI and changes in their grandchildren’s BMI (r=0.40; p<0.01); (2) changes in grandparents’ levels of moderate-to-vigorous physical activity (MVPA)/sedentary time was positively associated with changes in grandchildren’s levels of MVPA/sedentary time (r=0.52, p<0.01; r=0.55, p<0.01, respectively).

Conclusions:
We demonstrated moderate associations between changes in children’s BMI/MVPA/sedentary time and changes in their grandparents’ BMI/MVPA/sedentary time. Our findings show that enrolling adult caregivers in weight loss programs could represent an effective delivery vehicle for improving childhood obesity. Additionally, our findings can help demonstrate to grandparent-caregivers that they can act as agents for improving health outcomes in their grandchildren by improving their own weight-related health, offering encouragement for grandparent-caregivers to enroll in weight-loss programs.
Abstract 17266: Right Atrial Volumes Changes in Tetralogy of Fallot
Authors: Patel Ashish , Shakti Divya , Blackshear Chad
Published: July 2021

Introduction & Hypothesis:
There is limited information on right atrial (RA) function in the congenital heart defects. RA volume and function may give insight into the right ventricle (RV) diastolic function. We sought to assess RA function in tetralogy of Fallot (TOF) patients prior to and after complete surgical repair.

Methods:
Infants with TOF prior to complete repair were included for retrospective chart review and offline analysis of 2-dimensional echocardiograms (echo) before and after surgical repair. RA phasic volumes and stroke volumes were calculated. All volumes were indexed to body surface area.

Results:
There were 40 infants with TOF (45% females), of which 70% had pulmonary stenosis, 30% pulmonary atresia. Roughly 85% and 60% had 3, or more, echo available pre- and postoperatively. Table 1 (attached) shows the patient characteristics and phasic RA volumes. The indexed RA phasic volumes were in normal range in initial echo prior to surgery. We used normal index RA phasic volumes published by European Society of Echocardiography. There was the increasing trend of indexed RA phasic volume on follow up echo immediately before TOF repair. These phasic volumes continued to remain elevated after complete surgical repair (Table 1). Trends in RA stroke volumes for all available echos before and after surgery were modeled using a population-averaged model with an exchangeable within-panel correlation structure (Figure 2), showing no statistically significant difference after surgery. But there was statistical significance noted in RA ejection fraction. Please see attached image for statistical analysis and results of the study.

Conclusions:
The indexed RA phasic volumes in children with TOF are normal initially and increases before TOF repair and it continued to increase after TOF repair. The increase RA phasic volumes suggest RV diastolic dysfunction similar to the findings of LA phasic volumes and left ventricular diastolic dysfunction. Our findings indicate slow worsening RV diastolic function in patients with TOF after surgical repair. RA volume and function can be the novel marker to diagnose and monitor right ventricular diastolic dysfunction.
Abstract 17268: ApoA-I Mimetic Peptide 4F Suppresses the Elevation of Pro-Inflammatory Lipid Mediators in Mouse Models of Inflammatory Bowel Disease
Authors: Meriwether David , Volpe Carmen , Grijalva Victor , O’Connor Ellen , Dorreh Nasrin , Fogelman Alan M , Reddy Srinivasa T
Published: July 2021

Introduction:
Inflammatory bowel disease (IBD) has been linked to an increased prevalence of early stage vascular disease. ApoA-I mimetic peptides including 4F are potential therapeutic agents for the treatment of inflammatory diseases including atherosclerosis, and their mechanism of action appears localized to the intestine. We have reported that 4F protects against the development of disease in both the piroxicam-accelerated IL10-/- and myeloid COX2-/- mouse models of IBD.

Hypothesis:
We previously reported that plasma and lesion levels of oxidized products of linoleic and arachidonic acid correlate with disease in mouse models of atherosclerosis, and that 4F protects against disease in these models while inhibiting accumulation of these pro-inflammatory mediators. We thus sought to determine the complete lipid pro-inflammatory mediator profiles of both the COX2- and IL10-dependent models of IBD, while also determining the effect of 4F on the pro-inflammatory lipid profiles.

Methods:
We developed and validated a LC-ESI-MS/MS method for determining the levels of 40 lipid inflammatory mediators in both intestinal tissue and plasma, and we analyzed the effects of both disease and 4F upon these mediators in both IBD models. We also employed Ussing chambers to investigate ex vivo the direct effect of 4F on the clearance of pro-inflammatory lipid mediators from intestinal explants and serosal-side lipoproteins.

Results:
Disease in both models correlated with significantly elevated tissue and plasma levels of multiple lipid pro-inflammatory mediators, while the protective effects of 4F correlated with the significant suppression of most of these mediators. Of interest, 4F inhibited the disease dependent increase of 15HETE, 12HETE, 5HETE, 13HODE, LTB4, 6ketoPGF1α, PGF2α, and TXB2 in the COX2-/- model; and 15HETE, 12HETE, 13HODE, LTB4, and LTE4 in the IL10-/- model. Ex vivo, we showed that 4F could directly clear the pro-inflammatory mediators from inflamed intestinal explants, while also mediating their trans-intestinal efflux from serosal-side lipoproteins.

Conclusions:
4F appears to protect against IBD in part by inhibiting the accumulation of pro-inflammatory lipid mediators, through a mechanism that involves the intestinal clearance of these mediators from tissue and plasma.
Abstract 17273: Long Non-Coding RNA Ppp1r1b Regulates Myogenic Differentiation Through Modulating Histone 3 Methylation
Authors: Kang Xuedong , Zhao Yan , Touma Marlin
Published: July 2021

Introduction:
Long noncoding RNAs (lncRNAs), emerged as critical epigenetic regulators of transcriptome, play important roles in cardiac development and might be targeted to treat human cardiomyocyte dysfunction. In our work, we identified a novel lncRNA that regulates myogenesis.

Hypothesis:
LncRNA Ppp1r1b regulates myogenesis by modulating Histone 3 methylation

Methods:
After treated with antisense oligonucleotides (GapmeR) or siRNA against Ppp1r1b-LncRNA, real time PCR and Western blot analyses were performed to examine the expression of myogenic and sarcomere genes. Chromatin immunoprecipitation (CHIP) was used to comparatively analyze gene specific histone modification level. RNA pull-down was employed to identify the protein molecules that interact with Ppp1r1b-LncRNA.

Results:
By silencing Ppp1r1b-LncRNA with GapmeR, C2C12, a skeletal myoblast cell line, did not develop fully differentiated myotubes, but tend to remain in a quiescent mono-nucleated status.
In vivo
analysis of GapmeR injected neonatal mouse heart and
in vitro
siRNA silenced human skeletal myoblasts further confirmed the important role of Ppp1r1b-LncRNA on myogenesis. Members of the MyoD family of muscle-specific transcription factors (MyoD and myogenin) failed to be up-regulated during myogenic differentiation when treated with Ppp1r1b-LncRNA specific GapmeR or siRNA. Key proteins essential for establishing and maintaining normal skeletal muscle architecture, including Tcap and Dystropnin, are also suppressed in Ppp1r1b LncRNA- deficient heart. Analysis of histone modification levels at Myogenin, MyoD1 and Tcap in C2C12 cells revealed more histone tri-methylation at these myogenic and sarcomere structural genes compared to untreated cells. Additional lncRNA- protein complex isolation has further revealed insight into the biological roles of Ppp1r1b-LncRNA.

Conclusions:
Our results support the role of Ppp1r1b-LncRNA in promoting myogenic differentiation. Ppp1r1b-lncRNA function is mediated by inhibiting histone methylation on promoters of multiple myogenic and sarcomere genes. In particular, the identification of EZH2 in pulled Pp1r1b LncRNA: protein complex implies that Polycomb repressive complex 2 (PRC2) is involved in Ppp1r1b-LncRNA modulated myoblast differentiation.
Abstract 17278: Concomitant Use of Ivabradine in the Setting of Cardiogenic Shock: A Case Series
Authors: Chiu Michael H , Howlett Jonathan G , Sharma Nakul C
Published: July 2021

Background:
Ivabradine, a selective sinus node inhibitor, is indicated for patients with chronic heart failure with reduced ejection fraction (HFrEF). Use in cardiogenic shock is currently contraindicated. However, studies have suggested increasing heart rate may be deleterious for patients with HFrEF due to an inverted Bowditch-Treppe response. Limited case series have suggested use of Ivabradine in decompensated HFrEF may be beneficial. We present a case series of patients who presented with severely decompensated HFrEF and received inotropic support and concomitant ivabradine.

Methods:
We selected four patients with HFrEF presenting with elevated sinus heart rate and cardiogenic shock (cardiac index <2.0L/min*m2with pulmonary artery wedge pressure > 20 mmHg by invasive hemodynamic monitoring) while on inotropic therapy and were intolerant of beta blockade due to hypotension. Ivabradine 2.5 mg 12 h was initiated and subsequently titrated with continued monitoring with baseline, 24 h and latest obtained parameters recorded. Other treatments occurred at the discretion of the attending physician.

Results:
Four male patients (mean age 44 years) with non-ischemic cardiomyopathy (mean EF 17%, mean NT-pro-BNP 5104 pg/ml) were included. Ivabradine was tolerated in all cases, with a mean dose of 6 mg q12h. Mean heart rate and pulmonary wedge pressure fell 20% and 32% respectively from baseline to last measurement, while stroke volume increased with an overall improvement in cardiac index. (Table 1) There were no changes noted in mean arterial blood pressure. All patients underwent successful wean of inotropic support within 48 hours and were discharged alive on beta blocker and ACE inhibitor therapy. No adverse events attributed to use of Ivabradine were observed.

Conclusion:
In our small series of patients with cardiogenic shock, beta blocker intolerance and elevated sinus heart rate, Ivabradine was added without any deleterious hemodynamic effect and associated with early clinical improvement. Further studies are needed to better assess its potential use in this population.
Abstract 17288: Low Pulsatility is Associated With Vasoplegic Syndrome in Heartmate II LVAD Explants During Heart Transplantation
Authors: Chinnadurai Thiru , Jahufar Fathima , Borukhov Edward , Rangasamy Sabarivinoth , Saeed Omar , Vukelic Sasha , Murthy Sandhya , Shin Julia , Sims Daniel , Forest Stephen , Goldstein Daniel , Jorde Ulrich P , Patel Snehal R
Published: July 2021

Introduction:
Continuous flow-left ventricular assist devices (CF-LVAD) have been implicated as a risk factor for vasoplegic syndrome (VS) after orthotopic heart transplantation (OHT). Although a lack of pulsatility has been postulated as the cause, there is currently no data to support this hypothesis.

Hypothesis:
We hypothesized that low pulsatility as measured by the Pulsatility Index of HeartMate II CF-LVADs at OHT admission was associated with VS during CF-LVAD explant and OHT.

Methods:
A retrospective chart review of all adult patients that had underwent heart transplants at our center were reviewed from 2014-2017. VS was defined as a profound vasodilatory shock (SVR < 800 dyne/s/cm
5
) despite persistent vasopressor support with a preserved cardiac index (≥ 2.2 L/min/m
2
) occurring at any time between 6 and 48 hours post OHT. Pulsatility Index of HeartMate II CF-LVADs were obtained at the day of OHT admission.

Results:
A total of 103 patients underwent OHT during the 4-year study period. The median age was 57 (48-64) years, 29 (28%) were females, 75 (73%) had CF-LVAD. Overall 23 (22%) patients developed VS. As expected, VS was more prevalent in CF-LVAD explants compared to primary heart transplant (27% vs 11%, p=0.09). Mean Pulsatility Index in CF-LVAD explants with VS (n =20/75) was lower compared to CF-LVAD explants absent VS (n=55/75) (5.9 ± 1.1 vs 6.5 ± 0.9, p=0.03) (Figure 1). Multivariate logistic regression analysis of all pre-operative variables found BMI (OR 1.23, 95% CI 1.03-1.50; p=0.01) and Pulsatility Index (OR 0.43, 95% CI 0.19-0.94; p=0.03) as the only independent risk factors associated with VS among CF-LVAD explants patients post OHT.

Conclusions:
In conclusion, lower pulsatility index is associated with vasoplegic syndrome in HeartMate II CF-LVAD post OHT. This association warrants further investigation in order to develop strategies to avoid this complication.
Abstract 17330: Predictors of Acute Myocardial Infarction During Pregnancy
Authors: Tripathi Byomesh , Kumar Varun , Sharma Purnima , Arora Shilpkumar , Malhotra Shikha , Lahewala sopan , Mishra Abhishek , Deshmukh Abhishek
Published: July 2021

Introduction:
Risk stratification of the pregnant population is critical to improving outcomes associated with pregnancy-related Acute myocardial infarction (AMI).

Methods:
Pregnancy-related hospitalizations (antepartum as well as postpartum) and AMI were identified using appropriate International classification of disease-Ninth revision (ICD-9) codes from nationwide inpatient sample database (2005-2014). Simple logistic regression was used to calculate predictors of AMI during pregnancy.

Results:
We identified 3,786 cases of AMI from a total of 43,437,621 pregnancy related hospitalization during study period. Compared to pregnant women <20-year, we noted more than 10-fold risk of AMI among patients ≥ 40 years (OR 10.1, 95% CI 5.3-19.0, p<0.001). Other significant predictors of AMI during pregnancy were black race compared to white ( OR 1.6, 95% CI 1.3-1.9, p<0.001), co-existing comorbidities such as hypertension (OR 1.9, 95% CI 1.5-2.5, p<0.001),, thrombophilia (OR 4.8, 95% CI 2.7-8.5, p<0.001), diabetes milletus (OR 1.4, 95% CI 1.0-1.9, p<0.027),hyperlipidemia (OR 13.2, 95% CI 9.9-17.6, p<0.001),smoking (OR 3.3, 95% CI 2.3-4.6, p<0.001), substance abuse (OR 1.7, 95% CI 1.2-2.6, p=0.007), congestive heart failure (OR 26.0, 95% CI 20.3-33.2 p<0.001), deep venous thrombosis (OR 2.8, 95% CI 1.3-6.2, p=0.010) as well as obstetric condition including postpartum hemorrhage (OR 1.8, 95% CI 1.3-2.4, p<0.001),, transfusion during pregnancy (OR 3.2, 95% CI 2.4-4.2, p<0.001), postpartum infection (OR 2,7, 95% CI 1.9-3.9, p<0.001),, fluid and electrolyte imbalance (OR 5.2, 95% CI 4.2- 6.6, p<0.001), and postpartum depression (OR 1.4, 95% CI 1.1-1.9 p=0.013).

Conclusions:
We identified certain patient-level characteristics which correlated to high risk of AMI. This information can be utilized to decide resource allocation and the introduction of early multidisciplinary intervention among high-risk population
Abstract 17333: Myeloid-Specific Deletion of Epsins 1 and 2 Reduces Atherosclerosis by Preventing LRP-1 Downregulation
Authors: Chen Hong , Brophy Megan
Published: July 2021

Introduction:
Atherosclerosis is in part caused by immune and inflammatory cell infiltration into the vascular wall, leading to enhanced inflammation and lipid accumulation in the aortic endothelium. Understanding the molecular mechanisms underlying this disease is critical for the development of new therapies. Our recent studies demonstrate that epsins, a family of ubiquitin-binding endocytic adaptors, are critical regulators of atherogenicity. Given the fundamental contribution lesion macrophages make to fuel atherosclerosis, whether and how myeloid specific epsins promote atherogenesis is an open and significant question.

Hypothesis:
We hypothesize that myeloid specific epsins regulate lesion macrophage function during atherosclerosis.

Methods and Results:
We engineered myeloid cell-specific epsins double knockout mice (LysM-DKO)on an ApoE
-/-
background. On Western diet, these mice exhibited marked decrease in atherosclerotic lesion formation, diminished immune and inflammatory cell content in aortas, and reduced necrotic core content but increased smooth muscle cell content in aortic root sections.Epsins deficiency hindered foam cell formation and suppressed the pro-inflammatory macrophage phenotype but increased efferocytosis and the anti-inflammatory macrophage phenotype in primary macrophages.Mechanistically, we show that epsins loss specifically increased total and surface levels of LRP-1, an efferocytosis receptor with anti-atherosclerotic properties. We further show thatepsin and LRP-1 interact via epsin’s Ubiquitin Interacting Motif (UIM) domain. Oxidized LDL treatment increased LRP-1 ubiquitination and subsequent binding to epsin while mutation of cytoplasmic lysine residues attenuated LRP-1 ubiquitination, suggesting that epsins promote the ubiquitin-dependent internalization and downregulation of LRP-1. Crossing ApoE
-/-
/LysM-DKO mice onto a LRP-1 heterozygous background restored, in part, atherosclerosis, suggesting that epsin-mediated LRP-1 downregulation in macrophages plays a pivotal role in propelling atherogenesis.

Conclusions:
Myeloid epsins promote atherogenesis by facilitating pro-inflammatory macrophage recruitment and inhibiting efferocytosis in part by downregulating LRP-1, implicating that targeting epsins in macrophages may serve as a novel therapeutic strategy to treat atherosclerosis.

Key words:
epsin, macrophage, atherosclerosis, LRP-1, inflammation, efferocytosis
Abstract 17344: Efficient Purification of Human iPSC-Derived Cardiomyocytes in a Large Scale Using a Synthetic microRNA Switch and Magnetic-Activated Cell Sorting
Authors: Hatani Takeshi , Chonabayashi Kazuhisa , Fujita Yoshihiko , Kimura Takeshi , Saito Hirohide , Yoshida Yoshinori
Published: July 2021

Background:
Although studies have demonstrated the feasibility of
in vivo
cardiac transplantation of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) using large animals, it requires large quantities of purified PSC-CMs. Moreover, genetic modification and contamination of non-CMs are inappropriate for clinical application. Using antibodies on the surface of the transplanted cells is one of the useful methods, but can be immunogenic and cause local inflammation or graft failure. We have shown the synthetic mRNAs encoding a fluorescent protein tagged with sequences targeted by microRNAs (miRNAs) expressed in specific cell types can efficiently detect and purify the particular cell populations. Using a miRNA switch and magnetic-activated cell sorting (MACS), we evaluated the efficiency of purification of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) in a large scale.

Methods:
We used CD4 as a selection marker for MACS and miR-208a as a specific mRNA of CMs. We synthesized CD4 mRNA and transfected it into differentiated cells from iPSCs to confirm CD4 expressing on the surface of the transfected cells. We also synthesized a miRNA switch encoding CD4 tagged with sequences targeted by miR-208a (CD4-208a switch) and transfected it into differentiated cells to demonstrate transfected non-CMs expressing CD4 and transfected CMs non-expressing CD4. Finally, we transfected the CD4-208a switch and puromycin resistance mRNA simultaneously, and purified iPSC-CMs by eliminating CD4+ cells using MACS and untransfected cells using puromycin. Purified cells were transplanted into NOG mouse hearts with myocardial infarction by direct injections into the myocardium.

Results:
After transfecting CD4 mRNA into differentiated cells from iPSCs, 78±5% expressed CD4 on the surface. We also confirmed that the CD4-208a switch separated CMs and non-CMs. Using MACS and puromycin selection, we purified iPS-CMs 69±5% to 97±2% assessed by troponin T. Purified cells were also engrafted as CMs in mouse hearts.

Conclusions:
We demonstrated that CD4-208a switch purifies iPSC-CMs efficiently in a large scale. Synthetic microRNA switches can apply for many studies of stem cell-based cell replacement therapy for clinical application.
Abstract 17360: Vulnerability of Body Surface Rotor Mapping Using the Cardioinsight Cardiac Mapping System
Authors: Tomaiko Emrie D , Orme Geoffrey , Su Wilber , Su Stephen
Published: July 2021

Introduction:
CardioInsightTM (CIT) high density body surface electrode mapping of atria has been used to identify rotor activities in the atria to guide atrial fibrillation ablation. However, intraprocedural reliability and reproducibility of CIT rotor has not been well-validated.

Methods:
Eight patients with persistent and long-standing persistent atrial fibrillation were studied prior to ablation with CIT mapping to identify rotors projected onto cardiac CT scan per protocol. Pre-identified CIT rotor activities were used as the baseline for comparison to post ablation CIT rotor map. Ablation of the identified rotors were performed and confirmed by voltage map using the EnSite Velocity System pre and post procedure. Repeated CIT mappings were obtained after each large area modification containing the identified high yield rotor activities area. CIT identified rotors post ablation were compared to pre-ablation.

Results:
12 significant rotors were identified by CIT in eight patients. Successful ablation of all of the rotor area with large area ablation was performed with confirmation of no significant residual voltage (<0.1 mV). Intraprocedural post-ablation CIT re-map identified 7/12 rotors in areas of no significant voltage.

Conclusions:
CIT projection of rotor activity was seen in significant number of confirmed electrically silent areas. The CIT’s ability to correctly project rotor activity on the atrial surfaces was poor. More validation of CIT true projection is needed to guide the ablation of atrial fibrillation.
Abstract 17368: The Novel P2X7 Receptor Antagonist SMW139 Inhibits Inflammasome Activation in STEMI Monocytes
Authors: Hansen Thomas , Bubb Kristen , Kassiou Michael , Figtree Gemma
Published: July 2021

Introduction:
The inflammasome and the downstream pro-inflammatory cytokine interleukin-1ß (IL-1ß) have emerged as critical modulators of atherosclerosis and acute coronary syndromes (ACS). It therefore represents an important therapeutic target to treat coronary artery disease. This study investigates the activation of the inflammasome in circulating monocytes of ACS patients, and the effectiveness of SMW139- a compound selected from a panel of over 70 novel P2X7 antagonists based upon its excellent pharmacokinetic properties- on modulating the downstream inflammatory signalling pathway.

Hypothesis:
The P2X7 antagonist SMW139 reduces inflammasome activation.

Methods:
In vitro:
THP-1 monocytic cells were treated with interferon-
γ
and lipopolysaccharide for 3 hours, then pre-incubated with SMW139 (1-1000nM), prior to ATP stimulation to activate the inflammasome, and collection of supernatant for IL-1ß measurement.
Ex vivo:
Peripheral blood mononuclear cells (PBMCs) were collected from 19 STEMI patients at time of infarct, and 3 healthy controls. Monocytes were pre-incubated with SMW139 or DMSO control prior to ATP stimulation. IL-1ß and caspase-1 activity were measured by ELISA and fluorometric assay.

Results:
In vitro:
Sigmoidal dose-response curve demonstrated a LogEC50 of -8.069±0.16.
Ex vivo:
High levels of detectable P2X7 expression in PBMCs was confirmed by flow cytometry. Baseline levels of secreted IL-1ß were significantly elevated in PBMCs from STEMI patients compared with healthy controls (STEMI: 8.2±0.6, Control: 4.2±0.1;p=0.02). There was a significant increase in IL-1ß secretion post ATP-induced inflammasome activation in STEMI PBMCs (53.8±9.4;p<0.0001) but not control (9.8±0.9). P2X7 inhibition significantly attenuated this ATP-induced IL-1ß secretion in STEMI cells (13.9±2.4;p<0.0001) but had no effect in controls (7.5±2.8). Similarly, P2X7 inhibition resulted in approximately 60% reduction of ATP-induced caspase-1 activity in STEMI cells (p=0.01).

Conclusions:
The P2X7 antagonist compound SMW139 effectively inhibits the inflammasome, causing a significant reduction in caspase-1 activity and IL-1ß cytokine levels, and holds promise as a novel therapy for patients with atherosclerosis and ACS.
Abstract 17377: The Effect of Mechanical Circulatory Support on HLA Antibodies and Antibody-Mediated Rejection in Cardiac Allografts
Authors: Wassilew Katharina , Potapov Evgenij
Published: July 2021

Introduction:
Due to the shortage of donor organs, mechanical circulatory support systems (MCS) are now widely used as a treatment option to bridge the failing heart to transplant. It has been observed that MCS patients show a higher frequency of antibody-mediated rejection (AMR) episodes. The latter is thought to represent an immune reaction directed against the device in terms of allosensitation.

Hypothesis:
Capillary C4d and/or C3d depositions are required to diagnose AMR in cardiac allografts. We aimed to analyze the effect of MCS on pre- and post-HTx HLA antibodies and their correlation to cardiac AMR with due regards to capillary C3d and C4d depositions.

Methods:
We evaluated all consecutive right ventricular protocol endomyocardial biopsies (EMBs) of cardiac allografts which fulfilled the ISHLT- criteria (254 patients) during two consecutive calendar years. With regards to pre- transplant MCS treatment patients were divided into two groups (MCS group n=82 patients, non MCS group n= 138 patients). Conventional histology and immunohistochemical stains were used on formalin-fixed paraffin-embedded tissue sections (FFPE) to evaluate the EMBs regarding AMR (complements C3d and C4d). Permutation test (x
2
) was performed to analyze the relationship between C4d and C3d and pre-and post-transplant HLA-antibodies, measured using Luminex assay, in all patient subgroups. Cochran-Mantel-Haenzsel was performed to assure the significance of the difference of interactions in both tables.

Results:
The statistical analysis showed in the MCS group a highly significant positive correlation between C3d and Pre-Tx-HLA (p=0.012, Pre-Tx-HLA Class I and II p= 0.042, respectively vs p=0.884 and p=0.349 in non-MCS group), which levelled out following HTx (p= 0.867 and 0.697 for HLA Class I and II, vs p=0.212 and p=0.682 in non-MCS group, respectively). Statistical significance was not reached between C4d and pre-or post Tx HLA-antibodies in any group (p=0.349 vs. p=0.694 for entire study population).

Conclusions:
We demonstrated that C3d correlates solely in the MCS group with pre-Tx HLA antibodies and could therefore add to the diagnosis of AMR if the pre-transplant treatment is being considered in the diagnostic setting.
Abstract 17382: Jumonji-C Histone Demethylases Are Cellular Iron Sensors That Control mTORC1 and Mitophagy
Authors: Shapiro Jason S , Chang Hsiang-Chun , Ardehali Hossein
Published: July 2021

Iron is an essential nutrient and is critical for cellular growth and metabolism. Here, we delineate a novel mechanism by which iron alters amino acid homeostasis and mTOR activity by remodeling the cellular epigenetic landscape. We find that iron deficiency inactivates Jumonji-C domain containing histone-demethylases, resulting in histone hyper-methylation and silencing of the leucine transporter LAT3 and obligatory mTORC1 cofactor RAPTOR. Additionally, we identify that mTOR-mediated regulation of RNA stability through tristetraprolin (TTP) is a novel and requisite step in selective-autophagy. In the absence of TTP, mitochondria damaged by the loss of iron cannot undergo fission, rendering the mitochondria too large for engulfment and subsequent recycling. Accumulation of damaged mitochondria leads to defective oxidative metabolism and impairs hepatic gluconeogenesis in response to fasting. These studies uncover a novel pathway that integrates iron sensing with cellular metabolism, mitochondrial dynamics and autophagy.
Abstract 17414: Increased Activity of Brain Region Governing Stress Perception is Associated With Plaque Vulnerability and Vascular Inflammation in Acute Myocardial Infarction Population; Retrospective and Prospective Study Evaluated by
18
FDG-PET/CT and OCT
Authors: Park Eun Jin , Eo Jae Seon , Jang Won-Young , Kang Dong Oh , Choi Cheol Ung , Kim Eung Ju , Rha Seung-Woon , Park Chang Gyu , Seo Hong Seog , Kim Jin Won
Published: July 2021

Backgrounds:
Chronic mental stress is a major risk factor of coronary artery disease, but there is a lack of direct mechanistic evidence between brain amygdala activity, a neural stress center, versus plaque vulnerability in acute coronary syndrome. In this study, we aimed to evaluate whether brain amygdala activity in AMI patients assessed by
18
F-FDG PET/CT could be associated with vascular inflammation in carotid beds and high-risk coronary plaque features evaluated by OCT.

Methods and Results:
In retrospective analysis, the patients who underwent
18
F-FDG PET/CT and CAG at Korea University Guro Hospital (Seoul, Korea). Among 1802 patients underwent
18
F-FDG PET/CT from October 1 2009 to 31 December 31 2015, 230 patients received CAG. After excluding 36 patients who had active cancer or brain disease, 198 were stratified according to degree of coronary severity by syntax score [none (n=159); mild to moderate (n=26); severe (n=13)]. Brain amygdalar activity on PET was quantified as target-to-background ratio (TBR) of standardized uptake value (amygdalar SUV
max
/temporal SUV
mean
). The amygdalar TBR was significantly higher in patients with severe coronary disease rather than those without coronary stenosis or mild to moderate stenosis assessed by syntax score (P=0.03). Intriguingly, among 13 patients with severe CAD, the amygdalar TBR significantly increased in the 6 patients presented as AMI compared to non-MI patients (P=0.03). In following prospective study, we performed
18
F-FDG PET/CT in AMI patients underwent percutaneous coronary intervention within index admission period, and in patients with chronic stable angina (CSA) as control. The plaque morphology in non-culprit segment of infarct-related artery (IRA) was estimated by OCT in AMI patients. Brain amygdalar TBR was significantly higher in AMI patients compared to CSA patients (p<0.05). In AMI patients, amygdalar activity was significantly associated with vascular inflammation quantified as carotid TBR (p<0.05). The increased amygdalar activity was associated with high-risk plaque characteristics of non-culprit segments of IRA.

Conclusions:
The amygdalar activity assessed by
18
F-FDG PET/CT was significantly higher in patients with AMI than CSA. This amygdalar activity was related to vulnerable plaque characteristics of IRA. Our results suggest that brain emotional activity in ACS could contribute to plaque instability in pan-vascular beds.
Abstract 04: The Most Accurate Massive Transfusion Prediction Score at the Scene of Injury: The Pre-Hospital Traumatic Bleeding Severity Score
Authors: Ogura Takayuki , Liu Keibun , Machida Hiroshi , Fujizuka Kenji , Nakamura Mitsunobu , Nakano Minoru
Published: July 2021

Background:
Determination of the need for massive transfusion (MT) at the scene of injury is ideal for early activation of a MT protocol. We created and reported The Pre-hospital Traumatic Bleeding Severity Score (ph-TBSS) that is a simple and highly accurate scoring system to predict the need for MT at the scene of injury. However, the comparison study about the predictive value between the ph-TBSS and other MT predictors is not performed. Patients and

Methods:
A diagnostic comparison study using the registry data of the Gunma Prefectural Helicopter Emergency Medical Service (HEMS) was conducted. Records between Sep. 2012 and Apr. 2017 were reviewed, and adult trauma patients transported by the HEMS were included. A physician in the HEMS is always on board, primary survey including abdominal sonography scanning is performed at the scene of injury, and lactate was measured by portable equipment. The potential predictors of MT (10 units or more of packed red blood cells transfusion within 24 hours of injury) at the scene of injury were defined as following; The ph-TBSS, Assessment of Blood Consumption (ABS) score, the shock index, lactate concentration, and the presence of cold sweat. Each predictor was retrospectively calculated or reviewed from the registry data. Each predictive value was analyzed by the area under the receiver operating characteristic curve (AUROC) and the AUROC comparison analysis was performed.

Results:
1025 patients were analyzed. Each AUROC for MT was following; ph-TBSS vs ABC score vs shock index vs lactate concentration vs presence of cold sweat = 0.97 [0.96-0.98] vs 0.83 [0.81-0.85] vs 0.89 [0.87-0.91] vs 0.91 [0.90-0.93] vs 0.70 [0.67-0.72]. The AUROC of the ph-TBSS was significantly higher compared to the AUROC of the other predictors (Bonferroni adjusted p<0.01).

Conclusion:
At the scene of injury, the ph-TBSS represented the highest predictive value for MT, compared to the ABC score, shock index, lactate concentration, or presence of cold sweat.
Abstract 111: Impact of Time to Return of Spontaneous Circulation on Neurologically Intact Survival in Patients With Out-of-Hospital Cardiac Arrest According to Age: Evidence From a Large-Scale Registry in Japan
Authors: Funada Akira , Goto Yoshikazu , Tada Hayato , Shimojima Masaya , Okada Hirofumi , Kawashiri Masa-aki
Published: July 2021

Introduction:
Time to return of spontaneous circulation (ROSC) is a more important predictor of neurologically intact survival than the presence of ROSC in patients with out-of-hospital cardiac arrest (OHCA). However, the differences in the relationship between time to ROSC and neurologically intact survival in patients with OHCA based on age is unclear.

Hypothesis:
We hypothesized that the impact of time to ROSC on neurologically intact survival differs according to age.

Methods:
We analyzed the data of 34,905 patients with OHCA (age ≥18 years) who exhibited prehospital ROSC from the prospectively recorded all-Japan OHCA registry (2011-2014). The primary outcome was neurologically intact survival at 1 month after OHCA (cerebral performance category [CPC] 1 or 2). Time to ROSC was defined as the interval from the initiation of cardiopulmonary resuscitation (CPR) by emergency medical service (EMS) providers to the achievement of ROSC. We categorized time to ROSC by every 4-min interval (2 cycles of CPR) from 1 to 32 min and ≥33 min, and age into 4 groups: 18-64, 65-74, 75-89, and ≥90 years.

Results:
The overall CPC 1-2 rate was 21.1% (7,353/34,905). Increasing time to ROSC (per min) was negatively associated with CPC 1-2 (adjusted odds ratio, 0.91; 95% confidence interval, 0.90-0.91). The CPC 1-2 rates decreased as time to ROSC increased in each age group: from 58.8% (1,247/2,122) in 1-4 min to 2.8% (7/246) in ≥33 min for patients aged 18-64 years, from 51.1% (721/1,410) in 1-4 min to 1.6% (4/244) in ≥33 min for 65-74 years, from 37.3% (765/2,051) in 1-4 min to 0.7% (4/539) in 29-32 min for 75-89 years, and from 23.4% (92/393) in 1-4 min to 0.2% (1/481) in 17-20 min for ≥90 years (all p for trend <0.001).

Conclusions:
The CPC 1-2 rates of patients aged 18-64 and 65-74 years were above the 1% futility rate when prehospital ROSC was achieved after prolonged CPR, ≥33 min from initiation by EMS providers. However, the CPC 1-2 rates were below the 1% futility rate when prehospital ROSC was achieved ≥29 min and ≥17 min for patients aged 75-89 years and ≥90 years, respectively.
Abstract 112: Internal Consistency Between Cognitive Tests for Survivors of Cardiac Arrest
Authors: Flickinger Katharyn L , Repine Melissa J , Koller Allison C , Faro John , Skidmore Elizabeth , Callaway Clifton W , Rittenberger Jon C
Published: July 2021

Introduction:
Cardiac arrest survivors suffer cognitive impairment easily missed on a clinical examination. We evaluated a battery of cognitive tests including the Cerebral Performance Category Extended (CPC-E), Montreal Cognitive Assessment (MoCA), and the Computer Assessment of Cognitive Impairment (CAMCI) to evaluate these deficits.

Hypothesis:
The CPC-E, MoCA and CAMCI tests correlate with one another, but the internal consistency of each test differs.

Methods:
Chart review of 201 cardiac arrest survivors occurred between October 2010 and January 2018. Pearson’s correlation was used to assess between-test correlation while Cronbach’s alpha was used to assess internal consistency of each test. We evaluated both the overall measure score and individual items in the measure.

Results:
Complete assessments were available for 50 subjects, 75 completed both the MoCA and the CAMCI, 57 completed both the CPC-E and the CAMCI, and 76 completed the MoCA and the CPC-E. Internal consistencies existed within both the MoCA and the CPC-E (Cronbach alpha = 0.661, and 0.738, respectively), while only borderline internal consistency was found within the CAMCI (Cronbach alpha = 0.638). At the scale level moderate or limited correlation existed between tests (Figure). At the item level, the CAMCI had little to no correlation with items of the CPC-E or MoCA. Moderate correlations existed between item specific domains of visuospatial, attention and delayed recall items of the MoCA and domains of alert, logical thinking, attention, and short term memory of the CPC-E (r=0.3-0.5).

Conclusions:
Strong correlation between the CAMCI and MoCA suggests they evaluate similar domains of function. The MoCA is shorter, easily administered and inexpensive, arguing for its use over the CAMCI. The CPC-E’s strong internal consistency and moderate correlation with the MoCA suggests it may provide additional discrimination of cognitive function in the cardiac arrest population.
Abstract 113: Signs of Perfusion During Cardiopulmonary Resuscitation as Noted by First Responders is Predictive of Good Neurologic Outcome in Cardiac Arrest
Authors: Moore Johanna C , Grahl Michael , Marko Tracy , Blythe-Reske Ariel , Lage Amber , Hedge Erin , Bancroft-Howard Andrew , Klein Lauren , Scharber Sarah , Garthe Clayton , Ho Jeffrey
Published: July 2021

Background:
Rates of neurologically intact survival after cardiac arrest remain abysmal. Neuro-prognostication intra-arrest is challenging, with few real-time factors that can be used to determine patient prognosis. During the implementation of a new cardiopulmonary resuscitation (CPR) protocol in a large urban pre-hospital system, first responders prospectively recorded the presence of signs of perfusion during CPR.

Hypothesis:
Positive signs of perfusion would be a predictor of a good neurologic outcome in this observational study, as defined by Cerebral Performance Category (CPC) Score of 1 or 2.

Methods:
Basic life support first responders (n = 420) and paramedics (n = 207) underwent training including didactic and hands-on sessions to learn the new protocol, which included active compression-decompression CPR with an impedance threshold device. In addition to patient demographics and circumstances of cardiac arrest, signs of perfusion during CPR were prospectively recorded and included improved color, pulse during CPR, gasping, and movement during CPR. Chart review was performed to determine CPC score at discharge. Data were analyzed using descriptive statistics and calculation of unadjusted odds ratios.

Results:
The new protocol began May 1, 2017. Cases from May 2017-November 2017 (n= 102) were reviewed, with complete data available for 96 patients (94%). The median age was 56 (range 25-97), 54/91 (59%) male, 43/102 (42%) witnessed, 31/90 (34%) shockable rhythm, and 51/102 (50%) receiving bystander CPR. Improved color during CPR was seen in 23/102 (23%), pulse during CPR in 17/102 (17%), gasping in 18/102 (18%), and movement during CPR in 5/102 (5%). Any sign of perfusion during CPR was seen in 47/102 (46%), and 13/96 (13.5%) had a CPC score of 1 or 2 at discharge. The unadjusted OR for any sign of perfusion during CPR for a CPC score of 1 or 2 was 26 (95% CI 3 - 213) and for any sign of perfusion during CPR for ROSC was 9 (95% CI 3 - 24).

Conclusions:
Positive signs of perfusion during CPR noted by first responders strongly predicted ROSC and neurologically intact survival in this small sample. This suggests the importance of prospectively recording signs of perfusion during resuscitation, and communicating these observations during transfer of care.