bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15753: Comparative Transcriptomics Analysis of Histone (De)acetylases and Cardiac Ion Channels in Human Induced Pluripotent Stem-Cell-Derived Cardiomyocytes vs. the Adult Human Heart
Authors: Pozo Maria R , Pressler Michael P , Entcheva Emilia
Published: June 2023

Epigenetic regulation is critical for cardiac electrophysiology and pathology. Epigenetic modulators, such as histone deacetylases (HDACs) and histone acetyltransferases (HATs) are known master regulators of gene expression. Recently, novel pharmacological agents, HDAC inhibitors, have been developed as treatments for cancer and immune diseases. The effects of HDAC inhibitors on cardiac ion channels (ICs) are of great interest. To exert specific gene modulation, we used small interfering RNAs against the known HDACs, including sirtuins, and deployed them in human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). Follow-up RNAseq data (n = 61) were compared to identically processed and normalized RNAseq data from human left ventricle (LV) from the GTEx database (n = 84). Gene expression of cardiac ICs displayed similar patterns, with some differences. For example, hiPSC-CMs showed upregulated
CACNA1C, SLC8A1
and downregulated
KCNJ2
and
RYR2
compared to the adult LV, most of which are known distinctions (Fig. 1A). Correlative analysis (Fig. 1B) and partial least square regression models helped visualize links between HDACs/HATs, key transcription factors (TFs) and cardiac ICs. Powerful TFs, including
MEF2A, GATA4, 6
exerted positive effect on ICs in hiPSC-CM and the adult LV. In the hiPSC-CMs,
HDAC1, HDAC10
and
SIRT6
were found to be the strongest predictors of the expression of individual cardiac ICs, as revealed by permutation importance. Further studies will involve determination of the role of different cell types using single-cell sequencing data from the adult LV. Our analysis offers new insights about the role of epigenetic modifiers on cardiac electrophysiology and informs the utility of hiPSC-CM as a scalable, experimental model for cardiotoxicity testing of HDAC inhibitors.
Abstract 15755: Reduced STEMI Activations but Worse STEMI Outcomes During the COVID-19 Pandemic
Authors: Kyazimzade Sayyad , Lateef Azalfa , Jackson Cory , Mostertz William , Evans Matthew , Maran Arasi , Nielsen Chris , Fernandes VALERIAN
Published: June 2023

Introduction:
ST-elevation myocardial infarctions (STEMIs) are emergencies requiring rapid intervention. COVID-19 has been associated with a reduction in acute presentations to ER’s, however the effect on STEMI presentations (incidence, mortality, and severity) remains unclear.

Methods:
STEMI presentation data from 2012 to 2022 were obtained from our database. There were 647 STEMI activations pre-pandemic (81 per year) and 61 STEMI activations during the pandemic (30 per year). The STEMI activations were further characterized as false alerts or true STEMIs (undergoing emergent catheterization). Unpaired t-tests were conducted to analyze the difference between the groups.

Results:
The percentage of true STEMIs during COVID-19 was higher than pre-COVID-19 (85.9% vs 71.4%;
p<0.01
). Mean age pre-COVID-19 vs during COVID-19 was 60.4 years vs 58.4 years, while male sex was equal between both groups (72% vs 75%). Mean peak troponin levels of patients presenting during COVID-19 were lower than pre-COVID-19 (16.9 ng/L vs 51.5 ng/L;
p< 0.03
). The 30-day mortality rate was higher in the COVID-19 group than in the pre-COVID-19 (12.9% vs 9.8% p-value: NS) group. Use of mechanical support was higher during COVID-19, relative to pre-COVID-19 (21% vs 8.5%;
p<0.001
). One young patient presented as a delayed STEMI with a post-infarct VSD ultimately needing cardiac transplantation during the pandemic.

Conclusion:
During COVID-19, the overall STEMI activations decreased significantly. There was a higher incidence of true STEMIs, demonstrated by a lower rate of false alerts. This suggests that patients with more severe symptoms came to the hospital while patients with less severe/atypical symptoms may have avoided care. Lower peak troponin levels, yet more severe clinical outcomes (increased need for mechanical circulatory support, and a trend towards worse mortality), suggests delayed STEMI presentations during the pandemic. Further investigation is needed, given the ongoing dynamic nature of the pandemic.
Abstract 15765: Left Ventricular Strain on Echocardiogram is Associated With Abnormal Cardiac MRI Findings in Pediatric Patients With Covid-19
Authors: Rye-Buckingham Summer , Bhimani Salima , Vasilopoulos Terrie , Degroff Curt G , Co-Vu Jennifer G
Published: June 2023

Introduction:
Cardiac injury in COVID-19 may manifest as myocarditis, cardiomyopathy, ventricular arrhythmia, heart failure or cardiogenic shock. Although cardiac manifestations of COVID-19 is known, there is little literature regarding myocardial involvement in pediatric patients with COVID-19. Adult studies have suggested up to 80% of patients who have recovered from COVID-19 have abnormal cardiac MRI (CMR) findings. They have also suggested that up to 80% of adult patients hospitalized with COVID-19 have abnormal left ventricular global longitudinal strain (LV-GLS) and have used this to determine the extent of myocardial involvement. These findings can indicate potential long term cardiac sequalae. Our aim was to assess if abnormal LV-GLS from echocardiogram correlates with abnormal CMR findings in pediatric patients with history of COVID-19.

Methods:
This study is an IRB-approved retrospective chart review of pediatric patients less than 18 years old with a history of COVID-19 with evaluation of CMR and transthoracic echocardiograms (TTE) from 2020-2022. LV ejection fraction (LVEF) and LV-GLS were analyzed from TTE. CMR data includes LVEF, late gadolinium enhancement (LGE), parametric mapping (T1, T2 and extracellular volume). Comparisons between patient groups were made using Student's t-test, and p<0.05 was considered statistically significant.

Results:
Of the 47 patients with history of COVID-19, 24 patients were analyzed (mean age 14
+
4 years). All patients had preserved LVEF by TTE and CMR. 13 patients had abnormal CMR findings including LGE, and/or abnormal parametric mapping. In these 13 patients, mean LV-GLS was -16.6
+
2.1 (95%CI: -17.6, -15.5). Of the 11 patients with normal CMR findings, the mean LV-GLS was -19.3
+
2.9 (95%CI: -20.9, -17.8). There was significant difference in LV-GLS when comparing patients with CMR abnormalities versus those with normal CMR (t=-3.2, df=32, p=0.003).

Conclusions:
Abnormal LV-GLS on TTE despite normal LVEF may be associated with abnormal CMR findings in patients with a history of COVID-19. These findings suggest that cardiac involvement may persist in pediatric patients who had recovered from COVID-19. This may have implications on which patients will need CMR imaging and long-term follow-up.
Abstract 15800: Dissecting Cardiomyocyte-Fibroblast Communication During Homeostasis and Cardiac Fibrosis in a Compartmentalized Biomimetic Tissue Model
Authors: DePalma Samuel J , Huang Darcy , Stis Austin , Baker Brendon M
Published: June 2023

Introduction:
Cardiac fibroblasts (CFs) maintain cardiac structure and function by synthesizing and remodeling the extracellular matrix (ECM) found throughout the heart. Homeostatic maintenance of the ECM required for healthy tissue function depends on CF communication with cardiomyocytes (CMs). During cardiac fibrosis, signals resulting from tissue injury and dysregulated CF-CM communication promote CF differentiation into α-smooth muscle actin
+
(αSMA) myofibroblasts (MFs), which deposit excess ECM that mechanically impairs heart function. Given the challenges involved in parsing the dynamic and multifactorial heterocellular interactions underlying tissue homeostasis versus fibrosis, we engineered a compartmentalized, bilayer cardiac tissues where iPSC-derived CMs and CFs can be cultured on either side of a shared fibrous ECM to study CM-CF communication.

Methods:
Dextran vinyl sulfone (DVS) fibers were electrospun onto arrays of microfabricated PDMS wells. Matrix stiffness and alignment were controlled by modulating the speed of the collecting surface and UV light exposure, respectively. iPSC-CMs and primary human CFs were seeded onto opposing sides of the matrix. Immunostaining for αSMA was conducted to assess CF differentiation to MFs.

Results:
In CF monocultures on matrices varying in alignment and stiffness, MF differentiation was greatest on stiff (17.3 kPa) aligned matrices with exogenous TGFβ1 compared to soft (0.68 kPa) aligned matrices and both soft/stiff random matrices. We also observed increased nuclear YAP expression on stiff/aligned matrices, indicating altered mechanosensing in response to matrix properties. However, the presence of co-cultured CMs inhibited MF differentiation despite exogenous TGFβ1. MF differentiation was also impaired in CFs cultured on glass below matrix-seeded CMs, implying the role of protective paracrine signaling from CMs to CFs.

Conclusions:
We developed a microfabricated biomimetic coculture platform to examine CM-CF communication driving tissue homeostasis versus fibrosis. Specifically, we find that fibrous mechanical cues modulate YAP-mediated signaling and αSMA expression. Further, CM-CF paracrine signaling mitigates MF differentiation on aligned fibrous matrices.
Abstract 15817: Hemodynamics of the UNOS Heart Allocation System: Is it Time to Add Objectivity to an Subjective System?
Authors: Belkin Mark N , Plana Alejandro , Parker William F , Pinney Sean P , Grinstein Jonathan
Published: June 2023

Introduction:
In the current United States Organ Sharing heart transplant allocation system, hemodynamic criteria, systolic blood pressure (SBP), cardiac index (CI), and pulmonary capillary wedge pressure (PCWP), are utilized to justify certain listing statuses.

Hypothesis:
We sought to identify how currently utilized, and advanced, hemodynamics discriminated patients by listing status.

Methods:
Retrospective analysis of the Scientific Registry of Transplant Candidates including all adults listed for heart transplant since the updated listing criteria went live in October 2018 was completed. In addition to SBP, CI, and PCWP, the mean advanced hemodynamic metrics of aortic pulsatility index (API), cardiac power output (CPO), left ventricular stroke work index (LVSWI), right ventricular stroke work index (RVSWI), and pulmonary artery pulsatility index (PAPI), were calculated for each status.

Results:
Since October 2018, 9,418 patients were listed for heart transplant, and 8,636 had complete hemodynamic data at time of listing. Currently utilized hemodynamic metrics failed to discriminate lower acuity statuses (3 through 6 for PCWP and CI; 4 through 6 for SBP). For advanced hemodynamic metrics, mean API was lowest for Status 1 patients, and rose consistently with increasing status with a clear stepwise and statistically significant difference for sequential statuses (p < 0.001). CPO and LVSWI were unable to discriminate statuses 3-6. For right-sided hemodynamics, PAPI was unable to discriminate statuses 2 through 6, and there were no significant differences across any status for RVSWI.

Conclusions:
API is the only hemodynamic metric that is able to differentiate patients on the heart transplant waiting list across all active statuses by increasing in a stepwise fashion. Incorporation of API into future iterations of the UNOS heart allocation system may help better risk stratify patients and minimize waitlist mortality.
Abstract 15835: Deep Learning Based Personalized Treatment Recommender System for HFpEF Patients in the TOPCAT Americas Population
Authors: Gani Areeb , Gani Nuha , Dandi Gauri , Atkinson Ian , Mallick Zyannah , Xin Victoria , Husain Anwar , Rosenberg Yves , Hasan Ahmed A
Published: June 2023

Introduction:
The NHLBI supported TOPCAT trial (NCT00094302) investigated whether treatment with spironolactone (SPL) reduces hospitalization due to heart failure (hHF) in 3,445 adults with prior heart failure and preserved ejection fraction (HFpEF). We reused publicly available patient-level data from NHLBI Data Repository (BioLINCC) to perform hypothesis-generating secondary analyses with deep learning (DL) on the American TOPCAT cohort to generate treatment recommendations for HFpEF.

Methods:
Clinical phenogroups based on baseline characteristics of the American TOPCAT cohort (n = 1,053) were created using KPrototypes, suited for mixed data clustering. Treatment outcomes were assessed for hHF by DeepSurv, a DL generalization of Cox proportional hazards model, and Random Survival Forest (RSF), a tree-based survival analysis model. Comparison of survival probabilities from both models was used to create a recommender system used to guide treatments.

Results:
Cluster 1 was composed of younger patients with high cardiometabolic risk compared with Cluster 2. Diabetic patients (type 1 and type 2) comprised 93.2% of patients in cluster 1 and 10.1% of patients in Cluster 2.

Among both clusters, DeepSurv and RSF trained well based on calculated C-indices, with DeepSurv often outperforming the RSF model (C-index = 0.797 vs. 0.698). Both approaches corroborated with each other and recommended the SPL treatment for the majority of patients in Cluster 1 (Figure 1). The models also recommended the SPL treatment for the majority of patients in cluster 2, although DeepSurv was less confident in this suggestion than RSF (Figure 1).

Conclusions:
This preliminary analysis shows the potential effectiveness of tailoring SPL as a treatment for HFpEF. The efficacy of deep learning models shows how advanced techniques can be used to promote precision medicine. Further analyses will be done to establish guided treatment efficacy in DL-generated subgroups of HFpEF patients.
Abstract 15863: Impact of Right and Left Ventricular Dysfunction on Mortality in Secondary Mitral Regurgitation Patients Without Surgical and Interventional Treatment
Authors: Liu Dan , hu kai , Lau Kolja , Müntze Jonas , Maniuc Octavian , Nordbeck Peter
Published: June 2023

Introduction:
Secondary mitral regurgitation (SMR) is related with poor clinical outcome. Impact of right ventricular (RV) dysfunction with or without left ventricular (LV) dysfunction in SMR patients remains unclear.

Hypothesis:
This study aimed to investigate the prevalence of isolated LV, RV, and biventricular dysfunction, and to determine their prognostic implication in moderate-to-severe SMR without surgical and interventional treatment.

Methods:
A total of 1090 consecutive moderate-to-severe SMR patients without surgical and interventional treatment hospitalized in our hospital center between 2009 and 2018 (aged 75±12years, 60.4% male) were included. Clinical and echocardiographic characteristics were analyzed. All patients completed at least 1-year clinical follow-up. The primary endpoint was defined as all-cause death.

Results:
Mean left ventricular ejection fraction (LVEF) was 44.6±16.2%, and 59.3% of patients had LVEF <50% (defined as LV dysfunction). RV dysfunction was defined as a reduced tricuspid annular plane excursion (TAPSE<17mm) or an increased systolic pulmonary artery disease (sPAP>40mmHg). All-cause mortality was 47.8% [follow-up period: median 23 (8-40) months]. Patients were divided into 4 subgroups: 1) preserved biventricular function: n=136 (12.5%); 2) isolated LV dysfunction: n=97 (8.9%); 3) isolated RV dysfunction: n=308 (28.3%); 4) biventricular dysfunction: n=549 (50.4%). The mortality in above groups was 27.2%, 36.1%, 50.0% and 53.7%, respectively. Multivariable survival analysis showed that isolated LV dysfunction, isolated RV dysfunction, or biventricular dysfunction were all independently associated with increased all-cause mortality, after adjustment for age, sex and other clinical covariates associated with mortality.

Conclusions:
Compared to patients with preserved biventricular function or isolated LV dysfunction, RV and biventricular dysfunction are associated with significantly higher all-cause mortality in SMR patients without surgical/interventional treatment. This might constitute important implications for planning and timing of therapy.
Abstract 15867: A Swimming Heart: A Unique Complication of Gastropericardial Fistula
Authors: Requena Armas Carlos , Del Cid Fratti Juan , mungee sudhir
Published: June 2023

Background:
Gastropericardial fistula is a rare clinical entity associated with gastroesophageal operations.

Case:
63-year-old female with medical history of hypertension, GERD, and hiatal hernia status post Nissen fundoplication presented to the ER with one week of chest pain and dyspnea. Six months prior to presentation, she was found with ischemic colitis, candida esophagitis and slipped Nissen. In the ER, she was febrile and hypoxic. Chest x-ray showed a large hydropneumopericardium with air-fluid level. CT chest showed pneumomediastinum. Upon arrival to our facility, an echocardiogram showed normal EF 65% and a large complex pericardial effusion with presence of gas, liquid, and organized material without evidence of tamponade. Repeat CT abdomen showed a thin-walled collection of gas and fluid projecting from the area of the Nissen through the diaphragmatic hiatus in contact with the pericardium suspicious for a gastropericardial fistula. She went to the OR for pericardial window with drainage of 700 cc of purulent fluid and findings of chronic-appearing granulation of the pericardium. Intraoperative endoscopy noted a perforation near the GE junction that was stented with a 155 x 23 mm covered esophageal stent. Cultures grew Candida and gramnegative bacilli. She then underwent staged right thoracotomy with repair of fistula with intercostal muscle flap. Postoperative course was complicated with posterior wall hemorrhage requiring embolization of the left eight intercostal artery. The esophageal stent was removed three months post insertion due to distal migration causing superficial ulceration and esophagitis. Patient has since recovered gradually without further complications.

Discussion:
Gastropericardial fistula is associated with high morbidity and mortality. The treatment is surgical with early pericardial drainage usually by pericardial window and de-functioning esophagostomy or gastrostomy plus repair of the defect.
Abstract 15919: Adverse Outcomes Related Amiodarone Toxicity in Early Rhythm Control of Patients With Atrial Fibrillation: A Nationwide Cohort Study
Authors: Lim Ha Jeong , Yang Pil-sung , Sung Jung-Hoon , JOUNG BOYOUNG
Published: June 2023

Background:
Early rhythm control therapy was associated with a lower risk of adverse cardiovascular outcomes than usual care among patients who had recently (within 1 year) been diagnosed with atrial fibrillation (AF). In real-world data, the most commonly selected initial rhythm control strategy was the Class III anti-arrhythmic drug (AAD) amiodarone, but adverse outcomes related amiodarone toxicity was not well reported in this population. This study sought to investigate the fatal and non-fatal adverse outcomes related amiodarone toxicity in early rhythm control of patients with AF.

Methods:
Using the database of Korean National Health Insurance Service, we analyzed the adverse outcomes related amiodarone toxicity in 140,908 (rhythm control: 57,148, rate control: 83,760) patients with AF undergoing rhythm control or rate control therapy, initiated within 1 year of AF diagnosis, between 2005 and 2015.

Results:
The most commonly used rhythm control strategy was the class III drug amiodarone (22,877 (40.0%) of 57,148 patients in early rhythm control), followed by class Ic drugs. Patients with amiodarone for initial rhythm control strategy showed higher rate of interstitial lung disease (1.43% vs. 0.75%, p<0.001), sudden cardia arrest duet to Torsade de Pointes (0.31% vs. 0.17%, p=0.001), and hypothyroidism (16.5% vs. 8.12%, p<0.001). But incidence rate of bradycardia needing a temporary pacemaker, bradycardia needing a permanent pacemaker, and toxic hepatitis were higher in early rhythm control patients with other AADs compared to patients with amiodarone.

Conclusions:
The most commonly used rhythm control strategy was amiodarone in AF patients undergoing early rhythm control. Using amiodarone for the initial rhythm control strategy showed a higher rate of interstitial lung disease, sudden cardia arrest duet to Torsade de Pointes, and hypothyroidism. Attention should be paid to amiodarone toxicity in selecting rhythm control strategy for these patients.
Abstract 164: Efficacy Of Thoracic Impedance For Ventilation Detection During Continuous Chest Compressions
Authors: Jaureguibeitia Xabier , ARAMENDI ELISABETE , Idris Ahamed H , Wang Henry
Published: June 2023

Introduction:
Current technologies to identify ventilations during out-of-hospital cardiac arrest (OHCA) are limited. Thoracic impedance (TI) recorded by defibrillator pads can be used to identify ventilations, but these are often obscured by artifacts due to chest compressions (CC) and electrode motion. We tested a novel automatic algorithm to detect ventilations in TI during continuous CC.

Methods:
We analyzed Philips MRx CPR processed data from Dallas - Fort Worth patients in the Pragmatic Airway Resuscitation Trial. We extracted one-minute TI segments during continuous CC with concurrent capnogram recordings. We applied a novel algorithm to identify ventilation in the TI signal, which combined a) adaptive signal processing to remove CC artifacts, b) a recurrent neural network to discriminate TI fluctuations as ventilations, and c) a quality control stage to anticipate TI segments in which ventilation detection could be defective. We evaluated the performance of the algorithm in detecting ground truth capnogram ventilations in terms of sensitivity (SE), proportion of correctly identified ventilations, and Positive Predictive Value (PPV), proportion of detections corresponding to actual ventilations.

Results:
We extracted 2,551 one-minute TI segments from 367 OHCA patients; median of 6 (IQR 3-10) minutes per patient. Median patient-wise SE and PPV were 86.5 (IQR 71.6 - 95.1) % and 85.4 (68.3 - 94.7) %, respectively. The quality control was successful at discriminating TI segments by ventilation detection performance (Figure). For the 75% and 50% of data with highest quality estimates, SE improved to 90.6 (76.8 - 96.7) % and 95.5 (87.1 - 100.0) %, respectively, and PPV improved to 89.5 (75.0 - 96.4) % and 94.9 (87.3 - 99.8) %, respectively.

Conclusions:
We demonstrated the accuracy of an algorithm to detect ventilations using TI during continuous CC. Ventilation detection using TI during continuous CC is feasible.
Abstract 168: Hypoxia On Arrival At The Hospital Among Major Traumatic Brain Injury Patients Who Were Non-Hypoxic In The Field: Support For “Hyper-oxic” Prehospital Treatment?
Authors: Spaite Daniel W , Hu Chengcheng , Bobrow Bentley J , Barnhart Bruce J , Gaither Joshua B , Rice Amber D , Chikani Vatsal , Denninghoff Kurt R , Bradley Gail H , Howard Jeffrey T , Keim Samuel M
Published: June 2023

Background:
Prehospital and early hospital hypoxia powerfully affect traumatic brain injury (TBI) outcomes. However, the correlations between EMS and hospital O2 saturations are unknown. Using the EPIC Study data (NIH-1R01NS071049; DOD-W81XWH-19-C-0058), we assessed correlations between EMS SpO2 and the risk of major TBI patients arriving at the trauma center (TC) with hypoxia (initial ED SpO2<90%).

Methods:
Subjects meeting EPIC Study criteria, age ≥10 years, and transported directly to the TC were included. Basic statistics were determined by Kruskal-Wallis, Chi-square or Fisher’s exact test. Adjusted odds (aOR) were assessed using logistic regression, controlling for significant confounders.

Results:
A total of 10,370 subjects were included. Compared to no hypoxia, aORs for death were: EMS, but no TC hypoxia: 2.1 (1.7-2.6), TC, but no EMS hypoxia: 2.5 (1.7-3.8), both EMS/TC hypoxia: 3.2 (2.1-4.8; p<0.0001). Among the 9,243 cases with no EMS hypoxia, only 242 [2.6% (2.3%-3.0%) were hypoxic at TC arrival, compared to 215 of 1127 cases that had EMS hypoxia [19.1% (16.8%, 21.5%); OR: 8.8 (7.2, 10.7); aOR: 4.6 (3.7, 5.7); p<0.0001]. The Figure shows the odds of arriving hypoxic at the TC, based upon the lowest recorded EMS SpO2 (whether hypoxic or not).

Conclusion:
As expected, hypoxia upon TC arrival was highly correlated with EMS hypoxia (OR 8.8, aOR 4.6). However, it is remarkable that even a single EMS SpO2 below
100%
was associated with 2.4 greater odds of TC hypoxia (<90%). Given our recent findings that the optimal odds of survival occurs in patients whose recorded EMS SpO2s were always 100%, these findings argue against the popular concept of preventing “
hyper
-oxia” by titrating O2 to maintain SpO2 in the mid/upper 90s. Our results imply that keeping EMS SpO2 as high as possible prevents subsequent hypoxic episodes (i.e., “pre-oxygenation” for unexpected deterioration) and supports maintaining an SpO2 of 100% during the prehospital interval in major TBI.
Abstract 169: End Tidal CO2 In Multimodal Vest CPR
Authors: Paradis Norman A , Baumgaertner Ryan , Neri Luca , Ronzio Elisha , Sarah Fink , Paradis Aidan , Oberdier Matt T , Ostafe Magda M , Kern Karl B , Halperin Henry R
Published: June 2023

Introduction:
Circumferential constriction vest CPR is more effective at creating forward blood flow than traditional sternal compression only CPR. Active compression-decompression plus the impedance threshold device CPR (ACD-ITD-CPR) incorporates multiple hemodynamic pump mechanisms and also appears more effective. We have developed a new multimodal CPR that combines vest CPR with additional pump mechanisms, one of which is abdominal counterpulsation. Traditional coronary perfusion pressure (CPP) has not been validated during CPR that incorporates compression modalities applied during the relaxation phase. End tidal carbon dioxide (ET-CO2), however, is an indicator of forward blood flow during CPR that is unaffected by relaxation phase compressions.

Hypothesis:
Multimodal vest CPR that incorporates multiple pump mechanisms may be more effective than standard alternatives as indicated by ET-CO2.

Methods:
Utilizing a porcine model of ventricular fibrillation, we measured ET-CO2 in: 1) traditional sternal compression CPR (S-CPR), 2) active compression-decompression plus the impedance threshold device CPR (ACD-ITD-CPR) and 3) a new multimodal CPR comprised of circumferential constriction plus abdominal counterpulsation and active sternal decompression (MM-CPR) . After onset of cardiac arrest, 1 min. epochs of each CPR were randomly performed.

Results:
Seven experiments were performed with a mean number of epochs per experiment of 7. The mean (M
+
SD) ET-CO2 for S-CPR was 9
+
3 mmHg, for ACD-ITD-CPR 12
+
6, and for MM-CPR 19+8 (P<.05).

Conclusions:
Multimodal CPR comprising circumferential constriction plus abdominal counterpulsation and active sternal decompression is a promising new type of non-invasive circulatory support.
Abstract 184: Symptoms And Functional Impairment Among First Aid Providers
Authors: Oevsteboe Anna Marie Moe , Bjorshol Conrad A , Lindner Thomas Werner
Published: June 2023

Symptoms and Functional Impairment among First Aid Providers
Øvstebø AMM, Bjørshol CA, Lindner TW.

Introduction:
A first aid provider (FAP) follow-up program was initiated in Norway in 2020. FAPs are people who have been present or provided first aid to an unconscious person. The aim was to measure symptoms and functional impairments of FAPs following first aid incidents, and change over time.

Hypothesis:
Our hypothesis was that FAPs have significant psychological impairment.

Methods:
FAPs filled out an International Trauma Questionnaire (ITQ) at follow-up and after 6 months. ITQ focuses on core features of post-traumatic stress disorder (PTSD) and complex post-traumatic stress disorder (CPTSD). Endorsement of a symptom or functional impairment is defined as a score ≥ 2 (scale 0-4).The number of FAPs with a score ≥ 2 were counted for each question, and the five questions with the highest count were identified. We found the number of FAPs attending after more than 31 days who met the criteria of PTSD and CPTSD. Results were compared using Wilcoxon Signed Ranks test.

Results:
63 of 75 (84%) FAPs scored ≥ 2 on at least one question.
ITQ questions with highest count, and no. of answers ≥ 2 (%):
Being “super-alert”, watchful, or on guard: 34 of 75 (45%). Affected any other important part of your life: 32 of 75 (43%). Avoiding internal reminders of the experience: 31 of 75 (41%). Having powerful images or memories that sometimes come into your mind: 29 of 75 (39%). Affected your work or ability to work: 27 of 75 (36%). Five of 24 FAPs (21%) who attended more than 31 days after the incident fulfilled the criteria of PTSD/CPTSD. Median ITQ score when attending follow-up was 12.0, this was significantly reduced to 9.0 at 6 months (n =23, p=0.047).

Conclusions:
A high number of FAPs have endorsement of a symptom or functional impairment. Some meet the criteria for PTSD or CPTSD after more than 31 days. There was a significant reduction in ITQ score after 6 months. This might be a result of FAP follow-up.
Abstract 187: Synergy Of Elevation Of The Head And Thorax And Resuscitative Endovascular Balloon Occlusion Of The Aorta In A Porcine Model Of Prolonged Cardiac Arrest: A Pilot Study
Authors: Moore Johanna C , Salverda Bayert , Lick Michael , Arango Susana , Suresh Mithun , Metzger Anja , Lurie Keith G , Johnson Michael
Published: June 2023

Background:
Two new approaches to improve cardiac arrest outcomes, active compression-decompression (ACD) with an impedance threshold device (ITD) CPR with automated Head Up Positioning, (AHUP-CPR), and resuscitative endovascular balloon occlusion (REBOA) have been studied separately but never together. This was a pilot animal study exploring potential hemodynamic synergy of AHUP+ REBOA after prolonged CPR.

Methods:
Farm pigs (~40 kg) were sedated, intubated, and anesthetized. Central venous, and intracranial pressures were measured. Bilateral femoral arterial access was obtained for arterial pressure measurement and REBOA placement in the proximal thoracic aorta. Hemodynamics were measured with solid state pressure catheters. The arterial pressure catheter was placed in the thoracic aorta and confirmed via fluoroscopy. After 35 minutes of AHUP CPR, animals underwent two-minute epochs of AHUP-CPR, AHUP+REBOA CPR, ACD+ITD CPR flat + REBOA, and ACD+ITD CPR flat. Pressures are reported as mean (mmHg) ± standard deviation. Comparison testing was not performed in this pilot study.

Results:
In 4 pigs after 35 minutes, the AHUP CPR cerebral perfusion pressure (CerPP) was 21.1 ± 10.4, aortic compression (AOC) and decompression (AOD) pressures were 43.4 ± 9.1 and 14.1 ± 9.4, and intracranial compression (ICP) and decompression (DIP) pressures were 9.2 ± 2.7 and 6.5 ± 3.6, respectively. With AHUP+REBOA, CerPP was 39.0 ± 8.7, AOC and AOD pressures were 69.2 ± 10.7 and 21.0 ± 8.9, and ICP and DIP 9.7 ± 2.6 and 5.8 ± 2.9. The ACD+ITD CPR flat + REBOA CerPP was 21.7 ± 11.8, AOC and AOD pressures were 57.1 ± 9.5, and ICP and DIP were 20.5 ± 4.1 and 15.9 ± 3.2. The ACD+ITD CPR flat CerPP was 11.2 ± 7.5, AOC and AOD pressures were 38.8 ± 6.7 and 15.9 ± 6.6, and ICP and DIB were 17.4 ± 1.1 and 15.0 ± 1.6. A representative study tracing is shown.

Conclusions:
The combination of AHUP CPR with REBOA is feasible and may work synergistically after prolonged resuscitation in this ongoing animal study.
Abstract 190: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) After Traumatic Brain Injury
Authors: Nordham Kristen , Ninokawa Scott , Broome Jacob , McCraney Scott , Simpson John , Tatum Danielle , Jackson-Weaver Olan , Taghavi Sharven , MCGREW PATRICK , duchesne juan
Published: June 2023

Aim:
The effects of resuscitative endovascular balloon occlusion of the aorta (REBOA) on progression of traumatic brain injury (TBI) are unclear. Swine models have shown conflicting results, and human data is lacking. Two hypotheses largely prevail: increased mean arterial pressure caused by REBOA may improve cerebral perfusion, or conversely, cause cerebral edema due to elevated blood and intracranial pressure. This study aims to compare outcomes in patients with TBI treated with and without REBOA.

Methods:
A retrospective analysis compared blunt trauma patients with TBI treated with REBOA to those treated without. REBOA patients were selected from the Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery (AORTA) registry, and non-REBOA patients were selected from an institutional trauma registry. Patients with SBP > 0mmHg at admission and at initiation of aortic occlusion were included. Patients requiring CPR at ED were excluded. Propensity score matching was performed using age, gender, ISS, AIS-Head, and admission SBP.

Results:
After matching, 106 REBOA patients and 106 non-REBOA patients remained for analysis. REBOA patients had significantly higher ISS, but there was no difference in AIS-Head, pre-hospital or ED GCS, ED SBP, or in-hospital mortality (Table). Despite longer hospital stays for REBOA patients, there was no difference in ICU length of stay or rate of discharge home between groups.

Conclusion:
REBOA was used in more severely injured patients, but was not associated with higher mortality rate. Despite longer hospital stays for REBOA patients, discharge GCS and rate of discharge home, both favorable patient-centered outcomes, were similar between groups. REBOA use should be considered for use in patients with non-compressible torso hemorrhage and concomitant TBI, as it here it did not increase mortality, and outcomes upon discharge are similar to patients treated without REBOA.
Abstract 191: Alcohol Consumption Before Injury Did Not Improve Neurological Outcomes In Patients With Severe Traumatic Brain Injury: A Nationwide, Retrospective Cohort Study
Authors: Nojima Tsuyoshi , Naito Hiromichi , Hongo Takashi , Obara Takafumi , Yamamoto Hirotsugu , Yumoto Tetsuya , Tsukahara Kohei , Nakao Atsunori
Published: June 2023

Introduction:
Traumatic brain injury (TBI) is a major global public health concern. Notably, alcohol may confer neuroprotective effects by inhibiting of N-methyl-D-aspartate receptors; however, the impact of alcohol exposure before injury on neurological outcomes in patients with TBI has not been well studied.

Hypothesis:
We evaluated whether alcohol consumption before injury was associated with favorable neurological outcomes in patients with severe TBI using a large, national trauma registry.

Methods:
This study was a retrospective analysis of data collected into the Japan Trauma Data Bank from 2017 to 2021. Patients over 20 years old with severe TBI, defined as head Abbreviated Injury Scale score of 4 or 5, were included. We excluded patients with unknown alcohol status or outcomes. Subjects were divided into two groups (alcohol group vs. non-alcohol group) based on whether or not they were exposed to alcohol before injury. The primary outcome was favorable neurological outcomes (Glasgow Outcome Scale score of 4 or 5) at hospital discharge. A multivariate logistic regression analysis was conducted to adjust potential cofounders including age, sex, injury severity, emergency treatment, and emergency transfusion.

Results:
A total of 1,482 patients were included, with a median age of 73 years old; 381 of the patients were women. Median Injury Severity Score was 24. Of the 1,482 patients, 284 were in the alcohol group and 1,208 were in the non-alcohol group. Favorable neurological outcomes were observed in 159 (56%) and 563 (47%) of patients, with median hospital length of stay of 21 days and 18 days in the alcohol group and non-alcohol group, respectively. Multivariate logistic regression analysis showed alcohol consumption before injury was not associated with favorable neurological outcomes (adjusted OR: 0.96, 95% CI: 0.72 - 1.29).

Conclusions:
Alcohol consumption before injury had no positive impact on neurological outcomes in patients with severe TBI.
Abstract 212: The Effect Of 33 °C Vs. 36 °C Targeted Temperature Management To The Metabolism Following Out-of-hospital Cardiac Arrest.
Authors: Beske Rasmus Paulin P , Obling Laust E , Kjaergaard Jesper , Nielsen Niklas , Bro-Jeppesen John , Johansson Pär I , Hassager Christian
Published: June 2023

Targeted Temperature Management (TTM) following shockable out-of-hospital cardiac arrest (OHCA) has been recommended. The effect of different targeted temperatures on the human metabolome has not been compared. Elevated levels of metabolites from the Krebs cycle have recently been associated with a poor outcome in OHCA patients. Similarly, decreased levels of the amino acids valine and leucine have been linked with a poor outcome in septic shock patients.

Method:
From a single center in the randomized clinical TTM trial, we analyzed blood samples from resuscitated unconscious OHCA patients at two timepoints (hospital arrival and 48 hours later) using ultra-performance liquid mass-spectrometry. Patients were randomized to either 33°C or 36°C hypothermia for the first 28 hours. Sixty-one metabolites of the ~3000 compounds detected were prespecified for quantification and analyzed in the current study. Differences (95% CI) in metabolite concentrations from a constrained linear mixed model are reported, and p-values from the interaction term timepoint x TTM arm.

Results:
Of the 146 patients, 70 (48 %) were randomized to TTM 33°C. The baseline characteristics (age, gender, shockable rhythm, time to return of spontaneous circulation) and outcome (180 days mortality) were similar in the TTM groups. After 48 hours, approx. 24 hours from the cessation of TTM, fourteen metabolites differed significantly between the two groups. Among these, lactate acid (190 μM (74-305 μM),
p<0.001
), pyruvic acid (26 μM (8-44 μM),
p<0.
0
1
), 2-oxoglutaric acid (2.7 μM (1.0-4.4 μM),
p<0.01
) and prostaglandin E2 (0.60 nM (0.24-1.0 nM),
p<0.01
) were increased in the TTM 33 °C arm whereas valine (25 μM (15-35 μM),
p<0.001
) and leucine (14 μM (8.3 - 20 μM),
p<0.001
) were decreased.

Conclusion:
TTM at 33°C for 24 hours after OHCA results in a prognostically poorer metabolome even 24 hours later compared with TTM at 36°C.
Abstract 220: The Prediction Of Pulseless Electrical Activity Evolution During In-hospital Cardiac Arrest Using Machine Learning
Authors: Urteaga Jon , Aramendi Elisabete , Elola Andoni , Norvik Anders , Unneland Eirik , Bhardwaj Abhishek , Buckler David , Abella Benjamin , Skogvoll Eirik
Published: June 2023

Background:
Pulseless electrical activity (PEA) is the most common rhythm during in-hospital cardiac arrest (IHCA) with a prevalence around 50%. Knowing the prognosis of PEA evolution towards return of spontaneous circulation (ROSC) could help optimizing both resuscitation maneuvers and pharmacological therapy. The aim of this study was to develop an automatic method to predict the evolution of PEA during resuscitation based on the ECG-waveform.

Materials and Methods:
The dataset consists of 164 IHCA cases recorded by St. Olav University Hospital (Norway), Hospital of the University of Pennsylvania (USA) and Penn Presbyterian Medical Center (USA). ROSC was verified in 108 cases of the patients by physicians and bioengineers based on episode waveforms and clinical data. PEA segments of 5 sec were extracted from the last 10 min before ROSC or the end of resuscitation therapy. Three machine learning models were designed for segment binary classification based on an SVM (Gaussian) model using: 1) ECG-waveform features (9); 2) QRS-features (8); and 3) both ECG-waveform and QRS-features (17). Ten-fold cross validation was applied to train and test the models, and the performance was given in terms of area under the curve (AUC), sensitivity (Se) to correctly detect cases evolving to ROSC, specificity (Sp) and balanced accuracy (BAC).

Results:
A total of 780 segments were extracted (472 with ROSC). The median (IQR) for the models with the best feature combination are shown in the Table. The most important ECG-waveform features are associated to the ECG spectral distribution. QRS features that showed relevant information about the evolution of PEA were heart rate median and standard deviation, and QRS width, slope and amplitude.

Conclusions:
ROSC/no ROSC prediction of PEA segments is feasible using ECG signal information. The combination of ECG-waveform and QRS features enhances performance of predictive model.
Abstract 254: The Epidemiology Of Paediatric Out-of-hospital Cardiac Arrest In Australia And New Zealand
Authors: Bray Janet , Howell Stuart , Acworth Jason , Finn Judith C , Ball Stephen , Smith Karen L , Heriot Natalie , Bosley Emma , Faddy Steven , Doan Tan , Thomas Andrew , Wilson Alex , Dicker Bridget , SWAIN Andy , Thorrowgood Melanie , Perillo Sam ,   Aus-ROC Epistry Management Committee
Published: June 2023

Introduction:
Adult OHCA has been well described in Australasian studies, however little is known about paediatric OHCA in our region. This study describes the epidemiology of paediatric OHCA across Australia and New Zealand.

Method:
Data for paediatric OHCA were extracted from the Aus-ROC Epistry for the period 2017-2019. The Aus-ROC Epistry captures data nationwide across Australia and New Zealand covering a target population of roughly 30 million people. Paediatric OHCA was defined as an OHCA occurring in persons aged less than 18 years and classified as < 1 year, 1-5 years, 6-11 years and 12-17 years.

Results:
There were 2008 paediatric OHCA during the study: 701 aged below 1 year, 363 aged 1-5 years, 217 aged 6-11 years and 728 aged 12-17 years. There was considerable variation across age groups with respect to core arrest features, including home arrests (range: 61% to 89%), witnessed arrests (range: 22%-51%), arrests of medical aetiologies (range: 33%-95%) and arrests with a shockable initial rhythm (range: 1% to 10%). Bystander CPR in non-EMS witnessed cases was 63% and ranged from 58% in 12-17 year-olds to 73% in 1-5 year-olds.Resuscitation was attempted in 1319 cases (65.7%): 490 aged <1 year, 267 aged 1-5 years, 154 aged 6-11 years and 408 aged 12-17 years. Resuscitation rates varied across age groups ranging from 56% amongst 12-17 year-olds to 73% amongst 1-5 year-olds. In EMS treated cases, 28% had a return of spontaneous circulation (ROSC) in the prehospital setting (range: 19% to 38%) and 24% had ROSC on hospital arrival (range: 17%-33%). Rates of survival to hospital discharge/30 days was 6.8% overall, and ranged from 6.1% in infants (<1 year) to 11.8% in children aged 6-11 years.

Conclusion:
There is considerable heterogeneity in paediatric OHCA, characterised by differences on key measures across age groups.
Abstract 265: Social Determinants Of Health Impact Phenotype-based Outcome Prediction After Pediatric Arrest
Authors: Fink Ericka L , Kochanek Patrick M , Panigrahy Ashok , Beers Sue , Berger Rachel , BAYIR HULYA , Wang Chunyan , Pineda Jose , Topjian Alexis A , maddux aline , Willyerd Frederick , Hunt Elizabeth A , Chung Melissa G , Newth Christopher , Smith Lincoln , Doughty Lesley , Diddle J Wesley , Piantino Juan , Walson Karen H , Balakrishnan Binod , friess stuart , Siems Ashley , Press Craig , Patregnani Jason , Meyer Michael T , Haller Tamara , Treble-Barna Amery , Clark Robert , Fabio Anthony ,   POCCA Investigators
Published: June 2023

The Personalizing Outcomes after Child Cardiac Arrest-1 (POCCA-1) trial showed that blood-based brain injury biomarkers have promise to prognosticate outcome post-pediatric cardiac arrest. However, whether POCCA-1 biomarkers perform accurately among all children is unknown.

Hypothesis
We hypothesized that POCCA-1 biomarkers will have different performance accuracy by distinct clinical phenotypes after pediatric cardiac arrest.

Methods:
Fourteen US centers enrolled 164 children aged < 18 y with pediatric intensive care unit admission post-arrest. Glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal esterase L1, neurofilament light, and Tau proteins were measured in blood post-arrest d1-3. Patient ZIP codes linked to US census data provided socioeconomic neighborhood characteristics. We analyzed 120 children with evaluable data (n=50, unfavorable outcome [Vineland Adaptive Behavioral Scale < 70 or dead]) to create 3 clinical phenotypes using latent class analysis. POCCA-1 biomarker levels and outcomes were analyzed by phenotype. The POCCA-1 model was analyzed to predict 1 y unfavorable outcome using multivariate AUROC by phenotype for all 4 biomarkers on d1- 3 post-arrest.

Results:
Group 1 (n=35, 22%) were older, of White race, with private insurance and out-of-hospital cardiac arrests (OOHCA), fewer fever post-arrest, living in neighborhoods of mostly White race and lower poverty. Group 2 patients (n=77, 47%) were younger, of White race, with in-hospital cardiac arrests living in more socioeconomically diverse neighborhoods. Group 3 (n=51, 31%) were diverse in race and age, of more male sex, with Medicaid insurance and asphyxial, OOHCA, living in more impoverished neighborhoods. Unfavorable outcome was higher in Group 3 (69%) vs 1 (48%) and 2 (28%), p<0.001. All biomarkers (except Tau) were significantly increased on d1-3 in Group 3. Biomarker accuracy to predict outcome was excellent for Group 1 with 11/12 AUROCs significant. Models were less accurate for Group 2 (7/12) and marginal for Group 3 (3/12).

Conclusions:
The POCCA-1 prediction model performance varied by patient, arrest, and neighborhood context, suggesting that prediction models need to be personalized using clinically relevant and equitable phenotypes.
Abstract 271: The Time Dependence Of The Effect Of Extracorporeal Cpr For Out-of-hospital Cardiac Arrest Patients
Authors: Matsuyama Tasuku , Kitamura Tetsuhisa , Ohta Bon
Published: June 2023

Background:
Extracorporeal cardiopulmonary resuscitation (ECPR) has been considered as a rescue therapy for refractory cardiac arrest patients. However, little is known about who is refractory to conventional CPR and when to judge the initiation of ECPR.

Method:
We performed a secondary analysis of the nationwide hospital-based prospective observational study (The JAAM-OHCA registry) in Japan. This study included adult OHCA patients aged ≥18 years who had an initial shockable rhythm between June, 2014 and December, 2019. We classified the included patients into the ECPR group or the conventional CPR group based on whether to receive ECPR or not. Low flow duration (LFD) was defined as the time from call to the initiation of ECPR or to the time of return of spontaneous circulation or termination of resuscitation. The primary outcome was 1-month survival with favorable neurological outcomes defined by cerebral performance category 1 or 2. We visually described the nonlinear relationship between LFD and the predictive probability of favorable neurological outcome using a restricted cubic spline by each group.

Results:
Of 57,754 patients registered in the JAAM-OHCA registry, 3807 patients were included in analyses (ECPR group, n = 865 and Conventional CPR group, n = 2942). In both groups, shorter LFD was associated with favorable neurological outcome. For first 30 minutes, the overall proportion of favorable neurological was higher in the Conventional CPR group, but due to the rapid decrease in Conventional CPR, it dropped down to almost the same probability before 20 min as that of shortest LFD around 25 min in the ECPR group. After that, the probability of favorable neurological outcome was constantly higher in the ECPR group.

Conclusion:
The judgement of refractory cardiac arrests and decision for ECPR should be delivered before 20 min from call to maximize the probability of favorable neurological outcome for those with an initial shockable rhythm.