Ischemic Ventricular Tachycardia Presenting as a Narrow Complex Tachycardia

PubMed Central

Page, Stephen P; Watts, Troy; Yeo, Wee Tiong; Mehul, Dhinoja

2014-01-01

This report describes a patient presenting with a narrow complex tachycardia in the context of prior myocardial infarction and impaired ventricular function. Electrophysiological studies confirmed ventricular tachycardia and activation and entrainment mapping demonstrated a critical isthmus within an area of scar involving the His-Purkinje system accounting for the narrow QRS morphology. This very rare case shares some similarities with upper septal ventricular tachycardia seen in patients with structurally normal hearts, but to our knowledge has not been seen previously in patients with ischemic heart disease. PMID:25057222

Visualization of Fiber Structurein the Left and Right Ventricleof a Human Heart

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rohmer, Damien; Sitek, Arkadiusz; Gullberg, Grant T.

2006-07-12

The human heart is composed of a helical network of musclefibers. Anisotropic least squares filtering followed by fiber trackingtechniques were applied to Diffusion Tensor Magnetic Resonance Imaging(DTMRI) data of the excised human heart. The fiber configuration wasvisualized by using thin tubes to increase 3-dimensional visualperception of the complex structure. All visualizations were performedusing the high-quality ray-tracing software POV-Ray. The fibers are shownwithin the left and right ventricles. Both ventricles exhibit similarfiber architecture and some bundles of fibers are shown linking right andleft ventricles on the posterior region of the heart.

Assessing Cardiac Metabolism: A Scientific Statement From the American Heart Association.

PubMed

Taegtmeyer, Heinrich; Young, Martin E; Lopaschuk, Gary D; Abel, E Dale; Brunengraber, Henri; Darley-Usmar, Victor; Des Rosiers, Christine; Gerszten, Robert; Glatz, Jan F; Griffin, Julian L; Gropler, Robert J; Holzhuetter, Hermann-Georg; Kizer, Jorge R; Lewandowski, E Douglas; Malloy, Craig R; Neubauer, Stefan; Peterson, Linda R; Portman, Michael A; Recchia, Fabio A; Van Eyk, Jennifer E; Wang, Thomas J

2016-05-13

In a complex system of interrelated reactions, the heart converts chemical energy to mechanical energy. Energy transfer is achieved through coordinated activation of enzymes, ion channels, and contractile elements, as well as structural and membrane proteins. The heart's needs for energy are difficult to overestimate. At a time when the cardiovascular research community is discovering a plethora of new molecular methods to assess cardiac metabolism, the methods remain scattered in the literature. The present statement on "Assessing Cardiac Metabolism" seeks to provide a collective and curated resource on methods and models used to investigate established and emerging aspects of cardiac metabolism. Some of those methods are refinements of classic biochemical tools, whereas most others are recent additions from the powerful tools of molecular biology. The aim of this statement is to be useful to many and to do justice to a dynamic field of great complexity. © 2016 American Heart Association, Inc.

Contemporary management of tricuspid regurgitation: an updated clinical review.

PubMed

Taylor, Joshua T; Chidsey, Geoffrey; Disalvo, Thomas G; Byrne, John G; Maltais, Simon

2013-01-01

Tricuspid regurgitation (TR) is a complex and insidious valvular pathology that represents a complex decision and management algorithm for patients. TR is present in a significant proportion of the population and is especially prevalent in patients with advanced heart failure. Patients with TR have been demonstrated to have a decreased survival even with normal left heart function. TR can be a result of pathology that directly affects the valvular structure (i.e., Ebstein anomaly) or as a result of increased forward pressures (ie, pulmonary hypertension, left heart failure). Conservative management of patients with TR is primarily symptomatic relief. Definitive therapy involves surgical repair of the tricuspid valve. Furthermore, as more patients develop advanced heart failure, the management of TR in patients with left ventricular assist devices has become necessary because of the evidence of increased in-hospital morbidity and a trend toward decreased survival.

Temporally Distinct Six2-Positive Second Heart Field Progenitors Regulate Mammalian Heart Development and Disease.

PubMed

Zhou, Zhengfang; Wang, Jingying; Guo, Chaoshe; Chang, Weiting; Zhuang, Jian; Zhu, Ping; Li, Xue

2017-01-24

The embryonic process of forming a complex structure such as the heart remains poorly understood. Here, we show that Six2 marks a dynamic subset of second heart field progenitors. Six2-positive (Six2 + ) progenitors are rapidly recruited and assigned, and their descendants are allocated successively to regions of the heart from the right ventricle (RV) to the pulmonary trunk. Global ablation of Six2 + progenitors resulted in RV hypoplasia and pulmonary atresia. An early stage-specific ablation of a small subset of Six2 + progenitors did not cause any apparent structural defect at birth but rather resulted in adult-onset cardiac hypertrophy and dysfunction. Furthermore, Six2 expression depends in part on Shh signaling, and Shh deletion resulted in severe deficiency of Six2 + progenitors. Collectively, these findings unveil the chronological features of cardiogenesis, in which the mammalian heart is built sequentially by temporally distinct populations of cardiac progenitors, and provide insights into late-onset congenital heart disease. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Pacing in congenital heart disease - A four-decade experience in a single tertiary centre.

PubMed

Midha, Disha; Chen, Zhong; Jones, David G; Williams, Howell J; Lascelles, Karen; Jarman, Julian; Clague, Jonathan; Till, Janice; Dimopoulos, Konstatinos; Babu-Narayan, Sonya V; Markides, Vias; Gatzoulis, Michael A; Wong, Tom

2017-08-15

The increased risk of brady- and tachy-arrhythmias in the congenital heart disease (CHD) population means that cardiac rhythm management devices are often required at an early age and expose patients to device-related complications. The present study drew upon four decades of experience at a tertiary adult congenital heart disease ACHD center and aimed to investigate the indication for cardiac implantable electronic devices (CIEDs) and predictors of late device-related complication requiring re-intervention. A retrospective review of pacing records of ACHD patients over forty years was carried out. The primary outcome measure was device related complication requiring re-intervention. Between 1970 and 2009, 238 structural CHD patients who received CIEDs with follow-up data were identified (structural group). As a comparator group, 98 patients with congenital conduction disease or long QT syndrome with a structurally normal heart (electrical group) were included in the study. During a mean follow-up of 9.6±8.5years, 72 (21%) patients (44 structural group, 28 electrical group) required ≥1 re-intervention due to device related complications. Multivariate analysis showed that age at the time of device implant was an independent predictor of late device-related complications (HR 0.77, 95% CI 0.60-0.98, p=0.04). Sub-analysis of the structural group showed that ACHD complexity (Bethesda guideline) was the only predictor late device-related complication in the structural group (HR 2.96, 95% CI: 1.67-5.26, p<0.01). Increasing age at device implant was inversely associated with late device-related complications. ACHD patients with complex anatomy are at increased risk of device-related complications at mid and long-term follow-up. Copyright © 2017 Elsevier B.V. All rights reserved.

Echocardiographic and Fluoroscopic Fusion Imaging for Procedural Guidance: An Overview and Early Clinical Experience.

PubMed

Thaden, Jeremy J; Sanon, Saurabh; Geske, Jeffrey B; Eleid, Mackram F; Nijhof, Niels; Malouf, Joseph F; Rihal, Charanjit S; Bruce, Charles J

2016-06-01

There has been significant growth in the volume and complexity of percutaneous structural heart procedures in the past decade. Increasing procedural complexity and accompanying reliance on multimodality imaging have fueled the development of fusion imaging to facilitate procedural guidance. The first clinically available system capable of echocardiographic and fluoroscopic fusion for real-time guidance of structural heart procedures was approved by the US Food and Drug Administration in 2012. Echocardiographic-fluoroscopic fusion imaging combines the precise catheter and device visualization of fluoroscopy with the soft tissue anatomy and color flow Doppler information afforded by echocardiography in a single image. This allows the interventionalist to perform precise catheter manipulations under fluoroscopy guidance while visualizing critical tissue anatomy provided by echocardiography. However, there are few data available addressing this technology's strengths and limitations in routine clinical practice. The authors provide a critical review of currently available echocardiographic-fluoroscopic fusion imaging for guidance of structural heart interventions to highlight its strengths, limitations, and potential clinical applications and to guide further research into value of this emerging technology. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

Integrative computational models of cardiac arrhythmias -- simulating the structurally realistic heart

PubMed Central

Trayanova, Natalia A; Tice, Brock M

2009-01-01

Simulation of cardiac electrical function, and specifically, simulation aimed at understanding the mechanisms of cardiac rhythm disorders, represents an example of a successful integrative multiscale modeling approach, uncovering emergent behavior at the successive scales in the hierarchy of structural complexity. The goal of this article is to present a review of the integrative multiscale models of realistic ventricular structure used in the quest to understand and treat ventricular arrhythmias. It concludes with the new advances in image-based modeling of the heart and the promise it holds for the development of individualized models of ventricular function in health and disease. PMID:20628585

Deterministic chaos and fractal complexity in the dynamics of cardiovascular behavior: perspectives on a new frontier.

PubMed

Sharma, Vijay

2009-09-10

Physiological systems such as the cardiovascular system are capable of five kinds of behavior: equilibrium, periodicity, quasi-periodicity, deterministic chaos and random behavior. Systems adopt one or more these behaviors depending on the function they have evolved to perform. The emerging mathematical concepts of fractal mathematics and chaos theory are extending our ability to study physiological behavior. Fractal geometry is observed in the physical structure of pathways, networks and macroscopic structures such the vasculature and the His-Purkinje network of the heart. Fractal structure is also observed in processes in time, such as heart rate variability. Chaos theory describes the underlying dynamics of the system, and chaotic behavior is also observed at many levels, from effector molecules in the cell to heart function and blood pressure. This review discusses the role of fractal structure and chaos in the cardiovascular system at the level of the heart and blood vessels, and at the cellular level. Key functional consequences of these phenomena are highlighted, and a perspective provided on the possible evolutionary origins of chaotic behavior and fractal structure. The discussion is non-mathematical with an emphasis on the key underlying concepts.

Deterministic Chaos and Fractal Complexity in the Dynamics of Cardiovascular Behavior: Perspectives on a New Frontier

PubMed Central

Sharma, Vijay

2009-01-01

Physiological systems such as the cardiovascular system are capable of five kinds of behavior: equilibrium, periodicity, quasi-periodicity, deterministic chaos and random behavior. Systems adopt one or more these behaviors depending on the function they have evolved to perform. The emerging mathematical concepts of fractal mathematics and chaos theory are extending our ability to study physiological behavior. Fractal geometry is observed in the physical structure of pathways, networks and macroscopic structures such the vasculature and the His-Purkinje network of the heart. Fractal structure is also observed in processes in time, such as heart rate variability. Chaos theory describes the underlying dynamics of the system, and chaotic behavior is also observed at many levels, from effector molecules in the cell to heart function and blood pressure. This review discusses the role of fractal structure and chaos in the cardiovascular system at the level of the heart and blood vessels, and at the cellular level. Key functional consequences of these phenomena are highlighted, and a perspective provided on the possible evolutionary origins of chaotic behavior and fractal structure. The discussion is non-mathematical with an emphasis on the key underlying concepts. PMID:19812706

Universal structures of normal and pathological heart rate variability.

PubMed

Gañán-Calvo, Alfonso M; Fajardo-López, Juan

2016-02-25

The circulatory system of living organisms is an autonomous mechanical system softly tuned with the respiratory system, and both developed by evolution as a response to the complex oxygen demand patterns associated with motion. Circulatory health is rooted in adaptability, which entails an inherent variability. Here, we show that a generalized N-dimensional normalized graph representing heart rate variability reveals two universal arrhythmic patterns as specific signatures of health one reflects cardiac adaptability, and the other the cardiac-respiratory rate tuning. In addition, we identify at least three universal arrhythmic profiles whose presences raise in proportional detriment of the two healthy ones in pathological conditions (myocardial infarction; heart failure; and recovery from sudden death). The presence of the identified universal arrhythmic structures together with the position of the centre of mass of the heart rate variability graph provide a unique quantitative assessment of the health-pathology gradient.

Event Structure and Grammatical Patterns: Resultative Constructions

ERIC Educational Resources Information Center

Lee, Leslie

2013-01-01

This thesis investigates the nature of grammatical patterns through an in-depth study of resultative constructions in Mandarin and Thai. At the heart of the thesis lies the proposal that event structure templates--complex, meaning-based grammatical patterns--must be recognised as primary objects of linguistic analysis. As content-theoretic objects…

Recurrence-plot-based measures of complexity and their application to heart-rate-variability data.

PubMed

Marwan, Norbert; Wessel, Niels; Meyerfeldt, Udo; Schirdewan, Alexander; Kurths, Jürgen

2002-08-01

The knowledge of transitions between regular, laminar or chaotic behaviors is essential to understand the underlying mechanisms behind complex systems. While several linear approaches are often insufficient to describe such processes, there are several nonlinear methods that, however, require rather long time observations. To overcome these difficulties, we propose measures of complexity based on vertical structures in recurrence plots and apply them to the logistic map as well as to heart-rate-variability data. For the logistic map these measures enable us not only to detect transitions between chaotic and periodic states, but also to identify laminar states, i.e., chaos-chaos transitions. The traditional recurrence quantification analysis fails to detect the latter transitions. Applying our measures to the heart-rate-variability data, we are able to detect and quantify the laminar phases before a life-threatening cardiac arrhythmia occurs thereby facilitating a prediction of such an event. Our findings could be of importance for the therapy of malignant cardiac arrhythmias.

Cardiac myocyte diversity and a fibroblast network in the junctional region of the zebrafish heart revealed by transmission and serial block-face scanning electron microscopy.

PubMed

Lafontant, Pascal J; Behzad, Ali R; Brown, Evelyn; Landry, Paul; Hu, Norman; Burns, Alan R

2013-01-01

The zebrafish has emerged as an important model of heart development and regeneration. While the structural characteristics of the developing and adult zebrafish ventricle have been previously studied, little attention has been paid to the nature of the interface between the compact and spongy myocardium. Here we describe how these two distinct layers are structurally and functionally integrated. We demonstrate by transmission electron microscopy that this interface is complex and composed primarily of a junctional region occupied by collagen, as well as a population of fibroblasts that form a highly complex network. We also describe a continuum of uniquely flattened transitional cardiac myocytes that form a circumferential plate upon which the radially-oriented luminal trabeculae are anchored. In addition, we have uncovered within the transitional ring a subpopulation of markedly electron dense cardiac myocytes. At discrete intervals the transitional cardiac myocytes form contact bridges across the junctional space that are stabilized through localized desmosomes and fascia adherentes junctions with adjacent compact cardiac myocytes. Finally using serial block-face scanning electron microscopy, segmentation and volume reconstruction, we confirm the three-dimensional nature of the junctional region as well as the presence of the sheet-like fibroblast network. These ultrastructural studies demonstrate the previously unrecognized complexity with which the compact and spongy layers are structurally integrated, and provide a new basis for understanding development and regeneration in the zebrafish heart.

Current state of knowledge on Takotsubo syndrome: a Position Statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology.

PubMed

Lyon, Alexander R; Bossone, Eduardo; Schneider, Birke; Sechtem, Udo; Citro, Rodolfo; Underwood, S Richard; Sheppard, Mary N; Figtree, Gemma A; Parodi, Guido; Akashi, Yoshihiro J; Ruschitzka, Frank; Filippatos, Gerasimos; Mebazaa, Alexandre; Omerovic, Elmir

2016-01-01

Takotsubo syndrome is an acute reversible heart failure syndrome that is increasingly recognized in modern cardiology practice. This Position Statement from the European Society of Cardiology Heart Failure Association provides a comprehensive review of the various clinical and pathophysiological facets of Takotsubo syndrome, including nomenclature, definition, and diagnosis, primary and secondary clinical subtypes, anatomical variants, triggers, epidemiology, pathophysiology, clinical presentation, complications, prognosis, clinical investigations, and treatment approaches. Novel structured approaches to diagnosis, risk stratification, and management are presented, with new algorithms to aid decision-making by practising clinicians. These also cover more complex areas (e.g. uncertain diagnosis and delayed presentation) and the management of complex cases with ongoing symptoms after recovery, recurrent episodes, or spontaneous presentation. The unmet needs and future directions for research in this syndrome are also discussed. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Crystallization of Mitochondrial Respiratory Complex II from Chicken Heart: a Membrane Protein Complex Diffracting to 2.0 Å.

PubMed Central

Huang, Li-shar; Borders, Toni M.; Shen, John T.; Wang, Chung-Jen; Berry, Edward

2006-01-01

Synopsis A multi-subunit mitochondrial membrane protein complex involved in the Krebs Cycle and respiratory chain has been crystallized in a form suitable for near-atomic resolution structure determination. A procedure is presented for preparation of diffraction-quality crystals of a vertebrate mitochondrial respiratory Complex II. The crystals have the potential to diffract to at least 2.0 Å with optimization of post-crystal-growth treatment and cryoprotection. This should allow determination of the structure of this important and medically relevant membrane protein complex at near-atomic resolution and provide great detail of the mode of binding of substrates and inhibitors at the two substrate-binding sites. PMID:15805592

The complex nature of informal care in home-based heart failure management.

PubMed

Clark, Alexander M; Reid, Margaret E; Morrison, Caroline E; Capewell, Simon; Murdoch, David L; McMurray, John J

2008-02-01

This paper is a report of a study to examine the complexities of informal caregiving for people with chronic heart failure. Little is known of the activities involved and underlying informal care. Heart failure is a common and burdensome condition in which carers play an important management role. Semi-structured interviews were carried out with 30 informal carers nominated by patients with mild-to-moderate heart failure (24 spouses, four children, one sibling and one neighbour). Interviews examined knowledge of heart failure, its effects, reported management practices and concerns, decision making and support. The data were collected in 2001. The management of heart failure was a shared and ongoing responsibility between the carer and patient. Carers' clinical knowledge of the condition and management was often limited, but they developed extensive knowledge of its personal effects on the patient. Invisible care activities included monitoring signs of symptom exacerbation and energy boundaries against perceived current and future demands and priorities. Visible care activities included medication management, dressing, bathing and help-seeking. Carers responded to patients' capacities, and adopted philosophies that sought to foster independence while facilitating as normal a life for the patient as was possible and safe. Interventions for informal carers around effective chronic heart failure management should address both visible and invisible informal caring. Future research is needed to develop interventions with carers to improve quality of care, reduce costs and improve patient quality of life. More research is needed to explore the complexities of lay caregiving and to explore the invisible dimensions of informal care further.

Lp-Norm Regularization in Volumetric Imaging of Cardiac Current Sources

PubMed Central

Rahimi, Azar; Xu, Jingjia; Wang, Linwei

2013-01-01

Advances in computer vision have substantially improved our ability to analyze the structure and mechanics of the heart. In comparison, our ability to observe and analyze cardiac electrical activities is much limited. The progress to computationally reconstruct cardiac current sources from noninvasive voltage data sensed on the body surface has been hindered by the ill-posedness and the lack of a unique solution of the reconstruction problem. Common L2- and L1-norm regularizations tend to produce a solution that is either too diffused or too scattered to reflect the complex spatial structure of current source distribution in the heart. In this work, we propose a general regularization with Lp-norm (1 < p < 2) constraint to bridge the gap and balance between an overly smeared and overly focal solution in cardiac source reconstruction. In a set of phantom experiments, we demonstrate the superiority of the proposed Lp-norm method over its L1 and L2 counterparts in imaging cardiac current sources with increasing extents. Through computer-simulated and real-data experiments, we further demonstrate the feasibility of the proposed method in imaging the complex structure of excitation wavefront, as well as current sources distributed along the postinfarction scar border. This ability to preserve the spatial structure of source distribution is important for revealing the potential disruption to the normal heart excitation. PMID:24348735

Structure-based design and mechanisms of allosteric inhibitors for mitochondrial branched-chain α-ketoacid dehydrogenase kinase

PubMed Central

Qi, Xiangbing; Gui, Wen-Jun; Morlock, Lorraine K.; Wallace, Amy L.; Ahmed, Kamran; Laxman, Sunil; Campeau, Philippe M.; Lee, Brendan H.; Hutson, Susan M.; Tu, Benjamin P.; Williams, Noelle S.; Tambar, Uttam K.; Wynn, R. Max; Chuang, David T.

2013-01-01

The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are elevated in maple syrup urine disease, heart failure, obesity, and type 2 diabetes. BCAA homeostasis is controlled by the mitochondrial branched-chain α-ketoacid dehydrogenase complex (BCKDC), which is negatively regulated by the specific BCKD kinase (BDK). Here, we used structure-based design to develop a BDK inhibitor, (S)-α-chloro-phenylpropionic acid [(S)-CPP]. Crystal structures of the BDK-(S)-CPP complex show that (S)-CPP binds to a unique allosteric site in the N-terminal domain, triggering helix movements in BDK. These conformational changes are communicated to the lipoyl-binding pocket, which nullifies BDK activity by blocking its binding to the BCKDC core. Administration of (S)-CPP to mice leads to the full activation and dephosphorylation of BCKDC with significant reduction in plasma BCAA concentrations. The results buttress the concept of targeting mitochondrial BDK as a pharmacological approach to mitigate BCAA accumulation in metabolic diseases and heart failure. PMID:23716694

Structure of Human G Protein-Coupled Receptor Kinase 2 in Complex with the Kinase Inhibitor Balanol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tesmer, John J.G.; Tesmer, Valerie M.; Lodowski, David T.

2010-07-19

G protein-coupled receptor kinase 2 (GRK2) is a pharmaceutical target for the treatment of cardiovascular diseases such as congestive heart failure, myocardial infarction, and hypertension. To better understand how nanomolar inhibition and selectivity for GRK2 might be achieved, we have determined crystal structures of human GRK2 in complex with G{beta}{gamma} in the presence and absence of the AGC kinase inhibitor balanol. The selectivity of balanol among human GRKs is assessed.

Analysis of the SWI/SNF chromatin-remodeling complex during early heart development and BAF250a repression cardiac gene transcription during P19 cell differentiation

PubMed Central

Singh, Ajeet Pratap; Archer, Trevor K.

2014-01-01

The regulatory networks of differentiation programs and the molecular mechanisms of lineage-specific gene regulation in mammalian embryos remain only partially defined. We document differential expression and temporal switching of BRG1-associated factor (BAF) subunits, core pluripotency factors and cardiac-specific genes during post-implantation development and subsequent early organogenesis. Using affinity purification of BRG1 ATPase coupled to mass spectrometry, we characterized the cardiac-enriched remodeling complexes present in E8.5 mouse embryos. The relative abundance and combinatorial assembly of the BAF subunits provides functional specificity to Switch/Sucrose NonFermentable (SWI/SNF) complexes resulting in a unique gene expression profile in the developing heart. Remarkably, the specific depletion of the BAF250a subunit demonstrated differential effects on cardiac-specific gene expression and resulted in arrhythmic contracting cardiomyocytes in vitro. Indeed, the BAF250a physically interacts and functionally cooperates with Nucleosome Remodeling and Histone Deacetylase (NURD) complex subunits to repressively regulate chromatin structure of the cardiac genes by switching open and poised chromatin marks associated with active and repressed gene expression. Finally, BAF250a expression modulates BRG1 occupancy at the loci of cardiac genes regulatory regions in P19 cell differentiation. These findings reveal specialized and novel cardiac-enriched SWI/SNF chromatin-remodeling complexes, which are required for heart formation and critical for cardiac gene expression regulation at the early stages of heart development. PMID:24335282

Role of organic cation/carnitine transporter 1 in uptake of phenformin and inhibitory effect on complex I respiration in mitochondria.

PubMed

Shitara, Yoshihisa; Nakamichi, Noritaka; Norioka, Misaki; Shima, Hiroyo; Kato, Yukio; Horie, Toshiharu

2013-03-01

Phenformin causes lactic acidosis in clinical situations due to inhibition of mitochondrial respiratory chain complex I. It is reportedly taken up by hepatocytes and exhibits mitochondrial toxicity in the liver. In this study, uptake of phenformin and [(14)C]tetraethylammonium (TEA) and complex I inhibition by phenformin were examined in isolated liver and heart mitochondria. Uptake of phenformin into isolated rat liver mitochondria was higher than that into heart mitochondria. It was inhibited by several cat ionic compounds, which suggests the involvement of multispecific transport system(s). Similar characteristics were also observed for uptake of TEA; however, uptake of phenformin into mitochondria of organic cation/carnitine transporter 1 (OCTN1) knockout mice was lower than that in wild-type mice, whereas uptake of TEA was comparable between the two strains, suggesting the involvement of distinct transport mechanisms for these two cations in mitochondria. Inhibition by phenformin of oxygen consumption via complex I respiration in isolated rat liver mitochondria was greater than that in heart mitochondria, whereas inhibitory effect of phenformin on complex I respiration was similar in inside-out structured submitochondrial particles prepared from rat livers and hearts. Lactic acidosis provoked by iv infusion of phenformin was weaker in octn1(-/-) mice than that in wild-type mice. These observations suggest that uptake of phenformin into liver mitochondria is at least partly mediated by OCTN1 and functionally relevant to its inhibition potential of complex I respiration. This study was, thus, the first to demonstrate OCTN1-mediated mitochondrial transport and toxicity of biguanide in vivo in rodents.

Classification and Quality Standards of Heart Failure Units: Scientific Consensus of the Spanish Society of Cardiology.

PubMed

Anguita Sánchez, Manuel; Lambert Rodríguez, José Luis; Bover Freire, Ramón; Comín Colet, Josep; Crespo Leiro, María G; González Vílchez, Francisco; Manito Lorite, Nicolás; Segovia Cubero, Javier; Ruiz Mateas, Francisco; Elola Somoza, Francisco Javier; Íñiguez Romo, Andrés

2016-10-01

The prevalence of heart failure remains high and represents the highest disease burden in Spain. Heart failure units have been developed to systematize the diagnosis, treatment, and clinical follow-up of heart failure patients, provide a structure to coordinate the actions of various entities and personnel involved in patient care, and improve prognosis and quality of life. There is ample evidence on the benefits of heart failure units or programs, which have become widespread in Spain. One of the challenges to the analysis of heart failure units is standardization of their classification, by determining which "programs" can be identified as heart failure "units" and by characterizing their complexity level. The aim of this article was to present the standards developed by the Spanish Society of Cardiology to classify and establish the requirements for heart failure units within the SEC-Excellence project. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

The helical ventricular myocardial band of Torrent-Guasp: potential implications in congenital heart defects.

PubMed

Corno, Antonio F; Kocica, Mladen J; Torrent-Guasp, Francisco

2006-04-01

The new concepts of cardiac anatomy and physiology, based on the observations made by Francisco Torrent-Guasp's discovery of the helical ventricular myocardial band, can be useful in the context of the surgical strategies currently used to manage patients with congenital heart defects. The potential impact of the Torrent-Guasp's Heart on congenital heart defects have been analyzed in the following settings: ventriculo-arterial discordance (transposition of the great arteries), double (atrio-ventricular and ventriculo-arterial) discordance (congenitally corrected transposition of the great arteries), Ebstein's anomaly, pulmonary valve regurgitation after repair of tetralogy of Fallot, Ross operation, and complex intra-ventricular malformations. The functional interaction of right and left ventricles occurs not only through their arrangements in series but also thanks to the structural spiral features. Changes in size and function of either ventricle may influence the performance of the other ventricle. The variety and complexity of congenital heart defects make the recognition of the relationship between form and function a vital component, especially when compared to acquired disease. The new concepts of cardiac anatomy and function proposed by Francisco Torrent-Guasp, based on his observations, should stimulate further investigations of alternative surgical strategies by individuals involved with the management of patients with congenital heart defects.

Conditional Creation and Rescue of Nipbl-Deficiency in Mice Reveals Multiple Determinants of Risk for Congenital Heart Defects

PubMed Central

Jacobs, Russell E.; Lopez-Burks, Martha E.; Choi, Hojae; Wikenheiser, Jamie; Hallgrimsson, Benedikt; Jamniczky, Heather A.; Fraser, Scott E.; Lander, Arthur D.; Calof, Anne L.

2016-01-01

Elucidating the causes of congenital heart defects is made difficult by the complex morphogenesis of the mammalian heart, which takes place early in development, involves contributions from multiple germ layers, and is controlled by many genes. Here, we use a conditional/invertible genetic strategy to identify the cell lineage(s) responsible for the development of heart defects in a Nipbl-deficient mouse model of Cornelia de Lange Syndrome, in which global yet subtle transcriptional dysregulation leads to development of atrial septal defects (ASDs) at high frequency. Using an approach that allows for recombinase-mediated creation or rescue of Nipbl deficiency in different lineages, we uncover complex interactions between the cardiac mesoderm, endoderm, and the rest of the embryo, whereby the risk conferred by genetic abnormality in any one lineage is modified, in a surprisingly non-additive way, by the status of others. We argue that these results are best understood in the context of a model in which the risk of heart defects is associated with the adequacy of early progenitor cell populations relative to the sizes of the structures they must eventually form. PMID:27606604

Tricuspid Regurgitation – Medical Management and Evolving Interventional Concepts

PubMed Central

Beckhoff, Frederik; Alushi, Brunilda; Jung, Christian; Navarese, Eliano; Franz, Marcus; Kretzschmar, Daniel; Wernly, Bernhard; Lichtenauer, Michael; Lauten, Alexander

2018-01-01

Severe tricuspid regurgitation (TR) is a complex condition of the right ventricle (RV) and tricuspid valve apparatus and is frequently associated with symptomatic heart failure and a significant morbidity and mortality. In these patients, left heart pathologies lead to chronic pressure overload of the RV, eventually causing progressive RV dilatation and functional TR. Therefore, TR cannot be considered as isolated heart valve disease pathology but has to be understood and treated as one component of a complex structural RV pathology and is frequently also a marker of an advanced stage of cardiac disease. In these patients, medical therapy restricted to diuretics and heart failure medication is frequently ineffective. Also, severe TR in the setting of advanced heart failure constitutes a high risk for cardiac surgery. Neither one of these treatment options has demonstrated a beneficial effect on long-term prognosis. The recent innovations in transcatheter technology led to efforts to develop interventional approaches to severe TR. Multiple innovative treatment concepts are currently under preclinical and clinical investigation to replace or repair TV function. However, up to date none of these approaches is established and there is still a lack of clinical data to support the efficacy of transcatheter TR treatment. PMID:29892601

A system for rapid prototyping of hearts with congenital malformations based on the medical imaging interaction toolkit (MITK)

NASA Astrophysics Data System (ADS)

Wolf, Ivo; Böttger, Thomas; Rietdorf, Urte; Maleike, Daniel; Greil, Gerald; Sieverding, Ludger; Miller, Stephan; Mottl-Link, Sibylle; Meinzer, Hans-Peter

2006-03-01

Precise knowledge of the individual cardiac anatomy is essential for diagnosis and treatment of congenital heart disease. Complex malformations of the heart can best be comprehended not from images but from anatomic specimens. Physical models can be created from data using rapid prototyping techniques, e.g., lasersintering or 3D-printing. We have developed a system for obtaining data that show the relevant cardiac anatomy from high-resolution CT/MR images and are suitable for rapid prototyping. The challenge is to preserve all relevant details unaltered in the produced models. The main anatomical structures of interest are the four heart cavities (atria, ventricles), the valves and the septum separating the cavities, and the great vessels. These can be shown either by reproducing the morphology itself or by producing a model of the blood-pool, thus creating a negative of the morphology. Algorithmically the key issue is segmentation. Practically, possibilities allowing the cardiologist or cardiac surgeon to interactively check and correct the segmentation are even more important due to the complex, irregular anatomy and imaging artefacts. The paper presents the algorithmic and interactive processing steps implemented in the system, which is based on the open-source Medical Imaging Interaction Toolkit (MITK, www.mitk.org). It is shown how the principles used in MITK enable to assemble the system from modules (functionalities) developed independently from each other. The system allows to produce models of the heart (and other anatomic structures) of individual patients as well as to reproduce unique specimens from pathology collections for teaching purposes.

Insulin Signaling and Heart Failure

PubMed Central

Riehle, Christian; Abel, E. Dale

2016-01-01

Heart failure is associated with generalized insulin resistance. Moreover, insulin resistant states such as type 2 diabetes and obesity increases the risk of heart failure even after adjusting for traditional risk factors. Insulin resistance or type 2 diabetes alters the systemic and neurohumoral milieu leading to changes in metabolism and signaling pathways in the heart that may contribute to myocardial dysfunction. In addition, changes in insulin signaling within cardiomyocytes develop in the failing heart. The changes range from activation of proximal insulin signaling pathways that may contribute to adverse left ventricular remodeling and mitochondrial dysfunction to repression of distal elements of insulin signaling pathways such as forkhead (FOXO) transcriptional signaling or glucose transport which may also impair cardiac metabolism, structure and function. This article will review the complexities of insulin signaling within the myocardium and ways in which these pathways are altered in heart failure or in conditions associated with generalized insulin resistance. The implications of these changes for therapeutic approaches to treating or preventing heart failure will be discussed. PMID:27034277

Perspective of Islamic Self: Rethinking Ibn al-Qayyim's Three-Heart Model from the Scope of Dynamical Social Psychology.

PubMed

Briki, Walid; Amara, Mahfoud

2018-06-01

The present article proposes the perspective of Islamic self (PIS), which is guided by three core principles. First, the Islamic self is shaped by the God's predicament: The life test. Second, the structure of the self and its spiritual virtues represent means to succeed the life test. Third, the complex dynamics of the self can be mathematically formalized into a parsimonious framework. Specifically, the PIS considers the self as a dynamical system characterized by the emergence of self-organized stable and unstable patterns taking the form of positive ("illuminating heart") or negative ("darkened heart") dynamics.

Case complexity scores in congenital heart surgery: a comparative study of the Aristotle Basic Complexity score and the Risk Adjustment in Congenital Heart Surgery (RACHS-1) system.

PubMed

Al-Radi, Osman O; Harrell, Frank E; Caldarone, Christopher A; McCrindle, Brian W; Jacobs, Jeffrey P; Williams, M Gail; Van Arsdell, Glen S; Williams, William G

2007-04-01

The Aristotle Basic Complexity score and the Risk Adjustment in Congenital Heart Surgery system were developed by consensus to compare outcomes of congenital cardiac surgery. We compared the predictive value of the 2 systems. Of all index congenital cardiac operations at our institution from 1982 to 2004 (n = 13,675), we were able to assign an Aristotle Basic Complexity score, a Risk Adjustment in Congenital Heart Surgery score, and both scores to 13,138 (96%), 11,533 (84%), and 11,438 (84%) operations, respectively. Models of in-hospital mortality and length of stay were generated for Aristotle Basic Complexity and Risk Adjustment in Congenital Heart Surgery using an identical data set in which both Aristotle Basic Complexity and Risk Adjustment in Congenital Heart Surgery scores were assigned. The likelihood ratio test for nested models and paired concordance statistics were used. After adjustment for year of operation, the odds ratios for Aristotle Basic Complexity score 3 versus 6, 9 versus 6, 12 versus 6, and 15 versus 6 were 0.29, 2.22, 7.62, and 26.54 (P < .0001). Similarly, odds ratios for Risk Adjustment in Congenital Heart Surgery categories 1 versus 2, 3 versus 2, 4 versus 2, and 5/6 versus 2 were 0.23, 1.98, 5.80, and 20.71 (P < .0001). Risk Adjustment in Congenital Heart Surgery added significant predictive value over Aristotle Basic Complexity (likelihood ratio chi2 = 162, P < .0001), whereas Aristotle Basic Complexity contributed much less predictive value over Risk Adjustment in Congenital Heart Surgery (likelihood ratio chi2 = 13.4, P = .009). Neither system fully adjusted for the child's age. The Risk Adjustment in Congenital Heart Surgery scores were more concordant with length of stay compared with Aristotle Basic Complexity scores (P < .0001). The predictive value of Risk Adjustment in Congenital Heart Surgery is higher than that of Aristotle Basic Complexity. The use of Aristotle Basic Complexity or Risk Adjustment in Congenital Heart Surgery as risk stratification and trending tools to monitor outcomes over time and to guide risk-adjusted comparisons may be valuable.

Knitting for heart valve tissue engineering

PubMed Central

Ayad, Nadia; Wojciechowska, Dorota; Zielińska, Dorota; Struszczyk, Marcin H.; Latif, Najma; Yacoub, Magdi

Knitting is a versatile technology which offers a large portfolio of products and solutions of interest in heart valve (HV) tissue engineering (TE). One of the main advantages of knitting is its ability to construct complex shapes and structures by precisely assembling the yarns in the desired position. With this in mind, knitting could be employed to construct a HV scaffold that closely resembles the authentic valve. This has the potential to reproduce the anisotropic structure that is characteristic of the heart valve with the yarns, in particular the 3-layered architecture of the leaflets. These yarns can provide oriented growth of cells lengthwise and consequently enable the deposition of extracellular matrix (ECM) proteins in an oriented manner. This technique, therefore, has a potential to provide a functional knitted scaffold, but to achieve that textile engineers need to gain a basic understanding of structural and mechanical aspects of the heart valve and in addition, tissue engineers must acquire the knowledge of tools and capacities that are essential in knitting technology. The aim of this review is to provide a platform to consolidate these two fields as well as to enable an efficient communication and cooperation among these two research areas. PMID:29043276

Structure and Function of Cardiac Troponin C (TNNC1): Implications for Heart Failure, Cardiomyopathies, and Troponin Modulating Drugs

PubMed Central

Li, Monica X.; Hwang, Peter M.

2015-01-01

In striated muscle, the protein troponin complex turns contraction on and off in a calcium-dependent manner. The calcium-sensing component of the complex is troponin C, which is expressed from the TNNC1 gene in both cardiac muscle and slow-twitch skeletal muscle (identical transcript in both tissues) and the TNNC2 gene in fast-twitch skeletal muscle. Cardiac troponin C (cTnC) is made up of two globular EF-hand domains connected by a flexible linker. The structural C-domain (cCTnC) contains two high affinity calcium-binding sites that are always occupied by Ca2+ or Mg2+ under physiologic conditions, stabilizing an open conformation that remains anchored to the rest of the troponin complex. In contrast, the regulatory N-domain (cNTnC) contains a single low affinity site that is largely unoccupied at resting calcium concentrations. During muscle activation, calcium binding to cNTnC favors an open conformation that binds to the switch region of troponin I, removing adjacent inhibitory regions of troponin I from actin and allowing muscle contraction to proceed. Regulation of the calcium binding affinity of cNTnC is physiologically important, because it directly impacts the calcium sensitivity of muscle contraction. Calcium sensitivity can be modified by drugs that stabilize the open form of cNTnC, post-translational modifications like phosphorylation of troponin I, or downstream thin filament protein interactions that impact the availability of the troponin I switch region. Recently, mutations in cTnC have been associated with hypertrophic or dilated cardiomyopathy. A detailed understanding of how calcium sensitivity is regulated through the troponin complex is necessary for explaining how mutations perturb its function to promote cardiomyopathy and how post-translational modifications in the thin filament affect heart function and heart failure. Troponin modulating drugs are being developed for the treatment of cardiomyopathies and heart failure. PMID:26232335

Fractals in physiology and medicine

NASA Technical Reports Server (NTRS)

Goldberger, Ary L.; West, Bruce J.

1987-01-01

The paper demonstrates how the nonlinear concepts of fractals, as applied in physiology and medicine, can provide an insight into the organization of such complex structures as the tracheobronchial tree and heart, as well as into the dynamics of healthy physiological variability. Particular attention is given to the characteristics of computer-generated fractal lungs and heart and to fractal pathologies in these organs. It is shown that alterations in fractal scaling may underlie a number of pathophysiological disturbances, including sudden cardiac death syndromes.

Heart and brain interaction in patients with heart failure: overview and proposal for a taxonomy. A position paper from the Study Group on Heart and Brain Interaction of the Heart Failure Association.

PubMed

Doehner, Wolfram; Ural, Dilek; Haeusler, Karl Georg; Čelutkienė, Jelena; Bestetti, Reinaldo; Cavusoglu, Yuksel; Peña-Duque, Marco A; Glavas, Duska; Iacoviello, Massimo; Laufs, Ulrich; Alvear, Ricardo Marmol; Mbakwem, Amam; Piepoli, Massimo F; Rosen, Stuart D; Tsivgoulis, Georgios; Vitale, Cristiana; Yilmaz, M Birhan; Anker, Stefan D; Filippatos, Gerasimos; Seferovic, Petar; Coats, Andrew J S; Ruschitzka, Frank

2018-02-01

Heart failure (HF) is a complex clinical syndrome with multiple interactions between the failing myocardium and cerebral (dys-)functions. Bi-directional feedback interactions between the heart and the brain are inherent in the pathophysiology of HF: (i) the impaired cardiac function affects cerebral structure and functional capacity, and (ii) neuronal signals impact on the cardiovascular continuum. These interactions contribute to the symptomatic presentation of HF patients and affect many co-morbidities of HF. Moreover, neuro-cardiac feedback signals significantly promote aggravation and further progression of HF and are causal in the poor prognosis of HF. The diversity and complexity of heart and brain interactions make it difficult to develop a comprehensive overview. In this paper a systematic approach is proposed to develop a comprehensive atlas of related conditions, signals and disease mechanisms of the interactions between the heart and the brain in HF. The proposed taxonomy is based on pathophysiological principles. Impaired perfusion of the brain may represent one major category, with acute (cardio-embolic) or chronic (haemodynamic failure) low perfusion being sub-categories with mostly different consequences (i.e. ischaemic stroke or cognitive impairment, respectively). Further categories include impairment of higher cortical function (mood, cognition), of brain stem function (sympathetic over-activation, neuro-cardiac reflexes). Treatment-related interactions could be categorized as medical, interventional and device-related interactions. Also interactions due to specific diseases are categorized. A methodical approach to categorize the interdependency of heart and brain may help to integrate individual research areas into an overall picture. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Late Administration of a Palladium Lipoic Acid Complex (POLY-MVA) Modifies Cardiac Mitochondria but Not Functional or Structural Manifestations of Radiation-Induced Heart Disease in a Rat Model

PubMed Central

Sridharan, Vijayalakshmi; Seawright, John W.; Antonawich, Francis J.; Garnett, Merrill; Cao, Maohua; Singh, Preeti; Boerma, Marjan

2017-01-01

Exposure of the heart to ionizing radiation can cause adverse myocardial remodeling. In small animal models, local heart irradiation causes persistent alterations in cardiac mitochondrial function and swelling. POLY-MVA is a dietary supplement that contains a palladium lipoic acid complex that targets mitochondrial complex I and has been demonstrated to have greater redox potential than lipoic acid alone. POLY-MVA improves mitochondrial function and anti-oxidant enzyme activity in the aged rat heart. In this study, we tested whether POLY-MVA can mitigate cardiac effects of ionizing radiation. Adult male rats were exposed to local heart X rays with a daily dose of 9 Gy for 5 consecutive days. Eighteen weeks after irradiation, POLY-MVA was administered orally at 1 ml/kg bodyweight per day during weekdays, for 6 weeks. Alterations in cardiac function as measured with echocardiography coincided with enhanced mitochondrial swelling, a reduction in mitochondrial expression of complex II, manifestations of adverse remodeling such as a reduction in myocardial microvessel density and an increase in collagen deposition and mast cell numbers. POLY-MVA enhanced left ventricular expression of superoxide dismutase 2, but only in sham-irradiated animals. In irradiated animals, POLY-MVA caused a reduction in markers of inflammatory infiltration, CD2 and CD68. Moreover, POLY-MVA mitigated the effects of radiation on mitochondria. Nonetheless, POLY-MVA did not mitigate adverse cardiac remodeling, suggesting that this tissue remodeling may not be alleviated by altering cardiac mitochondria alone. However, we cannot exclude the possibility that an earlier onset of POLY-MVA administration may have more profound effects on radiation-induced cardiac remodeling. PMID:28231026

Sudden cardiac death in adults with congenital heart disease: does QRS-complex fragmentation discriminate in structurally abnormal hearts?

PubMed

Vehmeijer, Jim T; Koyak, Zeliha; Bokma, Jouke P; Budts, Werner; Harris, Louise; Mulder, Barbara J M; de Groot, Joris R

2018-06-01

Sudden cardiac death (SCD) causes a large portion of all mortality in adult congenital heart disease (ACHD) patients. However, identification of high-risk patients remains challenging. Fragmented QRS-complexes (fQRS) are a marker for SCD in patients with acquired heart disease but data in ACHD patients are lacking. We therefore aim to evaluate the prognostic value of fQRS for SCD in ACHD patients. From a multicentre cohort of 25 790 ACHD patients, we included tachyarrhythmic SCD cases (n = 147), and controls (n = 266) matched by age, gender, congenital defect and (surgical) intervention. fQRS was defined as ≥1 discontinuous deflection in narrow QRS-complexes, and ≥2 in wide QRS-complexes (>120 ms), in two contiguous ECG leads. We calculated odds ratios (OR) using univariable and multivariable conditional logistic regression models correcting for impaired systemic ventricular function, heart failure and QRS duration >120 ms. ECGs of 147 SCD cases (65% male, median age of death 34 years) and of 266 controls were assessed. fQRS was present in 51% of cases and 34% of controls (OR 2.0, P = 0.003). In multivariable analysis, fQRS was independently associated with SCD (OR 1.9, P = 0.01). The most common diagnose of SCD cases was tetralogy of Fallot (ToF, 34 cases). In ToF, fQRS was present in 71% of cases vs. 43% of controls (OR for SCD 2.8, P = 0.03). fQRS was independently associated with SCD in ACHD patients in a cohort of SCD patients and matched controls. fQRS may therefore contribute to the decision when evaluating ACHD patients for primary prevention of SCD.

Channelopathies from Mutations in the Cardiac Sodium Channel Protein Complex

PubMed Central

Adsit, Graham S.; Vaidyanathan, Ravi; Galler, Carla M.; Kyle, John W.; Makielski, Jonathan C.

2013-01-01

The cardiac sodium current underlies excitability in heart, and inherited abnormalities of the proteins regulating and conducting this current cause inherited arrhythmia syndromes. This review focuses on inherited mutations in non-pore forming proteins of sodium channel complexes that cause cardiac arrhythmia, and the deduced mechanisms by which they affect function and dysfunction of the cardiac sodium current. Defining the structure and function of these complexes and how they are regulated will contribute to understanding the possible roles for this complex in normal and abnormal physiology and homeostasis. PMID:23557754

Cultural factors influencing dietary and fluid restriction behaviour: perceptions of older Chinese patients with heart failure.

PubMed

Rong, Xiaoshan; Peng, Youqing; Yu, Hai-Ping; Li, Dan

2017-03-01

To explore the cultural factors related to dietary and fluid restriction behaviours among older Chinese patients. Excess dietary sodium and fluid intake are risk factors contributing to the worsening and rehospitalisation for heart failure in older patients. Managing the complex fluid and diet requirements of heart failure patients is challenging and is made more complicated by cultural variations in self-management behaviours in response to a health threat. Qualitative study using semi-structured in interviews and framework analysis. The design of this study is qualitative descriptive. Semi-structured in-depth interviews were conducted with 15 heart failure patients. Data were analysed through content analysis. Seven cultural themes emerged from the qualitative data: the values placed on health and illness, customary way of life, preference for folk care and the Chinese healthcare system, and factors related to kinship and social ties, religion, economics and education. Dietary change and management in response to illness, including heart failure, is closely related to individuals' cultural background. Healthcare providers should have a good understanding of cultural aspects that can influence patients' conformity to medical recommendations. Heart failure patients need support that considers their cultural needs. Healthcare providers must have a good understanding of the experiences of people from diverse cultural backgrounds. © 2016 John Wiley & Sons Ltd.

Bioinorganic Activity of Technetium Radiopharmaceuticals.

ERIC Educational Resources Information Center

Pinkerton, Thomas C.; And Others

1985-01-01

Technetium radiopharmaceuticals are diagnostic imaging agents used in the field of nuclear medicine to visualize tissues, anatomical structures, and metabolic disorders. Bioavailability of technetium complexes, thyroid imaging, brain imaging, kidney imaging, imaging liver function, bone imaging, and heart imaging are the major areas discussed. (JN)

Myocardin-related transcription factors are required for cardiac development and function

PubMed Central

Mokalled, Mayssa H.; Carroll, Kelli J.; Cenik, Bercin K.; Chen, Beibei; Liu, Ning; Olson, Eric N.; Bassel-Duby, Rhonda

2016-01-01

Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the developing or adult heart has not been explored. Through cardiac-specific deletion of MRTF alleles in mice, we show that either MRTF-A or MRTF-B is dispensable for cardiac development and function, whereas deletion of both MRTF-A and MRTF-B causes a spectrum of structural and functional cardiac abnormalities. Defects observed in MRTF-A/B null mice ranged from reduced cardiac contractility and adult onset heart failure to neonatal lethality accompanied by sarcomere disarray. RNA-seq analysis on neonatal hearts identified the most altered pathways in MRTF double knockout hearts as being involved in cytoskeletal organization. Together, these findings demonstrate redundant but essential roles of the MRTFs in maintenance of cardiac structure and function and as indispensible links in cardiac cytoskeletal gene regulatory networks. PMID:26386146

Pathophysiologic Mechanisms in Heart Failure: Role of the Sympathetic Nervous System.

PubMed

Antoine, Steve; Vaidya, Gaurang; Imam, Haider; Villarreal, Daniel

2017-01-01

The syndrome of heart failure involves complex pathophysiologic mechanisms and is associated with extremely high-morbidity, mortality and economic costs. This growing global epidemic has diverse etiologies and is fundamentally characterized by dyshomeostasis between heart and kidneys, leading to development and progression of the cardiorenal syndrome. Excessive and sustained sympathoexcitation has emerged as a single prominent factor involved in the structural and functional dysfunction of multiple organ systems during this disease. Studies in experimental models of heart failure indicate that ablation of the renal nerves may help restore renal sodium and water equilibrium as well as the attenuation of adverse cardiac remodeling. With the recent development of minimally invasive endovascular renal denervation in humans, it is anticipated that this technology would become a novel and important paradigm shift in the management of heart failure. Copyright © 2017. Published by Elsevier Inc.

Mitochondrial Bioenergetics and Dysfunction in Failing Heart.

PubMed

Sheeran, Freya L; Pepe, Salvatore

2017-01-01

Energy insufficiency has been recognized as a key feature of systolic heart failure. Although mitochondria have long been known to sustain myocardial work energy supply, the capacity to therapeutically target mitochondrial bioenergetics dysfunction is hampered by a complex interplay of multiple perturbations that progressively compound causing myocardial failure and collapse. Compared to non-failing human donor hearts, activity rates of complexes I and IV, nicotinamide nucleotide transhydrogenase (NADPH-transhydrogenase, Nnt) and the Krebs cycle enzymes isocitrate dehydrogenase, malate dehydrogenase and aconitase are markedly decreased in end-stage heart failure. Diminished REDOX capacity with lower total glutathione and coenzyme Q 10 levels are also a feature of chronic left ventricular failure. Decreased enzyme activities in part relate to abundant and highly specific oxidative, nitrosylative, and hyperacetylation modifications. In this brief review we highlight that energy deficiency in end-stage failing human left ventricle predominantly involves concomitantly impaired activities of key electron transport chain and Krebs cycle enzymes rather than altered expression of respective genes or proteins. Augmented oxidative modification of these enzyme subunit structures, and the formation of highly reactive secondary metabolites, implicates dysfunction due to diminished capacity for management of mitochondrial reactive oxygen species, which contribute further to progressive decreases in bioenergetic capacity and contractile function in human heart failure.

Bioengineering Human Myocardium on Native Extracellular Matrix

PubMed Central

Guyette, Jacques P.; Charest, Jonathan M; Mills, Robert W; Jank, Bernhard J.; Moser, Philipp T.; Gilpin, Sarah E.; Gershlak, Joshua R.; Okamoto, Tatsuya; Gonzalez, Gabriel; Milan, David J.; Gaudette, Glenn R.; Ott, Harald C.

2015-01-01

Rationale More than 25 million individuals suffer from heart failure worldwide, with nearly 4,000 patients currently awaiting heart transplantation in the United States. Donor organ shortage and allograft rejection remain major limitations with only about 2,500 hearts transplanted each year. As a theoretical alternative to allotransplantation, patient-derived bioartificial myocardium could provide functional support and ultimately impact the treatment of heart failure. Objective The objective of this study is to translate previous work to human scale and clinically relevant cells, for the bioengineering of functional myocardial tissue based on the combination of human cardiac matrix and human iPS-derived cardiac myocytes. Methods and Results To provide a clinically relevant tissue scaffold, we translated perfusion-decellularization to human scale and obtained biocompatible human acellular cardiac scaffolds with preserved extracellular matrix composition, architecture, and perfusable coronary vasculature. We then repopulated this native human cardiac matrix with cardiac myocytes derived from non-transgenic human induced pluripotent stem cells (iPSCs) and generated tissues of increasing three-dimensional complexity. We maintained such cardiac tissue constructs in culture for 120 days to demonstrate definitive sarcomeric structure, cell and matrix deformation, contractile force, and electrical conduction. To show that functional myocardial tissue of human scale can be built on this platform, we then partially recellularized human whole heart scaffolds with human iPSC-derived cardiac myocytes. Under biomimetic culture, the seeded constructs developed force-generating human myocardial tissue, showed electrical conductivity, left ventricular pressure development, and metabolic function. Conclusions Native cardiac extracellular matrix scaffolds maintain matrix components and structure to support the seeding and engraftment of human iPS-derived cardiac myocytes, and enable the bioengineering of functional human myocardial-like tissue of multiple complexities. PMID:26503464

Automated assessment of blood flow in developing embryonic hearts by extending dynamic range of Doppler OCT using a MHz FDML swept laser source (Conference Presentation)

NASA Astrophysics Data System (ADS)

Elahi, Sahar; Thrane, Lars; Rollins, Andrew M.; Jenkins, Michael W.

2017-02-01

Altered hemodynamics in developing embryonic hearts lead to congenital heart diseases, motivating close monitoring of blood flow over several stages of development. Doppler OCT can assess blood flow in tubular hearts, but the maximum velocity increases drastically during the period of cardiac cushion (valve precursors) formation. Therefore, the limited dynamic range of Doppler OCT velocity measurement makes it difficult to conduct longitudinal studies without phase wrapping at high velocities or loss of sensitivity to slow velocities. We have built a high-speed OCT system using an FDML laser (Optores GmbH, Germany) at a sweep rate of 1.68 MHz (axial resolution - 12 μm, sensitivity - 105 dB, phase stability - 17 mrad). The speed of this OCT system allows us to acquire high-density B-scans to obtain an extended velocity dynamic range without sacrificing the frame rate. The extended dynamic range within a frame is achieved by varying the A-scan interval at which the phase difference is found, enabling detection of velocities ranging from tens of microns per second to hundreds of mm per second. The extra lines in a frame can also be utilized to improve the structural and Doppler images via complex averaging. In structural images where presence of blood causes additional scattering, complex averaging helps retrieve features located deeper in the tissue. Moreover, high-density frames can be registered to 4D volumes to determine the orthogonal direction of flow and calculate shear stress. In conclusion, our high-speed OCT system will enable automated Doppler imaging of embryonic hearts in cohort studies.

Reliable Real-time Calculation of Heart-rate Complexity in Critically Ill Patients Using Multiple Noisy Waveform Sources

DTIC Science & Technology

2014-01-01

systems Machine learning Automatic data processing 1 Introduction Heart-rate complexity (HRC) is a method of quantifying the amount of complex...5. Batchinsky AI, Skinner J, Necsoiu C, et al. New measures of heart-rate complexity: effect of chest trauma and hemorrhage. J Trauma. 2010;68:1178–85

A machine learning model to predict the risk of 30-day readmissions in patients with heart failure: a retrospective analysis of electronic medical records data.

PubMed

Golas, Sara Bersche; Shibahara, Takuma; Agboola, Stephen; Otaki, Hiroko; Sato, Jumpei; Nakae, Tatsuya; Hisamitsu, Toru; Kojima, Go; Felsted, Jennifer; Kakarmath, Sujay; Kvedar, Joseph; Jethwani, Kamal

2018-06-22

Heart failure is one of the leading causes of hospitalization in the United States. Advances in big data solutions allow for storage, management, and mining of large volumes of structured and semi-structured data, such as complex healthcare data. Applying these advances to complex healthcare data has led to the development of risk prediction models to help identify patients who would benefit most from disease management programs in an effort to reduce readmissions and healthcare cost, but the results of these efforts have been varied. The primary aim of this study was to develop a 30-day readmission risk prediction model for heart failure patients discharged from a hospital admission. We used longitudinal electronic medical record data of heart failure patients admitted within a large healthcare system. Feature vectors included structured demographic, utilization, and clinical data, as well as selected extracts of un-structured data from clinician-authored notes. The risk prediction model was developed using deep unified networks (DUNs), a new mesh-like network structure of deep learning designed to avoid over-fitting. The model was validated with 10-fold cross-validation and results compared to models based on logistic regression, gradient boosting, and maxout networks. Overall model performance was assessed using concordance statistic. We also selected a discrimination threshold based on maximum projected cost saving to the Partners Healthcare system. Data from 11,510 patients with 27,334 admissions and 6369 30-day readmissions were used to train the model. After data processing, the final model included 3512 variables. The DUNs model had the best performance after 10-fold cross-validation. AUCs for prediction models were 0.664 ± 0.015, 0.650 ± 0.011, 0.695 ± 0.016 and 0.705 ± 0.015 for logistic regression, gradient boosting, maxout networks, and DUNs respectively. The DUNs model had an accuracy of 76.4% at the classification threshold that corresponded with maximum cost saving to the hospital. Deep learning techniques performed better than other traditional techniques in developing this EMR-based prediction model for 30-day readmissions in heart failure patients. Such models can be used to identify heart failure patients with impending hospitalization, enabling care teams to target interventions at their most high-risk patients and improving overall clinical outcomes.

Three-dimensional printing of complex biological structures by freeform reversible embedding of suspended hydrogels

PubMed Central

Hinton, Thomas J.; Jallerat, Quentin; Palchesko, Rachelle N.; Park, Joon Hyung; Grodzicki, Martin S.; Shue, Hao-Jan; Ramadan, Mohamed H.; Hudson, Andrew R.; Feinberg, Adam W.

2015-01-01

We demonstrate the additive manufacturing of complex three-dimensional (3D) biological structures using soft protein and polysaccharide hydrogels that are challenging or impossible to create using traditional fabrication approaches. These structures are built by embedding the printed hydrogel within a secondary hydrogel that serves as a temporary, thermoreversible, and biocompatible support. This process, termed freeform reversible embedding of suspended hydrogels, enables 3D printing of hydrated materials with an elastic modulus <500 kPa including alginate, collagen, and fibrin. Computer-aided design models of 3D optical, computed tomography, and magnetic resonance imaging data were 3D printed at a resolution of ~200 μm and at low cost by leveraging open-source hardware and software tools. Proof-of-concept structures based on femurs, branched coronary arteries, trabeculated embryonic hearts, and human brains were mechanically robust and recreated complex 3D internal and external anatomical architectures. PMID:26601312

Current Interventional and Surgical Management of Congenital Heart Disease: Specific Focus on Valvular Disease and Cardiac Arrhythmias.

PubMed

Holst, Kimberly A; Said, Sameh M; Nelson, Timothy J; Cannon, Bryan C; Dearani, Joseph A

2017-03-17

Successful outcome in the care of patients with congenital heart disease depends on a comprehensive multidisciplinary team. Surgery is offered for almost every heart defect, despite complexity. Early mortality for cardiac surgery in the neonatal period is ≈10% and beyond infancy is <5%, with 90% to 95% of patients surviving with a good quality of life into the adult years. Advances in imaging have facilitated accurate diagnosis and planning of interventions and surgical procedures. Similarly, advances in the perioperative medical management of patients, particularly with intensive care, has also contributed to improving outcomes. Arrhythmias and heart failure are the most common late complications for the majority of defects, and reoperation for valvar problems is common. Lifelong surveillance for monitoring of recurrent or residual structural heart defects, as well as periodic assessment of cardiac function and arrhythmia monitoring, is essential for all patients. The field of congenital heart surgery is poised to incorporate new innovations such as bioengineered cells and scaffolds that will iteratively move toward bioengineered patches, conduits, valves, and even whole organs. © 2017 American Heart Association, Inc.

Implantation of VVI pacemaker in a patient with dextrocardia, persistent left superior vena cava, and sick sinus syndrome

PubMed Central

Guo, Gongliang; Yang, Lili; Wu, Jinyi; Sun, Liqun

2017-01-01

Abstract Background: Dextrocardia, or right-lying heart, is an uncommon congenital heart disease in which the apex of the heart is located on the right side of chest. Persistent left superior vena cava (PLSVA) is a rare venous anomaly that is often associated with the abnormalities of cardiac transduction system. A case with combination of dextrocardia, persistent left superior vena cava, and sick sinus syndrome has not been reported. Methods: We used different techniques including cardiac color Doppler echocardiography, 24-hour Holter monitoring, and abdominal ultrasound to make a diagnosis and treated the patient by implanting a VVI pacemaker. Results: A 50-year-old woman was admitted with a syncope. Angiography of the right atrium and superior vena cava, echocardiography, electrocardiography, and abdominal ultrasound revealed the presence of the combination of mirror image dextrocardia, PLSVA, and sick sinus syndrome. The complex structural anomalies presented great technical challenges for interventional treatments. After thorough examination and understanding of the structural anatomy and anomalies of the superior and inferior vena cava and cardiac chambers, we successfully treated this patient by implanting a VVI pacemaker. Conclusion: Physicians must be aware of the complexity of the morphological and anatomical structures of dextrocardia accompanying PLSVC. Given that the diagnosis of situs inversus was performed at a relatively advanced age, it is therefore important to make such a correct diagnosis followed by appropriate therapeutic intervention. PMID:28151908

[Recurrence plot analysis of HRV for brain ischemia and asphyxia].

PubMed

Chen, Xiaoming; Qiu, Yihong; Zhu, Yisheng

2008-02-01

Heart rate variability (HRV) is the tiny variability existing in the cycles of the heart beats, which reflects the corresponding balance between sympathetic and vagus nerves. Since the nonlinear characteristic of HRV is confirmed, the Recurrence Plot method, a nonlinear dynamic analysis method based on the complexity, could be used to analyze HRV. The results showed the recurrence plot structures and some quantitative indices (L-Mean, L-Entr) during asphyxia insult vary significantly as compared to those in normal conditions, which offer a new method to monitor brain asphyxia injury.

Respiration and heart rate complexity: Effects of age and gender assessed by band-limited transfer entropy

PubMed Central

Nemati, Shamim; Edwards, Bradley A.; Lee, Joon; Pittman-Polletta, Benjamin; Butler, James P.; Malhotra, Atul

2013-01-01

Aging and disease are accompanied with a reduction of complex variability in the temporal patterns of heart rate. This reduction has been attributed to a break down of the underlying regulatory feedback mechanisms that maintain a homeodynamic state. Previous work has established the utility of entropy as an index of disorder, for quantification of changes in heart rate complexity. However, questions remain regarding the origin of heart rate complexity and the mechanisms involved in its reduction with aging and disease. In this work we use a newly developed technique based on the concept of band-limited transfer entropy to assess the aging-related changes in contribution of respiration and blood pressure to entropy of heart rate at different frequency bands. Noninvasive measurements of heart beat interval, respiration, and systolic blood pressure were recorded from 20 young (21–34 years) and 20 older (68–85 years) healthy adults. Band-limited transfer entropy analysis revealed a reduction in high-frequency contribution of respiration to heart rate complexity (p < 0.001) with normal aging, particularly in men. These results have the potential for dissecting the relative contributions of respiration and blood pressure-related reflexes to heart rate complexity and their degeneration with normal aging. PMID:23811194

Infant health after heart surgery.

PubMed

2016-11-08

Background The number of infants who survive initial surgery for complex congenital heart disease (CHD), such as hypoplastic left heart syndrome, is increasing, but they are often left with residual complex health needs.

Heart transplantation in adults with congenital heart disease.

PubMed

Houyel, Lucile; To-Dumortier, Ngoc-Tram; Lepers, Yannick; Petit, Jérôme; Roussin, Régine; Ly, Mohamed; Lebret, Emmanuel; Fadel, Elie; Hörer, Jürgen; Hascoët, Sébastien

2017-05-01

With the advances in congenital cardiac surgery and postoperative care, an increasing number of children with complex congenital heart disease now reach adulthood. There are already more adults than children living with a congenital heart defect, including patients with complex congenital heart defects. Among these adults with congenital heart disease, a significant number will develop ventricular dysfunction over time. Heart failure accounts for 26-42% of deaths in adults with congenital heart defects. Heart transplantation, or heart-lung transplantation in Eisenmenger syndrome, then becomes the ultimate therapeutic possibility for these patients. This population is deemed to be at high risk of mortality after heart transplantation, although their long-term survival is similar to that of patients transplanted for other reasons. Indeed, heart transplantation in adults with congenital heart disease is often challenging, because of several potential problems: complex cardiac and vascular anatomy, multiple previous palliative and corrective surgeries, and effects on other organs (kidney, liver, lungs) of long-standing cardiac dysfunction or cyanosis, with frequent elevation of pulmonary vascular resistance. In this review, we focus on the specific problems relating to heart and heart-lung transplantation in this population, revisit the indications/contraindications, and update the long-term outcomes. Copyright © 2017. Published by Elsevier Masson SAS.

The Diamond Light Source and the challenges ahead for structural biology: some informal remarks.

PubMed

Ramakrishnan, V

2015-03-06

The remarkable advances in structural biology in the past three decades have led to the determination of increasingly complex structures that lie at the heart of many important biological processes. Many of these advances have been made possible by the use of X-ray crystallography using synchrotron radiation. In this short article, some of the challenges and prospects that lie ahead will be summarized. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Crystal Structure of Heart 6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase (PFKFB2) and the Inhibitory Influence of Citrate on Substrate Binding

PubMed Central

Crochet, Robert B.; Kim, Jeong-Do; Lee, Herie; Yim, Young-Sun; Kim, Song-Gun; Neau, David; Lee, Yong-Hwan

2016-01-01

The heart-specific isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB2) is an important regulator of glycolytic flux in cardiac cells. Here, we present the crystal structures of two PFKFB2 orthologues, human and bovine, at resolutions of 2.0 and 1.8Å, respectively. Citrate, a TCA cycle intermediate and well-known inhibitor of PFKFB2, co-crystallized in the 2-kinase domains of both orthologues, occupying the fructose-6-phosphate binding-site and extending into the γ-phosphate binding pocket of ATP. This steric and electrostatic occlusion of the γ-phosphate site by citrate proved highly consequential to the binding of co-complexed ATP analogues. The bovine structure, which co-crystallized with ADP, closely resembled the overall structure of other PFKFB isoforms, with ADP mimicking the catalytic binding mode of ATP. The human structure, on the other hand, co-complexed with AMPPNP, which, unlike ADP, contains a γ-phosphate. The presence of this γ-phosphate made adoption of the catalytic ATP binding mode impossible for AMPPNP, forcing the analogue to bind atypically with concomitant conformational changes to the ATP binding-pocket. Inhibition kinetics were used to validate the structural observations, confirming citrate’s inhibition mechanism as competitive for F6P and noncompetitive for ATP. Together, these structural and kinetic data establish a molecular basis for citrate’s negative feed-back loop of the glycolytic pathway via PFKFB2. PMID:27802586

Cardiac troponin T is necessary for normal development in the embryonic chick heart.

PubMed

England, Jennifer; Pang, Kar Lai; Parnall, Matthew; Haig, Maria Isabel; Loughna, Siobhan

2016-09-01

The heart is the first functioning organ to develop during embryogenesis. The formation of the heart is a tightly regulated and complex process, and alterations to its development can result in congenital heart defects. Mutations in sarcomeric proteins, such as alpha myosin heavy chain and cardiac alpha actin, have now been associated with congenital heart defects in humans, often with atrial septal defects. However, cardiac troponin T (cTNT encoded by gene TNNT2) has not. Using gene-specific antisense oligonucleotides, we have investigated the role of cTNT in chick cardiogenesis. TNNT2 is expressed throughout heart development and in the postnatal heart. TNNT2-morpholino treatment resulted in abnormal atrial septal growth and a reduction in the number of trabeculae in the developing primitive ventricular chamber. External analysis revealed the development of diverticula from the ventricular myocardial wall which showed no evidence of fibrosis and still retained a myocardial phenotype. Sarcomeric assembly appeared normal in these treated hearts. In humans, congenital ventricular diverticulum is a rare condition, which has not yet been genetically associated. However, abnormal haemodynamics is known to cause structural defects in the heart. Further, structural defects, including atrial septal defects and congenital diverticula, have previously been associated with conduction anomalies. Therefore, to provide mechanistic insights into the effect that cTNT knockdown has on the developing heart, quantitative PCR was performed to determine the expression of the shear stress responsive gene NOS3 and the conduction gene TBX3. Both genes were differentially expressed compared to controls. Therefore, a reduction in cTNT in the developing heart results in abnormal atrial septal formation and aberrant ventricular morphogenesis. We hypothesize that alterations to the haemodynamics, indicated by differential NOS3 expression, causes these abnormalities in growth in cTNT knockdown hearts. In addition, the muscular diverticula reported here suggest a novel role for mutations of structural sarcomeric proteins in the pathogenesis of congenital cardiac diverticula. From these studies, we suggest TNNT2 is a gene worthy of screening for those with a congenital heart defect, particularly atrial septal defects and ventricular diverticula. © 2016 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.

Revascularization heart team recommendations as an adjunct to appropriate use criteria for coronary revascularization in patients with complex coronary artery disease.

PubMed

Sanchez, Carlos E; Dota, Anthony; Badhwar, Vinay; Kliner, Dustin; Smith, A J Conrad; Chu, Danny; Toma, Catalin; Wei, Lawrence; Marroquin, Oscar C; Schindler, John; Lee, Joon S; Mulukutla, Suresh R

2016-10-01

To evaluate how a comprehensive evidence-based clinical review by a multidisciplinary revascularization heart team on treatment decisions for revascularization in patients with complex coronary artery disease using SYNTAX scores combined with Society of Thoracic Surgeons-derived clinical variables can be additive to the utilization of Appropriate Use Criteria for coronary revascularization. Decision-making regarding the use of revascularization for coronary artery disease has come under major scrutiny due to inappropriate overuse of revascularization. There is little data in routine clinical practice evaluating how a structured, multidisciplinary heart team approach may be used in combination with the Appropriate Use Criteria for revascularization. From May 1, 2012 to January 1, 2015, multidisciplinary revascularization heart team meetings were convened to discuss evidence-based management of 301 patients with complex coronary artery disease. Heart team recommendations were adjudicated with the Appropriate Use Criteria for coronary revascularization for each clinical scenario using the Society for Cardiovascular Angiography and Interventions' Quality Improvement Toolkit (SCAI-QIT) Appropriate Use Criteria App. Concordance of the Heart Team to Appropriate Use Criteria had a 99.3% appropriate primary indication for coronary revascularization. Among patients who underwent percutaneous revascularization, 34.9% had an inappropriate or uncertain indication as recommended by the Heart Team. Patients with uncertain or inappropriate percutaneous coronary interventions had significantly higher SYNTAX score (27.3 ± 6.6; 28.5 ± 5.5; 19.2 ± 6; P < 0.0001) and Society of Thoracic Surgeons-Predicted Risk of Mortality (6.1% ± 4.7%; 8.1% ± 6.3%; 3.7% ± 4.1%; P < 0.0081) compared to appropriate indications, frequently had concomitant forms of advanced comorbidities and frailty in the setting of symptomatic coronary artery disease. A formal, multidisciplinary revascularization heart team can provide proper validation for clinical decisions and should be considered in combination with the Appropriate Use Criteria for coronary revascularization to formulate revascularization strategies for individuals in a patient-centered fashion. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Titanium dioxide nanoparticle-induced cytotoxicity and the underlying mechanism in mouse myocardial cells

NASA Astrophysics Data System (ADS)

Zhou, Yingjun; Hong, Fashui; Wang, Ling

2017-11-01

Exposure to fine particulate matter (PM) is known to cause cardiovascular disease. While extensive research has focused on the risk of atmospheric PM to public health, particularly heart disease, limited studies to date have attempted to clarify the molecular mechanisms underlying myocardial cell damage caused by exposure to titanium dioxide nanoparticles (TiO2 NPs). Data from the current investigation showed that TiO2 NPs are deposited in myocardial mitochondria via the blood circulation accompanied by obvious ultrastructural changes and impairment of mitochondrial structure and function in mouse myocardial cells, including reduction in mitochondrial membrane potential and ATP production, aggravation of oxidative stress along with increased levels of reactive oxygen species, malondialdehyde and protein carbonyl, and decreased glutathione content and enzymatic activities, including superoxide dismutase and glutathione peroxidase. Furthermore, TiO2 NPs induced a significant decrease in the activities of complex I, complex II, complex III, complex IV, succinate dehydrogenase, NADH oxidase, Ca2+-ATPase, Na+/K+-ATPase, and Ca2+/Mg2+-ATPase, and upregulation of cytokine expression (including cytochrome c, caspase-3, and p-JNK) in mitochondria-mediated apoptosis while downregulating Bcl-2 expression in mouse myocardial cells. Our results collectively indicate that chronic exposure to TiO2 NPs induces damage in mitochondrial structure and function as well as mitochondria-mediated apoptosis in mouse myocardial cells, which may be closely associated with heart disease in animals and humans.

Geographic differences in heart failure trials.

PubMed

Ferreira, João Pedro; Girerd, Nicolas; Rossignol, Patrick; Zannad, Faiez

2015-09-01

Randomized controlled trials (RCTs) are essential to develop advances in heart failure (HF). The need for increasing numbers of patients (without substantial cost increase) and generalization of results led to the disappearance of international boundaries in large RCTs. The significant geographic differences in patients' characteristics, outcomes, and, most importantly, treatment effect observed in HF trials have recently been highlighted. Whether the observed regional discrepancies in HF trials are due to trial-specific issues, patient heterogeneity, structural differences in countries, or a complex interaction between factors are the questions we propose to debate in this review. To do so, we will analyse and review data from HF trials conducted in different world regions, from heart failure with preserved ejection fraction (HF-PEF), heart failure with reduced ejection fraction (HF-REF), and acute heart failure (AHF). Finally, we will suggest objective and actionable measures in order to mitigate regional discrepancies in future trials, particularly in HF-PEF where prognostic modifying treatments are urgently needed and in which trials are more prone to selection bias, due to a larger patient heterogeneity. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis.

PubMed

Luna-Zurita, Luis; Stirnimann, Christian U; Glatt, Sebastian; Kaynak, Bogac L; Thomas, Sean; Baudin, Florence; Samee, Md Abul Hassan; He, Daniel; Small, Eric M; Mileikovsky, Maria; Nagy, Andras; Holloway, Alisha K; Pollard, Katherine S; Müller, Christoph W; Bruneau, Benoit G

2016-02-25

Transcription factors (TFs) are thought to function with partners to achieve specificity and precise quantitative outputs. In the developing heart, heterotypic TF interactions, such as between the T-box TF TBX5 and the homeodomain TF NKX2-5, have been proposed as a mechanism for human congenital heart defects. We report extensive and complex interdependent genomic occupancy of TBX5, NKX2-5, and the zinc finger TF GATA4 coordinately controlling cardiac gene expression, differentiation, and morphogenesis. Interdependent binding serves not only to co-regulate gene expression but also to prevent TFs from distributing to ectopic loci and activate lineage-inappropriate genes. We define preferential motif arrangements for TBX5 and NKX2-5 cooperative binding sites, supported at the atomic level by their co-crystal structure bound to DNA, revealing a direct interaction between the two factors and induced DNA bending. Complex interdependent binding mechanisms reveal tightly regulated TF genomic distribution and define a combinatorial logic for heterotypic TF regulation of differentiation. Copyright © 2016 Elsevier Inc. All rights reserved.

Site-specific quantitative analysis of cardiac mitochondrial protein phosphorylation.

PubMed

Lam, Maggie P Y; Lau, Edward; Scruggs, Sarah B; Wang, Ding; Kim, Tae-Young; Liem, David A; Zhang, Jun; Ryan, Christopher M; Faull, Kym F; Ping, Peipei

2013-04-09

We report the development of a multiple-reaction monitoring (MRM) strategy specifically tailored to the detection and quantification of mitochondrial protein phosphorylation. We recently derived 68 MRM transitions specific to protein modifications in the respiratory chain, voltage-dependent anion channel, and adenine nucleotide translocase. Here, we have now expanded the total number of MRM transitions to 176 to cover proteins from the tricarboxylic acid cycle, pyruvate dehydrogenase complex, and branched-chain alpha-keto acid dehydrogenase complex. We utilized the transition set to analyze endogenous protein phosphorylation in human heart, mouse heart, and mouse liver. The data demonstrate the potential utility of the MRM workflow for studying the functional details of mitochondrial phosphorylation signaling. This article is part of a Special Issue entitled: From protein structures to clinical applications. Copyright © 2012 Elsevier B.V. All rights reserved.

A novel low-complexity digital filter design for wearable ECG devices

PubMed Central

Mehrnia, Alireza

2017-01-01

Wearable and implantable Electrocardiograph (ECG) devices are becoming prevailing tools for continuous real-time personal health monitoring. The ECG signal can be contaminated by various types of noise and artifacts (e.g., powerline interference, baseline wandering) that must be removed or suppressed for accurate ECG signal processing. Limited device size, power consumption and cost are critical issues that need to be carefully considered when designing any portable health monitoring device, including a battery-powered ECG device. This work presents a novel low-complexity noise suppression reconfigurable finite impulse response (FIR) filter structure for wearable ECG and heart monitoring devices. The design relies on a recently introduced optimally-factored FIR filter method. The new filter structure and several of its useful features are presented in detail. We also studied the hardware complexity of the proposed structure and compared it with the state-of-the-art. The results showed that the new ECG filter has a lower hardware complexity relative to the state-of-the-art ECG filters. PMID:28384272

A novel low-complexity digital filter design for wearable ECG devices.

PubMed

Asgari, Shadnaz; Mehrnia, Alireza

2017-01-01

Wearable and implantable Electrocardiograph (ECG) devices are becoming prevailing tools for continuous real-time personal health monitoring. The ECG signal can be contaminated by various types of noise and artifacts (e.g., powerline interference, baseline wandering) that must be removed or suppressed for accurate ECG signal processing. Limited device size, power consumption and cost are critical issues that need to be carefully considered when designing any portable health monitoring device, including a battery-powered ECG device. This work presents a novel low-complexity noise suppression reconfigurable finite impulse response (FIR) filter structure for wearable ECG and heart monitoring devices. The design relies on a recently introduced optimally-factored FIR filter method. The new filter structure and several of its useful features are presented in detail. We also studied the hardware complexity of the proposed structure and compared it with the state-of-the-art. The results showed that the new ECG filter has a lower hardware complexity relative to the state-of-the-art ECG filters.

An Electromechanical Left Ventricular Wedge Model to Study the Effects of Deformation on Repolarization during Heart Failure

PubMed Central

Rocha, B. M.; Toledo, E. M.; Barra, L. P. S.; dos Santos, R. Weber

2015-01-01

Heart failure is a major and costly problem in public health, which, in certain cases, may lead to death. The failing heart undergo a series of electrical and structural changes that provide the underlying basis for disturbances like arrhythmias. Computer models of coupled electrical and mechanical activities of the heart can be used to advance our understanding of the complex feedback mechanisms involved. In this context, there is a lack of studies that consider heart failure remodeling using strongly coupled electromechanics. We present a strongly coupled electromechanical model to study the effects of deformation on a human left ventricle wedge considering normal and hypertrophic heart failure conditions. We demonstrate through a series of simulations that when a strongly coupled electromechanical model is used, deformation results in the thickening of the ventricular wall that in turn increases transmural dispersion of repolarization. These effects were analyzed in both normal and failing heart conditions. We also present transmural electrograms obtained from these simulations. Our results suggest that the waveform of electrograms, particularly the T-wave, is influenced by cardiac contraction on both normal and pathological conditions. PMID:26550570

Gender- and age-related differences in heart rate dynamics: are women more complex than men?

NASA Technical Reports Server (NTRS)

Ryan, S. M.; Goldberger, A. L.; Pincus, S. M.; Mietus, J.; Lipsitz, L. A.

1994-01-01

OBJECTIVES. This study aimed to quantify the complex dynamics of beat-to-beat sinus rhythm heart rate fluctuations and to determine their differences as a function of gender and age. BACKGROUND. Recently, measures of heart rate variability and the nonlinear "complexity" of heart rate dynamics have been used as indicators of cardiovascular health. Because women have lower cardiovascular risk and greater longevity than men, we postulated that there are important gender-related differences in beat-to-beat heart rate dynamics. METHODS. We analyzed heart rate dynamics during 8-min segments of continuous electrocardiographic recording in healthy young (20 to 39 years old), middle-aged (40 to 64 years old) and elderly (65 to 90 years old) men (n = 40) and women (n = 27) while they performed spontaneous and metronomic (15 breaths/min) breathing. Relatively high (0.15 to 0.40 Hz) and low (0.01 to 0.15 Hz) frequency components of heart rate variability were computed using spectral analysis. The overall "complexity" of each heart rate time series was quantified by its approximate entropy, a measure of regularity derived from nonlinear dynamics ("chaos" theory). RESULTS. Mean heart rate did not differ between the age groups or genders. High frequency heart rate power and the high/low frequency power ratio decreased with age in both men and women (p < 0.05). The high/low frequency power ratio during spontaneous and metronomic breathing was greater in women than men (p < 0.05). Heart rate approximate entropy decreased with age and was higher in women than men (p < 0.05). CONCLUSIONS. High frequency heart rate spectral power (associated with parasympathetic activity) and the overall complexity of heart rate dynamics are higher in women than men. These complementary findings indicate the need to account for gender-as well as age-related differences in heart rate dynamics. Whether these gender differences are related to lower cardiovascular disease risk and greater longevity in women requires further study.

Model-specific selection of molecular targets for heart failure gene therapy

PubMed Central

Katz, Michael G.; Fargnoli, Anthony S.; Tomasulo, Catherine E.; Pritchette, Louella A.; Bridges, Charles R.

2013-01-01

Heart failure (HF) is a complex multifaceted problem of abnormal ventricular function and structure. In recent years, new information has been accumulated allowing for a more detailed understanding of the cellular and molecular alterations that are the underpinnings of diverse causes of HF, including myocardial ischemia, pressure-overload, volume-overload or intrinsic cardiomyopathy. Modern pharmacological approaches to treat HF have had a significant impact on the course of the disease, although they do not reverse the underlying pathological state of the heart. Therefore gene-based therapy holds a great potential as a targeted treatment for cardiovascular diseases. Here, we survey the relative therapeutic efficacy of genetic modulation of β-adrenergic receptor signaling, Ca2+ handling proteins and angiogenesis in the most common extrinsic models of HF. PMID:21954055

3D characterization of EMT cell density in developing cardiac cushions using optical coherence tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Yu, Siyao; Gu, Shi; Zhao, Xiaowei; Liu, Yehe; Jenkins, Michael W.; Watanabe, Michiko; Rollins, Andrew M.

2017-02-01

Congenital heart defects (CHDs) are the most common birth defect, affecting between 4 and 75 per 1,000 live births depending on the inclusion criteria. Many of these defects can be traced to defects of cardiac cushions, critical structures during development that serve as precursors to many structures in the mature heart, including the atrial and ventricular septa, and all four sets of cardiac valves. Epithelial-mesenchymal transition (EMT) is the process through which cardiac cushions become populated with cells. Altered cushion size or altered cushion cell density has been linked to many forms of CHDs, however, quantitation of cell density in the complex 3D cushion structure poses a significant challenge to conventional histology. Optical coherence tomography (OCT) is a technique capable of 3D imaging of the developing heart, but typically lacks the resolution to differentiate individual cells. Our goal is to develop an algorithm to quantitatively characterize the density of cells in the developing cushion using 3D OCT imaging. First, in a heart volume, the atrioventricular (AV) cushions were manually segmented. Next, all voxel values in the region of interest were pooled together to generate a histogram. Finally, two populations of voxels were classified using either K-means classification, or a Gaussian mixture model (GMM). The voxel population with higher values represents cells in the cushion. To test the algorithm, we imaged and evaluated avian embryonic hearts at looping stages. As expected, our result suggested that the cell density increases with developmental stages. We validated the technique against scoring by expert readers.

Effects of head-down bed rest on complex heart rate variability: Response to LBNP testing

NASA Technical Reports Server (NTRS)

Goldberger, Ary L.; Mietus, Joseph E.; Rigney, David R.; Wood, Margie L.; Fortney, Suzanne M.

1994-01-01

Head-down bed rest is used to model physiological changes during spaceflight. We postulated that bed rest would decrease the degree of complex physiological heart rate variability. We analyzed continuous heart rate data from digitized Holter recordings in eight healthy female volunteers (age 28-34 yr) who underwent a 13-day 6 deg head-down bed rest study with serial lower body negative pressure (LBNP) trials. Heart rate variability was measured on a 4-min data sets using conventional time and frequency domain measures as well as with a new measure of signal 'complexity' (approximate entropy). Data were obtained pre-bed rest (control), during bed rest (day 4 and day 9 or 11), and 2 days post-bed rest (recovery). Tolerance to LBNP was significantly reduced on both bed rest days vs. pre-bed rest. Heart rate variability was assessed at peak LBNP. Heart rate approximate entropy was significantly decreased at day 4 and day 9 or 11, returning toward normal during recovery. Heart rate standard deviation and the ratio of high- to low-power frequency did not change significantly. We conclude that short-term bed rest is associated with a decrease in the complex variability of heart rate during LBNP testing in healthy young adult women. Measurement of heart rate complexity, using a method derived from nonlinear dynamics ('chaos theory'), may provide a sensitive marker of this loss of physiological variability, complementing conventional time and frequency domain statistical measures.

The characterisation of blood rotation in a human heart chamber based on statistical analysis of vorticity maps

NASA Astrophysics Data System (ADS)

Wong, Kelvin K. L.; Kelso, Richard M.; Worthley, Stephen G.; Sanders, Prashanthan; Mazumdar, Jagannath; Abbott, Derek

2008-12-01

Modelling of non-stationary cardiac structures is complicated by the complexity of their intrinsic and extrinsic motion. The first known study of haemodynamics due to the beating of heart was made by Leonardo Da Vinci, giving the idea of fluid-solid interaction by describing how vortices develop during cardiac structural interaction with the blood. Heart morphology affects in changes of cardio dynamics during the systolic and diastolic phrases. In a chamber of the heart, vortices are discovered to exist as the result of the unique morphological changes of the cardiac chamber wall by using flow-imaging techniques such as phase contrast magnetic resonance imaging. The first part of this paper attempts to quantify vortex characteristics by means of calculating vorticity numerically and devising two dimensional vortical flow maps. The technique relies on determining the properties of vorticity using a statistical quantification of the flow maps and comparison of these quantities based on different scenarios. As the characteristics of our vorticity maps vary depending on the phase of a cardiac cycle, there is a need for robust quantification method to analyse vorticity. In the second part of the paper, the approach is then utilised for examining vortices within the human right atrium. Our study has shown that a proper quantification of vorticity for the flow field can indicate the strength and number of vortices within a heart chamber.

Real-time three dimensional CT and MRI to guide interventions for congenital heart disease and acquired pulmonary vein stenosis.

PubMed

Suntharos, Patcharapong; Setser, Randolph M; Bradley-Skelton, Sharon; Prieto, Lourdes R

2017-10-01

To validate the feasibility and spatial accuracy of pre-procedural 3D images to 3D rotational fluoroscopy registration to guide interventional procedures in patients with congenital heart disease and acquired pulmonary vein stenosis. Cardiac interventions in patients with congenital and structural heart disease require complex catheter manipulation. Current technology allows registration of the anatomy obtained from 3D CT and/or MRI to be overlaid onto fluoroscopy. Thirty patients scheduled for interventional procedures from 12/2012 to 8/2015 were prospectively recruited. A C-arm CT using a biplane C-arm system (Artis zee, VC14H, Siemens Healthcare) was acquired to enable 3D3D registration with pre-procedural images. Following successful image fusion, the anatomic landmarks marked in pre-procedural images were overlaid on live fluoroscopy. The accuracy of image registration was determined by measuring the distance between overlay markers and a reference point in the image. The clinical utility of the registration was evaluated as either "High", "Medium" or "None". Seventeen patients with congenital heart disease and 13 with acquired pulmonary vein stenosis were enrolled. Accuracy and benefit of registration were not evaluated in two patients due to suboptimal images. The distance between the marker and the actual anatomical location was 0-2 mm in 18 (64%), 2-4 mm in 3 (11%) and >4 mm in 7 (25%) patients. 3D3D registration was highly beneficial in 18 (64%), intermediate in 3 (11%), and not beneficial in 7 (25%) patients. 3D3D registration can facilitate complex congenital and structural interventions. It may reduce procedure time, radiation and contrast dose.

Decoding the Heart through Next Generation Sequencing Approaches.

PubMed

Pawlak, Michal; Niescierowicz, Katarzyna; Winata, Cecilia Lanny

2018-06-07

: Vertebrate organs develop through a complex process which involves interaction between multiple signaling pathways at the molecular, cell, and tissue levels. Heart development is an example of such complex process which, when disrupted, results in congenital heart disease (CHD). This complexity necessitates a holistic approach which allows the visualization of genome-wide interaction networks, as opposed to assessment of limited subsets of factors. Genomics offers a powerful solution to address the problem of biological complexity by enabling the observation of molecular processes at a genome-wide scale. The emergence of next generation sequencing (NGS) technology has facilitated the expansion of genomics, increasing its output capacity and applicability in various biological disciplines. The application of NGS in various aspects of heart biology has resulted in new discoveries, generating novel insights into this field of study. Here we review the contributions of NGS technology into the understanding of heart development and its disruption reflected in CHD and discuss how emerging NGS based methodologies can contribute to the further understanding of heart repair.

Addressing the conundrum of multimorbidity in heart failure: Do we need a more strategic approach to improve health outcomes?

PubMed

Stewart, Simon; Riegel, Barbara; Thompson, David R

2016-02-01

There is clear evidence across the globe that the clinical complexity of patients presenting to hospital with the syndrome of heart failure is increasing - not only in terms of the presence of concurrent disease states, but with additional socio-demographic risk factors that complicate treatment. Management strategies that treat heart failure as the main determinant of health outcomes ignores the multiple and complex issues that will inevitably erode the efficacy and efficiency of current heart failure management programmes. This complex problem (or conundrum) requires a different way of thinking around the complex interactions that underpin poor outcomes in heart failure. In this context, we present the COordinated NUrse-led inteNsified Disease management for continuity of caRe for mUltiMorbidity in Heart Failure (CONUNDRUM-HF) matrix that may well inform future research and models of care to achieve better health outcomes in this rapidly increasing patient population. © The European Society of Cardiology 2015.

STUDIES ON MAMMALIAN AND HUMAN PYRUVATE AND ALPHA-KETOGLUTARATE DEHYDROGENATION COMPLEXES.

DTIC Science & Technology

Enzyme systems that catalyze a coenzyme A- and nicotinamide adenine dinucleotide-linked oxidative decarboxylation of pyruvate and alpha - ketoglutarate ...The pig heart pyruvate dehydrogenase complex was strongly inhibited by EDTA at low concentration, but the pig heart alpha - ketoglutarate ...On the oxidative decarboxylation of alpha -keto acids in pig heart complexes, Ca(2+) was strongly stimulatory to the same or more extent than Mg(2

An immersogeometric variational framework for fluid–structure interaction: application to bioprosthetic heart valves

PubMed Central

Kamensky, David; Hsu, Ming-Chen; Schillinger, Dominik; Evans, John A.; Aggarwal, Ankush; Bazilevs, Yuri; Sacks, Michael S.; Hughes, Thomas J. R.

2014-01-01

In this paper, we develop a geometrically flexible technique for computational fluid–structure interaction (FSI). The motivating application is the simulation of tri-leaflet bioprosthetic heart valve function over the complete cardiac cycle. Due to the complex motion of the heart valve leaflets, the fluid domain undergoes large deformations, including changes of topology. The proposed method directly analyzes a spline-based surface representation of the structure by immersing it into a non-boundary-fitted discretization of the surrounding fluid domain. This places our method within an emerging class of computational techniques that aim to capture geometry on non-boundary-fitted analysis meshes. We introduce the term “immersogeometric analysis” to identify this paradigm. The framework starts with an augmented Lagrangian formulation for FSI that enforces kinematic constraints with a combination of Lagrange multipliers and penalty forces. For immersed volumetric objects, we formally eliminate the multiplier field by substituting a fluid–structure interface traction, arriving at Nitsche’s method for enforcing Dirichlet boundary conditions on object surfaces. For immersed thin shell structures modeled geometrically as surfaces, the tractions from opposite sides cancel due to the continuity of the background fluid solution space, leaving a penalty method. Application to a bioprosthetic heart valve, where there is a large pressure jump across the leaflets, reveals shortcomings of the penalty approach. To counteract steep pressure gradients through the structure without the conditioning problems that accompany strong penalty forces, we resurrect the Lagrange multiplier field. Further, since the fluid discretization is not tailored to the structure geometry, there is a significant error in the approximation of pressure discontinuities across the shell. This error becomes especially troublesome in residual-based stabilized methods for incompressible flow, leading to problematic compressibility at practical levels of refinement. We modify existing stabilized methods to improve performance. To evaluate the accuracy of the proposed methods, we test them on benchmark problems and compare the results with those of established boundary-fitted techniques. Finally, we simulate the coupling of the bioprosthetic heart valve and the surrounding blood flow under physiological conditions, demonstrating the effectiveness of the proposed techniques in practical computations. PMID:25541566

Opposite and tissue-specific effects of coenzyme Q2 on mPTP opening and ROS production between heart and liver mitochondria: role of complex I.

PubMed

Gharib, Abdallah; De Paulis, Damien; Li, Bo; Augeul, Lionel; Couture-Lepetit, Elisabeth; Gomez, Ludovic; Angoulvant, Denis; Ovize, Michel

2012-05-01

Coenzyme Q(2) (CoQ(2)) is known to inhibit mitochondrial permeability transition pore (mPTP) opening in isolated rat liver mitochondria. In this study, we investigated and compared the effects of CoQ(2) on mPTP opening and ROS production in isolated rabbit heart and rat liver mitochondria. Mitochondria were isolated from New Zealand White rabbit hearts and Wistar rat livers. Oxygen consumption, Ca(2+)-induced mPTP opening, ROS production and NADH DUb-reductase activity were measured. Rotenone was used to investigate the effect of CoQ(2) on respiratory complex I activity. CoQ(2) (23 μM) reduced the respiratory control index by 32% and 57% (p<0.01) in heart and liver mitochondria respectively, mainly through an increased oxygen consumption in state 4. CoQ(2) induced a 60% (p<0.05) decrease of calcium retention capacity (CRC) in heart mitochondria and inversely a 46% (p<0.05) increase in liver mitochondria. In basal condition, CoQ(2) induced a 170% (p<0.05) increase of H(2)O(2) production in heart mitochondria and 21% (ns) decrease of H(2)O(2) production in liver mitochondria. Because rotenone, a complex I inhibitor, increases H(2)O(2) production in heart but not in liver mitochondria we investigated the CoQ(2) effect in a dose-response assay of complex I inhibition by rotenone in both mitochondria. CoQ(2) antagonized the effect of rotenone on respiratory complex I activity in liver but not in heart mitochondria. CoQ(2) significantly reduced NADH DUb-reductase activity in liver (-47%) and heart (-37%) mitochondria. In conclusion, our data showed that on the contrary to what was observed in liver mitochondria, CoQ(2) favors mPTP opening and ROS production in heart mitochondria through an opposite effect on respiratory complex I activity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Mitochondrial Reactive Oxygen Species Mediate Cardiac Structural, Functional, and Mitochondrial Consequences of Diet-Induced Metabolic Heart Disease.

PubMed

Sverdlov, Aaron L; Elezaby, Aly; Qin, Fuzhong; Behring, Jessica B; Luptak, Ivan; Calamaras, Timothy D; Siwik, Deborah A; Miller, Edward J; Liesa, Marc; Shirihai, Orian S; Pimentel, David R; Cohen, Richard A; Bachschmid, Markus M; Colucci, Wilson S

2016-01-11

Mitochondrial reactive oxygen species (ROS) are associated with metabolic heart disease (MHD). However, the mechanism by which ROS cause MHD is unknown. We tested the hypothesis that mitochondrial ROS are a key mediator of MHD. Mice fed a high-fat high-sucrose (HFHS) diet develop MHD with cardiac diastolic and mitochondrial dysfunction that is associated with oxidative posttranslational modifications of cardiac mitochondrial proteins. Transgenic mice that express catalase in mitochondria and wild-type mice were fed an HFHS or control diet for 4 months. Cardiac mitochondria from HFHS-fed wild-type mice had a 3-fold greater rate of H2O2 production (P=0.001 versus control diet fed), a 30% decrease in complex II substrate-driven oxygen consumption (P=0.006), 21% to 23% decreases in complex I and II substrate-driven ATP synthesis (P=0.01), and a 62% decrease in complex II activity (P=0.002). In transgenic mice that express catalase in mitochondria, all HFHS diet-induced mitochondrial abnormalities were ameliorated, as were left ventricular hypertrophy and diastolic dysfunction. In HFHS-fed wild-type mice complex II substrate-driven ATP synthesis and activity were restored ex vivo by dithiothreitol (5 mmol/L), suggesting a role for reversible cysteine oxidative posttranslational modifications. In vitro site-directed mutation of complex II subunit B Cys100 or Cys103 to redox-insensitive serines prevented complex II dysfunction induced by ROS or high glucose/high palmitate in the medium. Mitochondrial ROS are pathogenic in MHD and contribute to mitochondrial dysfunction, at least in part, by causing oxidative posttranslational modifications of complex I and II proteins including reversible oxidative posttranslational modifications of complex II subunit B Cys100 and Cys103. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Reversible heart rhythm complexity impairment in patients with primary aldosteronism

NASA Astrophysics Data System (ADS)

Lin, Yen-Hung; Wu, Vin-Cent; Lo, Men-Tzung; Wu, Xue-Ming; Hung, Chi-Sheng; Wu, Kwan-Dun; Lin, Chen; Ho, Yi-Lwun; Stowasser, Michael; Peng, Chung-Kang

2015-08-01

Excess aldosterone secretion in patients with primary aldosteronism (PA) impairs their cardiovascular system. Heart rhythm complexity analysis, derived from heart rate variability (HRV), is a powerful tool to quantify the complex regulatory dynamics of human physiology. We prospectively analyzed 20 patients with aldosterone producing adenoma (APA) that underwent adrenalectomy and 25 patients with essential hypertension (EH). The heart rate data were analyzed by conventional HRV and heart rhythm complexity analysis including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We found APA patients had significantly decreased DFAα2 on DFA analysis and decreased area 1-5, area 6-15, and area 6-20 on MSE analysis (all p < 0.05). Area 1-5, area 6-15, area 6-20 in the MSE study correlated significantly with log-transformed renin activity and log-transformed aldosterone-renin ratio (all p < = 0.01). The conventional HRV parameters were comparable between PA and EH patients. After adrenalectomy, all the altered DFA and MSE parameters improved significantly (all p < 0.05). The conventional HRV parameters did not change. Our result suggested that heart rhythm complexity is impaired in APA patients and this is at least partially reversed by adrenalectomy.

Exercise echocardiography for structural heart disease.

PubMed

Izumo, Masaki; Akashi, Yoshihiro J

2016-03-01

Since the introduction of transcatheter structural heart intervention, the term "structural heart disease" has been widely used in the field of cardiology. Structural heart disease refers to congenital heart disease, valvular heart disease, and cardiomyopathy. In structural heart disease, valvular heart disease is frequently identified in the elderly. Of note, the number of patients who suffer from aortic stenosis (AS) and mitral regurgitation (MR) is increasing in developed countries because of the aging of the populations. Transcatheter aortic valve replacement and percutaneous mitral valve repair has been widely used for AS and MR, individually. Echocardiography is the gold standard modality for initial diagnosis and subsequent evaluation of AS and MR, although the difficulties in assessing patients with these diseases still remain. Here, we review the clinical usefulness and prognostic impact of exercise echocardiography on structural heart disease, particularly on AS and MR.

Improving the quality of transition and transfer of care in young adults with congenital heart disease.

PubMed

Everitt, Ian K; Gerardin, Jennifer F; Rodriguez, Fred H; Book, Wendy M

2017-05-01

The transition and transfer from pediatric to adult care is becoming increasingly important as improvements in the diagnosis and management of congenital heart disease allow patients to live longer. Transition is a complex and continuous process that requires careful planning. Inadequate transition has adverse effects on patients, their families and healthcare delivery systems. Currently, significant gaps exist in patient care as adolescents transfer to adult care and there are little data to drive the informed management of transition and transfer of care in adolescent congenital heart disease patients. Appropriate congenital heart disease care has been shown to decrease mortality in the adult population. This paper reviews the transition and transfer of care processes and outlines current congenital heart disease specific guidelines in the United States and compares these recommendations to Canadian and European guidelines. It then reviews perceived and real barriers to successful transition and identifies predictors of success during transfer to adult congenital heart disease care. Lastly, it explores how disease-specific markers of outcomes and quality indicators are being utilized to guide transition and transfer of care in other chronic childhood illnesses, and identifies existing knowledge gaps and structural impediments to improving the management of transition and transfer among congenital heart disease patients. © 2017 Wiley Periodicals, Inc.

Dystrophic Cardiomyopathy: Complex Pathobiological Processes to Generate Clinical Phenotype

PubMed Central

Tsuda, Takeshi; Fitzgerald, Kristi K.

2017-01-01

Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked dilated cardiomyopathy (XL-DCM) consist of a unique clinical entity, the dystrophinopathies, which are due to variable mutations in the dystrophin gene. Dilated cardiomyopathy (DCM) is a common complication of dystrophinopathies, but the onset, progression, and severity of heart disease differ among these subgroups. Extensive molecular genetic studies have been conducted to assess genotype-phenotype correlation in DMD, BMD, and XL-DCM to understand the underlying mechanisms of these diseases, but the results are not always conclusive, suggesting the involvement of complex multi-layers of pathological processes that generate the final clinical phenotype. Dystrophin protein is a part of dystrophin-glycoprotein complex (DGC) that is localized in skeletal muscles, myocardium, smooth muscles, and neuronal tissues. Diversity of cardiac phenotype in dystrophinopathies suggests multiple layers of pathogenetic mechanisms in forming dystrophic cardiomyopathy. In this review article, we review the complex molecular interactions involving the pathogenesis of dystrophic cardiomyopathy, including primary gene mutations and loss of structural integrity, secondary cellular responses, and certain epigenetic and other factors that modulate gene expressions. Involvement of epigenetic gene regulation appears to lead to specific cardiac phenotypes in dystrophic hearts. PMID:29367543

[Analysis of Foetal Heart Rate Data using Complex Software: Comparison of Recurrence Plot of Foetal Heart Rate with the Course of Pregnancy -].

PubMed

Jörn, H; Morgenstern, B; Wassenberg, B; Rath, W

2004-08-01

Is it useful to further analyse foetal heart rate to improve the prediction of pregnancy complications? The analysis of the foetal heart rate is usually based on the variability of the heart rate, i. e. the more variable the heart rate presents - except a decrease - the better the condition of the foetus is. The same concept is applied in our own analysis which differs only in the presentation of the data. We analysed 25 non-stress-tests from unselected third trimester pregnancies using sophisticated software. The recurrence plot (RP) is able to rearrange data from foetal heart rate monitoring in order to make the heart rate variability visible. We developed criteria for a normal and an abnormal test result describing the structure of the diagram to predict an uneventful and a high-risk pregnancy, respectively. 11 out of 11 patients with uneventful course and outcome of pregnancy showed a coarse and blurred RP pattern. 12 out of 14 (86 %) patients developing either intrauterine growth retardation or preeclampsia and requiring caesarean section because of foetal heart rate abnormalities showed a fine and clear RP pattern. Our preliminary results show that it makes sense to further evaluate foetal heart rate variability in order to predict pregnancy complications. Computer programs including the algorithms needed (calculation of the recurrence plot) are not expensive and easy to handle. A widespread use of these programs represents the basis requirement for large controlled clinical trials.

Multiphysics and multiscale modelling, data-model fusion and integration of organ physiology in the clinic: ventricular cardiac mechanics.

PubMed

Chabiniok, Radomir; Wang, Vicky Y; Hadjicharalambous, Myrianthi; Asner, Liya; Lee, Jack; Sermesant, Maxime; Kuhl, Ellen; Young, Alistair A; Moireau, Philippe; Nash, Martyn P; Chapelle, Dominique; Nordsletten, David A

2016-04-06

With heart and cardiovascular diseases continually challenging healthcare systems worldwide, translating basic research on cardiac (patho)physiology into clinical care is essential. Exacerbating this already extensive challenge is the complexity of the heart, relying on its hierarchical structure and function to maintain cardiovascular flow. Computational modelling has been proposed and actively pursued as a tool for accelerating research and translation. Allowing exploration of the relationships between physics, multiscale mechanisms and function, computational modelling provides a platform for improving our understanding of the heart. Further integration of experimental and clinical data through data assimilation and parameter estimation techniques is bringing computational models closer to use in routine clinical practice. This article reviews developments in computational cardiac modelling and how their integration with medical imaging data is providing new pathways for translational cardiac modelling.

Decursin and decursinol angelate selectively inhibit NADH-fumarate reductase of Ascaris suum.

PubMed

Shiomi, Kazuro; Hatano, Hiroko; Morimoto, Hiromi; Ui, Hideaki; Sakamoto, Kimitoshi; Kita, Kiyoshi; Tomoda, Hiroshi; Lee, Eun Woo; Heo, Tae Ryeon; Kawagishi, Hirokazu; Omura, Satoshi

2007-11-01

NADH-fumarate reductase (NFRD) is a key enzyme in many anaerobic helminths. Decursin and decursinol angelate have been isolated from the roots of ANGELICA GIGAS Nakai (Apiaceae) as NFRD inhibitors. They inhibited ASCARIS SUUM NFRD with IC (50) values of 1.1 and 2.7 microM, respectively. Their target is the electron transport enzyme complex I. Since the inhibitory activities of decursin against bovine heart complexes are weak, it is a selective inhibitor of the nematode complex I. In contrast, decursinol angelate moderately inhibits bovine heart complexes II and III. Decursinol inhibits A. SUUM NFRD to a similar extent, but its target is complex II. It also inhibits bovine heart complexes II and III.

Ventricular arrhythmias in the absence of structural heart disease.

PubMed

Prystowsky, Eric N; Padanilam, Benzy J; Joshi, Sandeep; Fogel, Richard I

2012-05-15

Ventricular arrhythmia (VA) in structurally normal hearts can be broadly considered under non-life-threatening monomorphic and life-threatening polymorphic rhythms. Monomorphic VA is classified on the basis of site of origin in the heart, and the most common areas are the ventricular outflow tracts and left ventricular fascicles. The morphology of the QRS complexes on electrocardiogram is an excellent tool to identify the site of origin of the rhythm. Although these arrhythmias are common and generally carry an excellent prognosis, rare sudden death events have been reported. Very frequent ventricular ectopy may also result in a cardiomyopathy in a minority of patients. Suppression of VA may be achieved using calcium-channel blockers, beta-adrenergic blockers, and class I or III antiarrhythmic drugs. Radiofrequency ablation has emerged as an excellent option to eliminate these arrhythmias, although certain foci including aortic cusps and epicardium may be technically challenging. Polymorphic ventricular tachycardia (VT) is rare and generally occurs in patients with genetic ion channel disorders including long QT syndrome, Brugada syndrome, catecholaminergic polymorphic VT, and short QT syndrome. Unlike monomorphic VT, these arrhythmic syndromes are associated with sudden death. While the cardiac gross morphology is normal, suggesting a structurally normal heart, abnormalities exist at the molecular level and predispose them to arrhythmias. Another fascinating area, idiopathic ventricular fibrillation and early repolarization syndrome, are undergoing research for a genetic basis. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Experiences of informational needs and received information following a prenatal diagnosis of congenital heart defect

PubMed Central

Bergman, Gunnar; Wadensten, Barbro; Mattsson, Elisabet

2016-01-01

Abstract Objective To explore the need for information and what information was actually received following prenatal diagnosis of a congenital heart defect, in a country where termination of pregnancy beyond 22 weeks of gestation is not easily possible because of legal constraints. Methods Twenty‐six Swedish‐speaking pregnant women (n = 14) and partners (n = 12) were consecutively recruited for semi‐structured telephone interviews following the prenatal diagnosis of a congenital heart defect. Data were analyzed using content analysis. Results Although high satisfaction with the specialist information was described, the information was considered overwhelming and complex. Objective, honest, and detailed information about multiple subjects were needed, delivered repeatedly, and supplemented by written information/illustrations. Eighteen respondents had used the Internet to search for information and identified issues involving searching difficulties, low quality, and that it was too complex, insufficient, or unspecific. Those who terminated their pregnancy criticized that there was a lack of information about termination of pregnancy, both from health professionals and online sources, resulting in unanswered questions and unpreparedness. Conclusion Individuals faced with a prenatal diagnosis of a congenital heart defect need individualized and repeated information. These needs are not all adequately met, as individuals are satisfied with the specialist consultation but left with unanswered questions regarding pregnancy termination. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. PMID:26991536

Experiences of informational needs and received information following a prenatal diagnosis of congenital heart defect.

PubMed

Carlsson, Tommy; Bergman, Gunnar; Wadensten, Barbro; Mattsson, Elisabet

2016-06-01

To explore the need for information and what information was actually received following prenatal diagnosis of a congenital heart defect, in a country where termination of pregnancy beyond 22 weeks of gestation is not easily possible because of legal constraints. Twenty-six Swedish-speaking pregnant women (n = 14) and partners (n = 12) were consecutively recruited for semi-structured telephone interviews following the prenatal diagnosis of a congenital heart defect. Data were analyzed using content analysis. Although high satisfaction with the specialist information was described, the information was considered overwhelming and complex. Objective, honest, and detailed information about multiple subjects were needed, delivered repeatedly, and supplemented by written information/illustrations. Eighteen respondents had used the Internet to search for information and identified issues involving searching difficulties, low quality, and that it was too complex, insufficient, or unspecific. Those who terminated their pregnancy criticized that there was a lack of information about termination of pregnancy, both from health professionals and online sources, resulting in unanswered questions and unpreparedness. Individuals faced with a prenatal diagnosis of a congenital heart defect need individualized and repeated information. These needs are not all adequately met, as individuals are satisfied with the specialist consultation but left with unanswered questions regarding pregnancy termination. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

Association of intraventricular mechanical dyssynchrony with response to cardiac resynchronization therapy in heart failure patients with a narrow QRS complex

PubMed Central

van Bommel, Rutger J.; Tanaka, Hidekazu; Delgado, Victoria; Bertini, Matteo; Borleffs, Carel Jan Willem; Ajmone Marsan, Nina; Holzmeister, Johannes; Ruschitzka, Frank; Schalij, Martin J.; Bax, Jeroen J.; Gorcsan, John

2010-01-01

Aims Current criteria for cardiac resynchronization therapy (CRT) are restricted to patients with a wide QRS complex (>120 ms). Overall, only 30% of heart failure patients demonstrate a wide QRS complex, leaving the majority of heart failure patients without this treatment option. However, patients with a narrow QRS complex exhibit left ventricular (LV) mechanical dyssynchrony, as assessed with echocardiography. To further elucidate the possible beneficial effect of CRT in heart failure patients with a narrow QRS complex, this two-centre, non-randomized observational study focused on different echocardiographic parameters of LV mechanical dyssynchrony reflecting atrioventricular, interventricular and intraventricular dyssynchrony, and the response to CRT in these patients. Methods and results A total of 123 consecutive heart failure patients with a narrow QRS complex (<120 ms) undergoing CRT was included at two centres. Several widely accepted measures of mechanical dyssynchrony were evaluated: LV filling ratio (LVFT/RR), LV pre-ejection time (LPEI), interventricular mechanical dyssynchrony (IVMD), opposing wall delay (OWD), and anteroseptal posterior wall delay with speckle tracking (ASPWD). Response to CRT was defined as a reduction ≥15% in left ventricular end-systolic volume at 6 months follow-up. Measures of dyssynchrony can frequently be observed in patients with a narrow QRS complex. Nonetheless, for LVFT/RR, LPEI, and IVMD, presence of predefined significant dyssynchrony is <20%. Significant intraventricular dyssynchrony is more widely observed in these patients. With receiver operator characteristic curve analyses, both OWD and ASPWD demonstrated usefulness in predicting response to CRT in narrow QRS patients with a cut-off value of 75 and 107 ms, respectively. Conclusion Mechanical dyssynchrony can be widely observed in heart failure patients with a narrow QRS complex. In particular, intraventricular measures of mechanical dyssynchrony may be useful in predicting LV reverse remodelling at 6 months follow-up in heart failure patients with a narrow QRS complex, but with more stringent cut-off values than currently used in ‘wide’ QRS patients. PMID:20864484

Molecular assembly and subcellular distribution of ATP-sensitive potassium channel proteins in rat hearts.

PubMed

Kuniyasu, Akihiko; Kaneko, Kazuyoshi; Kawahara, Kohichi; Nakayama, Hitoshi

2003-09-25

Cardiac ATP-sensitive K(+) (K(ATP)) channels are proposed to contribute to cardio-protection and ischemic preconditioning. Although mRNAs for all subunits of K(ATP) channels (Kir6.0 and sulfonylurea receptors SURs) were detected in hearts, subcellular localization of their proteins and the subunit combination are not well elucidated. We address these questions in rat hearts, using anti-peptide antibodies raised against each subunit. By immunoblot analysis, all of the subunits were detected in microsomal fractions including sarcolemmal membranes, while they were not detected in mitochondrial fractions at all. Immunoprecipitation and sucrose gradient sedimentation of the digitonin-solubilized microsomes indicated that Kir6.2 exclusively assembled with SUR2A. The molecular mass of the Kir6.2-SUR2A complex estimated by sucrose sedimentation was 1150 kDa, significantly larger than the calculated value for (Kir6.2)(4)-(SUR2A)(4), suggesting a potential formation of micellar complex with digitonin but no indication of hybrid channel formation under the conditions. These findings provide additional information on the structural and functional relationships of cardiac K(ATP) channel proteins involving subcellular localization and roles for cardioprotection and ischemic preconditioning.

Computational approaches to understand cardiac electrophysiology and arrhythmias

PubMed Central

Roberts, Byron N.; Yang, Pei-Chi; Behrens, Steven B.; Moreno, Jonathan D.

2012-01-01

Cardiac rhythms arise from electrical activity generated by precisely timed opening and closing of ion channels in individual cardiac myocytes. These impulses spread throughout the cardiac muscle to manifest as electrical waves in the whole heart. Regularity of electrical waves is critically important since they signal the heart muscle to contract, driving the primary function of the heart to act as a pump and deliver blood to the brain and vital organs. When electrical activity goes awry during a cardiac arrhythmia, the pump does not function, the brain does not receive oxygenated blood, and death ensues. For more than 50 years, mathematically based models of cardiac electrical activity have been used to improve understanding of basic mechanisms of normal and abnormal cardiac electrical function. Computer-based modeling approaches to understand cardiac activity are uniquely helpful because they allow for distillation of complex emergent behaviors into the key contributing components underlying them. Here we review the latest advances and novel concepts in the field as they relate to understanding the complex interplay between electrical, mechanical, structural, and genetic mechanisms during arrhythmia development at the level of ion channels, cells, and tissues. We also discuss the latest computational approaches to guiding arrhythmia therapy. PMID:22886409

Parental overprotection and heart-focused anxiety in adults with congenital heart disease.

PubMed

Ong, Lephuong; Nolan, Robert P; Irvine, Jane; Kovacs, Adrienne H

2011-09-01

The care of adult patients with congenital heart disease (CHD) is challenging from a mental health perspective, as these patients continue to face a variety of biopsychosocial issues that may impact emotional functioning. Despite these issues, there are limited data on the psychosocial functioning of adults with CHD, and there are no data on the impact of parental overprotection on heart-focused anxiety in this patient population. The aim of this study was to examine the relationships between patient recollections of parental overprotection and current heart-focused anxiety in adults with CHD. A cross-sectional sample of 190 adult patients with CHD (51% male; mean age = 32.28, SD = 11.86 years) completed validated measures of perceived parental overprotection (Parental Bonding Instrument) and heart-focused anxiety (Cardiac Anxiety Questionnaire). The results indicated that perceived parental overprotection (β = 0.19, p = 0.02) and heart defect complexity (β = 0.17, p = 0.03) were significantly related to heart-focused anxiety. Contrary to hypotheses, perceived parental overprotection did not vary as a function of heart defect complexity (F (2, 169) = 0.02, p = 0.98). Perceived parental overprotection and heart defect complexity are associated with heart-focused anxiety in adults with congenital heart disease. These results can inform the development of clinical interventions aimed at improving the psychosocial adjustment of this patient population.

Role of sinoatrial node architecture in maintaining a balanced source-sink relationship and synchronous cardiac pacemaking

PubMed Central

Unudurthi, Sathya D.; Wolf, Roseanne M.; Hund, Thomas J.

2014-01-01

Normal heart rhythm (sinus rhythm) depends on regular activity of the sinoatrial node (SAN), a heterogeneous collection of specialized myocytes in the right atrium. SAN cells, in general, possess a unique electrophysiological profile that promotes spontaneous electrical activity (automaticity). However, while automaticity is required for normal pacemaking, it is not necessarily sufficient. Less appreciated is the importance of the elaborate structure of the SAN complex for proper pacemaker function. Here, we review the important structural features of the SAN with a focus on how these elements help manage a precarious balance between electrical charge generated by the SAN (“source”) and the charge needed to excite the surrounding atrial tissue (“sink”). We also discuss how compromised “source-sink” balance due, for example to fibrosis, may promote SAN dysfunction, characterized by slow and/or asynchronous pacemaker activity and even failure, in the setting of cardiovascular disease (e.g., heart failure, atrial fibrillation). Finally, we discuss implications of the “source-sink” balance in the SAN complex for cell and gene therapies aimed at creating a biological pacemaker as replacement or bridge to conventional electronic pacemakers. PMID:25505419

Can complexity decrease in congestive heart failure?

NASA Astrophysics Data System (ADS)

Mukherjee, Sayan; Palit, Sanjay Kumar; Banerjee, Santo; Ariffin, M. R. K.; Rondoni, Lamberto; Bhattacharya, D. K.

2015-12-01

The complexity of a signal can be measured by the Recurrence period density entropy (RPDE) from the reconstructed phase space. We have chosen a window based RPDE method for the classification of signals, as RPDE is an average entropic measure of the whole phase space. We have observed the changes in the complexity in cardiac signals of normal healthy person (NHP) and congestive heart failure patients (CHFP). The results show that the cardiac dynamics of a healthy subject is more complex and random compare to the same for a heart failure patient, whose dynamics is more deterministic. We have constructed a general threshold to distinguish the border line between a healthy and a congestive heart failure dynamics. The results may be useful for wide range for physiological and biomedical analysis.

Neurocognitive and executive functioning in adult survivors of congenital heart disease.

PubMed

Klouda, Leda; Franklin, Wayne J; Saraf, Anita; Parekh, Dhaval R; Schwartz, David D

2017-01-01

Congenital heart disease (CHD) can affect the developing central nervous system, resulting in neurocognitive and behavioral deficits. Preoperative neurological abnormalities as well as sequelae of the open heart operations required to correct structural abnormalities of the heart contribute to these deficits. There are few studies examining the neurocognitive functioning of adults with CHD. This study sought to investigate multiple domains of neurocognitive functioning in adult survivors of CHD who had childhood cardiac surgery with either moderate or severe disease complexity. A total of 48 adults (18-49 years of age) who had undergone cardiac surgery for CHD prior to five years of age participated in the study. CHD severity was classified as moderate or severe according to the 32nd Bethesda Guidelines. A computerized battery of standardized neurocognitive tests (CNS-Vital Signs), a validated rating scale of executive functioning, and demographic questionnaires were administered. There were no significant differences between the moderate CHD group and normative data on any cognitive measure. In contrast, the severe CHD group differed from norms in multiple domains: psychomotor speed, processing speed, complex attention, reaction time, and on the overall neurocognitive index. Number of surgeries was strongly related to worse executive functioning. There was no association between age at first surgery or time since last surgery and neuropsychological functioning. Number of surgeries was also unrelated to neurocognitive test performance. Patients with severe CHD performed significantly worse on measures of processing speed, attention, and executive functioning. These findings may be useful in the long-term care of adults with congenital heart disease. © 2016 Wiley Periodicals, Inc.

QRS peak detection for heart rate monitoring on Android smartphone

NASA Astrophysics Data System (ADS)

Pambudi Utomo, Trio; Nuryani, Nuryani; Darmanto

2017-11-01

In this study, Android smartphone is used for heart rate monitoring and displaying electrocardiogram (ECG) graph. Heart rate determination is based on QRS peak detection. Two methods are studied to detect the QRS complex peak; they are Peak Threshold and Peak Filter. The acquisition of ECG data is utilized by AD8232 module from Analog Devices, three electrodes, and Microcontroller Arduino UNO R3. To record the ECG data from a patient, three electrodes are attached to particular body’s surface of a patient. Patient’s heart activity which is recorded by AD8232 module is decoded by Arduino UNO R3 into analog data. Then, the analog data is converted into a voltage value (mV) and is processed to get the QRS complex peak. Heart rate value is calculated by Microcontroller Arduino UNO R3 uses the QRS complex peak. Voltage, heart rate, and the QRS complex peak are sent to Android smartphone by Bluetooth HC-05. ECG data is displayed as the graph by Android smartphone. To evaluate the performance of QRS complex peak detection method, three parameters are used; they are positive predictive, accuracy and sensitivity. Positive predictive, accuracy, and sensitivity of Peak Threshold method is 92.39%, 70.30%, 74.62% and for Peak Filter method are 98.38%, 82.47%, 83.61%, respectively.

Xenopus: An Emerging Model for Studying Congenital Heart Disease

PubMed Central

Kaltenbrun, Erin; Tandon, Panna; Amin, Nirav M.; Waldron, Lauren; Showell, Chris; Conlon, Frank L.

2011-01-01

Congenital heart defects affect nearly 1% of all newborns and are a significant cause of infant death. Clinical studies have identified a number of congenital heart syndromes associated with mutations in genes that are involved in the complex process of cardiogenesis. The African clawed frog, Xenopus, has been instrumental in studies of vertebrate heart development and provides a valuable tool to investigate the molecular mechanisms underlying human congenital heart diseases. In this review, we discuss the methodologies that make Xenopus an ideal model system to investigate heart development and disease. We also outline congenital heart conditions linked to cardiac genes that have been well-studied in Xenopus and describe some emerging technologies that will further aid in the study of these complex syndromes. PMID:21538812

A novel gallium bisaminothiolate complex as a myocardial perfusion imaging agent

PubMed Central

Plössl, Karl; Chandra, Rajesh; Qu, Wenchao; Lieberman, Brian P.; Kung, Mei-Ping; Zhou, Rong; Huang, Bin; Kung, Hank F.

2010-01-01

The development of new myocardial perfusion imaging agents for positron emission tomography (PET) may improve the resolution and quantitation of changes in regional myocardial perfusion measurement. It is known that a 68Ge/68Ga generator can provide a convenient source of PET tracers because of the long physical half-life of 68Ge (271 days). A new ligand, 7,8-dithia-16,24-diaza-trispiro[5.2.5.2.5.3] pentacosa-15,24-diene, which consists of a N2S2-chelating core incorporated into three cyclohexyl rings, was prepared. To test feasibility and potential utility, the N2S2 ligand was successfully labeled and tested with 67Ga (half-life=3.26 day; γ=93.3, 184.6 and 300.2 keV), which showed >92% radiochemical purity. The corresponding “cold” Ga complex was synthesized, and its structure containing a pyramidal N2S2 chloride core was elucidated with X-ray crystallography. In vivo biodistribution of this novel 67Ga complex, evaluated in normal rats, exhibited excellent heart uptake and retention, with 2.1% and 0.9% initial dose/organ at 2 and 60 min, respectively, after an intravenous injection. Autoradiography was performed in normal rats and in rats that had the left anterior descending coronary artery permanently ligated surgically. Autoradiography showed an even uptake of activity in the normal heart, and there was a distinctively lower uptake in the damaged side of the surgically modified heart. In conclusion, the new N2S2 ligand was readily prepared and labeled with radioactive 67Ga. Biodistribution in rats revealed high initial heart uptake and relatively high retention reflecting regional myocardial perfusion. PMID:18158947

Initial fractal exponent of heart-rate variability is associated with success of early resuscitation in patients with severe sepsis or septic shock: a prospective cohort study

PubMed Central

Brown, Samuel M.; Tate, Quinn; Jones, Jason P.; Knox, Daniel; Kuttler, Kathryn G.; Lanspa, Michael; Rondina, Matthew T.; Grissom, Colin K.; Behera, Subhasis; Mathews, V.J.; Morris, Alan

2013-01-01

Introduction Heart-rate variability reflects autonomic nervous system tone as well as the overall health of the baroreflex system. We hypothesized that loss of complexity in heart-rate variability upon ICU admission would be associated with unsuccessful early resuscitation of sepsis. Methods We prospectively enrolled patients admitted to ICUs with severe sepsis or septic shock from 2009 to 2011. We studied 30 minutes of EKG, sampled at 500 Hz, at ICU admission and calculated heart-rate complexity via detrended fluctuation analysis. Primary outcome was vasopressor independence at 24 hours after ICU admission. Secondary outcome was 28-day mortality. Results We studied 48 patients, of whom 60% were vasopressor independent at 24 hours. Five (10%) died within 28 days. The ratio of fractal alpha parameters was associated with both vasopressor independence and 28-day mortality (p=0.04) after controlling for mean heart rate. In the optimal model, SOFA score and the long-term fractal alpha parameter were associated with vasopressor independence. Conclusions Loss of complexity in heart rate variability is associated with worse outcome early in severe sepsis and septic shock. Further work should evaluate whether complexity of heart rate variability (HRV) could guide treatment in sepsis. PMID:23958243

Matrix metalloproteinase-10/TIMP-2 structure and analyses define conserved core interactions and diverse exosite interactions in MMP/TIMP complexes.

PubMed

Batra, Jyotica; Soares, Alexei S; Mehner, Christine; Radisky, Evette S

2013-01-01

Matrix metalloproteinases (MMPs) play central roles in vertebrate tissue development, remodeling, and repair. The endogenous tissue inhibitors of metalloproteinases (TIMPs) regulate proteolytic activity by binding tightly to the MMP active site. While each of the four TIMPs can inhibit most MMPs, binding data reveal tremendous heterogeneity in affinities of different TIMP/MMP pairs, and the structural features that differentiate stronger from weaker complexes are poorly understood. Here we report the crystal structure of the comparatively weakly bound human MMP-10/TIMP-2 complex at 2.1 Å resolution. Comparison with previously reported structures of MMP-3/TIMP-1, MT1-MMP/TIMP-2, MMP-13/TIMP-2, and MMP-10/TIMP-1 complexes offers insights into the structural basis of binding selectivity. Our analyses identify a group of highly conserved contacts at the heart of MMP/TIMP complexes that define the conserved mechanism of inhibition, as well as a second category of diverse adventitious contacts at the periphery of the interfaces. The AB loop of the TIMP N-terminal domain and the contact loops of the TIMP C-terminal domain form highly variable peripheral contacts that can be considered as separate exosite interactions. In some complexes these exosite contacts are extensive, while in other complexes the AB loop or C-terminal domain contacts are greatly reduced and appear to contribute little to complex stability. Our data suggest that exosite interactions can enhance MMP/TIMP binding, although in the relatively weakly bound MMP-10/TIMP-2 complex they are not well optimized to do so. Formation of highly variable exosite interactions may provide a general mechanism by which TIMPs are fine-tuned for distinct regulatory roles in biology.

Current progress in tissue engineering of heart valves: multiscale problems, multiscale solutions.

PubMed

Cheung, Daniel Y; Duan, Bin; Butcher, Jonathan T

2015-01-01

Heart valve disease is an increasingly prevalent and clinically serious condition. There are no clinically effective biological diagnostics or treatment strategies. The only recourse available is replacement with a prosthetic valve, but the inability of these devices to grow or respond biologically to their environments necessitates multiple resizing surgeries and life-long coagulation treatment, especially in children. Tissue engineering has a unique opportunity to impact heart valve disease by providing a living valve conduit, capable of growth and biological integration. This review will cover current tissue engineering strategies in fabricating heart valves and their progress towards the clinic, including molded scaffolds using naturally derived or synthetic polymers, decellularization, electrospinning, 3D bioprinting, hybrid techniques, and in vivo engineering. Whereas much progress has been made to create functional living heart valves, a clinically viable product is not yet realized. The next leap in engineered living heart valves will require a deeper understanding of how the natural multi-scale structural and biological heterogeneity of the tissue ensures its efficient function. Related, improved fabrication strategies must be developed that can replicate this de novo complexity, which is likely instructive for appropriate cell differentiation and remodeling whether seeded with autologous stem cells in vitro or endogenously recruited cells.

Current Progress in Tissue Engineering of Heart Valves: Multiscale Problems, Multiscale Solutions

PubMed Central

Cheung, Daniel Y; Duan, Bin; Butcher, Jonathan T.

2016-01-01

Introduction Heart valve disease is an increasingly prevalent and clinically serious condition. There are no clinically effective biological diagnostics or treatment strategies. The only recourse available is replacement with a prosthetic valve, but the inability of these devices to grow or respond biologically to their environments necessitates multiple resizing surgeries and life-long coagulation treatment, especially in children. Tissue engineering has a unique opportunity to impact heart valve disease by providing a living valve conduit, capable of growth and biological integration. Areas covered This review will cover current tissue engineering strategies in fabricating heart valves and their progress towards the clinic, including molded scaffolds using naturally-derived or synthetic polymers, decellularization, electrospinning, 3D bioprinting, hybrid techniques, and in vivo engineering. Expert opinion While much progress has been made to create functional living heart valves, a clinically viable product is not yet realized. The next leap in engineered living heart valves will require a deeper understanding of how the natural multi-scale structural and biological heterogeneity of the tissue ensures its efficient function. Related, improved fabrication strategies must be developed that can replicate this de novo complexity, which is likely instructive for appropriate cell differentiation and remodeling whether seeded with autologous stem cells in vitro or endogenously recruited cells. PMID:26027436

Heart transplantation for adults with congenital heart disease: current status and future prospects.

PubMed

Matsuda, Hikaru; Ichikawa, Hajime; Ueno, Takayoshi; Sawa, Yoshiki

2017-06-01

Increased survival rates after corrective or palliative surgery for complex congenital heart disease (CHD) in infancy and childhood are now being coupled with increased numbers of patients who survive to adulthood with various residual lesions or sequelae. These patients are likely to deteriorate in cardiac function or end-organ function, eventually requiring lifesaving treatment including heart transplantation. Although early and late outcomes of heart transplantation have been improving for adult survivors of CHD, outcomes and pretransplant management could still be improved. Survivors of Fontan procedures are a vulnerable cohort, particularly when single ventricle physiology fails, mostly with protein-losing enteropathy and hepatic dysfunction. Therefore, we reviewed single-institution and larger database analyses of adults who underwent heart transplantation for CHD, to enable risk stratification by identifying the indications and outcomes. As the results, despite relatively high early mortality, long-term results were encouraging after heart transplantation. However, further investigations are needed to improve the indication criteria for complex CHD, especially for failed Fontan. In addition, the current system of status criteria and donor heart allocation system in heart transplantation should be arranged as suitable for adults with complex CHD. Furthermore, there is a strong need to develop ventricular assist devices as a bridge to transplantation or destination therapy, especially where right-sided circulatory support is needed.

Probability of detection of clinical seizures using heart rate changes.

PubMed

Osorio, Ivan; Manly, B F J

2015-08-01

Heart rate-based seizure detection is a viable complement or alternative to ECoG/EEG. This study investigates the role of various biological factors on the probability of clinical seizure detection using heart rate. Regression models were applied to 266 clinical seizures recorded from 72 subjects to investigate if factors such as age, gender, years with epilepsy, etiology, seizure site origin, seizure class, and data collection centers, among others, shape the probability of EKG-based seizure detection. Clinical seizure detection probability based on heart rate changes, is significantly (p<0.001) shaped by patients' age and gender, seizure class, and years with epilepsy. The probability of detecting clinical seizures (>0.8 in the majority of subjects) using heart rate is highest for complex partial seizures, increases with a patient's years with epilepsy, is lower for females than for males and is unrelated to the side of hemisphere origin. Clinical seizure detection probability using heart rate is multi-factorially dependent and sufficiently high (>0.8) in most cases to be clinically useful. Knowledge of the role that these factors play in shaping said probability will enhance its applicability and usefulness. Heart rate is a reliable and practical signal for extra-cerebral detection of clinical seizures originating from or spreading to central autonomic network structures. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

The effect of orthostatic stress on multiscale entropy of heart rate and blood pressure.

PubMed

Turianikova, Zuzana; Javorka, Kamil; Baumert, Mathias; Calkovska, Andrea; Javorka, Michal

2011-09-01

Cardiovascular control acts over multiple time scales, which introduces a significant amount of complexity to heart rate and blood pressure time series. Multiscale entropy (MSE) analysis has been developed to quantify the complexity of a time series over multiple time scales. In previous studies, MSE analyses identified impaired cardiovascular control and increased cardiovascular risk in various pathological conditions. Despite the increasing acceptance of the MSE technique in clinical research, information underpinning the involvement of the autonomic nervous system in the MSE of heart rate and blood pressure is lacking. The objective of this study is to investigate the effect of orthostatic challenge on the MSE of heart rate and blood pressure variability (HRV, BPV) and the correlation between MSE (complexity measures) and traditional linear (time and frequency domain) measures. MSE analysis of HRV and BPV was performed in 28 healthy young subjects on 1000 consecutive heart beats in the supine and standing positions. Sample entropy values were assessed on scales of 1-10. We found that MSE of heart rate and blood pressure signals is sensitive to changes in autonomic balance caused by postural change from the supine to the standing position. The effect of orthostatic challenge on heart rate and blood pressure complexity depended on the time scale under investigation. Entropy values did not correlate with the mean values of heart rate and blood pressure and showed only weak correlations with linear HRV and BPV measures. In conclusion, the MSE analysis of heart rate and blood pressure provides a sensitive tool to detect changes in autonomic balance as induced by postural change.

Atrial Fibrillation: Mechanisms, Therapeutics, and Future Directions

PubMed Central

Pellman, Jason; Sheikh, Farah

2017-01-01

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, affecting 1% to 2% of the general population. It is characterized by rapid and disorganized atrial activation leading to impaired atrial function, which can be diagnosed on an EKG by lack of a P-wave and irregular QRS complexes. AF is associated with increased morbidity and mortality and is a risk factor for embolic stroke and worsening heart failure. Current research on AF support and explore the hypothesis that initiation and maintenance of AF require pathophysiological remodeling of the atria, either specifically as in lone AF or secondary to other heart disease as in heart failure-associated AF. Remodeling in AF can be grouped into three categories that include: (i) electrical remodeling, which includes modulation of L-type Ca2+ current, various K+ currents and gap junction function; (ii) structural remodeling, which includes changes in tissues properties, size, and ultrastructure; and (iii) autonomic remodeling, including altered sympathovagal activity and hyperinnervation. Electrical, structural, and autonomic remodeling all contribute to creating an AF-prone substrate which is able to produce AF-associated electrical phenomena including a rapidly firing focus, complex multiple reentrant circuit or rotors. Although various remodeling events occur in AF, current AF therapies focus on ventricular rate and rhythm control strategies using pharmacotherapy and surgical interventions. Recent progress in the field has started to focus on the underlying substrate that drives and maintains AF (termed upstream therapies); however, much work is needed in this area. Here, we review current knowledge of AF mechanisms, therapies, and new areas of investigation. PMID:25880508

STUDIES ON MAMMALIAN AND HUMAN PYRUVATE AND ALPHA-KETOGLUTARATE DEHYDROGENATION COMPLEXES.

DTIC Science & Technology

The pig heart pyruvate and alpha - ketoglutarate dehydrogenase complex were isolated in highly purified state as multienzyme units with molecular...weights of approximately 9 million and 2.8 million, respectively. The aims were to resolve the pig heart pyruvate and alpha - ketoglutarate dehydrogenase...complexes was isolated from three sources; (1) pyruvate dehydrogenase complex, (2) alpha - ketoglutarate dehydrogenase, and (3) amber-color extract free

Heart transplantation experiences: a phenomenological approach.

PubMed

Sadala, Maria Lúcia Araújo; Stolf, Noedir Antônio Groppo

2008-04-01

The aim of this study was to understand the heart transplantation experience based on patients' descriptions. To patients with heart failure, heart transplantation represents a possibility to survive and improve their quality of life. Studies have shown that more quality of life is related to patients' increasing awareness and participation in the work of the healthcare team in the post-transplantation period. Deficient relationships between patients and healthcare providers result in lower compliance with the postoperative regimen. A phenomenological approach was used to interview 26 patients who were heart transplant recipients. Patients were interviewed individually and asked this single question: What does the experience of being heart transplanted mean? Participants' descriptions were analysed using phenomenological reduction, analysis and interpretation. Three categories emerged from data analysis: (i) the time lived by the heart recipient; (ii) donors, family and caregivers and (iii) reflections on the experience lived. Living after heart transplant means living in a complex situation: recipients are confronted with lifelong immunosuppressive therapy associated with many side-effects. Some felt healthy whereas others reported persistence of complications as well as the onset of other pathologies. However, all participants celebrated an improvement in quality of life. Health caregivers, their social and family support had been essential for their struggle. Participants realised that life after heart transplantation was a continuing process demanding support and structured follow-up for the rest of their lives. The findings suggest that each individual has unique experiences of the heart transplantation process. To go on living participants had to accept changes and adapt: to the organ change, to complications resulting from rejection of the organ, to lots of pills and food restrictions. Stimulating a heart transplant patients spontaneous expression about what they are experiencing and granting them the actual status of the main character in their own story is important to their care.

Loss of Intralipid®- but Not Sevoflurane-Mediated Cardioprotection in Early Type-2 Diabetic Hearts of Fructose-Fed Rats: Importance of ROS Signaling

PubMed Central

Zhang, Liyan; Affolter, Andreas; Gandhi, Manoj; Hersberger, Martin; Warren, Blair E.; Lemieux, Hélène; Sobhi, Hany F.; Clanachan, Alexander S.; Zaugg, Michael

2014-01-01

Background Insulin resistance and early type-2 diabetes are highly prevalent. However, it is unknown whether Intralipid® and sevoflurane protect the early diabetic heart against ischemia-reperfusion injury. Methods Early type-2 diabetic hearts from Sprague-Dawley rats fed for 6 weeks with fructose were exposed to 15 min of ischemia and 30 min of reperfusion. Intralipid® (1%) was administered at the onset of reperfusion. Peri-ischemic sevoflurane (2 vol.-%) served as alternative protection strategy. Recovery of left ventricular function was recorded and the activation of Akt and ERK 1/2 was monitored. Mitochondrial function was assessed by high-resolution respirometry and mitochondrial ROS production was measured by Amplex Red and aconitase activity assays. Acylcarnitine tissue content was measured and concentration-response curves of complex IV inhibition by palmitoylcarnitine were obtained. Results Intralipid® did not exert protection in early diabetic hearts, while sevoflurane improved functional recovery. Sevoflurane protection was abolished by concomitant administration of the ROS scavenger N-2-mercaptopropionyl glycine. Sevoflurane, but not Intralipid® produced protective ROS during reperfusion, which activated Akt. Intralipid® failed to inhibit respiratory complex IV, while sevoflurane inhibited complex I. Early diabetic hearts exhibited reduced carnitine-palmitoyl-transferase-1 activity, but palmitoylcarnitine could not rescue protection and enhance postischemic functional recovery. Cardiac mitochondria from early diabetic rats exhibited an increased content of subunit IV-2 of respiratory complex IV and of uncoupling protein-3. Conclusions Early type-2 diabetic hearts lose complex IV-mediated protection by Intralipid® potentially due to a switch in complex IV subunit expression and increased mitochondrial uncoupling, but are amenable to complex I-mediated sevoflurane protection. PMID:25127027

Complexity of the heart rhythm after heart transplantation by entropy of transition network for RR-increments of RR time intervals between heartbeats.

PubMed

Makowiec, Danuta; Struzik, Zbigniew; Graff, Beata; Wdowczyk-Szulc, Joanna; Zarczynska-Buchnowiecka, Marta; Gruchala, Marcin; Rynkiewicz, Andrzej

2013-01-01

Network models have been used to capture, represent and analyse characteristics of living organisms and general properties of complex systems. The use of network representations in the characterization of time series complexity is a relatively new but quickly developing branch of time series analysis. In particular, beat-to-beat heart rate variability can be mapped out in a network of RR-increments, which is a directed and weighted graph with vertices representing RR-increments and the edges of which correspond to subsequent increments. We evaluate entropy measures selected from these network representations in records of healthy subjects and heart transplant patients, and provide an interpretation of the results.

Diminished heart rate complexity in adolescent girls: a sign of vulnerability to anxiety disorders?

PubMed

Fiol-Veny, Aina; De la Torre-Luque, Alejandro; Balle, Maria; Bornas, Xavier

2018-07-01

Diminished heart rate variability has been found to be associated with high anxiety symptomatology. Since adolescence is the period of onset for many anxiety disorders, this study aimed to determine sex- and anxiety-related differences in heart rate variability and complexity in adolescents. We created four groups according to sex and anxiety symptomatology: high-anxiety girls (n = 24) and boys (n = 25), and low-anxiety girls (n = 22) and boys (n = 24) and recorded their cardiac function while they performed regular school activities. A series of two-way (sex and anxiety) MANOVAs were performed on time domain variability, frequency domain variability, and non-linear complexity. We obtained no multivariate interaction effects between sex and anxiety, but highly anxious participants had lower heart rate variability than the low-anxiety group. Regarding sex, girls showed lower heart rate variability and complexity than boys. The results suggest that adolescent girls have a less flexible cardiac system that could be a marker of the girls' vulnerability to developing anxiety disorders.

Nutrition and growth in congenital heart disease: a challenge in children.

PubMed

Medoff-Cooper, Barbara; Ravishankar, Chitra

2013-03-01

Growth failure secondary to feeding problems after complex neonatal cardiac surgery is well documented, but not well understood. The purpose of this review is to describe feeding and growth pattern in children with congenital heart defects. Nearly half of the infants with univentricular heart defects require supplementation with nasogastric or gastrostomy tube at discharge from neonatal surgery. Feeding challenges contribute to parental stress, and persist beyond infancy. These infants are 'stunted' with both weight and height being below normal. Nearly a quarter of these infants meet the definition of 'failure to thrive' in the first year of life. Short stature is a significant problem for many of these children, and has an impact on neurodevelopmental outcomes. A structured nutritional program can have a positive impact on growth in the interstage period prior to the superior cavopulmonary connection. Optimizing nutritional intake has been targeted as a key component of the National Pediatric Cardiology Quality Improvement Collaborative. This initiative has enabled the development of best practices that have the potential to mitigate poor growth in children with congenital heart defects.

A molecular chaperone for mitochondrial complex I assembly is mutated in a progressive encephalopathy

PubMed Central

Ogilvie, Isla; Kennaway, Nancy G.; Shoubridge, Eric A.

2005-01-01

NADH:ubiquinone oxidoreductase (complex I) deficiency is a common cause of mitochondrial oxidative phosphorylation disease. It is associated with a wide range of clinical phenotypes in infants, including Leigh syndrome, cardiomyopathy, and encephalomyopathy. In at least half of patients, enzyme deficiency results from a failure to assemble the holoenzyme complex; however, the molecular chaperones required for assembly of the mammalian enzyme remain unknown. Using whole genome subtraction of yeasts with and without a complex I to generate candidate assembly factors, we identified a paralogue (B17.2L) of the B17.2 structural subunit. We found a null mutation in B17.2L in a patient with a progressive encephalopathy and showed that the associated complex I assembly defect could be completely rescued by retroviral expression of B17.2L in patient fibroblasts. An anti-B17.2L antibody did not associate with the holoenzyme complex but specifically recognized an 830-kDa subassembly in several patients with complex I assembly defects and coimmunoprecipitated a subset of complex I structural subunits from normal human heart mitochondria. These results demonstrate that B17.2L is a bona fide molecular chaperone that is essential for the assembly of complex I and for the normal function of the nervous system. PMID:16200211

Four-chamber heart modeling and automatic segmentation for 3-D cardiac CT volumes using marginal space learning and steerable features.

PubMed

Zheng, Yefeng; Barbu, Adrian; Georgescu, Bogdan; Scheuering, Michael; Comaniciu, Dorin

2008-11-01

We propose an automatic four-chamber heart segmentation system for the quantitative functional analysis of the heart from cardiac computed tomography (CT) volumes. Two topics are discussed: heart modeling and automatic model fitting to an unseen volume. Heart modeling is a nontrivial task since the heart is a complex nonrigid organ. The model must be anatomically accurate, allow manual editing, and provide sufficient information to guide automatic detection and segmentation. Unlike previous work, we explicitly represent important landmarks (such as the valves and the ventricular septum cusps) among the control points of the model. The control points can be detected reliably to guide the automatic model fitting process. Using this model, we develop an efficient and robust approach for automatic heart chamber segmentation in 3-D CT volumes. We formulate the segmentation as a two-step learning problem: anatomical structure localization and boundary delineation. In both steps, we exploit the recent advances in learning discriminative models. A novel algorithm, marginal space learning (MSL), is introduced to solve the 9-D similarity transformation search problem for localizing the heart chambers. After determining the pose of the heart chambers, we estimate the 3-D shape through learning-based boundary delineation. The proposed method has been extensively tested on the largest dataset (with 323 volumes from 137 patients) ever reported in the literature. To the best of our knowledge, our system is the fastest with a speed of 4.0 s per volume (on a dual-core 3.2-GHz processor) for the automatic segmentation of all four chambers.

Ryanodine receptors/calcium release channels in heart failure and sudden cardiac death.

PubMed

Marks, A R

2001-04-01

Calcium (Ca2+) ions are second messengers in signaling pathways in all types of cells. They regulate muscle contraction, electrical signals which determine the cardiac rhythm and cell growth pathways in the heart. In the past decade cDNA cloning has provided clues as to the molecular structure of the intracellular Ca2+ release channels (ryanodine receptors, RyR, and inositol 1,4,5-trisphosphate receptors, IP3R) on the sarcoplasmic and endoplasmic reticulum (SR/ER) and an understanding of how these molecules regulate Ca2+ homeostasis in the heart is beginning to emerge. The intracellular Ca2+ release channels form a distinct class of ion channels distinguished by their structure, size, and function. Both RyRs and IP3Rs have gigantic cytoplasmic domains that serve as scaffolds for modulatory proteins that regulate the channel pore located in the carboxy terminal 10% of the channel sequence. The channels are tetramers comprised of four RyR or IP3R subunits. RyR2 is required for excitation-contraction (EC) coupling in the heart. Using co-sedimentation and co-immunoprecipitation we have defined a macromolecular complex comprised of RyR2, FKBP12.6, PKA, the protein phosphatases PP1 and PP2A, and an anchoring protein mAKAP. We have shown that protein kinase A (PKA) phosphorylation of RyR2 dissociates FKBP12.6 and regulates the channel open probability (P(o)). In failing human hearts RyR2 is PKA hyperphosphorylated resulting in defective channel function due to increased sensitivity to Ca2+-induced activation.

[Is iron important in heart failure?].

PubMed

Murín, Ján; Pernický, Miroslav

2015-01-01

Iron deficiency is a frequent comorbidity in a patient with chronic heart failure, and it associates with a worse pro-gnosis of that patient. Mainly worse quality of life and more rehospitalizations are in these iron deficient patients. Iron metabolism is rather complex and there is some new information concerning this complexity in heart failure. We distinquish an absolute and a functional iron deficiency in heart failure. It is this deficit which is important and not as much is anemia important here. Prevalence of anaemia in heart failure is about 30-50 %, higher it is in patients suffering more frequently heart failure decompensations. Treatment of iron deficiency is important and it improves prognosis of these patients. Most experiences there are with i.v. iron treatment (FERRIC HF, FAIR HF and CONFIRM HF studies), less so with per oral treatment. There are no clinical trials which analysed mortality influences. heart failure - iron metabolism in heart failure - prevalence of iron deficit - treatment of iron deficiency in heart failure.

Pathophysiology of Degenerative Mitral Regurgitation: New 3-Dimensional Imaging Insights.

PubMed

Antoine, Clemence; Mantovani, Francesca; Benfari, Giovanni; Mankad, Sunil V; Maalouf, Joseph F; Michelena, Hector I; Enriquez-Sarano, Maurice

2018-01-01

Despite its high prevalence, little is known about mechanisms of mitral regurgitation in degenerative mitral valve disease apart from the leaflet prolapse itself. Mitral valve is a complex structure, including mitral annulus, mitral leaflets, papillary muscles, chords, and left ventricular walls. All these structures are involved in physiological and pathological functioning of this valvuloventricular complex but up to now were difficult to analyze because of inherent limitations of 2-dimensional imaging. The advent of 3-dimensional echocardiography, computed tomography, and cardiac magnetic resonance imaging overcoming these limitations provides new insights into mechanistic analysis of degenerative mitral regurgitation. This review will detail the contribution of quantitative and qualitative dynamic analysis of mitral annulus and mitral leaflets by new imaging methods in the understanding of degenerative mitral regurgitation pathophysiology. © 2018 American Heart Association, Inc.

A BAG3 chaperone complex maintains cardiomyocyte function during proteotoxic stress

PubMed Central

Judge, Luke M.; Perez-Bermejo, Juan A.; Truong, Annie; Ribeiro, Alexandre J.S.; Yoo, Jennie C.; Jensen, Christina L.; Mandegar, Mohammad A.; Huebsch, Nathaniel; Kaake, Robyn M.; So, Po-Lin; Srivastava, Deepak; Krogan, Nevan J.

2017-01-01

Molecular chaperones regulate quality control in the human proteome, pathways that have been implicated in many diseases, including heart failure. Mutations in the BAG3 gene, which encodes a co-chaperone protein, have been associated with heart failure due to both inherited and sporadic dilated cardiomyopathy. Familial BAG3 mutations are autosomal dominant and frequently cause truncation of the coding sequence, suggesting a heterozygous loss-of-function mechanism. However, heterozygous knockout of the murine BAG3 gene did not cause a detectable phenotype. To model BAG3 cardiomyopathy in a human system, we generated an isogenic series of human induced pluripotent stem cells (iPSCs) with loss-of-function mutations in BAG3. Heterozygous BAG3 mutations reduced protein expression, disrupted myofibril structure, and compromised contractile function in iPSC-derived cardiomyocytes (iPS-CMs). BAG3-deficient iPS-CMs were particularly sensitive to further myofibril disruption and contractile dysfunction upon exposure to proteasome inhibitors known to cause cardiotoxicity. We performed affinity tagging of the endogenous BAG3 protein and mass spectrometry proteomics to further define the cardioprotective chaperone complex that BAG3 coordinates in the human heart. Our results establish a model for evaluating protein quality control pathways in human cardiomyocytes and their potential as therapeutic targets and susceptibility factors for cardiac drug toxicity. PMID:28724793

A BAG3 chaperone complex maintains cardiomyocyte function during proteotoxic stress.

PubMed

Judge, Luke M; Perez-Bermejo, Juan A; Truong, Annie; Ribeiro, Alexandre Js; Yoo, Jennie C; Jensen, Christina L; Mandegar, Mohammad A; Huebsch, Nathaniel; Kaake, Robyn M; So, Po-Lin; Srivastava, Deepak; Pruitt, Beth L; Krogan, Nevan J; Conklin, Bruce R

2017-07-20

Molecular chaperones regulate quality control in the human proteome, pathways that have been implicated in many diseases, including heart failure. Mutations in the BAG3 gene, which encodes a co-chaperone protein, have been associated with heart failure due to both inherited and sporadic dilated cardiomyopathy. Familial BAG3 mutations are autosomal dominant and frequently cause truncation of the coding sequence, suggesting a heterozygous loss-of-function mechanism. However, heterozygous knockout of the murine BAG3 gene did not cause a detectable phenotype. To model BAG3 cardiomyopathy in a human system, we generated an isogenic series of human induced pluripotent stem cells (iPSCs) with loss-of-function mutations in BAG3. Heterozygous BAG3 mutations reduced protein expression, disrupted myofibril structure, and compromised contractile function in iPSC-derived cardiomyocytes (iPS-CMs). BAG3-deficient iPS-CMs were particularly sensitive to further myofibril disruption and contractile dysfunction upon exposure to proteasome inhibitors known to cause cardiotoxicity. We performed affinity tagging of the endogenous BAG3 protein and mass spectrometry proteomics to further define the cardioprotective chaperone complex that BAG3 coordinates in the human heart. Our results establish a model for evaluating protein quality control pathways in human cardiomyocytes and their potential as therapeutic targets and susceptibility factors for cardiac drug toxicity.

Spatiotemporal Permutation Entropy as a Measure for Complexity of Cardiac Arrhythmia

NASA Astrophysics Data System (ADS)

Schlemmer, Alexander; Berg, Sebastian; Lilienkamp, Thomas; Luther, Stefan; Parlitz, Ulrich

2018-05-01

Permutation entropy (PE) is a robust quantity for measuring the complexity of time series. In the cardiac community it is predominantly used in the context of electrocardiogram (ECG) signal analysis for diagnoses and predictions with a major application found in heart rate variability parameters. In this article we are combining spatial and temporal PE to form a spatiotemporal PE that captures both, complexity of spatial structures and temporal complexity at the same time. We demonstrate that the spatiotemporal PE (STPE) quantifies complexity using two datasets from simulated cardiac arrhythmia and compare it to phase singularity analysis and spatial PE (SPE). These datasets simulate ventricular fibrillation (VF) on a two-dimensional and a three-dimensional medium using the Fenton-Karma model. We show that SPE and STPE are robust against noise and demonstrate its usefulness for extracting complexity features at different spatial scales.

Heart Rate Complexity in Response to Upright Tilt in Persons with Down Syndrome

ERIC Educational Resources Information Center

Agiovlasitis, Stamatis; Baynard, Tracy; Pitetti, Kenneth H.; Fernhall, Bo

2011-01-01

People with Down syndrome (DS) show altered autonomic response to sympatho-excitation. Cardiac autonomic modulation may be examined with heart rate (HR) complexity which is associated uniquely with cardiovascular risk. This study examined whether the response of HR complexity to passive upright tilt differs between persons with and without DS and…

Conjoined twins: morphogenesis of the heart and a review.

PubMed

Gilbert-Barness, Enid; Debich-Spicer, Diane; Opitz, John M

2003-08-01

Five cases of conjoined twins have been studied. These included three thoracopagus twins, one monocephalus diprosopus (prosop = face), and one dicephalus dipus dibrachus. The thoracopagus twins were conjoined only from the upper thorax to the umbilicus with a normal foregut. These three cases shared a single complex multiventricular heart, one with a four chambered heart with one atrium and one ventricle belonging to each twin with complex venous and arterial connection; two had a seven chambered heart with four atria and three ventricles. The mono-cephalus diprosopus twins had a single heart with tetralogy of Fallot. The dicephalus twins had two separate axial skeletons to the sacrum, two separate hearts were connected between the right atria with a shared inferior vena cava. Thoracopagus twinning is associated with complex cardiac malformations. The cardiac anlagen in cephalopagus or diprosopus are diverted and divided along with the entire rostral end of the embryonic disc and result in two relatively normal shared hearts. However, in thoracopagus twins the single heart is multiventricular and suggests very early union with fusion of the cardiac anlagen before significant differentiation. Cardiac morphogenesis in conjoined twins therefore appears to depend on the site of the conjoined fusion and the temporal and spatial influence that determines morphogenesis as well as abnormally oriented embryonic axes. Copyright 2003 Wiley-Liss, Inc.

Deciphering the interaction of bovine heart cystatin with ZnO nanoparticles: Spectroscopic and thermodynamic approach.

PubMed

Sohail, Aamir; Faraz, Mohd; Arif, Hussain; Bhat, Sheraz Ahmad; Siddiqui, Azad Alam; Bano, Bilqees

2017-02-01

ZnO-NPs have been widely used in biomedical fields such as therapeutics, cellular imaging, and drug delivery. However, the risk of exposure of nanoparticles to the biological system is not well understood. Nanoparticle-protein interaction is pivotal to understand their biological behavior and predict nanoparticle toxicity that is crucial for its safer applications. In the present study zinc oxide nanoparticles (ZnO-NPs) were synthesized and subjected to interact with buffalo heart cystatin (BHC), purified from buffalo heart, to assess the effect(s) of ZnO-NPs on the structure and function of BHC. In vitro toxicity assessments revealed that BHC, upon interaction with ZnO-NPs, led to the altered protein conformation and perturbed function. A decrease in the anti-papain activity of BHC was observed. Spectroscopic studies demonstrated that formation of BHC-ZnO-NPs complex accompanied by structural changes in BHC along with a significant decrease in its α-helical content. ITC determined the thermodynamic parameters of binding between ZnO-NPs and BHC quantitatively. Increased surface hydrophobicity (change in the tertiary structure) was observed by ANS fluorescence that demonstrated the formation of molten globular intermediates that were found to be stable without any signs of aggregation as depicted by ThT fluorescence. TEM images gave the physical evidence of the formation of ZnO-NPs-BHC corona. Copyright © 2016. Published by Elsevier B.V.

An Analysis of Chemical Ingredients Network of Chinese Herbal Formulae for the Treatment of Coronary Heart Disease

PubMed Central

Ding, Fan; Zhang, Qianru; Ung, Carolina Oi Lam; Wang, Yitao; Han, Yifan; Hu, Yuanjia; Qi, Jin

2015-01-01

As a complex system, the complicated interactions between chemical ingredients, as well as the potential rules of interactive associations among chemical ingredients of traditional Chinese herbal formulae are not yet fully understood by modern science. On the other hand, network analysis is emerging as a powerful approach focusing on processing complex interactive data. By employing network approach in selected Chinese herbal formulae for the treatment of coronary heart disease (CHD), this article aims to construct and analyze chemical ingredients network of herbal formulae, and provide candidate herbs, chemical constituents, and ingredient groups for further investigation. As a result, chemical ingredients network composed of 1588 ingredients from 36 herbs used in 8 core formulae for the treatment of CHD was produced based on combination associations in herbal formulae. In this network, 9 communities with relative dense internal connections are significantly associated with 14 kinds of chemical structures with P<0.001. Moreover, chemical structural fingerprints of network communities were detected, while specific centralities of chemical ingredients indicating different levels of importance in the network were also measured. Finally, several distinct herbs, chemical ingredients, and ingredient groups with essential position in the network or high centrality value are recommended for further pharmacology study in the context of new drug development. PMID:25658855

Emergent explosive synchronization in adaptive complex networks

NASA Astrophysics Data System (ADS)

Avalos-Gaytán, Vanesa; Almendral, Juan A.; Leyva, I.; Battiston, F.; Nicosia, V.; Latora, V.; Boccaletti, S.

2018-04-01

Adaptation plays a fundamental role in shaping the structure of a complex network and improving its functional fitting. Even when increasing the level of synchronization in a biological system is considered as the main driving force for adaptation, there is evidence of negative effects induced by excessive synchronization. This indicates that coherence alone cannot be enough to explain all the structural features observed in many real-world networks. In this work, we propose an adaptive network model where the dynamical evolution of the node states toward synchronization is coupled with an evolution of the link weights based on an anti-Hebbian adaptive rule, which accounts for the presence of inhibitory effects in the system. We found that the emergent networks spontaneously develop the structural conditions to sustain explosive synchronization. Our results can enlighten the shaping mechanisms at the heart of the structural and dynamical organization of some relevant biological systems, namely, brain networks, for which the emergence of explosive synchronization has been observed.

Emergent explosive synchronization in adaptive complex networks.

PubMed

Avalos-Gaytán, Vanesa; Almendral, Juan A; Leyva, I; Battiston, F; Nicosia, V; Latora, V; Boccaletti, S

2018-04-01

Adaptation plays a fundamental role in shaping the structure of a complex network and improving its functional fitting. Even when increasing the level of synchronization in a biological system is considered as the main driving force for adaptation, there is evidence of negative effects induced by excessive synchronization. This indicates that coherence alone cannot be enough to explain all the structural features observed in many real-world networks. In this work, we propose an adaptive network model where the dynamical evolution of the node states toward synchronization is coupled with an evolution of the link weights based on an anti-Hebbian adaptive rule, which accounts for the presence of inhibitory effects in the system. We found that the emergent networks spontaneously develop the structural conditions to sustain explosive synchronization. Our results can enlighten the shaping mechanisms at the heart of the structural and dynamical organization of some relevant biological systems, namely, brain networks, for which the emergence of explosive synchronization has been observed.

Management of Pregnancy in Patients With Complex Congenital Heart Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association.

PubMed

Canobbio, Mary M; Warnes, Carole A; Aboulhosn, Jamil; Connolly, Heidi M; Khanna, Amber; Koos, Brian J; Mital, Seema; Rose, Carl; Silversides, Candice; Stout, Karen

2017-02-21

Today, most female children born with congenital heart disease will reach childbearing age. For many women with complex congenital heart disease, carrying a pregnancy carries a moderate to high risk for both the mother and her fetus. Many such women, however, do not have access to adult congenital heart disease tertiary centers with experienced reproductive programs. Therefore, it is important that all practitioners who will be managing these women have current information not only on preconception counseling and diagnostic evaluation to determine maternal and fetal risk but also on how to manage them once they are pregnant and when to refer them to a regional center with expertise in pregnancy management. © 2017 American Heart Association, Inc.

Critical role of mitochondrial ROS is dependent on their site of production on the electron transport chain in ischemic heart.

PubMed

Madungwe, Ngonidzashe B; Zilberstein, Netanel F; Feng, Yansheng; Bopassa, Jean C

2016-01-01

Reactive oxygen species (ROS) generation has been implicated in many pathologies including ischemia/reperfusion (I/R) injury. This led to multiple studies on antioxidant therapies to treat cardiovascular diseases but paradoxically, results have so far been mixed as ROS production can be beneficial as a signaling mechanism and in cardiac protection via preconditioning interventions. We investigated whether the differential impact of increased ROS in injury as well as in protection could be explained by their site of production on the mitochondrial electron transport chain. Using amplex red to measure ROS production, we found that mitochondria isolated from hearts after I/R produced more ROS than non-ischemic when complex I substrate (glutamate/malate) was used. Interestingly, the substrates of complex II (succinate) and ubiquinone (sn-glycerol 3-phosphate, G3P) produced less ROS in mitochondria from I/R hearts compared to normal healthy hearts. The inhibitors of complex I (rotenone) and complex III (antimycin A) increased ROS production when glutamate/malate and G3P were used; in contrast, they reduced ROS production when the complex II substrate was used. Mitochondrial calcium retention capacity required to induce mitochondrial permeability transition pore (mPTP) opening was measured using calcium green fluorescence and was found to be higher when mitochondria were treated with G3P and succinate compared to glutamate/malate. Furthermore, Langendorff hearts treated with glutamate/malate exhibited reduced cardiac functional recovery and increased myocardial infarct size compared to hearts treated with G3P. Thus, ROS production by the stimulated respiratory chain complexes I and III has opposite roles: cardio-deleterious when produced in complex I and cardio-protective when produced in complex III. The mechanism of these ROS involves the inhibition of the mPTP opening, a key event in cell death following ischemia/reperfusion injury.

Photosensitization of Intact Heart Mitochondria by the Phthalocyanine Pc 4: Correlation of Structural and Functional Deficits with Cytochrome c Release

PubMed Central

Kim, Junhwan; Fujioka, Hisashi; Oleinick, Nancy L.; Anderson, Vernon E.

2010-01-01

Singlet oxygen is produced by absorption of red light by the phthalocyanine dye, Pc 4, followed by energy transfer to dissolved triplet oxygen. Mitochondria pre-incubated with Pc 4 were illuminated by red light and the damage to mitochondrial structure and function by the generated singlet oxygen was studied. At early illumination times (3–5 min. of red light exposure), state 3 respiration was inhibited (50%) while state 4 activity increased, resulting in effectively complete uncoupling. Individual complex activities were measured and only complex IV activity was significantly reduced and exhibited a dose response while the activities of electron transport complexes I, II and III were not significantly affected. Cyt c release was an increasing function of irradiation time with 30% being released following 5 min. of illumination. Mitochondrial expansion along with changes in the structure of the cristae were observed by transmission electron microscopy following 5 min. of irradiation with an increase of large vacuoles and membrane rupture occurring following more extensive exposures. PMID:20510354

The fractal heart — embracing mathematics in the cardiology clinic

PubMed Central

Captur, Gabriella; Karperien, Audrey L.; Hughes, Alun D.; Francis, Darrel P.; Moon, James C.

2017-01-01

For clinicians grappling with quantifying the complex spatial and temporal patterns of cardiac structure and function (such as myocardial trabeculae, coronary microvascular anatomy, tissue perfusion, myocyte histology, electrical conduction, heart rate, and blood-pressure variability), fractal analysis is a powerful, but still underused, mathematical tool. In this Perspectives article, we explain some fundamental principles of fractal geometry and place it in a familiar medical setting. We summarize studies in the cardiovascular sciences in which fractal methods have successfully been used to investigate disease mechanisms, and suggest potential future clinical roles in cardiac imaging and time series measurements. We believe that clinical researchers can deploy innovative fractal solutions to common cardiac problems that might ultimately translate into advancements for patient care. PMID:27708281

Developing Therapies for Heart Failure with Preserved Ejection Fraction: Current State and Future Directions

PubMed Central

Butler, Javed; Fonarow, Gregg C.; Zile, Michael R.; Lam, Carolyn S.; Roessig, Lothar; Schelbert, Erik B.; Shah, Sanjiv J.; Ahmed, Ali; Bonow, Robert O.; Cleland, John GF; Cody, Robert J.; Chioncel, Ovidiu; Collins, Sean P.; Dunnmon, Preston; Filippatos, Gerasimos; Lefkowitz, Martin P.; Marti, Catherine N.; McMurray, John J.; Misselwitz, Frank; Nodari, Savina; O’Connor, Christopher; Pfeffer, Marc A.; Pieske, Burkert; Pitt, Bertram; Rosano, Guiseppe; Sabbah, Hani N.; Senni, Michele; Solomon, Scott D.; Stockbridge, Norman; Teerlink, John R.; Georgiopoulou, Vasiliki V.; Gheorghiade, Mihai

2014-01-01

The burden of heart failure with preserved ejection fraction (HFpEF) is considerable and is projected to worsen. To date, there are no approved therapies available for reducing mortality or hospitalizations for these patients. The pathophysiology of HFpEF is complex and includes alterations in cardiac structure and function, systemic and pulmonary vascular abnormalities, end-organ involvement, and comorbidities. There remain major gaps in our understanding of HFpEF pathophysiology. To facilitate a discussion of how to proceed effectively in future with development of therapies for HFpEF, a meeting was facilitated by the FDA and included representatives from academia, industry and regulatory agencies. This document summarizes the proceedings from this meeting. PMID:24720916

MDCT Venography Evaluation of a Rare Collateral Vein Draining from the Left Subclavian Vein to the Great Cardiac Vein

PubMed Central

Abchee, Antoine; Saade, Charbel; Al-Mohiy, Hussain; El-Merhi, Fadi

2014-01-01

Congenital vascular anomalies of the venous drainage in the chest affect both cardiac and non-cardiac structures. Collateral venous drainage from the left subclavian vein to the great cardiac vein is a rare venous drainage pattern. These anomalies present a diagnostic challenge. Multi-detector computed tomography (MDCT) is useful in the diagnosis and treatment planning of these clinically complex disorders. We present a case report of an 18-year-old Caucasian male who came to our institute for evaluation of venous drainage patterns to the heart. We describe the contrast technique of bilateral dual injection MDCT venography and the imaging features of the venous drainage patterns to the heart. PMID:25379351

MDCT Venography Evaluation of a Rare Collateral Vein Draining from the Left Subclavian Vein to the Great Cardiac Vein.

PubMed

Abchee, Antoine; Saade, Charbel; Al-Mohiy, Hussain; El-Merhi, Fadi

2014-01-01

Congenital vascular anomalies of the venous drainage in the chest affect both cardiac and non-cardiac structures. Collateral venous drainage from the left subclavian vein to the great cardiac vein is a rare venous drainage pattern. These anomalies present a diagnostic challenge. Multi-detector computed tomography (MDCT) is useful in the diagnosis and treatment planning of these clinically complex disorders. We present a case report of an 18-year-old Caucasian male who came to our institute for evaluation of venous drainage patterns to the heart. We describe the contrast technique of bilateral dual injection MDCT venography and the imaging features of the venous drainage patterns to the heart.

X-ray structure of the mammalian GIRK2-βγ G-protein complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whorton, Matthew R.; MacKinnon, Roderick

2013-07-30

G-protein-gated inward rectifier K + (GIRK) channels allow neurotransmitters, through G-protein-coupled receptor stimulation, to control cellular electrical excitability. In cardiac and neuronal cells this control regulates heart rate and neural circuit activity, respectively. Here we present the 3.5Å resolution crystal structure of the mammalian GIRK2 channel in complex with βγ G-protein subunits, the central signalling complex that links G-protein-coupled receptor stimulation to K + channel activity. Short-range atomic and long-range electrostatic interactions stabilize four βγ G-protein subunits at the interfaces between four K + channel subunits, inducing a pre-open state of the channel. The pre-open state exhibits a conformation thatmore » is intermediate between the closed conformation and the open conformation of the constitutively active mutant. The resultant structural picture is compatible with ‘membrane delimited’ activation of GIRK channels by G proteins and the characteristic burst kinetics of channel gating. The structures also permit a conceptual understanding of how the signalling lipid phosphatidylinositol-4,5-bisphosphate (PIP 2) and intracellular Na + ions participate in multi-ligand regulation of GIRK channels.« less

Purification of Ovine Respiratory Complex I Results in a Highly Active and Stable Preparation*

PubMed Central

Letts, James A.; Degliesposti, Gianluca; Fiedorczuk, Karol; Skehel, Mark; Sazanov, Leonid A.

2016-01-01

NADH-ubiquinone oxidoreductase (complex I) is the largest (∼1 MDa) and the least characterized complex of the mitochondrial electron transport chain. Because of the ease of sample availability, previous work has focused almost exclusively on bovine complex I. However, only medium resolution structural analyses of this complex have been reported. Working with other mammalian complex I homologues is a potential approach for overcoming these limitations. Due to the inherent difficulty of expressing large membrane protein complexes, screening of complex I homologues is limited to large mammals reared for human consumption. The high sequence identity among these available sources may preclude the benefits of screening. Here, we report the characterization of complex I purified from Ovis aries (ovine) heart mitochondria. All 44 unique subunits of the intact complex were identified by mass spectrometry. We identified differences in the subunit composition of subcomplexes of ovine complex I as compared with bovine, suggesting differential stability of inter-subunit interactions within the complex. Furthermore, the 42-kDa subunit, which is easily lost from the bovine enzyme, remains tightly bound to ovine complex I. Additionally, we developed a novel purification protocol for highly active and stable mitochondrial complex I using the branched-chain detergent lauryl maltose neopentyl glycol. Our data demonstrate that, although closely related, significant differences exist between the biochemical properties of complex I prepared from ovine and bovine mitochondria and that ovine complex I represents a suitable alternative target for further structural studies. PMID:27672209

Brain volumes predict neurodevelopment in adolescents after surgery for congenital heart disease.

PubMed

von Rhein, Michael; Buchmann, Andreas; Hagmann, Cornelia; Huber, Reto; Klaver, Peter; Knirsch, Walter; Latal, Beatrice

2014-01-01

Patients with complex congenital heart disease are at risk for neurodevelopmental impairments. Evidence suggests that brain maturation can be delayed and pre- and postoperative brain injury may occur, and there is limited information on the long-term effect of congenital heart disease on brain development and function in adolescent patients. At a mean age of 13.8 years, 39 adolescent survivors of childhood cardiopulmonary bypass surgery with no structural brain lesions evident through conventional cerebral magnetic resonance imaging and 32 healthy control subjects underwent extensive neurodevelopmental assessment and cerebral magnetic resonance imaging. Cerebral scans were analysed quantitatively using surface-based and voxel-based morphometry. Compared with control subjects, patients had lower total brain (P = 0.003), white matter (P = 0.004) and cortical grey matter (P = 0.005) volumes, whereas cerebrospinal fluid volumes were not different. Regional brain volume reduction ranged from 5.3% (cortical grey matter) to 11% (corpus callosum). Adolescents with cyanotic heart disease showed more brain volume loss than those with acyanotic heart disease, particularly in the white matter, thalami, hippocampi and corpus callosum (all P-values < 0.05). Brain volume reduction correlated significantly with cognitive, motor and executive functions (grey matter: P < 0.05, white matter: P < 0.01). Our findings suggest that there are long-lasting cerebral changes in adolescent survivors of cardiopulmonary bypass surgery for congenital heart disease and that these changes are associated with functional outcome.

Mitochondrial protein hyperacetylation in the failing heart

PubMed Central

Horton, Julie L.; Martin, Ola J.; Lai, Ling; Richards, Alicia L.; Vega, Rick B.; Leone, Teresa C.; Pagliarini, David J.; Muoio, Deborah M.; Bedi, Kenneth C.; Coon, Joshua J.

2016-01-01

Myocardial fuel and energy metabolic derangements contribute to the pathogenesis of heart failure. Recent evidence implicates posttranslational mechanisms in the energy metabolic disturbances that contribute to the pathogenesis of heart failure. We hypothesized that accumulation of metabolite intermediates of fuel oxidation pathways drives posttranslational modifications of mitochondrial proteins during the development of heart failure. Myocardial acetylproteomics demonstrated extensive mitochondrial protein lysine hyperacetylation in the early stages of heart failure in well-defined mouse models and the in end-stage failing human heart. To determine the functional impact of increased mitochondrial protein acetylation, we focused on succinate dehydrogenase A (SDHA), a critical component of both the tricarboxylic acid (TCA) cycle and respiratory complex II. An acetyl-mimetic mutation targeting an SDHA lysine residue shown to be hyperacetylated in the failing human heart reduced catalytic function and reduced complex II–driven respiration. These results identify alterations in mitochondrial acetyl-CoA homeostasis as a potential driver of the development of energy metabolic derangements that contribute to heart failure. PMID:26998524

Mitochondrial protein hyperacetylation in the failing heart.

PubMed

Horton, Julie L; Martin, Ola J; Lai, Ling; Riley, Nicholas M; Richards, Alicia L; Vega, Rick B; Leone, Teresa C; Pagliarini, David J; Muoio, Deborah M; Bedi, Kenneth C; Margulies, Kenneth B; Coon, Joshua J; Kelly, Daniel P

2016-02-01

Myocardial fuel and energy metabolic derangements contribute to the pathogenesis of heart failure. Recent evidence implicates posttranslational mechanisms in the energy metabolic disturbances that contribute to the pathogenesis of heart failure. We hypothesized that accumulation of metabolite intermediates of fuel oxidation pathways drives posttranslational modifications of mitochondrial proteins during the development of heart failure. Myocardial acetylproteomics demonstrated extensive mitochondrial protein lysine hyperacetylation in the early stages of heart failure in well-defined mouse models and the in end-stage failing human heart. To determine the functional impact of increased mitochondrial protein acetylation, we focused on succinate dehydrogenase A (SDHA), a critical component of both the tricarboxylic acid (TCA) cycle and respiratory complex II. An acetyl-mimetic mutation targeting an SDHA lysine residue shown to be hyperacetylated in the failing human heart reduced catalytic function and reduced complex II-driven respiration. These results identify alterations in mitochondrial acetyl-CoA homeostasis as a potential driver of the development of energy metabolic derangements that contribute to heart failure.

Medication regimen complexity in ambulatory older adults with heart failure.

PubMed

Cobretti, Michael R; Page, Robert L; Linnebur, Sunny A; Deininger, Kimberly M; Ambardekar, Amrut V; Lindenfeld, JoAnn; Aquilante, Christina L

2017-01-01

Heart failure prevalence is increasing in older adults, and polypharmacy is a major problem in this population. We compared medication regimen complexity using the validated patient-level Medication Regimen Complexity Index (pMRCI) tool in "young-old" (60-74 years) versus "old-old" (75-89 years) patients with heart failure. We also compared pMRCI between patients with ischemic cardiomyopathy (ISCM) versus nonischemic cardiomyopathy (NISCM). Medication lists were retrospectively abstracted from the electronic medical records of ambulatory patients aged 60-89 years with heart failure. Medications were categorized into three types - heart failure prescription medications, other prescription medications, and over-the-counter (OTC) medications - and scored using the pMRCI tool. The study evaluated 145 patients (n=80 young-old, n=65 old-old, n=85 ISCM, n=60 NISCM, mean age 73±7 years, 64% men, 81% Caucasian). Mean total pMRCI scores (32.1±14.4, range 3-84) and total medication counts (13.3±4.8, range 2-30) were high for the entire cohort, of which 72% of patients were taking eleven or more total medications. Total and subtype pMRCI scores and medication counts did not differ significantly between the young-old and old-old groups, with the exception of OTC medication pMRCI score (6.2±4 young-old versus 7.8±5.8 old-old, P =0.04). With regard to heart failure etiology, total pMRCI scores and medication counts were significantly higher in patients with ISCM versus NISCM (pMRCI score 34.5±15.2 versus 28.8±12.7, P =0.009; medication count 14.1±4.9 versus 12.2±4.5, P =0.008), which was largely driven by other prescription medications. Medication regimen complexity is high in older adults with heart failure, and differs based on heart failure etiology. Additional work is needed to address polypharmacy and to determine if medication regimen complexity influences adherence and clinical outcomes in this population.

Molecular architecture of the human Mediator-RNA polymerase II-TFIIF assembly.

PubMed

Bernecky, Carrie; Grob, Patricia; Ebmeier, Christopher C; Nogales, Eva; Taatjes, Dylan J

2011-03-01

The macromolecular assembly required to initiate transcription of protein-coding genes, known as the Pre-Initiation Complex (PIC), consists of multiple protein complexes and is approximately 3.5 MDa in size. At the heart of this assembly is the Mediator complex, which helps regulate PIC activity and interacts with the RNA polymerase II (pol II) enzyme. The structure of the human Mediator-pol II interface is not well-characterized, whereas attempts to structurally define the Mediator-pol II interaction in yeast have relied on incomplete assemblies of Mediator and/or pol II and have yielded inconsistent interpretations. We have assembled the complete, 1.9 MDa human Mediator-pol II-TFIIF complex from purified components and have characterized its structural organization using cryo-electron microscopy and single-particle reconstruction techniques. The orientation of pol II within this assembly was determined by crystal structure docking and further validated with projection matching experiments, allowing the structural organization of the entire human PIC to be envisioned. Significantly, pol II orientation within the Mediator-pol II-TFIIF assembly can be reconciled with past studies that determined the location of other PIC components relative to pol II itself. Pol II surfaces required for interacting with TFIIB, TFIIE, and promoter DNA (i.e., the pol II cleft) are exposed within the Mediator-pol II-TFIIF structure; RNA exit is unhindered along the RPB4/7 subunits; upstream and downstream DNA is accessible for binding additional factors; and no major structural re-organization is necessary to accommodate the large, multi-subunit TFIIH or TFIID complexes. The data also reveal how pol II binding excludes Mediator-CDK8 subcomplex interactions and provide a structural basis for Mediator-dependent control of PIC assembly and function. Finally, parallel structural analysis of Mediator-pol II complexes lacking TFIIF reveal that TFIIF plays a key role in stabilizing pol II orientation within the assembly.

Molecular Architecture of the Human Mediator–RNA Polymerase II–TFIIF Assembly

PubMed Central

Bernecky, Carrie; Grob, Patricia; Ebmeier, Christopher C.; Nogales, Eva; Taatjes, Dylan J.

2011-01-01

The macromolecular assembly required to initiate transcription of protein-coding genes, known as the Pre-Initiation Complex (PIC), consists of multiple protein complexes and is approximately 3.5 MDa in size. At the heart of this assembly is the Mediator complex, which helps regulate PIC activity and interacts with the RNA polymerase II (pol II) enzyme. The structure of the human Mediator–pol II interface is not well-characterized, whereas attempts to structurally define the Mediator–pol II interaction in yeast have relied on incomplete assemblies of Mediator and/or pol II and have yielded inconsistent interpretations. We have assembled the complete, 1.9 MDa human Mediator–pol II–TFIIF complex from purified components and have characterized its structural organization using cryo-electron microscopy and single-particle reconstruction techniques. The orientation of pol II within this assembly was determined by crystal structure docking and further validated with projection matching experiments, allowing the structural organization of the entire human PIC to be envisioned. Significantly, pol II orientation within the Mediator–pol II–TFIIF assembly can be reconciled with past studies that determined the location of other PIC components relative to pol II itself. Pol II surfaces required for interacting with TFIIB, TFIIE, and promoter DNA (i.e., the pol II cleft) are exposed within the Mediator–pol II–TFIIF structure; RNA exit is unhindered along the RPB4/7 subunits; upstream and downstream DNA is accessible for binding additional factors; and no major structural re-organization is necessary to accommodate the large, multi-subunit TFIIH or TFIID complexes. The data also reveal how pol II binding excludes Mediator–CDK8 subcomplex interactions and provide a structural basis for Mediator-dependent control of PIC assembly and function. Finally, parallel structural analysis of Mediator–pol II complexes lacking TFIIF reveal that TFIIF plays a key role in stabilizing pol II orientation within the assembly. PMID:21468301

Left ventricular dysfunction in ischemic heart disease: fundamental importance of the fibrous matrix.

PubMed

Swan, H J

1994-05-01

The contractile function of the myocardium is coordinated by a fibrous matrix of exquisite organization and complexity. In the normal heart, and apparently in physiological hypertrophy, this matrix is submicroscopic. In pathological states changes are frequent, and usually progressive. Thickening of the many elements of the fine structure is due to an increased synthesis of Type I collagen, This change, which affects the myocardium in a global manner, can be observed by light microscopy using special techniques. Perivascular fibrosis, with an increase in vascular smooth muscle, is accompanied by development of fibrous septa, with a decrease in diastolic compliance. These structural changes are believed to be due to increased activation of the renin-angiotensin-aldosterone system, and to be independent of the processes of myocyte hypertrophy. Reparative or replacement fibrosis is a separate process by means of which small and large areas of necrosis heal, with the development of coarse collagen structures, which lack a specific organizational pattern. Regarding ischemic heart disease, an increase in tissue collagenase is found in experimental myocardial "stunning" and in the very early phase of acute infarction. Absence of elements of the fibrous matrix allow for myocyte slippage, and--if the affected area is large--cardiac dilatation. If, subsequently, the necrosis becomes transmural, there is further disturbance of collagen due to both mechanical strain and continued autolysis, During healing collagen synthesis increases greatly to allow for reparative scarring in the available tissue matrix. In cases of infarction with moderate or severe initial dilatation, pathological hypertrophy of the spared myocardium is progressive, accounting for late heart failure and poor survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Extended dynamic range of Doppler OCT by application of a new method to high density B-scans using a MHz FDML swept laser source (Conference Presentation)

NASA Astrophysics Data System (ADS)

Elahi, Sahar; Thrane, Lars; Rollins, Andrew M.; Jenkins, Michael W.

2017-02-01

The limited dynamic range of optical coherence tomography (OCT) Doppler velocity measurements makes it difficult to conduct experiments on samples requiring a large dynamic range without phase wrapping at high velocities or loss of sensitivity at slow velocities. Hemodynamics and wall motion undergo significant increases in velocity as the embryonic heart develops. Experimental studies indicate that altered hemodynamics in early-stage embryonic hearts can lead to congenital heart diseases (CHDs), motivating close monitoring of blood flow over several stages of development. We have built a high-speed OCT system using an FDML laser (Optores GmbH, Germany) at a sweep rate of 1.68 MHz (axial resolution - 12 μm, sensitivity - 105 dB, phase stability - 17 mrad). The speed of this OCT system allows us to acquire high-density B-scans to obtain an extended velocity dynamic range without sacrificing the frame rate (100 Hz). The extended dynamic range within a frame is achieved by varying the A-scan interval at which the phase difference is found, enabling detection of velocities ranging from tens of microns per second to hundreds of millimeters per second. The extra lines in a frame can also be utilized to improve the structural and Doppler images via complex averaging. In structural images where the presence of blood causes additional scattering, complex averaging helps retrieve features located deeper in the tissue. Moreover, high-density frames can be registered to 4D volumes to determine the orthogonal direction of flow for calculating shear stress as well as estimating the cardiac output. In conclusion, high density B-scans acquired by our high-speed OCT system enable image enhancement and direct measurement of biological parameters in cohort studies.

Multiscale entropy-based methods for heart rate variability complexity analysis

NASA Astrophysics Data System (ADS)

Silva, Luiz Eduardo Virgilio; Cabella, Brenno Caetano Troca; Neves, Ubiraci Pereira da Costa; Murta Junior, Luiz Otavio

2015-03-01

Physiologic complexity is an important concept to characterize time series from biological systems, which associated to multiscale analysis can contribute to comprehension of many complex phenomena. Although multiscale entropy has been applied to physiological time series, it measures irregularity as function of scale. In this study we purpose and evaluate a set of three complexity metrics as function of time scales. Complexity metrics are derived from nonadditive entropy supported by generation of surrogate data, i.e. SDiffqmax, qmax and qzero. In order to access accuracy of proposed complexity metrics, receiver operating characteristic (ROC) curves were built and area under the curves was computed for three physiological situations. Heart rate variability (HRV) time series in normal sinus rhythm, atrial fibrillation, and congestive heart failure data set were analyzed. Results show that proposed metric for complexity is accurate and robust when compared to classic entropic irregularity metrics. Furthermore, SDiffqmax is the most accurate for lower scales, whereas qmax and qzero are the most accurate when higher time scales are considered. Multiscale complexity analysis described here showed potential to assess complex physiological time series and deserves further investigation in wide context.

Heart Transplantation in Congenital Heart Disease: In Whom to Consider and When?

PubMed Central

Attenhofer Jost, Christine H.; Schmidt, Dörthe; Huebler, Michael; Balmer, Christian; Noll, Georg; Caduff, Rosmarie; Greutmann, Matthias

2013-01-01

Due to impressive improvements in surgical repair options, even patients with complex congenital heart disease (CHD) may survive into adulthood and have a high risk of end-stage heart failure. Thus, the number of patients with CHD needing heart transplantation (HTx) has been increasing in the last decades. This paper summarizes the changing etiology of causes of death in heart failure in CHD. The main reasons, contraindications, and risks of heart transplantation in CHD are discussed and underlined with three case vignettes. Compared to HTx in acquired heart disease, HTx in CHD has an increased risk of perioperative death and rejection. However, outcome of HTx for complex CHD has improved over the past 20 years. Additionally, mechanical support options might decrease the waiting list mortality in the future. The number of patients needing heart-lung transplantation (especially for Eisenmenger's syndrome) has decreased in the last years. Lung transplantation with intracardiac repair of a cardiac defect is another possibility especially for patients with interatrial shunts. Overall, HTx will remain an important treatment option for CHD in the near future. PMID:23577237

Radiopharmaceuticals for imaging the heart

DOEpatents

Green, Mark A.; Tsang, Brenda W.

1994-01-01

Radiopharmaceuticals for imaging myocardial tissues are prepared by forming lipophilic, cationic complexes of radioactive metal ions with metal chelating ligands comprising the Schiff base adducts of triamines and tetraamines with optionally substituted salicylaldehydes. The lipophilic, cationic, radioactive complexes of the invention exhibit high uptake and retention in myocardial tissues. Preferred gallium-68(III) complexes in accordance with this invention can be used to image the heart using positron emission tomography.

Pathophysiology of chronic heart failure.

PubMed

Francis, G S

2001-05-07

Heart failure is a changing paradigm. The hemodynamic model, which served our needs well from the 1950s through the early 1980s, has now been largely abandoned, except for the management of decompensated patients in the hospital. The pathophysiology is exceedingly complex and involves structural changes, such as loss of myofilaments, apoptosis and disorganization of the cytoskeleton, as well as disturbances in Ca(2+) homeostasis, alteration in receptor density, signal transduction, and collagen synthesis. A more contemporary working hypothesis is that heart failure is a progressive disorder of left ventricular remodeling, usually resulting from an index event, that culminates in a clinical syndrome characterized by impaired cardiac function and circulatory congestion. This change in the framework of our understanding of the pathophysiology of heart failure is predicated on the results of numerous clinical trials conducted during the past 20 years. New therapies are now evolving that are designed to inhibit neuroendocrine and cytokine activation, whereas drugs specifically designed to heighten cardiac contractility and "unload" the left ventricle have proven to be unhelpful in long-term management of patients with chronic heart failure. However, the hemodynamic model is still relevant for patients in the hospital with decompensated heart failure, where positive inotropic drugs and vasodilators are still widely used. The modern treatment of chronic heart failure is now largely based on the neurohormonal hypothesis, which states that neuroendocrine activation is important in the progression of heart failure and that inhibition of neurohormones is likely to have long-term benefit with regard to morbidity and mortality. Thus, the evolution of treatment for chronic heart failure as a result of clinical trials has provided much enlightenment for our understanding of the fundamental biology of the disorder, a reversal of the usual flow of information from basic science to clinical investigation.

Outcome of patients undergoing open heart surgery at the Uganda heart institute, Mulago hospital complex.

PubMed

Aliku, Twalib O; Lubega, Sulaiman; Lwabi, Peter; Oketcho, Michael; Omagino, John O; Mwambu, Tom

2014-12-01

Heart disease is a disabling condition and necessary surgical intervention is often lacking in many developing countries. Training of the superspecialties abroad is largely limited to observation with little or no opportunity for hands on experience. An approach in which open heart surgeries are conducted locally by visiting teams enabling skills transfer to the local team and helps build to build capacity has been adopted at the Uganda Heart Institute (UHI). We reviewed the progress of open heart surgery at the UHI and evaluated the postoperative outcomes and challenges faced in conducting open heart surgery in a developing country. Medical records of patients undergoing open heart surgery at the UHI from October 2007 to June 2012 were reviewed. A total of 124 patients underwent open heart surgery during the study period. The commonest conditions were: venticular septal defects (VSDs) 34.7% (43/124), Atrial septal defects (ASDs) 34.7% (43/124) and tetralogy of fallot (TOF) in 10.5% (13/124). Non governmental organizations (NGOs) funded 96.8% (120/124) of the operations, and in only 4 patients (3.2%) families paid for the surgeries. There was increasing complexity in cases operated upon from predominantly ASDs and VSDs at the beginning to more complex cases like TOFs and TAPVR. The local team independently operated 19 patients (15.3%). Postoperative morbidity was low with arrhythmias, left ventricular dysfunction and re-operations being the commonest seen. Post operative sepsis occurred in only 2 cases (1.6%). The overall mortality rate was 3.2. Open heart surgery though expensive is feasible in a developing country. With increased direct funding from governments and local charities to support open heart surgeries, more cardiac patients access surgical treatment locally.

[Endothelial dysfunction as a marker of vascular aging syndrome on the background of hypertension, coronary heart disease, gout and obesity].

PubMed

Vatseba, M O

2013-09-01

Under observation were 40 hypertensive patients with coronary heart disease, gout and obesity I and II degree. Patients with hypertension in combination with coronary heart disease, gout and obesity, syndrome of early vascular aging is shown by increased stiffness of arteries, increased peak systolic flow velocity, pulse blood presure, the thickness of the intima-media complex, higher level endotelinemia and reduced endothelial vasodilation. Obtained evidence that losartan in complex combination with basic therapy and metamaks in complex combination with basic therapy positively affect the elastic properties of blood vessels and slow the progression of early vascular aging syndrome.

Involvement of adolescents in decision making for heart transplants.

PubMed

Sinclair, Sarah J

2009-01-01

Every year, hundreds of children and adolescents are faced with the need for heart transplantation to survive end-stage cardiac disease. This experience extends far beyond the surgical intervention, for it begins with a waiting period that may involve invasive and distressing interventions, and proceeds through a lifetime of lifestyle changes and complicated ongoing medical management. Adolescents may wish to forgo heart transplantation, even at the expense of their own lives. Such refusals leave patients, parents, and healthcare professionals grappling with complex ethical issues. It is incumbent upon professionals to allow adolescents a role in making this important decision; this requires that nurses understand ethical concepts including autonomy, competence, and assent. Because autonomy develops over time, an evaluation of the adolescent's maturity and competence is necessary. By incorporating the concepts of child development and measures of competence developed to govern pediatric involvement in research, a structured and ethically sound method for involving adolescents in this process can be put into practice.

Numerical Simulations of Blood Flows in the Left Atrium

NASA Astrophysics Data System (ADS)

Zhang, Lucy

2008-11-01

A novel numerical technique of solving complex fluid-structure interactions for biomedical applications is introduced. The method is validated through rigorous convergence and accuracy tests. In this study, the technique is specifically used to study blood flows in the left atrium, one of the four chambers in the heart. Stable solutions are obtained at physiologic Reynolds numbers by applying pulmonary venous inflow, mitral valve outflow and appropriate constitutive equations to closely mimic the behaviors of biomaterials. Atrial contraction is also implemented as a time-dependent boundary condition to realistically describe the atrial wall muscle movements, thus producing accurate interactions with the surrounding blood. From our study, the transmitral velocity, filling/emptying velocity ratio, durations and strengths of vortices are captured numerically for sinus rhythms (healthy heart beat) and they compare quite well with reported clinical studies. The solution technique can be further used to study heart diseases such as the atrial fibrillation, thrombus formation in the chamber and their corresponding effects in blood flows.

Acute hypoxia stress induced abundant differential expression genes and alternative splicing events in heart of tilapia.

PubMed

Xia, Jun Hong; Li, Hong Lian; Li, Bi Jun; Gu, Xiao Hui; Lin, Hao Ran

2018-01-10

Hypoxia is one of the critical environmental stressors for fish in aquatic environments. Although accumulating evidences indicate that gene expression is regulated by hypoxia stress in fish, how genes undergoing differential gene expression and/or alternative splicing (AS) in response to hypoxia stress in heart are not well understood. Using RNA-seq, we surveyed and detected 289 differential expressed genes (DEG) and 103 genes that undergo differential usage of exons and splice junctions events (DUES) in heart of a hypoxia tolerant fish, Nile tilapia, Oreochromis niloticus following 12h hypoxic treatment. The spatio-temporal expression analysis validated the significant association of differential exon usages in two randomly selected DUES genes (fam162a and ndrg2) in 5 tissues (heart, liver, brain, gill and spleen) sampled at three time points (6h, 12h, and 24h) under acute hypoxia treatment. Functional analysis significantly associated the differential expressed genes with the categories related to energy conservation, protein synthesis and immune response. Different enrichment categories were found between the DEG and DUES dataset. The Isomerase activity, Oxidoreductase activity, Glycolysis and Oxidative stress process were significantly enriched for the DEG gene dataset, but the Structural constituent of ribosome and Structural molecule activity, Ribosomal protein and RNA binding protein were significantly enriched only for the DUES genes. Our comparative transcriptomic analysis reveals abundant stress responsive genes and their differential regulation function in the heart tissues of Nile tilapia under acute hypoxia stress. Our findings will facilitate future investigation on transcriptome complexity and AS regulation during hypoxia stress in fish. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficient physics-based tracking of heart surface motion for beating heart surgery robotic systems.

PubMed

Bogatyrenko, Evgeniya; Pompey, Pascal; Hanebeck, Uwe D

2011-05-01

Tracking of beating heart motion in a robotic surgery system is required for complex cardiovascular interventions. A heart surface motion tracking method is developed, including a stochastic physics-based heart surface model and an efficient reconstruction algorithm. The algorithm uses the constraints provided by the model that exploits the physical characteristics of the heart. The main advantage of the model is that it is more realistic than most standard heart models. Additionally, no explicit matching between the measurements and the model is required. The application of meshless methods significantly reduces the complexity of physics-based tracking. Based on the stochastic physical model of the heart surface, this approach considers the motion of the intervention area and is robust to occlusions and reflections. The tracking algorithm is evaluated in simulations and experiments on an artificial heart. Providing higher accuracy than the standard model-based methods, it successfully copes with occlusions and provides high performance even when all measurements are not available. Combining the physical and stochastic description of the heart surface motion ensures physically correct and accurate prediction. Automatic initialization of the physics-based cardiac motion tracking enables system evaluation in a clinical environment.

Information Theory to Probe Intrapartum Fetal Heart Rate Dynamics

NASA Astrophysics Data System (ADS)

Granero-Belinchon, Carlos; Roux, Stéphane; Abry, Patrice; Doret, Muriel; Garnier, Nicolas

2017-11-01

Intrapartum fetal heart rate (FHR) monitoring constitutes a reference tool in clinical practice to assess the baby health status and to detect fetal acidosis. It is usually analyzed by visual inspection grounded on FIGO criteria. Characterization of Intrapartum fetal heart rate temporal dynamics remains a challenging task and continuously receives academic research efforts. Complexity measures, often implemented with tools referred to as \\emph{Approximate Entropy} (ApEn) or \\emph{Sample Entropy} (SampEn), have regularly been reported as significant features for intrapartum FHR analysis. We explore how Information Theory, and especially {\\em auto mutual information} (AMI), is connected to ApEn and SampEn and can be used to probe FHR dynamics. Applied to a large (1404 subjects) and documented database of FHR data, collected in a French academic hospital, it is shown that i) auto mutual information outperforms ApEn and SampEn for acidosis detection in the first stage of labor and continues to yield the best performance in the second stage; ii) Shannon entropy increases as labor progresses, and is always much larger in the second stage;iii) babies suffering from fetal acidosis additionally show more structured temporal dynamics than healthy ones and that this progressive structuration can be used for early acidosis detection.

Automated Texture Analysis and Determination of Fibre Orientation of Heart Tissue: A Morphometric Study.

PubMed

Zach, Bernhard; Hofer, Ernst; Asslaber, Martin; Ahammer, Helmut

2016-01-01

The human heart has a heterogeneous structure, which is characterized by different cell types and their spatial configurations. The physical structure, especially the fibre orientation and the interstitial fibrosis, determines the electrical excitation and in further consequence the contractility in macroscopic as well as in microscopic areas. Modern image processing methods and parameters could be used to describe the image content and image texture. In most cases the description of the texture is not satisfying because the fibre orientation, detected with common algorithms, is biased by elements such as fibrocytes or endothelial nuclei. The goal of this work is to figure out if cardiac tissue can be analysed and classified on a microscopic level by automated image processing methods with a focus on an accurate detection of the fibre orientation. Quantitative parameters for identification of textures of different complexity or pathological attributes inside the heart were determined. The focus was set on the detection of the fibre orientation, which was calculated on the basis of the cardiomyocytes' nuclei. It turned out that the orientation of these nuclei corresponded with a high precision to the fibre orientation in the image plane. Additionally, these nuclei also indicated very well the inclination of the fibre.

Increasing mortality burden among adults with complex congenital heart disease.

PubMed

Greutmann, Matthias; Tobler, Daniel; Kovacs, Adrienne H; Greutmann-Yantiri, Mehtap; Haile, Sarah R; Held, Leonhard; Ivanov, Joan; Williams, William G; Oechslin, Erwin N; Silversides, Candice K; Colman, Jack M

2015-01-01

Progress in management of congenital heart disease has shifted mortality largely to adulthood. However, adult survivors with complex congenital heart disease are not cured and remain at risk of premature death as young adults. Thus, our aim was to describe the evolution and mortality risk of adult patient cohorts with complex congenital heart disease. Among 12,644 adults with congenital heart disease followed at a single center from 1980 to 2009, 176 had Eisenmenger syndrome, 76 had unrepaired cyanotic defects, 221 had atrial switch operations for transposition of the great arteries, 158 had congenitally corrected transposition of the great arteries, 227 had Fontan palliation, and 789 had repaired tetralogy of Fallot. We depict the 30-year evolution of these 6 patient cohorts, analyze survival probabilities in adulthood, and predict future number of deaths through 2029. Since 1980, there has been a steady increase in numbers of patients followed, except in cohorts with Eisenmenger syndrome and unrepaired cyanotic defects. Between 1980 and 2009, 308 patients in the study cohorts (19%) died. At the end of 2009, 85% of survivors were younger than 50 years. Survival estimates for all cohorts were markedly lower than for the general population, with important differences between cohorts. Over the upcoming two decades, we predict a substantial increase in numbers of deaths among young adults with subaortic right ventricles, Fontan palliation, and repaired tetralogy of Fallot. Anticipatory action is needed to prepare clinical services for increasing numbers of young adults at risk of dying from complex congenital heart disease. © 2014 The Authors. Congenital Heart Disease Published by Wiley Periodicals, Inc.

Decoding the complex genetic causes of heart diseases using systems biology.

PubMed

Djordjevic, Djordje; Deshpande, Vinita; Szczesnik, Tomasz; Yang, Andrian; Humphreys, David T; Giannoulatou, Eleni; Ho, Joshua W K

2015-03-01

The pace of disease gene discovery is still much slower than expected, even with the use of cost-effective DNA sequencing and genotyping technologies. It is increasingly clear that many inherited heart diseases have a more complex polygenic aetiology than previously thought. Understanding the role of gene-gene interactions, epigenetics, and non-coding regulatory regions is becoming increasingly critical in predicting the functional consequences of genetic mutations identified by genome-wide association studies and whole-genome or exome sequencing. A systems biology approach is now being widely employed to systematically discover genes that are involved in heart diseases in humans or relevant animal models through bioinformatics. The overarching premise is that the integration of high-quality causal gene regulatory networks (GRNs), genomics, epigenomics, transcriptomics and other genome-wide data will greatly accelerate the discovery of the complex genetic causes of congenital and complex heart diseases. This review summarises state-of-the-art genomic and bioinformatics techniques that are used in accelerating the pace of disease gene discovery in heart diseases. Accompanying this review, we provide an interactive web-resource for systems biology analysis of mammalian heart development and diseases, CardiacCode ( http://CardiacCode.victorchang.edu.au/ ). CardiacCode features a dataset of over 700 pieces of manually curated genetic or molecular perturbation data, which enables the inference of a cardiac-specific GRN of 280 regulatory relationships between 33 regulator genes and 129 target genes. We believe this growing resource will fill an urgent unmet need to fully realise the true potential of predictive and personalised genomic medicine in tackling human heart disease.

Human Heart Mitochondrial DNA Is Organized in Complex Catenated Networks Containing Abundant Four-way Junctions and Replication Forks*

PubMed Central

Pohjoismäki, Jaakko L. O.; Goffart, Steffi; Tyynismaa, Henna; Willcox, Smaranda; Ide, Tomomi; Kang, Dongchon; Suomalainen, Anu; Karhunen, Pekka J.; Griffith, Jack D.; Holt, Ian J.; Jacobs, Howard T.

2009-01-01

Analysis of human heart mitochondrial DNA (mtDNA) by electron microscopy and agarose gel electrophoresis revealed a complete absence of the θ-type replication intermediates seen abundantly in mtDNA from all other tissues. Instead only Y- and X-junctional forms were detected after restriction digestion. Uncut heart mtDNA was organized in tangled complexes of up to 20 or more genome equivalents, which could be resolved to genomic monomers, dimers, and linear fragments by treatment with the decatenating enzyme topoisomerase IV plus the cruciform-cutting T7 endonuclease I. Human and mouse brain also contained a population of such mtDNA forms, which were absent, however, from mouse, rabbit, or pig heart. Overexpression in transgenic mice of two proteins involved in mtDNA replication, namely human mitochondrial transcription factor A or the mouse Twinkle DNA helicase, generated abundant four-way junctions in mtDNA of heart, brain, and skeletal muscle. The organization of mtDNA of human heart as well as of mouse and human brain in complex junctional networks replicating via a presumed non-θ mechanism is unprecedented in mammals. PMID:19525233

The role of Pyruvate Dehydrogenase Complex in cardiovascular diseases.

PubMed

Sun, Wanqing; Liu, Quan; Leng, Jiyan; Zheng, Yang; Li, Ji

2015-01-15

The regulation of mammalian myocardial carbohydrate metabolism is complex; many factors such as arterial substrate and hormone levels, coronary flow, inotropic state and the nutritional status of the tissue play a role in regulating mammalian myocardial carbohydrate metabolism. The Pyruvate Dehydrogenase Complex (PDHc), a mitochondrial matrix multienzyme complex, plays an important role in energy homeostasis in the heart by providing the link between glycolysis and the tricarboxylic acid (TCA) cycle. In TCA cycle, PDHc catalyzes the conversion of pyruvate into acetyl-CoA. This review determines that there is altered cardiac glucose in various pathophysiological states consequently causing PDC to be altered. This review further summarizes evidence for the metabolism mechanism of the heart under normal and pathological conditions including ischemia, diabetes, hypertrophy and heart failure. Copyright © 2014 Elsevier Inc. All rights reserved.

Aging and cardiovascular complexity: effect of the length of RR tachograms

PubMed Central

Nagaraj, Nithin

2016-01-01

As we age, our hearts undergo changes that result in a reduction in complexity of physiological interactions between different control mechanisms. This results in a potential risk of cardiovascular diseases which are the number one cause of death globally. Since cardiac signals are nonstationary and nonlinear in nature, complexity measures are better suited to handle such data. In this study, three complexity measures are used, namely Lempel–Ziv complexity (LZ), Sample Entropy (SampEn) and Effort-To-Compress (ETC). We determined the minimum length of RR tachogram required for characterizing complexity of healthy young and healthy old hearts. All the three measures indicated significantly lower complexity values for older subjects than younger ones. However, the minimum length of heart-beat interval data needed differs for the three measures, with LZ and ETC needing as low as 10 samples, whereas SampEn requires at least 80 samples. Our study indicates that complexity measures such as LZ and ETC are good candidates for the analysis of cardiovascular dynamics since they are able to work with very short RR tachograms. PMID:27957395

Intact Imaging of Human Heart Structure Using X-ray Phase-Contrast Tomography.

PubMed

Kaneko, Yukihiro; Shinohara, Gen; Hoshino, Masato; Morishita, Hiroyuki; Morita, Kiyozo; Oshima, Yoshihiro; Takahashi, Masashi; Yagi, Naoto; Okita, Yutaka; Tsukube, Takuro

2017-02-01

Structural examination of human heart specimens at the microscopic level is a prerequisite for understanding congenital heart diseases. It is desirable not to destroy or alter the properties of such specimens because of their scarcity. However, many of the currently available imaging techniques either destroy the specimen through sectioning or alter the chemical and mechanical properties of the specimen through staining and contrast agent injection. As a result, subsequent studies may not be possible. X-ray phase-contrast tomography is an imaging modality for biological soft tissues that does not destroy or alter the properties of the specimen. The feasibility of X-ray phase-contrast tomography for the structural examination of heart specimens was tested using infantile and fetal heart specimens without congenital diseases. X-ray phase-contrast tomography was carried out at the SPring-8 synchrotron radiation facility using the Talbot grating interferometer at the bending magnet beamline BL20B2 to visualize the structure of five non-pretreated whole heart specimens obtained by autopsy. High-resolution, three-dimensional images were obtained for all specimens. The images clearly showed the myocardial structure, coronary vessels, and conduction bundle. X-ray phase-contrast tomography allows high-resolution, three-dimensional imaging of human heart specimens. Intact imaging using X-ray phase-contrast tomography can contribute to further structural investigation of heart specimens with congenital heart diseases.

Radiopharmaceuticals for imaging the heart

DOEpatents

Green, M.A.; Tsang, B.W.

1994-06-28

Radiopharmaceuticals for imaging myocardial tissues are prepared by forming lipophilic, cationic complexes of radioactive metal ions with metal chelating ligands comprising the Schiff base adducts of triamines and tetraamines with optionally substituted salicylaldehydes. The lipophilic, cationic, radioactive complexes of the invention exhibit high uptake and retention in myocardial tissues. Preferred gallium-68(III) complexes in accordance with this invention can be used to image the heart using positron emission tomography. 6 figures.

Ischemic preconditioning enhances integrity of coronary endothelial tight junctions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Zhao; Jin, Zhu-Qiu, E-mail: zhu-qiu.jin@sdstate.edu

2012-08-31

Highlights: Black-Right-Pointing-Pointer Cardiac tight junctions are present between coronary endothelial cells. Black-Right-Pointing-Pointer Ischemic preconditioning preserves the structural and functional integrity of tight junctions. Black-Right-Pointing-Pointer Myocardial edema is prevented in hearts subjected to ischemic preconditioning. Black-Right-Pointing-Pointer Ischemic preconditioning enhances translocation of ZO-2 from cytosol to cytoskeleton. -- Abstract: Ischemic preconditioning (IPC) is one of the most effective procedures known to protect hearts against ischemia/reperfusion (IR) injury. Tight junction (TJ) barriers occur between coronary endothelial cells. TJs provide barrier function to maintain the homeostasis of the inner environment of tissues. However, the effect of IPC on the structure and function of cardiacmore » TJs remains unknown. We tested the hypothesis that myocardial IR injury ruptures the structure of TJs and impairs endothelial permeability whereas IPC preserves the structural and functional integrity of TJs in the blood-heart barrier. Langendorff hearts from C57BL/6J mice were prepared and perfused with Krebs-Henseleit buffer. Cardiac function, creatine kinase release, and myocardial edema were measured. Cardiac TJ function was evaluated by measuring Evans blue-conjugated albumin (EBA) content in the extravascular compartment of hearts. Expression and translocation of zonula occludens (ZO)-2 in IR and IPC hearts were detected with Western blot. A subset of hearts was processed for the observation of ultra-structure of cardiac TJs with transmission electron microscopy. There were clear TJs between coronary endothelial cells of mouse hearts. IR caused the collapse of TJs whereas IPC sustained the structure of TJs. IR increased extravascular EBA content in the heart and myocardial edema but decreased the expression of ZO-2 in the cytoskeleton. IPC maintained the structure of TJs. Cardiac EBA content and edema were reduced in IPC hearts. IPC enhanced the translocation of ZO-2 from cytosol to cytoskeleton. In conclusion, TJs occur in normal mouse heart. IPC preserves the integrity of TJ structure and function that are vulnerable to IR injury.« less

[Heart disease in sports horses: Current recommendations of the 2014 ACVIM / ECEIM consensus statement].

PubMed

Schwarzwald, C

2016-10-01

Heart murmurs and arrhythmias are common in horses. Assessment of their clinical relevance concerning health, performance, safety and longevity of sports horses is of highest importance. A comprehensive cardiovascular examination is crucial for diagnosis and assessment of the severity of disease. Recently, an expert panel of the American College of Veterinary Internal Medicine (ACVIM) and the European College of Equine Internal Medicine (ECEIM) developed a consensus statement containing recommendations for sports horses with heart disease. This article summarizes the most relevant recommendations for practitioners, considering the most common and most important cardiac disorders in adult sports horses. These include mitral, aortic and tricuspid insufficiency, ventricular septal defects, atrial fibrillation as well as supraventricular and ventricular arrhythmias. Despite the fact that most horses with cardiovascular disease maintain a sufficient performance capacity, regular evaluations are indicated in horses with clinically relevant disorders. Under certain circumstances, horses with moderate to severe structural disease, with persistent untreated atrial fibrillation and with certain ventricular arrhythmias might still be used by informed adult riders. Horses with complex ventricular arrhythmias, pulmonary hypertension or congestive heart failure must not be ridden or driven and should be retired.

Immune-Mediated Heart Disease.

PubMed

Generali, Elena; Folci, Marco; Selmi, Carlo; Riboldi, Piersandro

2017-01-01

The heart involvement in systemic autoimmune diseases represents a growing burden for patients and health systems. Cardiac function can be impaired as a consequence of systemic conditions and manifests with threatening clinical pictures or chronic myocardial damage. Direct injuries are mediated by the presence of inflammatory infiltrate which, even though unusual, is one of the most danger manifestations requiring prompt recognition and treatment. On the other hand, a not well-managed inflammatory status leads to accelerated atherosclerosis that precipitates ischemic disease. All cardiac structures may be damaged with different grades of intensity; moreover, lesions can appear simultaneously or more frequently at a short distance from each other leading to the onset of varied clinical pictures. The pathogenesis of heart damages in systemic autoimmune conditions is not yet completely understood for the great part of situations, even if several mechanisms have been investigated. The principal biochemical circuits refer to the damaging role of autoantibodies on cardiac tissues and the precipitation of immune complexes on endocardium. These events are finally responsible of inflammatory infiltration which leads to subsequent worsening of the previous damage. For these reasons, it appears of paramount importance a regular and deepened cardiovascular assessment to prevent a progressive evolution toward heart failure in patient affected by autoimmune diseases.

Palladium alpha-lipoic acid complex formulation enhances activities of Krebs cycle dehydrogenases and respiratory complexes I-IV in the heart of aged rats.

PubMed

Sudheesh, N P; Ajith, T A; Janardhanan, K K; Krishnan, C V

2009-08-01

Age-related decline in the capacity to withstand stress, such as ischemia and reperfusion, results in congestive heart failure. Though the mechanisms underlying cardiac decay are not clear, age dependent somatic damages to mitochondrial DNA (mtDNA), loss of mitochondrial function, and a resultant increase in oxidative stress in heart muscle cells may be responsible for the increased risk for cardiovascular diseases. The effect of a safe nutritional supplement, POLY-MVA, containing the active ingredient palladium alpha-lipoic acid complex, was evaluated on the activities of the Krebs cycle enzymes such as isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase as well as mitochondrial complexes I, II, III, and IV in heart mitochondria of aged male albino rats of Wistar strain. Administration of 0.05 ml/kg of POLY-MVA (which is equivalent to 0.38 mg complexed alpha-lipoic acid/kg, p.o), once daily for 30 days, was significantly (p<0.05) effective to enhance the Krebs cycle dehydrogenases, and mitochondrial electron transport chain complexes. The unique electronic and redox properties of palladium alpha-lipoic acid complex appear to be a key to this physiological effectiveness. The results strongly suggest that this formulation might be effective to protect the aging associated risk of cardiovascular and neurodegenerative diseases.

Analysis of Morphological Characteristics and Origins of Idiopathic Premature Ventricular Contractions Under a 12-Lead Electrocardiogram in Children with Structurally Normal Hearts.

PubMed

Jiang, Jianbin; He, Yuee; Qiu, Huixian; Zhang, Yuanhai; Chu, Maoping; Li, Yuechun; Chen, Qi

2017-10-21

Up to 40% of healthy children have premature ventricular complexes or contractions (PVCs) detected with 24-hour Holter monitoring. We aimed to investigate the morphological characteristics and origins of idiopathic PVCs under a 12-lead electrocardiogram in children with structurally normal hearts. All asymptomatic monomorphic PVC patients with structurally normal hearts under 18 years of age were included in this retrospective study. Characteristics of PVCs in lead V 1 under a 12-lead electrocardiogram were classified as left bundle branch block (PVC-LBBB) or right bundle branch block (PVC-RBBB). According to limb leads, PVC-LBBB or PVC-RBBB was divided into: PVCs-LBBB type I; PVCs-LBBB type II; PVCs-RBBB type I; PVCs-RBBB type II; and PVCs-RBBB type III. Out of 178 PVC patients, 94 cases of PVCs-LBBB (PVCs-LBBB type I = 60; PVCs-LBBB type II = 34) and 84 cases of PVCs-RBBB (PVCs-RBBB type I = 3; PVCs-RBBB type II = 55; PVCs-RBBB type III = 26) were identified. The frequency of PVCs-LBBB type I increased with age and the frequency of PVCs-RBBB type II and III decreased with age. Among the children monitor tested, from 1 years old to 18 years old, PVCs originating from the left or right ventricular outflow tract gradually increased with age, while PVCs originating from the branch sources decreased with age.

Cardiolipin modulates allosterically peroxynitrite detoxification by horse heart cytochrome c

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ascenzi, Paolo, E-mail: ascenzi@uniroma3.it; Ciaccio, Chiara; Interuniversity Consortium for the Research on the Chemistry of Metals in Biological Systems, I-70126 Bari

2011-01-07

Research highlights: {yields} Cardiolipin binding to cytochrome c. {yields} Cardiolipin-dependent peroxynitrite isomerization by cytochrome c. {yields} Cardiolipin-cytochrome c complex plays pro-apoptotic effects. {yields} Cardiolipin-cytochrome c complex plays anti-apoptotic effects. -- Abstract: Upon interaction with bovine heart cardiolipin (CL), horse heart cytochrome c (cytc) changes its tertiary structure disrupting the heme-Fe-Met80 distal bond, reduces drastically the midpoint potential out of the range required for its physiological role, binds CO and NO with high affinity, and displays peroxidase activity. Here, the effect of CL on peroxynitrite isomerization by ferric cytc (cytc-Fe(III)) is reported. In the absence of CL, hexa-coordinated cytc does notmore » catalyze peroxynitrite isomerization. In contrast, CL facilitates cytc-Fe(III)-mediated isomerization of peroxynitrite in a dose-dependent fashion inducing the penta-coordination of the heme-Fe(III)-atom. The value of the second order rate constant for CL-cytc-Fe(III)-mediated isomerization of peroxynitrite (k{sub on}) is (3.2 {+-} 0.4) x 10{sup 5} M{sup -1} s{sup -1}. The apparent dissociation equilibrium constant for CL binding to cytc-Fe(III) is (5.1 {+-} 0.8) x 10{sup -5} M. These results suggest that CL-cytc could play either pro-apoptotic or anti-apoptotic effects facilitating lipid peroxidation and scavenging of reactive nitrogen species, such as peroxynitrite, respectively.« less

Sickle cell disease and complex congenital cardiac surgery: a case report and review of the pathophysiology and perioperative management.

PubMed

Sanders, D B; Smith, B P; Sowell, S R; Nguyen, D H; Derby, C; Eshun, F; Nigro, J J

2014-03-01

Sickle cell anemia and thalassemia are hemoglobinopathies rarely encountered in the United States. Compounded with congenital heart disease, patients with sickle cell disease (SCD) requiring cardiopulmonary bypass and open-heart surgery represent the proverbial "needle in the haystack". As such, there is some trepidation on the part of clinicians when these patients present for complex cardiac surgery. SCD is an autosomal, recessive condition that results from a single nucleotide polymorphism in the β-globin gene. Hemoglobin SS molecules (HgbSS) with this point mutation can polymerize under the right conditions, stiffening the erythrocyte membrane and distorting the cellular structure to the characteristic sickle shape. This shape change alters cellular transit through the microvasculature. As a result, circumstances such as hypoxia, hypothermia, acidosis or diminished blood flow can lead to aggregation, vascular occlusion and thrombosis. Chronically, SCD can give rise to multiorgan damage secondary to hemolysis and vascular obstruction. This review and case study details an 11-year-old African-American male with known SCD who presented to the cardiothoracic surgical service with congenital heart disease consisting of an anomalous, intramural right coronary artery arising from the left coronary sinus for surgical consultation and subsequent surgical correction. This case report will include a review of the pathophysiology and current literature regarding preoperative, intraoperative and postoperative management of SCD patients.

Multiple heart-cutting and comprehensive two-dimensional liquid chromatography hyphenated to mass spectrometry for the characterization of the antibody-drug conjugate ado-trastuzumab emtansine.

PubMed

Sandra, Koen; Vanhoenacker, Gerd; Vandenheede, Isabel; Steenbeke, Mieke; Joseph, Maureen; Sandra, Pat

2016-10-01

Antibody-drug conjugates might be the magic bullets referred to by Paul Ehrlich over 100 years ago. Together with a huge therapeutic potential, these molecules come with a structural complexity that drives state-of-the-art chromatography and mass spectrometry to its limits. The use of multiple heart-cutting (mLC-LC) and comprehensive (LC×LC) multidimensional LC in combination with high resolution mass spectrometry for the characterization of the lysine conjugated antibody-drug conjugate ado-trastuzumab emtansine, commercialized as Kadcyla, is presented. By combining protein and peptide measurements, attributes such as drug loading, drug distribution and drug conjugation sites can be assessed in an elegant manner. Copyright © 2016 Elsevier B.V. All rights reserved.

Stage call: Cardiovascular reactivity to audition stress in musicians

PubMed Central

Chanwimalueang, Theerasak; Aufegger, Lisa; Adjei, Tricia; Wasley, David; Cruder, Cinzia; Mandic, Danilo P.

2017-01-01

Auditioning is at the very center of educational and professional life in music and is associated with significant psychophysical demands. Knowledge of how these demands affect cardiovascular responses to psychosocial pressure is essential for developing strategies to both manage stress and understand optimal performance states. To this end, we recorded the electrocardiograms (ECGs) of 16 musicians (11 violinists and 5 flutists) before and during performances in both low- and high-stress conditions: with no audience and in front of an audition panel, respectively. The analysis consisted of the detection of R-peaks in the ECGs to extract heart rate variability (HRV) from the notoriously noisy real-world ECGs. Our data analysis approach spanned both standard (temporal and spectral) and advanced (structural complexity) techniques. The complexity science approaches—namely, multiscale sample entropy and multiscale fuzzy entropy—indicated a statistically significant decrease in structural complexity in HRV from the low- to the high-stress condition and an increase in structural complexity from the pre-performance to performance period, thus confirming the complexity loss theory and a loss in degrees of freedom due to stress. Results from the spectral analyses also suggest that the stress responses in the female participants were more parasympathetically driven than those of the male participants. In conclusion, our findings suggest that interventions to manage stress are best targeted at the sensitive pre-performance period, before an audition begins. PMID:28437466

Purification of Ovine Respiratory Complex I Results in a Highly Active and Stable Preparation.

PubMed

Letts, James A; Degliesposti, Gianluca; Fiedorczuk, Karol; Skehel, Mark; Sazanov, Leonid A

2016-11-18

NADH-ubiquinone oxidoreductase (complex I) is the largest (∼1 MDa) and the least characterized complex of the mitochondrial electron transport chain. Because of the ease of sample availability, previous work has focused almost exclusively on bovine complex I. However, only medium resolution structural analyses of this complex have been reported. Working with other mammalian complex I homologues is a potential approach for overcoming these limitations. Due to the inherent difficulty of expressing large membrane protein complexes, screening of complex I homologues is limited to large mammals reared for human consumption. The high sequence identity among these available sources may preclude the benefits of screening. Here, we report the characterization of complex I purified from Ovis aries (ovine) heart mitochondria. All 44 unique subunits of the intact complex were identified by mass spectrometry. We identified differences in the subunit composition of subcomplexes of ovine complex I as compared with bovine, suggesting differential stability of inter-subunit interactions within the complex. Furthermore, the 42-kDa subunit, which is easily lost from the bovine enzyme, remains tightly bound to ovine complex I. Additionally, we developed a novel purification protocol for highly active and stable mitochondrial complex I using the branched-chain detergent lauryl maltose neopentyl glycol. Our data demonstrate that, although closely related, significant differences exist between the biochemical properties of complex I prepared from ovine and bovine mitochondria and that ovine complex I represents a suitable alternative target for further structural studies. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

New strategy for protein interactions and application to structure-based drug design

NASA Astrophysics Data System (ADS)

Zou, Xiaoqin

One of the greatest challenges in computational biophysics is to predict interactions between biological molecules, which play critical roles in biological processes and rational design of therapeutic drugs. Biomolecular interactions involve delicate interplay between multiple interactions, including electrostatic interactions, van der Waals interactions, solvent effect, and conformational entropic effect. Accurate determination of these complex and subtle interactions is challenging. Moreover, a biological molecule such as a protein usually consists of thousands of atoms, and thus occupies a huge conformational space. The large degrees of freedom pose further challenges for accurate prediction of biomolecular interactions. Here, I will present our development of physics-based theory and computational modeling on protein interactions with other molecules. The major strategy is to extract microscopic energetics from the information embedded in the experimentally-determined structures of protein complexes. I will also present applications of the methods to structure-based therapeutic design. Supported by NSF CAREER Award DBI-0953839, NIH R01GM109980, and the American Heart Association (Midwest Affiliate) [13GRNT16990076].

Flow interactions with cells and tissues: cardiovascular flows and fluid-structure interactions. Sixth International Bio-Fluid Mechanics Symposium and Workshop, March 28-30, 2008, Pasadena, California.

PubMed

Friedman, Morton H; Krams, Rob; Chandran, Krishnan B

2010-03-01

Interactions between flow and biological cells and tissues are intrinsic to the circulatory, respiratory, digestive and genitourinary systems. In the circulatory system, an understanding of the complex interaction between the arterial wall (a living multi-component organ with anisotropic, nonlinear material properties) and blood (a shear-thinning fluid with 45% by volume consisting of red blood cells, platelets, and white blood cells) is vital to our understanding of the physiology of the human circulation and the etiology and development of arterial diseases, and to the design and development of prosthetic implants and tissue-engineered substitutes. Similarly, an understanding of the complex dynamics of flow past native human heart valves and the effect of that flow on the valvular tissue is necessary to elucidate the etiology of valvular diseases and in the design and development of valve replacements. In this paper we address the influence of biomechanical factors on the arterial circulation. The first part presents our current understanding of the impact of blood flow on the arterial wall at the cellular level and the relationship between flow-induced stresses and the etiology of atherosclerosis. The second part describes recent advances in the application of fluid-structure interaction analysis to arterial flows and the dynamics of heart valves.

Three Dimensional Energetics of Left Ventricle Flows Using Time-Resolved DPIV

NASA Astrophysics Data System (ADS)

Pierrakos, Olga; Vlachos, Pavlos

2006-11-01

Left ventricular (LV) flows in the human heart are very complex and in the presence of unhealthy or prosthetic heart valves (HV), the complexity of the flow is further increased. Yet to date, no study has documented the complex 3D hemodynamic characteristics and energetics of LV flows. We present high sampling frequency Time Resolved DPIV results obtained in a flexible, transparent LV documenting the evolution of eddies and turbulence. The purpose is to characterize the energetics of the LV flow field in the presence of four orientations of the most commonly implanted mechanical bileaflet HV and a porcine valve. By decomposing the energy scales of the flow field, the ultimate goal is to quantify the total energy losses associated with vortex ring formation and turbulence dissipation. The energies associated to vortex ring formation give a measure of the energy trapped within the structure while estimations of the turbulence dissipation rate (TDR) give a measure of the energy dissipated at the smaller scales. For the first time in cardiovascular applications, an LES-based PIV method, which overcomes the limitations of conventional TDR estimation methods that assume homogeneous isotropic turbulence, was employed. We observed that energy lost at the larger scales (vortex ring) is much higher than the energy lost at the smaller scales due to turbulence dissipation.

Differential susceptibility of mitochondrial complex II to inhibition by oxaloacetate in brain and heart.

PubMed

Stepanova, Anna; Shurubor, Yevgeniya; Valsecchi, Federica; Manfredi, Giovanni; Galkin, Alexander

2016-09-01

Mitochondrial Complex II is a key mitochondrial enzyme connecting the tricarboxylic acid (TCA) cycle and the electron transport chain. Studies of complex II are clinically important since new roles for this enzyme have recently emerged in cell signalling, cancer biology, immune response and neurodegeneration. Oxaloacetate (OAA) is an intermediate of the TCA cycle and at the same time is an inhibitor of complex II with high affinity (Kd~10(-8)M). Whether or not OAA inhibition of complex II is a physiologically relevant process is a significant, but still controversial topic. We found that complex II from mouse heart and brain tissue has similar affinity to OAA and that only a fraction of the enzyme in isolated mitochondrial membranes (30.2±6.0% and 56.4±5.6% in the heart and brain, respectively) is in the free, active form. Since OAA could bind to complex II during isolation, we established a novel approach to deplete OAA in the homogenates at the early stages of isolation. In heart, this treatment significantly increased the fraction of free enzyme, indicating that OAA binds to complex II during isolation. In brain the OAA-depleting system did not significantly change the amount of free enzyme, indicating that a large fraction of complex II is already in the OAA-bound inactive form. Furthermore, short-term ischemia resulted in a dramatic decline of OAA in tissues, but it did not change the amount of free complex II. Our data show that in brain OAA is an endogenous effector of complex II, potentially capable of modulating the activity of the enzyme. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Anesthetic management of the neonate with congenital complete heart block: a 16-year review.

PubMed

Kussman, Barry D; Madril, Danielle R; Thiagarajan, Ravi R; Walsh, Edward P; Laussen, Peter C

2005-12-01

Anesthesia for patients with complete heart block can be associated with significant hemodynamic instability. The aim of this study is to review our anesthetic experience of neonates with congenital complete heart block (CCHB) who underwent placement of either a temporary epicardial pacing system or a permanent epicardial pacemaker. The anesthetic management of neonates with CCHB who underwent pacemaker placement at a single institution over a 16-year period was reviewed. Twenty-four neonates were identified, 17 with a structurally normal heart (NL) and seven with associated congenital heart defects (CHD). Median (range) gestational age was 36.9 (26-41) weeks, birth weight 2.9 (1.0-4.1) kg, and baseline heart rate 47 (38-80) b.min(-1). A temporary epicardial pacing system was placed in six patients (four CHD, two NL; P = 0.003) following institution of mechanical ventilation and inotropic support for a low cardiac output state, and a permanent epicardial pacemaker was placed in 18 patients. Atropine 0.02 mg.kg(-1) IV prior to induction (n = 5) increased heart rate less than 20%. Intraoperative hypotension was documented in nine neonates, five of seven with CHD and four of 17 with NL (P = 0.02). In four patients (44%) hypotension occurred despite concurrent inotropic support. Intraoperative cardiac arrest occurred in one neonate, necessitating institution of extracorporeal membrane oxygenation. Two patients (8.3%) died in hospital from complex CHD and complications of prematurity. Early institution of mechanical ventilation, inotropic support and pacing are necessary in the neonate with CCHB and poor hemodynamic function, particularly with coexisting CHD or prematurity.

Critically Underdeveloped Left Heart Morphology Associated with Prematurity and Low Birth Weight: Conditional Staged Rehabilitation Towards Biventricular Repair and Time-Related Growth of Left Heart Structures.

PubMed

Ahmad, Fareed; Mangano, Robert; Shore, Shirah; Polimenakos, Anastasios

2017-10-01

This is a case report of premature low birth weight infant with hypoplasia of left heart structures and a large malaligned VSD who underwent successful staged approach of biventricular repair. We obtained qualitative and quantitative echocardiographic, MRI, and conventional catheterization data to support stepwise strategy towards LV rehabilitation to sustain adequate cardiac output. A thorough and intense follow-up has shown significant growth of left heart structures and favorable clinical status following staged biventricular repair. Our data indicate usefulness of qualitative and quantitative advanced complimentary multi-imaging modalities in predicting the postnatal growth potential of critically underdeveloped left heart structures.

Complexity of heart rate fluctuations in near-term sheep and human fetuses during sleep.

PubMed

Frank, Birgit; Frasch, Martin G; Schneider, Uwe; Roedel, Marcus; Schwab, Matthias; Hoyer, Dirk

2006-10-01

We investigated how the complexity of fetal heart rate fluctuations (fHRF) is related to the sleep states in sheep and human fetuses. The complexity as a function of time scale for fetal heart rate data for 7 sheep and 27 human fetuses was estimated in rapid eye movement (REM) and non-REM sleep by means of permutation entropy and the associated Kullback-Leibler entropy. We found that in humans, fHRF complexity is higher in non-REM than REM sleep, whereas in sheep this relationship is reversed. To show this relation, choice of the appropriate time scale is crucial. In sheep fetuses, we found differences in the complexity of fHRF between REM and non-REM sleep only for larger time scales (above 2.5 s), whereas in human fetuses the complexity was clearly different between REM and non-REM sleep over the whole range of time scales. This may be due to inherent time scales of complexity, which reflect species-specific functions of the autonomic nervous system. Such differences have to be considered when animal data are translated to the human situation.

Clinical application of three-dimensional printing to the management of complex univentricular hearts with abnormal systemic or pulmonary venous drainage.

PubMed

McGovern, Eimear; Kelleher, Eoin; Snow, Aisling; Walsh, Kevin; Gadallah, Bassem; Kutty, Shelby; Redmond, John M; McMahon, Colin J

2017-09-01

In recent years, three-dimensional printing has demonstrated reliable reproducibility of several organs including hearts with complex congenital cardiac anomalies. This represents the next step in advanced image processing and can be used to plan surgical repair. In this study, we describe three children with complex univentricular hearts and abnormal systemic or pulmonary venous drainage, in whom three-dimensional printed models based on CT data assisted with preoperative planning. For two children, after group discussion and examination of the models, a decision was made not to proceed with surgery. We extend the current clinical experience with three-dimensional printed modelling and discuss the benefits of such models in the setting of managing complex surgical problems in children with univentricular circulation and abnormal systemic or pulmonary venous drainage.

Out-patient management of chronic heart failure.

PubMed

Terrovitis, John V; Anastasiou-Nana, Maria I; Nanas, John N

2005-09-01

Chronic heart failure is a clinical syndrome associated with an ominous long-term prognosis and major economic consequences for Western societies. In recent years, considerable progress has been made in the pharmacological management of heart failure, and several treatments have been confirmed to confer survival and symptomatic benefits. However, pharmaceuticals remain underutilised, and the combination of several different drugs present challenges for their optimal prescription, requiring a thorough knowledge of potential side effects and complex interactions. This article reviews in detail the evidence pertaining to the out-patient pharmacological management of chronic heart failure, and offers recommendations on the use of various drugs in complex clinical conditions, or in areas of ongoing controversy.

Rapid recovery from congestive heart failure following successful radiofrequency catheter ablation in a patient with late onset of Wolff-Parkinson-White syndrome.

PubMed

Yodogawa, Kenji; Ono, Norihiko; Seino, Yoshihiko

2012-01-01

A 56-year-old man was admitted because of palpitations and dyspnea. A 12-lead electrocardiogram showed irregular wide QRS complex tachycardia with a slur at the initial portion of the QRS complex. He had preexisting long-standing persistent atrial fibrillation, but early excitation syndrome had never been noted. Chest X-ray showed heart enlargement and pulmonary congestion. He was diagnosed with late onset of Wolff-Parkinson-White syndrome, and congestive heart failure was probably caused by rapid ventricular response of atrial fibrillation through the accessory pathway. Emergency catheter ablation for the accessory pathway was undertaken, and heart failure was dramatically improved.

Three-Dimensional Printing of Complex Structures by Freeform Reversible Embedding of Suspended Hydrogels (FRESH)

NASA Astrophysics Data System (ADS)

Feinberg, Adam

We demonstrate the additive manufacturing of complex three-dimensional (3D) structures using soft protein and polysaccharide hydrogels that are challenging or impossible to create using traditional fabrication approaches. These structures are built by embedding the printed hydrogel within a secondary hydrogel that serves as a temporary, thermoreversible, and biocompatible support. This process, termed freeform reversible embedding of suspended hydrogels (FRESH), enables 3D printing of hydrated materials with an elastic modulus less than 500 kPa including alginate, collagen, hyaluronic acid and fibrin. A range of crosslinking mechanisms can be used depending on the polymer being printed, including ionic, enzymatic, pH, thermal and light based approaches. CAD models of 3D optical, computed tomography, and magnetic resonance imaging data can be 3D printed at a resolution of 100 μm and at low cost by leveraging open-source hardware and software tools. Proof-of-concept structures based on femurs, branched coronary arteries, trabeculated embryonic hearts, and human brains are mechanically robust and recreate complex 3D internal and external anatomical architectures. Recent advances have improved the resolution and broadened the range of materials that can be FRESH 3D printed. This work was supported in part by the NIH Director's New Innovator Award (DP2HL117750) and the NSF CAREER Award (1454248).

Hypoxic pulmonary vasoconstriction in reptiles: a comparative study of four species with different lung structures and pulmonary blood pressures.

PubMed

Skovgaard, Nini; Abe, Augusto S; Andrade, Denis V; Wang, Tobias

2005-11-01

Low O2 levels in the lungs of birds and mammals cause constriction of the pulmonary vasculature that elevates resistance to pulmonary blood flow and increases pulmonary blood pressure. This hypoxic pulmonary vasoconstriction (HPV) diverts pulmonary blood flow from poorly ventilated and hypoxic areas of the lung to more well-ventilated parts and is considered important for the local matching of ventilation to blood perfusion. In the present study, the effects of acute hypoxia on pulmonary and systemic blood flows and pressures were measured in four species of anesthetized reptiles with diverse lung structures and heart morphologies: varanid lizards (Varanus exanthematicus), caimans (Caiman latirostris), rattlesnakes (Crotalus durissus), and tegu lizards (Tupinambis merianae). As previously shown in turtles, hypoxia causes a reversible constriction of the pulmonary vasculature in varanids and caimans, decreasing pulmonary vascular conductance by 37 and 31%, respectively. These three species possess complex multicameral lungs, and it is likely that HPV would aid to secure ventilation-perfusion homogeneity. There was no HPV in rattlesnakes, which have structurally simple lungs where local ventilation-perfusion inhomogeneities are less likely to occur. However, tegu lizards, which also have simple unicameral lungs, did exhibit HPV, decreasing pulmonary vascular conductance by 32%, albeit at a lower threshold than varanids and caimans (6.2 kPa oxygen in inspired air vs. 8.2 and 13.9 kPa, respectively). Although these observations suggest that HPV is more pronounced in species with complex lungs and functionally divided hearts, it is also clear that other components are involved.

Feasibility of a Team Approach to Complex Congenital Heart Defect Neurodevelopmental Follow-Up: Early Experience of a Combined Cardiology/Neonatal Intensive Care Unit Follow-Up Program.

PubMed

Chorna, Olena; Baldwin, H Scott; Neumaier, Jamie; Gogliotti, Shirley; Powers, Deborah; Mouvery, Amanda; Bichell, David; Maitre, Nathalie L

2016-07-01

Infants with complex congenital heart disease are at high risk for poor neurodevelopmental outcomes. However, implementation of dedicated congenital heart disease follow-up programs presents important infrastructure, personnel, and resource challenges. We present the development, implementation, and retrospective review of 1- and 2-year outcomes of a Complex Congenital Heart Defect Neurodevelopmental Follow-Up program. This program was a synergistic approach between the Pediatric Cardiology, Cardiothoracic Surgery, Pediatric Intensive Care, and Neonatal Intensive Care Unit Follow-Up teams to provide a feasible and responsible utilization of existing infrastructure and personnel, to develop and implement a program dedicated to children with congenital heart disease. Trained developmental testers administered the Ages and Stages Questionnaire-3 over the phone to the parents of all referred children at least once between 6 and 12 months' corrected age. At 18 months' corrected age, all children were scheduled in the Neonatal Intensive-Care Unit Follow-Up Clinic for a visit with standardized neurological exams, Bayley III, multidisciplinary therapy evaluations and continued follow-up. Of the 132 patients identified in the Cardiothoracic Surgery database and at discharge from the hospital, a total number of 106 infants were reviewed. A genetic syndrome was identified in 23.4% of the population. Neuroimaging abnormalities were identified in 21.7% of the cohort with 12.8% having visibly severe insults. As a result, 23 (26.7%) received first-time referrals for early intervention services, 16 (13.8%) received referrals for new services in addition to their existing ones. We concluded that utilization of existing resources in collaboration with established programs can ensure targeted neurodevelopmental follow-up for all children with complex congenital heart disease. © 2016 American Heart Association, Inc.

The ABCs of managing systolic heart failure: Past, present, and future.

PubMed

Okwuosa, Ike Stanley; Princewill, Oluseyi; Nwabueze, Chiemeke; Mathews, Lena; Hsu, Steven; Gilotra, Nisha A; Lewsey, Sabra; Blumenthal, Roger S; Russell, Stuart D

2016-10-01

Heart failure management is complex and constantly evolving. The American College of Cardiology and the American Heart Association (ACC/AHA) last issued evidence-based guidelines in 2013, and since then, new drugs and devices have been developed. This review presents an evidence-based approach to current heart failure management. Copyright © 2016 Cleveland Clinic.

Profiling analysis of low molecular weight heparins by multiple heart-cutting two dimensional chromatography with quadruple time-of-flight mass spectrometry.

PubMed

Ouyang, Yilan; Zeng, Yangyang; Rong, Yinxiu; Song, Yue; Shi, Lv; Chen, Bo; Yang, Xinlei; Xu, Naiyu; Linhardt, Robert J; Zhang, Zhenqing

2015-09-01

Low molecular weight heparins (LMWHs) are polydisperse and microheterogenous mixtures of polysaccharides used as anticoagulant drugs. Profiling analysis is important for obtaining deeper insights into the structure of LMWHs. Previous oligosaccharide mapping methods are relatively low resolution and are unable to show an entire picture of the structural complexity of LMWHs. In the current study a profiling method was developed relying on multiple heart-cutting, two-dimensional, ultrahigh performance liquid chromatography with quadruple time-of-flight mass spectrometry. This represents an efficient, automated, and robust approach for profiling LMWHs. Using size-exclusion chromatography and ion-pairing reversed-phase chromatography in a two-dimensional separation, LMW components of different sizes and LMW components of the same size but with different charges and polarities can be resolved, providing a more complete picture of a LMWH. Structural information on each component was then obtained with quadrupole time-of-flight mass spectrometry. More than 80 and 120 oligosaccharides were observed and unambiguously assigned from the LMWHs, nadroparin and enoxaparin, respectively. This method might be useful for quality control of LMWHs and as a powerful tool for heparin-related glycomics.

Rational screening of peroxisome proliferator-activated receptor-γ agonists from natural products: potential therapeutics for heart failure.

PubMed

Chen, Rui; Wan, Jing; Song, Jing; Qian, Yan; Liu, Yong; Gu, Shuiming

2017-12-01

Peroxisome proliferator-activated receptor-γ (PPARγ) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Activation of PPARγ pathway has been shown to enhance fatty acid oxidation, improve endothelial cell function, and decrease myocardial fibrosis in heart failure. Thus, the protein has been raised as an attractive target for heart failure therapy. This work attempted to discover new and potent PPARγ agonists from natural products using a synthetic strategy of computer virtual screening and transactivation reporter assay. A large library of structurally diverse, drug-like natural products was compiled, from which those with unsatisfactory pharmacokinetic profile and/or structurally redundant compounds were excluded. The binding mode of remaining candidates to PPARγ ligand-binding domain (LBD) was computationally modelled using molecular docking and their relative binding potency was ranked by an empirical scoring scheme. Consequently, eight commercially available hits with top scores were selected and their biological activity was determined using a cell-based reporter-gene assay. Four natural product compounds, namely ZINC13408172, ZINC4292805, ZINC44179 and ZINC901461, were identified to have high or moderate agonistic potency against human PPARγ with EC 50 values of 0.084, 2.1, 0.35 and 5.6 μM, respectively, which are comparable to or even better than that of the approved PPARγ full agonists pioglitazone (EC 50  =   0.16 μM) and rosiglitazone (EC 50  =   0.034 μM). Hydrophobic interactions and van der Waals contacts are the primary chemical forces to stabilize the complex architecture of PPARγ LBD domain with these agonist ligands, while few hydrogen bonds, salt bridges and/or π-π stacking at the complex interfaces confer selectivity and specificity for the domain-agonist recognition. The integrated in vitro-in silico screening strategy can be successfully applied to rational discovery of biologically active compounds. The newly identified natural products with PPARγ agonistic potency are considered as promising lead scaffolds to develop novel chemical therapeutics for heart failure.

Cell counting in whole mount tissue volumes using expansion OCT (Conference Presentation)

NASA Astrophysics Data System (ADS)

Liu, Yehe; Gu, Shi; Watanabe, Michiko; Rollins, Andrew M.; Jenkins, Michael W.

2017-02-01

Abnormal cell proliferation and migration during heart development can lead to severe congenital heart defects (CHDs). Studying the spatial distribution of cells during embryonic development helps our understanding of how the heart develops and the etiology of certain CHDs. However, imaging large groups of single cells in intact tissue volumes is challenging. No current technique can accomplish this task in both a time-efficient and cost-effective manner. OCT has potential with its large field of view and micron-scale resolution, but even the highest resolution OCT systems have poor contrast for counting cells and have a small field of view compared to conventional OCT. We propose using a conventional OCT system and processing the sample to enhance cellular contrast. Inspired by the recently developed Expansion Microscopy, we permeated whole-mount embryonic tissue with a superabsorbent monomer solution and polymerized into a hydrogel. When hydrated in DI water, the tissue-hydrogel complex was uniformly enlarged ( 5X in all dimensions) without distorting the microscopic structure. This had a twofold effect: it increased the resolution by a factor of 5 and decreased scattering, which allowed us to resolve cellular level features deep in the tissue with high contrast using conventional OCT. We noted that cell nuclei caused significantly more backscattering than the other subcellular structures after expansion. Based on this property, we were able to distinguish individual cell nuclei, and thus count cells, in expanded OCT images with simple intensity thresholding. We demonstrate the technique with embryonic quail hearts at various developmental stages.

Multiple-Step Injection Molding for Fibrin-Based Tissue-Engineered Heart Valves

PubMed Central

Weber, Miriam; Gonzalez de Torre, Israel; Moreira, Ricardo; Frese, Julia; Oedekoven, Caroline; Alonso, Matilde; Rodriguez Cabello, Carlos J.

2015-01-01

Heart valves are elaborate and highly heterogeneous structures of the circulatory system. Despite the well accepted relationship between the structural and mechanical anisotropy and the optimal function of the valves, most approaches to create tissue-engineered heart valves (TEHVs) do not try to mimic this complexity and rely on one homogenous combination of cells and materials for the whole construct. The aim of this study was to establish an easy and versatile method to introduce spatial diversity into a heart valve fibrin scaffold. We developed a multiple-step injection molding process that enables the fabrication of TEHVs with heterogeneous composition (cell/scaffold material) of wall and leaflets without the need of gluing or suturing components together, with the leaflets firmly connected to the wall. The integrity of the valves and their functionality was proved by either opening/closing cycles in a bioreactor (proof of principle without cells) or with continuous stimulation over 2 weeks. We demonstrated the potential of the method by the two-step molding of the wall and the leaflets containing different cell lines. Immunohistology after stimulation confirmed tissue formation and demonstrated the localization of the different cell types. Furthermore, we showed the proof of principle fabrication of valves using different materials for wall (fibrin) and leaflets (hybrid gel of fibrin/elastin-like recombinamer) and with layered leaflets. The method is easy to implement, does not require special facilities, and can be reproduced in any tissue-engineering lab. While it has been demonstrated here with fibrin, it can easily be extended to other hydrogels. PMID:25654448

Multiple-Step Injection Molding for Fibrin-Based Tissue-Engineered Heart Valves.

PubMed

Weber, Miriam; Gonzalez de Torre, Israel; Moreira, Ricardo; Frese, Julia; Oedekoven, Caroline; Alonso, Matilde; Rodriguez Cabello, Carlos J; Jockenhoevel, Stefan; Mela, Petra

2015-08-01

Heart valves are elaborate and highly heterogeneous structures of the circulatory system. Despite the well accepted relationship between the structural and mechanical anisotropy and the optimal function of the valves, most approaches to create tissue-engineered heart valves (TEHVs) do not try to mimic this complexity and rely on one homogenous combination of cells and materials for the whole construct. The aim of this study was to establish an easy and versatile method to introduce spatial diversity into a heart valve fibrin scaffold. We developed a multiple-step injection molding process that enables the fabrication of TEHVs with heterogeneous composition (cell/scaffold material) of wall and leaflets without the need of gluing or suturing components together, with the leaflets firmly connected to the wall. The integrity of the valves and their functionality was proved by either opening/closing cycles in a bioreactor (proof of principle without cells) or with continuous stimulation over 2 weeks. We demonstrated the potential of the method by the two-step molding of the wall and the leaflets containing different cell lines. Immunohistology after stimulation confirmed tissue formation and demonstrated the localization of the different cell types. Furthermore, we showed the proof of principle fabrication of valves using different materials for wall (fibrin) and leaflets (hybrid gel of fibrin/elastin-like recombinamer) and with layered leaflets. The method is easy to implement, does not require special facilities, and can be reproduced in any tissue-engineering lab. While it has been demonstrated here with fibrin, it can easily be extended to other hydrogels.

Multiscale entropy analysis of heart rate variability in heart failure, hypertensive, and sinoaortic-denervated rats: classical and refined approaches.

PubMed

Silva, Luiz Eduardo Virgilio; Lataro, Renata Maria; Castania, Jaci Airton; da Silva, Carlos Alberto Aguiar; Valencia, Jose Fernando; Murta, Luiz Otavio; Salgado, Helio Cesar; Fazan, Rubens; Porta, Alberto

2016-07-01

The analysis of heart rate variability (HRV) by nonlinear methods has been gaining increasing interest due to their ability to quantify the complexity of cardiovascular regulation. In this study, multiscale entropy (MSE) and refined MSE (RMSE) were applied to track the complexity of HRV as a function of time scale in three pathological conscious animal models: rats with heart failure (HF), spontaneously hypertensive rats (SHR), and rats with sinoaortic denervation (SAD). Results showed that HF did not change HRV complexity, although there was a tendency to decrease the entropy in HF animals. On the other hand, SHR group was characterized by reduced complexity at long time scales, whereas SAD animals exhibited a smaller short- and long-term irregularity. We propose that short time scales (1 to 4), accounting for fast oscillations, are more related to vagal and respiratory control, whereas long time scales (5 to 20), accounting for slow oscillations, are more related to sympathetic control. The increased sympathetic modulation is probably the main reason for the lower entropy observed at high scales for both SHR and SAD groups, acting as a negative factor for the cardiovascular complexity. This study highlights the contribution of the multiscale complexity analysis of HRV for understanding the physiological mechanisms involved in cardiovascular regulation. Copyright © 2016 the American Physiological Society.

Loan applications in adult patients with congenital heart disease: a French study.

PubMed

Ladouceur, Magalie; Dugardin, Bertrand; Gourdin, Stéphanie; Sidi, Daniel; Bonnet, Damien; Iserin, Laurence

2011-01-01

Improvements in the treatment of children with congenital heart disease have led to most of these patients reaching adulthood. Despite the increase in lifespan, very little is known about their quality of life - in particular, their ability to obtain a mortgage or consumer loan. To investigate the outcome of mortgage and loan applications made by adults with differential severities of congenital heart disease. Four hundred and seventy-six patients were invited to participate in a questionnaire-based interview by phone. Of these patients, one hundred and forty-two responded. Respondents were classified into three categories ('significant', 'complex' and 'mild') based on congenital heart disease severity according to the Bethesda conference. Ninety patients (64%) had applied for loans; 17 (16.5%) did not report their heart disease to the insurance company, 13 were refused insurance and 39 were asked to pay surplus fees. The imposed fees concerned patients classified in the 'significant' and 'complex' groups (P<0.0001 and P<0.003, respectively, compared with those classified in the 'mild' group). Age, sex, other diseases, cardiovascular risk factors and duration of the loan had no influence on loan application outcomes. Adults with congenital heart disease are considerably more likely to have difficulty obtaining a mortgage or loan, independent of their congenital heart disease severity. Moreover, despite an increased obtainment of a loan in patients classified as 'mild', the refusal rates were identical for patients classified as having 'significant' or 'complex' congenital heart disease, although their prognosis is different. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Paradigms of Complexity: Fractals and Structures in the Sciences

NASA Astrophysics Data System (ADS)

Novak, Miroslav M.

The Table of Contents for the book is as follows: * Preface * The Origin of Complexity (invited talk) * On the Existence of Spatially Uniform Scaling Laws in the Climate System * Multispectral Backscattering: A Fractal-Structure Probe * Small-Angle Multiple Scattering on a Fractal System of Point Scatterers * Symmetric Fractals Generated by Cellular Automata * Bispectra and Phase Correlations for Chaotic Dynamical Systems * Self-Organized Criticality Models of Neural Development * Altered Fractal and Irregular Heart Rate Behavior in Sick Fetuses * Extract Multiple Scaling in Long-Term Heart Rate Variability * A Semi-Continous Box Counting Method for Fractal Dimension Measurement of Short Single Dimension Temporal Signals - Preliminary Study * A Fractional Brownian Motion Model of Cracking * Self-Affine Scaling Studies on Fractography * Coarsening of Fractal Interfaces * A Fractal Model of Ocean Surface Superdiffusion * Stochastic Subsurface Flow and Transport in Fractal Fractal Conductivity Fields * Rendering Through Iterated Function Systems * The σ-Hull - The Hull Where Fractals Live - Calculating a Hull Bounded by Log Spirals to Solve the Inverse IFS-Problem by the Detected Orbits * On the Multifractal Properties of Passively Convected Scalar Fields * New Statistical Textural Transforms for Non-Stationary Signals: Application to Generalized Mutlifractal Analysis * Laplacian Growth of Parallel Needles: Their Mullins-Sekerka Instability * Entropy Dynamics Associated with Self-Organization * Fractal Properties in Economics (invited talk) * Fractal Approach to the Regional Seismic Event Discrimination Problem * Fractal and Topological Complexity of Radioactive Contamination * Pattern Selection: Nonsingular Saffman-Taylor Finger and Its Dynamic Evolution with Zero Surface Tension * A Family of Complex Wavelets for the Characterization of Singularities * Stabilization of Chaotic Amplitude Fluctuations in Multimode, Intracavity-Doubled Solid-State Lasers * Chaotic Dynamics of Elastic-Plastic Beams * The Riemann Non-Differentiable Function and Identities for the Gaussian Sums * Revealing the Multifractal Nature of Failure Sequence * The Fractal Nature of wood Revealed by Drying * Squaring the Circle: Diffusion Volume and Acoustic Behaviour of a Fractal Structure * Relationship Between Acupuncture Holographic Units and Fetus Development; Fractal Features of Two Acupuncture Holographic Unit Systems * The Fractal Properties of the Large-Scale Magnetic Fields on the Sun * Fractal Analysis of Tide Gauge Data * Author Index

Heart rate measurement based on face video sequence

NASA Astrophysics Data System (ADS)

Xu, Fang; Zhou, Qin-Wu; Wu, Peng; Chen, Xing; Yang, Xiaofeng; Yan, Hong-jian

2015-03-01

This paper proposes a new non-contact heart rate measurement method based on photoplethysmography (PPG) theory. With this method we can measure heart rate remotely with a camera and ambient light. We collected video sequences of subjects, and detected remote PPG signals through video sequences. Remote PPG signals were analyzed with two methods, Blind Source Separation Technology (BSST) and Cross Spectral Power Technology (CSPT). BSST is a commonly used method, and CSPT is used for the first time in the study of remote PPG signals in this paper. Both of the methods can acquire heart rate, but compared with BSST, CSPT has clearer physical meaning, and the computational complexity of CSPT is lower than that of BSST. Our work shows that heart rates detected by CSPT method have good consistency with the heart rates measured by a finger clip oximeter. With good accuracy and low computational complexity, the CSPT method has a good prospect for the application in the field of home medical devices and mobile health devices.

Systems Biology and Biomechanical Model of Heart Failure

PubMed Central

Louridas, George E; Lourida, Katerina G

2012-01-01

Heart failure is seen as a complex disease caused by a combination of a mechanical disorder, cardiac remodeling and neurohormonal activation. To define heart failure the systems biology approach integrates genes and molecules, interprets the relationship of the molecular networks with modular functional units, and explains the interaction between mechanical dysfunction and cardiac remodeling. The biomechanical model of heart failure explains satisfactorily the progression of myocardial dysfunction and the development of clinical phenotypes. The earliest mechanical changes and stresses applied in myocardial cells and/or myocardial loss or dysfunction activate left ventricular cavity remodeling and other neurohormonal regulatory mechanisms such as early release of natriuretic peptides followed by SAS and RAAS mobilization. Eventually the neurohormonal activation and the left ventricular remodeling process are leading to clinical deterioration of heart failure towards a multi-organic damage. It is hypothesized that approaching heart failure with the methodology of systems biology we promote the elucidation of its complex pathophysiology and most probably we can invent new therapeutic strategies. PMID:22935019

Management of heart failure in the new era: the role of scores.

PubMed

Mantegazza, Valentina; Badagliacca, Roberto; Nodari, Savina; Parati, Gianfranco; Lombardi, Carolina; Di Somma, Salvatore; Carluccio, Erberto; Dini, Frank Lloyd; Correale, Michele; Magrì, Damiano; Agostoni, Piergiuseppe

2016-08-01

Heart failure is a widespread syndrome involving several organs, still characterized by high mortality and morbidity, and whose clinical course is heterogeneous and hardly predictable.In this scenario, the assessment of heart failure prognosis represents a fundamental step in clinical practice. A single parameter is always unable to provide a very precise prognosis. Therefore, risk scores based on multiple parameters have been introduced, but their clinical utility is still modest. In this review, we evaluated several prognostic models for acute, right, chronic, and end-stage heart failure based on multiple parameters. In particular, for chronic heart failure we considered risk scores essentially based on clinical evaluation, comorbidities analysis, baroreflex sensitivity, heart rate variability, sleep disorders, laboratory tests, echocardiographic imaging, and cardiopulmonary exercise test parameters. What is at present established is that a single parameter is not sufficient for an accurate prediction of prognosis in heart failure because of the complex nature of the disease. However, none of the scoring systems available is widely used, being in some cases complex, not user-friendly, or based on expensive or not easily available parameters. We believe that multiparametric scores for risk assessment in heart failure are promising but their widespread use needs to be experienced.

[Generation of Superoxide Radicals by Complex III in Heart Mitochondria and Antioxidant Effect of Dinitrosyl Iron Complexes at Different Partial Pressure of Oxygen].

PubMed

Dudylina, A L; Ivanova, M V; Shumaev, K B; Ruuge, E K

2016-01-01

The EPR spin-trapping technique and EPR-oximetry were used to study generation of superoxide radicals in heart mitochondria isolated from Wistar rats under conditions of variable oxygen concentration. Lithium phthalocyanine and TEMPONE-15N-D16 were chosen to determine oxygen content in a gas-permeable capillary tube containing mitochondria. TIRON was used as a spin trap. We investigated the influence of different oxygen concentrations in incubation mixture and demonstrated that heart mitochondria can generate superoxide in complex III at different partial pressure of oxygen as well as under the conditions of deep hypoxia (< 5% O2). Dinitrosyl iron complexes with glutathione (the pharmaceutical drug "Oxacom") exerted an antioxidant effect, regardless of the value of the partial pressure of oxygen, but the magnitude and kinetic characteristics of the effect depended on the concentration of the drug.

Aging reduces complexity of heart rate variability assessed by conditional entropy and symbolic analysis.

PubMed

Takahashi, Anielle C M; Porta, Alberto; Melo, Ruth C; Quitério, Robison J; da Silva, Ester; Borghi-Silva, Audrey; Tobaldini, Eleonora; Montano, Nicola; Catai, Aparecida M

2012-06-01

Increasing age is associated with a reduction in overall heart rate variability as well as changes in complexity of physiologic dynamics. The aim of this study was to verify if the alterations in autonomic modulation of heart rate caused by the aging process could be detected by Shannon entropy (SE), conditional entropy (CE) and symbolic analysis (SA). Complexity analysis was carried out in 44 healthy subjects divided into two groups: old (n = 23, 63 ± 3 years) and young group (n = 21, 23 ± 2). It was analyzed SE, CE [complexity index (CI) and normalized CI (NCI)] and SA (0V, 1V, 2LV and 2ULV patterns) during short heart period series (200 cardiac beats) derived from ECG recordings during 15 min of rest in a supine position. The sequences characterized by three heart periods with no significant variations (0V), and that with two significant unlike variations (2ULV) reflect changes in sympathetic and vagal modulation, respectively. The unpaired t test (or Mann-Whitney rank sum test when appropriate) was used in the statistical analysis. In the aging process, the distributions of patterns (SE) remain similar to young subjects. However, the regularity is significantly different; the patterns are more repetitive in the old group (a decrease of CI and NCI). The amounts of pattern types are different: 0V is increased and 2LV and 2ULV are reduced in the old group. These differences indicate marked change of autonomic regulation. The CE and SA are feasible techniques to detect alteration in autonomic control of heart rate in the old group.

Complex cardiac defects after ethanol exposure during discrete cardiogenic events in zebrafish: Prevention with folic acid

PubMed Central

Sarmah, Swapnalee; Marrs, James A.

2014-01-01

BACKGROUND Fetal alcohol spectrum disorder (FASD) describes a range of birth defects including various congenital heart defects (CHDs). Mechanisms of FASD-associated CHDs are not understood. Whether alcohol interferes with a single critical event or with multiple events in heart formation is not known. RESULTS Our zebrafish embryo experiments showed that ethanol interrupts different cardiac regulatory networks and perturbed multiple steps of cardiogenesis (specification, myocardial migration, looping, chamber morphogenesis and endocardial cushion formation). Ethanol exposure during gastrulation until cardiac specification or during myocardial midline migration did not produce severe or persistent heart development defects. However, exposure comprising gastrulation until myocardial precursor midline fusion or during heart patterning stages produced aberrant heart looping and defective endocardial cushions. Continuous exposure during entire cardiogenesis produced complex cardiac defects leading to severely defective myocardium, endocardium, and endocardial cushions. Supplementation of retinoic acid with ethanol partially rescued early heart developmental defects, but the endocardial cushions did not form correctly. In contrast, supplementation of folic acid rescued normal heart development, including the endocardial cushions. CONCLUSIONS Our results indicate that ethanol exposure interrupted divergent cardiac morphogenesis events causing heart defects. Folic acid supplementation was effective in preventing a wide spectrum of ethanol-induced heart developmental defects. PMID:23832875

Evaluation of athletes with complex congenital heart disease.

PubMed

Bates, Benjamin A; Richards, Camille; Hall, Michael; Kerut, Edmund K; Campbell, William; McMullan, Michael R

2017-06-01

As a result of improvements in congenital heart surgery, there are more adults alive today with congenital heart disease (CHD) than children. Individuals with cardiac birth defects may be able to participate in physical activities but require proper cardiovascular evaluation. The American Heart Association and American College of Cardiology released guidelines in 2015 for athletes with cardiovascular abnormalities. The guidelines express that although restriction from competitive athletics may be indicated for some, the majority of individuals with CHD can and should engage in some form of physical activity. This case study demonstrates the importance of combining all aspects of history, physical examination, ECG, and imaging modalities to evaluate cardiac anatomy and function in young athletes with complex CHD. © 2017, Wiley Periodicals, Inc.

TRPC6 counteracts TRPC3-Nox2 protein complex leading to attenuation of hyperglycemia-induced heart failure in mice.

PubMed

Oda, Sayaka; Numaga-Tomita, Takuro; Kitajima, Naoyuki; Toyama, Takashi; Harada, Eri; Shimauchi, Tsukasa; Nishimura, Akiyuki; Ishikawa, Tatsuya; Kumagai, Yoshito; Birnbaumer, Lutz; Nishida, Motohiro

2017-08-08

Excess production of reactive oxygen species (ROS) caused by hyperglycemia is a major risk factor for heart failure. We previously reported that transient receptor potential canonical 3 (TRPC3) channel mediates pressure overload-induced maladaptive cardiac fibrosis by forming stably functional complex with NADPH oxidase 2 (Nox2). Although TRPC3 has been long suggested to form hetero-multimer channels with TRPC6 and function as diacylglycerol-activated cation channels coordinately, the role of TRPC6 in heart is still obscure. We here demonstrated that deletion of TRPC6 had no impact on pressure overload-induced heart failure despite inhibiting interstitial fibrosis in mice. TRPC6-deficient mouse hearts 1 week after transverse aortic constriction showed comparable increases in fibrotic gene expressions and ROS production but promoted inductions of inflammatory cytokines, compared to wild type hearts. Treatment of TRPC6-deficient mice with streptozotocin caused severe reduction of cardiac contractility with enhancing urinary and cardiac lipid peroxide levels, compared to wild type and TRPC3-deficient mice. Knockdown of TRPC6, but not TRPC3, enhanced basal expression levels of cytokines in rat cardiomyocytes. TRPC6 could interact with Nox2, but the abundance of TRPC6 was inversely correlated with that of Nox2. These results strongly suggest that Nox2 destabilization through disrupting TRPC3-Nox2 complex underlies attenuation of hyperglycemia-induced heart failure by TRPC6.

Myocyte repolarization modulates myocardial function in aging dogs

PubMed Central

Sorrentino, Andrea; Signore, Sergio; Borghetti, Giulia; Meo, Marianna; Cannata, Antonio; Zhou, Yu; Wybieralska, Ewa; Luciani, Marco; Kannappan, Ramaswamy; Zhang, Eric; Matsuda, Alex; Webster, Andrew; Cimini, Maria; Kertowidjojo, Elizabeth; D'Alessandro, David A.; Wunimenghe, Oriyanhan; Michler, Robert E.; Royer, Christopher; Goichberg, Polina; Leri, Annarosa; Barrett, Edward G.; Anversa, Piero; Hintze, Thomas H.

2016-01-01

Studies of myocardial aging are complex and the mechanisms involved in the deterioration of ventricular performance and decreased functional reserve of the old heart remain to be properly defined. We have studied a colony of beagle dogs from 3 to 14 yr of age kept under a highly regulated environment to define the effects of aging on the myocardium. Ventricular, myocardial, and myocyte function, together with anatomical and structural properties of the organ and cardiomyocytes, were evaluated. Ventricular hypertrophy was not observed with aging and the structural composition of the myocardium was modestly affected. Alterations in the myocyte compartment were identified in aged dogs, and these factors negatively interfere with the contractile reserve typical of the young heart. The duration of the action potential is prolonged in old cardiomyocytes contributing to the slower electrical recovery of the myocardium. Also, the remodeled repolarization of cardiomyocytes with aging provides inotropic support to the senescent muscle but compromises its contractile reserve, rendering the old heart ineffective under conditions of high hemodynamic demand. The defects in the electrical and mechanical properties of cardiomyocytes with aging suggest that this cell population is an important determinant of the cardiac senescent phenotype. Collectively, the delayed electrical repolarization of aging cardiomyocytes may be viewed as a critical variable of the aging myopathy and its propensity to evolve into ventricular decompensation under stressful conditions. PMID:26801307

Impact of the canine double-deletion β1 adrenoreceptor polymorphisms on protein structure and heart rate response to atenolol, a β1-selective β-blocker.

PubMed

Meurs, Kathryn M; Stern, Josh A; Reina-Doreste, Yamir; Maran, Brian A; Chdid, Lhoucine; Lahmers, Sunshine; Keene, Bruce W; Mealey, Katrina L

2015-09-01

β-Adrenergic receptor antagonists are widely utilized for the management of cardiac diseases in dogs. We have recently identified two deletion polymorphisms in the canine adrenoreceptor 1 (ADRB1) gene.We hypothesized that canine ADRB1 deletions would alter the structure of the protein, as well as the heart rate response to the β-adrenergic receptor antagonist, atenolol. The objectives of this study were to predict the impact of these deletions on the predicted structure of the protein and on the heart rate response to atenolol in a population of healthy adult dogs. Eighteen apparently healthy, mature dogs with (11) and without (seven) ADRB1 deletions were evaluated. The heart rate of the dogs was evaluated with a baseline ambulatory ECG before and 14-21 days after atenolol therapy (1 mg/kg orally q12 h). Minimum, average, and maximum heart rates were compared between groups of dogs (deletions, controls) using an unpaired t-test and within each group of dogs using a paired t-test. The protein structure of ADRB1 was predicted by computer modeling. Deletions were predicted to alter the structure of the ADRB1 protein. The heart rates of the dogs with deletions were lower than those of the control dogs (the average heart rates were significantly lower). ADRB1 deletions appear to have structural and functional consequences. Individual genome-based treatment recommendations could impact the management of dogs with heart disease.

'Hearts and minds': association, causation and implication of cognitive impairment in heart failure.

PubMed

Cannon, Jane A; McMurray, John Jv; Quinn, Terry J

2015-01-01

The clinical syndrome of heart failure is one of the leading causes of hospitalisation and mortality in older adults. An association between cognitive impairment and heart failure is well described but our understanding of the relationship between the two conditions remains limited. In this review we provide a synthesis of available evidence, focussing on epidemiology, the potential pathogenesis, and treatment implications of cognitive decline in heart failure. Most evidence available relates to heart failure with reduced ejection fraction and the syndromes of chronic cognitive decline or dementia. These conditions are only part of a complex heart failure-cognition paradigm. Associations between cognition and heart failure with preserved ejection fraction and between acute delirium and heart failure also seem evident and where data are available we will discuss these syndromes. Many questions remain unanswered regarding heart failure and cognition. Much of the observational evidence on the association is confounded by study design, comorbidity and insensitive cognitive assessment tools. If a causal link exists, there are several potential pathophysiological explanations. Plausible underlying mechanisms relating to cerebral hypoperfusion or occult cerebrovascular disease have been described and it seems likely that these may coexist and exert synergistic effects. Despite the prevalence of the two conditions, when cognitive impairment coexists with heart failure there is no specific guidance on treatment. Institution of evidence-based heart failure therapies that reduce mortality and hospitalisations seems intuitive and there is no signal that these interventions have an adverse effect on cognition. However, cognitive impairment will present a further barrier to the often complex medication self-management that is required in contemporary heart failure treatment.

Paroxetine Is a Direct Inhibitor of G Protein-Coupled Receptor Kinase 2 and Increases Myocardial Contractility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thal, David M.; Homan, Kristoff T.; Chen, Jun

2012-08-10

G protein-coupled receptor kinase 2 (GRK2) is a well-established therapeutic target for the treatment of heart failure. In this paper we identify the selective serotonin reuptake inhibitor (SSRI) paroxetine as a selective inhibitor of GRK2 activity both in vitro and in living cells. In the crystal structure of the GRK2·paroxetine–Gβγ complex, paroxetine binds in the active site of GRK2 and stabilizes the kinase domain in a novel conformation in which a unique regulatory loop forms part of the ligand binding site. Isolated cardiomyocytes show increased isoproterenol-induced shortening and contraction amplitude in the presence of paroxetine, and pretreatment of mice withmore » paroxetine before isoproterenol significantly increases left ventricular inotropic reserve in vivo with no significant effect on heart rate. Neither is observed in the presence of the SSRI fluoxetine. Our structural and functional results validate a widely available drug as a selective chemical probe for GRK2 and represent a starting point for the rational design of more potent and specific GRK2 inhibitors.« less

Branchial cleft anomaly, congenital heart disease, and biliary atresia: Goldenhar complex or Lambert syndrome?

PubMed

Cohen, J; Schanen, N C

2000-01-01

The features of Goldenhar complex have been well-described and classically include branchial arch abnormalities, epibulbar dermoid and vertebral abnormalities. We have identified an infant with these features in association with complex congenital heart disease and intrahepatic biliary atresia. Although Lambert described an autosomal recessive disorder with an association of biliary atresia and branchial arch abnormalities, none of those cases had epibulbar dermoid. Diagnostic considerations in this case include inclusion of biliary atresia as a new feature in the expanding spectrum of the Goldenhar complex, versus Lambert syndrome with epibulbar dermoid.

Methods to assess Drosophila heart development, function and aging

PubMed Central

Ocorr, Karen; Vogler, Georg; Bodmer, Rolf

2014-01-01

In recent years the Drosophila heart has become an established model of many different aspects of human cardiac disease. This model has allowed identification of disease-causing mechanisms underlying congenital heart disease and cardiomyopathies and has permitted the study underlying genetic, metabolic and age-related contributions to heart function. In this review we discuss methods currently employed in the analysis of the Drosophila heart structure and function, such as optical methods to infer heart function and performance, electrophysiological and mechanical approaches to characterize cardiac tissue properties, and conclude with histological techniques used in the study of heart development and adult structure. PMID:24727147

Required, tissue-specific roles for Fgf8 in outflow tract formation and remodeling.

PubMed

Park, Eon Joo; Ogden, Lisa A; Talbot, Amy; Evans, Sylvia; Cai, Chen-Leng; Black, Brian L; Frank, Deborah U; Moon, Anne M

2006-06-01

Fibroblast growth factor 8 (Fgf8) is a secreted signaling protein expressed in numerous temporospatial domains that are potentially relevant to cardiovascular development. However, the pathogenesis of complex cardiac and outflow tract defects observed in Fgf8-deficient mice, and the specific source(s) of Fgf8 required for outflow tract formation and subsequent remodeling are unknown. A detailed examination of the timing and location of Fgf8 production revealed previously unappreciated expression in a subset of primary heart field cells; Fgf8 is also expressed throughout the anterior heart field (AHF) mesoderm and in pharyngeal endoderm at the crescent and early somite stages. We used conditional mutagenesis to examine the requirements for Fgf8 function in these different expression domains during heart and outflow tract morphogenesis. Formation of the primary heart tube and the addition of right ventricular and outflow tract myocardium depend on autocrine Fgf8 signaling in cardiac crescent mesoderm. Loss of Fgf8 in this domain resulted in decreased expression of the Fgf8 target gene Erm, and aberrant production of Isl1 and its target Mef2c in the anterior heart field, thus linking Fgf8 signaling with transcription factor networks that regulate survival and proliferation of the anterior heart field. We further found that mesodermal- and endodermal-derived Fgf8 perform specific functions during outflow tract remodeling: mesodermal Fgf8 is required for correct alignment of the outflow tract and ventricles, whereas activity of Fgf8 emanating from pharyngeal endoderm regulates outflow tract septation. These findings provide a novel insight into how the formation and remodeling of primary and anterior heart field-derived structures rely on Fgf8 signals from discrete temporospatial domains.

Heart Rate Monitoring in Team Sports-A Conceptual Framework for Contextualizing Heart Rate Measures for Training and Recovery Prescription.

PubMed

Schneider, Christoph; Hanakam, Florian; Wiewelhove, Thimo; Döweling, Alexander; Kellmann, Michael; Meyer, Tim; Pfeiffer, Mark; Ferrauti, Alexander

2018-01-01

A comprehensive monitoring of fitness, fatigue, and performance is crucial for understanding an athlete's individual responses to training to optimize the scheduling of training and recovery strategies. Resting and exercise-related heart rate measures have received growing interest in recent decades and are considered potentially useful within multivariate response monitoring, as they provide non-invasive and time-efficient insights into the status of the autonomic nervous system (ANS) and aerobic fitness. In team sports, the practical implementation of athlete monitoring systems poses a particular challenge due to the complex and multidimensional structure of game demands and player and team performance, as well as logistic reasons, such as the typically large number of players and busy training and competition schedules. In this regard, exercise-related heart rate measures are likely the most applicable markers, as they can be routinely assessed during warm-ups using short (3-5 min) submaximal exercise protocols for an entire squad with common chest strap-based team monitoring devices. However, a comprehensive and meaningful monitoring of the training process requires the accurate separation of various types of responses, such as strain, recovery, and adaptation, which may all affect heart rate measures. Therefore, additional information on the training context (such as the training phase, training load, and intensity distribution) combined with multivariate analysis, which includes markers of (perceived) wellness and fatigue, should be considered when interpreting changes in heart rate indices. The aim of this article is to outline current limitations of heart rate monitoring, discuss methodological considerations of univariate and multivariate approaches, illustrate the influence of different analytical concepts on assessing meaningful changes in heart rate responses, and provide case examples for contextualizing heart rate measures using simple heuristics. To overcome current knowledge deficits and methodological inconsistencies, future investigations should systematically evaluate the validity and usefulness of the various approaches available to guide and improve the implementation of decision-support systems in (team) sports practice.

Heart Rate Monitoring in Team Sports—A Conceptual Framework for Contextualizing Heart Rate Measures for Training and Recovery Prescription

PubMed Central

Schneider, Christoph; Hanakam, Florian; Wiewelhove, Thimo; Döweling, Alexander; Kellmann, Michael; Meyer, Tim; Pfeiffer, Mark; Ferrauti, Alexander

2018-01-01

A comprehensive monitoring of fitness, fatigue, and performance is crucial for understanding an athlete's individual responses to training to optimize the scheduling of training and recovery strategies. Resting and exercise-related heart rate measures have received growing interest in recent decades and are considered potentially useful within multivariate response monitoring, as they provide non-invasive and time-efficient insights into the status of the autonomic nervous system (ANS) and aerobic fitness. In team sports, the practical implementation of athlete monitoring systems poses a particular challenge due to the complex and multidimensional structure of game demands and player and team performance, as well as logistic reasons, such as the typically large number of players and busy training and competition schedules. In this regard, exercise-related heart rate measures are likely the most applicable markers, as they can be routinely assessed during warm-ups using short (3–5 min) submaximal exercise protocols for an entire squad with common chest strap-based team monitoring devices. However, a comprehensive and meaningful monitoring of the training process requires the accurate separation of various types of responses, such as strain, recovery, and adaptation, which may all affect heart rate measures. Therefore, additional information on the training context (such as the training phase, training load, and intensity distribution) combined with multivariate analysis, which includes markers of (perceived) wellness and fatigue, should be considered when interpreting changes in heart rate indices. The aim of this article is to outline current limitations of heart rate monitoring, discuss methodological considerations of univariate and multivariate approaches, illustrate the influence of different analytical concepts on assessing meaningful changes in heart rate responses, and provide case examples for contextualizing heart rate measures using simple heuristics. To overcome current knowledge deficits and methodological inconsistencies, future investigations should systematically evaluate the validity and usefulness of the various approaches available to guide and improve the implementation of decision-support systems in (team) sports practice. PMID:29904351

Development of multiscale complexity and multifractality of fetal heart rate variability.

PubMed

Gierałtowski, Jan; Hoyer, Dirk; Tetschke, Florian; Nowack, Samuel; Schneider, Uwe; Zebrowski, Jan

2013-11-01

During fetal development a complex system grows and coordination over multiple time scales is formed towards an integrated behavior of the organism. Since essential cardiovascular and associated coordination is mediated by the autonomic nervous system (ANS) and the ANS activity is reflected in recordable heart rate patterns, multiscale heart rate analysis is a tool predestined for the diagnosis of prenatal maturation. The analyses over multiple time scales requires sufficiently long data sets while the recordings of fetal heart rate as well as the behavioral states studied are themselves short. Care must be taken that the analysis methods used are appropriate for short data lengths. We investigated multiscale entropy and multifractal scaling exponents from 30 minute recordings of 27 normal fetuses, aged between 23 and 38 weeks of gestational age (WGA) during the quiet state. In multiscale entropy, we found complexity lower than that of non-correlated white noise over all 20 coarse graining time scales investigated. Significant maturation age related complexity increase was strongest expressed at scale 2, both using sample entropy and generalized mutual information as complexity estimates. Multiscale multifractal analysis (MMA) in which the Hurst surface h(q,s) is calculated, where q is the multifractal parameter and s is the scale, was applied to the fetal heart rate data. MMA is a method derived from detrended fluctuation analysis (DFA). We modified the base algorithm of MMA to be applicable for short time series analysis using overlapping data windows and a reduction of the scale range. We looked for such q and s for which the Hurst exponent h(q,s) is most correlated with gestational age. We used this value of the Hurst exponent to predict the gestational age based only on fetal heart rate variability properties. Comparison with the true age of the fetus gave satisfying results (error 2.17±3.29 weeks; p<0.001; R(2)=0.52). In addition, we found that the normally used DFA scale range is non-optimal for fetal age evaluation. We conclude that 30 min recordings are appropriate and sufficient for assessing fetal age by multiscale entropy and multiscale multifractal analysis. The predominant prognostic role of scale 2 heart beats for MSE and scale 39 heart beats (at q=-0.7) for MMA cannot be explored neither by single scale complexity measures nor by standard detrended fluctuation analysis. Copyright © 2013 Elsevier B.V. All rights reserved.

Biventricular non-compaction hypertrophic cardiomyopathy in association with congenital complete heart block and type I mitochondrial complex deficiency.

PubMed

Dhar, Ranjana; Reardon, William; McMahon, Colin J

2015-06-01

We report a baby girl with an antenatal diagnosis of biventricular non-compaction and complete heart block detected at 22 weeks' gestation. Postnatal echocardiography confirmed severe biventricular non-compaction hypertrophic cardiomyopathy, multiple muscular ventricular septal defects, and mild-moderate pulmonary valve stenosis. Skeletal muscle biopsy confirmed complex 1 mitochondrial respiratory chain deficiency. An epicardial VVI pacemaker was implanted on day 3 of life and revised at 7 years of age. She remains stable at 8 years of age following pacing and medical treatment with carvedilol, aspirin, co-enzyme Q10, and carnitine. This represents the first report of biventricular non-compaction hypertrophic phenotype in association with congenital complete heart block and complex 1 mitochondrial respiratory chain deficiency in a child.

A Case Study of Infant Physiologic Response to Skin-to-Skin Contact After Surgery for Complex Congenital Heart Disease.

PubMed

Harrison, Tondi M; Ludington-Hoe, Susan

2015-01-01

Infants with complex congenital heart disease requiring surgical intervention within the first days or weeks of life may be the most seriously ill infants needing intensive nursing and medical care. Skin-to-skin contact (SSC) is well accepted and practiced as a positive therapeutic intervention in premature infants but is not routinely offered to infants in cardiac intensive care units. The physiologic effects of SSC in the congenital heart disease population must be examined before recommending incorporation of SSC into standard care routines. The purpose of this case study was to describe the physiologic response to a single session of SSC in an 18-day-old infant with hypoplastic left heart syndrome. Repeated measures of heart rate, respiratory rate, oxygen saturation, blood pressure, and temperature were recorded 30 minutes before SSC, during SSC (including interruptions for bottle and breast feedings), and 10 minutes after SSC was completed. All physiologic parameters were clinically acceptable throughout the 135-minute observation. This case study provides beginning evidence that SSC is safe in full-term infants after surgery for complex congenital heart disease. Further research with a larger sample is needed to examine the effects of SSC on infant physiology before surgery and earlier in the postoperative time period as well as on additional outcomes such as length of stay, maternal-infant interaction, and neurodevelopment.

Multidsciplinary heart failure management and end of life care.

PubMed

Ryder, Mary; Beattie, James M; O'Hanlon, Rory; McDonald, Kenneth

2011-12-01

There has been much improvement in the treatment of heart failure over the past decade through the implementation of a multidisciplinary team approach to disease management focused on optimizing medication, the application of device-based therapy, surgical intervention and in promoting the education of patients and carers in self-management. This multidisciplinary strategy has now been extended to try and improve the care of those with advanced heart failure in the latter phases of the disease trajectory nearing the end of their lives. A growing consensus has emerged in the literature that confirms the need to extend multidisciplinary management beyond the early targets of reducing heart failure-related mortality and morbidity to address the significant care needs of those who decline due to the often inexorable progression of this syndrome. Multidisciplinary management facilitates the development of a comprehensive care plan that is specifically tailored to accommodate the requirements of individual patients and their families and fosters a collaborative approach to care to optimize symptom management, avoid potential treatments conflicts, and to fulfil their supportive care needs. Partnership working between the three principal clinical disciplines of cardiology, specialist palliative care and general practice is central to this process and promotes coordinated care across hospital, hospice and community-based services. Advanced heart failure management has improved over time; however, the incorporation of a multidisciplinary care model appears to offer significant promise in dealing with complex care needs of heart failure patients towards the end of life. Delivery of this practice requires the development of bespoke care structures that are relevant to the spectrum of healthcare service environments.

Ligand placement based on prior structures: the guided ligand-replacement method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klei, Herbert E.; Bristol-Myers Squibb, Princeton, NJ 08543-4000; Moriarty, Nigel W., E-mail: nwmoriarty@lbl.gov

2014-01-01

A new module, Guided Ligand Replacement (GLR), has been developed in Phenix to increase the ease and success rate of ligand placement when prior protein-ligand complexes are available. The process of iterative structure-based drug design involves the X-ray crystal structure determination of upwards of 100 ligands with the same general scaffold (i.e. chemotype) complexed with very similar, if not identical, protein targets. In conjunction with insights from computational models and assays, this collection of crystal structures is analyzed to improve potency, to achieve better selectivity and to reduce liabilities such as absorption, distribution, metabolism, excretion and toxicology. Current methods formore » modeling ligands into electron-density maps typically do not utilize information on how similar ligands bound in related structures. Even if the electron density is of sufficient quality and resolution to allow de novo placement, the process can take considerable time as the size, complexity and torsional degrees of freedom of the ligands increase. A new module, Guided Ligand Replacement (GLR), was developed in Phenix to increase the ease and success rate of ligand placement when prior protein–ligand complexes are available. At the heart of GLR is an algorithm based on graph theory that associates atoms in the target ligand with analogous atoms in the reference ligand. Based on this correspondence, a set of coordinates is generated for the target ligand. GLR is especially useful in two situations: (i) modeling a series of large, flexible, complicated or macrocyclic ligands in successive structures and (ii) modeling ligands as part of a refinement pipeline that can automatically select a reference structure. Even in those cases for which no reference structure is available, if there are multiple copies of the bound ligand per asymmetric unit GLR offers an efficient way to complete the model after the first ligand has been placed. In all of these applications, GLR leverages prior knowledge from earlier structures to facilitate ligand placement in the current structure.« less

Developing a Measurement for Task Complexity in Flight.

PubMed

Zheng, Yiyuan; Lu, Yanyu; Wang, Zhen; Huang, Dan; Fu, Shan

2015-08-01

Task complexity is regarded as an essential metric that is related to a pilot's performance and workload. Normally, pilots follow Standard Operating Procedures (SOPs) during a flight. In this study, we developed a measurement named Task Complexity in Flight (TCIF) to represent the task complexity in the SOPs. The TCIF measurement combined four complexity components into one index: actions logic complexity (ALC), actions size complexity (ASC), information control exchange complexity (ICEC), and control mode complexity (CMC).To verify the measurement, we calculated 11 tasks during the takeoff and landing phases from the SOPs, and invited 10 pilots to perform the same tasks in a flight simulator. After flight, the TCIF results were compared with two workload measurements: the Bedford scale and heart rate. The results of TCIF and the 4 components of the 11 tasks were calculated. Further, the TCIF results showed a significant correlation with the Bedford scores (R=0.851) and were also consistent with the difference in heart rate (R=0.816). Therefore, with the increased TCIF results, both the Bedford scale and the difference in heart rate increased. TCIF was proposed based on the flight operating conditions. Although additional studies of TCIF are necessary, the results of this study suggest this measurement could effectively indicate task complexity in flight, and could also be used to guide pilot training and task allocation on the flight deck.

TRPM2 Channels Protect against Cardiac Ischemia-Reperfusion Injury

PubMed Central

Miller, Barbara A.; Hoffman, Nicholas E.; Merali, Salim; Zhang, Xue-Qian; Wang, JuFang; Rajan, Sudarsan; Shanmughapriya, Santhanam; Gao, Erhe; Barrero, Carlos A.; Mallilankaraman, Karthik; Song, Jianliang; Gu, Tongda; Hirschler-Laszkiewicz, Iwona; Koch, Walter J.; Feldman, Arthur M.; Madesh, Muniswamy; Cheung, Joseph Y.

2014-01-01

Cardiac TRPM2 channels were activated by intracellular adenosine diphosphate-ribose and blocked by flufenamic acid. In adult cardiac myocytes the ratio of GCa to GNa of TRPM2 channels was 0.56 ± 0.02. To explore the cellular mechanisms by which TRPM2 channels protect against cardiac ischemia/reperfusion (I/R) injury, we analyzed proteomes from WT and TRPM2 KO hearts subjected to I/R. The canonical pathways that exhibited the largest difference between WT-I/R and KO-I/R hearts were mitochondrial dysfunction and the tricarboxylic acid cycle. Complexes I, III, and IV were down-regulated, whereas complexes II and V were up-regulated in KO-I/R compared with WT-I/R hearts. Western blots confirmed reduced expression of the Complex I subunit and other mitochondria-associated proteins in KO-I/R hearts. Bioenergetic analyses revealed that KO myocytes had a lower mitochondrial membrane potential, mitochondrial Ca2+ uptake, ATP levels, and O2 consumption but higher mitochondrial superoxide levels. Additionally, mitochondrial Ca2+ uniporter (MCU) currents were lower in KO myocytes, indicating reduced mitochondrial Ca2+ uptake was likely due to both lower ψm and MCU activity. Similar to isolated myocytes, O2 consumption and ATP levels were also reduced in KO hearts. Under a simulated I/R model, aberrant mitochondrial bioenergetics was exacerbated in KO myocytes. Reactive oxygen species levels were also significantly higher in KO-I/R compared with WT-I/R heart slices, consistent with mitochondrial dysfunction in KO-I/R hearts. We conclude that TRPM2 channels protect the heart from I/R injury by ameliorating mitochondrial dysfunction and reducing reactive oxygen species levels. PMID:24492610

Heart transplantation in the setting of complex congenital heart disease and physiologic single lung.

PubMed

Zuckerman, Warren A; Richmond, Marc E; Lee, Teresa M; Bacha, Emile A; Chai, Paul J; Chen, Jonathan M; Addonizio, Linda J

2015-12-01

To highlight the success of heart transplantation in patients with complex congenital heart disease and physiologic single lung by providing an update on the world's largest reported cohort. Demographic, perioperative, postoperative, and outcomes data were collected retrospectively on all patients undergoing heart transplant to single lung at Columbia University Medical Center since 1992, and compared with all other patients undergoing transplants performed for single ventricle or tetralogy of Fallot during that time. Twenty-two patients (mean age, 20.6 years; range, 5 months-47 years) underwent heart transplant to single lung. Compared with controls (n = 67), the single lung group had more male patients and a greater proportion of tetralogy compared with single ventricle patients, although the single lung group had fewer post-Fontan patients. Age, weight, and body surface area were similar between the groups as were use of mechanical circulatory support and mechanical ventilation before transplant. Median time to extubation, time on inotropes, and length of stay were similar. There were 3 perioperative deaths, including a patient who died during postoperative day 1 from primary graft failure, likely related to a combination of elevated pulmonary vascular resistance and volume load. There were 5 additional mortalities during intermediate- and long-term follow-up, none of which were related to single-lung physiology. There was no significant survival difference between the groups. In patients with complex congenital heart disease and single lung physiology, heart transplant alone remains an excellent option, with comparable outcomes to patients undergoing transplant with similar cardiac anatomy and dual lung physiology. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure

PubMed Central

Rosa-Garrido, Manuel; Chapski, Douglas J.; Schmitt, Anthony D.; Kimball, Todd H.; Karbassi, Elaheh; Monte, Emma; Balderas, Enrique; Pellegrini, Matteo; Shih, Tsai-Ting; Soehalim, Elizabeth; Liem, David; Ping, Peipei; Galjart, Niels J.; Ren, Shuxun; Wang, Yibin; Ren, Bing

2017-01-01

Background: Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined. Methods: To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload–induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype. Transcriptome analyses by RNA-seq were conducted as a functional readout of the epigenomic structural changes. Results: Depletion of CTCF was sufficient to induce heart failure in mice, and human patients with heart failure receiving mechanical unloading via left ventricular assist devices show increased CTCF abundance. Chromatin structural analyses revealed interactions within the cardiac myocyte genome at 5-kb resolution, enabling examination of intra- and interchromosomal events, and providing a resource for future cardiac epigenomic investigations. Pressure overload or CTCF depletion selectively altered boundary strength between topologically associating domains and A/B compartmentalization, measurements of genome accessibility. Heart failure involved decreased stability of chromatin interactions around disease-causing genes. In addition, pressure overload or CTCF depletion remodeled long-range interactions of cardiac enhancers, resulting in a significant decrease in local chromatin interactions around these functional elements. Conclusions: These findings provide a high-resolution chromatin architecture resource for cardiac epigenomic investigations and demonstrate that global structural remodeling of chromatin underpins heart failure. The newly identified principles of endogenous chromatin structure have key implications for epigenetic therapy. PMID:28802249

High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure.

PubMed

Rosa-Garrido, Manuel; Chapski, Douglas J; Schmitt, Anthony D; Kimball, Todd H; Karbassi, Elaheh; Monte, Emma; Balderas, Enrique; Pellegrini, Matteo; Shih, Tsai-Ting; Soehalim, Elizabeth; Liem, David; Ping, Peipei; Galjart, Niels J; Ren, Shuxun; Wang, Yibin; Ren, Bing; Vondriska, Thomas M

2017-10-24

Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined. To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload-induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype. Transcriptome analyses by RNA-seq were conducted as a functional readout of the epigenomic structural changes. Depletion of CTCF was sufficient to induce heart failure in mice, and human patients with heart failure receiving mechanical unloading via left ventricular assist devices show increased CTCF abundance. Chromatin structural analyses revealed interactions within the cardiac myocyte genome at 5-kb resolution, enabling examination of intra- and interchromosomal events, and providing a resource for future cardiac epigenomic investigations. Pressure overload or CTCF depletion selectively altered boundary strength between topologically associating domains and A/B compartmentalization, measurements of genome accessibility. Heart failure involved decreased stability of chromatin interactions around disease-causing genes. In addition, pressure overload or CTCF depletion remodeled long-range interactions of cardiac enhancers, resulting in a significant decrease in local chromatin interactions around these functional elements. These findings provide a high-resolution chromatin architecture resource for cardiac epigenomic investigations and demonstrate that global structural remodeling of chromatin underpins heart failure. The newly identified principles of endogenous chromatin structure have key implications for epigenetic therapy. © 2017 The Authors.

Structure, Chemistry and Property Correlations in FeSe and 122 Pnictides

NASA Astrophysics Data System (ADS)

Cava, Robert

2010-03-01

Determining how crystal structure and chemical bonding influence the properties of solids is at the heart of collaborative research programs between materials physicists and solid state chemists. In some materials, the high Tc copper oxides and colossal magnetoresistance manganates, for example, the subtleties of how structure, bonding and properties are coupled yields an almost baffling complexity, while in others, such as many classical intermetallic superconductors, the properties are more easily understood, with bonding and structure playing a less profound role. The new superconducting pnictides appear to fall somewhere between these two limits, and have so far been the subject of relatively little study by solid state chemists. Here I will describe some of our recent work on superconducting FeSe and superconductor-related ``122'' (ThCr2Si2-type) solid solution phases as examples of the kinds of insights that structural and chemical studies can contribute to understanding these important materials.

Dietary nitrate increases arginine availability and protects mitochondrial complex I and energetics in the hypoxic rat heart

PubMed Central

Ashmore, Tom; Fernandez, Bernadette O; Branco-Price, Cristina; West, James A; Cowburn, Andrew S; Heather, Lisa C; Griffin, Julian L; Johnson, Randall S; Feelisch, Martin; Murray, Andrew J

2014-01-01

Hypoxic exposure is associated with impaired cardiac energetics in humans and altered mitochondrial function, with suppressed complex I-supported respiration, in rat heart. This response might limit reactive oxygen species generation, but at the cost of impaired electron transport chain (ETC) activity. Dietary nitrate supplementation improves mitochondrial efficiency and can promote tissue oxygenation by enhancing blood flow. We therefore hypothesised that ETC dysfunction, impaired energetics and oxidative damage in the hearts of rats exposed to chronic hypoxia could be alleviated by sustained administration of a moderate dose of dietary nitrate. Male Wistar rats (n = 40) were given water supplemented with 0.7 mmol l−1 NaCl (as control) or 0.7 mmol l−1 NaNO3, elevating plasma nitrate levels by 80%, and were exposed to 13% O2 (hypoxia) or normoxia (n = 10 per group) for 14 days. Respiration rates, ETC protein levels, mitochondrial density, ATP content and protein carbonylation were measured in cardiac muscle. Complex I respiration rates and protein levels were 33% lower in hypoxic/NaCl rats compared with normoxic/NaCl controls. Protein carbonylation was 65% higher in hearts of hypoxic rats compared with controls, indicating increased oxidative stress, whilst ATP levels were 62% lower. Respiration rates, complex I protein and activity, protein carbonylation and ATP levels were all fully protected in the hearts of nitrate-supplemented hypoxic rats. Both in normoxia and hypoxia, dietary nitrate suppressed cardiac arginase expression and activity and markedly elevated cardiac l-arginine concentrations, unmasking a novel mechanism of action by which nitrate enhances tissue NO bioavailability. Dietary nitrate therefore alleviates metabolic abnormalities in the hypoxic heart, improving myocardial energetics. PMID:25172947

Potential Impact and Study Considerations of Metabolomics in Cardiovascular Health and Disease: A Scientific Statement From the American Heart Association.

PubMed

Cheng, Susan; Shah, Svati H; Corwin, Elizabeth J; Fiehn, Oliver; Fitzgerald, Robert L; Gerszten, Robert E; Illig, Thomas; Rhee, Eugene P; Srinivas, Pothur R; Wang, Thomas J; Jain, Mohit

2017-04-01

Through the measure of thousands of small-molecule metabolites in diverse biological systems, metabolomics now offers the potential for new insights into the factors that contribute to complex human diseases such as cardiovascular disease. Targeted metabolomics methods have already identified new molecular markers and metabolomic signatures of cardiovascular disease risk (including branched-chain amino acids, select unsaturated lipid species, and trimethylamine- N -oxide), thus in effect linking diverse exposures such as those from dietary intake and the microbiota with cardiometabolic traits. As technologies for metabolomics continue to evolve, the depth and breadth of small-molecule metabolite profiling in complex systems continue to advance rapidly, along with prospects for ongoing discovery. Current challenges facing the field of metabolomics include scaling throughput and technical capacity for metabolomics approaches, bioinformatic and chemoinformatic tools for handling large-scale metabolomics data, methods for elucidating the biochemical structure and function of novel metabolites, and strategies for determining the true clinical relevance of metabolites observed in association with cardiovascular disease outcomes. Progress made in addressing these challenges will allow metabolomics the potential to substantially affect diagnostics and therapeutics in cardiovascular medicine. © 2017 American Heart Association, Inc.

SU-E-P-10: Imaging in the Cardiac Catheterization Lab - Technologies and Clinical Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fetterly, K

2014-06-01

Purpose: Diagnosis and treatment of cardiovascular disease in the cardiac catheterization laboratory is often aided by a multitude of imaging technologies. The purpose of this work is to highlight the contributions to patient care offered by the various imaging systems used during cardiovascular interventional procedures. Methods: Imaging technologies used in the cardiac catheterization lab were characterized by their fundamental technology and by the clinical applications for which they are used. Whether the modality is external to the patient, intravascular, or intracavity was specified. Specific clinical procedures for which multiple modalities are routinely used will be highlighted. Results: X-ray imaging modalitiesmore » include fluoroscopy/angiography and angiography CT. Ultrasound imaging is performed with external, trans-esophageal echocardiography (TEE), and intravascular (IVUS) transducers. Intravascular infrared optical coherence tomography (IVOCT) is used to assess vessel endothelium. Relatively large (>0.5 mm) anatomical structures are imaged with x-ray and ultrasound. IVUS and IVOCT provide high resolution images of vessel walls. Cardiac CT and MRI images are used to plan complex cardiovascular interventions. Advanced applications are used to spatially and temporally merge images from different technologies. Diagnosis and treatment of coronary artery disease frequently utilizes angiography and intra-vascular imaging, and treatment of complex structural heart conditions routinely includes use of multiple imaging modalities. Conclusion: There are several imaging modalities which are routinely used in the cardiac catheterization laboratory to diagnose and treat both coronary artery and structural heart disease. Multiple modalities are frequently used to enhance the quality and safety of procedures. The cardiac catheterization laboratory includes many opportunities for medical physicists to contribute substantially toward advancing patient care.« less

The effect of the physical activity on polymorphic premature ventricular complexes in chronic kidney disease.

PubMed

Kiuchi, Márcio G; Chen, Shaojie

2017-06-01

Polymorphic premature ventricular complexes (PVCs) are very common, appearing most frequently in patients with hypertension, obesity, sleep apnea, and structural heart disease. Sympathetic hyperactivity plays a critical role in the development, maintenance, and aggravation of ventricular arrhythmias. Endurance exercise training clearly lowers sympathetic activity in sympatho-excitatory disease states and may be tolerated by patients with chronic kidney disease (CKD). We assessed 40 CKD patients with hypertension with polymorphic PVCs. Patients underwent a complete medical history and physical examination. We evaluated the effectiveness of β blocker only or β blocker + exercise during 12 months of follow-up regarding the changes of the numbers of PVCs and mean heart rate (HR) by 24-hour-Holter. We observed in the β blocker group a significant decrease in the number of polymorphic PVCs from baseline 36,515 ± 3,518 to 3, 6, 9 and 12 months of follow-up, 28,314 ± 2,938, 23,709 ± 1,846, 22,564 ± 1,673, and 22,725 ± 1,415, respectively ( P < 0.001). In the β blocker + exercise group a significant decrease in the number of polymorphic PVCs also occurred from baseline 36,091 ± 3,327 to 3, 6, 9 and 12 months of follow-up, 29,252 ± 3,211, 20,948 ± 2,386, 14,238 ± 3,338, and 6,225 ± 2,319, respectively ( P < 0.001). Comparisons between the two groups at the same time point showed differences from the sixth month onwards: the 6th (Δ = -2,761, P = 0.045), 9th (Δ = -8,325, P < 0.001) and 12th (Δ = -16,500, P < 0.001) months. There was an improvement during the 12 months of follow-up vs. baseline, after the β blocker or β blocker + exercise in mean 24-hour HR Holter monitoring, creatinine values, eGFR, and ACR. Polymorphic PVCs may be modifiable by physical activity in CKD patients with hypertension without structural heart disease.

Regression equations for calculation of z scores for echocardiographic measurements of left heart structures in healthy Han Chinese children.

PubMed

Wang, Shan-Shan; Hong, Wen-Jing; Zhang, Yu-Qi; Chen, Shu-Bao; Huang, Guo-Ying; Zhang, Hong-Yan; Chen, Li-Jun; Wu, Lan-Ping; Shen, Rong; Liu, Yi-Qing; Zhu, Jun-Xue

2018-06-01

Clinical decision making in children with heart disease relies on detailed measurements of cardiac structures using two-dimensional and M-mode echocardiography. However, no echocardiographic reference values are available for the Chinese children. We aimed to establish z-score regression equations for left heart structures in a population-based cohort of healthy Chinese Han children. Echocardiography was performed in 545 children with a normal heart. The dimensions of the aortic valve annulus (AVA), aortic sinuses of Valsalva (ASV), sinotubular junction (STJ), ascending aorta (AAO), left atrium (LA), mitral valve annulus (MVA), interventricular septal end-diastolic thickness (IVSd), interventricular septal end-systolic thickness (IVSs), left ventricular end-diastolic diameter (LVIDd), left ventricular end-systolic diameter (LVIDs), left ventricular posterior wall end-diastolic thickness (LVPWd), left ventricular posterior wall end-systolic thickness (LVPWs) were measured. Regression analyses were conducted to relate the measurements of left heart structures to body surface area (BSA). Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were calculated. Several models were used, and the adjusted R2 values were compared for each model. AVA, ASV, STJ, AAO, LA, MVA, IVSd, IVSs, LVIDd, LVIDs, LVPWd, and LVPWs had a cubic relationship with BSA. LVEF and LVFS fell within a narrow range. Our results provide reference values for z scores and regression equations for left heart structures in Han Chinese children. These data may help make a quick and accurate judgment of the routine clinical measurement of left heart structures in children with heart disease. © 2018 Wiley Periodicals, Inc.

Systems approach to the study of stretch and arrhythmias in right ventricular failure induced in rats by monocrotaline

PubMed Central

Benoist, David; Stones, Rachel; Benson, Alan P.; Fowler, Ewan D.; Drinkhill, Mark J.; Hardy, Matthew E.L.; Saint, David A.; Cazorla, Olivier; Bernus, Olivier; White, Ed

2014-01-01

We demonstrate the synergistic benefits of using multiple technologies to investigate complex multi-scale biological responses. The combination of reductionist and integrative methodologies can reveal novel insights into mechanisms of action by tracking changes of in vivo phenomena to alterations in protein activity (or vice versa). We have applied this approach to electrical and mechanical remodelling in right ventricular failure caused by monocrotaline-induced pulmonary artery hypertension in rats. We show arrhythmogenic T-wave alternans in the ECG of conscious heart failure animals. Optical mapping of isolated hearts revealed discordant action potential duration (APD) alternans. Potential causes of the arrhythmic substrate; structural remodelling and/or steep APD restitution and dispersion were observed, with specific remodelling of the Right Ventricular Outflow Tract. At the myocyte level, [Ca2+]i transient alternans were observed together with decreased activity, gene and protein expression of the sarcoplasmic reticulum Ca2+-ATPase (SERCA). Computer simulations of the electrical and structural remodelling suggest both contribute to a less stable substrate. Echocardiography was used to estimate increased wall stress in failure, in vivo. Stretch of intact and skinned single myocytes revealed no effect on the Frank-Starling mechanism in failing myocytes. In isolated hearts acute stretch-induced arrhythmias occurred in all preparations. Significant shortening of the early APD was seen in control but not failing hearts. These observations may be linked to changes in the gene expression of candidate mechanosensitive ion channels (MSCs) TREK-1 and TRPC1/6. Computer simulations incorporating MSCs and changes in ion channels with failure, based on altered gene expression, largely reproduced experimental observations. PMID:25016242

Inheritance Analysis of Congenital Left Ventricular Outflow Tract Obstruction Malformations: Segregation, Multiplex Relative Risk, and Heritability

PubMed Central

McBride, Kim L.; Pignatelli, Ricardo; Lewin, Mark; Ho, Trang; Fernbach, Susan; Menesses, Andres; Lam, Wilbur; Leal, Suzanne M.; Kaplan, Norman; Schliekelman, Paul; Towbin, Jeffrey A.; Belmont, John W.

2006-01-01

The left ventricular outflow tract (LVOTO) malformations, aortic valve stenosis (AVS), coarctation of the aorta (COA), and hypoplastic left heart (HLH) constitute a mechanistically defined subgroup of congenital heart defects that have substantial evidence for a genetic component. Evidence from echocardiography studies has shown that bicuspid aortic valve (BAV) is found frequently in relatives of children with LVOTO defects. However, formal inheritance analysis has not been performed. We ascertained 124 families by an index case with AVS, COA, or HLH. A total of 413 relatives were enrolled in the study, of which 351 had detailed echocardiography exams for structural heart defects and measurements of a variety of aortic arch, left ventricle, and valve structures. LVOTO malformations were noted in 30 relatives (18 BAV, 5 HLH, 3 COA, and 3 AVS), along with significant congenital heart defects (CHD) in 2 others (32/413; 7.7%). Relative risk for first-degree relatives in this group was 36.9, with a heritability of 0.71–0.90. Formal segregation analysis suggests that one or more minor loci with rare dominant alleles may be operative in a subset of families. Multiplex relative risk analysis, which estimates number of loci, had the highest maximum likelihood score in a model with 2 loci (range of 1–6 in the lod-1 support interval). Heritability of several aortic arch measurements and aortic valve was significant. These data support a complex but most likely oligogenic pattern of inheritance. A combination of linkage and association study designs is likely to enable LVOTO risk gene identification. This data can also provide families with important information for screening asymptomatic relatives for potentially harmful cardiac defects. PMID:15690347

Analysis of selected sugars and sugar phosphates in mouse heart tissue by reductive amination and liquid chromatography-electrospray ionization mass spectrometry.

PubMed

Han, Jun; Tschernutter, Vera; Yang, Juncong; Eckle, Tobias; Borchers, Christoph H

2013-06-18

Sensitive and reliable analysis of sugars and sugar phosphates in tissues and cells is essential for many biological and cell engineering studies. However, the successful analysis of these endogenous compounds in biological samples by liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) is often difficult because of their poor chromatographic retention properties in reversed-phase LC, the complex biological matrices, and the ionization suppression in ESI. This situation is further complicated by the existence of their multiple structural isomers in vivo. This work describes the combination of reductive amination using 3-amino-9-ethylcarbazole, with a new LC approach using a pentafluorophenyl core-shell ultrahigh performance (UP) LC column and methylphosphonic acid as an efficient tail-sweeping reagent for improved chromatographic separation. This new method was used for selected detection and accurate quantitation of the major free and phosphorylated reducing sugars in mouse heart tissue. Among the detected compounds, accurate quantitation of glyceraldehyde, ribose, glucose, glycerylaldehyde-3-phosphate, ribose-5-phosphate, glucose-6-phosphate, and mannose-6-phosphate was achieved by UPLC/multiple-reaction monitoring (MRM)-MS, with analytical accuracies ranging from 87.4% to 109.4% and CVs of ≤8.5% (n = 6). To demonstrate isotope-resolved metabolic profiling, we used UPLC/quadrupole time-of-flight (QTOF)-MS to analyze the isotope distribution patterns of C3 to C6 free and phosphorylated reducing sugars in heart tissues from (13)C-labeled wild type and knockout mice. In conclusion, the preanalytical derivatization-LC/ESI-MS method has resulted in selective determination of free and phosphorylated reducing sugars without the interferences from their nonreducing structural isomers in mouse heart tissue, with analytical sensitivities in the femtomole to low picomole range.

Modifying the mechanics of healing infarcts: Is better the enemy of good?

PubMed

Clarke, Samantha A; Richardson, William J; Holmes, Jeffrey W

2016-04-01

Myocardial infarction (MI) is a major source of morbidity and mortality worldwide, with over 7 million people suffering infarctions each year. Heart muscle damaged during MI is replaced by a collagenous scar over a period of several weeks, and the mechanical properties of that scar tissue are a key determinant of serious post-MI complications such as infarct rupture, depression of heart function, and progression to heart failure. Thus, there is increasing interest in developing therapies that modify the structure and mechanics of healing infarct scar. Yet most prior attempts at therapeutic scar modification have failed, some catastrophically. This article reviews available information about the mechanics of healing infarct scar and the functional impact of scar mechanical properties, and attempts to infer principles that can better guide future attempts to modify scar. One important conclusion is that collagen structure, mechanics, and remodeling of healing infarct scar vary so widely among experimental models that any novel therapy should be tested across a range of species, infarct locations, and reperfusion protocols. Another lesson from past work is that the biology and mechanics of healing infarcts are sufficiently complex that the effects of interventions are often counterintuitive; for example, increasing infarct stiffness has little effect on heart function, and inhibition of matrix metalloproteases (MMPs) has little effect on scar collagen content. Computational models can help explain such counterintuitive results, and are becoming an increasingly important tool for integrating known information to better identify promising therapies and design experiments to test them. Moving forward, potentially exciting new opportunities for therapeutic modification of infarct mechanics include modulating anisotropy and promoting scar compaction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Paediatric cardiac rehabilitation in congenital heart disease: a systematic review.

PubMed

Tikkanen, Ana Ubeda; Oyaga, Ainhoa Rodriguez; Riaño, Olga Arroyo; Álvaro, Enrique Maroto; Rhodes, Jonathan

2012-06-01

Advances in medical and surgical care have contributed to an important increase in the survival rates of children with congenital heart disease. However, survivors often have decreased exercise capacity and health-related issues that affect their quality of life. Cardiac Rehabilitation Programmes have been extensively studied in adults with acquired heart disease. In contrast, studies of children with congenital heart disease have been few and of limited scope. We therefore undertook a systematic review of the literature on cardiac rehabilitation in children with congenital heart disease to systematically assess the current evidence regarding the use, efficacy, benefits, and risks associated with this therapy and to identify the components of a successful programme. We included studies that incorporated a cardiac rehabilitation programme with an exercise training component published between January, 1981 and November, 2010 in patients under 18 years of age. A total of 16 clinical studies were found and were the focus of this review. Heterogeneous methodology and variable quality was observed. Aerobic and resistance training was the core component of most studies. Diverse variables were used to quantify outcomes. No adverse events were reported. Cardiac Rehabilitation Programmes in the paediatric population are greatly underutilised, and clinical research on this promising form of therapy has been limited. Questions remain regarding the optimal structure and efficacy of the programmes. The complex needs of this unique population also mandate that additional outcome measures, beyond serial cardiopulmonary exercise testing, be identified and studied.

[Embryology of the heart walls].

PubMed

Tardy, M-M; Galvaing, G; Sakka, L; Garcier, J-M; Chazal, J; Filaire, M

2013-03-01

Although anatomically simple structures, the atrial septum and the ventricular septum have complex embryological origins. Recent findings in molecular biology allowed better comprehension of their formation. As soon as the heart tube is formed, cells migrate from several cardiogenic fields to take part in the septation. Elongation, ballooning, and later inflexion of the heart tube create chamber separating grooves, facing the future septa. The systemic venous tributaries conflate at the venous pole of the heart; it will partially involute while contributing to the atrial septum. The primary atrial septum grows from the atrial roof towards the atrioventricular canal. It fuses there with the atrioventricular cushions, while its upper margin breaks down to form the ostium secundum. Then a deep fold develops from the atrial roof and partly covers the ostium secundum, leaving a flap-like interatrial communication through the oval foramen. It will close at birth. The interventricular septum has three embryological origins. The ventricular septum primum, created during the ballooning process, origins from the primary heart tube. It will form the trabecular septum and the inlet septum. The interventricular ring, surrounding the interventricular foramen, will participate in the inlet septum and also form the atrioventricular conduction axis. The outflow cushions will separate the outflow tract in the aorta and pulmonary artery, and grow to create the outlet septum. After merging with the atrioventricular cushions, they will also be part of the membranous septum. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Congenital heart disease

MedlinePlus

... page: //medlineplus.gov/ency/article/001114.htm Congenital heart disease To use the sharing features on this page, please enable JavaScript. Congenital heart disease (CHD) is a problem with the heart's structure ...

Left atrial function in heart failure with impaired and preserved ejection fraction.

PubMed

Fang, Fang; Lee, Alex Pui-Wai; Yu, Cheuk-Man

2014-09-01

Left atrial structural and functional changes in heart failure are relatively ignored parts of cardiac assessment. This review illustrates the pathophysiological and functional changes in left atrium in heart failure as well as their prognostic value. Heart failure can be divided into those with systolic dysfunction and heart failure with preserved ejection fraction (HFPEF). Left atrial enlargement and dysfunction commonly occur in systolic heart failure, in particular, in idiopathic dilated cardiomyopathy. Atrial enlargement and dysfunction also carry important prognostic value in systolic heart failure, independently of known parameters such as left ventricular ejection fraction. In HFPEF, there is evidence of left atrial enlargement, impaired atrial compliance, and reduction of atrial pump function. This occurs not only at rest but also during exercise, indicating significant impairment of atrial contractile reserve. Furthermore, atrial dyssynchrony is common in HFPEF. These factors further contribute to the development of new onset or progression of atrial arrhythmias, in particular, atrial fibrillation. Left atrial function is an integral part of cardiac function and its structural and functional changes in heart failure are common. As changes of left atrial structure and function have different clinical implications in systolic heart failure and HFPEF, routine assessment is warranted.

The importance of sphingolipids and reactive oxygen species in cardiovascular development.

PubMed

de Faria Poloni, Joice; Chapola, Henrique; Feltes, Bruno César; Bonatto, Diego

2014-06-01

The heart is the first organ in the embryo to form. Its structural and functional complexity is the result of a thorough developmental program, where sphingolipids play an important role in cardiogenesis, heart maturation, angiogenesis, the regulation of vascular tone and vessel permeability. Sphingolipids are necessary for signal transduction and membrane microdomain formation. In addition, recent evidence suggests that sphingolipid metabolism is directly interconnected to the modulation of oxidative stress. However, cardiovascular development is highly sensitive to excessive reactive species production, and disturbances in sphingolipid metabolism can lead to abnormal development and cardiac disease. Therefore, in this review, we address the molecular link between sphingolipids and oxidative stress, connecting these pathways to cardiovascular development and cardiovascular disease. © 2014 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

A Novel Cardiotoxic Mechanism for a Pervasive Global Pollutant

NASA Astrophysics Data System (ADS)

Brette, Fabien; Shiels, Holly A.; Galli, Gina L. J.; Cros, Caroline; Incardona, John P.; Scholz, Nathaniel L.; Block, Barbara A.

2017-01-01

The Deepwater Horizon disaster drew global attention to the toxicity of crude oil and the potential for adverse health effects amongst marine life and spill responders in the northern Gulf of Mexico. The blowout released complex mixtures of polycyclic aromatic hydrocarbons (PAHs) into critical pelagic spawning habitats for tunas, billfishes, and other ecologically important top predators. Crude oil disrupts cardiac function and has been associated with heart malformations in developing fish. However, the precise identity of cardiotoxic PAHs, and the mechanisms underlying contractile dysfunction are not known. Here we show that phenanthrene, a PAH with a benzene 3-ring structure, is the key moiety disrupting the physiology of heart muscle cells. Phenanthrene is a ubiquitous pollutant in water and air, and the cellular targets for this compound are highly conserved across vertebrates. Our findings therefore suggest that phenanthrene may be a major worldwide cause of vertebrate cardiac dysfunction.

[Current ideas of a complex relationship between atrial fibrillation and ischemic heart disease and of optimum tactics for anticoagulant therapy to prevent embolism in systemic circulation].

PubMed

Golshmid, M V; Gilyarevskiy, S R; Kuzmina, I M; Sinitsina, I I

The article discusses the issue of searching for optimum oral anticoagulants to prevent thrombosis and embolism induced by heart disease both in patients with atrial fibrillation and sinus rhythm. A complex bidirectional relationship between atrial fibrillation and coronary atherosclerosis is considered along with possible mechanisms for development of myocardial infarction in patients with atrial fibrillation. The authors provided evidence-based data which can be used in selecting an anticoagulant for prevention of heart disease induced thrombosis and embolism taking into account both the efficacy and safety established in randomized clinical studies.

Quantifying the Physiological Stress Response to Simulated Maritime Pilotage Tasks: The Influence of Task Complexity and Pilot Experience.

PubMed

Main, Luana C; Wolkow, Alexander; Chambers, Timothy P

2017-11-01

The aim of this study was to quantify the stress associated with performing maritime pilotage tasks in a high-fidelity simulator. Eight trainee and 13 maritime pilots completed two simulated pilotage tasks of varying complexity. Salivary cortisol samples were collected pre- and post-simulation for both trials. Heart rate was measured continuously throughout the study. Significant changes in salivary cortisol (P = 0.000, η = 0.139), average (P = 0.006, η = 0.087), and peak heart rate (P = 0.013, η = 0.077) from pre- to postsimulation were found. Varying task complexity did partially influence stress response; average (P = 0.016, η = 0.026) and peak heart rate (P = 0.034, η = 0.020) were higher in the experimental condition. Trainees also recorded higher average (P = 0.000, η = 0.054) and peak heart rates (P = 0.027, η = 0.022). Performing simulated pilotage tasks evoked a measurable stress response in both trainee and expert maritime pilots.

Proof of concept study: renal sympathetic denervation for treatment of polymorphic premature ventricular complexes.

PubMed

Kiuchi, Márcio Galindo; E Silva, Gustavo Ramalho; Paz, Luis Marcelo Rodrigues; Chen, Shaojie; Souto, Gladyston Luiz Lima

2016-11-01

Polymorphic premature ventricular complexes (PVCs) are very common, appearing most frequently in patients with hypertension, obesity, sleep apnea, and structural heart disease. Sympathetic hyperactivity plays a critical role in the development, maintenance, and aggravation of ventricular arrhythmias. Recently, the relevance of sympathetic activation in patients with ventricular arrhythmias was reported, and this finding suggested a potential role for catheter-based renal sympathetic denervation in reducing the arrhythmic burden. We evaluated the effectiveness of the renal sympathetic denervation (RSD) in comparison to antiarrhythmic pharmacologic therapy in reducing polymorphic PVCs refractory to medication therapy and cardiac parameters assessed by 24-h Holter monitoring and cardiac magnetic resonance (CRM), respectively, in patients with structurally normal heart. Thirty-four patients were included in this study, 14 served as control, and 20 were treated with an ablation cardiac catheter with open irrigated tip. RSD was performed by a single operator following the standard technique. All the patients included had polymorphic PVCs and structurally normal heart. Data were obtained at baseline at the 12th month of follow-up (sixth month after RSD or adjustment of antiarrhythmic dosage). In RSD group, we observed a significant decrease in the number of polymorphic PVCs from baseline 36,091 ± 3327 to 3, 6, 7 (first month after RSD, without drugs), and 12 months (sixth month after RSD, without drugs) of follow-up, 31,009 ± 3251, 20,411 ± 3820, 7701 ± 1549, and 1274 ± 749, respectively, in all patients, P < 0.0001 to all the comparisons between the mean of each time point with the mean of every other time point. No changes in mean 24-h ABPM and renal function in both groups were observed at 12th month of follow-up. However, 24-h Holter mean heart rate decreased in control group at 12th month of follow-up, which did not happen with the RSD group. At the sixth month post-RSD in comparison to baseline, a significant reduction in the number of polymorphic PVCs (∆ = -34,817 ± 3590, P < 0.0001) was observed, as well as, in CRM parameters such as left ventricular mass/body surface area (∆ = -5.4 ± 2.1 g/m 2 , P < 0.0001) and left ventricular ejection fraction (∆ = +3.0 ± 1.8 %, P < 0.0001). In comparison to control group at the same time point, these findings were statistically superior in RSD group (P > 0.05). A significant correlation was found between the Δ number of polymorphic PVCs at the sixth month (r = -0.6723, P = 0.0012) after the RSD and the total number of RSD ablated spots. Polymorphic PVCs refractory to medication therapy may be modifiable by RSD in patients without structural heart disease. Although encouraging, our data are preliminary and need to be validated in a large population and in long term.

[Combined heart-kidney transplantation in Mexic].

PubMed

Careaga-Reyna, Guillermo; Zetina-Tun, Hugo Jesús; Lezama-Urtecho, Carlos Alberto; Hernández-Domínguez, José Mariano; Santos-Caballero, Marlene

In our country, heart and kidney transplantation is a novel option for treatment of combined terminal heart and kidney failure. This program began in 2012 for selected patients with documented terminal heart failure and structural kidney damage with renal failure. Description of cases: Between January 1, 2012 and April 30, 2016, we made 92 orthotopic heart transplantations. In five of these cases the heart transplantation was combined with kidney transplantation. There were three male and two female patients with a mean age 25.6 ± 5.2 years (range, 17-29). The patients improved their renal function and the heart transplantation was successful with an improved quality of life. One patient died from abdominal sepsis. The other patients are doing well. The combined heart-kidney transplantation is a safe and efficient procedure for patients with structural kidney and heart damage as a cause of terminal failure.

EDITORIAL: Focus on Heart and Mind

NASA Astrophysics Data System (ADS)

Bodenschatz, Eberhard; Wolf, Fred

2008-01-01

Among the organs of our body, the function of heart and brain are unique in that their operation emerges from the collective dynamics of millions of strongly interacting cells well organized in their geometrical structure and connectivity. In the heart muscle the propagation of a nonlinear wave pulse, the cardiac action potential, controls the contraction. Usually the propagation is well-organized both in space and time and the heart functions as an efficient biological pump. Instabilities triggered by diseased tissue but also by dynamical heterogeneities, may, however, induce cardiac arrhythmia and fibrillation, where the pacemaker looses control to dynamically generated, high-frequency self-excitation of the muscle. In this state the coherence of contraction is lost and may lead within minutes to death. The appearance of arrhythmias can be associated with topological singularities, the so called spiral or scroll waves, and how the occurrence of this malfunctioning pattern-formation process can be understood is a dominant subject of current research. This is all the more important as cardiac arrhythmias and fibrillation are the main cause of premature death in the developed world. Similarly, in the brain the propagation of a nonlinear wave pulse, namely the neural action potential, is at the basis of the computational and memory power of the brain, i.e. what determines the workings of our 'minds'. Here, however, due to the high degree of interconnectivity and topological complexity of the neuronal network, the coordinated activity of millions of interacting nerve cells is more complex, although the basic principles of action potential generation at the level of each cell are quite similar. The currently emerging field of network dynamical systems is largely driven by the mathematical challenge and the steady stream of novel dynamical phenomena that results from the interplay of local nonlinear dynamics and complex network structure in models of biological neuronal networks. The brain, however, would be only incompletely understood when just viewed as a complex dynamical system. Understanding the operation of the mind also requires describing and analyzing its emergent information processing functions. To achieve this, many aspects of neural computation have been successfully formulated as problems of statistical inference and optimal decision making, phrasing them in the mathematical language of statistical physics. Both subjects, heart and mind, are thus united through the similarity of current models for the emergence of collective capabilities. They rely conceptually and technically essentially on the paradigms and tools of statistical physics and nonlinear dynamics. In general, none of the functions and processes of the heart or mind can be appropriately understood without a thorough analysis of the collective dynamics of the underlying biological networks and nonlinear media. Approaching any of these problems with necessity requires a coordinated interdisciplinary effort utilizing approaches from nonlinear dynamics and pattern formation to genetics, molecular biology and biological imaging. Because of their thorough understanding and advanced methodology for dissecting nonlinear and collective phenomena, physicists are playing an increasingly important role in unravelling the dynamical principles governing the operation as well as the malfunction of heart and mind. Current research in the physics of heart and mind spans a wide spectrum of theoretical, experimental, and computational approaches. Many are guided by the aim for a transparent picture of systems function that links the biophysics of individual cells to the operation of the entire organ or information processing system. Theoretical work thus often centres on the construction and analysis of models that contain sufficient biophysical detail to represent reliably all cellular mechanisms of importance, but that are still theoretically sufficiently transparent and tractable to support a comprehensive analysis of functional performance at the systems level. Analogously, experimental work increasingly probes the system dynamics simultaneously at multiple levels from cell to whole organ. Here an invaluable contribution of physics to the experimental characterization of large scale activity in cardiac and neuronal tissues is the currently emerging high level of quantitative precision and control. Long-term high precision recording of large scale activity patterns of neural and cardiac tissues increasingly supports the formulation of quantitative phenomenological theories of complex dynamical states as well the realization of algorithms for manipulating and controlling them. Both quantitative phenomenology and control are not only essential for bridging theory and experiment in complex systems; they are also indispensable for turning scientific insight into diagnostic progress and improved treatment for the affected heart and mind. The present Focus Issue in New Journal of Physics reflects well the richness and excitement of this currently rapidly evolving field. It combines theoretical and experimental approaches and covers analyses ranging from the organ level over investigations of model systems to the biophysics of individual cells. The articles below represent the first contributions to this collection and further additions will appear in the near future. Focus on Heart and Mind Contents 'Heart' contributions Spiral wave drift and complex-oscillatory spiral waves caused by heterogeneities in two-dimensional in vitro cardiac tissues Sung-Jae Woo, Jin Hee Hong, Tae Yun Kim, Byung Wook Bae and Kyoung J Lee Epicardial wavefronts arise from widely distributed transient sources during ventricular fibrillation in the isolated swine heart J M Rogers, G P Walcott, J D Gladden, S B Melnick, R E Ideker and M W Kay Efficient control of spiral wave location in an excitable medium with localized heterogeneities J Schlesner, V S Zykov, H Brandtstädter, I Gerdes and H Engel 'Mind' contributions Eigenanalysis of a neural network for optic flow processing F Weber, H Eichner, H Cuntz and A Borst Time-warp invariant pattern detection with bursting neurons Tim Gollisch Leader neurons in population bursts of 2D living neural networks J-P Eckmann, Shimshon Jacobi, Shimon Marom, Elisha Moses and Cyrille Zbinden Decoding spatiotemporal spike sequences via the finite state automata dynamics of spiking neural networks Dezhe Z Jin Self-organization and the selection of pinwheel density in visual cortical development Matthias Kaschube, Michael Schnabel and Fred Wolf Free association transitions in models of cortical latching dynamics Eleonora Russo, Vijay M K Namboodiri, Alessandro Treves and Emilio Kropff The mechanism of synchronization in feed-forward neuronal networks S Goedeke and M Diesmann On diffusion processes with variable drift rates as models for decision making during learning P Eckhoff, P Holmes, C Law, P M Connolly and J I Gold

Combined Inhibition of the Renin-Angiotensin System and Neprilysin Positively Influences Complex Mitochondrial Adaptations in Progressive Experimental Heart Failure

PubMed Central

Reinders, Jörg; Schröder, Josef; Dietl, Alexander; Schmid, Peter M.; Jungbauer, Carsten; Resch, Markus; Maier, Lars S.; Luchner, Andreas; Birner, Christoph

2017-01-01

Background Inhibitors of the renin angiotensin system and neprilysin (RAS-/NEP-inhibitors) proved to be extraordinarily beneficial in systolic heart failure. Furthermore, compelling evidence exists that impaired mitochondrial pathways are causatively involved in progressive left ventricular (LV) dysfunction. Consequently, we aimed to assess whether RAS-/NEP-inhibition can attenuate mitochondrial adaptations in experimental heart failure (HF). Methods and Results By progressive right ventricular pacing, distinct HF stages were induced in 15 rabbits, and 6 animals served as controls (CTRL). Six animals with manifest HF (CHF) were treated with the RAS-/NEP-inhibitor omapatrilat. Echocardiographic studies and invasive blood pressure measurements were undertaken during HF progression. Mitochondria were isolated from LV tissue, respectively, and further worked up for proteomic analysis using the SWATH technique. Enzymatic activities of citrate synthase and the electron transfer chain (ETC) complexes I, II, and IV were assessed. Ultrastructural analyses were performed by transmission electron microscopy. During progression to overt HF, intricate expression changes were mainly detected for proteins belonging to the tricarboxylic acid cycle, glucose and fat metabolism, and the ETC complexes, even though ETC complex I, II, or IV enzymatic activities were not significantly influenced. Treatment with a RAS-/NEP-inhibitor then reversed some maladaptive metabolic adaptations, positively influenced the decline of citrate synthase activity, and altered the composition of each respiratory chain complex, even though this was again not accompanied by altered ETC complex enzymatic activities. Finally, ultrastructural evidence pointed to a reduction of autophagolytic and degenerative processes with omapatrilat-treatment. Conclusions This study describes complex adaptations of the mitochondrial proteome in experimental tachycardia-induced heart failure and shows that a combined RAS-/NEP-inhibition can beneficially influence mitochondrial key pathways. PMID:28076404

The effect of orthostasis on recurrence quantification analysis of heart rate and blood pressure dynamics.

PubMed

Javorka, M; Turianikova, Z; Tonhajzerova, I; Javorka, K; Baumert, M

2009-01-01

The purpose of this paper is to investigate the effect of orthostatic challenge on recurrence plot based complexity measures of heart rate and blood pressure variability (HRV and BPV). HRV and BPV complexities were assessed in 28 healthy subjects over 15 min in the supine and standing positions. The complexity of HRV and BPV was assessed based on recurrence quantification analysis. HRV complexity was reduced along with the HRV magnitude after changing from the supine to the standing position. In contrast, the BPV magnitude increased and BPV complexity decreased upon standing. Recurrence quantification analysis (RQA) of HRV and BPV is sensitive to orthostatic challenge and might therefore be suited to assess changes in autonomic neural outflow to the cardiovascular system.

Design, synthesis and evaluation of a new Mn - Contrast agent for MR imaging of myocardium based on the DTPA-phenylpentadecanoic acid complex

NASA Astrophysics Data System (ADS)

Belyanin, Maxim L.; Stepanova, Elena V.; Valiev, Rashid R.; Filimonov, Victor D.; Usov, Vladimir Y.; Borodin, Oleg Y.; Ågren, Hans

2016-11-01

In the present paper we describe the first synthesis and evaluation of a novel Mn (II) complex (DTPA-PPDA Mn (II)) which contains a C-15 fatty acid moiety that has high affinity to the heart muscle. The complexation energy of DTPA-PPDA Mn (II) evaluated by quantum chemistry methodology indicates that it essentially exceeds the corresponding value for the known DTPA Mn (II) complex. Molecular docking revealed that the affinity of the designed complex to the heart-type transport protein H-FABP well exceeds that of lauric acid. Phantom experiments in low-field MRI the designed contrast agent provides MR imaging comparable to gadopentetic acid.

A case study of infant physiologic response to skin-to-skin contact following surgery for complex congenital heart disease

PubMed Central

Harrison, Tondi M.; Ludington-Hoe, Susan

2014-01-01

Background Infants with complex congenital heart disease requiring surgical intervention within the first days or weeks of life may be the most seriously ill infants needing intensive nursing and medical care immediately after birth. Skin to skin contact (SSC) is well-accepted and practiced as a positive therapeutic intervention in premature infants, but is not routinely offered to infants in cardiac intensive care units. Physiologic effects of SSC in the congenital heart disease population must be examined before recommending incorporation of SSC into standard care routines. Objective The purpose of this case study was to describe the physiologic response to a single session of SSC in an 18-day-old infant with hypoplastic left heart syndrome. Methods Repeated measures of heart rate, respiratory rate, oxygen saturation, blood pressure, and temperature were recorded 30 minutes prior to SSC, during SSC (including interruptions for bottle and breast feedings), and 10 minutes after SSC was completed. Results All physiologic parameters were clinically acceptable throughout the 135-minute observation. Conclusion This case study provides beginning evidence that SSC is safe in full-term infants following surgery for complex congenital heart disease. Further research with a larger sample is needed to examine effects of SSC on infant physiology before surgery and earlier in the postoperative time period as well as on additional outcomes such as length of stay, maternal-infant interaction, and neurodevelopment. PMID:25325374

Simulation for transthoracic echocardiography of aortic valve

PubMed Central

Nanda, Navin C.; Kapur, K. K.; Kapoor, Poonam Malhotra

2016-01-01

Simulation allows interactive transthoracic echocardiography (TTE) learning using a virtual three-dimensional model of the heart and may aid in the acquisition of the cognitive and technical skills needed to perform TTE. The ability to link probe manipulation, cardiac anatomy, and echocardiographic images using a simulator has been shown to be an effective model for training anesthesiology residents in transesophageal echocardiography. A proposed alternative to real-time reality patient-based learning is simulation-based training that allows anesthesiologists to learn complex concepts and procedures, especially for specific structures such as aortic valve. PMID:27397455

Some aspects of radical cascade and relay reactions

PubMed Central

Quiclet-Sire, Béatrice; Zard, Samir Z.

2017-01-01

The ability to create carbon–carbon bonds is at the heart of organic synthesis. Radical processes are particularly apt at creating such bonds, especially in cascade or relay sequences where more than one bond is formed, allowing for a rapid assembly of complex structures. In the present brief overview, examples taken from the authors' laboratory will serve to illustrate the strategic impact of radical-based approaches on synthetic planning. Transformations involving nitrogen-centred radicals, electron transfer from metallic nickel and the reversible degenerative exchange of xanthates will be presented and discussed. The last method has proved to be a particularly powerful tool for the intermolecular creation of carbon–carbon bonds by radical additions even to unactivated alkenes. Various functional groups can be brought into the same molecule in a convergent manner and made to react together in order to further increase the structural complexity. One important benefit of this chemistry is the so-called RAFT/MADIX technology for the manufacture of block copolymers of almost any desired architecture. PMID:28484329

Thermoelectric Properties of Complex Oxide Heterostructures

NASA Astrophysics Data System (ADS)

Cain, Tyler Andrew

Thermoelectrics are a promising energy conversion technology for power generation and cooling systems. The thermal and electrical properties of the materials at the heart of thermoelectric devices dictate conversion efficiency and technological viability. Studying the fundamental properties of potentially new thermoelectric materials is of great importance for improving device performance and understanding the electronic structure of materials systems. In this dissertation, investigations on the thermoelectric properties of a prototypical complex oxide, SrTiO3, are discussed. Hybrid molecular beam epitaxy (MBE) is used to synthesize La-doped SrTiO3 thin films, which exhibit high electron mobilities and large Seebeck coefficients resulting in large thermoelectric power factors at low temperatures. Large interfacial electron densities have been observed in SrTiO3/RTiO 3 (R=Gd,Sm) heterostructures. The thermoelectric properties of such heterostructures are investigated, including the use of a modulation doping approach to control interfacial electron densities. Low-temperature Seebeck coefficients of extreme electron-density SrTiO3 quantum wells are shown to provide insight into their electronic structure.

Bioprinting a cardiac valve.

PubMed

Jana, Soumen; Lerman, Amir

2015-12-01

Heart valve tissue engineering could be a possible solution for the limitations of mechanical and biological prostheses, which are commonly used for heart valve replacement. In tissue engineering, cells are seeded into a 3-dimensional platform, termed the scaffold, to make the engineered tissue construct. However, mimicking the mechanical and spatial heterogeneity of a heart valve structure in a fabricated scaffold with uniform cell distribution is daunting when approached conventionally. Bioprinting is an emerging technique that can produce biological products containing matrix and cells, together or separately with morphological, structural and mechanical diversity. This advance increases the possibility of fabricating the structure of a heart valve in vitro and using it as a functional tissue construct for implantation. This review describes the use of bioprinting technology in heart valve tissue engineering. Copyright © 2015 Elsevier Inc. All rights reserved.

Mitochondria selective S-nitrosation by mitochondria-targeted S-nitrosothiol protects against post-infarct heart failure in mouse hearts.

PubMed

Methner, Carmen; Chouchani, Edward T; Buonincontri, Guido; Pell, Victoria R; Sawiak, Stephen J; Murphy, Michael P; Krieg, Thomas

2014-07-01

Recently it has been shown that the mitochondria-targeted S-nitrosothiol MitoSNO protects against acute ischaemia/reperfusion (IR) injury by inhibiting the reactivation of mitochondrial complex I in the first minutes of reperfusion of ischaemic tissue, thereby preventing free radical formation that underlies IR injury. However, it remains unclear how this transient inhibition of mitochondrial complex I-mediated free radicals at reperfusion affects the long-term recovery of the heart following IR injury. Here we determined whether the acute protection by MitoSNO at reperfusion prevented the subsequent development of post-myocardial infarction heart failure. Mice were subjected to 30 min left coronary artery occlusion followed by reperfusion and recovery over 28 days. MitoSNO (100 ng/kg) was applied 5 min before the onset of reperfusion followed by 20 min infusion (1 ng/kg/min). Infarct size and cardiac function were measured by magnetic resonance imaging (MRI) 24 h after infarction. MitoSNO-treated mice exhibited reduced infarct size and preserved function. In addition, MitoSNO at reperfusion improved outcome measures 28 days post-IR, including preserved systolic function (63.7 ±1.8% LVEF vs. 53.7 ± 2.1% in controls, P = 0.01) and tissue fibrosis. MitoSNO action acutely at reperfusion reduces infarct size and protects from post-myocardial infarction heart failure. Therefore, targeted inhibition of mitochondrial complex I in the first minutes of reperfusion by MitoSNO is a rational therapeutic strategy for preventing subsequent heart failure in patients undergoing IR injury. © 2014 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Cardiac-resynchronization therapy in heart failure with a narrow QRS complex.

PubMed

Ruschitzka, Frank; Abraham, William T; Singh, Jagmeet P; Bax, Jeroen J; Borer, Jeffrey S; Brugada, Josep; Dickstein, Kenneth; Ford, Ian; Gorcsan, John; Gras, Daniel; Krum, Henry; Sogaard, Peter; Holzmeister, Johannes

2013-10-10

Cardiac-resynchronization therapy (CRT) reduces morbidity and mortality in chronic systolic heart failure with a wide QRS complex. Mechanical dyssynchrony also occurs in patients with a narrow QRS complex, which suggests the potential usefulness of CRT in such patients. We conducted a randomized trial involving 115 centers to evaluate the effect of CRT in patients with New York Heart Association class III or IV heart failure, a left ventricular ejection fraction of 35% or less, a QRS duration of less than 130 msec, and echocardiographic evidence of left ventricular dyssynchrony. All patients underwent device implantation and were randomly assigned to have CRT capability turned on or off. The primary efficacy outcome was the composite of death from any cause or first hospitalization for worsening heart failure. On March 13, 2013, the study was stopped for futility on the recommendation of the data and safety monitoring board. At study closure, the 809 patients who had undergone randomization had been followed for a mean of 19.4 months. The primary outcome occurred in 116 of 404 patients in the CRT group, as compared with 102 of 405 in the control group (28.7% vs. 25.2%; hazard ratio, 1.20; 95% confidence interval [CI], 0.92 to 1.57; P=0.15). There were 45 deaths in the CRT group and 26 in the control group (11.1% vs. 6.4%; hazard ratio, 1.81; 95% CI, 1.11 to 2.93; P=0.02). In patients with systolic heart failure and a QRS duration of less than 130 msec, CRT does not reduce the rate of death or hospitalization for heart failure and may increase mortality. (Funded by Biotronik and GE Healthcare; EchoCRT ClinicalTrials.gov number, NCT00683696.).

Prenatal diagnosis of left isomerism with normal heart: a case report

PubMed Central

De Paola, Nico; Ermito, Santina; Nahom, Antonella; Dinatale, Angela; Pappalardo, Elisa Maria; Carrara, Sabina; Cavaliere, Alessandro; Brizzi, Cristiana

2009-01-01

Objective: Left isomerism, also called polysplenia, is a laterality disturbance associated with with paired leftsidedness viscera and multiple small spleens. Left isomerism, heart congenital abnormalities and gastrointestinal malformation are strongly associated. Methods: We present a case of prenatal diagnosis of left isomerism in a fetus with a structurally normal heart. Conclusion: Left isomerism syndrone may coesist with a structurally normal heart. If prenatal left isomerism is suspected, even in presence of a normal heart, is mandatory to esclude sign of gastrointestinal abnormalities, as late poly hy dramnios, and cardiac rhytm disturbance during the pregnancy and neonatal age. PMID:22439041

Antenatal diagnosis of congenital heart disease and Down's syndrome: the potential effect on the practice of paediatric cardiology.

PubMed Central

Abu-Harb, M.; Wyllie, J.; Hey, E.; Richmond, S.; Wren, C.

1995-01-01

OBJECTIVE--To predict the effect of antenatal ultrasound screening for congenital heart disease and maternal serum screening of Down's syndrome on the practice of paediatric cardiology and paediatric cardiac surgery. DESIGN--A retrospective and prospective ascertainment of all congenital heart disease diagnosed in infancy in 1985-1991. SETTING--One English health region. PATIENTS--All congenital heart disease diagnosed in infancy by echocardiography, cardiac catheterisation, surgery, or necropsy was classified as "complex", "significant", or "minor" and as "detectable" or "not detectable" on a routine antenatal ultrasound scan. RESULTS--1347 infants had congenital heart disease which was "complex" in 13%, "significant" in 55%, and "minor" in 32%. 15% of cases were "detectable" on routine antenatal ultrasound. Assuming 20% detection and termination of 67% of affected pregnancies, liveborn congenital heart disease would be reduced by 2%, infant mortality from congenital heart disease by 5%, and paediatric cardiac surgical activity by 3%. Maternal screening for Down's syndrome, assuming 75% uptake, 60% detection, and termination of all affected pregnancies, would reduce liveborn cases of Down's syndrome by 45%, liveborn cases of congenital heart disease by 3.5%, and cardiac surgery by 2.6%. CONCLUSIONS--Screening for congenital heart disease using the four chamber view in routine obstetric examinations and maternal serum screening for Down's syndrome is likely to have only a small effect on the requirements for paediatric cardiology services and paediatric cardiac surgery. PMID:7547001

Fetal Echocardiography/Your Unborn Baby's Heart

MedlinePlus

... heart for the doctor to evaluate. The sound waves can also detect blood flow throughout the baby's heart. This enables the doctor to evaluate the structure and function of the fetal heart. Who needs one? Fetal ...

Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association.

PubMed

Page, Robert L; O'Bryant, Cindy L; Cheng, Davy; Dow, Tristan J; Ky, Bonnie; Stein, C Michael; Spencer, Anne P; Trupp, Robin J; Lindenfeld, JoAnn

2016-08-09

Heart failure is a common, costly, and debilitating syndrome that is associated with a highly complex drug regimen, a large number of comorbidities, and a large and often disparate number of healthcare providers. All of these factors conspire to increase the risk of heart failure exacerbation by direct myocardial toxicity, drug-drug interactions, or both. This scientific statement is designed to serve as a comprehensive and accessible source of drugs that may cause or exacerbate heart failure to assist healthcare providers in improving the quality of care for these patients. © 2016 American Heart Association, Inc.

Burden and impact of congenital syndromes and comorbidities among adults with congenital heart disease.

PubMed

Bracher, Isabelle; Padrutt, Maria; Bonassin, Francesca; Santos Lopes, Bruno; Gruner, Christiane; Stämpfli, Simon F; Oxenius, Angela; De Pasquale, Gabriella; Seeliger, Theresa; Lüscher, Thomas F; Attenhofer Jost, Christine; Greutmann, Matthias

2017-08-01

Our aim was to assess the overall burden of congenital syndromes and non-cardiac comorbidities among adults with congenital heart disease and to assess their impact on circumstances of living and outcomes. Within a cohort of 1725 adults with congenital heart defects (65% defects of moderate or great complexity) followed at a single tertiary care center, congenital syndromes and comorbidities were identified by chart review. Their association with arrhythmias, circumstances of living and survival was analyzed. Within the study cohort, 232 patients (13%) had a genetic syndrome, 51% at least one comorbidity and 23% ≥2 comorbidities. Most prevalent comorbidities were systemic arterial hypertension (11%), thyroid dysfunction (9%), psychiatric disorders (9%), neurologic disorders (7%), chronic lung disease (7%), and previous stroke (6%). In contrast to higher congenital heart defect complexity, the presence of comorbidities had no impact on living circumstances but patients with comorbidities were less likely to work full-time. Atrial arrhythmias were more common among patients with moderate/great disease complexity and those with comorbidities but were less common among patients with congenital syndromes (p<0.01 for all comparisons). Patients with ≥2 comorbidities had lower survival estimates compared to those with ≤1 comorbidity (p=0.013). Congenital syndromes and comorbidities are highly prevalent in adults with congenital heart disease followed at specialist centers and add to the overall complexity of care. The presence of these additional factors has an impact on living circumstances, is associated with arrhythmias and needs to be further explored as prognostic markers. Copyright © 2017 Elsevier B.V. All rights reserved.

Mitochondrial reactive oxygen species production and respiratory complex activity in rats with pressure overload-induced heart failure

PubMed Central

Schwarzer, Michael; Osterholt, Moritz; Lunkenbein, Anne; Schrepper, Andrea; Amorim, Paulo; Doenst, Torsten

2014-01-01

We investigated the impact of cardiac reactive oxygen species (ROS) during the development of pressure overload-induced heart failure. We used our previously described rat model where transverse aortic constriction (TAC) induces compensated hypertrophy after 2 weeks, heart failure with preserved ejection fraction at 6 and 10 weeks, and heart failure with systolic dysfunction after 20 weeks. We measured mitochondrial ROS production rates, ROS damage and assessed the therapeutic potential of in vivo antioxidant therapies. In compensated hypertrophy (2 weeks of TAC) ROS production rates were normal at both mitochondrial ROS production sites (complexes I and III). Complex I ROS production rates increased with the appearance of diastolic dysfunction (6 weeks of TAC) and remained high thereafter. Surprisingly, maximal ROS production at complex III peaked at 6 weeks of pressure overload. Mitochondrial respiratory capacity (state 3 respiration) was elevated 2 and 6 weeks after TAC, decreased after this point and was significantly impaired at 20 weeks, when contractile function was also impaired and ROS damage was found with increased hydroxynonenal. Treatment with the ROS scavenger α-phenyl-N-tert-butyl nitrone or the uncoupling agent dinitrophenol significantly reduced ROS production rates at 6 weeks. Despite the decline in ROS production capacity, no differences in contractile function between treated and untreated animals were observed. Increased ROS production occurs early in the development of heart failure with a peak at the onset of diastolic dysfunction. However, ROS production may not be related to the onset of contractile dysfunction. PMID:24951621

Hydroxytyrosol and its complex forms (secoiridoids) modulate aorta and heart proteome in healthy rats: Potential cardio-protective effects.

PubMed

Catalán, Úrsula; Rubió, Laura; López de Las Hazas, Maria-Carmen; Herrero, Pol; Nadal, Pedro; Canela, Núria; Pedret, Anna; Motilva, Maria-José; Solà, Rosa

2016-10-01

Hydroxytyrosol (HT) is the major phenolic compound in virgin olive oil (VOO) in both free and complex forms (secoiridoids; SEC). Proteomics of cardiovascular tissues such as aorta or heart represents a promising tool to uncover the mechanisms of action of phenolic compounds in healthy animals. Twelve female Wistar rats were separated into three groups: a standard diet and two diets supplemented in phenolic compounds (HT and SEC) adjusted to 5 mg/kg/day during 21 days. Proteomic analyses of aorta and heart tissues were performed by nano-LC and MS. Ingenuity Pathway Analysis was used to generate interaction networks. HT or SEC modulated aorta and heart proteome compared to the standard diet. The top-scored networks were related to Cardiovascular System. HT and SEC downregulated proteins related to proliferation and migration of endothelial cells and occlusion of blood vessels in aorta and proteins related to heart failure in heart tissue. SEC showed higher fold change values compared to HT, attributed to higher concentration of HT detected in heart tissue. Changes at proteomic level in cardiovascular tissues may partially account for the underlying mechanisms of VOO phenols cardiovascular protection being the SEC effects higher than free HT. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bartonella endocarditis in complex congenital heart disease.

PubMed

Hoffman, Risa M; AboulHosn, Jamil; Child, John S; Pegues, David A

2007-01-01

Bartonella species are an important cause of culture-negative endocarditis, with recognized risk factors of alcoholism, homelessness, cat exposure, and pre-existing valvular disease. We report a case of Bartonella henselae endocarditis in a 36-year-old woman with complex congenital heart disease who presented with a 7-month history of hemolytic anemia, leukocytoclastic vasculitis, and recurrent fevers. Transesophageal echocardiogram revealed vegetations on the patient's native aortic valve and in the right ventricular to pulmonary artery conduit and associated bioprosthetic valve. Diagnosis of B. henselae was confirmed with serum antibody and polymerase chain reaction (PCR) testing and tissue stains. The patient was treated successfully with surgical resection and prolonged antimicrobial therapy with ceftriaxone, gentamicin, and doxycycline. A review of the literature suggests prosthetic valves and complex congenital heart disease are risk factors for Bartonella endocarditis, and a high index of suspicion with antibody and PCR testing can expedite diagnosis and improve outcomes.

Using complexity metrics with R-R intervals and BPM heart rate measures.

PubMed

Wallot, Sebastian; Fusaroli, Riccardo; Tylén, Kristian; Jegindø, Else-Marie

2013-01-01

Lately, growing attention in the health sciences has been paid to the dynamics of heart rate as indicator of impending failures and for prognoses. Likewise, in social and cognitive sciences, heart rate is increasingly employed as a measure of arousal, emotional engagement and as a marker of interpersonal coordination. However, there is no consensus about which measurements and analytical tools are most appropriate in mapping the temporal dynamics of heart rate and quite different metrics are reported in the literature. As complexity metrics of heart rate variability depend critically on variability of the data, different choices regarding the kind of measures can have a substantial impact on the results. In this article we compare linear and non-linear statistics on two prominent types of heart beat data, beat-to-beat intervals (R-R interval) and beats-per-min (BPM). As a proof-of-concept, we employ a simple rest-exercise-rest task and show that non-linear statistics-fractal (DFA) and recurrence (RQA) analyses-reveal information about heart beat activity above and beyond the simple level of heart rate. Non-linear statistics unveil sustained post-exercise effects on heart rate dynamics, but their power to do so critically depends on the type data that is employed: While R-R intervals are very susceptible to non-linear analyses, the success of non-linear methods for BPM data critically depends on their construction. Generally, "oversampled" BPM time-series can be recommended as they retain most of the information about non-linear aspects of heart beat dynamics.

Using complexity metrics with R-R intervals and BPM heart rate measures

PubMed Central

Wallot, Sebastian; Fusaroli, Riccardo; Tylén, Kristian; Jegindø, Else-Marie

2013-01-01

Lately, growing attention in the health sciences has been paid to the dynamics of heart rate as indicator of impending failures and for prognoses. Likewise, in social and cognitive sciences, heart rate is increasingly employed as a measure of arousal, emotional engagement and as a marker of interpersonal coordination. However, there is no consensus about which measurements and analytical tools are most appropriate in mapping the temporal dynamics of heart rate and quite different metrics are reported in the literature. As complexity metrics of heart rate variability depend critically on variability of the data, different choices regarding the kind of measures can have a substantial impact on the results. In this article we compare linear and non-linear statistics on two prominent types of heart beat data, beat-to-beat intervals (R-R interval) and beats-per-min (BPM). As a proof-of-concept, we employ a simple rest-exercise-rest task and show that non-linear statistics—fractal (DFA) and recurrence (RQA) analyses—reveal information about heart beat activity above and beyond the simple level of heart rate. Non-linear statistics unveil sustained post-exercise effects on heart rate dynamics, but their power to do so critically depends on the type data that is employed: While R-R intervals are very susceptible to non-linear analyses, the success of non-linear methods for BPM data critically depends on their construction. Generally, “oversampled” BPM time-series can be recommended as they retain most of the information about non-linear aspects of heart beat dynamics. PMID:23964244

Influence of trimetazidine on the synthesis of complex lipids in the heart and other target organs

NASA Technical Reports Server (NTRS)

Sentex, E.; Helies-Toussaint, C.; Rousseau, D.; Lucien, A.; Ferrary, E.; Grynberg, A.

2001-01-01

Trimetazidine exerts antianginal properties at the cellular level, without haemodynamic effect in clinical and experimental conditions. This cytoprotection was attributed to a decreased utilization of fatty acids for energy production, balanced by an increased incorporation in structural lipids. This study evaluated the influence of Trimetazidine on complex lipid synthesis from [2-(3)H] glycerol, in ventricular myocytes, isolated rat hearts and in vivo in the myocardium and several other tissues. In cardiomyocytes, Trimetazidine increased the synthesis of phosphatidyl-choline (+ 80%), phosphatidyl-ethanolamine (+ 210%), phosphatidyl-inositol (+ 250%) and cardiolipid (+ 100%). The common precursor diacylglycerol was also increased (+ 40%) whereas triacylglycerol was decreased (-70%). Similar results were obtained in isolated hearts with 10 microm Trimetazidine (phosphatidyl-choline + 60%, phosphatidyl-ethanolamine + 60%, phosphatidyl-inositol + 100% and cardiolipid + 50%), the last two phospholipids containing 85% of the radioactivity. At 1 microm, Trimetazidine still stimulated the phospholipid synthesis although the difference was found significant only in phosphatidyl-inositol and cardiolipid. In vivo studies (10 mg/kg per day for 7 days and 5 mg/kg, i.p. before the experiment) revealed significant changes in the intracellular lipid biosynthesis, with increased labelling of phospholipids and reduced incorporation of glycerol in nonphosphorous lipids. Trimetazidine increased the glycerol uptake from plasma to the other tissues (liver, cochlea, retina), resulting in an altered lipid synthesis. The anti-anginal properties of Trimetazidine involve a reorganisation of the glycerol-based lipid synthesis balance in cardiomyocytes, associated with an increased uptake of plasma glycerol that may contribute to explain the pharmacological properties reported in other organs.

Functional and structural regeneration in the axolotl heart (Ambystoma mexicanum) after partial ventricular amputation.

PubMed

Cano-Martínez, Agustina; Vargas-González, Alvaro; Guarner-Lans, Verónica; Prado-Zayago, Esteban; León-Oleda, Martha; Nieto-Lima, Betzabé

2010-01-01

"In the present study we evaluated the effect of partial ventricular amputation (PVA) in the heart of the adult urodele amphibian (Ambystoma mexicanum) in vivo on spontaneous heart contractile activity recorded in vitro in association to the structural recovery at one, five, 30 and 90 days after injury. One day after PVA, ventricular-tension (VT) (16 ± 3%), atrium-tension (AT) (46 ± 4%) and heart rate (HR) (58+10%) resulted lower in comparison to control hearts. On days five, 30 and 90 after damage, values achieved a 61 ± 5, 93 ± 3, and 98 ± 5% (VT), 60 ± 4, 96 ± 3 and 99 ± 5% (AT) and 74 ± 5, 84 ± 10 and 95 ± 10% (HR) of the control values, respectively. Associated to contractile activity recovery we corroborated a gradual tissue restoration by cardiomyocyte proliferation. Our results represent the first quantitative evidence about the recovery of heart of A. mexicanum restores its functional capacity concomitantly to the structural recovery of the myocardium by proliferation of cardiomyocytes after PVA. These properties make the heart of A. mexicanum a potential model to study the mechanisms underlying heart regeneration in adult vertebrates in vivo.

Equine Cardiovascular Therapeutics.

PubMed

Sleeper, Meg M

2017-04-01

Heart disease can be defined as any abnormality of the heart whether it is a cardiac dysrhythmia or structural heart disease, either congenital or acquired. Heart failure occurs when a cardiac abnormality results in the inability of the heart to pump enough blood to meet the body's needs. Heart disease can be present without leading to heart failure. Heart failure, however, is a consequence of heart disease. There are 4 main areas where the clinician can intervene to improve cardiac output with heart failure: preload, afterload, myocardial contractility, and heart rate. Copyright © 2016 Elsevier Inc. All rights reserved.

Cardiorespiratory interactions previously identified as mammalian are present in the primitive lungfish

PubMed Central

Monteiro, Diana A.; Taylor, Edwin W.; Sartori, Marina R.; Cruz, André L.; Rantin, Francisco T.; Leite, Cleo A. C.

2018-01-01

The present study has revealed that the lungfish has both structural and functional features of its system for physiological control of heart rate, previously considered solely mammalian, that together generate variability (HRV). Ultrastructural and electrophysiological investigation revealed that the nerves connecting the brain to the heart are myelinated, conferring rapid conduction velocities, comparable to mammalian fibers that generate instantaneous changes in heart rate at the onset of each air breath. These respiration-related changes in beat-to-beat cardiac intervals were detected by complex analysis of HRV and shown to maximize oxygen uptake per breath, a causal relationship never conclusively demonstrated in mammals. Cardiac vagal preganglionic neurons, responsible for controlling heart rate via the parasympathetic vagus nerve, were shown to have multiple locations, chiefly within the dorsal vagal motor nucleus that may enable interactive control of the circulatory and respiratory systems, similar to that described for tetrapods. The present illustration of an apparently highly evolved control system for HRV in a fish with a proven ancient lineage, based on paleontological, morphological, and recent genetic evidence, questions much of the anthropocentric thinking implied by some mammalian physiologists and encouraged by many psychobiologists. It is possible that some characteristics of mammalian respiratory sinus arrhythmia, for which functional roles have been sought, are evolutionary relics that had their physiological role defined in ancient representatives of the vertebrates with undivided circulatory systems. PMID:29507882

Cardiorespiratory interactions previously identified as mammalian are present in the primitive lungfish.

PubMed

Monteiro, Diana A; Taylor, Edwin W; Sartori, Marina R; Cruz, André L; Rantin, Francisco T; Leite, Cleo A C

2018-02-01

The present study has revealed that the lungfish has both structural and functional features of its system for physiological control of heart rate, previously considered solely mammalian, that together generate variability (HRV). Ultrastructural and electrophysiological investigation revealed that the nerves connecting the brain to the heart are myelinated, conferring rapid conduction velocities, comparable to mammalian fibers that generate instantaneous changes in heart rate at the onset of each air breath. These respiration-related changes in beat-to-beat cardiac intervals were detected by complex analysis of HRV and shown to maximize oxygen uptake per breath, a causal relationship never conclusively demonstrated in mammals. Cardiac vagal preganglionic neurons, responsible for controlling heart rate via the parasympathetic vagus nerve, were shown to have multiple locations, chiefly within the dorsal vagal motor nucleus that may enable interactive control of the circulatory and respiratory systems, similar to that described for tetrapods. The present illustration of an apparently highly evolved control system for HRV in a fish with a proven ancient lineage, based on paleontological, morphological, and recent genetic evidence, questions much of the anthropocentric thinking implied by some mammalian physiologists and encouraged by many psychobiologists. It is possible that some characteristics of mammalian respiratory sinus arrhythmia, for which functional roles have been sought, are evolutionary relics that had their physiological role defined in ancient representatives of the vertebrates with undivided circulatory systems.

Decrease of cardiac chaos in congestive heart failure

NASA Astrophysics Data System (ADS)

Poon, Chi-Sang; Merrill, Christopher K.

1997-10-01

The electrical properties of the mammalian heart undergo many complex transitions in normal and diseased states. It has been proposed that the normal heartbeat may display complex nonlinear dynamics, including deterministic chaos,, and that such cardiac chaos may be a useful physiological marker for the diagnosis and management, of certain heart trouble. However, it is not clear whether the heartbeat series of healthy and diseased hearts are chaotic or stochastic, or whether cardiac chaos represents normal or abnormal behaviour. Here we have used a highly sensitive technique, which is robust to random noise, to detect chaos. We analysed the electrocardiograms from a group of healthy subjects and those with severe congestive heart failure (CHF), a clinical condition associated with a high risk of sudden death. The short-term variations of beat-to-beat interval exhibited strongly and consistently chaotic behaviour in all healthy subjects, but were frequently interrupted by periods of seemingly non-chaotic fluctuations in patients with CHF. Chaotic dynamics in the CHF data, even when discernible, exhibited a high degree of random variability over time, suggesting a weaker form of chaos. These findings suggest that cardiac chaos is prevalent in healthy heart, and a decrease in such chaos may be indicative of CHF.

The Jackson Heart KIDS Pilot Study: Theory-Informed Recruitment in an African American Population.

PubMed

Beech, Bettina M; Bruce, Marino A; Crump, Mary E; Hamilton, Gina E

2017-04-01

Recruitment for large cohort studies is typically challenging, particularly when the pool of potential participants is limited to the descendants of individuals enrolled in a larger, longitudinal "parent" study. The increasing complexity of family structures and dynamics can present challenges for recruitment in offspring. Few best practices exist to guide effective and efficient empirical approaches to participant recruitment. Social and behavioral theories can provide insight into social and cultural contexts influencing individual decision-making and facilitate the development strategies for effective diffusion and marketing of an offspring cohort study. The purpose of this study was to describe the theory-informed recruitment approaches employed by the Jackson Heart KIDS Pilot Study (JHKS), a prospective offspring feasibility study of 200 African American children and grandchildren of the Jackson Heart Study (JHS)-the largest prospective cohort study examining cardiovascular disease among African American adults. Participant recruitment in the JHKS was founded on concepts from three theoretical perspectives-the Diffusion of Innovation Theory, Strength of Weak Ties, and Marketing Theory. Tailored recruitment strategies grounded in participatory strategies allowed us to exceed enrollment goals for JHKS Pilot Study and develop a framework for a statewide study of African American adolescents.

Weaving for heart valve tissue engineering.

PubMed

Liberski, Albert; Ayad, Nadia; Wojciechowska, Dorota; Kot, Radoslaw; Vo, Duy M P; Aibibu, Dilibaier; Hoffmann, Gerald; Cherif, Chokri; Grobelny-Mayer, Katharina; Snycerski, Marek; Goldmann, Helmut

2017-11-01

Weaving is a resourceful technology which offers a large selection of solutions that are readily adaptable for tissue engineering (TE) of artificial heart valves (HV). The different ways that the yarns are interlaced in this technique could be used to produce complex architectures, such as the three-layer architecture of the leaflets. Once the assembly is complete, growth of cells in the scaffold would occur in the orientation of the yarn, enabling the deposition of extra cellular matrixes proteins in an oriented manner. Weaving technology is a rapidly evolving field that, first, needs to be understood, and then explored by tissue engineers, so that it could be used to create efficient scaffolds. Similarly, the textile engineers need to gain a basic understanding of key structural and mechanical aspects of the heart valve. The aim of this review is to provide the platform for joining these two fields and to enable cooperative research efforts. Moreover, examples of woven medical products and patents as well as related publication are discussed in this review, nevertheless due to the large, and continuously growing volume of data, only the aspects strictly associated with HVTE lay in the scope of this paper. Copyright © 2017 Elsevier Inc. All rights reserved.

The Jackson Heart KIDS Pilot Study: Theory-Informed Recruitment in an African American Population

PubMed Central

Beech, Bettina M.; Bruce, Marino A.; Crump, Mary E.; Hamilton, Gina E.

2016-01-01

Recruitment for large cohort studies is typically challenging, particularly when the pool of potential participants is limited to the descendants of individuals enrolled in a larger, longitudinal “parent” study. The increasing complexity of family structures and dynamics can present challenges for recruitment in offspring. Few best practices exist to guide effective and efficient empirical approaches to participant recruitment. Social and behavioral theories can provide insight into social and cultural contexts influencing individual decision-making and facilitate the development strategies for effective diffusion and marketing of an offspring cohort study. The purpose of this study was to describe the theory-informed recruitment approaches employed by the Jackson Heart KIDS Pilot Study (JHKS), a prospective offspring feasibility study of 200 African American children and grandchildren of the Jackson Heart Study (JHS)—the largest prospective cohort study examining cardiovascular disease among African American adults. Participant recruitment in the JHKS was founded on concepts from three theoretical perspectives—the Diffusion of Innovation Theory, Strength of Weak Ties, and Marketing Theory. Tailored recruitment strategies grounded in participatory strategies allowed us to exceed enrollment goals for JHKS Pilot Study and develop a framework for a statewide study of African American adolescents. PMID:27129858

Heart failure: not a single organ disease but a multisystem syndrome.

PubMed

Warriner, David; Sheridan, Paul; Lawford, Patricia

2015-06-01

Heart failure is not simply a single organ disease; rather it is a complex multi-system clinical syndrome, with impairment of endocrine, haematological, musculoskeletal, renal, respiratory and vascular systems, which influence morbidity and mortality.

Treating hypertension while protecting the vulnerable islet in the cardiometabolic syndrome

PubMed Central

Hayden, Melvin R.; Sowers, James R.

2008-01-01

Hypertension, a multifactorial-polygenic disease, interacts with multiple environmental stressors and results in functional and structural changes in numerous end organs, including the cardiovascular system. This can result in coronary heart disease, stroke, peripheral vascular disease, congestive heart failure, end-stage renal disease, insulin resistance, and damage to the pancreatic islet. Hypertension is the most important modifiable risk factor for major health problems encountered in clinical practice. Whereas hypertension was once thought to be a medical condition based on discrete blood pressure readings, a new concept has emerged defining hypertension as part of a complex and progressive metabolic and cardiovascular disease, an important part of a cardiometabolic syndrome. The central role of insulin resistance, oxidative stress, endothelial dysfunction, metabolic signaling defects within tissues, and the role of enhanced tissue renin-angiotensin-aldosterone system activity as it relates to hypertension and type 2 diabetes mellitus is emphasized. Additionally, this review focuses on the effect of hypertension on functional and structural changes associated with the vulnerable pancreatic islet. Various classes of antihypertensive drugs are reviewed, especially their roles in delaying or preventing damage to the vulnerable pancreatic islet, and thus delaying the development of type 2 diabetes mellitus. PMID:20409906

'My heart belongs to daddy'. Some reflections on the difference between generations as the organiser of the triangular structure of the mind.

PubMed

Sapisochin, G

1999-08-01

The author begins his paper with a historical review of the concept of the difference between generations, which is in his opinion a metaphorical transformation that underpins the three-dimensional functioning of the psychic apparatus by introducing a differentiating intergenerational space between subject and object. He postulates that at the point of intersection between the intersubjective and the intrapsychic the subject clings to the specific fragments of his parents' history that are consistent with a belief about himself and the oedipal couple in which intergenerational links are severed and infantile incestuous wishes are seen as fulfilled. Disavowal of this generation gap is considered to lead to failure of post-oedipal secondary identifications, resulting in disturbance of the triangular structuring of the mind and consequent impairment of the genesis of thought processes. These ideas are compared with related conceptions of other authors and illustrated, with an account of the associated transference/countertransference vicissitudes, by a clinical example of the constellation the author calls 'My heart belongs to daddy', which he sees as a way station in the negotiation of the female Oedipus complex.

Quantification of fetal heart rate regularity using symbolic dynamics

NASA Astrophysics Data System (ADS)

van Leeuwen, P.; Cysarz, D.; Lange, S.; Geue, D.; Groenemeyer, D.

2007-03-01

Fetal heart rate complexity was examined on the basis of RR interval time series obtained in the second and third trimester of pregnancy. In each fetal RR interval time series, short term beat-to-beat heart rate changes were coded in 8bit binary sequences. Redundancies of the 28 different binary patterns were reduced by two different procedures. The complexity of these sequences was quantified using the approximate entropy (ApEn), resulting in discrete ApEn values which were used for classifying the sequences into 17 pattern sets. Also, the sequences were grouped into 20 pattern classes with respect to identity after rotation or inversion of the binary value. There was a specific, nonuniform distribution of the sequences in the pattern sets and this differed from the distribution found in surrogate data. In the course of gestation, the number of sequences increased in seven pattern sets, decreased in four and remained unchanged in six. Sequences that occurred less often over time, both regular and irregular, were characterized by patterns reflecting frequent beat-to-beat reversals in heart rate. They were also predominant in the surrogate data, suggesting that these patterns are associated with stochastic heart beat trains. Sequences that occurred more frequently over time were relatively rare in the surrogate data. Some of these sequences had a high degree of regularity and corresponded to prolonged heart rate accelerations or decelerations which may be associated with directed fetal activity or movement or baroreflex activity. Application of the pattern classes revealed that those sequences with a high degree of irregularity correspond to heart rate patterns resulting from complex physiological activity such as fetal breathing movements. The results suggest that the development of the autonomic nervous system and the emergence of fetal behavioral states lead to increases in not only irregular but also regular heart rate patterns. Using symbolic dynamics to examine the cardiovascular system may thus lead to new insight with respect to fetal development.

Predominance of Intrinsic Mechanism of Resting Heart Rate Control and Preserved Baroreflex Sensitivity in Professional Cyclists after Competitive Training.

PubMed

Azevedo, Luciene Ferreira; Perlingeiro, Patricia; Hachul, Denise Tessariol; Gomes-Santos, Igor Lucas; Tsutsui, Jeane Mike; Negrao, Carlos Eduardo; De Matos, Luciana D N J

2016-01-01

Different season trainings may influence autonomic and non-autonomic cardiac control of heart rate and provokes specific adaptations on heart's structure in athletes. We investigated the influence of transition training (TT) and competitive training (CT) on resting heart rate, its mechanisms of control, spontaneous baroreflex sensitivity (BRS) and relationships between heart rate mechanisms and cardiac structure in professional cyclists (N = 10). Heart rate (ECG) and arterial blood pressure (Pulse Tonometry) were recorded continuously. Autonomic blockade was performed (atropine-0.04 mg.kg-1; esmolol-500 μg.kg-1 = 0.5 mg). Vagal effect, intrinsic heart rate, parasympathetic (n) and sympathetic (m) modulations, autonomic influence, autonomic balance and BRS were calculated. Plasma norepinephrine (high-pressure liquid chromatography) and cardiac structure (echocardiography) were evaluated. Resting heart rate was similar in TT and CT. However, vagal effect, intrinsic heart rate, autonomic influence and parasympathetic modulation (higher n value) decreased in CT (P≤0.05). Sympathetic modulation was similar in both trainings. The autonomic balance increased in CT but still showed parasympathetic predominance. Cardiac diameter, septum and posterior wall thickness and left ventricular mass also increased in CT (P<0.05) as well as diastolic function. We observed an inverse correlation between left ventricular diastolic diameter, septum and posterior wall thickness and left ventricular mass with intrinsic heart rate. Blood pressure and BRS were similar in both trainings. Intrinsic heart rate mechanism is predominant over vagal effect during CT, despite similar resting heart rate. Preserved blood pressure levels and BRS during CT are probably due to similar sympathetic modulation in both trainings.

High-Speed, Three Dimensional Object Composition Mapping Technology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ishikawa, M Y

2001-02-14

This document overviews an entirely new approach to determining the composition--the chemical-elemental, isotopic and molecular make-up--of complex, highly structured objects, moreover with microscopic spatial resolution in all 3 dimensions. The front cover depicts the new type of pulsed laser system at the heart of this novel technology under adjustment by Alexis Wynne, and schematically indicates two of its early uses: swiftly analyzing the 3-D composition governed structure of a transistor circuit with both optical and mass-spectrometric detectors, and of fossilized dinosaur and turtle bones high-speed probed by optical detection means. Studying the composition-cued 3-D micro-structures of advanced composite materials andmore » the microscopic scale composition-texture of biological tissues are two near-term examples of the rich spectrum of novel applications enabled by this field-opening analytic tool-set.« less

The effect of nursing professional pay structures and pay levels on hospitals' heart attack outcomes.

PubMed

Brown, Mark P

2006-01-01

The effect of nursing professionals (i.e., nurse aid/orderly, licensed practical nurse, registered nurse) pay structures and pay levels on hospitals risk-adjusted heart attack outcomes was determined. Operationalizing hospitals' heart attack outcomes as their thirty-day risk-adjusted mortality rates, a positive curvilinear relation is hypothesized between pay dispersion and hospitals' heart attack outcomes, whereas a direct relation is hypothesized between pay level and hospitals' heart attack outcomes. Pay level is also hypothesized as a moderator of the relation between pay dispersion and hospitals' heart attack outcomes. Using a sample of 138 California hospitals, support is not found for either the curvilinear relation between hospitals' nursing professionals pay dispersion and hospitals' heart attack outcomes, or the direct relation between nursing professionals' pay level and hospitals' heart attack outcomes. Support is found for the moderation hypothesis in which nursing professionals' pay level moderates the relation between hospitals' nursing professionals pay dispersion and hospitals' heart attack outcomes. Implications for practice are discussed in light of the study's results.

Ventricular Tachycardia or not? An Unexpected Reason of Wide QRS Complex Tachycardia in a Young Healthy Man: Sodium Bicarbonate.

PubMed

Eyuboglu, Mehmet

2016-10-01

Ventricular tachycardia (VT) is life-threatening subgroup of wide QRS complex tachycardia (WCT). VT is usually associated with structural heart diseases, but it can occur in the absence of any cardiovascular diseases. Adverse cardiac effect of sodium bicarbonate in healthy subjects is not well described. A 30-year-old healthy man with excessive intake of sodium bicarbonate-related VT is presented. He was using sodium bicarbonate during last 2 months to lose weight. He has no risk factors and any cardiovascular or systemic diseases. After intravenous administration of amiodarone, tachycardia ended and his rhythm converted to sinus rhythm with normal electrocardiogram. Patient is asymptomatic, and no VT was observed without any medications at 1 year of follow-up.

Semantic enrichment of clinical models towards semantic interoperability. The heart failure summary use case.

PubMed

Martínez-Costa, Catalina; Cornet, Ronald; Karlsson, Daniel; Schulz, Stefan; Kalra, Dipak

2015-05-01

To improve semantic interoperability of electronic health records (EHRs) by ontology-based mediation across syntactically heterogeneous representations of the same or similar clinical information. Our approach is based on a semantic layer that consists of: (1) a set of ontologies supported by (2) a set of semantic patterns. The first aspect of the semantic layer helps standardize the clinical information modeling task and the second shields modelers from the complexity of ontology modeling. We applied this approach to heterogeneous representations of an excerpt of a heart failure summary. Using a set of finite top-level patterns to derive semantic patterns, we demonstrate that those patterns, or compositions thereof, can be used to represent information from clinical models. Homogeneous querying of the same or similar information, when represented according to heterogeneous clinical models, is feasible. Our approach focuses on the meaning embedded in EHRs, regardless of their structure. This complex task requires a clear ontological commitment (ie, agreement to consistently use the shared vocabulary within some context), together with formalization rules. These requirements are supported by semantic patterns. Other potential uses of this approach, such as clinical models validation, require further investigation. We show how an ontology-based representation of a clinical summary, guided by semantic patterns, allows homogeneous querying of heterogeneous information structures. Whether there are a finite number of top-level patterns is an open question. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Risk factors for surgery of congenital heart disease in adults: twenty-two years of experience. Who should operate them?].

PubMed

Aroca, Angel; Polo, Luz; Pérez-Farinós, Napoleón; González, Ana E; Bret, Montserrat; Aguilar, Elizabeth; Oliver, José M

2014-01-01

To assess the association between mortality in surgery of congenital heart disease in adults, and factors related to patients and operations. Descriptive study of operations performed by specialized surgeons in congenital heart surgery (238), adult acquired surgery (117), and specialty residents (108). The association of mortality with surgical risk and complexity, specialization of surgeon, cardiopulmonary by-pass and aortic cross clamping was assessed fitting logistic regression models. A total of 463 operations were included (442 with cardiopulmonary by-pass) in the study performed between 1991 and 2012. Median age at surgery: 34; 52.8% were women. First surgery: 295, reoperation: 168. Median score of Aristotle was 6.8, with significantly higher complexity since 2001, after restructuring the Unit. Overall hospital mortality was 3.9%. Mortality was significantly associated to number of previous surgeries (OR: 5.02; 95%CI: 1.44-17.52), operations by acquired heart disease surgeons (OR: 3.53; 95%CI: 1.14-10.98), higher Aristotle (OR: 1,64; 95%CI: 1.18-2.29), and high cardiopulmonary by-pass time (OR: 1.13; 95%CI: 1.07-1.19). Surgery of congenital heart disease in adults has been performed with low mortality. High complexity interventions, prolonged cardiopulmonary by-pass times and multiple reoperations were associated to higher mortality. Participation of cardiac surgeons specialized in congenital heart disease is associated with better outcomes. Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

Compliance with Adult Congenital Heart Disease Guidelines: Are We Following the Recommendations?

PubMed

Gerardin, Jennifer F; Menk, Jeremiah S; Pyles, Lee A; Martin, Cindy M; Lohr, Jamie L

2016-05-01

As the adult congenital heart disease population increases, poor transition from pediatric to adult care can lead to suboptimal quality of care and an increase in individual and institutional costs. In 2008, the American College of Cardiology and American Heart Association updated the adult congenital heart disease practice guidelines and in 2011, the American Heart Association recommended transition guidelines to standardize and encourage appropriate timing of transition to adult cardiac services. The objective of this study was to evaluate if patient age or complexity of congenital heart disease influences pediatric cardiologists' decision to transfer care to adult providers and to evaluate the compliance of different types of cardiology providers with current adult congenital heart disease treatment guidelines. A single-center retrospective review of 991 adult congenital heart disease patients identified by ICD-9 code from 2010 to 2012. Academic and community outpatient cardiology clinics. Nine hundred ninety-one patients who are 18 years and older with congenital heart disease. None. The compliance with health maintenance and transfer of care recommendations in the outpatient setting. For patients seen by pediatric cardiologists, only 20% had transfer of care discussions documented, most often in younger simple patients. Significant differences in compliance with preventative health guidelines were found between cardiology provider types. Even though a significant number of adults with congenital heart disease are lost to appropriate follow-up in their third and fourth decades of life, pediatric cardiologists discussed transfer of care with moderate and complex congenital heart disease patients less frequently. Appropriate transfer of adults with congenital heart disease to an adult congenital cardiologist provides an opportunity to reinforce the importance of regular follow-up in adulthood and may improve outcomes as adult congenital cardiologists followed the adult congenital heart disease guidelines more consistently than pediatric or adult cardiologists. © 2015 Wiley Periodicals, Inc.

The Aristotle Comprehensive Complexity score predicts mortality and morbidity after congenital heart surgery.

PubMed

Bojan, Mirela; Gerelli, Sébastien; Gioanni, Simone; Pouard, Philippe; Vouhé, Pascal

2011-04-01

The Aristotle Comprehensive Complexity (ACC) score has been proposed for complexity adjustment in the analysis of outcome after congenital heart surgery. The score is the sum of the Aristotle Basic Complexity score, largely used but poorly related to mortality and morbidity, and of the Comprehensive Complexity items accounting for comorbidities and procedure-specific and anatomic variability. This study aims to demonstrate the ability of the ACC score to predict 30-day mortality and morbidity assessed by the length of the intensive care unit (ICU) stay. We retrospectively enrolled patients undergoing congenital heart surgery in our institution. We modeled the ACC score as a continuous variable, mortality as a binary variable, and length of ICU stay as a censored variable. For each mortality and morbidity model we performed internal validation by bootstrapping and assessed overall performance by R(2), calibration by the calibration slope, and discrimination by the c index. Among all 1,454 patients enrolled, 30-day mortality rate was 3.4% and median length of ICU stay was 3 days. The ACC score strongly related to mortality, but related to length of ICU stay only during the first postoperative week. For the mortality model, R(2) = 0.24, calibration slope = 0.98, c index = 0.86, and 95% confidence interval was 0.82 to 0.91. For the morbidity model, R(2) = 0.094, calibration slope = 0.94, c index = 0.64, and 95% confidence interval was 0.62 to 0.66. The ACC score predicts 30-day mortality and length of ICU stay during the first postoperative week. The score is an adequate tool for complexity adjustment in the analysis of outcome after congenital heart surgery. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Utilizing Three-Dimensional Printing Technology to Assess the Feasibility of High-Fidelity Synthetic Ventricular Septal Defect Models for Simulation in Medical Education.

PubMed

Costello, John P; Olivieri, Laura J; Krieger, Axel; Thabit, Omar; Marshall, M Blair; Yoo, Shi-Joon; Kim, Peter C; Jonas, Richard A; Nath, Dilip S

2014-07-01

The current educational approach for teaching congenital heart disease (CHD) anatomy to students involves instructional tools and techniques that have significant limitations. This study sought to assess the feasibility of utilizing present-day three-dimensional (3D) printing technology to create high-fidelity synthetic heart models with ventricular septal defect (VSD) lesions and applying these models to a novel, simulation-based educational curriculum for premedical and medical students. Archived, de-identified magnetic resonance images of five common VSD subtypes were obtained. These cardiac images were then segmented and built into 3D computer-aided design models using Mimics Innovation Suite software. An Objet500 Connex 3D printer was subsequently utilized to print a high-fidelity heart model for each VSD subtype. Next, a simulation-based educational curriculum using these heart models was developed and implemented in the instruction of 29 premedical and medical students. Assessment of this curriculum was undertaken with Likert-type questionnaires. High-fidelity VSD models were successfully created utilizing magnetic resonance imaging data and 3D printing. Following instruction with these high-fidelity models, all students reported significant improvement in knowledge acquisition (P < .0001), knowledge reporting (P < .0001), and structural conceptualization (P < .0001) of VSDs. It is feasible to use present-day 3D printing technology to create high-fidelity heart models with complex intracardiac defects. Furthermore, this tool forms the foundation for an innovative, simulation-based educational approach to teach students about CHD and creates a novel opportunity to stimulate their interest in this field. © The Author(s) 2014.

Complexity analysis of fetal heart rate preceding intrauterine demise.

PubMed

Schnettler, William T; Goldberger, Ary L; Ralston, Steven J; Costa, Madalena

2016-08-01

Visual non-stress test interpretation lacks the optimal specificity and observer-agreement of an ideal screening tool for intrauterine fetal demise (IUFD) syndrome prevention. Computational methods based on traditional heart rate variability have also been of limited value. Complexity analysis probes properties of the dynamics of physiologic signals that are otherwise not accessible and, therefore, might be useful in this context. To explore the association between fetal heart rate (FHR) complexity analysis and subsequent IUFD. Our specific hypothesis is that the complexity of the fetal heart rate dynamics is lower in the IUFD group compared with controls. This case-control study utilized cases of IUFD at a single tertiary-care center among singleton pregnancies with at least 10min of continuous electronic FHR monitoring on at least 2 weekly occasions in the 3 weeks immediately prior to fetal demise. Controls delivered a live singleton beyond 35 weeks' gestation and were matched to cases by gestational age, testing indication, and maternal age in a 3:1 ratio. FHR data was analyzed using the multiscale entropy (MSE) method to derive their complexity index. In addition, pNNx, a measure of short-term heart rate variability, which in adults is ascribable primarily to cardiac vagal tone modulation, was also computed. 211 IUFDs occurred during the 9-year period of review, but only 6 met inclusion criteria. The median gestational age at the time of IUFD was 35.5 weeks. Three controls were matched to each case for a total of 24 subjects, and 87 FHR tracings were included for analysis. The median gestational age at the first fetal heart rate tracing was similar between groups (median [1st-3rd quartiles] weeks: IUFD cases: 34.7 (34.4-36.2); controls: 35.3 (34.4-36.1); p=.94). The median complexity of the cases' tracings was significantly less than the controls' (12.44 [8.9-16.77] vs. 17.82 [15.21-22.17]; p<.0001). Furthermore, the cases' median complexity decreased as gestation advanced whereas the controls' median complexity increased over time. However, this difference was not statistically significant [-0.83 (-2.03 to 0.47) vs. 0.14 (-1.25 to 0.94); p=.62]. The degree of short-term variability of FHR tracings, as measured by the pNN metric, was significantly lower (p<.005) for the controls (1.1 [0.8-1.3]) than the IUFD cases (1.3 [1.1-1.6]). FHR complexity analysis using multiscale entropy analysis may add value to other measures in detecting and monitoring pregnancies at the highest risk for IUFD. The decrease in complexity and short-term variability seen in the IUFD cases may reflect perturbations in neuroautonomic control due to multiple maternal-fetal factors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Structural and Functional Phenotyping of the Failing Heart: Is the Left Ventricular Ejection Fraction Obsolete?

PubMed

Bristow, Michael R; Kao, David P; Breathett, Khadijah K; Altman, Natasha L; Gorcsan, John; Gill, Edward A; Lowes, Brian D; Gilbert, Edward M; Quaife, Robert A; Mann, Douglas L

2017-11-01

Diagnosis, prognosis, treatment, and development of new therapies for diseases or syndromes depend on a reliable means of identifying phenotypes associated with distinct predictive probabilities for these various objectives. Left ventricular ejection fraction (LVEF) provides the current basis for combined functional and structural phenotyping in heart failure by classifying patients as those with heart failure with reduced ejection fraction (HFrEF) and those with heart failure with preserved ejection fraction (HFpEF). Recently the utility of LVEF as the major phenotypic determinant of heart failure has been challenged based on its load dependency and measurement variability. We review the history of the development and adoption of LVEF as a critical measurement of LV function and structure and demonstrate that, in chronic heart failure, load dependency is not an important practical issue, and we provide hemodynamic and molecular biomarker evidence that LVEF is superior or equal to more unwieldy methods of identifying phenotypes of ventricular remodeling. We conclude that, because it reliably measures both left ventricular function and structure, LVEF remains the best current method of assessing pathologic remodeling in heart failure in both individual clinical and multicenter group settings. Because of the present and future importance of left ventricular phenotyping in heart failure, LVEF should be measured by using the most accurate technology and methodologic refinements available, and improved characterization methods should continue to be sought. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Homoarginine—A prognostic indicator in adolescents and adults with complex congenital heart disease?

PubMed Central

Mueller, Marieke; Meinitzer, Andreas; Maerz, Winfried; Dschietzig, Thomas

2017-01-01

Background Homoarginine (hArg) has been shown to be of prognostic value in patients with chronic left heart failure. The present study aims to assess the clinical utility and prognostic value of hArg levels in patients with complex congenital heart disease (CHD). Methods Plasma hArg levels were measured in 143 patients with complex CHD and compared to clinical status, echocardiographic and laboratory parameters as well as the occurrence of adverse cardiac events. Results Median hArg levels were 1.5 μmol/l in CHD patients as compared to 1.70 μmol/l in healthy controls (p = 0.051). Median hArg levels were lowest in patients with Fontan palliation (1.27 μmol/l) and Eisenmenger physiology (0.99 μmol/l) and decreased with the severity of adverse cardiac events with lowest values found in patients prior to death or overt heart failure (0.89 μmol/l). According to ROC analysis, the most important predictors of adverse cardiac events were hArg levels (AUC 0.837, p<0.001, CI 0.726–0.947), NYHA class (AUC 0.800, p<0.001, CI 0.672–0.928) and NT-proBNP levels (AUC 0.780, p<0.001, CI 0.669–0.891). The occurrence of overt heart failure or death due to progressive heart failure were best predicted by NYHA class (AUC 0.945, p<0.001, CI 0.898–0.992), hArg levels (AUC 0.911, p<0.001, CI 0.850–0.971) and NT-proBNP levels (AUC 0.877, p<0.001, CI 0.791–0.962), respectively. Conclusion In patients with complex CHD, hArg levels can predict adverse cardiac events as reliably as or even better than NT-proBNP levels and thus might be of prognostic value in this subset of patients. PMID:28886170

Application of higher-order cepstral techniques in problems of fetal heart signal extraction

NASA Astrophysics Data System (ADS)

Sabry-Rizk, Madiha; Zgallai, Walid; Hardiman, P.; O'Riordan, J.

1996-10-01

Recently, cepstral analysis based on second order statistics and homomorphic filtering techniques have been used in the adaptive decomposition of overlapping, or otherwise, and noise contaminated ECG complexes of mothers and fetals obtained by a transabdominal surface electrodes connected to a monitoring instrument, an interface card, and a PC. Differential time delays of fetal heart beats measured from a reference point located on the mother complex after transformation to cepstra domains are first obtained and this is followed by fetal heart rate variability computations. Homomorphic filtering in the complex cepstral domain and the subuent transformation to the time domain results in fetal complex recovery. However, three problems have been identified with second-order based cepstral techniques that needed rectification in this paper. These are (1) errors resulting from the phase unwrapping algorithms and leading to fetal complex perturbation, (2) the unavoidable conversion of noise statistics from Gaussianess to non-Gaussianess due to the highly non-linear nature of homomorphic transform does warrant stringent noise cancellation routines, (3) due to the aforementioned problems in (1) and (2), it is difficult to adaptively optimize windows to include all individual fetal complexes in the time domain based on amplitude thresholding routines in the complex cepstral domain (i.e. the task of `zooming' in on weak fetal complexes requires more processing time). The use of third-order based high resolution differential cepstrum technique results in recovery of the delay of the order of 120 milliseconds.

Effect of shilajit on the heart of Daphnia: A preliminary study.

PubMed

Gaikwad, N S; Panat, A V; Deshpande, M S; Ramya, K; Khalid, P U; Augustine, P

2012-01-01

Shilajit is a mineral-rich complex organic compound used in the traditional system of Ayurvedic medicine for treating hypertension and improving the cardiac function with many herbomineral preparations. However, very little experimental evidence is available about its effect on the cardiac function. We used Daphnia as a model organism for observing the effect of shilajit on its heart due to its myogenic properties and its response to number of cardioactive drugs that are known to affect human heart function. Genome of Daphnia shows the strongest homology with the human genome. These characteristics of Daphnia make it an ideal organism for biomedical research. Our results suggest that this complex organic compound lowers the heart beats as its concentration increases from 1.0 to 100 ppm. The beats come to near normal condition at 1000 ppm. Above 1000 ppm, the beats are very fast and impossible to count. These results indicate a negative chronotropic effect on the Daphnia heart at low concentrations and a positive chronotropic effect to arrhythmia and finally failure at increasing higher concentrations of shilajit.

Effect of shilajit on the heart of Daphnia: A preliminary study

PubMed Central

Gaikwad, N. S.; Panat, A. V.; Deshpande, M. S.; Ramya, K.; Khalid, P. U.; Augustine, P.

2012-01-01

Shilajit is a mineral-rich complex organic compound used in the traditional system of Ayurvedic medicine for treating hypertension and improving the cardiac function with many herbomineral preparations. However, very little experimental evidence is available about its effect on the cardiac function. We used Daphnia as a model organism for observing the effect of shilajit on its heart due to its myogenic properties and its response to number of cardioactive drugs that are known to affect human heart function. Genome of Daphnia shows the strongest homology with the human genome. These characteristics of Daphnia make it an ideal organism for biomedical research. Our results suggest that this complex organic compound lowers the heart beats as its concentration increases from 1.0 to 100 ppm. The beats come to near normal condition at 1000 ppm. Above 1000 ppm, the beats are very fast and impossible to count. These results indicate a negative chronotropic effect on the Daphnia heart at low concentrations and a positive chronotropic effect to arrhythmia and finally failure at increasing higher concentrations of shilajit. PMID:22529672

Marital Status, Hypertension, Coronary Heart Disease, Diabetes, and Death among African American Women and Men: Incidence and Prevalence in the Atherosclerosis Risk in Communities (ARIC) Study Participants

ERIC Educational Resources Information Center

Schwandt, Hilary M.; Coresh, Josef; Hindin, Michelle J.

2010-01-01

Heart disease is the leading cause of death in the United States, and African Americans disproportionately experience more cardiovascular disease, including coronary heart disease (CHD), hypertension, and diabetes. The literature documents a complex relationship between marital status and health, which varies by gender. We prospectively examine…

Self-care confidence may be more important than cognition to influence self-care behaviors in adults with heart failure: Testing a mediation model.

PubMed

Vellone, Ercole; Pancani, Luca; Greco, Andrea; Steca, Patrizia; Riegel, Barbara

2016-08-01

Cognitive impairment can reduce the self-care abilities of heart failure patients. Theory and preliminary evidence suggest that self-care confidence may mediate the relationship between cognition and self-care, but further study is needed to validate this finding. The aim of this study was to test the mediating role of self-care confidence between specific cognitive domains and heart failure self-care. Secondary analysis of data from a descriptive study. Three out-patient sites in Pennsylvania and Delaware, USA. A sample of 280 adults with chronic heart failure, 62 years old on average and mostly male (64.3%). Data on heart failure self-care and self-care confidence were collected with the Self-Care of Heart Failure Index 6.2. Data on cognition were collected by trained research assistants using a neuropsychological test battery measuring simple and complex attention, processing speed, working memory, and short-term memory. Sociodemographic data were collected by self-report. Clinical information was abstracted from the medical record. Mediation analysis was performed with structural equation modeling and indirect effects were evaluated with bootstrapping. Most participants had at least 1 impaired cognitive domain. In mediation models, self-care confidence consistently influenced self-care and totally mediated the relationship between simple attention and self-care and between working memory and self-care (comparative fit index range: .929-.968; root mean squared error of approximation range: .032-.052). Except for short-term memory, which had a direct effect on self-care maintenance, the other cognitive domains were unrelated to self-care. Self-care confidence appears to be an important factor influencing heart failure self-care even in patients with impaired cognition. As few studies have successfully improved cognition, interventions addressing confidence should be considered as a way to improve self-care in this population. Copyright © 2016 Elsevier Ltd. All rights reserved.

Double symbolic joint entropy in nonlinear dynamic complexity analysis

NASA Astrophysics Data System (ADS)

Yao, Wenpo; Wang, Jun

2017-07-01

Symbolizations, the base of symbolic dynamic analysis, are classified as global static and local dynamic approaches which are combined by joint entropy in our works for nonlinear dynamic complexity analysis. Two global static methods, symbolic transformations of Wessel N. symbolic entropy and base-scale entropy, and two local ones, namely symbolizations of permutation and differential entropy, constitute four double symbolic joint entropies that have accurate complexity detections in chaotic models, logistic and Henon map series. In nonlinear dynamical analysis of different kinds of heart rate variability, heartbeats of healthy young have higher complexity than those of the healthy elderly, and congestive heart failure (CHF) patients are lowest in heartbeats' joint entropy values. Each individual symbolic entropy is improved by double symbolic joint entropy among which the combination of base-scale and differential symbolizations have best complexity analysis. Test results prove that double symbolic joint entropy is feasible in nonlinear dynamic complexity analysis.

Improving kNowledge Transfer to Efficaciously RAise the level of Contemporary Treatment in Heart Failure (INTERACT-in-HF): Study protocol of a mixed methods study.

PubMed

Baldewijns, Karolien; Bektas, Sema; Boyne, Josiane; Rohde, Carla; De Maesschalck, Lieven; De Bleser, Leentje; Brandenburg, Vincent; Knackstedt, Christian; Devillé, Aleidis; Sanders-Van Wijk, Sandra; Brunner La Rocca, Hans-Peter

2017-12-01

Heart failure is a complex disease with poor outcome. This complexity may prevent care providers from covering all aspects of care. This could not only be relevant for individual patient care, but also for care organisation. Disease management programmes applying a multidisciplinary approach are recommended to improve heart failure care. However, there is a scarcity of research considering how disease management programme perform, in what form they should be offered, and what care and support patients and care providers would benefit most. Therefore, the Improving kNowledge Transfer to Efficaciously Raise the level of Contemporary Treatment in Heart Failure (INTERACT-in-HF) study aims to explore the current processes of heart failure care and to identify factors that may facilitate and factors that may hamper heart failure care and guideline adherence. Within a cross-sectional mixed method design in three regions of the North-West part of Europe, patients (n = 88) and their care providers (n = 59) were interviewed. Prior to the in-depth interviews, patients were asked to complete three questionnaires: The Dutch Heart Failure Knowledge scale, The European Heart Failure Self-care Behaviour Scale and The global health status and social economic status. In parallel, retrospective data based on records from these (n = 88) and additional patients (n = 82) are reviewed. All interviews were audiotaped and transcribed verbatim for analysis.

Improving kNowledge Transfer to Efficaciously RAise the level of Contemporary Treatment in Heart Failure (INTERACT-in-HF): Study protocol of a mixed methods study

PubMed Central

Boyne, Josiane; Rohde, Carla; De Maesschalck, Lieven; De Bleser, Leentje; Brandenburg, Vincent; Knackstedt, Christian; Devillé, Aleidis; Sanders-Van Wijk, Sandra; Brunner La Rocca, Hans-Peter

2017-01-01

Heart failure is a complex disease with poor outcome. This complexity may prevent care providers from covering all aspects of care. This could not only be relevant for individual patient care, but also for care organisation. Disease management programmes applying a multidisciplinary approach are recommended to improve heart failure care. However, there is a scarcity of research considering how disease management programme perform, in what form they should be offered, and what care and support patients and care providers would benefit most. Therefore, the Improving kNowledge Transfer to Efficaciously Raise the level of Contemporary Treatment in Heart Failure (INTERACT-in-HF) study aims to explore the current processes of heart failure care and to identify factors that may facilitate and factors that may hamper heart failure care and guideline adherence. Within a cross-sectional mixed method design in three regions of the North-West part of Europe, patients (n = 88) and their care providers (n = 59) were interviewed. Prior to the in-depth interviews, patients were asked to complete three questionnaires: The Dutch Heart Failure Knowledge scale, The European Heart Failure Self-care Behaviour Scale and The global health status and social economic status. In parallel, retrospective data based on records from these (n = 88) and additional patients (n = 82) are reviewed. All interviews were audiotaped and transcribed verbatim for analysis. PMID:29472989

Use of Intracardiac Echocardiography in Interventional Cardiology: Working With the Anatomy Rather Than Fighting It.

PubMed

Enriquez, Andres; Saenz, Luis C; Rosso, Raphael; Silvestry, Frank E; Callans, David; Marchlinski, Francis E; Garcia, Fermin

2018-05-22

The indications for catheter-based structural and electrophysiological procedures have recently expanded to more complex scenarios, in which an accurate definition of the variable individual cardiac anatomy is key to obtain optimal results. Intracardiac echocardiography (ICE) is a unique imaging modality able to provide high-resolution real-time visualization of cardiac structures, continuous monitoring of catheter location within the heart, and early recognition of procedural complications, such as pericardial effusion or thrombus formation. Additional benefits are excellent patient tolerance, reduction of fluoroscopy time, and lack of need for general anesthesia or a second operator. For these reasons, ICE has largely replaced transesophageal echocardiography as ideal imaging modality for guiding certain procedures, such as atrial septal defect closure and catheter ablation of cardiac arrhythmias, and has an emerging role in others, including mitral valvuloplasty, transcatheter aortic valve replacement, and left atrial appendage closure. In electrophysiology procedures, ICE allows integration of real-time images with electroanatomic maps; it has a role in assessment of arrhythmogenic substrate, and it is particularly useful for mapping structures that are not visualized by fluoroscopy, such as the interatrial or interventricular septum, papillary muscles, and intracavitary muscular ridges. Most recently, a three-dimensional (3D) volumetric ICE system has also been developed, with potential for greater anatomic information and a promising role in structural interventions. In this state-of-the-art review, we provide guidance on how to conduct a comprehensive ICE survey and summarize the main applications of ICE in a variety of structural and electrophysiology procedures. © 2018 American Heart Association, Inc.

Risk of thromboembolic complications in adult congenital heart disease: A literature review.

PubMed

Karsenty, Clement; Zhao, Alexandre; Marijon, Eloi; Ladouceur, Magalie

2018-05-30

Adult congenital heart disease (ACHD) is a constantly expanding population with challenging issues. Initial medical and surgical treatments are seldom curative, and the majority of patients still experience late sequelae and complications, especially thromboembolic events. These common and potentially life-threating adverse events are probably dramatically underdiagnosed. Better identification and understanding of thromboembolic risk factors are essential to prevent long-term related morbidities. In addition to specific situations associated with a high risk of thromboembolic events (Fontan circulation, cyanotic congenital heart disease), atrial arrhythmia has been recognized as an important risk factor for thromboembolic events in ACHD. Unlike in patients without ACHD, thromboembolic risk stratification scores, such as the CHA 2 DS 2 -VASc score, may not be applicable in ACHD. Overall, after a review of the scientific data published so far, it is clear that the complexity of the underlying congenital heart disease represents a major risk factor for thromboembolic events. As a consequence, prophylactic anticoagulation is indicated in patients with complex congenital heart disease and atrial arrhythmia, regardless of the other risk factors, as opposed to simple heart defects. The landscape of ACHD is an ongoing evolving process, and specific thromboembolic risk scores are needed, especially in the setting of simple heart defects; these should be coupled with specific trials or long-term follow-up of multicentre cohorts. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Optogenetic pacing in Drosophila models (Conference Presentation)

NASA Astrophysics Data System (ADS)

Wu, Penghe; Li, Airong; Men, Jing; Tans, Rudolph E.; Zhou, Chao

2017-02-01

The Drosophila melanogaster shares many similarities with vertebrates in heart development. Comparison of heart structural and functional characteristic between male and female Drosophila melanogaster at different developmental stages is helpful to understand heart morphogenesis and function for different genders. And also, it opens up the possibility to uncover the role of sex-related genes in heart development. In this longitudinal study, we cultured and tracked dozens of individually labeled flies throughout their lifecycle. The heart characteristic was measured at different developmental stages during culturing. The gender of each individual fly was determined by adult stage so that the collected data of early stages could be classified to male or female group. We adapted a high-speed optical coherence microscopy (OCM) system with axial and transverse resolution of 2um and 4um, respectively, to perform non-invasive M-mode imaging at a frame rate of 132Hz in Drosophila heart at third instar larva, early pupa and adult stage. Based on those GPU processed M-mode OCM images, we segmented the fly heart region and then quantified the cardiac structural and functional parameters such as heart rate, heart chamber size and so on. Despite large variances of wild type Drosophila in terms of some cardiac characteristic, our results suggest that the heart rate is lower for male flies than for female flies, especially at third instar larva stage. The end diastolic area (EDA) and end systolic area (ESA) of the heart are both slightly larger in female flies than in male flies at larva and adult stage. In summary, we showed gender differences of wild type drosophila in heart functional and structural characteristic.

Imaging techniques for visualizing and phenotyping congenital heart defects in murine models.

PubMed

Liu, Xiaoqin; Tobita, Kimimasa; Francis, Richard J B; Lo, Cecilia W

2013-06-01

Mouse model is ideal for investigating the genetic and developmental etiology of congenital heart disease. However, cardiovascular phenotyping for the precise diagnosis of structural heart defects in mice remain challenging. With rapid advances in imaging techniques, there are now high throughput phenotyping tools available for the diagnosis of structural heart defects. In this review, we discuss the efficacy of four different imaging modalities for congenital heart disease diagnosis in fetal/neonatal mice, including noninvasive fetal echocardiography, micro-computed tomography (micro-CT), micro-magnetic resonance imaging (micro-MRI), and episcopic fluorescence image capture (EFIC) histopathology. The experience we have gained in the use of these imaging modalities in a large-scale mouse mutagenesis screen have validated their efficacy for congenital heart defect diagnosis in the tiny hearts of fetal and newborn mice. These cutting edge phenotyping tools will be invaluable for furthering our understanding of the developmental etiology of congenital heart disease. Copyright © 2013 Wiley Periodicals, Inc.

Mechanism of ubiquinol oxidation by the bc(1) complex: role of the iron sulfur protein and its mobility.

PubMed

Crofts, A R; Guergova-Kuras, M; Huang, L; Kuras, R; Zhang, Z; Berry, E A

1999-11-30

Native structures of ubihydroquinone:cytochrome c oxidoreductase (bc(1) complex) from different sources, and structures with inhibitors in place, show a 16-22 A displacement of the [2Fe-2S] cluster and the position of the C-terminal extrinsic domain of the iron sulfur protein. None of the structures shows a static configuration that would allow catalysis of all partial reactions of quinol oxidation. We have suggested that the different conformations reflect a movement of the subunit necessary for catalysis. The displacement from an interface with cytochrome c(1) in native crystals to an interface with cytochrome b is induced by stigmatellin or 5-n-undecyl-6-hydroxy-4,7-dioxobenzothiazole (UHDBT) and involves ligand formation between His-161 of the [2Fe-2S] binding cluster and the inhibitor. The movement is a rotational displacement, so that the same conserved docking surface on the iron sulfur protein interacts with cytochrome c(1) and with cytochrome b. The mobile extrinsic domain retains essentially the same tertiary structure, and the anchoring N-terminal tail remains in the same position. The movement occurs through an extension of a helical segment in the short linking span. We report details of the protein structure for the two main configurations in the chicken heart mitochondrial complex and discuss insights into mechanism provided by the structures and by mutant strains in which the docking at the cytochrome b interface is impaired. The movement of the iron sulfur protein represents a novel mechanism of electron transfer, in which a tethered mobile head allows electron transfer through a distance without the entropic loss from free diffusion.

Complex Regional Pain Syndrome

MedlinePlus

... Other major and minor traumas — such as surgery, heart attacks, infections and even sprained ankles — can also lead to complex regional pain syndrome. It's not well-understood why these injuries can trigger complex regional pain syndrome. Not everyone who has ...

Prenatal chromosomal microarray analysis in fetuses with congenital heart disease: a prospective cohort study.

PubMed

Wang, Yan; Cao, Li; Liang, Dong; Meng, Lulu; Wu, Yun; Qiao, Fengchang; Ji, Xiuqing; Luo, Chunyu; Zhang, Jingjing; Xu, Tianhui; Yu, Bin; Wang, Leilei; Wang, Ting; Pan, Qiong; Ma, Dingyuan; Hu, Ping; Xu, Zhengfeng

2018-02-01

Currently, chromosomal microarray analysis is considered the first-tier test in pediatric care and prenatal diagnosis. However, the diagnostic yield of chromosomal microarray analysis for prenatal diagnosis of congenital heart disease has not been evaluated based on a large cohort. Our aim was to evaluate the clinical utility of chromosomal microarray as the first-tier test for chromosomal abnormalities in fetuses with congenital heart disease. In this prospective study, 602 prenatal cases of congenital heart disease were investigated using single nucleotide polymorphism array over a 5-year period. Overall, pathogenic chromosomal abnormalities were identified in 125 (20.8%) of 602 prenatal cases of congenital heart disease, with 52.0% of them being numerical chromosomal abnormalities. The detection rates of likely pathogenic copy number variations and variants of uncertain significance were 1.3% and 6.0%, respectively. The detection rate of pathogenic chromosomal abnormalities in congenital heart disease plus additional structural anomalies (48.9% vs 14.3%, P < .0001) or intrauterine growth retardation group (50.0% vs 14.3%, P = .044) was significantly higher than that in isolated congenital heart disease group. Additionally, the detection rate in congenital heart disease with additional structural anomalies group was significantly higher than that in congenital heart disease with soft markers group (48.9% vs 19.8%, P < .0001). No significant difference was observed in the detection rates between congenital heart disease with additional structural anomalies and congenital heart disease with intrauterine growth retardation groups (48.9% vs 50.0%), congenital heart disease with soft markers and congenital heart disease with intrauterine growth retardation groups (19.8% vs 50.0%), or congenital heart disease with soft markers and isolated congenital heart disease groups (19.8% vs 14.3%). The detection rate in fetuses with congenital heart disease plus mild ventriculomegaly was significantly higher than in those with other types of soft markers (50.0% vs 15.6%, P < .05). Our study suggests chromosomal microarray analysis is a reliable and high-resolution technology and should be used as the first-tier test for prenatal diagnosis of congenital heart disease in clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

Study of Simvastatin Self-Association Using Electrospray-Ionization Mass Spectrometry

NASA Astrophysics Data System (ADS)

Vetrova, E. V.; Lekar, A. V.; Filonova, O. V.; Borisenko, S. N.; Maksimenko, E. V.; Borisenko, N. I.

2015-07-01

Self-association of simvastatin, which is widely used to treat coronary heart disease, was investigated using electrospray-ionization mass spectrometry. Formation of simvastatin self-associates in various solvents was demonstrated using mass spectrometry. Solvation effects were shown to play a special role in the formation of the self-associates. Self-associates containing from two to fi ve simvastatin molecules were detected in mass spectra of an aqueous MeOH (20%) solution of simvastatin. The formation of simvastatin self-associates could compete with the complexation of supramolecular structures during the synthesis of new generation drugs.

[Polycystic ovary syndrome: an example of obesity-related cardiovascular complication affecting young women].

PubMed

Orio, Francesco; Cascella, Teresa; Giallauria, Francesco; Palomba, Stefano; De Lorenzo, Anna; Lucci, Rosa; Ambrosino, Elena; Lombardi, Gaetano; Colao, Annamaria; Vigorito, Carlo

2006-03-01

Polycystic ovary syndrome (PCOS) is a good example of obesity-related cardiovascular complication affecting young women. PCOS is not only considered a reproductive problem but rather represents a complex endocrine, multifaceted syndrome with important health implications. Several evidences suggest an increased cardiovascular risk of cardiovascular disease associated with this syndrome, characterized by an impairment of heart structure and function, endothelial dysfunction and lipid abnormalities. All these features, probably linked to insulin-resistance, are often present in obese PCOS patients. Cardiovascular abnormalities represent important long-term sequelae of PCOS that need further investigations.

Cardiac haemangioma associated with a duct-dependent congenital heart disease in a newborn infant.

PubMed

Djordjevic, Stefan A; Glumac, Sofija; Kalanj, Jasna

2017-07-01

Cardiac haemangiomas are exceedingly rare; however, they can cause significant haemodynamic impairment and disturbances in heart rhythm. Rarely, cardiac tumours may also coexist with congenital heart lesions. We present an extremely unusual case of a cardiac haemangioma in the setting of complex transposition of the great arteries that caused functional tricuspid atresia. To our knowledge, this is the first such case described in the literature.

[Influence Mildrocard on the morfo-functional condition of cardio-respiratory system at patients with chronic heart failure with concomitant chronic obstructive pulmonary disease].

PubMed

Ignatenko, G A; Mukhin, I V; Faierman, A O; Pola, M K; Taktashov, G S; Goncharov, O M; Rybalko, G S; Volodkina, N O

2011-01-01

In paper influence of a cytoprotective drug "Mildrocard" on morfo-functional condition of cardiorespiratory system at patients with chronic heart failure with concomitant chronic obstructive pulmonary disease is estimated. It is established, that joining "Mildrocard" to complex therapy associated to pathology promotes reduction clinical display of heart failure, shows cardioprotective and pulmoprotective effects.

Surgical management of congenital heart disease: contribution of the Aristotle complexity score to planning and budgeting in the German diagnosis-related groups system.

PubMed

Sinzobahamvya, Nicodème; Photiadis, Joachim; Kopp, Thorsten; Arenz, Claudia; Haun, Christoph; Schindler, Ehrenfried; Hraska, Viktor; Asfour, Boulos

2012-01-01

Planning and budgeting for congenital heart surgery depend primarily on how closely reimbursement matches costs and on the number and complexity of the surgical procedures. Aristotle complexity scores for the year 2010 were correlated with hospital costs and with reimbursement according to the German diagnosis-related groups (DRG) system. Unit surgical performance was estimated as surgical performance (complexity score × hospital survival) times the number of primary procedures. This study investigated how this performance evolved during years 2006 to 2010. Hospital costs and reimbursements correlated highly with Aristotle comprehensive complexity levels (Spearman r = 1). Mean costs and reimbursement reached 35,050 ± 32,665 and 31,283 ± 34,732, respectively, for an underfunding of 10.7%. Basic and comprehensive unit surgical performances were respectively 3036 ± 1009 and 3891 ± 1591 points in 2006. Both performances increased in sigmoid fashion to reach 3883 ± 1344 and 5335 ± 1314 points, respectively, in 2010. Top performances would be achieved in year 2011, and extrapolated costs would comprise about 19,434,094.92 (95% confidence interval, 11,961,491.22-22,495,764.42). The current underfunding of congenital heart surgery needs correction. The Aristotle score can help to adjust reimbursement according to complexity of procedures. Unit surgical performance allows accurate budgeting in the current German DRG system.

Complexity of cardiac signals for predicting changes in alpha-waves after stress in patients undergoing cardiac catheterization

NASA Astrophysics Data System (ADS)

Chiu, Hung-Chih; Lin, Yen-Hung; Lo, Men-Tzung; Tang, Sung-Chun; Wang, Tzung-Dau; Lu, Hung-Chun; Ho, Yi-Lwun; Ma, Hsi-Pin; Peng, Chung-Kang

2015-08-01

The hierarchical interaction between electrical signals of the brain and heart is not fully understood. We hypothesized that the complexity of cardiac electrical activity can be used to predict changes in encephalic electricity after stress. Most methods for analyzing the interaction between the heart rate variability (HRV) and electroencephalography (EEG) require a computation-intensive mathematical model. To overcome these limitations and increase the predictive accuracy of human relaxing states, we developed a method to test our hypothesis. In addition to routine linear analysis, multiscale entropy and detrended fluctuation analysis of the HRV were used to quantify nonstationary and nonlinear dynamic changes in the heart rate time series. Short-time Fourier transform was applied to quantify the power of EEG. The clinical, HRV, and EEG parameters of postcatheterization EEG alpha waves were analyzed using change-score analysis and generalized additive models. In conclusion, the complexity of cardiac electrical signals can be used to predict EEG changes after stress.

Complexity of cardiac signals for predicting changes in alpha-waves after stress in patients undergoing cardiac catheterization

PubMed Central

Chiu, Hung-Chih; Lin, Yen-Hung; Lo, Men-Tzung; Tang, Sung-Chun; Wang, Tzung-Dau; Lu, Hung-Chun; Ho, Yi-Lwun; Ma, Hsi-Pin; Peng, Chung-Kang

2015-01-01

The hierarchical interaction between electrical signals of the brain and heart is not fully understood. We hypothesized that the complexity of cardiac electrical activity can be used to predict changes in encephalic electricity after stress. Most methods for analyzing the interaction between the heart rate variability (HRV) and electroencephalography (EEG) require a computation-intensive mathematical model. To overcome these limitations and increase the predictive accuracy of human relaxing states, we developed a method to test our hypothesis. In addition to routine linear analysis, multiscale entropy and detrended fluctuation analysis of the HRV were used to quantify nonstationary and nonlinear dynamic changes in the heart rate time series. Short-time Fourier transform was applied to quantify the power of EEG. The clinical, HRV, and EEG parameters of postcatheterization EEG alpha waves were analyzed using change-score analysis and generalized additive models. In conclusion, the complexity of cardiac electrical signals can be used to predict EEG changes after stress. PMID:26286628

Atrial fibrillation driver mechanisms: Insight from the isolated human heart.

PubMed

Csepe, Thomas A; Hansen, Brian J; Fedorov, Vadim V

2017-01-01

Although there have been great technological advances in the treatment of atrial fibrillation (AF), current therapies remain limited due to a narrow understanding of AF mechanisms in the human heart. This review will highlight our recent studies on explanted human hearts where we developed and employed a novel functional-structural mapping approach by integrating high-resolution simultaneous endo-epicardial and panoramic optical mapping with 3D gadolinium-enhanced MRI to define the spatiotemporal characteristics of AF drivers and their structural substrates. The results allow us to postulate that the primary mechanism of AF maintenance in human hearts is a limited number of localized intramural microanatomic reentrant AF drivers anchored to heart-specific 3D fibrotically insulated myobundle tracks, which may remain hidden to clinical single-surface electrode mapping. We suggest that ex vivo human heart studies, by using an integrated 3D functional and structural mapping approach, will help to reveal defining features of AF drivers as well as validate and improve clinical approaches to detect and target these AF drivers in patients with cardiac diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Complex sleep apnoea in congestive heart failure.

PubMed

Bitter, Thomas; Westerheide, Nina; Hossain, Mohammed Sajid; Lehmann, Roman; Prinz, Christian; Kleemeyer, Astrid; Horstkotte, Dieter; Oldenburg, Olaf

2011-05-01

Sleep disordered breathing is common and of prognostic significance in patients with congestive heart failure (CHF). Complex sleep apnoea (complexSA) is defined as the emergence of central sleep apnoea during continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnoea (OSA). This study aims to determine the prevalence and predictors for complexSA in patients with CHF with OSA, and to assess the effects of treatment with adaptive servoventilation. 192 patients with CHF (left ventricular ejection fraction (LVEF) ≤45%, New York Heart Association (NYHA) class ≥2) and OSA (apnoea-hypopnoea index (AHI) ≥15) were investigated using echocardiography, cardiopulmonary exercise testing, measurement of hyperoxic, hypercapnic ventilatory response, 6 min walk test and measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) prior to CPAP introduction. If patients demonstrated complexSA (AHI >15/h with <10% obstructive events) during CPAP titration, adaptive servoventilation was introduced and the investigations were repeated at 3 monthly follow-up visits. ComplexSA developed in 34 patients (18%) during CPAP titration. After adjustment for demographic and cardiac parameters, measures of CO(2) sensitivity (higher hyperoxic, hypercapnic ventilatory response) were independently associated with complexSA. Patients using adaptive servoventilation had improved AHI, NYHA class, NT-proBNP concentration, LVEF, hyperoxic, hypercapnic ventilatory response, oxygen uptake during cardiopulmonary exercise testing and the relationship between minute ventilation and the rate of CO(2) elimination (VE/Vco(2) slope) at last individual follow-up (14±4 months). There is a high prevalence of complexSA in patients with OSA and CHF, and those who develop complexSA have evidence of higher respiratory controller gain before application of CPAP. Treatment with adaptive servoventilation effectively suppressed complexSA and had positive effects on cardiac function and respiratory stability.

A Computer Story: Complexity from Simplicity

ERIC Educational Resources Information Center

DeLeo, Gary; Weidenhammer, Amanda; Wecht, Kristen

2012-01-01

In this technological age, digital devices are conspicuous examples of extraordinary complexity. When a user clicks on computer icons or presses calculator buttons, these devices channel electricity through a complex system of decision-making circuits. Yet, in spite of this remarkable complexity, the hearts of these devices are components that…

Developing an instrument to measure heart failure disease management program intensity and complexity.

PubMed

Riegel, Barbara; Lee, Christopher S; Sochalski, Julie

2010-05-01

Comparing disease management programs and their effects is difficult because of wide variability in program intensity and complexity. The purpose of this effort was to develop an instrument that can be used to describe the intensity and complexity of heart failure (HF) disease management programs. Specific composition criteria were taken from the American Heart Association (AHA) taxonomy of disease management and hierarchically scored to allow users to describe the intensity and complexity of the domains and subdomains of HF disease management programs. The HF Disease Management Scoring Instrument (HF-DMSI) incorporates 6 of the 8 domains from the taxonomy: recipient, intervention content, delivery personnel, method of communication, intensity/complexity, and environment. The 3 intervention content subdomains (education/counseling, medication management, and peer support) are described separately. In this first test of the HF-DMSI, overall intensity (measured as duration) and complexity were rated using an ordinal scoring system. Possible scores reflect a clinical rationale and differ by category, with zero given only if the element could potentially be missing (eg, surveillance by remote monitoring). Content validity was evident as the instrument matches the existing AHA taxonomy. After revision and refinement, 2 authors obtained an inter-rater reliability intraclass correlation coefficient score of 0.918 (confidence interval, 0.880 to 0.944, P<0.001) in their rating of 12 studies. The areas with most variability among programs were delivery personnel and method of communication. The HF-DMSI is useful for describing the intensity and complexity of HF disease management programs.

Helical structure of the cardiac ventricular anatomy assessed by diffusion tensor magnetic resonance imaging with multiresolution tractography.

PubMed

Poveda, Ferran; Gil, Debora; Martí, Enric; Andaluz, Albert; Ballester, Manel; Carreras, Francesc

2013-10-01

Deeper understanding of the myocardial structure linking the morphology and function of the heart would unravel crucial knowledge for medical and surgical clinical procedures and studies. Several conceptual models of myocardial fiber organization have been proposed but the lack of an automatic and objective methodology prevented an agreement. We sought to deepen this knowledge through advanced computer graphical representations of the myocardial fiber architecture by diffusion tensor magnetic resonance imaging. We performed automatic tractography reconstruction of unsegmented diffusion tensor magnetic resonance imaging datasets of canine heart from the public database of the Johns Hopkins University. Full-scale tractographies have been built with 200 seeds and are composed by streamlines computed on the vector field of primary eigenvectors at the diffusion tensor volumes. We also introduced a novel multiscale visualization technique in order to obtain a simplified tractography. This methodology retains the main geometric features of the fiber tracts, making it easier to decipher the main properties of the architectural organization of the heart. Output analysis of our tractographic representations showed exact correlation with low-level details of myocardial architecture, but also with the more abstract conceptualization of a continuous helical ventricular myocardial fiber array. Objective analysis of myocardial architecture by an automated method, including the entire myocardium and using several 3-dimensional levels of complexity, reveals a continuous helical myocardial fiber arrangement of both right and left ventricles, supporting the anatomical model of the helical ventricular myocardial band described by F. Torrent-Guasp. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Single-Cell Resolution of Temporal Gene Expression during Heart Development.

PubMed

DeLaughter, Daniel M; Bick, Alexander G; Wakimoto, Hiroko; McKean, David; Gorham, Joshua M; Kathiriya, Irfan S; Hinson, John T; Homsy, Jason; Gray, Jesse; Pu, William; Bruneau, Benoit G; Seidman, J G; Seidman, Christine E

2016-11-21

Activation of complex molecular programs in specific cell lineages governs mammalian heart development, from a primordial linear tube to a four-chamber organ. To characterize lineage-specific, spatiotemporal developmental programs, we performed single-cell RNA sequencing of >1,200 murine cells isolated at seven time points spanning embryonic day 9.5 (primordial heart tube) to postnatal day 21 (mature heart). Using unbiased transcriptional data, we classified cardiomyocytes, endothelial cells, and fibroblast-enriched cells, thus identifying markers for temporal and chamber-specific developmental programs. By harnessing these datasets, we defined developmental ages of human and mouse pluripotent stem-cell-derived cardiomyocytes and characterized lineage-specific maturation defects in hearts of mice with heterozygous mutations in Nkx2.5 that cause human heart malformations. This spatiotemporal transcriptome analysis of heart development reveals lineage-specific gene programs underlying normal cardiac development and congenital heart disease. Copyright © 2016 Elsevier Inc. All rights reserved.

There Is More to the Dissection of a Pig's Heart

ERIC Educational Resources Information Center

Lee, Yeung Chung

2004-01-01

The dissection of the mammalian heart in secondary biology classes need not be restricted to revealing the internal structure of the heart and its function. It could also be used to demonstrate other important aspects of blood circulation, including the blood supply to the heart itself as well as the causes and effects of coronary heart disease.…

Sex-related differences in the development of fetal heart rate dynamics.

PubMed

Kim, Kyu Nam; Park, Young-Sun; Hoh, Jeong-Kyu

2016-02-01

Despite previous efforts to explain the general advantages of female fetuses over males regarding health, sex-related differences in the dynamics or complexity of fetal heart rate (FHR) variability and FHR maturation patterns have not yet been identified. To make linear and nonlinear comparisons of antepartum FHR indices, dynamics, complexity, and reactivity to the non-stress test (NST) and vibroacoustic-stimulation test (VAST) in male and female fetuses. A total of 3835 singleton term deliveries without maternal and fetal complications were divided into female (n=1849) and male (n=1986) groups, and subjected to comparison and analyses. Linear FHR indices, approximate entropy (ApEn), sample entropy (SampEn), short-term/long-term exponents (α1/α2), correlation dimension (CD), NST and VAST criteria, and modified nonlinear reactive criteria (MNRC) were used to evaluate outcomes. ApEn was consistently higher in female fetuses than in male ones. ApEn in female fetuses was maximal at 29-30 gestational weeks, while the increase in ApEn was delayed in male fetuses but more rapid, reaching its peak at 31-32 gestational weeks. In both sexes, CD increased up to term, and α2 rapidly decreased up to 31-32weeks in an analogous manner. The two sexes differed significantly in response to VAST at <31 gestational weeks and there was a structural difference in reactive patterns under MNRC. Female fetuses exhibit greater heart rate dynamics in early gestational periods, suggesting that their cardiovascular system matures earlier than that of males. Male fetuses undergo a compensatory period of rapid change to catch up with females at term. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Spallanzani's mouse: a model of restoration and regeneration.

PubMed

Heber-Katz, E; Leferovich, J M; Bedelbaeva, K; Gourevitch, D

2004-01-01

The ability to regenerate is thought to be a lost phenotype in mammals, though there are certainly sporadic examples of mammalian regeneration. Our laboratory has identified a strain of mouse, the MRL mouse, which has a unique capacity to heal complex tissue in an epimorphic fashion, i.e., to restore a damaged limb or organ to its normal structure and function. Initial studies using through-and-through ear punches showed rapid full closure of the ear holes with cartilage growth, new hair follicles, and normal tissue architecture reminiscent of regeneration seen in amphibians as opposed to the scarring usually seen in mammals. Since the ear hole closure phenotype is a quantitative trait, this has been used to show-through extensive breeding and backcrossing--that the trait is heritable. Such analysis reveals that there is a complex genetic basis for this trait with multiple loci. One of the major phenotypes of the MRL mouse is a potent remodeling response with the absence or a reduced level of scarring. MRL healing is associated with the upregulation of the metalloproteinases MMP-2 and MMP-9 and the downregulation of their inhibitors TIMP-2 and TIMP-3, both present in inflammatory cells such as neutrophils and macrophages. This model has more recently been extended to the heart. In this case, a cryoinjury to the right ventricle leads to near complete scarless healing in the MRL mouse whereas scarring is seen in the control mouse. In the MRL heart, bromodeoxyuridine uptake by cardiomyocytes filling the wound site can be seen 60 days after injury. This does not occur in the control mouse. Function in the MRL heart, as measured by echocardiography, returns to normal.

At the Atrioventricular Crossroads: Dual Pathway Electrophysiology in the Atrioventricular Node and its Underlying Heterogeneities

PubMed Central

George, Sharon A; Faye, N Rokhaya; Murillo-Berlioz, Alejandro; Lee, K Benjamin; Trachiotis, Gregory D; Efimov, Igor R

2017-01-01

The atrioventricular node (AVN) is a complex structure that performs a variety of functions in the heart. The AVN is primarily an electrical gatekeeper between the atria and ventricles and introduces a delay between atrial and ventricular excitation, allowing for efficient ventricular filling. The AVN is composed of several compartments that safely transmit electrical excitation from the atria to the ventricles via the fast or slow pathways. There are many electrophysiological differences between these pathways, including conduction time and electrical refractoriness, that increase the predisposition of the atrioventricular junction to arrhythmias such as atrioventricular nodal re-entrant tachycardia. These varied electrophysiological characteristics of the fast and slow pathways stem from their unique structural and molecular composition (tissue and cellular geometry, ion channels and gap junctions). This review summarises the structural and molecular heterogeneities of the human AVN and how they result in electrophysiological variations and arrhythmias. PMID:29326832

Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink

PubMed Central

Pati, Falguni; Jang, Jinah; Ha, Dong-Heon; Won Kim, Sung; Rhie, Jong-Won; Shim, Jin-Hyung; Kim, Deok-Ho; Cho, Dong-Woo

2014-01-01

The ability to print and pattern all the components that make up a tissue (cells and matrix materials) in three dimensions to generate structures similar to tissues is an exciting prospect of bioprinting. However, the majority of the matrix materials used so far for bioprinting cannot represent the complexity of natural extracellular matrix (ECM) and thus are unable to reconstitute the intrinsic cellular morphologies and functions. Here, we develop a method for the bioprinting of cell-laden constructs with novel decellularized extracellular matrix (dECM) bioink capable of providing an optimized microenvironment conducive to the growth of three-dimensional structured tissue. We show the versatility and flexibility of the developed bioprinting process using tissue-specific dECM bioinks, including adipose, cartilage and heart tissues, capable of providing crucial cues for cells engraftment, survival and long-term function. We achieve high cell viability and functionality of the printed dECM structures using our bioprinting method. PMID:24887553

Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink

NASA Astrophysics Data System (ADS)

Pati, Falguni; Jang, Jinah; Ha, Dong-Heon; Won Kim, Sung; Rhie, Jong-Won; Shim, Jin-Hyung; Kim, Deok-Ho; Cho, Dong-Woo

2014-06-01

The ability to print and pattern all the components that make up a tissue (cells and matrix materials) in three dimensions to generate structures similar to tissues is an exciting prospect of bioprinting. However, the majority of the matrix materials used so far for bioprinting cannot represent the complexity of natural extracellular matrix (ECM) and thus are unable to reconstitute the intrinsic cellular morphologies and functions. Here, we develop a method for the bioprinting of cell-laden constructs with novel decellularized extracellular matrix (dECM) bioink capable of providing an optimized microenvironment conducive to the growth of three-dimensional structured tissue. We show the versatility and flexibility of the developed bioprinting process using tissue-specific dECM bioinks, including adipose, cartilage and heart tissues, capable of providing crucial cues for cells engraftment, survival and long-term function. We achieve high cell viability and functionality of the printed dECM structures using our bioprinting method.

Flow in prosthetic heart valves: state-of-the-art and future directions.

PubMed

Yoganathan, Ajit P; Chandran, K B; Sotiropoulos, Fotis

2005-12-01

Since the first successful implantation of a prosthetic heart valve four decades ago, over 50 different designs have been developed including both mechanical and bioprosthetic valves. Today, the most widely implanted design is the mechanical bileaflet, with over 170,000 implants worldwide each year. Several different mechanical valves are currently available and many of them have good bulk forward flow hemodynamics, with lower transvalvular pressure drops, larger effective orifice areas, and fewer regions of forward flow stasis than their earlier-generation counterparts such as the ball-and-cage and tilting-disc valves. However, mechanical valve implants suffer from complications resulting from thrombus deposition and patients implanted with these valves need to be under long-term anti-coagulant therapy. In general, blood thinners are not needed with bioprosthetic implants, but tissue valves suffer from structural failure with, an average life-time of 10-12 years, before replacement is needed. Flow-induced stresses on the formed elements in blood have been implicated in thrombus initiation within the mechanical valve prostheses. Regions of stress concentration on the leaflets during the complex motion of the leaflets have been implicated with structural failure of the leaflets with bioprosthetic valves. In vivo and in vitro experimental studies have yielded valuable information on the relationship between hemodynamic stresses and the problems associated with the implants. More recently, Computational Fluid Dynamics (CFD) has emerged as a promising tool, which, alongside experimentation, can yield insights of unprecedented detail into the hemodynamics of prosthetic heart valves. For CFD to realize its full potential, however, it must rely on numerical techniques that can handle the enormous geometrical complexities of prosthetic devices with spatial and temporal resolution sufficiently high to accurately capture all hemodynamically relevant scales of motion. Such algorithms do not exist today and their development should be a major research priority. For CFD to further gain the confidence of valve designers and medical practitioners it must also undergo comprehensive validation with experimental data. Such validation requires the use of high-resolution flow measuring tools and techniques and the integration of experimental studies with CFD modeling.

Energy expenditure in frontotemporal dementia: a behavioural and imaging study

PubMed Central

Ahmed, Rebekah M; Landin-Romero, Ramon; Collet, Tinh-Hai; van der Klaauw, Agatha A; Devenney, Emma; Henning, Elana; Kiernan, Matthew C; Piguet, Olivier; Farooqi, I Sadaf; Hodges, John R

2017-01-01

Abstract See Finger (doi:10.1093/aww312) for a scientific commentary on this article. Abnormal eating behaviour and metabolic parameters including insulin resistance, dyslipidaemia and body mass index are increasingly recognized as important components of neurodegenerative disease and may contribute to survival. It has previously been established that behavioural variant frontotemporal dementia is associated with abnormal eating behaviour characterized by increased sweet preference. In this study, it was hypothesized that behavioural variant frontotemporal dementia might also be associated with altered energy expenditure. A cohort of 19 patients with behavioural variant frontotemporal dementia, 13 with Alzheimer’s disease and 16 (age- and sex-matched) healthy control subjects were studied using Actiheart devices (CamNtech) to assess resting and stressed heart rate. Actiheart devices were fitted for 7 days to measure sleeping heart rate, activity levels, and resting, active and total energy expenditure. Using high resolution structural magnetic resonance imaging the neural correlates of increased resting heart rate were investigated including cortical thickness and region of interest analyses. In behavioural variant frontotemporal dementia, resting (P = 0.001), stressed (P = 0.037) and sleeping heart rate (P = 0.038) were increased compared to control subjects, and resting heart rate (P = 0.020) compared to Alzheimer disease patients. Behavioural variant frontotemporal dementia was associated with decreased activity levels compared to controls (P = 0.002) and increased resting energy expenditure (P = 0.045) and total energy expenditure (P = 0.035). Increased resting heart rate correlated with behavioural (Cambridge Behavioural Inventory) and cognitive measures (Addenbrooke’s Cognitive Examination). Increased resting heart rate in behavioural variant frontotemporal dementia correlated with atrophy involving the mesial temporal cortex, insula, and amygdala, regions previously suggested to be involved exclusively in social and emotion processing in frontotemporal dementia. These neural correlates overlap the network involved in eating behaviour in frontotemporal dementia, suggesting a complex interaction between eating behaviour, autonomic function and energy homeostasis. As such the present study suggests that increased heart rate and autonomic changes are prevalent in behavioural variant frontotemporal dementia, and are associated with changes in energy expenditure. An understanding of these changes and neural correlates may have potential relevance to disease progression and prognosis. PMID:27789521

Recurrence quantification analysis of heart rate variability and respiratory flow series in patients on weaning trials.

PubMed

Arcentales, Andrés; Giraldo, Beatriz F; Caminal, Pere; Benito, Salvador; Voss, Andreas

2011-01-01

Autonomic nervous system regulates the behavior of cardiac and respiratory systems. Its assessment during the ventilator weaning can provide information about physio-pathological imbalances. This work proposes a non linear analysis of the complexity of the heart rate variability (HRV) and breathing duration (T(Tot)) applying recurrence plot (RP) and their interaction joint recurrence plot (JRP). A total of 131 patients on weaning trials from mechanical ventilation were analyzed: 92 patients with successful weaning (group S) and 39 patients that failed to maintain spontaneous breathing (group F). The results show that parameters as determinism (DET), average diagonal line length (L), and entropy (ENTR), are statistically significant with RP for T(Tot) series, but not with HRV. When comparing the groups with JRP, all parameters have been relevant. In all cases, mean values of recurrence quantification analysis are higher in the group S than in the group F. The main differences between groups were found on the diagonal and vertical structures of the joint recurrence plot.

In Situ Optical Mapping of Voltage and Calcium in the Heart

PubMed Central

Ewart, Paul; Ashley, Euan A.; Loew, Leslie M.; Kohl, Peter; Bollensdorff, Christian; Woods, Christopher E.

2012-01-01

Electroanatomic mapping the interrelation of intracardiac electrical activation with anatomic locations has become an important tool for clinical assessment of complex arrhythmias. Optical mapping of cardiac electrophysiology combines high spatiotemporal resolution of anatomy and physiological function with fast and simultaneous data acquisition. If applied to the clinical setting, this could improve both diagnostic potential and therapeutic efficacy of clinical arrhythmia interventions. The aim of this study was to explore this utility in vivo using a rat model. To this aim, we present a single-camera imaging and multiple light-emitting-diode illumination system that reduces economic and technical implementation hurdles to cardiac optical mapping. Combined with a red-shifted calcium dye and a new near-infrared voltage-sensitive dye, both suitable for use in blood-perfused tissue, we demonstrate the feasibility of in vivo multi-parametric imaging of the mammalian heart. Our approach combines recording of electrophysiologically-relevant parameters with observation of structural substrates and is adaptable, in principle, to trans-catheter percutaneous approaches. PMID:22876327

[Organ damage and cardiorenal syndrome in acute heart failure].

PubMed

Casado Cerrada, Jesús; Pérez Calvo, Juan Ignacio

2014-03-01

Heart failure is a complex syndrome that affects almost all organs and systems of the body. Signs and symptoms of organ dysfunction, in particular kidney dysfunction, may be accentuated or become evident for the first time during acute decompensation of heart failure. Cardiorenal syndrome has been defined as the simultaneous dysfunction of both the heart and the kidney, regardless of which of the two organs may have suffered the initial damage and regardless also of their previous functional status. Research into the mechanisms regulating the complex relationship between the two organs is prompting the search for new biomarkers to help physicians detect renal damage in subclinical stages. Hence, a preventive approach to renal dysfunction may be adopted in the clinical setting in the near future. This article provides a general overview of cardiorenal syndrome and an update of the physiopathological mechanisms involved. Special emphasis is placed on the role of visceral congestion as an emergent mechanism in this syndrome. Copyright © 2014 Elsevier España, S.L. All rights reserved.

Experiences of mothers of infants with congenital heart disease before, during, and after complex cardiac surgery.

PubMed

Harvey, Kayla A; Kovalesky, Andrea; Woods, Ronald K; Loan, Lori A

2013-01-01

Experiences of mothers of infants undergoing complex heart surgery were explored to build evidence-based family-centered interventions. Congenital heart disease is the most frequent birth defect in the United States and is common worldwide. Eight mothers recalled through journal entries their experiences of the days before, during, and after their infant's surgery and shared advice for other mothers. Colaizzi's phenomenological method was utilized for data analysis. A validation survey of seven additional mothers from a support group occurred via email. Six themes were identified and validated: Feeling Intense Fluctuating Emotion; Navigating the Medical World; Dealing with the Unknown; Facing the Possibility of My Baby Dying, Finding Meaning and Spiritual Connection, and the umbrella theme of Mothering Through It All. Through a clearer understanding of experiences as described by mothers, health-care providers may gain insight as to how to better support mothers of infants undergoing heart surgery. Copyright © 2013 Elsevier Inc. All rights reserved.

Deficiency in Cardiac Dystrophin Affects the Abundance of the α-/β-Dystroglycan Complex

PubMed Central

2005-01-01

Although Duchenne muscular dystrophy is primarily categorised as a skeletal muscle disease, deficiency in the membrane cytoskeletal protein dystrophin also affects the heart. The central transsarcolemmal linker between the actin membrane cytoskeleton and the extracellular matrix is represented by the dystrophin-associated dystroglycans. Chemical cross-linking analysis revealed no significant differences in the dimeric status of the α-/β-dystroglycan subcomplex in the dystrophic mdx heart as compared to normal cardiac tissue. In analogy to skeletal muscle fibres, heart muscle also exhibited a greatly reduced abundance of both dystroglycans in dystrophin-deficient cells. Immunoblotting demonstrated that the degree of reduction in α-dystroglycan is more pronounced in matured mdx skeletal muscle as contrasted to the mdx heart. The fact that the deficiency in dystrophin triggers a similar pathobiochemical response in both types of muscle suggests that the cardiomyopathic complications observed in x-linked muscular dystrophy might be initiated by the loss of the dystrophin-associated surface glycoprotein complex. PMID:15689636

Studying the Microanatomy of the Heart in Three Dimensions: A Practical Update

PubMed Central

Jarvis, Jonathan C.; Stephenson, Robert

2013-01-01

The structure and function of the heart needs to be understood in three dimensions. We give a brief historical summary of the methods by which such an understanding has been sought, and some practical details of the relatively new technique of micro-CT with iodine contrast enhancement in samples from rat and rabbit. We discuss how the improved anatomical detail available in fixed cadaveric hearts will enhance our ability to model and to understand the integrated function of the cardiomyocytes, conducting tissues, and fibrous supporting structures that generate the pumping function of the heart. PMID:24400272

Complex regression Doppler optical coherence tomography

NASA Astrophysics Data System (ADS)

Elahi, Sahar; Gu, Shi; Thrane, Lars; Rollins, Andrew M.; Jenkins, Michael W.

2018-04-01

We introduce a new method to measure Doppler shifts more accurately and extend the dynamic range of Doppler optical coherence tomography (OCT). The two-point estimate of the conventional Doppler method is replaced with a regression that is applied to high-density B-scans in polar coordinates. We built a high-speed OCT system using a 1.68-MHz Fourier domain mode locked laser to acquire high-density B-scans (16,000 A-lines) at high enough frame rates (˜100 fps) to accurately capture the dynamics of the beating embryonic heart. Flow phantom experiments confirm that the complex regression lowers the minimum detectable velocity from 12.25 mm / s to 374 μm / s, whereas the maximum velocity of 400 mm / s is measured without phase wrapping. Complex regression Doppler OCT also demonstrates higher accuracy and precision compared with the conventional method, particularly when signal-to-noise ratio is low. The extended dynamic range allows monitoring of blood flow over several stages of development in embryos without adjusting the imaging parameters. In addition, applying complex averaging recovers hidden features in structural images.

Bone marrow cells adopt the cardiomyogenic fate in vivo

PubMed Central

Rota, Marcello; Kajstura, Jan; Hosoda, Toru; Bearzi, Claudia; Vitale, Serena; Esposito, Grazia; Iaffaldano, Grazia; Padin-Iruegas, M. Elena; Gonzalez, Arantxa; Rizzi, Roberto; Small, Narissa; Muraski, John; Alvarez, Roberto; Chen, Xiongwen; Urbanek, Konrad; Bolli, Roberto; Houser, Steven R.; Leri, Annarosa; Sussman, Mark A.; Anversa, Piero

2007-01-01

The possibility that adult bone marrow cells (BMCs) retain a remarkable degree of developmental plasticity and acquire the cardiomyocyte lineage after infarction has been challenged, and the notion of BMC transdifferentiation has been questioned. The center of the controversy is the lack of unequivocal evidence in favor of myocardial regeneration by the injection of BMCs in the infarcted heart. Because of the interest in cell-based therapy for heart failure, several approaches including gene reporter assay, genetic tagging, cell genotyping, PCR-based detection of donor genes, and direct immunofluorescence with quantum dots were used to prove or disprove BMC transdifferentiation. Our results indicate that BMCs engraft, survive, and grow within the spared myocardium after infarction by forming junctional complexes with resident myocytes. BMCs and myocytes express at their interface connexin 43 and N-cadherin, and this interaction may be critical for BMCs to adopt the cardiomyogenic fate. With time, a large number of myocytes and coronary vessels are generated. Myocytes show a diploid DNA content and carry, at most, two sex chromosomes. Old and new myocytes show synchronicity in calcium transients, providing strong evidence in favor of the functional coupling of these two cell populations. Thus, BMCs transdifferentiate and acquire the cardiomyogenic and vascular phenotypes restoring the infarcted heart. Together, our studies reveal that locally delivered BMCs generate de novo myocardium composed of integrated cardiomyocytes and coronary vessels. This process occurs independently of cell fusion and ameliorates structurally and functionally the outcome of the heart after infarction. PMID:17965233

Determinants of Adiponectin Levels in Patients with Chronic Systolic Heart Failure

PubMed Central

Biolo, Andreia; Shibata, Rei; Ouchi, Noriyuki; Kihara, Shinji; Sonoda, Mina; Walsh, Kenneth; Sam, Flora

2010-01-01

Adiponectin, an adipocytokine, is secreted by adipocytes and mediates anti-hypertrophic and anti-inflammatory effects in the heart. Plasma concentrations of adiponectin are decreased in obesity, insulin resistance and obesity-associated conditions such as hypertension and coronary heart disease. However, a paradoxical increase in adiponectin levels is observed in human systolic heart failure (HF). We sought to investigate the determinants of adiponectin levels in patients with chronic systolic HF. Total adiponectin levels were measured in 99 patients with stable HF and left ventricular (LV) ejection fraction (EF) <40%. Determinants of adiponectin levels by univariate analysis were included in a multivariate linear regression model. At baseline patients were 62% black, 63% male, mean age of 60±13 years, LVEF of 21±9% and a body mass index (BMI) of 30.6±6.7kg/m2. Mean adiponectin levels were 15.8±15µg/ml. Beta-blocker use, BMI, and blood urea nitrogen (BUN) were significant determinants of adiponectin levels by multivariate analysis. LV mass, structure, and LVEF were not related to adiponectin levels by multivariate analysis. Interestingly, the effect of beta-blocker therapy was most marked in non-obese patients with BMI < 30kg/m2. In conclusion, in chronic systolic HF patients, beta-blocker therapy is correlated with lower adiponectin levels, especially in non-obese patients. This relation should be taken into account when studying the complex role of adiponectin in chronic systolic HF. PMID:20381668

Abnormal lung function in adults with congenital heart disease: prevalence, relation to cardiac anatomy, and association with survival.

PubMed

Alonso-Gonzalez, Rafael; Borgia, Francesco; Diller, Gerhard-Paul; Inuzuka, Ryo; Kempny, Aleksander; Martinez-Naharro, Ana; Tutarel, Oktay; Marino, Philip; Wustmann, Kerstin; Charalambides, Menelaos; Silva, Margarida; Swan, Lorna; Dimopoulos, Konstantinos; Gatzoulis, Michael A

2013-02-26

Restrictive lung defects are associated with higher mortality in patients with acquired chronic heart failure. We investigated the prevalence of abnormal lung function, its relation to severity of underlying cardiac defect, its surgical history, and its impact on outcome across the spectrum of adult congenital heart disease. A total of 1188 patients with adult congenital heart disease (age, 33.1±13.1 years) undergoing lung function testing between 2000 and 2009 were included. Patients were classified according to the severity of lung dysfunction based on predicted values of forced vital capacity. Lung function was normal in 53% of patients with adult congenital heart disease, mildly impaired in 17%, and moderately to severely impaired in the remainder (30%). Moderate to severe impairment of lung function related to complexity of underlying cardiac defect, enlarged cardiothoracic ratio, previous thoracotomy/ies, body mass index, scoliosis, and diaphragm palsy. Over a median follow-up period of 6.7 years, 106 patients died. Moderate to severe impairment of lung function was an independent predictor of survival in this cohort. Patients with reduced force vital capacity of at least moderate severity had a 1.6-fold increased risk of death compared with patients with normal lung function (P=0.04). A reduced forced vital capacity is prevalent in patients with adult congenital heart disease; its severity relates to the complexity of the underlying heart defect, surgical history, and scoliosis. Moderate to severe impairment of lung function is an independent predictor of mortality in contemporary patients with adult congenital heart disease.

Selective Heart, Brain and Body Perfusion in Open Aortic Arch Replacement.

PubMed

Maier, Sven; Kari, Fabian; Rylski, Bartosz; Siepe, Matthias; Benk, Christoph; Beyersdorf, Friedhelm

2016-09-01

Open aortic arch replacement is a complex and challenging procedure, especially in post dissection aneurysms and in redo procedures after previous surgery of the ascending aorta or aortic root. We report our experience with the simultaneous selective perfusion of heart, brain, and remaining body to ensure optimal perfusion and to minimize perfusion-related risks during these procedures. We used a specially configured heart-lung machine with a centrifugal pump as arterial pump and an additional roller pump for the selective cerebral perfusion. Initial arterial cannulation is achieved via femoral artery or right axillary artery. After lower body circulatory arrest and selective antegrade cerebral perfusion for the distal arch anastomosis, we started selective lower body perfusion simultaneously to the selective antegrade cerebral perfusion and heart perfusion. Eighteen patients were successfully treated with this perfusion strategy from October 2012 to November 2015. No complications related to the heart-lung machine and the cannulation occurred during the procedures. Mean cardiopulmonary bypass time was 239 ± 33 minutes, the simultaneous selective perfusion of brain, heart, and remaining body lasted 55 ± 23 minutes. One patient suffered temporary neurological deficit that resolved completely during intensive care unit stay. No patient experienced a permanent neurological deficit or end-organ dysfunction. These high-risk procedures require a concept with a special setup of the heart-lung machine. Our perfusion strategy for aortic arch replacement ensures a selective perfusion of heart, brain, and lower body during this complex procedure and we observed excellent outcomes in this small series. This perfusion strategy is also applicable for redo procedures.

The Infant with Aortic Arch Hypoplasia and Small Left Heart Structures: Echocardiographic Indices of Mitral and Aortic Hypoplasia Predicting Successful Biventricular Repair.

PubMed

Plymale, Jennifer M; Frommelt, Peter C; Nugent, Melodee; Simpson, Pippa; Tweddell, James S; Shillingford, Amanda J

2017-08-01

In infants with aortic arch hypoplasia and small left-sided cardiac structures, successful biventricular repair is dependent on the adequacy of the left-sided structures. Defining accurate thresholds of echocardiographic indices predictive of successful biventricular repair is paramount to achieving optimal outcomes. We sought to identify pre-operative echocardiographic indices of left heart size that predict intervention-free survival in infants with small left heart structures undergoing primary aortic arch repair to establish biventricular circulation (BVC). Infants ≤2 months undergoing aortic arch repair from 1999 to 2010 with aortic and/or mitral valve hypoplasia, (Z-score ≤-2) were included. Pre-operative and follow-up echocardiograms were reviewed. Primary outcome was successful biventricular circulation (BVC), defined as freedom from death, transplant, or single ventricular conversion at 1 year. Need for catheter based or surgical re-intervention (RI), valve annular growth, and significant late aortic or mitral valve obstruction were additional outcomes. Fifty one of 73 subjects (79%) had successful BVC and were free of RI at 1 year. Seven subjects failed BVC; four of those died. The overall 1 year survival for the cohort was 95%. Fifteen subjects underwent a RI but maintained BVC. In univariate analysis, larger transverse aorta (p = 0.006) and aortic valve (p = 0.02) predicted successful BVC without RI. In CART analysis, the combination of mitral valve (MV) to tricuspid valve (TV) ratio ≤0.66 with an aortic valve (AV) annulus Z-score ≤-3 had the greatest power to predict BVC failure (sensitivity 71%, specificity 94%). In those with successful BVC, the combination of both AV and MV Z-score ≤-2.5 increased the odds of RI (OR 3.8; CI 1.3-11.4). Follow-up of non-RI subjects revealed improvement in AV and MV Z-score (median AV annulus changed over time from -2.34 to 0.04 (p < 0.001) and MV changed from -2.88 to -1.41 (p < 0.001), but residual mitral valve stenosis and aortic arch obstruction were present in one-third of subjects. In this cohort of infants requiring initial aortic arch repair with concomitant small left heart structures, successful BVC can be predicted from combined echocardiographic indices. In this complex population, 1 year survival is high, but the need for RI and the presence of residual lesions are common.

Supravalvar mitral ring with a parachute mitral valve and subcoarctation of the aorta in a child with hemodynamically significant VSD. A study of the morphology, echocardiographic diagnostics and surgical therapy.

PubMed

Mądry, Wojciech; Karolczak, Maciej A; Grabowski, Krzysztof

2017-09-01

The authors present a case of echocardiographic diagnosis of supravalvar mitral ring (a fibromembranous structure that arose from the atrial surface of the mitral leaflets) in a child with a parachute mitral valve, a ventricular septal defect, and mild narrowing of the aortic isthmus. The supravalvar mitral stenosis is a typical but very infrequently detected element of the complex of anatomical abnormalities located within the left heart and the proximal aorta, called the Shone's complex (syndrome). Diagnosing an additional, hemodynamically significant anatomic defect during echocardiography was possible thanks to the detection of marked mobility limitation of the ring-adjacent part of the mitral valve mural leaflet as well as of an atypical image of turbulence occurring during the inflow from the left atrium to the left ventricle. The early diagnosis made it possible to perform complete correction of this complex congenital defect within a single operation.

3D bioprinting of tissues and organs.

PubMed

Murphy, Sean V; Atala, Anthony

2014-08-01

Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.

Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association.

PubMed

Baddour, Larry M; Wilson, Walter R; Bayer, Arnold S; Fowler, Vance G; Tleyjeh, Imad M; Rybak, Michael J; Barsic, Bruno; Lockhart, Peter B; Gewitz, Michael H; Levison, Matthew E; Bolger, Ann F; Steckelberg, James M; Baltimore, Robert S; Fink, Anne M; O'Gara, Patrick; Taubert, Kathryn A

2015-10-13

Infective endocarditis is a potentially lethal disease that has undergone major changes in both host and pathogen. The epidemiology of infective endocarditis has become more complex with today's myriad healthcare-associated factors that predispose to infection. Moreover, changes in pathogen prevalence, in particular a more common staphylococcal origin, have affected outcomes, which have not improved despite medical and surgical advances. This statement updates the 2005 iteration, both of which were developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It includes an evidence-based system for diagnostic and treatment recommendations used by the American College of Cardiology and the American Heart Association for treatment recommendations. Infective endocarditis is a complex disease, and patients with this disease generally require management by a team of physicians and allied health providers with a variety of areas of expertise. The recommendations provided in this document are intended to assist in the management of this uncommon but potentially deadly infection. The clinical variability and complexity in infective endocarditis, however, dictate that these recommendations be used to support and not supplant decisions in individual patient management. © 2015 American Heart Association, Inc.

Surgical management of congenital heart disease: correlation between hospital costs and the Aristotle complexity score.

PubMed

Sinzobahamvya, N; Kopp, T; Photiadis, J; Arenz, C; Schindler, E; Haun, C; Hraska, V; Asfour, B

2010-09-01

Hospital costs are expected to correlate with clinical complexity. Do costs for congenital heart surgery correlate with Aristotle complexity scores? 442 inpatient stays in 2008 were evaluated. Aristotle scores and levels were determined. Costs were estimated according to the German Institute for Hospital Reimbursement system. Pearson and Spearman R correlation coefficients and corresponding goodness-of-fit regression coefficients R2 were calculated. Mean basic and comprehensive Aristotle scores were 7.60 +/- 2.74 and 9.23 +/- 2.94 points, respectively. Mean expenses per hospital stay amounted to 29,369 +/- 30,823 Euros. Aristotle basic and comprehensive scores and levels were positively correlated with hospital costs. With a Spearman R of 1 and related R2 of 0.9436, scores of the 6 Aristotle comprehensive levels correlated best. Mean hospital reimbursement was 26,412 +/- 17,962 Euros. Compensation was higher than expenses for patients in comprehensive levels 1 to 3, but much lower for those in levels 4 to 6. Aristotle comprehensive complexity scores were highly correlated with hospital costs. The Aristotle score could be used as a scale to establish the correct reimbursement after congenital heart surgery. Georg Thieme Verlag KG Stuttgart, New York.

Specialized probes based on hydroxyapatite calcium for heart tissues research by atomic force microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhukov, Mikhail, E-mail: cloudjyk@yandex.ru; Golubok, Alexander; Institute for Analytical Instrumentation, Russian Academy of Sciences

The new specialized AFM-probes with hydroxyapatite structures for atomic force microscopy of heart tissues calcification were created and studied. A process of probe fabrication is demonstrated. The adhesive forces between specialized hydroxyapatite probe and endothelium/subendothelial layers were investigated. It was found that the adhesion forces are significantly higher for the subendothelial layers. We consider that it is connected with the formation and localization of hydroxyapatite in the area of subendothelial layers of heart tissues. In addition, the roughness analysis and structure visualization of the endothelial surface of the heart tissue were carried out. The results show high efficiency of createdmore » specialized probes at study a calcinations process of the aortic heart tissues.« less

Cardiomyocyte-Specific Ablation of Med1 Subunit of the Mediator Complex Causes Lethal Dilated Cardiomyopathy in Mice.

PubMed

Jia, Yuzhi; Chang, Hsiang-Chun; Schipma, Matthew J; Liu, Jing; Shete, Varsha; Liu, Ning; Sato, Tatsuya; Thorp, Edward B; Barger, Philip M; Zhu, Yi-Jun; Viswakarma, Navin; Kanwar, Yashpal S; Ardehali, Hossein; Thimmapaya, Bayar; Reddy, Janardan K

2016-01-01

Mediator, an evolutionarily conserved multi-protein complex consisting of about 30 subunits, is a key component of the polymerase II mediated gene transcription. Germline deletion of the Mediator subunit 1 (Med1) of the Mediator in mice results in mid-gestational embryonic lethality with developmental impairment of multiple organs including heart. Here we show that cardiomyocyte-specific deletion of Med1 in mice (csMed1-/-) during late gestational and early postnatal development by intercrossing Med1fl/fl mice to α-MyHC-Cre transgenic mice results in lethality within 10 days after weaning due to dilated cardiomyopathy-related ventricular dilation and heart failure. The csMed1-/- mouse heart manifests mitochondrial damage, increased apoptosis and interstitial fibrosis. Global gene expression analysis revealed that loss of Med1 in heart down-regulates more than 200 genes including Acadm, Cacna1s, Atp2a2, Ryr2, Pde1c, Pln, PGC1α, and PGC1β that are critical for calcium signaling, cardiac muscle contraction, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy and peroxisome proliferator-activated receptor regulated energy metabolism. Many genes essential for oxidative phosphorylation and proper mitochondrial function such as genes coding for the succinate dehydrogenase subunits of the mitochondrial complex II are also down-regulated in csMed1-/- heart contributing to myocardial injury. Data also showed up-regulation of about 180 genes including Tgfb2, Ace, Atf3, Ctgf, Angpt14, Col9a2, Wisp2, Nppa, Nppb, and Actn1 that are linked to cardiac muscle contraction, cardiac hypertrophy, cardiac fibrosis and myocardial injury. Furthermore, we demonstrate that cardiac specific deletion of Med1 in adult mice using tamoxifen-inducible Cre approach (TmcsMed1-/-), results in rapid development of cardiomyopathy and death within 4 weeks. We found that the key findings of the csMed1-/- studies described above are highly reproducible in TmcsMed1-/- mouse heart. Collectively, these observations suggest that Med1 plays a critical role in the maintenance of heart function impacting on multiple metabolic, compensatory and reparative pathways with a likely therapeutic potential in the management of heart failure.

Scleraxis is required for cell lineage differentiation and extracellular matrix remodeling during murine heart valve formation in vivo.

PubMed

Levay, Agata K; Peacock, Jacqueline D; Lu, Yinhui; Koch, Manuel; Hinton, Robert B; Kadler, Karl E; Lincoln, Joy

2008-10-24

Heart valve structures, derived from mesenchyme precursor cells, are composed of differentiated cell types and extracellular matrix arranged to facilitate valve function. Scleraxis (scx) is a transcription factor required for tendon cell differentiation and matrix organization. This study identified high levels of scx expression in remodeling heart valve structures at embryonic day 15.5 through postnatal stages using scx-GFP reporter mice and determined the in vivo function using mice null for scx. Scx(-/-) mice display significantly thickened heart valve structures from embryonic day 17.5, and valves from mutant mice show alterations in valve precursor cell differentiation and matrix organization. This is indicated by decreased expression of the tendon-related collagen type XIV, increased expression of cartilage-associated genes including sox9, as well as persistent expression of mesenchyme cell markers including msx1 and snai1. In addition, ultrastructure analysis reveals disarray of extracellular matrix and collagen fiber organization within the valve leaflet. Thickened valve structures and increased expression of matrix remodeling genes characteristic of human heart valve disease are observed in juvenile scx(-/-) mice. In addition, excessive collagen deposition in annular structures within the atrioventricular junction is observed. Collectively, our studies have identified an in vivo requirement for scx during valvulogenesis and demonstrate its role in cell lineage differentiation and matrix distribution in remodeling valve structures.

A holistic approach to managing a patient with heart failure.

PubMed

Duncan, Alison; Cunnington, Colin

2013-03-01

Despite varied and complex therapeutic strategies for managing patients with heart failure, the prognosis may remain poor in certain groups. Recognition that patients with heart failure frequently require input from many care groups formed the basis of The British Society of Heart Failure Annual Autumn Meeting in London (UK), in November 2012, entitled: 'Heart failure: a multidisciplinary approach'. Experts in cardiology, cardiac surgery, general practice, care of the elderly, palliative care and cardiac imaging shared their knowledge and expertise. The 2-day symposium was attended by over 500 participants from the UK, Europe and North America, and hosted physicians, nurses, scientists, trainees and representatives from the industry, as well as patient and community groups. The symposium, accredited by the Royal College of Physicians and the Royal College of Nursing, focused on the multidisciplinary approach to heart failure, in particular, current therapeutic advances, cardiac remodeling, palliative care, atrial fibrillation, heart rate-lowering therapies, management of acute heart failure and the management of patients with mitral regurgitation and heart failure.

Pulmonary function and adverse cardiovascular outcomes: Can cardiac function explain the link?

PubMed

Burroughs Peña, Melissa S; Dunning, Allison; Schulte, Phillip J; Durheim, Michael T; Kussin, Peter; Checkley, William; Velazquez, Eric J

2016-12-01

The complex interaction between pulmonary function, cardiac function and adverse cardiovascular events has only been partially described. We sought to describe the association between pulmonary function with left heart structure and function, all-cause mortality and incident cardiovascular hospitalization. This study is a retrospective analysis of patients evaluated in a single tertiary care medical center. We used multivariable linear regression analyses to examine the relationship between FVC and FEV1 with left ventricular ejection fraction (LVEF), left ventricular internal dimension in systole and diastole (LVIDS, LVIDD) and left atrial diameter, adjusting for baseline characteristics, right ventricular function and lung hyperinflation. We also used Cox proportional hazards models to examine the relationship between FVC and FEV1 with all-cause mortality and cardiac hospitalization. A total of 1807 patients were included in this analysis with a median age of 61 years and 50% were female. Decreased FVC and FEV1 were both associated with decreased LVEF. In individuals with FVC less than 2.75 L, decreased FVC was associated with increased all-cause mortality after adjusting for left and right heart echocardiographic variables (hazard ratio [HR] 0.49, 95% CI 0.29, 0.82, respectively). Decreased FVC was associated with increased cardiac hospitalization after adjusting for left heart size (HR 0.80, 95% CI 0.67, 0.96), even in patients with normal LVEF (HR 0.75, 95% CI 0.57, 0.97). In a tertiary care center reduced pulmonary function was associated with adverse cardiovascular events, a relationship that is not fully explained by left heart remodeling or right heart dysfunction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sliding to predict: vision-based beating heart motion estimation by modeling temporal interactions.

PubMed

Aviles-Rivero, Angelica I; Alsaleh, Samar M; Casals, Alicia

2018-03-01

Technical advancements have been part of modern medical solutions as they promote better surgical alternatives that serve to the benefit of patients. Particularly with cardiovascular surgeries, robotic surgical systems enable surgeons to perform delicate procedures on a beating heart, avoiding the complications of cardiac arrest. This advantage comes with the price of having to deal with a dynamic target which presents technical challenges for the surgical system. In this work, we propose a solution for cardiac motion estimation. Our estimation approach uses a variational framework that guarantees preservation of the complex anatomy of the heart. An advantage of our approach is that it takes into account different disturbances, such as specular reflections and occlusion events. This is achieved by performing a preprocessing step that eliminates the specular highlights and a predicting step, based on a conditional restricted Boltzmann machine, that recovers missing information caused by partial occlusions. We carried out exhaustive experimentations on two datasets, one from a phantom and the other from an in vivo procedure. The results show that our visual approach reaches an average minima in the order of magnitude of [Formula: see text] while preserving the heart's anatomical structure and providing stable values for the Jacobian determinant ranging from 0.917 to 1.015. We also show that our specular elimination approach reaches an accuracy of 99% compared to a ground truth. In terms of prediction, our approach compared favorably against two well-known predictors, NARX and EKF, giving the lowest average RMSE of 0.071. Our approach avoids the risks of using mechanical stabilizers and can also be effective for acquiring the motion of organs other than the heart, such as the lung or other deformable objects.

Integration of nodal and BMP signals in the heart requires FoxH1 to create left-right differences in cell migration rates that direct cardiac asymmetry.

PubMed

Lenhart, Kari F; Holtzman, Nathalia G; Williams, Jessica R; Burdine, Rebecca D

2013-01-01

Failure to properly establish the left-right (L/R) axis is a major cause of congenital heart defects in humans, but how L/R patterning of the embryo leads to asymmetric cardiac morphogenesis is still unclear. We find that asymmetric Nodal signaling on the left and Bmp signaling act in parallel to establish zebrafish cardiac laterality by modulating cell migration velocities across the L/R axis. Moreover, we demonstrate that Nodal plays the crucial role in generating asymmetry in the heart and that Bmp signaling via Bmp4 is dispensable in the presence of asymmetric Nodal signaling. In addition, we identify a previously unappreciated role for the Nodal-transcription factor FoxH1 in mediating cell responsiveness to Bmp, further linking the control of these two pathways in the heart. The interplay between these TGFβ pathways is complex, with Nodal signaling potentially acting to limit the response to Bmp pathway activation and the dosage of Bmp signals being critical to limit migration rates. These findings have implications for understanding the complex genetic interactions that lead to congenital heart disease in humans.

Actin cytoskeletal remodeling with protrusion formation is essential for heart regeneration in Hippo-deficient mice

PubMed Central

Morikawa, Yuka; Zhang, Min; Heallen, Todd; Leach, John; Tao, Ge; Xiao, Yang; Bai, Yan; Li, Wei; Willerson, James T.; Martin, James F.

2015-01-01

The mammalian heart regenerates poorly, and damage commonly leads to heart failure. Hippo signaling is an evolutionarily conserved kinase cascade that regulates organ size during development and prevents adult mammalian cardiomyocyte regeneration by inhibiting the transcriptional coactivator Yap, which also responds to mechanical signaling in cultured cells to promote cell proliferation. To identify Yap target genes that are activated during cardiomyocyte renewal and regeneration, we performed Yap chromatin immunoprecipitation sequencing (ChIP-Seq) and mRNA expression profiling in Hippo signaling-deficient mouse hearts. We found that Yap directly regulated genes encoding cell cycle progression proteins, as well as genes encoding proteins that promote F-actin polymerization and that link the actin cytoskeleton to the extracellular matrix. Included in the latter group were components of the dystrophin glycoprotein complex (DGC), a large molecular complex that, when defective, results in muscular dystrophy in humans. Cardiomyocytes near scar tissue of injured Hippo signaling-deficient mouse hearts showed cellular protrusions suggestive of cytoskeletal remodeling. The hearts of mdx mutant mice, which lack functional dystrophin and are a model for muscular dystrophy, showed impaired regeneration and cytoskeleton remodeling, but normal cardiomyocyte proliferation after injury. Our data showed that, in addition to genes encoding cell cycle progression proteins, Yap regulated genes that enhance cytoskeletal remodeling Thus, blocking the Hippo pathway input to Yap may tip the balance so that Yap responds to the mechanical changes associated with heart injury to promote repair. PMID:25943351

Construct validity of the Chinese version of the Self-care of Heart Failure Index determined using structural equation modeling.

PubMed

Kang, Xiaofeng; Dennison Himmelfarb, Cheryl R; Li, Zheng; Zhang, Jian; Lv, Rong; Guo, Jinyu

2015-01-01

The Self-care of Heart Failure Index (SCHFI) is an empirically tested instrument for measuring the self-care of patients with heart failure. The aim of this study was to develop a simplified Chinese version of the SCHFI and provide evidence for its construct validity. A total of 182 Chinese with heart failure were surveyed. A 2-step structural equation modeling procedure was applied to test construct validity. Factor analysis showed 3 factors explaining 43% of the variance. Structural equation model confirmed that self-care maintenance, self-care management, and self-care confidence are indeed indicators of self-care, and self-care confidence was a positive and equally strong predictor of self-care maintenance and self-care management. Moreover, self-care scores were correlated with the Partners in Health Scale, indicating satisfactory concurrent validity. The Chinese version of the SCHFI is a theory-based instrument for assessing self-care of Chinese patients with heart failure.

Large Mammalian Animal Models of Heart Disease

PubMed Central

Camacho, Paula; Fan, Huimin; Liu, Zhongmin; He, Jia-Qiang

2016-01-01

Due to the biological complexity of the cardiovascular system, the animal model is an urgent pre-clinical need to advance our knowledge of cardiovascular disease and to explore new drugs to repair the damaged heart. Ideally, a model system should be inexpensive, easily manipulated, reproducible, a biological representative of human disease, and ethically sound. Although a larger animal model is more expensive and difficult to manipulate, its genetic, structural, functional, and even disease similarities to humans make it an ideal model to first consider. This review presents the commonly-used large animals—dog, sheep, pig, and non-human primates—while the less-used other large animals—cows, horses—are excluded. The review attempts to introduce unique points for each species regarding its biological property, degrees of susceptibility to develop certain types of heart diseases, and methodology of induced conditions. For example, dogs barely develop myocardial infarction, while dilated cardiomyopathy is developed quite often. Based on the similarities of each species to the human, the model selection may first consider non-human primates—pig, sheep, then dog—but it also depends on other factors, for example, purposes, funding, ethics, and policy. We hope this review can serve as a basic outline of large animal models for cardiovascular researchers and clinicians. PMID:29367573

Coronary veins determine the pattern of sympathetic innervation in the developing heart

PubMed Central

Nam, Joseph; Onitsuka, Izumi; Hatch, John; Uchida, Yutaka; Ray, Saugata; Huang, Siyi; Li, Wenling; Zang, Heesuk; Ruiz-Lozano, Pilar; Mukouyama, Yoh-suke

2013-01-01

Anatomical congruence of peripheral nerves and blood vessels is well recognized in a variety of tissues. Their physical proximity and similar branching patterns suggest that the development of these networks might be a coordinated process. Here we show that large diameter coronary veins serve as an intermediate template for distal sympathetic axon extension in the subepicardial layer of the dorsal ventricular wall of the developing mouse heart. Vascular smooth muscle cells (VSMCs) associate with large diameter veins during angiogenesis. In vivo and in vitro experiments demonstrate that these cells mediate extension of sympathetic axons via nerve growth factor (NGF). This association enables topological targeting of axons to final targets such as large diameter coronary arteries in the deeper myocardial layer. As axons extend along veins, arterial VSMCs begin to secrete NGF, which allows axons to reach target cells. We propose a sequential mechanism in which initial axon extension in the subepicardium is governed by transient NGF expression by VSMCs as they are recruited to coronary veins; subsequently, VSMCs in the myocardium begin to express NGF as they are recruited by remodeling arteries, attracting axons toward their final targets. The proposed mechanism underlies a distinct, stereotypical pattern of autonomic innervation that is adapted to the complex tissue structure and physiology of the heart. PMID:23462468

Improving finite element results in modeling heart valve mechanics.

PubMed

Earl, Emily; Mohammadi, Hadi

2018-06-01

Finite element analysis is a well-established computational tool which can be used for the analysis of soft tissue mechanics. Due to the structural complexity of the leaflet tissue of the heart valve, the currently available finite element models do not adequately represent the leaflet tissue. A method of addressing this issue is to implement computationally expensive finite element models, characterized by precise constitutive models including high-order and high-density mesh techniques. In this study, we introduce a novel numerical technique that enhances the results obtained from coarse mesh finite element models to provide accuracy comparable to that of fine mesh finite element models while maintaining a relatively low computational cost. Introduced in this study is a method by which the computational expense required to solve linear and nonlinear constitutive models, commonly used in heart valve mechanics simulations, is reduced while continuing to account for large and infinitesimal deformations. This continuum model is developed based on the least square algorithm procedure coupled with the finite difference method adhering to the assumption that the components of the strain tensor are available at all nodes of the finite element mesh model. The suggested numerical technique is easy to implement, practically efficient, and requires less computational time compared to currently available commercial finite element packages such as ANSYS and/or ABAQUS.

Rare association of anophthalmia, complex congenital heart disease and pulmonary hypertension: case report.

PubMed

Ríos-Méndez, Raúl Enrique; Lozano Chinga, Michell Marola

2016-10-07

Clinical congenital anophthalmia is described as the uni- or bilateral absence of the eyeball that might occur in isolation or as part of a syndrome. It has a very low prevalence and its etiology is heterogeneous. Complex congenital cardiac malformations are also rare. The association of congenital anophthalmia and congenital heart disease is rarer still, and the etiology of those associations is not well understood yet. We report the case of a patient who had the very rare association of bilateral anophthalmia, multiple cardiac malformations and severe pulmonary hypertension.

Zebrafish heart failure models: opportunities and challenges.

PubMed

Shi, Xingjuan; Chen, Ru; Zhang, Yu; Yun, Junghwa; Brand-Arzamendi, Koroboshka; Liu, Xiangdong; Wen, Xiao-Yan

2018-05-03

Heart failure is a complex pathophysiological syndrome of pumping functional failure that results from injury, infection or toxin-induced damage on the myocardium, as well as genetic influence. Gene mutations associated with cardiomyopathies can lead to various pathologies of heart failure. In recent years, zebrafish, Danio rerio, has emerged as an excellent model to study human cardiovascular diseases such as congenital heart defects, cardiomyopathy, and preclinical development of drugs targeting these diseases. In this review, we will first summarize zebrafish genetic models of heart failure arose from cardiomyopathy, which is caused by mutations in sarcomere, calcium or mitochondrial-associated genes. Moreover, we outline zebrafish heart failure models triggered by chemical compounds. Elucidation of these models will improve the understanding of the mechanism of pathogenesis and provide potential targets for novel therapies.

The role of nitric oxide in regulation of the cardiovascular system in reptiles.

PubMed

Skovgaard, Nini; Galli, Gina; Abe, Augusto; Taylor, Edwin W; Wang, Tobias

2005-10-01

The roles that nitric oxide (NO) plays in the cardiovascular system of reptiles are reviewed, with particular emphasis on its effects on central vascular blood flows in the systemic and pulmonary circulations. New data is presented that describes the effects on hemodynamic variables in varanid lizards of exogenously administered NO via the nitric oxide donor sodium nitroprusside (SNP) and inhibition of nitric oxide synthase (NOS) by l-nitroarginine methyl ester (l-NAME). Furthermore, preliminary data on the effects of SNP on hemodynamic variables in the tegu lizard are presented. The findings are compared with previously published data from our laboratory on three other species of reptiles: pythons (), rattlesnakes () and turtles (). These five species of reptiles possess different combinations of division of the heart and structural complexity of the lungs. Comparison of their responses to NO donors and NOS inhibitors may reveal whether the potential contribution of NO to vascular tone correlates with pulmonary complexity and/or with blood pressure. All existing studies on reptiles have clearly established a potential role for NO in regulating vascular tone in the systemic circulation and NO may be important for maintaining basal systemic vascular tone in varanid lizards, pythons and turtles, through a continuous release of NO. In contrast, the pulmonary circulation is less responsive to NO donors or NOS inhibitors, and it was only in pythons and varanid lizards that the lungs responded to SNP. Both species have a functionally separated heart, so it is possible that NO may exert a larger role in species with low pulmonary blood pressures, irrespective of lung complexity.

4D blood flow mapping using SPIM-microPIV in the developing zebrafish heart

NASA Astrophysics Data System (ADS)

Zickus, Vytautas; Taylor, Jonathan M.

2018-02-01

Fluid-structure interaction in the developing heart is an active area of research in developmental biology. However, investigation of heart dynamics is mostly limited to computational uid dynamics simulations using heart wall structure information only, or single plane blood ow information - so there is a need for 3D + time resolved data to fully understand cardiac function. We present an imaging platform combining selective plane illumination microscopy (SPIM) with micro particle image velocimetry (μPIV) to enable 3D-resolved flow mapping in a microscopic environment, free from many of the sources of error and bias present in traditional epi uorescence-based μPIV systems. By using our new system in conjunction with optical heart beat synchronization, we demonstrate the ability obtain non-invasive 3D + time resolved blood flow measurements in the heart of a living zebrafish embryo.

Regression equations for calculation of z scores for echocardiographic measurements of right heart structures in healthy Han Chinese children.

PubMed

Wang, Shan-Shan; Zhang, Yu-Qi; Chen, Shu-Bao; Huang, Guo-Ying; Zhang, Hong-Yan; Zhang, Zhi-Fang; Wu, Lan-Ping; Hong, Wen-Jing; Shen, Rong; Liu, Yi-Qing; Zhu, Jun-Xue

2017-06-01

Clinical decision making in children with congenital and acquired heart disease relies on measurements of cardiac structures using two-dimensional echocardiography. We aimed to establish z-score regression equations for right heart structures in healthy Chinese Han children. Two-dimensional and M-mode echocardiography was performed in 515 patients. We measured the dimensions of the pulmonary valve annulus (PVA), main pulmonary artery (MPA), left pulmonary artery (LPA), right pulmonary artery (RPA), right ventricular outflow tract at end-diastole (RVOTd) and at end-systole (RVOTs), tricuspid valve annulus (TVA), right ventricular inflow tract at end-diastole (RVIDd) and at end-systole (RVIDs), and right atrium (RA). Regression analyses were conducted to relate the measurements of right heart structures to 4body surface area (BSA). Right ventricular outflow-tract fractional shortening (RVOTFS) was also calculated. Several models were used, and the best model was chosen to establish a z-score calculator. PVA, MPA, LPA, RPA, RVOTd, RVOTs, TVA, RVIDd, RVIDs, and RA (R 2  = 0.786, 0.705, 0.728, 0.701, 0.706, 0.824, 0.804, 0.663, 0.626, and 0.793, respectively) had a cubic polynomial relationship with BSA; specifically, measurement (M) = β0 + β1 × BSA + β2 × BSA 2  + β3 × BSA. 3 RVOTFS (0.28 ± 0.02) fell within a narrow range (0.12-0.51). Our results provide reference values for z scores and regression equations for right heart structures in Han Chinese children. These data may help interpreting the routine clinical measurement of right heart structures in children with congenital or acquired heart disease. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:293-303, 2017. © 2017 Wiley Periodicals, Inc.

Cardiac structure and function across the glycemic spectrum in elderly men and women free of prevalent heart disease: the Atherosclerosis Risk In the Community study.

PubMed

Skali, Hicham; Shah, Amil; Gupta, Deepak K; Cheng, Susan; Claggett, Brian; Liu, Jiankang; Bello, Natalie; Aguilar, David; Vardeny, Orly; Matsushita, Kunihiro; Selvin, Elizabeth; Solomon, Scott

2015-05-01

Individuals with diabetes mellitus and pre-diabetes mellitus are at particularly high risk of incident heart failure or death, even after accounting for known confounders. Nevertheless, the extent of impairments in cardiac structure and function in elderly individuals with diabetes mellitus and pre-diabetes mellitus is not well known. We aimed to assess the relationship between echocardiographic measures of cardiac structure and function and dysglycemia. We assessed measures of cardiac structure and function in 4419 participants without prevalent coronary heart disease or heart failure who attended the Atherosclerosis Risk In the Community (ARIC) visit 5 examination (2011-2013) and underwent transthoracic echocardiography (age, 75±6 years; 61% women, 23% black). Subjects were grouped across the dysglycemia spectrum as normal (39%), pre-diabetes mellitus (31%), or diabetes mellitus (30%) based on medical history, antidiabetic medication use, and glycated hemoglobin levels. Glycemic status was related to measures of cardiac structure and function. Worsening dysglycemia was associated with increased left ventricular mass, worse diastolic function, and subtle reduction in left ventricular systolic function (P≤0.01 for all). For every 1% higher glycated hemoglobin, left ventricular mass was higher by 3.0 g (95% confidence interval, 1.5-4.6 g), E/E' by 0.5 (95% confidence interval, 0.4-0.7), and global longitudinal strain by 0.3% (95% confidence interval, 0.2-0.4) in multivariable analyses. In a large contemporary biracial cohort of elderly subjects without prevalent cardiovascular disease or heart failure, dysglycemia was associated with subtle and subclinical alterations of cardiac structure, and left ventricular systolic and diastolic function. It remains unclear whether these are sufficient to explain the heightened risk of heart failure in individuals with diabetes mellitus. © 2015 American Heart Association, Inc.

EDUCATIONAL SERIES IN CONGENITAL HEART DISEASE: Congenital left-sided heart obstruction

PubMed Central

Carr, Michelle; Curtis, Stephanie; Marek, Jan

2018-01-01

Congenital obstruction of the left ventricular outflow tract remains a significant problem and multilevel obstruction can often coexist. Obstruction can take several morphological forms and may involve the subvalvar, valvar or supravalvar portion of the aortic valve complex. Congenital valvar stenosis presenting in the neonatal period represents a spectrum of disorders ranging from the hypoplastic left heart syndrome to almost normal hearts. Treatment options vary dependent on the severity of the left ventricular outflow tract obstruction (LVOTO) and the variable degree of left ventricular hypoplasia as well as the associated lesions such as arch hypoplasia and coarctation. PMID:29681546

Heart Failure: From Research to Clinical Practice.

PubMed

Islam, Md Shahidul

2018-01-01

"Heart failure: from research to clinical practice", a collection of selected reviews, which comes out also as a book, covers essentially all important aspects of heart failure, including the pathogenesis, clinical features, biomarkers, imaging techniques, medical treatment and surgical treatments, use of pacemakers and implantable cardioverter defibrillators, and palliative care. The reviews include essential background information, state of the art, critical and in-depth analysis, and directions for future researches for elucidation of the unresolved issues. Everyone interested in heart failure is expected to find this compilation helpful for a deeper understanding of some of the complex issues.

A perspective on diuretic resistance in chronic congestive heart failure.

PubMed

Shah, Niel; Madanieh, Raef; Alkan, Mehmet; Dogar, Muhammad U; Kosmas, Constantine E; Vittorio, Timothy J

2017-10-01

Chronic congestive heart failure (CHF) is a complex disorder characterized by inability of the heart to keep up the demands on it, followed by the progressive pump failure and fluid accumulation. Although the loop diuretics are widely used in heart failure (HF) patients, both pharmacodynamic and pharmacokinetic alterations are thought to be responsible for diuretic resistance in these patients. Strategies to overcome diuretic resistance include sodium intake restriction, changes in diuretic dose and route of administration and sequential nephron diuretic therapy. In this review, we discuss the definition, prevalence, mechanism of development and management strategies of diuretic resistance in HF patients.

Statistical physics and physiology: monofractal and multifractal approaches

NASA Technical Reports Server (NTRS)

Stanley, H. E.; Amaral, L. A.; Goldberger, A. L.; Havlin, S.; Peng, C. K.

1999-01-01

Even under healthy, basal conditions, physiologic systems show erratic fluctuations resembling those found in dynamical systems driven away from a single equilibrium state. Do such "nonequilibrium" fluctuations simply reflect the fact that physiologic systems are being constantly perturbed by external and intrinsic noise? Or, do these fluctuations actually, contain useful, "hidden" information about the underlying nonequilibrium control mechanisms? We report some recent attempts to understand the dynamics of complex physiologic fluctuations by adapting and extending concepts and methods developed very recently in statistical physics. Specifically, we focus on interbeat interval variability as an important quantity to help elucidate possibly non-homeostatic physiologic variability because (i) the heart rate is under direct neuroautonomic control, (ii) interbeat interval variability is readily measured by noninvasive means, and (iii) analysis of these heart rate dynamics may provide important practical diagnostic and prognostic information not obtainable with current approaches. The analytic tools we discuss may be used on a wider range of physiologic signals. We first review recent progress using two analysis methods--detrended fluctuation analysis and wavelets--sufficient for quantifying monofractual structures. We then describe recent work that quantifies multifractal features of interbeat interval series, and the discovery that the multifractal structure of healthy subjects is different than that of diseased subjects.

Social Vocalizations of Big Brown Bats Vary with Behavioral Context

PubMed Central

Gadziola, Marie A.; Grimsley, Jasmine M. S.; Faure, Paul A.; Wenstrup, Jeffrey J.

2012-01-01

Bats are among the most gregarious and vocal mammals, with some species demonstrating a diverse repertoire of syllables under a variety of behavioral contexts. Despite extensive characterization of big brown bat (Eptesicus fuscus) biosonar signals, there have been no detailed studies of adult social vocalizations. We recorded and analyzed social vocalizations and associated behaviors of captive big brown bats under four behavioral contexts: low aggression, medium aggression, high aggression, and appeasement. Even limited to these contexts, big brown bats possess a rich repertoire of social vocalizations, with 18 distinct syllable types automatically classified using a spectrogram cross-correlation procedure. For each behavioral context, we describe vocalizations in terms of syllable acoustics, temporal emission patterns, and typical syllable sequences. Emotion-related acoustic cues are evident within the call structure by context-specific syllable types or variations in the temporal emission pattern. We designed a paradigm that could evoke aggressive vocalizations while monitoring heart rate as an objective measure of internal physiological state. Changes in the magnitude and duration of elevated heart rate scaled to the level of evoked aggression, confirming the behavioral state classifications assessed by vocalizations and behavioral displays. These results reveal a complex acoustic communication system among big brown bats in which acoustic cues and call structure signal the emotional state of a caller. PMID:22970247

Brain alpha-ketoglutarate dehydrogenase complex: kinetic properties, regional distribution, and effects of inhibitors.

PubMed

Lai, J C; Cooper, A J

1986-11-01

The substrate and cofactor requirements and some kinetic properties of the alpha-ketoglutarate dehydrogenase complex (KGDHC; EC 1.2.4.2, EC 2.3.1.61, and EC 1.6.4.3) in purified rat brain mitochondria were studied. Brain mitochondrial KGDHC showed absolute requirement for alpha-ketoglutarate, CoA and NAD, and only partial requirement for added thiamine pyrophosphate, but no requirement for Mg2+ under the assay conditions employed in this study. The pH optimum was between 7.2 and 7.4, but, at pH values below 7.0 or above 7.8, KGDHC activity decreased markedly. KGDHC activity in various brain regions followed the rank order: cerebral cortex greater than cerebellum greater than or equal to midbrain greater than striatum = hippocampus greater than hypothalamus greater than pons and medulla greater than olfactory bulb. Significant inhibition of brain mitochondrial KGDHC was noted at pathological concentrations of ammonia (0.2-2 mM). However, the purified bovine heart KGDHC and KGDHC activity in isolated rat heart mitochondria were much less sensitive to inhibition. At 5 mM both beta-methylene-D,L-aspartate and D,L-vinylglycine (inhibitors of cerebral glucose oxidation) inhibited the purified heart but not the brain mitochondrial enzyme complex. At approximately 10 microM, calcium slightly stimulated (by 10-15%) the brain mitochondrial KGDHC. At concentrations above 100 microM, calcium (IC50 = 1 mM) inhibited both brain mitochondrial and purified heart KGDHC. The present results suggest that some of the kinetic properties of the rat brain mitochondrial KGDHC differ from those of the purified bovine heart and rat heart mitochondrial enzyme complexes. They also suggest that the inhibition of KGDHC by ammonia and the consequent effect on the citric acid cycle fluxes may be of pathophysiological and/or pathogenetic importance in hyperammonemia and in diseases (e.g., hepatic encephalopathy, inborn errors of urea metabolism, Reye's syndrome) where hyperammonemia is a consistent feature. Brain accumulation of calcium occurs in a number of pathological conditions. Therefore, it is possible that such a calcium accumulation may have a deleterious effect on KGDHC activity.

American Heart Association's Life's Simple 7: Avoiding Heart Failure and Preserving Cardiac Structure and Function.

PubMed

Folsom, Aaron R; Shah, Amil M; Lutsey, Pamela L; Roetker, Nicholas S; Alonso, Alvaro; Avery, Christy L; Miedema, Michael D; Konety, Suma; Chang, Patricia P; Solomon, Scott D

2015-09-01

Many people may underappreciate the role of lifestyle in avoiding heart failure. We estimated whether greater adherence in middle age to American Heart Association's Life's Simple 7 guidelines—on smoking, body mass, physical activity, diet, cholesterol, blood pressure, and glucose—is associated with lower lifetime risk of heart failure and greater preservation of cardiac structure and function in old age. We studied the population-based Atherosclerosis Risk in Communities Study cohort of 13,462 adults ages 45-64 years in 1987-1989. From the 1987-1989 risk factor measurements, we created a Life's Simple 7 score (range 0-14, giving 2 points for ideal, 1 point for intermediate, and 0 points for poor components). We identified 2218 incident heart failure events using surveillance of hospital discharge and death codes through 2011. In addition, in 4855 participants free of clinical cardiovascular disease in 2011-2013, we performed echocardiography from which we quantified left ventricular hypertrophy and diastolic dysfunction. One in four participants (25.5%) developed heart failure through age 85 years. Yet, this lifetime heart failure risk was 14.4% for those with a middle-age Life's Simple 7 score of 10-14 (optimal), 26.8% for a score of 5-9 (average), and 48.6% for a score of 0-4 (inadequate). Among those with no clinical cardiovascular event, the prevalence of left ventricular hypertrophy in late life was approximately 40% as common, and diastolic dysfunction was approximately 60% as common, among those with an optimal middle-age Life's Simple 7 score, compared with an inadequate score. Greater achievement of American Heart Association's Life's Simple 7 in middle age is associated with a lower lifetime occurrence of heart failure and greater preservation of cardiac structure and function. Copyright © 2015 Elsevier Inc. All rights reserved.

Risk factors and outcomes of in-hospital cardiac arrest following pediatric heart operations of varying complexity.

PubMed

Gupta, Punkaj; Rettiganti, Mallikarjuna; Jeffries, Howard E; Scanlon, Matthew C; Ghanayem, Nancy S; Daufeldt, Jennifer; Rice, Tom B; Wetzel, Randall C

2016-08-01

Multi center data regarding cardiac arrest in children undergoing heart operations of varying complexity are limited. Children <18 years undergoing heart surgery (with or without cardiopulmonary bypass) in the Virtual Pediatric Systems (VPS, LLC) Database (2009-2014) were included. Multivariable mixed logistic regression models were adjusted for patient's characteristics, surgical risk category (STS-EACTS Categories 1, 2, and 3 classified as "low" complexity and Categories 4 and 5 classified as "high" complexity), and hospital characteristics. Overall, 26,909 patients (62 centers) were included. Of these, 2.7% had cardiac arrest after cardiac surgery with an associated mortality of 31%. The prevalence of cardiac arrest was lower among patients undergoing low complexity operations (low complexity vs. high complexity: 1.7% vs. 5.9%). Unadjusted outcomes after cardiac arrest were significantly better among patients undergoing low complexity operations (mortality: 21.6% vs. 39.1%, good neurological outcomes: 78.7% vs. 71.6%). In adjusted models, odds of cardiac arrest were significantly lower among patients undergoing low complexity operations (OR: 0.55, 95% CI: 0.46-0.66). Adjusted models, however, showed no difference in mortality or neurological outcomes after cardiac arrest regardless of surgical complexity. Further, our results suggest that incidence of cardiac arrest and mortality after cardiac arrest are a function of patient characteristics, surgical risk category, and hospital characteristics. Presence of around the clock in-house attending level pediatric intensivist coverage was associated with lower incidence of post-operative cardiac arrest, and presence of a dedicated cardiac ICU was associated with lower mortality after cardiac arrest. This study suggests that the patients undergoing high complexity operations are a higher risk group with increased prevalence of post-operative cardiac arrest. These data further suggest that patients undergoing high complexity operations can be rescued after cardiac arrest with a high survival rate. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Direct reading of electrocardiograms and respiration rates

NASA Technical Reports Server (NTRS)

Wise, J. P.

1969-01-01

Technique for reading heart and respiration rates is more accurate and direct than the previous method. Index of a plastic calibrated card is aligned with a point on the electrocardiogram. Complexes are counted as indicated on the card and heart or respiration rate is read directly from the appropriate scale.

The Role of Beta-Blocker in Heart Failure in Adults with Congenital Heart Disease.

PubMed

Norozi, Kambiz

2014-01-01

Thanks to the enormous progress in the field of cardiac surgery and paediatric cardiology since the mid of 20th century, more and more children with congenital heart defects reach the adulthood. This on the other hand encounter physician and patients various problems due to late complications after the heart surgery like congestive heart failure, arrhythmia and sudden death. One of the challenging area is the medical management of heart failure in these patients with complex anatomy and hemodynamics. The lack of evidence of the effectiveness of the anti congestive medications in this population in from of large randomized controlled trials, makes it difficult to establish universally accepted therapy guidelines. In this article we will review the evidence of the beta-blockers in heart failure in patients with congenital heart disease. Also we will discuss the mechanisms of heart failure in this patient's cohort and will review the literature with respect to the use of neurohormonal antagonists in congenital heart disease. There is an urgent need to initiate well-designed clinical trials to prove if the positive results of neurohormonal blockade in acquired heart failure in adults can be translated in patients with congenital heart disease.

Radiofrequency catheter ablation of ventricular tachycardia in patients without structural heart disease.

PubMed

Klein, L S; Shih, H T; Hackett, F K; Zipes, D P; Miles, W M

1992-05-01

Radiofrequency energy has been used safely and successfully to eliminate accessory pathways in patients with the Wolff-Parkinson-White syndrome and the substrate for atrioventricular nodal reentrant tachycardia. However, this form of ablation has had only limited success in eliminating ventricular tachycardia in patients with structural heart disease. In contrast, direct-current catheter ablation has been used successfully to eliminate ventricular tachycardia in patients with and without structural heart disease. The purpose of this study was to test whether radiofrequency energy can safely and effectively ablate ventricular tachycardia in patients without structural heart disease. Sixteen patients (nine women and seven men; mean age, 38 years; range, 18-55 years) without structural heart disease who had ventricular tachycardia underwent radiofrequency catheter ablation to eliminate the ventricular tachycardia. Two patients presented with syncope, nine with presyncope, and five with palpitations only. Mean duration of symptoms was 6.7 years (range, 0.5-20 years). Radiofrequency catheter ablation successfully eliminated ventricular tachycardia in 15 of 16 patients (94%). Sites of ventricular tachycardia origin included the high right ventricular outflow tract (12 patients), the right ventricular septum near the tricuspid valve (three patients), and the left ventricular septum (one patient). The only ablation failure was in a patient whose ventricular tachycardia arose from a region near the His bundle. An accurate pace map, early local endocardial activation, and firm catheter contact with endocardium were associated with successful ablation. Radiofrequency ablation did not cause arrhythmias, produced minimal cardiac enzyme rise, and resulted in no detectable change in cardiac function by Doppler echocardiography. Radiofrequency catheter ablation of ventricular tachycardia in patients without structural heart disease is effective and safe and may be considered as early therapy in these patients.

Heart rate-induced modifications of concentric left ventricular hypertrophy: exploration of a novel therapeutic concept.

PubMed

Klein, Franziska J; Bell, Stephen; Runte, K Elisabeth; Lobel, Robert; Ashikaga, Takamuru; Lerman, Lilach O; LeWinter, Martin M; Meyer, Markus

2016-10-01

Lowering the heart rate is considered to be beneficial in heart failure (HF) with reduced ejection fraction (HFrEF). In a dilated left ventricle (LV), pharmacological heart rate lowering is associated with a reduction in LV chamber size. In patients with HFrEF, this structural change is associated with better survival. HF with preserved ejection fraction (HFpEF) is increasingly prevalent but, so far, without any evidence-based treatment. HFpEF is typically associated with LV concentric remodeling and hypertrophy. The effects of heart rate on this structural phenotype are not known. Analogous with the benefits of a low heart rate on a dilated heart, we hypothesized that increased heart rates could lead to potentially beneficial remodeling of a concentrically hypertrophied LV. This was explored in an established porcine model of concentric LV hypertrophy and fibrosis. Our results suggest that a moderate increase in heart rate can be used to reduce wall thickness, normalize LV chamber volumes, decrease myocardial fibrosis, and improve LV compliance. Our results also indicate that the effects of heart rate can be titrated, are reversible, and do not induce HF. These findings may provide the rationale for a novel therapeutic approach for HFpEF and its antecedent disease substrate. Copyright © 2016 the American Physiological Society.

Heart disease and gender in mass print media.

PubMed

Clarke, Juanne

2010-03-01

Heart disease is a major cause of death, disease and disability in the developed world for both men and women. Women appear to be under-diagnosed and treated both because they fail to visit the doctor or hospital with relevant symptoms and because doctors tend to dismiss the seriousness of women's symptoms of heart disease. This review examined the way that popular mass print media present the possible association between gender and heart disease. It found that there was: [1] an under-representation of heart disease as a possible concern to women, [2] a dismissing or sensationalization of women's heart disease, [3] a tendency to blame women's complex menopausal bodies for the causes of heart disease, [4] an association of women with the heart disease of their husbands, [5] a linking of heart disease with masculinity and [6] a promotion of the idea of the need for women to fear of heart disease and the necessity of taking cholesterol-lowering drugs. The review concluded with suggestions for further research and for practice. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Nonlinear dynamics in cardiac conduction

NASA Technical Reports Server (NTRS)

Kaplan, D. T.; Smith, J. M.; Saxberg, B. E.; Cohen, R. J.

1988-01-01

Electrical conduction in the heart shows many phenomena familiar from nonlinear dynamics. Among these phenomena are multiple basins of attraction, phase locking, and perhaps period-doubling bifurcations and chaos. We describe a simple cellular-automation model of electrical conduction which simulates normal conduction patterns in the heart as well as a wide range of disturbances of heart rhythm. In addition, we review the application of percolation theory to the analysis of the development of complex, self-sustaining conduction patterns.

Src Homology 2 Domain-containing Phosphatase 2 (Shp2) Is a Component of the A-kinase-anchoring Protein (AKAP)-Lbc Complex and Is Inhibited by Protein Kinase A (PKA) under Pathological Hypertrophic Conditions in the Heart*

PubMed Central

Burmeister, Brian T.; Taglieri, Domenico M.; Wang, Li; Carnegie, Graeme K.

2012-01-01

Pathological cardiac hypertrophy (an increase in cardiac mass resulting from stress-induced cardiac myocyte growth) is a major factor underlying heart failure. Our results identify a novel mechanism of Shp2 inhibition that may promote cardiac hypertrophy. We demonstrate that the tyrosine phosphatase, Shp2, is a component of the A-kinase-anchoring protein (AKAP)-Lbc complex. AKAP-Lbc facilitates PKA phosphorylation of Shp2, which inhibits its protein-tyrosine phosphatase activity. Given the important cardiac roles of both AKAP-Lbc and Shp2, we investigated the AKAP-Lbc-Shp2 interaction in the heart. AKAP-Lbc-tethered PKA is implicated in cardiac hypertrophic signaling; however, mechanism of PKA action is unknown. Mutations resulting in loss of Shp2 catalytic activity are also associated with cardiac hypertrophy and congenital heart defects. Our data indicate that AKAP-Lbc integrates PKA and Shp2 signaling in the heart and that AKAP-Lbc-associated Shp2 activity is reduced in hypertrophic hearts in response to chronic β-adrenergic stimulation and PKA activation. Thus, while induction of cardiac hypertrophy is a multifaceted process, inhibition of Shp2 activity through AKAP-Lbc-anchored PKA is a previously unrecognized mechanism that may promote compensatory cardiac hypertrophy. PMID:23045525

TRPV2 is critical for the maintenance of cardiac structure and function in mice

PubMed Central

Katanosaka, Yuki; Iwasaki, Keiichiro; Ujihara, Yoshihiro; Takatsu, Satomi; Nishitsuji, Koki; Kanagawa, Motoi; Sudo, Atsushi; Toda, Tatsushi; Katanosaka, Kimiaki; Mohri, Satoshi; Naruse, Keiji

2014-01-01

The heart has a dynamic compensatory mechanism for haemodynamic stress. However, the molecular details of how mechanical forces are transduced in the heart are unclear. Here we show that the transient receptor potential, vanilloid family type 2 (TRPV2) cation channel is critical for the maintenance of cardiac structure and function. Within 4 days of eliminating TRPV2 from hearts of the adult mice, cardiac function declines severely, with disorganization of the intercalated discs that support mechanical coupling with neighbouring myocytes and myocardial conduction defects. After 9 days, cell shortening and Ca2+ handling by single myocytes are impaired in TRPV2-deficient hearts. TRPV2-deficient neonatal cardiomyocytes form no intercalated discs and show no extracellular Ca2+-dependent intracellular Ca2+ increase and insulin-like growth factor (IGF-1) secretion in response to stretch stimulation. We further demonstrate that IGF-1 receptor/PI3K/Akt pathway signalling is significantly downregulated in TRPV2-deficient hearts, and that IGF-1 administration partially prevents chamber dilation and impairment in cardiac pump function in these hearts. Our results improve our understanding of the molecular processes underlying the maintenance of cardiac structure and function. PMID:24874017

TRPV2 is critical for the maintenance of cardiac structure and function in mice.

PubMed

Katanosaka, Yuki; Iwasaki, Keiichiro; Ujihara, Yoshihiro; Takatsu, Satomi; Nishitsuji, Koki; Kanagawa, Motoi; Sudo, Atsushi; Toda, Tatsushi; Katanosaka, Kimiaki; Mohri, Satoshi; Naruse, Keiji

2014-05-29

The heart has a dynamic compensatory mechanism for haemodynamic stress. However, the molecular details of how mechanical forces are transduced in the heart are unclear. Here we show that the transient receptor potential, vanilloid family type 2 (TRPV2) cation channel is critical for the maintenance of cardiac structure and function. Within 4 days of eliminating TRPV2 from hearts of the adult mice, cardiac function declines severely, with disorganization of the intercalated discs that support mechanical coupling with neighbouring myocytes and myocardial conduction defects. After 9 days, cell shortening and Ca(2+) handling by single myocytes are impaired in TRPV2-deficient hearts. TRPV2-deficient neonatal cardiomyocytes form no intercalated discs and show no extracellular Ca(2+)-dependent intracellular Ca(2+) increase and insulin-like growth factor (IGF-1) secretion in response to stretch stimulation. We further demonstrate that IGF-1 receptor/PI3K/Akt pathway signalling is significantly downregulated in TRPV2-deficient hearts, and that IGF-1 administration partially prevents chamber dilation and impairment in cardiac pump function in these hearts. Our results improve our understanding of the molecular processes underlying the maintenance of cardiac structure and function.

Polarization-resolved SHG microscopy in cardiac hypertrophy study (Conference Presentation)

NASA Astrophysics Data System (ADS)

Wang, Zhonghai; Yuan, Cai; Shao, Yonghong; Bradshaw, Amy D.; Borg, Thomas K.; Gao, Bruce Z.

2017-02-01

Cardiac hypertrophy, a process initiated by mechanical alterations, is hypothesized to cause long-term molecular-level alteration in the sarcomere lattice, which is the main force-generating component in the heart muscle. This molecular-level alteration is beyond the resolving capacity of common light microscopy. Second harmonic generation (SHG) microscopy has unique capability for visualizing ordered molecular structures in biological tissues without labeling. Combined with polarization imaging technique, SHG microscopy is able to extract structural details of myosin at the molecular level so as to reveal molecular-level alterations that occur during hypertrophy. The myosin filaments are believed to possess C6 symmetry; thus, the nonlinear polarization response relationship between generated second harmonic light I^2ωand incident fundamental light I^ω is determined by nonlinear coefficients, χ_15, χ_31 and χ_33. χ_31/χ_15 is believed to be an indicator of the molecular symmetry of myosin filament, whileχ_33/χ_15represents the intramyosin orientation angle of the double helix. By changing the polarization of the incident light and evaluating the corresponding SHG signals, the molecular structure of the myosin, reflected by the χ coefficients, can be revealed. With this method, we studied the structural properties of heart tissues in different conditions, including those in normal, physiologically hypertrophic (heart tissue from postpartum female rats), and pathologically hypertrophic (heart tissue from transverse-aorta constricted rats) conditions. We found that ratios of χ_31/χ_15 showed no significant difference between heart tissues from different conditions; their values were all close to 1, which demonstrated that Kleinman symmetry held for all conditions. Ratios of χ_33/χ_15 from physiologically or pathologically hypertrophic heart tissues were raised and showed significant difference from those from normal heart tissues, which indicated that the intramyosin orientation angle of the double helix was altered when heart tissues hypertrophied. Polarization-resolved SHG microscopy permitted us to study heart tissues at the molecular level and may serve as a diagnostic tool for cardiac hypertrophy.

Executive Functioning and School Performance Among Pediatric Survivors of Complex Congenital Heart Disease

PubMed Central

Gerstle, Melissa; Beebe, Dean W.; Drotar, Dennis; Cassedy, Amy; Marino, Bradley S.

2016-01-01

Objective To investigate the presence and severity of real-world impairments in executive functioning– responsible for children’s regulatory skills (metacognition, behavioral regulation) – and its potential impact on school performance among pediatric survivors of complex congenital heart disease (CHD). Study design Survivors of complex CHD aged 8–16 years (n=143)and their parents/guardians from a regional CHD survivor registry participated (81% participation rate). Parents completed proxy measures of executive functioning, school competency, and school-related quality of life (QOL). Patients also completed a measure of school QOL and underwent IQ testing. Patients were categorized into two groups based on heart lesion complexity: two-ventricle or single-ventricle. Results Survivors of complex CHD performed significantly worse than norms for executive functioning, IQ, school competency, and school QOL. Metacognition was more severely affected than behavioral regulation, and metacognitive deficits were more often present in older children. Even after taking into account demographic factors, disease severity, and IQ, metacognition uniquely and strongly predicted poorer school performance. In exploratory analyses, patients with single-ventricle lesions were rated as having lower school competency and school QOL, and patients with two-ventricle lesions were rated as having poorer behavioral regulation. Conclusions Survivors of complex CHD experience greater executive functioning difficulties than healthy peers, with metacognition particularly impacted and particularly relevant for day-to-day school performance. Especially in older children, clinicians should watch for metacognitive deficits, such as problems with organization, planning, self-monitoring, and follow-through on tasks. PMID:26875011

Distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle.

PubMed

Zhang, Xuemeng; Kampourakis, Thomas; Yan, Ziqian; Sevrieva, Ivanka; Irving, Malcolm; Sun, Yin-Biao

2017-02-23

The Frank-Starling relation is a fundamental auto-regulatory property of the heart that ensures the volume of blood ejected in each heartbeat is matched to the extent of venous filling. At the cellular level, heart muscle cells generate higher force when stretched, but despite intense efforts the underlying molecular mechanism remains unknown. We applied a fluorescence-based method, which reports structural changes separately in the thick and thin filaments of rat cardiac muscle, to elucidate that mechanism. The distinct structural changes of troponin C in the thin filaments and myosin regulatory light chain in the thick filaments allowed us to identify two aspects of the Frank-Starling relation. Our results show that the enhanced force observed when heart muscle cells are maximally activated by calcium is due to a change in thick filament structure, but the increase in calcium sensitivity at lower calcium levels is due to a change in thin filament structure.

Diabetes mellitus is associated with adverse structural and functional cardiac remodelling in chronic heart failure with reduced ejection fraction.

PubMed

Walker, Andrew Mn; Patel, Peysh A; Rajwani, Adil; Groves, David; Denby, Christine; Kearney, Lorraine; Sapsford, Robert J; Witte, Klaus K; Kearney, Mark T; Cubbon, Richard M

2016-09-01

Diabetes mellitus is associated with an increased risk of death and hospitalisation in patients with chronic heart failure. Better understanding of potential underlying mechanisms may aid the development of diabetes mellitus-specific chronic heart failure therapeutic strategies. Prospective observational cohort study of 628 patients with chronic heart failure associated with left ventricular systolic dysfunction receiving contemporary evidence-based therapy. Indices of cardiac structure and function, along with symptoms and biochemical parameters, were compared in patients with and without diabetes mellitus at study recruitment and 1 year later. Patients with diabetes mellitus (24.2%) experienced higher rates of all-cause [hazard ratio, 2.3 (95% confidence interval, 1.8-3.0)] and chronic heart failure-specific mortality and hospitalisation despite comparable pharmacological and device-based therapies. At study recruitment, patients with diabetes mellitus were more symptomatic, required greater diuretic doses and more frequently had radiologic evidence of pulmonary oedema, despite higher left ventricular ejection fraction. They also exhibited echocardiographic evidence of increased left ventricular wall thickness and pulmonary arterial pressure. Diabetes mellitus was associated with reduced indices of heart rate variability and increased heart rate turbulence. During follow-up, patients with diabetes mellitus experienced less beneficial left ventricular remodelling and greater deterioration in renal function. Diabetes mellitus is associated with features of adverse structural and functional cardiac remodelling in patients with chronic heart failure. © The Author(s) 2016.

Insulin receptor substrate signaling controls cardiac energy metabolism and heart failure.

PubMed

Guo, Cathy A; Guo, Shaodong

2017-06-01

The heart is an insulin-dependent and energy-consuming organ in which insulin and nutritional signaling integrates to the regulation of cardiac metabolism, growth and survival. Heart failure is highly associated with insulin resistance, and heart failure patients suffer from the cardiac energy deficiency and structural and functional dysfunction. Chronic pathological conditions, such as obesity and type 2 diabetes mellitus, involve various mechanisms in promoting heart failure by remodeling metabolic pathways, modulating cardiac energetics and impairing cardiac contractility. Recent studies demonstrated that insulin receptor substrates 1 and 2 (IRS-1,-2) are major mediators of both insulin and insulin-like growth factor-1 (IGF-1) signaling responsible for myocardial energetics, structure, function and organismal survival. Importantly, the insulin receptor substrates (IRS) play an important role in the activation of the phosphatidylinositide-3-dependent kinase (PI-3K) that controls Akt and Foxo1 signaling cascade, regulating the mitochondrial function, cardiac energy metabolism and the renin-angiotensin system. Dysregulation of this branch in signaling cascades by insulin resistance in the heart through the endocrine system promotes heart failure, providing a novel mechanism for diabetic cardiomyopathy. Therefore, targeting this branch of IRS→PI-3K→Foxo1 signaling cascade and associated pathways may provide a fundamental strategy for the therapeutic and nutritional development in control of metabolic and cardiovascular diseases. In this review, we focus on insulin signaling and resistance in the heart and the role energetics play in cardiac metabolism, structure and function. © 2017 Society for Endocrinology.

Histological, chemical, and morphological reexamination of the ``heart'' of a small Late Cretaceous Thescelosaurus

NASA Astrophysics Data System (ADS)

Cleland, Timothy P.; Stoskopf, Michael K.; Schweitzer, Mary H.

2011-03-01

A three-dimensional, iron-cemented structure found in the anterior thoracic cavity of articulated Thescelosaurus skeletal remains was hypothesized to be the fossilized remains of the animal's four-chambered heart. This was important because the finding could be interpreted to support a hypothesis that non-avian dinosaurs were endothermic. Mammals and birds, the only extant organisms with four-chambered hearts and single aortae, are endotherms. The hypothesis that this Thescelosaurus has a preserved heart was controversial, and therefore, we reexamined it using higher-resolution computed tomography, paleohistological examination, X-ray diffraction analysis, X-ray photoelectron spectroscopy, and scanning electron microscopy. This suite of analyses allows for detailed morphological and chemical examination beyond what was provided in the original work. Neither the more detailed examination of the gross morphology and orientation of the thoracic "heart" nor the microstructural studies supported the hypothesis that the structure was a heart. The more advanced computed tomography showed the same three areas of low density as the earlier studies with no evidence of additional low-density areas as might be expected from examinations of an ex situ ostrich heart. Microstructural examination of a fragment taken from the "heart" was consistent with cemented sand grains, and no chemical signal consistent with a biological origin was detected. However, small patches of cell-like microstructures were preserved in the sandstone matrix of the thoracic structure. A possible biological origin for these microstructures is the focus of ongoing investigation.

Twenty-four hour Holter monitoring in finishing cattle housed outdoors.

PubMed

Frese, D A; Thomason, J D; Reinhardt, C; Bartle, S; Rethorst, D; Loneragan, G H; Thomson, D

2017-04-01

Atrial premature complexes have been reported to be the most common arrhythmia in cattle and is suspected to be secondary to systemic disease, especially gastrointestinal disease. In order to properly identify pathologic arrhythmia in cattle, the normal rhythm and arrhythmia prevalence should be defined. The objective of this study was to determine the normal heart rate, rhythm, number of ventricular premature complexes (VPCs), and atrial premature complexes (APCs) in unrestrained Angus steers. Twenty-seven client owned steers with unremarkable physical examinations and serum biochemical analyses were used. Twenty-four hour Holter monitors, attached by a custom-made harness, were retrospectively evaluated. Three lead electrocardiographic registrations of good quality and normal sinus rhythm were obtained from all steers in the study. The mean heart rate was 66.8 bpm ± 16.4 bpm. Ventricular premature complexes were rare (noted in 14.8% of steers), and APCs were common (noted in 85% of the steers). Simple second degree AV block was observed in 18.5% of the steers. In summary, healthy steers have rare single VPCs, although it is possible for an individual animal to have apparent more frequent VPCs. Mean heart rate varies with a diurnal pattern similar to other species. Atrial premature complexes are the most prevalent abnormality observed in feedlot steers. Copyright © 2016 Elsevier B.V. All rights reserved.

Complex Decision-Making in Heart Failure: A Systematic Review and Thematic Analysis.

PubMed

Hamel, Aimee V; Gaugler, Joseph E; Porta, Carolyn M; Hadidi, Niloufar Niakosari

Heart failure follows a highly variable and difficult course. Patients face complex decisions, including treatment with implantable cardiac defibrillators, mechanical circulatory support, and heart transplantation. The course of decision-making across multiple treatments is unclear yet integral to providing informed and shared decision-making. Recognizing commonalities across treatment decisions could help nurses and physicians to identify opportunities to introduce discussions and support shared decision-making. The specific aims of this review are to examine complex treatment decision-making, specifically implantable cardiac defibrillators, ventricular assist device, and cardiac transplantation, and to recognize commonalities and key points in the decisional process. MEDLINE, CINAHL, PsycINFO, and Web of Science were searched for English-language studies that included qualitative findings reflecting the complexity of heart failure decision-making. Using a 3-step process, findings were synthesized into themes and subthemes. Twelve articles met criteria for inclusion. Participants included patients, caregivers, and clinicians and included decisions to undergo and decline treatment. Emergent themes were "processing the decision," "timing and prognostication," and "considering the future." Subthemes described how participants received and understood information about the therapy, making and changing a treatment decision, timing their decision and gauging health status outcomes in the context of their decision, the influence of a life or death decision, and the future as a factor in their decisional process. Commonalities were present across therapies, which involved the timing of discussions, the delivery of information, and considerations of the future. Exploring this further could help support patient-centered care and optimize shared decision-making interventions.

Initiation of Electron Transport Chain Activity in the Embryonic Heart Coincides with the Activation of Mitochondrial Complex 1 and the Formation of Supercomplexes

PubMed Central

Beutner, Gisela; Eliseev, Roman A.; Porter, George A.

2014-01-01

Mitochondria provide energy in form of ATP in eukaryotic cells. However, it is not known when, during embryonic cardiac development, mitochondria become able to fulfill this function. To assess this, we measured mitochondrial oxygen consumption and the activity of the complexes (Cx) 1 and 2 of the electron transport chain (ETC) and used immunoprecipitation to follow the generation of mitochondrial supercomplexes. We show that in the heart of mouse embryos at embryonic day (E) 9.5, mitochondrial ETC activity and oxidative phosphorylation (OXPHOS) are not coupled, even though the complexes are present. We show that Cx-1 of the ETC is able to accept electrons from the Krebs cycle, but enzyme assays that specifically measure electron flow to ubiquinone or Cx-3 show no activity at this early embryonic stage. At E11.5, mitochondria appear functionally more mature; ETC activity and OXPHOS are coupled and respond to ETC inhibitors. In addition, the assembly of highly efficient respiratory supercomplexes containing Cx-1, -3, and -4, ubiquinone, and cytochrome c begins at E11.5, the exact time when Cx-1 becomes functional activated. At E13.5, ETC activity and OXPHOS of embryonic heart mitochondria are indistinguishable from adult mitochondria. In summary, our data suggest that between E9.5 and E11.5 dramatic changes occur in the mitochondria of the embryonic heart, which result in an increase in OXPHOS due to the activation of complex 1 and the formation of supercomplexes. PMID:25427064

Does the Aristotle Score predict outcome in congenital heart surgery?

PubMed

Kang, Nicholas; Tsang, Victor T; Elliott, Martin J; de Leval, Marc R; Cole, Timothy J

2006-06-01

The Aristotle Score has been proposed as a measure of 'complexity' in congenital heart surgery, and a tool for comparing performance amongst different centres. To date, however, it remains unvalidated. We examined whether the Basic Aristotle Score was a useful predictor of mortality following open-heart surgery, and compared it to the Risk Adjustment in Congenital Heart Surgery (RACHS-1) system. We also examined the ability of the Aristotle Score to measure performance. The Basic Aristotle Score and RACHS-1 risk categories were assigned retrospectively to 1085 operations involving cardiopulmonary bypass in children less than 18 years of age. Multiple logistic regression analysis was used to determine the significance of the Aristotle Score and RACHS-1 category as independent predictors of in-hospital mortality. Operative performance was calculated using the Aristotle equation: performance = complexity x survival. Multiple logistic regression identified RACHS-1 category to be a powerful predictor of mortality (Wald 17.7, p < 0.0001), whereas Aristotle Score was only weakly associated with mortality (Wald 4.8, p = 0.03). Age at operation and bypass time were also highly significant predictors of postoperative death (Wald 13.7 and 33.8, respectively, p < 0.0001 for both). Operative performance was measured at 7.52 units. The Basic Aristotle Score was only weakly associated with postoperative mortality in this series. Operative performance appeared to be inflated by the fact that the overall complexity of cases was relatively high in this series. An alternative equation (performance = complexity/mortality) is proposed as a fairer and more logical method of risk-adjustment.

Stratification of complexity in congenital heart surgery: comparative study of the Risk Adjustment for Congenital Heart Surgery (RACHS-1) method, Aristotle basic score and Society of Thoracic Surgeons-European Association for Cardio- Thoracic Surgery (STS-EACTS) mortality score.

PubMed

Cavalcanti, Paulo Ernando Ferraz; Sá, Michel Pompeu Barros de Oliveira; Santos, Cecília Andrade dos; Esmeraldo, Isaac Melo; Chaves, Mariana Leal; Lins, Ricardo Felipe de Albuquerque; Lima, Ricardo de Carvalho

2015-01-01

To determine whether stratification of complexity models in congenital heart surgery (RACHS-1, Aristotle basic score and STS-EACTS mortality score) fit to our center and determine the best method of discriminating hospital mortality. Surgical procedures in congenital heart diseases in patients under 18 years of age were allocated to the categories proposed by the stratification of complexity methods currently available. The outcome hospital mortality was calculated for each category from the three models. Statistical analysis was performed to verify whether the categories presented different mortalities. The discriminatory ability of the models was determined by calculating the area under the ROC curve and a comparison between the curves of the three models was performed. 360 patients were allocated according to the three methods. There was a statistically significant difference between the mortality categories: RACHS-1 (1) - 1.3%, (2) - 11.4%, (3)-27.3%, (4) - 50 %, (P<0.001); Aristotle basic score (1) - 1.1%, (2) - 12.2%, (3) - 34%, (4) - 64.7%, (P<0.001); and STS-EACTS mortality score (1) - 5.5 %, (2) - 13.6%, (3) - 18.7%, (4) - 35.8%, (P<0.001). The three models had similar accuracy by calculating the area under the ROC curve: RACHS-1- 0.738; STS-EACTS-0.739; Aristotle- 0.766. The three models of stratification of complexity currently available in the literature are useful with different mortalities between the proposed categories with similar discriminatory capacity for hospital mortality.

Initiation of electron transport chain activity in the embryonic heart coincides with the activation of mitochondrial complex 1 and the formation of supercomplexes.

PubMed

Beutner, Gisela; Eliseev, Roman A; Porter, George A

2014-01-01

Mitochondria provide energy in form of ATP in eukaryotic cells. However, it is not known when, during embryonic cardiac development, mitochondria become able to fulfill this function. To assess this, we measured mitochondrial oxygen consumption and the activity of the complexes (Cx) 1 and 2 of the electron transport chain (ETC) and used immunoprecipitation to follow the generation of mitochondrial supercomplexes. We show that in the heart of mouse embryos at embryonic day (E) 9.5, mitochondrial ETC activity and oxidative phosphorylation (OXPHOS) are not coupled, even though the complexes are present. We show that Cx-1 of the ETC is able to accept electrons from the Krebs cycle, but enzyme assays that specifically measure electron flow to ubiquinone or Cx-3 show no activity at this early embryonic stage. At E11.5, mitochondria appear functionally more mature; ETC activity and OXPHOS are coupled and respond to ETC inhibitors. In addition, the assembly of highly efficient respiratory supercomplexes containing Cx-1, -3, and -4, ubiquinone, and cytochrome c begins at E11.5, the exact time when Cx-1 becomes functional activated. At E13.5, ETC activity and OXPHOS of embryonic heart mitochondria are indistinguishable from adult mitochondria. In summary, our data suggest that between E9.5 and E11.5 dramatic changes occur in the mitochondria of the embryonic heart, which result in an increase in OXPHOS due to the activation of complex 1 and the formation of supercomplexes.

Cardiac interbeat interval dynamics from childhood to senescence : comparison of conventional and new measures based on fractals and chaos theory

NASA Technical Reports Server (NTRS)

Pikkujamsa, S. M.; Makikallio, T. H.; Sourander, L. B.; Raiha, I. J.; Puukka, P.; Skytta, J.; Peng, C. K.; Goldberger, A. L.; Huikuri, H. V.

1999-01-01

BACKGROUND: New methods of R-R interval variability based on fractal scaling and nonlinear dynamics ("chaos theory") may give new insights into heart rate dynamics. The aims of this study were to (1) systematically characterize and quantify the effects of aging from early childhood to advanced age on 24-hour heart rate dynamics in healthy subjects; (2) compare age-related changes in conventional time- and frequency-domain measures with changes in newly derived measures based on fractal scaling and complexity (chaos) theory; and (3) further test the hypothesis that there is loss of complexity and altered fractal scaling of heart rate dynamics with advanced age. METHODS AND RESULTS: The relationship between age and cardiac interbeat (R-R) interval dynamics from childhood to senescence was studied in 114 healthy subjects (age range, 1 to 82 years) by measurement of the slope, beta, of the power-law regression line (log power-log frequency) of R-R interval variability (10(-4) to 10(-2) Hz), approximate entropy (ApEn), short-term (alpha(1)) and intermediate-term (alpha(2)) fractal scaling exponents obtained by detrended fluctuation analysis, and traditional time- and frequency-domain measures from 24-hour ECG recordings. Compared with young adults (<40 years old, n=29), children (<15 years old, n=27) showed similar complexity (ApEn) and fractal correlation properties (alpha(1), alpha(2), beta) of R-R interval dynamics despite lower spectral and time-domain measures. Progressive loss of complexity (decreased ApEn, r=-0.69, P<0.001) and alterations of long-term fractal-like heart rate behavior (increased alpha(2), r=0.63, decreased beta, r=-0.60, P<0.001 for both) were observed thereafter from middle age (40 to 60 years, n=29) to old age (>60 years, n=29). CONCLUSIONS: Cardiac interbeat interval dynamics change markedly from childhood to old age in healthy subjects. Children show complexity and fractal correlation properties of R-R interval time series comparable to those of young adults, despite lower overall heart rate variability. Healthy aging is associated with R-R interval dynamics showing higher regularity and altered fractal scaling consistent with a loss of complex variability.

EFFECTS OF CYCLIC FLEXURAL FATIGUE ON PORCINE BIOPROSTHETIC HEART VALVE HETEROGRAFT BIOMATERIALS

PubMed Central

Mirnajafi, Ali; Zubiate, Brett; Sacks, Michael S.

2009-01-01

While bioprosthetic heart valves (BHV) remain the primary treatment modality for adult heart valve replacement, continued problems with durability remain. Several studies have implicated flexure as a major damage mode in porcine-derived heterograft biomaterials used in BHV fabrication. While conventional accelerated wear testing can provide valuable insights into BHV damage phenomena, the constituent tissues are subjected to complex, time-varying deformation modes (i.e. tension and flexure), that do not allow for the control of the amount, direction, and location of flexure. Thus, in the present study customized fatigue testing devices were developed to subject circumferentially oriented porcine BHV tissue strips to controlled cyclic flexural loading. By using this approach, we were able to study layer-specific structural damage induced by cyclic flexural tensile and compressive stresses alone. 10×106, 25×106 and 50×106 cycle levels were used, with resulting changes in flexural stiffness and collagen structure assessed. Results indicated that flexural rigidity was markedly reduced after only 10×106 cycles, and progressively decayed at a lower rate with cycle number thereafter. Moreover, the against-curvature fatigue direction induced the most damage, suggesting that the ventricularis and fibrosa layers have low resistance to cyclic flexural compressive and tensile loads, respectively. The histological analyses indicated progressive collagen fiber delamination as early as 10×106 cycles, but otherwise no change in gross collagen orientation. Our results underscore that porcine-derived heterograft biomaterials are very sensitive to flexural fatigue, with delamination of the tissue layers the primary underlying mechanism. This appears to be in contrast to pericardial BHV, wherein high tensile stresses are considered to be the major cause of structural failure. These findings point towards the need for the development of chemical fixation technologies that minimize flexure induced damage to extend porcine heterograft biomaterial durability. PMID:20166221

Mitochondrial complex I and NAD(P)H oxidase are major sources of exacerbated oxidative stress in pressure-overloaded ischemic-reperfused hearts.

PubMed

Mozaffari, Mahmood S; Baban, Babak; Liu, Jun Yao; Abebe, Worku; Sullivan, Jennifer C; El-Marakby, Ahmed

2011-03-01

We tested the hypothesis that pressure overload exacerbates oxidative stress associated with augmented mitochondrial permeability transition (MPT) pore opening and cell death in ischemic-reperfused hearts. Pressure overload decreased the level of reduced glutathione but increased nitrotyrosine and 8-hydroxydeoxyguanosine levels in ischemic-reperfused hearts. The activity of catalase, but not superoxide dismutase (SOD), was lower in ischemic-reperfused hearts perfused at higher pressure. Mitochondria from ischemic-reperfused hearts subjected to higher perfusion pressure displayed significantly greater [³H]-2-deoxyglucose-6-P entrapment suggestive of greater MPT pore opening and consistent with greater necrosis and apoptosis. Tempol (SOD mimetic) reduced infarct size in both groups but it remained greater in the higher pressure group. By contrast, uric acid (peroxynitrite scavenger) markedly reduced infarct size at higher pressure, effectively eliminating the differential between the two groups. Inhibition of xanthine oxidase, with allopurinol, reduced infarct size but did not eliminate the differential between the two groups. However, amobarbital (inhibitor of mitochondrial complex I) or apocynin [inhibitor of NAD(P)H oxidase] reduced infarct size at both pressures and also abrogated the differential between the two groups. Consistent with the effect of apocynin, pressure-overloaded hearts displayed significantly higher NAD(P)H oxidase activity. Furthermore, pressure-overloaded hearts displayed increased nitric oxide synthase activity which, along with increased propensity to superoxide generation, may underlie uric acid-induced cardioprotection. In conclusion, increased oxidative and nitrosative stress, coupled with lack of augmented SOD and catalase activities, contributes importantly to the exacerbating impact of pressure overload on MPT pore opening and cell death in ischemic-reperfused hearts.

Successes and future outlook for microfluidics-based cardiovascular drug discovery.

PubMed

Skommer, Joanna; Wlodkowic, Donald

2015-03-01

The greatest advantage of using microfluidics as a platform for the assessment of cardiovascular drug action is its ability to finely regulate fluid flow conditions, including flow rate, shear stress and pulsatile flow. At the same time, microfluidics provide means for modifying the vessel geometry (bifurcations, stenoses, complex networks), the type of surface of the vessel walls, and for patterning cells in 3D tissue-like architecture, including generation of lumen walls lined with cells and heart-on-a-chip structures for mimicking ventricular cardiomyocyte physiology. In addition, owing to the small volume of required specimens, microfluidics is ideally suited to clinical situations whereby monitoring of drug dosing or efficacy needs to be coupled with minimal phlebotomy-related drug loss. In this review, the authors highlight potential applications for the currently existing and emerging technologies and offer several suggestions on how to close the development cycle of microfluidic devices for cardiovascular drug discovery. The ultimate goal in microfluidics research for drug discovery is to develop 'human-on-a-chip' systems, whereby several organ cultures, including the vasculature and the heart, can mimic complex interactions between the organs and body systems. This would provide in vivo-like pharmacokinetics and pharmacodynamics for drug ADMET assessment. At present, however, the great variety of available designs does not go hand in hand with their use by the pharmaceutical community.

Heart failure and atrial fibrillation: current concepts and controversies.

PubMed Central

Van den Berg, M. P.; Tuinenburg, A. E.; Crijns, H. J.; Van Gelder, I. C.; Gosselink, A. T.; Lie, K. I.

1997-01-01

Heart failure and atrial fibrillation are very common, particularly in the elderly. Owing to common risk factors both disorders are often present in the same patient. In addition, there is increasing evidence of a complex, reciprocal relation between heart failure and atrial fibrillation. Thus heart failure may cause atrial fibrillation, with electromechanical feedback and neurohumoral activation playing an important mediating role. In addition, atrial fibrillation may promote heart failure; in particular, when there is an uncontrolled ventricular rate, tachycardiomyopathy may develop and thereby heart failure. Eventually, a vicious circle between heart failure and atrial fibrillation may form, in which neurohumoral activation and subtle derangement of rate control are involved. Treatment should aim at unloading of the heart, adequate control of ventricular rate, and correction of neurohumoral activation. Angiotensin converting enzyme inhibitors may help to achieve these goals. Treatment should also include an attempt to restore sinus rhythm through electrical cardioversion, though appropriate timing of cardioversion is difficult. His bundle ablation may be used to achieve adequate rate control in drug refractory cases. PMID:9155607

Molecular Evidence of Stress-Induced Acute Heart Injury in a Mouse Model Simulating Posttraumatic Stress Disorder

DTIC Science & Technology

2014-02-25

risk of drug or alcohol abuse. In addition, patients with PTSD often display structural changes in the pre- frontal cortex, the amygdala, and the... triglyceride levels (12–15). An 1871 report noted that serious cardiac disorders (car- diomyopathies, heart failure, heart pain, etc.) were a consequence of...epicardium probably play a key role in the EMT process (30, 31). Maintaining the proper ECM structure is critical to pre- serving the architecture and

The Complex Genetic Basis of Congenital Heart Defects

PubMed Central

Akhirome, Ehiole; Walton, Nephi A.; Nogee, Julie M.; Jay, Patrick Y.

2017-01-01

Twenty years ago, chromosomal abnormalities were the only identifiable genetic causes of a small fraction of congenital heart defects (CHD). Today, a de novo or inherited genetic abnormality can be identified as pathogenic in one-third of cases. We refer to them here as monogenic causes, insofar as the genetic abnormality has a readily detectable, large effect. What explains the other two-thirds? This review considers a complex genetic basis. That is, a combination of genetic mutations or variants that individually may have little or no detectable effect contribute to the pathogenesis of a heart defect. Genes in the embryo that act directly in cardiac developmental pathways have received the most attention, but genes in the mother that establish the gestational milieu via pathways related to metabolism and aging also have an effect. A growing body of evidence highlights the pathogenic significance of genetic interactions in the embryo and maternal effects that have a genetic basis. The investigation of CHD as guided by a complex genetic model could help estimate risk more precisely and logically lead to a means of prevention. PMID:28381817

Two case reports of anophthalmia and congenital heart disease: Adding a new dimension to this association.

PubMed

Wang, Jenny; Steelman, Charlotte K; Vincent, Robert; Richburg, Delene; Chang, Tiffany S; Shehata, Bahig M

2010-01-01

Anophthalmia is the congenital absence of ocular tissue from the orbit. Many syndromes and malformations (e.g., anophthalmia-esophageal-genital syndrome, Matthew-Wood syndrome, CHARGE syndrome, oculo-facial-cardio-dental-syndome, heterotaxy, and Fraser syndrome) have been associated with anophthalmia. However, its relation with congenital heart disease has not been fully elucidated. In this article, we discuss two cases of patients with anophthalmia and congenital heart defects, and we compare these findings with other syndromes with which anophthalmia has been associated. One of our two patients showed complex congenital heart disease with heterotaxia, polysplenia, and normal lung lobation. These findings may reflect a new dimension of anophthalmia, heterotaxia, and congenital heart disease associations.

Left thoracotomy HeartWare implantation with outflow graft anastomosis to the descending aorta: a simplified bridge for patients with multiple previous sternotomies.

PubMed

Umakanthan, Ramanan; Haglund, Nicholas A; Stulak, John M; Joyce, Lyle D; Ahmad, Rashid; Keebler, Mary E; Maltais, Simon

2013-01-01

Advances in mechanical circulatory support have been critical in bridging patients awaiting heart transplantation. In addition, improvement in device durability has enabled left ventricular assist device therapy to be applied as destination therapy in those not felt to be transplant candidate. Because of the increasing complexity of patients, there continues to be a need for alternative strategies for device implantation to bridge high-risk patients awaiting heart transplantation, wherein the risks of numerous previous sternotomies may be prohibitive. We present a unique technique for placement of the HeartWare ventricular assist device via left anterior thoracotomy to the descending aorta in a patient awaiting heart transplantation with a history of multiple previous sternotomies.

The evolution of heart gene delivery vectors.

PubMed

Wasala, Nalinda B; Shin, Jin-Hong; Duan, Dongsheng

2011-10-01

Gene therapy holds promise for treating numerous heart diseases. A key premise for the success of cardiac gene therapy is the development of powerful gene transfer vehicles that can achieve highly efficient and persistent gene transfer specifically in the heart. Other features of an ideal vector include negligible toxicity, minimal immunogenicity and easy manufacturing. Rapid progress in the fields of molecular biology and virology has offered great opportunities to engineer various genetic materials for heart gene delivery. Several nonviral vectors (e.g. naked plasmids, plasmid lipid/polymer complexes and oligonucleotides) have been tested. Commonly used viral vectors include lentivirus, adenovirus and adeno-associated virus. Among these, adeno-associated virus has shown many attractive features for pre-clinical experimentation in animal models of heart diseases. We review the history and evolution of these vectors for heart gene transfer. Copyright © 2011 John Wiley & Sons, Ltd.

The evolution of heart gene delivery vectors

PubMed Central

Wasala, Nalinda B.; Shin, Jin-Hong; Duan, Dongsheng

2012-01-01

Gene therapy holds promise for treating numerous heart diseases. A key premise for the success of cardiac gene therapy is the development of powerful gene transfer vehicles that can achieve highly efficient and persistent gene transfer specifically in the heart. Other features of an ideal vector include negligible toxicity, minimal immunogenicity and easy manufacturing. Rapid progress in the fields of molecular biology and virology has offered great opportunities to engineer various genetic materials for heart gene delivery. Several nonviral vectors (e.g. naked plasmids, plasmid lipid/polymer complexes and oligonucleotides) have been tested. Commonly used viral vectors include lentivirus, adenovirus and adeno-associated virus. Among these, adeno-associated virus has shown many attractive features for pre-clinical experimentation in animal models of heart diseases. We review the history and evolution of these vectors for heart gene transfer. PMID:21837689

State-of-the-Art Review of 3D Bioprinting for Cardiovascular Tissue Engineering.

PubMed

Duan, Bin

2017-01-01

3D bioprinting is a group of rapidly growing techniques that allows building engineered tissue constructs with complex and hierarchical structures, mechanical and biological heterogeneity. It enables implementation of various bioinks through different printing mechanisms and precise deposition of cell and/or biomolecule laden biomaterials in predefined locations. This review briefly summarizes applicable bioink materials and various bioprinting techniques, and presents the recent advances in bioprinting of cardiovascular tissues, with focusing on vascularized constructs, myocardium and heart valve conduits. Current challenges and further perspectives are also discussed to help guide the bioink and bioprinter development, improve bioprinting strategies and direct future organ bioprinting and translational applications.

Putting Text Complexity in Context: Refocusing on Comprehension of Complex Text

ERIC Educational Resources Information Center

Valencia, Sheila W.; Wixson, Karen K.; Pearson, P. David

2014-01-01

The Common Core State Standards for English Language Arts have prompted enormous attention to issues of text complexity. The purpose of this article is to put text complexity in perspective by moving from a primary focus on the text itself to a focus on the comprehension of complex text. We argue that a focus on comprehension is at the heart of…

[The effect of combined treatment with the use of magnetotherapy on the systemic hemodynamics of patients with ischemic heart disease and spinal osteochondrosis].

PubMed

Dudchenko, M A; Vesel'skiĭ, I Sh; Shtompel', V Iu

1992-05-01

The authors examined 66 patients with ischemic heart disease and concomitant cervico-thoracic osteochondrosis and 22 patients without osteochondrosis. Differences were revealed in values of the systemic hemodynamics with prevalence of the hypokinetic type in patients with combined pathology. Inclusion of magnetotherapy in the treatment complex of patients with ischemic heart disease and osteochondrosis favours clinical improvement, normalization of indices of central and regional blood circulation.

Utility of a super-flexible three-dimensional printed heart model in congenital heart surgery.

PubMed

Hoashi, Takaya; Ichikawa, Hajime; Nakata, Tomohiro; Shimada, Masatoshi; Ozawa, Hideto; Higashida, Akihiko; Kurosaki, Kenichi; Kanzaki, Suzu; Shiraishi, Isao

2018-05-28

The objective of this study was to assess the utility of 3D printed heart models of congenital heart disease for preoperative surgical simulation. Twenty patient-specific 3D models were created between March 2015 and August 2017. All operations were performed by a young consultant surgeon who had no prior experience with complex biventricular repair. All 15 patients with balanced ventricles had outflow tract malformations (double-outlet right ventricle in 7 patients, congenitally corrected transposition of great arteries in 5, transposition of great arteries in 1, interrupted aortic arch Type B in 1, tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries in 1). One patient had hypoplastic left heart complex, and the remaining 4 patients had a functional single ventricle. The median age at operation was 1.4 (range 0.1-5.9) years. Based on a multislice computed tomography data set, the 3D models were made of polyurethane resins using stereolithography as the printing technology and vacuum casting as the manufacturing method. All but 4 patients with a functional single ventricle underwent complete biventricular repair. The median cardiopulmonary bypass time and aortic cross-clamp time were 345 (110-570) min and 114 (35-293) min, respectively. During the median follow-up period of 1.3 (0.1-2.5) years, no mortality was observed. None of the patients experienced surgical heart block or systemic ventricular outflow tract obstruction. Three-dimensional printed heart models showed potential utility, especially in understanding the relationship between intraventricular communications and great vessels, as well as in simulation for creating intracardiac pathways.

Glutaredoxin-2 is required to control oxidative phosphorylation in cardiac muscle by mediating deglutathionylation reactions.

PubMed

Mailloux, Ryan J; Xuan, Jian Ying; McBride, Skye; Maharsy, Wael; Thorn, Stephanie; Holterman, Chet E; Kennedy, Christopher R J; Rippstein, Peter; deKemp, Robert; da Silva, Jean; Nemer, Mona; Lou, Marjorie; Harper, Mary-Ellen

2014-05-23

Glutaredoxin-2 (Grx2) modulates the activity of several mitochondrial proteins in cardiac tissue by catalyzing deglutathionylation reactions. However, it remains uncertain whether Grx2 is required to control mitochondrial ATP output in heart. Here, we report that Grx2 plays a vital role modulating mitochondrial energetics and heart physiology by mediating the deglutathionylation of mitochondrial proteins. Deletion of Grx2 (Grx2(-/-)) decreased ATP production by complex I-linked substrates to half that in wild type (WT) mitochondria. Decreased respiration was associated with increased complex I glutathionylation diminishing its activity. Tissue glucose uptake was concomitantly increased. Mitochondrial ATP output and complex I activity could be recovered by restoring the redox environment to that favoring the deglutathionylated states of proteins. Grx2(-/-) hearts also developed left ventricular hypertrophy and fibrosis, and mice became hypertensive. Mitochondrial energetics from Grx2 heterozygotes (Grx2(+/-)) were also dysfunctional, and hearts were hypertrophic. Intriguingly, Grx2(+/-) mice were far less hypertensive than Grx2(-/-) mice. Thus, Grx2 plays a vital role in modulating mitochondrial metabolism in cardiac muscle, and Grx2 deficiency leads to pathology. As mitochondrial ATP production was restored by the addition of reductants, these findings may be relevant to novel redox-related therapies in cardiac disease. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Methylene blue improves mitochondrial respiration and decreases oxidative stress in a substrate-dependent manner in diabetic rat hearts.

PubMed

Duicu, Oana M; Privistirescu, Andreea; Wolf, Adrian; Petruş, Alexandra; Dănilă, Maria D; Raţiu, Corina D; Muntean, Danina M; Sturza, Adrian

2017-11-01

Diabetic cardiomyopathy has been systematically associated with compromised mitochondrial energetics and increased generation of reactive oxygen species (ROS) that underlie its progression to heart failure. Methylene blue is a redox drug with reported protective effects mainly on brain mitochondria. The purpose of the present study was to characterize the effects of acute administration of methylene blue on mitochondrial respiration, H 2 O 2 production, and calcium sensitivity in rat heart mitochondria isolated from healthy and 2 months (streptozotocin-induced) diabetic rats. Mitochondrial respiratory function was assessed by high-resolution respirometry. H 2 O 2 production and calcium retention capacity were measured spectrofluorimetrically. The addition of methylene blue (0.1 μmol·L -1 ) elicited an increase in oxygen consumption of mitochondria energized with complex I and II substrates in both normal and diseased mitochondria. Interestingly, methylene blue elicited a significant increase in H 2 O 2 release in the presence of complex I substrates (glutamate and malate), but had an opposite effect in mitochondria energized with complex II substrate (succinate). No changes in the calcium retention capacity of healthy or diabetic mitochondria were found in the presence of methylene blue. In conclusion, in cardiac mitochondria isolated from diabetic and nondiabetic rat hearts, methylene blue improved respiratory function and elicited a dichotomic, substrate-dependent effect on ROS production.

Electronic sensor and actuator webs for large-area complex geometry cardiac mapping and therapy

PubMed Central

Kim, Dae-Hyeong; Ghaffari, Roozbeh; Lu, Nanshu; Wang, Shuodao; Lee, Stephen P.; Keum, Hohyun; D’Angelo, Robert; Klinker, Lauren; Su, Yewang; Lu, Chaofeng; Kim, Yun-Soung; Ameen, Abid; Li, Yuhang; Zhang, Yihui; de Graff, Bassel; Hsu, Yung-Yu; Liu, ZhuangJian; Ruskin, Jeremy; Xu, Lizhi; Lu, Chi; Omenetto, Fiorenzo G.; Huang, Yonggang; Mansour, Moussa; Slepian, Marvin J.; Rogers, John A.

2012-01-01

Curved surfaces, complex geometries, and time-dynamic deformations of the heart create challenges in establishing intimate, nonconstraining interfaces between cardiac structures and medical devices or surgical tools, particularly over large areas. We constructed large area designs for diagnostic and therapeutic stretchable sensor and actuator webs that conformally wrap the epicardium, establishing robust contact without sutures, mechanical fixtures, tapes, or surgical adhesives. These multifunctional web devices exploit open, mesh layouts and mount on thin, bio-resorbable sheets of silk to facilitate handling in a way that yields, after dissolution, exceptionally low mechanical moduli and thicknesses. In vivo studies in rabbit and pig animal models demonstrate the effectiveness of these device webs for measuring and spatially mapping temperature, electrophysiological signals, strain, and physical contact in sheet and balloon-based systems that also have the potential to deliver energy to perform localized tissue ablation. PMID:23150574

Modeling of long-term fatigue damage of soft tissue with stress softening and permanent set effects

PubMed Central

Martin, Caitlin; Sun, Wei

2012-01-01

One of the major failure modes of bioprosthetic heart valves is non-calcific structural deterioration due to fatigue of the tissue leaflets. Experimental methods to characterize tissue fatigue properties are complex and time-consuming. A constitutive fatigue model that could be calibrated by isolated material tests would be ideal for investigating the effects of more complex loading conditions. However, there is a lack of tissue fatigue damage models in the literature. To address these limitations, in this study, a phenomenological constitutive model was developed to describe the stress softening and permanent set effects of tissue subjected to long-term cyclic loading. The model was used to capture characteristic uniaxial fatigue data for glutaraldehyde-treated bovine pericardium and was then implemented into finite element software. The simulated fatigue response agreed well with the experimental data and thus demonstrates feasibility of this approach. PMID:22945802

Assessing Cardiac Metabolism

PubMed Central

Taegtmeyer, Heinrich; Young, Martin E.; Lopaschuk, Gary D.; Abel, E. Dale; Brunengraber, Henri; Darley-Usmar, Victor; Des Rosiers, Christine; Gerszten, Robert; Glatz, Jan F.; Griffin, Julian L.; Gropler, Robert J.; Holzhuetter, Hermann-Georg; Kizer, Jorge R.; Lewandowski, E. Douglas; Malloy, Craig R.; Neubauer, Stefan; Peterson, Linda R.; Portman, Michael A.; Recchia, Fabio A.; Van Eyk, Jennifer E.; Wang, Thomas J.

2016-01-01

In a complex system of interrelated reactions, the heart converts chemical energy to mechanical energy. Energy transfer is achieved through coordinated activation of enzymes, ion channels, and contractile elements, as well as structural and membrane proteins. The heart’s needs for energy are difficult to overestimate. At a time when the cardiovascular research community is discovering a plethora of new molecular methods to assess cardiac metabolism, the methods remain scattered in the literature. The present statement on “Assessing Cardiac Metabolism” seeks to provide a collective and curated resource on methods and models used to investigate established and emerging aspects of cardiac metabolism. Some of those methods are refinements of classic biochemical tools, whereas most others are recent additions from the powerful tools of molecular biology. The aim of this statement is to be useful to many and to do justice to a dynamic field of great complexity. PMID:27012580

Hekate: Software Suite for the Mass Spectrometric Analysis and Three-Dimensional Visualization of Cross-Linked Protein Samples

PubMed Central

2013-01-01

Chemical cross-linking of proteins combined with mass spectrometry provides an attractive and novel method for the analysis of native protein structures and protein complexes. Analysis of the data however is complex. Only a small number of cross-linked peptides are produced during sample preparation and must be identified against a background of more abundant native peptides. To facilitate the search and identification of cross-linked peptides, we have developed a novel software suite, named Hekate. Hekate is a suite of tools that address the challenges involved in analyzing protein cross-linking experiments when combined with mass spectrometry. The software is an integrated pipeline for the automation of the data analysis workflow and provides a novel scoring system based on principles of linear peptide analysis. In addition, it provides a tool for the visualization of identified cross-links using three-dimensional models, which is particularly useful when combining chemical cross-linking with other structural techniques. Hekate was validated by the comparative analysis of cytochrome c (bovine heart) against previously reported data.1 Further validation was carried out on known structural elements of DNA polymerase III, the catalytic α-subunit of the Escherichia coli DNA replisome along with new insight into the previously uncharacterized C-terminal domain of the protein. PMID:24010795

Capability of Sputtered Micro-patterned NiTi Thick Films

NASA Astrophysics Data System (ADS)

Bechtold, Christoph; Lima de Miranda, Rodrigo; Quandt, Eckhard

2015-09-01

Today, most NiTi devices are manufactured by a combination of conventional metal fabrication steps, e.g., melting, extrusion, cold working, etc., and are subsequently structured by high accuracy laser cutting. This combination has been proven to be very successful; however, there are several limitations to this fabrication route, e.g., in respect to the fabrication of more complex device designs, device miniaturization or the combination of different materials for the integration of further functionality. These issues have to be addressed in order to develop new devices and applications. The fabrication of micro-patterned films using magnetron sputtering, UV lithography, and wet etching has great potential to overcome limitations of conventional device manufacturing. Due to its fabrication characteristics, this method allows the production of devices with complex designs, high structural accuracy, smooth edge profile, at layer thicknesses up to 75 µm. The aim of this study is to present recent developments in the field of NiTi thin film technology, its advantages and limitations, as well as new possible applications in the medical and in non-medical fields. These developments include among others NiTi scaffold structures covered with NiTi membranes for their potential use as filters, heart valve components or aneurysm treatments, as well as micro-actuators for consumable electronics or automotive applications.

Changes in the Anatomic and Microscopic Structure and the Expression of HIF-1α and VEGF of the Yak Heart with Aging and Hypoxia

PubMed Central

He, Yanyu; Yu, Sijiu; Hu, Junwei; Cui, Yan; Liu, Penggang

2016-01-01

The study aimed to identify the changes of anatomic and microscopic structure and the expression and localization of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) in the myocardium and coronary artery of the yak heart adapted to chronic hypoxia with aging. Thirty-two yaks (1 day, 6 months, 1 year, 2 years, and 5 year old) were included, and immunoelectronmicroscopy, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) were used. Right ventricular hypertrophy was not present in yaks with aging. There was no intima thickening phenomenon in the coronary artery. The ultrastructure of myofibrils, mitochondria, and collagen fibers and the diameter and quantity of collagen changed significantly with aging. The enzymatic activity of complexes I, II, and V increased with age. Immunogold labeling showed the localization of HIF-1α protein in the cytoplasm and nuclei of endothelial cells and cytoplasm of cardiac muscle cells, and VEGF protein in the nuclei and perinuclei areas of smooth muscle cells of coronary artery, and in the cytoplasm and nuclei of endothelial cells. ELISA results showed that HIF-1α secretion significantly increased in the myocardium and coronary artery from an age of 1 day to 2 years of yaks and decreased in old yaks. However, VEGF protein always increased with aging. The findings of this study suggest that 6 months is a key age of yak before which there are some adaptive changes to deal with low-oxygen environment, and there is a maturation of the yak heart from the age of 6 months to 2 years. PMID:26914488

Device therapy in heart failure with reduced ejection fraction-cardiac resynchronization therapy and more.

PubMed

Duncker, D; Veltmann, C

2018-05-09

In patients with heart failure with reduced ejection fraction (HFrEF), optimal medical treatment includes beta-blockers, ACE inhibitors/angiotensinreceptor-neprilysin inhibitors (ARNI), mineralocorticoid receptor antagonists, and ivabradine when indicated. In device therapy of HFrEF, implantable cardioverter-defibrillators and cardiac resynchronization therapy (CRT) have been established for many years. CRT is the therapy of choice (class I indication) in symptomatic patients with HFrEF and a broad QRS complex with a left bundle branch block (LBBB) morphology. However, the vast majority of heart failure patients show a narrow QRS complex or a non-LBBB morphology. These patients are not candidates for CRT and alternative electrical therapies such as baroreflex activation therapy (BAT) and cardiac contractility modulation (CCM) may be considered. BAT modulates vegetative dysregulation in heart failure. CCM improves contractility, functional capacity, and symptoms. Although a broad data set is available for BAT and CCM, mortality data are still lacking for both methods. This article provides an overview of the device-based therapeutic options for patients with HFrEF.

Serial heart rhythm complexity changes in patients with anterior wall ST segment elevation myocardial infarction

NASA Astrophysics Data System (ADS)

Chiu, Hung-Chih; Ma, Hsi-Pin; Lin, Chen; Lo, Men-Tzung; Lin, Lian-Yu; Wu, Cho-Kai; Chiang, Jiun-Yang; Lee, Jen-Kuang; Hung, Chi-Sheng; Wang, Tzung-Dau; Daisy Liu, Li-Yu; Ho, Yi-Lwun; Lin, Yen-Hung; Peng, Chung-Kang

2017-03-01

Heart rhythm complexity analysis has been shown to have good prognostic power in patients with cardiovascular disease. The aim of this study was to analyze serial changes in heart rhythm complexity from the acute to chronic phase of acute myocardial infarction (MI). We prospectively enrolled 27 patients with anterior wall ST segment elevation myocardial infarction (STEMI) and 42 control subjects. In detrended fluctuation analysis (DFA), the patients had significantly lower DFAα2 in the acute stage (within 72 hours) and lower DFAα1 at 3 months and 12 months after MI. In multiscale entropy (MSE) analysis, the patients had a lower slope 5 in the acute stage, which then gradually increased during the follow-up period. The areas under the MSE curves for scale 1 to 5 (area 1-5) and 6 to 20 (area 6-20) were lower throughout the chronic stage. Area 6-20 had the greatest discriminatory power to differentiate the post-MI patients (at 1 year) from the controls. In both the net reclassification improvement and integrated discrimination improvement models, MSE parameters significantly improved the discriminatory power of the linear parameters to differentiate the post-MI patients from the controls. In conclusion, the patients with STEMI had serial changes in cardiac complexity.

Phase Transition in a Healthy Human Heart Rate

NASA Astrophysics Data System (ADS)

Kiyono, Ken; Struzik, Zbigniew R.; Aoyagi, Naoko; Togo, Fumiharu; Yamamoto, Yoshiharu

2005-07-01

A healthy human heart rate displays complex fluctuations which share characteristics of physical systems in a critical state. We demonstrate that the human heart rate in healthy individuals undergoes a dramatic breakdown of criticality characteristics, reminiscent of continuous second order phase transitions. By studying the germane determinants, we show that the hallmark of criticality—highly correlated fluctuations—is observed only during usual daily activity, and a breakdown of these characteristics occurs in prolonged, strenuous exercise and sleep. This finding is the first reported discovery of the dynamical phase transition phenomenon in a biological control system and will be a key to understanding the heart rate control system in health and disease.

A perspective on diuretic resistance in chronic congestive heart failure

PubMed Central

Shah, Niel; Madanieh, Raef; Alkan, Mehmet; Dogar, Muhammad U.; Kosmas, Constantine E.; Vittorio, Timothy J.

2017-01-01

Chronic congestive heart failure (CHF) is a complex disorder characterized by inability of the heart to keep up the demands on it, followed by the progressive pump failure and fluid accumulation. Although the loop diuretics are widely used in heart failure (HF) patients, both pharmacodynamic and pharmacokinetic alterations are thought to be responsible for diuretic resistance in these patients. Strategies to overcome diuretic resistance include sodium intake restriction, changes in diuretic dose and route of administration and sequential nephron diuretic therapy. In this review, we discuss the definition, prevalence, mechanism of development and management strategies of diuretic resistance in HF patients. PMID:28728476

lncRNA Structure: Message to the Heart.

PubMed

Fazal, Furqan M; Chang, Howard Y

2016-10-06

In this issue, Xue et al. (2016) describe the secondary structure of the heart-specific long non-coding RNA Braveheart, leading to the discovery of a short, asymmetric G-rich loop that controls cardiac lineage commitment by interacting with the transcription factor CNBP. Copyright © 2016 Elsevier Inc. All rights reserved.

Structural Adaptation

ERIC Educational Resources Information Center

Crowley, Julianne; Titmus, Morgan

2016-01-01

This article explores an alternative conception held by high school and first-year university biology students regarding the structure of the left and right ventricles of the heart and the significance of the left ventricular wall being thicker than the right. The left ventricular wall of the heart is thicker than the right ventricular wall due to…

History of cardiac anatomy: a comprehensive review from the Egyptians to today.

PubMed

Loukas, Marios; Youssef, Pamela; Gielecki, Jerzy; Walocha, Jerzy; Natsis, Kostantinos; Tubbs, R Shane

2016-04-01

The nature, function, and anatomy of the heart have been extensively studied since 3500 B.C. Greek and Egyptian science developed a basic understanding of the heart, although this was primarily related to religious beliefs. During the Hippocratic era, Hippocrates and his colleagues developed a more scientific and less religious understanding of the cardiovascular system. The post-Hippocratic era was characterized by more advanced descriptions of the location, structure, and function of the heart. The Alexandrian, Roman, Medieval Islamic, and European eras included turning points in the history of cardiac anatomy. Subsequently, after the structure and function of the heart were established, its connection with the lungs was investigated. Description of the pulmonary circulation was followed by the discovery of the conductive system and innervation of the heart. © 2016 Wiley Periodicals, Inc.

Complex Roads from Genotype to Phenotype in Dilated Cardiomyopathy: Scientific update from the Working Group of Myocardial Function of the European Society of Cardiology

PubMed

Bondue, Antoine; Arbustini, Eloisa; Bianco, Anna M; Ciccarelli, Michele; Dawson, Dana; De Rosa, Matteo; Hamdani, Nazha; Hilfiker-Kleiner, Denise; Meder, Benjamin; Leite Moreira, Adelino; Thum, Thomas; Gabriele Tocchetti, Carlo; Varricchi, Gilda; Van der Velden, Jolanda; Walsh, Roddy; Heymans, Stephane

2018-05-23

Dilated cardiomyopathy (DCM) frequently affects relatively young, economically and socially active adults, and is an important cause of heart failure and transplantation. DCM is a complex disease and its pathological architecture encounters many genetic determinants interacting with environmental factors. The old perspective that every pathogenic gene mutation would lead to a diseased heart, is now being replaced by the novel observation that the phenotype depends not only on the penetrance -malignancy of the mutated gene- but also on epigenetics, age, toxic factors, pregnancy and a diversity of acquired diseases. This review discusses how gene mutations will result in mutation-specific molecular alterations in the heart including increased mitochondrial oxidation (sarcomeric gene e.g. TTN), decreased calcium sensitivity (sarcomeric genes), fibrosis (e.g. LMNA and TTN) or inflammation. Therefore, getting a complete picture of the DCM patient will include genomic data, molecular assessment by preference from cardiac samples, stratification according to co-morbidities, and phenotypic description. Those data will help to better guide the heart failure and anti-arrhythmic treatment, predict response to therapy, develop novel siRNA-based gene silencing for malignant gene mutations, or intervene with mutation-specific altered gene pathways in the heart.

Improving the Prediction of Mortality and the Need for Life-Saving Interventions in Trauma Patients Using Standard Vital Signs With Heart-Rate Variability and Complexity

DTIC Science & Technology

2015-06-01

Trauma 69:S10YS13, 2010. 2. Liu NT, Holcomb JB, Wade CE, Darrah MI, Salinas J: Utility of vital signs, heart-rate variability and complexity, and machine ... learning for identifying the need for life-saving interventions in trauma patients. Shock 42:108Y114, 2014. 3. Pickering TG, Shimbo D, Hass D...Ann Emerg Med 45:68Y76, 2005. 8. Liu NT, Holcomb JB, Wade CE, Batchinsky AI, Cancio LC, Darrah MI, Salinas J: Development and validation of a machine

Problems experienced by informal caregivers of individuals with heart failure: An integrative review.

PubMed

Grant, Joan S; Graven, Lucinda J

2018-04-01

The purpose of this review was to examine and synthesize recent literature regarding problems experienced by informal caregivers when providing care for individuals with heart failure in the home. Integrative literature review. A review of current empirical literature was conducted utilizing PubMed, CINAHL, Embase, Sociological Abstracts, Social Sciences Full Text, PsycARTICLES, PsycINFO, Health Source: Nursing/Academic Edition, and Cochrane computerized databases. 19 qualitative, 16 quantitative, and 2 mixed methods studies met the inclusion criteria for review. Computerized databases were searched for a combination of subject terms (i.e., MeSH) and keywords related to informal caregivers, problems, and heart failure. The title and abstract of identified articles and reference lists were reviewed. Studies were included if they were published in English between January 2000 and December 2016 and examined problems experienced by informal caregivers in providing care for individuals with heart failure in the home. Studies were excluded if not written in English or if elements of caregiving in heart failure were not present in the title, abstract, or text. Unpublished and duplicate empirical literature as well as articles related to specific end-stage heart failure populations also were excluded. Methodology described by Cooper and others for integrative reviews of quantitative and qualitative research was used. Quality appraisal of the included studies was evaluated using the Joanna Briggs Institute critical appraisal tools for cross-sectional quantitative and qualitative studies. Informal caregivers experienced four key problems when providing care for individuals with heart failure in the home, including performing multifaceted activities and roles that evolve around daily heart failure demands; maintaining caregiver physical, emotional, social, spiritual, and financial well-being; having insufficient caregiver support; and performing caregiving with uncertainty and inadequate knowledge. Informal caregivers of individuals with heart failure experience complex problems in the home when providing care which impact all aspects of their lives. Incorporating advice from informal caregivers of individuals with heart failure will assist in the development of interventions to reduce negative caregiver outcomes. Given the complex roles in caring for individuals with heart failure, multicomponent interventions are potentially promising in assisting informal caregivers in performing these roles. Published by Elsevier Ltd.

Cardiac voltage gated calcium channels and their regulation by β-adrenergic signaling.

PubMed

Kumari, Neema; Gaur, Himanshu; Bhargava, Anamika

2018-02-01

Voltage-gated calcium channels (VGCCs) are the predominant source of calcium influx in the heart leading to calcium-induced calcium release and ultimately excitation-contraction coupling. In the heart, VGCCs are modulated by the β-adrenergic signaling. Signaling through β-adrenergic receptors (βARs) and modulation of VGCCs by β-adrenergic signaling in the heart are critical signaling and changes to these have been significantly implicated in heart failure. However, data related to calcium channel dysfunction in heart failure is divergent and contradictory ranging from reduced function to no change in the calcium current. Many recent studies have highlighted the importance of functional and spatial microdomains in the heart and that may be the key to answer several puzzling questions. In this review, we have briefly discussed the types of VGCCs found in heart tissues, their structure, and significance in the normal and pathological condition of the heart. More importantly, we have reviewed the modulation of VGCCs by βARs in normal and pathological conditions incorporating functional and structural aspects. There are different types of βARs, each having their own significance in the functioning of the heart. Finally, we emphasize the importance of location of proteins as it relates to their function and modulation by co-signaling molecules. Its implication on the studies of heart failure is speculated. Copyright © 2017 Elsevier Inc. All rights reserved.

How Can Music Influence the Autonomic Nervous System Response in Patients with Severe Disorder of Consciousness?

PubMed

Riganello, Francesco; Cortese, Maria D; Arcuri, Francesco; Quintieri, Maria; Dolce, Giuliano

2015-01-01

Activations to pleasant and unpleasant musical stimuli were observed within an extensive neuronal network and different brain structures, as well as in the processing of the syntactic and semantic aspects of the music. Previous studies evidenced a correlation between autonomic activity and emotion evoked by music listening in patients with Disorders of Consciousness (DoC). In this study, we analyzed retrospectively the autonomic response to musical stimuli by mean of normalized units of Low Frequency (nuLF) and Sample Entropy (SampEn) of Heart Rate Variability (HRV) parameters, and their possible correlation to the different complexity of four musical samples (i.e., Mussorgsky, Tchaikovsky, Grieg, and Boccherini) in Healthy subjects and Vegetative State/Unresponsive Wakefulness Syndrome (VS/UWS) patients. The complexity of musical sample was based on Formal Complexity and General Dynamics parameters defined by Imberty's semiology studies. The results showed a significant difference between the two groups for SampEn during the listening of Mussorgsky's music and for nuLF during the listening of Boccherini and Mussorgsky's music. Moreover, the VS/UWS group showed a reduction of nuLF as well as SampEn comparing music of increasing Formal Complexity and General Dynamics. These results put in evidence how the internal structure of the music can change the autonomic response in patients with DoC. Further investigations are required to better comprehend how musical stimulation can modify the autonomic response in DoC patients, in order to administer the stimuli in a more effective way.

The future of heart valve banking and of homografts: perspective from the Deutsches Herzzentrum Berlin.

PubMed

Delmo Walter, E M; de By, T M M H; Meyer, R; Hetzer, R

2012-01-01

Ever since the early days of homograft implantation in 1956, and the introduction into clinical practice by Ross and Barrat Boyes, homograft heart valves have proven to have many advantages. Its disadvantages became evident during long-term follow up. Factors, such as donor and recipient morbidity, tissue banking techniques, and the often complex surgical technique required to implant, are of great influence on the long term results. Because of European Directives, legally binding quality assurance regulations have been introduced in homograft banks. However, still not all processing methods have been scientifically sub-structured on their effects on the final product and its durability. The donor shortage has stimulated researchers and industries to develop and improve mechanical and biological valve substitutes such as the stentless bioprostheses. In general, candidates for homograft valve implantation include patients with: endocarditis, congenital defects and women who wish to become pregnant. For each category of patients different implantation techniques are required. The results of homograft banking and homograft transplantation in the German Heart Institute Berlin are satisfactory. Freedom of re-infection rate after homograft implantation is 91.9% +/- 3.6% after 15 years. Current developments show an increased interest in tissue engineered as well as in de- and re-cellularization of heart valve homografts. The advantages and disadvantages of the several processing techniques have not yet been proven in long term clinical results. For homograft bankers these developments pose as a challenge to join forces and to initiate cooperate projects aimed at scientific and organizational development.

Bioengineering an electro-mechanically functional miniature ventricular heart chamber from human pluripotent stem cells.

PubMed

Li, Ronald A; Keung, Wendy; Cashman, Timothy J; Backeris, Peter C; Johnson, Bryce V; Bardot, Evan S; Wong, Andy O T; Chan, Patrick K W; Chan, Camie W Y; Costa, Kevin D

2018-05-01

Tissue engineers and stem cell biologists have made exciting progress toward creating simplified models of human heart muscles or aligned monolayers to help bridge a longstanding gap between experimental animals and clinical trials. However, no existing human in vitro systems provide the direct measures of cardiac performance as a pump. Here, we developed a next-generation in vitro biomimetic model of pumping human heart chamber, and demonstrated its capability for pharmaceutical testing. From human pluripotent stem cell (hPSC)-derived ventricular cardiomyocytes (hvCM) embedded in collagen-based extracellular matrix hydrogel, we engineered a three-dimensional (3D) electro-mechanically coupled, fluid-ejecting miniature human ventricle-like cardiac organoid chamber (hvCOC). Structural characterization showed organized sarcomeres with myofibrillar microstructures. Transcript and RNA-seq analyses revealed upregulation of key Ca 2+ -handling, ion channel, and cardiac-specific proteins in hvCOC compared to lower-order 2D and 3D cultures of the same constituent cells. Clinically-important, physiologically complex contractile parameters such as ejection fraction, developed pressure, and stroke work, as well as electrophysiological properties including action potential and conduction velocity were measured: hvCOC displayed key molecular and physiological characteristics of the native ventricle, and showed expected mechanical and electrophysiological responses to a range of pharmacological interventions (including positive and negative inotropes). We conclude that such "human-heart-in-a-jar" technology could facilitate the drug discovery process by providing human-specific preclinical data during early stage drug development. Copyright © 2018. Published by Elsevier Ltd.

Thromboprophylaxis for atrial arrhythmias in congenital heart disease: A multicenter study.

PubMed

Khairy, Paul; Aboulhosn, Jamil; Broberg, Craig S; Cohen, Scott; Cook, Stephen; Dore, Annie; Fernandes, Susan M; Fournier, Anne; Kay, Joseph; Levesque, Sylvie; Macle, Laurent; Marcotte, François; Mondésert, Blandine; Mongeon, François-Pierre; Opotowsky, Alexander R; Proietti, Anna; Rivard, Lena; Ting, Jennifer; Thibault, Bernard; Zaidi, Ali; Hamilton, Robert

2016-11-15

There is a paucity of data to guide decisions regarding thromboprophylaxis for atrial arrhythmias in congenital heart disease. A retrospective multicenter cohort study enrolled patients with documented sustained atrial arrhythmias and congenital heart disease from 12 North American centers to quantify thromboembolic and bleeding rates associated with antiplatelet and anticoagulation therapy, and explore associated factors. A blinded committee adjudicated all qualifying arrhythmias and outcomes. A total of 482 patients, 45.2% female, age 32.0±18.0years, were followed for 11.3±9.4years since the qualifying arrhythmia. Antiplatelet therapy was administered to 37.8%, anticoagulation to 54.4%, and neither to 7.9%. Congenital heart disease complexity was simple, moderate, and severe in 18.5%, 34.4%, and 47.1%, respectively. Freedom from thromboembolic events was 84.7±2.7% at 15years, with no difference between anticoagulation versus antiplatelet therapy (P=0.97). Congenital heart disease complexity was independently associated with thromboembolic events, with rates of 0.00%, 0.93%, and 1.95%/year in those with simple, moderate, and severe forms (P<0.001). CHADS 2 and CHA 2 DS 2 -VASc scores were not predictive of thromboembolic risk. Annualized bleeding rates with antiplatelet and anticoagulation therapy were 0.66% and 1.82% (P=0.039). In multivariable analyses, anticoagulation [hazard ratio (HR) 4.76, 95% CI (1.05-21.58), P=0.043] and HAS-BLED score [HR 3.15, 95% CI (1.02, 9.78), P=0.047] were independently associated with major bleeds. Current management of atrial arrhythmias in congenital heart disease is associated with a modest rate of thromboembolic events, which is predicted by disease complexity but not CHADS 2 /CHA 2 DS 2 -VASc scores. HAS-BLED score is applicable to the congenital population in predicting major bleeds. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Intracardiac Echocardiography for Structural Heart and Electrophysiological Interventions.

PubMed

Basman, Craig; Parmar, Yuvrajsinh J; Kronzon, Itzhak

2017-09-06

With an increasing number of interventional procedures performed for structural heart disease and cardiac arrhythmias each year, echocardiographic guidance is necessary for safe and efficient results. The purpose of this review article is to overview the principles of intracardiac echocardiography (ICE) and describes the peri-interventional role of ICE in a variety of structural heart disease and electrophysiological interventions. Both transthoracic (TTE) and transesophageal echocardiography have limitations. ICE provides the advantage of imaging from within the heart, providing shorter image distances and higher resolution. ICE may be performed without sedation and avoids esophageal intubation as with transesophageal echocardiography (TEE). Limitations of ICE include the need for additional venous access with possibility of vascular complications, potentially higher costs, and a learning curve for new operators. Data supports the use of ICE in guiding device closure of interatrial shunts, transseptal puncture, and electrophysiologic procedures. This paper reviews the more recent reports that ICE may be used for primary guidance or as a supplement to TEE in patients undergoing left atrial appendage (LAA) closure, interatrial shunt closure, transaortic valve implantation (TAVI), percutaneous mitral valve repair (PMVR), paravalvular leak (PVL) closure, aortic interventions, transcatheter pulmonary valve replacement (tPVR), ventricular septal defect (VSD), and patent ductus arteriosus (PDA) closure. ICE imaging technology will continue to expand and help improve structural heart and electrophysiology interventions.

Effect of experimental coronary sinus ligation on myocardial structure and function in the presence or absence of structural heart disease: an insight for the interventional electrophysiologist.

PubMed

Diab, Osama Ali; Amer, Mohammed Said; Salah El-Din, Rania Ahmed

2016-12-01

To study the effect of coronary sinus (CS) occlusion on normal hearts and hearts with structural disease. We included 32 dogs, divided into 4 groups: (1) CS ligation (CSL): subjected to CSL; (2) control group: no intervention; (3) MI-CSL group: subjected to myocardial infarction (MI) induction followed by CSL after 1 week; and (4) MI-control group: subjected to MI induction, then open thoracotomy after 1 week without CSL. Electrocardiography, echocardiography, histopathology, and immunohistochemistry were done before and after CSL. In CSL group, there were no significant electrocardiographic or echocardiographic changes after CSL, although there was interstitial oedema that decreased after 1 week with the appearance of Thebesian vessels and positive staining for vascular endothelial growth factor. In MI-CSL group, there was significant increase in left ventricular (LV) end-systolic diameter (P = 02), decrease in LV fractional shortening (P = 0.0001), and LV ejection fraction (P = 0.002) in comparison with MI-control group, associated with severe myocardial degeneration. Acute CS occlusion could be compensated in normal hearts, but may be detrimental in the presence of structural heart disease. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Rationale and design of a multicenter echocardiographic study to assess the relationship between cardiac structure and function and heart failure risk in a biracial cohort of community-dwelling elderly persons: the Atherosclerosis Risk in Communities study.

PubMed

Shah, Amil M; Cheng, Susan; Skali, Hicham; Wu, Justina; Mangion, Judy R; Kitzman, Dalane; Matsushita, Kunihiro; Konety, Suma; Butler, Kenneth R; Fox, Ervin R; Cook, Nakela; Ni, Hanyu; Coresh, Josef; Mosley, Thomas H; Heiss, Gerardo; Folsom, Aaron R; Solomon, Scott D

2014-01-01

Heart failure is an important public health concern, particularly among persons>65 years of age. Women and blacks are critically understudied populations that carry a sizeable portion of the heart failure burden. Limited normative and prognostic data exist on measures of cardiac structure, diastolic function, and novel measures of systolic deformation in older adults living in the community. The Atherosclerosis Risk in Communities (ARIC) study is a large, predominantly biracial, National Heart, Lung, and Blood Institute-sponsored epidemiological cohort study. Between 2011 and 2013, ≈6000 surviving participants, now in their seventh to ninth decade of life, are expected to return for a fifth study visit during which comprehensive 2-dimensional, Doppler, tissue Doppler, and speckle-tracking echocardiography will be performed uniformly in all cohort clinic visit participants. The following objectives will be addressed: (1) to characterize cardiac structural and functional abnormalities among the elderly and to determine how they differ by sex and race/ethnicity, (2) to determine the relationship between ventricular and vascular abnormalities, and (3) to prospectively examine the extent to which these noninvasive measures associate with incident heart failure. We describe the design, imaging acquisition and analysis methods, and quality assurance metrics for echocardiography in visit 5 of the ARIC cohort. A better understanding of the differences in cardiac structure and function through the spectrum of heart failure stages in elderly persons generally, and between sexes and racial/ethnic groups specifically, will deepen our understanding of the pathophysiology driving heart failure progression in these at-risk populations and may inform novel prevention or therapeutic strategies.

T-tubule disease: Relationship between t-tubule organization and regional contractile performance in human dilated cardiomyopathy.

PubMed

Crossman, David J; Young, Alistair A; Ruygrok, Peter N; Nason, Guy P; Baddelely, David; Soeller, Christian; Cannell, Mark B

2015-07-01

Evidence from animal models suggest that t-tubule changes may play an important role in the contractile deficit associated with heart failure. However samples are usually taken at random with no regard as to regional variability present in failing hearts which leads to uncertainty in the relationship between contractile performance and possible t-tubule derangement. Regional contraction in human hearts was measured by tagged cine MRI and model fitting. At transplant, failing hearts were biopsy sampled in identified regions and immunocytochemistry was used to label t-tubules and sarcomeric z-lines. Computer image analysis was used to assess 5 different unbiased measures of t-tubule structure/organization. In regions of failing hearts that showed good contractile performance, t-tubule organization was similar to that seen in normal hearts, with worsening structure correlating with the loss of regional contractile performance. Statistical analysis showed that t-tubule direction was most highly correlated with local contractile performance, followed by the amplitude of the sarcomeric peak in the Fourier transform of the t-tubule image. Other area based measures were less well correlated. We conclude that regional contractile performance in failing human hearts is strongly correlated with the local t-tubule organization. Cluster tree analysis with a functional definition of failing contraction strength allowed a pathological definition of 't-tubule disease'. The regional variability in contractile performance and cellular structure is a confounding issue for analysis of samples taken from failing human hearts, although this may be overcome with regional analysis by using tagged cMRI and biopsy mapping. Copyright © 2015 Elsevier Ltd. All rights reserved.

TTK Chitra tilting disc heart valve model TC2: An assessment of fatigue life and durability.

PubMed

Subhash, N N; Rajeev, Adathala; Sujesh, Sreedharan; Muraleedharan, C V

2017-08-01

Average age group of heart valve replacement in India and most of the Third World countries is below 30 years. Hence, the valve for such patients need to be designed to have a service life of 50 years or more which corresponds to 2000 million cycles of operation. The purpose of this study was to assess the structural performance of the TTK Chitra tilting disc heart valve model TC2 and thereby address its durability. The TC2 model tilting disc heart valves were assessed to evaluate the risks connected with potential structural failure modes. To be more specific, the studies covered the finite element analysis-based fatigue life prediction and accelerated durability testing of the tilting disc heart valves for nine different valve sizes. First, finite element analysis-based fatigue life prediction showed that all nine valve sizes were in the infinite life region. Second, accelerated durability test showed that all nine valve sizes remained functional for 400 million cycles under experimental conditions. The study ensures the continued function of TC2 model tilting disc heart valves over duration in excess of 50 years. The results imply that the TC2 model valve designs are structurally safe, reliable and durable.

Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology.

PubMed

Gorter, Thomas M; van Veldhuisen, Dirk J; Bauersachs, Johann; Borlaug, Barry A; Celutkiene, Jelena; Coats, Andrew J S; Crespo-Leiro, Marisa G; Guazzi, Marco; Harjola, Veli-Pekka; Heymans, Stephane; Hill, Loreena; Lainscak, Mitja; Lam, Carolyn S P; Lund, Lars H; Lyon, Alexander R; Mebazaa, Alexandre; Mueller, Christian; Paulus, Walter J; Pieske, Burkert; Piepoli, Massimo F; Ruschitzka, Frank; Rutten, Frans H; Seferovic, Petar M; Solomon, Scott D; Shah, Sanjiv J; Triposkiadis, Filippos; Wachter, Rolf; Tschöpe, Carsten; de Boer, Rudolf A

2018-01-01

There is an unmet need for effective treatment strategies to reduce morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively focused on the left side. However, it is now increasingly recognized that right heart dysfunction is common and contributes importantly to poor prognosis in HFpEF. More insights into the development of right heart dysfunction in HFpEF may aid to our knowledge about this complex disease and may eventually lead to better treatments to improve outcomes in these patients. In this position paper from the Heart Failure Association of the European Society of Cardiology, the Committee on Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis, and pathophysiology of right heart dysfunction and failure in patients with HFpEF. Finally, potential treatment strategies, important knowledge gaps and future directions regarding the right side in HFpEF are discussed. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Low frequency of cardniac arrhythmias and lack of structural heart disease in medically-naïve acromegaly patients: a prospective study at baseline and after 1 year of somatostatin analogs treatment.

PubMed

Warszawski, Leila; Kasuki, Leandro; Sá, Rodrigo; Dos Santos Silva, Cintia Marques; Volschan, Isabela; Gottlieb, Ilan; Pedrosa, Roberto Coury; Gadelha, Mônica R

2016-12-01

The incidence of arrhythmias may be increased in acromegaly, but the pathophysiologic mechanisms involved are still unclear, and it has never been correlated with structural heart changes analyzed by the gold-standard method cardiac magnetic resonance (CMR). Evaluate the frequency of arrhythmias in drug-naïve acromegaly patients at baseline and after 1 year of somatostatin analogs (SA) treatment and to correlate the occurrence of arrhythmias with the presence of structural heart changes. Consecutive drug-naïve acromegaly patients were recruited. The occurrence of arrhythmias and structural heart changes were studied through 24-h Holter and CMR, respectively, at baseline and after 1-year SA treatment. Thirty-six patients were studied at baseline and 28 were re-evaluated after 1 year of SA treatment. There were 13 females and median age was 48 years (20-73 years). Nine patients (32 %) were controlled after treatment. No sustained arrhythmias were reported in the 24-h Holter. No arrhythmia-related symptoms were observed. Only two patients presented left ventricular hypertrophy and three patients presented fibrosis at baseline. There was no correlation of the left ventricular mass with the number of episodes of arrhythmias and they were not more prevalent in the patients presenting cardiac fibrosis. We found no sustained arrhythmias and a lack of arrhythmia-related symptoms at baseline and after 1 year of SA treatment in a contemporary cohort of acromegaly patients that also present a low frequency of structural heart changes, indicating that these patients may have a lower frequency of heart disease than previously reported.

Components of the cellular defense and detoxification system of the common cuttlefish Sepia officinalis (Mollusca, Cephalopoda).

PubMed

Beuerlein, Knut; Löhr, Sandra; Westermann, Bettina; Ruth, Peter; Schipp, Rudolf

2002-12-01

Endocytotic-active cells in the branchial heart complex of Sepia officinalis were studied by in situ injection of different types of xenobiotics and by in vitro perfusion of the organ complex with a bacterial suspension. The rhogocytes (ovoid cells) ingest particles of all tested sizes by endocytosis and phagocytosis. The hemocytes of the circulating blood and the adhesive hemocytes in the wall of the branchial heart incorporate all tested kinds of foreign materials, including bacterial cells due to phagocytosis achieved by the triangular mesenchymatic cells. The ultrastructural findings also give strong evidence that the triangular mesenchymatic cells are fixed hemocytes that have migrated into the branchial heart tissue. The ingestion and digestion of allogeneic substances and bacteria or their debris by rhogocytes and/or all (forms of) hemocytes suggests the involvement of these either fixed or mobile endocytotic-active cells in the defense and detoxification system of cephalopods.

The Congenital Heart Surgeons Society Datacenter: unique attributes as a research organization.

PubMed

Caldarone, Christopher A; Williams, William G

2010-01-01

Over the last 25 years, the Congenital Heart Surgeons Society (CHSS) has evolved from an informal club to a mature organization. A central feature of the CHSS has been dedication to evaluating outcomes of congenital heart surgery across a wide array of clinical diagnoses. These research activities have been orchestrated through the CHSS Datacenter, which has developed a unique organizational structure that has strengths and weaknesses in comparison to other research organizational structures (e.g., prospective randomized trials, registries, etc). This review will highlight the unique attributes of the CHSS Datacenter with emphasis on the Datacenter's strengths and weaknesses in comparison to other organizational structures. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Advances in heart rate variability signal analysis: joint position statement by the e-Cardiology ESC Working Group and the European Heart Rhythm Association co-endorsed by the Asia Pacific Heart Rhythm Society.

PubMed

Sassi, Roberto; Cerutti, Sergio; Lombardi, Federico; Malik, Marek; Huikuri, Heikki V; Peng, Chung-Kang; Schmidt, Georg; Yamamoto, Yoshiharu

2015-09-01

Following the publication of the Task Force document on heart rate variability (HRV) in 1996, a number of articles have been published to describe new HRV methodologies and their application in different physiological and clinical studies. This document presents a critical review of the new methods. A particular attention has been paid to methodologies that have not been reported in the 1996 standardization document but have been more recently tested in sufficiently sized populations. The following methods were considered: Long-range correlation and fractal analysis; Short-term complexity; Entropy and regularity; and Nonlinear dynamical systems and chaotic behaviour. For each of these methods, technical aspects, clinical achievements, and suggestions for clinical application were reviewed. While the novel approaches have contributed in the technical understanding of the signal character of HRV, their success in developing new clinical tools, such as those for the identification of high-risk patients, has been rather limited. Available results obtained in selected populations of patients by specialized laboratories are nevertheless of interest but new prospective studies are needed. The investigation of new parameters, descriptive of the complex regulation mechanisms of heart rate, has to be encouraged because not all information in the HRV signal is captured by traditional methods. The new technologies thus could provide after proper validation, additional physiological, and clinical meaning. Multidisciplinary dialogue and specialized courses in the combination of clinical cardiology and complex signal processing methods seem warranted for further advances in studies of cardiac oscillations and in the understanding normal and abnormal cardiac control processes. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Effects of eHealth physical activity encouragement in adolescents with complex congenital heart disease: The PReVaiL randomized clinical trial.

PubMed

Klausen, Susanne Hwiid; Andersen, Lars L; Søndergaard, Lars; Jakobsen, Janus Christian; Zoffmann, Vibeke; Dideriksen, Kasper; Kruse, Anne; Mikkelsen, Ulla Ramer; Wetterslev, Jørn

2016-10-15

To assess benefit and harms of adding an eHealth intervention to health education and individual counseling in adolescents with congenital heart disease. Randomized clinical trial. Denmark. A total of 158 adolescents aged 13-16years with no physical activity restrictions after repaired complex congenital heart disease. PReVaiL consisted of individually tailored eHealth encouragement physical activity for 52weeks. All patients received 45min of group-based health education and 15min of individual counseling involving patients' parents. The primary outcome was maximal oxygen uptake (VO2 peak) at 52weeks after randomization. The secondary outcome was physical activity. Exploratory outcomes were generic and disease-specific questionnaires. In the intervention group, 58 patients (72%) completed the final test, but of those, only 46 (57%) fulfilled the compliance criteria of using the eHealth application for at least 2 consecutive weeks. In the control group, 61 patients (79%) completed both exercise tests. Adjusted for baseline values, the difference between the intervention group and the control group in mean VO2 peak at 1year was -0.65ml·kg(-1)·min(-1) (95% CI -2.66 to 1.36). Between-group differences at 1year in physical activity, generic health-related quality of life, and disease-specific quality of life were not statistically significant. Adding a tailored eHealth intervention to health education and individual counseling did not affect outcomes among adolescents with congenital heart disease. Our results do not support the use of this eHealth intervention in adolescents with complex congenital heart disease. Clinical trials.gov identifier: NCT01189981. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Healthcare Disparities in Outcomes of a Metropolitan Congenital Heart Surgery Center: The Effect of Clinical and Socioeconomic Factors.

PubMed

Peterson, Jennifer K; Catton, Kirsti G; Setty, Shaun P

2018-04-01

The purpose of this study is to identify the impact of demographic, socioeconomic, and clinical factors on congenital heart surgery outcomes. This retrospective cohort study included 234 congenital heart surgery patients from 2011 through 2015, in a racially/ethnically diverse metropolitan children's hospital. Outcomes included length of stay (LOS), age at first echocardiogram, length of mechanical ventilation, and incidence of complications. Compared to others, black children underwent their first echocardiogram at a later age (median 23 versus 2 days, p = 0.014) and were more likely to be diagnosed with congenital heart disease in the emergency room (p = 0.026). Hispanic children were more likely to have major non-cardiac congenital anomalies (p = 0.045). Increased LOS during elective admissions was associated with higher surgical complexity (STAT category 4 and 5 Estimate 3.905 days, p = 0.001), compared to STAT category 1, and number of complications (Estimate = 2.306 days per complication, p < 0.001). Increased LOS in non-elective admissions was associated with the number of complex chronic conditions (Estimate = 15.446 days, p = 0.045) and the number of complications (Estimate = 11.591 days per complication, p < 0.001). However, in multivariate analysis, race and ethnicity was not associated with increased LOS or age at first echocardiogram. In this diverse setting, race/ethnicity was not associated with increased LOS, age at first echocardiogram, length of ventilation, or complications. Surgical complexity, chronic conditions, and complications were associated with increased LOS. We discuss some interventions to reduce disparities in congenital heart surgery outcomes.

A heart that beats for 500 years: age-related changes in cardiac proteasome activity, oxidative protein damage and expression of heat shock proteins, inflammatory factors, and mitochondrial complexes in Arctica islandica, the longest-living noncolonial animal.

PubMed

Sosnowska, Danuta; Richardson, Chris; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan; Ridgway, Iain

2014-12-01

Study of negligibly senescent animals may provide clues that lead to better understanding of the cardiac aging process. To elucidate mechanisms of successful cardiac aging, we investigated age-related changes in proteasome activity, oxidative protein damage and expression of heat shock proteins, inflammatory factors, and mitochondrial complexes in the heart of the ocean quahog Arctica islandica, the longest-lived noncolonial animal (maximum life span potential: 508 years). We found that in the heart of A. islandica the level of oxidatively damaged proteins did not change significantly up to 120 years of age. No significant aging-induced changes were observed in caspase-like and trypsin-like proteasome activity. Chymotrypsin-like proteasome activity showed a significant early-life decline, then it remained stable for up to 182 years. No significant relationship was observed between the extent of protein ubiquitination and age. In the heart of A. islandica, an early-life decline in expression of HSP90 and five mitochondrial electron transport chain complexes was observed. We found significant age-related increases in the expression of three cytokine-like mediators (interleukin-6, interleukin-1β, and tumor necrosis factor-α) in the heart of A. islandica. Collectively, in extremely long-lived molluscs, maintenance of protein homeostasis likely contributes to the preservation of cardiac function. Our data also support the concept that low-grade chronic inflammation in the cardiovascular system is a universal feature of the aging process, which is also manifest in invertebrates. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Carcinoid heart disease.

PubMed

Bernheim, Alain M; Connolly, Heidi M; Hobday, Timothy J; Abel, Martin D; Pellikka, Patricia A

2007-01-01

Carcinoid heart disease is a rare form of valvular heart disease. The management of these patients is complex, as the systemic malignant disease and the cardiac involvement have to be considered at the same time. Progress in the treatment of patients with carcinoid disease has resulted in improved symptom control and survival. Development and progression of carcinoid heart disease are associated with increased morbidity and mortality. In patients with severe cardiac involvement and well-controlled systemic disease, cardiac surgery has been recognized as the only effective treatment option. Valve replacement surgery may not only be beneficial in terms of symptom relief, but may also contribute to the improved survival observed over the past 2 decades in patients with carcinoid heart disease. Early diagnosis and early surgical treatment in appropriately selected patients may provide the best results. In this article, we review the current literature regarding the biology, diagnosis, treatment, and prognosis of carcinoid heart disease.

The Total Artificial Heart in End-Stage Congenital Heart Disease.

PubMed

Villa, Chet R; Morales, David L S

2017-01-01

The development of durable ventricular assist devices (VADs) has improved mortality rates and quality of life in patients with end stage heart failure. While the use of VADs has increased dramatically in recent years, there is limited experience with VAD implantation in patients with complex congenital heart disease (CHD), despite the fact that the number of patients with end stage CHD has grown due to improvements in surgical and medical care. VAD use has been limited in patients with CHD and end stage heart failure due to anatomic (systemic right ventricle, single ventricle, surgically altered anatomy, valve dysfunction, etc.) and physiologic constraints (diastolic dysfunction). The total artificial heart (TAH), which has right and left sided pumps that can be arranged in a variety of orientations, can accommodate the anatomic variation present in CHD patients. This review provides an overview of the potential use of the TAH in patients with CHD.

The Total Artificial Heart in End-Stage Congenital Heart Disease

PubMed Central

Villa, Chet R.; Morales, David L. S.

2017-01-01

The development of durable ventricular assist devices (VADs) has improved mortality rates and quality of life in patients with end stage heart failure. While the use of VADs has increased dramatically in recent years, there is limited experience with VAD implantation in patients with complex congenital heart disease (CHD), despite the fact that the number of patients with end stage CHD has grown due to improvements in surgical and medical care. VAD use has been limited in patients with CHD and end stage heart failure due to anatomic (systemic right ventricle, single ventricle, surgically altered anatomy, valve dysfunction, etc.) and physiologic constraints (diastolic dysfunction). The total artificial heart (TAH), which has right and left sided pumps that can be arranged in a variety of orientations, can accommodate the anatomic variation present in CHD patients. This review provides an overview of the potential use of the TAH in patients with CHD. PMID:28536530

Structural Model of psychological risk and protective factors affecting on quality of life in patients with coronary heart disease: A psychocardiology model

PubMed Central

Nekouei, Zohreh Khayyam; Yousefy, Alireza; Doost, Hamid Taher Neshat; Manshaee, Gholamreza; Sadeghei, Masoumeh

2014-01-01

Background: Conducted researches show that psychological factors may have a very important role in the etiology, continuity and consequences of coronary heart diseases. This study has drawn the psychological risk and protective factors and their effects in patients with coronary heart diseases (CHD) in a structural model. It aims to determine the structural relations between psychological risk and protective factors with quality of life in patients with coronary heart disease. Materials and Methods: The present cross-sectional and correlational studies were conducted using structural equation modeling. The study sample included 398 patients of coronary heart disease in the university referral Hospital, as well as other city health care centers in Isfahan city. They were selected based on random sampling method. Then, in case, they were executed the following questionnaires: Coping with stressful situations (CISS- 21), life orientation (LOT-10), general self-efficacy (GSE-10), depression, anxiety and stress (DASS-21), perceived stress (PSS-14), multidimensional social support (MSPSS-12), alexithymia (TAS-20), spiritual intelligence (SQ-23) and quality of life (WHOQOL-26). Results: The results showed that protective and risk factors could affect the quality of life in patients with CHD with factor loadings of 0.35 and −0.60, respectively. Moreover, based on the values of the framework of the model such as relative chi-square (CMIN/DF = 3.25), the Comparative Fit Index (CFI = 0.93), the Parsimony Comparative Fit Index (PCFI = 0.68), the Root Mean Square Error of Approximation (RMSEA = 0.07) and details of the model (significance of the relationships) it has been confirmed that the psychocardiological structural model of the study is the good fitting model. Conclusion: This study was among the first to research the different psychological risk and protective factors of coronary heart diseases in the form of a structural model. The results of this study have emphasized the necessity of noticing the psychological factors in primary prevention by preventive programs and in secondary prevention by rehabilitation centers to improve the quality of life of the people with heart diseases. PMID:24778660

Left Thoracotomy HeartWare Implantation With Outflow Graft Anastomosis to the Descending Aorta: A Simplified Bridge for Patients With Multiple Previous Sternotomies

PubMed Central

Umakanthan, Ramanan; Haglund, Nicholas A.; Stulak, John M.; Joyce, Lyle D.; Ahmad, Rashid; Keebler, Mary E.; Maltais, Simon

2014-01-01

Advances in mechanical circulatory support have been critical in bridging patients awaiting heart transplantation. In addition, improvement in device durability has enabled left ventricular assist device therapy to be applied as destination therapy in those not felt to be transplant candidate. Because of the increasing complexity of patients, there continues to be a need for alternative strategies for device implantation to bridge high-risk patients awaiting heart transplantation, wherein the risks of numerous previous sternotomies may be prohibitive. We present a unique technique for placement of the HeartWare ventricular assist device via left anterior thoracotomy to the descending aorta in a patient awaiting heart transplantation with a history of multiple previous sternotomies. PMID:24172273

[Analysis of the heart sound with arrhythmia based on nonlinear chaos theory].

PubMed

Ding, Xiaorong; Guo, Xingming; Zhong, Lisha; Xiao, Shouzhong

2012-10-01

In this paper, a new method based on the nonlinear chaos theory was proposed to study the arrhythmia with the combination of the correlation dimension and largest Lyapunov exponent, through computing and analyzing these two parameters of 30 cases normal heart sound and 30 cases with arrhythmia. The results showed that the two parameters of the heart sounds with arrhythmia were higher than those with the normal, and there was significant difference between these two kinds of heart sounds. That is probably due to the irregularity of the arrhythmia which causes the decrease of predictability, and it's more complex than the normal heart sound. Therefore, the correlation dimension and the largest Lyapunov exponent can be used to analyze the arrhythmia and for its feature extraction.

Towards Computing the Battle for Hearts and Minds: Lessons from the Vendée

NASA Astrophysics Data System (ADS)

Hurwitz, Roger

We analyze the conditions and processes that spawned a historic case of insurgency in the context of regime change. The analysis is an early step in the development of formal models that capture the complex dynamics of insurgencies, resistance and other conflicts that are often characterized as "battles for hearts and minds" (henceforth BHAM). The characterization, however, flattens the complexities of the conflict. It suggests bloodless engagements where victories come from public relations and demonstration projects that foster positive attitudes among a subject population. Officials conducting these battles sometimes use the label to mask their ignorance of the complexities and sometimes with the intention of minimizing their difficulties in dealing with them. Modeling can therefore be a constructive step in overcoming their impoverished thinking.

Complex character analysis of heart rate variability following brain asphyxia.

PubMed

Cai, Yuanyuan; Qiu, Yihong; Wei, Lan; Zhang, Wei; Hu, Sijun; Smith, Peter R; Crabtree, Vincent P; Tong, Shanbao; Thakor, Nitish V; Zhu, Yisheng

2006-05-01

In the present study Renyi entropy and L-Z complexity were used to characterize heart rate variability (HRV) of rats that were suffered from brain asphyxia and ischemia. Two groups of rats were studied: (a) rats (n=5) injected with NAALADase inhibitor, 2-PMPA, which has been proven neuroprotective in asphyxia injury and (b) control subjects (n=5) without medication. Renyi entropy and L-Z complexity of the R-R intervals (RRI) at different experiment stages were investigated in the two groups. The results show that both measures indicate less injury and better recovery in the drug injection group. The dynamic change of 90 min RRI signal after the asphyxia was investigated. The sudden reduction of the two parameters shows their sensitivity to the asphyxia insult.

Visibility graph analysis of heart rate time series and bio-marker of congestive heart failure

NASA Astrophysics Data System (ADS)

Bhaduri, Anirban; Bhaduri, Susmita; Ghosh, Dipak

2017-09-01

Study of RR interval time series for Congestive Heart Failure had been an area of study with different methods including non-linear methods. In this article the cardiac dynamics of heart beat are explored in the light of complex network analysis, viz. visibility graph method. Heart beat (RR Interval) time series data taken from Physionet database [46, 47] belonging to two groups of subjects, diseased (congestive heart failure) (29 in number) and normal (54 in number) are analyzed with the technique. The overall results show that a quantitative parameter can significantly differentiate between the diseased subjects and the normal subjects as well as different stages of the disease. Further, the data when split into periods of around 1 hour each and analyzed separately, also shows the same consistent differences. This quantitative parameter obtained using the visibility graph analysis thereby can be used as a potential bio-marker as well as a subsequent alarm generation mechanism for predicting the onset of Congestive Heart Failure.

Mitochondrial function as a therapeutic target in heart failure

PubMed Central

Brown, David A.; Perry, Justin B.; Allen, Mitchell E.; Sabbah, Hani N.; Stauffer, Brian L.; Shaikh, Saame Raza; Cleland, John G. F.; Colucci, Wilson S.; Butler, Javed; Voors, Adriaan A.; Anker, Stefan D.; Pitt, Bertram; Pieske, Burkert; Filippatos, Gerasimos; Greene, Stephen J.; Gheorghiade, Mihai

2017-01-01

Heart failure is a pressing worldwide public-health problem with millions of patients having worsening heart failure. Despite all the available therapies, the condition carries a very poor prognosis. Existing therapies provide symptomatic and clinical benefit, but do not fully address molecular abnormalities that occur in cardiomyocytes. This shortcoming is particularly important given that most patients with heart failure have viable dysfunctional myocardium, in which an improvement or normalization of function might be possible. Although the pathophysiology of heart failure is complex, mitochondrial dysfunction seems to be an important target for therapy to improve cardiac function directly. Mitochondrial abnormalities include impaired mitochondrial electron transport chain activity, increased formation of reactive oxygen species, shifted metabolic substrate utilization, aberrant mitochondrial dynamics, and altered ion homeostasis. In this Consensus Statement, insights into the mechanisms of mitochondrial dysfunction in heart failure are presented, along with an overview of emerging treatments with the potential to improve the function of the failing heart by targeting mitochondria. PMID:28004807

CryoTEM as an Advanced Analytical Tool for Materials Chemists.

PubMed

Patterson, Joseph P; Xu, Yifei; Moradi, Mohammad-Amin; Sommerdijk, Nico A J M; Friedrich, Heiner

2017-07-18

Morphology plays an essential role in chemistry through the segregation of atoms and/or molecules into different phases, delineated by interfaces. This is a general process in materials synthesis and exploited in many fields including colloid chemistry, heterogeneous catalysis, and functional molecular systems. To rationally design complex materials, we must understand and control morphology evolution. Toward this goal, we utilize cryogenic transmission electron microscopy (cryoTEM), which can track the structural evolution of materials in solution with nanometer spatial resolution and a temporal resolution of <1 s. In this Account, we review examples of our own research where direct observations by cryoTEM have been essential to understanding morphology evolution in macromolecular self-assembly, inorganic nucleation and growth, and the cooperative evolution of hybrid materials. These three different research areas are at the heart of our approach to materials chemistry where we take inspiration from the myriad examples of complex materials in Nature. Biological materials are formed using a limited number of chemical components and under ambient conditions, and their formation pathways were refined during biological evolution by enormous trial and error approaches to self-organization and biomineralization. By combining the information on what is possible in nature and by focusing on a limited number of chemical components, we aim to provide an essential insight into the role of structure evolution in materials synthesis. Bone, for example, is a hierarchical and hybrid material which is lightweight, yet strong and hard. It is formed by the hierarchical self-assembly of collagen into a macromolecular template with nano- and microscale structure. This template then directs the nucleation and growth of oriented, nanoscale calcium phosphate crystals to form the composite material. Fundamental insight into controlling these structuring processes will eventually allow us to design such complex materials with predetermined and potentially unique properties.

Stratification of complexity in congenital heart surgery: comparative study of the Risk Adjustment for Congenital Heart Surgery (RACHS-1) method, Aristotle basic score and Society of Thoracic Surgeons-European Association for Cardio- Thoracic Surgery (STS-EACTS) mortality score

PubMed Central

Cavalcanti, Paulo Ernando Ferraz; Sá, Michel Pompeu Barros de Oliveira; dos Santos, Cecília Andrade; Esmeraldo, Isaac Melo; Chaves, Mariana Leal; Lins, Ricardo Felipe de Albuquerque; Lima, Ricardo de Carvalho

2015-01-01

Objective To determine whether stratification of complexity models in congenital heart surgery (RACHS-1, Aristotle basic score and STS-EACTS mortality score) fit to our center and determine the best method of discriminating hospital mortality. Methods Surgical procedures in congenital heart diseases in patients under 18 years of age were allocated to the categories proposed by the stratification of complexity methods currently available. The outcome hospital mortality was calculated for each category from the three models. Statistical analysis was performed to verify whether the categories presented different mortalities. The discriminatory ability of the models was determined by calculating the area under the ROC curve and a comparison between the curves of the three models was performed. Results 360 patients were allocated according to the three methods. There was a statistically significant difference between the mortality categories: RACHS-1 (1) - 1.3%, (2) - 11.4%, (3)-27.3%, (4) - 50 %, (P<0.001); Aristotle basic score (1) - 1.1%, (2) - 12.2%, (3) - 34%, (4) - 64.7%, (P<0.001); and STS-EACTS mortality score (1) - 5.5 %, (2) - 13.6%, (3) - 18.7%, (4) - 35.8%, (P<0.001). The three models had similar accuracy by calculating the area under the ROC curve: RACHS-1- 0.738; STS-EACTS-0.739; Aristotle- 0.766. Conclusion The three models of stratification of complexity currently available in the literature are useful with different mortalities between the proposed categories with similar discriminatory capacity for hospital mortality. PMID:26107445

Comparative study of the Aristotle Comprehensive Complexity and the Risk Adjustment in Congenital Heart Surgery scores.

PubMed

Bojan, Mirela; Gerelli, Sébastien; Gioanni, Simone; Pouard, Philippe; Vouhé, Pascal

2011-09-01

The Aristotle Comprehensive Complexity (ACC) and the Risk Adjustment in Congenital Heart Surgery (RACHS-1) scores have been proposed for complexity adjustment in the analysis of outcome after congenital heart surgery. Previous studies found RACHS-1 to be a better predictor of outcome than the Aristotle Basic Complexity score. We compared the ability to predict operative mortality and morbidity between ACC, the latest update of the Aristotle method and RACHS-1. Morbidity was assessed by length of intensive care unit stay. We retrospectively enrolled patients undergoing congenital heart surgery. We modeled each score as a continuous variable, mortality as a binary variable, and length of stay as a censored variable. We compared performance between mortality and morbidity models using likelihood ratio tests for nested models and paired concordance statistics. Among all 1,384 patients enrolled, 30-day mortality rate was 3.5% and median length of intensive care unit stay was 3 days. Both scores strongly related to mortality, but ACC made better prediction than RACHS-1; c-indexes 0.87 (0.84, 0.91) vs 0.75 (0.65, 0.82). Both scores related to overall length of stay only during the first postoperative week, but ACC made better predictions than RACHS-1; U statistic=0.22, p<0.001. No significant difference was noted after adjusting RACHS-1 models on age, prematurity, and major extracardiac abnormalities. The ACC was a better predictor of operative mortality and length of intensive care unit stay than RACHS-1. In order to achieve similar performance, regression models including RACHS-1 need to be further adjusted on age, prematurity, and major extracardiac abnormalities. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

American Heart Association’s Life’s Simple 7: Avoiding Heart Failure and Preserving Cardiac Structure and Function

PubMed Central

Folsom, Aaron R.; Shah, Amil M.; Lutsey, Pamela L.; Roetker, Nicholas S.; Alonso, Alvaro; Avery, Christy L.; Miedema, Michael D.; Konety, Suma; Chang, Patricia P.; Solomon, Scott D.

2015-01-01

BACKGROUND Many people may underappreciate the role of lifestyle in avoiding heart failure. We estimated whether greater adherence in middle age to American Heart Association’s Life’s Simple 7 guidelines -- on smoking, body mass, physical activity, diet, cholesterol, blood pressure, and glucose -- is associated with lower lifetime risk of heart failure and greater preservation of cardiac structure and function in old age. METHODS We studied the population-based Atherosclerosis Risk in Communities Study cohort of 13,462 adults aged 45-64 years in 1987-89. From the 1987-89 risk factor measurements, we created a Life’s Simple 7 score (range 0-14, giving 2 points for ideal, 1 point for intermediate, and 0 points for poor components). We identified 2,218 incident heart failure events using surveillance of hospital discharge and death codes through 2011. In addition, in 4,855 participants free of clinical cardiovascular disease in 2011-13, we performed echocardiography from which we quantified left ventricular hypertrophy and diastolic dysfunction. RESULTS One in four participants (25.5%) developed heart failure through age 85. Yet, this lifetime heart failure risk was 14.4% for those with a middle-age Life’s Simple 7 score of 10-14 (optimal), 26.8% for a score of 5-9 (average), and 48.6% for a score of 0-4 (inadequate). Among those with no clinical cardiovascular event, the prevalence of left ventricular hypertrophy in late life was approximately 40% as common, and diastolic dysfunction was approximately 60% as common, among those with an optimal middle-age Life’s Simple 7 score compared with an inadequate score. CONCLUSIONS Greater achievement of American Heart Association’s Life’s Simple 7 in middle-age is associated with a lower lifetime occurrence of heart failure and greater preservation of cardiac structure and function. PMID:25908393

State-level minimum wage and heart disease death rates in the United States, 1980-2015: A novel application of marginal structural modeling.

PubMed

Van Dyke, Miriam E; Komro, Kelli A; Shah, Monica P; Livingston, Melvin D; Kramer, Michael R

2018-07-01

Despite substantial declines since the 1960's, heart disease remains the leading cause of death in the United States (US) and geographic disparities in heart disease mortality have grown. State-level socioeconomic factors might be important contributors to geographic differences in heart disease mortality. This study examined the association between state-level minimum wage increases above the federal minimum wage and heart disease death rates from 1980 to 2015 among 'working age' individuals aged 35-64 years in the US. Annual, inflation-adjusted state and federal minimum wage data were extracted from legal databases and annual state-level heart disease death rates were obtained from CDC Wonder. Although most minimum wage and health studies to date use conventional regression models, we employed marginal structural models to account for possible time-varying confounding. Quasi-experimental, marginal structural models accounting for state, year, and state × year fixed effects estimated the association between increases in the state-level minimum wage above the federal minimum wage and heart disease death rates. In models of 'working age' adults (35-64 years old), a $1 increase in the state-level minimum wage above the federal minimum wage was on average associated with ~6 fewer heart disease deaths per 100,000 (95% CI: -10.4, -1.99), or a state-level heart disease death rate that was 3.5% lower per year. In contrast, for older adults (65+ years old) a $1 increase was on average associated with a 1.1% lower state-level heart disease death rate per year (b = -28.9 per 100,000, 95% CI: -71.1, 13.3). State-level economic policies are important targets for population health research. Copyright © 2018 Elsevier Inc. All rights reserved.

Energy expenditure in frontotemporal dementia: a behavioural and imaging study.

PubMed

Ahmed, Rebekah M; Landin-Romero, Ramon; Collet, Tinh-Hai; van der Klaauw, Agatha A; Devenney, Emma; Henning, Elana; Kiernan, Matthew C; Piguet, Olivier; Farooqi, I Sadaf; Hodges, John R

2017-01-01

SEE FINGER DOI101093/AWW312 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Abnormal eating behaviour and metabolic parameters including insulin resistance, dyslipidaemia and body mass index are increasingly recognized as important components of neurodegenerative disease and may contribute to survival. It has previously been established that behavioural variant frontotemporal dementia is associated with abnormal eating behaviour characterized by increased sweet preference. In this study, it was hypothesized that behavioural variant frontotemporal dementia might also be associated with altered energy expenditure. A cohort of 19 patients with behavioural variant frontotemporal dementia, 13 with Alzheimer's disease and 16 (age- and sex-matched) healthy control subjects were studied using Actiheart devices (CamNtech) to assess resting and stressed heart rate. Actiheart devices were fitted for 7 days to measure sleeping heart rate, activity levels, and resting, active and total energy expenditure. Using high resolution structural magnetic resonance imaging the neural correlates of increased resting heart rate were investigated including cortical thickness and region of interest analyses. In behavioural variant frontotemporal dementia, resting (P = 0.001), stressed (P = 0.037) and sleeping heart rate (P = 0.038) were increased compared to control subjects, and resting heart rate (P = 0.020) compared to Alzheimer disease patients. Behavioural variant frontotemporal dementia was associated with decreased activity levels compared to controls (P = 0.002) and increased resting energy expenditure (P = 0.045) and total energy expenditure (P = 0.035). Increased resting heart rate correlated with behavioural (Cambridge Behavioural Inventory) and cognitive measures (Addenbrooke's Cognitive Examination). Increased resting heart rate in behavioural variant frontotemporal dementia correlated with atrophy involving the mesial temporal cortex, insula, and amygdala, regions previously suggested to be involved exclusively in social and emotion processing in frontotemporal dementia. These neural correlates overlap the network involved in eating behaviour in frontotemporal dementia, suggesting a complex interaction between eating behaviour, autonomic function and energy homeostasis. As such the present study suggests that increased heart rate and autonomic changes are prevalent in behavioural variant frontotemporal dementia, and are associated with changes in energy expenditure. An understanding of these changes and neural correlates may have potential relevance to disease progression and prognosis. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Psychometric properties of HeartQoL, a core heart disease-specific health-related quality of life questionnaire, in Danish implantable cardioverter defibrillator recipients.

PubMed

Zangger, Graziella; Zwisler, Ann-Dorthe; Kikkenborg Berg, Selina; Kristensen, Marie S; Grønset, Charlotte N; Uddin, Jamal; Pedersen, Susanne S; Oldridge, Neil B; Thygesen, Lau C

2018-01-01

Background Patient-reported health-related quality of life is increasingly used as an outcome measure in clinical trials and as a performance measure to evaluate quality of care. The objective of this study was to assess the psychometric properties of the Danish HeartQoL questionnaire, a core heart disease-specific health-related quality of life questionnaire, in implantable cardioverter defibrillator recipients. Design This study involved cross-sectional and test-retest study designs. Method Implantable cardioverter defibrillator recipients in the cross-sectional study completed the HeartQoL, the Short-Form 36 Health Survey, and the Hospital Anxiety and Depression Scale. The HeartQoL structure, construct-related validity (convergent and discriminative) and reliability (internal consistency) were assessed. HeartQoL reproducibility (test-retest) was assessed in an independent sample of implantable cardioverter defibrillator recipients. Results Mokken scale analysis supported the bi-dimensional structure of HeartQoL among 358 implantable cardioverter defibrillator recipients. Convergent ( r > 0.72) and discriminative validity were confirmed. The HeartQoL scales demonstrated satisfactory internal consistency (Cronbach's alpha > 0.90). Test-retest reliability (two weeks interval) was assessed in 89 implantable cardioverter defibrillator recipients and found to be acceptable for each scale (intra-class correlation > 0.90). Conclusion The Danish HeartQoL questionnaire demonstrated satisfactory key psychometric attributes of validity and reliability in this implantable cardioverter defibrillator population. This study adds support for the HeartQoL as a core heart-specific health-related quality of life questionnaire in a broad group of patients with heart disease including implantable cardioverter defibrillator recipients.

Live dynamic OCT imaging of cardiac structure and function in mouse embryos with 43 Hz direct volumetric data acquisition

NASA Astrophysics Data System (ADS)

Wang, Shang; Singh, Manmohan; Lopez, Andrew L.; Wu, Chen; Raghunathan, Raksha; Schill, Alexander; Li, Jiasong; Larin, Kirill V.; Larina, Irina V.

2016-03-01

Efficient phenotyping of cardiac dynamics in live mouse embryos has significant implications on understanding of early mammalian heart development and congenital cardiac defects. Recent studies established optical coherence tomography (OCT) as a powerful tool for live embryonic heart imaging in various animal models. However, current four-dimensional (4D) OCT imaging of the beating embryonic heart largely relies on gated data acquisition or postacquisition synchronization, which brings errors when cardiac cycles lack perfect periodicity and is time consuming and computationally expensive. Here, we report direct 4D OCT imaging of the structure and function of cardiac dynamics in live mouse embryos achieved by employing a Fourier domain mode-locking swept laser source that enables ~1.5 MHz A-line rate. Through utilizing both forward and backward scans of a resonant mirror, we obtained a ~6.4 kHz frame rate, which allows for a direct volumetric data acquisition speed of ~43 Hz, around 20 times of the early-stage mouse embryonic heart rate. Our experiments were performed on mouse embryos at embryonic day 9.5. Time-resolved 3D cardiodynamics clearly shows the heart structure in motion. We present analysis of cardiac wall movement and its velocity from the primitive atrium and ventricle. Our results suggest that the combination of ultrahigh-speed OCT imaging with live embryo culture could be a useful embryonic heart phenotyping approach for mouse mutants modeling human congenital heart diseases.

Interpreting T-Cell Cross-reactivity through Structure: Implications for TCR-Based Cancer Immunotherapy.

PubMed

Antunes, Dinler A; Rigo, Maurício M; Freitas, Martiela V; Mendes, Marcus F A; Sinigaglia, Marialva; Lizée, Gregory; Kavraki, Lydia E; Selin, Liisa K; Cornberg, Markus; Vieira, Gustavo F

2017-01-01

Immunotherapy has become one of the most promising avenues for cancer treatment, making use of the patient's own immune system to eliminate cancer cells. Clinical trials with T-cell-based immunotherapies have shown dramatic tumor regressions, being effective in multiple cancer types and for many different patients. Unfortunately, this progress was tempered by reports of serious (even fatal) side effects. Such therapies rely on the use of cytotoxic T-cell lymphocytes, an essential part of the adaptive immune system. Cytotoxic T-cells are regularly involved in surveillance and are capable of both eliminating diseased cells and generating protective immunological memory. The specificity of a given T-cell is determined through the structural interaction between the T-cell receptor (TCR) and a peptide-loaded major histocompatibility complex (MHC); i.e., an intracellular peptide-ligand displayed at the cell surface by an MHC molecule. However, a given TCR can recognize different peptide-MHC (pMHC) complexes, which can sometimes trigger an unwanted response that is referred to as T-cell cross-reactivity. This has become a major safety issue in TCR-based immunotherapies, following reports of melanoma-specific T-cells causing cytotoxic damage to healthy tissues (e.g., heart and nervous system). T-cell cross-reactivity has been extensively studied in the context of viral immunology and tissue transplantation. Growing evidence suggests that it is largely driven by structural similarities of seemingly unrelated pMHC complexes. Here, we review recent reports about the existence of pMHC "hot-spots" for cross-reactivity and propose the existence of a TCR interaction profile (i.e., a refinement of a more general TCR footprint in which some amino acid residues are more important than others in triggering T-cell cross-reactivity). We also make use of available structural data and pMHC models to interpret previously reported cross-reactivity patterns among virus-derived peptides. Our study provides further evidence that structural analyses of pMHC complexes can be used to assess the intrinsic likelihood of cross-reactivity among peptide-targets. Furthermore, we hypothesize that some apparent inconsistencies in reported cross-reactivities, such as a preferential directionality, might also be driven by particular structural features of the targeted pMHC complex. Finally, we explain why TCR-based immunotherapy provides a special context in which meaningful T-cell cross-reactivity predictions can be made.

Interpreting T-Cell Cross-reactivity through Structure: Implications for TCR-Based Cancer Immunotherapy

PubMed Central

Antunes, Dinler A.; Rigo, Maurício M.; Freitas, Martiela V.; Mendes, Marcus F. A.; Sinigaglia, Marialva; Lizée, Gregory; Kavraki, Lydia E.; Selin, Liisa K.; Cornberg, Markus; Vieira, Gustavo F.

2017-01-01

Immunotherapy has become one of the most promising avenues for cancer treatment, making use of the patient’s own immune system to eliminate cancer cells. Clinical trials with T-cell-based immunotherapies have shown dramatic tumor regressions, being effective in multiple cancer types and for many different patients. Unfortunately, this progress was tempered by reports of serious (even fatal) side effects. Such therapies rely on the use of cytotoxic T-cell lymphocytes, an essential part of the adaptive immune system. Cytotoxic T-cells are regularly involved in surveillance and are capable of both eliminating diseased cells and generating protective immunological memory. The specificity of a given T-cell is determined through the structural interaction between the T-cell receptor (TCR) and a peptide-loaded major histocompatibility complex (MHC); i.e., an intracellular peptide–ligand displayed at the cell surface by an MHC molecule. However, a given TCR can recognize different peptide–MHC (pMHC) complexes, which can sometimes trigger an unwanted response that is referred to as T-cell cross-reactivity. This has become a major safety issue in TCR-based immunotherapies, following reports of melanoma-specific T-cells causing cytotoxic damage to healthy tissues (e.g., heart and nervous system). T-cell cross-reactivity has been extensively studied in the context of viral immunology and tissue transplantation. Growing evidence suggests that it is largely driven by structural similarities of seemingly unrelated pMHC complexes. Here, we review recent reports about the existence of pMHC “hot-spots” for cross-reactivity and propose the existence of a TCR interaction profile (i.e., a refinement of a more general TCR footprint in which some amino acid residues are more important than others in triggering T-cell cross-reactivity). We also make use of available structural data and pMHC models to interpret previously reported cross-reactivity patterns among virus-derived peptides. Our study provides further evidence that structural analyses of pMHC complexes can be used to assess the intrinsic likelihood of cross-reactivity among peptide-targets. Furthermore, we hypothesize that some apparent inconsistencies in reported cross-reactivities, such as a preferential directionality, might also be driven by particular structural features of the targeted pMHC complex. Finally, we explain why TCR-based immunotherapy provides a special context in which meaningful T-cell cross-reactivity predictions can be made. PMID:29046675

Cardiopulmonary Resuscitation in Infants and Children With Cardiac Disease: A Scientific Statement From the American Heart Association.

PubMed

Marino, Bradley S; Tabbutt, Sarah; MacLaren, Graeme; Hazinski, Mary Fran; Adatia, Ian; Atkins, Dianne L; Checchia, Paul A; DeCaen, Allan; Fink, Ericka L; Hoffman, George M; Jefferies, John L; Kleinman, Monica; Krawczeski, Catherine D; Licht, Daniel J; Macrae, Duncan; Ravishankar, Chitra; Samson, Ricardo A; Thiagarajan, Ravi R; Toms, Rune; Tweddell, James; Laussen, Peter C

2018-05-29

Cardiac arrest occurs at a higher rate in children with heart disease than in healthy children. Pediatric basic life support and advanced life support guidelines focus on delivering high-quality resuscitation in children with normal hearts. The complexity and variability in pediatric heart disease pose unique challenges during resuscitation. A writing group appointed by the American Heart Association reviewed the literature addressing resuscitation in children with heart disease. MEDLINE and Google Scholar databases were searched from 1966 to 2015, cross-referencing pediatric heart disease with pertinent resuscitation search terms. The American College of Cardiology/American Heart Association classification of recommendations and levels of evidence for practice guidelines were used. The recommendations in this statement concur with the critical components of the 2015 American Heart Association pediatric basic life support and pediatric advanced life support guidelines and are meant to serve as a resuscitation supplement. This statement is meant for caregivers of children with heart disease in the prehospital and in-hospital settings. Understanding the anatomy and physiology of the high-risk pediatric cardiac population will promote early recognition and treatment of decompensation to prevent cardiac arrest, increase survival from cardiac arrest by providing high-quality resuscitations, and improve outcomes with postresuscitation care. © 2018 American Heart Association, Inc.

Effects of protein-protein interactions and ligand binding on the ion permeation in KCNQ1 potassium channel.

PubMed

Jalily Hasani, Horia; Ganesan, Aravindhan; Ahmed, Marawan; Barakat, Khaled H

2018-01-01

The voltage-gated KCNQ1 potassium ion channel interacts with the type I transmembrane protein minK (KCNE1) to generate the slow delayed rectifier (IKs) current in the heart. Mutations in these transmembrane proteins have been linked with several heart-related issues, including long QT syndromes (LQTS), congenital atrial fibrillation, and short QT syndrome. Off-target interactions of several drugs with that of KCNQ1/KCNE1 ion channel complex have been known to cause fatal cardiac irregularities. Thus, KCNQ1/KCNE1 remains an important avenue for drug-design and discovery research. In this work, we present the structural and mechanistic details of potassium ion permeation through an open KCNQ1 structural model using the combined molecular dynamics and steered molecular dynamics simulations. We discuss the processes and key residues involved in the permeation of a potassium ion through the KCNQ1 ion channel, and how the ion permeation is affected by (i) the KCNQ1-KCNE1 interactions and (ii) the binding of chromanol 293B ligand and its derivatives into the complex. The results reveal that interactions between KCNQ1 with KCNE1 causes a pore constriction in the former, which in-turn forms small energetic barriers in the ion-permeation pathway. These findings correlate with the previous experimental reports that interactions of KCNE1 dramatically slows the activation of KCNQ1. Upon ligand-binding onto the complex, the energy-barriers along ion permeation path are more pronounced, as expected, therefore, requiring higher force in our steered-MD simulations. Nevertheless, pulling the ion when a weak blocker is bound to the channel does not necessitate high force in SMD. This indicates that our SMD simulations have been able to discern between strong and week blockers and reveal their influence on potassium ion permeation. The findings presented here will have some implications in understanding the potential off-target interactions of the drugs with the KCNQ1/KCNE1 channel that lead to cardiotoxic effects.

Curvilinear Immersed Boundary Method for Simulating Fluid Structure Interaction with Complex 3D Rigid Bodies

PubMed Central

Borazjani, Iman; Ge, Liang; Sotiropoulos, Fotis

2010-01-01

The sharp-interface CURVIB approach of Ge and Sotiropoulos [L. Ge, F. Sotiropoulos, A Numerical Method for Solving the 3D Unsteady Incompressible Navier-Stokes Equations in Curvilinear Domains with Complex Immersed Boundaries, Journal of Computational Physics 225 (2007) 1782–1809] is extended to simulate fluid structure interaction (FSI) problems involving complex 3D rigid bodies undergoing large structural displacements. The FSI solver adopts the partitioned FSI solution approach and both loose and strong coupling strategies are implemented. The interfaces between immersed bodies and the fluid are discretized with a Lagrangian grid and tracked with an explicit front-tracking approach. An efficient ray-tracing algorithm is developed to quickly identify the relationship between the background grid and the moving bodies. Numerical experiments are carried out for two FSI problems: vortex induced vibration of elastically mounted cylinders and flow through a bileaflet mechanical heart valve at physiologic conditions. For both cases the computed results are in excellent agreement with benchmark simulations and experimental measurements. The numerical experiments suggest that both the properties of the structure (mass, geometry) and the local flow conditions can play an important role in determining the stability of the FSI algorithm. Under certain conditions unconditionally unstable iteration schemes result even when strong coupling FSI is employed. For such cases, however, combining the strong-coupling iteration with under-relaxation in conjunction with the Aitken’s acceleration technique is shown to effectively resolve the stability problems. A theoretical analysis is presented to explain the findings of the numerical experiments. It is shown that the ratio of the added mass to the mass of the structure as well as the sign of the local time rate of change of the force or moment imparted on the structure by the fluid determine the stability and convergence of the FSI algorithm. The stabilizing role of under-relaxation is also clarified and an upper bound of the required for stability under-relaxation coefficient is derived. PMID:20981246

Curvilinear immersed boundary method for simulating fluid structure interaction with complex 3D rigid bodies

NASA Astrophysics Data System (ADS)

Borazjani, Iman; Ge, Liang; Sotiropoulos, Fotis

2008-08-01

The sharp-interface CURVIB approach of Ge and Sotiropoulos [L. Ge, F. Sotiropoulos, A numerical method for solving the 3D unsteady incompressible Navier-Stokes equations in curvilinear domains with complex immersed boundaries, Journal of Computational Physics 225 (2007) 1782-1809] is extended to simulate fluid structure interaction (FSI) problems involving complex 3D rigid bodies undergoing large structural displacements. The FSI solver adopts the partitioned FSI solution approach and both loose and strong coupling strategies are implemented. The interfaces between immersed bodies and the fluid are discretized with a Lagrangian grid and tracked with an explicit front-tracking approach. An efficient ray-tracing algorithm is developed to quickly identify the relationship between the background grid and the moving bodies. Numerical experiments are carried out for two FSI problems: vortex induced vibration of elastically mounted cylinders and flow through a bileaflet mechanical heart valve at physiologic conditions. For both cases the computed results are in excellent agreement with benchmark simulations and experimental measurements. The numerical experiments suggest that both the properties of the structure (mass, geometry) and the local flow conditions can play an important role in determining the stability of the FSI algorithm. Under certain conditions the FSI algorithm is unconditionally unstable even when strong coupling FSI is employed. For such cases, however, combining the strong coupling iteration with under-relaxation in conjunction with the Aitken's acceleration technique is shown to effectively resolve the stability problems. A theoretical analysis is presented to explain the findings of the numerical experiments. It is shown that the ratio of the added mass to the mass of the structure as well as the sign of the local time rate of change of the force or moment imparted on the structure by the fluid determine the stability and convergence of the FSI algorithm. The stabilizing role of under-relaxation is also clarified and the upper bound of the under-relaxation coefficient, required for stability, is derived.

[Review of wireless energy transmission system for total artificial heart].

PubMed

Zhang, Chi; Yang, Ming

2009-11-01

This paper sums up the fundamental structure of wireless energy transmission system for total artificial heart, and compares the key parameters and performance of some representative systems. After that, it is discussed that the future development trend of wireless energy transmission system for total artificial heart.

Psychometric Evaluation of Two Appetite Questionnaires in Patients With Heart Failure.

PubMed

Andreae, Christina; Strömberg, Anna; Sawatzky, Richard; Årestedt, Kristofer

2015-12-01

Decreased appetite in heart failure (HF) may lead to undernutrition which could negatively influence prognosis. Appetite is a complex clinical issue that is often best measured with the use of self-report instruments. However, there is a lack of self-rated appetite instruments. The Council on Nutrition Appetite Questionnaire (CNAQ) and the Simplified Nutritional Appetite Questionnaire (SNAQ) are validated instruments developed primarily for elderly people. Yet, the psychometric properties have not been evaluated in HF populations. The aim of the present study was to evaluate the psychometric properties of CNAQ and SNAQ in patients with HF. A total of 186 outpatients with reduced ejection fraction and New York Heart Association (NYHA) functional classifications II-IV were included (median age 72 y; 70% men). Data were collected with the use of a questionnaire that included the CNAQ and SNAQ. The psychometric evaluation included data quality, factor structure, construct validity, known-group validity, and internal consistency. Unidimensionality was supported by means of parallel analysis and confirmatory factor analyses (CFAs). The CFA results indicated sufficient model fit. Both construct validity and known-group validity were supported. Internal consistency reliability was acceptable, with ordinal coefficient alpha estimates of 0.82 for CNAQ and 0.77 for SNAQ. CNAQ and SNAQ demonstrated sound psychometric properties and can be used to measure appetite in patients with HF. Copyright © 2015 Elsevier Inc. All rights reserved.

Identifying improvements to complex pathways: evidence synthesis and stakeholder engagement in infant congenital heart disease

PubMed Central

Crowe, Sonya; Knowles, Rachel; Wray, Jo; Tregay, Jenifer; Ridout, Deborah A; Utley, Martin; Franklin, Rodney; Bull, Catherine L; Brown, Katherine L

2016-01-01

Objectives Many infants die in the year following discharge from hospital after surgical or catheter intervention for congenital heart disease (3–5% of discharged infants). There is considerable variability in the provision of care and support in this period, and some families experience barriers to care. We aimed to identify ways to improve discharge and postdischarge care for this patient group. Design A systematic evidence synthesis aligned with a process of eliciting the perspectives of families and professionals from community, primary, secondary and tertiary care. Setting UK. Results A set of evidence-informed recommendations for improving the discharge and postdischarge care of infants following intervention for congenital heart disease was produced. These address known challenges with current care processes and, recognising current resource constraints, are targeted at patient groups based on the number of patients affected and the level and nature of their risk of adverse 1-year outcome. The recommendations include: structured discharge documentation, discharging certain high-risk patients via their local hospital, enhanced surveillance for patients with certain (high-risk) cardiac diagnoses and an early warning tool for parents and community health professionals. Conclusions Our recommendations set out a comprehensive, system-wide approach for improving discharge and postdischarge services. This approach could be used to address challenges in delivering care for other patient populations that can fall through gaps between sectors and organisations. PMID:27266768

A review of state-of-the-art numerical methods for simulating flow through mechanical heart valves.

PubMed

Sotiropoulos, Fotis; Borazjani, Iman

2009-03-01

In nearly half of the heart valve replacement surgeries performed annually, surgeons prefer to implant bileaflet mechanical heart valves (BMHV) because of their durability and long life span. All current BMHV designs, however, are prone to thromboembolic complications and implant recipients need to be on a life-long anticoagulant medication regiment. Non-physiologic flow patterns and turbulence generated by the valve leaflets are believed to be the major culprit for the increased risk of thromboembolism in BMHV implant recipients. In this paper, we review recent advances in developing predictive fluid-structure interaction (FSI) algorithms that can simulate BMHV flows at physiologic conditions and at resolution sufficiently fine to start probing the links between hemodynamics and blood-cell damage. Numerical simulations have provided the first glimpse into the complex hemodynamic environment experienced by blood cells downstream of the valve leaflets and successfully resolved for the first time the experimentally observed explosive transition to a turbulent-like state at the start of the decelerating flow phase. The simulations have also resolved a number of subtle features of experimentally observed valve kinematics, such as the asymmetric opening and closing of the leaflets and the leaflet rebound during closing. The paper also discusses a future research agenda toward developing a powerful patient-specific computational framework for optimizing valve design and implantation in a virtual surgery environment.

A review of state-of-the-art numerical methods for simulating flow through mechanical heart valves

PubMed Central

Borazjani, Iman

2009-01-01

In nearly half of the heart valve replacement surgeries performed annually, surgeons prefer to implant bileaflet mechanical heart valves (BMHV) because of their durability and long life span. All current BMHV designs, however, are prone to thromboembolic complications and implant recipients need to be on a life-long anticoagulant medication regiment. Non-physiologic flow patterns and turbulence generated by the valve leaflets are believed to be the major culprit for the increased risk of thromboembolism in BMHV implant recipients. In this paper, we review recent advances in developing predictive fluid–structure interaction (FSI) algorithms that can simulate BMHV flows at physiologic conditions and at resolution sufficiently fine to start probing the links between hemodynamics and blood-cell damage. Numerical simulations have provided the first glimpse into the complex hemodynamic environment experienced by blood cells downstream of the valve leaflets and successfully resolved for the first time the experimentally observed explosive transition to a turbulent-like state at the start of the decelerating flow phase. The simulations have also resolved a number of subtle features of experimentally observed valve kinematics, such as the asymmetric opening and closing of the leaflets and the leaflet rebound during closing. The paper also discusses a future research agenda toward developing a powerful patient-specific computational framework for optimizing valve design and implantation in a virtual surgery environment. PMID:19194734

The Pathogenesis of Atrial and Atrioventricular Septal Defects with Special Emphasis on the Role of the Dorsal Mesenchymal Protrusion

PubMed Central

Briggs, Laura E.; Kakarla, Jayant; Wessels, Andy

2012-01-01

Partitioning of the four-chambered heart requires the proper formation, interaction and fusion of several mesenchymal tissues derived from different precursor populations that together form the atrioventricular mesenchymal complex. This includes the major endocardial cushions and the mesenchymal cap of the septum primum, which are of endocardial origin, and the dorsal mesenchymal protrusion (DMP), which is derived from the Second Heart Field. Failure of these structures to develop and/or fully mature results in atrial septal defects (ASDs) and atrioventricular septal defects (AVSD). AVSDs are congenital malformations in which the atria are permitted to communicate due to defective septation between the inferior margin of the septum primum and the atrial surface of the common atrioventricular valve. The clinical presentation of AVSDs is variable and depends on both the size and/or type of defect; less severe defects may be asymptomatic while the most severe defect, if untreated, results in infantile heart failure. For many years, maldevelopment of the endocardial cushions was thought to be the sole etiology of AVSDs. More recent work, however, has demonstrated that perturbation of DMP development also results in AVSD. Here, we discuss in detail the formation of the DMP, its contribution to cardiac septation and describe the morphological features as well as potential etiologies of ASDs and AVSDs. PMID:22709652

Bioprosthetic heart valve heterograft biomaterials: structure, mechanical behavior and computational simulation.

PubMed

Sacks, Michael S; Mirnajafi, Ali; Sun, Wei; Schmidt, Paul

2006-11-01

The present review surveys significant developments in the biomechanical characterization and computational simulation of biologically derived chemically cross-linked soft tissues, or 'heterograft' biomaterials, used in replacement bioprosthetic heart valve (BHV). A survey of mechanical characterization techniques, relevant mechanical properties and computational simulation approaches is presented for both the source tissues and cross-linked biomaterials. Since durability remains the critical problem with current bioprostheses, changes with the mechanical behavior with fatigue are also presented. Moreover, given the complex nature of the mechanical properties of heterograft biomaterials it is not surprising that most constitutive (stress-strain) models, historically used to characterize their behavior, were oversimplified. Simulations of BHV function utilizing these models have inevitably been inaccurate. Thus, more recent finite element simulations utilizing nonlinear constitutive models, which achieve greater model fidelity, are reviewed. An important conclusion of this review is the need for accurate constitutive models, rigorously validated with appropriate experimental data, in order that the design benefits of computational models can be realized. Finally, for at least the coming 20 years, BHVs fabricated from heterograft biomaterials will continue to be extensively used, and will probably remain as the dominant valve design. We should thus recognize that rational, scientifically based approaches to BHV biomaterial development and design can lead to significantly improved BHV, over the coming decades, which can potentially impact millions of patients worldwide with heart valve disease.

A bio-inspired microstructure induced by slow injection moulding of cylindrical block copolymers.

PubMed

Stasiak, Joanna; Brubert, Jacob; Serrani, Marta; Nair, Sukumaran; de Gaetano, Francesco; Costantino, Maria Laura; Moggridge, Geoff D

2014-08-28

It is well known that block copolymers with cylindrical morphology show alignment with shear, resulting in anisotropic mechanical properties. Here we show that well-ordered bi-directional orientation can be achieved in such materials by slow injection moulding. This results in a microstructure, and anisotropic mechanical properties, similar to many natural tissues, making this method attractive for engineering prosthetic fibrous tissues. An application of particular interest to us is prosthetic polymeric heart valve leaflets, mimicking the shape, microstructure and hence performance of the native valve. Anisotropic layers have been observed for cylinder-forming block copolymers centrally injected into thin circular discs. The skin layers exhibit orientation parallel to the flow direction, whilst the core layer shows perpendicularly oriented domains; the balance of skin to core layers can be controlled by processing parameters such as temperature and injection rate. Heart valve leaflets with a similar layered structure have been prepared by injection moulding. Numerical modelling demonstrates that such complex orientation can be explained and predicted by the balance of shear and extensional flow.

Crystallization of beef heart cytochrome c oxidase

NASA Astrophysics Data System (ADS)

Yoshikawa, Shinya; Shinzawa, Kyoko; Tsukihara, Tomitake; Abe, Toshio; Caughey, Winslow S.

1991-03-01

The three-dimensional structure of cytochrome c oxidase, a complex (multimetal, multisubunit) membrane protein is critical to elucidation of the mechanism of the enzymic reactions and their control. Our recent developments in the crystallization of the enzyme isolated from beef hearts are presented. The crystals appeared more readily at higher protein concentration, lower ionic strength, higher detergent concentration (Brij-35) and lower temperature. Large crystals were obtained by changing one of these parameters to the crystallization point as slowly as possible, keeping the other parameters constant. Increasing the detergent concentration was the most successful method, producing green crystals of the resting oxidized form as hexagonal bipyramids with typical dimensions of 0.6 mm. The usual procedures for crystallization of water soluble proteins, such as increasing ionic strength by vapor diffusion, were not applicable for this enzyme. Crystals of the resting oxidized enzyme belong to a space group of P6 2 or P6 4 with cell dimensions, a = b = 208.7 Å and c = 282.3 Å. The Patterson function shows that the crystal exhibited a non-crystallographic two-fold axis parallel to the c-axis in the asymmetric unit.

[Results of duplex scanning of brachiocephalic arteries and estimation of the lipid spectrum in coronary heart disease and arterial hypertension in indigenous and alien population of Yamalo-Nenetsky Autonomous District].

PubMed

Gapon, L I; Sereda, T V; Leont'eva, A V; Gul'tiaeva, E P

2013-01-01

The work aimed at studying atherosclerotic lesions in brachiocephalic arteries and lipid spectrum in coronary heart disease (CHD) and arterial hypertension (AH) in indigenous and alien population of Yamalo-Nenetsky Autonomous District. It included 200 patients with CHD and AH (men and women aged 21-55 years, mean 48.2 +/- 07 yr). They were allocated to indigenous and alien groups (100 persons each). The patients matched for age and sex were examined by duplex scanning based at an outpatient facility (Salekhard). The indigenous population showed more pronounced thickening of the intima-media complex (IMC) of the common carotid artery (p = 0.001) and more frequent lesions of the main head arteries with stenosis of different severity (especially in internal carotid arteries). Total cholesterol, LDLP and atherogenicity index were similar in both groups and higher than normal. Indigenous subjects had less atherogenic structure of the lipid spectrum due to lower TG and VLDLP but higher HDLP levels.

Latest Results on Complex Plasmas with the PK-3 Plus Laboratory on Board the International Space Station

NASA Astrophysics Data System (ADS)

Schwabe, M.; Du, C.-R.; Huber, P.; Lipaev, A. M.; Molotkov, V. I.; Naumkin, V. N.; Zhdanov, S. K.; Zhukhovitskii, D. I.; Fortov, V. E.; Thomas, H. M.

2018-03-01

Complex plasmas are low temperature plasmas that contain microparticles in addition to ions, electrons, and neutral particles. The microparticles acquire high charges, interact with each other and can be considered as model particles for effects in classical condensed matter systems, such as crystallization and fluid dynamics. In contrast to atoms in ordinary systems, their movement can be traced on the most basic level, that of individual particles. In order to avoid disturbances caused by gravity, experiments on complex plasmas are often performed under microgravity conditions. The PK-3 Plus Laboratory was operated on board the International Space Station from 2006 - 2013. Its heart consisted of a capacitively coupled radio-frequency plasma chamber. Microparticles were inserted into the low-temperature plasma, forming large, homogeneous complex plasma clouds. Here, we review the results obtained with recent analyzes of PK-3 Plus data: We study the formation of crystallization fronts, as well as the microparticle motion in, and structure of crystalline complex plasmas. We investigate fluid effects such as wave transmission across an interface, and the development of the energy spectra during the onset of turbulent microparticle movement. We explore how abnormal particles move through, and how macroscopic spheres interact with the microparticle cloud. These examples demonstrate the versatility of the PK-3 Plus Laboratory.

Coenzyme Q10 for the treatment of heart failure: a review of the literature

PubMed Central

DiNicolantonio, James J; Bhutani, Jaikrit; McCarty, Mark F; O'Keefe, James H

2015-01-01

Coenzyme Q10 (CoQ10) is an endogenously synthesised and diet-supplied lipid-soluble cofactor that functions in the mitochondrial inner membrane to transfer electrons from complexes I and II to complex III. In addition, its redox activity enables CoQ10 to act as a membrane antioxidant. In patients with congestive heart failure, myocardial CoQ10 content tends to decline as the degree of heart failure worsens. A number of controlled pilot trials with supplemental CoQ10 in heart failure found improvements in functional parameters such as ejection fraction, stroke volume and cardiac output, without side effects. Subsequent meta-analyses have confirmed these findings, although the magnitude of benefit tends to be less notable in patients with severe heart failure, or within the context of ACE inhibitor therapy. The multicentre randomised placebo-controlled Q-SYMBIO trial has assessed the impact of supplemental CoQ10 on hard endpoints in heart failure. A total of 420 patients received either CoQ10 (100 mg three times daily) or placebo and were followed for 2 years. Although short-term functional endpoints were not statistically different in the two groups, CoQ10 significantly reduced the primary long-term endpoint—a major adverse cardiovascular event—which was observed in 15% of the treated participants compared to 26% of those receiving placebo (HR=0.50, CI 0.32 to 0.80, p=0.003). Particularly in light of the excellent tolerance and affordability of this natural physiological compound, supplemental CoQ10 has emerged as an attractive option in the management of heart failure, and merits evaluation in additional large studies. PMID:26512330

Src homology 2 domain-containing phosphatase 2 (Shp2) is a component of the A-kinase-anchoring protein (AKAP)-Lbc complex and is inhibited by protein kinase A (PKA) under pathological hypertrophic conditions in the heart.

PubMed

Burmeister, Brian T; Taglieri, Domenico M; Wang, Li; Carnegie, Graeme K

2012-11-23

AKAP-Lbc is a scaffold protein that coordinates cardiac hypertrophic signaling. AKAP-Lbc interacts with Shp2, facilitating its regulation by PKA. AKAP-Lbc integrates PKA and Shp2 signaling in the heart. Under pathological hypertrophic conditions Shp2 is phosphorylated by PKA, and phosphatase activity is inhibited. Inhibition of Shp2 activity through AKAP-Lbc-anchored PKA is a previously unrecognized mechanism that may promote pathological cardiac hypertrophy. Pathological cardiac hypertrophy (an increase in cardiac mass resulting from stress-induced cardiac myocyte growth) is a major factor underlying heart failure. Our results identify a novel mechanism of Shp2 inhibition that may promote cardiac hypertrophy. We demonstrate that the tyrosine phosphatase, Shp2, is a component of the A-kinase-anchoring protein (AKAP)-Lbc complex. AKAP-Lbc facilitates PKA phosphorylation of Shp2, which inhibits its protein-tyrosine phosphatase activity. Given the important cardiac roles of both AKAP-Lbc and Shp2, we investigated the AKAP-Lbc-Shp2 interaction in the heart. AKAP-Lbc-tethered PKA is implicated in cardiac hypertrophic signaling; however, mechanism of PKA action is unknown. Mutations resulting in loss of Shp2 catalytic activity are also associated with cardiac hypertrophy and congenital heart defects. Our data indicate that AKAP-Lbc integrates PKA and Shp2 signaling in the heart and that AKAP-Lbc-associated Shp2 activity is reduced in hypertrophic hearts in response to chronic β-adrenergic stimulation and PKA activation. Thus, while induction of cardiac hypertrophy is a multifaceted process, inhibition of Shp2 activity through AKAP-Lbc-anchored PKA is a previously unrecognized mechanism that may promote compensatory cardiac hypertrophy.

Pathological Ace2-to-Ace enzyme switch in the stressed heart is transcriptionally controlled by the endothelial Brg1–FoxM1 complex

PubMed Central

Yang, Jin; Feng, Xuhui; Zhou, Qiong; Cheng, Wei; Shang, Ching; Han, Pei; Lin, Chiou-Hong; Chen, Huei-Sheng Vincent; Quertermous, Thomas; Chang, Ching-Pin

2016-01-01

Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown. Here we report that the Brahma-related gene-1 (Brg1) chromatin remodeler and forkhead box M1 (FoxM1) transcription factor cooperate within cardiac (coronary) endothelial cells of pathologically stressed hearts to trigger the Ace2-to-Ace enzyme switch, angiotensin I-to-II conversion, and cardiac hypertrophy. In mice, cardiac stress activates the expression of Brg1 and FoxM1 in endothelial cells. Once activated, Brg1 and FoxM1 form a protein complex on Ace and Ace2 promoters to concurrently activate Ace and repress Ace2, tipping the balance to Ace2 expression with enhanced angiotensin II production, leading to cardiac hypertrophy and fibrosis. Disruption of endothelial Brg1 or FoxM1 or chemical inhibition of FoxM1 abolishes the stress-induced Ace2-to-Ace switch and protects the heart from pathological hypertrophy. In human hypertrophic hearts, BRG1 and FOXM1 expression is also activated in endothelial cells; their expression levels correlate strongly with the ACE/ACE2 ratio, suggesting a conserved mechanism. Our studies demonstrate a molecular interaction of Brg1 and FoxM1 and an endothelial mechanism of modulating Ace/Ace2 ratio for heart failure therapy. PMID:27601681

Pathological Ace2-to-Ace enzyme switch in the stressed heart is transcriptionally controlled by the endothelial Brg1-FoxM1 complex.

PubMed

Yang, Jin; Feng, Xuhui; Zhou, Qiong; Cheng, Wei; Shang, Ching; Han, Pei; Lin, Chiou-Hong; Chen, Huei-Sheng Vincent; Quertermous, Thomas; Chang, Ching-Pin

2016-09-20

Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown. Here we report that the Brahma-related gene-1 (Brg1) chromatin remodeler and forkhead box M1 (FoxM1) transcription factor cooperate within cardiac (coronary) endothelial cells of pathologically stressed hearts to trigger the Ace2-to-Ace enzyme switch, angiotensin I-to-II conversion, and cardiac hypertrophy. In mice, cardiac stress activates the expression of Brg1 and FoxM1 in endothelial cells. Once activated, Brg1 and FoxM1 form a protein complex on Ace and Ace2 promoters to concurrently activate Ace and repress Ace2, tipping the balance to Ace2 expression with enhanced angiotensin II production, leading to cardiac hypertrophy and fibrosis. Disruption of endothelial Brg1 or FoxM1 or chemical inhibition of FoxM1 abolishes the stress-induced Ace2-to-Ace switch and protects the heart from pathological hypertrophy. In human hypertrophic hearts, BRG1 and FOXM1 expression is also activated in endothelial cells; their expression levels correlate strongly with the ACE/ACE2 ratio, suggesting a conserved mechanism. Our studies demonstrate a molecular interaction of Brg1 and FoxM1 and an endothelial mechanism of modulating Ace/Ace2 ratio for heart failure therapy.

Brain Injury in Neonates with Complex Congenital Heart Disease: What Is the Predictive Value of MRI in the Fetal Period?

PubMed

Brossard-Racine, M; du Plessis, A; Vezina, G; Robertson, R; Donofrio, M; Tworetzky, W; Limperopoulos, C

2016-07-01

Brain injury in neonates with congenital heart disease is an important predictor of adverse neurodevelopmental outcome. Impaired brain development in congenital heart disease may have a prenatal origin, but the sensitivity and specificity of fetal brain MR imaging for predicting neonatal brain lesions are currently unknown. We sought to determine the value of conventional fetal MR imaging for predicting abnormal findings on neonatal preoperative MR imaging in neonates with complex congenital heart disease. MR imaging studies were performed in 103 fetuses with confirmed congenital heart disease (mean gestational age, 31.57 ± 3.86 weeks) and were repeated postnatally before cardiac surgery (mean age, 6.8 ± 12.2 days). Each MR imaging study was read by a pediatric neuroradiologist. Brain abnormalities were detected in 17/103 (16%) fetuses by fetal MR imaging and in 33/103 (32%) neonates by neonatal MR imaging. Only 9/33 studies with abnormal neonatal findings were preceded by abnormal findings on fetal MR imaging. The sensitivity and specificity of conventional fetal brain MR imaging for predicting neonatal brain abnormalities were 27% and 89%, respectively. Brain abnormalities detected by in utero MR imaging in fetuses with congenital heart disease are associated with higher risk of postnatal preoperative brain injury. However, a substantial proportion of anomalies on postnatal MR imaging were not present on fetal MR imaging; this result is likely due to the limitations of conventional fetal MR imaging and the emergence of new lesions that occurred after the fetal studies. Postnatal brain MR imaging studies are needed to confirm the presence of injury before open heart surgery. © 2016 by American Journal of Neuroradiology.

Epigenomic and transcriptomic approaches in the post-genomic era: path to novel targets for diagnosis and therapy of the ischaemic heart? Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart

PubMed Central

Perrino, Cinzia; Barabási, Albert-Laszló; Condorelli, Gianluigi; Davidson, Sean Michael; De Windt, Leon; Dimmeler, Stefanie; Engel, Felix Benedikt; Hausenloy, Derek John; Hill, Joseph Addison; Van Laake, Linda Wilhelmina; Lecour, Sandrine; Leor, Jonathan; Madonna, Rosalinda; Mayr, Manuel; Prunier, Fabrice; Sluijter, Joost Petrus Geradus; Schulz, Rainer; Thum, Thomas; Ytrehus, Kirsti

2017-01-01

Despite advances in myocardial reperfusion therapies, acute myocardial ischaemia/reperfusion injury and consequent ischaemic heart failure represent the number one cause of morbidity and mortality in industrialized societies. Although different therapeutic interventions have been shown beneficial in preclinical settings, an effective cardioprotective or regenerative therapy has yet to be successfully introduced in the clinical arena. Given the complex pathophysiology of the ischaemic heart, large scale, unbiased, global approaches capable of identifying multiple branches of the signalling networks activated in the ischaemic/reperfused heart might be more successful in the search for novel diagnostic or therapeutic targets. High-throughput techniques allow high-resolution, genome-wide investigation of genetic variants, epigenetic modifications, and associated gene expression profiles. Platforms such as proteomics and metabolomics (not described here in detail) also offer simultaneous readouts of hundreds of proteins and metabolites. Isolated omics analyses usually provide Big Data requiring large data storage, advanced computational resources and complex bioinformatics tools. The possibility of integrating different omics approaches gives new hope to better understand the molecular circuitry activated by myocardial ischaemia, putting it in the context of the human ‘diseasome’. Since modifications of cardiac gene expression have been consistently linked to pathophysiology of the ischaemic heart, the integration of epigenomic and transcriptomic data seems a promising approach to identify crucial disease networks. Thus, the scope of this Position Paper will be to highlight potentials and limitations of these approaches, and to provide recommendations to optimize the search for novel diagnostic or therapeutic targets for acute ischaemia/reperfusion injury and ischaemic heart failure in the post-genomic era. PMID:28460026

Prenatal Mechanistic Target of Rapamycin Complex 1 (m TORC1) Inhibition by Rapamycin Treatment of Pregnant Mice Causes Intrauterine Growth Restriction and Alters Postnatal Cardiac Growth, Morphology, and Function.

PubMed

Hennig, Maria; Fiedler, Saskia; Jux, Christian; Thierfelder, Ludwig; Drenckhahn, Jörg-Detlef

2017-08-04

Fetal growth impacts cardiovascular health throughout postnatal life in humans. Various animal models of intrauterine growth restriction exhibit reduced heart size at birth, which negatively influences cardiac function in adulthood. The mechanistic target of rapamycin complex 1 (mTORC1) integrates nutrient and growth factor availability with cell growth, thereby regulating organ size. This study aimed at elucidating a possible involvement of mTORC1 in intrauterine growth restriction and prenatal heart growth. We inhibited mTORC1 in fetal mice by rapamycin treatment of pregnant dams in late gestation. Prenatal rapamycin treatment reduces mTORC1 activity in various organs at birth, which is fully restored by postnatal day 3. Rapamycin-treated neonates exhibit a 16% reduction in body weight compared with vehicle-treated controls. Heart weight decreases by 35%, resulting in a significantly reduced heart weight/body weight ratio, smaller left ventricular dimensions, and reduced cardiac output in rapamycin- versus vehicle-treated mice at birth. Although proliferation rates in neonatal rapamycin-treated hearts are unaffected, cardiomyocyte size is reduced, and apoptosis increased compared with vehicle-treated neonates. Rapamycin-treated mice exhibit postnatal catch-up growth, but body weight and left ventricular mass remain reduced in adulthood. Prenatal mTORC1 inhibition causes a reduction in cardiomyocyte number in adult hearts compared with controls, which is partially compensated for by an increased cardiomyocyte volume, resulting in normal cardiac function without maladaptive left ventricular remodeling. Prenatal rapamycin treatment of pregnant dams represents a new mouse model of intrauterine growth restriction and identifies an important role of mTORC1 in perinatal cardiac growth. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

The nuclear contacts and short range correlations in nuclei

NASA Astrophysics Data System (ADS)

Weiss, R.; Cruz-Torres, R.; Barnea, N.; Piasetzky, E.; Hen, O.

2018-05-01

Atomic nuclei are complex strongly interacting systems and their exact theoretical description is a long-standing challenge. An approximate description of nuclei can be achieved by separating its short and long range structure. This separation of scales stands at the heart of the nuclear shell model and effective field theories that describe the long-range structure of the nucleus using a mean-field approximation. We present here an effective description of the complementary short-range structure using contact terms and stylized two-body asymptotic wave functions. The possibility to extract the nuclear contacts from experimental data is presented. Regions in the two-body momentum distribution dominated by high-momentum, close-proximity, nucleon pairs are identified and compared to experimental data. The amount of short-range correlated (SRC) nucleon pairs is determined and compared to measurements. Non-combinatorial isospin symmetry for SRC pairs is identified. The obtained one-body momentum distributions indicate dominance of SRC pairs above the nuclear Fermi-momentum.

The catalyst layer and its dimensionality - A look into its ingredients and how to characterize their effects

NASA Astrophysics Data System (ADS)

Zamel, Nada

2016-03-01

Development of polymer electrolyte membrane (PEM) fuel cells throughout the years is established through its component optimization. This is especially true of its catalyst layer, where structuring of the layer has led to many breakthroughs. The catalyst layer acts as the heart of the cell, where it controls the half-cell reactions and their products. The complex nature of various transport phenomena simultaneously taking place in the layer requires the layer to be heterogeneous in structure. Hence, a delicate balance of the layer's ingredients, coupled with the understanding of the ingredients' interaction, is required. State-of-the-art catalyst layers are composed of a catalyst, its support, a solvent and a binder. Changes in the morphology, structure or material of any of these components ultimately affects the layer's activity and durability. In this review paper, we provide an overview of the various works tailored to understand how each component in the catalyst's ink affects the stability and life-time of the layer.

Right heart on multidetector CT

PubMed Central

Gopalan, D

2011-01-01

Right ventricular function plays an integral role in the pathogenesis and outcome of many cardiovascular diseases. Imaging the right ventricle has long been a challenge because of its complex geometry. In recent years there has been a tremendous expansion in multidetector row CT (MDCT) and its cardiac applications. By judicious modification of contrast medium protocol, it is possible to achieve good opacification of the right-sided cardiac chambers, thereby paving the way for exploring the overshadowed right heart. This article will describe the key features of right heart anatomy, review MDCT acquisition techniques, elaborate the various morphological and functional information that can be obtained, and illustrate some important clinical conditions associated with an abnormal right heart. PMID:22723537