bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 20451: Hedgehog Signaling and Cardiomyocyte Proliferation
Authors: Singh Bhairab N , Kren Stefan M , Gong Wuming , Weaver Cyprian , Bowlin Kathy , Braunlin Elizabeth , Garry Mary G , Koyano-Nakagawa Naoko , Garry Daniel J
Published: July 2021

Background:
In contrast to adult mammalian heart, lower vertebrates such as newt exhibit a dramatic capacity for regeneration in response to injury. Understanding the underlying mechanisms and signaling pathways in newt could form the basis for regenerative therapies in mammals. In the present study, we explored the role of hedgehog (HH) signaling during cardiac regeneration.

Methods and Results:
To investigate cardiac regeneration (CR) in vivo, we performed ventricular resection studies in adult newt heart. Whole mount and histochemical studies revealed CR within 30 d of resection injury. Functional assessment by echocardiographic analysis showed improved ejection fraction from 22 ± 5% at 4 d to 42 ± 3% at 30 d of regeneration relative to control (60 ± 3%). Gene clustering and qRT-PCR analysis at 7d post injury indicated enrichment of hedgehog (HH) signaling factors including Shh and ptch1 by 3- and 2-fold respectively, suggesting a critical requirement of HH signaling at early stages of CR. We determined HH signaling is essential as pharmacological inhibition of the HH pathway resulted in complete ablation of CR. Using EdU-labeling and immunohistochemical analyses, we showed that HH signaling regulates proliferation of both epicardial and myocardial cells, as inhibition of the HH pathway reduced EdU-positive nuclei from 15 ± 2% to 5 ± 3%. In contrast, qRT-PCR analysis from murine hearts postnatal day (P) 2 to P14, showed reduced levels of HH signaling factors and cell-cycle associated mRNAs by 3.5-fold with concomitant increase of p21 by 2-fold. This implies HH signals are required for the proliferative process. Consistent with the newt studies, activation of HH in murine neonatal ventricular cardiomyocytes (NVCM) promoted cardiomyocyte proliferation, increasing positive nuclei from 10 ± 2% to 25 ± 3%, while inhibition of HH signaling reduced positivity to 6 ± 3%. qRT-PCR analysis established that activation of HH signaling in NVCM resulted in up regulation of transcripts associated with cardiomyocyte proliferation.

Conclusion:
These data indicated that HH signaling pathways modulate cardiomyocyte proliferation providing potential therapeutic targets for achieving mammalian cardiac regeneration.
Abstract 20510: Aortic Valve Calcium Score for Paravalvular Aortic Insufficiency (AVCS II) Study in Transapical Aortic Valve Implantation
Authors: Haensig Martin , Lehmkuhl Lukas , Foldyna Borek , Linke Axel , Mukherjee Chirojit , Schuler Gerhard , Gutberlet Matthias , Mohr Friedrich W , Holzhey David
Published: July 2021

Introduction:
Transapical-aortic valve implantation (TA-AVI) has evolved into a routine procedure in selected elderly high-risk patients. However, more-than-mild paravalvular leaks remain a significant drawback of current TAVI systems. The aim was to study the impact of native aortic valve calcification on paravalvular leaks in cardiac contrast-enhanced computed tomography (CT).

Methods:
The degree and distribution of native valve calcification were quantified using an Aortic Valve Calcium Score (AVCS) for each cusp separately (3mensio Valves™ workstation, version 7.0, 3mensio Medical Imaging B.V., Netherlands). To exclude an artificial increase of the AVCS due to the presence of contrast material, we used a threshold for density [mean aortic density + 2*D] and volume [0, 3, 5, 25 and 50 mm
3
] of calcification. AVCS was compared to the rate of paravalvular leaks, assessed intraoperatively by echocardiography and root angiography.

Results:
Eighty-eight consecutive patients prior to TA-AVI with preoperative CT aged 80.0 ± 5.7 years, 51.1 % female were included. Three prosthesis sizes were used for annular diameters up to 23 mm (n = 29), 26 mm (n = 45) and 29 mm (n = 14). Mean log. EuroSCORE was 24.6 ± 15.4 % and mean STS-Score was 8.4 ± 8.3 %. The mean AVCS in patients without paravalvular leaks (n = 42) was 606.4 ± 374.3; with mild paravalvular leaks (n = 39) was 761.2 ± 530.4; and with moderate paravalvular leaks (n = 5) was 792.4 ± 515.3 with the highest calcification in the non-coronary cusp. There was no significant association between the total AVCS and paravalvular leaks (χ
2
-statistic = 2.9; P = 0.13, 551 hounsfield units). The additional use of the volume-based threshold did not lead to an increase of the association between the AVCS and paravalvular leakages. Paravalvular leaks were significantly associated with the degree (r
Spearman
= 0.34; χ
2
-statistic = 10.0; P = 0.02) and location of eccentric calcified plaques.

Conclusions:
Quantification of aortic valve calcification in contrast enhanced computed tomography shows only a weak correlation with paravalvular leakage and is therefore not reliable as a predictor, respectively. The degree of eccentric cusp calcification was significantly associated with the occurrence and location of paravalvular leaks.
Abstract 20531: C-Abl Mediated Tyrosine Phosphorylation of Paxillin is Essential for LPS-Induced Endothelial Barrier Dysfunction and Acute Lung Injury
Authors: Fu Panfeng , Cress Anne E , Wang Ting , Garcia Joe G , Natarajan Viswanathan
Published: July 2021

Paxillin, a multi-domain scaffold-adapter focal adhesion (FA) protein, plays an important role in facilitating protein networking and efficient signaling transduction. Paxillin is phosphorylated at multiple serine/threonine and tyrosine residues; however, the role of tyrosine phosphorylation of paxillin in endothelial barrier dysfunction and the acute respiratory distress syndrome (ARDS) remains unclear. In this study, we used paxillin-specific siRNA and site-specific non-phosphorylatable mutants of paxillin to abrogate the function of paxillin, both in vitro and in vivo, to determine its role in the regulation of lung endothelial permeability and ARDS. In vitro, lipopolysaccharide (LPS) challenge of human lung microvascular endothelial cells (ECs) resulted in paxillin accumulation at focal adhesions, enhanced tyrosine phosphorylation of paxillin at Y31 and Y118, and significant endothelial barrier dysfunction. However no significant changes in Y181 phosphorylation by LPS challenge was observed. Paxillin silencing (siRNA) attenuated LPS-induced endothelial barrier dysfunction and dissociation of VE-cadherin from adherens junctions. LPS-induced paxillin phosphorylation at Y31 and Y118 was mediated by c-Abl tyrosine kinase and not by Src or focal adhesion kinase (FAK) in human lung microvascular ECs. Furthermore, down-regulation of c-Abl (siRNA) significantly reduced LPS-mediated endothelial barrier dysfunction. Transfection of human lung microvascular ECs with paxillin Y31, Y118 and Y31/Y118 mutants mitigated LPS-induced barrier dysfunction and VE-cadherin destabilization at adherens junctions. In vivo, knockdown of paxillin with siRNA in mouse lungs ameliorated LPS-induced pulmonary protein leak and lung inflammation. Together, these results suggest that c-Abl-mediated tyrosine phosphorylation of paxillin at Y31 and Y118 regulates LPS-mediated pulmonary vascular permeability and injury.
Abstract 20539: Frailty Assessment in Advanced Heart Failure
Authors: Gunda Sampath , Kargoli Faraj , Gentile Kevin , Shin Jooyoung J , Patel Snehal R
Published: July 2021

Introduction:
There is growing literature supporting the significance of frailty in a broad array of cardiovascular diseases. To our knowledge, there are no studies specifically examining the application of frailty assessment to an advanced heart failure population.

Methods:
Forty consecutive elderly (>65 yrs of age) subjects were enrolled from the heart failure clinic at Montefiore Medical Center, if they had advanced heart failure as defined by: LVEF < 35%, NYHA Class 3 or 4, and a 6 minute walk (6mwt) < 300 meters. At baseline, subjects were assessed for frailty with the Fried Frailty Index, which consists of 5 components: hand grip strength (HGS), 15 meter walk time (WT), weight loss, low physical activity and exhaustion. Each component is assigned a score of 0 or 1 and summed for the total score: 0 = not frail, 1-2 = intermediately frail, ≥3 = frail. Subjects were prospectively followed at 3 month intervals for mortality or heart failure related hospitalizations.

Results:
Follow-up was available for 38 subjects at a median length of 437 days (range: 12-549). At baseline, the mean age of the cohort was 74±7 yrs, LVEF 27±7%, and 6mwt 189±80m. None of the patients tested were not frail, 32% (12) were intermediately frail, and 68% (26) were frail. More patients in the frail group (N=7) expired during follow up then those in the intermediately frail group (N=1) although this did not reach statistically significance (Figure; 1). Since there was a limited spectrum of frailty in this cohort, HGS and WT were assessed as continuous measures for association with outcomes. Both objective tools demonstrated a strong trend towards mortality (p=0.08). There was no association between the composite or individual score and hospitalizations.

Conclusions:
In this pilot study of frailty assessment in advanced heart failure, the objective tools of WT and HGS tended to be associated with mortality. These preliminary results warrant further investigation.
Abstract 20635: Dipeptidyl-Peptidiase 4 Inhibitors and the Risk of Heart Failure - A Nationwide Case-Crossover Study
Authors: Chang Yi-Cheng , Chang Chia-Hsuin , Lin Jou Wei , Chuang Lee-Ming , Lai Mei-Shu
Published: July 2021

Introduction:
Dipeptidyl-peptidiase 4 (DPP4) inhibitors, a new type of oral hypoglycemic agents, have been widely used in the treatment of type 2 diabetes mellitus (DM). However, recent studies showed that the use of DPP4 inhibitors, especially saxagliptin, could be associated with an increased risk of heart failure (HF).

Methods:
We conducted a retrospective case-crossover study by identifying DM patients aged 20 years and above hospitalized for HF between 2009 and 2011 from Taiwan National Health Insurance Database. Diagnosis codes from inpatient claims databases were used to ascertain the index date of hospitalization. For each patient, we defined case period as 1 to 30 days before the index date and control period as 91 to 120 days before the index date. The use of DPP4 inhibitors during the case and control periods were identified from the pharmacy claims database. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated by a conditional logistic regression model.

Results:
A total of 47,506 patients hospitalized for HF (48.2% mean and 51.8% women) was included in the analysis (mean age: 72.7±12.4 years). Among them, 2,874 patients (6.05%) used sitagliptin in the case period, and 2,318 (4.88%) did in the control period. Use of other DPP4 inhibitors, i.e., saxagliptin and vildagliptin, was rare. The analysis of the discordant medication in the two periods showed that sitagliptin use was associated with an increased risk of HF (OR: 2.85, 95% CI: 2.46-3.30). Additional analyses using different time frames as the control period showed similar results. In contrast, there was no increased risk for HF in the use of sulfonylureas or metformin.

Conclusions:
The nationwide case-crossover study demonstrated that sitagliptin was associated with an increased risk of hospitalization for HF. Further studies are needed to examine whether the potential risk of HF is a class effect of DPP4 inhibitors.
Abstract 20678: A Systematic Review of World-Wide Characteristics and Management of Patients With ST-Segment Elevation Myocardial Infarction
Authors: Zhan Yang , Huynh Thao
Published: July 2021

Background:
Management of ST elevation myocardial infarction (STEMI) has made tremendous progresses during the last decades. However, it remains uncertain whether all STEMI patients are receiving optimal care and whether variation in care has any impact on their outcomes. We aim to characterize the contemporary global characteristics, managements, and outcomes of STEMI patients.

Methods and Results:
We searched EMBASE/MedLINE Ovid for observational data of patients with STEMI. We identified 17 studies enrolling 112 772 patients in 20 countries during the last 5 years (2008-2013). The median age ranged from 54 to 66 years with 13%-33% females. Twelve percent to 39% of patients presented in Killip heart failure class 2-4. In-hospital use of aspirin (ASA), P2Y12 inhibitor/thienopyridines, and systemic anticoagulation was 90-99%, 77-97%, and 61-100% respectively. Reperfusion was provided for 63%-97% of patients. Fibrinolysis was used in 0.7%-66% with a door-to-needle (D2N) time of 28-65 minutes; 12%-74% with D2N <30minutes. Primary percutaneous coronary intervention was performed for 17%-97% with a door-to-balloon (D2B) time of 40-125 minutes; 40%-94% had D2B <90 minutes. Emergency cardiac surgery was performed in 0.4%-8% of patients. Discharge prescriptions included ASA, thienopyridines/P2Y12 inhibitors, beta-blockers, and statins in 85%-99%, 77%-97%, 54%-83%, and 64%-95% respectively. In-hospital outcomes included death (2%-10%), recurrent myocardial infarction (0.4%-5%), stroke (0.2%-1.6%), major bleeding (0.3%-7%). The median hospital stay ranged from 4-6 days.

Conclusion:
Despite recent progresses in STEMI care, there remains marked heterogeneity in STEMI care and outcomes worldwide that warrants further attention. Identification of gaps to STEMI care and remedial actions may improve the global outcomes of STEMI patients.
Abstract 20707: Macrophage Mitochondrial Fission is Essential for Continued Clearance of Apoptotic Cells and Plays a Protective Role in Advanced Atherosclerosis
Authors: Wang Ying , Tabas Ira , Nomura Masatoshi
Published: July 2021

Introduction:
The mitochondrial dynamic processes of fission and fusion influence and integrate with multiple physiologic and pathophysiologic processes. Mitochondrial dynamics dysregulation has been implicated in atherosclerosis, but little is known about the role of myeloid cell specific mitochondrial dynamics in the progression of atherosclerosis. In macrophage-enriched murine atherosclerosis lesion areas, we have found that levels of mitochondrial fission protein DRP1 down-regulated as the lesion progresses. In contrast, the mitochondrial fusion protein MFN2 is up-regulated. Further, mitochondria in lesional macrophages show hyperfusion morphology as the lesion develops. These suggest that mitochondria in macrophages undergo hyperfusion during the lesion progression.

Hypothesis:
We hypothesize that mitochondrial hyperfusion plays a significant role in atherosclerosis.

Methods:
We used a model Drp1fl/fl LysmCre+/-Ldlr-/-mice who have hyperfused mitochondria in Mϕs to test the functional significance of mitochondrial hyperfusion in atherosclerosis.

Results:
We have found that inhibition of Mϕ mitochondrial fission leads to a striking increase of necrotic core area and the accumulation of apoptotic cells, which are likely due to the defective phagocytic clearance of apoptotic cells (efferocytosis) in the advanced stage of atherosclerosis in vivo. This is further verified by another in vivo efferocytosis assay: Drp1fl/fl LysmCre+/-mice are defective of clearing apoptotic thymocytes in vivo. Mechanistically, the continued uptake of apoptotic cellsis impaired in Mϕs with hyperfused mitochondria. This is because of the lower level of uncoupling protein 2 (UCP2), the mitochondrial inner membrane protein that prevents the sustained elevation of inner membrane potential (Δψ). Chemical uncoupler FCCP or restoration of UCP2 can correct the efferocytosis deficiency in DRP1 knockout Mϕs.

Conclusions:
Macrophage mitochondrial fission is essential for continued clearance of apoptotic cells and plays a protective role in advanced atherosclerosis. This study indicates that mitochondrial fusion/fission could be a novel therapeutic target to prevent lesion necrosis and stabilize the advanced plaques in humans.
Abstract 220: Comparison of 3 Cognitive Exams in Cardiac Arrest Survivors
Authors: Koller Allison , Rittenberger Jon , Morgan Patrick , Repine Melissa , Kristan Jeffrey , Callaway Clifton
Published: July 2021

Background:
Cognitive deficits may detract from quality of life after cardiac arrest (CA). The pattern and prevalence of these deficits are not well documented. We used the Computer Assessment of Mild Cognitive Impairment (CAMCI), the Montreal Cognitive Assessment (MOCA) and the 41 Cent Test to assess cognitive impairment in survivors of CA. We hypothesized that CAMCI subscales and other scores that were highly correlated could identify specific domains of impairment in CA survivors.

Methods:
Four researchers administered the CAMCI, MOCA, and/or the 41 Cent Test to CA survivors after discharge from the intensive care unit between 2010 and 2014. Physicians screened patients with the Mini-Mental State Exam to determine when this cognitive testing was feasible. We compared the distribution of scores between patients who presented with coma and those who awoke immediately after CA. Pairwise correlations between the different subscales and tests were considered significant with alpha error of 0.05.

Results:
Ninety-two participants completed the CAMCI, of which 18 participants completed the CAMCI, MOCA and 41 Cent Test. The mean (SD) percentile score for CAMCI was 32.2 (20.3) out of possible 100, for the MOCA was 20.3 (5.2) out of a possible 30 points and the 41 Cent Test was 5.4 (1.1) out of a possible 7 points. MOCA correlated strongly with the overall CAMCI score (r = 0.82) and with the executive accuracy subscale of the CAMCI (r = 0.75). The executive accuracy subscale and overall CAMCI score correlated with one another (r = 0.81) when all 92 CAMCI exams were considered. The MOCA and 41 Cent Test were correlated with each other (r = 0.63).

Conclusion:
The CAMCI detects cognitive impairment after CA; the MOCA correlates strongly with the overall CAMCI and the executive function subscale of the CAMCI. The 41 Cent Test may not be as effective as the MOCA in detecting cognitive deficits.
Abstract 246: Reduced Prehospital Survival Rate After Out-of-Hospital Cardiac Arrest in Patients with Diabetes Mellitus Type 2: A Prospective Community-Based Study
Authors: van Hoeijen Daniel A , Blom Marieke T , Bardai Abdennasser , Souverein Patrick C , de Boer Anthonius , Tan Hanno L
Published: July 2021

Objectives:
Out-of-hospital cardiac arrest (OHCA) remains a major cause of death. We aimed to determine whether diabetes mellitus type 2 (T2DM) is associated with survival to hospital admission and to hospital discharge after OHCA.

Methods:
We performed a community-based cohort study of 1549 OHCA patients with ECG-documented ventricular tachycardia/ventricular fibrillation (VT/VF). Survival to hospital admission and to hospital discharge was compared between patients with T2DM and non-DM patients using multivariate logistic regression analysis. Among discharged patients, we compared the proportions of neurologically intact (NI) survival. All analyses were stratified according to T2DM disease severity.

Results:
Patients with T2DM (n=275) had lower survival rates to hospital admission than non-DM patients (n=1274, 48.7% vs. 55.8%, P=0.032). Patients with severe T2DM had lower survival rates to admission than patients with mild T2DM (37.3% vs. 53.3%, P=0.034). Multivariate analysis revealed that T2DM was an independent determinant of survival to hospital admission (OR 0.75 [95% CI 0.58-0.98]). Survival rates to hospital discharge were also lower in patients with T2DM (n=134) than in non-DM patients (n=711, 40.3% vs. 57.7%, P<0.001). Multivariate logistic regression analysis among patients admitted to hospital showed that T2DM was associated with lower survival to discharge (OR 0.57 [95% CI 0.38-0.84]). NI-status at discharge was high in both patients with T2DM and non-DM patients (94.4% vs. 94.6%, P=0.954)

Conclusion:
Patients with T2DM had lower survival rates to hospital admission and to hospital discharge after OHCA than non-DM patients. T2DM was an independent determinant of lower survival.
Abstract 260: Impact of Viewing an Ultrabrief Chest Compression--Only Video or Teaching a Chest Compression--Only Class on Lay Bystander CPR Performance in a High School
Authors: Beskind Daniel , Thiede Rebecca , Hoyer Riley , Ludgate Melissa , McMorrow Devin , Tiutan Tim , Shane Romy , Brown Jeffrey , Smith Ann , Smith Mike , Pleasants Michael , Panchal Ashish , Burns Whitney E , Stoltz Uwe
Published: July 2021

Introduction:
Cardiac arrest is responsible for 300,000 deaths in the United States. Bystander CPR has been shown to improve survival, but is only performed 30-50% of the time.

Objectives:
To determine if a chest compression-only (CCO) ultra-brief video (UBV) and a CCO-CPR class are effective at teaching CCO-CPR to high school students.

Methods:
This was a prospective cluster-randomized controlled trial with three arms: 1) CCO- UBV, 2) CCO-Class, 3) a control group (college recruiting video). High school students enrolled in a health course were randomized by class into of the 3 study arms. CPR performance was assessed with Laerdal Skillreporter mannequins after presentation of a scenario (sudden witnessed collapse) before (Pre), after (Post), and at 2 months following each intervention. CPR performance measures included the following: calling 911/starting compressions within 2 minutes, mean rate and depth of compressions.

Results:
168/206 students 14-18 years of age, representing 5 classes, participated in this study. Results are shown in the Table. The proportion of participants that called 911 and/or started compressions within 2 minutes, as well as chest compression rate, significantly improved following the UBV and CCO-Class Post and at 2 months. Chest compression depth significantly improved following the CCO-Class both Post and at 2 months. No performance measure improved Pre to Post for the control arm.

Limitations:
More than one model of mannequin was used, observers and participants were not blinded to the intervention, and the study population represented a single public high school.

Conclusions:
A CCO-UBV and a brief CCO-CPR Class were effective at increasing the likelihood of calling 911, initiating CCO-CPR within 2 minutes and improving chest compression rate up to 2 months after the video or class in a population of high school students. The CCO-CPR class also significantly improved chest compression depth up to 2 months after the class.
Abstract 263: Emergencies and Resuscitation in the Catheter Laboratory: High-Fidelity Simulation as a Training Tool to Improve Multidisciplinary Team Communication and Confidence
Authors: Butcher Charles J , Sarang Zubair , Green Rebecca , Duke Oscar , Knowles Timothy , Eneje Odiri , McVeigh Geraldine , Bowers Mark , Mason Mark , Jones David
Published: July 2021

Purpose:
Multi disciplinary team (MDT) emergency and resuscitation training for acute device related complications in the catheter laboratory commonly takes the form of didactic instruction or post event debriefing. High fidelity simulation offers the opportunity to role-play clinical emergencies in a controlled environment in a dynamic and interactive setting. This technique allows for immersive training whilst protecting patients from unnecessary risk and may enhance performance.

Methods:
Two sessions, each with two high fidelity in-situ resuscitation scenarios, using a simulation manikin, were run as a pilot (Session 1 - pacing failure during device generator change; tamponade during lead extraction, Session 2 - Primary angioplasty with cardio pulmonary arrest, Primary angioplasty requiring acute temporary pacing). These were viewed by other members of the department on a live video feed. 45 members of the MDT (including Cardiologists, Anesthetists, Radiographers, Nurses and Physiologists of all levels) participated in each the session, attending a formal facilitated debrief after each scenario. The debrief outcome of scenario 1 was designed to influence the behavioral strategy during the conduct of scenario 2. Anonymous pre and post scenario questionnaires measured improvement in confidence, clinical knowledge and inter-professional relationships.

Results:
We collected 72 pre-course and 67 post-course questionnaires in total. 92% agreed or strongly agreed that the session enhanced inter-professional working relationships and communication skills. 73% felt their clinical knowledge was increased. The number of people who felt ‘confident’ or ‘very confident’ in ‘speaking up about something they disagreed with in a clinical emergency’ increased from 45% to 65% (p<0.05). All respondents would recommend the session to a colleague & attend themselves again.

Conclusions:
High fidelity in-situ simulation may be a useful tool to actively engage the MDT in improving clinical knowledge and communication in emergency resuscitation situations, whilst enhancing inter-professional relationships. This may have important implications for patient safety in the Catheter Laboratory.
Abstract 269: How Much Exposure to Resuscitation Do Emergency Medical Services Personnel Get?
Authors: Dyson Kylie , Bray Janet , Smith Karen , Bernard Stephen , Straney Lahn , Finn Judith
Published: July 2021

Objectives:
The exposure of emergency medical service personnel (paramedics) to out-of-hospital cardiac arrest (OHCA) and resuscitation procedures could be an important factor in skill maintenance and quality of care. This study aims to describe paramedic exposure to OHCA resuscitation in the state of Victoria, Australia (population 5.8 million).

Methods:
We extracted and linked data from the Victorian Ambulance Cardiac Arrest Registry (VACAR) and Ambulance Victoria’s employment dataset for the period 2003-2012. Paramedics were considered to have ‘exposure’ to OHCA if they attended a case where resuscitation was attempted. Individual rates were calculated for annual exposure (number of OHCA exposures for each paramedic/years employed in study period) and days between exposures (total paramedic days/total number of exposures).

Results:
Over the 10-year period, there were 49,107 OHCAs and 5,673 paramedics employed. Resuscitation was attempted in 44% of patients. An average of 3.2 (SD±1.1) paramedics attended each case. The median average exposure of paramedics was 2.2 (IQR=1.2-3.5) OHCAs/year. The proportion with no exposures in a year increased from 39% in 2003 to 43% in 2012 (p=0.036). OHCA exposure was significantly less in those employed part-time or casual (p<0.001), in a rural area (p<0.001) or with a lower qualification (p<0.001) (Table). Annual exposure to pediatric and traumatic OHCAs was particularly low (Table). Paramedics were exposed to an average of 0.006 OHCAs/day, meaning it would take an average of 163 days be exposed to OHCA and up to 12.5 years for rare cases, such as pediatric OHCAs.

Conclusion:
Our study identified paramedic exposure to resuscitation is low and has decreased over time. This highlights the importance of supplementing paramedic exposure with other methods, such as simulation, to maintain resuscitation skills. This may be particularly important to paramedics with low exposure and for rare case types, such as pediatric OHCA.
Abstract 304: The Effects of Compression Waveforms on the Outcomes of Cardiopulmonary Resuscitation in a Porcine Model of Cardiac Arrest
Authors: Wu Xiaobo , Yang Zhengfei , Tang Wanchun
Published: July 2021

Background:
Previous studies have demonstrated that different mechanical compression waveforms yield different hemodynamic efficacy. In the present study, we investigated the effects of two different compression waveforms on the hemodynamics and defibrillation efficacy in a pig model of CPR.

Methods:
Ventricular fibrillation was electrically induced in ten male domestic pigs weighing between 35 - 40 kg and untreated for 7 mins. The animals were then randomized to receive chest compression with either trapezoidal (TW) or sinusoidal (SW) waveform. After a total 5 mins of CPR, defibrillation was attempted. ECG, aortic blood pressure (AP), right atrium blood pressure (RAP) and carotid blood flow (CBF) were continuously record and analyzed after the experiments were completed.

Results:
All animals were resuscitated. The total defibrillation attempts in the TW group were significantly fewer than the SW group (1.6±0.9 vs. 11±7.8, p=0.03) prior to successful resuscitation. Amplitude spectrum analysis (AMSA) and signal integral were significantly greater in each minute of CPR in the TW group when compared with the SW group (Figure 1). Significantly greater CPPs were observed in the TW group during the last 3 mins of CPR. Mean CBF showed no difference during CPR between the two groups, but the dynamic forward CBF in the first 4 mins of CPR was significantly greater in the TW group (Figure 2).

Conclusions:
Chest compression with trapezoidal waveform improved hemodynamics and defibrillation efficacy in the pig model of CPR. Compression waveform therefore became another important factor to be considered during mechanical chest compression.
Abstract 4: The Effect of Prehospital Hypoxia and Hypotension on Outcome in Major Traumatic Brain Injury: A Deadly Combination
Authors: Spaite Daniel W , Stolz Uwe , Bobrow Bentley J , Chikani Vatsal , Sherrill Duane , Sotelo Michael , Barnhart Bruce , Gaither Joshua B , Adelson P D , Viscusi Chad , Mullins Terry , Humble Will , Denninghoff Kurt R
Published: July 2021

BACKGROUND:
Hypoxia (HOx) or hypotension (HT) occurring during the EMS management of major traumatic brain injury-TBI reduces survival. However, little is known about the impact of both HOx and HT, occurring together, on outcome. Only a handful of reports have studied the combination of prehospital HOx/HT in TBI and the largest of these only had 14 cases with both.

Objectives:
To evaluate the associations between mortality and prehospital HOx and HT, both separately and in combination.

METHODS:
All moderate/severe TBI cases (CDC Barell Matrix Type-1) in the Excellence in Prehospital Injury Care (EPIC) TBI Study (a statewide, before/after controlled study of the impact of implementing the EMS TBI Treatment Guidelines-NIH/NINDS: 1R01NS071049) from 1/1/08-6/30/12 were evaluated [exclusions: age<10; death before ED arrival; EMS O2 saturation-“sat”<11%; EMS SBP less than 40 or greater than 200; missing sat (5.4% of cases) or SBP (3.1% of cases)]. The relationship between mortality and HOx (sat <90) and/or HT (SBP<90) was assessed with crude and adjusted odds ratios (cOR, aOR) using multivariable logistic regression, controlling for important confounders (see Figure) and accounting for clustering by Trauma Center.

RESULTS:
9194 cases were included [Median age: 46 (IQR: 26-65); Male: 68.1%]. 8109 (88.2%) had no HOx/HT, 535 (5.8%) had HOx only, 419 (4.6%) had HT only, and 131 (1.4%) had both HOx/HT. The Figure shows the cORs and aORs for death.

CONCLUSION:
In this large analysis of major TBI, prehospital HOx and HT were associated with significantly increased mortality. However, the combination of HT and HOx together had a profoundly-negative effect on survival even after controlling for significant confounders. In fact, the aOR for death in patients with both HOx/HT was more than 3 times greater than for those with HOx or HT alone. Since the TBI Guidelines emphasize the prevention and treatment of HOx and HT, their implementation has the potential to significantly impact outcome.
Abstract 68: Compression Depth Was Correlated with SNR in VF but Not in Nonshockable Rhythms During CPR
Authors: Li Yongqin , Gong Yushun , Chen Bihua , He Mi
Published: July 2021

Introduction:
Artifacts produced by chest compression (CC) during cardiopulmonary resuscitation (CPR) preclude reliable automated ECG rhythm analysis. Several filtering techniques have been proposed to remove the artifact with the use of compression related signals as reference. In order to test the performance of the filters, CPR-corrupted signals were usually generated at different signal-to-noise ratio (SNR) levels and the improvements in SNR were evaluated. However, SNR in real cardiac arrest data and the relationship between compression depth (CD) and SNR are still unknown.

Method:
ECG, together with CD signals were recorded through defibrillators in 146 patients who experienced cardiac arrest and CPR. A total of 306 segments (6 seconds length, sample rate 250Hz), including 152 ventricular fibrillation (VF), 91 pulseless electrical activity (PEA) and 63 asystole were analyzed. Each segment consisted of 3 seconds corrupted and adjacent 3 seconds artifact-free signal. The power of signal was calculated from the artifact-free signal and the power of artifact was obtained through subtracting the power of corrupted ECG by the power of artifact-free signal. The relationship between CD and SNR was tested with Pearson correlation coefficients.

Results:
The average CD was 4.76±1.24cm. SNR of asystole was significantly lower compared to that of VF and PEA (-21.93±7.37 dB vs. -5.04±8.53 dB and -3.70±7.16 dB, p<0.01). As shown in the Figure, the correlation coefficient was -0.16 (p<0.01) between CD and SNR. When each of the rhythms was investigated individually, negative correlation between CD and SNR was only observed in VF (r =–0.21, p < 0.01).

Conclusion:
In this patient population, SNR of corrupted ECG was not correlated with CD when the underlying rhythms were non-shockable. This may, at least in part, accounted for the reported high sensitivity but low specificity when adaptive filters were used to remove artifact using CD related signals as reference.
Abstract 92: Efficacy of Continuous Venovenous Hemodiafiltration on Survival of Cardiac Arrest in Humans
Authors: Shinozaki Koichiro , Sato Yasunori , Becker Lance B , Oda Shigeto , Hirasawa Hiroyuki
Published: July 2021

Introduction:
The efficacy of continuous venovenous hemodiafiltration (CVVHDF) on patients suffering cardiac arrest (CA) is unclear.

Objective:
To identify any efficacy of CVVHDF on post cardiac arrest syndrome (PCAS) in humans.

Methods:
This was a multicenter study conducted between 2006-09 in Chiba, Japan, involving non-trauma CA adult patients. Patients admitted to acute care units were included. The primary outcome was mortality through the end of the study. Cerebral Performance Category (CPC) score was recorded at 6 months and the blood levels of IL-6 on admission, at 6hr, and 24hr after CA were measured as the secondary outcomes. The application of CVVHDF was left to each physician. The dialysate flow and filtration rate were set at 10-20mL/kg/h and 6-10mL/kg/h, respectively. We evaluated the effect of CVVHDF on survival using the Kaplan-Meier method. A Cox proportional hazard model with a step-wise selection procedure was used to identify independent variables associated with survival time. A matching process based on propensity-score was done to compare neurological outcome and blood IL-6 levels between groups.

Results:
A total of 227 patients were included. The survival time in the CVVHDF group (n=33) was significantly longer than non-CVVHDF group (long rank, p<0.001). Three factors were identified as indicators of earlier death; Initial ECG of non-VF, whether or not CA occurred before EMS arrival, and if therapeutic hypothermia was used. When being adjusted for those 3 factors, there was no significant difference in association of CVVHDF with mortality (hazard ratio, 1.33; 95% confidential interval, 0.81-2.18; p=0.26). Between the matched groups, there were no differences in the number of patients with good neurological outcome (p=0.24) and in IL-6 levels at 24hr (p=0.08). IL-6 levels on admission (median and interquartile, 69pg/mL [25-193]) and at 6hr (116pg/mL [33-499]) of non-CVVHDF group were significantly lower than those (350pg/mL [142-1493] and 247pg/mL [89-1104]) of CVVHDF group (p=0.002 and p=0.035, respectively).

Conclusions:
We found no association with the use of CVVHDF and mortality of PCAS patients. The use of CVVHDF was not seen to lower the circulating levels of IL-6 levels in this cohort of patients.
Abstract 95: Coronary Intervention After Out-of-Hospital Cardiopulmonary Resuscitation: Chances and Limitations
Authors: Arntz Hans-Richard , Strauss Simon , Mochmann Hans-Christian
Published: July 2021

Background:
Actual guidelines recommend an invasive approach (CORO) in case an ischemic cause of sudden cardiac arrest (SCD) can`t be excluded.

Methods:
In a retrospective study we investigated procedures and course of 767 consecutive OHCA pts. of whom 220 pts who survived to hospital admission and 166 were admitted to our hospital.

Results:
CORO was performed in 91 pts. Of these 83 had a prehospital ECG or an ECG at admission: Thirty-nine (47%) of the pts with CORO had typical ECG signs of a STEMI (SECG), 44 pts had CORO without a SECG. On the other side 52 of 58 (89%) pts without CORO had not a typical SECG. A “culprit lesion” was detected in 30 of 39 (70%) of pts with an SECG but also in 21 of 44 (46%) pts without an SECG. Creatinine levels a admission were elevated in pts with CORO (1.4 mg/l) as well as in pts without CORO (1.8 mg/l). During hospital stay hemodialysis/CVVH was considered necessary in 28 of 91 pts (31%) with CORO and 21 of 75 pts (28%) without CORO (p=ns). We did not observe a selection bias concerning admission of pts to our hospital or other hospitals respectively. With regard to perform CORO, however, there was a significant tendency to preference of prognostic favorable groups i.e. younger pts <65years (p=0.042), pts with VF/VT as initial rhythm (p<0.01) and a trend to pts with bystander resuscitation. With CORO survived 42 of 55 pts (76%) with a CPC score of 1 or 2 and 22 of 32 pts (69%) with a CPC score of 3 or 4. Twenty-seven of the 91 pts (36%) with CORO and 48 of the 71 pts (67%) without CORO died (p<0.001).

Conclusion:
Intervention is principally justified in resuscitated pts in whom an ischemic cause has to be assumed. Without a randomized prospective study, however, it will remain unclear, to which extend CORO improves prognosis after CPR or if CORO is only an “add-on” of minor relevance in a group of pts with a basically good prognosis.
Abstract 9523: Comparison of Guideline Based Pretest Probability Scores Applied to Patients Undergoing Coronary Computed Angiography - The Partners Registry
Authors: Bittencourt Marcio S , Hulten Edward , Nasir Khurram , Cheezum Michael , Abbara Suhny , Gohshhajra Brian , Hoffmann Udo , Di Carli Marcelo , Blankstein Ron
Published: July 2021

Introduction:
According to current guidelines, the initial test for the evaluation of coronary artery disease (CAD) in individuals with no known disease should be chosen according to the pre-test probability of obstructive CAD. While U.S. guidelines use the Diamond and Forrester (DF) classification, the recent European guidelines have proposed the use of other methods to estimate the pretest probability.

Hypothesis:
The performance of newer CAD prediction scores will be superior to the DF classification in patients referred to a coronary CTA.

Methods:
Exam findings were classified as non-obstructive (no CAD or <50% stenosis) or obstructive (≥50%). For each individual we calculated a continuous version of the Diamond and Forrester score, the first version of the CAD consortium score (CAD1), and the two versions of the CAD consortium 2, the basic version (CAD2b), which includes the same variables as the DF classification, and a complete version (CAD2c), which also includes risk factors. We compared the calibration (predicted vs. observed prevalence of obstructive CAD) and discrimination (area under the ROC curves).

Results:
We included 2580 individuals (mean age 55±13 years, 58% males) with complete information on symptoms and risk factors needed to calculate the scores. 545 (21%) individuals had obstructive CAD on coronary CTA. The estimated probability of CAD by DF was higher than observed, especially among those with an intermediate-high pretest probability (Figure). When evaluating the discrimination, the c-statistic for the DF=0.718 (95%CI: 0.695 - 0.742), for CAD1= 0.7265 (0.703 - 0.750), for CAD2b =0.753 (0.730 - 0.776) and for the CAD2c = 0.791 (0.771 - 0.811). The CAD2c had a significantly higher c-statistic than the other models (p<0.0001)

Conclusions:
The CAD2c provides better discrimination and calibration to predict obstructive CAD. Thus, the CAD consortium complete score should be preferred against current risk prediction strategies.
Abstract 9610: Aortic Stiffness and Increased Left Ventricular Mass Predict Progress From Prehypertension to Hypertension
Authors: Kim Yong H , Kim Seong-Hwan , Kim Jin-Seok , Shin Chol , Lee Seung-Ku
Published: July 2021

Introduction:
Whether aortic stiffness and increased left ventricular (LV) mass can predict progress from prehypertension to hypertension is not well investigated.

Hypothesis:
The aim of this study was to find predictors of hypertension and evaluate the clinical implications of aortic stiffness and increased LV mass in disease-free prehypertensive population.

Methods:
510 prehypertensive subjects in the Korean Genome Epidemiology Study (KoGES) were observed for four years. In addition to clinical information, left ventricular mass index (LVMI), left atrial volume index (LAVI), aortic pulse wave velocity (PWV), carotid intima-media thickness (cIMT) and other cardiovascular characteristics were obtained at baseline. Baseline clinical and cardiovascular characteristics were compared between subjects that developed hypertension and did not, and independent predictors of hypertension were determined.

Results:
Out of 510 participants, 237 subjects developed hypertension during four years (46%). After multivariate adjustment, high range prehypertension (OR=4.27 [2.63-9.63], p=0.000), 5th quintile of LAVI (OR=3.38 [1.63-7.04], p=0.001), 5th quintile of LVMI (OR=2.982 [1.399-6.359], p=0.005), 4th (OR=2.881 [1.372-6.049], p=0.005) and 5th quintiles of PWV (OR=2.283 [1.067-4.885], p=0.033) predicted development of hypertension. Subjects in low range prehypertension at baseline and hypertension at the final visit (“fast increase in blood pressure (BP)”) had the highest baseline LVMI, while those with high range prehypertension at baseline and not-hypertension at the final visit ("slow increase in BP") had the lowest baseline LVMI (p=0.005 for fast BP increase vs. slow BP increase).

Conclusions:
In prehypertensive population, presence of aortic stiffness and increased LV mass independently predicted development of hypertension. Further, increased LVMI at baseline was correlated with fast increase in BP in the future. PWV and echocardiography should be performed to recognize subjects at high risk of hypertension, because they possibly benefit from pre-emptive medical treatment.
Abstract 9629: Combination Therapy of Cilostazol and Bepridil Suppresses Recurrent Ventricular Fibrillation Related to J-Wave Syndromes
Authors: Shinohara Tetsuji , Nakagawa Mikiko , Takahashi Naohiko
Published: July 2021

Introduction:
Brugada syndrome (BrS) and idiopathic ventricular fibrillation (VF) associated with infero-lateral early repolarization patterns (early repolarization syndrome (ERS)) are termed “J-wave syndromes”. In such patients, an implantable cardioverter-defibrillator (ICD) is first-line therapy for prevention of sudden cardiac death. However, frequent ICD shocks due to recurrent VF remain serious problems. We investigated if combination therapy using cilostazol and bepridil could suppress recurrent VF.

Methods:
Our cohort comprised 22 consecutive patients (BrS, 16; ERS, 3; unknown, 3) with J-wave syndromes in whom ICDs were implanted for spontaneous episodes of VF. We enrolled 7 patients with J-wave syndromes who experienced ICD shocks due to recurrent VF after ICD implantation. At first, cilostazol was instituted. In all subjects, palpitations due to sinus tachycardia caused by cilostazol were symptomatic. Addition of bepridil attenuated cilostazol-induced palpitations (87±12 to 66±7 bpm, P<0.01) and maintained the suppressive effect of cilostazol against VF.

Results:
Prior to the onset of the cilostazol/bepridil combination therapy, all 7 patients had a total of 20 shocks over an accumulated period of 79 months. In contrast, after the onset of therapy, they accumulated a combined follow-up period of 375 months, and during that significantly longer period only one of them received 2 shocks. Three patients underwent replacement of the ICD generator 4-5 years after ICD implantation. Cilostazol was discontinued 2 days before replacement because of its anti-platelet effects. In all 3 patients, temporary discontinuation of cilostazol led to the reappearance of J waves, culminating in VF and an appropriate ICD shock in one of them. J waves disappeared upon re-institution of cilostazol.

Conclusions:
These data suggest that combination therapy of cilostazol and bepridil may be effective and safe in suppressing VF recurrence in some cases of J-wave syndromes.
Abstract 9690: Does Testosterone Therapy Increase Risk of Cardiovascular Event Among Men? A Meta-Analysis
Authors: makki nader , Karrowni Wassef , Karrowni Wassef
Published: July 2021

Background:
Testosterone therapy has been increasingly promoted and prescribed over the past decade. However, there is rising concern about its safety, and randomized data adequately powered to assess its effect on cardiovascular outcomes is not available.

Aim:
We conducted a meta-analysis and systematic review of published randomized and observational studies to examine the overall risk of cardiovascular events associated with testosterone therapy.

Methods:
We searched Medline (1966-2014), Embase (1966-2014), and Cochrane central (2000-2014). Data was collected and analyzed using random and fixed effect model, as appropriate, with inverse variance weighting.

Results:
Of 2,800 studies identified, 34 were eligible including 76,270 patients with a mean follow up of 11.7 months. Testosterone therapy was associated with increased risk of cardiovascular events (adjusted HR=1.41, 95% CI = 1.18-1.70, p<0.05), all-cause mortality (adjusted HR=1.51, 95% CI = 1.05-2.18, p<0.05), and ischemic heart disease (adjusted HR=1.32, 95% CI = 1.11-1.57, p<0.05), but not cerebrovascular events (adjusted HR=1.22, 95% CI = 0.98-1.53, p=0.08). Using meta-regression and sensitivity analyses to account for factors such as baseline cardiovascular disease, timing of testosterone collection, and industry funding did not change the results of our main analysis.

Conclusions:
Our meta-analysis demonstrates that testosterone therapy may be associated with increased risk of all-cause mortality, cardiovascular events, and ischemic heart disease.