tbuckley/cabot-search huggingface dataset:
Abstract 9419: A Novel Global Strain Imaging Diastolic Index for the Estimation of Left Ventricular Filling Pressure
Authors: Shuo-Ju Chiang, Masao Daimon, Katsuhisa Ishii, Kuniaki Hirose, Takayuki Kawata, Katsumi Miyauchi, Mei-Hsiu Yah, Nen-Chung Chang, Hiroyuki Daida
Journal: Circulation (2012)

Background: Recently, strain imaging diastolic index (SIDI) has been proposed to assess left ventricular (LV) regional abnormal relaxation induced by myocardial ischemia. We aimed to examine whether non-invasive global SIDI obtained using 2D speckle tracking imaging (2DSI) could predict elevated levels of LV filling pressure. Methods: One hundred and twenty patients (age 63±13 years) with suspected coronary artery disease underwent echocardiography and 2DSI during simultaneous cardiac catheterization. Mean LV ejection fraction was 46.3±17.6%. LV pressure curve was obtained to measure pre-atrial contraction (Pre-AC) pressure as a surrogate for LV filling pressure. SI-DI was defined as LV longitudinal changes during the first one-third of diastolic duration. In 2DSI, LV longitudinal SIDI of 18 LV segments were measured from the apical 2-, 3-, and 4-chamber views. Then, longitudinal global SIDI (L-global SIDI) was calculated as a mean SIDI of 18 LV segments. Mitral inflow and tissue Doppler imaging were also assessed. Results: Among 120 patients, 64 cases had Pre-AC pressure &gt; 15 mmHg. L-global SIDI had a significant and better correlation with pre-AC pressure (p&lt;0.001, R=0.47)(Figure 1), than E/e’ (p&lt;0.01, R=0.26) . In multiple stepwise regression analysis, L-global SIDI was the strongest independent determinant of pre-AC pressure (β=-0.66, P&lt;0.001), among E/A, left atrium volume index, E/e’, and e’. In addition, L-global&lt;0.50 was the optimum cutoff value to predict LV pre-AC pressure &gt;15mmHg (sensitivity, 89%; specificity, 51%)(Figure 2), while E/e’&gt;11.2, the optimum cutoff value of E/e’ predicted LV pre-A contraction pressure &gt;15mmHg (sensitivity, 65%; specificity, 75%). Conclusions: L-global SIDI derived from 2DSI can be used to estimate LV filling pressure noninvasively. Global SI-DI may provide more accurate estimation of LV filling pressure, compared with conventional mitral inflow and tissue speckle tracking.
Abstract 9571: Activation of LXRα but Not LXRβ Protects the Heart from Ischemia/Reperfusion Injury
Authors: Jun Pu, Qing He, Erhe Gao, Wayne Bond Lau, Walter J. Koch, Xin-Liang Ma, Ben He
Journal: Circulation (2012)

Objective: Liver X receptors (LXRs) play a critical regulatory role in metabolism and inflammation, and have been demonstrated to be involved in vascular physiology/pathology. However, LXR function in cardiac biology remains largely unknown. Importantly, no data exists concerning the role of LXRs in myocardial ischemia/reperfusion (MI/R) injury. Methods and Results: Two LXR isoforms, LXRα (NR1H3) and LXRβ (NR1H2), were detected in the mouse heart. Exposure to MI/R resulted in upregulated LXRα expression in ischemic/reperfused myocardium, whereas LXRβ expression remained largely unaffected. LXR activation by natural and synthetic agonists reduced myocardial infarction and improved contractile function following MI/R injury. The cardioprotective effects of LXR agonists were completely abrogated by knock-down of endogenous cardiac LXRα, but not LXRβ, via in vivo intramyocardial siRNA transfection. LXRα knock-out mice manifested exacerbated apoptosis and infarct size with poorer contractile function post-MI/R compared to WT mice, whereas MI/R injury was similar between LXRβ knock-out and WT mice. Mechanistically, LXR agonists inhibited both endoplasmic reticulum stress (as evidenced by decreased activation of CCAAT/enhancer-binding protein homologous protein and caspase-12) and mitochondrial dysregulation (as evidenced by decreased release of mitochondrial cytochrome c and attenuated caspases-9 activation), and subsequently reduced cardiomyocyte apoptosis. Furthermore, LXR activation inhibited MI/R-induced oxidative stress (i.e., superoxide production and NADPH oxidase expression) and nitrative stress (i.e., peroxynitrite formation and inducible nitric oxide synthase expression) in ischemic/reperfused myocardium. Conclusion: Our study provides the first evidence supporting LXRα as a novel cardiac protective receptor against MI/R injury via inhibition of both endoplasmic reticular stress and the mitochondrial apoptotic pathway. LXRα may potentially be an attractive molecular target for the treatment of ischemic heart disease.
Abstract 13101: Mst1-mediated Phosphorylation of Beclin1 in its BH3 Domain Promotes Beclin1-Bcl-2 Interaction, Thereby Negatively Regulating Autophagy in the Heart
Authors: Yasuhiro Maejima, Shiori Kyoi, Peiyong Zhai, Tong Liu, Hong Li, Junichi Sadoshima
Journal: Circulation (2011)

Yasuhiro Maejima, 2011 Finalist and Presenting Author
Abstract 47: ECG Changes and Poor Outcomes for In-Hospital Cardiopulmonary Arrest in Patients with Multiple Organ Dysfunction
Authors: Justin Hayase, Duc Do, Sunghan Kim, Xiao Hu, Noel Boyle
Journal: Circulation (2012)

Background: The likelihood of surviving to discharge after cardiac arrest (CA) is very low for patients with multi-organ dysfunction. However, at time of CA, many patients often undergo resuscitation attempts, which are either unsuccessful or lead to a prolonged, complicated and costly hospital course, ultimately ending in withdrawal of care. In this study, we evaluate the frequency ECG changes occurring prior to CA in patients with multi-organ failure and implications for “code status” discussions. Methods: We evaluated all “Code Blue” events at UCLA Medical Center, a 520 bed tertiary care hospital, from April 2010 to March 2012, and included all adult CA cases that had significant organ dysfunction in two or more systems with at least 3 hours of continuous telemetry data preceding CA available. We analyzed up to 24 hours of telemetry data prior to CA for any ECG changes from baseline including PR prolongation, QRS widening, ST segment changes, QT prolongation and new onset atrial fibrillation. Charts were reviewed for survival outcomes and code status at time of CA. All cases were adjudicated by a second observer. Results: There were 30 cases meeting inclusion criteria and included in this study. Of these 15 (50%) were classified as pulseless electrical activity (PEA) arrest, 11 (37%) were bradycardic arrests and 4 (13%) were ventricular tachycardia/ventricular fibrillation arrests. Amongst the PEA group, 13/15 (87%) had any ECG change up to 24 hours prior to CA with QRS widening in 10/15 (67%) and ST segment changes in 6/15 (40%). Amongst the bradycardic group, 8/11 (73%) had any ECG change up to 18.5 hours prior to CA, with QRS widening in 5/11 (45%) and ST segment changes in 4/11 (36%). Survival to discharge was 2/30 (7%) for all patients, with both survivors being discharged to hospice care. At the time of CA, 25/30 (83%) were full code status. Conclusions: In this limited case series, ECG changes within the 24 hours preceding CA were seen in 77% of patients with multiple organ dysfunction. Survival for this group after CA remains low, with a disproportionately high percentage of patients undergoing extreme life-saving measures despite poor prognosis. These findings may have important implications for discussions regarding the urgency of “code status” with such patients.
Abstract 5: Prehospital Hypotension Is Associated with Emergent In-Hospital Procedures and Mortality in Trauma Patients
Authors: Ahamed H Idris, Eric Meier, Karen J Brasel, Mohamud Daya, Debra Egan, Delores Kannas, Jeffrey D Kerby, Steve Lin, Brent McCleod, Joseph Minei, Craig D Newgard, Donald Reiff, John Trickett, Rardi van Heest, Lynn K Wittwer, Eileen Bulger, None The Resuscitation Outcomes Consortium Investigators
Journal: Circulation (2012)

Background: Prehospital vital signs are the basis of many triage and transport guidelines. They serve to activate prehospital and in-hospital trauma systems, and to direct prehospital and in-hospital resuscitation efforts and other interventions. Objective: The purpose of this study was to determine the relationship of prehospital systolic blood pressure with emergent in-hospital procedures and mortality. Methods: Included in this secondary analysis of the Resuscitation Outcomes Consortium (ROC) Hypertonic Saline Clinical Trial are patients 15 years or older who were enrolled in the study shock cohort. These patients had traumatic injury and a systolic blood pressure (SBP) ≤70 mm Hg or 71 - 90 mm Hg and a heart rate ≥108 beats/min. Emergent in-hospital procedures are defined as any blood transfusion, thoracotomy, laparotomy, craniotomy, neck exploration, or angiographic control of hemorrhage within 24 hours of emergency department admission or death within 6 hours of admission. We estimated between-group differences for mortality and the likelihood of emergent procedures for lowest SBP categories of &lt;55, 55-64, 65-74, 75-84, and 85-90 (reference) mm Hg using a multiple logistic regression model adjusted for age, sex, Glasgow Coma Scale score, heart rate, penetrating trauma, prehospital advanced airway attempt, and ROC site. Results: From May 2006 to August 2008, 853 patients were enrolled, 38 were excluded for incomplete data, and 815 form the analyzable cohort. Mean age was 37 years and 78% were male. Mean (±SD) injury severity score was 24±16, 40% required a prehospital advanced airway, 73% required an emergent procedure, and overall mortality was 26%. We observed a significant relationship between lowest prehospital SBP and in-hospital emergent procedures and mortality (Table). Conclusion: Prehospital hypotension is significantly associated with in-hospital emergent procedures and mortality, especially when SBP is less than 65 mm Hg.
Abstract 59: Treatment at a STEMI Center Is Associated with Favorable Outcomes Following Out-of-Hospital Cardiac Arrest
Authors: Bryn E Mumma, Deborah B Diercks, Beate Danielsen, James F Holmoes
Journal: Circulation (2012)

Introduction: The American Heart Association recommends regionalized post-OOHCA care at cardiac resuscitation centers that are closely aligned with ST elevation myocardial infarction (STEMI) centers. However, the effect of STEMI centers on outcomes following OOHCA remains unknown. Hypothesis: We hypothesize that treatment at a STEMI center is associated with increased survival and neurologic recovery among OOHCA patients. Methods: We included patients age 18 years or older with OOHCA in the 2010 California Emergency Medical Services Information Systems (CEMSIS) database whose CEMSIS record was linked to an inpatient record from the California Office of Statewide Health Planning and Development (OHSPD) database. The CEMSIS database is a unified EMS data collection system, and the OSHPD database contains patient-level data for all inpatient and emergency department encounters. We linked CEMSIS and OSHPD records using probabilistic linkage. Multiple logistic regression models including age, sex, race, ethnicity, payer category, hospital size, teaching status, and trauma center status were used to evaluate the association between STEMI center treatment and outcomes. A STEMI center was defined as one with 24-7 percutaneous coronary intervention capability. Good neurologic recovery was defined as discharge to home, residential care facility, psychiatric facility, prison/jail, and against medical advice. Results: We identified 8481 patients with OOHCA in the CEMSIS database; 3620 were linked to OSHPD inpatient records. The majority (74.0%) were treated at STEMI centers. Median age was 73 years (IQR 60-83). Survival to hospital discharge was similar between the two groups (26.3% vs 25.8%; p=0.76), but good neurologic recovery was higher among those treated at STEMI centers (18.2% vs 10.4%; p&lt;0.0001). In the adjusted analysis, treatment at a STEMI center was associated with survival (OR 1.2, 95% CI 1.0-1.5; p=0.047) and good neurologic recovery (OR 2.1, 95% CI 1.6-2.8; p&lt;0.0001). Conclusions: Treatment at a STEMI center following OOHCA was associated with favorable outcomes recovery. Our data suggest that regionalized post-OOHCA care in accordance with American Heart Association guidelines may improve neurologic recovery following OOHCA.
Abstract 37: External Validation of Termination of Resuscitation Guidelines in the Setting of Intra-arrest Cold Saline, Mechanical CPR and Comprehensive Postresuscitation Care
Authors: Francis J Diskin, Michael C Kurz, Teresa R Camp-Rogers, Mary Ann Peberdy, Joseph P Ornato
Journal: Circulation (2012)

Background: The development of Advanced Life Support (ALS) Termination of Resuscitation (TOR) guidelines for Out-of-Hospital Cardiac Arrest (OOH-CA) seeks to improve the efficiency of scarce pre-hospital resources. However, as pre-hospital treatment for OOH-CA evolves and survival improves, these TOR guidelines must be reevaluated in a contemporary context of EMS providing advanced resuscitation care. Methods: Retrospective review of all adult (&gt;18 years old), non-traumatic, OOH-CA patients (defined as patients with absence of pulse who received either CPR and/or defibrillation) treated by EMS in Richmond, Virginia, from January 1, 2009 to December 31, 2010. In addition to standard ALS, intra-arrest cold saline, mechanical CPR, and transportation to a comprehensive post-resuscitation center (CPRC) was provided. Survival at 30 days was presumed when death could not be verified from publically reportable sources. Results: Of the 333 OOH-CA patients enrolled, the majority were male (59%), unwitnessed (52%), received no bystander CPR (67%), presented in a non-shockable initial rhythm (79%), with an average age of 62.5 years. Follow up data was obtained 324 (97.3%) of patients with overall survival of 19%, 15%, and 13% at 7, 14, and 30 days respectively. Of the 77 patients TOR guidelines recommended termination, none survived yielding both 100% specificity (95% CI 100- 92.8%) and positive predictive value (95% CI 100-94.1%). However, TOR guidelines recommended transport of 192 of the 269 patient who died, resulting in a sensitivity of 28.6% (95% CI 34.5-23.4%). Conclusion: The TOR guidelines continue to have a reliable positive predictive value for death even in the setting of advanced EMS resuscitation methods and access to a CPRC. However, as the potential for survival from OOH-CA improves, the efficiency gained from their use is impacted greatly.
Abstract 9649: Lipid-modifying Effects of Anacetrapib in Patients with Lower versus Higher Baseline Levels Of HDL-C, LDL-C, And TG: Pre-Specified Subgroup Analyses of the DEFINE (Determining the Efficacy and Tolerability of CETP INhibition with AnacEtrapib) Trial
Authors: Eliot Brinton, Sherry Liu, Michael Stepanavage, Christopher P Cannon, Michael Davidson, Antonio M Gotto, Sukrut Shah, Hayes Dansky, Yale Mitchel, Philip Barter
Journal: Circulation (2011)

Purpose : Low HDL-C is a risk factor for coronary heart disease which partly accounts for residual risk despite statin therapy. After 24 weeks of treatment, the addition of anacetrapib (ANA), a cholesteryl ester transfer protein (CETP) inhibitor to statin therapy increased HDL-C by 138% and reduced LDL-C by 40% in a 1623 patient safety and lipid efficacy Phase III trial (DEFINE). Sub-group analyses were performed to determine the degree to which ANA raises HDL-C and lowers LDL-C in patients with low baseline HDL-C and in patients with diabetes and other subgroups. Methods: Percent placebo-corrected HDL-C increases and LDL-C decreases from baseline after 24 weeks of ANA, 100 mg/day, were compared among patients according to baseline HDL-C, LDL-C, and TG levels above or below the median and in patients with diabetes. Results: Median baseline HDL-C, LDL-C, and TG were 40 mg/dL, 81 mg/dL, and 128 mg/dL, respectively. ANA produced robust increases in HDL-C in patients with baseline HDL-C below (152%) and above (127%) the median. In the lowest baseline quartile of HDL-C (15 to 34 mg/dL) levels also increased to a mean on-treatment HDL-C of 85 mg/dL. The percent increase in HDL-C was similar in patients with lower vs. higher baseline TG levels. ANA increased HDL-C similarly in diabetics compared to non-diabetics (130% vs 150%) with a mean on-treatment HDL-C of 100 vs. 102 respectively. The percent reduction in LDL-C with ANA was generally similar in patients with lower vs higher baseline LDL-C, HDL-C or TG levels and in patients with or without diabetes. Conclusion: ANA robustly increased HDL-C in all patients especially those with low HDL-C. Reductions in LDL-C with ANA were independent of baseline LDL-C, HDL-C, or TG levels. The clinical impact of these lipid-modifying effects of ANA in these sub-groups will be assessed in REVEAL-HPS3/TIMI55, a 30,000 patient clinical outcomes trial.
Abstract 9578: Single-Item Self-Report Medication Adherence Question Predicts Hospitalization and Death in Patients with Heart Failure
Authors: Jia-rong Wu, Darren A DeWalt, David W Baker, Dean Schillinger, Bernice Ruo, Kirsten Bibbins-Domingo, Aurelia Macabasco-O'Connell, George M Holmes, Kimberly A Broucksou, Brian Erman, Victoria Hawk, Crystal W Cene, Christine DeLong Jones, Michael Pignone
Journal: Circulation (2011)

Background: Sub-optimal adherence to heart failure (HF) medications contributes to worse outcomes. Having a simple means of identifying sub-optimal adherence could help identify at-risk patients for interventions. Objective: To determine whether a single-item self-report medication adherence question predicts hospitalization and death in patients with HF. Methods: We performed an observational study in 597 patients with HF (male 52%, age 61±13 years, NYHA III/IV 31%) within a 4-site randomized trial. Patient demographic and clinical variables were collected at baseline by interview and medical record review. Self-report medication adherence was assessed at baseline using a single item question: “Over the past 7 days, how many times did you miss a dose of any of your heart medication?” Patients who reported no missing dose were defined as adherent; those missing ≥ 1 dose were non-adherent. The primary outcome was combined all-cause hospitalization or death over 1 year; secondary endpoint was HF hospitalization. Outcomes were assessed based on blinded chart reviews and HF outcomes were determined by a blinded adjudication committee. We used negative binomial regression to examine the relationship between medication adherence and incidence of hospitalization and death, adjusting for site, demographic (age, gender, ethnicity, socioeconomic status) and clinical (HF symptoms, systolic dysfunction, β-blocker use, hypertension, and history of CVD) factors. Results: Seventy-three percent of patients reported perfect adherence to their heart medicine at baseline. Patients with perfect medication adherence had a lower rate of events (0.71 events / year) compared with those with any non-adherence (0.90 event / year). After adjusting for site, adherent patients had an incidence rate ratio (IRR) of 0.79 (95% CI: 0.67-0.92) for all-cause hospitalization or death, and 0.79 (95% CI: 0.75-0.83) for HF hospitalization. When adding demographic and clinical factors to the model, the adjusted IRR for all-cause hospitalization and death = 0.77 (95% CI: 0.68-0.86) and for HF hospitalization = 0.83 (95% CI: 0.65-1.06). Conclusion: A single question on medication adherence at baseline predicts hospitalization and death over 1 year in patients with HF.
Abstract 73: Association of Serum Lactate and Survival Outcomes in Patients Undergoing Therapeutic Hypothermia After Cardiac Arrest
Authors: Roksolana Starodub, Benjamin S Abella, Anne V Grossestreuer, Frances S Shofer, Sarah M Perman, Marion Leary, David F Gaieski
Journal: Circulation (2012)

Introduction : Recent studies have suggested that serum lactate may serve as a marker to predict mortality after resuscitation from cardiac arrest (CA). The relationship between serum lactate and CA outcomes requires further characterization, especially among patients treated with therapeutic hypothermia (TH) and aggressive post-arrest care. Methods: A retrospective analysis of patients resuscitated from non-traumatic CA at three urban U.S. hospitals was performed using an established internet-based post-arrest registry. Adult (≥18 y) patients resuscitated from CA and receiving TH treatment were included. Logistic regression analysis was used to adjust for potential confounders to survival outcomes. Survival to discharge served as the primary endpoint. Results: A total of 199 post-CA patients treated with TH between 5/2005 and 11/2011 were included in this analysis. The mean age was 56.9±16.5 years, 85/199 (42.7%) patients were female, and survival to discharge was attained in 84/199 (42.2%). While lower initial post-CA serum lactate levels were not associated with increased survival to discharge, subsequent lactate measurements were significantly associated with outcomes (24-h serum lactate levels in survivors vs non-survivors, 2.7±0.5 vs 4.2±0.4 mmol/L, p&lt;0.01). Multivariable logistic regression confirmed this relationship with survival to discharge (p &lt; 0.01). Conclusion: Lower serum lactate levels at 12 h and 24 h, but not initially following cardiac arrest, are associated with survival to hospital discharge after resuscitation from CA and TH treatment. Prospective investigation of serum lactate as a potential prognostic tool in CA is needed.
Abstract 9614: Ca <sup>2+</sup> -Independent Di-phosphorylation of Myosin Light Chain by Rho-associated Coiled-Coil Protein Kinase (ROCK) in the Subjunctional Regions of Cell-Cell Contact Mediates Thrombin-Induced Barrier Dysfunction in Vascular Endothelial Cells
Authors: Mayumi Hirano, Akiko Hanada, Katsuya Hirano
Journal: Circulation (2011)

A disruption of endothelial barrier function is a predisposing factor for the development of atherosclerosis. The phosphorylation of myosin light chain (MLC) is a key signal of barrier dysfunction. MLC phosphorylation is thought to take place sequentially at S19 and then T18, induces actin stress fiber formation and generates traction force to disrupt cell-cell contact. However, it is unclear how the phosphorylation at two sites contributes to barrier dysfunction. The present study investigated the role of mono- and di-phosphorylation of MLC (MLC-P and MLC-PP) in thrombin-induced barrier dysfunction. Thrombin (1 u/mL) increased the cytosolic Ca 2+ concentration and decreased the transendothelial electrical resistance (TEER) with a peak at 1 and 3-5 min, respectively, in porcine aortic endothelial cells (PAEC). A new SDS-PAGE method using a Phos-tag TM compound, which specifically binds to a phosphate group, allowed separate quantification of MLC-P and MLC-PP. PAEC at confluence contained 25% MLC-P and 2% MLC-PP under resting conditions. Thrombin stimulation only slightly increased MLC-P at 3 min, while it showed up on stress fibers. MLC-PP increased to a peak of 35% at 3-5 min, and thereafter declined to the resting level within 15 min. MLC-PP was localized in the subjunctional region of cell-cell contact in addition to the stress fibers at 3 min. ROCK inhibitors, Y27632 and H1152, inhibited the thrombin-induced decrease in TEER, the increase in MLC-PP and the subjunctional localization of MLC-PP, while having no effect on the Ca 2+ response. The MLC-P level remained unaffected by Y27632, while the stress fiber localization was inhibited. Gαq inhibitor, YM254890, inhibited the Ca 2+ response and the decrease in TEER, but it had no effect on the increase in MLC-PP. The introduction of dominant negative mutants of Gα12, Gα13 and Gαq using a cell-penetrating peptide inhibited the thrombin-induced decrease in TEER. The present study provides the first evidence that MLC-P and MLC-PP are differentially regulated in endothelial cells, and that Ca 2+ -independent, ROCK-mediated MLC-PP in the subjunctional regions plays a critical role in the thrombin-induced barrier dysfunction. Inhibition of MLC-PP is thus necessary to restore endothelial barrier dysfunction.