bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18904: Cardiac Arrhythmias During Long Duration Spaceflight
Authors: Hastings Jeffrey L , Kowal Jaime , Daniels James , Shibata Shigeki , Platts Steven H , Hamilton Doug R , Page Richard L , Ng Jason , Goldberger Jeffrey J , Bungo Michael W , Levine Benjamin D
Published: April 2024

PURPOSE:
Whether cardiac arrhythmias are increased during spaceflight has been a long standing question for the human space program. Few data are available from long duration flight. To evaluate the incidence of in-flight arrhythmias we studied 12 astronauts during 4-6 months on the International Space Station with high-fidelity Holter monitoring. We hypothesized that spaceflight does not increase the incidence of cardiac arrhythmias, and when arrhythmias are observed they represent a benign substrate.

METHODS:
Twelve astronauts (3 women) wore 48hr Holter monitors: two preflight; in-Flight Day (FD)-14, 30, 75, 135; 15 days prior to return; and immediately upon landing. Individuals recorded symptoms in a diary. Arrhythmia frequency was assessed blindly by an experienced electrophysiologist.

RESULTS:
Baseline data showed 125±359 (range 1-1262) supraventricular ectopic beats (SEB) per 48hr period, while in-flight recordings showed 320±1137 SEB (range 0-5405); ventricular ectopy (VEB) at baseline was 286±944 beats (range 0-3282) and 305±775 beats (range 0-3439) in-flight confirming the substantial inter-individual variability. SEB and VEB at baseline were 0.06±0.16% and 0.13 ± 0.42% of all beats respectively, while the 48hr Holter with the largest number of ectopic beats for each astronaut was 0.25±0.74% (p=0.284) and 0.24±0.51% (p=0.177) respectively, demonstrating no significant change in ambient ectopy. There were no sustained arrhythmias in flight; short runs of NSVT (all <5 beats) were observed both pre and in-flight in some astronauts. Filtered QRS duration (baseline: 84.5±8.2; in-flight maximum: 90.5±12.1 msec, p<0.001), and low amplitude signal duration (baseline: 23.2±6.4; in-flight maximum: 27.1±6.4 msec, p<0.01) increased subtly, but remained within normal limits; root mean square voltage of the terminal 40 ms did not change (baseline: 62.5±34.3; in-flight maximum: 73.0±29.4 microV, p=0.19). T wave alternans was not present at any time. Analysis of QT variability and T wave morphology in the first 6 astronauts did not change.

CONCLUSIONS:
Baseline arrhythmias are quite variable between astronauts; data suggest that long duration spaceflight is not associated with changes in arrhythmia frequency or arrhythmic substrate.
Abstract 18959: Mesp1 Marked Cardiac Progenitor Cells Repair Infarcted Mouse Hearts
Authors: Liu Yu , Chen Li , Diaz Andrea A , Xu Xueping , Cooney Austin J , McConnell Bradley K , Schwartz Robert J
Published: April 2024

Mesp1 directs multipotential cardiovascular cell fates, even though it’s transiently induced prior to the appearance of the cardiac progenitor program. Because of Mesp1’s transitory nature, Mesp1-CPC lineages were traced by following EYFP expression in murine Mesp1Cre/+; Rosa26EYFP/+ ES cells. These earliest CPCs strongly expressed cardiac mesoderm markers (Flk1, PDGFRα, Hand2), cardiac transcription factors (Nkx2-5, Tbx5, Mef2c), but not pluripotent markers (Oct4, Sox2, Nanog) nor nascent mesoderm markers (T, Fgf8). These CPCs expressed miRNAs involved in early cell fate decisions but not those in terminal cardiomyocytes. The early EYFP+ cells represented a sub-population of the Flk1+/PDGFRα+ cells, which were widely used to isolate CPCs. BMPs, canonical Wnts and Activin were required for induction and accumulation of Mesp1-CPCs, but extended BMP4 was not compatible with cardiomyocyte formation. Meantime, canonical Wnt inhibitor IWR1 was sufficient to drive CPCs toward cardiomyocyte, suggesting drastic change of extracellular cues is essential for the switch from CPC specification to differentiation. In a post-myocardium infarction mouse model, injected Mesp1-CPCs differentiated into cardiac muscle cells, vascular smooth muscle cells and endothelial cells, with evident neovascularization in both infarct and border zones. Mesp1-CPC proliferation remained evident 12 weeks after injection into the post-MI murine hearts. Injected mouse pre-contractile Mesp-1/EYFP+ CPCs improved the survivability of injured mice and restored the functional performance of infarcted hearts for at least 3 months. In summary, Mesp1-EYFP+ cells are bona fide CPCs and they integrated well in infarcted hearts and emerged de novo into terminally differentiated cardiac myocytes, smooth muscle and vascular endothelial cells.
Abstract 18998: Macrophage-Specific Mineralocorticoid Receptor Antagonists for Cardiovascular Disease
Authors: Goonewardena Sascha N , Tsuchida Ryan E , Pitt Bertram , Zong Hong
Published: April 2024

Background:
Mineralocorticoid receptor antagonists (MRA) have consistently led to improved clinical outcomes in patients with cardiovascular disease. Despite these benefits, off-target effects have limited the use of MRAs. Studies have begun to define the molecular mechanisms underlying cell-specific MR signaling, with several groups demonstrating a pathologic role for macrophage-MR activation in animal models of heart failure.

Objective:
We sought to engineer and evaluate a macrophage-specific MRA (Mf-MRA) composed of three elements: a nanoparticle delivery platform, the MRA eplerenone, and a fluorogenic biomarker for therapeutic monitoring.

Methods and Results:
The individual elements of the Mf-MRA were assembled using click chemistry. Bone marrow-derived macrophages (BMDM) and control cell models were used to evaluate the cell-specificity and therapeutic efficacy of the Mf-MRA. Using flow cytometry, we found that the Mf-MRA internalizes and is activated specifically in macrophages and not other cells. To confirm the functionality of the Mf-MRA, we evaluated oxidative stress induction and inflammatory gene expression in BMDM in response to aldosterone (Aldo). Equivalent concentrations (1 μM) of spironolactone and the Mf-MRA blocked Aldo induced superoxide production (Figure 1). Additionally, the Mf-MRA blocked Aldo induction of TNFα gene transcription (p<0.005). Finally, preliminary studies in a murine heart failure model confirmed the macrophage-specific delivery and activation of the Mf-MRA.

Conclusions:
We have developed a novel, macrophage-specific MRA using a synthetic nanoparticle, a fluorogenic biomarker, and an established MRA. This cell-specific MRA combines targeted-delivery with therapeutic monitoring. We believe that this innovative platform will have unique diagnostic and therapeutic applications for a broad spectrum of cardiovascular diseases.
Abstract 19039: Higher Burden of Sudden Cardiac Death in African Americans: A Prospective, Community-Based Study
Authors: Reinier Kyndaron
Published: April 2024

Introduction:
Sudden cardiac death (SCD) is a major contributor to mortality in the US, but there is limited data on SCD in non-white minorities.

Hypothesis:
Incidence rates and clinical profile of SCD vary significantly by race.

Methods:
All SCD cases in a large northwest US community (pop. 679,348; 2002 - 2005) were identified prospectively using multi-source ascertainment. Race and ethnicity were obtained for 98% of 1174 total cases from medical records or death certificate and categorized as White, African American (AA), Asian (all non-Hispanic); and Hispanic (regardless of race). Age-specific incidence rates were calculated using US census 2003 county population estimates. Age-adjusted rates were calculated using the US standard 2000 population.

Results:
In this predominantly white community, 971 (84.5%) of SCA cases were white, 106 (9.2%) were AA, 34 were Asian (3.0%), and 22 (1.9%) were Hispanic. Age-adjusted rates were highest among AA (122/100,000), 59/100,000 in Whites, 52/100,000 in Hispanics, and lowest among Asians (36/100,000). Age-specific rates showed AA had higher rates across all age categories (Figure). No race/ethnic differences were observed (p≥0.28) by sex, history of MI or CAD, or circumstances of SCD (cardiac arrest location, response time, percent with resuscitation attempted, initial rhythm, witnessed SCD, return of spontaneous circulation, or survival to hospital discharge). AA were younger than whites at the time of SCD (63.8 ± 18.7 vs. 69.8 ± 15.3, p=0.007). A higher proportion of AA were diabetic (50% vs. ≤33% in other groups; p=0.0001); and there was a trend toward higher comorbidity burden (35% AA with Charlson Index ≥4 vs. ≤25% in other groups; p=0.06).

Conclusions:
In this US Community, African Americans had more than double the incidence of SCD compared to other race/ethnic groups, suffered SCD at a younger age, and with higher rates of diabetes.
Abstract 19083: Macrophage Expression of Pcsk9 Influences Atherosclerosis Development
Authors: Giunzioni Ilaria , Tavori Hagai , Covarrubias Roman , Major Amy , Linton MacRae F , Fazio Sergio
Published: April 2024

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory protein that regulates low-density lipoprotein (LDL) cholesterol levels by binding and degrading hepatic LDL receptor (LDLR), thus contributing to atherosclerosis. Little is known of PCSK9 effect in macrophages and whether this contributes to the development of the atheroma.

First, we demonstrated that murine peritoneal macrophages (MPM) express endogenous (m) PCSK9 both at the mRNA and protein level. Then, to test the effect of human (h) PCSK9 on atherosclerosis we developed transgenic mice expressing hPCSK9 from multiple tissues and cells, including macrophages. As it occurs in hepatocytes, hPCSK9 reduced LDLR levels in MPM. The effect on LDLR was more evident in resident than in elicited MPM, and was completely abolished after culturing MPM in medium containing FBS or LPDS, that cause LDLR upregulation. Co-immunoprecipitation experiments showed a direct interaction of hPCSK9 with LDL-R. In addition, we found that PCSK9 also interacts with LRP-1, a member of the LDL-R gene family involved in modulation of inflammatory responses and cell survival. It has been recently reported that PCSK9 reduces LRP1 levels in transduced renal HEK293T cells. However, we found that the interaction of hPCSK9 with LRP1 did not affect either total or membrane levels of the receptor. Surprisingly, analyses of spleen lysates from hPCSK9 transgenics revealed an increase in the percentage of Ly6C
hi
and CD11b positive cells compared with WT. To study the effect of macrophage PCSK9 in the atheroma, bone marrow from hPCSK9/apoE
-/-
or apoE
-/-
mice was transplanted into apoE
-/-
recipients. Low levels of hPCSK9 were detected in serum of hPCSK9/apoE
-/-
marrow recipients, but no effects on cholesterol were noted. Although lesion size was not different, lesion composition analyses showed a higher percentage of Ly6C
hi
positive cells in recipients of hPCSK9/apoE
-/-
marrow compared to controls (7.4±1.5% vs. 5.6±1.1%, respectively,
p
<0.05).

Our results show for first time that PCSK9 expression by macrophages directly influences atherosclerotic plaque composition in the absence of changes in serum cholesterol levels, suggesting a direct effect of macrophage PCSK9 in inflammation and plaque development.
Abstract 19100: Comparison of Exercise Blood Pressure Response in Patients With Coarctation of Aorta: Surgical Repair vs. Endovascular Stent
Authors: Ross Michael M , Ho Jason G , Sterrett Lauren E , Breinholt John P
Published: April 2024

Background:
Percutaneous stent placement has been shown to be a safe and effective treatment option for patients with coarctation of the aorta. Immediate post-procedural and short term hemodynamic assessments comparing stent placement to surgical correction show equivalency. Little is known about the effects of either treatment modality on blood pressure response during exercise.

Methods:
This study prospectively compares the hemodynamic response to exercise by treadmill testing in patients at least one year after intervention. Patients included were greater than seven years of age without complex congenital heart disease or single ventricle physiology. Patients underwent standard Bruce Protocol treadmill testing with periodic arm leg blood pressure and metabolic measurements.

Results:
Twenty-five patients underwent treadmill testing: 18 with surgical correction, 7 with stent placement. Median age was 13 years (IQR: 11-15.5yrs). The median arm-leg gradient prior to exercise was 12mmHg (IQR: 9.25-21.75mmHg) for surgical patients and 16mmHg (IQR: 3 - 25mmHg) for stented patients. The median peak exercise arm-leg gradient was 28mmHg (IQR:16 - 44mmHg) for surgical patients and 30mmHg (IQR:17.5 - 40mmHg) for stented patients. The median increase in the arm leg gradient with exercise was 16mmHg for surgical patients and 14mmHg for stented patients. Median Actual VO2Max/Predicted VO2Max was 100% for surgical patients compared to 96% for stented patients. Median Actual VO2Max/Predicted VO2Max was 100% for surgical patients compared to 96% for stented patients.

Conclusions:
Few studies have compared surgery and endovascular stenting for coarctation of the aorta, with only one prior study comparing the effects of exercise on blood pressure. Stenting and surgery offer excellent hemodynamic results acutely and at maximal exercise. Stent placement demonstrates equivalent results in blood pressure response during exercise testing when compared to surgical therapy.
Abstract 19124: Ca Overload Induced Pathological Cardiac Remodeling Rescued by Na-ca Exchanger Overexpression
Authors: Li Jing , Li Ying , Zhang Xiaoying M , Cheung Joseph , Chen Xiongwen
Published: April 2024

Aims:
Sarcoplasmic reticulum (SR) Ca2+ overload plays an essential role in pathological cardiac remodeling including hypertrophy, cell death, fibrosis and arrhythmias. Normalization of SR Ca2+ load holds a great promise for the prevention and treatment of heart failure. Here we test this hypothesis by determining if normalization of Ca2+ overload with Na-Ca exchange overexpression in the murine hearts or cultured feline myocytes overexpressing Cav1.2β2a subunit rescues the adverse remodeling and cell death.

Results:
1. In vivo, overexpression of β2a for 4 months induced cardiac hypertrophy (HW/BW, Control: 4.16±0.1mg/g, β2a: 4.64±0.24mg/g) accompanied by cell death and fibrosis while these parameters were largely normalized in NCX-coexpression mice (HW/BW, β2a-ncx: 4.24±0.11mg/g). 2. The structural remodeling was supported by ECHO data showing less increases in left ventricular posterior wall and interventricular septal wall thickness and better preserved cardiac function (fractional shortening: β2a: 30.5±9.8%; β2a-ncx: 48.1±7.85); 3. Patch-clamp studies revealed that β2a transgenic myocytes had larger Ca2+ currents (Control: -12.7±2.1 pA/pF; β2a: -17.3±3.4 pA/pF) and co-expression of NCX did not normalize the increased Ica (β2a-ncx: -15.7±1.5 pA/pF). 4. Overexpressing Cav1.2β2a in cultured feline ventricular myocytes increased ICa significantly (control:-2.1±0.3 pA/pF, β2a:-19.4±5.9 pA/pF, β2a-NCX:-16.4±2.3 pA/pF). 5. Overexpression of β2a in feline cells for 48 h resulted in prominent SR Ca2+ overload (caffeine induced Ca2+ transient peak by Fluo-4: F/F0, control:3.2±1.0, β2a:4.8±1.2) while co-expression of NCX prevented it (β2a-NCX: 3.4±1.3). 6. Prominent cell death was also confirmed in β2a-overexpressing feline myocytes (survival rate: Control: 69.9±9.5%, β2a:26.2±6.4%) and cell death was partially protected by the coexpression of NCX (β2a-ncx: 44.6±5.7%).

Conclusion:
Over-expression of NCX is sufficient for blocking pathological cardiac remodeling as induced by SR Ca2+ overload and may represent a novel therapeutic strategy for heart failure.
Abstract 19178: Cost Effectiveness of Therapeutic Drug Monitoring in Facilitating BP Control in Resistant Hypertension
Authors: Brinker Stephanie K , Pandey Ambarish , Ayers Colby , Raza Fayez , Price Angela , Arbique Debbie , Das Sandeep , Halm Ethan A , Kaplan Norman , Vongpatanasin Wanpen
Published: April 2024

Nonadherence to antihypertensive medications is a major contributor to cardiovascular morbidity and mortality in the U.S. Recent studies have implicated Therapeutic Drug Monitoring (TDM) as a reliable method in monitoring adherence to antihypertensive medications in patients with resistant hypertension (RH) defined as BP 140/90 mmHg despite self-reported adherence to ≥ 3 antihypertensive drugs. However, the relationship between cost of testing and potential benefit of TDM in RH has not been assessed. We performed retrospective analysis of all new patients referred to the University of Texas Southwestern Medical Center Hypertension Clinic with RH between 2009-2012. Of 397 patients referred, 185 met criteria for RH. We found that 32 of 57 patients (57%) had undetectable serum levels of ≥ 1 drug screened, indicating medication nonadherence. Despite higher baseline BP (170/103 for non-adherent vs. 166/87 mmHg for adherent, p < 0.01), the magnitude of BP reduction was significantly greater for non-adherent vs. adherent patients (reduction in SBP 43±7/23±4 mmHg vs. 15±5/5±2 mmHg, p < 0.01) when the nonadherent patients were given feedback regarding their undetectable serum drug levels as part of their care. This greater reduction in BP was not explained by differences in treatment intensification (intensification score 0.02 for adherent vs -0.02 for non-adherent, p = 0.2). The median cost of TDM was $301 (224-544) in the non-adherent group vs. $277(140-375) in the adherent group (p = 0.2). Using bootstrap analysis with 1000 replication, we found the incremental cost per mmHg reduction in BP associated with TDM was $4.9, (3.8, 5.9), which is comparable to cost associated with many antihypertensive devices shown to be effective in reducing BP in resistant hypertension. In summary, our data suggested that therapeutic drug monitoring is cost effective in optimizing BP control in RH.
Abstract 19241: Evolving Techniques and Outcomes in Left Main Pci With Des
Authors: Van Rothem Jérôme , boudou Nicolas , Rosencher Julien , Fajadet Jean , Carrie Didier
Published: April 2024

Objective:
To evaluate the impact of technical evolutions on clinical outcomes for patients undergoing percutaneous coronary intervention (PCI) with drug eluting stent (DES) for left main (LM) disease.

Background:
PCI techniques and materials are improving. Those evolutions could have a positive clinical impact for patients undergoing PCI for LM disease.

Methods:
We compared baseline characteristics, procedural and clinical outcomes in 601 consecutive patients undergoing PCI for LM stenosis with DES from 2004 to 2009. Patients were analyzed in 3 separate groups according to the PCI timing: 2004/2005 (group 1); 2006/2007 (group 2); 2008/2009 (group 3). The primary outcome was death at 1-year.

Results:
Comparing to 2004/2005, patients undergoing PCI in 2008/2009 were at higher risk (Logistic Euroscore 8.4±0.7% in group 3 vs. 7.4±0.6% in group 1; p=0.045). The radial approach was increasingly used (28.2% in 2004/2005; 34.2% in 2006/2007 and 61.4% in 2008/2009; p<0.0001), a predilation was more frequently performed (32.1% in 2004/2005; 42.7% in 2006/2007 and 45.8% in 2008/2009; p=0.046) and a second generation DES was more frequently used (38.2% in group 3 vs. 0% in group 1; p<0.0001). The stent diameter significantly increased with time (3.5±0.02mm in group 1; 3.6±0.02mm in group 2; 3.7±0.02mm in group 3; p<0.0001) and a post dilation was more often performed (32.1% in group 1; 37.9% in group 2; 46.4% in group 3; p=0.021). One-year mortality is significantly decreasing with time (9.9% in 2004/2005; 8.9% in 2006/2007; 4.1% in 2008/2009; p=0.028), and this difference is driven by fewer deaths in patients treated for distal LM (13.2% in 2004/2005; 8.6% in 2006/2007; 4.2% in 2008/2009; p=0.033).

Conclusion:
In this observational study, clinical outcome are improving for patients undergoing LM PCI with DES, because of fewer death at one year for patients with a distal LM lesion.
Abstract 19343: Pharmacokinetic and Triglyceride-Lowering Pharmacodynamic Effects of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) Across Clinical Studies
Authors: Braeckman Rene , Harold Harold E , Ballantyne Christie M , Stirtan William G , Soni Paresh N
Published: April 2024

Background:
Icosapent ethyl (IPE; formerly AMR101) is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester approved to reduce triglyceride (TG) levels in patients with severe (>=500 mg/dL) hypertriglyceridemia.

Objective:
To examine the effects of IPE on EPA concentrations in plasma and red blood cells (RBCs) in response to dose and the relationship to TG lowering across 3 clinical studies.

Methods:
MARINE and ANCHOR were 12-week, phase 3, double-blind studies that randomized patients to IPE 4 g/day, 2 g/day, or placebo. MARINE randomized 229 patients with TG >=500 and <=2000 mg/dL while ANCHOR randomized 702 high-risk patients with TG >=200 and <500 mg/dL despite low-density lipoprotein cholesterol (LDL-C) control while on statin therapy. IPE 4 g/day and 2 g/day was also investigated in 48 healthy subjects for 4 weeks in a phase 1 PK study.

Results:
In all studies, a greater increase in EPA concentrations in both plasma and RBCs was observed with IPE 4 g/day than with 2 g/day, indicating a dose-dependent increase in EPA exposure. EPA concentration data from healthy volunteers and in patients with hypertriglyceridemia indicate that the PK of EPA are linear with dose. In MARINE and ANCHOR, median percent reductions in TG from baseline were higher with IPE 4 g/day than with 2 g/day and demonstrated a dose-proportional relationship. In plasma and RBCs, a linear PD relationship between EPA levels and TG reduction was also observed, demonstrating a linear concentration-response relationship. The figure shows TG median % change from baseline versus EPA mean % change from baseline in plasma from the ANCHOR study (error bars are 95% CIs).

Conclusions:
Taken together, the linear-dose-PK and dose-concentration-response PD relationships indicate that the PK/PD of IPE are predictable as the results demonstrate a trend of increasing TG-lowering efficacy with respect to both the IPE dose and EPA concentration in plasma and RBCs.
Abstract 199: Relationship Between the Blood Hemoglobin Concentration and the Initial Rhythm in Out-of-Hospital Cardiac Arrest (Interim Analysis From SOS-KANTO 2012)
Authors: Suzuki Masaru , Satoh Yukio , Hayashida Kei , Hori Shingo , Tahara Yoshio , Yaguchi Arino , Morimura Naoto , Nagao Ken ,   SOS-KANTO 2012 Study Group
Published: April 2024

BACKGROUND:
Tissue metabolism that is reflected by oxygen consumption is regulated by the blood hemoglobin concentration (Hb) and cardiac output. Cardiac output during cardiac arrest has been suggested to be related to the quality of CPR. Although Hb might theoretically play a crucial role in maintaining tissue metabolism during cardiac arrest, this has not yet been well studied. If myocyte metabolism during cardiac arrest were affected by Hb, the sustainability of myocytes’ electrical activities may be correlated with the Hb.

HYPOTHESIS:
The probability of asystole being observed as the initial rhythm by emergency personnel at the scene of a cardiac arrest (CA) is higher in cardiac arrest patients with lower Hb than in those with higher Hb.

METHODS:
In an interim analysis of the data in the SOS-KANTO 2012 Study, a multicenter prospective observational study, there were 6,019 CA registrations in the KANTO area, Japan. Of these, Hb was checked in 4,611 cases. Of the 4611 cases, there were 705 subjects 15 years old or over of out-of-hospital CA with a presumed cardiac etiology, in whom the CA was confirmed by emergency personnel at the scene and who were identified as having no disabilities of daily living. Of the 705, 130 males who received bystander chest compressions in whom Hb ranged between 5.0 and 20 g/dl (median 13 g/dl) were included in this study.

Results:
Of the 130 cases, asystole and VE/VT were confirmed as the initial rhythm at the scene by emergency personnel in 39 (30%) and 61 (47%) cases, respectively. Hb was lower in the asystole group than that in the non-asystole group (12.3+/-2.7 g/dl vs. 13.3+/-2.6 g/dl, P=0.04). A multivariate logistic regression analysis showed that Hb and later arrival of emergency personnel at the scene of emergency collapse were independent predictors of identification of asystole as the initial rhythm at the site of CA (odds ratio [95%CI]: 0.82 [0.75-0.90], P<0.01, 1.18 [1.06-1.30], P<0.01, respectively).

CONCLUSIONS:
Lower Hb in the blood was associated with a higher likelihood of asystole at the scene of CA. Our findings suggested that VF/VT and/or PEA easily disappear and change to asystole in victims with lower Hb, although further study is needed.
Abstract 206: Characterization of Glycocalyx Shedding in Trauma Patients
Authors: Rahbar Elaheh , Baer Lisa A , Cotton Bryan A , Holcomb John B , Wade Charles E
Published: April 2024

Background:
The endothelial glycocalyx layer is a key regulator of vascular permeability, cell adhesion, and inflammation. This organized mesh of membranous proteins is primarily composed of syndecan-1, hyaluronic acid (HA), heparan sulfate (HS) and chondroitin sulfate (CS). While many studies have observed increased shedding of syndecan-1 during hemorrhagic shock, none have investigated the other three components of the glycocalyx in response to injury. In this study, we characterized the shedding of all four primary components of the glycocalyx in trauma patients.

Methods and Results:
Plasma samples were collected from five healthy consented volunteers and 20 severely injured trauma patients upon admission to the emergency department. ELISA assays were performed to determine amounts of shed HA, HS, CS and syndecan-1 in plasma. Oncotic pressure and serum protein levels were also measured. Initial vital signs, routine laboratory values, and injury severity scores (ISS) were recorded. ANOVA was used to compare statistical significance between groups; median values are reported. We observed increased shedding of all four components compared to normal controls: 32.3 vs. 23.1 U/L of CS, 180 vs. 136.1 ng/ml of HS, 29.2 vs. 11.6 ng/ml of HA and 45.8 vs. 27 ng/ml of syndecan-1 (p<0.05). Further, we found a correlation between ISS, plasma oncotic pressure, shed syndecan-1 and HA levels. Patients with reduced oncotic pressure (<16 mmHg) had exponentially increased shedding of syndecan-1 (221.7 vs. 34.6 ng/ml, p=0.03) and HA (146 vs. 23.4 ng/ml, p=0.02), which correlated to higher ISS (34 vs. 19, p=0.04) compared to those with normal oncotic pressures. Surprisingly, CS and HS levels did not correlate with ISS and remained constant for all trauma patients.

Conclusions:
All four components of the glycocalyx are shed in trauma patients compared to normal controls. However, only syndecan-1 and HA shedding strongly correlated with increased severity of anatomic injury and reduced plasma oncotic pressure. These data suggest that syndecan-1 and HA could play a role in the restoration of the glycocalyx during hemorrhagic shock and resuscitation, especially in more severely injured patients who experience glycocalyx shedding and increased membrane permeability.
Abstract 243: High Survival Rate of Patients Following In-Hospital Cardiac Arrest in Center Hospital for Cardiac and Cerebrovascular Diseases: A Single-Center Prospective Observational, Utstein Style Study
Authors: Sakamoto Shingo , Yokoyama Hiroyuki , Harada Koichiro , Kawarada Osami , Yamane Takafumi , Ishibashi Kohei , Matsumoto Manabu , Ishihara Masaharu , Yasuda Satoshi , Ogawa Hisao
Published: April 2024

Background:
In-hospital cardiac arrest (IHCA) is a significant public health problem with a low survival rate of approximately 15-20% in general hospitals. However, few data are available on the clinical outcome of patients following IHCA in the center hospital for cardiac and cerebrovascular diseases.

Methods:
Between June 2006 and May 2013, Utstein style resuscitation data were prospectively collected on 535 consecutive patients aged 18 years or older who developed IHCA in National Cerebral and Cardiovascular Center (Osaka, Japan). Of these, we excluded 95 patients with multiple cardiac arrests (only the first episode was included) and also excluded 9 patients due to the lack of 30-day follow-up data. We finally assessed the data of the clinical characteristics and 30-day survival of 428 patients.

Results:
The number of patients who were hospitalized due to cardiac diseases and cerebrovascular diseases was 293 (68.5%) and 84 (19.6%), respectively. The location of hospital where IHCA developed was intensive care unit in 153 (35.7%), general ward in 157 (36.6%), emergency department in 54 (12.6%) and others in 64 (15%). Importantly, the majority of IHCA (n=379, 88.5%) occurred under the monitoring of electrocardiography. The first documented rhythm was pulseless electrical activity in 215 (50.2%), asystole in 77 (18%), ventricular fibrillation (VF) in 73 (17.1%), and pulseless ventricular tachycardia in 63 (14.7%). In only 4 patients who were not originally monitored, an automated external defibrillator was used following documentation of VF as initial rhythm of IHCA. Overall, the 30-day survival rate was 38%. The presence of electrocardiography monitoring was associated with higher survival rate than the absence of monitoring (39.5% vs. 22.4%, P=0.02). However, the survival rate was not significantly affected by the location of hospital, time (day vs. night), and day of the week (weekday vs. weekend).

Conclusions:
The survival rate following IHCA seems to be high in the center hospital for cardiac and cerebrovascular diseases in comparisons with the previous reports from general hospitals. The present finding of over 30% survival indicates the potential impact of electrocardiography monitoring for particular patients with risk for IHCA.
Abstract 270: Developing a Ventricular Fibrillation Cardiac Arrest Rat Model - Pitfalls and Challenges
Authors: Ettl Florian , Magnet Ingrid A , Weihs Wolfgang , Warenits Alexandra , Grassmann Daniel , Wagner Michael , Sipötz Johann , Teubenbacher Ursula , Sterz Fritz , Janata Andreas
Published: April 2024

Introduction:
The ideal rodent model of ventricular fibrillation (VF) cardiac arrest (CA) produces consistent histologic and neurologic damage as target for novel therapies and shows a high survival rate to minimize animal use and allow for long term outcome. VF induction, chest compressions and ventilation are crucial techniques and published in many variants in literature. We report our experiences during model development.

Materials and Methods:
A non-randomized cohort study evaluating different methods of VF induction, chest compressions techniques, mechanical ventilation and defibrillation was performed with regards to it’s feasibility, complications, ROSC rate and survival.

Results:
Male Sprague-Dawley rats (350g, anesthetised, instrumented) underwent VF induction with 2 min endocardial fibrillation via a transjugular neonatal pacing catheter with minimal current use, low incidence of autodefibrillation and good resuscitability. Mechanical chest compressions with approx. 30% of thorax diameter depth were applied with a pneumatic thumper 200/min placed mid-sternally, tilted upwards. Strong fixation with tapes avoided throrax-instability. Epinephrine (20μg/kg) and NaHCO3 (1mmol/ kg) were administered before CPR start and epinephrine repeatedly given after defibrillations every 2min. For defibrillations (5J, biphasic) modified paediatric defi pads were used.

ROSC was achieved in 7/10 animals in a 6 min CA group and 6/11 in a 8 min CA group. CPR time was 2.6±1.0 min (mean±SD), number of defibrillations needed 2±1 and a cumulative epinephrine dose of 46±10 μg/kg with no differences between groups.

Conclusions:
Researchers developing a VF CA model are facing a multitude of difficulties, a lack of data on model development and many variations published in literature, often without detailed description. We developed a CPR rat model for VF CA with graded cognitive deficits and long-term survival. We propose detailed description of model development, including ineffective methods, to facilitate experience exchange between research groups, to avoid that future experimental groups repeat possible mistakes.
Abstract 301: Tc-99m ECD SPECT Brain Perfusion as a Novel Indicator Predicting Neurological Prognosis in Patients Resuscitated From Cardiac Arrest
Authors: Chang Wei-Tien , Yu Ping-Hsun , Wu Yen-Wen , Cheng Mei-Fang , Huang Chien-Hua , Yuan Ang , Tsai Min-Shan , Wang Chih-Hung , Kao Hsiu-O , Ma Matthew Huei-Ming , Chen Shyr-Chyr , Chen Wen-Jone
Published: April 2024

Background:
To date there are limited prognostic indicators that well predict the neurological outcomes in patients resuscitated from cardiac arrest.
99m
Tc-ethylcysteinate dimer (ECD) brain perfusion scan has been shown to implicate the viability of neurons. We therefore investigate the role of this novel indicator in predicting post-resuscitation neurological prognoses.

Methods:
Post-cardiac arrest patients who remained unconsciousness after CPR were prospectively enrolled from Jan. 2010 to May 2013. Brain perfusion scan with
99m
Tc ECD SPECT were performed within 3-10 days post-CPR. All images were interpreted and scored independently by two nuclear medicine physicians blinded to the patients’ clinical information. Nine distinct regions of the brain were scored, including upper brain stem and bilateral thalamus, basal ganglia, cerebral cortex and cerebellum. The scores ranged from 0 (normal) to 4 (worst), and were correlated with all clinical factors and the neurological outcome of the patients.

Results:
Ninety-one patients (64.1 ± 16.3 years old; 62 men) were enrolled during the study period. Fifty-nine survived to hospital discharge and 23 had neurological recovery with cerebral performance category (CPC) scale 1 or 2. Younger age, Vf/VT, shorter CPR time, lower epinephrine dose and therapeutic hypothermia were associated with good neurological recovery. For brain perfusion scan, the scores in all 9 areas were significantly lower in patients with good neurological recovery (all
P
< 0.05). Patients receiving therapeutic hypothermia (n=69) had better survival and neurological outcomes (both
P
< 0.05). The
99m
Tc ECD perfusion was significantly better in the upper brain stem and bilateral basal ganglia in these patients (all
P
< 0.05). In binary logistic regression analysis, the
99m
Tc ECD perfusion in the upper brain stem, together with age, Vf/VT and CPR time, served as independent prognostic factors for neurological recovery. The perfusion score of greater than 2 in the upper brain stem exclusively predicted a poor neurological prognosis.

Conclusions:
99m
Tc ECD brain perfusion may serve as a novel independent indicator for post-resuscitation neurological prognosis. Poor perfusion in upper brain stem predicts a poor neurological outcome.
Abstract 338: Therapeutic Hypothermia for Patients With Post-Resuscitation Shock After Out-of-Hospital Cardiac Arrest
Authors: Soga Taketomo , Nagao Ken , Yokoyama Hiroyuki , Yonemoto Naohiro , Nonogi Hiroshi ,   J-PULSE-Hypo investigators
Published: April 2024

Background:
Animal data have suggested a beneficial effect of therapeutic hypothermia following return of spontaneous circulation (ROSC) (post-ROSC cooling) in cardiogenic shock, but there are few human studies of patients with post-resuscitation shock who were treated with post-ROSC cooling.

METHODS:
From the J-PULSE HYPO registry, a multi-center registry in Japan, we selected the patients who met the following inclusion criteria: bystander-witnessed cardiac arrest due to ventricular fibrillation (VF), target core temperature of 32-34°C, and cooling duration of 12-72 hours. Study patients were divided into two groups based on hemodynamic status. The post-resuscitation shock group consisted of patients with systolic blood pressure < 90 mmHg and/or mechanical circulation support. The remaining patients constituted the non-shock group. The primary endpoint was favorable neurological outcome at 30 days after cardiac arrest.

Results:
Of the 452 adult patients treated with post-ROSC cooling, 292 met the inclusion criteria; 149 (51%) were post-resuscitation shock and 143 (49%) were non-shock. No significant difference was observed between the two groups in the frequency of 30-day favorable neurological outcome (63% [94/149] post-resuscitation shock group vs. 68% [97/143] non-shock group; p=0.39). However, the median collapse-to-ROSC interval was significantly longer in the post-resuscitation shock group than in the non-shock group (27 minutes vs. 20 minutes, p<0.001). In the quartiles of collapse-to-ROSC interval and 30-day favorable neurological outcome, both groups exhibited high frequencies of 30-day favorable neurological outcome in Quartile 1, in which the collapse to ROSC interval was 15 minutes or less (93% post-resuscitation shock group vs. 87% non-shock group, p=0.40), and a significant decrease in 30-day favorable neurological outcome was found in each group as the quartile value of collapse-to-ROSC interval increased (p<0.001, respectively). The 30-day favorable neurological outcome in each Quartile 2, 3 and 4 did not differ between the two groups.

Conclusion:
Due to the effects of post-ROSC cooling, post-resuscitation shock patients were able to achieve the same level of neurological benefit as non-shock patients.
Abstract 351: The Family Study: Assessment of the Risk for Sudden Cardiac Arrest in Family Members of Cardiac Arrest Patients
Authors: Allan Katherine S , Aves Theresa , Morrison Laurie J , Tu Jack , Guttman Matthew , Dorian Paul
Published: April 2024

Background:
Sudden cardiac arrest (SCA) is devastating for the patient’s family, friends, and community. There is limited information on its identifiable familial predisposition.

Objectives:
To evaluate the familial risk pattern for SCA in family members of cases compared to age-and-sex matched control groups. Incidence of prior symptoms and SCA triggers were also compared.

Methods:
We used a prospectively collected, population-based registry of all out-of-hospital cardiac arrests (OHCAs) in the Greater Toronto Area, to identify cases from 2010-2012. Cases were defined as SCA patients aged 18-65 who arrested from a cardiac cause and were treated by Emergency Medical Services. Two relatives per patient were interviewed regarding symptoms prior to the arrest, cardiac history and family history of SCA. Control patients with known coronary heart disease (CHD) and healthy participants were recruited from PCI procedures and the Family Practice Units at St. Michael’s Hospital.

Results:
Complete family and medical history was obtained for 66 SCA cases, 56 heart disease patients and 27 healthy controls. Underlying diseases were CHD in 77%, non-CHD structural heart disease in 9%, primary arrhythmic in 3% and presumed cardiac of unknown etiology in 11%. A higher proportion of SCA individuals had a family history of SCA in 1st degree relatives (19/66; 28.8%) than 1st degree relatives of healthy controls (2/27; 7%; p=0.006) and 1st degree relatives of patients with heart disease (14/56; 25%) (Table 1). Among families with SCA, 3/66 (4.5%) had a history of >1 relative with SCA, vs. none in either control group. Most SCA patients experienced one or more warning symptoms in the hour preceding an arrest (40/66; 61%); 24/66 (36%) experienced a cardiac arrest during or following exercise.

Conclusion:
Family members of SCA patients have a higher SCA prevalence than family members of healthy controls. A high proportion of SCA patients experienced symptoms in the hour preceding their arrest.
Abstract 352: Risk Index of Sudden Death by Long QT Syndrome and Wolff-Parkinson-White Syndrome in School
Authors: Ayusawa Mamoru , Sumitomo Naokata
Published: April 2024

Objectives:
To clarify the epidemiological risk of sudden death by QT prolongation and WPW syndrome in school life.

Materials and Methods:
Based on the data reported to the mutual aid insurance system for school from 1993 to 2009, sudden deaths of long QT syndrome and WPW syndrome those who had been found by screening system in school. Epidemiological data was compared. Prevalence of both diseases found in the screening system in this period to calculate the risk index of sudden death was compared in both diseases.

Results:
The prevalence of QT prolongation was 0.14 in 1,000. Fourteen sudden death cases were reported in 17 years, girls occupied 58.8%. Seven cases were in elementary school, and five cases in middle school students. Time zone is known in eight cases, six cases are in the morning, two cases in the afternoon.

The prevalence of WPW syndrome found by screening system was 1.07 in 1,000. Eighteen sudden death cases were reported in 17 years, girls occupied 16.7%, one case in elementary school; two cases in the junior high school, and 15 cases were high school students. Time zone is known in six cases, all cases occurred in the afternoon.

The number of sudden death in each disease divided by prevalence found by screening system was 8.6 in QT prolongation cases, and 1.2 in WPW syndrome cases.

Risk of sudden death by QT prolongation was about seven times of WPW syndrome.

Conclusion:
This index is informative for a better understanding to the description of the risk need for attention of family, students and caregivers in schools.
Abstract 361: Time Interval From Collapse to Return of Spontaneous Circulation and Neurologically Intact Survival for Out-of-Hospital Shockable (Ventricular Fibrillation or Pulseless Ventricular Tachycardia) Cardiac Arrest
Authors: Nagao Ken , Tachibana Eizo , Yagi Tukasa , Yonemoto Naohiro , Takayama Morimasa , Tani Sigemasa , Nonogi Hiroshi , Shirai Shinichi , Kimura Takeshi
Published: April 2024

Background:
Early achievement of return of spontaneous circulation (ROSC) after cardiac arrest is critical to neurologically intact survival, but few data are available concerning this interval for shockable cardiac arrest (ventricular fibrillation or pulseless ventricular tachycardia).

Methods:
From the All-Japan Utstein Registry, a prospective, nationwide, population-based registry of out-of-hospital cardiac arrest (OHCA) between 2005 and 2011, we included adult patients who received resuscitation care after witnessed OHCA due to shockable arrest, whose ROSC was achieved before hospital arrival and who received post cardiac arrest care after hospital arrival. We evaluated the relationship between the collapse-to-ROSC interval and favorable neurological outcome 30 days after cardiac arrest.

Results:
Of the 31,845 patients who achieved ROSC after witnessed OHCA, 11,621 (36.5%) achieved ROSC after shockable cardiac arrest. Of these, 54.5% (6,187/11,621) had a 30-day favorable neurological outcome. The favorable group had a significantly shorter collapse-to-ROSC interval compared to the unfavorable group (13.5±8.2 vs. 19.2±10.7 minutes, p<0.0001). After adjustment for resuscitation, the likelihood of favorable neurological outcome decreased for every 1 minute increment in the collapse-to-ROSC interval (adjusted OR; 0.94, 95% CI, 0.93 to 0.94). Non-linear regression analysis showed that frequency of favorable neurological outcome decreased from 76.4% to 0% for every minute that passed between collapse and ROSC. For favorable neurological outcome, a collapse-to-ROSC interval of 57.5 minute had a sensitivity of 100% with a negative predictive value of 99.8%. Furthermore, a collapse-to-ROSC interval with a sensitivity of 100% for favorable neurological outcome was 55.5 minutes in patients receiving bystander CPR, and 58.5 minutes in patients not receiving bystander CPR.

Conclusion:
Resuscitation efforts to achieve ROSC, contributing to neurologically intact survival, are needed for about 60 minutes for patients with witnessed out-of-hospital shockable cardiac arrest irrespective of bystander CPR attempt.
Abstract 5: Secular Trends in Community Cardiac Arrest Survival: Results From the Resuscitation Outcomes Consortium (ROC)
Authors: Daya Mohamud R , Schmicker Robert , Zive Dana , Rea Thomas , Christenson James , Nichol Graham , May Susanne , MacPhee Renee , Rittenberger Jon , Buick Jason E , Brooks Steven , Craig Alan , Davis Dan P , Wigginton Jane , Wang Henry E
Published: April 2024

Background:
The Resuscitation Outcomes Consortium (ROC) is a research network evaluating interventions in out-of-hospital cardiac arrest (OHCA) which maintains an epidemiologic registry of consecutive cases of OHCA assessed by emergency medical services (EMS) agencies. ROC has completed 3 cardiac arrest clinical trials with no significant survival differences. However, we hypothesize that OHCA survival may have changed over time due to participation in ROC.

Objectives:
To evaluate changes in OHCA survival to hospital discharge over time in ROC sites.

Methods:
We included OHCA cases treated by 139 participating EMS agencies between 1/1/06-12/31/10. We excluded cases with definite non-cardiac etiology and months with incomplete case capture. The association between survival and year was assessed using multi-level mixed effects logistic regression with agency nested in region and region nested in site. Covariates included: age; sex; EMS response interval; witness status; bystander CPR; location of arrest and first rhythm. We used an independent covariance structure with random intercepts.

Results:
Mean EMS response interval, median age and male gender proportion were similar over time. Survival to hospital discharge increased over time for treated cases between 2006 and 2010, as well as for the subgroups of VT/VF and witnessed VT/VF (Table). Survival increase compared to 2006 remained significant for each subsequent year after covariate adjustment with OR’s (95% CI) for survival in 2010 of 1.73 (1.52, 1.95) for all cases, 1.66 (1.42, 1.95) for VT/VF and 1.59 (1.33, 1.89) for witnessed VT/VF. Test for trend according to year was significant for all cases and among the VT/VF subgroups (p=<0.001).

Conclusion:
Survival from OHCA increased over time within the ROC research network despite a lack of survival differences in the clinical trials. Further research is required to identify the specific factors associated with this improvement.
Abstract 11565: The Unfolded Protein Response Directly Activates the Hexosamine Biosynthetic Pathway to Protect the Heart from Ischemia/Reperfusion Injury
Authors: Wang Zhao V. , Deng Yingfeng , Gao Ningguo , Pedrozo Zully , Li Dan L. , Tan Wei , Jiang Nan , Lehrman Mark A. , Rothermel Beverly A. , Lee Ann-Hwee , Lavandero Sergio , Ferdous Anwarul , Gillette Thomas G. , Scherer Philipp E. , Hill Joseph A.
Published: April 2024

Zhao Wang, 2013 Finalist and Presenting Author
Acute Aortic Syndromes: New Insights From IRAD and GenTAC Registries
Authors: Eagle Kim
Published: April 2024

In his presentation entitled “Acute Aortic Syndromes: New Insights from IRAD and GenTAC Registries”, Dr. Eagle will review the latest in the approaches to diagnosis and treatment of acute aortic syndromes and thoracic aortic disease. In particular, new insights as to the underlying causes of aortic syndromes, the optimal use of biomarkers, and the evolving role of genetics as it relates to diagnosis and screening will be emphasized. In addition, recent advances in best medical and interventional therapy for thoracic aortic disease will be discussed. Finally, Dr. Eagle will discuss where translational and imaging research advances are likely to shape the future care for patients with or at risk for thoracic aortic disease.