tbuckley/cabot-search huggingface dataset:
Abstract 18444: Constitutive Expression of a Dominant Negative TGF-β Type II Receptor in the Posterior Left Atrium Interrupts Heart Failure Induced Conduction Changes, with a Resulting Decrease in Atrial Fibrillation
Authors: Jason Ng, Haitham M Al-Angari, David Gordon, Gary L Aistrup, Suzanne Browne, Aaron Kunamalla, Alan V Sahakian, Bradley P Knight, Rod S Passman, Alan H Kadish, Jeffrey J Goldberger, Rishi Arora
Journal: Circulation (2012)

Introduction: Fibrosis is thought to be a key contributor to the conduction slowing and heterogeneity seen in the heart failure (HF) atrium, providing a substrate for atrial fibrillation (AF). Hypothesis: Since the TGF-β pathway contributes to the creation of atrial fibrosis, we hypothesized that decreasing TGF-β signaling in the HF posterior left atrium (PLA) by expressing a dominant-negative TGF-β type II receptor (TGF-β-II-DN) will, by attenuating formation of fibrosis, decrease conduction slowing and in-homogeneity and thereby decrease AF. Methods: 17 dogs underwent injection+electroporation in the PLA of either an HA-tagged plasmid expressing TGF-β-II-DN (pUBc-TGFβdnRII) (Group A, N=8) or control vector (pUBc-LacZ) (Group B, N=7), followed by 3-4 weeks of right ventricular tachypacing (240 bpm) to induce HF. The following were assessed both at baseline and the terminal study: left atrial effective refractory periods (ERPs), high density activation maps of the PLA, and the number of AF episodes &gt;30s by burst pacing. Total activation time and a conduction in-homogeneity index were determined from the activation maps. Tissue was assayed for gene expression and fibrosis (Trichrome staining). Results: RT-PCR and western blotting showed robust gene expression in the PLA. Group A developed significantly less fibrosis as a percentage of the PLA than group B (41.6±5.6 vs. 56.4±4.5%, p=0.05). ERP increases after ventricular tachypacing were equal in both groups (32 vs. 34.5 ms, p=NS). Ventricular tachypacing significantly increased the PLA activation time in Group B (from 22.8±2.9 to 43.3±8.6 ms, p&lt;0.002), but not in Group A (from 25.3±5.2 to 28.7±11.3, p=0.6). The in-homogeneity index was also significantly increased in Group B (from 1.9±0.9 to 4.4±1.9, p=0.05) but not in Group A (p=0.12). This was accompanied by a lower number of sustained AF episodes in Group A compared to Group B (0.33±0.21 vs. 3±1.1, p&lt;0.05). Conclusions: Targeted non-viral gene-therapy aimed at reducing TGF-β signaling - and consequent development of fibrosis - in the PLA interrupts the development of conduction slowing and in-homogeneity in the HF atrium, with a significant decrease in AF. Further optimization of this gene therapy approach may translate into effective AF therapies.
Abstract 18972: A 36-Year-Old Man with Stroke and Severe Hyperlipidemia: From Phenotype to Genotype
Authors: Eric M Green, Judy Hung, Thomas E Macgillivray, James R Stone, Calum A Macrae
Journal: Circulation (2012)

A 36-year-old man with a history of hypertension and hyperlipidemia was admitted to the hospital with headaches, a left visual field deficit and a right occipital lobe infarct. Family history is notable for multiple maternal relatives with premature coronary artery disease and severe hyperlipidemia. Laboratory testing revealed an LDL level of 325 mg/dl. Echocardiography demonstrated a bicuspid aortic valve and two highly mobile thrombi at the sinotubular junction. Because there was no aortic false lumen and the clinical picture was most suspicious for a ruptured aortic root atheroma, we administered intravenous heparin with plans for aortic thrombectomy pending his hemodynamics, neurological status and changes in the echocardiographic apperance of the presumed thrombi. On day three, the patient experienced acute chest pain and ST elevation concerning for abrupt occlusion of the right coronary artery. He was taken emergently to the operating room where two thrombi_one of which was lodged in the right coronary ostium_were removed and aortic endarterectomy was performed. Histology of the aortic specimen showed atherosclerosis and inflammation but no evidence of medial degeneration. The histologic evidence of atherosclerosis focused attention on the patient’s personal and family history of severe hypercholesterolemia. To assess for a genetic defect in cholesterol metabolism, we directly sequenced the LDL receptor gene and identified a heterozygous missense mutation associated with familial hypercholesterolemia (FH). Aortic root disease is common in FH homozygotes, but its presence in a heterozygote suggests an additional inherited or acquired risk factor and prompts further investigation. The bicuspid valve raises the possibility of a subclinical aortic condition that may have contributed to this unusual syndrome. This case directly illustrates the consequences of aortic plaque rupture and emphasizes the multidisciplinary clinical approaches that are central to understanding the complex links between genotype and phenotype even in a well-characterized "simple" monogenic disorder.
Abstract 8398: Trends in Clinical and Demographic Features of Patients with Acute Myocardial Infarction in the First Decade of the 21st Century. A Report from the American Heart Association Get-With-The-Guidelines Coronary Artery Disease Program
Authors: Nathan M Boyer, Warren K Laskey, Margueritte Cox, Deepak L Bhatt, Adrian F Hernandez, Eric D Peterson, Christopher P Cannon, Gregg C Fonarow
Journal: Circulation (2011)

Introduction Decreases in incidence of acute myocardial infarction (AMI) in the U.S. have been observed over the last 40 years, in part due to beneficial changes in risk factors. The composition of the U.S. population from 2000-2010 has changed and it remains unknown whether the clinical (CLIN) and demographic (DEMO) features of patients with AMI may also have changed. Methods We reviewed data collected from 136,238 patients with AMI admitted from 2003-2008 to hospitals participating in the American Heart Association - Get With The Guidelines Coronary Artery Disease program. The dataset was analyzed in total and stratified by type of AMI (STEMI or NSTEMI). CLIN and DEMO characteristics were assessed for each year and the odds of change in prevalence of each characteristic with time (per 1 year increase) was analyzed with univariable and multivariable logistic regression. Results Overall, the prevalence of obesity (30.4%) and the proportion of patients with HDL &lt; 40 mg/dl (39.8%) increased while the prevalence of hypertension remained stable but high (68%). The proportion of patients with LDL &gt; 100 mg/dL (32.8%) decreased over time. There was a significant increase over time in the proportion of patients with NSTEMI. Racial distribution of patients also varied significantly over time. Differences in DEMO and CLIN factors within and between AMI strata varied from the observations in the combined patient sample. Conclusions We observed, overall, a decreasing prevalence of younger individuals and an increasing prevalence of obesity and low HDL, findings which represent continuation of a pattern observed at the end of the 20th century. Stratum-specific differences in the prevalence of key risk factors warrant caution considering AMI a uniform entity. In light of changes in the DEMO composition of the US population from 2000-2010, these trends have important implications for projections of disease burden and targeting prevention efforts.
Abstract 18819: Multi-Center, First-In-Man Evaluation of the Myolimus-Eluting Bioresorbable Coronary Scaffold: 6-Month Clinical and Imaging Results
Authors: Stefan Verheye, mark webster, Jim Stewart, Alexandre Abizaid, Ricardo Costa, J. Ribamar Costa, John Yan, Vinayak Bhat, Lynn Morrison, sara toyloy, John Ormiston
Journal: Circulation (2012)

Aims: To evaluate the clinical safety and effectiveness of the DESolve™ Myolimus-Eluting Bioresorbable Coronary Scaffold (DESolve) in patients with single de novo native coronary artery lesions through clinical endpoints and multiple imaging modalities. Methods and Results: Background: The DESolve Bioresorbable Scaffold is a novel drug eluting device that combines a PLLA-based scaffold coated with a bioresorbable polylactide-based polymer and the drug Myolimus. Myolimus, a macrocyclic lactone mTOR inhibitor has demonstrated potent anti-proliferative properties in two First-in-Man (FIM) trials using Elixir’s metallic Myolimus-eluting coronary stents. The drug dose is 3 mcg per mm of scaffold length; the same dose as used as in the FIM studies. Sixteen patients with single, de novo coronary artery lesions were enrolled in this prospective, multi-center, single-arm FIM study. One patient did not receive a study stent and was deregistered. The 15 remaining patients are being analysed for multiple clinical endpoints: Device and Procedure Success; Major Adverse Cardiac Events (MACE), a composite endpoint of cardiac death, target vessel MI, and clinically-indicated target lesion revascularization (CI-TLR); clinically-indicated Target Lesion and Target Vessel Revascularization, (CI-TVR) and stent thrombosis assessed at 1, 6 and 12 months and annually to 5 years. Multiple assessments by angiographic, IVUS and OCT at 6 months were completed. An additional analysis using multislice computed tomography (MSCT) will be completed at 12 and 24 months. At 6 months, the in-scaffold late lumen loss was 0.19 ± 0.19 by QCA, the % volume obstruction was 7.18 ± 3.37 by IVUS, and by OCT 98.68 ± 2.44% of struts were demonstrated as covered. There was one MACE, event, a TLR, during the follow-up period. Detailed clinical and imaging results through 6 months will be presented. Conclusion: The DESolve™ Myolimus-Eluting Bioresorbable Coronary Scaffold demonstrated both excellent safety and effectiveness in this FIM study, thus warranting further clinical evaluation of the novel technology in larger clinical studies. Detailed clinical and imaging results through 6 months will be presented.
Abstract 18122: The Severity and Extent of Coronary Artery Stenosis Predicts Long-Term Mortality Even in Patients with Non-Obstructive Disease
Authors: Daniel W Mudrick, John R Horton, Linda K Shaw, Pamela S Douglas
Journal: Circulation (2011)

Introduction: The influence of non-obstructive coronary artery disease (CAD) on long-term mortality, and therefore optimal intensity of treatment, has not been well defined. Hypothesis: Increasing grades of coronary stenosis at invasive angiography will predict long-term all-cause mortality, even among patients with non-obstructive disease. Methods: We identified 31,121 consecutive adult patients without acute coronary syndrome or prior revascularization undergoing first invasive coronary angiography at Duke Hospital to evaluate CAD between 1986 and 2007. We evaluated all-cause death using Cox proportional hazards models including CAD severity (as defined by a Modified Duke CAD Index - see figure legend), baseline characteristics, and risk factors. Complete follow-up was obtained in 99% of patients by survey, Social Security Master Death File search and National Death Index search. Results: Median follow-up time was 9.3 years (IQR 5.0-15.5 years) with 14,588 deaths. Unadjusted hazard ratio of death increased with CAD grade, even with non-obstructive CAD (Figure). In multivariable analysis, Modified Duke CAD Index remained the strongest predictor of mortality after age, CHF class, and ejection fraction (Wald X 2 = 411.0, HR 1.10 per grade, p&lt;0.0001). Adjusted mortality increased with increasing CAD grade at 5 years (10%, 15%, 18%, 19%, 22%, 27%, 31%) and 10 years (19%, 29%, 34%, 36%, 41%, 48%, 53%). Conclusions: The relationship between CAD severity and mortality is continuous, including non-obstructive CAD. Studies to determine optimal treatment strategies for patients with non-obstructive CAD may be indicated.
Abstract 18650: Impact of Severity of Aortic Stenosis on Left Ventricular Apical Rotation
Authors: Mohammad Najib, Jhansi Ganji, Hari Chaliki
Journal: Circulation (2012)

Introduction- Two dimensional speckle tracking echocardiography is a novel non-invasive method to assess subtle changes in left ventricular (LV) function such as strain and rotational dynamics. Limited data exists for assessing the impact of severity of aortic stenosis (AS) on LV apical rotation Objective- To determine the impact of severity of AS on LV longitudinal strain as well as LV apical rotation in patients with preserved LV ejection fraction and various degrees of AS. Methods- We prospectively measured longitudinal LV strain and apical rotation in 74patients with preserved LV ejection fraction but no (n= 22), mild (MG 10-25 mmHg; n= 20), moderate (MG 25-40 mmHg; n= 18), or severe (MG &gt;40 mmHg; n= 14) AS who were undergoing echocardiographic examination at our institution. Two dimensional speckle tracking method was used to obtain average peak longitudinal strain using apical 4, 2-chamber and long-axis views while apical short axis view was used to obtain the LV apical rotation. Results- Mean age between no vs. mild vs. mod vs. severe AS groups (73±11yrs; 70±13yrs; 77±6yrs; 76±14 yrs) was not different (p=0.26). Presence of hypertension (64%, 65%, 78%, 71%) and coronary artery disease (14%, 6%, 25%, 29%) were also not different between the groups (p = 0.76 and p = 0.23 respectively). Average LV peak global longitudinal strain was not different between groups (-17.5±3%; -17.5±5%;-16.6±4%; -16.6±3% (p=0.82). However LV peak apical rotation was higher with worsening severity of aortic stenosis (14.8±8°; 14.7±9°; 21.3±11°; 23.7±12°) (overall p=0.02) (Figure). Conclusions- 1) LV peak longitudinal strain was not different between patients with no stenosis when compared to patients with various levels of aortic stenosis. 2) However, LV apical rotation increases with worsening levels of AS probably to maintain the LV stroke volume. Further studies are needed to evaluate the role of LV apical rotation in deciding the timing of surgery in patients with severe AS.
Abstract 18783: Contrasting Roles Of E2F2 And E2F3 in Endothelial Cell Growth and Ischemic Angiogenesis
Authors: Junlan Zhou, Gangjian Qin
Journal: Circulation (2012)

Background: Endothelial cell (EC) growth is essential for angiogenesis and ischemic tissue repair. The E2F family of transcription factors are master regulators of genes responsible for cell-cycle regulation; however, the specific roles of individual E2Fs in ECs are largely unknown. Here, we investigated the roles of E2F2 and E2F3 in EC growth, angiogenesis, and their functional impact on limb ischemia and myocardial infarction (MI). Methods and Results: We generated an endothelial-specific E2F3-deficient mouse strain, Tie2-Cre;E2F3 fl/fl (EndoE2F3 Δ / Δ ). The animals were embryonic lethal with a penetrance equivalent to the global E2F3-knockout mice (live birth at ∼8% of the expected frequency). The survived EndoE2F3 Δ / Δ mice grew to adulthood relatively normally, however, developed limb and toe necrosis (25% and 50%, respectively) after surgically-induced hindlimb ischemia and displayed a larger infarct size and worsened LV EF than Tie2-Cre;E2F3 +/+ littermates after surgical MI. Notably, in the ischemic tissues, the capillary density and rate of EC proliferation (BrdU staining) were significant lower in EndoE2F3 Δ / Δ mice than in the controls. In contrast, E2F2 -/- mice displayed better functional parameters after the surgical injuries and an increase in local vessel density and EC proliferation as compared to WT littermates. Ex vivo aortic ring assays confirmed that microvessel outgrowth was impaired in EndoE2F3 Δ / Δ explants, however, enhanced in E2F2 -/- explants. We then evaluated the roles of E2F2 and E2F3 on EC proliferation in vitro . ECs were isolated from lungs of the genetic mice, with E2F3 fl/fl ECs being transduced with Adeno-Cre/GFP or Adeno-GFP. The E2F3 fl/fl /AdenoCre-GFP ECs exhibited a dramatically lowered growth rate and reduced DNA synthesis than E2F3 fl/fl /AdenoGFP ECs. Furthermore, the expression of E2F target genes, including CyclinA, Cdc2, Cyclin D, B-Myb, DHFR and Cdc6, was significantly downregulated in E2F3 fl/fl /AdenoCre-GFP ECs. In contrast, E2F2 -/- ECs displayed an increased rate of cell growth, DNA synthesis and the expression of E2F-regulated genes. Conclusions: E2F3 promotes while E2F2 suppresses ischemic tissue repair via reciprocal regulation of cell-cycle gene expression, EC proliferation and angiogenesis.
Abstract 205: The Effect of Chest Compressions on ETCO <sub>2</sub> Levels During Out-of-Hospital Cardiac Arrest
Authors: Ahamed H Idris, Saeed Babaeizadeh, Mohamud Daya, Dana Edelson, Reza Firoozabadi, Eric Helfenbein, Sophia Zhou
Journal: Circulation (2011)

Background Previous investigations have suggested that end-tidal CO2 (EtCO2) values are proportional to cardiac output over a wide range of flow rates, including very low flow rates. Cardiopulmonary resuscitation (CPR) is an integral part of therapy that provides circulatory support for cardiac arrest patients. Therefore, we hypothesize that during cardiac arrest, EtCO2 levels are higher during periods when chest compressions are being performed compared to periods without chest compressions. Objective Compare EtCO2 values during periods of CPR with and without chest compressions in out-of-hospital cardiac arrest (OHCA) patients. Methods Recordings from 128 OHCA patients with both capnogram and chest compression waveforms were collected from 2008 to 2010 in two EMS agencies in Oregon and Texas. Recordings were manually reviewed to select segments recorded during cardiac arrest. An automated technique separated the intervals with chest compressions (27 hours) and intervals without chest compressions (15 hours). For each patient, the average EtCO2 values in the intervals with and without chest compressions were calculated and compared to determine the impact of chest compressions on the EtCO2 levels. Results The table below summarizes the results. For 112 patients the mean EtCO2 value was higher in intervals with chest compressions compared to those without chest compressions. For the other 16 patients, there was a small decrease in EtCO2 values during chest compressions. A paired t-test shows that the mean EtCO2 values with chest compressions (27.1 ± 13.1 mmHg) and without chest compressions (22.2 ± 12.1 mmHg) are significantly different (p &lt; 0.0001). Conclusion For most OHCA patients, chest compressions increased the EtCO2 level, which may reflect an improvement in cardiac output. Monitoring EtCO2 during CPR could provide valuable feedback on the quality of CPR. Further study is required to determine factors that increase the EtCO2 during chest compression.
Abstract 168: Age Alone Is Not a Predictor of Outcome in Post Cardiac Arrest
Authors: Brandon Giberson, Justin Salciccioli, Michael Cocchi, Tyler Giberson, Matthew Bivens, Shiva Gautam, Michael Donnino
Journal: Circulation (2011)

Introduction: Age is an independent predictor of morbidity and mortality in most forms of acute illness, including in cardiac arrest. However, the independent effect of age on outcome for a cardiac arrest patient who regains return of spontaneous circulation has not been well examined. We hypothesize that age is not a determining factor in post-cardiac arrest mortality or neurological outcome. Methods: We performed an observational cohort study of survivors of cardiac arrest. Data was collected prospectively between 12/2007 and 2/2011. Inclusion criteria: age &gt; 18 years; out-of-hospital or in-hospital cardiac arrest; successful return of spontaneous circulation (ROSC). Traumatic arrests were excluded. Data collected included baseline demographics including age. Outcomes data included neurologic outcome (Cerebral Performance Category) and mortality. We describe the population with simple descriptive statistics including means or medians with standard deviations or interquartile ranges or frequencies with percentages, as appropriate. We performed a univariate logistic regression with age as the independent variable to predict primary (death) and secondary outcome (poor neurologic outcome) and report Odds Ratios with 95% Confidence Intervals. Results: A total of 229 patients were analyzed. The median age of the cohort was 70 (IQR: 56 - 79) and 72/229 (31.6%) were female. As a continuous predictor age was neither a predictor of in-hospital mortality (OR: 1.01, 95% CI: 0.99 - 1.03) nor of poor neurologic outcome (OR: 1.01 95% CI: 0.99 - 1.03). When categorized by 5- and 10-year intervals age remained unassociated with mortality (5-year OR: 1.07, 95% CI: 0.99 - 1.16; 10-year OR: 1.14, 95% CI 0.97 - 1.34) or neurological outcome (5-year OR: 1.07, 95% CI: 0.98 - 1.16; 10-year OR: 1.14, 95% CI 0.97 - 1.34). Conclusion: As an independent variable, age is a poor predictor of morbidity and mortality in cardiac arrest patients who achieve return of spontaneous circulation. These data suggest that treatment strategies in post-cardiac arrest patients should be executed without regard to age and that age-adjusted analysis in post-cardiac arrest may not be necessary. Validation of this finding in a large cohort of post-cardiac arrest patients is necessary.
Abstract 19105: Response in Left Ventricular Twist During Dobutamine Stress Echocardiography After ST-segment Elevation Myocardial Infarction Predicts Reverse Remodeling
Authors: Emer Joyce, Darryl P Leong, Georgette E Hoogslag, Paul L Van Herck, Phillipe J Debonnaire, Eduard R Holman, Martin J Schalij, Jeroen J Bax, Victoria Delgado, Nina Ajmone Marsan
Journal: Circulation (2012)

PURPOSE Left ventricular (LV) twist, an emerging marker of global LV function, has not been evaluated during full-protocol dobutamine stress echocardiography (DSE) in patients following ST-segment elevation myocardial infarction (STEMI). HYPOTHESIS We aimed to evaluate if the response of LV twist during DSE could predict follow-up LV reverse remodeling. METHODS Consecutive patients admitted with first STEMI undergoing primary percutaneous coronary intervention, standard protocol DSE at 3 months and 2-dimensional echocardiographic studies at baseline (48 hours) and follow-up (6-months) were selected. DSE studies positive for ischemia were excluded. Speckle-tracking analysis was used to calculate LV twist - defined as the net difference (in degrees) between apical and basal rotation at isochronal time points -at each stage. LV reverse remodeling was defined as a ≥10% decrease in LV end-systolic volume at follow-up. RESULTS In total, 82 patients (mean age 61 ± 12 years, 85% male, mean LVEF 49 ± 9%) had complete DSE studies feasible for speckle-tracking. Overall LV reverse remodeling occurred in 28 (34%) patients, who showed significantly higher peak-stress LV twist (8.51° versus 6.69°, p=0.01) (Figure). On univariate analysis, baseline LVEF (p=0.03), family history of CAD (p=0.05) and the increase in LV twist from rest to peak stress (p=0.005) were significantly related to LV reverse remodeling; however only LV twist increase remained independently related on multivariate analysis (OR 1.3, 95% CI 1.1-1.5, p=0.005). The ability of LV twist increase to predict reverse remodeling remained significant for subgroup analysis of patients with LV ejection fraction &lt;50%. (OR 1.62, 95% CI 1.1 - 2.3, p=0.01). CONCLUSIONS The increase in LV twist from rest to peak-stress on 3-month DSE in post-STEMI patients independently predicts 6-month LV reverse remodelling, suggesting a novel, clinical use for LV twist as a marker of contractile reserve.