bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19796: Vascular eNOS S-Glutathionylation is Increased in Hypertension and Atherosclerosis with eNOS uncoupling: Data from Animal Models and Human Aortic Tissue of Patients Undergoing Surgical Revascularization
Authors: Varadharaj Saradhadevi , Reyes Levy , Crestenello Juan , Kilic Ahmed , Talukder Hassan , Chen Chun-An , Zweier Jay L
Published: April 2024

Background:
In vascular diseases, including hypertension (HTN) and atherosclerosis, endothelial dysfunction (ED) occurs secondary to altered function of endothelial NO synthase (eNOS); however, questions remain regarding the mechanism by which this occurs and how it can be reversed. We recently identified a novel redox regulated pathway through which eNOS is uncoupled due to S-glutathionylation. In vessels from spontaneous hypertensive rats (SHR) and in aortic tissue from patients undergoing coronary bypass (CABG) surgery, we measure eNOS S-glutathionylation and its effect on eNOS coupling.

Methods:
Studies were performed in aortic, femoral and carotid vessels from adult SHR rats and in aortic tissue from patients undergoing CABG or other vascular surgery. S-glutathionylation of eNOS was studied using anti-glutathione antibody, anti-eNOS antibody and an antibody specific for eNOS C689 S-glutathionylation. NO and superoxide (•O2--) was measured using fluorescent probes CuFL and DHE, respectively, in the absence or presence of the NOS inhibitor, L-NAME, NO scavenger, PTIO, or the SOD mimetic, MnTBAP.

Results & Conclusion:
Immunohistology and immunoblotting revealed increased eNOS S-glutathionylation in vessels of SHR rats compared to matched WKY controls. The reducing agent DTT reversed this glutathionylation and reversed the impairment in endothelial-dependent relaxation measured from aortic rings. Mass spectroscopy on immunoprecipitated eNOS demonstrated modification at C689 in aorta of SHR but not WKY rats. Immunohistology with a specific eNOS C689 S-glutathionylation antibody confirmed endothelial C689 S-glutathionylation. Decreased NO and increased •O2-- was seen in these vessels. In patients undergoing CABG, high levels of C689 S-glutathionylation was seen abolished by DTT. Thus, eNOS S-glutathionylation is increased in an animal model of HTN with resultant ED and present in patients with coronary disease undergoing bypass surgery.
Abstract 203: Potential Dependence on Type of Bystander Basic Life Support Response and Outcomes in Out-of-Hospital Cardiac Arrests Managed Without Any Involvement of Physicians
Authors: Inaba Hideo , Kamikura Takahisa , Nishi Taiki , Takase Keiko , Sakagami Manabu , Hamada Hidetsuyo , Maeda Tetsuo
Published: April 2024

Objectives:
The present study was conducted to test our hypothesis that relation of bystander to cardiac arrest victim may affect the BLAs response and outcomes in bystander-witnessed OHCAs.

Methods:
We obtained the Japanese nation-wide database for 547,218 OHCAs that occurred from Jan. 2005 to Dec. 2009, and extracted a dataset for 139,265 bystander-witnessed OHCAs without any involvement of physicians, that has all information for analysis. We first compared the BLS response of the four bystander groups (family members, friends and colleagues, passers-by and others). Then, we compared the outcomes of bystander-witnessed OHCAs having bystander CPR among the four groups.

Results:
The intervals between collapse and emergency call and between call and arrival at patient were shortest in OHCAs witnessed by pass-by. The telephone-CPR was most frequently attempted (45.8%, 41,442/90,426) but failed (39.4%, 16,315/41,442) in OHCAs witnessed by family. Consequently, the rate of bystander CPR was lowest (36.5%, 33,008/90,426), CPR was most frequently initiated following the telephone-CPR (76.1%, 25,127/33,008), and type of CPR was most frequently “chest-compression-only” (67.9%, 22,406/33,008) in OHCAs witnessed by family members. Multiple logistic regression analysis revealed that family as a type of bystander was an independent factor associated with lack of bystander CPR (Odds ratio=1.54 against passers-by, 2.09 against friends and colleagues, and 5.15 against others) . In all subcategories, the incidences of shockable initial rhythms and outcomes were lowest in the OHCAs witnessed by family members. Multiple logistic regression disclosed that that family member as a bystander group is one of the independent factor associated with 1-M unfavorable neurological outcomes in all subcategories of bystander-witnessed OHCAs.

Conclusions:
Family members do not quickly respond to OHCAs and unwilling to perform CPR on their own initiative. OHCAs witnessed by family and having bystander CPR have low incidences of shockable initial rhythm and 1-M favourable neurolofical survival. The first responder system that enable a good BLS performer to quickly reach the scene may be necessary in OHCAs witnessed by family.
Abstract 226: Neuromuscular Blockade in Post--Cardiac Arrest: Practice Patterns and Association with Outcome Measures
Authors: Salciccioli Justin D , Cocchi Michael N , Rittenberger Jon C , Peberdy Mary Ann , Abella Benjamin S , Gaieski David F , Ornato Joseph P , Callaway Clifton , Clore John N , Gautam Shiva , Donnino Michael W
Published: April 2024

Introduction: Neuromuscular blockade (NMB) may improve outcomes in acute respiratory distress syndrome. In post-cardiac arrest (CA) patients receiving therapeutic hypothermia (TH) NMB is sometimes used to prevent shivering. Whether NMB improves outcomes from CA is unknown.

Objective: To assess the association between NMB and outcomes from CA.

Methods: A
post-hoc
analysis of a prospective multicenter observational study of adult CA from 6/2011 to 3/2012. Inclusion criteria were: adult (> 18 years), out-of-hospital CA, return of spontaneous circulation (ROSC), comatose following ROSC. Traumatic CA were excluded. Patient characteristics, vital signs, laboratory data and discharge data were recorded. The exposure of interest was NMB within 24hrs of ROSC. The primary outcome was in-hospital survival. Secondary outcomes were neurological status (Modified Rankin [MR]), oxygenation (PaO
2
:FiO
2
), and lactate clearance. We used simple descriptive statistics to describe the study population, Chi-square for unadjusted tests, and multivariable (age, downtime, rhythm, SOFA score) logistic regression or linear mixed-models for the relationship between NMB and outcomes.

Results: 111 patients were analyzed. The median age was 63 years (IQR: 50 - 75) and 41% were female. TH was completed in 97% and overall survival was 47%. 60% received any NMB within 12hrs of ROSC and 69% received any NMB within 24hrs of ROSC. With 12hrs of sustained NMB, the crude survival rate was 15/21 (71%) compared to 37/90 (41%) without 12hrs of NMB (p = 0.01). With 24hrs of sustained NMB, the crude survival rate was 14/18 (78%) compared to 38/93 (41%) in patients without sustained NMB (p = 0.004). There was a trend toward improved neurologic outcome with NMB: MR 0 - 2: 44% vs. 23% (p = 0.05). After multivariable adjustment, NMB was not associated with survival (adjusted OR: 3.35, 95% CI: 0.83 - 13.57, p = 0.09; H-L goodness-of-fit: p = 0.95). Sustained NMB improved lactate clearance over 24hrs (adjusted p = 0.03). There was no effect of NMB on PaO
2
:FiO
2
(p = 0.5).

Conclusion: In post-CA early NMB is common. Early, sustained NMB is associated with improved lactate clearance and a trend in improved survival, but no effect was observed on PaO
2
:FiO
2
ratio.
Abstract 240: Teaching Basic Life Support: Controlled Study with a 2-Stage Versus the Standard 4-Stage Approach
Authors: Sopka Sasa , Biermann Henning , Ott Matthieu , Skorning Max , Rossaint Rolf , Beckers Stefan K
Published: April 2024

Introduction

Quality of external chest compressions (ECC) is of paramount relevance within Basic Life Support (BLS). Recent guidelines describe the so called 4-Stage-Approach for teaching practical skills within resuscitation training. However, this methodology was questioned in recent studies when used for simple skills teaching.

Hypothesis

To observe whether a structured 2-Stage-Approach leads to sufficient practical performance in BLS-Training compared to the standard 4-Stage-Approach.

Methods

Overall 270 Laypersons were trained in BLS after randomization either to the standard method group using a 4-Stage-Approach (4S) or a modified 2-Stage-Approach-group (2S) lasting the same course duration. All participants were tested on a manikin (Skillreporter ResusciAnne® with PC SkillReporting Software (Version 1.3.0), Laerdal, Stavanger, Norway) in the same cardiac arrest mock scenario prior to the BLS-course and after one week with each time 2 min of continuous ECC each. Practical Endpoints: mean compression rate; mean compression depth.

Results

Data from 255 subjects (4S: n=127; 2S: n=128) was analyzed. The standard group (4S) as well as the intervention group (2S) improved significantly compared to baseline testing after one week concerning compression depth (4S: 47.8±10.4 mm to 52.4±7.6 mm, p<0.0001; 2S: 47.7±10.7 mm to 55.8±5.4 mm; p<0.0001) and compression rate (4S: 116.1±23.4 min-1 to 118.7±16.0 min-1, p<0.0001; 2S: 114.1±22.8 min-1 to 119.6±13.8 min-1; p<0.0001). The participants trained with the 2-Stage-Approach showed superior performance one week after training in respect of the mean compression depth (4S: 52.4±7.6 mm vs. 2S: 55.8±5.4 mm; p<0.0001).

Conclusions

Teaching ECC within BLS is sufficiently accomplished with a structured 2-Stage-Approach. Compared to the standard 4-Stage-Approach this methodology leads to comparable skill performance with significantly improved compression depth. Therefore this approach should be further evaluated and offers the option to standardize instructors performance more easily.
Abstract 255: CT Imaging of Pediatric Heart Deformation During Chest Compressions
Authors: Glass George F , Kent Richard , Maltese Matthew , Bass Dale , Sochor Mark
Published: April 2024

Background: Adequate chest compression (CC) depth is associated with increased survival to hospital discharge, yet specific data guiding CC depth targets in children are lacking. Current guidelines for pediatric CCs are based on extrapolation from adults, animal models, and expert consensus. Given this lack of data, investigation into the biomechanical effect of CCs on the pediatric thorax is warranted.

Methods: Three non-injurious CC simulations were performed on a single 7 year-old post-mortem human subject with intended compression depth of 0%, 15%, and 25% of external thoracic depth. A Phillips CPR Force Deflection Sensor replica was positioned at the inter-nipple line of the subject. Force was statically applied to reach the desired compression depth. Non contrast-enhanced CT imaging was obtained for each compression level. External thoracic depths were measured at the inter-nipple level from the most anterior to most posterior skin surface at midline. Internal depths were measured from the posterior sternal border to the anterior border of the corresponding vertebral body. Left ventricular volumes were calculated using three-dimensional multiplanar reconstruction and a 4-level modified Simpson method.

Results: Intended 25% compression resulted in change of 25mm in external chest depth and 20mm of internal depth (a 16.4% and 29.6% change, respectively). Total left ventricular volume (inclusive of myocardium and ventricular cavity) was reduced by 8.8% (62.7cm
3
to 57.2cm
3
). Right ventricular volumes were not measured due to difficulty in right heart border visualization, but subjective deformation of the right heart was greater than left.

Conclusions: This is the first reported CT visualization of thoracic contents during compression of the pediatric chest. Our results indicate a proportionally greater decrease in internal thoracic depth than external depth for a given compression depth. Previous studies extrapolating the desired compression depth from CT-data have assumed internal compression directly proportional to external compression depth. These studies may overestimate the target depth necessary to achieve a given amount of internal thoracic compression.
Abstract 259: National Variability in Survival Outcomes of Out-of-Hospital Cardiac Arrest: The All-Japan Utstein Registry
Authors: Hasegawa Kohei , Tsugawa Yusuke , Hiraide Atsushi , Brown David F M
Published: April 2024

Introduction

Health and policy implications of national variability in survival outcomes of out-of-hospital cardiac arrest (OHCA) remain to be determined.

Hypothesis

We tested the hypothesis that survival outcomes of OHCA would differ across geographic regions in Japan.

Methods

Analysis of a prospective nation-wide population-based dataset of the whole population across Japan involving all patients who had a non-traumatic OHCA resuscitated by emergency responders from January 2005 through December 2010. The study endpoints were 1-month survival and favorable neurological survival 1 month after an OHCA, defined as Cerebral Performance Category 1 or 2. We compared unadjusted and multivariable-adjusted rates of the outcomes among 7 geographic regions using regression model with generalized estimating equations to control for patient- and prehospital-level characteristics (Table).

Results

In the total catchment population of 128 million, 670 313 patients with OHCA were documented. Of 660 672 resuscitation attempts, 539 641 non-traumatic OHCA patients were eligible for analysis. The adjusted incidence of OHCA per 100 000 population ranged from 58.9 to 78.8 (median, 65.3). One-month survival ranged from 3.7% to 6.1%, with a median of 5.6%; we observed a large variation among regions in multivariable adjusted rate of 1-month survival, ranging from 3.8% to 6.5% (median, 4.7%). Similarly, neurologically favorable survival varied by region from 1.9% to 3.0%, with a median of 2.5%; adjusted rate of neurologically favorable survival ranged from 1.9% to 3.6% (median, 2.7%), with significant differences across regions (P<.001).

Conclusion

In this nation-wide population-based study in Japan, there were significant and important regional differences in OHCA survival outcomes.
Abstract 264: Beneficial Effects of Therapeutic Hypothermia After Cardiac Arrest and CPR in Mice Require Nitric Oxide Synthase 3
Authors: Kida Kotaro , Mandeville Joseph B , Bloch Kenneth D , Ichinose Fumito
Published: April 2024

Background
: Therapeutic hypothermia (TH) improves neurological outcomes after ventricular fibrillation (VF)-induced cardiac arrest (CA), but the mechanisms by which TH elicits its beneficial effects are incompletely elucidated. Recently, we reported that inhaled nitric oxide (NO) improves outcomes after CA and CPR in mice. In this study, we tested the hypothesis that NO signaling is required for TH to improve outcomes after CA/CPR. We also sought to determine whether inhaled NO remains beneficial in mice treated with TH after CA and CPR.

Methods
: Adult male wild-type (WT) and NO synthase 3-deficient (NOS3
-/-
) mice were subjected to potassium-induced CA at 37°C for 8 and 6.5 minutes, respectively, at which time, CPR was performed with chest compression and mechanical ventilation. Body temperature was maintained at 37°C or reduced to 33°C starting 30 min after return of spontaneous circulation (ROSC) for 24h. TH-treated mice contemporaneously breathed air without or with NO (40 ppm). T2-weighted magnetic resonance imaging (MRI) was performed in live WT mice at 24h after CA/CPR.

Results:
Normothermic (NT) WT mice exhibited 100% mortality within 24h after CA/CPR. TH markedly improved the survival rate at 10 days in WT mice (43%; P<0.05 vs NT). In WT mice treated with TH, breathing NO (NO+TH) further improved the survival rate after CA/CPR (88%, P<0.05, NO+TH vs TH). NT NOS3
-/-
mice exhibited 100% mortality within 24h after CA/CPR. TH failed to improve survival rate in NOS3
-/-
mice, suggesting that NOS3 is required for the beneficial effects of TH after CA/CPR. NO breathing combined with TH improved the survival rate in NOS3
-/-
mice after CA/CPR (67%, P<0.01 vs NOS3
-/-
TH). T2-weighted MRI in live mice showed hyperintense areas in the brainstem and ventral hippocampus of mice that were treated with TH alone consistent with development of vasogenic edema. NO+TH largely prevented the development of brain hyperintense regions (P<0.05, NO+TH vs TH).

Conclusions
: The ability of TH to improve survival in mice subjected to CA/CPR requires NOS3 suggesting that NO signaling plays a critical role in the beneficial effects of TH. Inhaled NO can improve survival and reduce brain injury after CA/CPR even in mice treated with TH.
Abstract 271: Detection of Ventricular Fibrillation with Continuing Chest Compression Using Adaptive Least Mean-Square Estimation of Cardiopulmonary Resuscitation Artifacts and Removal of the Artifacts
Authors: Lin Chen , Ko Patrick Chow-In , Lo Men-Tzung , Chiang Wen-Chu , Hsieh Wan-Hsin , Lin Lian-Yu , Huang Chien-Hua , Lin Jiunn-Lee , Chen Wen-Jone , Ma Matthew Huei-Ming
Published: April 2024

Introduction: Adequate perfusion during cardiopulmonary resuscitation (CPR) is crucial for successful defibrillation after ventricular fibrillation (VF), but the effects of chest compressions (CC) are compromised from interruptions due to rhythm analysis. A novel algorithm utilizing corrupted ECG signal to detect VF during continuing CC is developed.

Method: VF waveforms were retrieved from automatic external defibrillator (AED) records of adult non-traumatic cardiac arrests. Ten CC artifacts were retrieved from arrests with asystole. Corrupted ECG was constructed by adding a scaled CC artifact to a VF with strength determined by signal-to-interference ratio (SIR). Using empirical mode decomposition, the fluctuation and frequency of CC were retrieved. VF was detected by subtracting the CC artifacts, modeled by least mean-square (LMS) algorithm, from ECG signals. Amplitude spectrum analysis (AMSA) was used to quantify the component with frequency range 0.7[[Unable to Display Character: ‐]]30 Hz.

Result: One-hundred and fifty VF (36 successful and 114 unsuccessful defibrillation, p<0.01) were included. After removing CC artifacts with the algorithm, successful vs unsuccessful cases remained distinguished (p<0.05) in SIR ranged 0 to -9dB. The detected and the original VFs had similar AMSA with correlation of 0.98, 0.95, 0.93 and 0.86 when SIR were 0, -3, -6 and -9dB (p<0.001). The mean of difference between the detected VFs and the original VFs were 0.19, 0.56, 1.36 and 3.33 for SIR of 0, -3, -6 and -9dB, respectively, in Bland-Altman plot.

Conclusions: The proposed adaptive algorithm using LMS could model CPR artifact without external signals, and effectively detect VF with continuing CC.
Abstract 29: Inhibition of Mst1 Kinase by Protein-l-Isoaspartate (d-aspartate) O-Methyltransferase Protects Cardiomyocytes from Hypoxia-Induced Apoptosis
Authors: Qin Qing , Yan Guijun , Yi Bing , Chuprun Kurt , Sun Haixiang , Huang Shengdong , Sun Jianxin
Published: April 2024

Background:
Mammalian sterile 20-like kinase 1 (Mst1) is a mammalian homolog of Hippo kinase from Drosophila and it is a critical component of the Hippo signaling pathway, which regulates a variety of biological processes ranging from cell contact inhibition, organ size control, apoptosis and tumor suppression in mammals. Activation of Mst1 causes cardiomyocyte apoptosis and dilated cardiomyopathy. However, the mechanism underlying Mst1 activation in the heart is not known.

Method and result:
In a yeast two-hybrid screen of a human heart cDNA library with a dominant-negative Mst1 (K59R) mutant used as bait, protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) was identified as an Mst1-interacting protein. The interaction of PCMT1 with Mst1 was confirmed by co-immunoprecipitation in both co-transfected HEK-293 cells and native cardiomyocytes, in which PCMT1 interacted with the kinase domain of Mst1, but not with its C-terminal regulatory domain. Knockdown of PCMT1 augments hypoxia/reoxygenation induced Mst1 activation and apoptosis. Overexpression of PCMT1 did not affect the Mst1 expression, but significantly attenuated the Mst1 activation and its apoptotic effects in response to the hypoxia/reoxygenation induced injury in cardiomyocytes. Moreover, upregulation of PCMT1 by CGP3466B, a compound related to the anti-Parkinson’s drug R-(-)-deprenyl with potent antiapoptotic effects, inhibited the hypoxia/reoxygenation induced Mst1 activation and cardiomyocyte apoptosis.

Conclusion:
PCMT1 is a novel inhibitor of Mst1 activation in cardiomyocytes and suggest that targeting PCMT1 may prevent myocardial apoptosis through inhibition of Mst1.
Abstract 3: Detailed Description of All Deaths in Both the Shock and Traumatic Brain Injury Cohorts of the Resuscitation Outcomes Consortium Hypertonic Saline Trials
Authors: Tisherman Samuel A , Schmicker Robert , Brasel Karen J , Bulger Eileen M , Kerby Jeffrey D , Minei Joseph P , Powell Judy , Reiff Donald A , Rizoli Sandro B , Schreiber Martin A
Published: April 2024

Introduction: In trials conducted by the Resuscitation Outcomes Consortium (ROC) in patients with traumatic hypovolemic shock (shock) or traumatic brain injury (TBI), hypertonic saline failed to demonstrate improved survival. We sought to identify causes of mortality in this patient population to determine targets for future studies.

Methods: Retrospective review of patients enrolled in a multicenter, randomized, clinical trial performed 2006-2009 by 114 EMS agencies in North America within ROC. Inclusion criteria were injured patients, age ≥ 15 years with hypovolemic shock (SBP ≤ 70 mm Hg or SBP 71-90 mm Hg with HR ≥ 108) or severe TBI [Glasgow Coma Score (GCS) ≤8]. Initial resuscitation fluid administered by out-of-hospital providers was 250 mL of either 7.5% saline with 6% dextran 70, 7.5% saline or 0.9% saline.

Results: 2071 subjects were enrolled (821 shock, 1250 TBI). Survivors were younger than non-survivors [30(IQR 23) vs 42(34)] and had a higher GCS, though similar hemodynamics. Greater than 90% of deaths occurred despite ongoing resuscitative efforts. Forty six percent of the deaths in the TBI cohort were within 24 hours, compared with 81% in the shock cohort and 72% in the cohort with both shock and TBI. Median time to death was 29 hours in the TBI cohort, 2 hours in the shock cohort, and 4 hours in patients with both.

Conclusion: Most deaths from trauma occur within the first 24 hrs from hypovolemic shock or TBI. Late deaths from sepsis and multiple organ failure are rare. Novel resuscitation strategies should focus on early deaths.
Abstract 39: Donating Automated External Defibrillators May Not Be Enough
Authors: Ludgate Melissa B , Kern Karl B , Bobrow Bentley J , Ewy Gordon A
Published: April 2024

Background: In response to the out-of-hospital sudden death of their son, parents and friends established a local foundation in Tucson, Arizona to help prevent sudden cardiac death. One of their projects was to provide Automated External Defibrillators (AEDs) predominately to public and private schools, places of worship, boys and girls clubs and museums in Tucson, Arizona and surrounding area. Prior to receiving the AED, the majority of sites attended training in the use of the AED, that included information concerning the need to replace the electrodes pads before they expired.

Methods: The first author of this abstract (a trained Emergency Medical Technician and a recent college graduate) visited sites that responded to the offer of assistance to retrain individuals in the proper use of their AED. Included in the visit, she determined the status of the donated AED and provided education about future maintenance.

Results: Each site visited had received their AED between 7/2009 and 4/2011. Of the 36 sites visited, the majority of the units had potential problems. One had been stolen, and one was missing (2/36 or 6%). Of the remaining 34 units, 23/34 (68%) had outdated electrode pads, and in 2/34 (6%) the battery had expired. Thus only 11/34 (32%) were emergency ready. Of these, 7/11 had been donated within two years (the average shelf-life of AED electrode pads). The other 4/11 had replaced their expired AED electrode pads.

Conclusions: Providing AEDs alone may not be the optimal approach. A system must be in place to assure that they are properly stored and maintained. AED pads with longer “shelf-life” should also be a goal of AED manufacturers.
Abstract 44: Outcomes of OHCA Not Improved After New Guideline Implementation in Taiwan: Nationwide Population-Based Research Using National Health Insurance Data
Authors: Harnod Dorji , Ma Mathew Huei-Ming , Chang Chu-Hui
Published: April 2024

Background:
Survival after out-of-hospital cardiac arrest (OHCA) depends on the integrity of the community chain of survival, including high quality CPR, early defibrillation, better hospital and post-resuscitation care. Recent studies from US showed the outcomes from OHCAs improved significantly after implementation of new resuscitation guideline. Our study, by using the population- based National Health Insurance data, was aimed to assess the factors associated patient outcomes and the improvement after guidelines 2005 implementation in Taiwan.

Methods:
From the claim data of one million beneficiaries of Taiwan National Health Insurance during the year of 2005 to 2008, all of patients who were sent to emergency department with diagnosis of OHCA were identified from the database (ICD 798, 798.1, 798.2, 798.9). Traumatic OHCA and patients without codes for intubation and CPR were excluded in our study. Factors such as age, gender, preexisting co-morbidities and different hospital levels were adjusted in a logistic regression model for survival analysis. All the survival cases were followed up for one year in our data-set.

Results:
2,375 OHCA cases were identified from the four-year dataset. The survival rates were 7.3%(2005), 7.5%(2006), 7.2%(2007) and 6.5%(2008) (p>0.05). And the survival rates was 7.4% in medical centers, 7.8% in regional hospitals and 5.0% in district hospitals (p>0.05). In the logistic regression analysis model, for all the OHCA patients admitted to ER and to hospitals, none of the factors (including the age, gender, preexisting co-morbidities and different hospital levels) were significant for survival.

Conclusions:
After adjusting for age, gender and preexisting co-morbidities, our study shows that OHCA patients had equal outcomes between medical centers and non-medical centers. And our data also showed non-significant outcome improvement after guidelines 2005 implementation in Taiwan.
Abstract 9576: A Nuclear Receptor-microRNA Circuit Links Control of Muscle Fiber Type to Energy Metabolism
Authors: Gan Zhenji , Rumsey John , Hazen Bethany C , Lai Ling , Leone Teresa C , Vega Richard B , Auwerx Johan , Olson Eric N , Kralli Anastasia , Kelly Daniel P
Published: April 2024

Zhenji Gan, 2012 Finalist and Presenting Author
Abstract 11404: MicroRNA Associated with Atherogenic Dyslipidemia In South Asian Men
Authors: Flowers Elena , Singh Komal , Molina Cesar , Mathur Ashish , Froelicher Erika S , Aouizerat Bradley E
Published: April 2024

Elena Flowers, 2012 Finalist and Presenting Author
Abstract 14447: Dose Response Effect of Cigarette Smoking on Cardiac Function and Heart Failure in the Multi-Ethnic Study of Atherosclerosis
Authors: Gjesdal Ola , Mewton Nathan , Yoneyama Kihei , Wu Colin , Heart Natl , Jacobs David , Sydney Stephen , Lewis Cora E , Liu Kiang , Bluemke David A , Lima Joao A
Published: April 2024

Ola Gjesdal, 2012 Finalist and Presenting Author
Abstract 55: VA ECMO for Cardiac Arrest and Severe Refractory Cardiogenic Shock
Authors: Shreenivas Satya , Mathelier Hansie , Epps Kelly , Lilly Scott , Atluri Pavan , Rame Jesus E
Published: April 2024

Background:
Critically ill cardiac patients, in cardiogenic shock or cardiac arrest, have worse outcomes than those who are less ill. Frequently, these patients require emergent initiation of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to sustain them until a LVAD can be placed. We report the profile and outcomes of patients supported with VA-ECMO.

Methods:
This is a retrospective cohort study of all adult patients who received mechanical circulatory support with VA-ECMO at the Hospital of the University of Pennsylvania from January 2010 to November 2011 for the indication of progressive severe refractory cardiogenic shock or cardiac arrest. Patients who were placed on ECMO post cardiac surgery were excluded from this study.

Results:
During the study period, 33 patients required VA ECMO, 15 for cardiac arrest and 18 for progressive severe refractory cardiogenic shock. The etiology of the acute heart failure included the following: coronary artery disease (48.5%), unstable arrhythmia (12.1%), post-procedural (15.2%), rejection (6%), and others (18.1%). The mean age was 50±13 year old, with 64% being male. The mean age of the patients who survived was 42±11 year old compared with 52 ±13 year old for non-survivors. The overall survival was 7/33 (21.2%). There was no difference in survival based on if the cause of the cardiac decompensation was cardiac arrest (survival rate: 20%) or progressive cardiogenic shock (survival rate: 22%). The survival in patients with ischemia was 6.25%, while survival in all other causes was 35.3% (p-value 0.041). The most common cause of death was refractory shock resulting in multisystem organ failure.

Discussion:
In this small cohort of critically ill patients, these findings are surprising and suggest that progressive cardiogenic shock has a prognosis that equates to cardiac arrest. A significant portion of cardiac arrest patients did not undergo hypothermia due to concern for excess hypercoagulability. The baseline coagulopathy is thought to be secondary to a DIC-like process brought on by blood interaction with the ECMO plastic tubing. Decision making regarding hypothermia is based on a patient’s underlying hypercoaguable state, which may lead to lack of neurologic protection.
Abstract 11282: Maintaining Prostaglandin E2 Levels Prevents Rejection of Implanted Allogeneic Mesenchymal Stem Cells and Restores Post-Infarction Ventricular Function
Authors: Dhingra Sanjiv , Li Peng , Huang Xi-Ping , Guo Jian , Wu Jun , Li Shu-Hong , Zang Wang-Fu , Singal Pawan K , Weisel Richard D , Li Ren-Ke
Published: April 2024

Sanjiv Dhingra, 2012 Finalist and Presenting Author
Abstract 60: Prognostic Performance of Diffusion-Weighted Magnetic Resonance Imaging in Comatose Patients Treated with Mild Hypothermia After Cardiac Arrest and Its Added Value in the Context of Neuron-Specific Enolase-Based Prognostication
Authors: Noh Kyonghee , Kim Joonghee , Kim Kyuseok , Choi Byung Se , Jung Cheolkyu , Lee Jae Hyuk , Jo You Hwan , Rhee Joong Eui , Kim Tae Yun , Kang Kyeong Won
Published: April 2024

Objective: MRI-based prognostication of comatous resuscitated cardiac arrest patient has shown promising results. However, it was not validated in patients treated with therapeutic hypothermia and it is unknown how it might add to NSE-based prognostication. We sought to evaluate the prognostic performance of regional apparent diffusion coefficient (ADC) in comatose OHCA patients treated with mild hypothermia and its added value to NSE-based prognostication.

Methods: OHCA registry was analyzed to identify OHCA patients older than fifteen who were treated with therapeutic hypothermia and underwent brain MRI between 2008 and 2011. Quantitative measurement of regional ADC was done by a radiologist blinded to clinical outcome.

Results: Among 43 eligible patients, 11(18.6%) achieved good outcome (6-month CPC 1 or 2). Regional ADC of occipital cortex showed highest discriminatory power with its area under the curve of receiver- operating-characteristic (AUROC) 0.943 (95% CI, 0.872-1.000) and predicted poor outcome with a sensitivity of 90.6% and a specificity of 100%. For NSE (48-hour), its AUROC was 0.911 (95% CI, 0.801- 1.000) and it was correlated with the regional ADC significantly (Pearson’s r=-0.674, p<.001). The ADC- based prognostication could identify additional 5 (35.7%) poor outcome patients among 14 with 48- hour NSE <78.9ng/mL, a cutoff point suggested by a previous study. However, it did not provided additional prognostic information if 48-hour NSE was >78.9ng/mL.

Conclusions: Regional ADC-based prognostication was accurate in OHCA patients treated with mild hypothermia. However, in the context of 48-hour NSE-based prognostication, it provided additional prognostic information only when 48-hour NSE indicated good prognosis (48-hour NSE <78.9ng/mL).

Uploaded image: A scatterplot depicting the relationship between 48-hour NSE level and regional (occipital) ADC value. Vertical gray dash line: 33 ng/mL; Vertical black dash line: 78.9ng/mL
HDL: A Novel Target or Marker for Cardiovascular Risk
Authors: Brewer H. Bryan
Published: April 2024

HDL has become a potential therapeutic target to reduce the residual cardiovascular (CV) risk in statin treated patients. Over the last several years it has been established that HDL is heterogeneous and contains several discrete lipoproteins particles with different lipid compositions and separate anti-atherosclerotic functions. These functions include increasing ABCA1 and ABCG1 mediated cholesterol efflux from cholesterol loaded macrophages, and decreasing inflammation, LDL oxidation, and thrombosis. Epidemiological data, animal models and initial imaging and pilot trials have shown promise, however proof that increasing HDL-C levels will reduce CV clinical events independent of changes in plasma levels of LDL-C and triglycerides has been elusive. HDL cholesterol is now recognized as an ineffective biomarker for accessing HDL mediated changes in CV events since HDL-C is a static measurement with no information on the dynamic flux through the HDL-C pathway, the variability of the cholesterol content in the different HDL particles, and the recognition that >90% of HDL-C is derived from the liver and intestine with <2% coming from the cholesterol loaded peripheral vascular tissue macrophages. The focus of the elucidation of the role of HDL in CV disease has now shifted from the quantitation of HDL-C to a systematic analysis of HDL particle number, HDL proteome, HDL lipidome and functions of the individual HDL particles. Low HDL due to genetic mutations in apoA-I, the structural protein of HDL, is causative in the pathway of increased vascular disease. In contrast HDL can also be a marker of a generalized dyslipoproteinemia as is present in the metabolic syndrome and diabetes Thus; HDL can be both a player in the development of CV disease as well as a marker of CV disease risk. Novel therapeutic agents that may substantiate the potential importance of HDL as a therapeutic target under development include niacin/laropiprant, CETP inhibitors and HDL infusions in acute coronary syndrome patients. The outcome of clinical trials with these new therapeutic modalities will provide definitive data on the future of HDL as an importance approach to decreasing CV events in high risk patients with cardiovascular disease.
Role of LRP1 in Protecting the Vasculature
Authors: Strickland Dudley
Published: April 2024

Since the early studies of Russell Ross, numerous investigators have confirmed that inflammation is a driving force behind chronic diseases such as atherosclerosis, and key to this process is the recruitment and activation of macrophages. Our studies reveal that the LDL receptor-related protein (LRP1) plays an important role in macrophage biology by regulating the adhesive properties of the integrin α
M
ß
2
. LRP1 is a large endocytic and signaling receptor that is widely expressed and mediates the endocytosis and subsequent degradation of several ligands. Deletion of the
Lrp1
gene is lethal in mice, and genome wide association studies reveal that the
Lrp1
gene represents a susceptibility locus for migraine, for elevated plasma lipids, and for coronary heart disease. LRP1 is abundantly expressed in macrophages where it functions to protect the vasculature from the development of disease. By employing macrophage specific knockout mice (macLRP1-/- mice) we discovered that LRP1 expressed in these cells protects the vasculature from excessive remodeling upon injury by regulating the TGFß signaling pathway and by influencing vascular smooth muscle cell (SMC) recruitment into the developing neo-intima. It is well established that an important contribution to cardiovascular diseases is the transdifferentiation of SMC. Under normal physiological conditions, SMC are fully differentiated and in a contractile phenotype. However, under pathological conditions SMC switch to a proliferative and migratory phenotype and contribute to lesion development in atherosclerosis and/or neo-intima formation. Significant effort is underway to define molecular mechanisms regulating SMC transdifferentiation, and substantial evidence suggests an important role for the LDL receptor related protein 1 (LRP1) in this process by modulating the PDGF signaling pathway. Our data in SMC LRP1 deficient mice (smLRP1-/-) reveal that LRP1 modulates SMC transdifferentiation and regulates pathways relevant to neo-intima and aneurysm formation.
Abstract 75: Time to Awakening Is Often Delayed After Therapeutic Hypothermia for Post--Cardiac Arrest Patients
Authors: Swor Robert , Pinawin Ashley , Sawyer Kelly , Jung Dawn , Devore Nancy J , Capoccia Diane
Published: April 2024

Introduction Withdrawal of care in patients after cardiac arrest has traditionally been based on the neurological exam at 72 hours after hospital arrival. For patients receiving post-cardiac arrest therapeutic hypothermia (TH), however, there is limited data to guide prognostication. We sought to describe the time to awakening for patients treated with TH and the relationships between time to awakening and outcome.

Methods We performed a retrospective chart review of adult (age > 18) cardiac arrest patients from January 2006 to January 2012 who were subsequently treated with TH at a large, academic community hospital. We abstracted demographic data, neurological assessments recorded by ICU nurses, including Glasgow Coma Scale (GCS), and survival data, including cerebral performance category (CPC) at discharge. We abstracted time intervals including intervals from arrival to target temperature (33.5°), interval to rewarming (35°C), and interval from arrival and rewarming to awakening. We defined awakening as GCS greater than 8, or GCS motor >4 for intubated patients. Our primary outcome measure was good neurological outcome at discharge (CPC of 1 or 2). Descriptive statistics are reported.

Results During the study period, 96 patients received TH (average age 60.3 years, 64.2% male). Overall, 39 (40.6%) patients survived to discharge, six were excluded (five did not awaken, one missing time data). Time (median, IQR) from ED arrival to rewarming was 41.0 (39,43) hours, ED arrival to awakening was 52.8 (43, 89) hours, and awakening to rewarming was 12.0 (2, 42) hours. The relationship between awakening and outcome is shown in table 1.

Conclusion Although most patients with a good outcome awoke within 72 hours of hospital arrival or shortly after rewarming, a number of patients had awakening delayed more than 72 hours post arrival and rewarming. Our results support the need for longer periods of observation to determine outcomes for patients who receive post arrest TH.
Abstract 8892: Manganese Deficiency May Play a Role in Coronary Spasm, and Selenium Deficiency May Induce Cardiac Dysfunction Through the Microcirculatory Disturbance
Authors: Hiraoka Yuji , Nakayama Akihiro , Iida Yutaka , Yamazaki Taketoshi , Tanabe Masato , Fujita Masatoshi
Published: April 2024

Background:
Although manganese, zinc and copper are essential cofactors for superoxide dismutase (SOD) activation, and selenium is an essential cofactor required for activation of glutathione peroxidase (GSHPx), their roles in cardiac diseases remain unclear. We therefore investigated the relationship between levels of these trace elements and cardiac diseases using sera from patients with vasospastic angina(VSA), DCM and AMI.

Methods:
We compared serum concentrations of 19 elements (Li, B, Al, Ti, V, Cr, Mn, Co, Ni, As, Se, Sr, Mo, Cd, Sn, Sb, Ba, Pt and Pb) by high resolution inductively coupled plasma (ICP) mass spectrometry and of 6 other elements (Ca, Mg, P, Fe, Cu and Zn) by ICP atomic emission spectroscopy, among patients with VSA(n =12), DCM(n=41), AMI(n=18) and control subjects with normal cardiac function(n=29). We also determined serum GSHPx and free radical-generating activities and measured perivascular fibrosis ratio (PVFR) in histological preparations of autopsied hearts in DCM patients.

Results:
Compared to the control subjects, manganese concentrations were lower in VSA patients (0.60±0.12 vs. 0.40±0.14 ng/ml, p<0.001), while selenium and manganese concentrations were markedly lower in DCM patients (146.0±23.3 vs. 95.1±21.5 ng/ml, p<0.00001 ; 0.60±0.12 vs. 0.37±0.16 ng/ml, p<0.0001, respectively). A significant correlation was found between serum selenium concentrations and left ventricular ejection fraction (p=0.0012). The GSHPx activity was significantly lower in DCM patients than in the control subjects (221±34 vs. 328±44 μ mol/min/L, p<0.001). Furthermore, the DCM patients enhanced radical generation in the serum, and the PVFR was also increased in this group(p<0.001).

Conclusions:
The present study indicates that manganese deficiency may play a significant role in coronary spasm via reduction in SOD activity, resulting in increased superoxide levels which in turn inactivate NO, leading to coronary spasm. The study also suggests the possibility that selenium deficiency may play an important role in cardiac dysfunction via reduction in GSHPx activity; the resultant increase in oxidative stress induces microcirculatory disturbance, which in turn induces cardiac dysfunction.
Abstract 8975: A Study of Left Ventricular Septal Wall 2D Radial and Circumferential Strain in Dyssynchrony
Authors: Dicks Bethany , DesRochers Keith , Ashraf Muhammad , Sahn David J
Published: April 2024

Background:
This study used 2D speckle tracking to analyze the effects of simulated synchrony and dyssynchrony on left ventricular (LV) septal strain.

Methods:
The atria were removed from 8 pig hearts and balloons were sewn into both ventricles at the annulus of the mitral and tricuspid valves. Each ventricular balloon was attached to a separate pulsatile pump. Each heart was imaged in a water bath at 4 different stroke volumes (SV) (30-60) at a pump rate of 50bpm. End diastolic volume (EDV) was increased incrementally with each increase in SV by injecting water into the closed system. For each SV, images were obtained in states of ventricular synchrony and dyssynchrony. 2D echo images in the short axis view were obtained using a GE Vivid 7 echocardiography system and analyzed using EchoPac PC 2D Q analysis of strain.

Results:
Statistically significant differences in septal strain were observed in states of synchrony vs. dyssynchrony. In dyssynchrony, radial septal strain (RS) showed a significant decrease compared to synchronous at each stroke volume (RS: SV 30, p = 0.051; SV 40, p = 0.016; SV 50, p = 0.043; SV 60, p = 0.029). Dyssynchronous circumferential strain (CS) showed a significant increase compared to synchronous at each stroke volume (CS: SV 30, p = 0.006; SV 40, p = 0.013; SV 50, p = 0.1739; SV 60, p = 0.02).

Conclusions:
There are significant differences in the radial and circumferential strain of segments of the left ventricular wall during states of dyssynchrony.
Abstract 9110: Elevated Glucose Increases ATP-Binding Cassette Transporter A1 mRNA Expression in Human Leukocytes and Murine Bone Marrow-Derived Macrophages and Decreases Cholesterol Efflux
Authors: Spartano Nicole L , Ronxhi Janey , Lamon-Fava Stefania , Matthan Nirupa R , Greenberg Andrew S , Obin Martin S , Lichtenstein Alice H
Published: April 2024

Background:
Individuals with diabetes are at increased CVD risk. Limited evidence suggests that this is partially attributed to hyperglycemic suppression of macrophage ATP-binding cassette (ABC) transporter mediated cholesterol efflux. The relationship between glucose concentrations and expression of ABC-transporters (ABCA1 and ABCG1) was assessed in human monocytes and leukocytes (study 1) and murine bone marrow-derived macrophages (BMDM) as well as cholesterol efflux in BMDM (study 2).

Methods:
Ten healthy subjects (4F/6M, 50-85 yrs, BMI 25-35 kg/m²) were recruited for study 1. At baseline, 1- and 2-hour post oral glucose challenge (50 g glucose), RNA was extracted from blood leukocytes (Paxgene RNA kit) and from monocytes isolated by magnetic cell sorting to assess ABC-transporter mRNA expression. For study 2, bone marrow cells were isolated from C57BL/6 mice and differentiated to BMDM with macrophage-colony stimulating factor. BMDM were stimulated with a 20mmol/L challenge of D- or L-glucose and/or 5mmol/L D-glucose (control), 16 hrs, followed by exposure to oxLDL (25 ug/mL, 24 hrs). Triglyceride (TG) and cholesteryl ester (CE) accumulation, ABC-transporter mRNA and protein expression, as well as HDL-mediated cholesterol efflux were evaluated.

Results:
A glucose challenge caused a 35% rise in human leukocyte ABCA1 mRNA expression after 1- (p=0.003) and 2- (p=0.020) hrs, but no significant effect on leukocyte ABCG1, or monocyte ABCA1 or ABCG1. Elevated glucose concentrations in BMDM culture media led to a 120% increase in ABCA1 mRNA (p=0.001) but no significant effects on expression of ABCG1 transcripts, ABCA1 or ABCG1 protein, or on intracellular TG or CE accumulation. Elevated glucose suppressed HDL-mediated cholesterol efflux by 10% (p=0.005).

Conclusion:
These results support the concept that hyperglycemia attenuates HDL-mediated cholesterol efflux from macrophages, potentially contributing to diabetes-associated CVD. Moreover, in the absence of altered ABC-transporter protein expression, our data suggest that hyperglycemia impairs HDL-mediated cholesterol efflux perhaps by attenuating transporter activity. Correspondingly, we found human monocyte ABC-transporter gene expression unresponsive to a glucose challenge.
Abstract 9193: Variation in Quality of Care Among Patients Hospitalized With Acute Heart Failure in an International Trial: Findings From ASCEND-HF
Authors: Howlett Jonathan G , Ezekowitz Justin A , Podder Mohua , Hernandez Adrian F , Diaz Rafael , Dickstein Kenneth , Armstrong Paul W , Fonarow Gregg C
Published: April 2024

BACKGROUND: Translation of evidence-based heart failure (HF) therapies to clinical practice is incomplete and may be subject to international variation. We compared key HF quality indicators in acute HF (AHF) patients enrolled in the international Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) trial.

METHODS: Patients were admitted to hospital for AHF and comprised 5 regions (North America n=3149, Latin America n=658, Asia- Pacific n=1744, Central Europe n=966 and Western Europe n=490). Quality indicators assessed at hospital discharge from the US-based Get With The Guidelines program were used, including: medications (ACEI/ARB, beta blockers, aldosterone inhibitors, hydralazine-nitrates, statin therapy and warfarin) for eligible patients, use (or planned use) of implantable intracardiac devices (ICD, CRT) for eligible patients and blood pressure control (<140/90 mmHg).

RESULTS: 7007 intent-to-treat AHF patients in 398 centres were enrolled. There was significant variation in conformity between different quality indicators, ranging from 0% to 89% (See Table). Of all potential performance opportunities, 24,807 of 39874 (62%) were met, with Central Europe highest at 68%, followed by North America (65%), Western Europe (63%), Latin America (59%) and Asia-Pacific (56%), P<0.0001.

CONCLUSION: Quality of care for patients hospitalized with AHF remains suboptimal even within a randomized clinical trial. Moreover, significant unexplained inter-regional variability in quality of care exists. Further study is required to understand and overcome the global barriers to delivery of optimal evidence-based care.