bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18910: Deciphering and Exploiting Transcriptome-Wide MicroRNA Binding Profiles in Human Tissues
Authors: Boudreau Ryan L , Jiang Peng , Gilmore Brian L , Spengler Ryan M , Nelson Jay , Ross Christopher A , Xing Yi , Davidson Beverly L
Published: April 2024

The orchestration of complex biological functions requires gene regulatory networks that are modulated, in part, by microRNAs (miRNAs). During the past decade, miRNAs have emerged as key biological effectors, and growing evidence indicates that miRNAs play critical roles in an array of human diseases, including neurological and cardiovascular conditions. These noncoding RNAs associate with Argonaute (Ago) proteins to direct post-transcriptional gene suppression via base-pairing with target transcripts. To better understand how miRNAs contribute to protective and pathogenic responses to disease, identifying their targets in affected tissues is of paramount importance. As an initial step towards addressing the latter, we profiled Ago2:RNA interactions using crosslinking immunoprecipitation coupled with high-throughput sequencing (CLIP-seq) to generate the first transcriptome-wide map of miRNA binding sites in a human primary tissue, the brain. We uncovered ~7000 stringent Ago2 binding sites which are highly enriched for conserved sequences corresponding to abundant brain miRNAs. This dataset points to functional miRNA:target pairs across more than 3000 genes and represents a valuable resource for accelerating our understanding of miRNA function in the central nervous system, and beyond. We explored this interactome for clinically-relevant miRNA binding sites and discovered sites overlapping single nucleotide polymorphisms linked to common and rare neuropsychiatric conditions, including Parkinson’s and Alzheimer’s. In addition, we identified nearly 50 miRNA target sites across 20 genes previously implicated in stroke and arterial disease. These findings provide clues which may facilitate the discovery of novel and refined pathogenic mechanisms and therapeutics for complex diseases of the brain and vasculature. Overall, this work lays the foundation for translating this methodology to characterize the diverse landscapes of miRNA:target interactions across normal and diseased human tissues, particularly heart, where miRNAs are well-established mediators of cardiac development and disease.
Abstract 18975: Increased Arterial Blood Pressure and Vascular Fibrosis/remodeling in Mice Lacking Salt-inducible Kinase 1 (sik1)
Authors: Brion Laura , Pires Nuno , Igreja Bruno , Pinho Maria Joço , Wågsäter Dick , Wikström Johannes , Behrendt Margareta , Hamsten Anders , Eriksson Per , Soares-da-Silva Patricio , Bertorello Alejandro M.
Published: April 2024

Arterial fibrosis is one of the main underlying causes of vascular stiffness and is increasingly recognized as an important prognostic factor in the development of high blood pressure (BP), yet its physiophatology is not fully known. Therefore, elucidating the precise mechanism leading to arterial fibrosis will help improving current anti-hypertensive therapies. We previously described in human genetic studies a single nucleotide polymorphism within the salt-inducible kinase 1 (SIK1) gene, affecting the activity of the protein, which is associated with hypertension (lower SIK1 activity is associated with higher BP). Also, lower SIK1 expression induces the expression of transcription factors commonly involved in fibrosis. Therefore, we hypothesized that SIK1 can regulate BP by reducing vascular fibrosis and hence vascular stiffness. To test this, BP and aortic wall structure/composition was evaluated in

sik1
-/-

and

sik1
+/+

mice challenged with a chronic high salt (HS) or normal salt diet (NS). The results showed that the
s

ik1
-/-

mice challenged with HS developed high BP and presented signs of cardiac hypertrophy (increased left ventricle wall thickness and enhanced expression of hypertrophic genes) when compared to their counterparts on NS. On the contrary, BP and cardiac parameters remained unaffected in the

sik1
+/+

mice under HS when compared to NS fed mice. Immunohistochemistry analysis revealed increased intima/media thickness and collagen deposition in the aorta of the

sik1
-/-

vs.

sik1
+/+

mice under NS and before becoming hypertensive. Also, qPCR analysis of the aorta of the

sik1
-/-

mice showed increased expression of other extracellular matrix (ECM) components such as fibronectin and laminin-β1. In addition, the transient knock-down of the SIK1 gene in vascular smooth muscle cell (VSMC) cultures using siRNAs showed a similar increase in the expression of collagen as well as other ECM genes. The present study shows that SIK1 activity is necessary to prevent the development of hypertension, possibly through an anti-fibrotic mechanism regulating vascular wall structure and function. Therefore, SIK1 could become a novel therapeutic target in the treatment of hypertension and other vascular fibrosis-associated diseases.
Abstract 18978: Predictive Modeling of 30-day Readmission of Heart Failure Patients Using Admit Labs, Early Clinical Tests, and History and Physical Exam for In-Hospital Modification of Readmission Risk
Authors: Horne Benjamin D , Budge Deborah , Benuzillo José G , Bradshaw Alejandra , Bair Tami L , Roberts Colleen A , Rasmusson Kismet D , Nixon Jen , Alharethi Rami , Kfoury Abdallah G , Lappé Donald L
Published: April 2024

Background:
All 30-day readmission risk models created to date use hospital discharge data gathered at the end of a hospital’s direct patient impact. Since 30-day readmission penalties are charged to hospitals, predictive models should use data from the time of index admission. This study created risk scores for 30-day readmission from factors available at admission among heart failure (HF) patients.

Methods:
HF patients aged 65 years or older who were admitted as inpatients to Intermountain Healthcare hospitals from 2005-2012 and not discharged to hospice were studied. Data included 205 predictor variables gathered within 24 hours of index admission and the 30-day readmission outcome. Patients were randomly divided into derivation (70%) and validation (30%) groups. Logistic regression was used to build sex-specific predictive models for 30-day readmission, including all variables (full model), only clinical and H&P factors (clinical model), and only laboratory tests (lab model).

Results:
C-statistics for Intermountain HF risk scores (iHF) were greater than previous 30-day readmission models for HF patients (Table). Odds ratios (OR) for 30-day readmission for iHF (full model) in validation patients were, for females, OR=1.77 (95% CI=1.17, 2.66; p=0.007) and OR=1.62 (CI=1.07, 2.45) for tertiles 3 vs. 1 and 2 vs. 1, respectively. Among males in the validation group, the iHF full model had OR=2.28 (CI=1.53, 3.38; p<0.001) for tertile 3 vs. 1 for 30-day readmission and, for tertile 2 vs. 1, OR=1.59 (CI=1.05, 2.41). Clinical and lab models were also very predictive despite using a reduced set of variables.

Conclusions:
The iHF readmission risk scores strongly stratified 30-day readmission risk using HF patient data available within 24 hours of index hospital admission. Discrimination was better than other HF 30-day readmission models, including those created for CMS. Use of iHF at the time of admission empowers hospital-based modification of 30-day readmission risk.
Abstract 19000: Shear Stress Responsive PKCe Modulates Mitochondrial Redox State With an Implication in Vascular Repair
Authors: Beebe Tyler , Jen Nelson , Lee Juhyun , Li Rongsong , Ping Peipei , Hsiai Tzung K
Published: April 2024

Pulsatile (PSS) versus oscillatory (OSS) shear stress differentially modulates mechano-signal transduction with implications in atheroprotection and atherogenesis. In response to ischemia and reperfusion injury, Protein Kinase C isoform epsilon (PKCε) signaling in mitochondria confers cardioprotection. It is unknown whether PKCε was shear stress responsive via endothelial growth factor receptor (VEGFR) signaling with an implication in vascular endothelial repair. Both PSS (time-averaged shear stress (τave) = 25 dyne/cm2 at 1 Hz for 4 hr) and OSS (τave= 0.1±3 dyne/cm2 at 1 Hz for 4 hr) up-regulated PKCε mRNA by 1.7±0.2-fold and 1.5±0.1-fold in human aortic endothelial cells (HAEC), respectively, and protein expression by 1.5±0.1-fold and by 1.4±0.1-fold, respectively, which were inhibited in the presence of VEGFR-inhibitor, Cediranib (p < 0.05, n=4). Treatment with VEGF (100ng/ml) further up-regulated PKCε mRNA expression by 2.3±0.2-fold at 1 hour (p < 0.01, n=3). Matrigel assays revealed that both PKCε siRNA knockdown and VEGFR inhibitor disrupted endothelial tube formation in terms of reduction in tube lengths by 3.0±0.2-fold and by 3.8±0.2-fold, respectively, whereas over-expression of PKCε via adenovirus transfection rescued the formation in the presence and absence of VEGF inhibitor (p < 0.02, n=3). Furthermore, H2O2 increased MitoSox intensity for mitochondrial O2.- production (mtO2.-) by 1.4±0.2-fold, which was significantly attenuated by Adv-PKCε over-expression (p < 0.01, n=3). H2O2-induced mtO2.- production further disrupted tube formation, which was restored in the presence of Adv-PKCε over-expression. The phenotypic effect of PKCε was further recapitulated in the Tg(fli1:EGFP) transgenic zebrafish model, in which treatment with morpholinos to block either splicing or translation were used to inhibit PKCε protein expression, which interrupted repair of intersegmental vessels (ISV) after 3 days post tail amputation (n=6). Thus, our findings suggest that PKCε was shear stress responsive via endothelial growth factor receptor (VEGFR) signaling with an implication in vascular endothelial repair.
Abstract 19006: Peripartum Aortic Dissection in Women With Marfan Syndrome
Authors: Morris Shaine A , Shamszad Pirouz , Franklin Wayne J , Braverman Alan C , Milewicz Dianna M
Published: April 2024

Purpose:
There is a known increased risk of aortic dissection (AD) in Marfan Syndrome (MFS) during pregnancy, although quantification of that risk has been difficult to obtain. The purpose of this study was to assess the incidence of AD in pregnant women with MFS and to compare the risk in MFS to other known risk factors.

Methods:
The Texas Inpatient Public Use Data File (TIPUDF) contains administrative data on the majority of Texas hospital discharges. Inclusion criteria were all TIPUDF discharges 1999-2012 associated with pregnancy, including antepartum status, delivery, or postpartum status using designated ICD9 codes. Patients with MFS were then identified, as were patients with aortic dissection or rupture. MFS patient admissions were reviewed for readmission and repeat pregnancy by matching zip code, age, and race. Diagnoses of Turner Syndrome (TS), Ehlers-Danlos Syndrome (EDS), bicuspid aortic valve (BAV), coarctation, other aortic valve disorders, atherosclerosis, hypertension (HTN), and cocaine use were also identified.

Results:
Of >37 million admissions, 5286576 were associated with pregnancy. Among those, there were 208 admissions in 152 patients with MFS, representing 171 pregnancies. Aortic dissection was coded in 41 admissions, representing 38 total ADs. Six ADs were in MFS, for an incidence in MFS and pregnancy of 3.5%. No AD was reported in TS, EDS, or BAV, although 2 events were in patients with isolated aortic valve disorders. The majority of the MFS AD events were post-partum (n=5), 3 of which were on an admission coincident with delivery. The site of AD was thoracic or thoracoabdominal in 5 (85%), with 1 limited to the abdomen, compared to abdominal site only in 40% of the non-MFS pregnant women with AD. After controlling for HTN and other known risk factors, there was a high risk for AD in MFS pregnancies compared to non-MFS pregnancies (OR >1000 [95%CI >999 to >999]. All MFS AD patients survived, although overall mortality in AD with pregnancy was 10.5%.

Conclusions:
Although AD is rare in pregnancy, it is common in pregnant women with MFS, often occurring postpartum. Careful reproductive planning and close cardiac monitoring during pregnancy, but also after delivery in MFS are warranted.
Abstract 19109: Hypoxia-Induced Reprogramming of Exosomal MicroRNAs From Human CD34+ Progenitor Cells Promotes Its Angiogenic Activity and Ischemic Tissue Repair
Authors: Sahoo Susmita , Gupta Rajesh , Misener Sol , Kim David , Vaughan Douglas E , Losordo Douglas W
Published: April 2024

Introduction:
In early clinical trials, human CD34+ stem cells have been shown to improve exercise tolerance in pts with myocardial ischemia and reduce amputation rates in pts with critical limb ischemia. Recently, we have demonstrated that adult human CD34+ stem cells secrete microRNA containing membrane bound nanovesicles called exosomes (Exo) that mimic the angiogenic and therapeutic activity of the cells.

We hypothesized that the regenerative efficacy of the cell-free Exo derived from human CD34+ cells can be improved by hypoxic pre-conditioning, modulating its pro-angiogenic miRNA content.

Methods and Results:
Exo from human peripheral blood-derived CD34+ cells cultured under hypoxia (H-Exo) were significantly more proliferative, anti-apoptotic and angiogenic in vitro, as compared to Exo from cells under normoxia (N-Exo). Treatment with H-Exo significantly improved perfusion (ratio: 0.93±0.05 v 0.77±0.02), increased capillary density (1.6±0.2 v 1.1±0.1/HPF) and prevented ischemic limb amputation (0% v 37.5%) as compared to N-Exo (p<0.05; n=7-8), in a mouse model of hind limb ischemia. H-Exo were not significantly different in size, quantity of Exo secreted per cell, or, in the expression of major proteins as compared to N-Exo, measured using DLS and 2-D differential gel electrophoresis (DIGE) and mass spectrometry analyses. Interestingly, H-Exo had significantly higher expression of several pro-angiogenic miRNAs. Trafficking studies using confocal microscopy and flow cytometry revealed that fluorescent-labeled CD34 Exo were selectively internalized by endothelial cells in the ischemic tissue and directly transfer pro-angiogenic miRNA content, inducing cell cycle changes and cell division in the recipient endothelial cells. Currently, we are investigating the role of transcription factors in hypoxia-induced miRNA expression.

Conclusion:
Hypoxia modulates the miRNA content of adult human CD34+ progenitor cell-derived exosomes improving their angiogenic and therapeutic potency. Use of hypoxia to enhance microRNA composition of CD34+ exosomes could have important clinical implications for therapeutic angiogenesis, especially in diabetic and cardiovascular patients with compromised stem cell population.
Abstract 19112: Retardation of Progression of Mild Aortic Stenosis (AS) by Angiotensin or Aldosterone Antagonism
Authors: Waldo Oral , Parikh Pragnesh P , Blackshear Joseph
Published: April 2024

Aortic stenosis is the most common acquired valvular heart disease. Currently, there are no medications approved to slow its progression. We set out to investigate the effect of ACE inhibitors/angiotensin receptor blockers and aldosterone antagonists on the rate of progression of mild aortic stenosis. We retrospectively reviewed the charts of 2,613 patients over 45 years old, who had a peak velocity between 1.8 and 3 meters/second on initial echo. Over 8 years of followup, 491 patients were prescribed angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) and 130 patients were prescribed aldosterone receptor blockers. Patients prescribed ACE inhibitors/ARBs had a slower rate of progression of aortic stenosis compared to those not prescribed ACE inhibitors/ARBs (2.2 to 2.5 vs. 2.3 to 2.8 meters/second) (Figure 1). Also, patients prescribed aldosterone receptor blockers had a slower rate of progression of aortic stenosis compared to those who were not 2.2 to 2.4 vs. 2.3 to 2.8 meters/second) (Figure 2). Our findings suggest that angiotensin or aldosterone antagonism is associated with slower rate of progression of mild aortic stenosis.
Abstract 19158: MRI Based Non-Invasive Measures Correlates With Invasive Measurements of Left Atrial Diastolic Function in Atrial Fibrillation Patients
Authors: Khurram Irfan , Maqbool Farhan , Beinart Roy , Zipunnikov Vadim , Calkins Hugh , Nazarian Saman , Zimmerman Stefan L
Published: April 2024

Background:
Atrial fibrillation (AF) is associated with diminished cardiac functions. This study describes a novel methodology for non-invasive measurement of left atrial (LA) function in patients with AF.

Methods:
A total of 55 patients (81% male, 55% paroxysmal, 60.4±10.2 years) underwent cardiac MRI prior to AF ablation. Invasive LA pressure was measured during sinus rhythm following trans-septal puncture for AF ablation. LA pressure and volume (MRI derived) loops were prepared for all patients. LA diastolic function was defined as the ratio of the change in LA pressure to the change in LA volume during passive LA filling. Additionally, the ratio of pulmonary vein flow velocities during ventricular systole and diastole were obtained using phase contrast MRI (Figure top panel, S/D ratio). Patients with ventricular diastolic dysfunction (as seen by E/A ratio) were excluded. LA systolic functions were calculated from the active emptying fraction during atrial contraction. Diastolic dysfunction scores greater than the 90th %tile (>1.6mmHg/ml) were considered to signify severe diastolic dysfunction.

Results:
The mean diastolic dysfunction score was 0.76±0.7 mmHg/ml. The score was higher in patients with persistent versus paroxysmal AF (1.0±0.9 vs. 0.60±0.5,p=0.02). The mean S/D ratio was 1.04±0.6; and was lower in patients with persistent versus paroxysmal AF (0.9±0.5 vs. 1.2±0.7, p=0.04). There was a negative linear association between diastolic dysfunction scores and S/D ratio measures (Figure bottom panel, p <0.001). In a multivariate analysis adjusting for age, LA systolic function and CHADS2 score, the severe diastolic dysfunction was independently associated with lower S/D ratio (p-0.03).

Conclusion:
The non-invasive MRI derived ratio of pulmonary vein flow velocities during systole and diastole are associated with the MRI/invasive derived diastolic dysfunction score, and appear to be a fair surrogate of LA diastolic function.
Abstract 192: Relationship Between Zolpidem Use and Aortic Dissection Risk: A Taiwanese Population-Based Case-Control Study
Authors: Lin Yen-Nien , Ko Po-Yen , Chang Chih-Ping , Yang Chen-Chia , Lin Jen-Jyh , Chang Kuan-Cheng
Published: April 2024

Objective:
To evaluate the relationship between the use of zolpidem and risk of subsequent aortic dissection in Taiwanese patients.

Method:
This case-control study used data obtained from the National Health Insurance Research Database to determine whether the use of zolpidem is associated with an increased risk of aortic dissection. The case group comprised 1314 patients who were newly diagnosed with aortic dissection between January 1, 2003, and December 31, 2010. We also randomly selected a 4-fold greater number of patients without aortic dissection as a control group. Patients were frequency-matched with controls on sex, age, and year of index date. We measured the effect of zolpidem, and determined the adjusted odds ratios (ORs) with 95% confidence intervals (CIs).

Results:
We found that exposure to zolpidem was associated with increased risk of aortic dissection (OR=1.59; 95% CI, 1.36-1.86). The risk of aortic dissection increased significantly with increasing exposure to zolpidem; for average exposures of ≦ 40, 41-160, 161-690, and > 690 mg/year, the ORs were 1.45, 1.36, 2.08 and 1.55, respectively; the P value for the trend was <0.001. Regardless of whether people presented with a sleep disorder, the risk of aortic dissection increased with zolpidem exposure; the adjusted OR was 1.70 without sleep disorder and 1.62 with sleep disorder.

Conclusions:
This population-based study positively associated the use of zolpidem with increased risk of Aortic dissection. Our findings warrant further large-scale and in-depth investigations in this area.
Abstract 200: Pressure Overload Causes Right Ventricular Lethal Arrhythmias: Analysis by Optical Mapping in Pulmonary Artery Banding and Pneumonectomy Model
Authors: Takase Bonpei , Tanaka Yoshihiro
Published: April 2024

Right ventricular (RV) pressure overload due to severe pulmonary hypertension (svr-PH > 40 mmHg) sometimes causes lethal arrhythmias, although the mechanisms are unclear. To investigate if RV pressure overload produces RV arryhythmogenic vulnerability, we serially performed optical mapping analysis (OMP) with electrophysiological study (EPS) to the heart excised from pneumonectomy-induced (LP+H) and/or pulmonary artery banding-induced (PBI) svr-PH rats. In PBI-svr-PH, experiments were only conducted for 2 hours after PB because PBI-svr-PH was lethal. Action potential duration dispersion (APDd) and connexin43 (Cx43) expression were measured in RV. LP+H-svr-PH transiently sustained. OMP revealed abnormal RV conduction and increased APDd accompanying ventricular fibrillation/tachycardia (VF/VT) induction by EPS with normal Cx-43 in LP+H -svr-PH while PBI-svr-PH showed abnormal RV conduction and nonsustained VF/VT induction, but not increased APDd and without Cx-43 abnormality.

Conclusions:
Transiently sustained (>24-hours) svr-PH can cause lethal arrhythmias possibly due to the mechanoelectric transduction not including Cx43degradation.
Abstract 210: Temporal Changes in Detrended Fluctuation Analysis (DFA) of Ventricular Fibrillation From Out-of-Hospital Cardiac Arrests in an Asian Community
Authors: Chen Matt, Weiting , Ko Patrick, Chow-In , Chiang Wen-Chu , Chang Chun-Yi , Lin Liang-Yu , Lin Chen , Hsieh Wan-Hsin , Chang Yi-Chung , Lo Men-Tzung , Ma Matthew, Huei-Ming
Published: April 2024

Introduction:
Ventricular fibrillation (VF) is the most common arrhythmia causing out-of-hospital cardiac arrest (OOHCA) and electrical defibrillation remains the mainstay of its treatment. Successful defibrillation is linked to VF morphology characteristics, and is affected by VF duration, quality of cardiopulmonary resuscitation (CPR) and emergency medical service (EMS) responsiveness. This study aimed at comparing VF morphology characteristics between two study periods in an Asian community.

Method:
Electrocardiographic recordings of VF signals from automated external defibrillators (AEDs) were obtained from OOHCA subjects in Taipei city, a metropolitan with 2.65 million residents in 272km
2
. Root-mean-squared (RMS) amplitude, mean amplitude, amplitude spectrum analysis (AMSA), frequency analysis, and fractal measurements including scaling exponent (SE) and DFA were calculated and compared between early (2000-2001) vs. late (2006-2007) periods.

Results:
A total of 137 OOHCA subjects with VF, 61 in early and 76 in late period, were included for analysis. For patients converted to normal sinus rhythm (NSR) at 10 seconds after the first shock, DFAα2 was significantly lower in the late period (0.29±0.17 vs. 0.44±0.27, p=0.047). Similarly, for those converted to nonVF at 30 seconds after the first shock, the DFAα2 was lower in the late period (0.37±0.21 vs. 0.50±0.27, p=0.012). Differences in late vs. early period were not observed among any other parameters studied.

Conclusions:
DFAα2, but not AMSA or other VF waveform characteristics, decreased over time. This might reflect changes in EMS responses and community quality of CPR in different study time periods.
Abstract 231: The Effect of Dispatcher Call Processing Interval and Ambulance Response Interval for Survival From Cardiac Arrest
Authors: Ljunggren Malin , Castrén Maaret , Bohm Katarina
Published: April 2024

Introduction:
Out-of hospital cardiac arrest (OHCA) affects millions of people in the world annually but the survival rate is low. Survival from OHCA has been associated with the ambulance response interval, but not demonstrated to be associated with the dispatcher call processing interval. We assessed the hypothesis that the dispatcher call processing interval and the ambulance response interval were related to survival from OHCA.

Aim:
To describe the dispatcher call processing interval and the ambulance response interval and their association with 30-day survival from OHCA with ventricular fibrillation (VF) or ventricular tachycardia (VT) as the presenting rhythm. The secondary aim was to investigate the association to the secondary outcome measure 1-day survival.

Methods:
This retrospective cohort study included 400 witnessed OHCAs with VF/VT as the presenting rhythm in Sweden between February 2005 and January 2009. The patients were randomized to different types of telephone-instructed cardiopulmonary resuscitation in accordance with the previous study (TANGO) which the current study is based on. Patients that the ambulance personnel did not attempt to resuscitate, children below 8 years of age, and OHCAs caused by trauma, airway obstruction, drowning or intoxication were excluded. Logistic regression models were used to investigate the association between survival and the intervals.

Results:
The odds of survival were increased when the dispatcher call processing interval (median = 1 minute) was shortened from ≥ 4 minutes to 2-3 minutes (OR 3.8; CI 1.03-14.3) and 0-1 minutes (OR 1.9; CI 0.5-7.1, after adjusting for differences in baseline characteristics (overall p=0.026). The odds of survival were increased when the ambulance response interval (median = 8 minutes) was shortened from ≥ 11 minutes to 5-10 minutes (OR 2.1; CI 0.94-4.7) and 0-4 minutes (OR 4.5; CI 1.8-11), after adjusting for differences in baseline characteristics (overall p=0.026).

Conclusions:
Survival from out-of-hospital VF/VT is increased, not only by shortening the ambulance response interval, but also by shortening the dispatcher call processing interval.
Abstract 233: The Relationship of Maximum Troponin Values Post Out-of-hospital Cardiac Arrest with Electrocardiographic Findings, Cardiac Procedures and Survival to Discharge; A Sub-study of ROC PRIMED
Authors: Morrison Laurie J , Devlin Sean M , Kontos Michael C , Cheskes Sheldon , Thomas Andrew J , Stiell Ian G , Ornato Joseph P , Christenson Jim , Rac Valeria E , Aufderheide Tom P , Wigginton Jane G , Dorian Paul
Published: April 2024

Objective:
To describe the relationship between maximum Troponin (Tn) levels recorded within 48 hours post arrest and clinical outcomes in out-of-hospital cardiac arrest (OHCA) patients enrolled in the Resuscitation Outcomes Consortium (ROC) Prehospital Resuscitation using an IMpedance valve and Early versus Delayed analysis (PRIMED) trial.

Methods:
A prospective observational cohort study of all treated non-traumatic OHCAs enrolled in ROC PRIMED. Patients were classified based on first presenting in-hospital ECG as ST elevation myocardial infarction (STEMI) or not a STEMI (including NSTEMI). Peak Tn levels, evaluated on a logarithmic scale, were compared across patient and treatment characteristics using a t-test or ANOVA. The association between categories of Tn levels (<0.1, 0.1-2, >2) and survival to discharge was evaluated using logistic regression adjusted for Utstein predictors of survival and ROC site.

Results:
Of the 15617 enrolled patients, 3661 (23%) survived at least 48 hours, 17% (693) were STEMI and 78% (3188) were not a STEMI with 5% unknown and 83% (3460) with at least one Tn level measured. The mean (SD) age was 64.6 (15.9). The STEMI group had more men (74.5% STEMI, 62% not a STEMI) and was more likely to have an initial shockable rhythm (73% STEMI, 39% not a STEMI). In-hospital survival was higher with STEMI (OR 1.93, 95% CI 1.63-2.3, p<0.001). The logarithm of Tn values was higher in STEMI patients (p <0.001). Adjusted in-hospital survival for STEMI patients was significantly better in those patients with higher Tn values (p=0.01). Adjusted in-hospital survival was significantly worse with higher Tn levels in the not a STEMI group (p<0.001). When treated with reperfusion, adjusted survival in the not a STEMI group was significantly better than the survival rate without reperfusion (OR 3.6, 95% CI 2.4-5.4 for trop>0.1, p<0.001).

Conclusion:
High Tn levels were associated with increased rates of reperfusion and better in-hospital survival in post-arrest patients with STEMI on first ECG. High Tn levels in not a STEMI patients post arrest were associated with decreased survival. Survival in not a STEMI patients was significantly higher when treated with reperfusion.
Abstract 252: Accurate ECG Interpretation With Use of the Analysis During Compressions With Fast Reconfirmation (ADC-FR) Technology
Authors: Tan Qing , Silver Annemarie , Geheb Frederick J
Published: April 2024

Background:
Use of Analysis during Compressions with Fast Reconfirmation (ADC-FR) technology, which features automated rhythm analysis and charging during chest compressions (CCs) with a brief reconfirmation analysis during CC pause, has been shown to reduce CC interruptions compared with standard AED operation. The purpose of this study was to determine the accuracy of the ADC-FR algorithm.

Methods:
A retrospective analysis was conducted of AED Pro and AED Plus defibrillator records (ZOLL Medical) containing ECG and CC acceleration data, collected as part of a registry, from the treatment of 624 out-of-hospital cardiac arrest patients. With ADC-FR, the ECG rhythm is interpreted during CCs using an advanced algorithm and the defibrillator is charged the last 10 seconds of the CC interval. A quick reconfirmation analysis is initiated after the rescuer stands clear to confirm the shock/no-shock result of the analysis performed during CCs. If the analysis during CC and reconfirmation analysis agree, the defibrillator is immediately armed (if shockable) or disarmed (if non-shockable). If the reconfirmation analysis and analysis during CCs differ, an additional analysis is conducted. For ADC-FR testing, the CC acceleration signal was used to identify CC intervals followed by a CC-free period of at least 6 seconds (for reconfirmation analysis) and the ADC-FR algorithm was applied. The analysis results were saved in text files, which were used to calculate algorithm accuracy.

Results:
A total of 2059 advisories were generated by the ADC-FR algorithm. As shown in the table, the ADC-FR advisory algorithm accuracy exceeded the AHA performance goals for all rhythms.

Conclusions:
The ADC-FR algorithm produces accuracies better than performance goals recommended by AHA even though the performance goals are for algorithm tests with artifact-free ECG signal. Therefore, the ADC-FR can be used to reduce CC pauses while preserving shock decision accuracy.
Abstract 273: A Comparison of Two Methods for Measuring Pediatric CPR Quality in a Pediatric Emergency Department
Authors: Hsieh Ting-Chang , Wolfe Heather , Hoyte Natasha , Sutton Robert , Nadkarni Vinay , Donoghue Aaron
Published: April 2024

Background:
Studies examining CPR using a sensor/accelerometer device (Q-CPR) have demonstrated that pediatric CPR is often performed suboptimally. The majority of children receiving CPR in the ED are ineligible for Q-CPR use. Recent data has shown that video recording of critical procedures in the pediatric ED is reliable for measuring outcomes.

Objective:
To determine the correlation between video review and Q-CPR measurement in quantifying chest compression parameters in pediatric patients.

Methods:
Children > 8 years who received CPR using the Q-CPR device and whose events were video recorded were eligible for inclusion. Videos were reviewed by study personnel; compressions were measured in 30-second epochs. Compression rate was counted directly; compression depth and chest wall release were scored dichotomously as ‘adequate’ or ‘inadequate’ based on a threshold of 80% of observed compressions meeting parameters. Q-CPR data was measured for compression rate, percent compressions with depth > 38 mm, and percent compressions with leaning force > 2.5 kg; epochs were designated as ‘adequate’ or ‘inadequate’ for depth and leaning with 80% as a threshold for parameters. Correlation between video and Q-CPR data was done by Spearman’s ρ (rate) and f coefficient (depth, release).

Results:
Four patients were captured on video receiving CPR using the Q-CPR device; complete data was available for 79 30-second epochs of compressions. By Q-CPR measurement, median rate of compressions was 114 per minute (range 91 - 127). A median of 53% (range 0 - 100%) of compressions were > 38 mm per epoch. A median of 2% (range 0 - 100%) compressions had residual leaning force of > 2.5 kg. By video review, median rate was 108 compressions per minute (range 66 - 132); depth was scored as adequate in 72/79 (91%) of epochs; release was scored as adequate in 72/79 (91%) of epochs. Correlation was very good for rate (ρ = 0.73) and poor for release (f = 0.06) and depth (f = 0.02).

Conclusions:
Video review of CPR in children measures compression rate reliably when compared with Q-CPR data. Video review does not accurately determine compression depth or chest wall release. Future studies should examine whether video recording can be optimized to allow reliable measurement of depth and leaning in children.
Abstract 278: Sodium Nitroprusside Combined With Epinephrine for Prolonged Ventricular Fibrillation Cardiac Arrest
Authors: Kern Karl B , Zuercher Mathias , Hilwig Ronald W , Sanders Arthur B , Otto Charles W , Ewy Gordon A
Published: April 2024

Background:
A new approach to resuscitation using the potent vasodilator sodium nitroprusside (SNP) combined with mechanical efforts to maintain both coronary and cerebral perfusion pressures (active compression/decompression CPR combined with an impedance threshold device and abdominal binding) has reported improved survival with good neurological function. We hypothesized that a potent vasoconstricting agent like epinephrine (E) might replace the multiple mechanical components of this approach without compromising outcomes.

Methods:
We studied a total of 24 swine (25±5 kg) utilizing a 10-min period of untreated ventricular fibrillation. This was followed by 2-min of chest compressions and then an attempted defibrillation. The 2-min compression and subsequent defibrillation effort was repeated. Next another 2-min of chest compressions, during which both medications were administered, followed by attempted defibrillation. This first drug administration period occurred at 14 min 20 seconds after the onset of cardiac arrest. A total of five such 2-min of chest compressions followed by drug administration were performed if needed for ROSC. Animals were randomized to receive either SNP/E or placebo. Doses included 0.5 mg of SNP every 2 min for a maximum dose of 2.5 mg over 15 min and 1.3 mg of E every 2 min for a maximum dose of 6.75 mg. The primary endpoint was normal neurological function (CPC =1) at 24 hours. Statistical analysis utilized Fisher’s Exact testing.

Results:
Three subjects were successfully resuscitated prior to receiving any medications and were eliminated from this comparison. A total of 7/9 SNP/E animals were resuscitated in contrast to 6/13 animal receiving placebo (p=0.2). At 24 hours a CPC score of 1 was seen in 1/7 SNP/E animals compared to 5/6 placebo animals (p=0.03).

Conclusion:
Sodium nitroprusside combined with epinephrine failed to improve 24-hour neurological function in this protocol designed to mimic the late administration of medications during ACLS resuscitation. Epinephrine was unable to successfully replace the previously reported mechanical components of sodium nitroprusside-enhanced CPR (SNPeCPR). The propensity for epinephrine to increase ROSC, but not longer-term endpoints, remains a concern.
Abstract 287: Shock Success Rates with Sternal-apical vs. Anterior-posterior Pad Positioning During Out-of-hospital Cardiac Arrest
Authors: Olsen Jan-Aage , Persse David , Souders Chris , Brunborg Cathrine , Wik Lars
Published: April 2024

Background:
Shock success rates for sternal-apical (SA) and anterior-posterior (AP) defibrillator pad positions have not been compared clinically. Houston Fire EMS historically used AP, but changed to SA position, enabling shock success rate comparisons in out-of-hospital cardiac arrest (OHCA) patients.

Methods:
Patients treated with manual CPR and biphasic LifePak 500/12 defibrillators (Physio-Control, Redmond, US) were included from January 2006 to April 2007 for AP and from March 2009 to January 2011 for SA, this excluded the transition period when either position may have been used. ECG files were reviewed and initial rhythm, immediate pre-shock and five seconds post-shock rhythms were recorded as shockable or non-shockable. Only indicated shocks were included in analysis of shock success defined as termination of ventricular arrhythmias for at least five seconds. Data were analyzed using SPSS, and differences between the SA and AP groups were calculated using chi-square test and odds ratios (OR).

Results:
Of 989 shocked patients, 917 (93%) received 3074 indicated shocks. Of these indicated shocks 1163 of 1436 (81.0%) were successful in 476 SA patients vs. 1303 of 1638 (79.5%) in 441 AP patients (OR 1.10, 95% CI: 0.92-1.31, p=0.32). Median number of indicated shocks was 3 (IQR 1-4) in SA group and 3 (IQR 1-5) in AP group. Initial rhythm was shockable in 269 (57%) SA patients and in 277 (63%) AP patients (p=0.05) with 797 of 993 shocks (80.3%) being successful in this subgroup of SA patients vs. 859 of 1069 (80.4%) in the AP patients (OR 0.99, 95% CI: 0.80-1.24, p=0.96).

Conclusion:
There was no significant difference in shock success rate between sternal-apical and anterior-posterior defibrillator pads positioning during manual CPR of OHCA patients.
Abstract 314: Continuous Intravenous Administration is the Method of Epinephrine Administration Recommended for Treating Anaphylaxis
Authors: Fujizuka Kenji , Nakano Minoru , Nakamura Mitunobu , Ogura Takayuki
Published: April 2024

Objective:
In general, epinephrine treatment for anaphylaxis involves intravenous bolus administration or intramuscular injection. It is said that intravenous bolus administration has many side effects. Thus it is necessary to exercise caution when using this method. We perform continuous intravenous administration with an initial starting amount of 0.1 μg/kg/min because it can be administered reliably into a blood vessel and it is easy to adjust the dose. In this study, we compared the efficacy and safety of the continuous intravenous administration of epinephrine with those of other administration methods.

Methods:
The survey period was from April 2005 until March 2013. The patients were those diagnosed with anaphylaxis who were admitted to our hospital`s emergency department, and who were treated with epinephrine. We retrospectively investigated the occurrences of side effects and the course of symptom improvement following administration of epinephrine in two groups: continuous intravenous administration and other.

Results:
A total of 108 patients were included in the study, 51 in the continuous intravenous administration group and 57 in the other group. SBP was lower in the continuous intravenous administration group than in the other group (88.06 ± 30.04 mmHg vs 98.35 ± 23.78 mmHg, p = 0.006). Otherwise, there were no significant differences in the backgrounds of the two groups. There were zero cases of side effects in the continuous intravenous administration group, and six cases in the other group, and this difference was significant (p = 0.028). Of the patients showing side effects, three received intravenous bolus administration and three received intramuscular administration. There was no significant difference in the time to symptom improvement with treatment from the time of admission.

Conclusions:
Continuous intravenous administration of epinephrine produced no side effects relating to anaphylaxis, and there was no significant difference in the time to symptom improvement with regard to the method of administering epinephrine.
Abstract 316: Emergency Medical Services Response Time to Cardiac Arrest May be Delayed When Using European Emergency Phone Number in the Czech Republic
Authors: Truhlar Anatolij , Jezek Tomas , Castrén Maaret , Plodr Michal , Masek Jiri , Cerny Vladimir , Nikolaou Nikolaos I
Published: April 2024

Introduction:
Survival of people in cardiac arrest depends on EMS response time. Laypeople may use both national (155) and European (112) phone numbers for requesting EMS in the Czech Republic. The 155 medical dispatchers deal with the request directly while 112 fire-brigade operators have to transfer the call to EMS. It was unclear, whether use of the different systems may cause any delay when calling for help. This study was aimed to compare times needed for contacting medical dispatch.

Methods:
A prospective observational study was performed during a 1-month period in the Hradec Kralove region (0.55 mil.) as a part of the EUROCALL study conducted on behalf of ERC. The 180 test calls (6 per day) were simulating request for EMS and randomly distributed to follow diurnal distribution, day of the week, use of a landline or a mobile phone, and 155 or 112 numbers. Multiple successive time intervals were recorded with an online timer. Data analysis was performed using Prism 6.0 for Mac OS X (GraphPad, La Jolla, USA).

Results:
There were no differences in response times until the first 155 or 112 operator answered the call (11.9 ± 0.4 vs. 11.5 ± 0.3 seconds, p = 0.42). However, the 155 operators were all qualified paramedics/nurses able to provide dispatcher-assisted CPR and (pre)alarm appropriate response teams immediately, while the 112 operators had to transfer the calls to EMS dispatch. The overall time interval “number dialed - call answered by medical dispatcher” was faster if a direct number (155) was used (11.9 ± 0.4 vs. 62.0 ± 1.8 seconds, p < 0.0001). Difference between means was 50.2 ± 1.9 seconds. The longest recorded connection times were 24.5, and 117.5 seconds respectively. There were no differences between landline and mobile phone calls. No call was aborted. A location of the caller service provided by 112 worked precisely especially if public phone-boxes were used. However, location misunderstandings appeared when connections of landline calls were technically performed via internet access.

Conclusion:
When requesting EMS, laypeople should (be taught to) use national emergency phone number when response time is critical, e.g. cardiac arrest. The European number 112 causes delay but may be used as an alternative in specific situations (e.g. foreigners, no SIM card).
Abstract 318: Is Systolic Blood Pressure on Arrival at Hospital Associated with Survival to Discharge in Out-of-hospital Cardiac Arrests
Authors: Bray Janet E , Cantwell Kate , Bernard Stephen , Stephenson Michael , Smith Karen
Published: April 2024

Background:
The optimal blood pressure target in patients with return-of-spontaneous-circulation (ROSC) following resuscitation from out-of-hospital cardiac arrest (OHCA) is uncertain. This study aimed to determine the relationship between systolic blood pressure (SBP) on arrival at hospital and survival to hospital discharge.

Methods:
A retrospective review was conducted using data between 2003 and 2012 from the Victorian Ambulance Cardiac Arrest Register (VACAR). Inclusion criteria were: adults (≥18 years), OHCA of presumed cardiac etiology, not paramedic witnessed, and pulse present on hospital arrival. Adjusted logistic regression models stratified by initial monitored rhythm (shockable and non-shockable) were performed to examine the relationship between SBP at hospital arrival in 10mmHg increments and outcome. The models were adjusted for factors known to predict survival, including duration of attempted EMS resuscitation.

Results:
There were 3620 OHCA eligible cases. Median age was 69 years (IQR=20), 70% were male, and 60% in a shockable rhythm on ambulance arrival. Hypotension (SBP<90mmHg) at hospital was reported in 14% (10% in shockable and 19% in non-shockable rhythms). For patients initially in a shockable rhythm, survival was maximal at 120-129mmHg (54%) and in the adjusted model (using ≥120mmHg as reference) became significantly associated with mortality at increments below 90mmHg. In non-shockable patients, the relationship between arrival SBP and survival was linear, but was not significant after duration of the arrest was added to the model.

Conclusions:
In an EMS system using intravenous epinephrine and fluids to achieve and/or maintain post-ROSC SBP >120mmHg, an SBP<90mmHg on arrival to hospital was independently associated with increased mortality in shockable OHCAs. This level may indicate patients who require more aggressive post-resuscitation blood pressure management.
Abstract 335: Gender Disparities in the Use of Therapeutic Hypothermia After Cardiac Arrest: An Analysis From the Penn Alliance for Therapeutic Hypothermia (PATH) Registry
Authors: Perman Sarah M , Grossestreuer Anne V , Gaieski David F , Abella Benjamin S , Merchant Raina M , Becker Lance B
Published: April 2024

Background:
Recent studies have shown that gender disparities exist in cardiac arrest outcomes and are thought to be multifactorial. Gender disparities in the use of therapeutic hypothermia have not been fully investigated and may contribute to disparities in survival and neurologic recovery after cardiac arrest.

Objectives:
We examined gender disparities in cardiac arrest care in a multi-center registry of post-arrest patients.

Methods:
The Penn Alliance for Therapeutic Hypothermia (PATH) Registry contains data from 18 hospitals nationwide. Patients are >18 years of age, suffered either an in-hospital (IHCA) or out-of-hospital (OHCA) cardiac arrest, and presented to one of the enrolling centers. Demographic and arrest characteristics were analyzed with descriptive statistics, and gender comparisons were made for age, initial rhythm, bystander CPR, return of spontaneous circulation (ROSC), use of therapeutic hypothermia (TH) and neurologic outcome (cerebral performance category (CPC)).

Results:
The PATH registry contained 1,767 eligible patients who suffered a cardiac arrest between 5/1/2005 and 4/30/2013. In total, 666 (42%) were female and mean age of women was 65.4 ± 18.1 years vs. men who were 62.3 ± 16.6 years (p<0.001). There was no gender difference in the proportion of patients who suffered OHCA (1270) vs. IHCA (497). Of patients who suffered an out-of-hospital cardiac arrest, 40% of men versus 34% of women received by-stander CPR (p=0.07). Women had a higher proportion of non-shockable rhythms (80% vs. 72%; p <0.001), however, there was no difference in rate of ROSC (54% vs. 51%; p=0.11). Female patients who remained comatose after ROSC received TH less often then their male counterparts (56% vs. 62%; p=0.06), and demonstrated worse neurological outcomes at hospital discharge (CPC 1 or 2: 16% vs. 20%; p=0.03).

Conclusion:
Female patients were older, more likely to have non-shockable rhythms, and less likely to get by-stander CPR. There is disparity in the use of TH in female patients, with a trend towards more men receiving TH. Consequently, women have significantly worse rates of neurologic recovery then male victims of cardiac arrest. Future identification of the component factors responsible for this disparity may be amenable to change.