tbuckley/cabot-search huggingface dataset:
Abstract 9468: Spectrum of ST Amplitude: Athletes and an Ambulatory Clinical Population
Authors: David Muramoto, Clarence Findley, Myo Wong, Chandana Adhikarla, David Hadley, Victor Froelicher
Journal: Circulation (2012)

INTRODUCTION: Despite the relationship of the ST segment to chest pain, channelopathies, and early repolarization, there is limited data describing ST amplitudes in apparently healthy populations and athletes. HYPOTHESIS: We sought to better characterize the spectrum of ST amplitude with the hypothesis that there is a meaningful difference in ST levels between an ambulatory clinical population and healthy athletes. METHODS: We performed a retrospective study of 5,085 computerized ECGs from February, 1997 to December, 1999 at the Veterans Affairs Palo Alto Health Care System, with 4,041 analyzed after exclusion of ECGs with pathological conditions that could cause ST elevation. Twelve-lead ECGs were also analyzed from all 1,117 Stanford University athletes undergoing annual pre-participation physical exams in 2007 and 2008. Using the PR interval as the isoelectric line and an amplitude criterion of &gt;0.1mV, ST amplitudes were measured from the end of the QRS complex. RESULTS: Of the clinical subjects, 87% were male, 13% African American (AA), a nd 87% Caucasian or other, with a mean age of 55 ± 14 years. Of the athletes, 55% were male, 14% African American, with a mean age of 19 ± 1.5 years. The precordial leads exhibited the largest median ST amplitudes and largest differences in comparison by gender, ethnicity, and group. Compared to females, males had greater median ST levels within both populations with a larger percentage of males with ST amplitudes &gt;0.1mV (for V2: 28.3% versus 17.1%, p&lt;0.0001). Compared to clinical subjects, athletes had greater median ST levels and a greater proportion had ST amplitudes &gt;0.1mV (for V2: 53.0% versus 17.7%, p&lt;0.0001). Compared to Caucasions and others, African Americans had more than twice the prevalence of ST elevation &gt;0.1mV in V5 (8.1% versus 2.9%, p&lt;0.001). CONCLUSIONS: When assessing the clinical significance of ST elevation, the differences due to athletic status, gender, and ethnicity illustrated here must be considered.
Abstract 9300: Gene Polymorphisms In Il-10 And Inf-γ are Associated With Early Atherosclerosis In Coronary but not in Carotid Arteries: A Study Of 122 Autopsy Cases of Young Adults
Authors: Débora S Faffe, José Carlos P EsperanÇa, William R Miranda, José B Netto, Fabiane S Lima, Turán P Urményi, Rosane Silva, Pedro H Cabello, Edson Rondinelli
Journal: Circulation (2012)

Atherosclerosis is a complex disease that involves both genetic and environmental factors. However, the influence of genetic variations to its early development remains unclear. We examined the association of single-nucleotide polymorphisms (SNPs) with atherosclerotic severity in the anterior descendent coronary (DA, n=103) and carotid arteries (CA, n=66) in individuals under 30 years autopsied at the Legal Medical Institute of Rio de Janeiro. Histological sections, stained with hematoxilin-eosin, were classified for atherosclerosis severity accordingly to the American Heart Association. SNPs in the ECA, TNF-α (-308G/A and -238 G/A), IFN-γ (+874 A/T), MMP-9 (-1562 C/T), IL-10 (-1082 A/G and -819 C/T), NOS3 (894 G/T), ApoA1 ( rs964184 ), and ApoE (E2E3E4 isoforms) genes were genotyped by automatic sequencing. Population mean age was 26 years (107 males and 15 females). DA and CA histology showed, respectively: normal arteries in 2 and 1 cases; level I atherosclerotic lesion in 0 and 5; level II in 16 and 12; level III in 71 and 26; level IV in 6 and 19; and level V in 8 and 3 cases. Genotype distribution was as follow: ECA: 49 DD (related to high ECA levels), 18 II (related with low ECA levels) and 48 DI; TNF-α: 59 GG, 21 GA, and 8 AA at position -308 (allele A associated with high TNF-α level), and 84 GG, 3 GA, and 2 AA at position -238; INF-γ: 45 subjects with allele T (related to high INF-γ levels); MMP-9: 49 CC, 14 CT, and 3 TT; IL-10: 31 AA, 10 AG, and 7 GG at position -1082 (allele G related to high IL-10 levels), and 25 CC, 12 TC, and 15 TT at position -819; NOS3: 59 GG, 35 GT, and 0 TT; ApoA1: 55 CC, 39 CG, and 0 GG; ApoE: 56 E3E3, 30 E3E4, 12 E2E3, 1 E2E4, and 1E4E4. IFN-γ and IL-10 (-1082 A/G) were significantly related to atherosclerotic severity in DA artery, while no association was observed for CA. In conclusion, we observed a high prevalence of early atherosclerosis in young adults, with significant association of IFN-γ (p &lt; 0.001) and IL-10 (p = 0.013) genotypes with coronary disease severity.
Abstract 9542: HDL is Dysfunctional in Patients with Ischemic Cardiomyopathy
Authors: Parin J Patel, Amit V Khera, Daniel J Rader
Journal: Circulation (2012)

Objectives: Various pathologic changes lead to the development of systolic heart failure. We previously showed that HDL is dysfunctional in both acute coronary syndrome (ACS), as measured by the HDL inflammatory index (HII) assay, and stable CAD, as measured by cholesterol efflux capacity. We therefore hypothesized that these functions of HDL are also impaired in subjects with ischemic heart failure. Methods: A nested case-control study was performed on subjects in the PennCath cohort of patients with angina undergoing cardiac catheterization. Cases had ejection fraction (EF) less than 55% (measured by ventriculography) and angiographic CAD (≥20% stenosis of any vessel; n=23); controls included those with EF≥55% and no CAD (n=46). The HII and cholesterol efflux assays were performed as previously described. Briefly, apo-B depleted serum from subjects was incubated with either oxidized LDL and a lipid substrate that fluoresces when oxidized, or macrophages and tritium-labeled cholesterol. Impaired anti-oxidative capacity corresponds with a higher HII value, and reduced cholesterol efflux capacity corresponds with lower percent efflux. Results: Mean HII was higher in subjects with ischemic heart failure (0.26 v. -0.028; p = 0.012); mean cholesterol efflux was lower in the same population (0.80 v. 0.92; p = 0.021). Subjects with ischemic heart failure also had more incident diabetes and hypertension, worse renal function, and lower HDL mass. In a multivariable linear regression model for risk factors of heart failure, both high HII and low efflux capacity were significant risk factors (Table). Conclusion: Subjects with ischemic cardiomyopathy have lower HDL mass and also impaired HDL function. This research supports prior findings of dysfunctional HDL in nonischemic cardiomyopathy, ACS, and chronic CAD. HDL is a versatile molecule with various anti-inflammatory and vasoprotective functions, whose impairment may contribute to heart failure.
Abstract 9821: Calcium-Dependent Changes in Myocardial Sheet Mechanics Reveal Reversible Diastolic Dysfunction in Aged Duchenne Muscular Dystrophy ( <i>mdx</i> ) Mice
Authors: Ya-Jian Cheng, Junjie Chen, Shelton D Caruthers, Gregory M Lanza, Samuel A Wickline
Journal: Circulation (2011)

INTRODUCTION: The relationship between abnormal sarcoplasmic Ca 2+ handling and cardiac structural mechanics in mdx mice has not been defined. Diffusion tensor MRI (DTI) has been used to quantify the contribution of myocardial sheet architecture in ventricular wall thickening mechanics. In this study, DTI was employed to assess altered sheet mechanics due to impaired intracellular calcium homeostasis. METHODS: Sixteen-month old mdx (n = 10) and age matched wildtype (WT, n = 10) mice were used. Hearts were excised and prepared for Langendorff retrograde perfusion to be sequentially arrested in diastole and systole for DTI. The first group was perfused with regular St. Thomas’ cardioplegic solution containing normal [Ca 2+ ] (1.2 mM) to arrest hearts in diastole. To assess the regulatory effect of [Ca 2+ ] on diastolic sheet mechanics, the second group was perfused with modified cardioplegic solution containing low [Ca 2+ ] (0.078 mM). All hearts were then reperfused with Krebs buffer to resume beating followed by 2.5mM barium-induced systolic arrest for DTI. Magnitude of sheet angle, |β|, of each heart was calculated from the diffusion tensors. MANOVA was used for statistical analysis. RESULTS: In diastole, mdx hearts exhibited lower |β| in midventricle than WT (Fig. A). Reducing [Ca 2+ ] in cardioplegic solution restored diastolic |β| in mdx hearts to normal level but had no detectable effect on WT hearts. No significant difference of systolic |β| was observed between mdx and WT hearts (Fig. B). CONCLUSION: The observed lower diastolic |β| in mdx hearts indicated mdx cardiomyocytes failed to fully relax at resting state. The regulatory effect of [Ca 2+ ] on diastolic |β| of mdx hearts suggested sheet structural abnormality is reversible despite the advance age of mdx mice. Thus, the disturbed sheet mechanics may reflect functional consequences of abnormal Ca 2+ handling in vivo, which may correlate with membrane calcium channel dysfunction preceding eventual cardiac failure.
Abstract 9374: Zinc Finger Nuclease Technology for Human Pluripotent Stem Cell Genomic Modification and <i>In Vivo</i> Tracking
Authors: Wendy Y Zhang, Yongming Wang, Shijun Hu, Feng Lan, Joseph C Wu
Journal: Circulation (2012)

INTRODUCTION &amp; HYPOTHESIS: Heart disease is the leading cause of death in developed nations and remains a significant public health problem both in the United States and globally. Human embryonic stem cell therapy demonstrates to be an effective means of treating ischemic heart diseases, as it possesses the capability of generating de novo tissue populations. To investigate such populations’ in vivo and in vitro behavioral characteristics as well as clinical potentials, molecular imaging proves to be a vital tool. However, thus far, genetic integration mainly relies upon the unsafe, unstable, and untranslatable method of random integration. We hypothesized that to address such barrier, we can utilize novel zinc finger nuclease (ZFN) technology to integrate reporter genes into human pluripotent stem cells for cardiac cell derivation, delivery, and molecular imaging. METHODS &amp; RESULTS: Using ZFN technology, we integrated a triple fusion gene construct of mRFP-Fluc-HSVtk into the safe AAVS1 locus for fluorescence, bioluminescence, and positron emission tomography imaging. No discernible off-target cleavages or random integration was detected, and we achieved a high efficiency of ZFN-mediated targeted integration. We observed long-term reporter gene expression as well as pluripotency conservation; the cells retained both expression of pluripotency markers - Oct4, Tra-1-60, Sox2, Tra-1-81, Nanog and SSEA4 - as wells as ability to differentiate into 3 germ layers via in vivo teratoma formation and in vitro embryoid body formation. We then differentiated the ZFN-modified ESCs into cardiomyocytes and endothelial cells in vitro . Parallel characterization of differentiation efficiency and cardiac marker expression of ZFN-modified ESCs and blank ESCs showed no significant differences between the two. Functionally, we tracked the survival of ZFN-edited pluripotent cells in murine models, demonstrating the cardiovascular applicability of ZFN-edited cells. CONCLUSION: This study demonstrates the great potentials and applicability of ZFN transgenesis technology use in safe, stable, and effective genetic integration for the molecular imaging of human pluripotent stem cells and beyond.
Abstract 9570: Advanced Endothelial Dysfunction in Patients with Coexistence of Coronary Artery Disease and Peripheral Artery Disease -Effect of Cilostazol on the Advanced Endothelial Dysfunction-
Authors: Hirofumi Maeda, Seigo Sugiyama, Yasushi Matsuzawa, Keisuke Ohba, Eiichi Akiyama, Junichi Matsubara, Toshimitsu Nozaki, Hitoshi Sumida, Hisao Ogawa, Hideaki Jinnouchi
Journal: Circulation (2012)

Backgrounds In patients with coronary artery disease (CAD), coexistence of peripheral arterial disease (PAD) indicates poor cardiovascular prognosis. Endothelial dysfunction plays a crucial role in cardiovascular diseases and reactive hyperemia peripheral arterial tonometry (RH-PAT) can noninvasively examine endothelial function. We hypothesized that advanced endothelial dysfunction might associate with the coexistence of CAD and PAD and we investigated effects of cilostazol on the endothelial dysfunction in diabetic patients with PAD. Methods and Results We measured RH-PAT index (RHI) and ankle-brachial index (ABI) in consecutive stable patients with coronary risk factors (n=511). CAD was defined by coronary angiography (stenosis≥50%, n=358) and PAD was diagnosed by ABI&lt;0.9, ABI&gt;1.4 with vascular imaging evidence of PAD, previous history of peripheral revascularization, or Fontaine classification≥II (n=73). CAD group (n=358) demonstrated significant lower RHI than non-CAD group (n=153) (RHI: 0.52±0.20 vs. 0.60±0.20, p&lt;0.001). RHI were significantly attenuated in patients with coexistence of CAD and PAD (n=63) compared to CAD patients without PAD (n=295) (RHI: 0.40±0.17 vs. 0.54±0.19, p&lt;0.001). In patients with CAD, univariate logistic regression analysis revealed that age (odd ratio (OR)=1.09, p=0.006), smoking (OR=9.94, p&lt;0.001), body mass index (OR=0.76, p=0.001), high density lipoprotein-cholesterol (OR=0.96, p=0.038), estimated glomerular filtration ratio (OR=0.96, p=0.001), and RHI (per 0.1) (OR=0.57, p&lt;0.001) correlated with the presence of PAD. Multivariate logistic regression analysis demonstrated independent correlation of RHI with the coexistence of PAD in CAD-patients (OR: 0.60, 95% confidence interval 0.451 to 0.798, p&lt;0.001). 12 weeks cilostazol treatment (200mg/day) significantly improved the endothelial dysfunction in diabetic patients with PAD (n=21, age 67±7) (RHI; 0.48±0.11 to 0.68±0.25, p&lt;0.001). Conclusions: Advanced endothelial dysfunction is associated with coexistence of PAD in CAD patients and cilostazol ameliorated the endothelial dysfunction in diabetic patients with PAD. Severe impairment of endothelial function might be a key component in the concomitant CAD and PAD.
Abstract 9264: Do Interventional Cardiology Training Programs Have Worse Outcomes Early in the Academic Year? An Assessment of the “July Effect” from the NCDR <sup>®</sup>
Authors: Beau Hawkins, Lisa Kaltenbach, Daniel Shivapour, Megan Neely, Sunil Rao, Robert Yeh
Journal: Circulation (2012)

Introduction: Prior studies have demonstrated worse patient outcomes at training institutions during the early months of the academic year, a concept commonly referred to as the “July effect.” Whether the July effect exists in modern interventional cardiology practice is unknown. We hypothesized that percutaneous coronary intervention (PCI) outcomes at training institutions are worse early in the academic year. Methods: All patients undergoing PCI for non-salvage indications from 2009-2011 within the CathPCI Registry ® were eligible for inclusion. To identify training hospitals, we obtained a list of accredited interventional cardiology fellowship programs, matched them to their affiliated hospitals, and linked these training hospitals to the CathPCI Registry database through hospital identification numbers. PCI procedures were categorized as early (July 1-August 31) or non-early (September 1- June 30) based on timing within the academic year. Risk-adjusted in-hospital bleeding and mortality rates were compared for early and non-early time periods using validated risk models. Results: A total of 216,927 procedures were performed in training hospitals during the study period. Early and non-early PCI outcomes were similar (Table 1, early vs. non-early bleeding OR 0.97, CI 0.92-1.02, mortality OR 0.94, CI 0.85-1.03). The associations between PCI timing and in-hospital bleeding and mortality were similar between hospitals with and without training programs (P for interaction 0.59, and 0.95, respectively). Discussion: PCIs performed early in the academic year at training institutions are not associated with worse patient outcomes. Importantly for patients, within these training hospitals, this finding provides reassurance that care is not compromised when it involves trainees early in the academic year.
Abstract 9344: Tobacco Smoke Exposure is Associated with Alterations of Cerebrovascular Flow Velocities and Regulation in Children
Authors: Kenji Harada, Tomohiro Abe, Yukiko Harada
Journal: Circulation (2012)

Background: Passive smoking (PS) is associated with increased risk for cerebrovascular and cardiovascular events, however, there has been little focus on cerebrovascular function. The purpose of this study is to assess cerebrovascular flow velocities and regulation in PS children. Methods: Noninvasive ultrasonographic measurements were made in 51 children (age:9 ± 4years) who have been exposed to tobacco smoking since intrauterine life and 35 age-matched children without PS. Using transcranial color Doppler sonography, peak systolic (PSV), end-diastolic (EDV), and average peak flow (APV) velocities of middle cerebral artery were measured during supine rest and 3 minutes-upright posture. Pulsatile index as a parameter of vascular resistance was calculated. Pulsatile index was defined as (PSV-EDV)/APV. Quantitative B-mode ultrasound scans were used to measure intima-media thickness and diameters of the common carotid artery. Urine cotinine concentrations were assessed. Results: Flow velocities and pulsatile index were not significantly different between controls and PS children (p &gt; 0.05). In controls and PS children with urine cotinine concentrations &lt;5ng/ml (n = 26), pulsatile index did not change during upright position (p &gt; 0.05). However, in PS children with urine cotinine concentrations ≥ 5ng/ml (n = 25), there was a significant increase in pulsatile index during upright position (0.93 ± 0.14 vs. 0.87 ± 0.12, p &lt; 0.01), because APV and EDV were significantly lower (69 ± 16 vs. 76 ±17 cm/sec and 44 ± 9 vs. 50 ± 11 cm/sec, p &lt;0.05, respectively), although PSV was not significantly different. The percent change in pulsatile index during an upright position correlated significantly with urine cotinine level (r =0.57, p &lt; 0.01). Intima-media thickness at carotid artery and stiffness did not correlate with cerebral blood flow velocities. Conclusions: The present study indicates that passive smoking can adversely affect cerebral blood flow and regulation in the cerebrovascular bed in childhood. Passive smoking not only is a risk factor for later cardiovascular disease, but also is associated with significant impairment of cerebral flow dynamics.
Abstract 9462: Endothelial Progenitor Cells Predict Five-Year Prognosis In Patients With Stable Angina Treated With Percutaneous Coronary Intervention
Authors: Francesco Pelliccia, Giuseppe Marazzi, Vincenzo Pasceri, Giuseppe Rosano, Luigi Mattioli, Cesare Greco, Carlo Gaudio
Journal: Circulation (2012)

Background. Endothelial progenitor cells (EPCs) have a pathogenetic role in stent restenosis after percutaneous coronary intervention (PCI). It remains undefined, however, if an association between numbers of EPCs at time of PCI and the subsequent long-term clinical outcome exists. To address this issue, we performed a pre-specified analysis of follow-up data of the PROCREATION (PROgenitor Cells role in Restenosis and progression of coronary ATherosclerosis after percutaneous coronary intervention) study. Methods. A total of 155 patients (92 men, age 60±11 years) with stable angina treated with PCI were originally included in the PROCREATION study. All patients had flow cytometry the day before elective PCI in order to derive subpopulations of EPCs. After the index PCI, patients underwent 1-year control angiography and were then evaluated at 6-month intervals up to 5 years. The occurrence of major adverse cardiac events (MACE) was recorded in all patients. Results. During the 5-year follow-up, all-cause death occurred in 16 patients (10%), cardiovascular death in 9 (6%), non fatal myocardial infarction in 6 (4%), and target vessel revascularization in 41 (26%). There were no significant differences in clinical and angiographic variables between patients with or without MACE. After adjusting for age, sex, left ventricular function, and number of diseased vessels, it was found that halving of numbers of CD34+/KDR+/CD45- cells and CD133+/KDR+/CD45- cells (i.e., progenitors of endothelial lineage) increased the risk of MACE by 75% (hazard ratio: 1.75; 95% confidence intervals: 1.1 to 2.8) and 66% (hazard ratio: 1.32; 95% confidence intervals: 0.9 to 2.3), respectively. Conversely, there were no relationships between outcome and numbers of CD14+/CD45+ cells (i.e., which play a role in angiogenesis via a paracrine effect) and CD105+/CD45-/CD34- cells (i.e., which have a receptor for transforming growth factor-beta). Conclusions. Patients with stable angina treated with PCI who have a worse clinical outcome have lower numbers of circulating EPCs subtypes that are progenitors of endothelial lineage at time of the procedure. Assessment of EPCs at PCI can improve characterization of long-term prognosis. (ClinicalTrials.gov Identifier: NCT01575431 )
Abstract 9918: The ATP-Binding Cassette Transporter ABCG2 Protects Against Pressure Overload-Induced Cardiac Hypertrophy and Heart Failure by Promoting Angiogenesis and Antioxidant Response
Authors: Yasutomi Higashikuni, Ryozo Nagai, Masataka Sata
Journal: Circulation (2011)

Background: ATP-binding cassette transporter subfamily G member 2 (ABCG2), originally identified in cancer cells, was shown to be expressed in various normal organs, including the heart, and was suggested to regulate several tissue defense mechanisms via modulation of survival and function of ABCG2-expressing cells. However, its role in pressure overload-induced cardiac hypertrophy remains unknown. Methods and Results: Immunohistochemistry demonstrated that ABCG2 was mainly expressed in endothelial cells of microvessels in the heart. Pressure overload was induced in 8- to 12-week-old wild-type (WT) and Abcg2 knock-out (KO) mice by transverse aortic constriction (TAC). In the absence of pressure overload, cardiac function and morphology did not differ between WT and KO mice. In WT mice, ABCG2 mRNA expression was increased about 3 times at 4 days and 28 days after TAC compared with that before surgery. At 28 days after TAC, mortality due to heart failure was higher in KO mice than in WT mice (KO mice, 53.2%, n=62, versus WT mice, 21.2%, n=33, p=0.002). Most of dead KO mice died at 4 days after TAC. KO mice showed exaggerated concentric hypertrophy at 4 days after TAC, and exacerbated ventricular remodeling and impaired systolic function at 28 days after TAC compared with WT mice. At 4 days after TAC, impaired angiogenesis and exaggerated oxidative stress in myocardium were found in KO mice compared with those in WT mice, although expression levels of angiogenesis-related and antioxidant genes were comparable or higher in KO mice than in WT mice. In vitro experiments demonstrated that inhibition of ABCG2 led to impaired survival of human microvascular endothelial cells from the heart (HMVEC-Cs) under oxidative stress. In addition, ABCG2 inhibition resulted in impaired migration and tube formation of HMVEC-Cs even under normal condition. Moreover, ABCG2 regulated extracellular concentrations of glutathione, an important endogenous antioxidant, in HMVEC-Cs under external stimuli. Conclusions: ABCG2 protects against pressure overload-induced cardiac hypertrophy and subsequent heart failure by promoting angiogenesis and antioxidant response. ABCG2 may be of interest for a therapeutic target to improve clinical outcomes of hypertrophic heart disease.
Abstract 15448: Blood Monocyte Recruitment in Microvascular Obstruction and Intramyocardial Hemorrhage: New Insights from Fluorine-19 Cellular Magnetic Resonance Imaging in Experimental Reperfused Myocardial Infarction
Authors: Yuxiang Ye, Thomas C Basse-Luesebrink, Paula-Anahi Arias-Loza, Vladimir Kocoski, Thomas Kampf, Qiang Gan, Elisabeth Bauer, Stefanie Sparka, Xavier Helluy, Kai Hu, Valerie Biovin, Karl-Heinz Hiller, Peter M Jakob, Roland Jahns, Wolfgang R Bauer
Journal: Circulation (2011)

Yuxiang Ye, 2011 Finalist and Presenting Author