tbuckley/cabot-search huggingface dataset:
Abstract Su1001: Biomarker Trends after Return of Spontaneous Circulation in Out-of-Hospital Cardiac Arrests
Authors: Pavitra Kotini-Shah, Shaveta Khosla, Ruth Pobee, Heng Wang, Jing Li, Terry Vanden Hoek
Journal: Circulation (2024)

Background: Progressive post-cardiac arrest syndrome (PCAS) ensues within seconds of an out-of-hospital cardiac arrest (OHCA) and results in damage over days, yet longitudinal changes in blood biomarkers during PCAS are poorly understood. We characterize novel biomarkers at early time points after return of spontaneous circulation (ROSC) and determine associations with survival. Methods: Blood plasma samples from OHCA patients were collected at 1, 6, 24, 48, 72 hours and 7 days after ROSC. Samples were analyzed using a Meso Scale Diagnostics 40-plex assay which included proinflammatory, cytokine, chemokine, angiogenesis, and vascular injury panels. The data distribution was heavily skewed, requiring log-transformation. Biomarkers were compared between survivors and non-survivors at each follow-up time point using a two-sample t-test. Mixed-effect and Generalized Estimation Equation models were used to examine the association between biomarkers and survival and assess trends over time. Results: Thirty-three patients were included, of which 54% (N=18) were males, the mean age was 57 (+/-15) years, and 54% (N=18) survived to discharge. Six out of the 40 biomarkers had a statistically significant difference in biomarker levels between survivors and non-survivors at one or more time points. At the 1-hour, macrophage derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC) were significantly higher in survivors. At 6-hour, interleukin-13 (IL-13) was the only pro-inflammatory biomarker that was significantly higher in non-survivors. At 24-hour, pro-inflammatory biomarkers interleukin-12p70 (IL-12p70) and IL-13 were higher in non-survivors, whereas vascular endothelial growth factor A (VEGF-A) was significantly higher in survivors. At 48-hours, VEGF-A was also significantly higher in survivors. At 72 hours, interleukin-8 was the only biomarker with significantly higher levels in non-survivors. Overall, IL-12p70, IL-13, and MDC levels decreased over time (p=0.02, p=0.003, p=0.01, respectively) for both survivors and non-survivors. Survivors had a lower average level for IL-12p70 (p=0.03) and for IL-13 (p=0.04), but higher average level for MDC (p=0.01) than non-survivors at discharge. Conclusion: This pilot investigation extends prior biomarker work by highlighting new biomarkers, their longitudinal changes during PCAS, and their relation to survival. Future analysis will explore differences in biomarkers for neurological outcomes after OHCA.
Abstract Sa806: Prognostic Predictions after Pediatric Cardiac Arrest: A Single Center Prospective Study
Authors: Megan McSherry, Bingqing Zhang, Lauren Louderback, Aubree Little, Kathleen Walsh, Kathryn Graham, Craig Press, Jennifer McGuire, Rebecca Ichord, Rebecca Douglas, Ryan Morgan, Matthew Kirschen, Charlotte Woods-Hill, Alexis Topjian
Journal: Circulation (2024)

Background: Almost half of children who have a cardiac arrest die after withdrawal of life sustaining therapy (WLST), which is influenced by provider outcome predictions. Clinical factors used by providers to predict outcomes after pediatric cardiac arrest and the prognostic accuracy of providers are not known. Aims: We describe clinical factors providers report using to predict outcomes in the first week post-arrest and determine the concordance of prognostic predictions with patient outcome at hospital discharge. Hypothesis: We hypothesized that the use of post-arrest factors would increase within the first week and that the concordance of prognostic predictions with patient outcome would increase over time from return of circulation (ROC). Methods: This is a single-center prospective cohort study from 7/2023 to 4/2024. We included children with an index pediatric in-hospital (IHCA) or out-of-hospital (OHCA) cardiac arrest with ROC who received post-arrest care in the PICU. Multidisciplinary team members completed real-time surveys on post-arrest days 1, 2, 3, and 7. Surveys assessed provider demographics, top 3 factors used to form their prediction, and prediction of patient discharge outcome (Pediatric Cerebral Performance Category [PCPC] score). Actual outcome was PCPC at hospital discharge or 30 days, whichever was later, and was compared to provider prediction. Prognostic concordance is defined in Table 3. Mixed-effect models explored changes in factors used for prediction and concordance between prognostic predictions and patient outcomes over survey time points. Results: Fifty cardiac patients (median age: 4 years [IQR: 1, 10], 60% OHCA, and 52% pre-arrest PCPC = 1) were analyzed; survival at discharge/30 days was 76%. There were 461 surveys completed by 217 providers (Table 1). Over all survey time points, the top 3 factors reported to predict outcomes were pre-arrest neurologic function, post-arrest neurologic exam and EEG (Table 2). Use of neurologic exam, other organ dysfunction, and MRI findings increased over the first 3 days, OR 1.6 (95% CI 1.2-2.2). More than 75% of provider predictions were concordant with the actual outcome, by all definitions, with no significant change over the first week (Table 3). Conclusions: During the first week post-arrest, providers report increasing incorporation of the post arrest factors to prognosticate outcomes. Concordance of outcome prediction was more than 75% and did not change over the first week.
Abstract 4146917: Role of left ventricular anisotropy in the outcome of myocardial infarction: Insights from a rodent model
Authors: Sunder Neelakantan, Emilio Mendiola, Rana Raza Mehdi, Qian Xiang, Xiaoxiao Zhang, Kyle Myers, Peter Vanderslice, Reza Avazmohammadi
Journal: Circulation (2024)

Introduction: Myocardial infarction (MI) leads to cardiac myocyte death and scarring, resulting in significant biomechanical remodeling of the left ventricle (LV). Maladaptive LV remodeling post-MI is known to contribute to the development of heart failure (HF). Understanding the role of LV free wall (LVFW) biomechanical remodeling in the transition of infarcted hearts to HF will improve prognostic capabilities and intervention strategies. Our objective in this study was to assess the association between LVFW anisotropic stiffening and organ-level functional adaptations. Methods: MI was induced in WKY rats via the ligation of the LAD artery, and transthoracic echocardiography was performed to measure ejection fraction (EF). Fresh LVFW myocardial samples were harvested and subjected to biaxial tensile loading hearts were harvested at five timepoints: sham, and weekly from 1wk to 4wk post-MI (n=6 for each timepoint). The samples were stretched to 30% along the circumferential and longitudinal directions, and stiffness (slope of stress-stretch curves at 30% stretch) in each direction was measured. The ratio between longitudinal and circumferential stiffnesses was defined as the LVFW anisotropy. Results: EF reduced post-MI (Fig. 1A), and pre- and post-MI changes in EF (denoted by ΔEF) showed a significant reduction at later timepoints (Fig. 1B). Although circumferential stiffness remained unchanged with time (Fig. 1C), longitudinal stiffness tended to increase post-MI, thus altering the overall anisotropy of LVFW tissues (Fig. 1C). The correlation between the anisotropy and EF indicated that an increased longitudinal bias post-MI was strongly correlated with reduced EF and LV decompensation (Fig. 1D). Conclusions: Our results suggest that the myocardium stiffness changes anisotropically with a bias in the longitudinal direction post-MI. The strong correlation between myocardial anisotropy and EF suggests that studying alterations in LVFW biomechanical markers and their relationships with deteriorations in LV function could provide insights into the mechanisms of transition to HF post-MI. The quantification of these markers through cardiac imaging offers to improve early prognostication of HF post-MI.
Abstract Sa908: Evaluating the Alignment of Recent Cardiac Arrest Randomized Controlled Trials with the Top Resuscitation Science Knowledge Gaps
Authors: Ryan Coute, Jake Toy, Kelsey Wilhelm, Michael Kim, Lauren Friend, Claire Gahm, Marianne Gausche-Hill, Ashish Panchal, James Menegazzi
Journal: Circulation (2024)

Objective: To determine if recently published cardiac arrest randomized controlled trials (RCTs) align with and address the top scientific gaps previously identified in the American Heart Association (AHA) cardiac arrest treatment guidelines. Methods: All RCTs involving human subjects experiencing non-traumatic cardiac arrest, published between January 1, 2015, and December 31, 2022, were identified through searches in MEDLINE, Embase, and Web of Science. Abstracts, and full manuscripts when needed, were individually reviewed and categorized according to the themes and rationale for the ten most urgent knowledge gaps in the 2015 AHA cardiac arrest guidelines published by Panchal et al. The data were analyzed descriptively. Results: A total of 87 cardiac arrest RCTs were identified over the study period. Most trials included the adult population (84, 96.5%) and out-of-hospital cardiac arrest (62, 71.3%). The RCTs addressed the following top scientific gaps: optimization of post-cardiac arrest care (40, 46.0%), optimal airway management strategies (9, 10.3%), hemodynamic monitoring/goal-directed resuscitation (1, 1.1%), dispatch-directed CPR (1, 1.1%), individualizing resuscitation strategies (1, 1.1%), and novel technology for out-of-hospital cardiac arrest identification and response (1, 1.1%). Recognized gaps in early neuroprognostication, optimizing educational strategies for providers, and prediction of patients at risk of cardiac arrest were not specifically addressed. A total of 34 RCTs (39.0%) targeted other knowledge gaps outside of the top 10. Conclusion: More than half of cardiac arrest RCTs published since 2015 have focused on optimizing post-resuscitative care or airway management strategies, leaving a disparity among other well-recognized knowledge gaps in the AHA cardiac arrest treatment guidelines. Future RCTs aligned with other high-priority gaps in cardiac arrest recognition and treatment are warranted.
Abstract Sa308: Augmentation of Intraventricular Stroke Volume during Head Up Position CPR: Implications for Clinical Outcomes
Authors: Pouria Pourzand, Johanna Moore, Anja Metzger, Mithun Suresh, Bayert Salverda, Hamza Hai, Sue Duval, kerry bachista, Keith Lurie
Journal: Circulation (2024)

Background: Active compression-decompression (ACD) cardiopulmonary resuscitation (CPR), an impedance threshold device (ITD) and controlled, gradual, automated head and thorax elevation, collectively termed automated Head Up Position (AHUP) CPR, increases cerebral perfusion pressure (CerPP), brain blood flow, coronary perfusion pressure (CorPP), end tidal CO2 (ETCO2) and cerebral oximetry (rSO2) in animal models when compared with conventional (C) CPR. AHUP-CPR in patients is associated with increased neurologically favorable survival versus C-CPR. This study tested the hypothesis that AHUP CPR will increase cardiac stroke volume (SV) and other hemodynamics compared with C-CPR in a porcine model of cardiac arrest. Methods: Farm pigs (n=15) were sedated, anesthetized, and ventilated. Hemodynamics, including intracardiac conductance catheter based biventricular (BiV) pressure-volume (PV) loops, were continuously measured and recorded. After 10 minutes of untreated ventricular fibrillation, C-CPR was performed for 2 minutes in the supine position using an automated CPR device designed for pigs at a rate of 100 compressions/minute, depth of 21% of the chest antero-postero diameter, a 50% duty cycle, and no active decompression. ACD+ITD was then performed with 3 cm of active decompression for 2 minutes, followed by AHUP-CPR, where the head and thorax were initially raised to 10 cm and 8 cm for a 2-minute priming phase, followed by elevation over the next 2 minutes to 24 cm and 9 cm. A linear mixed-effects model with a random intercept for individual pigs was used for statistical analysis. Results: CerPP, CorPP, ETCO2, and rSO2, as well as BiV SV and cardiac output, increased progressively and significantly with implementation of AHUP-CPR (p&lt;0.05). C-CPR generated a right ventricular (RV) SV of 25.0 mL (48% of baseline pre-VF) and left ventricular (LV) SV of 17.5 mL (39% of baseline). ACD+ITD significantly increased RV and LV SV by an average of ~ 48% versus C-CPR; AHUP-CPR further increased BiV SV by an average of ~ 83%, reaching 85% and 75% of RV and LV pre-VF values, respectively. (Figure 1) Conclusion: This study demonstrated biventricular stroke volume is significantly augmented with AHUP-CPR versus C-CPR or ACD+ITD in the flat position. These findings, together with AHUP-enhanced higher ETCO2, rSO2, and CerPP values versus C-CPR or ACD-CPR in the flat position, help explain the improved clinical outcomes associated with early use of AHUP-CPR.
Abstract Sa604: Trapezoidal wave chest compression plays neuroprotective role by alleviating neuronal ferroptosis in mice after CA-CPR-ROSC via cerebral microvascular endothelial cell derived extracellular microvesicles
Authors: mengyao jian, Lu Gan, Yu Cao
Journal: Circulation (2024)

Background: Nowadays, cardiopulmonary resuscitation (CPR) instruments used worldwide utilize sinusoidal wave for chest compression. The instrument independently invented by our research group performs chest compression through trapezoidal wave, which can achieve higher carotid blood flow and cerebral microcirculation blood perfusion, and ultimately reduce neuron death and blood brain barrier (BBB) injury after CPR, ultimately, improve the prognosis. However, the underlying mechanisms are complicated and remain largely unknown. Therefore, this study investigated the specific mechanisms so as to make contribution to the popularization of TWCC. Methods: Cardiac arrest-CPR-return of spontaneous circulation (CA-CPR-ROSC) mouse models attained by TWCC/sinusoidal wave chest compression (SWCC) and the oxygen-glucose deprivation reoxygenation (OGD/R) model of primary neurons treated by brain tissue derived sEV TWCC /sEV SWCC were established, and the level of neuronal ferroptosis was detected. AAV-BR1-CD63-GFP was injected via lateral cerebral ventricle to lable brain microvascular endothelial cells-derived small extracellular vesicles (BMEC-sEV), and AAV9-BR1- Rab27a-shRNA was used to suppress the generation of BMEC-sEV. The effects of ferroptosis on ROSC rate and neurological prognosis in mice were confirmed by ferroptosis activators/inhibitors. Results: It was confirmed that, compared with SWCC/ OGDR+sEV TWCC group, the ferroptosis level of neurons in TWCC/OGDR+sEV TWCC group was significantly higher, which was mainly manifested by the changes of mitochondrial morphology, ferroptosis related proteins and lipid peroxidation levels. Immunofluorescence showed that BMEC-sEV labeled by green fluorescent protein (GFP) could be taken in by neurons. Compared with SWCC+AAV-BR1-CD63-Rab27a-NC group, the ferroptosis level of neurons in SWCC+ AAV-BR1-CD63-RAB27A-shRNA group was significantly reduced, indicating that the neuroprotective effect of TWCC was closely related to BMEC-sEV. In addition, the ROSC rate, neurological function score and 7-day survival rate were higher in SWCC group treated with Fer-1 and Lip-1 than SWCC group, while, mice given RSL3 and Erastin were completely opposite to that. Conclusion: In general, our results demonstrate that TWCC exacerbates brain damage after CPR by facilitating neuronal ferroptosis via BMEC-sEV. Key words: cardiac arrest; neurons; ferroptosis; small extracellular vesicles
Abstract Su101: Mesenchymal Stem Cell-Derived Extracellular Vesicles Mitigate Lipopolysaccharide Activation of Porcine Peripheral Blood Mononuclear Cells
Authors: Tyler Rolland, Sumbule Zahra, Daniel Cucinotta, Brian Weil
Journal: Circulation (2024)

Objective: Systemic inflammation is a well-established component of post-cardiac arrest syndrome (PCAS), a condition responsible for significant morbidity and mortality in patients who achieve return of spontaneous circulation (ROSC) following sudden cardiac arrest. Immune cell activation is pivotal in PCAS pathophysiology and commonly presents ~12hr post-ROSC with endotoxemia (“sterile sepsis”) where lipopolysaccharide (LPS) is present in systemic circulation. Given the paucity of available interventions to inhibit LPS-induced immune activation in the context of PCAS, we investigated the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) to modulate the inflammatory response of porcine peripheral blood mononuclear cells (PBMCs) activated by LPS in vitro. Methods: Porcine bone marrow-derived MSCs (P2) were cultured for 5 days and serum-starved for 3 days to collect MSC-EVs. These EVs were isolated from conditioned media using size exclusion chromatography and ultracentrifugation, then characterized by nanoparticle tracking analysis (ZetaView) and ExoCheck. Naïve PBMCs from healthy swine were cultured for 1 week before stimulation with either basal media or LPS (5ug/mL). MSC-EVs were added to activated PBMCs (2.5e8–2e9 EVs/well) and inflammatory surface marker expression (flow cytometry), inflammatory cytokine transcripts (qPCR) and release (ELISA), and reactive oxygen/nitrogen species (ROS/RNS) production were assessed 24 hours later. Results: LPS-stimulated PBMC populations exhibited altered surface marker expression consistent with enrichment of inflammatory granulocytes (CD172+CD163-), macrophages (CD14+CD163+), and adhesion molecules (CD172+) compared to basal media (all p&lt;0.05). Addition of MSC-EVs significantly reduced the number of all inflammatory cell populations, with the most prominent effects achieved at the highest EV dose (2e9 EVs/well). Likewise, MSC-EVs significantly attenuated LPS-activated PBMC expression and secretion of TNFα and IL-6 (Figure 1) and decreased ROS/RNS production (Figure 2) in a dose-dependent manner. Conclusion: MSC-EVs attenuate LPS-induced activation of PBMCs in a dose-dependent manner, as determined by reductions in pro-inflammatory surface marker expression, inflammatory cytokine gene expression and secretion, and ROS/RNS production. These findings indicate that MSC-EVs or MSCs alone, may be a viable therapeutic approach to modulate LPS-mediated immune activation in PCAS.
Abstract 4147314: Contemporary Diagnosis, Management, and Outcomes of Patients With Low-Gradient Severe Aortic Stenosis: A Multi-Center Analysis
Authors: Sreekanth Vemulapalli, Brian Lindman, Sammy Elmariah, Philippe Pibarot, Benjamin Peterson, Evelio Rodriguez, Martin Leon, Michael Mack, Kyle Eberst, Philippe Genereux
Journal: Circulation (2024)

Background: The American College of Cardiology/American Heart Association guidelines recommend assessing aortic stenosis (AS) using American Society of Echocardiography-endorsed parameters and referring patients with severe symptomatic AS for treatment. Yet, multi-site real-world assessment of guideline adherence is lacking. Methods: We assessed consecutive echocardiographic reports for patients &gt;18 years of age from 30 US institutions with appropriate permissions between January 2018–March 2024 (egnite Database; egnite, Inc.). Completeness of echocardiographic evaluation of AS was assessed. Patients with severe AS were stratified into high- and low-gradient (HG, mean aortic gradient [MG] ≥40 mm Hg; LG, MG &lt;40 mm Hg). Rates of Heart Team evaluation within 60 days and aortic valve replacement (AVR) within 6 months were assessed via the Kaplan-Meier method. Results: Of 2,829,095 echocardiographic reports, V max , MG, aortic valve area (AVA), stroke volume index, left ventricular ejection fraction (LVEF), and AS severity were missing in 25%, 30%, 35%, 83%, 5%, and 36%, respectively. Of 1,189,382 patients with available AS severity assessment, 45,967 had an AVA ≤1.0 cm 2 and/or V max ≥4.0 m/s with only 52% being diagnosed with severe AS and 20% being diagnosed as &lt;moderate AS. Of 26,903 patients (2.3%) diagnosed with severe AS, there was a greater proportion of LG cases (LG: 52%, HG: 48%). Regardless of LVEF or symptoms, a lower proportion of severe LG AS patients were evaluated by a Heart Team within 60 days (LG: 37%, HG: 53%) and received an AVR within 6 months (LG: 35%, HG: 61%). Patients not evaluated by the Heart Team were older and more likely to be female and non-White than those who were evaluated, despite a comparable history of heart failure. A greater number of mortality events was observed among LG vs HG patients seen (877/10,241 vs. 381/9304) and not seen (2679/10,121 vs. 914 / 3453) by the Heart Team. Conclusions: Key parameters needed to diagnose the severity of AS are often missing in echocardiographic reports. Compared to HG, severe LG AS patients have lower Heart Team evaluation rates, with racial, sex, and age disparities, as well as lower AVR rates and more observed mortality events. Further work is needed to enhance guideline adherence for the diagnosis and management of patients with severe LG AS.
Abstract Sa801: Physiologic Response To Vasopressin Rescue During Pediatric In-Hospital Cardiac Arrest
Authors: Morgann Loaec, Garrett Keim, Kathryn Graham, Samridhi Sawhney, Marion Donoghue, Kellimarie Cooper, Martha Kienzle, Amanda O'Halloran, Lindsay Shepard, Sanjiv Mehta, Todd Kilbaugh, Alexis Topjian, Robert Berg, Vinay Nadkarni, Robert Sutton, Ryan Morgan
Journal: Circulation (2024)

Introduction: The physiologic response to epinephrine during pediatric CPR varies and poor response is associated with worse outcomes. Though vasopressin is not recommended by CPR guidelines, laboratory data show a physiologic response to vasopressin among epinephrine non-responders. We aimed to explore the physiologic response to vasopressin during pediatric IHCA. Hypothesis: Vasopressin is associated with an increase in diastolic blood pressure (DBP) compared to epinephrine in patients with ≥1 dose of epinephrine. Methods: Single-center retrospective cohort study of pediatric ICU IHCAs with prospectively collected physiologic and arrest event data (2017-2023). Vasopressin subjects received ≥1 dose of epinephrine preceding vasopressin and were matched to patients who received epinephrine at the same time in CPR based on age, illness category (cardiac vs. non-cardiac) and total epinephrine doses prior to the matched dose. DBP response to vasopressor was analyzed with regression discontinuity and the per subject responsiveness (≥5mmHg increase following the dose). A secondary analysis explored time to ROSC from time of vasopressin or epinephrine using Cox regression with censoring of all subjects 20 minutes post-dose. Results: Of 556 IHCAs with ≥1 dose epinephrine, 52 received vasopressin, and 41 met inclusion criteria and matched with epinephrine-only subjects. Median CPR duration was 36.5 [IQR 23, 48] minutes; median time to study dose was 14.5 [10.8, 19] minutes. ROSC occurred in 10/41 (24%) vasopressin subjects and 15/41 (36%) epinephrine subjects (p=0.34). There was no difference in time to ROSC from study dose (aHR 0.73 [95% CI 0.31 -1.7]). Arterial BP waveform data were evaluable in 12/41 (29%) vasopressin and 7/41 (17%) epinephrine subjects. Vasopressor responsiveness occurred in 4/12 (33%) vasopressin and 1/7 (14%) epinephrine subjects (p=0.60). Figure 1 shows trend in DBP by treatment group around drug delivery, along with regression discontinuity plots of DBP for each drug. Regression discontinuity showed a change in DBP of +2.3mmHg after vasopressin (95% CI: –11.4, 16.0) and -5.67mmHg after epinephrine (–15.13, 3.80). Conclusion: In a small cohort of IHCA patients with ≥1 epinephrine dose, we did not detect a DBP response to vasopressin or epinephrine. Prolonged time to vasopressin in this cohort may have played a role in these findings; a larger sample of children receiving vasopressin earlier in IHCA will be required for future work.