tbuckley/cabot-search huggingface dataset:
Abstract 9907: Cardiac Adiponectin Resistance Develops Early After MI and Contributes to Heart Failure Progression
Authors: Yajing Wang, Xin Ma, Xiaoliang Wang, Wayne Bond Lau, Yuexing Yuan, Bernard Lopez, Theodore Christopher, Erhe Gao, Walter Koch
Journal: Circulation (2013)

Deficiency of adiponectin (APN), a cardioprotective adipokine, as a risk factor of cardiovascular disease is well-defined. Recent clinical studies report that plasma APN levels are increased in heart failure (HF) patients, suggesting APN resistance might be another unrecognized risk factor. However, direct evidence supporting cardiac APN resistance during HF progression is currently lacking. Adult male mice were subjected to HF by coronary artery occlusion. The biological functions of APN were determined during the course of HF development (0-6 weeks). Plasma APN levels were reduced 3 days post-MI (P&lt;0.01), gradually recovered thereafter, and reached a level greater than control 14 days post-MI (P&lt;0.05). Consistent with APN level reduction, cardiac AMPK phosphorylation (a readout of APN intracellular signaling) was decreased 3 days post-MI (P&lt;0.05). However, cardiac AMPK phosphorylation remained lower than control 14 days post-MI (P&lt;0.01), despite significantly increased plasma APN levels at this time, suggesting reduced cardiac response to endogenous APN. APN administration via osmotic pump beginning 14 days post-MI for the remaining duration of MI did not protect against MI/R injury, in contrast to numerous previous studies demonstrating the cardioprotective effects of APN in acute MI/R. At the molecular level, APN treatment significantly increased both GLUT4 membrane recruitment and 18 F-FDG uptake in the normal heart (P&lt;0.01). However, these responses were dramatically reduced 14-days post-MI. To gain more direct evidence demonstrating impaired cardiomyocyte response to APN during HF development, left ventricular cardiomyocytes were isolated from normal or MI mice (14 days), and incubated with human recombinant APN. APN-induced AMPK phosphorylation and PKA activation were significantly reduced in CM from MI mice compared to control (P&lt;0.01). Together, these results demonstrate that APN resistance develops 2 weeks after MI, a critical period when the transition from adaptive to pathological remodeling occurs. APN resistance renders a potent endogenous cardioprotective molecule ineffective, thus facilitating HF progression. Interventions restoring cardiac APN response may be a novel approach against post-MI HF development.
Abstract 9815: Loss of Inhibitory Fcgamma Receptor II is not Sufficient to Promote Atherosclerosis in Hyperlipidemic Apoe Knockout Mice
Authors: Xinmei Zhu, Hangpong Ng, Shanmugam Nagarajan
Journal: Circulation (2013)

Hypothesis: Elevated anti-oxidized LDL IgG and its interaction with Fcgamma receptors (FcR) have been suggested to be associated with the progression of atherosclerosis. Four different classes of FcRs, FcRI, FcRII, FcRIII, and FcRIV, have been characterized in mice. Functionally, FcRs can be classified into the activating (FcRI, III, and IV) and inhibitory (FcRII) receptors. Previous finding from our lab and others have shown that deletion of activating Fcgamma receptors (I, III and IV) in apoE KO mice decreased atherosclerosis. This led to our hypothesis that deficiency of inhibitory FcRII exacerbates atherosclerosis. Methods and Results: We tested this hypothesis using apoE-FcRIIb double knockout (congenic to C57BL/6, FcRIIb B6 ) mice. On the contrary to our hypothesis, compared to apoE KO mice apoE-FcRIIb double knockout mice (FcRIIb B6 ) fed chow or high-fat diets did not show exacerbated atherosclerotic lesions (n=10/group). Our finding is in contrast to previous reports showing exacerbated lesions in apoE-FcRIIb mice in a mixed background (129s/v and C57BL/6, FcRIIb mixed ). Molecular mechanisms to understand the difference revealed that FcRIIb mixed mice showed more Th1 response (more IFN-gamma, TNF-alpha), while congenic FcRIIb B6 showed predominant Th2 responses (more IL-10, IL5, and IL-13). Moreover, anti-oxLDL IgG subtypes analyses showed elevated mIgG2a (Th1) response in FcRIIb mixed mice, while mIgG1 (Th2) levels were more predominant in FcRIIb B6 mice. Interestingly, circulating levels of autoantibodies, anti-nuclear antibodies, which have been implicated in autoimmune diseases such as lupus also was elevated in FcRIIb mixed compared to FcRIIb B6 mice. Conclusion: These findings revealed a novel paradigm that inhibitory FcRIIb does not directly contribute to atherosclerosis. However, in the presence of lupus susceptible gene loci, inhibitory FcRIIb exacerbates the progression of atherosclerosis. As FcRIIb polymorphism has been implicated in lupus susceptibility, the role of FcRIIb, as pro-atherosclerotic mediators in vivo in lupus-associated cardiovascular disease need to be investigated.
Abstract 96: Normalization of Left Ventricle Ejection Fraction, Not Initial Left Ventricle Ejection Fraction, is Associated with Outcomes After Cardiac Arrest
Authors: Anne V Grossestreuer, Sarah M Perman, David B Seder, Richard R Riker, Yuan Yao, David F Gaieski
Journal: Circulation (2013)

Background: Many patients with cardiac arrest are initially resuscitated but far fewer survive to hospital discharge. Post-arrest myocardial dysfunction is common and associated with higher mortality. We describe myocardial dysfunction and its association with outcome at 4 hospitals. Objectives: To discover the prevalence of left ventricle (LV) dysfunction in the first 24 hours post-arrest, the normalization of LV ejection fraction (LVEF) post-arrest, and determine their relationship to functional outcome at hospital discharge. Methods: A multicenter retrospective study of 464 patients who underwent post-arrest echocardiography at 4 hospitals with aggressive post-arrest protocols including therapeutic hypothermia. Abnormal LVEF was defined as &lt;50%. Results: 357/464 (77%) patients had an echo within the 1 st 24 hours post-arrest (mean age: 59±16 years, 62% male, 37% VT/VF, and 70% out-of-hospital). 206/357 (58%) had an abnormal LVEF within 24 hours. Analysis of survival and neurologic outcome of patients with an echo in the 1 st 24 hours as well as a subsequent echo prior to discharge (180/357; 50%) showed patients with an abnormal LVEF that recovered had the best outcomes, while patients who had an initially normal LVEF had the worst outcomes, regardless of whether their LVEF changed (Table 1). Conclusions: More than half of successfully resuscitated post-arrest patients had an abnormal LVEF in the 24 hours post arrest. An abnormal LVEF in the first 24 hours post-arrest did not predict negative outcome, and normalization of LVEF predicted good outcome. Prospective studies with echocardiography obtained at predetermined time points post-arrest are needed to further elucidate these findings.
Abstract 19067: Rehospitalization Characteristics in Patients With Continuous Flow Left Ventricular Assist Devices
Authors: Sunu S Thomas, Jason Han, Nadav Nahumi, Matthew Lippel, Arthur R Garan, Melana Yuzefpolskaya, Paolo Colombo, Hiroo Takayama, Yoshifumi Naka, Nir Uriel, Ulrich P Jorde
Journal: Circulation (2013)

Background: Readmission diagnoses, timing and hospital length of stay have become a major clinical and health policy focus in the management of patients with continuous flow left ventricular assist devices (CF-LVADs). The aim of this study was to characterize CF-LVAD rehospitalizations at a large volume center. Methods: We performed a retrospective analysis of patients implanted with HeartMate II (Thoratec, Pleasanton, CA) CF-LVADs from March 31, 2004 to September 20, 2012. Readmission metrics were evaluated in discharged patients following CF-LVAD placement as either a bridge to transplant (BTT) or destination therapy (DT) strategy. Data are reported as median and interquartile range, unless otherwise stated. Results: HeartMate II CF-LVADs were implanted in 205 patients (BTT 150; DT 55). Total time on LVAD support was 247.0 yrs (BTT 147.4 yrs; DT 99.6 yrs). Of 741 non-transplant readmissions, the majority were due to cardiac (BTT 27%; DT 24%), bleeding (BTT 12%; DT 29%), infection (BTT 19%; DT 11%) and device (BTT 12%; DT 9%) related diagnoses. Freedom from readmission at 30 days post-discharge following device implantation was 73.5% (SE 0.03). Table 1 lists 30 day and 1 yr event rates for common readmission diagnoses. DT patients had significantly higher 1 yr gastrointestinal bleeding (GIB) event rates than BTT (0.41 vs 0.21, p&lt;0.01). Median length of stay per readmitting diagnosis included drive-line infection (10.5 days (6.8-17.0)); heart failure (9.5 days (5.0-15.0)); device malfunction (7.0 days (2.0-18.8)); and GIB (7.0 days (3.0-11.0)) for all CF-LVAD patients. Conclusion: Readmissions following CF-LVAD implantation are frequent and consume significant hospital inpatient time. Bleeding, cardiac, infection, and device related diagnoses contribute to the greatest burden of CF-LVAD rehospitalizations.
Abstract 273: A Comparison of Two Methods for Measuring Pediatric CPR Quality in a Pediatric Emergency Department
Authors: Ting-Chang Hsieh, Heather Wolfe, Natasha Hoyte, Robert Sutton, Vinay Nadkarni, Aaron Donoghue
Journal: Circulation (2013)

Background: Studies examining CPR using a sensor/accelerometer device (Q-CPR) have demonstrated that pediatric CPR is often performed suboptimally. The majority of children receiving CPR in the ED are ineligible for Q-CPR use. Recent data has shown that video recording of critical procedures in the pediatric ED is reliable for measuring outcomes. Objective: To determine the correlation between video review and Q-CPR measurement in quantifying chest compression parameters in pediatric patients. Methods: Children &gt; 8 years who received CPR using the Q-CPR device and whose events were video recorded were eligible for inclusion. Videos were reviewed by study personnel; compressions were measured in 30-second epochs. Compression rate was counted directly; compression depth and chest wall release were scored dichotomously as ‘adequate’ or ‘inadequate’ based on a threshold of 80% of observed compressions meeting parameters. Q-CPR data was measured for compression rate, percent compressions with depth &gt; 38 mm, and percent compressions with leaning force &gt; 2.5 kg; epochs were designated as ‘adequate’ or ‘inadequate’ for depth and leaning with 80% as a threshold for parameters. Correlation between video and Q-CPR data was done by Spearman’s ρ (rate) and f coefficient (depth, release). Results: Four patients were captured on video receiving CPR using the Q-CPR device; complete data was available for 79 30-second epochs of compressions. By Q-CPR measurement, median rate of compressions was 114 per minute (range 91 - 127). A median of 53% (range 0 - 100%) of compressions were &gt; 38 mm per epoch. A median of 2% (range 0 - 100%) compressions had residual leaning force of &gt; 2.5 kg. By video review, median rate was 108 compressions per minute (range 66 - 132); depth was scored as adequate in 72/79 (91%) of epochs; release was scored as adequate in 72/79 (91%) of epochs. Correlation was very good for rate (ρ = 0.73) and poor for release (f = 0.06) and depth (f = 0.02). Conclusions: Video review of CPR in children measures compression rate reliably when compared with Q-CPR data. Video review does not accurately determine compression depth or chest wall release. Future studies should examine whether video recording can be optimized to allow reliable measurement of depth and leaning in children.
Abstract 9: Remote Ischemic Pre- and Post-Conditioning Produce Similar Improvement of Myocardial and Cerebral Function in a Rat Model of Cardiac Arrest and Resuscitation
Authors: Jiefeng Xu, Shijie Sun, Xiaoye Lu, Xianwen Hu, Jena Cahoon, Wanchun Tang
Journal: Circulation (2013)

Introduction: Remote ischemic pre-conditioning (RPC) has been demonstrated to provide powerful protection of the heart and the brain against ischemia reperfusion injury. However, it is not a practical use in the clinical settings of cardiac arrest and resuscitation. We investigated the effects of remote ischemic post-conditioning (RpostC) on post-resuscitation myocardial and cerebral function in a rat model of cardiac arrest. Hypothesis: RpostC is as effective as RPC in reducing post-resuscitation myocardial and cerebral dysfunction in a rat model of cardiac arrest. Methods: Twenty-one male Spague Dawley rats were randomized into three groups: 1) RPC, initiated 40 mins before induction of ventricular fibrillation (VF); 2) RpostC, initiated 5 mins after successful resuscitation; 3) Control. Remote ischemic conditioning was induced by four cycles of 5 mins of limb ischemia, followed by 5 mins of reperfusion. VF was induced and untreated for 6 mins while defibrillation was attempted after 8 mins of CPR. The animals were then monitored for 4 hours and observed for an additional 68 hours. Results: Equally improved post-resuscitation myocardial and neurological function were observed in the RPC and the RpostC groups, which were significantly better than the Control group (Table). Conclusion: In a rat model of cardiac arrest and resuscitation, remote ischemic pre- and post-conditioning produced similar improvement of myocardial and cerebral function.
Abstract 9297: Incidence and Implications of Aborted Myocardial Infarction in STREAM
Authors: Neda Dianati-Maleki, Frans Van de Werf, Patrick Goldstein, Jennifer Adgey, Yves Lambert, Vitaly Sulimov, Fernando Rosell-Ortiz, Anthony H Gershlick, Yinggan Zheng, Paul W Armstrong
Journal: Circulation (2013)

Background: Timely and effective reperfusion therapy in patients (pts) with ST-segment elevation myocardial infarction (STEMI) may avoid significant necrosis. Aborted MI (AbMI) was a pre-specified (previously unreported) endpoint in the STREAM (STrategic Reperfusion therapy Early After MI) trial comparing a pharmacoinvasive strategy (Gp A) vs. primary PCI (Gp B) in STEMI pts presenting within 3 hours of symptom onset. Methods: 1754 pts with interpretable electrocardiograms (ECGs) and sequential biomarkers were included. AbMI was defined by successful reperfusion i.e. core laboratory assessed worst lead ST-elevation resolution ≥50% (90-min post-tenecteplase (TNK) in Gp A or 30-min post-PCI in Gp B), and minimal rise in biomarkers (≤2 times ULN rise in CK or CKMB) or if unavailable, ≤5xULN rise in troponin. All pts received heparin and clopidogrel at first medical contact. Results: In Gp A, 11.1% (n=99) had AbMI vs. 6.9% (n=59) in Gp B (p&lt; 0.01). AbMI pts were younger, more often had prior MI, exhibited Killip I, had less baseline ΣST-deviation, and fewer Q waves within their acute infarct zone (Table). Within Gp A, AbMI pts had faster time to TNK and a lower all-cause death/shock/congestive heart failure (CHF)/re-MI than non-AbMI pts; this distinction was not evident in Gp B. Total ischemic time was 100 minutes longer in Gp B AbMI pts. Forty-five pts (i.e. 2.5%; evenly distributed by treatment) had masquerading MI with minimal biomarker elevation and persistent ST-elevation in sequential ECGs related to left ventricular hypertrophy, pericarditis, or early repolarization. Conclusions: These data demonstrate that fibrinolysis coupled with anti-thrombotic and antiplatelet therapy more frequently aborts MI: such pts have more favorable outcomes compared to non-AbMIs. Diligent review of ECG evolution in STEMI is necessary to distinguish AbMI from infarct masquerade.
Abstract 9796: The Presence of Post-bronchodilator Airflow Limitation Deteriorates Cardiac Prognosis in Patients With Chronic Heart Failure
Authors: Yuki Honda, Tetsu Watanabe, Shunsuke Netsu, Daisuke Kinoshita, Miyuki Yokoyama, Shinpei Kadowaki, Taro Narumi, Yoichiro Otaki, Satoshi Nishiyama, Hiroki Takahashi, Takanori Arimoto, Tetsuro Shishido, Takehiko Miyashita, Takuya Miyamoto, Isao Kubota
Journal: Circulation (2013)

Background: Chronic obstructive pulmonary disease has begun to gather attention as important comorbidity in patients with cardiovascular disease. However, it is undetermined whether airflow limitation is associated with cardiac prognosis of patients with chronic heart failure (CHF). The aim of the present study was to examine whether post-bronchodilator pulmonary function can predict cardiac prognosis in patients with CHF. Methods and Results: We performed post-bronchodilator spirometry in consecutive 198 patients with CHF. Airflow limitation is assessed by the ratio of post-bronchodilator forced expiratory volume in the first 1 second and forced vital capacity (FEV 1 /FVC), and by the ratio of FEV 1 and predicted FEV 1 (%FEV 1 ). %FEV 1 but not FEV 1 /FVC was decreased with advancing New York Heart Association (NYHA) functional class. There were 45 cardiac events including 3 cardiac deaths and 42 re-hospitalizations for exacerbation of CHF during a median follow-up period of 446 days. Both FEV 1 /FVC and %FEV 1 were significantly lower in patients with cardiac events than in event-free patients (67.6 ± 12.5% v.s. 73.5 ± 9.4%, P &lt;0.001; 66.6 ± 16.5% v.s. 80.6 ± 19.9%, P &lt;0.0001, respectively). The receiver operating characteristic curve showed the area under the curve of FEV 1 /FVC and %FEV 1 for cardiac events were 0.667 and 0.701, respectively. Mean pulmonary arterial pressure and mean pulmonary arterial wedge pressure significantly correlated with %FEV 1 but not FEV 1 /FVC. Multivariate Cox proportional hazard analysis showed that %FEV 1 was an independent predictor of cardiac events after adjustment of possible confounders (hazard ratio per 1SD increase: 0.558; 95% confidence interval, 0.312-0.978). The patients were divided into tertiles of %FEV 1 . Kaplan-Meier analysis showed that patients in the lowest tertile had the highest event rate. Conclusion: Post-bronchodilator airflow limitation may deteriorate cardiac prognosis in patients with CHF.
Abstract 9618: Real-World Effectiveness of ICDs Implanted During Unplanned Medicare Hospitalizations
Authors: Chih-Ying Chen, Garrick C Stewart, Lynne W Stevenson, Deepak L Bhatt, Manisha Desai, John D Seeger, Lauren Williams, Jessica J Jalbert, Soko Setoguchi
Journal: Circulation (2013)

Background: Benefits of ICDs for primary prevention are well established in ambulatory HF population. Aim: To examine clinical effectiveness of primary ICDs in Medicare patients(pts) receiving the device during unplanned hospitalizations for HF or other acute conditions. Methods: Linking data from the CMS/National Cardiovascular Data Registry (NCDR®) ICD Registry™, a national HF registry, and the Medicare files (04-09), we identified 23,111 hospitalized pts ≥ 66 yrs with EF ≤35% who were eligible for primary ICDs from the ICD registry (ICD recipients) or the HF registry (non-ICD recipients). To account for potential bias due to ICD recipients being healthier, we employed latency analysis conditioning on the 1st 6 months survival and adjusted for high-dimension propensity score (hdPS). Cox models were used to derive adjusted hazard ratios (HRs) for all-cause mortality and sudden cardiac death (SCD). Results: The mean follow-up was 2.8 yrs. ICD recipients were younger, had lower EF, more prior cardiac hospitalizations, yet, non-ICD recipients had lower eGFR, more prior non-cardiac hospitalizations and non-CV comorbidities. ICD recipients had lower crude mortality than non-ICD recipients (Figure), but, the difference was most notable within the 1st 3-6 months of follow-up, likely reflecting selection of healthier pts for ICDs. Conditioning on the 1st 6-month survival and with hdPS adjustment, ICD use was not associated with a significant decrease in mortality (HR=0.91 95% CI=0.81, 1.00) or SCD (HR=0.95, 95% CI=0.78, 1.17). No significant treatment heterogeneity was observed among various demographic subgroups. Conclusion: ICD use did not appear to be associated with a lower mortality risk among non-ambulatory Medicare patients receiving primary ICD during unplanned hospitalization for HF or other acute conditions after accounting for selection bias and confounding. The effectiveness of primary ICD therapy likely did not differ among demographic subgroups.
Abstract 9819: Elevated Plasma Serotonin and Endothelin-1 in Coronary Artery Disease Patients: A Potential for Novel Pharmacotherapeutic Targets?
Authors: Sherif Shousha, Jean G Diodati, Erick Schampaert, Chantal Pharand
Journal: Circulation (2013)

Background: High on-treatment platelet reactivity (HTPR) was reported in patients with coronary artery disease (CAD) on dual antiplatelet therapy with aspirin and clopidogrel, particularly in diabetic patients. We sought to investigate the potential for targeting platelet and endothelium-derived vasoactive substances (such as thromboxane A 2 [TXA 2 ], serotonin [5-HT], and endothelin-1 [ET-1]) released upon platelet activation to complement current antiplatelet therapy without increasing the risk of bleeding. Methods: Three groups of subjects were recruited: a) 20 diabetic patients with known CAD (DM), b) 24 non-diabetic patients with known CAD (ND) and c) 27 healthy subjects without diabetes or CAD (CTL). Subject groups were compared to each other with respect to plasma and platelet concentrations of various vasoactive substances measured by ELISA and to platelet reactivity measured by light transmission aggregometry (LTA) and VerifyNow ® . Results: Significantly higher ET-1 (CTL: 0.372 0.1 pg/mL; ND: 0.564 ± 0.2 pg/mL, P&lt;0.005 vs. CTL; DM: 0.961 ± 0.2 pg/mL, P&lt;0.02 vs. CTL) and 5-HT (CTL: 600.5 ± 52.5 ng/mL; ND: 679.6 ± 68.7 ng/mL, P&lt;0.05 vs. CTL; DM: 729.7 ± 81.8 pg/mL, P&lt;0.02 vs. CTL) plasma concentrations were found in CAD patients, with a more pronounced increase in the DM group. Platelet 5-HT was lower in the DM group (335.8 ± 71 ng/10 9 platelets) compared to both CTL subjects (447.1 ± 88.5 ng/10 9 platelets) and ND patients (374.6 ± 58.8 ng/10 9 platelets), which may be due to increased platelet activation and release. Plasma TXB 2 concentrations were higher in the DM group (557.4 ± 172.4 pg/mL) compared to the ND group (350.7 ± 42.4 pg/mL), which indicates higher platelet reactivity in DM patients despite the regular use of ASA. Platelet function tests such as VerifyNow ® (ASA) and LTA (AA 1.6 mM) showed higher HTPR in DM patients (VerifyNow ® : 445 ± 29.1 ARU; LTA: 16.78 ± 3.9% aggregation) compared to ND patients (VerifyNow®: 419.1 ± 13.4 ARU; LTA: 3.76 ± 0.8% aggregation). Conclusion: This study identifies ET-1 and 5-HT as new potential pharmacological targets in the platelet activation pathway for management of HTPR in CAD patients to reduce the risk of incidence and recurrence of ischemic events.