bluuebunny/crossref_metadata_2025 huggingface dataset:
Do all HEART Scores beat the same: evaluating the interoperator reliability of the HEART Score
Authors: Niven William G P , Wilson David , Goodacre Steve , Robertson Alexander , Green Samira Jane , Harris Tim
Published: September 2018

Background

Patients presenting with chest pain represent a significant proportion of attendances to the ED. The History, ECG, Age, Risk Factors and Troponin (HEART) Score is validated for the risk stratification of suspected ischaemic chest pain within the ED. The goal of this research was to establish the interoperator reliability of the HEART Score as performed in the ED by different grades of doctor and nurse.

Methodology

Patients with suspected ischaemic chest pain presenting to the ED of an inner city, London Hospital, were recruited prospectively between January and May 2016. Patients that had been enrolled in the study were interviewed by clinicians from four different categories: senior doctor, junior doctor, senior nurse and junior nurse. Clinicians, blinded to other raters’ results, calculated the HEART Scores for each patient with the assistance of a pocket-sized HEART Score card. The intraclass correlation coefficient (ICC) was calculated as the primary measure of reliability. 120 patients were required to achieve a desired power of 80%.

Results

88 complete comparisons were obtained. There were no significant differences between the distributions of HEART Scores for each clinician group (p=0.95). The ICC for the overall HEART Score was 0.91 (95% CI 0.87 to 0.93). The ICC for troponin and age were ‘1’, for ‘history’ 0.41 (95% CI 0.30 to 0.52), ‘ECG’ 0.64 (95% CI 0.54 to0.73) and ‘risk factors’ 0.84 (95% CI 0.79 to 0.89).

Conclusion

This study demonstrates very strong overall interoperator reliability between the four groups of clinicians studied. This suggests that the HEART Score is reproducible when used by different professional groups and grade of clinician.
New physics through interference of nonstandard interactions with Standard Model in rare decays of Bc+ meson
Authors: Mahmood Shakeel , Tahir Farida , Mir Azeem
Published: September 2018

We investigate the nonstandard neutrino interactions (NSI) in the rare decays of [Formula: see text] mesons involving neutrinos in the final state. It is suggested that the interference between Standard Model and nonstandard interaction can provide sizeable contribution. We calculate the limits on NSI free parameters ([Formula: see text], [Formula: see text]) and compare them with experimental data.
Forces inside hadrons: Pressure, surface tension, mechanical radius, and all that
Authors: Polyakov Maxim V. , Schweitzer Peter
Published: September 2018

The physics related to the form factors of the energy–momentum tensor spans a wide spectrum of problems, and includes gravitational physics, hard-exclusive reactions, hadronic decays of heavy quarkonia, and the physics of exotic hadrons described as hadroquarkonia. It also provides access to the “last global unknown property:” the D-term. We review the physics associated with the form factors of the energy–momentum tensor and the D-term, their interpretations in terms of mechanical properties, their applications, and the current experimental status.
Is there an upper bound on the size of a black hole?
Authors: Bhattacharya Swastik , Shankaranarayanan S.
Published: September 2018

According to the third law of Thermodynamics, it takes an infinite number of steps for any object, including black holes, to reach zero temperature. For any physical system, the process of cooling to absolute zero corresponds to erasing information or generating pure states. In contrast with the ordinary matter, the black hole temperature can be lowered only by adding matter–energy into it. However, it is impossible to remove the statistical fluctuations of the infalling matter–energy. The fluctuations lead to the fact that the black holes have a finite lower temperature and, hence, an upper bound on the horizon radius. We make an estimate of the upper bound for the horizon radius which is curiously comparable to Hubble horizon. We compare this bound with known results and discuss its implications.
Reference-Free Breathing Crack Identification of Beam-Like Structures Using an Enhanced Spatial Fourier Power Spectrum with Exponential Weighting Functions
Authors: Prawin J. , Rama Mohan Rao A.
Published: September 2018

Detection of incipient damage of structures at the earliest possible stage is desirable for successful implementation of any health monitoring system. In this paper, we focus on breathing crack problem and present a new reference-free algorithm for fatigue crack detection, localization, and characterization for beam-like structures. We use the spatial curvature of the Fourier power spectrum as a damage sensitive feature for fatigue crack identification. An exponential weighting function that takes into account nonlinear dynamic signatures, such as sub- and superharmonics, is proposed in the Fourier power spectrum in order to enrich the damage-sensitive features of the structure. Both numerical and experimental studies have been carried out to test and verify the proposed algorithm.
Lower bound of concurrence based on D-type positive map
Authors: Niu Lifang , Duan Zhoubo
Published: September 2018

In this paper, by using the D-type map, we provide an analytical lower bound of concurrence of arbitrary dimensional bipartite quantum system. It is shown that this lower bound is able to improve the existing bounds and detect entanglement better.
New Fixed Point Theorems via Contraction Mappings in Complete Intuitionistic Fuzzy Normed Linear Space
Authors: Konwar Nabanita , Esi Ayhan , Debnath Pradip
Published: September 2018

Contraction mappings provide us with one of the major sources of fixed point theorems. In many mathematical models, the existence of a solution may often be described by the existence of a fixed point for a suitable map. Therefore, study of such mappings and fixed point results becomes well motivated in the setting of intuitionistic fuzzy normed linear spaces (IFNLSs) as well. In this paper, we define some new contraction mappings and establish fixed point theorems in a complete IFNLS. Our results unify and generalize several classical results existing in the literature.
Precursor Selection for Sol–Gel Synthesis of Titanium Carbide Nanopowders by a New Hesitant CUBIC Fuzzy Multi-Attribute Group Decision-Making Model
Authors: Fahmi Aliya , Amin Fazli
Published: September 2018

In this paper, we define hesitant cubic TOPSIs method. We develop the numerical application and different method. We define the new idea of Hesitant Cubic Gray Analysis Set. We proposed the HCF-MAGDM model and relationships among hesitant cubic TOPSIS method with hesitant cubic gray relation analysis method being introduced. Finally, using the proposed method to Sol–Gel synthesis of titanium carbide (TiC) nanopowders for selection, we analyzed the proposed method by using a numerical application to Sol–Gel synthesis of TiC nanopowders.
Different Operators in Automata Theory Based on Residuated and Co-Residuated Lattices
Authors: Pal Priyanka , Tiwari S. P. , Verma Renu
Published: September 2018

This paper is towards the algebraic and topological study of automata based on residuated and co-residuated lattices via different operators. The interrelationships among the operators are discussed. Interestingly, we show that the algebraic concepts of an automaton based on a residuated and co-residuated lattice can be expressed in terms of [Formula: see text]-topology/co-topology induced by operators. Finally, a composition of such automata is introduced and its categorical significance is discussed.
Furstenberg families and transitivity in non-autonomous systems
Authors: Vasisht Radhika , Das Ruchi
Published: September 2018

We obtain necessary and sufficient conditions for a non-autonomous system to be [Formula: see text]-transitive and [Formula: see text]-mixing, where [Formula: see text] is a Furstenberg family. We also obtain some characterizations for topologically ergodic non-autonomous systems. We provide examples/counter examples related to our results.
Low temperature rapid fabrication of magnesium silicide for thermoelectric application
Authors: Alinejad Babak , Ikeda Teruyuki
Published: September 2018

A mechanism for rapid, single-step synthesis and fabrication of intermetallic compounds having brittle–ductile ingredients at low temperature is suggested. Employing this mechanism, highly pure, dense Mg2Si pellets were obtained using silicon nanoparticles and micron-sized magnesium particles as starting materials. Silicon nanoparticles chop magnesium particles and produce highly-activated mixture through a planetary ball-milling. Magnesium/silicon interface increases by increasing dispersity of silicon nano-particles in magnesium. Consequently, final product was prepared only by consolidation at 300∘C for 5[Formula: see text]min without any post-treatment. The pure phase of Mg2Si with grain sizes about 200[Formula: see text]nm and with no evidence of presence of MgO was achieved. The Seebeck coefficient, electrical and thermal conductivity were measured to be [Formula: see text]220 [Formula: see text]VK[Formula: see text], 72 [Formula: see text][Formula: see text]cm[Formula: see text] and 3.48[Formula: see text]Wm[Formula: see text][Formula: see text]K[Formula: see text] at 823[Formula: see text]K for nondoped Mg2Si, indicating that this method does not degrade the properties of the product, despite the fact that fabrication is performed rapidly and at low temperature.
One-pot synthesis of Ag nanoparticle/Ag-doped SiO2composite film and their enhancement effect for CdSe QDs
Authors: Yin Naiqiang , Zhao Shihua , Li Peng , Liu Ling
Published: September 2018

In this work, Ag nanoparticle/Ag-doped SiO2composite films were prepared with AgNO3and tetraethoxysilane precursors through a simple and environmentally friendly sol–gel method under high annealing temperatures. The effect of different annealing temperatures (400[Formula: see text]C, 500[Formula: see text]C, 600[Formula: see text]C, and 700[Formula: see text]C) on the structural and optical characters of the composite films was investigated. The localized surface plasmon resonance (LSPR) effect of the Ag nanoparticle/Ag-doped SiO2composite films enhanced the fluorescence intensity of CdSe quantum dots (QDs). Scanning electron microscopy (SEM), UV-vis spectrophotometer and photoluminescence (PL) spectroscopy were used to characterize the morphology and optical properties of the composite nanostructure.
Research on the Mechanism of the Spatial Contagion of Global Financial Crises: From the Perspective of Pure Contagion
Authors: WU Zhanyun
Published: September 2018

In the post financial crisis era, the contagion of a financial crisis remains an important issue. Drawing upon the idea of absolute physical space in classical cartography, this paper attempts to construct the space of political and economic systems for the contagion of financial crisis through a decomposition and re-synthesis of Index of Economic Freedom. It then utilizes the Spatial Autocorrelation Model to analyze the characteristics of the spatial distribution, structure, and interactions of the contagion. The empirical findings show that the contagion of international financial crisis has dependence on both geographical space and space of economic systems, and the spatial dependence on the latter is more significant and intense than that on the former. These findings verify the pure contagion of a financial crisis, that is, similar political and economic systems rather than geographical proximity among countries are more likely to lead to the contagion of a financial crisis.
Evaluation and Analysis on the Efficiency of Urbanization in China: From the Perspective of Environment and Resource Efficiency
Authors: WEI Houkai , SU Hongjian , HAN Zhenyu
Published: September 2018

The efficiency of urbanization is one of the important dimensions of urbanization quality. From the perspective of environment and resource efficiency, it mainly includes four aspects: land use efficiency, energy use efficiency, water use efficiency and environmental efficiency. This paper, through a review of previous studies and based on the connotations of the four aspects, builds an input–output indicator system with the 2013 data of Chinese cities at prefecture and above levels and evaluates the efficiency of urbanization comprehensively with a single-input and multi-output DEA-BCC model. According to the evaluation results, all indicators including the overall technical efficiency, pure technical efficiency, scale efficiency and the efficiencies of the four elements (land, energy, water and environment) present certain scale and regional characteristics; the indicators of technical efficiency and the urbanization rate show a significant U-shaped relationship; and other indicators also show a certain correlation with the urbanization rate.
Elastic wave propagation in a periodic composite beam structure: A new model for band gaps incorporating surface energy, transverse shear and rotational inertia effects
Authors: Gao R. Z. , Zhang G. Y. , Ioppolo T. , Gao X.-L.
Published: September 2018

A new model for determining band gaps for elastic wave propagation in a periodic composite beam structure is developed using a non-classical Timoshenko beam model that incorporates the surface energy, transverse shear and rotational inertia effects. The Bloch theorem and transfer matrix method for periodic structures are employed in the formulation. The new model reduces to the classical elasticity-based model when the surface energy effect is not considered. It is shown that the band gaps predicted by the current model depend on the surface elastic constants of each constituent material, beam thickness, unit cell size, and volume fraction. The numerical results reveal that the band gap based on the current non-classical model is always larger than that given by the classical model when the beam thickness is very small, but the difference is diminishing as the thickness becomes large. Also, it is found that the first frequency for producing the band gap and the band gap size decrease with the increase of the unit cell length according to both the current and classical models. In addition, it is observed that the volume fraction has a significant effect on the band gap size, and large band gaps can be obtained by tailoring the volume fraction and material parameters.
Modes of arsenic occurrence in coal from the Santanghu Coalfield, Xinjiang, Northwest China: evidence from coal petrography, coal facies, mineralogy and geochemistry
Authors: Feng Shuo , Tian Jijun , Zhang Yuyao , Yang Feng , Lu Xingyu
Published: September 2018

The Santanghu Coalfield is an important coal reserve in China. It has been found that the arsenic content is at a very high level at some drilling locations in the Hanshuiquan ore district of the Santanghu Coalfield, with a maximum content as high as 190 µg/g. In order to determine the states of the occurrence of As, 22 coal samples from the Xishanyao Formation of the Hanshuiquan ore district were analysed using sequential chemical extraction experiments and atomic fluorescence spectrometry. The results show that the concentrations of As are ranked as follows, from high to low: ‘inorganic soluble’ state, ‘inorganic insoluble’ state (residual form state), and ‘organic’ state. Although arsenopyrites (FeAsS) and As-bearing pyrites were detected by electron probe microanalysis, they are not common in the samples. By combining the results of low-temperature ashing and X-ray diffraction (XRD) experiments, it was found that the modes of As occurrences are not mainly in arsenopyrites or As-bearing pyrites. To confirm the modes of As occurrence in coal, we used an improved experimental method: reductive difference. As a result, we found that most inorganic soluble As occurs in the form of arsenate minerals, followed by pyrite via isomorphism.
Sex differences in endothelial function important to vascular health and overall cardiovascular disease risk across the lifespan
Authors: Stanhewicz Anna E. , Wenner Megan M. , Stachenfeld Nina S.
Published: September 2018

Diseases of the cardiovascular system are the leading cause of morbidity and mortality in men and women in developed countries, and cardiovascular disease (CVD) is becoming more prevalent in developing countries. The prevalence of atherosclerotic CVD in men is greater than in women until menopause, when the prevalence of CVD increases in women until it exceeds that of men. Endothelial function is a barometer of vascular health and a predictor of atherosclerosis that may provide insights into sex differences in CVD as well as how and why the CVD risk drastically changes with menopause. Studies of sex differences in endothelial function are conflicting, with some studies showing earlier decrements in endothelial function in men compared with women, whereas others show similar age-related declines between the sexes. Because the increase in CVD risk coincides with menopause, it is generally thought that female hormones, estrogens in particular, are cardioprotective. Moreover, it is often proposed that androgens are detrimental. In truth, the relationships are more complex. This review first addresses female and male sex hormones and their receptors and how these interact with the cardiovascular system, particularly the endothelium, in healthy young women and men. Second, we address sex differences in sex steroid receptor-independent mechanisms controlling endothelial function, focusing on vascular endothelin and the renin-angiotensin systems, in healthy young women and men. Finally, we discuss sex differences in age-associated endothelial dysfunction, focusing on the role of attenuated circulating sex hormones in these effects.
Salt stress in the renal tubules is linked to TAL-specific expression of uromodulin and an upregulation of heat shock genes
Authors: Graham Lesley A. , Aman Alisha , Campbell Desmond D. , Augley Julian , Graham Delyth , McBride Martin W. , Fraser Niall J. , Ferreri Nicholas R. , Dominiczak Anna F. , Padmanabhan Sandosh
Published: September 2018

Previously, our comprehensive cardiovascular characterization study validated Uromodulin as a blood pressure gene. Uromodulin is a glycoprotein exclusively synthesized at the thick ascending limb of the loop of Henle and is encoded by the Umod gene. Umod−/−mice have significantly lower blood pressure than Umod+/+mice, are resistant to salt-induced changes in blood pressure, and show a leftward shift in pressure-natriuresis curves reflecting changes of sodium reabsorption. Salt stress triggers transcription factors and genes that alter renal sodium reabsorption. To date there are no studies on renal transcriptome responses to salt stress. Here we aimed use RNA-Seq to delineate salt stress pathways in tubules isolated from Umod+/+mice (a model of sodium retention) and Umod−/−mice (a model of sodium depletion) ± 300 mosmol sodium chloride ( n = 3 per group). In response to salt stress, the tubules of Umod+/+mice displayed an upregulation of heat shock transcripts. The greatest changes occurred in the expression of: Hspa1a (Log2 fold change 4.35, P = 2.48 e−12) and Hspa1b (Log2 fold change 4.05, P = 2.48 e−12). This response was absent in tubules of Umod−/−mice. Interestingly, seven of the genes discordantly expressed in the Umod−/−tubules were electrolyte transporters. Our results are the first to show that salt stress in renal tubules alters the transcriptome, increasing the expression of heat shock genes. This direction of effect in Umod+/+tubules suggest the difference is due to the presence of Umod facilitating greater sodium entry into the tubule cell reflecting a specific response to salt stress.
A Nonpump Function of Sodium Iodide Symporter in Thyroid Cancer via Cross-talk with PTEN Signaling
Authors: Feng Fang , Yehia Lamis , Ni Ying , Chang Yi Seok , Jhiang Sissy Meihua , Eng Charis
Published: September 2018

The sodium iodide symporter (NIS) is a classical iodide pump typically localized within the cell plasma membrane in thyroid cells, where NIS expression is believed to ensure success of mainstay radioiodide therapy in thyroid cancers. Although radioiodide uptake is generally reduced in thyroid cancer tissue, intracellular nonmembranous NIS has been reported to increase, suggesting that NIS serves a pump-independent function. Thyroid cancer is one of the major component cancers of Cowden syndrome, a subset of which is caused by germline mutations in PTEN. In this study, we explored the noncanonical tumorigenic role of NIS in thyroid cancer cells in relation to PTEN signaling. PTEN knockdown in thyroid cancer cell lines stabilized intracellular NIS protein by promoting an interaction with NIS-LARG (leukemia-associated RhoA guanine exchange factor). Increased protein levels of cytoplasmic NIS enhanced RhoA activation and resulted in a promigration tumorigenic phenotype. Inhibition of NIS glycosylation through activation of the PI3K/AKT/mTOR signaling pathway contributed to mislocalization of NIS in the cytoplasm, facilitating its nonpump tumorigenic function through an interaction with LARG, which predominantly localized in the cytoplasm. Moreover, PTEN or PI3K/AKT/mTOR signaling could affect DPAGT1, a glycosylating enzyme involved in the initial step of N-linked glycosylation, to inhibit glycosylation of NIS. In summary, our results elucidate a pump-independent, protumorigenic role for NIS in thyroid cancer via its cross-talk with PTEN signaling.

Significance: A novel pump-independent protumorigenic role of nonmembranous NIS challenges the presumption that radioiodine treatment of thyroid cancer is ineffective when transmembrane NIS is not expressed. Cancer Res; 78(21); 6121–33. ©2018 AACR.
Compartmentalized Structure of the Moderator Band Provides a Unique Substrate for Macroreentrant Ventricular Tachycardia
Authors: Walton Richard D. , Pashaei Ali , Martinez Marine E. , Constantin Marion , Duchateau Josselin , Bear Laura , Cros Caroline , Pascarel-Auclerc Caroline , Guo Yunbo , Benoist David , Dubes Virginie , Faye Ndeye Rokhaya , Chaigne Sebastien , Dupuis Sebastien , Détaille Dominique , Pourtau Line , Pasdois Philippe , Brette Fabien , Rogier Julien , Labrousse Louis , Hocini Mélèze , Vigmond Edward J. , Haïssaguerre Michel , Bernus Olivier
Published: September 2018

Background

Papillary muscles are an important source of ventricular tachycardia (VT). Yet little is known about the role of the right ventricular (RV) endocavity structure, the moderator band (MB). The aim of this study was to determine the characteristics of the MB that may predispose to arrhythmia substrates.

Methods

Ventricular wedge preparations with intact MBs were studied from humans (n=2) and sheep (n=15; 40–50 kg). RV endocardium was optically mapped, and electrical recordings were measured along the MB and septum. S1S2 pacing of the RV free wall, MB, or combined S1-RV S2-MB sites were assessed. Human (n=2) and sheep (n=4) MB tissue constituents were assessed histologically.

Results

The MB structure was remarkably organized as 2 excitable, yet uncoupled compartments of myocardium and Purkinje. In humans, action potential duration heterogeneity between MB and RV myocardium was found (324.6±12.0 versus 364.0±8.4 ms;
P
<0.0001). S1S2-MB pacing induced unidirectional propagation via MB myocardium, permitting sustained macroreentrant VT. In sheep, the incidence of VT for RV, MB, and S1-RV S2-MB pacing was 1.3%, 5.1%, and 10.3%. Severing the MB led to VT termination, confirming a primary arrhythmic role. Inducible preparations had shorter action potential duration in the MB than RV (259.3±45.2 versus 300.7±38.5 ms;
P
<0.05), whereas noninducible preparations showed no difference (312.0±30.3 versus 310.0±24.6 ms, respectively).

Conclusions

The MB presents anatomic and electrical compartmentalization between myocardium and Purkinje fibers, providing a substrate for macroreentry. The vulnerability to sustain VT via this mechanism is dependent on MB structure and action potential duration gradients between the RV free wall and MB.
Activation Mapping With Integration of Vector and Velocity Information Improves the Ability to Identify the Mechanism and Location of Complex Scar-Related Atrial Tachycardias
Authors: Anter Elad , Duytschaever Mattias , Shen Changyu , Strisciuglio Teresa , Leshem Eran , Contreras-Valdes Fernando M. , Waks Jonathan W. , Zimetbaum Peter J. , Kumar Kapil , Spector Peter S. , Lee Adam , Gerstenfeld Edward P. , Nakar Elad , Bar-Tal Meir , Buxton Alfred E.
Published: September 2018

Background:

Activation mapping of scar-related atrial tachycardias (ATs) can be difficult to interpret because of inaccurate time annotation of complex electrograms and passive diastolic activity. We examined whether integration of a vector map can help to describe patterns of propagation to better explain the mechanism and location of ATs.

Methods:

The investigational mapping algorithm calculates vectors and applies physiological constraints of electrical excitation in human atrial tissue to determine the arrhythmia source and circuit. Phase I consisted of retrospective evaluation in 35 patients with ATs. Phase II consisted of prospective validation in 20 patients with ATs. Macroreentry was defined as a continuous propagation in a circular path >30 mm; localized reentry was defined as a circular path ≤30 mm; a focal source had a centrifugal spread from a point source.

Results:

In phase I, standard activation mapping identified 28 of 40 ATs (70%): 25 macroreentry and 3 focal tachycardias. In the remaining 12 ATs, the mechanism and location could not be identified by activation and required entrainment or empirical ablation for termination (radiofrequency time, 17.3±6.6 minutes). In comparison, the investigational algorithm identified 37 of 40 (92.5%) ATs, including 5 macroreentry, 3 localized reentry, and 1 focal AT not identified by standard mapping. It also predicted the successful termination site of all 37 of 40 ATs. In phase II, the investigational algorithm identified 12 macroreentry, 6 localized reentry, and 2 focal tachycardias that all terminated with limited ablation (3.2±1.7 minutes). It identified 3 macroreentry, 3 localized reentry, and 1 focal AT not well characterized by standard mapping. The diagnosis of localized reentry was supported by highly curved vectors, resetting with increasing curve and termination with limited ablation (22±6 s).

Conclusions:

Activation mapping integrating vectors can help determine the arrhythmia mechanism and identify its critical components. It has particular value for identifying complex macroreentrant circuits and for differentiating a focal source from a localized reentry.
Impact of Baseline Hemodynamics on the Effects of a Transcatheter Interatrial Shunt Device in Heart Failure With Preserved Ejection Fraction
Authors: Wessler Jeffrey , Kaye David , Gustafsson Finn , Petrie Mark C. , Hasenfuβ Gerd , Lam Carolyn S.P. , Borlaug Barry A. , Komtebedde Jan , Feldman Ted , Shah Sanjiv J. , Burkhoff Daniel ,   on behalf of the REDUCE-LAP-HF Trial Investigators and Advisors
Published: September 2018

Background

Interatrial shunt device (IASD) effects have been described in patients with heart failure and ejection fractions (EFs) ≥40%. However, baseline characteristics that correlate with greatest hemodynamic effects are unknown. On the basis of fundamental principles, we hypothesized that larger pressure gradients between left and right atria would yield greater shunt flow and greater hemodynamic effects.

Methods and Results

REDUCE LAP-HF (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) was a multicenter study that investigated IASD safety and performance. Sixty-four patients with EF ≥40% underwent device implantation followed by hemodynamic assessments at rest and exercise, including pulmonary capillary wedge pressure (PCWP, surrogate for left atrial pressure) and central venous pressure (CVP). At 6 months, IASD resulted in an average pulmonary-to-systemic blood flow ratio of 1.27 and increased exercise tolerance. The PCWP-CVP gradient (ie, the driving pressure for shunt flow) decreased at peak exercise from 16.8±6.9 to 11.4±5.5 mm Hg, because of increased CVP (17.5±5.4 to 20.3±7.9 mm Hg;
P
=0.04) and decreased PCWP (34.1±7.6 to 31.6±8.0 mm Hg;
P
=0.025). Baseline PCWP-CVP gradient during exercise correlated with changes of both PCWP-CVP and PCWP: Δ(PCWP-CVP)=10.0−0.89·(PCWP-CVP)
baseline
(
r
2
=0.56) and ΔPCWP=7.54−0.60·(PCWP-CVP)
baseline
(
P
=0.001). Hemodynamics of patients with EF ≥50% and those with EF <50% responded similarly to IASD.

Conclusions

In heart failure patients with EF ≥40%, IASD significantly reduced PCWP and PCWP-CVP at peak exercise. Patients with higher baseline PCWP-CVP gradient had greater reductions in both parameters at follow-up. Results were sustained through 12 months and were independent of whether EF was ≥50% or between 40% and 49%. Additional studies will help further define the baseline hemodynamic predictors of exercise, hemodynamic, and clinical efficacy of the IASD.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01913613.
A Small Peptide Ac-SDKP Inhibits Radiation-Induced Cardiomyopathy
Authors: Sharma Umesh C. , Sonkawade Swati D. , Spernyak Joseph A. , Sexton Sandra , Nguyen Juliane , Dahal Suraj , Attwood Kristopher M. , Singh Anurag K. , van Berlo Jop H. , Pokharel Saraswati
Published: September 2018

Background:

Advances in radiotherapy for thoracic cancers have resulted in improvement of survival. However, radiation exposure to the heart can induce cardiotoxicity. No therapy is currently available to inhibit these untoward effects. We examined whether a small tetrapeptide, N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP), can counteract radiation-induced cardiotoxicity by inhibiting macrophage-dependent inflammatory and fibrotic pathways.

Methods and Results:

After characterizing a rat model of cardiac irradiation with magnetic resonance imaging protocols, we examined the effects of Ac-SDKP in radiation-induced cardiomyopathy. We treated rats with Ac-SDKP for 18 weeks. We then compared myocardial contractile function and extracellular matrix by cardiac magnetic resonance imaging and the extent of inflammation, fibrosis, and Mac-2 (galectin-3) release by tissue analyses. Because Mac-2 is a crucial macrophage-derived mediator of fibrosis, we performed studies to determine Mac-2 synthesis by macrophages in response to radiation, and change in profibrotic responses by
Mac-2
gene depleted cardiac fibroblasts after radiation. Cardiac irradiation diminished myocardial contractile velocities and enhanced extracellular matrix deposition. This was accompanied by macrophage infiltration, fibrosis, cardiomyocyte apoptosis, and cardiac Mac-2 expression. Ac-SDKP strongly inhibited these detrimental effects. Ac-SDKP migrated into the perinuclear cytoplasm of the macrophages and inhibited radiation-induced Mac-2 release. Cardiac fibroblasts lacking the
Mac-2
gene showed reduced transforming growth factor β1, collagen I, and collagen III expression after radiation exposure.

Conclusions:

Our study identifies novel cardioprotective effects of Ac-SDKP in a model of cardiac irradiation. These protective effects are exerted by inhibiting inflammation, fibrosis, and reducing macrophage activation. This study shows a therapeutic potential of this endogenously released peptide to counteract radiation-induced cardiomyopathy.
IL-1 Blockade in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Van Tassell Benjamin W. , Trankle Cory R. , Canada Justin M. , Carbone Salvatore , Buckley Leo , Kadariya Dinesh , Del Buono Marco G. , Billingsley Hayley , Wohlford George , Viscusi Michele , Oddi-Erdle Claudia , Abouzaki Nayef A. , Dixon Dave , Biondi-Zoccai Giuseppe , Arena Ross , Abbate Antonio
Published: September 2018

Background

Enhanced inflammation may lead to exercise intolerance in heart failure with preserved ejection fraction. The aim of the current study was to determine whether IL (interleukin)-1 blockade with anakinra improved cardiorespiratory fitness in heart failure with preserved ejection fraction.

Methods and Results

Thirty-one patients with heart failure with preserved ejection fraction and CRP (C-reactive protein) >2 mg/L were randomized to anakinra (100 mg subcutaneously daily, N=21) or placebo (N=10) for 12 weeks. We measured peak oxygen consumption (V
o
2
), ventilatory efficiency (V
E
/V
co
2
slope), and high-sensitivity CRP and NT-proBNP (N-terminal pro-B-type natriuretic peptide) at 4, 12, and 24 weeks. Twenty-eight patients completed ≥2 visits, 18 women (64%), 27 (96%) obese. There were no differences in peak V
o
2
or V
E
/V
co
2
slope between groups at baseline. Peak V
o
2
was not changed after 12 weeks of anakinra (from 13.6 [11.8–18.0] to 14.2 [11.2–18.5] mL·kg
−1
·min
−1
,
P
=0.89), or placebo (14.9 [11.7–17.2] to 15.0 [13.8–16.9] mL·kg
−1
·min
−1
,
P
=0.40), without significant between-group differences in changes at 12 weeks (−0.4 [95% CI, −2.2 to +1.4],
P
=0.64). V
E
/V
co
2
slope was also unchanged with anakinra (from 28.3 [27.2–33.0] to 30.5 [26.3–32.8],
P
=0.97) or placebo (from 31.6 [27.3–36.9] to 31.2 [27.8–33.4],
P
=0.78), without significant between-group differences in changes at 12 weeks (+1.2 [95% CI, −1.8 to +4.3],
P
=0.97). Within the anakinra-treated patients, high-sensitivity CRP and NT-proBNP levels were lower at 4 weeks compared with baseline (
P
=0.026 and
P
=0.022 versus placebo [between-group analysis], respectively).

Conclusions

Treatment with anakinra for 12 weeks failed to improve peak V
o
2
and V
E
/V
co
2
slope in a group of obese heart failure with preserved ejection fraction patients. The favorable trends in high-sensitivity CRP and NT-proBNP with anakinra deserve exploration in future studies.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02173548.
Tropoelastin
Authors: Phinikaridou Alkystis , Lacerda Sara , Lavin Begoña , Andia Marcelo E. , Smith Alberto , Saha Prakash , Botnar René M.
Published: September 2018

Background:

Elastolysis and ineffective elastogenesis favor the accumulation of tropoelastin, rather than cross-linked elastin, in atherosclerotic plaques. We developed gadolinium-labeled tropoelastin-specific magnetic resonance contrast agents for tropoelastin imaging in animal models.

Methods and Results:

Two peptides, VVGSPSAQDEASPLS and YPDHVQYTHY, were selected to target tropoelastin. In vitro binding, relaxivity, and biodistribution experiments enabled characterization of the probes and selecting the best candidate for in vivo magnetic resonance imaging. Magnetic resonance imaging was performed in atherosclerotic apolipoprotein E–deficient mice and New Zealand white rabbits with stable and rupture-prone plaques using a gadolinium-labeled tropoelastin-specific magnetic resonance contrast agent. In addition, human carotid endarterectomy specimens were imaged ex vivo. The VVGSPSAQDEASPLS-based probe discriminated between tropoelastin and cross-linked elastin (64%±7% versus 1%±2%;
P
=0.001), had high in vitro relaxivity in solution (r
1-free
=11.7±0.6 [mmol/L]
−1
s
−1
, r
1-bound to tropoelastin
=44±1 [mmol/L]
−
1
s
−
1
), and favorable pharmacokinetics. In vivo mice vascular enhancement (4 weeks=0.13±0.007 mm
2
, 8 weeks=0.22±0.01 mm
2
, 12 weeks=0.33±0.01 mm
2
;
P
<0.001) and R
1
relaxation rate (4 weeks=[0.90±0.01]/s, 8 weeks=[1.40±0.03]/s, 12 weeks=[1.87±0.04]/s;
P
<0.001) increased with atherosclerosis progression after gadolinium-labeled tropoelastin-specific magnetic resonance contrast agent injection. Conversely, statin-treated (0.13±0.01 mm
2
; R
1
=[1.37±0.03]/s) and control (0.10±0.005 mm
2
; R
1
=[0.87±0.05]/s) mice showed less enhancement. Rupture-prone rabbit plaques had higher R
1
relaxation rate compared with stale plaques (R
1
=[2.26±0.1]/s versus R
1
=[1.43±0.02]/s;
P
=0.001) after administration of the gadolinium-labeled tropoelastin-specific magnetic resonance contrast agent that allowed detection of rupture-prone plaques with high sensitivity (84.4%) and specificity (92.3%). Increased vascular R
1
relaxation rate was observed in carotid endarterectomy plaques after soaking (R
1pre
=[1.1±0.26]/s versus R
1post
=[3.0±0.1]/s;
P
=0.01). Ex vivo analyses confirmed the magnetic resonance imaging findings and showed uptake of the contrast agent to be specific for tropoelastin.

Conclusions:

Magnetic resonance imaging of tropoelastin provides a novel biomarker for atherosclerotic plaque progression and instability.
Drug-Eluting Versus Bare-Metal Stent Implantation With or Without Cilostazol in the Treatment of the Superficial Femoral Artery
Authors: Miura Takashi , Miyashita Yusuke , Soga Yoshimitsu , Hozawa Koji , Doijiri Tatsuki , Ikeda Uichi , Kuwahara Koichiro ,   on behalf of the DEBATE in SFA Investigators
Published: September 2018

Background:

New-generation bare-metal nitinol (BNS) and drug-eluting stents have improved long-term outcomes in patients undergoing endovascular therapy for femoropopliteal lesions. Furthermore, cilostazol reduces in-stent restenosis (ISR) after first-generation BNS implantation for femoropopliteal lesions.

Methods and Results:

We studied 255 patients with femoropopliteal lesions treated at 25 cardiovascular centers. Patients were randomly assigned to the BNS group (Misago stent implantation without cilostazol), BNS with cilostazol group (Misago stent implantation with cilostazol), or drug-eluting stents group (Zilver PTX stent implantation without cilostazol). Primary end point was 1-year restenosis noted using duplex ultrasound (peak systolic velocity ratio, >2.0). Secondary end point was major adverse limb events (limb-related death, target lesion revascularization, major amputation, and major bleeding). During the 1-year follow-up, 12 patients (4.7%) died and 237 (92.9%) had relevant ultrasound findings. The 1-year ISR rate did not differ significantly among the BNS, BNS with cilostazol, and drug-eluting stents groups (28.4% versus 12.2% versus 21.0%;
P
=0.052). Although the 1-year ISR rate was significantly lower in the BNS with cilostazol group than in the BNS group, it was similar to that in the drug-eluting stents group (
P
=0.16). Major adverse limb event was significantly higher in the BNS group (16.9% versus 6.5% versus 6.3%;
P
=0.034); however, target lesion revascularization and major bleeding were similar (9.7% versus 5.1% versus 3.6%;
P
=0.25, 4.8% versus 1.2% versus 2.4%;
P
=0.37, respectively).

Conclusions:

Misago stent implantation with cilostazol showed a comparable 1-year ISR rate with Zilver PTX. Cilostazol reduced the 1-year ISR rate after endovascular therapy when used with new-generation BNS.

Clinical Trial Registration:

URL:
http://www.umin.ac.jp/ctr/
. Unique identifier: UMIN 000010071.
Population‐Based Study of Incidence of Acute Abdominal Aortic Aneurysms With Projected Impact of Screening Strategy
Authors: Howard Dominic P. J. , Banerjee Amitava , Fairhead Jack F. , Handa Ashok , Silver Louise E. , Rothwell Peter M. ,   the Oxford Vascular Study
Published: September 2018

Background

Current abdominal aortic aneurysm (
AAA
) screening in men age 65 might have limited impact on overall
AAA
death rates if incidence is moving to older ages. Up‐to‐date population‐based studies of age‐specific incidence, risk factors, and outcome of acute
AAA
are needed to inform screening policy.

Methods and Results

In a prospective, population‐based study (Oxfordshire,
UK
, 2002–2014), the incidence and outcome of acute
AAA
events were determined. Based on population projections and current incidence trends, the impact of screening strategies in the
UK
was estimated. Over the 12‐year period, 103 incident acute
AAA
events occurred in the study population of 92 728. Incidence/100 000/year was 55 in men ages 65 to 74 years, but increased to 112 at 75 to 85 and 298 at ≥85, with 66.0% of all events occurring at age ≥75 years. Incidence at ages 65 to 74 was highest in male smokers (274), with 96.4% of events in men <75 years occurring in ever‐smokers. Extrapolating rates to the
UK
population, using trial evidence of screening efficacy, the current
UK
screening program would prevent 5.6% of aneurysm‐related deaths (315 200 scans/year: 1426/death prevented, 121/year‐of‐life saved). Screening only male smokers age 65 and then all men at age 75 would prevent 21.1% of deaths (247 900 scans/year; 297/death prevented, 34/year‐of‐life saved). By 2030, 91.0% of deaths will occur at age ≥75, 61.6% at ≥85, and 28.6% in women.

Conclusions

Given that two thirds of acute
AAA
occurred at ≥75 years of age, screening older age groups should be considered. Screening nonsmokers at age 65 is likely to have very little impact on
AAA
event rates.
Optimal Lifestyle Components in Young Adulthood Are Associated With Maintaining the Ideal Cardiovascular Health Profile Into Middle Age
Authors: Gooding Holly C. , Shay Christina M. , Ning Hongyan , Gillman Matthew W. , Chiuve Stephanie E. , Reis Jared P. , Allen Norrina B. , Lloyd‐Jones Donald M.
Published: September 2018

Background

Middle‐aged adults with ideal blood pressure, cholesterol, and glucose levels exhibit substantially lower cardiovascular mortality than those with unfavorable levels. Four healthy lifestyle components—optimal body weight, diet, physical activity, and not smoking—are recommended for cardiovascular health (
CVH
). This study quantified associations between combinations of healthy lifestyle components measured in young adulthood and loss of the ideal
CVH
profile into middle age.

Methods and Results

Analyses included 2164 young adults in the Coronary Artery Risk Development in Young Adults study with the ideal
CVH
profile (defined as untreated blood pressure <120/80 mm Hg, total cholesterol <200 mg/
dL
, fasting blood glucose <100 mg/
dL
, and absence of cardiovascular disease) at baseline. Cox proportional hazards regression models estimated hazard ratios for loss of the ideal
CVH
profile over 25 years according to 4 individual and 16 combinations of optimal healthy lifestyle components measured in young adulthood: body mass index, physical activity, nonsmoking status, and diet quality. Models were adjusted for age, sex, race, education, study center, and baseline blood pressure, cholesterol, and glucose. Eighty percent (n=1737) of participants lost the ideal
CVH
profile by middle age; loss was greatest for young adults with no optimal healthy lifestyle components at baseline. Relative to young adults with no optimal healthy lifestyle components, those with all 4 were less likely to lose the ideal
CVH
profile (hazard ratio 0.59, 95%
CI
0.44–0.80). Combinations that included optimal body mass index and nonsmoking status were each associated with lower risk.

Conclusions

Optimal body mass index and not smoking in young adulthood were protective against loss of the ideal
CVH
profile through middle age. Importance of diet and physical activity may be included through their effects on healthy weight.
Are Changes in Heart Rate Variability in Middle‐Aged and Older People Normative or Caused by Pathological Conditions? Findings From a Large Population‐Based Longitudinal Cohort Study
Authors: Jandackova Vera K. , Scholes Shaun , Britton Annie , Steptoe Andrew
Published: September 2018

Background

No study to date has investigated longitudinal trajectories of cardiac autonomic modulation changes with aging; therefore, we lack evidence showing whether these changes occur naturally or are secondary to disease or medication use. This study tested whether heart rate variability (
HRV
) trajectories from middle to older age are largely normative or caused by pathological changes with aging in a large prospective cohort. We further assessed whether
HRV
changes were modified by socioeconomic status, ethnicity, or habitual physical activity.

Methods and Results

This study involved 3176 men and 1238 women initially aged 44 to 69 years (1997–1999) from the
UK
Whitehall
II
population‐based cohort. We evaluated time‐ and frequency‐domain
HRV
measures of short‐term recordings at 3 time points over a 10‐year period. Random mixed models with time‐varying covariates were applied. Cross‐sectionally,
HRV
measures were lower for men than for women, for participants with cardiometabolic conditions, and for participants reporting use of medications other than beta blockers. Longitudinally,
HRV
measures decreased significantly with aging in both sexes, with faster decline in younger age groups.
HRV
trajectories were not explained by increased prevalence of cardiometabolic problems and/or medication use. In women, cardiometabolic problems were associated with faster decline in the standard deviation of all intervals between R waves with normal‐to‐normal conduction, in low‐frequency
HRV
, and in low‐frequency
HRV
in normalized units. Socioeconomic status, ethnicity, and habitual physical activity did not have significant effects on
HRV
trajectories.

Conclusions

Our investigation showed a general pattern and timing of changes in indices of cardiac autonomic modulation from middle to older age. These changes seem likely to reflect the normal aging process rather than being secondary to cardiometabolic problems and medication use.
Vascular Smooth Muscle Sirtuin‐1 Protects Against Aortic Dissection During Angiotensin II–Induced Hypertension
Authors: Fry Jessica L. , Shiraishi Yasunaga , Turcotte Raphaël , Yu Xunjie , Gao Yuan Z. , Akiki Rachid , Bachschmid Markus , Zhang Yanhang , Morgan Kathleen G. , Cohen Richard A. , Seta Francesca
Published: September 2018

Background

Sirtuin‐1 (SirT1), a nicotinamide adenine dinucleotide
+
–dependent deacetylase, is a key enzyme in the cellular response to metabolic, inflammatory, and oxidative stresses; however, the role of endogenous SirT1 in the vasculature has not been fully elucidated. Our goal was to evaluate the role of vascular smooth muscle SirT1 in the physiological response of the aortic wall to angiotensin
II
, a potent hypertrophic, oxidant, and inflammatory stimulus.

Methods and Results

Mice lacking SirT1 in vascular smooth muscle (ie, smooth muscle SirT1 knockout) had drastically high mortality (70%) caused by aortic dissection after angiotensin
II
infusion (1 mg/kg per day) but not after an equipotent dose of norepinephrine, despite comparable blood pressure increases. Smooth muscle SirT1 knockout mice did not show any abnormal aortic morphology or blood pressure compared with wild‐type littermates. Nonetheless, in response to angiotensin
II
, aortas from smooth muscle SirT1 knockout mice had severely disorganized elastic lamellae with frequent elastin breaks, increased oxidant production, and aortic stiffness compared with angiotensin
II
–treated wild‐type mice. Matrix metalloproteinase expression and activity were increased in the aortas of angiotensin
II
–treated smooth muscle SirT1 knockout mice and were prevented in mice overexpressing SirT1 in vascular smooth muscle or with use of the oxidant scavenger tempol.

Conclusions

Endogenous SirT1 in aortic smooth muscle is required to maintain the structural integrity of the aortic wall in response to oxidant and inflammatory stimuli, at least in part, by suppressing oxidant‐induced matrix metalloproteinase activity. SirT1 activators could potentially be a novel therapeutic approach to prevent aortic dissection and rupture in patients at risk, such as those with hypertension or genetic disorders, such as Marfan's syndrome.