tbuckley/cabot-search huggingface dataset:
Abstract 260: Automatic Shock Advisory Without Interrupting Chest Compression by Filtering Compression Artifact
Authors: Saeed Babaeizadeh
Journal: Circulation (2013)

Background: Both AHA and ERC Guidelines 2010 focus on minimizing “hands-off time” - the time interval a patient in cardiac arrest is not receiving chest compressions (CC). The primary device-related cause of CC interruption is automated ECG rhythm analysis for accurate shock advisory. The mechanical activity of CC produces artifact on the ECG waveform that most automated ECG analysis programs cannot fully differentiate from the patient’s inherent ECG morphology. Furthermore, clinicians observing an ECG waveform on the defibrillator’s display cannot see the patient’s underlying rhythm through the electrical noise created by CC, forcing an interruption to CC for rhythm assessment. Objective: Improving the performance of ECG analysis programs by filtering artifacts due to CC in out of hospital cardiac arrest (OHCA) patients. Methods: Recordings from 175 OHCA patients collected for a separate study using Laerdal HeartStart 4000 defibrillators in 6 ambulances in 3 European regions between March 2002 and October 2003. The transition times from CC to hands-off were marked. Assuming no rhythm change within a few seconds around the transition time, experts selected 1378 4.5-second ECG segments with CC artifact, and the same number without the artifact. Each category included 340 shockable ventricular fibrillation, 342 asystole, 646 pulseless electrical activity, and 50 pulsatile rhythms. A two-step process was designed to filter the CC artifact prior to the analysis by the shock advisory algorithm. By analyzing both ECG and thoracic impedance waveforms the fundamental frequency of CC was found, to then be filtered along with all its harmonics using a comb filter. Results: Defining a positive event as shock advice for shockable rhythm, the shock advisory algorithm achieved sensitivity of 97% and specificity of 99% when no CC was being performed. However during CC both sensitivity and specificity dropped to 63% and 91% respectively. Filtering the CC artifact increased the sensitivity back up to 89% at the expense of slightly reducing the specificity to 90%. Conclusion: It is possible to improve the performance of shock advisory algorithms during CC by filtering the CC artifact. However additional techniques may be needed to achieve accuracy high enough for practical use.
Abstract 327: Impaired Mitochondrial Function Following The Metabolic Phase Of Cardiac Arrest And Resuscitation: Differences In Tissue Vulnerability, Site And Severity Of Dysfunction
Authors: Joshua W Lampe, Mary A Selak, Tong Da, Wei Zhang, Ming Yin, Chih-Hsien Wang, Meagan J McManus, Douglas C Wallace, Lance B Becker
Journal: Circulation (2013)

Introduction: Mitochondrial dysfunction may be critical to reperfusion injury following the metabolic phase of prolonged cardiac arrest. However, specific intra-mitochondrial sites of dysfunction remain uncertain and differential tissue vulnerabilities have not been well characterized. HYPOTHESIS: The metabolic phase of prolonged cardiac arrest and resuscitation will provoke specific patterns of fixed localized defects in respiratory and phosphorylating activities of mitochondrial function and impact the heart, brain, and kidney differently. METHODS: A rodent model of prolonged cardiac arrest was employed with 30 min of untreated axphyxial arrest followed by 60 min of emergency cardiopulmonary bypass (ECPB). Electron transport and energy coupling were analyzed under four experimental conditions: no treatment (NORM), 30 min untreated cardiac arrest (CA30), 30 min arrest plus 60 min ECPB reperfusion (CA30R60) and 90 min arrest (CA90). Measurements of O 2 consumption (states 3 &amp; 4, and respiratory control ratio), NADH oxidase, and partial electron transport reactions (for Complex I+III, II+III, &amp; IV) were performed. Results: State 3 O 2 consumption (glutamate/malate) for: (a) the heart at NORM, CA30, CA30R60 and CA90 was 153±28, 90±13, 136±22, and 118±20, respectively (mean±s.d., nanoatoms oxygen/min/mg protein); (b) the kidney was128±32, 82±12, 114±18, and 53±8 respectively; and (c) the brain was 68±5, 57±4, 49±16, and 33±6 respectively. Similar patterns for succinate nourished State 3 O2 consumption and for respiratory control ratios were seen. ETC partial complex measures revealed dysfunction in brain &gt; heart &gt; kidney. CONCLUSION: Distinct mitochondrial defects develops after prolonged ischemia and reperfusion that are tissue specific and show unique intra-mitochondrial sites. Respiratory activities of heart &gt; kidney &gt; brain and this is inversely related to the sensitivity of the tissue to ischemia/reperfusion injury. All tissues demonstrate poor respiratory control ratios after 30 min of ischemia. However with 60 min of reperfusion the kidney and brain recover significantly while the brain does not improve. The vulnerability of the brain and heart to ischemia may be linked to mitochondrial pathways and a target for new therapies.
Abstract 9885: Pericardial Fat is Associated With Atrial Electrical Function: The Framingham Heart Study
Authors: Daniel J Friedman, Na Wang, James B Meigs, Udo Hoffmann, Joseph M Massaro, Caroline S Fox, Jared W Magnani
Journal: Circulation (2013)

Background: Obesity is a significant risk factor for atrial fibrillation (AF). Pericardial fat (Pfat) - unique for having direct myocardial contact - has been associated with AF. We hypothesized that Pfat is significantly related to atrial electrical function (AEF) as quantified by P wave indices (PWI), intermediate endophenotypes of AF risk. Methods: We performed a cross-sectional analysis of 1,946 Framingham Heart Study participants (45% female) to assess the relations between Pfat and AEF measured by PWI: PR interval, P wave duration (Pdur), P wave amplitude (Pamp), P wave area (Parea), and P wave terminal force (Pterm). We performed sex stratified, multivariable linear regression analyses adjusting for age, heart rate, blood pressure, AV nodal medications, hormone replacement therapy, hypertension, diabetes, and menopausal status in women, followed by adjustment for ectopic fat depots in secondary analyses. Results: We determined that a 1-SD increase in Pfat was significantly associated with PWI magnitude: PR interval (β=1.67, p=0.049), Pdur (β=2.32, p&lt;0.001), and Pterm (β=297, p&lt;0.001) among women; and Pdur (β=1.19, p=0.002), Pamp (β=-2.51, p&lt;0.001), and Pterm (β=160, p=0.002) among men. We constructed sex-stratified restricted cubic splines to assess the relation between Pfat and Pdur ( 1a) and Pterm ( 1b): Among both sexes, Pfat was significantly associated with Pdur in models additionally adjusting for visceral fat or intrathoracic fat; a similar trend existed with Pterm. Among women, Pfat was significantly associated with Parea after adjustment for visceral and intrathoracic fat. Conclusions: Pfat is associated with altered AEF quantified by PWI, and the associations are independent of thoracic and visceral fat. These findings suggest altered AEF may be an intermediate step in the relation of Pfat and AF.
Abstract 18226: Finding the Ideal Biomaterial for Aortic Valve Repair
Authors: Hadi Toeg, Ovais Abessi, None Al-Atassi, Laurent de Kerchove, Gebrine El-Khoury, Michel Labrosse, Munir Boodhwani
Journal: Circulation (2013)

Hadi Toeg, 2013 Finalist and Presenting Author
Abstract 349: Effects of Continuous Plasma Diafiltration Therapy in Septic Shock With Acute Liver Failure
Authors: Takumi Taniguchi, Masaki Okajima
Journal: Circulation (2013)

Background: Plasma diafiltration (PDF) is blood purification therapy in which simple plasma exchange is performed using a selective membrane plasma separator while the dialysate flows outside the hollow fibers. Several studies demonstrated that PDF therapy is one of the most useful blood purification therapies for use in cases of acute liver failure or severe sepsis. However, PDF therapy is very difficult to undergo in septic shock patients with acute liver failure because of unstable hemodynamics. Moreover, it is likely to deteriorate in acute liver failure immediately after PDF therapy. We have experienced that continuous PDF (CPDF) therapy can undergo in unstable patients with acute liver failure. Therefore, we evaluated the effects of CPDF therapy in septic shock patients with acute liver failure. Hypothesis: We hypothesis that CPDF therapy has beneficial effects for septic shock patients with acute liver failure. Methods: Nine patients (M/F 7/2, mean age 55 years) with septic shock, who combined acute liver failure, renal failure and respiratory failure, underwent CPDF therapy. The CPDF therapy was undergone for 7 days. Primary outcomes were changes in hemodynamics and inflammatory responses after CPDF therapy, and secondary outcomes were changes in liver functions and SOFA scores at 7 days after therapy and survival rate at 14days after therapy. Results: In primary outcomes, hemodynamics in all patients improved at one day after CPDF therapy. WBC counts improved (22,634 to 9,893; p&lt;0.05), C-reactive protein levels decreased (11.0 to 2.0 mg/dL; p&lt;0.05), and procalcitonin levels decreased (31.6 to 2.9 ng/mL; p&lt;0.05) at 7days after CPDF therapy. In secondary outcomes, total bilirubin decreased (8.3 to 3.4 mg/dL; p&lt;0.05) and PT-INR did not decreased (1.22 to 1.19) at 7 days after CPDF therapy. SOFA scores decreased (13.0 to 8.0; p&lt;0.05) at 7 days after CPDF therapy. All patients recovered and discharged in ICU. Conclusion: In the present study, CPDF therapy significant improved hemodynamics, inflammatory responses and severity in septic shock patients with acute liver failure.
Abstract 19057: Macrophage SR-BI Deletion Promotes Defective Efferocytosis via Src/Akt/Rac1 Signaling Pathway Resulting in Increased Atherosclerotic Lesion Necrosis
Authors: Huan Tao, Patricia G Yancey, Vladimir R Babaev, John Blakemore, Youmin Zhang, Lei Ding, Sergio Fazio, MacRae F Linton
Journal: Circulation (2013)

Apolipoprotein E (ApoE) and scavenger receptor class B type I (SR-BI) double knockout (DKO) mice exhibit accelerated coronary atherosclerosis and premature death, but the underlying mechanisms have not been fully elucidated. Defective phagocytosis of apoptotic cells (efferocytosis) is an important mechanism behind increased necrosis and inflammation in atherosclerosis. We performed bone marrow transplantation studies in apoE -/- mice to examine the impact of macrophage deficiency of SR-BI on atherosclerotic lesion cell death, efferocytosis, and inflammation. DKO→ApoE -/- mice developed 2.1-fold more atherosclerotic lesion area (P&lt;0.01) with 6.7-fold more apoptotic cells (P&lt;0.01), and 5.2-fold higher necrotic core content (P&lt;0.01), compared to ApoE -/- SRBI +/+ →ApoE -/- mice. Efferocytosis was dramatically defective as shown by a 17-fold higher ratio of free to macrophage associated apoptotic nuclei/bodies in atherosclerotic lesions of DKO→ApoE -/- mice(P&lt;0.01). Deletion of macrophage SR-BI resulted in 64.3% (P&lt;0.01) and 64.2 % (P&lt;0.01) decreases in efferocytosis of apoptotic WT thymocytes compared to WT macrophages in vitro and in vivo, respectively. Deletion of macrophage SR-BI elicited maladaptive inflammation with significantly higher expression of pro-inflammation genes (IL-1β, IL-6, TNF-α) and lower expression of anti-inflammation genes (IL-10 and TGF-β). Moreover, SR-BI bound phosphatidylserine in vitro and on the surface of apoptotic cells. SR-BI directly interacted with Src in macrophages. SR-BI deficiency caused significant decreases in Src/Akt/Rac1 activities during macrophage efferocytosis of apoptotic cells. Pharmacological activation of Rac1 rescued SR-BI deficiency-mediated defective efferocytosis, and inhibition of Src reduced macrophage efferocytosis. In conclusion, macrophage SR-BI deficiency promotes defective efferocytosis resulting in increased atherosclerotic lesion necrosis and maladaptive inflammation. Thus, macrophage SR-BI functions as a receptor for apoptotic cells and mediator of efferocytosis via the Src/Rac1 signaling pathway, supporting macrophage SR-BI expression and signaling as a potential target for the prevention and treatment of atherosclerosis.
Abstract 343: Poloxamer 188 Reduces the Infarct Size in Pigs Undergoing ST Elevation Myocadial infarction
Authors: Mohammad Sarraf, Timothy Matsuura, Emily Caldwell, Frank S Bates, Joseph M Metzger, Demetris Yannopoulos
Journal: Circulation (2013)

Introduction: Poloxamer 188 (P188) is a synthetic surfactant known to stabilize the cell membrane integrity and thus minimizes reperfusion injury (RI). RI protection protects the myocardial loss due to reperfusion phase of myocardial infarction. We hypothesized that treatment with P188 at the beginning of reperfusion in acute ST elevation myocardial infarction (STEMI) reduces the infarct size. Methods: Ten pigs underwent total occlusion of the middle left anterior descending artery with a 3.0x12mm balloon at 6 atmospheres for 40 minutes. EKG and angiogram confirmed the presence of STEMI. Amiodarone (40mg IV) was given before the STEMI to prevent fatal arrhythmias. We deflated the balloon at 40 min in the control group (n=5) and reperfused for 4 hours. In the P188 group (n=5), we administered a single bolus of 10gm of P188 immediately after balloon deflation, through the guide in the left main and subsequently 250mg/Kg of P188 was systemically infused over 4 hours of reperfusion. The area at risk (AAR), the infarct area (IA) and normal myocardium were stained by triphenyltetrazolium chloride and Evans blue, before euthanizing the animal. We harvested all hearts and weighed the left ventricle mass (LVM). The endpoint of the study was infarct size ratio (ISR); defined as IA/AAR. We cut the hearts in short axis to estimate the ISR by Photoshop®. We used unpaired t-test for statistical analysis. Results: All animals survived the STEMI phase without complication. There was no significant difference in LVM between the control and P188 groups (106±9 vs. 102±6gm, P=0.7). AAR was similar in P188 and control groups (43%±6% vs. 47±4%, p=0.5). The ISR (Figure) was significantly reduced in P188 group vs. the control group (13±4% vs. 61±3%, p&lt;0.0001). Conclusion: The RI protection is an important step of myocardial protection in STEMI after reperfusion. P188 protects the cell membrane and reduces the infarct size when applied immediately after establishing flow to the coronary artery.
Abstract 9895: Metformin Attenuates Atherosclerosis and Vascular Aging Beyond Glycemic Control
Authors: Farshad Forouzandeh, Gloria Salazar, Nikolay Patrushev, Shiquin Xiong, Lula Hilenski, Robert W Alexander
Journal: Circulation (2013)

Background: Cardiovascular disease due to atherosclerosis, the main cause of morbidity and mortality in most of the world, can be exacerbated by other age-related changes in blood vessels, including arterial stiffness mediated by angiotensin II (Ang II). Thus, strategies that can target atherosclerosis and vascular aging concomitantly are of special interest. Metformin, the first line medication for type 2 diabetes, was shown to attenuate all-cause mortality and myocardial infarction compared with other standard diabetes medications, suggesting that metformin has protective effects in the cardiovascular system beyond its glucose control activities. However, the exact mechanism(s) of action for metformin that are beyond its antihyperglycemic effects are still unknown. Methods and Results: We found that metformin even at concentrations as low as 20 μM can decrease Ang II-induced senescence of vascular smooth muscle cells. Using the ApoE-Knockout mice, we further tested whether metformin can diminish the progression of atherosclerosis and vascular aging and in response to Ang II treatment or high fat diet (HFD). We found that both Ang II induced hypertension and vascular aging were almost completely abolished by metformin treatment. Moreover, metformin treated animals had significantly less atherosclerotic plaque area compared with control groups. Similar vasculoprotective effects were observed when metformin was given to the mice fed HFD (Fig. 1). However, the vasculoprotective findings in both models were not accompanied by significant differences in blood glucose or cholesterol levels. Based on our ongoing studies, these effects of metformin could be explained, at least in part, by its role in modulation of the mTOR pathway that plays a major role in response to nutrition status. Conclusion: Metformin can be useful as a primary or secondary preventive therapy for patients at risk of suffering cardiovascular disease even in the absence of diabetes.
Abstract 9265: Differences in Negative T Waves Between Severe Acute Pulmonary Embolism and Acute Coronary Syndrome
Authors: Masami Kosuge, Toshiaki Ebina, Kiyoshi Hibi, Kengo Tsukhara, Nobuhiko Maejima, Noriaki Iwahashi, Yoshio Tahara, Masaaki Konishi, Satoshi Umemura, Kazuo Kimura
Journal: Circulation (2013)

Background: Patients with severe acute pulmonary embolism (APE) often have precordial negative T waves (NegT). However, this ECG finding is also found in acute coronary syndrome (ACS) due to the left anterior descending coronary artery (LAD) disease. Early differential diagnosis is essential to select an appropriate treatment strategy. Methods: We studied admission ECGs in 79 patients with APE who had right ventricular dysfunction and 202 patients with ACS who were admitted within 48 h from symptom onset and had NegT in leads V1-4. Right ventricular dysfunction was defined as right ventricular dilation, paradoxical septal wall motion, or moderare/severere tricuspid regurgitation on admission echocardiography. All patients with ACS underwent coronary angiography during hospitalization, and the most severe stenosis and/or intracoronary thrombus in the LAD was confirmed. Results: In patients with APE and ACS, at admission, systolic blood pressure was 109±27 and 151±26 mmHg (p&lt;0.01); heart rate was 103±20 and 74±15 bpm (p&lt;0.01); the rates of positive troponin T were 51% and 46% (p=0.36); and the amplitude of maximal NegT was 3.6±1.9 and 4.6±3.4 mm (p=0.02). The prevalence of NegT ≥1.0 mm is shown in Figure, using the anatomically contiguous Cabrera sequence to display limb leads, and it significantly differed in all leads except -aVR between 2 groups. NegT in both leads III and V1 were observed in 91% of patients with APE, as compared with only 3% of those with ACS (p&lt;0.01). This ECG finding identified APE with 91% sensitivity, 97% specificity, and 95% predictive accuracy, which had the highest diagnostic accuracy. Conclusions: In patients with severe APE and ACS caused by LAD disease who had precordial NegT, NegT in both leads III and V1 strongly suggests severe APE.
Abstract 9615: PP1-12, a Novel Protein Phosphatase-1 Inhibitor, Ameliorates Ventricular Function After Myocardial Infarction in Rats
Authors: Kunlun He
Journal: Circulation (2013)

Objectives: Myocardial apoptosis has been known to induce heart function damage after myocardial infarction(MI).PP1-12 was designed to inhibit endoplasmic reticulum stress (ERS)-related apoptosis. In this study, we tested the effect of PP1-12 on cardiomyocyte apoptosis as well as on heart function after MI in rats. Methods: In vitro, neonatal rat cardiomyocytes were cultured and exposed to different concentrations of PP1-12 (0.3, 1, and 3 μg/mL) for 30 min followed by tunicamycin, which can induce ERS, for 36h. Apoptosis was measured using multiparameter high content screening. Phosphorylation of eukaryotic translation initiation factor 2 subunit alpha (eIF2α) and C/EBP homologous protein (CHOP) were determined by western blotting. In vivo, rats that survived MI were divided into six groups: Normal; Vehicle; Perindopril (2mg/kg/d) and PP1-12 (1,3 and10 mg/kg/d). After 4 weeks, transthoracic echocardiographic and hemodynamic parameters were evaluated. The cardiac tissue sections were subjected to TUNEL to assess the level of apoptosis. Results: In vitro, compared with the vehicle group, PP1-12 suppressed cell apoptosis with maximum protection at a concentration of 3μg/mL. Western blotting showed that PP1-12 protected cardiomyocytes against apoptosis by inducing eIF2α phosphorylation and down-regulating CHOP. In vivo, the LVEDD and LVESD were significantly decreased while the EF and FS were greatest increased by PP1-12 at 10mg/kg/d. The hemodynamic parameters including LVEDP, +dp/dtmax and -dp/dtmax were ameliorated by PP1-12. By calculating the apoptotic index, we found that PP1-12 at 10 mg/kg/d had a great anti-apoptotic effect. Conclusions: PP1-12 can efficiently inhibit apoptosis and improve heart function. The mechanism was proved to be associated with its ability to depress myocardial apoptosis induced by ERS. Molecular structure of PP1-12:
Abstract 9463: Clinical and Genetic Evidence for Angiotensin Converting Enzyme Inhibition to Prevent Postoperative Tachyarrhythmias After Congenital Heart Surgery
Authors: Andrew H Smith, English C Flack, Kristie Y Borgman, Jill P Owen, Frank A Fish, David P Bichell, Prince J Kannankeril
Journal: Circulation (2013)

Background: The common insertion/deletion polymorphism in the gene encoding angiotensin-converting enzyme (ACE I/D) has been described in association with tachyarrhythmias. We prospectively examined the role of this polymorphism in a large cohort of pediatric patients undergoing congenital heart surgery with cardiopulmonary bypass (CPB). Methods: Subjects undergoing congenital heart surgery at our institution were consecutively recruited and enrolled from September 2007 through December 2012. In addition to DNA, demographic and perioperative clinical data were obtained from all subjects. Results: Over the study period, 886 subjects undergoing congenital heart surgery with CPB were enrolled. Postoperative tachyarrhythmias were documented in 45% of patients, most commonly ventricular tachycardia (16%), junctional ectopic tachycardia (11%), and atrial tachycardia (10%). Postoperative tachyarrhythmias were associated with prolonged mechanical ventilation (p&lt;0.001) and ICU length of stay (p&lt;0.001). ACE I/D was in Hardy-Weinberg equilibrium (19% I/I, 49% I/D, 32% D/D). Tachyarrhythmias were noted in 47% of index cases with I/D or D/D genotypes, relative to 36% of cases with an I/I genotype (p=0.01). Presence of the I/D or D/D genotype was associated with a 60% increase in odds of new tachyarrhythmia (OR 1.6, 95%CI 1.1-2.3, p=0.02), independent of significant univariate predictors. While preoperative ACE inhibitor administration was independently associated with a 47% reduction in odds of postoperative tachyarrhythmia in the entire cohort (OR 0.53, 95%CI 0.32-0.88, p=0.01), this reduction was driven primarily by a five-fold reduction in tachyarrhythmias among patients with the I/I genotype (OR 0.19, 95% CI 0.04-0.88, p=0.02). Conclusions: The risk of tachyarrhythmias after congenital heart surgery is affected by the ACE I/D polymorphism, independent of other known risk factors. Preoperative ACE inhibition is associated with a lower risk of postoperative tachyarrhythmias, and this antiarrhythmic effect appears genotype dependent. Given the associated morbidity of postoperative arrhythmias, an understanding of genotype variation may play an important role in the perioperative management of congenital heart surgery.