tbuckley/cabot-search huggingface dataset:
Abstract 329: Unrecognized Clinical Deterioration Prior to In-Hospital Cardiac Arrest and Associated In-Hospital Mortality
Authors: Kipp Shipley, Megan M Shifrin, Kathryn Roach
Journal: Circulation (2023)

Introduction: Physiologic abnormalities often precede in-hospital cardiac arrest (IHCA). Critical Care Outreach Teams (CCOTs) are designed to respond to patients that meet standardized rapid response team (RRT) activation criteria including vital sign abnormalities, neurologic changes, and nursing concern. However, these systems often rely on clinical staff recognizing signs of clinical deterioration and initiating a rapid response. Research Question: The purpose of this post-hoc analysis was to identify if there was an in-hospital mortality difference between two different adult patient groups: 1) patients who met standardized RRT criteria but did not receive an RRT prior to IHCA and 2) patients who had no evidence of clinical deterioration prior to IHCA. Goals: The primary goal was to explore the association of unrecognized clinical deterioration on patient mortality. A secondary goal was to identify the timing onset of RRT criteria in patients who had an IHCA but did not receive an RRT activation. Methods: All non-ICU IHCAs during a 5-year period (January 1st, 2018, to December 31st, 2022) were reviewed to identify whether: 1) standardized RRT criteria had been met in the 24 hours prior to IHCA, 2) the onset of RRT criteria if present, 3) sustained return of spontaneous circulation (ROSC) occurred during the IHCA, and 4) if the patient died during their hospitalization. Results: There were 271 adult non-ICU IHCAs without a preceding RRT activation. Of those, 203 (79.4%) met RRT criteria prior to IHCA. In patients who had evidence of clinical deterioration, patients displayed at least one RRT criterion an average of 13.1 hours prior to IHCA. Sustained ROSC was higher in the patient group without RRT criteria (79.4%, 54/68 vs 72.9%, 148/203), but this was not significant. In-hospital mortality was significantly higher patients who met RRT criteria without RRT activation compared to patients who did not meet RRT criteria prior to IHCA (67.9%, 65/138 vs 54.4%, 31/37, p&lt;0.05). Conclusions: Most patients who experienced an IHCA demonstrated physiologic abnormalities hours prior to IHCA. Patients who met RRT criteria without RRT activation had a significantly higher mortality rate when compared with patients who did not have evidence of clinical deterioration.
Abstract 15394: Caregivers’ Growing Contributions to Heart Failure Self-Care: An Updated Systematic Review
Authors: Chelsea Howland, Harleah G Buck, Michael A Stawnychy, Heba Aldossary, Yamnia I Cortes, Jennifer Deberg, Angela Durante, Lucinda J Graven, Elliane Irani, Saida Jaboob, Angela Massouh, Natany Da Costa Ferreira Ob, Martha Abshire Saylor, Rachel K Wion, Julie T Bidwell
Journal: Circulation (2023)

Introduction: In 2015, a seminal systematic review captured the body of literature surrounding the contributions of family caregivers to heart failure (HF) self-care. Since then, the body of HF caregiving research has expanded, necessitating an updated systematic review to inform research, practice, and policy. Goals: To provide an updated systematic review of the empiric literature on informal, unpaid caregivers contributions to HF patients’ self-care. Research Questions: 1) What specific activities do caregivers of people with HF take part in related to HF self-care?; 2) Have these caregiving activities changed over time?; 3) What are the gaps in the science? Methods: The review followed PRISMA guidelines; the protocol was pre-registered in PROSPERO. Comprehensive database search strategies were developed (PubMed, CINAHL, Embase, and Cochrane CENTRAL). The team independently screened and abstracted data; quality was assessed using CASP checklists. Meta-synthesis techniques using critical realist approaches were used to interpret activities, then relationships were analyzed. During data synthesis, activities were benchmarked against the Theory of Self-care in Chronic Illness (TSCI). Results: In total, 2154 research reports were identified, 64 of which were eligible for inclusion (2013-2022). Caregiver contributions to HF self-care activities occurred in TCSI domains of self-care maintenance (91%), monitoring (54%), and management (46%). Activities performed directly on or to the patient were reported more frequently than those performed for the patient. Frequently reported activities like transportation and activity of daily living are not included by the TCSI. Gaps due to ambiguous activity descriptions, inadequate caregiving time quantification, and underrepresented monitoring, supportive, and communication activities were elucidated. Conclusions: Findings support updating the TSCI to include activities antecedent to HF self-care. Identified gaps highlight the need to define specific caregiving activities, determine caregiver task difficulty and burden, and identify caregiver self-care strategy and education needs. The critical need to expose the hidden work of caregiving is essential to inform policy and practice.
Abstract 16828: Plaque Rupture is Not Associated With Worse Clinical Outcomes in Contemporary Patients With Acute Coronary Syndrome
Authors: Kiyoshi Asakura, Yoshiyasu Minami, Takako Nagata, Masahiro Katamine, Yusuke Muramatsu, Daisuke Kinoshita, Kazuhiro Fujiyoshi, Junya Ako
Journal: Circulation (2023)

Introduction: The worse clinical outcomes in patients with plaque rupture (PR) than those with other pathogenesis of acute coronary syndrome (ACS) including plaque erosion and calcified plaque-related ACS have been reported. Hypothesis: The incidence of recurrent adverse events in patients with PR is not higher than other ACS patients in the contemporary clinical setting of secondary prevention using high-intensity statin. Methods: A total of 329 consecutive patients with ACS who underwent optical coherence tomography imaging of culprit lesions were included. Patients were classified into either the PR group (n = 133) or the non-PR group (n = 196). The incidence of major adverse cardiovascular events (MACE) at 1-year was compared between the two groups. MACE included cardiac death, non-fatal myocardial infarction, target vessel revascularization (TVR), and non-TVR. Results: The prevalence of ST-elevation myocardial infarction (STEMI) as the initial clinical presentation was significantly higher in the PR group than in the non-PR group (58.6 vs. 42.3 %, p = 0.005). The prescription rate of high-intensity statin and/or ezetimibe at discharge was comparable in the two groups (84.2 vs. 84.7 %, p = 1.000). The incidence of MACE at 1-year was significantly lower in the PR group than in the non-PR group (log-rank p = 0.009) (Panel A). In the non-PR group, the levels of body mass index (26.5 ± 2.9 vs. 24.0 ± 3.9 kg/m 2 , p = 0.004) and hemoglobin A1c (7.2 ± 2.5 vs. 6.4 ± 1.2 %, p = 0.021) were significantly higher in patients with MACE than in those without (Panel B). Conclusions: The incidence of MACE at 1-year in patients with PR was significantly lower than in those without PR in contemporary patients with ACS despite of the higher prevalence of baseline STEMI presentation. Further tailored optimization of secondary prevention against obesity and diabetes may be still required in ACS patients without PR.
Abstract 370: Oral-Mucosal PCO <sub>2</sub> During Hemorrhagic Shock Closely Monitors Its Time Course, Severity, and Reversal Outperforming Blood Lactate Measurement
Authors: Armin Razi, Iyad Ayoub, Alvin Baetiong, Salvatore Aiello, Raul J Gazmuri
Journal: Circulation (2023)

Objective: Oral-Mucosal PCO 2 (P OM CO 2 ) has been shown to closely correlate with the splanchnic mucosal PCO 2 and provide information on its microcirculation. We used a swine model of controlled hemorrhagic shock to assess the potential clinical relevance of monitoring P OM CO 2 to assess its clinical course, severity, and treatment effect. Methods: The study was performed on six male domestic pigs (37.9±1.4 kg). P OM CO 2 was measured using a non-invasive disposable sensor clipped to the cheek, developed by ExoStat Medical. Blood was removed over 120 minutes from the right atrium using a LabVIEW-controlled pump according to a mono-exponential decay curve modeling spontaneous bleeding and reinfused in 20 minutes observing the animal for a total of 180 minutes. Results: A total of 1,491±193 ml corresponding to 65.5% of the estimated blood volume were removed inducing the characteristic hemodynamic features of hemorrhagic shock including tachycardia, hypotension, reduced cardiac output, and reduced systemic oxygen delivery with increased systemic oxygen extraction. P OM CO 2 closely paralleled the time course of blood removal showing an early and steady increase from 85±5 mmHg at baseline to 144±32 mmHg after 120 minutes. Blood reinfusion rapidly reduced the P OM CO 2 to 130±17 mmHg after 20 minutes and 96±14 mmHg at the end of 180 minutes, coincident with reversal of hemorrhagic shock. P OM CO 2 also closely tracked changes in systemic oxygen extraction. Concurrent measurements of blood lactate demonstrated a slower increase during the hemorrhagic shock period (from 1.1±0.3 to 3.0±0.3 mmol/l) with further increase (not decrease) to 5.4±2.0 mmol/l after blood reinfusion, remaining at 4.3±0.8 mmol/l by the end of the 180-minute observation period. Conclusions: The study demonstrated capability of P OM CO 2 to closely and non-invasively track hemodynamic and metabolic changes occurring during hemorrhagic shock. P OM CO 2 outperformed blood lactate which exhibited a slower and delayed response. Thus, P OM CO 2 may provide a clinically practical and non-invasive means to monitor hemorrhagic shock assessing its severity, clinical course, and treatment effect.
Abstract 16783: Discovery and Characterization of Transient Endothelial Stem-Like Cells Responsible for Rapid Lung Microvascular Regeneration Post Endothelial Ablation
Authors: Elmira Safaie Qamsari, Nicholas D Cober, Rafael Soares Godoy, Liyuan Wang, Ken Schlosser, Duncan Stewart
Journal: Circulation (2023)

Background: Single-cell RNA sequencing (scRNA-seq) has revealed two main types of alveolar capillary endothelial cells (ECs): aCap ECs (or aerocytes) express typical aCap markers, including apelin, whereas general (gCap) ECs express apelin receptor, Aplnr /APJ. Aerocytes constitute the air-blood barrier and are incapable of proliferation, unlike smaller gCap ECs that can proliferate. Hypothesis: After lung microvascular injury, gCap ECs give rise to stem-like ECs that can regenerate depleted lung EC populations, including highly specialized aerocytes. Approach: scRNA-seq was used to study depletion and regeneration of lung EC populations after intratracheal instillation of diphtheria toxin (DT) in transgenic mice harboring an EC-targeted human DT receptor. Results: DT resulted in ~80% loss of lung microvascular EC populations including aerocytes, associated with severe acute lung injury (ALI), and there was full spontaneous recovery by day 7. Interestingly, a novel EC population appeared at day 3 post injury in a transitional gCap EC cluster characterized by paradoxical expression of ‘aCap’ marker, apelin, together with endothelial progenitor/stem cell markers, Cd34 and endothelial protein C receptor ( Procr /EPCR). These ‘transient endothelial stem-like cells’ (TESCs) transitioned to highly proliferative progenitor-like FoxM1 + cells ultimately repopulating all depleted EC populations by day 7. Using flow cytometry of lung cells harvested at 3 days post DT instillation, TESCs were identified by unique co-expression of CD34 and EPCR (Figure), thereby allowing isolation and culture in vitro for further characterization of their proliferation and differentiation potential. Conclusions: Lung microvascular repair is orchestrated by the emergence of stem-like, gCap ECs (TESCs), transiently expressing aCap/aerocyte marker, apelin, together with Procr /EPCR, which have the capacity to regenerate lung microvasculature rapidly and efficiently.
Abstract 358: Coronary Features in Different Subsets of Out-of-Hospital Cardiac Arrest
Authors: Danilo Franco, Tomaz Goslar, Peter Radsel, Nicola De Luca, Alessandro Santoro, Tullio N Tesorio, Emanuele Barbato, Marko Noc
Journal: Circulation (2023)

Introduction: Coronary artery disease (CAD) is the leading cause of out-of-hospital cardiac arrest (OHCA) which is usually triggered by acute coronary event. Hypothesis: CAD is more complex if acute coronary event is associated with OHCA. CAD complexity progressively increases from patients with reestablishment of spontaneous circulation (ROSC) to patients with refractory OHCA. Aims: To investigate CAD features in different subgroups of OHCA and compare them to patients with acute coronary syndrome without OHCA. Methods: Consecutive conscious and comatose OHCA with ST-elevation myocardial infarction (STEMI) after ROSC and patients with refractory OHCA undergoing veno-arterial extracorporeal membrane oxygenation (E-CPR OHCA) were compared to STEMI without OHCA (STEMI no OHCA). Results: Between 2016 and 2022, 71 conscious OHCA, 157 comatose OHCA, 50 E-CPR OHCA and 101 randomly selected STEMI no OHCA underwent immediate coronary angiography. Acute culprit lesion was documented less often in OHCA subsets (88.1% vs 97%; p=0.009) but complete occlusion was more prevalent (68.8% vs 58.4%; p=0.038) (Figure A) . Incidence of multivessel disease, &gt; 50% unprotected left main stenosis, and presence of &gt; 1 chronic total occlusion progressively increased from STEMI no OHCA to E-CPR OHCA. This was reflected in baseline SYNTAX score which was 5.6 in STEMI no OHCA,10.2 in conscious OHCA, 13.4 in comatose OHCA and 26.8 in E-CPR OHCA (p&lt;0.001) (Figure B) . There was a linear correlation between SYNTAX score and delay to ROSC (r 2 =0.61; p&lt;0.001) (Figure C) . Baseline and residual SYNTAX scores were among independent predictors of 5-year survival which was significantly decreased in comatose (56.1%) and E-CPR (36.0%) OHCA (Figure D) . Conclusion: OHCA is associated with increased incidence of acute coronary occlusion and progressive complexity of CAD from conscious OHCA to E-CPR OHCA. Severity of CAD is associated with increased delays to ROSC and decreased long-term survival.
Abstract 16034: Heart Transplant in Older Adults: Outcomes in the Modern Era of Transplant
Authors: Stephanie Golob, Orly Leiva, Randal Goldberg, Bernard Kadosh, Jennifer Cruz, Haider Nazeer, John A Dodson, alex reyentovich
Journal: Circulation (2023)

Introduction: The total number and the proportion of older adults receiving heart transplants have increased over the last two decades. In 2016, the ISHLT guidelines for patients over 70 years of age were updated to remove the use of an alternate-type pool of donors, and now recommend transplanting carefully selected patients over 70 from the general pool. Aims: This study examines outcomes of older adults (&gt;70) who receive heart transplants in the modern era. Methods: Adult patients who received heart transplant between January 1, 2010 and December 31, 2021 were identified in the United Network for Organ Sharing (UNOS) registry. Outcomes of interest were mortality at 1 and 5 years after heart transplant. Results: Those over 70 were more likely to be male, white, have an ischemic etiology of their heart failure, and have had a prior malignancy. Overall mortality at 1 year was 10.8% for those over 70 and 8.9% for those under 70 (p&lt;0.033). Overall mortality at 5 years was 12.8% for those over 70 and 19.8% for those under 70 (p=0.37). Time to event survival analysis showed mortality was higher at 1 (HR 1.25, 1.04-1.51, p=0.019) and 5 years (HR 1.21, 1.05-1.39, p=0.006), however if patients conditionally survived the first year, 5-year conditional mortality was not different (HR 1.17, 0.95-1.43, p=0.135). Those over 70 were less likely to suffer from rejection, more likely to die from infectious disease or malignancy, but less likely to die from cardiovascular causes or graft failure. Conclusions: Older adults (over 70) who receive heart transplants have slightly worse 1- and 5-year survival but similar conditional 5-year survival to those under 70—the difference is driven by mortality in the first year. Both cohorts’ survival curves are improved compared to transplants in earlier eras. Those over 70 are less likely to experience rejection, consistent with the well-described phenomenon of immunosenescence.
Abstract 18550: Impaired Microtubule Mediated Protein Trafficking as a Mechanism of PLN R14del Dilated Cardiomyopathy
Authors: Rachel Baum, Rohin Ramchandani, Ioannis Karakikes, Jennifer Arthur, Nike Bharucha, Logan Dunkenberger
Journal: Circulation (2023)

Introduction: Phospholamban (PLN) regulates calcium handling and contractility in the heart by altering its phosphorylation status, thereby activating or inhibiting the calcium ATPase SERCA2a. A pathogenic mutation in PLN at the Arginine 14 codon (R14del) results in dilated cardiomyopathy characterized by ventricular arrythmias and sudden cardiac death. Cytoplasmic aggregation of PLN is a hallmark of the disease. However, exactly how the R14del mutation causes DCM remains largely unknown. As PLN is trafficked to the cell membrane before it localizes to the t-tubules, we hypothesize that PLN protein trafficking may be impaired, contributing to the PLN aggregation and DCM. Methods: Induced pluripotent stem cell derived cardiomyocytes (iPSC- iPSC-CMs) from patients carrying the PLN R14del mutation and isogenic controls generated by CRISPR-Cas9 genome editing were tagged with biotin to quantify membrane-bound protein expression. Western blotting and mass spectrometry was used to identify differences membrane protein expression, and immunocytochemistry was used to image microtubule layout, PLN and junctional protein expression at the cell borderintercalated disc (do you mean the intercalated disk?) in micropatterned iPSC-CMs. Results: Quantification of membrane-bound proteins showed a significant decrease of PLN at the cell membrane and connexin 43 expression in the intercalated disk of R14del iPSC-CMs compared to isogenic controls. Additionally, we observed significantly reduced levels of EB1, the microtubule tip protein, at the cell border of PLN R14del iPSC-CMs by immunofluorescence imaging and western blot analysis. Finally, disruption of microtube polymerization by Nocodazole treatment, induced PLN aggregate formation in iPSC-CMs. Conclusion: Our data suggest that the transportation of PLN and Cx43 proteins by microtubules is impaired in PLN R14del iPSC-CMs, which results in PLN accumulation in the cytoplasm and a decrease of Cx43 expression in the intercalated disc. These findings provide a novel mechanism for the pathogenesis of PLN R14del cardiomyopathy and a possible therapeutic target.
Abstract 15634: Primary Prevention Defibrillator Use in a Safety-Net Setting
Authors: Matthew S Durstenfeld, Anjali Thakkar, Diane Jeon, Robert Short, Yifei Ma, Thomas A Dewland, byron lee, Jonathan D Davis, Priscilla Y Hsue
Journal: Circulation (2023)

Introduction: Disparities in use of implantable cardioverter-defibrillators (ICD) for primary prevention have been documented; however, whether ICDs may be underutilized within a safety-net healthcare system has not been studied. Methods: Using an electronic health record cohort of all patients with heart failure (HF) who received care within the public safety-net system in San Francisco from 2001-2018 linked to device implantation records from two health systems, we identified all patients with ICD implantation (adjudicated with manual chart review) and primary prevention ICD-eligible with no indication for secondary prevention ICD, EF&lt;35% on 2 echocardiograms at least 90 days apart, HF hospitalization (to increase specificity for symptomatic HF), and prescribed beta blocker and ACEi/ARB. For exploratory survival analysis, eligibility and follow up started at the second echocardiogram. Results: Out of 14,230 patients with HF, at least 384 patients were potentially eligible for primary prevention ICD, but only 9 (2.3%) had an ICD implanted (2 CRT-D, 7 ICD). Of these 6 were nonischemic, and 3 had revascularized ischemic cardiomyopathy. Those who received ICD were younger (47 years vs 55 years; p=0.05), with lower rates of substance use (Table). Among 4 patients who died after ICD, median survival after device placement was 2.8 years (range 0.73 to 7.3); among 5 still alive, median follow up is 6.2 years (range 5.5 to 7.0). In an exploratory analysis, survival did not greatly differ by ICD placement (logrank p=0.53; age-adjusted HR 1.55; 95%CI 0.57-4.24). Conclusion: Among individuals receiving care at a safety-net system in San Francisco, even acknowledging that not all barriers to ICD placement are measured, very few guideline-eligible patients received primary prevention ICD. Additional studies are needed to identify patient-level and systems-level barriers to referral and implantation specific to a diverse, publicly insured patient population.
Abstract 14650: Risk Stratifying Individuals With Zero, Minimal, and Mild Coronary Artery Calcium for Cardiovascular Disease by Determining Coronary Plaque Burden
Authors: Salman Ansari, Leili Pourafkari, April Kinninger, Matthew J Budoff
Journal: Circulation (2023)

Background and Aims: Previous research has often categorized minimal CAC (1-10) and 0 CAC into a single low-risk category for CVD. However, the clinical significance of plaque burden between these two groups remains unclear. We sought to determine the plaque burden in individuals with CAC scores of 0, 1-10, and 11-100 to specify a more accurate risk stratification for minimal and 0 CAC scores. Methods: Retrospectively reviewed patients with CAC scores ≤100 and performed quantitative coronary plaque analysis (QAngio, Medis). CAC was categorized into three groups: zero (CAC=0), minimal (CAC 1-10), and mild (CAC 11-100). Plaque levels (low attenuated, fibrous, fibro-fatty, dense calcified, total non-calcified) were assessed using multivariable linear regression adjusted for cardiovascular risk factors (age, ethnicity, BMI, gender, hypertension, dyslipidemia, diabetes mellitus, past smoking) Results: 378 subjects were included, with an average age of 53.9±10.7 years and 53% female. Among them, 51% had 0 CAC, 16% had minimal CAC (scores 1-10), and 33% had mild CAC (scores 11-100). The minimal and mild CAC groups were significantly older, with higher rates of diabetes, hypertension, and hyperlipidemia. Multivariable analysis found no significant difference in low attenuated, fibro-fatty, and dense calcified plaque levels between the minimal and 0 CAC groups. However, minimal CAC subjects had significantly higher fibrous, total non-calcified, and total plaque volumes than zero CAC ( Table 3 ). All plaque types were significantly higher in the mild group when comparing mild CAC to minimal CAC." Conclusion: This study shows higher noncalcified coronary plaque and total plaque volume in individuals with minimal calcium scores (1-10) compared to those with 0 CAC. These findings hold clinical significance, challenging previous categorization of minimal CAC as low-risk. Therefore, those with minimal CAC scores need a more accurate risk stratification approach.