tbuckley/cabot-search huggingface dataset:
Abstract 222: Does Gender Matter for Postarrest Care?
Authors: Valeria E Rac, Paul Dorian, Arthur S Slutsky, Beth Abramson, Robert Fowler, Janet A Parsons, Alex Kiss, Katie N Dainty, Merrick Zwarenstein, Cathy C Zhan, Laurie J Morrison
Journal: Circulation (2012)

Introduction: Studies have shown that after cardiac arrest women have lower survival to discharge rates than men. These differences are surprising, considering that women are more often successfully resuscitated in the prehospital setting. Differences in survival to discharge rates might be partially attributed to disparity in post arrest care, similar to what is seen in myocardial infarction (MI). Hypothesis: There is gender disparity in the provision of targeted post arrest care interventions. Methods: This prospective study explores gender disparity in a prospective Canadian data set of non-traumatic, EMS treated, out of hospital cardiac arrest (OHCA) patients presenting to hospitals in the Strategies for Post Arrest Care (SPARC) network between March 16, 2010 and March 31, 2012. All patients with sustained return of spontaneous circulation (palpable pulse for &gt;20 mins) were included in the analysis. Unadjusted chi square tests and logistic regression models were employed to examine the relationship between gender, and provision of post arrest care interventions (coronary angiography, percutaneous coronary intervention (PCI), therapeutic hypothermia, electrical physiology consultation and internal cardiac defibrillator (ICD) placement and two or more neuroprognostic testing ≥ 72 hours). Results: From a total of 2,199 OHCA patients (1,447 men, 752 women), 992 had sustained return of spontaneous circulation (36.6% women, mean age 68.2 years; 63.4% men, mean age 63.9). There were gender differences in utilization of coronary angiography (12.1% in women vs. 20.8% in men, adjusted OR 0.53, 95% CI 0.36 to 0.77, p=0.013) and PCI (3.7% in women vs. 5.8% in men, adjusted OR 0.63, 95% CI 0.41 to 0.98, p=0.042). ICD was less utilized in women, but differences were not significantly different (4.9% in women vs. 8.1% in men, adjusted OR 0.59, 95% CI 0.33 to 1.02 p=0.062). There were no gender differences in utilization of therapeutic hypothermia and neuroprognostic testing ≥ 72 hours. Conclusion: The observed gender differences in utilization of coronary angiography and PCI intervention may be due to disparity in care and/or differences in underlying pathophysiology of cardiac arrest between men and women contributing to women’s unfavorable outcomes.
Abstract 9735: Identification of Phenotypes at Risk of Resistant Hypertension
Authors: Renata Giudice, Raffaele Izzo, Giovanni De Simone, Marina De Marco, Teresa Migliore, Claudia S Cimmino, Maria A RAO, Nicola De Luca, Bruno Trimarco
Journal: Circulation (2011)

Background: The presence of elevated blood pressure (BP) despite the use of at least three different medications, including a diuretic, is defined resistant hypertension (RH). RH is associated with high risk of stroke, myocardial infarction and arrhythmia. Detection of high risk phenotypes for RH could be of great help in better addressing and graduating initial therapy. Thus, predictors of RH were identified in a large population of hypertensive patients. Methods: We studied 6,215 hypertensive patients (age 53±11 years, 57% men, systolic BP [SBP]: 158±20, diastolic BP [DBP]: 99±10) without prevalent cardiovascular disease and with MDRD-estimated glomerular filtrate ratio (eGFR)&gt;30 mL/mmHg/1.73 m2. Results: After a mean follow up time of 61±43 months, 12% of the studied population was classified as RH (n=744). Patients with RH were older (57±10 vs 52±11, p&lt;0.0001), and more often women (p&lt;0.0001). At baseline, patients with follow-up RH were more often diabetics (11% vs 4%), more often had metabolic syndrome (MetS, 23% vs 14%; both p&lt;0.0001), and exhibited higher values of SBP, DBP, BMI, fasting triglycerydes and glucose, LV mass, carotid intima-media thickness (IMT), duration of hypertensive disease, pulse pressure/stroke index (PP/SVi), relative wall thickness and lower values of eGFR and serum potassium (all p&lt;0.001). In a Cox model including the variables that were different in the descriptive analysis, follow up RH was independently predicted by: female sex (p=0.015; HR=1.22; CI=1.04-1.42), older age (p&lt;0.0001; HR=1.03/year: CI=1.02-1.04), higher LV mass index (p=0.001; HR=1.02/g*m-2.7; CI=1.02-1.03) and SBP (p&lt;0.0001; HR=1.05/x 5 mmHg; CI 1.01-1.10), longer duration of hypertension (p&lt;0.0001; HR=1.02/year; CI 1.01-1.03) and MetS (p&lt;0.003; HR=1.36; CI 1.11-1.67), at the initial visit, without a significant impact for diabetes, BMI, smoking habits, DBP, eGFR, serum potassium, fasting triglycerides and glucose, IMT and PP/SVi. Conclusion: In essential hypertensive patients, resistance to maximal antihypertensive therapy is more frequent in women with MetS and is predicted by older age, higher initial values of SBP, longer duration of hypertensive disease and presence of cardiovascular target organ damage.
Abstract 9661: Differences in Pathophysiology of Plaques Between Target Lesion and Non-Target Lesion Events After Successful Percutanous Cornary Intervention: Insights from Integrated Backscatter Intravascular Ultrasound
Authors: Soichiro Kumagai, Hideki Ishii, Tetsuya Amano, Tadayuki Uetani, Mutsuharu Hayashi, Daiji Yoshikawa, Nobutake Kurebayashi, Bunmei Sato, Seiichi Hayakawa, Miho Tanaka, Tatsuaki Matsubara, Toyoaki Murohara
Journal: Circulation (2011)

Objectives: We sought to determine the morphologic predictors of major adverse cardiac events (MACEs) after perctaneous coronary intervention (PCI), using integrated backscatter intravascular ultrasound (IB-IVUS). Methods: Conventional and IB-IVUS using 40-MHz (motorized pullback 0.5mm/s) intravascular catheter were performed in 295 consecutive patients indicated for PCI. Three-dimensional analyses were performed to determine the total plaque volume and the volume of each plaque component (lipid, fibrous, and calcified). MACEs were defined as death, nonfatal myocardial infarction, heart failure required hospitalization, any repeat revascularization for the index target lesion (TLR), and non-target ischemic events. Non-target ischemic events were defined as nonfatal myocardial infarction, any repeat revascularization for angina involving the non-target vessel or the target vessel outside the index lesion. Results: The median follow-up interval was 982 days. During the follow-up period, MACEs were observed in 78 (26.4%) patients including TLR in 40 (13.6%) and non-target ischemic events in 31 (10.5%). With the Cox proportional hazard model after adjustment for confounders, MACEs were associated with chronic kidney disease (OR 2.26, 95% CI 1.25-4.08, p=0.007) and diabetes (OR 1.75, 95% CI 1.06-2.89, p=0.03). But as for each components, TLR were significantly associated with percentage of plaque volume (OR 1.06, 95% CI 1.01-1.10, p=0.04), and non-target lesion ischemic events were significantly associated with percentage of lipid volume (OR 1.03, 95% CI 1.00-1.06, p=0.03). Conclusions: Greater plaque burdens were significantly associated with TLR, while lipid-rich contents were relevant to non-target lesion events. These findings may have implications regarding the differences in pathophysiology of plaques between the TLR and non-target lesion events.
Abstract 19235: Infiltrating Macrophage-Derived Angiopoietin-Like Protein2 (Angptl2) Accelerates Abdominal Aortic Aneurysm by Inducing Chronic Inflammation and ECM Degradation
Authors: Hirokazu Tazume, Keishi Miyata, Eiji Horio, Hisashi Sakaguchi, Ken Okamoto, Michio Kawasuji, Yuichi Oike
Journal: Circulation (2012)

Abdominal Aortic Aneurysm (AAA) is characterized by aneurysmal morphological changes with low-grade chronic inflammation of atherosclerotic aortic walls. However, molecular mechanism has not been elucidated well. We recently reported that Angptl2 mediates various chronic inflammatory conditions, such as rheumatoid arthritis, dermatomyositis, cancer, and obesity-related metabolic disorder. In this study, we examined whether Angptl2 contributes to the pathogenesis of AAA formation. Firstly, we found expression of Angptl2 and pro-inflammatory cytokines mRNA in aneurysmal lesion of AAA patients were significantly increased compared to the non-dilating lesion. Angptl2 protein was abundantly expressed in infiltrating macrophages but not expressed in other inflammatory cells. We next examined whether Angptl2 deficiency affects the AAA formation in Angptl2-knockout (KO) mice. Interestingly, on day 28 after surgery, the sizes of AAA in Angptl2 KO mice were significantly decreased compared to wild-type mice (p&lt;0.01). And expression of TNF-α, IL-1β, IL-6 and MMP-9 mRNAs in tissues from the aortic wall of CaCl 2 -treated Angptl2 KO mice was markedly decreased compared with that seen in wild-type mice. To identify the culprit cells secreting Angptl2 in AAA lesion, we transplanted bone marrow (BM) cells from Angptl2 KO mice or littermate wild-type controls into lethally irradiated wild-type recipients. The sizes of AAA in the recipients of Angptl2-deficient BM cells were significantly attenuated compared to those in the recipients of wild-type control BM cells (p&lt;0.01). Finally, to investigate whether macrophage-derived Angptl2 could alter expression levels of proinflammatory cytokines and MMP-9 in macrophages, we analyzed expression of pro-inflammatory cytokines in thioglycollate(TGC)-induced peritoneal inflammatory macrophages. Significant decreases in TNF-α, IL-1β, IL-6 and MMP-9 expression were observed in macrophages from Angptl2 KO mice compared with similarly treated wild-type mice. These results suggest that infiltrating macrophage-derived Angptl2 promotes expression of proinflammatory cytokines and MMP-9 in these cells, resulting in progression of AAA pathogenesis.
Abstract 9551: Relative Contributions of Genetic Variants in PON <i>1, CYP2C19 And ABCB1 o</i> n in-hospital and One Year Clinical Outcomes in Patients Treated with Clopidogrel After an Acute Myocardial Infarction
Authors: Tabassome Simon, Philippe Gabriel Steg, Laurent becquemont, Celine Verstuyft, Salma Kotti, François Schiele, Emile Ferrari, Elodie Drouet, Gilles Grollier, Nicolas Danchin
Journal: Circulation (2011)

Background: Clopidogrel with aspirin reduces ischemic events in patients with acute myocardial infarction (AMI). Clopidogrel requires drug transport via P-glycoprotein, encoded by ABCB1 , and bioactivation by CYP450, mainly via CYP2C19 . The clinical response to clopidogrel is variable, depending in part on CYP2C19 and ABCB1 genetic polymorphisms. Recently however, paraoxonase-1 (PON1) was suggested as the crucial enzyme for clopidogrel bioactivation, with its Q192R polymorphism determining per se clopidogrel response on cardiovascular events. Methods We assessed the effect of PON1 (Q192R) polymorphisms by itself and alongside variants in CYP2C19 loss-of-function and ABCB1 on in-hospital and one-year cardiovascular events in clopidogrel-treated AMI patients participating in the Fast-MI study (n=2208), including the subset undergoing PCI (n=1538). Results : PON1 (Q192R) polymorphism was not associated with increased risk of in-hospital death and one year major adverse events: One-year adjusted hazard ratio [HR] for QQ versus RR individuals, 1.03; 95% CI, 0.66-1.61 in the whole population and HR, 0.77; 95% CI, 0.42-1.41 in PCI-treated patients. Adding ABCB1 and CYP2C19 polymorphisms had no impact on these risks. Presence of two CYP2C19 loss-of-function alleles was associated with the risk of in-hospital death and major clinical events at one year in the overall population (OR: 3.67; 95% CI, 1.05-12.80, and HR: 1.96, 95% CI, 1.08-3.54) and in PCI patients (OR, 6.87; 95% CI, 2.52-18.72, and HR: 3.06, 95% CI, 1.47-6.41). ABCB1 polymorphisms had an impact on the clinical response to clopidogrel in the overall population but not in PCI patients. Conclusion : PON1 polymorphism was not associated with an increased risk of events in clopidogrel-treated patients with AMI and those undergoing PCI. In contrast, CYP2C19 loss- -of-function polymorphism remained the major pharmacogenetic contributor of clinical response to clopidogrel in these populations.
Abstract 84: Relationship Between Chest Compression Rate and Depth During Cardiopulmonary Resuscitation
Authors: Saeed Babaeizadeh, Reza Firoozabadi, Eric Helfenbein, Mohamud Daya
Journal: Circulation (2012)

Background The 2010 AHA guidelines for healthcare providers encourage rescuers to focus on the delivery of high quality cardiopulmonary resuscitation (CPR). For adults, guidelines recommend chest compressions at a rate of at least 100 compressions per minute (cpm) with a depth of at least 51 millimeters (mm). Continuously pushing the chest hard and fast can be difficult and the compression depth may drop if the rescuer increases the compression rate. Objective Determine the distributions of and relationship between chest compression rate and depth during CPR in out-of-hospital cardiac arrest (OHCA) patients. Methods Recordings from a convenience sample of 234 OHCA patients with compression waveforms collected from 2006 to 2010 from a single EMS agency using the Philips HeartStart MRx defibrillator. Real-time audio and visual feedback was available to EMS personnel based on the 2005 depth guidelines (38 to 51 mm). Compression depth and rate were calculated based on the waveforms recorded by the Q-CPR TM measurement and feedback tool. The continuous distributions of rate and depth were generated using only the segments with good signal quality (total of 42 hours). Results The figure shows the distributions of and relationship between the rate and depth. In this dataset, 69% of the time the compression rate was at least 100 cpm and 48% of the compressions had a depth between 38 and 51 mm. Only 10% were performed slower than 90 cpm, and only 12% were less than 30 mm deep. With the compression rates between 73 to 88 cpm, the depth increased at a rate of 0.3 mm/cpm. However, at compression rates faster than 88 cpm, the depth decreased at almost the same rate of -0.3 mm/cpm. Conclusion Chest compressions at rates faster than 88 cpm are associated with a reduction in depth. The practical balance between compression rate and depth deserve consideration in the Guidelines process.
Abstract 9940: Novel Function of the P2y/cysteinyl-leukotriene Receptor Gpr17 in Recruitment of Circulating and Resident Myofibroblast Progenitors Following Acute Myocardial Infarction
Authors: Simona Cosentino, Laura Castiglioni, Elena Nobili, Francesca Colazzo, Elena Tremoli, Patrizia Rosa, Maria Pia Abbracchio, Luigi Sironi, Maurizio Pesce
Journal: Circulation (2012)

Background - GPR17 is a G i -coupled dual receptor activated by uracil-nucleotides and cysteinyl-leukotrienes, families of signaling molecules massively released into hypoxic tissues. In the normal heart GPR17 expression has been reported, while its role during ischemia is totally unknown. Aims and Results - To investigate GPR17 expression in mice hearts, before or after myocardial infarction (MI) induction, immunofluorescence was set up. In non ischemic hearts, GPR17 protein was confined into small cell groups localized between myocytes. These cells expressed the stem cell antigen-1 (Sca-1). At 24, 48 and 72 hrs post-MI, cell clusters expressing GPR17 were found to infiltrate the MI border zone and penetrate into the ischemic area. They expressed Sca-1, the myofibroblast/mesenchymal marker CD44 and the hematopoietic lineage marker CD45. Interestingly, not all cells expressing GPR17 also expressed CD45, suggesting a dual origin of GPR17 + cells recruited after MI. A flow-sorting experiment was performed to separate Sca-1 + /CD45 + from Sca-1 + /CD45 - cells at 48 hrs post-MI. RT-PCR showed that both cellular populations expressed GPR17, thus confirming their dual origin. A clonogenic Sca-1 + cell line was derived from non-ischemic hearts. In addition to CD44, these cells expressed mesenchymal markers CD29 and CD105, but not endothelial and hematopoietic markers, and showed a side population phenotype. Sca-1 + cells expressed GPR17 RNA/protein and were able to differentiate into cardiac lineage cells and myofibroblasts in culture. To investigate GPR17 functions, Sca-1 + cells were treated with receptor agonists UDP-Glucose (10nM) and LTD 4 (100nM). These ligands did not rescue cells from hypoxia-induced apoptosis. By contrast, they enhanced CSCs migratory activity (3.1±0.8 and 1.7±0.2, folds vs. control; P &lt; .05 paired t-test). Finally, addition of GPR17 antagonists montelukast and cangrelor abolished this migratory effect. Conclusions - The present results indicate a role of dual GPR17 receptor in early homing of Sca-1 + cardiac stem cells-derived and circulatory stem cells-derived myofibroblasts into the infarcted myocardium. These findings have implications for the pharmacologic control of heart remodeling at early times after infarction.
Abstract 8975: A Study of Left Ventricular Septal Wall 2D Radial and Circumferential Strain in Dyssynchrony
Authors: Bethany Dicks, Keith DesRochers, Muhammad Ashraf, David J Sahn
Journal: Circulation (2012)

Background: This study used 2D speckle tracking to analyze the effects of simulated synchrony and dyssynchrony on left ventricular (LV) septal strain. Methods: The atria were removed from 8 pig hearts and balloons were sewn into both ventricles at the annulus of the mitral and tricuspid valves. Each ventricular balloon was attached to a separate pulsatile pump. Each heart was imaged in a water bath at 4 different stroke volumes (SV) (30-60) at a pump rate of 50bpm. End diastolic volume (EDV) was increased incrementally with each increase in SV by injecting water into the closed system. For each SV, images were obtained in states of ventricular synchrony and dyssynchrony. 2D echo images in the short axis view were obtained using a GE Vivid 7 echocardiography system and analyzed using EchoPac PC 2D Q analysis of strain. Results: Statistically significant differences in septal strain were observed in states of synchrony vs. dyssynchrony. In dyssynchrony, radial septal strain (RS) showed a significant decrease compared to synchronous at each stroke volume (RS: SV 30, p = 0.051; SV 40, p = 0.016; SV 50, p = 0.043; SV 60, p = 0.029). Dyssynchronous circumferential strain (CS) showed a significant increase compared to synchronous at each stroke volume (CS: SV 30, p = 0.006; SV 40, p = 0.013; SV 50, p = 0.1739; SV 60, p = 0.02). Conclusions: There are significant differences in the radial and circumferential strain of segments of the left ventricular wall during states of dyssynchrony.
Abstract 9721: <i>Tmem100</i> , a Novel BMP9/10-Dependent Endothelial Gene Essential for Arterial Development and Morphogenesis
Authors: Satoshi Somekawa, Hisaki Hayashi, Masahide Sakabe, Tomoko Ioka, Genki Sato, Ken Inada, Shiro Uemura, Osamu Nakagawa, Yoshihiko Saito
Journal: Circulation (2011)

Introduction: Bone morphogenetic protein 9 (BMP9) and BMP10 play critical roles in regulating embryonic vascular development through their endothelium-specific ALK1 receptor. Mutations of the ALK1 gene cause human hereditary hemorrhagic telangiectasia and pulmonary hypertension, but their downstream functional proteins are largely unknown. Methods and Results: We attempted to identify novel endothelial genes downstream of BMP9/10-ALK1 signaling by an mRNA microarray analysis of BMP9-treated human umbilical artery endothelial cells. BMP9 treatment activated expression of various known BMP9/10-regulated genes such as ID1 up to ten fold. Intriguingly, we also found that BMP9 markedly induced mRNA expression of a previously-uncharacterized gene TMEM100 more than 100-fold. siRNA knockdown experiments confirmed that TMEM100 expression by BMP9 or BMP10 was mediated by the ALK1 receptor activation. TMEM100 encodes a transmembrane protein that is highly conserved among species, but its expression profiles and physiological significance had not been studied. Tmem100 was co-expressed with Alk1 specifically in aortic endothelial cells of mouse embryos (figure, panel A). Tmem100 null mice die around E10.5 due to impaired differentiation of arterial endothelium and defects of vascular morphogenesis, which phenocopied vascular abnormalities observed in Alk1 null embryos, indicating a major role of Tmem100 in the BMP9/10-ALK1 signaling pathway (panel B). Furthermore, expression of activated Notch1 receptor, Notch1-ICD, as well as various Notch-target genes including Hey/Hrt transcription factors significantly decreased in Tmem100 null embryos, suggesting that Tmem100 is indispensable for regulation of Notch signaling in proper vascular development. Conclusion: We identified Tmem100 to be a novel endothelial gene essential for arterial development and morphogenesis downstream of BMP9/10-ALK1 signaling.
Abstract 19783: Performance of Ultra-Low Dose Tc-99m Sestamibi Myocardial Perfusion Imaging Using Solid-State SPECT: Comparison to Coronary Angiography
Authors: Matthew G Taylor, Timothy M Bateman, Arthur I McGhie
Journal: Circulation (2012)

Introduction: Ultra-low dose (ULD) SPECT is feasible using solid-state detector systems, with advantages of lower dosimetry and lower radionuclide costs. Thus far, there have been no studies validating accuracy of ULD SPECT against coronary angiography. We therefore performed a 2-expert consensus blinded review of 37 patients who had coronary angiography and ULD SPECT (D-SPECT, Spectrum Dynamics) within 30 days, with a stress-first protocol utilizing &lt; 4 mCi Tc-99m sestaMIBI. Methods: Pts were imaged both supine &amp; upright for ∼10 6 myocardial counts; rest images were acquired for equivocal or abnormal stress images using ∼4X stress dose. Mean stress dose was 3.9 mCi +0.47 mCi and mean rest dose was 14.8 mCi +1.8 mCi (n=23). Patient mean age was 62 yrs; 32% were female; 43% underwent pharmacologic stress. Each study was interpreted as ischemic vs non-ischemic, and also evaluated semi-quantitatively (4-point scale) for perfusion and function using a 17 segment model. Significant CAD was defined as a stenosis &gt;70% on coronary angiography. Results: Coronary angiography was abnormal in 25 and normal in 12 pts; 11 had single vessel (SVD) &amp; 14 had multi-vessel disease (MVD). ULD SPECT sensitivity was 88% (22/25), specificity was 92 % (11/12), PPV was 96%, and NPV was 79%. Sensitivity for detection of SVD was 91% and for MVD was 92%. Detection of a 2 nd or 3 rd diseased vessel in pts with MVD was 54%. Conclusions: The results of this study are encouraging that ULD-SPECT with patient dosimetry ∼10% of typical rest/stress SPECT is diagnostically accurate for identification of significant CAD. Correct identification of MVD is currently suboptimal.